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Subjects and Topics in Basic Medical Science-A Imhotep Virtual Medical School Primer

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Subjects and Topics in Basic Medical Science-A Imhotep Virtual Medical School Primer

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Subjects and Topics in Basic Medical Science-A Imhotep Virtual Medical School Primer Subjects and Topics in Basic Medical Science-A Imhotep Virtual Medical School Primer Document Transcript

  • Subjects and Topics in BasicMedical Science A Imhotep Virtual Medical School Primer Compiled and Edited by Marc Imhotep Cray, M.D.
  • ContentsArticles Anatomy 1 Embryology 3 Biochemistry 6 Histology 14 Epidemiology 20 Biostatistics 31 Molecular biology 34 Genetics 39 Cell biology 55 Endocrinology 60 General pathology 65 Immunology 67 Microbiology 71 Physiology 76 Pathophysiology 78 Pathology 80 Pathogenesis 85 Neuroscience 85 Pharmacology 93 Toxicology 98 Medicine 100 Medical history 114 Chief complaint 116 History of the present illness 117 Past medical history 119 Review of systems 121 Biological system 123 Family history (medicine) 124 List of childhood diseases and disorders 125 Social history (medicine) 127 Allergy 128 Doctor-patient relationship 142 Differential diagnosis 146 Symptom 148 Compiled and Edited by Marc Imhotep Cray , M.D.
  • Medical sign 149 Physical examination 154 References Article Sources and Contributors 157 Image Sources, Licenses and Contributors 163 Article Licenses License 165Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Anatomy 1 Anatomy Anatomy (from the Greek ἀνατομία anatomia, from ἀνατέμνειν ana: separate, apart from, and temnein, to cut up, cut open) is a branch of biology and medicine that is the consideration of the structure of living things. It is a general term that includes human anatomy, animal anatomy (zootomy) and plant anatomy (phytotomy). In some of its facets anatomy is closely related to embryology, comparative anatomy and comparative embryology,[1] through common roots in evolution. Anatomy is subdivided into gross anatomy (or macroscopic anatomy) and microscopic anatomy.[1] Gross anatomy (also called topographical Anatomy lesson carried out in Java, Dutch East anatomy, regional anatomy, or anthropotomy) is the study of Indies, date unknown. anatomical structures that can be seen by unaided vision with the naked eye.[1] Microscopic anatomy is the study of minute anatomical structures assisted with microscopes, which includes histology (the study of the organization of tissues),[1] and cytology (the study of cells). The history of anatomy has been characterized, over time, by a continually developing understanding of the functions of organs and structures in the body. Methods have also improved dramatically, advancing from examination of animals through dissection of cadavers (dead human bodies) to technologically complex techniques developed in the 20th century including X-ray, ultrasound, and MRI imaging. Anatomy should not be confused with anatomical pathology (also called morbid anatomy or histopathology), which is the study of the gross and microscopic appearances of diseased organs. Superficial anatomy Superficial anatomy or surface anatomy is important in anatomy being the study of anatomical landmarks that can be readily seen from the contours or the surface of the body.[1] With knowledge of superficial anatomy, physicians or veterinary surgeons gauge the position and anatomy of the associated deeper structures. Superficial is a directional term that indicates one structure is located more externally than another, or closer to the surface of the body. Human anatomy Human anatomy, including gross human anatomy and histology, is primarily the scientific study of the morphology of the adult human body.[1] Generally, students of certain biological sciences, paramedics, prosthetists and orthotists, physiotherapists, occupational therapy, nurses, and medical students learn gross anatomy and microscopic anatomy from anatomical models, skeletons, textbooks, diagrams, photographs, lectures and tutorials. The study of microscopic anatomy (or histology) can be aided by practical experience examining histological preparations (or slides) under a microscope; and in addition, medical students generally also learn gross anatomy with practical experience of dissection and inspection of cadavers Para-sagittal MRI scan of the head (dead human bodies). Human anatomy, physiology and biochemistry are complementary basic medical sciences, which are generally taught to medical students in their first Compiled and Edited by Marc Imhotep Cray , M.D.
  • Anatomy 2 year at medical school. Human anatomy can be taught regionally or systemically;[1] that is, respectively, studying anatomy by bodily regions such as the head and chest, or studying by specific systems, such as the nervous or respiratory systems. The major anatomy textbook, Grays Anatomy, has recently been reorganized from a systems format to a regional format,[2] [3] in line with modern teaching methods. A thorough working knowledge of anatomy is required by all medical doctors, especially surgeons, and doctors working in some diagnostic specialities, such as histopathology and radiology. An X-ray of a human chest. Academic human anatomists are usually employed by universities, medical schools or teaching hospitals. They are often involved in teaching anatomy, and research into certain systems, organs, tissues or cells. Other branches • Comparative anatomy relates to the comparison of anatomical structures (both gross and microscopic) in different animals.[1] • Anthropological anatomy or physical anthropology relates to the comparison of the anatomy of different races of humans. • Artistic anatomy relates to anatomic studies for artistic reasons. Human heart and lungs, from an older edition of Grays Anatomy. Notes [1] "Introduction page, "Anatomy of the Human Body". Henry Gray. 20th edition. 1918" (http:/ / www. bartleby. com/ 107/ 1. html). . Retrieved 19 March 2007. [2] "Publishers page for Grays Anatomy. 39th edition (UK). 2004. ISBN 0-443-07168-3" (http:/ / web. archive. org/ web/ 20071012104507/ http:/ / intl. elsevierhealth. com/ catalogue/ title. cfm?ISBN=0443071683). Archived from the original (http:/ / www. intl. elsevierhealth. com/ catalogue/ title. cfm?ISBN=0443071683) on 2007-10-12. . Retrieved 19 March 2007. [3] "Publishers page for Grays Anatomy. 39th edition (US). 2004. ISBN 0-443-07168-3" (http:/ / web. archive. org/ web/ 20070209134753/ http:/ / www. us. elsevierhealth. com/ product. jsp?isbn=0443071683). Archived from the original (http:/ / www. us. elsevierhealth. com/ product. jsp?isbn=0443071683) on 9 February 2007. . Retrieved 19 March 2007. References • "Anatomy of the Human Body". 20th edition. 1918. Henry Gray (http://www.bartleby.com/107/) External links • Anatomy Mnemonics (http://www.lifehugger.com/anatomy) Mnemonics in Anatomy. • Journal - Journal of Anatomy (http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1469-7580)* • Anatomy (http://www.bbc.co.uk/programmes/p005488j) on In Our Time at the BBC. ( listen now (http:// www.bbc.co.uk/iplayer/console/p005488j/In_Our_Time_Anatomy)) • Anatomia 1522–1867: Anatomical Plates from the Thomas Fisher Rare Book Library (http://link.library. utoronto.ca/anatomia/) • Anatomy of the Human Body (http://www.bartleby.com/107/) Gray, Henry. Philadelphia: Lea & Febiger, 1918 • High-Resolution Cytoarchitectural Primate Brain Atlases (http://brainmaps.org/) • Anatomy in the 16th century (http://www.bium.univ-paris5.fr/histmed/medica/anatomie.htm#vonseng) studies and digitized texts by the BIUM (Bibliothèque interuniversitaire de médecine et dodontologie, Paris) Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Anatomy 3 (http://www.bium.parisdescartes.fr) see its digital library Medic@ (http://www.bium.univ-paris5.fr/ histmed/medica.htm). • 19th Century Anatomy Lesson (http://burkeandhare.com/bhlesson.htm) Animated dissection following Grays Anatomy Embryology Embryology (from Greek ἔμβρυον, embryon, "unborn, embryo"; and -λογία, -logia) is a science which is about the development of an embryo from the fertilization of the ovum to the fetus stage. After cleavage, the dividing cells, or morula, becomes a hollow ball, or blastula, which develops a hole or pore at one end. In bilateral animals, the blastula develops in one of two ways that divides the whole animal kingdom into two halves (see: Embryological origins of the mouth and anus). If in the blastula the first pore (blastopore) 1 - morula, 2 - blastula becomes the mouth of the animal, it is a protostome; if the first pore becomes the anus then it is a deuterostome. The protostomes include most invertebrate animals, such as insects, worms and molluscs, while the deuterostomes include the vertebrates. In due course, the blastula changes into a more differentiated structure called the gastrula. The gastrula with its blastopore soon develops three distinct layers of cells (the germ layers) from which all the bodily organs and tissues then develop: • The innermost layer, or endoderm, gives rise to the 1 - blastula, 2 - gastrula with blastopore; orange - ectoderm, red - endoderm. digestive organs, lungs and bladder. • The middle layer, or mesoderm, gives rise to the muscles, skeleton and blood system. • The outer layer of cells, or ectoderm, gives rise to the nervous system and skin. In humans, the term embryo refers to the ball of dividing cells from the moment the zygote implants itself in the uterus wall until the end of the eighth week after conception. Beyond the eighth week, the developing human is then called a fetus. Embryos in many species often appear similar to one another in early developmental stages. The reason for this similarity is because species have a shared evolutionary history. These similarities among species are called homologous structures, which are structures that have the same or similar function and mechanism having evolved from a common ancestor. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Embryology 4 History As recently as the 18th century, the prevailing notion in human embryology was preformation: the idea that semen contains an embryo — a preformed, miniature infant, or "homunculus" — that simply becomes larger during development. The competing explanation of embryonic development was epigenesis, originally proposed 2,000 years earlier by Aristotle. According to epigenesis, the form of an animal emerges gradually from a relatively formless egg. As microscopy improved during the 19th century, biologists could see that embryos took shape in a series of progressive steps, and epigenesis displaced preformation as the favored explanation among Human embryo at six weeks embryologists.[1] gestational age Modern embryological pioneers include Karl Ernst von Baer, Charles Darwin, Ernst Haeckel, J.B.S. Haldane, and Joseph Needham, while much early embryology came from the work of Aristotle and the great Italian anatomists: Aldrovandi, Aranzio, Leonardo da Vinci, Marcello Malpighi, Gabriele Falloppio, Girolamo Cardano, Emilio Parisano, Fortunio Liceti, Stefano Lorenzini, Spallanzani, Enrico Sertoli, Mauro Rusconi, etc.[2] Other important contributors include William Harvey, Kaspar Friedrich Wolff, Heinz Christian Pander, August Weismann, Gavin de Beer, Ernest Everett Just, and Edward B. Lewis. After the 1950s, with the DNA helical structure being unravelled and the increasing knowledge in the field of molecular biology, developmental biology emerged as a field of study which attempts to correlate the genes with morphological change, and so tries to determine which genes are responsible Histological film 10 day mouse embryo for each morphological change that takes place in an embryo, and how these genes are regulated. Vertebrate and invertebrate embryology Many principles of embryology apply to both invertebrate animals as well as to vertebrates.[3] Therefore, the study of invertebrate embryology has advanced the study of vertebrate embryology. However, there are many differences as well. For example, numerous invertebrate species release a larva before development is complete; at the end of the larval period, an animal for the first time comes to resemble an adult similar to its parent or parents. Although invertebrate embryology is similar in some ways for different invertebrate animals, there are also countless variations. For instance, while spiders proceed directly from egg to adult form many insects develop through at least one larval stage Modern embryology research Beetle larvae Currently, embryology has become an important research area for studying the genetic control of the development process (e.g. morphogens), its link to cell signalling, its importance for the study of certain diseases and mutations and in links to stem cell research. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Embryology 5 References [1] Campbell et al. (p. 987) [2] Massimo De Felici, Gregorio Siracus, The rise of embryology in Italy: from the Renaissance to the early 20th Century, (http:/ / www. ijdb. ehu. es/ fullaccess/ fulltext. 0009/ ft515. pdf) Int. J. Dev. Biol. 44: 515-521 (2000). [3] Parker, Sybil. "Invertebrate Embryology," McGraw-Hill Encyclopedia of Science & Technology (http:/ / books. google. com/ books?vid=ISBN0079115047& id=CMC32Rmo9tYC& q="invertebrate+ embryology"+ and+ "mcgraw-hill"& dq="invertebrate+ embryology"+ and+ "mcgraw-hill"& pgis=1) (McGraw-Hill 1997). Embryology - History of embryology as a science." Science Encyclopedia. Web. 06 Nov. 2009. <http://science.jrank.org/pages/2452/Embryology.html>. "Germ layer." Encyclopædia Britannica. 2009. Encyclopædia Britannica Online. 06 Nov. 2009 <http://www.britannica.com/EBchecked/topic/230597/germ-layer>. Further reading • Apostoli, Pietro; Catalani, Simona (2011). "Chapter 11. Metal Ions Affecting Reproduction and Development". In Astrid Sigel, Helmut Sigel and Roland K. O. Sigel. Metal Ions in Toxicology. Metal Ions in Life Sciences. 8. RSC Publishing. pp. 263-303. doi:10.1039/9781849732116-00263. • Scott F. Gilbert. Developmental Biology. Sinauer, 2003. ISBN 0-87893-258-5. • Lewis Wolpert. Principles of Development. Oxford University Press, 2006. ISBN 0-19-927536-X. External links • Indiana Universitys Human Embryology Animations (http://www.indiana.edu/~anat550/embryo_main/index. html) • What is a human admixed embryo? (http://www.cambridgenetwork.co.uk/views/biolines) • UNSW Embryology (http://embryology.med.unsw.edu.au/) | UNSW Embryology (http://php.med.unsw. edu.au/embryology/index.php?title=Main_Page) Large resource of information and media • Definition of embryo according to Webster (http://www2.merriam-webster.com/cgi-bin/ mwmednlm?book=Medical&va=embryo) Compiled and Edited by Marc Imhotep Cray , M.D.
  • Biochemistry 6 Biochemistry Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes. By controlling information flow through biochemical signalling and the flow of chemical energy through metabolism, biochemical processes give rise to the incredible complexity of life. Much of biochemistry deals with the structures and functions of cellular components such as proteins, carbohydrates, lipids, nucleic acids and other biomolecules although increasingly processes rather than individual molecules are the main focus. Over the last 40 years biochemistry has become so successful at explaining living processes that now almost all areas of the life sciences from botany to medicine are engaged in biochemical research. Today the main focus of pure biochemistry is in understanding how biological molecules give rise to the processes that occur within living cells which in turn relates greatly to the study and understanding of whole organisms. Among the vast number of different biomolecules, many are complex and large molecules (called biopolymers), which are composed of similar repeating subunits (called monomers). Each class of polymeric biomolecule has a different set of subunit types.[1] For example, a protein is a polymer whose subunits are selected from a set of 20 or more amino acids. Biochemistry studies the chemical properties of important biological molecules, like proteins, and in particular the chemistry of enzyme-catalyzed reactions. The biochemistry of cell metabolism and the endocrine system has been extensively described. Other areas of biochemistry include the genetic code (DNA, RNA), protein synthesis, cell membrane transport, and signal transduction. History It once was generally believed that life and its materials had some essential property or substance distinct from any found in non-living matter, and it was thought that only living beings could produce the molecules of life. Then, in 1828, Friedrich Wöhler published a paper on the synthesis of urea, proving that organic compounds can be created artificially.[2] [3] The dawn of biochemistry may have been the discovery of the first enzyme, diastase (today called amylase), in 1833 by Anselme Payen. Eduard Buchner contributed the first demonstration of a complex biochemical process outside of a cell in 1896: alcoholic fermentation in cell extracts of yeast. Although the term “biochemistry” seems to have been first used in 1882, it is generally accepted that the formal coinage of biochemistry occurred in 1903 by Carl Neuberg, a German chemist. Previously, this area would have been referred to as physiological chemistry. Since then, biochemistry has advanced, especially since the mid-20th century, with the development of new techniques such as chromatography, X-ray diffraction, dual polarisation interferometry, NMR spectroscopy, radioisotopic labeling, electron microscopy and molecular dynamics simulations. These techniques allowed for the discovery and detailed analysis of many molecules and metabolic pathways of the cell, such as glycolysis and the Krebs cycle (citric acid cycle). Another significant historic event in biochemistry is the discovery of the gene and its role in the transfer of information in the cell. This part of biochemistry is often called molecular biology. In the 1950s, James D. Watson, Francis Crick, Rosalind Franklin, and Maurice Wilkins were instrumental in solving DNA structure and suggesting its relationship with genetic transfer of information. In 1958, George Beadle and Edward Tatum received the Nobel Prize for work in fungi showing that one gene produces one enzyme. In 1988, Colin Pitchfork was the first person convicted of murder with DNA evidence, which led to growth of forensic science. More recently, Andrew Z. Fire and Craig C. Mello received the 2006 Nobel Prize for discovering the role of RNA interference (RNAi), in the silencing of gene expression. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Biochemistry 7 Today, there are three main types of biochemistry. Plant biochemistry involves the study of the biochemistry of autotrophic organisms such as photosynthesis and other plant specific biochemical processes. General biochemistry encompasses both plant and animal biochemistry. Human/medical/medicinal biochemistry focuses on the biochemistry of humans and medical illnesses. Biomolecules The four main classes of molecules in biochemistry are carbohydrates, lipids, proteins, and nucleic acids. Many biological molecules are polymers: in this terminology, monomers are relatively small micromolecules that are linked together to create large macromolecules, which are known as polymers. When monomers are linked together to synthesize a biological polymer, they undergo a process called dehydration synthesis. Carbohydrates Carbohydrates are made from monomers called monosaccharides. Some of these monosaccharides include glucose (C6H O ), fructose (C H O ), and deoxyribose 12 6 6 12 6 (C5H10O4). When two monosaccharides undergo dehydration synthesis, water is produced, as two hydrogen atoms and one oxygen atom are lost from the two monosaccharides hydroxyl group. A molecule of sucrose (glucose + fructose), a disaccharide. Lipids Lipids are usually made from one molecule of glycerol combined with other molecules. In triglycerides, the main group of bulk lipids, there is one molecule of glycerol and three fatty acids. Fatty acids are considered the monomer in that case, and may be saturated (no double bonds in the carbon chain) or unsaturated (one or more double bonds in the carbon chain). A triglyceride with a glycerol molecule on the left and three fatty acids coming Lipids, especially phospholipids, are also used in various pharmaceutical off it. products, either as co-solubilisers (e.g. in parenteral infusions) or else as drug carrier components (e.g. in a liposome or transfersome). Proteins Proteins are very large molecules – macro-biopolymers – made from monomers called amino acids. There are 20 standard amino acids, each containing a carboxyl group, an amino group, and a side chain (known as an "R" group). The "R" group is what makes each amino acid different, and the properties of the side chains greatly influence the overall three-dimensional conformation of a protein. When amino acids combine, they form a special bond called a peptide bond through dehydration synthesis, and become a The general structure of an α-amino acid, with the polypeptide, or protein. amino group on the left and To determine if two proteins are related or in other words to decide whether they are the carboxyl group on the right. homologous or not, scientists use sequence-comparison methods. Methods like Sequence Alignments and Structural Alignments are powerful tools that help scientist identify homologies between related molecules. The relevance of finding homologies among proteins goes beyond forming an evolutionary pattern of protein families. By finding how similar two protein sequences are, we acquire knowledge about their structure and therefore their function. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Biochemistry 8 Nucleic acids Nucleic acids are the molecules that make up DNA, an extremely important substance which all cellular organisms use to store their genetic information. The most common nucleic acids are deoxyribonucleic acid and ribonucleic acid. Their monomers are called nucleotides. The most common nucleotides are Adenine, Cytosine, Guanine, Thymine, and Uracil. Adenine binds with thymine and uracil; Thymine only binds with Adenine; and Cytosine and Guanine can only bind with each other. Carbohydrates The function of carbohydrates includes energy storage and providing structure. Sugars are carbohydrates, but not all carbohydrates are sugars. There are more carbohydrates on Earth than any other known type of biomolecule; they are used to store The structure of deoxyribonucleic acid (DNA), the picture shows the monomers being put together. energy and genetic information, as well as play important roles in cell to cell interactions and communications. Monosaccharides The simplest type of carbohydrate is a monosaccharide, which among other properties contains carbon, hydrogen, and oxygen, mostly in a ratio of 1:2:1 (generalized formula CnH O , where n is at least 3). 2n n Glucose, one of the most important carbohydrates, is an example of a monosaccharide. So is fructose, the sugar commonly associated with the sweet taste of fruits.[4] [a] Some carbohydrates (especially after condensation to oligo- and polysaccharides) contain less carbon Glucose relative to H and O, which still are present in 2:1 (H:O) ratio. Monosaccharides can be grouped into aldoses (having an aldehyde group at the end of the chain, e. g. glucose) and ketoses (having a keto group in their chain; e. g. fructose). Both aldoses and ketoses occur in an equilibrium (starting with chain lengths of C4) cyclic forms. These are generated by bond formation between one of the hydroxyl groups of the sugar chain with the carbon of the aldehyde or keto group to form a hemiacetal bond. This leads to saturated five-membered (in furanoses) or six-membered (in pyranoses) heterocyclic rings containing one O as heteroatom. Disaccharides Two monosaccharides can be joined together using dehydration synthesis, in which a hydrogen atom is removed from the end of one molecule and a hydroxyl group (—OH) is removed from the other; the remaining residues are then attached at the sites from which the atoms were removed. The H—OH or H2O is then released as a molecule of water, hence the term dehydration. The new molecule, consisting of two monosaccharides, is called a disaccharide and is conjoined Sucrose: ordinary table sugar and probably the together by a glycosidic or ether bond. The reverse reaction can also most familiar carbohydrate. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Biochemistry 9 occur, using a molecule of water to split up a disaccharide and break the glycosidic bond; this is termed hydrolysis. The most well-known disaccharide is sucrose, ordinary sugar (in scientific contexts, called table sugar or cane sugar to differentiate it from other sugars). Sucrose consists of a glucose molecule and a fructose molecule joined together. Another important disaccharide is lactose, consisting of a glucose molecule and a galactose molecule. As most humans age, the production of lactase, the enzyme that hydrolyzes lactose back into glucose and galactose, typically decreases. This results in lactase deficiency, also called lactose intolerance. Sugar polymers are characterised by having reducing or non-reducing ends. A reducing end of a carbohydrate is a carbon atom which can be in equilibrium with the open-chain aldehyde or keto form. If the joining of monomers takes place at such a carbon atom, the free hydroxy group of the pyranose or furanose form is exchanged with an OH-side chain of another sugar, yielding a full acetal. This prevents opening of the chain to the aldehyde or keto form and renders the modified residue non-reducing. Lactose contains a reducing end at its glucose moiety, whereas the galactose moiety form a full acetal with the C4-OH group of glucose. Saccharose does not have a reducing end because of full acetal formation between the aldehyde carbon of glucose (C1) and the keto carbon of fructose (C2). Oligosaccharides and polysaccharides When a few (around three to six) monosaccharides are joined together, it is called an oligosaccharide (oligo- meaning "few"). These molecules tend to be used as markers and signals, as well as having some other uses. Many monosaccharides joined together make a polysaccharide. They can be joined together in one long linear chain, or they may be branched. Two of the most common polysaccharides Cellulose as polymer of β-D-glucose are cellulose and glycogen, both consisting of repeating glucose monomers. • Cellulose is made by plants and is an important structural component of their cell walls. Humans can neither manufacture nor digest it. • Glycogen, on the other hand, is an animal carbohydrate; humans and other animals use it as a form of energy storage. Use of carbohydrates as an energy source Glucose is the major energy source in most life forms. For instance, polysaccharides are broken down into their monomers (glycogen phosphorylase removes glucose residues from glycogen). Disaccharides like lactose or sucrose are cleaved into their two component monosaccharides. Glycolysis (anaerobic) Glucose is mainly metabolized by a very important ten-step pathway called glycolysis, the net result of which is to break down one molecule of glucose into two molecules of pyruvate; this also produces a net two molecules of ATP, the energy currency of cells, along with two reducing equivalents in the form of converting NAD+ to NADH. This does not require oxygen; if no oxygen is available (or the cell cannot use oxygen), the NAD is restored by converting the pyruvate to lactate (lactic acid) (e. g. in humans) or to ethanol plus carbon dioxide (e. g. in yeast). Other monosaccharides like galactose and fructose can be converted into intermediates of the glycolytic pathway. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Biochemistry 10 Aerobic In aerobic cells with sufficient oxygen, like most human cells, the pyruvate is further metabolized. It is irreversibly converted to acetyl-CoA, giving off one carbon atom as the waste product carbon dioxide, generating another reducing equivalent as NADH. The two molecules acetyl-CoA (from one molecule of glucose) then enter the citric acid cycle, producing two more molecules of ATP, six more NADH molecules and two reduced (ubi)quinones (via FADH2 as enzyme-bound cofactor), and releasing the remaining carbon atoms as carbon dioxide. The produced NADH and quinol molecules then feed into the enzyme complexes of the respiratory chain, an electron transport system transferring the electrons ultimately to oxygen and conserving the released energy in the form of a proton gradient over a membrane (inner mitochondrial membrane in eukaryotes). Thereby, oxygen is reduced to water and the original electron acceptors NAD+ and quinone are regenerated. This is why humans breathe in oxygen and breathe out carbon dioxide. The energy released from transferring the electrons from high-energy states in NADH and quinol is conserved first as proton gradient and converted to ATP via ATP synthase. This generates an additional 28 molecules of ATP (24 from the 8 NADH + 4 from the 2 quinols), totaling to 32 molecules of ATP conserved per degraded glucose (two from glycolysis + two from the citrate cycle). It is clear that using oxygen to completely oxidize glucose provides an organism with far more energy than any oxygen-independent metabolic feature, and this is thought to be the reason why complex life appeared only after Earths atmosphere accumulated large amounts of oxygen. Gluconeogenesis In vertebrates, vigorously contracting skeletal muscles (during weightlifting or sprinting, for example) do not receive enough oxygen to meet the energy demand, and so they shift to anaerobic metabolism, converting glucose to lactate. The liver regenerates the glucose, using a process called gluconeogenesis. This process is not quite the opposite of glycolysis, and actually requires three times the amount of energy gained from glycolysis (six molecules of ATP are used, compared to the two gained in glycolysis). Analogous to the above reactions, the glucose produced can then undergo glycolysis in tissues that need energy, be stored as glycogen (or starch in plants), or be converted to other monosaccharides or joined into di- or oligosaccharides. The combined pathways of glycolysis during exercise, lactates crossing via the bloodstream to the liver, subsequent gluconeogenesis and release of glucose into the bloodstream is called the Cori cycle. Proteins Like carbohydrates, some proteins perform largely structural roles. For instance, movements of the proteins actin and myosin ultimately are responsible for the contraction of skeletal muscle. One property many proteins have is that they specifically bind to a certain molecule or class of molecules—they may be extremely selective in what they bind. Antibodies are an example of proteins that attach to one specific type of molecule. In fact, the enzyme-linked immunosorbent assay (ELISA), which uses antibodies, is currently one of the most sensitive tests modern medicine uses to detect various biomolecules. Probably the most important proteins, however, are the enzymes. These molecules recognize specific reactant A schematic of hemoglobin. The red and molecules called substrates; they then catalyze the reaction between them. By blue ribbons represent the protein globin; lowering the activation energy, the enzyme speeds up that reaction by a rate the green structures are the heme groups. of 1011 or more: a reaction that would normally take over 3,000 years to complete spontaneously might take less than a second with an enzyme. The enzyme itself is not used up in the process, and is free to catalyze the same reaction with a new set of substrates. Using various modifiers, the activity of the enzyme can be regulated, enabling control of the biochemistry of the cell as a whole. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Biochemistry 11 In essence, proteins are chains of amino acids. An amino acid consists of a carbon atom bound to four groups. One is an amino group, —NH , and one is a carboxylic acid group, —COOH (although these exist as —NH + and —COO− 2 3 under physiologic conditions). The third is a simple hydrogen atom. The fourth is commonly denoted "—R" and is different for each amino acid. There are twenty standard amino acids. Some of these have functions by themselves or in a modified form; for instance, glutamate functions as an important neurotransmitter. Amino acids can be joined together via a peptide bond. In this dehydration synthesis, a water molecule is removed and the peptide bond connects the nitrogen of one amino acids amino group to the carbon of the others Generic amino acids (1) in neutral form, (2) as they exist physiologically, and (3) joined carboxylic acid group. The resulting together as a dipeptide. molecule is called a dipeptide, and short stretches of amino acids (usually, fewer than thirty) are called peptides or polypeptides. Longer stretches merit the title proteins. As an example, the important blood serum protein albumin contains 585 amino acid residues. The structure of proteins is traditionally described in a hierarchy of four levels. The primary structure of a protein simply consists of its linear sequence of amino acids; for instance, "alanine-glycine-tryptophan-serine-glutamate-asparagine-glycine-lysine-…". Secondary structure is concerned with local morphology (morphology being the study of structure). Some combinations of amino acids will tend to curl up in a coil called an α-helix or into a sheet called a β-sheet; some α-helixes can be seen in the hemoglobin schematic above. Tertiary structure is the entire three-dimensional shape of the protein. This shape is determined by the sequence of amino acids. In fact, a single change can change the entire structure. The alpha chain of hemoglobin contains 146 amino acid residues; substitution of the glutamate residue at position 6 with a valine residue changes the behavior of hemoglobin so much that it results in sickle-cell disease. Finally quaternary structure is concerned with the structure of a protein with multiple peptide subunits, like hemoglobin with its four subunits. Not all proteins have more than one subunit. Ingested proteins are usually broken up into single amino acids or dipeptides in the small intestine, and then absorbed. They can then be joined together to make new proteins. Intermediate products of glycolysis, the citric acid cycle, and the pentose phosphate pathway can be used to make all twenty amino acids, and most bacteria and plants possess all the necessary enzymes to synthesize them. Humans and other mammals, however, can only synthesize half of them. They cannot synthesize isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. These are the essential amino acids, since it is essential to ingest them. Mammals do possess the enzymes to synthesize alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, and tyrosine, the nonessential amino acids. While they can synthesize arginine and histidine, they cannot produce it in sufficient amounts for young, growing animals, and so these are often considered essential amino acids. If the amino group is removed from an amino acid, it leaves behind a carbon skeleton called an α-keto acid. Enzymes called transaminases can easily transfer the amino group from one amino acid (making it an α-keto acid) to another α-keto acid (making it an amino acid). This is important in the biosynthesis of amino acids, as for many of the pathways, intermediates from other biochemical pathways are converted to the α-keto acid skeleton, and then an amino group is added, often via transamination. The amino acids may then be linked together to make a protein. A similar process is used to break down proteins. It is first hydrolyzed into its component amino acids. Free ammonia (NH3), existing as the ammonium ion (NH +) in blood, is toxic to life forms. A suitable method for 4 excreting it must therefore exist. Different strategies have evolved in different animals, depending on the animals needs. Unicellular organisms, of course, simply release the ammonia into the environment. Similarly, bony fish can release the ammonia into the water where it is quickly diluted. In general, mammals convert the ammonia into urea, Compiled and Edited by Marc Imhotep Cray , M.D.
  • Biochemistry 12 via the urea cycle. Lipids The term lipid comprises a diverse range of molecules and to some extent is a catchall for relatively water-insoluble or nonpolar compounds of biological origin, including waxes, fatty acids, fatty-acid derived phospholipids, sphingolipids, glycolipids and terpenoids (e.g. retinoids and steroids). Some lipids are linear aliphatic molecules, while others have ring structures. Some are aromatic, while others are not. Some are flexible, while others are rigid. Most lipids have some polar character in addition to being largely nonpolar. Generally, the bulk of their structure is nonpolar or hydrophobic ("water-fearing"), meaning that it does not interact well with polar solvents like water. Another part of their structure is polar or hydrophilic ("water-loving") and will tend to associate with polar solvents like water. This makes them amphiphilic molecules (having both hydrophobic and hydrophilic portions). In the case of cholesterol, the polar group is a mere -OH (hydroxyl or alcohol). In the case of phospholipids, the polar groups are considerably larger and more polar, as described below. Lipids are an integral part of our daily diet. Most oils and milk products that we use for cooking and eating like butter, cheese, ghee etc., are composed of fats. Vegetable oils are rich in various polyunsaturated fatty acids (PUFA). Lipid-containing foods undergo digestion within the body and are broken into fatty acids and glycerol, which are the final degradation products of fats and lipids. Nucleic acids A nucleic acid is a complex, high-molecular-weight biochemical macromolecule composed of nucleotide chains that convey genetic information. The most common nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nucleic acids are found in all living cells and viruses. Aside from the genetic material of the cell, nucleic acids often play a role as second messengers, as well as forming the base molecule for adenosine triphosphate, the primary energy-carrier molecule found in all living organisms. Nucleic acid, so called because of its prevalence in cellular nuclei, is the generic name of the family of biopolymers. The monomers are called nucleotides, and each consists of three components: a nitrogenous heterocyclic base (either a purine or a pyrimidine), a pentose sugar, and a phosphate group. Different nucleic acid types differ in the specific sugar found in their chain (e.g. DNA or deoxyribonucleic acid contains 2-deoxyriboses). Also, the nitrogenous bases possible in the two nucleic acids are different: adenine, cytosine, and guanine occur in both RNA and DNA, while thymine occurs only in DNA and uracil occurs in RNA. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Biochemistry 13 Relationship to other "molecular-scale" biological sciences Researchers in biochemistry use specific techniques native to biochemistry, but increasingly combine these with techniques and ideas from genetics, molecular biology and biophysics. There has never been a hard-line between these disciplines in terms of content and technique. Today the terms molecular biology and biochemistry are nearly interchangeable. The following figure is a schematic that depicts one possible view of the relationship between the fields: • Biochemistry is the study of the chemical substances and vital processes occurring in living organisms. Biochemists focus heavily on the role, function, and structure of biomolecules. The study of the chemistry behind biological processes and the synthesis of biologically active molecules are Schematic relationship between biochemistry, genetics and examples of biochemistry. molecular biology • Genetics is the study of the effect of genetic differences on organisms. Often this can be inferred by the absence of a normal component (e.g. one gene). The study of "mutants" – organisms with a changed gene that leads to the organism being different with respect to the so-called "wild type" or normal phenotype. Genetic interactions (epistasis) can often confound simple interpretations of such "knock-out" or "knock-in" studies. • Molecular biology is the study of molecular underpinnings of the process of replication, transcription and translation of the genetic material. The central dogma of molecular biology where genetic material is transcribed into RNA and then translated into protein, despite being an oversimplified picture of molecular biology, still provides a good starting point for understanding the field. This picture, however, is undergoing revision in light of emerging novel roles for RNA. • Chemical Biology seeks to develop new tools based on small molecules that allow minimal perturbation of biological systems while providing detailed information about their function. Further, chemical biology employs biological systems to create non-natural hybrids between biomolecules and synthetic devices (for example emptied viral capsids that can deliver gene therapy or drug molecules). Notes a.   It should be noted that fructose is not the only sugar found in fruits. Glucose and sucrose are also found in varying quantities in various fruits, and indeed sometimes exceed the fructose present. For example, 32 % of the edible portion of date is glucose, compared with 23.70 % fructose and 8.20 % sucrose. Conversely, peaches contain more sucrose (6.66 %) than they do fructose (0.93 %) or glucose (1.47 %).[5] References [1] Campbell, Neil A.; Brad Williamson; Robin J. Heyden (2006). Biology: Exploring Life (http:/ / www. phschool. com/ el_marketing. html). Boston, Massachusetts: Pearson Prentice Hall. ISBN 0-13-250882-6. . [2] Wöhler, F. (1828). "Ueber künstliche Bildung des Harnstoffs". Ann. Phys. Chem. 12: 253–256. [3] Kauffman, G. B. and Chooljian, S.H. (2001). "Friedrich Wöhler (1800–1882), on the Bicentennial of His Birth". The Chemical Educator 6 (2): 121–133. doi:10.1007/s00897010444a. [4] Whiting, G.C (1970). "Sugars". In A.C. Hulme. The Biochemistry of Fruits and their Products. Volume 1. London & New York: Academic Press. pp. 1=31 Compiled and Edited by Marc Imhotep Cray , M.D.
  • Biochemistry 14 [5] Whiting, G.C. (1970), p.5 Further reading • Hunter, Graeme K. (2000). Vital Forces: The Discovery of the Molecular Basis of Life. San Diego: Academic Press. ISBN 0-12-361810-X. OCLC 162129355 191848148 44187710. External links • The Virtual Library of Biochemistry and Cell Biology (http://www.biochemweb.org/) • Biochemistry, 5th ed. (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=stryer. TOC&depth=2) Full text of Berg, Tymoczko, and Stryer, courtesy of NCBI. • Biochemistry, 2nd ed. (http://www.web.virginia.edu/Heidi/home.htm) Full text of Garrett and Grisham. • Biochemistry Animation (http://www.1lec.com/Biochemistry/) (Narrated Flash animations.) • SystemsX.ch - The Swiss Initiative in Systems Biology (http://www.systemsX.ch/) • Biochemistry Online Resources (http://www.icademic.org/97445/Biochemistry/) – Lists of Biochemistry departments, websites, journals, books and reviews, employment opportunities and events. biochemical families: prot · nucl · carb (glpr, alco, glys) · lipd (fata/i, phld, strd, gllp, eico) · amac/i · ncbs/i · ttpy/i Histology Histology (compound of the Greek words: ἱστός "tissue", and -λογία -logia) is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining a thin slice (section) of tissue under a light microscope or electron microscope. The ability to visualize or differentially identify microscopic structures is frequently enhanced through the use of histological stains. Histology is an essential tool of biology and medicine. Histopathology, the microscopic study of diseased tissue, is an important tool in A stained histologic specimen, sandwiched between a glass microscope slide and anatomical pathology, since accurate coverslip, mounted on the stage of a light microscope. diagnosis of cancer and other diseases usually requires histopathological examination of samples. Trained medical doctors, frequently board-certified as pathologists, are the personnel who perform histopathological examination and provide diagnostic information based on their observations. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Histology 15 The trained scientists who perform the preparation of histological sections are histotechnicians, histology technicians (HT), histology technologists (HTL), medical scientists, medical laboratory technicians, or biomedical scientists. Their field of study is called histotechnology. Histology Fixing Chemical fixation with formaldehyde or other chemicals Microscopic view of a histologic specimen of human lung tissue stained with hematoxylin and eosin. Chemical fixatives are used to preserve tissue from degradation, and to maintain the structure of the cell and of sub-cellular components such as cell organelles (e.g., nucleus, endoplasmic reticulum, mitochondria). The most common fixative for light microscopy is 10% neutral buffered formalin (4% formaldehyde in phosphate buffered saline). For electron microscopy, the most commonly used fixative is glutaraldehyde, usually as a 2.5% solution in phosphate buffered saline. These fixatives preserve tissues or cells mainly by irreversibly cross-linking proteins. The main action of these aldehyde fixatives is to cross-link amino groups in proteins through the formation of CH2 (methylene) linkage, in the case of formaldehyde, or by a C5H10 cross-links in the case of glutaraldehyde. This process, while preserving the structural integrity of the cells and tissue can damage the biological functionality of proteins, particularly enzymes, and can also denature them to a certain extent. This can be detrimental to certain histological techniques. Further fixatives are often used for electron microscopy such as osmium tetroxide or uranyl acetate Formalin fixation leads to degradation of mRNA, miRNA and DNA in tissues. However, extraction, amplification and analysis of these nucleic acids from formalin-fixed, paraffin-embedded tissues is possible using appropriate protocols.[1] Frozen section fixation Frozen section is a rapid way to fix and mount histology sections. It is used in surgical removal of tumors, and allow rapid determination of margin (that the tumor has been completely removed). It is done using a refrigeration device called a cryostat. The frozen tissue is sliced using a microtome, and the frozen slices are mounted on a glass slide and stained the same way as other methods. It is a necessary way to fix tissue for certain stain such as antibody linked immunofluorescence staining. It can also be used to determine if a tumour is malignant when it is found incidentally during surgery on a patient. Processing - dehydration, clearing, and infiltration The aim of Tissue Processing is to remove water from tissues and replace with a medium that solidifies to allow thin sections to be cut. Biological tissue must be supported in a hard matrix to allow sufficiently thin sections to be cut, typically 5 μm (micrometres; 1000 micrometres = 1 mm) thick for light microscopy and 80-100 nm (nanometre; 1,000,000 nanometres = 1 mm) thick for electron microscopy. For light microscopy, paraffin wax is most frequently used. Since it is immiscible with water, the main constituent of biological tissue, water must first be removed in the process of dehydration. Samples are transferred through baths of progressively more concentrated ethanol to remove Compiled and Edited by Marc Imhotep Cray , M.D.
  • Histology 16 the water. This is followed by a hydrophobic clearing agent (such as xylene) to remove the alcohol, and finally molten paraffin wax, the infiltration agent, which replaces the xylene. Paraffin wax does not provide a sufficiently hard matrix for cutting very thin sections for electron microscopy. Instead, resins are used. Epoxy resins are the most commonly employed embedding media, but acrylic resins are also used, particularly where immunohistochemistry is required. Thicker sections (0.35μm to 5μm) of resin-embedded tissue can also be cut for light microscopy. Again, the immiscibility of most epoxy and acrylic resins with water necessitates the use of dehydration, usually with ethanol. Embedding After the tissues have been dehydrated, cleared, and infiltrated with the embedding material, they are ready for external embedding. During this process the tissue samples are placed into molds along with liquid embedding material (such as agar, gelatine, or wax) which is then hardened. This is achieved by cooling in the case of paraffin wax and heating (curing) in the case of the epoxy resins. The acrylic resins are polymerised by heat, ultraviolet light, or chemical catalysts. The hardened blocks containing the tissue samples are then ready to be sectioned. Because Formalin-fixed, paraffin-embedded (FFPE) tissues may be stored indefinitely at room temperature, and nucleic acids (both DNA and RNA) may be recovered from them decades after fixation, FFPE tissues are an important resource for historical studies in medicine. Embedding can also be accomplished using frozen, non-fixed tissue in a water-based medium. Pre-frozen tissues are placed into molds with the liquid embedding material, usually a water-based glycol, OCT, TBS, Cryogel, or resin, which is then frozen to form hardened blocks. Sectioning Sectioning can be done in limited ways. Vertical sectioning perpendicular to the surface of the tissue is the usual method. Horizontal sectioning is often done in the evaluation of the hair follicles and pilosebaceous units. Tangential to horizontal sectioning is done in Mohs surgery and in methods of CCPDMA. For light microscopy, a steel knife mounted in a microtome is used to cut 10-micrometer-thick tissue sections which are mounted on a glass microscope slide. For transmission electron microscopy, a diamond knife mounted in an ultramicrotome is used to cut 50-nanometer-thick tissue sections which are mounted on a 3-millimeter-diameter copper grid. Then the mounted sections are treated with the appropriate stain. Frozen tissue embedded in a freezing medium is cut on a microtome in a cooled machine called a cryostat. Staining Biological tissue has little inherent contrast in either the light or electron microscope. Staining is employed to give both contrast to the tissue as well as highlighting particular features of interest. Where the underlying mechanistic chemistry of staining is understood, the term histochemistry is used. Hematoxylin and eosin (H&E stain) is the most commonly used light microscopical stain in histology and histopathology. Hematoxylin, a basic dye, stains nuclei blue due to an affinity to nucleic acids in the cell nucleus; eosin, an acidic dye, stains the cytoplasm pink. Uranyl acetate and lead citrate are commonly used to impart contrast to tissue in the electron microscope. Special staining: There are hundreds of various other techniques that have been used to selectively stain cells and cellular components. Other compounds used to color tissue sections include safranin, oil red o, Congo red, fast green FCF, silver salts, and numerous natural and artificial dyes that were usually originated from the development dyes for the textile industry. Histochemistry refers to the science of using chemical reactions between laboratory chemicals and components within tissue. A commonly performed histochemical technique is the Perls Prussian blue reaction, used to demonstrate iron deposits in diseases like hemochromatosis. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Histology 17 Histology samples have often been examined by radioactive techniques. In historadiography, a slide (sometimes stained histochemically) is X-rayed. More commonly, autoradiography is used to visualize the locations to which a radioactive substance has been transported within the body, such as cells in S phase (undergoing DNA replication) which incorporate tritiated thymidine, or sites to which radiolabeled nucleic acid probes bind in in situ hybridization. For autoradiography on a microscopic level, the slide is typically dipped into liquid nuclear tract emulsion, which dries to form the exposure film. Individual silver grains in the film are visualized with dark field microscopy. Recently, antibodies have been used to specifically visualize proteins, carbohydrates, and lipids. This process is called immunohistochemistry, or when the stain is a fluorescent molecule, immunofluorescence. This technique has greatly increased the ability to identify categories of cells under a microscope. Other advanced techniques, such as nonradioactive in situ hybridization, can be combined with immunochemistry to identify specific DNA or RNA molecules with fluorescent probes or tags that can be used for immunofluorescence and enzyme-linked fluorescence amplification (especially alkaline phosphatase and tyramide signal amplification). Fluorescence microscopy and confocal microscopy are used to detect fluorescent signals with good intracellular detail. Digital cameras are increasingly used to capture histological and histopathological image Common laboratory stains Stain Common use Nucleus Red blood Collagen Specifically stains Cytoplasm cell (RBC) fibers Haematoxylin General staining Blue N/A N/A N/A Nucleic acids—blue ER (endoplasmic when paired with reticulum)—blue eosin (i.e. H&E) Eosin General staining N/A Pink Orange/red Pink Elastic fibers—pink Collagen fibers—pink when paired with Reticular fibers—pink haematoxylin (i.e. H&E) Toluidine blue General staining Blue Blue Blue Blue Mast cells granules—purple Massons Connective tissue Black Red/pink Red Blue/green Cartilage—blue/green Muscle fibers—red trichrome stain Mallorys Connective tissue Red Pale red Orange Deep blue Keratin—orange Cartilage—blue Bone trichrome stain matrix—deep blue Muscle fibers—red Weigerts elastic Elastic fibers Blue/black N/A N/A N/A Elastic fibers—blue/black stain Heidenhains Distinguishing cells Red/purple Pink Red Blue Muscle fibers—red Cartilage—blue Bone AZAN trichrome from extracellular matrix—blue stain components Silver stain Reticular fibers, N/A N/A N/A N/A Reticular fibers—brown/black Nerve nerve fibers, fungi fibers—brown/black Wrights stain Blood cells Bluish/purple Bluish/gray Red/pink N/A Neutrophil granules—purple/pink Eosinophil granules—bright red/orange Basophil granules—deep purple/violet Platelet granules—red/purple Orcein stain Elastic fibres Deep blue [or N/A Bright red Pink Elastic fibres—dark brown Mast cells crazy red] granules—purple Smooth muscle—light blue Periodic Basement membrane, Blue N/A N/A Pink Glycogen and other acid-Schiff stain localizing carbohydrates—magenta (PAS) carbohydrates Compiled and Edited by Marc Imhotep Cray , M.D.
  • Histology 18 Table sourced from Michael H. Ross, Wojciech Pawlina, (2006). Histology: A Text and Atlas. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 0-7817-5056-3. The Nissl method and Golgis method are useful in identifying neurons. Alternative techniques Alternative techniques include cryosection. The tissue is frozen using a cryostat, and cut. Tissue staining methods are similar to those of wax sections. Plastic embedding is commonly used in the preparation of material for electron microscopy. Tissues are embedded in epoxy resin. Very thin sections (less than 0.1 micrometer) are cut using diamond or glass knives. The sections are stained with electron dense stains (uranium and lead) so that they can possibly be seen with the electron microscope. History In the 19th century, histology was an academic discipline in its own right. The 1906 Nobel Prize in Physiology or Medicine was awarded to histologists Camillo Golgi and Santiago Ramon y Cajal. They had dueling interpretations of the neural structure of the brain based in differing interpretations of the same images. Cajal won the prize for his correct theory and Golgi for the staining technique he invented to make it possible. Histological classification of animal tissues There are four basic types of tissues: muscle tissue, nervous tissue, connective tissue, and epithelial tissue. All tissue types are subtypes of these four basic tissue types (for example, blood cells are classified as connective tissue, since they generally originate inside bone marrow). • Epithelium: the lining of glands, bowel, skin, and some organs like the liver, lung, and kidney • Endothelium: the lining of blood and lymphatic vessels • Mesothelium: the lining of pleural and pericardial spaces • Mesenchyme: the cells filling the spaces between the organs, including fat, muscle, bone, cartilage, and tendon cells • Blood cells: the red and white blood cells, including those found in lymph nodes and spleen • Neurons: any of the conducting cells of the nervous system • Germ cells: reproductive cells (spermatozoa in men, oocytes in women) • Placenta: an organ characteristic of true mammals during pregnancy, joining mother and offspring, providing endocrine secretion and selective exchange of soluble, but not particulate, blood-borne substances through an apposition of uterine and trophoblastic vascularised parts • Stem cells: cells with the ability to develop into different cell types Note that tissues from plants, fungi, and microorganisms can also be examined histologically. Their structure is very different from animal tissues. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Histology 19 Related sciences • Cell biology is the study of living cells, their DNA and RNA and the proteins they express. • Anatomy is the study of organs visible by the naked eye. • Morphology studies entire organisms. Artifacts Artifacts are structures or features in tissue that interfere with normal histological examination. These are not always present in normal tissue and can come from outside sources. Artifacts interfere with histology by changing the tissues appearance and hiding structures. These can be divided into two categories: Pre-histology These are features and structures that have being introduced prior to the collection of the tissues. A common example of these include: ink from tattoos and freckles (melanin) in skin samples. Post-histology Artifacts can result from tissue processing. Processing commonly leads to changes like shrinkage, washing out of particular cellular components, color changes in different tissues types and alterations of the structures in the tissue. Because these are caused in a laboratory the majority of post histology artifacts can be avoided or removed after being discovered. A common example is mercury pigment left behind after using Zenkers fixative to fix a section. Notes [1] Weiss AT, Delcour NM, Meyer A, Klopfleisch R. (2010). "Efficient and Cost-Effective Extraction of Genomic DNA From Formalin-Fixed and Paraffin-Embedded Tissues.". Veterinary Pathology 227. PMID 20817894. References 1. Merck Source (2002). Dorlands Medical Dictionary. Retrieved 2005-01-26. 2. Stedmans Medical Dictionaries (2005). Stedmans Online Medical Dictionary (http://stedmans.com/). Retrieved 2005-01-26. 3. 4,000‫ﻱ‬online histology images (2007). (http://histology-online.com) External links • Histology Protocols (http://www.ihcworld.com/protocol_database.htm) • Histoweb (http://www.kumc.edu/instruction/medicine/anatomy/histoweb) • SIU SOM Histology (http://www.siumed.edu/~dking2/index.htm) • Visual Histology Atlas (http://www.visualhistology.com/Visual_Histology_Atlas/) • Histology Glossary (http://www.histology-world.com/glossary/glossary1.htm) • Histology Group of Victoria Incorporated (http://www.hgv.org.au) • Histology Photomicrographs (http://www.histology-world.com/photoalbum/) • Virtual Slidebox (http://www.path.uiowa.edu/virtualslidebox) • Blue Histology (http://www.lab.anhb.uwa.edu.au/mb140/) Compiled and Edited by Marc Imhotep Cray , M.D.
  • Epidemiology 20 Epidemiology Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a society. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive medicine. Epidemiologists are involved in the design of studies, collection and statistical analysis of data, and interpretation and dissemination of results (including peer review and occasional systematic review). Major areas of epidemiologic work include outbreak investigation, disease surveillance and screening (medicine), biomonitoring, and comparisons of treatment effects such as in clinical trials. Epidemiologists rely on a number of other scientific disciplines such as biology (to better understand disease processes), biostatistics (to make efficient use of the data and draw appropriate conclusions), and exposure assessment and social science disciplines (to better understand proximate and distal risk factors, and their measurement). Etymology Epidemiology, literally meaning "the study of what is upon the people", is derived from Greek epi, meaning "upon, among", demos, meaning "people, district", and logos, meaning "study, word, discourse", suggesting that it applies only to human populations. However, the term is widely used in studies of zoological populations (veterinary epidemiology), although the term epizoology is available, and it has also been applied to studies of plant populations (botanical epidemiology).[1] The distinction between epidemic and endemic was first drawn by Hippocrates,[2] to distinguish between diseases that are visited upon a population (epidemic) from those that reside within a population (endemic).[3] The term epidemiology appears to have first been used to describe the study of epidemics in 1802 by the Spanish physician Villalba in Epidemiología Española.[3] Epidemiologists also study the interaction of diseases in a population, a condition known as a syndemic. The term epidemiology is now widely applied to cover the description and causation of not only epidemic disease, but of disease in general, and even many non-disease health-related conditions, such as high blood pressure and obesity. History The Greek physician Hippocrates has been called the father of epidemiology.[4] He is the first person known to have examined the relationships between the occurrence of disease and environmental influences.[5] He coined the terms endemic (for diseases usually found in some places but not in others) and epidemic (for disease that are seen at some times but not others).[6] Epidemiology is defined as the study of distribution and determinants of health related states in populations and use of this study to address health related problems. One of the earliest theories on the origin of disease was that it was primarily the fault of human luxury. This was expressed by philosophers such as Plato[7] and Rousseau,[8] and social critics like Jonathan Swift.[9] In the middle of the 16th century, a doctor from Verona named Girolamo Fracastoro was the first to propose a theory that these very small, unseeable, particles that cause disease were alive. They were considered to be able to spread by air, multiply by themselves and to be destroyable by fire. In this way he refuted Galens miasma theory (poison gas in sick people). In 1543 he wrote a book De contagione et contagiosis morbis, in which he was the first to promote personal and environmental hygiene to prevent disease. The development of a sufficiently powerful microscope by Anton van Leeuwenhoek in 1675 provided visual evidence of living particles consistent with a germ theory of disease. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Epidemiology 21 John Graunt, a professional haberdasher and serious amateur scientist, published Natural and Political Observations ... upon the Bills of Mortality in 1662. In it, he used analysis of the mortality rolls in London before the Great Plague to present one of the first life tables and report time trends for many diseases, new and old. He provided statistical evidence for many theories on disease, and also refuted many widespread ideas on them. Dr. John Snow is famous for his investigations into the causes of the 19th century cholera epidemics. He began with noticing the significantly higher death rates in two areas supplied by Southwark Company. His identification of the Broad Street pump as the cause of the Soho Original map by John Snow showing the clusters of cholera cases in the London epidemic is considered the classic example epidemic of 1854 of epidemiology. He used chlorine in an attempt to clean the water and had the handle removed, thus ending the outbreak. This has been perceived as a major event in the history of public health and can be regarded as the founding event of the science of epidemiology. Other pioneers include Danish physician Peter Anton Schleisner, who in 1849 related his work on the prevention of the epidemic of neonatal tetanus on the Vestmanna Islands in Iceland.[10] [11] Another important pioneer was Hungarian physician Ignaz Semmelweis, who in 1847 brought down infant mortality at a Vienna hospital by instituting a disinfection procedure. His findings were published in 1850, but his work was ill received by his colleagues, who discontinued the procedure. Disinfection did not become widely practiced until British surgeon Joseph Lister discovered antiseptics in 1865 in light of the work of Louis Pasteur. In the early 20th century, mathematical methods were introduced into epidemiology by Ronald Ross, Anderson Gray McKendrick and others. Another breakthrough was the 1954 publication of the results of a British Doctors Study, led by Richard Doll and Austin Bradford Hill, which lent very strong statistical support to the suspicion that tobacco smoking was linked to lung cancer. • History of emerging infectious diseases The profession To date, few universities offer epidemiology as a course of study at the undergraduate level. Many epidemiologists are physicians, or hold graduate degrees such as a Master of Public Health (MPH), Master of Science or Epidemiology (MSc.). Doctorates include the Doctor of Public Health (DrPH), Doctor of Pharmacy (PharmD), Doctor of Philosophy (PhD), Doctor of Science (ScD), or for clinically trained physicians, Doctor of Medicine (MD) and Doctor of Veterinary Medicine (DVM) . In the United Kingdom, the title of doctor is by long custom used to refer to general medical practitioners, whose professional degrees are usually those of Bachelor of Medicine and Surgery (MBBS or MBChB). As public health/health protection practitioners, epidemiologists work in a number of different settings. Some epidemiologists work in the field; i.e., in the community, commonly in a public Compiled and Edited by Marc Imhotep Cray , M.D.
  • Epidemiology 22 health/health protection service and are often at the forefront of investigating and combating disease outbreaks. Others work for non-profit organizations, universities, hospitals and larger government entities such as the Centers for Disease Control and Prevention (CDC), the Health Protection Agency, The World Health Organization (WHO), or the Public Health Agency of Canada. Epidemiologists can also work in for-profit organizations such as pharmaceutical and medical device companies in groups such as market research or clinical development. The practice Epidemiologists employ a range of study designs from the observational to experimental and generally categorized as descriptive, analytic (aiming to further examine known associations or hypothesized relationships), and experimental (a term often equated with clinical or community trials of treatments and other interventions). Epidemiological studies are aimed, where possible, at revealing unbiased relationships between exposures such as alcohol or smoking, biological agents, stress, or chemicals to mortality or morbidity. The identification of causal relationships between these exposures and outcomes is an important aspect of epidemiology. Modern epidemiologists use informatics as a tool. The term epidemiologic triad is used to describe the intersection of Host, Agent, and Environment in analyzing an outbreak. As causal inference Although epidemiology is sometimes viewed as a collection of statistical tools used to elucidate the associations of exposures to health outcomes, a deeper understanding of this science is that of discovering causal relationships. It is nearly impossible to say with perfect accuracy how even the most simple physical systems behave beyond the immediate future, much less the complex field of epidemiology, which draws on biology, sociology, mathematics, statistics, anthropology, psychology, and policy; "Correlation does not imply causation" is a common theme for much of the epidemiological literature. For epidemiologists, the key is in the term inference. Epidemiologists use gathered data and a broad range of biomedical and psychosocial theories in an iterative way to generate or expand theory, to test hypotheses, and to make educated, informed assertions about which relationships are causal, and about exactly how they are causal. Epidemiologists Rothman and Greenland emphasize that the "one cause - one effect" understanding is a simplistic mis-belief. Most outcomes, whether disease or death, are caused by a chain or web consisting of many component causes. Causes can be distinguished as necessary, sufficient or probabilistic conditions. If a necessary condition can be identified and controlled (e.g., antibodies to a disease agent), the harmful outcome can be avoided. Bradford-Hill criteria In 1965 Austin Bradford Hill detailed criteria for assessing evidence of causation.[12] These guidelines are sometimes referred to as the Bradford-Hill criteria, but this makes it seem like it is some sort of checklist. For example, Phillips and Goodman (2004) note that they are often taught or referenced as a checklist for assessing causality, despite this not being Hills intention.[13] Hill himself said "None of my nine viewpoints can bring indisputable evidence for or against the cause-and-effect hypothesis and none can be required sine qua non".[12] 1. Strength: A small association does not mean that there is not a causal effect, though the larger the association, the more likely that it is causal.[12] 2. Consistency: Consistent findings observed by different persons in different places with different samples strengthens the likelihood of an effect.[12] 3. Specificity: Causation is likely if a very specific population at a specific site and disease with no other likely explanation. The more specific an association between a factor and an effect is, the bigger the probability of a causal relationship.[12] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Epidemiology 23 4. Temporality: The effect has to occur after the cause (and if there is an expected delay between the cause and expected effect, then the effect must occur after that delay).[12] 5. Biological gradient: Greater exposure should generally lead to greater incidence of the effect. However, in some cases, the mere presence of the factor can trigger the effect. In other cases, an inverse proportion is observed: greater exposure leads to lower incidence.[12] 6. Plausibility: A plausible mechanism between cause and effect is helpful (but Hill noted that knowledge of the mechanism is limited by current knowledge).[12] 7. Coherence: Coherence between epidemiological and laboratory findings increases the likelihood of an effect. However, Hill noted that "... lack of such [laboratory] evidence cannot nullify the epidemiological effect on associations".[12] 8. Experiment: "Occasionally it is possible to appeal to experimental evidence".[12] 9. Analogy: The effect of similar factors may be considered.[12] Legal interpretation Epidemiological studies can only go to prove that an agent could have caused, but not that it did cause, an effect in any particular case: "Epidemiology is concerned with the incidence of disease in populations and does not address the question of the cause of an individuals disease. This question, sometimes referred to as specific causation, is beyond the domain of the science of epidemiology. Epidemiology has its limits at the point where an inference is made that the relationship between an agent and a disease is causal (general causation) and where the magnitude of excess risk attributed to the agent has been determined; that is, epidemiology addresses whether an agent can cause a disease, not whether an agent did cause a specific plaintiffs disease."[14] In United States law, epidemiology alone cannot prove that a causal association does not exist in general. Conversely, it can be (and is in some circumstances) taken by US courts, in an individual case, to justify an inference that a causal association does exist, based upon a balance of probability. The subdiscipline of forensic epidemiology is directed at the investigation of specific causation of disease or injury in individuals or groups of individuals in instances in which causation is disputed or is unclear, for presentation in legal settings. Advocacy As a public health discipline, epidemiologic evidence is often used to advocate both personal measures like diet change and corporate measures like removal of junk food advertising, with study findings disseminated to the general public to help people to make informed decisions about their health. Often the uncertainties about these findings are not communicated well; news articles often prominently report the latest result of one study with little mention of its limitations, caveats, or context. Epidemiological tools have proved effective in establishing major causes of diseases like cholera and lung cancer,[12] but experience difficulty in regards to more subtle health issues where causation is not as clear. Notably, conclusions drawn from observational studies may be reconsidered as later data from randomized controlled trials becomes available, as was the case with the association between the use of hormone replacement therapy and cardiac risk.[15] Compiled and Edited by Marc Imhotep Cray , M.D.
  • Epidemiology 24 Population-based health management Epidemiological practice and the results of epidemiological analysis make a significant contribution to emerging population-based health management frameworks. Population-based health management encompasses the ability to: • Assess the health states and health needs of a target population; • Implement and evaluate interventions that are designed to improve the health of that population; and • Efficiently and effectively provide care for members of that population in a way that is consistent with the communitys cultural, policy and health resource values. Modern population-based health management is complex, requiring a multiple set of skills (medical, political, technological, mathematical etc.) of which epidemiological practice and analysis is a core component, that is unified with management science to provide efficient and effective health care and health guidance to a population. This task requires the forward looking ability of modern risk management approaches that transform health risk factors, incidence, prevalence and mortality statistics (derived from epidemiological analysis) into management metrics that not only guide how a health system responds to current population health issues, but also how a health system can be managed to better respond to future potential population health issues. Examples of organizations that use population-based health management that leverage the work and results of epidemiological practice include Canadian Strategy for Cancer Control, Health Canada Tobacco Control Programs, Rick Hansen Foundation, Canadian Tobacco Control Research Initiative.[16] [17] [18] Each of these organizations use a population-based health management framework called Life at Risk that combines epidemiological quantitative analysis with demographics, health agency operational research and economics to perform: • Population Life Impacts Simulations: Measurement of the future potential impact of disease upon the population with respect to new disease cases, prevalence, premature death as well as potential years of life lost from disability and death; • Labour Force Life Impacts Simulations: Measurement of the future potential impact of disease upon the labour force with respect to new disease cases, prevalence, premature death and potential years of life lost from disability and death; • Economic Impacts of Disease Simulations: Measurement of the future potential impact of disease upon private sector disposable income impacts (wages, corporate profits, private health care costs) and public sector disposable income impacts (personal income tax, corporate income tax, consumption taxes, publicly funded health care costs). Types of studies Case series Case-series may refer to the qualititative study of the experience of a single patient, or small group of patients with a similar diagnosis, or to a statistical technique comparing periods during which patients are exposed to some factor with the potential to produce illness with periods when they are unexposed. The former type of study is purely descriptive and cannot be used to make inferences about the general population of patients with that disease. These types of studies, in which an astute clinician identifies an unusual feature of a disease or a patients history, may lead to formulation of a new hypothesis. Using the data from the series, analytic studies could be done to investigate possible causal factors. These can include case control studies or prospective studies. A case control study would involve matching comparable controls without the disease to the cases in the series. A prospective study would involve following the case series over time to evaluate the diseases natural history.[19] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Epidemiology 25 The latter type, more formally described as self-controlled case-series studies, divide individual patient follow-up time into exposed and unexposed periods and use fixed-effects Poisson regression processes to compare the incidence rate of a given outcome between exposed and unexposed periods. This technique has been extensively used in the study of adverse reactions to vaccination, and has been shown in some circumstances to provide statistical power comparable to that available in cohort studies. Case control studies Case control studies select subjects based on their disease status. A group of individuals that are disease positive (the "case" group) is compared with a group of disease negative individuals (the "control" group). The control group should ideally come from the same population that gave rise to the cases. The case control study looks back through time at potential exposures that both groups (cases and controls) may have encountered. A 2x2 table is constructed, displaying exposed cases (A), exposed controls (B), unexposed cases (C) and unexposed controls (D). The statistic generated to measure association is the odds ratio (OR), which is the ratio of the odds of exposure in the cases (A/C) to the odds of exposure in the controls (B/D), i.e. OR = (A/C) / (B/D) . ..... Cases Controls Exposed A B Unexposed C D If the OR is clearly greater than 1, then the conclusion is "those with the disease are more likely to have been exposed," whereas if it is close to 1 then the exposure and disease are not likely associated. If the OR is far less than one, then this suggests that the exposure is a protective factor in the causation of the disease. Case control studies are usually faster and more cost effective than cohort studies, but are sensitive to bias (such as recall bias and selection bias). The main challenge is to identify the appropriate control group; the distribution of exposure among the control group should be representative of the distribution in the population that gave rise to the cases. This can be achieved by drawing a random sample from the original population at risk. This has as a consequence that the control group can contain people with the disease under study when the disease has a high attack rate in a population. Cohort studies Cohort studies select subjects based on their exposure status. The study subjects should be at risk of the outcome under investigation at the beginning of the cohort study; this usually means that they should be disease free when the cohort study starts. The cohort is followed through time to assess their later outcome status. An example of a cohort study would be the investigation of a cohort of smokers and non-smokers over time to estimate the incidence of lung cancer. The same 2x2 table is constructed as with the case control study. However, the point estimate generated is the Relative Risk (RR), which is the probability of disease for a person in the exposed group, Pe = A / (A+B) over the probability of disease for a person in the unexposed group, P  = C / (C+D), i.e. RR = P  / P . u e u Compiled and Edited by Marc Imhotep Cray , M.D.
  • Epidemiology 26 ..... Case Non case Total Exposed A B (A+B) Unexposed C D (C+D) As with the OR, a RR greater than 1 shows association, where the conclusion can be read "those with the exposure were more likely to develop disease." Prospective studies have many benefits over case control studies. The RR is a more powerful effect measure than the OR, as the OR is just an estimation of the RR, since true incidence cannot be calculated in a case control study where subjects are selected based on disease status. Temporality can be established in a prospective study, and confounders are more easily controlled for. However, they are more costly, and there is a greater chance of losing subjects to follow-up based on the long time period over which the cohort is followed. Outbreak investigation For information on investigation of infectious disease outbreaks, please see outbreak investigation. Validity: precision and bias Random error Random error is the result of fluctuations around a true value because of sampling variability. Random error is just that: random. It can occur during data collection, coding, transfer, or analysis. Examples of random error include: poorly worded questions, a misunderstanding in interpreting an individual answer from a particular respondent, or a typographical error during coding. Random error affects measurement in a transient, inconsistent manner and it is impossible to correct for random error. There is random error in all sampling procedures. This is called sampling error. Precision in epidemiological variables is a measure of random error. Precision is also inversely related to random error, so that to reduce random error is to increase precision. Confidence intervals are computed to demonstrate the precision of relative risk estimates. The narrower the confidence interval, the more precise the relative risk estimate. There are two basic ways to reduce random error in an epidemiological study. The first is to increase the sample size of the study. In other words, add more subjects to your study. The second is to reduce the variability in measurement in the study. This might be accomplished by using a more precise measuring device or by increasing the number of measurements. Note, that if sample size or number of measurements are increased, or a more precise measuring tool is purchased, the costs of the study are usually increased. There is usually an uneasy balance between the need for adequate precision and the practical issue of study cost. Systematic error A systematic error or bias occurs when there is a difference between the true value (in the population) and the observed value (in the study) from any cause other than sampling variability. An example of systematic error is if, unbeknown to you, the pulse oximeter you are using is set incorrectly and adds two points to the true value each time a measurement is taken. The measuring device could be precise but not accurate. Because the error happens in every instance, it is systematic. Conclusions you draw based on that data will still be incorrect. But the error can be reproduced in the future (e.g., by using the same mis-set instrument). A mistake in coding that affects all responses for that particular question is another example of a systematic error. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Epidemiology 27 The validity of a study is dependent on the degree of systematic error. Validity is usually separated into two components: • Internal validity is dependent on the amount of error in measurements, including exposure, disease, and the associations between these variables. Good internal validity implies a lack of error in measurement and suggests that inferences may be drawn at least as they pertain to the subjects under study. • External validity pertains to the process of generalizing the findings of the study to the population from which the sample was drawn (or even beyond that population to a more universal statement). This requires an understanding of which conditions are relevant (or irrelevant) to the generalization. Internal validity is clearly a prerequisite for external validity. Three types of bias Selection bias Selection bias is one of three types of bias that can threaten the validity of a study. Selection bias occurs when study subjects are selected or become part of the study as a result of a third, unmeasured variable which is associated with both the exposure and outcome of interest.[20] Examples of selection bias are volunteer bias (the opposite of which is non-response bias)[21] in which participants and non participants differ in terms of exposure and outcome. For instance, it has repeatedly been noted that cigarette smokers and non smokers tend to differ in their study participation rates. (Sackett D cites the example of Seltzer et al., in which 85% of non smokers and 67% of smokers returned mailed questionnaires)[21] It is important to note that such a difference in response will not lead to bias if it is not also associated with a systematic difference in outcome between the two response groups. Confounding Confounding has traditionally been defined as bias arising from the co-occurrence or mixing of effects of extraneous factors, referred to as confounders, with the main effect(s) of interest.[22] [23] A more recent definition of confounding invokes the notion of counterfactual effects.[23] According to this view, when one observes an outcome of interest, say Y=1 (as opposed to Y=0), in a given population A which is entirely exposed (i.e. exposure X=1 for every unit of the population) the risk of this event will be RA1. The counterfactual or unobserved risk RA0 corresponds to the risk which would have been observed if these same individuals had been unexposed (i.e. X=0 for every unit of the population). The true effect of exposure therefore is: RA1 - RA0 (if one is interested in risk differences) or RA1/RA0 (if one is interested in relative risk). Since the counterfactual risk RA0 is unobservable we approximate it using a second population B and we actually measure the following relations: RA1 - RB0 or RA1/RB0. In this situation, confounding occurs when RA0 ≠ RB0.[23] (NB: Example assumes binary outcome and exposure variables.) Information bias Information bias is bias arising from systematic error in the assessment of a variable.[22] An example of this is recall bias. A typical example is again provided by Sackett in his discussion of a study examining the effect of specific exposures on fetal health: "in questioning mothers whose recent pregnancies had ended in fetal death or malformation (cases) and a matched group of mothers whose pregnancies ended normally (controls) it was found that 28%; of the former, but only 20%,; of the latter, reported exposure to drugs which could not be substantiated either in earlier prospective interviews or in other health records".[21] In this example, recall bias probably occurred as a result of women who had had miscarriages having an apparent tendency to better recall and therefore report previous exposures. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Epidemiology 28 Journals A list of journals:[24] General journals: Specialty journals: [30] • American Journal of Epidemiology • Cancer Epidemiology Biomarkers and Prevention [25] • Canadian Journal of Epidemiology and Biostatistics • Genetic epidemiology [26] • Epidemiologic Reviews • Journal of Clinical Epidemiology • Epidemiology • Epidemiology and Infection [31] • International Journal of Epidemiology • Paediatric Perinatal Epidemiology [32] • Annals of Epidemiology • Pharmacoepidemiology and Drug Safety [27] [33] • Journal of Epidemiology and Community Health • Preventive Medicine • European Journal of Epidemiology • Emerging themes in epidemiology [28] • Epidemiologic Perspectives and Innovations [29] • Eurosurveillance Areas By physiology/disease: By methodological approach: • Infectious disease epidemiology • Environmental epidemiology • Occupational Injury & Illness epidemiology • Economic epidemiology • Cardiovascular disease epidemiology • Clinical epidemiology • Cancer epidemiology • Conflict epidemiology • Neuroepidemiology • Cognitive epidemiology • Epidemiology of Aging • Genetic epidemiology • Oral/Dental epidemiology • Molecular epidemiology • Reproductive epidemiology • Nutritional epidemiology • Obesity/diabetes epidemiology • Social epidemiology • Renal epidemiology • Lifecourse epidemiology • Intestinal epidemiology • Epi methods development / Biostatistics • Psychiatric epidemiology • Meta-analysis • Veterinary epidemiology • Spatial epidemiology • Epidemiology of zoonosis • Tele-epidemiology • Respiratory Epidemiology • Biomarker epidemiology • Pediatric Epidemiology • Pharmacoepidemiology • Quantitative parasitology • Primary care epidemiology • Infection control and hospital epidemiology • Public Health practice epidemiology • Surveillance epidemiology (Clinical surveillance) • Disease Informatics Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Epidemiology 29 References Notes [1] Nutter, Jr., F.W. (1999). "Understanding the interrelationships between botanical, human, and veterinary epidemiology: the Ys and Rs of it all". Ecosys Health 5 (3): 131–40. doi:10.1046/j.1526-0992.1999.09922.x. [2] Hippocrates. (~200BC). Airs, Waters, Places. [3] Carol Buck, Alvaro Llopis, Enrique Nájera, Milton Terris. (1998). The Challenge of Epidemiology: Issues and Selected Readings. Scientific Publication No. 505. Pan American Health Organization. Washington, DC. p3. [4] Alfredo Morabia (2004). A history of epidemiologic methods and concepts (http:/ / books. google. com/ books?id=E-OZbEmPSTkC& pg=PA93& dq& hl=en#v=onepage& q=& f=false). Birkhäuser. p. 93. ISBN 3764368187. . [5] Ray M. Merrill (2010). Introduction to Epidemiology (http:/ / books. google. com/ books?id=RMDBh6gw1_UC& pg=PA24& dq& hl=en#v=onepage& q=& f=false). Jones & Bartlett Learning. p. 24. ISBN 0763766224. . [6] "Changing Concepts: Background to Epidemiology" (http:/ / www. duncan-associates. com/ changing_concepts. pdf). Duncan & Associates. . Retrieved 2008-02-03. [7] Plato. "The Republic" (http:/ / classics. mit. edu/ Plato/ republic. 4. iii. html). The Internet Classic Archive. . Retrieved 2008-02-03. [8] "A Dissertation on the Origin and Foundation of the Inequality of Mankind" (http:/ / www. constitution. org/ jjr/ ineq_03. htm). Constitution Society. . [9] Swift, Jonathan. "Gullivers Travels: Part IV. A Voyage to the Country of the Houyhnhnms" (http:/ / www. jaffebros. com/ lee/ gulliver/ bk4/ chap4-7. html). . Retrieved 2008-02-03. [10] Ólöf Garðarsdóttir; Loftur Guttormsson (June 2008). "An isolated case of early medical intervention. The battle against neonatal tetanus in the island of Vestmannaeyjar (Iceland) during the 19th century" (http:/ / ftp. ieg. csic. es/ workshop/ pdf/ olofpaper. pdf). Instituto de Economía y Geografía. . Retrieved 2011-04-19. [11] Ólöf Garðarsdóttir; Loftur Guttormsson (25 August 2009). "Public health measures against neonatal tetanus on the island of Vestmannaeyjar (Iceland) during the 19th century". The History of the Family 14 (3): 266–79. doi:10.1016/j.hisfam.2009.08.004. [12] Hill, Austin Bradford (1965). "The environment and disease: association or causation?" (http:/ / www. edwardtufte. com/ tufte/ hill). Proceedings of the Royal Society of Medicine 58: 295–300. PMC 1898525. PMID 14283879. . [13] Phillips, Carl V.; Karen J. Goodman (October 2004). "The missed lessons of Sir Austin Bradford Hill" (http:/ / www. epi-perspectives. com/ content/ 1/ 1/ 3). Epidemiologic Perspectives and Innovations 1 (3): 3. doi:10.1186/1742-5573-1-3. PMC 524370. PMID 15507128. . [14] Green, Michael D.; D. Michal Freedman, and Leon Gordis (PDF). Reference Guide on Epidemiology (http:/ / www. fjc. gov/ public/ pdf. nsf/ lookup/ sciman06. pdf/ $file/ sciman06. pdf). Federal Judicial Centre. . Retrieved 2008-02-03. [15] Gabriel Sanchez R, Sanchez Gomez LM, Carmona L, Roqué i Figuls M, Bonfill Cosp X. Hormone replacement therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD002229. DOI: 10.1002/14651858.CD002229.pub2 [16] Smetanin, P.; P. Kobak (October 2005). "Interdisciplinary Cancer Risk Management: Canadian Life and Economic Impacts". 1st International Cancer Control Congress (http:/ / www. cancercontrol2005. com). [17] Smetanin, P.; P. Kobak (July 2006). "A Population-Based Risk Management Framework for Cancer Control" (http:/ / www. riskanalytica. com/ Library/ Papers/ Population Based Risk Management Framework for Cancer Control. pdf) (PDF). The International Union Against Cancer Conference (http:/ / www. 2006conferences. org/ u-index. php). . [18] Smetanin, P.; P. Kobak (July 2005). "Selected Canadian Life and Economic Forecast Impacts of Lung Cancer" (http:/ / www. riskanalytica. com/ Library/ Papers/ Canadian Lung Cancer Abstract Jan 2005. pdf) (PDF). 11th World Conference on Lung Cancer. . [19] Hennekens, Charles H.; Julie E. Buring (1987). Mayrent, Sherry L. (Ed.). ed. Epidemiology in Medicine. Lippincott, Williams and Wilkins. ISBN 978-0316356367. [20] (http:/ / journals. lww. com/ epidem/ Fulltext/ 2004/ 09000/ A_Structural_Approach_to_Selection_Bias. 20. aspx) 23 [21] (http:/ / www. epidemiology. ch/ history/ PDF bg/ Sackett DL 1979 bias in analytic research. pdf) 24 [22] Special:BookSources/0195135547 21 [23] (http:/ / www. annualreviews. org/ doi/ full/ 10. 1146/ annurev. publhealth. 22. 1. 189) 22 [24] "Epidemiologic Inquiry: Impact Factors of leading epidemiology journals" (http:/ / www. epidemiologic. org/ 2006/ 10/ impact-factors-of-epidemiology-and. html). Epidemiologic.org. . Retrieved 2008-02-03. [25] http:/ / www. cjeb. ca/ [26] http:/ / epirev. oxfordjournals. org [27] http:/ / jech. bmj. com [28] http:/ / www. epi-perspectives. com [29] http:/ / www. eurosurveillance. org [30] http:/ / cebp. aacrjournals. org [31] http:/ / www. blackwellpublishing. com/ journal. asp?ref=0269-5022 [32] http:/ / eu. wiley. com/ WileyCDA/ WileyTitle/ productCd-PDS. html [33] http:/ / www. elsevier. com/ wps/ find/ journaldescription. cws_home/ 622934/ description#description Compiled and Edited by Marc Imhotep Cray , M.D.
  • Epidemiology 30 Bibliography • Clayton, David and Michael Hills (1993) Statistical Models in Epidemiology Oxford University Press. ISBN 0-19-852221-5 • Last JM (2001). "A dictionary of epidemiology", 4th edn, Oxford: Oxford University Press. 5th. edn (2008), edited by Miquel Porta (http://www.oup.com/us/catalog/general/subject/Medicine/ EpidemiologyBiostatistics/?view=usa&ci=9780195314502) • Morabia, Alfredo. ed. (2004) A History of Epidemiologic Methods and Concepts. Basel, Birkhauser Verlag. Part I. (http://books.google.es/books?id=Hgnnhu1ym-8C&dq=Morabia,+Alfredo.+ed.+(2004)+A+History+ of+Epidemiologic+Methods&printsec=frontcover&source=bn&hl=es&ei=U4ARSvbaEJGUjAew8LnCBg& sa=X&oi=book_result&ct=result&resnum=4) (http://www.springer.com/public+health/book/ 978-3-7643-6818-0) • Smetanin P., Kobak P., Moyer C., Maley O (2005) "The Risk Management of Tobacco Control Research Policy Programs" The World Conference on Tobacco OR Health Conference, July 12–15, 2006 in Washington DC. • Szklo MM & Nieto FJ (2002). "Epidemiology: beyond the basics", Aspen Publishers, Inc. • Rothman, Kenneth, Sander Greenland and Timothy Lash (2008). "Modern Epidemiology", 3rd Edition, Lippincott Williams & Wilkins. ISBN 0781755646, ISBN 978-0781755641 • Rothman, Kenneth (2002). "Epidemiology. An introduction", Oxford University Press. ISBN 0195135547, ISBN 978-0195135541 External links • The Health Protection Agency (http://www.hpa.org.uk) • The Collection of Biostatistics Research Archive (http://www.biostatsresearch.com/repository/) • Statistical Applications in Genetics and Molecular Biology (http://www.bepress.com/sagmb/) • The International Journal of Biostatistics (http://www.bepress.com/ijb/) • European Epidemiological Federation (http://www.iea-europe.org/index.htm) • BMJ (http://bmj.bmjjournals.com/epidem/epid.html) - Epidemiology for the Uninitiated (fourth edition), D. Coggon, G. Rose, D.J.P. Barker British Medical Journal • Epidem.com (http://www.epidem.com) - Epidemiology (peer reviewed scientific journal that publishes original research on epidemiologic topics) • NIH.gov (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.chapter.631) - Epidemiology (textbook chapter), Philip S. Brachman, Medical Microbiology (fourth edition), US National Center for Biotechnology Information • UTMB.edu (http://gsbs.utmb.edu/microbook/) - Epidemiology (plain format chapter), Philip S. Brachman, Medical Microbiology • Monash Virtual Laboratory (http://vlab.infotech.monash.edu.au/simulations/cellular-automata/epidemic/) - Simulations of epidemic spread across a landscape • EMER (http://sist-emer.net/?lang=en)- Epizootic Diseases, Emerging and Re-emerging Diseases • Umeå Centre for Global Health Research • Epidemiology and Public Health Sciences, Umeå International School of Public Health (http://www8.umu.se/ phmed/epidemi/index.html/) • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (http:// dceg.cancer.gov/) • The Centre for Research on the Epidemiology of Disasters (CRED) at the Université catholique de Louvain (UCL) (http://www.cred.be) • Peoples Epidemiology Library (http://www.epidemiology.ch/history/betaversion.htm) Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Biostatistics 31 Biostatistics Biostatistics (a contraction of biology and statistics; sometimes referred to as biometry or biometrics) is the application of statistics to a wide range of topics in biology. The science of biostatistics encompasses the design of biological experiments, especially in medicine and agriculture; the collection, summarization, and analysis of data from those experiments; and the interpretation of, and inference from, the results. Biostatistics and the history of biological thought Biostatistical reasoning and modeling were of critical importance to the foundation theories of modern biology. In the early 1900s, after the rediscovery of Mendels work, the conceptual gaps in understanding between genetics and evolutionary Darwinism led to vigorous debate between biometricians such as Walter Weldon and Karl Pearson and Mendelians such as Charles Davenport, William Bateson and Wilhelm Johannsen. By the 1930s statisticians and models built on statistical reasoning had helped to resolve these differences and to produce the neo-Darwinian modern evolutionary synthesis. The leading figures in the establishment of this synthesis all relied on statistics and developed its use in biology. • Sir Ronald A. Fisher developed several basic statistical methods in support of his work The Genetical Theory of Natural Selection • Sewall G. Wright used statistics in the development of modern population genetics • J. B. S Haldanes book, The Causes of Evolution, reestablished natural selection as the premier mechanism of evolution by explaining it in terms of the mathematical consequences of Mendelian genetics. These individuals and the work of other biostatisticians, mathematical biologists, and statistically inclined geneticists helped bring together evolutionary biology and genetics into a consistent, coherent whole that could begin to be quantitatively modeled. In parallel to this overall development, the pioneering work of DArcy Thompson in On Growth and Form also helped to add quantitative discipline to biological study. Despite the fundamental importance and frequent necessity of statistical reasoning, there may nonetheless have been a tendency among biologists to distrust or deprecate results which are not qualitatively apparent. One anecdote describes Thomas Hunt Morgan banning the Friden calculator from his department at Caltech, saying "Well, I am like a guy who is prospecting for gold along the banks of the Sacramento River in 1849. With a little intelligence, I can reach down and pick up big nuggets of gold. And as long as I can do that, Im not going to let any people in my department waste scarce resources in placer mining."[1] Educators are now adjusting their curricula to focus on more quantitative concepts and tools.[2] Education and training programs Almost all educational programmes in biostatistics are at postgraduate level. They are most often found in schools of public health, affiliated with schools of medicine, forestry, or agriculture or as a focus of application in departments of statistics. In the United States, while several universities have dedicated biostatistics departments, many other top-tier universities integrate biostatistics faculty into statistics or other departments, such as epidemiology. Thus departments carrying the name "biostatistics" may exist under quite different structures. For instance, relatively new biostatistics departments have been founded with a focus on bioinformatics and computational biology, whereas older departments, typically affiliated with schools of public health, will have more traditional lines of research involving epidemiological studies and clinical trials as well as bioinformatics. In larger universities where both a statistics and a biostatistics department exist, the degree of integration between the two departments may range from Compiled and Edited by Marc Imhotep Cray , M.D.
  • Biostatistics 32 the bare minimum to very close collaboration. In general, the difference between a statistics program and a biostatistics one is twofold: (i) statistics departments will often host theoretical/methodological research which are less common in biostatistics programs and (ii) statistics departments have lines of research that may include biomedical applications but also other areas such as industry (quality control), business and economics and biological areas other than medicine. Applications of biostatistics • Public health, including epidemiology, health services research, nutrition, and environmental health • Design and analysis of clinical trials in medicine • Population genetics, and statistical genetics in order to link variation in genotype with a variation in phenotype. This has been used in agriculture to improve crops and farm animals (animal breeding). In biomedical research, this work can assist in finding candidates for gene alleles that can cause or influence predisposition to disease in human genetics • Analysis of genomics data, for example from microarray or proteomics experiments.[3] [4] Often concerning diseases or disease stages.[5] • Ecology, ecological forecasting • Biological sequence analysis [6] • Systems biology for gene network inference or pathways analysis.[7] Statistical methods are beginning to be integrated into medical informatics, public health informatics, bioinformatics and computational biology. Biostatistics journals • Biometrics • Biometrika • Biostatistics • International Journal of Biostatistics, The • Canadian Journal of Epidemiology and Biostatistics [25] • Journal of Agricultural, Biological, and Environmental Statistics • Journal of Biometrics & Biostatistics • Journal of Biopharmaceutical Statistics • Pharmaceutical Statistics • Statistical Applications in Genetics and Molecular Biology • Statistics in Biopharmaceutical Research • Statistics in Medicine • Turkiye Klinikleri Journal of Biostatistics Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Biostatistics 33 Related fields Biostatistics shares several methods with quantitative fields such as: • computational biology • computer science, • operations research, • psychometrics, • statistics, • econometrics, and • mathematical demography References [1] Charles T. Munger (2003-10-03). "Academic Economics: Strengths and Faults After Considering Interdisciplinary Needs" (http:/ / www. tilsonfunds. com/ MungerUCSBspeech. pdf). . [2] "Spotlight:application of quantitative concepts and techniques in undergraduate biology" (http:/ / www. reinventioncenter. miami. edu/ Spotlights/ BioMath. htm). . [3] Helen Causton, John Quackenbush and Alvis Brazma (2003). "Statistical Analysis of Gene Expression Microarray Data". Wiley-Blackwell. [4] Terry Speed (2003). "Microarray Gene Expression Data Analysis: A Beginners Guide". Chapman & Hall/CRC. [5] Frank Emmert-Streib and Matthias Dehmer (2010). "Medical Biostatistics for Complex Diseases". Wiley-Blackwell. [6] Warren J. Ewens and Gregory R. Grant (2004). "Statistical Methods in Bioinformatics: An Introduction". Springer. [7] Matthias Dehmer, Frank Emmert-Streib, Armin Graber and Armindo Salvador (2011). "Applied Statistics for Network Biology: Methods in Systems Biology". Wiley-Blackwell. External links • The International Biometric Society (http://www.tibs.org) • The Collection of Biostatistics Research Archive (http://www.biostatsresearch.com/repository/) • Guide to Biostatistics (MedPageToday.com) (http://www.medpagetoday.com/Medpage-Guide-to-Biostatistics. pdf) Journals • Statistical Applications in Genetics and Molecular Biology (http://www.bepress.com/sagmb/) • Statistics in Medicine (http://www3.interscience.wiley.com/cgi-bin/jhome/2988) • The International Journal of Biostatistics (http://www.bepress.com/ijb/) • Journal of Agricultural, Biological, and Environmental Statistics (http://www.amstat.org/publications/jabes/) • Journal of Biopharmaceutical Statistics (http://www.tandf.co.uk/journals/titles/10543406.asp) • Biostatistics (http://www.biostatistics.oxfordjournals.org/) • Biometrics (http://www.tibs.org/biometrics/) • Biometrika (http://biomet.oxfordjournals.org/) • Biometrical Journal (http://www.biometrical-journal.de/) • Genetics Selection Evolution (http://www.gse-journal.org/) Compiled and Edited by Marc Imhotep Cray , M.D.
  • Molecular biology 34 Molecular biology Molecular biology (pronounced /məˈlɛkjʊlər .../) is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry. Molecular biology chiefly concerns itself with understanding and the interactions between the various systems of a cell, including the interactions between the different types of DNA, RNA and protein biosynthesis as well as learning how these interactions are regulated. Writing in Nature in 1961, William Astbury described molecular biology as not so much a technique as an approach, an approach from the viewpoint of the so-called basic sciences with the leading idea of searching below the large-scale manifestations of classical biology for the corresponding molecular plan. It is concerned particularly with the forms of biological molecules and [...] is predominantly three-dimensional and structural—which does not mean, however, that it is merely a refinement of morphology. It must at the same time inquire into genesis and function.[1] Relationship to other biological sciences Researchers in molecular biology use specific techniques native to molecular biology (see Techniques section later in article), but increasingly combine these with techniques and ideas from genetics and biochemistry. There is not a defined line between these disciplines. The figure above is a schematic that depicts one possible view of the relationship between the fields: • Biochemistry is the study of the chemical substances and vital processes occurring in living organisms. Biochemists focus heavily on the role, function, and structure of biomolecules. The study of the chemistry behind biological processes and the synthesis of biologically active molecules are examples of biochemistry. Schematic relationship between biochemistry, genetics, and • Genetics is the study of the effect of genetic molecular biology differences on organisms. Often this can be inferred by the absence of a normal component (e.g. one gene). The study of "mutants" – organisms which lack one or more functional components with respect to the so-called "wild type" or normal phenotype. Genetic interactions (epistasis) can often confound simple interpretations of such "knock-out" studies. • Molecular biology is the study of molecular underpinnings of the processes of replication, transcription, translation, and cell function. The central dogma of molecular biology where genetic material is transcribed into RNA and then translated into protein, despite being an oversimplified picture of molecular biology, still provides a good starting point for understanding the field. This picture, however, is undergoing revision in light of emerging novel roles for RNA. Much of the work in molecular biology is quantitative, and recently much work has been done at the interface of molecular biology and computer science in bioinformatics and computational biology. As of the early 2000s, the study of gene structure and function, molecular genetics, has been among the most prominent sub-field of molecular biology. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Molecular biology 35 Increasingly many other loops of biology focus on molecules, either directly studying their interactions in their own right such as in cell biology and developmental biology, or indirectly, where the techniques of molecular biology are used to infer historical attributes of populations or species, as in fields in evolutionary biology such as population genetics and phylogenetics. There is also a long tradition of studying biomolecules "from the ground up" in biophysics. Techniques of molecular biology Since the late 1950s and early 1960s, molecular biologists have learned to characterize, isolate, and manipulate the molecular components of cells and organisms. These components include DNA, the repository of genetic information; RNA, a close relative of DNA whose functions range from serving as a temporary working copy of DNA to actual structural and enzymatic functions as well as a functional and structural part of the translational apparatus; and proteins, the major structural and enzymatic type of molecule in cells. Expression cloning One of the most basic techniques of molecular biology to study protein function is expression cloning. In this technique, DNA coding for a protein of interest is cloned (using PCR and/or restriction enzymes) into a plasmid (known as an expression vector). A vector has 3 distinctive features: an origin of replication, a multiple cloning site (MCS), and a selective marker (usually antibiotic resistence). The origin of replication will have promoter regions upstream the replication/transcription start site. This plasmid can be inserted into either bacterial or animal cells. Introducing DNA into bacterial cells can be done by transformation (via uptake of naked DNA), conjugation (via cell-cell contact) or by transduction (via viral vector). Introducing DNA into eukaryotic cells, such as animal cells, by physical or chemical means is called transfection. Several different transfection techniques are available, such as calcium phosphate transfection, electroporation, microinjection and liposome transfection. DNA can also be introduced into eukaryotic cells using viruses or bacteria as carriers, the latter is sometimes called bactofection and in particular uses Agrobacterium tumefaciens. The plasmid may be integrated into the genome, resulting in a stable transfection, or may remain independent of the genome, called transient transfection. In either case, DNA coding for a protein of interest is now inside a cell, and the protein can now be expressed. A variety of systems, such as inducible promoters and specific cell-signaling factors, are available to help express the protein of interest at high levels. Large quantities of a protein can then be extracted from the bacterial or eukaryotic cell. The protein can be tested for enzymatic activity under a variety of situations, the protein may be crystallized so its tertiary structure can be studied, or, in the pharmaceutical industry, the activity of new drugs against the protein can be studied. Polymerase chain reaction (PCR) The polymerase chain reaction is an extremely versatile technique for copying DNA. In brief, PCR allows a single DNA sequence to be copied (millions of times), or altered in predetermined ways. For example, PCR can be used to introduce restriction enzyme sites, or to mutate (change) particular bases of DNA, the latter is a method referred to as "Quick change". PCR can also be used to determine whether a particular DNA fragment is found in a cDNA library. PCR has many variations, like reverse transcription PCR (RT-PCR) for amplification of RNA, and, more recently, real-time PCR (QPCR) which allow for quantitative measurement of DNA or RNA molecules. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Molecular biology 36 Gel electrophoresis Gel electrophoresis is one of the principal tools of molecular biology. The basic principle is that DNA, RNA, and proteins can all be separated by means of an electric field. In agarose gel electrophoresis, DNA and RNA can be separated on the basis of size by running the DNA through an agarose gel. Proteins can be separated on the basis of size by using an SDS-PAGE gel, or on the basis of size and their electric charge by using what is known as a 2D gel electrophoresis. Macromolecule blotting and probing The terms northern, western and eastern blotting are derived from what initially was a molecular biology joke that played on the term Southern blotting, after the technique described by Edwin Southern for the hybridisation of blotted DNA. Patricia Thomas, developer of the RNA blot which then became known as the northern blot actually didnt use the term.[2] Further combinations of these techniques produced such terms as southwesterns (protein-DNA hybridizations), northwesterns (to detect protein-RNA interactions) and farwesterns (protein-protein interactions), all of which are presently found in the literature. Southern blotting Named after its inventor, biologist Edwin Southern, the Southern blot is a method for probing for the presence of a specific DNA sequence within a DNA sample. DNA samples before or after restriction enzyme digestion are separated by gel electrophoresis and then transferred to a membrane by blotting via capillary action. The membrane is then exposed to a labeled DNA probe that has a complement base sequence to the sequence on the DNA of interest. Most original protocols used radioactive labels, however non-radioactive alternatives are now available. Southern blotting is less commonly used in laboratory science due to the capacity of other techniques, such as PCR, to detect specific DNA sequences from DNA samples. These blots are still used for some applications, however, such as measuring transgene copy number in transgenic mice, or in the engineering of gene knockout embryonic stem cell lines. Northern blotting The northern blot is used to study the expression patterns of a specific type of RNA molecule as relative comparison among a set of different samples of RNA. It is essentially a combination of denaturing RNA gel electrophoresis, and a blot. In this process RNA is separated based on size and is then transferred to a membrane that is then probed with a labeled complement of a sequence of interest. The results may be visualized through a variety of ways depending on the label used; however, most result in the revelation of bands representing the sizes of the RNA detected in sample. The intensity of these bands is related to the amount of the target RNA in the samples analyzed. The procedure is commonly used to study when and how much gene expression is occurring by measuring how much of that RNA is present in different samples. It is one of the most basic tools for determining at what time, and under what conditions, certain genes are expressed in living tissues. Western blotting Antibodies to most proteins can be created by injecting small amounts of the protein into an animal such as a mouse, rabbit, sheep, or donkey (polyclonal antibodies) or produced in cell culture (monoclonal antibodies). These antibodies can be used for a variety of analytical and preparative techniques. In western blotting, proteins are first separated by size, in a thin gel sandwiched between two glass plates in a technique known as SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis). The proteins in the gel are then transferred to a PVDF, nitrocellulose, nylon or other support membrane. This membrane can then be probed with solutions of antibodies. Antibodies that specifically bind to the protein of interest can then be visualized by a variety of techniques, including colored products, chemiluminescence, or autoradiography. Often, the antibodies are Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Molecular biology 37 labeled with enzymes. When a chemiluminescent substrate is exposed to the enzyme it allows detection. Using western blotting techniques allows not only detection but also quantitative analysis. Analogous methods to western blotting can be used to directly stain specific proteins in live cells or tissue sections. However, these immunostaining methods, such as FISH, are used more often in cell biology research. Eastern blotting Eastern blotting technique is to detect post-translational modification of proteins.[3] Proteins blotted on to the PVDF or nitrocellulose membrane are probed for modifications using specific substrates. Arrays A DNA array is a collection of spots attached to a solid support such as a microscope slide where each spot contains one or more single-stranded DNA oligonucleotide fragment. Arrays make it possible to put down a large quantities of very small (100 micrometre diameter) spots on a single slide. Each spot has a DNA fragment molecule that is complementary to a single DNA sequence (similar to Southern blotting). A variation of this technique allows the gene expression of an organism at a particular stage in development to be qualified (expression profiling). In this technique the RNA in a tissue is isolated and converted to labeled cDNA. This cDNA is then hybridized to the fragments on the array and visualization of the hybridization can be done. Since multiple arrays can be made with exactly the same position of fragments they are particularly useful for comparing the gene expression of two different tissues, such as a healthy and cancerous tissue. Also, one can measure what genes are expressed and how that expression changes with time or with other factors. For instance, the common bakers yeast, Saccharomyces cerevisiae, contains about 7000 genes; with a microarray, one can measure qualitatively how each gene is expressed, and how that expression changes, for example, with a change in temperature. There are many different ways to fabricate microarrays; the most common are silicon chips, microscope slides with spots of ~ 100 micrometre diameter, custom arrays, and arrays with larger spots on porous membranes (macroarrays). There can be anywhere from 100 spots to more than 10,000 on a given array. Arrays can also be made with molecules other than DNA. For example, an antibody array can be used to determine what proteins or bacteria are present in a blood sample. Allele Specific Oligonucleotide Allele specific oligonucleotide (ASO) is a technique that allows detection of single base mutations without the need for PCR or gel electrophoresis. Short (20-25 nucleotides in length), labeled probes are exposed to the non-fragmented target DNA. Hybridization occurs with high specificity due to the short length of the probes and even a single base change will hinder hybridization. The target DNA is then washed and the labeled probes that didnt hybridize are removed. The target DNA is then analyzed for the presence of the probe via radioactivity or fluorescence. In this experiment, as in most molecular biology techniques, a control must be used to ensure successful experimentation. The Illumina Methylation Assay is an example of a method that takes advantage of the ASO technique to measure one base pair differences in sequence. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Molecular biology 38 Antiquated technologies In molecular biology, procedures and technologies are continually being developed and older technologies abandoned. For example, before the advent of DNA gel electrophoresis (agarose or polyacrylamide), the size of DNA molecules was typically determined by rate sedimentation in sucrose gradients, a slow and labor-intensive technique requiring expensive instrumentation; prior to sucrose gradients, viscometry was used. Aside from their historical interest, it is often worth knowing about older technology, as it is occasionally useful to solve another new problem for which the newer technique is inappropriate. History While molecular biology was established in the 1930s, the term was first coined by Warren Weaver in 1938. Warren was the director of Natural Sciences for the Rockefeller Foundation at the time and believed that biology was about to undergo a period of significant change given recent advances in fields such as X-ray crystallography. He therefore channeled significant amounts of (Rockefeller Institute) money into biological fields. Clinical significance Clinical research and medical therapies arising from molecular biology are covered under gene therapy References [1] Astbury, W.T. (1961). "Molecular Biology or Ultrastructural Biology?" (http:/ / www. nature. com/ nature/ journal/ v190/ n4781/ pdf/ 1901124a0. pdf) (PDF). Nature 190 (4781): 1124. doi:10.1038/1901124a0. PMID 13684868. . Retrieved 2008-08-04. [2] Thomas, P.S. (1980). "Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose". PNAS 77 (9): 5201–5. doi:10.1073/pnas.77.9.5201. ISSN 1091-6490. PMC 350025. PMID 6159641. [3] Thomas S, Thirumalapura N, Crossley EC, Ismail N, and Walker DH (2009). Antigenic protein modifications in Ehrlichia. Parasite Immunology 31, 296-303. (http:/ / www3. interscience. wiley. com/ journal/ 121641379/ abstract) • Cohen, S.N., Chang, A.C.Y., Boyer, H. & Heling, R.B. Construction of biologically functional bacterial plasmids in vitro. Proc. Natl. Acad. Sci. 70, 3240 – 3244 (1973). • Rodgers, M. The Pandoras box congress. Rolling Stone 189, 37 – 77 (1975). Further reading • Keith Roberts, Martin Raff, Bruce Alberts, Peter Walter, Julian Lewis and Alexander Johnson, Molecular Biology of the Cell • 4th Edition, Routledge, March, 2002, hardcover, 1616 pages, 7.6 pounds, ISBN 0-8153-3218-1 • 3rd Edition, Garland, 1994, ISBN 0-8153-1620-8 • 2nd Edition, Garland, 1989, ISBN 0-8240-3695-6 External links • Biochemistry and Molecular Biology (http://www.dmoz.org/Science/Biology/ Biochemistry_and_Molecular_Biology/) at the Open Directory Project Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Genetics 39 Genetics Genetics (from Ancient Greek γενετικός genetikos, "genitive" and that from γένεσις genesis, "origin"),[1] [2] [3] a discipline of biology, is the science of genes, heredity, and variation in living organisms.[4] [5] Genetics deals with the molecular structure and function of genes, with gene behavior in the context of a cell or organism (e.g. dominance and epigenetics), with patterns of inheritance from parent to offspring, and with gene distribution, variation and change in populations. Given that genes are universal to living organisms, genetics can be applied to the study of all living systems, from viruses and bacteria, through plants (especially crops) and domestic animals, to humans (as in medical genetics). The fact that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding. However, the modern science of genetics, which seeks to understand the process of inheritance, only began with the work of Gregor Mendel in the mid-19th century.[6] Although he did not know the physical basis for heredity, Mendel observed that organisms inherit traits via discrete units of inheritance, which are now called genes. Genes correspond to regions within DNA, a molecule composed of a chain of four different types of nucleotides—the sequence of these nucleotides is the genetic information organisms inherit. DNA naturally occurs in a double stranded form, with nucleotides on each strand complementary to each other. Each strand can act as a template for creating a new partner strand. This is the physical method for making copies of genes that can be inherited. The sequence of nucleotides in a gene is translated by cells to produce a chain of amino acids, creating proteins—the order of amino acids in a protein corresponds to the order of nucleotides in the gene. This relationship between nucleotide sequence and amino acid sequence is known as the genetic code. The amino acids in a protein determine how it folds into a three-dimensional shape; this structure is, in turn, responsible for the proteins function. Proteins carry out almost all the functions needed for cells to live. A change to the DNA in a gene can change a proteins amino acids, changing its shape and function: this can have a dramatic effect in the cell and on the organism as a whole. Although genetics plays a large role in the appearance and behavior of organisms, it is the combination of genetics with what an organism experiences that determines the ultimate outcome. For example, while genes play a role in determining an organisms size, the nutrition and health it experiences after inception also have a large effect. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Genetics 40 History Although the science of genetics began with the applied and theoretical work of Gregor Mendel in the mid-19th century, other theories of inheritance preceded Mendel. A popular theory during Mendels time was the concept of blending inheritance: the idea that individuals inherit a smooth blend of traits from their parents. Mendels work disproved this, showing that traits are composed of combinations of distinct genes rather than a continuous blend. Another theory that had some support at that time was the inheritance of acquired characteristics: the belief that individuals inherit traits strengthened by their parents. This theory (commonly associated with Jean-Baptiste Lamarck) is now known to be wrong—the experiences of individuals do not affect the genes they pass to their children.[7] Other theories included the pangenesis of Charles Darwin (which had both acquired and inherited aspects) and Francis Galtons reformulation of pangenesis as both particulate and inherited.[8] Mendelian and classical genetics Modern genetics started with Gregor Johann Mendel, a German-Czech Augustinian monk and scientist who studied the nature of inheritance in plants. In his paper "Versuche über Pflanzenhybriden" ("Experiments on Plant Hybridization"), presented in 1865 to the Naturforschender Verein (Society for Research in Nature) in Brünn, DNA, the molecular basis Mendel traced the inheritance patterns of certain traits in pea plants and described them for inheritance. Each strand mathematically.[9] Although this pattern of inheritance could only be observed for a few of DNA is a chain of traits, Mendels work suggested that heredity was particulate, not acquired, and that the nucleotides, matching each inheritance patterns of many traits could be explained through simple rules and ratios. other in the center to form what look like rungs on a The importance of Mendels work did not gain wide understanding until the 1890s, after twisted ladder. his death, when other scientists working on similar problems re-discovered his research. [10] [11] William Bateson, a proponent of Mendels work, coined the word genetics in 1905. (The adjective genetic, derived from the Greek word genesis—γένεσις, "origin", predates the noun and was first used in a biological sense in 1860.)[12] Bateson popularized the usage of the word genetics to describe the study of inheritance in his inaugural address to the Third International Conference on Plant Hybridization in London, England, in 1906.[13] After the rediscovery of Mendels work, scientists tried to determine which molecules in the cell were responsible for inheritance. In 1910, Thomas Hunt Morgan argued that genes are on chromosomes, based on observations of a sex-linked white eye mutation in fruit flies.[14] In 1913, his student Alfred Sturtevant used the phenomenon of genetic linkage to show that genes are arranged linearly on the chromosome.[15] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Genetics 41 Molecular genetics Although genes were known to exist on chromosomes, chromosomes are composed of both protein and DNA—scientists did not know which of these is responsible for inheritance. In 1928, Frederick Griffith discovered the phenomenon of transformation (see Griffiths experiment): dead bacteria could transfer genetic material to "transform" other still-living bacteria. Sixteen years later, in 1944, Oswald Theodore Avery, Colin McLeod and Maclyn McCarty identified the molecule responsible for transformation as DNA.[16] The Hershey-Chase experiment in 1952 also showed that DNA (rather than Morgans observation of sex-linked inheritance of protein) is the genetic material of the viruses that infect bacteria, a mutation causing white eyes in Drosophila led providing further evidence that DNA is the molecule responsible for him to the hypothesis that genes are located upon chromosomes. inheritance.[17] James D. Watson and Francis Crick determined the structure of DNA in 1953, using the X-ray crystallography work of Rosalind Franklin and Maurice Wilkins that indicated DNA had a helical structure (i.e., shaped like a corkscrew).[18] [19] Their double-helix model had two strands of DNA with the nucleotides pointing inward, each matching a complementary nucleotide on the other strand to form what looks like rungs on a twisted ladder.[20] This structure showed that genetic information exists in the sequence of nucleotides on each strand of DNA. The structure also suggested a simple method for duplication: if the strands are separated, new partner strands can be reconstructed for each based on the sequence of the old strand. Although the structure of DNA showed how inheritance works, it was still not known how DNA influences the behavior of cells. In the following years, scientists tried to understand how DNA controls the process of protein production. It was discovered that the cell uses DNA as a template to create matching messenger RNA (a molecule with nucleotides, very similar to DNA). The nucleotide sequence of a messenger RNA is used to create an amino acid sequence in protein; this translation between nucleotide and amino acid sequences is known as the genetic code. With this molecular understanding of inheritance, an explosion of research became possible. One important development was chain-termination DNA sequencing in 1977 by Frederick Sanger. This technology allows scientists to read the nucleotide sequence of a DNA molecule.[21] In 1983, Kary Banks Mullis developed the polymerase chain reaction, providing a quick way to isolate and amplify a specific section of a DNA from a mixture.[22] Through the pooled efforts of the Human Genome Project and the parallel private effort by Celera Genomics, these and other methods culminated in the sequencing of the human genome in 2003.[23] Compiled and Edited by Marc Imhotep Cray , M.D.
  • Genetics 42 Features of inheritance Discrete inheritance and Mendels laws At its most fundamental level, inheritance in organisms occurs by means of discrete traits, called genes.[24] This property was first observed by Gregor Mendel, who studied the segregation of heritable traits in pea plants.[9] [25] In his experiments studying the trait for flower color, Mendel observed that the flowers of each pea plant were either purple or white—but never an intermediate between the two colors. These different, discrete versions of the same gene are called alleles. In the case of pea, which is a diploid species, each individual plant has two alleles of each gene, one allele inherited from each parent.[26] Many species, including humans, have this pattern of inheritance. Diploid organisms with two copies of the same allele of a given gene A Punnett square depicting a cross between two pea plants heterozygous for purple (B) and white are called homozygous at that gene locus, while organisms with two (b) blossoms different alleles of a given gene are called heterozygous. The set of alleles for a given organism is called its genotype, while the observable traits of the organism are called its phenotype. When organisms are heterozygous at a gene, often one allele is called dominant as its qualities dominate the phenotype of the organism, while the other allele is called recessive as its qualities recede and are not observed. Some alleles do not have complete dominance and instead have incomplete dominance by expressing an intermediate phenotype, or codominance by expressing both alleles at once.[27] When a pair of organisms reproduce sexually, their offspring randomly inherit one of the two alleles from each parent. These observations of discrete inheritance and the segregation of alleles are collectively known as Mendels first law or the Law of Segregation. Notation and diagrams Geneticists use diagrams and symbols to describe inheritance. A gene is represented by one or a few letters. Often a "+" symbol is used to mark the usual, non-mutant allele for a gene.[28] In fertilization and breeding experiments (and especially when discussing Mendels laws) the parents are referred to as the "P" generation and the offspring as the "F1" (first filial) generation. When the F1 offspring mate with each other, the offspring are called the "F2" (second filial) generation. One of the common diagrams used to predict the result of cross-breeding is the Punnett square. Genetic pedigree charts help track the inheritance patterns of When studying human genetic diseases, geneticists often traits. use pedigree charts to represent the inheritance of traits.[29] These charts map the inheritance of a trait in a family tree. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Genetics 43 Interactions of multiple genes Organisms have thousands of genes, and in sexually reproducing organisms these genes generally assort independently of each other. This means that the inheritance of an allele for yellow or green pea color is unrelated to the inheritance of alleles for white or purple flowers. This phenomenon, known as "Mendels second law" or the "Law of independent assortment", means that the alleles of different genes get shuffled between parents to form offspring with many different combinations. (Some genes do not assort independently, demonstrating genetic linkage, a topic discussed later in this article.) Often different genes can interact in a way that influences the same trait. In the Blue-eyed Mary (Omphalodes verna), for example, there exists a gene with alleles that determine the color of flowers: blue or magenta. Another gene, however, controls whether the flowers have Human height is a trait with complex genetic causes. Francis Galtons data from 1889 shows color at all or are white. When a plant has two copies of this white the relationship between offspring height as a allele, its flowers are white—regardless of whether the first gene has function of mean parent height. While correlated, blue or magenta alleles. This interaction between genes is called remaining variation in offspring heights indicates epistasis, with the second gene epistatic to the first.[30] environment is also an important factor in this trait. Many traits are not discrete features (e.g. purple or white flowers) but are instead continuous features (e.g. human height and skin color). These complex traits are products of many genes.[31] The influence of these genes is mediated, to varying degrees, by the environment an organism has [32] experienced. The degree to which an organisms genes contribute to a complex trait is called heritability. Measurement of the heritability of a trait is relative—in a more variable environment, the environment has a bigger influence on the total variation of the trait. For example, human height is a trait with complex causes. It has a heritability of 89% in the United States. In Nigeria, however, where people experience a more variable access to good nutrition and health care, height has a heritability of only 62%.[33] Compiled and Edited by Marc Imhotep Cray , M.D.
  • Genetics 44 Molecular basis for inheritance DNA and chromosomes The molecular basis for genes is deoxyribonucleic acid (DNA). DNA is composed of a chain of nucleotides, of which there are four types: adenine (A), cytosine (C), guanine (G), and thymine (T). Genetic information exists in the sequence of these nucleotides, and genes exist as stretches of sequence along the DNA chain.[34] Viruses are the only exception to this rule—sometimes viruses use the very similar molecule RNA instead of DNA as their genetic material.[35] DNA normally exists as a double-stranded molecule, coiled into the shape of a double-helix. Each nucleotide in DNA preferentially pairs with its partner nucleotide on the opposite strand: A pairs with T, and C pairs with G. Thus, in its two-stranded form, each strand effectively contains all necessary information, redundant with its partner strand. This structure of DNA is the physical basis for inheritance: DNA The molecular structure of DNA. Bases pair replication duplicates the genetic information by splitting the strands through the arrangement of hydrogen bonding and using each strand as a template for synthesis of a new partner between the strands. strand.[36] Genes are arranged linearly along long chains of DNA base-pair sequences. In bacteria, each cell usually contains a single circular genophore, while eukaryotic organisms (including plants and animals) have their DNA arranged in multiple linear chromosomes. These DNA strands are often extremely long; the largest human chromosome, for example, is about 247 million base pairs in length.[37] The DNA of a chromosome is associated with structural proteins that organize, compact, and control access to the DNA, forming a material called chromatin; in eukaryotes, chromatin is usually composed of nucleosomes, segments of DNA wound around cores of histone proteins.[38] The full set of hereditary material in an organism (usually the combined DNA sequences of all chromosomes) is called the genome. While haploid organisms have only one copy of each chromosome, most animals and many plants are diploid, containing two of each chromosome and thus two copies of every gene.[26] The two alleles for a gene are located on identical loci of sister chromatids, each allele inherited from a different parent. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Genetics 45 Many species have so called sex chromosomes. They are special in that they determine the sex of the organism.[39] In humans and many other animals, the Y-chromosome contains the gene that triggers the development of the specifically male characteristics. In evolution, this chromosome has lost most of its content and also most of its genes, while the X chromosome is similar to the other chromosomes and contains many genes. The X and Y chromosomes form a very heterogeneous pair before cell division. Reproduction When cells divide, their full genome is copied and each daughter cell inherits one copy. This process, called mitosis, is the simplest form of reproduction and is the basis for asexual reproduction. Asexual reproduction can also occur in multicellular organisms, producing offspring that inherit their genome from a single parent. Offspring that Walther Flemmings 1882 diagram of eukaryotic are genetically identical to their parents are called clones. cell division. Chromosomes are copied, Eukaryotic organisms often use sexual reproduction to generate condensed, and organized. Then, as the cell divides, chromosome copies separate into the offspring that contain a mixture of genetic material inherited from two daughter cells. different parents. The process of sexual reproduction alternates between forms that contain single copies of the genome (haploid) and double copies (diploid).[26] Haploid cells fuse and combine genetic material to create a diploid cell with paired chromosomes. Diploid organisms form haploids by dividing, without replicating their DNA, to create daughter cells that randomly inherit one of each pair of chromosomes. Most animals and many plants are diploid for most of their lifespan, with the haploid form reduced to single cell gametes such as sperm or eggs. Although they do not use the haploid/diploid method of sexual reproduction, bacteria have many methods of acquiring new genetic information. Some bacteria can undergo conjugation, transferring a small circular piece of DNA to another bacterium.[40] Bacteria can also take up raw DNA fragments found in the environment and integrate them into their genomes, a phenomenon known as transformation.[41] These processes result in horizontal gene transfer, transmitting fragments of genetic information between organisms that would be otherwise unrelated. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Genetics 46 Recombination and linkage The diploid nature of chromosomes allows for genes on different chromosomes to assort independently during sexual reproduction, recombining to form new combinations of genes. Genes on the same chromosome would theoretically never recombine, however, were it not for the process of chromosomal crossover. During crossover, chromosomes exchange stretches of DNA, effectively shuffling the gene alleles between the chromosomes.[42] This process of chromosomal crossover generally occurs during meiosis, a series of cell divisions that creates haploid cells. The probability of chromosomal crossover occurring between two given points on the chromosome is related to the distance between the points. For an arbitrarily long distance, the probability of crossover is high enough that the inheritance of the genes is effectively uncorrelated. For genes that are closer together, however, the lower probability of crossover means that the genes demonstrate genetic linkage—alleles for the two genes tend to be inherited together. The Thomas Hunt Morgans 1916 illustration of a amounts of linkage between a series of genes can be combined to form double crossover between chromosomes a linear linkage map that roughly describes the arrangement of the genes along the chromosome.[43] Gene expression Genetic code Genes generally express their functional effect through the production of proteins, which are complex molecules responsible for most functions in the cell. Proteins are made up of one or more polypeptide chains, each of which is composed of a sequence of amino acids, and the DNA sequence of a gene (through an RNA intermediate) is used to The genetic code: DNA, through a messenger produce a specific amino acid sequence. This process begins with the RNA intermediate, codes for protein with a triplet code. production of an RNA molecule with a sequence matching the genes DNA sequence, a process called transcription. This messenger RNA molecule is then used to produce a corresponding amino acid sequence through a process called translation. Each group of three nucleotides in the sequence, called a codon, corresponds either to one of the twenty possible amino acids in a protein or an instruction to end the amino acic sequence; this correspondence is called the genetic code.[44] The flow of information is unidirectional: information is transferred from nucleotide sequences into the amino acid sequence of proteins, but it never transfers from protein back into the sequence of DNA—a phenomenon Francis Crick called the central dogma of molecular biology.[45] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Genetics 47 The specific sequence of amino acids results in a unique three-dimensional structure for that protein, and the three-dimensional structures of proteins are related to their functions.[46] [47] Some are simple structural molecules, like the fibers formed by the protein collagen. Proteins can bind to other proteins and simple molecules, sometimes acting as enzymes by facilitating chemical reactions within the bound molecules (without changing the structure of the protein itself). Protein structure is dynamic; the protein hemoglobin bends into slightly different forms as it facilitates the capture, transport, and release of oxygen molecules within mammalian blood. A single nucleotide difference within DNA can cause a change in the amino acid sequence of a protein. Because protein structures are the result of their amino acid sequences, some changes can dramatically change the properties of a protein by destabilizing the structure or changing the surface of the protein in a way that changes its interaction with other proteins and molecules. For example, A single amino acid change causes sickle-cell anemia is a human genetic disease that results from a single base hemoglobin to form fibers. difference within the coding region for the β-globin section of hemoglobin, causing a single amino acid change that changes hemoglobins physical properties.[48] Sickle-cell versions of hemoglobin stick to themselves, stacking to form fibers that distort the shape of red blood cells carrying the protein. These sickle-shaped cells no longer flow smoothly through blood vessels, having a tendency to clog or degrade, causing the medical problems associated with this disease. Some genes are transcribed into RNA but are not translated into protein products—such RNA molecules are called non-coding RNA. In some cases, these products fold into structures which are involved in critical cell functions (e.g. ribosomal RNA and transfer RNA). RNA can also have regulatory effect through hybridization interactions with other RNA molecules (e.g. microRNA). Nature versus nurture Although genes contain all the information an organism uses to function, the environment plays an important role in determining the ultimate phenotype—a phenomenon often referred to as "nature vs. nurture". The phenotype of an organism depends on the interaction of genetics with the environment. One example of this is the case of temperature-sensitive mutations. Often, a single amino acid change within the sequence of a protein does not change its behavior and interactions with other molecules, but it does destabilize the structure. In a high temperature environment, where molecules are moving more quickly and hitting each other, this results in the protein losing its structure and failing to function. In a low temperature environment, however, the proteins structure is stable and it functions normally. This type of mutation is visible in the coat coloration of Siamese cats, where a mutation in an enzyme responsible for Siamese cats have a pigment production causes it to destabilize and lose function at high temperature-sensitive mutation in temperatures.[49] The protein remains functional in areas of skin that are pigment production. colder—legs, ears, tail, and face—and so the cat has dark fur at its extremities. Environment also plays a dramatic role in effects of the human genetic disease phenylketonuria.[50] The mutation that causes phenylketonuria disrupts the ability of the body to break down the amino acid phenylalanine, causing a toxic build-up of an intermediate molecule that, in turn, causes severe symptoms of progressive mental retardation and seizures. If someone with the phenylketonuria mutation follows a strict diet that avoids this amino acid, Compiled and Edited by Marc Imhotep Cray , M.D.
  • Genetics 48 however, they remain normal and healthy. A popular method to determine how much role nature and nurture play is to study identical and fraternal twins or siblings of multiple birth. Because identical siblings come from the same zygote they are genetically the same. Fraternal siblings however are as different genetically from one another as normal siblings. By comparing how often the twin of a set has the same disorder between fraternal and identical twins, scientists can see whether there is more of a nature or nurture effect. One famous example of a multiple birth study includes the Genain quadruplets, who were identical quadruplets all diagnosed with schizophrenia.[51] Gene regulation The genome of a given organism contains thousands of genes, but not all these genes need to be active at any given moment. A gene is expressed when it is being transcribed into mRNA (and translated into protein), and there exist many cellular methods of controlling the expression of genes such that proteins are produced only when needed by the cell. Transcription factors are regulatory proteins that bind to the start of genes, either promoting or inhibiting the transcription of the gene.[52] Within the genome of Escherichia coli bacteria, for example, there exists a series of genes necessary for the synthesis of the amino acid tryptophan. However, when tryptophan is already available to the cell, these genes for tryptophan synthesis are no longer needed. The presence of tryptophan directly affects the activity of the genes—tryptophan molecules bind to the tryptophan repressor (a transcription factor), changing the repressors structure such that the repressor binds to the genes. The tryptophan repressor blocks the transcription and expression of the genes, thereby creating negative feedback regulation of the tryptophan synthesis process.[53] Differences in gene expression are especially clear within multicellular organisms, where cells all contain the same genome but have very different structures and behaviors due to the expression of different sets of genes. All the cells in a multicellular organism derive from a single cell, differentiating into variant cell types in response to external and intercellular signals and gradually establishing different patterns of gene expression to create different behaviors. As no single gene is responsible for the development of structures within multicellular organisms, these patterns arise from the complex interactions Transcription factors bind to DNA, between many cells. influencing the transcription of associated genes. Within eukaryotes there exist structural features of chromatin that influence the transcription of genes, often in the form of modifications to DNA and chromatin that are stably inherited by daughter cells.[54] These features are called "epigenetic" because they exist "on top" of the DNA sequence and retain inheritance from one cell generation to the next. Because of epigenetic features, different cell types grown within the same medium can retain very different properties. Although epigenetic features are generally dynamic over the course of development, some, like the phenomenon of paramutation, have multigenerational inheritance and exist as rare exceptions to the general rule of DNA as the basis for inheritance.[55] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Genetics 49 Genetic change Mutations During the process of DNA replication, errors occasionally occur in the polymerization of the second strand. These errors, called mutations, can have an impact on the phenotype of an organism, especially if they occur within the protein coding sequence of a gene. Error rates are usually very low—1 error in every 10–100 million bases—due to the "proofreading" ability of DNA polymerases.[56] [57] (Without proofreading error rates are a thousandfold higher; because many viruses rely on DNA and RNA polymerases that lack proofreading ability, they experience higher mutation rates.) Processes that increase the rate of changes in DNA are called mutagenic: mutagenic chemicals promote errors in DNA replication, often by interfering with the structure of base-pairing, while UV radiation induces mutations by causing damage to the DNA structure.[58] Chemical damage to DNA occurs naturally as well, and cells use DNA repair mechanisms to repair mismatches and breaks in DNA—nevertheless, the repair sometimes fails to return the DNA to its original sequence. Gene duplication allows diversification by providing In organisms that use chromosomal crossover to exchange DNA and recombine redundancy: one gene can mutate genes, errors in alignment during meiosis can also cause mutations.[59] Errors in and lose its original function without harming the organism. crossover are especially likely when similar sequences cause partner chromosomes to adopt a mistaken alignment; this makes some regions in genomes more prone to mutating in this way. These errors create large structural changes in DNA sequence—duplications, inversions or deletions of entire regions, or the accidental exchanging of whole parts between different chromosomes (called translocation). Natural selection and evolution Further information: Natural selection Mutations alter an organisms genotype and occasionally this causes different phenotypes to appear. Most mutations have little effect on an organisms phenotype, health, or reproductive fitness. Mutations that do have an effect are usually deleterious, but occasionally some can be beneficial. Studies in the fly Drosophila melanogaster suggest that if a mutation changes a protein produced by a gene, about 70 percent of these mutations will be harmful with the remainder being either neutral or weakly beneficial.[60] Compiled and Edited by Marc Imhotep Cray , M.D.
  • Genetics 50 Population genetics studies the distribution of genetic differences within populations and how these distributions change over time.[61] Changes in the frequency of an allele in a population are mainly influenced by natural selection, where a given allele provides a selective or reproductive advantage to the organism,[62] as well as other factors such as mutation, genetic drift, genetic draft[63] , artificial selection and migration.[64] Over many generations, the genomes of organisms can change significantly, resulting in the phenomenon of evolution. Selection for beneficial mutations can cause a species to evolve into forms better An evolutionary tree of eukaryotic organisms, constructed by comparison of several orthologous able to survive in their environment, a process called adaptation.[65] gene sequences New species are formed through the process of speciation, often caused by geographical separations that prevent populations from exchanging [66] genes with each other. The application of genetic principles to the study of population biology and evolution is referred to as the modern synthesis. By comparing the homology between different species genomes it is possible to calculate the evolutionary distance between them and when they may have diverged (called a molecular clock).[67] Genetic comparisons are generally considered a more accurate method of characterizing the relatedness between species than the comparison of phenotypic characteristics. The evolutionary distances between species can be used to form evolutionary trees; these trees represent the common descent and divergence of species over time, although they do not show the transfer of genetic material between unrelated species (known as horizontal gene transfer and most common in bacteria). Research and technology Model organisms Although geneticists originally studied inheritance in a wide range of organisms, researchers began to specialize in studying the genetics of a particular subset of organisms. The fact that significant research already existed for a given organism would encourage new researchers to choose it for further study, and so eventually a few model organisms became the basis for most genetics research.[68] Common research topics in model organism genetics include the study of gene regulation and the involvement of genes in development and cancer. Organisms were chosen, in part, for convenience—short generation The common fruit fly (Drosophila melanogaster) times and easy genetic manipulation made some organisms popular is a popular model organism in genetics research. genetics research tools. Widely used model organisms include the gut bacterium Escherichia coli, the plant Arabidopsis thaliana, bakers yeast (Saccharomyces cerevisiae), the nematode Caenorhabditis elegans, the common fruit fly (Drosophila melanogaster), and the common house mouse (Mus musculus). Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Genetics 51 Medicine Medical genetics seeks to understand how genetic variation relates to human health and disease.[69] When searching for an unknown gene that may be involved in a disease, researchers commonly use genetic linkage and genetic pedigree charts to find the location on the genome associated with the disease. At the population level, researchers take advantage of Mendelian randomization to look for locations in the genome that are associated with diseases, a method especially useful for multigenic traits not clearly defined by a single gene.[70] Once a candidate gene is found, further research is often done on the corresponding gene (called an orthologous gene) in model organisms. In addition to studying genetic diseases, the increased availability of genotyping methods has led to the field of pharmacogenetics—studying how genotype can affect drug responses.[71] Individuals differ in their inherited tendency to develop cancer,[72] and cancer is a genetic disease.[73] The process of cancer development in the body is a combination of events. Mutations occasionally occur within cells in the body as they divide. Although these mutations will not be inherited by any offspring, they can affect the behavior of cells, sometimes causing them to grow and divide more frequently. There are biological mechanisms that attempt to stop this process; signals are given to inappropriately dividing cells that should trigger cell death, but sometimes additional mutations occur that cause cells to ignore these messages. An internal process of natural selection occurs within the body and eventually mutations accumulate within cells to promote their own growth, creating a cancerous tumor that grows and invades various tissues of the body. Research methods DNA can be manipulated in the laboratory. Restriction enzymes are commonly used enzymes that cut DNA at specific sequences, producing predictable fragments of DNA.[74] DNA fragments can be visualized through use of gel electrophoresis, which separates fragments according to their length. The use of ligation enzymes allows DNA fragments to be connected, and by ligating fragments of DNA together from different sources, researchers can create recombinant DNA. Often associated with genetically modified organisms, recombinant DNA is commonly used in the context of plasmids—short circular DNA fragments with a few genes on them. By inserting plasmids into bacteria and growing those bacteria on plates of agar (to isolate clones of bacteria cells), researchers can clonally amplify the inserted fragment of DNA (a process known as molecular cloning). (Cloning can also refer to creating clonal organisms, by various means.) DNA can also be amplified using a procedure called the polymerase chain reaction (PCR).[75] By using specific short sequences of DNA, PCR can isolate and exponentially amplify a targeted region of DNA. Because it can amplify from extremely small amounts of DNA, PCR is also often used to detect the presence of specific DNA sequences. DNA sequencing and genomics One of the most fundamental technologies developed to study genetics, DNA sequencing allows researchers to determine the sequence of nucleotides in DNA fragments. Developed in 1977 by Frederick Sanger Colonies of E. coli on a plate of agar, an and coworkers, chain-termination sequencing is now routinely used to example of cellular cloning and often used in sequence DNA fragments.[76] With this technology, researchers have molecular cloning. been able to study the molecular sequences associated with many human diseases. As sequencing has become less expensive, researchers have sequenced the genomes of many organisms, using computational tools to stitch together the sequences of many different fragments (a process called genome assembly).[77] These technologies were used to sequence the human genome, leading to the completion of the Compiled and Edited by Marc Imhotep Cray , M.D.
  • Genetics 52 Human Genome Project in 2003.[23] New high-throughput sequencing technologies are dramatically lowering the cost of DNA sequencing, with many researchers hoping to bring the cost of resequencing a human genome down to a thousand dollars.[78] The large amount of sequence data available has created the field of genomics, research that uses computational tools to search for and analyze patterns in the full genomes of organisms. Genomics can also be considered a subfield of bioinformatics, which uses computational approaches to analyze large sets of biological data. Notes [1] Genetikos, Henry George Liddell, Robert Scott, "A Greek-English Lexicon", at Perseus (http:/ / www. perseus. tufts. edu/ cgi-bin/ ptext?doc=Perseus:text:1999. 04. 0057:entry=#21880) [2] Genesis, Henry George Liddell, Robert Scott, "A Greek-English Lexicon", at Perseus (http:/ / www. perseus. tufts. edu/ cgi-bin/ ptext?doc=Perseus:text:1999. 04. 0057:entry=#21873) [3] Online Etymology Dictionary (http:/ / www. etymonline. com/ index. php?search=Genetic& searchmode=none) [4] Griffiths, William M.; Miller, Jeffrey H.; Suzuki, David T. et al., eds (2000). "Genetics and the Organism: Introduction" (http:/ / www. ncbi. nlm. nih. gov/ books/ bv. fcgi?rid=iga. section. 60). An Introduction to Genetic Analysis (7th ed.). New York: W. H. Freeman. ISBN 0-7167-3520-2. . [5] Hartl D, Jones E (2005) [6] Weiling, F (1991). "Historical study: Johann Gregor Mendel 1822–1884.". American journal of medical genetics 40 (1): 1–25; discussion 26. doi:10.1002/ajmg.1320400103. PMID 1887835. [7] Lamarck, J-B (2008). In Encyclopædia Britannica. Retrieved from Encyclopædia Britannica Online (http:/ / www. search. eb. com/ eb/ article-273180) on 16 March 2008. [8] Peter J. Bowler, The Mendelian Revolution: The Emergency of Hereditarian Concepts in Modern Science and Society (Baltimore: Johns Hopkins University Press, 1989): chapters 2 & 3. [9] Blumberg, Roger B.. "Mendels Paper in English" (http:/ / www. mendelweb. org/ Mendel. html). . [10] genetics, n., Oxford English Dictionary, 3rd ed. [11] Bateson W. "Letter from William Bateson to Alan Sedgwick in 1905" (http:/ / www. jic. ac. uk/ corporate/ about/ bateson. htm). The John Innes Centre. . Retrieved 15 March 2008. Note that the letter was to an Adam Sedgwick, a zoologist and "Reader in Animal Morphology" at Trinity College, Cambridge [12] genetic, adj., Oxford English Dictionary, 3rd ed. [13] Bateson, W (1907). "The Progress of Genetic Research". In Wilks, W. Report of the Third 1906 International Conference on Genetics: Hybridization (the cross-breeding of genera or species), the cross-breeding of varieties, and general plant breeding. London: Royal Horticultural Society. Initially titled the "International Conference on Hybridisation and Plant Breeding", Wilks changed the title for publication as a result of Batesons speech. [14] Moore, John A. (1983). "Thomas Hunt Morgan—The Geneticist". Integrative and Comparative Biology 23: 855. doi:10.1093/icb/23.4.855. [15] Sturtevant AH (1913). "The linear arrangement of six sex-linked factors in Drosophila, as shown by their mode of association" (http:/ / www. esp. org/ foundations/ genetics/ classical/ holdings/ s/ ahs-13. pdf). Journal of Experimental Biology 14: 43–59. . [16] Avery, OT; MacLeod, CM; McCarty, M (1944). 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  • Genetics 55 [78] Service, RF (2006). "Gene sequencing. The race for the $1000 genome.". Science 311 (5767): 1544–6. doi:10.1126/science.311.5767.1544. PMID 16543431. References • Alberts B, Johnson A, Lewis J, Raff M, Roberts K, and Walter P (2002). Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 0-8153-3218-1. • Griffiths, William M.; Miller, Jeffrey H.; Suzuki, David T. et al., eds (2000). An Introduction to Genetic Analysis (7th ed.). New York: W. H. Freeman. ISBN 0-7167-3520-2. • Hartl D, Jones E (2005). Genetics: Analysis of Genes and Genomes (6th ed.). Jones & Bartlett. ISBN 0-7637-1511-5. • Lodish H, Berk A, Zipursky LS, Matsudaira P, Baltimore D, and Darnell J (2000). Molecular Cell Biology (4th ed.). New York: Scientific American Books. ISBN 0-7167-3136-3. External links • Genetics (http://www.bbc.co.uk/programmes/p00547md) on In Our Time at the BBC. ( listen now (http:// www.bbc.co.uk/iplayer/console/p00547md/In_Our_Time_Genetics)) • Genetics (http://www.dmoz.org/Science/Biology/Genetics/) at the Open Directory Project Cell biology Cell biology (formerly cytology, from the Greek kytos, "container") is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level. Cell biology research encompasses both the great diversity of single-celled organisms like bacteria and protozoa, as well as the many specialized cells in multicellular organisms such as humans. Knowing the components of cells and how cells work is fundamental to all biological sciences. Appreciating the similarities and differences between cell types is particularly important to the fields of cell and molecular biology as well as to biomedical fields such as cancer research and developmental biology. These fundamental similarities and differences provide a unifying theme, sometimes allowing the principles learned from studying one cell type to be extrapolated and generalized to other cell types. Therefore, research in cell biology is closely related to genetics, biochemistry, molecular biology, immunology, and developmental biology. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Cell biology 56 Processes Understanding cells in terms of their molecular components. Movement of proteins Each type of protein is usually sent to a particular part of the cell. An important part of cell biology is the investigation of molecular mechanisms by which proteins are moved to different places inside cells or secreted from cells. Most proteins are synthesized by ribosomes in the cytoplasm. This process is known as protein biosynthesis. Biosynthesis (also called biogenesis) is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products (also simply known as protein translation). Some proteins, such as those to be incorporated in membranes (known as membrane proteins), are transported into the "rough" endoplasmic reticulum (ER) during Endothelial cells under the microscope. Nuclei synthesis. This process can be followed by transportation and are stained blue with DAPI, microtubles are processing in the Golgi apparatus. From the Golgi, membrane proteins marked green by an antibody and actin filaments can move to the plasma membrane, to other sub-cellular compartments, are labelled red with phalloidin. or they can be secreted from the cell. The ER and Golgi can be thought of as the "membrane protein synthesis compartment" and the "membrane protein processing compartment", respectively. There is a semi-constant flux of proteins through these compartments. ER and Golgi-resident proteins associate with other proteins but remain in their respective compartments. Other proteins "flow" through the ER and Golgi to the plasma membrane. Motor proteins transport membrane protein-containing vesicles along cytoskeletal tracks to distant parts of cells such as axon terminals. Some proteins that are made in the cytoplasm contain structural features that target them for transport into mitochondria or the nucleus. Some mitochondrial proteins are made inside mitochondria and are coded for by mitochondrial DNA. In plants, chloroplasts also make some cell proteins. Extracellular and cell surface proteins destined to be degraded can move back into intracellular compartments upon being incorporated into endocytosed vesicles some of which fuse with lysosomes where the proteins are broken Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Cell biology 57 down to their individual amino acids. The degradation of some membrane proteins begins while still at the cell surface when they are cleaved by secretases. Proteins that function in the cytoplasm are often degraded by proteasomes. Other cellular processes • Active transport and Passive transport - Movement of molecules into and out of cells. • Autophagy - The process whereby cells "eat" their own internal components or microbial invaders. • Adhesion - Holding together cells and tissues. • Reproduction - Made possible by the combination of sperm made in the testiculi(contained in some male cells nucleus) and the egg made in the ovary(contained in the nucleus of a female cell). When the sperm breaks through the hard outer shell of the egg a new cell embryo is formed, which, in humans, grows to full size in 9 months. • Cell movement: Chemotaxis, Contraction, cilia and flagella. • Cell signaling - Regulation of cell behavior by signals from outside. • DNA repair and Cell death • Metabolism: Glycolysis, respiration, Photosynthesis • Transcription and mRNA splicing - gene expression. Internal cellular structures • Chloroplast - key organelle for photosynthesis (only found in plant cells) • Cilia - motile microtubule-containing structures of eukaryotes • Cytoplasm - contents of the main fluid-filled space inside cells • Cytoskeleton - protein filaments inside cells • Endoplasmic reticulum - major site of membrane protein synthesis • Flagella - motile structures of bacteria, archaea and eukaryotes • Golgi apparatus - site of protein glycosylation in the endomembrane system • Lipid bilayer - fundamental organizational structure of cell membranes • Lysosome - break down cellular waste products and debris into simple Electron micrograph. compounds (only found in animal cells) • Membrane lipid and protein barrier • Mitochondrion - major energy-producing organelle by releasing it in the form of ATP • Nucleus - holds most of the DNA of eukaryotic cells and controls all cellular activities • Organelle - term used for major subcellular structures • Ribosome - RNA and protein complex required for protein synthesis in cells • Vesicle - small membrane-bounded spheres inside cells Compiled and Edited by Marc Imhotep Cray , M.D.
  • Cell biology 58 Techniques used to study cells Cells may be observed under the microscope. This includes the Optical Microscope, Transmission Electron Microscope, Scanning Electron Microscope, Fluorescence Microscope, and by Confocal Microscopy. Several different techniques exist to study cells. • Cell culture is the basic technique of growing cells in a laboratory independent of an organism. • Immunostaining, also known as immunohistochemistry, is a specialized histological method used to localize proteins in cells or tissue slices. Unlike regular histology, which uses stains to identify cells, cellular components or protein classes, immunostaining requires the reaction of an antibody directed against the protein of interest within the tissue or cell. Through the use of proper controls and published protocols (need to add reference links here), specificity of the antibody-antigen reaction can be achieved. Once this complex is formed, it is identified via either a "tag" attached directly to the antibody, or added in an additional technical step. Commonly used "tags" include fluorophores or enzymes. In the case of the former, detection of the location of the "immuno-stained" protein occurs via fluorescence microscopy. With an enzymatic tag, such as horse radish peroxidase, a chemical reaction is carried out that results in a dark color in the location of the protein of interest. This darkened pattern is then detected using light microscopy. • Computational genomics is used to find patterns in genomic information [1] • DNA microarrays identify changes in transcript levels between different experimental conditions. • Gene knockdown mutates a selected gene. • In situ hybridization shows which cells are expressing a particular RNA transcript. • PCR can be used to determine how many copies of a gene are present in a cell. • Transfection introduces a new gene into a cell, usually an expression construct Purification of cells and their parts Purification may be performed using the following methods: • Cell fractionation • Release of cellular organelles by disruption of cells. • Separation of different organelles by centrifugation. • Flow cytometry • Immunoprecipitation • Proteins extracted from cell membranes by detergents and salts or other kinds of chemicals. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Cell biology 59 References • Cell and Molecular Biology by Karp 5th Ed., ISBN 0471465801 •  This article incorporates public domain material from the NCBI document "Science Primer" [2]. [1] Cristianini, N. and Hahn, M. Introduction to Computational Genomics (http:/ / www. computational-genomics. net/ ), Cambridge University Press, 2006. (ISBN 9780521671910 | ISBN 0521671914) [2] http:/ / www. ncbi. nlm. nih. gov/ About/ primer/ index. html • Aging Cell (http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1474-9726) External links • Cell Centered Database (http://ccdb.ucsd.edu/sand/main?event=showMPByType&typeid=0&start=1&pl=y) • Cell Biology (http://www.dmoz.org/Science/Biology/Cell_Biology/) at the Open Directory Project Compiled and Edited by Marc Imhotep Cray , M.D.
  • Endocrinology 60 Endocrinology Endocrinologist Occupation Names Doctor, Medical Specialist Type Specialty Activity sectors Medicine Description Education required Doctor of Medicine, Doctor of Osteopathic Medicine Fields of employment Hospitals, Clinics Average salary USD $199,000 (M.D., D.O.) Endocrinology (from Greek ἔνδον, endo, "within"; κρῑνω, krīnō, "to separate"; and -λογία, -logia) is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions called hormones, the integration of developmental events such as proliferation, growth, and differentiation (including histogenesis and organogenesis) and the coordination of metabolism, respiration, excretion, movement, reproduction, and sensory perception depend on chemical cues, substances synthesized and secreted by specialized cells. Endocrinology is concerned with the study of the biosynthesis, storage, chemistry, Physiological function of hormones and Pathology with the cells of the endocrine glands and tissues that secrete them. The endocrine system consists of several glands, all and in different parts of the body, that secrete hormones directly into the blood rather than into a duct system. Hormones have many different functions and modes of action; one hormone may have several effects on different target organs, and, conversely, one target organ may be affected by more than one hormone. In the original 1902 definition by Bayliss and Starling (see below), they specified that, to be classified as a hormone, a chemical must be produced by an organ, be released (in small amounts) into the blood, and be transported by the blood to a distant organ to exert its specific function. This definition holds for most "classical" hormones, but there are also paracrine mechanisms (chemical communication between cells within a tissue or organ), autocrine signals (a chemical that acts on the same cell), and intracrine signals (a chemical that acts within the same cell).[1] A neuroendocrine signal is a "classical" hormone that is released into the blood by a neurosecretory neuron (see article on neuroendocrinology). Hormones act by binding to specific receptors in the target organ. As Baulieu notes, a receptor has at least two basic constituents: • a recognition site, to which the hormone binds • an effector site, which precipitates the modification of cellular function.[2] Between these is a "transdu | background color = white | image1 = Cortisol2.svg | width1 = 150 | caption1 = Cortisol | image2 = Cholecalciferol.svg | width2 = 150 | caption2 = Vitamin D3 }} Griffin and Ojeda identify three different classes of hormone based on their chemical composition:[3] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Endocrinology 61 Amines Amines, such as norepinephrine, epinephrine, and dopamine, are derived from single amino acids, in this case tyrosine. Thyroid hormones such as 3,5,3’-triiodothyronine (T3) and 3,5,3’,5’-tetraiodothyronine (thyroxine, T4) make up a subset of this class because they derive from the combination of two iodinated tyrosine amino acid residues. Peptide and protein Peptide hormones and protein hormones consist of three (in the case of thyrotropin-releasing hormone) to more than 200 (in the case of follicle-stimulating hormone) amino acid residues and can have molecular weights as large as 30,000. All hormones secreted by the pituitary gland are peptide hormones, as are leptin from adipocytes, ghrelin from the stomach, and insulin from the pancreas. Steroid Steroid hormones are converted from their parent compound, cholesterol. Mammalian steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestagens. History and key discoveries of endocrinology The study of endocrinology began in China. The Chinese were isolating sex and pituitary hormones from human urine and using them for medicinal purposes by 200 BC.[4] They used many complex methods, such as sublimation.[4] Eventually, when Berthold noted that castrated cockerels did not develop combs and wattles or exhibit overtly male behaviour, European endocrinology began (however, it should be noted that the Chinese anticipated the science by over 1500 years.) [5] He found that replacement of testes back into the abdominal cavity of the same bird or another castrated bird resulted in normal behavioural and morphological development, and he concluded (erroneously) that the testes secreted a substance that "conditioned" the blood that, in turn, acted on the body of the cockerel. In fact, one of two other things could have been true: that the testes modified or activated a constituent of the blood or that the testes removed an inhibitory factor from the blood. It was not proven that the testes released a substance that engenders male characteristics until it was shown that the extract of testes could replace their function in castrated animals. Pure, crystalline testosterone was isolated in 1938.[6] Although most of the relevant tissues and endocrine glands had been identified by early anatomists, a more humoral approach to understanding biological function and disease was favoured by the ancient Greek and Roman thinkers such as Aristotle, Hippocrates, Lucretius, Celsus, and Galen, according to Freeman et al.,[7] and these theories held sway until the advent of germ theory, physiology, and organ basis of pathology in the 19th century. In medieval Persia, Avicenna (980-1037) provided a detailed account on diabetes mellitus in The Canon of Medicine (c. 1025), "describing the abnormal appetite and the collapse of sexual functions and he documented the sweet taste of diabetic urine." Like Aretaeus of Cappadocia before him, Avicenna recognized a primary and secondary diabetes. He also described diabetic gangrene, and treated diabetes using a mixture of lupine, trigonella (fenugreek), and zedoary seed, which produces a considerable reduction in the excretion of sugar, a treatment which is still prescribed in modern times. Avicenna also "described diabetes insipidus very precisely for the first time", though it was later Johann Peter Frank (1745–1821) who first differentiated between diabetes mellitus and diabetes insipidus.[8] In the 12th century, Zayn al-Din al-Jurjani, another Muslim physician, provided the first description of Graves disease after noting the association of goitre and exophthalmos in his Thesaurus of the Shah of Khwarazm, the major medical dictionary of its time.[9] [10] Al-Jurjani also established an association between goitre and palpitation.[8] The disease was later named after Irish doctor Robert James Graves,[11] who described a case of goiter with exophthalmos in 1835. The German Karl Adolph von Basedow also independently reported the same constellation of Compiled and Edited by Marc Imhotep Cray , M.D.
  • Endocrinology 62 symptoms in 1840, while earlier reports of the disease were also published by the Italians Giuseppe Flajani and Antonio Giuseppe Testa, in 1802 and 1810 respectively,[12] and by the English physician Caleb Hillier Parry (a friend of Edward Jenner) in the late 18th century.[13] In 1902 Bayliss and Starling performed an experiment in which they observed that acid instilled into the duodenum caused the pancreas to begin secretion, even after they had removed all nervous connections between the two.[14] The same response could be produced by injecting extract of jejunum mucosa into the jugular vein, showing that some factor in the mucosa was responsible. They named this substance "secretin" and coined the term hormone for chemicals that act in this way. Von Mering and Minkowski made the observation in 1889 that removing the pancreas surgically led to an increase in blood sugar, followed by a coma and eventual death—symptoms of diabetes mellitus. In 1922, Banting and Best realized that homogenizing the pancreas and injecting the derived extract reversed this condition.[15] The hormone responsible, insulin, was not discovered until Frederick Sanger sequenced it in 1953. Neurohormones were first identified by Otto Loewi in 1921.[16] He incubated a frogs heart (innervated with its vagus nerve attached) in a saline bath, and left in the solution for some time. The solution was then used to bathe a non-innervated second heart. If the vagus nerve on the first heart was stimulated, negative inotropic (beat amplitude) and chronotropic (beat rate) activity were seen in both hearts. This did not occur in either heart if the vagus nerve was not stimulated. The vagus nerve was adding something to the saline solution. The effect could be blocked using atropine, a known inhibitor to heart vagal nerve stimulation. Clearly, something was being secreted by the vagus nerve and affecting the heart. The "vagusstuff" (as Loewi called it) causing the myotropic (muscle enhancing) effects was later identified to be acetylcholine and norepinephrine. Loewi won the Nobel Prize for his discovery. Recent work in endocrinology focuses on the molecular mechanisms responsible for triggering the effects of hormones. The first example of such work being done was in 1962 by Earl Sutherland. Sutherland investigated whether hormones enter cells to evoke action, or stayed outside of cells. He studied norepinephrine, which acts on the liver to convert glycogen into glucose via the activation of the phosphorylase enzyme. He homogenized the liver into a membrane fraction and soluble fraction (phosphorylase is soluble), added norepinephrine to the membrane fraction, extracted its soluble products, and added them to the first soluble fraction. Phosphorylase activated, indicating that norepinephrines target receptor was on the cell membrane, not located intracellularly. He later identified the compound as cyclic AMP (cAMP) and with his discovery created the concept of second-messenger-mediated pathways. He, like Loewi, won the Nobel Prize for his groundbreaking work in endocrinology.[17] Endocrinology as a profession Although every organ system secretes and responds to hormones (including the brain, lungs, heart, intestine, skin, and the kidney), the clinical specialty of endocrinology focuses primarily on the endocrine organs, meaning the organs whose primary function is hormone secretion. These organs include the pituitary, thyroid, adrenals, ovaries, testes, and pancreas. An endocrinologist is a doctor who specializes in treating disorders of the endocrine system, such as diabetes, hyperthyroidism, and many others (see list of diseases below). Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Endocrinology 63 Work The medical specialty of endocrinology involves the diagnostic evaluation of a wide variety of symptoms and variations and the long-term management of disorders of deficiency or excess of one or more hormones. The diagnosis and treatment of endocrine diseases are guided by laboratory tests to a greater extent than for most specialties. Many diseases are investigated through excitation/stimulation or inhibition/suppression testing. This might involve injection with a stimulating agent to test the function of an endocrine organ. Blood is then sampled to assess the changes of the relevant hormones or metabolites. An endocrinologist needs extensive knowledge of clinical chemistry and biochemistry to understand the uses and limitations of the investigations. A second important aspect of the practice of endocrinology is distinguishing human variation from disease. Atypical patterns of physical development and abnormal test results must be assessed as indicative of disease or not. Diagnostic imaging of endocrine organs may reveal incidental findings called incidentalomas, which may or may not represent disease. Endocrinology involves caring for the person biology as well as the nucleus the enzymes as well as the disease. Most endocrine disorders are chronic diseases that need life-long care. Some of the most common endocrine diseases include diabetes mellitus, hypothyroidism and the metabolic syndrome. Care of diabetes, obesity and other chronic diseases necessitates understanding the patient at the personal and social level as well as the molecular, and the physician–patient relationship can be an important therapeutic process. Apart from treating patients, many endocrinologists are involved in clinical science and medical research, teaching, and hospital management. Training There are roughly 4,000 endocrinologists in the United States. Endocrinologists are specialists of internal medicine or pediatrics. Reproductive endocrinologists deal primarily with problems of fertility and menstrual function—often training first in obstetrics. Most qualify as an internist, pediatrician, or gynecologist for a few years before specializing, depending on the local training system. In the U.S. and Canada, training for board certification in internal medicine, pediatrics, or gynecology after medical school is called residency. Further formal training to subspecialize in adult, pediatric, or reproductive endocrinology is called a fellowship. Typical training for a North American endocrinologist involves 4 years of college, 4 years of medical school, 3 years of residency, and 2 years of fellowship. Adult endocrinologists are board certified by the American Board of Internal Medicine (ABIM) in Endocrinology, Diabetes and Metabolism. Professional organizations In North America the principal professional organizations of endocrinologists include The Endocrine Society,[18] the American Association of Clinical Endocrinologists,[19] the American Diabetes Association,[20] the Lawson Wilkins Pediatric Endocrine Society,[21] and the American Thyroid Association.[22] In the United Kingdom, the Society for Endocrinology[23] and the British Society for Paediatric Endocrinology and Diabetes[24] are the main professional organisations. The European Society for Paediatric Endocrinology[25] is the largest international professional association dedicated solely to paediatric endocrinology. There are numerous similar associations around the world. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Endocrinology 64 Patient education Because endocrinology encompasses so many conditions and diseases, there are many organizations that provide education to patients and the public. The Hormone Foundation is the public education affiliate of The Endocrine Society and provides information on all endocrine-related conditions. Other educational organizations that focus on one or more endocrine-related conditions include the American Diabetes Association, National Osteoporosis Foundation, Human Growth Foundation, American Menopause Foundation, Inc., and Thyroid Foundation of America. Diseases See main article at Endocrine diseases A disease due to a disorder of the endocrine system is often called a "hormone imbalance", but is technically known as an endocrinopathy or endocrinosis. Such disease can be treated by reducing the hormone which has become imbalanced. In popular culture • Lisa Cuddy, a character on the television show House M.D. • Elliot Reid, a character who becomes an expert in the field in the Scrubs episode "My Way Home" • Naomi Bennett, a character on the television show Private Practice who did her residency in Obstetrics and Gynecology and her fellowship in Reproductive endocrinology and infertility References [1] Nussey S, Whitehead S (2001). Endocrinology: An Integrated Approach. Oxford: Bios Scientific Publ.. ISBN 1-85996-252-1. [2] Kelly, Paul; Baulieu, Etienne-Emile (1990). Hormones: from molecules to disease. Paris: Hermann. ISBN 2-7056-6030-5. [3] Ojeda, Sergio R.; Griffin, James Bennett (2000). Textbook of endocrine physiology (4th ed.). Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-513541-5. [4] Temple, Robert. The Genius of China.pp. 141, 142. ISBN 9781594772177. [5] Berthold AA (1849). "Transplantation der Hoden". Arch. Anat. Phsiol. Wiss. Med. 16: 42–6. [6] David K, Dingemanse E, Freud J et al. (1935). "Uber krystallinisches mannliches Hormon aus Hoden (Testosteron) wirksamer als aus harn oder aus Cholesterin bereitetes Androsteron". Hoppe Seylers Z Physiol Chem 233: 281. [7] Freeman ER, Bloom DA, McGuire EJ (2001). "A brief history of testosterone". J. Urol. 165 (2): 371–3. doi:10.1097/00005392-200102000-00004. PMID 11176375. [8] Nabipour, I. (2003). "Clinical Endocrinology in the Islamic Civilization in Iran". International Journal of Endocrinology and Metabolism 1: 43–45 [44–5]. [9] Basedows syndrome or disease (http:/ / www. whonamedit. com/ synd. cfm/ 1517. html) at Who Named It? - the history and naming of the disease [10] Ljunggren, J. G. (August 10, 1983). "Who was the man behind the syndrome: Ismail al-Jurjani, Testa, Flagani, Parry, Graves or Basedow? Use the term hyperthyreosis instead". Lakartidningen 80 (32–33): 2902. PMID 6355710. [11] Robert James Graves (http:/ / www. whonamedit. com/ doctor. cfm/ 695. html) at Who Named It? [12] Giuseppe Flajani (http:/ / www. whonamedit. com/ doctor. cfm/ 1471. html) at Who Named It? [13] Hull G (1998). "Caleb Hillier Parry 1755-1822: a notable provincial physician". Journal of the Royal Society of Medicine 91 (6): 335–8. PMC 1296785. PMID 9771526. [14] Bayliss WM, Starling EH. The mechanism of pancreatic secretion. J Physiol 1902;28:325–352. [15] Bliss M (1989). "J. J. R. Macleod and the discovery of insulin". Q J Exp Physiol 74 (2): 87–96. PMID 2657840. [16] Loewi, O. Uebertragbarkeit der Herznervenwirkung. Pflugers Arch. ges Physiol. 1921;189:239-42. [17] Sutherland EW (1972). "Studies on the mechanism of hormone action" (http:/ / www. sciencemag. org/ cgi/ pmidlookup?view=long& pmid=4339614). Science 177 (4047): 401–8. Bibcode 1972Sci...177..401S. doi:10.1126/science.177.4047.401. PMID 4339614. . [18] The Endocrine Society (http:/ / www. endo-society. org) [19] Association of Clinical Endocrinologists (http:/ / www. aace. com) [20] American Diabetes Association (http:/ / www. diabetes. org) [21] Lawson Wilkins Pediatric Endocrine Society (http:/ / www. lwpes. org) [22] American Thyroid Association (http:/ / www. thyroid. org) Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Endocrinology 65 [23] Society for Endocrinology (http:/ / www. endocrinology. org) [24] British Society for Paediatric Endocrinology and Diabetes (http:/ / www. bsped. org. uk) [25] European Society for Paediatric Endocrinology (http:/ / www. eurospe. org) External links • Endocrinology (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?call=bv.View..ShowTOC&rid=endocrin. TOC&depth=1) (British online textbook) • Endotext (http://www.endotext.org) (American online textbook) • Useful Endocrinology Resources for Residents (http://www.endocrinology.med.ucla.edu/resident.htm) • Endocrinology journals from Elsevier (http://www.intl.elsevierhealth.com/endocrinology/journals.cfm) • Endocrinology news updates from Elsevier (http://www.clinicalendocrinologynewsupdate.com) • MeSH Endocrinology (http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Endocrinology) • The Hormone Foundation (http://www.hormone.org) • Endocrinology Center medical in Thailand (http://www.vejthani.com/web-english/index-english.php) Societies and associations • Endocrine Society (http://www.endo-society.org/) • American Association of Clinical Endocrinologists (http://www.aace.com) • American Diabetes Association (http://www.diabetes.org) • Lawson Wilkins Pediatric Endocrine Society (http://www.lwpes.org) • Society for Endocrinology (http://www.endocrinology.org) • Society for Behavioral Neuroendocrinology (http://www.sbn.org) • British Society for Paediatric Endocrinology & Diabetes (http://www.bsped.org.uk) General pathology General pathology, also called investigative pathology, experimental pathology or theoretical pathology, is a broad and complex scientific field which seeks to understand the mechanisms of injury to cells and tissues, as well as the bodys means of responding to and repairing injury. Areas of study include cellular adaptation to injury, necrosis, inflammation, wound healing and neoplasia. It forms the foundation of pathology, the application of this knowledge to diagnose diseases in humans and animals. The term "general pathology" is also used to describe the practice of both anatomical and clinical pathology. Adaptation to injury Disease processes may be incited or exacerbated by a variety of external and internal influences, including trauma, infection, poisoning, loss of blood flow, autoimmunity, inherited or acquired genetic damage, or errors of development. One common theme in pathology is the way in which the bodys responses to injury, while evolved to protect health, can also contribute in some ways to disease processes.[1] Cells and tissues may respond to injury and stress by specific mechanisms, which may vary according to the cell types and nature of the injury. In the short term, cells may activate specific genetic programs to protect their vital proteins and organelles from heat shock or hypoxia, and may activate DNA repair pathways to repair damage to chromosomes from radiation or chemicals. Hyperplasia is a long-term adaptive response of cell division and multiplication, which can increase the ability of a tissue to compensate for an injury. For example, repeated irritation to the skin can cause a protective thickening due to hyperplasia of the epidermis. Hypertrophy is an increase in the size of cells in a tissue in response to stress, an example being hypertrophy of muscle cells in the heart in response to Compiled and Edited by Marc Imhotep Cray , M.D.
  • General pathology 66 increased resistance to blood flow as a result of narrowing of the hearts outflow valve. Metaplasia occurs when repeated damage to the cellular lining of an organ triggers its replacement by a different cell type.[1] Cell death Necrosis is the irreversible destruction of cells as a result of severe injury in a setting where the cell is unable to activate the needed metabolic pathways for survival or orderly degeneration. This is often due to external pathologic factors, such as toxins or loss of oxygen supply. Milder stresses may lead to a process called reversible cell injury, which mimics the cell swelling and vacuolization seen early in the necrotic process, but in which the cell is able to adapt and survive. In necrosis, the components of degenerating cells leak out, potentially contributing to inflammation and further damage. Apoptosis, in contrast, is a regulated, orderly degeneration of the cell which occurs in the settings of both injury and normal physiological processes.[1] Inflammation Inflammation is a particularly important and complex reaction to tissue injury, and is particularly important in fighting infection. Acute inflammation is generally a non-specific response triggered by the injured tissue cells themselves, as well as specialized cells of the innate immune system and previously developed adaptive immune mechanisms. A localized acute inflammatory response triggers vascular changes in the injured area, recruits pathogen-fighting neutrophils, and begins the process of developing a new adaptive immune response. Chronic inflammation occurs when the acute response fails to entirely clear the inciting factor. While chronic inflammation can lay a positive A transmission electron microscope image of an immune cell role in containing a continuing infectious hazard, it can crossing from the bone marrow into the circulation also lead to progressive tissue damage, as well as predisposing (in some cases) to the development of cancer.[1] Tissue repair Tissue repair, as seen in wound healing, is triggered by inflammation. The process may proceed even before the resolution of a precipitating insult, through the formation of granulation tissue. Healing involves the proliferation of connective tissue cells and blood vessel-forming cells as a result of hormonal growth signals. While healing is a critical adaptive response, an aberrant healing response can lead to progressive fibrosis, contractures, or other changes which can compromise function.[1] Neoplasia Neoplasia, or "new growth," is a proliferation of cells which is independent of any physiological process. The most familiar examples of neoplasia are benign tumors and cancers. Neoplasia results from genetic changes which cause cells to activate genetic programs inappropriately. Dysplasia is an early sign of a neoplastic process in a tissue, and is marked by persistence of immature, poorly differentiated cell forms. Interestingly, there are many similarities in the gene pathways activated in cancer cells, and those activated in cells involved in wound healing and inflammation.[1] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • General pathology 67 Choristoma Choristoma, ectopic tissue, heterotopic tissue, or aberrant tissue, is a mass of histologically normal tissue that is present in an abnormal location.[2] References [1] Ramzi Cotran, Vinay Kumar, Tucker Collins (1999). Robbins Pathologic Basis of Disease, Sixth Edition. W.B. Saunders. ISBN 072167335X. [2] MeSH classification C23.300.250 (http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2007/ MB_cgi?mode=& term=Pathological+ Conditions,+ Signs+ and+ Symptoms& field=entry#TreeC23) (pathological conditions, signs and symptoms Immunology Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms.[1] It deals with the physiological functioning of the immune system in states of both health and disease; malfunctions of the immune system in immunological disorders (autoimmune diseases, hypersensitivities, immune deficiency, transplant rejection); the physical, chemical and physiological characteristics of the components of the immune system in vitro, in situ, and in vivo. Immunology has applications in several disciplines of science, and as such is further divided. Histological examination of the immune system Even before the concept of immunity (from immunis, Latin for "exempt") was developed, numerous early physicians characterized organs that would later prove to be part of the immune system. The key primary lymphoid organs of the immune system are the thymus and bone marrow, and secondary lymphatic tissues such as spleen, tonsils, lymph vessels, lymph nodes, adenoids, and skin and liver. When health conditions warrant, immune system organs including the thymus, spleen, portions of bone marrow, lymph nodes and secondary lymphatic tissues can be surgically excised for examination while patients are still alive. Many components of the immune system are actually cellular in nature and not associated with any specific organ but rather are embedded or circulating in various tissues located throughout the body. Classical immunology Classical immunology ties in with the fields of epidemiology and medicine. It studies the relationship between the body systems, pathogens, and immunity. The earliest written mention of immunity can be traced back to the plague of Athens in 430 BCE. Thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without contracting the illness a second time. Many other ancient societies have references to this phenomenon, but it was not until the 19th and 20th centuries before the concept developed into scientific theory. The study of the molecular and cellular components that comprise the immune system, including their function and interaction, is the central science of immunology. The immune system has been divided into a more primitive innate immune system, and acquired or adaptive immune system of vertebrates, the latter of which is further divided into humoral and cellular components. The humoral (antibody) response is defined as the interaction between antibodies and antigens. Antibodies are specific proteins released from a certain class of immune cells (B lymphocytes). Antigens are defined as anything that elicits generation of antibodies, hence they are Antibody Generators. Immunology itself rests on an understanding of the properties of these two biological entities. However, equally important is the cellular response, which can not only kill infected cells in its own right, but is also crucial in controlling the antibody response. Put simply, both systems are highly interdependent. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Immunology 68 In the 21st century, immunology has broadened its horizons with much research being performed in the more specialized niches of immunology. This includes the immunological function of cells, organs and systems not normally associated with the immune system, as well as the function of the immune system outside classical models of immunity (Yemeserach 2010). Clinical immunology Clinical immunology is the study of diseases caused by disorders of the immune system (failure, aberrant action, and malignant growth of the cellular elements of the system). It also involves diseases of other systems, where immune reactions play a part in the pathology and clinical features. The diseases caused by disorders of the immune system fall into two broad categories: immunodeficiency, in which parts of the immune system fail to provide an adequate response (examples include chronic granulomatous disease), and autoimmunity, in which the immune system attacks its own hosts body (examples include systemic lupus erythematosus, rheumatoid arthritis, Hashimotos disease and myasthenia gravis). Other immune system disorders include different hypersensitivities, in which the system responds inappropriately to harmless compounds (asthma and other allergies) or responds too intensely. The most well-known disease that affects the immune system itself is AIDS, caused by HIV. AIDS is an immunodeficiency characterized by the lack of CD4+ ("helper") T cells and macrophages, which are destroyed by HIV. Clinical immunologists also study ways to prevent transplant rejection, in which the immune system attempts to destroy allografts os Developmental immunology The body’s capability to react to antigen depends on a persons age, antigen type, maternal factors and the area where the antigen is presented.[2] Neonates are said to be in a state of physiological immunodeficiency, because both their innate and adaptive immunological responses are greatly suppressed. Once born, a child’s immune system responds favorably to protein antigens while not as well to glycoproteins and polysaccharides. In fact, many of the infections acquired by neonates are caused by low virulence organisms like Staphylococcus and Pseudomonas. In neonates, opsonic activity and the ability to activate the complement cascade is very limited. For example, the mean level of C3 in a newborn is approximately 65% of that found in the adult. Phagocytic activity is also greatly impaired in newborns. This is due to lower opsonic activity, as well as diminished up-regulation of integrin and selectin receptors, which limit the ability of neutrophils to interact with adhesion molecules in the endothelium. Their monocytes are slow and have a reduced ATP production, which also limits the newborns phagocytic activity. Although, the number of total lymphocytes is significantly higher than in adults, the cellular and humoral immunity is also impaired. Antigen presenting cells in newborns have a reduced capability to activate T cells. Also, T cells of a newborn proliferate poorly and produce very small amounts of cytokines like IL-2, IL-4, IL-5, IL-12, and IFN-g which limits their capacity to activate the humoral response as well as the phagocitic activity of macrophage. B cells develop early in gestation but are not fully active.[3] Maternal factors also play a role in the body’s immune response. At birth most of the immunoglobulin is present is maternal IgG. Because IgM, IgD, IgE and IgA don’t cross the placenta, they are almost undetectable at birth. Although some IgA is provided in breast milk. These passively acquired antibodies can protect the newborn up to 18 months, but their response is usually short-lived and of low affinity.[3] Monocytes: An Artists Impression Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Immunology 69 These antibodies can also produce a negative response. If a child is exposed to the antibody for a particular antigen before being exposed to the antigen itself then the child will produce a dampened response. Passively acquired maternal antibodies can suppress the antibody response to active immunization. Similarly the response of T-cells to vaccination differs in children compared to adults, and vaccines that induce Th1 responses in adults do not readily elicit these same responses in neonates.[3] By 6-9 months after birth, a child’s immune system begins to respond more strongly to glycoproteins. Not until 12-24 months of age is there a marked improvement in the body’s response to polysaccharides. This can be the reason for the specific time frames found in vaccination schedules.[4] [5] During adolescence the human body undergoes several physical, physiological and immunological changes. These changes are started and mediated by different hormones. Depending on the sex either testosterone or 17-β-oestradiol, act on male and female bodies accordingly, start acting at ages of 12 and 10 years.[6] There is evidence that these steroids act directly not only on the primary and secondary sexual characteristics, but also have an effect on the development and regulation of the immune system.[7] There is an increased risk in developing autoimmunity for pubescent and post pubescent females and males.[8] There is also some evidence that cell surface receptors on B cells and macrophages may detect sex hormones in the system.[9] The female sex hormone 17-β-oestradiol has been shown to regulate the level of immunological response.[10] Similarly, some male androgens, like testosterone, seem to suppress the stress response to infection; but other androgens like DHEA have the opposite effect, as it increases the immune response instead of down playing it.[11] As in females, the male sex hormones seem to have more control of the immune system during puberty and the time right after than in fully developed adults. Other than hormonal changes physical changes like the involution of the Thymus during puberty will also affect the immunological response of the subject or patient.[12] Immunotherapy The use of immune system components to treat a disease or disorder is known as immunotherapy. Immunotherapy is most commonly used in the context of the treatment of cancers together with chemotherapy (drugs) and radiotherapy (radiation). However, immunotherapy is also often used in the immunosuppressed (such as HIV patients) and people suffering from other immune deficiencies or autoimmune diseases. Diagnostic immunology The specificity of the bond between antibody and antigen has made it an excellent tool in the detection of substances in a variety of diagnostic techniques. Antibodies specific for a desired antigen can be conjugated with a radiolabel, fluorescent label, or color-forming enzyme and are used as a "probe" to detect it. However, the similarity between some antigens can lead to false positives and other errors in such tests by antibodies cross-reacting with antigens that arent exact matches.[13] Evolutionary immunology Study of the immune system in extant species is capable of giving us a key understanding of the evolution of species and the immune system. A development of complexity of the immune system can be seen from simple phagocytotic protection of single celled organisms, to circulating antimicrobial peptides in insects to lymphoid organs in vertebrates. However, it is important to recognize that every organism living today has an immune system that has evolved to be absolutely capable of protecting it from most forms of harm; those organisms that did not adapt their immune systems to external threats are no longer around to be observed. Insects and other arthropods, while not possessing true adaptive immunity, show highly evolved systems of innate immunity, and are additionally protected from external injury (and exposure to pathogens) by their chitinous shells. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Immunology 70 Reproductive immunology This area of the immunology is devoted to the study of immunological aspects of the reproductive process including fetus acceptance. The term has also been used by fertility clinics to address fertility problems, recurrent miscarriages, premature deliveries, and dangerous complications such as pre-eclampsia. Immunologist Immunologist Occupation Type Profession, Specialty Activity sectors Science, Laboratory, Medicine Description Education required Doctor of Philosophy, Medical Doctor (M.D.), Doctor of Osteopathic Medicine (D.O.) Fields of employment Hospitals, Clinics, Academia Related jobs Physician, Research scientist Average salary [14] [15] USD $74,000 - $132,000 (Ph.D.) $50,000- >$200,000 (M.D. or D.O.) According to the American Academy of Allergy, Asthma, and Immunology (AAAAI), "an immunologist is a research scientist who investigates the immune system of vertebrates (including the human immune system). Immunologists include research scientists (Ph.D.) who work in laboratories. Immunologists also include physicians who, for example, treat patients with immune system disorders. Some immunologists are physician-scientists who combine laboratory research with patient care."[14] References [1] Janeways Immunobiology textbook (http:/ / www. ncbi. nlm. nih. gov/ books/ bv. fcgi?rid=imm. TOC& depth=2) Searchable free online version at the National Center for Biotechnology Information [2] Goldsby RA, Kindt TK, Osborne BA and Kuby J (2003) Immunology, 5th Edition, W.H. Freeman and Company, New York, New York, ISBN 0-7167-4947-5 [3] Jaspan Heather, S.D Lawn; et al. "The maturing immune system: implications for development and testing HIV-1 vaccines for children and adolescents" AIDS21 Mar. 2006, Vol 20 p.p 483-494. [4] Glezen WP. Maternal vaccines. Prim Care 2001(28):791. [5] Holt PG, Macaubas C, Cooper D, Nelson DJ, McWilliam AS. Th-1/Th-2 switch regulation in immune responses to inhaled antigens - role of dendritic cells in the aetiology of allergic respiratory disease. Dendritic Cells in Fundamental and Clinical Immunology 1997; (3) (417) 301–306. [6] Sizonenko PC, Paunier L. Hormonal changes in puberty III: Correlation of plasma dehydroepiandrosterone, testosterone, FSH, and LH with stages of puberty and bone age in normal boys and girls and in patients with Addisons disease or hypogonadism or with premature or late adrenarche. J Clin Endocrinol Metab 1975; 41:894–904. [7] Verthelyi D. Sex hormones as immunomodulators in health and disease. Int Immunopharmacol 2001; 1:983–993. [8] Stimson WH. Oestrogen and human T lymphocytes: presence of specific receptors in the T-suppressor/cytotoxic subset. Scand J Immunol 1998; 28:345–350. [9] Benten WPM, Stephan C, Wunderlich F. B cells express intracellular but not surface receptors for testosterone and estradiol. Steroids 2002; 67:647–654. [10] Beagley K, Gockel CM. Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone. FEMS Immunol Med Microbiol 2003; 38:13–22. [11] Kanda N, Tamaki K. Estrogen enhances immunoglobulin production by human PBMCs. J Allergy Clin Immunol 1999; 103:282–288. [12] McFarland RD, Douek DC, Koup RA, Picker LJ. Identification of a human recent thymic emigrant phenotype. Proc Natl Acad Sci USA 2000; 97:4215–4220. [13] Miller JJ and Valdes R, Jr. Approaches to minimizing interference by cross-reacting molecules in immunoassays. Clin Chem 1991 37: 144-153. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Immunology 71 [14] "Office of Science Education - LifeWorks - Immunologist" (http:/ / science. education. nih. gov/ LifeWorks. nsf/ Alphabetical+ List/ Immunologist). . Retrieved 2009-09-10. [15] "Immunologist | Bioscience Careers" (http:/ / www. aboutbioscience. org/ immunologist. html). . Retrieved 2009-09-10. External links • The Immunology Link, a rich resource for Immunology information (http://www.immunologylink.com/) • American Academy of Allergy, Asthma & Immunology (http://www.aaaai.org/) • British Society for Immunology (http://bsi.immunology.org/) • Annual Review of Immunology (journal) (http://arjournals.annualreviews.org/loi/immunol) • BMC: Immunology (http://www.biomedcentral.com/bmcimmunol/)- BioMed Central:Immunology is an open access journal publishing original peer-reviewed research articles. • journal home Nature Reviews Immunology (http://www.nature.com/nri/index.html) • The Immunology Database and Analysis Portal (http://www.immport.org) - an NIAID-funded database resource of reference and experiment data covering the entire immunology domain • Current discussions on Immunology in a scientific community (https://www.researchgate.net/group/ Immunology) Microbiology Microbiology (from Greek μῑκρος, mīkros, "small"; βίος, bios, "life"; and -λογία, -logia) is the study of microorganisms, which are microscopic, unicellular, and cell-cluster organisms.[1] This includes eukaryotes such as fungi and protists, and prokaryotes. Viruses[2] and prions, though not strictly classed as living organisms, are also studied. Microbiology typically includes the study of the immune system, or Immunology. Generally, immune systems interact with pathogenic microbes; these two disciplines often intersect which is why many colleges offer a paired degree such as "Microbiology and An agar plate streaked with microorganisms Immunology". Microbiology is a broad term which includes virology, mycology, parasitology, bacteriology and other branches. A microbiologist is a specialist in microbiology and these other topics. Microbiology is researched actively, and the field is advancing continually. It is estimated that only about one percent of all of the microbe species on Earth have been studied.[3] Although microbes were directly observed over three hundred years ago, the field of microbiology can be said to be in its infancy relative to older biological disciplines such as zoology and botany. History Ancient The existence of microorganisms was hypothesized for many centuries before their actual discovery. The existence of unseen microbiological life was postulated by Jainism which is based on Mahavira’s teachings as early as 6th century BCE.[4] Paul Dundas notes that Mahavira asserted existence of unseen microbiological creatures living in earth, water, air and fire.[5] Jain scriptures also describe nigodas which are sub-microscopic creatures living in large clusters and having a very short life and are said to pervade each and every part of the universe, even in tissues of plants and flesh of animals.[6] The Roman Marcus Terentius Varro made references to microbes when he warned Compiled and Edited by Marc Imhotep Cray , M.D.
  • Microbiology 72 against locating a homestead in the vicinity of swamps "because there are bred certain minute creatures which cannot be seen by the eyes, which float in the air and enter the body through the mouth and nose and there cause serious diseases."[7] In 1546 Girolamo Fracastoro proposed that epidemic diseases were caused by transferable seedlike entities that could transmit infection by direct or indirect contact, or even without contact over long distances. However, early claims about the existence of microorganisms were speculative, and not based on microscopic observation. Actual observation and discovery of microbes had to await the invention of the microscope in the 17th century. Modern In 1676, Antonie van Leeuwenhoek observed bacteria and other microorganisms, using a single-lens microscope of his own design.[1] While Van Leeuwenhoek is often cited as the first to observe microbes, Robert Hooke made the first recorded microscopic observation, of the fruiting bodies of molds, in 1665.[8] The first observation of microbes using a microscope is generally credited to the Dutch draper and haberdasher, Antonie van Leeuwenhoek, who lived for most of his life in Delft, Holland. It has, however, been suggested that a Jesuit priest called Athanasius Kircher was the first to observe micro-organisms.[9] He was among the first to design magic lanterns for projection purposes, so he must have been well acquainted with the properties of lenses.[9] One of his book contains a chapter in Latin, which reads in translation – ‘Concerning the wonderful structure of things in nature, investigated by Microscope. Here, he wrote ‘who would believe that Antonie van Leeuwenhoek, was considered to be the first to observe microorganisms using a vinegar and milk abound with an innumerable multitude of worms.’ He microscope. also noted that putrid material is full of innumerable creeping animalcule. These observations antedate Robert Hooke’s Micrographia by nearly 20 years and were published some 29 years before van Leeuwenhoek saw protozoa and 37 years before he described having seen bacteria.[9] The field of bacteriology (later a subdiscipline of microbiology) was founded in the 19th century by Ferdinand Cohn, a botanist whose studies on algae and photosynthetic bacteria led him to describe several bacteria including Bacillus and Beggiatoa. Cohn was also the first to formulate a scheme for the taxonomic classification of bacteria and discover spores.[10] Louis Pasteur and Robert Koch were contemporaries of Cohn’s and are often considered to be the father of microbiology[9] and medical microbiology, respectively.[11] Pasteur is most famous for his series of experiments designed to disprove the then widely held theory of spontaneous generation, thereby solidifying microbiology’s identity as a biological science.[12] Pasteur also designed methods for food preservation (pasteurization) and vaccines against several diseases such as anthrax, fowl cholera and rabies.[1] Koch is best known for his contributions to the germ theory of disease, proving that specific diseases were caused by specific pathogenic micro-organisms. He developed a series of criteria that have become known as the Kochs postulates. Koch was one of the first scientists to focus on the isolation of bacteria in pure culture resulting in his description of several novel bacteria including Mycobacterium tuberculosis, the causative agent of tuberculosis.[1] While Pasteur and Koch are often considered the founders of microbiology, their work did not accurately reflect the true diversity of the microbial world because of their exclusive focus on micro-organisms having direct medical relevance. It was not until the late 19th century and the work of Martinus Beijerinck and Sergei Winogradsky, the founders of general microbiology (an older term encompassing aspects of microbial physiology, diversity and ecology), that the true breadth of microbiology was revealed.[1] Beijerinck made two major contributions to Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Microbiology 73 microbiology: the discovery of viruses and the development of enrichment culture techniques.[13] While his work on the Tobacco Mosaic Virus established the basic principles of virology, it was his development of enrichment culturing that had the most immediate impact on microbiology by allowing for the cultivation of a wide range of microbes with wildly different physiologies. Winogradsky was the first to develop the concept of chemolithotrophy and to thereby reveal the essential role played by micro-organisms in geochemical processes.[14] He was responsible for the first isolation and description of both nitrifying and nitrogen-fixing bacteria.[1] Branches The branches of microbiology can be classified into pure and applied sciences.[15] Microbiology can be also classified based on taxonomy, in the cases of bacteriology, mycology, protozoology, and phycology. There is considerable overlap between the specific branches of microbiology with each other and with other disciplines. Branches of Pure Microbiology Taxonomic arrangement • Bacteriology: The study of bacteria. • Mycology: The study of fungi. • Protozoology: The study of protozoa. • Phycology (or algology): The study of algae. • Parasitology: The study of parasites. • Immunology: The study of the immune system. Integrative arrangement • Microbial cytology: The study of microscopic and submicroscopic details of microorganisms. • Microbial physiology: The study of how the microbial cell functions biochemically. Includes the study of microbial growth, microbial metabolism and microbial cell structure. • Microbial ecology: The relationship between microorganisms and their environment. • Microbial genetics: The study of how genes are organized and regulated in microbes in relation to their cellular functions. Closely related to the field of molecular biology. • Cellular microbiology: A discipline bridging microbiology and cell biology. • Evolutionary microbiology: The study of the evolution of microbes. This field can be subdivided into: • Microbial taxonomy: The naming and classification of microorganisms. • Microbial systematics: The study of the diversity and genetic relationship of microorganisms. • Generation microbiology: The study of those microorganisms that have the same characters as their parents. Other • Nano microbiology: The study of those microorganisms at nano level. • Exo microbiology (or Astro microbiology): The study of microorganisms in outer space. Branches of Applied Microbiology • Medical microbiology: The study of the pathogenic microbes and the role of microbes in human illness. Includes the study of microbial pathogenesis and epidemiology and is related to the study of disease pathology and immunology. • Pharmaceutical microbiology: The study of microorganisms that are related to the production of antibiotics, enzymes, vitamins,vaccines, and other pharmaceutical products and that cause pharmaceutical contamination and spoil. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Microbiology 74 • Industrial microbiology: The exploitation of microbes for use in industrial processes. Examples include industrial fermentation and wastewater treatment. Closely linked to the biotechnology industry. This field also includes brewing, an important application of microbiology. • Microbial biotechnology: The manipulation of microorganisms at the genetic and molecular level to generate useful products. • Food microbiology and Dairy microbiology: The study of microorganisms causing food spoilage and foodborne illness. Using microorganisms to produce foods, for example by fermentation. • Agricultural microbiology: The study of agriculturally relevant microorganisms. This field can be further classified into the following: • Plant microbiology and Plant pathology: The study of the interactions between microorganisms and plants and plant pathogens. • Soil microbiology: The study of those microorganisms that are found in soil. • Veterinary microbiology: The study of the role in microbes in veterinary medicine or animal taxonomy. • Environmental microbiology: The study of the function and diversity of microbes in their natural environments. This involves the characterization of key bacterial habitats such as the rhizosphere and phyllosphere, soil and groundwater ecosystems, open oceans or extreme environments (extremophiles). This field includes other branches of microbiology such as: • Microbial ecology • Microbially-mediated nutrient cycling • Geomicrobiology • Microbial diversity • Bioremediation • Water microbiology (or Aquatic microbiology): The study of those microorganisms that are found in water. • Aeromicrobiology (or Air microbiology): The study of airborne microorganisms. • Epidemiology: The study of the incidence, spread, and control of disease. Benefits Whilst there are undoubtedly some who fear all microbes due to the association of some microbes with various human illnesses, many microbes are also responsible for numerous beneficial processes such as industrial fermentation (e.g. the production of alcohol, vinegar and dairy products), antibiotic production and as vehicles for cloning in more complex organisms such as plants. Scientists have also exploited their knowledge of microbes to produce biotechnologically important enzymes such as Taq polymerase, reporter genes for use in other genetic systems and novel molecular biology techniques such as the Fermenting tanks with yeast being used to brew beer yeast two-hybrid system. Bacteria can be used for the industrial production of amino acids. Corynebacterium glutamicum is one of the most important bacterial species with an annual production of more than two million tons of amino acids, mainly L-glutamate and L-lysine.[16] A variety of biopolymers, such as polysaccharides, polyesters, and polyamides, are produced by microorganisms. Microorganisms are used for the biotechnological production of biopolymers with tailored properties suitable for high-value medical application such as tissue engineering and drug delivery. Microorganisms are used for the biosynthesis of xanthan, alginate, cellulose, cyanophycin, poly(gamma-glutamic acid), levan, hyaluronic acid, organic acids, oligosaccharides and polysaccharide, and polyhydroxyalkanoates.[17] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Microbiology 75 Microorganisms are beneficial for microbial biodegradation or bioremediation of domestic, agricultural and industrial wastes and subsurface pollution in soils, sediments and marine environments. The ability of each microorganism to degrade toxic waste depends on the nature of each contaminant. Since sites typically have multiple pollutant types, the most effective approach to microbial biodegradation is to use a mixture of bacterial species and strains, each specific to the biodegradation of one or more types of contaminants.[18] There are also various claims concerning the contributions to human and animal health by consuming probiotics (bacteria potentially beneficial to the digestive system) and/or prebiotics (substances consumed to promote the growth of probiotic microorganisms).[19] Recent research has suggested that microorganisms could be useful in the treatment of cancer. Various strains of non-pathogenic clostridia can infiltrate and replicate within solid tumors. Clostridial vectors can be safely administered and their potential to deliver therapeutic proteins has been demonstrated in a variety of preclinical models.[20] References [1] Madigan M, Martinko J (editors) (2006). Brock Biology of Microorganisms (11th ed.). Prentice Hall. ISBN 0-13-144329-1. [2] Rice G (2007-03-27). "Are Viruses Alive?" (http:/ / serc. carleton. edu/ microbelife/ yellowstone/ viruslive. html). . Retrieved 2007-07-23. [3] Amann RI, Ludwig W, Schleifer KH (1995). "Phylogenetic identification and in situ detection of individual microbial cells without cultivation". Microbiol. Rev. 59 (1): 143–169. PMC 239358. PMID 7535888. [4] Mahavira is dated 599 BCE - 527 BC. See. Dundas, Paul; John Hinnels ed. (2002). The Jain. London: Routledge. ISBN 0-415-26606-8. p. 24 [5] Dundas, Paul (2002) p. 88 [6] *Jaini, Padmanabh (1998). The Jaina Path of Purification. New Delhi: Motilal Banarsidass. ISBN 81-208-1578-5. p. 109 [7] Varro on Agriculture 1, xii Loeb. [8] Gest H (2005). "The remarkable vision of Robert Hooke (1635-1703): first observer of the microbial world". Perspect. Biol. Med. 48 (2): 266–72. doi:10.1353/pbm.2005.0053. PMID 15834198. [9] Wainwright, Milton (2003). An Alternative View of the Early History of Microbiology. 52. pp. 333–55. doi:10.1016/S0065-2164(03)01013-X. PMID 12964250. [10] Drews G (1999). "Ferdinand Cohn, among the Founder of Microbiology". ASM News 65 (8): 547. [11] Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 0-8385-8529-9. [12] Bordenave G (2003). "Louis Pasteur (1822-1895)". Microbes Infect. 5 (6): 553–60. doi:10.1016/S1286-4579(03)00075-3. PMID 12758285. [13] Johnson J (2001). "Martinus Willem Beijerinck" (http:/ / www. apsnet. org/ Education/ feature/ TMV/ intro. html). APSnet. American Phytopathological Society. . Retrieved May 2, 2010. [14] Paustian T, Roberts G (2009). "Beijerinck and Winogradsky Initiate the Field of Environmental Microbiology" (http:/ / www. microbiologytext. com/ index. php?module=Book& func=displayarticle& art_id=32). Through the Microscope: A Look at All Things Small (3rd ed.). Textbook Consortia. § 1–14. . Retrieved May 2, 2010. [15] Pharmaceutical Microbiology Principles and Applications (http:/ / books. google. com/ books?id=VN9Oj2MKTkQC& pg=SA1-PA1). Nirali Prakashan. pp. 1.1–1.2. ISBN 9788185790619. . Retrieved 18 June 2011. [16] Burkovski A (editor). (2008). Corynebacteria: Genomics and Molecular Biology (http:/ / www. horizonpress. com/ cory). Caister Academic Press. ISBN 1904455301. . . [17] Rehm BHA (editor). (2008). Microbial Production of Biopolymers and Polymer Precursors: Applications and Perspectives (http:/ / www. horizonpress. com/ biopolymers). Caister Academic Press. . . [18] Diaz E (editor). (2008). Microbial Biodegradation: Genomics and Molecular Biology (http:/ / www. horizonpress. com/ biod) (1st ed.). Caister Academic Press. ISBN 1904455174. . . [19] Tannock GW (editor). (2005). Probiotics and Prebiotics: Scientific Aspects (http:/ / www. horizonpress. com/ pro3). Caister Academic Press. . . [20] Mengesha et al. (2009). "Clostridia in Anti-tumor Therapy". Clostridia: Molecular Biology in the Post-genomic Era. Caister Academic Press. ISBN 978-1-904455-38-7. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Microbiology 76 External links • Microbiology (http://www.bbc.co.uk/programmes/b007753d) on In Our Time at the BBC. ( listen now (http:/ /www.bbc.co.uk/iplayer/console/b007753d/In_Our_Time_Microbiology)) Bacteriology Made Easy | Medchrome (http://medchrome.com/basic-science/microbiology/bacteriology-easy/) • Online lectures in microbiology (http://media.med.sc.edu/microbiology2007/) University of South Carolina • Microbiology Online (http://www.ocean.edu/academics/programs_of_study/science/MicrobiologyOnline. htm) • Online Microbiology textbook (http://www.microbiologytext.com/index.php?module=Book&func=toc& book_id=4) • Online Medical Microbiology textbook (http://www.microbiologybook.org/) • Institute of Microbiology of the Swiss Federal Institute of Technology (http://www.micro.biol.ethz.ch/) • Annual Review of Microbiology (http://arjournals.annualreviews.org/loi/micro/) Physiology Physiology English pronunciation: /ˌfɪziˈɒlədʒi/ is the science of the function of living systems. This includes how organisms, organ systems, organs, cells and biomolecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or Medicine, awarded since 1901 by the Royal Swedish Academy of Sciences. Many U.S. universities offer physiology as a major.[1] Etymology From Ancient Greek: φύσις- physis meaning "nature" or "origin" and -λογία -logia meaning the "study of". Human physiology Human physiology is the science of the mechanical, physical and biochemical functions of humans in good health, their organs, and the cells of which they are composed. The principal level of focus of physiology is at the level of organs and systems within systems. Much of the foundation of knowledge in human physiology was provided by animal experimentation. Physiology is closely related to anatomy; anatomy is the study of form, and physiology is the study of function. Due to the frequent connection between form and function physiology and anatomy are intrinsically linked and are studied in tandem as part of a medical curriculum. History The study of human physiology dates back to at least 420 B.C. and the time of Hippocrates, the father of medicine.[2] Physiology was first recognized in the early 1960s. The critical thinking of Aristotle and his emphasis on the relationship between structure and function marked the beginning of physiology in Ancient Greece, while Claudius Galenus (c. 126-199 A.D.), known as Galen, was the first to use experiments to probe the function of the body. Galen was the founder of experimental physiology.[3] The medical world moved on from Galenism only with the appearance of Andreas Vesalius and William Harvey.[4] During the Middle Ages, the ancient Greek and Indian medical traditions were further developed by Muslim physicians. Notable work in this period was done by Avicenna (980-1037), author of the The Canon of Medicine, and Ibn al-Nafis (1213–1288), among others. Following from the Middle Ages, the Renaissance brought an increase of physiological research in the Western world that triggered the modern study of anatomy and physiology. Andreas Vesalius was an author of one of the Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Physiology 77 most influential books on human anatomy, De humani corporis fabrica.[5] Vesalius is often referred to as the founder of modern human anatomy.[6] Anatomist William Harvey described the circulatory system in the 17th century,[7] demonstrating the fruitful combination of close observations and careful experiments to learn about the functions of the body, which was fundamental to the development of experimental physiology. Herman Boerhaave is sometimes referred to as a father of physiology due to his exemplary teaching in Leiden and textbook Institutiones medicae (1708). In the 18th century, important works in this field were by Pierre Cabanis, a French doctor and physiologist. In the 19th century, physiological knowledge began to accumulate at a rapid rate, particularly with the 1838 appearance of the Cell theory of Matthias Schleiden and Theodor Schwann. It radically stated that organisms are made up of units called cells. Claude Bernards (1813–1878) further discoveries ultimately led to his concept of milieu interieur (internal environment), which would later be taken up and championed as "homeostasis" by American physiologist Walter Cannon (1871–1945). In the 20th century, biologists also became interested in how organisms other than human beings function, eventually spawning the fields of comparative physiology and ecophysiology.[8] Major figures in these fields include Knut Schmidt-Nielsen and George Bartholomew. Most recently, evolutionary physiology has become a distinct subdiscipline.[9] The biological basis of the study of physiology, integration refers to the overlap of many functions of the systems of the human body, as well as its accompanied form. It is achieved through communication which occurs in a variety of ways, both electrical and chemical. In terms of the human body, the endocrine and nervous systems play major roles in the reception and transmission of signals which integrate function. Homeostasis is a major aspect with regards to the interactions within an organism, humans included. References [1] "The American Physiological Society - Departments and Programs (US)" (http:/ / www. the-aps. org/ sites/ us. htm). . Retrieved 2010-06-21. ( Non-US (http:/ / www. the-aps. org/ sites/ non-us. htm)) [2] "Physiology - History of physiology, Branches of physiology" (http:/ / www. scienceclarified. com/ Ph-Py/ Physiology. html). Scienceclarified.com. . Retrieved 2010-08-29. [3] Fell, C.; Griffith Pearson, F. (November 2007). "Thoracic Surgery Clinics: Historical Perspectives of Thoracic Anatomy" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/ S1547412706001034). Thorac Surg Clin 17 (4): 443–8, v.. . [4] "Galen" (http:/ / www. discoveriesinmedicine. com/ General-Information-and-Biographies/ Galen. html). Discoveriesinmedicine.com. . Retrieved 2010-08-29. [5] "Page through a virtual copy of Vesaliuss De Humanis Corporis Fabrica" (http:/ / archive. nlm. nih. gov/ proj/ ttp/ books. htm). Archive.nlm.nih.gov. . Retrieved 2010-08-29. [6] "Andreas Vesalius (1514-1567)" (http:/ / www. ingentaconnect. com/ content/ apl/ uivs/ 1999/ 00000012/ 00000003/ art00002?crawler=true). Ingentaconnect.com. 1999-05-01. . Retrieved 2010-08-29. [7] Zimmer, Carl (2004). "Soul Made Flesh: The Discovery of the Brain - and How It Changed the World". J Clin Invest 114 (5): 604–604. doi:10.1172/JCI22882. [8] Feder, Martin E. (1987). New directions in ecological physiology. New York: Cambridge Univ. Press. ISBN 9780521349383. [9] Garland, Jr, Theodore; Carter, P. A. (1994). "Evolutionary physiology" (http:/ / www. biology. ucr. edu/ people/ faculty/ Garland/ GarlCa94. pdf). Annual Review of Physiology (56): 579–621. . Compiled and Edited by Marc Imhotep Cray , M.D.
  • Physiology 78 External links • Developmental physiology (http://www.biol.unt.edu/developmentalphysiology/) • physiologyINFO.org (http://www.physiologyinfo.org/), a public information website sponsored by The American Physiological Society • Physiwiki (http://www.physiwiki.wetpaint.com) Pathophysiology Pathophysiology sample values BMP/ELECTROLYTES: BUN=20 / Na+=140 Cl−=100 Glu=150 CO2=22 PCr=1.0 K+=4 ARTERIAL BLOOD GAS: paCO2=40 paO2=95 pH=7.40 HCO3-=24 ALVEOLAR GAS: pACO2=36 pAO2=105 A-a g=10 OTHER: Ca=9.5 PO4=1 Mg2+=2.0 CK=55 BE=−0.36 AG=16 SERUM OSMOLARITY/RENAL: PMO = 300 PCO=295 POG=5 BUN:Cr=20 URINALYSIS: UAG=5 FENa=0.95 UNa+=80 UCl−=100 USG=1.01 UCr=60 UO=800 UK+=25 PROTEIN/GI/LIVER FUNCTION TESTS: LDH=100 TP=7.6 AST=25 TBIL=0.7 ALP=71 Alb=4.0 ALT=40 BC=0.5 AST/ALT=0.6 BU=0.2 AF alb=3.0 SAAG=1.0 SOG=60 CSF: CSF alb=30 CSF glu=60 CSF/S alb=7.5 CSF/S glu=0.4 Pathophysiology is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome.[1] More formally, it is the branch of medicine which deals with any disturbances of body functions, caused by disease or prodromal symptoms. An alternative definition is "the study of the biological and physical manifestations of disease as they correlate with the underlying abnormalities and physiological disturbances."[2] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Pathophysiology 79 The study of pathology and the study of pathophysiology often involves substantial overlap in diseases and processes, but pathology emphasizes direct observations, while pathophysiology emphasizes quantifiable measurements. Examples An example from the field of infectious disease would be the study of a toxin released by a bacterium, and what that toxin does to the body to cause harm, one possible result being sepsis. Another example is the study of the chemical changes that take place in body tissue due to inflammation. the intersection of two older, related disciplines: (normal) physiology and pathology. • Physiology is the study of normal, healthy bodily function (as opposed to anatomy, which is the study of normal structure). When something disrupts normal physiological processes, it enters the realm of pathophysiology. • Pathology, broadly speaking, is the "study of the nature and cause of disease."[3] or the results of disease in the body. Pathophysiology looks at the specific malfunctioning that comes from or - alternately - causes disease. One caution in this approach is that "healthy" structure and function is not precisely the same in any two individuals... Uses Pathophysiology is a required area of study for nearly all healthcare professional school programs (medical, dental, physician assistant, occupational therapy, physical therapy, nurse practitioner, pharmacy, nursing, and paramedic programs) in the United States and other countries. References [1] "Pathophysiology - Definition from the Merriam-Webster Online Dictionary" (http:/ / www. merriam-webster. com/ dictionary/ Pathophysiology). . Retrieved 2009-04-09. [2] Craig Scanlon and Evan Fawkes, Egans Fundamentals of Respiratory Therapy, St. Louis, 1999, p. 1186. [3] Tabers Cyclopedic Medical Dictionary, Clayton Thomas, Philadelphia, 1993, p. 1445. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Pathology 80 Pathology Pathology is the study and diagnosis of disease. The word pathology is from Ancient Greek πάθος, pathos, "feeling, suffering"; and -λογία, -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling. Pathologies is synonymous with diseases. The suffix "path" is used to indicate a disease, e.g. psychopath. Pathology addresses 4 components of disease: cause/etiology, mechanisms of development (pathogenesis), structural alterations of cells (morphologic changes), and the consequences of changes A renal cell carcinoma (chromophobe type) viewed on (clinical manifestations).[1] a hematoxylin & eosin stained slide Pathology is further separated into divisions, based on either the system being studied (e.g. veterinary pathology and animal disease) or the focus of the examination (e.g. forensic pathology and determining the cause of death). General pathology General pathology, also called investigative pathology, experimental pathology, or theoretical pathology, is a broad and complex scientific field which seeks to understand the mechanisms of injury to cells and tissues, as well as the bodys means of responding to and repairing injury. Areas of study include cellular adaptation to injury, necrosis, inflammation, wound healing, and neoplasia. It forms the foundation of pathology, the application of this knowledge to diagnose diseases in humans and animals. The term general pathology is also used to describe the practice of both anatomical and clinical pathology. Anatomical pathology Anatomical pathology (Commonwealth) or anatomic pathology (United States) is a medical specialty that is concerned with the diagnosis of disease based on the gross, microscopic, chemical, immunologic and molecular examination of organs, tissues, and whole bodies (autopsy). Anatomical pathology is itself divided in subspecialties, the main ones being surgical pathology, cytopathology, and forensic pathology. To be licensed to practice pathology, one has to complete medical school and secure a license to practice medicine. An approved residency program and certification (in the United Pathologist instructor and students of anatomical States, the American Board of Pathology or the American pathology. Osteopathic Board of Pathology) is usually required to obtain employment or hospital privileges. Anatomical pathology is one of two branches of pathology, the other being clinical pathology, the diagnosis of disease through the laboratory analysis of bodily fluids and tissues. Often, pathologists practice both anatomical and clinical pathology, a combination known as general pathology. The distinction between anatomic and clinical pathology is increasingly blurred by the introduction of technologies that require new expertise and the need to provide patients and referring physicians with integrated diagnostic reports. Similar specialties exist in veterinary Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Pathology 81 pathology. Clinical pathology Clinical pathology is a medical specialty that is concerned with the diagnosis of disease based on the laboratory analysis of bodily fluids such as blood and urine, and tissues using the tools of chemistry, microbiology, hematology and molecular pathology. Clinical pathologists work in close collaboration with medical technologists, hospital administrations, and referring physicians to ensure the accuracy and optimal utilization of laboratory testing. Clinical pathology is one of the two major divisions of pathology, the other being anatomical pathology. Often, pathologists practice both anatomical and clinical pathology, a combination sometimes known as general pathology. Clinical chemistry: an automated blood chemistry analyser. Dermatopathology Dermatopathology is a subspecialty of anatomic pathology that focuses on the skin as an organ. It is unique in that there are two routes which a physician can use to obtain this specialization. All general pathologists and general dermatologists are trained in the pathology of the skin; however, the dermatopathologist is a specialist in this organ. In the USA, either a general pathologist or a dermatologist can undergo a 1 to 2 year fellowship in the field of dermatopathology. The completion of this fellowship allows one to take a subspecialty board examination, and becomes a board certified dermatopathologist. Hematopathology Hematopathology is the study of diseases of blood cells (White blood cells, red blood cells, platelets) and cells/tissues/organs comprising the hematopoietic system. The term hematopoietic system refers to tissues and organs that produce and/or primarily host hematopoietic cells and include bone marrow, lymph node, thymus, spleen, and other lymphoid tissues. In the United States, hematopathology is a board certified subspecialty (American Board of Pathology) practiced by those physicians who have completed general pathology residency (anatomic, clinical, or combined) and an additional year of fellowship training in hematology. The hematopathologist reviews biopsies of lymph nodes, bone marrows and other tissues involved by an infiltrate of cells of the hematopoietic system. In addition, the hematopathologist may be in charge of flow cytometric and/or molecular hematopathology studies. After the hematopathologist Hematopathology: A Wrights stained bone marrow makes the diagnosis, the hematologist or hemato-oncologist can aspirate smear of patient with precursor B-cell acute make a decision about the best course of action. lymphoblastic leukemia. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Pathology 82 Oral and Maxillofacial Pathology Oral and Maxillofacial Pathology is one of nine dental specialties recognized by the American Dental Association. Oral Pathologists must complete three years of post doctoral training in an accredited program and subsequently obtain Diplomate status from the American Board of Oral and Maxillofacial Pathology. The specialty focuses on the diagnosis, clinical management and investigation of diseases that affect the oral cavity and surrounding maxillofacial structures including but not limited to odontogenic, infectious, epithelial, salivary gland, bone and soft tissue pathologies. Forensic pathology Forensic pathology is a branch of pathology concerned with determining the cause of death by examination of a cadaver. The autopsy is performed by the pathologist at the request of a coroner usually during the investigation of criminal law cases and civil law cases in some jurisdictions. Forensic pathologists are also frequently asked to confirm the identity of a cadaver. The word forensics is derived from the Latin forēnsis meaning forum. Veterinary pathology Birth defect Veterinary pathologists are doctors of veterinary medicine who specialize in the diagnosis of diseases through the examination of animal tissue and body fluids. As with medical pathology, veterinary pathology is divided in two branches, anatomical pathology and clinical pathology. Veterinary pathologists are critical participants in the drug development process. Psychopathology In psychology and psychiatry, psychopathology is the study of mental illness, mental distress and abnormal, maladaptive behavior. The term is most commonly used within psychiatry where pathology refers to disease processes. Abnormal psychology is a similar term used more frequently in the non-medical field of psychology. Plant pathology Plant pathology (also phytopathology) is the scientific study of plant diseases caused by pathogens (infectious diseases) and environmental conditions (physiological factors). Organisms that cause infectious disease include fungi, oomycetes, bacteria, viruses, viroids, virus-like organisms, phytoplasmas, protozoa, nematodes and parasitic plants. Not included are insects, mites, vertebrate or other pests that affect plant health by consumption of plant tissues. Plant pathology also involves the study of pathogen identification, disease etiology, disease cycles, economic impact, plant disease epidemiology, plant disease Powdery mildew, a biotrophic fungus resistance, how plant diseases affect humans and animals, pathosystem genetics, and management of plant diseases. The "disease triangle" is a central concept of plant pathology.[2] It is based on the principle that infectious diseases develop, or do not develop, based on three-way interactions between the host, the pathogen, and environmental Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Pathology 83 conditions. Molecular pathology Further information: Molecular pathology Molecular pathology is an emerging discipline within pathology, and focuses in the study and diagnosis of disease through the examination of molecules within organs, tissues or bodily fluids. Molecular pathology shares some aspects of practice with both anatomic pathology and clinical pathology, molecular biology, biochemistry, proteomics and genetics, and is sometimes considered a "crossover" discipline. It is multi-disciplinary in nature and focuses mainly on the sub-microscopic aspects of disease and unknown illnesses with strange causes. It is a scientific discipline that encompasses the development of molecular and genetic approaches to the diagnosis and classification of human tumors, the design and validation of predictive biomarkers for treatment response and disease progression, the susceptibility of individuals of different genetic constitution to develop cancer, and the environmental and lifestyle factors implicated in carcinogenesis.[3] Pathology as a medical specialty Pathologist Occupation Names Doctor, Medical Specialist Type Specialty Activity sectors Medicine Description Education required Degree in Medicine Fields of employment Hospitals, Clinics Average salary USD $242,000 Pathologists are doctors who diagnose and characterize disease in living patients by examining biopsies or bodily fluids. In addition, pathologists interpret medical laboratory tests to help prevent illness or monitor a chronic condition. The vast majority of cancer diagnoses are made by pathologists. Pathologists examine tissue biopsies to determine if they are benign or cancerous. Some pathologists specialize in genetic testing that can, for example, determine the most appropriate treatment for particular types of cancer. In addition, a pathologist analyzes blood samples from a patients annual physical and alerts their primary care physician to any changes in their health early, when successful treatment is most likely. Pathologists also review results of tests ordered or performed by specialists, such as blood tests ordered by a cardiologist, a biopsy of a skin lesion removed by a dermatologist, or a Pap test performed by a gynecologist, to detect abnormalities. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Pathology 84 Pathologists work with other doctors, medical specialty societies, medical laboratory professionals, and health care consumer organizations to set guidelines and standards for medical laboratory testing that help improve a patients medical care and guide treatment, as well as ensure the quality and safety of domestic and international medical laboratories. Pathologists may also conduct autopsies to investigate causes of death. Autopsy results can aid living patients by revealing a This mastectomy specimen contains an infiltrating hereditary disease unknown to a patients family. ductal carcinoma of the breast. A pathologist will use immunohistochemistry and fluorescent in-situ Pathology is a core discipline of medical school and many hybridization to detect markers which determine the pathologists are also teachers. As managers of medical laboratories optimal chemotherapy regimen for this patient. (which include chemistry, microbiology, cytology, the blood bank, etc.), pathologists play an important role in the development of laboratory information systems. Although the medical practice of pathology grew out of the tradition of investigative pathology, most modern pathologists do not perform original research. Pathology is a unique medical specialty. Pathology touches all of medicine, as diagnosis is the foundation of all patient care. In fact, more than 70 percent of all decisions about diagnosis and treatment, hospital admission, and discharge rest on medical test results. Pathologists play a critical role on the patient care team, working with other doctors to treat patients and guide care. To be licensed, candidates must complete medical training, an approved residency program, and be certified by an appropriate body. In the US, certification is by the American Board of Pathology or the American Osteopathic Board of Pathology. The organization of subspecialties within pathology varies between nations, but usually includes anatomic pathology and clinical pathology. References [1] Robbins, Stanley (2010). Robbins and Cotran pathologic basis of disease. (8th ed. / ed.). Philadelphia PA: Saunders/Elsevier. ISBN 9781416031215. [2] George N. Agrios (1997) Plant Pathology fourth edition, Academic Press. New York. [3] http:/ / www. molecularpathology. org. uk/ External links • College of American Pathologists (http://www.cap.org/) • Pathology Resident Wiki (http://pathinfo.wikia.com/wiki/Pathology_Resident_Wiki): Complete directory of pathology residency and fellowship training programs. • Flickr group: Pathology and Lab Medicine (http://www.flickr.com/groups/labmed/): numerous photos illustrating the work of pathologists. • humpath.com (http://www.humpath.com/) (Atlas in Human Pathology) • Pathological Society of Great Britain and Ireland (http://www.pathsoc.org.uk/) • Royal College of Pathologists (UK) (http://www.rcpath.org/) • Royal College of Pathologists of Australasia (Australia & Oceania) (http://www.rcpa.edu.au) • United States and Canadian Academy of Pathology (http://www.uscap.org/) • WebPath: The Internet Pathology Laboratory for Medical Education (http://library.med.utah.edu/WebPath/ webpath.html) • Atlases: High Resolution Pathology Images (http://atlases.muni.cz) • pathologybook.info (http://www.pathologybook.info/) the most comprehensive book information of pathology-related Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Pathogenesis 85 Pathogenesis The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent. The word comes from the Greek pathos, "disease", and genesis, "creation". Types of pathogenesis include microbial infection, inflammation, malignancy and tissue breakdown. Most diseases are caused by multiple pathogenetical processes together. For example, certain cancers arise from dysfunction of the immune system (skin tumors and lymphoma after a renal transplant, which requires immunosuppression).[1] Often, a potential etiology is identified by epidemiological observations before a pathological link can be drawn between the cause and the disease. References [1] Fox, Alvin (2010). General aspects of bacterial pathogenesis (http:/ / pathmicro. med. sc. edu/ fox/ bact-path. htm). University of South Carolina School of Medicine: Microbiology and Immunology On-line Textbook. . Further reading • Haugan, Salomon Avian Influenza: Etiology, Pathogenesis and Interventions (Public Health in the 21st Century. Nova Science Pub Inc. January 30, 2010) ISBN 1607418460, ISBN 978-1607418467 Neuroscience Neuroscience is the scientific study of the nervous system.[1] Traditionally, neuroscience has been seen as a branch of biology. However, it is currently an interdisciplinary science that collaborates with other fields such as chemistry, computer science, engineering, linguistics, mathematics, medicine and allied disciplines, philosophy, physics, and psychology. The term neurobiology is usually used interchangeably with the term neuroscience, although the former refers specifically to the biology of the nervous system, whereas the latter refers to the entire science of the nervous system. The scope of neuroscience has broadened to include different approaches used to study the molecular, cellular, developmental, structural, functional, evolutionary, computational, and medical aspects of the nervous system. The techniques used by neuroscientists have also expanded enormously, from molecular and Drawing by Santiago Ramón y Cajal (1899) of neurons in the pigeon cellular studies of individual nerve cells to imaging of cerebellum sensory and motor tasks in the brain. Recent theoretical advances in neuroscience have also been aided by the study of neural networks. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Neuroscience 86 Given the increasing number of scientists who study the nervous system, several prominent neuroscience organizations have been formed to provide a forum to all neuroscientists and educators. For example, the International Brain Research Organization was founded in 1960,[2] the International Society for Neurochemistry in 1963,[3] the European Brain and Behaviour Society in 1968,[4] and the Society for Neuroscience in 1969.[5] History The study of the nervous system dates back to ancient Egypt. Evidence of trepanation, the surgical practice of either drilling or scraping a hole into the skull with the purpose of curing headaches or mental disorders or relieving cranial pressure, being performed on patients dates back to Neolithic times and has been found in various cultures throughout the world. Manuscripts dating back to 1700 BC indicated that the Egyptians had some knowledge about symptoms of brain damage.[6] Early views on the function of the brain regarded it to be a "cranial stuffing" of sorts. In Egypt, from the late Illustration from Grays Anatomy (1918) of a lateral view of the Middle Kingdom onwards, the brain was regularly human brain, featuring the hippocampus among other removed in preparation for mummification. It was neuroanatomical features believed at the time that the heart was the seat of intelligence. According to Herodotus, the first step of mummification is to "take a crooked piece of iron, and with it draw out the brain through the nostrils, thus getting rid of a portion, while the skull is cleared of the rest by rinsing with drugs."[7] The view that the heart was the source of consciousness was not challenged until the time of Hippocrates. He believed that the brain was not only involved with sensation—since most specialized organs (e.g., eyes, ears, tongue) are located in the head near the brain—but was also the seat of intelligence. Plato also speculated that the brain was the seat of the rational part of the soul.[8] Aristotle, however, believed the heart was the center of intelligence and that the brain served to cool the blood. This view was generally accepted until the Roman physician Galen, a follower of Hippocrates and physician to Roman gladiators, observed that his patients lost their mental faculties when they had sustained damage to their brains. Abulcasis, Averroes, Avenzoar, and Maimonides, active in the Medieval Muslim world, described a number of medical problems related to the brain. In Renaissance Europe, Vesalius (1514–1564) and René Descartes (1596–1650) also made several contributions to neuroscience. Studies of the brain became more sophisticated after the invention of the microscope and the development of a staining procedure by Camillo Golgi during the late 1890s. The procedure used a silver chromate salt to reveal the intricate structures of individual neurons. His technique was used by Santiago Ramón y Cajal and led to the formation of the neuron doctrine, the hypothesis that the functional unit of the brain is the neuron. Golgi and Ramón y Cajal shared the Nobel Prize in Physiology or Medicine in 1906 for their extensive The Golgi stain first allowed for the visualization observations, descriptions, and categorizations of neurons throughout of individual neurons. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Neuroscience 87 the brain. The neuron doctrine was supported by experiments following Luigi Galvanis pioneering work in the electrical excitability of muscles and neurons. In the late 19th century, Emil du Bois-Reymond, Johannes Peter Müller, and Hermann von Helmholtz demonstrated that neurons were electrically excitable and that their activity predictably affected the electrical state of adjacent neurons. In parallel with this research, work with brain-damaged patients by Paul Broca suggested that certain regions of the brain were responsible for certain functions. At the time, Brocas findings were seen as a confirmation of Franz Joseph Galls theory that language was localized and that certain psychological functions were localized in specific areas of the cerebral cortex.[9] [10] The localization of function hypothesis was supported by observations of epileptic patients conducted by John Hughlings Jackson, who correctly inferred the organization of the motor cortex by watching the progression of seizures through the body. Carl Wernicke further developed the theory of the specialization of specific brain structures in language comprehension and production. Modern research still uses the Brodmann cerebral cytoarchitectonic map (referring to study of cell structure) anatomical definitions from this era in continuing to show that distinct areas of the cortex are activated in the execution of specific tasks.[11] In 1952, Alan Lloyd Hodgkin and Andrew Huxley presented a mathematical model for transmission of electrical signals in neurons of the giant axon of a squid, action potentials, and how they are initiated and propagated, known as the Hodgkin-Huxley model. In 1961-2, Richard FitzHugh and J. Nagumo simplified Hodgkin-Huxley, in what is called the FitzHugh–Nagumo model. In 1962, Bernard Katz modeled neurotransmission across the space between neurons known as synapses. In 1981 Catherine Morris and Harold Lecar combined these models in the Morris-Lecar model. In 1984, J. L. Hindmarsh and R.M. Rose further modeled neurotransmission. Beginning in 1966, Eric Kandel and James Schwartz examined the biochemical analysis of changes in neurons associated with learning and memory storage. Foundations of modern neuroscience The scientific study of the nervous system increased significantly during the second half of the twentieth century, principally due to revolutions in molecular biology, electrophysiology, and computational neuroscience. It has become possible to understand, in much detail, the complex processes occurring within a single neuron. However, how networks of neurons produce complex cognitions and behaviors is still poorly understood. Photograph of a stained neuron in a chicken embryo Compiled and Edited by Marc Imhotep Cray , M.D.
  • Neuroscience 88 “ The task of neural science is to explain behavior in terms of the activities of the brain. How does the brain marshal its millions of individual nerve cells to produce behavior, and how are these cells influenced by the environment...? The last frontier of the biological sciences—their ultimate challenge—is to understand the biological basis of consciousness and the mental processes by which we perceive, act, learn, and remember. — Eric Kandel, Principles of Neural Science, 4th ed. ” The nervous system is composed of a network of neurons along with other, supportive, cells (e.g., glial cells). Neurons form functional circuits, each responsible for specific functions of behavior at the organismal level. Thus, neuroscience can be studied at many different levels, ranging from the molecular and cellular levels to the systems and cognitive levels. At the molecular level, the basic questions addressed in molecular neuroscience include the mechanisms by which neurons express and respond to molecular signals and how axons form complex connectivity patterns. At this level, tools from molecular biology and genetics are used to understand how neurons develop and how genetic changes affect biological functions. The morphology, molecular identity, and physiological characteristics of neurons and how they relate to different types of behavior are also of considerable interest. At the cellular level, the fundamental questions addressed in cellular neuroscience include the mechanisms of how neurons process signals physiologically and electrochemically. They address how signals are processed by dendrites, somas and axons, and how neurotransmitters and electrical signals are used to process signals in a neuron. Another major area of neuroscience is directed at investigations of the development of the nervous system. These questions include the patterning and regionalization of the nervous system, neural stem cells, differentiation of neurons and glia, neuronal migration, axonal and dendritic development, trophic interactions, and synapse formation. At the systems level, the questions addressed in systems neuroscience include how neural circuits are formed and used anatomically and physiologically to produce functions such as reflexes, sensory integration, motor coordination, circadian rhythms, emotional responses, learning, and memory. In other words, they address how these neural circuits function and the mechanisms through which behaviors are generated. For example, systems level analysis addresses questions concerning specific sensory and motor modalities: how does vision work? How do songbirds learn new songs and bats localize with ultrasound? How does the somatosensory system process tactile information? The related fields of neuroethology and neuropsychology address the question of how neural substrates underlie specific animal and human behaviors. Neuroendocrinology and psychoneuroimmunology examine interactions between the nervous system and the endocrine and immune systems, respectively. At the cognitive level, cognitive neuroscience addresses the questions of how psychological functions are produced by neural circuitry. The emergence of powerful new measurement techniques such as neuroimaging (e.g., fMRI, PET, SPECT), electrophysiology, and human genetic analysis combined with sophisticated experimental techniques from cognitive psychology allows neuroscientists and psychologists to address abstract questions such as how human cognition and emotion are mapped to specific neural substrates. Neuroscience is also allied with the social and behavioral sciences as well as nascent interdisciplinary fields such as neuroeconomics, decision theory, and social neuroscience to address complex questions about interactions of the brain with its environment. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Neuroscience 89 Neuroscience and medicine Neurology, psychiatry, neurosurgery, psychosurgery, neuropathology, neuroradiology, clinical neurophysiology and addiction medicine are medical specialties that specifically address the diseases of the nervous system. These terms also refer to clinical disciplines involving diagnosis and treatment of these diseases. Neurology works with diseases of the central and peripheral nervous systems, such as amyotrophic lateral sclerosis (ALS) and stroke, and their medical treatment while psychiatry focuses on affective, behavioral, cognitive, and perceptual disorders. Neuropathology focuses upon the classification and underlying pathogenic mechanisms of central and peripheral nervous system and muscle diseases, with an emphasis on morphologic, microscopic, and chemically observable alterations. Neurosurgery and Parasagittal MRI of the head of a patient with benign familial psychosurgery work primarily with surgical treatment macrocephaly of diseases of the central and peripheral nervous systems. The boundaries between these specialties have been blurring recently as they are all influenced by basic research in neuroscience. Brain imaging also enables objective, biological insights into mental illness, which can lead to faster diagnosis, more accurate prognosis, and help assess patient progress over time.[12] Integrative neuroscience makes connections across these specialized areas of focus. Major branches Modern neuroscience education and research activities can be very roughly categorized into the following major branches, based on the subject and scale of the system in examination as well as distinct experimental or curricular approaches. Individual neuroscientists, however, often work on questions that span several distinct subfields. Branch Description Behavioral Behavioral neuroscience (also known as biological psychology, biopsychology, or psychobiology) is the application of the neuroscience principles of biology (viz., neurobiology) to the study of genetic, physiological, and developmental mechanisms of behavior in humans and non-human animals. Cellular Cellular neuroscience is the study of neurons at a cellular level including morphology and physiological properties. neuroscience Clinical This consists of medical specialties such as neurology and psychiatry, among others. Neurology is the medical specialty that neuroscience works with disorders of the nervous system. Psychiatry is the medical specialty that works with the disorders of the mind—which include various affective, behavioral, cognitive, and perceptual disorders. (Also see note below.) Cognitive Cognitive neuroscience is the study of biological substrates underlying cognition with a specific focus on the neural neuroscience substrates of mental processes. Computational Computational neuroscience is the study of brain function in terms of the information processing properties of the structures neuroscience that make up the nervous system. Computational neuroscience can also refer to the use of computer simulations and theoretical models to study the function of the nervous system. Cultural Cultural neuroscience is the study of how cultural values, practices and beliefs shape and are shaped by the mind, brain and neuroscience [13] genes across multiple timescales. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Neuroscience 90 Developmental Developmental neuroscience studies the processes that generate, shape, and reshape the nervous system and seeks to neuroscience describe the cellular basis of neural development to address underlying mechanisms. Molecular Molecular neuroscience is a branch of neuroscience that examines the biology of the nervous system with molecular biology, neuroscience molecular genetics, protein chemistry, and related methodologies. Neuroengineering Neuroengineering is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, or enhance neural systems. Neuroimaging Neuroimaging includes the use of various techniques to either directly or indirectly image the structure and function of the brain. Neuroinformatics Neuroinformatics is a discipline within bioinformatics that conducts the organization of neuroscience data and application of computational models and analytical tools. Neurolinguistics Neurolinguistics is the study of the neural mechanisms in the human brain that control the comprehension, production, and acquisition of language. Neurophysiology Neurophysiology is the study of the functioning of the nervous system, generally using physiological techniques that include measurement and stimulation with electrodes or optically with ion- or voltage-sensitive dyes or light-sensitive channels. Social neuroscience Social neuroscience is an interdisciplinary field devoted to understanding how biological systems implement social processes and behavior, and to using biological concepts and methods to inform and refine theories of social processes and behavior. Systems Systems neuroscience is the study the function of neural circuits and systems. neuroscience In 1990s, neuroscientist Jaak Panksepp coined the term "affective neuroscience" to emphasize that research of emotion should be a branch of the neurosciences, distinguishable from the nearby fields of cognitive neuroscience or behavioral neuroscience.[14] More recently, the social aspect of the emotional brain has been integrated in what is called "social-affective neuroscience" or simply social neuroscience. Future directions At this time in neuroscience research, several major questions remained unsolved, especially in cognitive neuroscience. For example, neuroscientists have yet to fully explain the neural basis of consciousness, learning, memory, perception, sensation, and sleep. Several questions regarding the development and evolution of the brain remain unsolved. Researchers have also yet to fully delineate the neural bases of mental disorders such as addiction, Alzheimers disease, Parkinsons disease, and psychotic disorders (e.g., schizophrenia). Neuroscientific research on free will is also in the early stages of understanding.[15] Thus, neuroscientists are continuously collaborating with other scientists and researchers to address many of these unresolved problems.[16] Finally, proponents of the science of morality, such as the neuroscientist and writer Sam Harris, maintain that neuroscience will play an important role in the search for optimal moral systems.[17] Public education and outreach In addition to conducting traditional research in laboratory settings, neuroscientists have also been involved in the promotion of awareness and knowledge about the nervous system among the general public and government officials. Such promotions have been done by both individual neuroscientists and large organizations. For example, individual neuroscientists have promoted neuroscience education among young students by organizing the International Brain Bee (IBB), which is an academic competition for high school or secondary school students worldwide.[18] In the United States, large organizations such as the Society for Neuroscience have promoted neuroscience education by developing a primer called Brain Facts,[19] collaborating with members of public education to develop Neuroscience Core Concepts for K-12 teachers and students,[20] and cosponsoring a campaign with the Dana Foundation called Brain Awareness Week to increase public awareness about the progress and benefits of brain research.[21] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Neuroscience 91 Finally, neuroscientists have also collaborated with other education experts to study and refine educational techniques to optimize learning among students, an emerging field called educational neuroscience.[22] Federal Agencies in the United States, such as the National Institute of Health (NIH) and National Science Foundation (NSF), have also funded research that pertain to best practices in teaching and learning of neuroscience concepts. References [1] "Neuroscience" (http:/ / www. merriam-webster. com/ medlineplus/ neuroscience). Merriam-Webster Medical Dictionary. . [2] "History of IBRO" (http:/ / www. ibro. info/ Pub/ Pub_Main_Display. asp?LC_Docs_ID=2343). International Brain Research Organization. 2010. . [3] The Beginning (http:/ / www. neurochemistry. org/ Information/ History/ TheBeginning. aspx), International Society for Neurochemistry [4] "About EBBS" (http:/ / www. ebbs-science. org/ cms/ general/ about-ebbs. html). European Brain and Behaviour Society. 2009. . [5] "About SfN" (http:/ / www. sfn. org/ index. aspx?pagename=about_sfn). Society for Neuroscience. . [6] Mohamed W (2008). "The Edwin Smith Surgical Papyrus: Neuroscience in Ancient Egypt" (http:/ / www. ibro. info/ Pub/ Pub_Main_Display. asp?LC_Docs_ID=3199). IBRO History of Neuroscience. . [7] Herodotus (440BCE). The Histories: Book II (Euterpe) (http:/ / classics. mit. edu/ Herodotus/ history. mb. txt). . [8] Plato (360BCE). Timaeus (http:/ / classics. mit. edu/ Plato/ timaeus. 1b. txt). . [9] Greenblatt SH (1995). "Phrenology in the science and culture of the 19th century" (http:/ / journals. lww. com/ neurosurgery/ Abstract/ 1995/ 10000/ Phrenology_in_the_Science_and_Culture_of_the_19th. 25. aspx). Neurosurg 37 (4): 790–805. PMID 8559310. . [10] Bear MF, Connors BW, Paradiso MA (2001). Neuroscience: Exploring the Brain (4th ed.). Philedelphia, PA: Lippincott Williams & Wilkins. ISBN 0781739446. [11] Kandel ER, Schwartz JH, Jessel TM (2000). Principles of Neural Science (4th ed.). New York, NY: McGraw-Hill. ISBN 0838577016. [12] Lepage M (2010). "Research at the Brain Imaging Centre" (http:/ / www. douglas. qc. ca/ page/ imagerie-cerebrale?locale=en). Douglas Mental Health University Institute. . [13] Chiao, J.Y. & Ambady, N. (2007). Cultural neuroscience: Parsing universality and diversity across levels of analysis. In Kitayama, S. and Cohen, D. (Eds.) Handbook of Cultural Psychology, Guilford Press, NY, pp. 237-254. [14] Panksepp J (1990). "A role for "affective neuroscience" in understanding stress: the case of separation distress circuitry". In Puglisi-Allegra S, Oliverio A. Psychobiology of Stress. Dordrecht, Netherlands: Kluwer Academic. pp. 41–58. ISBN 0792306821. [15] Balaguer M (2009). Free Will as an Open Scientific Problem. Cambridge, MA: MIT Press. ISBN 9780262013543. [16] Hemmen JL, Sejnowski TJ (2006). 23 Problems in Systems Neuroscience (http:/ / papers. cnl. salk. edu/ PDFs/ 23 Problems in Systems Neuroscience 2005-2921. pdf). New York NY: Oxford University Press. ISBN 0195148223. . [17] Koizumi H (2007). The Concept of “Brain-Science and Ethics. Journal Seizon and Life Sciences. [18] "About the International Brain Bee" (http:/ / www. internationalbrainbee. com/ about_bee. html). The International Brain Bee. . [19] "Brain Facts: A Primer on the Brain and Nervous System" (http:/ / www. sfn. org/ index. aspx?pagename=brainfacts). Society for Neuroscience. . [20] "Neuroscience Core Concepts: The Essential Principles of Neuroscience" (http:/ / www. sfn. org/ index. aspx?pagename=core_concepts). Society for Neuroscience. . [21] "Brain Awareness Week Campaign" (http:/ / www. dana. org/ brainweek/ ). The Dana Foundation. . [22] Goswami U (2004). "Neuroscience, education and special education" (http:/ / onlinelibrary. wiley. com/ doi/ 10. 1111/ j. 0952-3383. 2004. 00352. x/ abstract). Br J of Spec Educ 31 (4): 175–183. doi:10.1111/j.0952-3383.2004.00352.x. . Further reading • Bear, M. F.; B. W. Connors, and M. A. Paradiso (2006). Neuroscience: Exploring the Brain (3rd ed.). Philadelphia: Lippincott. ISBN 0781760038. • Binder/Hirokawa/Windhorst (2009, 4399pp, 5 vols). Encyclopedia of Neuroscience (http://www.springer.com/ biomed/neuroscience/book/978-3-540-23735-8). Springer. ISBN 978-3-540-23735-8. • Kandel, ER; Schwartz JH, Jessell TM (2000). Principles of Neural Science (4th ed.). New York: McGraw-Hill. ISBN 0-8385-7701-6. • Squire, L. et al. (2003). Fundamental Neuroscience, 2nd edition. Academic Press; ISBN 0-12-660303-0 • Byrne and Roberts (2004). From Molecules to Networks. Academic Press; ISBN 0-12-148660-5 • Sanes, Reh, Harris (2005). Development of the Nervous System, 2nd edition. Academic Press; ISBN 0-12-618621-9 • Siegel et al. (2005). Basic Neurochemistry, 7th edition. Academic Press; ISBN 0-12-088397-X • Rieke, F. et al. (1999). Spikes: Exploring the Neural Code. The MIT Press; Reprint edition ISBN 0-262-68108-0 Compiled and Edited by Marc Imhotep Cray , M.D.
  • Neuroscience 92 • section.47 Neuroscience (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books& doptcmdl=GenBookHL&term=The+Cellular+Components+of+the+Nervous+System+AND+ neurosci[book]+AND+231002[uid]&rid=neurosci.) 2nd ed. Dale Purves, George J. Augustine, David Fitzpatrick, Lawrence C. Katz, Anthony-Samuel LaMantia, James O. McNamara, S. Mark Williams. Published by Sinauer Associates, Inc., 2001. • section.18 Basic Neurochemistry: Molecular, Cellular, and Medical Aspects (http://www.ncbi.nlm.nih.gov/ entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=Characteristics+of+the+Neuron+ AND+bnchm[book]+AND+160014[uid]&rid=bnchm.) 6th ed. by George J. Siegel, Bernard W. Agranoff, R. Wayne Albers, Stephen K. Fisher, Michael D. Uhler, editors. Published by Lippincott, Williams & Wilkins, 1999. • Andreasen, Nancy C. (March 4 2004). Brave New Brain: Conquering Mental Illness in the Era of the Genome (http://www.oup.com/uk/catalogue/?ci=9780195145090). Oxford University Press. ISBN 9780195145090. • Damasio, A. R. (1994). Descartes Error: Emotion, Reason, and the Human Brain. New York, Avon Books. ISBN 0-399-13894-3 (Hardcover) ISBN 0-380-72647-5 (Paperback) • Gardner, H. (1976). The Shattered Mind: The Person After Brain Damage. New York, Vintage Books, 1976 ISBN 0-394-71946-8 • Goldstein, K. (2000). The Organism. New York, Zone Books. ISBN 0-942299-96-5 (Hardcover) ISBN 0-942299-97-3 (Paperback) • Lauwereyns, Jan (February 2010). The Anatomy of Bias: How Neural Circuits Weigh the Options (http:// mitpress.mit.edu/9780262123105). Cambridge, MA: The MIT Press. ISBN 026212310X. • Llinas R. (2001). I of the Vortex: From Neurons to Self MIT Press. ISBN 0-262-12233-2 (Hardcover) ISBN 0-262-62163-0 (Paperback) • Luria, A. R. (1997). The Man with a Shattered World: The History of a Brain Wound. Cambridge, Massachusetts, Harvard University Press. ISBN 0-224-00792-0 (Hardcover) ISBN 0-674-54625-3 (Paperback) • Luria, A. R. (1998). The Mind of a Mnemonist: A Little Book About A Vast Memory. New York, Basic Books, Inc. ISBN 0-674-57622-5 • Medina, J. (2008). Brain Rules: 12 Principles for Surviving and Thriving at Work, Home, and School. Seattle, Pear Press. ISBN 0-979-777704 (Hardcover with DVD) • Pinker, S. (1999). How the Mind Works. W. W. Norton & Company. ISBN 0-393-31848-6 • Pinker, S. (2002). The Blank Slate: The Modern Denial of Human Nature. Viking Adult. ISBN 0-670-03151-8 • Robinson, D. L. (2009). Brain, Mind and Behaviour: A New Perspective on Human Nature (2nd ed.). Dundalk, Ireland: Pontoon Publications. ISBN 978-0-9561812-0-6. • Ramachandran, V. S. (1998). Phantoms in the Brain. New York, New York Harper Collins. ISBN 0-688-15247-3 (Paperback) • Rose, S. (2006). 21st Century Brain: Explaining, Mending & Manipulating the Mind ISBN 0099429772 (Paperback) • Sacks, O. The Man Who Mistook His Wife for a Hat. Summit Books ISBN 0-671-55471-9 (Hardcover) ISBN 0-06-097079-0 (Paperback) • Sacks, O. (1990). Awakenings. New York, Vintage Books. (See also Oliver Sacks) ISBN 0-671-64834-9 (Hardcover) ISBN 0-06-097368-4 (Paperback) • Sternberg, E. (2007) Are You a Machine? The Brain, the Mind and What it Means to be Human. Amherst, NY: Prometheus Books. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Neuroscience 93 External links • Neuroscience (http://www.bbc.co.uk/programmes/b00fbd26) on In Our Time at the BBC. ( listen now (http:/ /www.bbc.co.uk/iplayer/console/b00fbd26/In_Our_Time_Neuroscience)) • Neuroscience Information Framework (NIF) (http://www.neuinfo.org) • Neurobiology (http://www.dmoz.org/Science/Biology/Neurobiology/) at the Open Directory Project • IBRO (International Brain Research Organization) (http://www.ibro.info) • Society for Neuroscience (SFN) (http://www.sfn.org) • American Society for Neurochemistry (http://www.asneurochem.org) • Neuroscience Online (electronic neuroscience textbook) (http://neuroscience.uth.tmc.edu/) • Faculty for Undergraduate Neuroscience (FUN) (http://www.funfaculty.org/drupal/) • Neuroscience for Kids (http://faculty.washington.edu/chudler/neurok.html) • Neuroscience Discussion Group (https://www.researchgate.net/group/Neuroscience) in ResearchGate • Neuroscience Discussion Forum (http://www.neuroscienceforums.com) • HHMI Neuroscience lecture series - Making Your Mind: Molecules, Motion, and Memory (http://www.hhmi. org/biointeractive/neuroscience/lectures.html) • British Neuroscience Association (http://www.bna.org.uk) Pharmacology Pharmacology (from Greek φάρμακον, pharmakon, "poison in classic Greek; drug in modern Greek"; and -λογία, "Study of" -logia) is the branch of medicine and biology concerned with the study of drug action.[1] More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals. The field encompasses drug composition and A variety of topics involved with pharmacology, including neuropharmacology, properties, interactions, toxicology, therapy, renal pharmacology, human metabolism, intracellular metabolism, and intracellular and medical applications and antipathogenic regulation. capabilities. The two main areas of pharmacology are pharmacodynamics and pharmacokinetics. The former studies the effects of the drugs on biological systems, and the latter the effects of biological systems on the drugs. In broad terms, pharmacodynamics discusses the interactions of chemicals with biological receptors, and pharmacokinetics discusses the absorption, distribution, metabolism, and excretion of chemicals from the biological systems. Pharmacology is not synonymous with pharmacy and the two terms are frequently confused. Pharmacology deals with how drugs interact within biological systems to affect function. It is the study of drugs, of the reactions of the body and drug on each other, the sources of drugs, their nature, and their properties. In contrast, pharmacy is a biomedical science concerned with preparation, dispensing, dosage, and the safe and effective use of medicines. Dioscorides De Materia Medica is often said to be the oldest and most valuable work in the history of pharmacology.[2] The origins of clinical pharmacology date back to the Middle Ages in Avicennas The Canon of Medicine, Peter of Spains Commentary on Isaac, and John of St Amands Commentary on the Antedotary of Compiled and Edited by Marc Imhotep Cray , M.D.
  • Pharmacology 94 Nicholas.[3] Clinical pharmacology owes much of its foundation to the work of William Withering.[4] Pharmacology as a scientific discipline did not further advance until the mid-19th century amid the great biomedical resurgence of that period.[5] Before the second half of the nineteenth century, the remarkable potency and specificity of the actions of drugs such as morphine, quinine and digitalis were explained vaguely and with reference to extraordinary chemical powers and affinities to certain organs or tissues.[6] The first pharmacology department was set up by Rudolf Buchheim in 1847, in recognition of the need to understand how therapeutic drugs and poisons produced their effects.[5] Early pharmacologists focused on natural substances, mainly plant extracts. Pharmacology developed in the 19th century as a biomedical science that applied the principles of scientific experimentation to therapeutic contexts.[7] Divisions Clinical pharmacology The medical field of medication effects on humans and animals. Neuropharmacology Effects of medication on nervous system functioning.. Psychopharmacology Effects of medication on the brain; observing changed behaviors of the body and read the effect of drugs on the brain. Pharmacogenetics Clinical testing of genetic variation that gives rise to differing response to drugs. Pharmacogenomics Application of genomic technologies to new drug discovery and further characterization of older drugs. Pharmacoepidemiology Study of effects of drugs in large numbers of people. Toxicology Study of harmful or toxic effects of drugs. Theoretical Pharmacology Study of metrics in Pharmacology. Dosology How medicines are dosed. It also depends upon various factors like age, climate, weight, sex, and so on. Pharmacognosy A branch of pharmacology dealing especially with the composition, use, and development of medicinal substances of biological origin and especially medicinal substances obtained from plants also known as deriving medicines from plants Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Pharmacology 95 Behavioral Pharmacology Behavioral pharmacology, also referred to as psychopharmacology, is an interdisciplinary field which studies behavioral effects of psychoactive drugs. It incorporates approaches and techniques from neuropharmacology, animal behavior and behavioral neuroscience, and is interested in the behavioral and neurobiological mechanisms of action of psychoactive drugs. Another goal of behavioral pharmacology is to develop animal behavioral models to screen chemical compounds with therapeutic potentials. People in this field (called behavioral pharmacologists) typically use small animals (e.g. rodents) to study psychotherapeutic drugs such as antipsychotics, antidepressants and anxiolytics, and drugs of abuse such as nicotine, cocaine, methamphetamine, etc. Environmental Pharmacology Environmental pharmacology is a new discipline.[8] Focus is being given to understand Gene–environment interaction, drug-environment interaction and toxin-environment interaction. There is a close collaboration between the Environmental science and Medical community in addressing these issues. It is recognised that healthcare can itself be a cause of Environmental damage as well as its remediation. Human health and ecology is intimately related. Demand for more pharmaceutical products is destroying countless species of animals and plants, placing the public at risk. The entry of chemicals and drugs into the Aquatic ecosystem is a more serious concern today. In addition, the production of some Illegal drugs pollutes drinking water supply by releasing carcinogens.[9] The pharmaceutical industry is encouraged to pay greater attention to the environmental impact of its products. More and more biodegradability of drugs are needed. It means environment friendly drugs could be designed. General standards for discharge of environment pollutants is implemented strictly and environmental impact assessment is checked frequently by health and other concerned regulators. Today, in Environmental Pharmacology, the topics which are covered includes Pharmacoenvironmentology[10] and Ecopharmacology[11] which is all about the study of Pharmaceuticals and personal care products in the environment. Scientific background The study of chemicals requires intimate knowledge of the biological system affected. With the knowledge of cell biology and biochemistry increasing, the field of pharmacology has also changed substantially. It has become possible, through molecular analysis of receptors, to design chemicals that act on specific cellular signaling or metabolic pathways by affecting sites directly on cell-surface receptors (which modulate and mediate cellular signaling pathways controlling cellular function). A chemical has, from the pharmacological point-of-view, various properties. Pharmacokinetics describes the effect of the body on the chemical (e.g. half-life and volume of distribution), and pharmacodynamics describes the chemicals effect on the body (desired or toxic). When describing the pharmacokinetic properties of a chemical, pharmacologists are often interested in LADME: • Liberation - disintegration (for solid oral forms {breaking down into smaller particles}), dispersal and dissolution • Absorption - How is the medication absorbed (through the skin, the intestine, the oral mucosa)? • Distribution - How does it spread through the organism? • Metabolism - Is the medication converted chemically inside the body, and into which substances. Are these active? Could they be toxic? • Excretion - How is the medication eliminated (through the bile, urine, breath, skin)? Medication is said to have a narrow or wide therapeutic index or therapeutic window. This describes the ratio of desired effect to toxic effect. A compound with a narrow therapeutic index (close to one) exerts its desired effect at a dose close to its toxic dose. A compound with a wide therapeutic index (greater than five) exerts its desired effect at a dose substantially below its toxic dose. Those with a narrow margin are more difficult to dose and administer, and may require therapeutic drug monitoring (examples are warfarin, some antiepileptics, aminoglycoside antibiotics). Compiled and Edited by Marc Imhotep Cray , M.D.
  • Pharmacology 96 Most anti-cancer drugs have a narrow therapeutic margin: toxic side-effects are almost always encountered at doses used to kill tumors. Medicine development and safety testing Development of medication is a vital concern to medicine, but also has strong economical and political implications. To protect the consumer and prevent abuse, many governments regulate the manufacture, sale, and administration of medication. In the United States, the main body that regulates pharmaceuticals is the Food and Drug Administration and they enforce standards set by the United States Pharmacopoeia. In the European Union, the main body that regulates pharmaceuticals is the EMEA and they enforce standards set by the European Pharmacopoeia. The metabolic stability and the reactivity of a library of candidate drug compounds have to be assessed for drug metabolism and toxicological studies. Many methods have been proposed for quantitative predictions in drug metabolism; one example of a recent computational method is SPORCalc [12].[13] If the chemical structure of a medicinal compound is altered slightly, this could slightly or dramatically alter the medicinal properties of the compound depending on the level of alteration as it relates to the structural composition of the substrate or receptor site on which it exerts its medicinal effect, a concept referred to as the structural activity relationship (SAR). This means that when a useful activity has been identified, chemists will make many similar compounds called analogues, in an attempt to maximize the desired medicinal effect(s) of the compound. This development phase can take anywhere from a few years to a decade or more and is very expensive.[14] These new analogues need to be developed. It needs to be determined how safe the medicine is for human consumption, its stability in the human body and the best form for delivery to the desired organ system, like tablet or aerosol. After extensive testing, which can take up to 6 years, the new medicine is ready for marketing and selling.[14] As a result of the long time required to develop analogues and test a new medicine and the fact that of every 5000 potential new medicines typically only one will ever reach the open market, this is an expensive way of doing things, costing millions of dollars. To recoup this outlay pharmaceutical companies may do a number of things:[14] • Carefully research the demand for their potential new product before spending an outlay of company funds.[14] • Obtain a patent on the new medicine preventing other companies from producing that medicine for a certain allocation of time.[14] Drug legislation and safety In the United States, the Food and Drug Administration (FDA) is responsible for creating guidelines for the approval and use of drugs. The FDA requires that all approved drugs fulfill two requirements: 1. The drug must be found to be effective against the disease for which it is seeking approval. 2. The drug must meet safety criteria by being subject to extensive animal and controlled human testing. Gaining FDA approval usually takes several years to attain. Testing done on animals must be extensive and must include several species to help in the evaluation of both the effectiveness and toxicity of the drug. The dosage of any drug approved for use is intended to fall within a range in which the drug produces a therapeutic effect or desired outcome.[15] The safety and effectiveness of prescription drugs in the U.S. is regulated by the federal Prescription Drug Marketing Act of 1987. The Medicines and Healthcare products Regulatory Agency (MHRA) has a similar role in the UK. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Pharmacology 97 Education The study of pharmacology is offered in many universities worldwide in programs that differ from pharmacy programs. Students of pharmacology are trained as researchers, studying the effects of substances in order to better understand the mechanisms which might lead to new drug discoveries for example. Whereas a pharmacy student will eventually work in a pharmacy dispensing medications or some other position focused on the patient, a pharmacologist will typically work within a laboratory setting. Footnotes [1] Vallance P, Smart TG (January 2006). "The future of pharmacology". British journal of pharmacology 147 Suppl 1: S304–7. doi:10.1038/sj.bjp.0706454. PMC 1760753. PMID 16402118. [2] Gulsel M. Kavalali (2003). " Urtica: therapeutic and nutritional aspects of stinging nettles (http:/ / books. google. com/ books?id=AoWtF1ruQJsC& pg=PA15& dq& hl=en#v=onepage& q=& f=false)". CRC Press. p.15. ISBN 041530833X [3] Brater DC, Daly WJ (May 2000). "Clinical pharmacology in the Middle Ages: principles that presage the 21st century". Clin. Pharmacol. Ther. 67 (5): 447–50. doi:10.1067/mcp.2000.106465. PMID 10824622. [4] Mannfred A. Hollinger (2003)." Introduction to pharmacology (http:/ / books. google. com/ books?id=bx-WfLwrVH8C& pg=PA4& dq& hl=en#v=onepage& q=& f=false)". CRC Press. p.4. ISBN 0415280338 [5] Rang HP (January 2006). "The receptor concept: pharmacologys big idea". Br. J. Pharmacol. 147 Suppl 1: S9–16. doi:10.1038/sj.bjp.0706457. PMC 1760743. PMID 16402126. [6] Maehle AH, Prüll CR, Halliwell RF (August 2002). "The emergence of the drug receptor theory". Nat Rev Drug Discov 1 (8): 637–41. doi:10.1038/nrd875. PMID 12402503. [7] Rang, H.P.; M.M. Dale, J.M. Ritter, R.J. Flower (2007). Pharmacology. China: Elsevier. ISBN 0-443-06911-5. [8] Rahman, SZ; Khan, RA (Dec 2006). "Environmental pharmacology: A new discipline" (http:/ / www. ijp-online. com/ text. asp?2006/ 38/ 4/ 229/ 27017). Indian J Pharmacol. 38 (4): 229–30. doi:10.4103/0253-7613.27017. . [9] Ilene Sue Ruhoy, Christian G. Daughton. Beyond the medicine cabinet: An analysis of where and why medications accumulate. Environment International 2008, Vol. 34 (8): 1157-1169 [10] SZ Rahman, RA Khan, V Gupta & Misbahuddin. Pharmacoenvironmentology–Ahead of Pharmacovigilance. In: Rahman SZ, Shahid M & Gupta A Eds. An Introduction to Environmental Pharmacology (ISBN 978-81-906070-4-9). Ibn Sina Academy, Aligarh, India, 2008: 35-42 [11] Rahman, SZ; Khan, RA; Gupta, V; Uddin, Misbah (July 2007). "Pharmacoenvironmentology–A Component of Pharmacovigilance" (http:/ / www. ehjournal. net/ content/ 6/ 1/ 20). Environmental Health 6 (20): 20. doi:10.1186/1476-069X-6-20. PMC 1947975. PMID 17650313. . [12] http:/ / www. freebase. com/ view/ en/ sporcalc [13] James Smith; Viktor Stein (2009). "SPORCalc: A development of a database analysis that provides putative metabolic enzyme reactions for ligand-based drug design". Computational Biology and Chemistry 33 (2): 149–159. doi:10.1016/j.compbiolchem.2008.11.002. PMID 19157988. [14] Newton, David; Alasdair Thorpe, Chris Otter (2004). Revise A2 Chemistry. Heinemann Educational Publishers. pp. 1. ISBN 0-435-58347-6. [15] Nagle, Hinter; Barbara Nagle (2005). Pharmacology: An Introduction. Boston: McGraw Hill. ISBN 0-07-312275-0. External links • British Pharmacological Society (http://www.bps.ac.uk). • Pharmaceutical company profiles at NNDB (http://www.nndb.com/lists/623/000098329/). • International Conference on Harmonisation (http://www.ich.org/). • US Pharmacopeia (http://www.usp.org). • International Union of Basic and Clinical Pharmacology (http://www.iuphar.org). • IUPHAR Committee on Receptor Nomenclature and Drug Classification (http://www.iuphar-db.org). Compiled and Edited by Marc Imhotep Cray , M.D.
  • Toxicology 98 Toxicology Toxicology (from the Greek words τοξικός - toxicos "poisonous" and logos) is a branch of biology, chemistry, and medicine concerned with the study of the adverse effects of chemicals on living organisms.[1] It is the study of symptoms, mechanisms, treatments and detection of poisoning, especially the poisoning of people. History Dioscorides, a Greek physician in the court of the Roman emperor Nero, made the first attempt to classify plants according to their toxic and therapeutic effect.[2] Ibn Wahshiya wrote the Book on Poisons in the 9th or 10th century.[3] Mathieu Orfila is considered to be the modern father of toxicology, having given the subject its first formal treatment in 1813 in his Traité des poisons, also called Toxicologie générale.[4] In 1850 Jean Stas gave the evidence that the Belgian Count Hypolyte Visart de Bocarmé killed his brother-in-law by poisoning with nicotine[5] Theophrastus Phillipus Auroleus Bombastus von Hohenheim (1493–1541) (also referred to as Paracelsus, from his belief that his studies were above or beyond the work of Celsus - a Lithograph of Mathieu Orfila Roman physician from the first century) is also considered "the father" of toxicology.[6] He is credited with the classic toxicology maxim, "Alle Dinge sind Gift und nichts ist ohne Gift; allein die Dosis macht, dass ein Ding kein Gift ist." which translates as, "All things are poison and nothing is without poison; only the dose makes a thing not a poison." This is often condensed to: "The dose makes the poison" or in Latin "Sola dosis facit venenum". The relationship between dose and its effects on the exposed organism is of high significance in toxicology. The chief criterion regarding the toxicity of a chemical is the dose, i.e. the amount of exposure to the substance. All substances are toxic under the right conditions. The term LD50 refers to the dose of a toxic substance that kills 50 percent of a test population (typically rats or other surrogates when the test concerns human toxicity). LD50 estimations in animals are no longer required for regulatory submissions as a part of pre-clinical development package. The conventional relationship (more exposure equals higher risk) has been challenged in the study of endocrine disruptors. Toxicity of metabolites Many substances regarded as poisons are toxic only indirectly. An example is "wood alcohol," or methanol, which is chemically converted to formaldehyde and formic acid in the liver. It is the formaldehyde and formic acid that cause the toxic effects of methanol exposure. As for drugs, many small molecules are made toxic in the liver, a good example being acetaminophen (paracetamol), especially in the presence of chronic alcohol use. The genetic variability of certain liver enzymes makes the toxicity of many compounds differ between one individual and the next. Because demands placed on one liver enzyme can induce activity in another, many molecules become toxic only in combination with others. A family of activities that many toxicologists engage includes identifying which Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Toxicology 99 liver enzymes convert a molecule into a poison, what are the toxic products of the conversion and under what conditions and in which individuals this conversion takes place. Subdisciplines of toxicology There are various specialized subdisciplines within the field of toxicology that concern diverse chemical and biological aspects of this area. For example, toxicogenomics involves applying molecular profiling approaches to the study of toxicology.[7] Other areas include Aquatic toxicology, Chemical (pharmaceutical) toxicology, Ecotoxicology, Environmental toxicology, Forensic toxicology, and Medical toxicology. Chemical (pharmaceutical) toxicology Chemical or pharmaceutical toxicology is a scientific discipline involving the study of structure and mechanism related to the toxic effects of chemical agents, and encompasses technology advances in research related to chemical aspects of toxicology. Research in this area is strongly multidisciplinary, spanning computational chemistry and synthetic chemistry, proteomics and metabolomics, drug discovery, drug metabolism and mechanisms of action, bioinformatics, bioanalytical chemistry, chemical biology, and molecular epidemiology. References [1] "What is Toxicology" -Schrager, TF, October 4, 2006 (http:/ / www. toxicologysource. com/ whatistoxicology. html) [2] Ernest Hodgson (2010). " A Textbook of Modern Toxicology (http:/ / books. google. com/ books?id=tWVjQDxcd9IC& pg=PA10& dq& hl=en#v=onepage& q=& f=false)". John Wiley and Sons. p.10. ISBN 047046206X [3] Martin Levey (1966), Medieval Arabic Toxicology: The Book on Poisons of ibn Wahshiya and its Relation to Early Native American and Greek Texts [4] U.S. National Library of Medicine (http:/ / www. nlm. nih. gov/ visibleproofs/ galleries/ biographies/ orfila. html), Biography of Mathieu Joseph Bonaventure Orfila (1787–1853) [5] Wennig, Robert (Apr. 2009). "Back to the roots of modern analytical toxicology: Jean Servais Stas and the Bocarmé murder case". Drug Test Anal (England) 1 (4): 153–155. doi:10.1002/dta.32. PMID 20355192. [6] Paracelsus Dose Response in the Handbook of Pesticide Toxicology WILLIAM C KRIEGER / Academic Press Oct01 (http:/ / www. mindfully. org/ Pesticide/ Paracelsus-Dose-ToxicologyOct01. htm) [7] Afshari CA, Hamadeh HK (2004). Toxicogenomics: principles and applications. New York: Wiley-Liss. ISBN 0-471-43417-5. Review: Omenn GS (November 2004). "Toxicogenomics: Principles and Applications". Environ Health Perspect 112 (16): A962. PMC 1247673. External links • Toxicology (http://www.dmoz.org/Science/Biology/Toxicology//) at the Open Directory Project Compiled and Edited by Marc Imhotep Cray , M.D.
  • Medicine 100 Medicine Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness. Contemporary medicine applies health science, biomedical research, and medical technology to diagnose and treat injury and disease, typically through medication or surgery, but also through therapies as diverse as psychotherapy, external splints & traction, prostheses, biologics, ionizing radiation and others. The word medicine is derived from the Latin ars medicina, meaning the art of healing.[1] [2] Though medical technology and clinical expertise are pivotal to contemporary medicine, successful face-to-face relief of actual suffering continues to require the application of ordinary human feeling and compassion, known in English as bedside manner.[3] History Prehistoric medicine incorporated plants (herbalism), animal parts and Statue of Asclepius, the Greek God of medicine, minerals. In many cases these materials were used ritually as magical holding the symbolic Rod of Asclepius with its substances by priests, shamans, or medicine men. Well-known spiritual coiled serpent systems include animism (the notion of inanimate objects having spirits), spiritualism (an appeal to gods or communion with ancestor spirits); shamanism (the vesting of an individual with mystic powers); and divination (magically obtaining the truth). The field of medical anthropology examines the ways in which culture and society are organized around or impacted by issues of health, health care and related issues. Early records on medicine have been discovered from ancient Egyptian medicine, Babylonian medicine, Ayurvedic medicine (in the Indian subcontinent), classical Chinese medicine (predecessor to the modern traditional Chinese Medicine), and ancient Greek medicine and Roman medicine. The Egyptian Imhotep (3rd millennium BC) is the first physician in history known by name. Earliest records of dedicated hospitals come from Mihintale in Sri Lanka where evidence of dedicated medicinal treatment facilities for patients are found.[4] [5] The Indian surgeon Sushruta described numerous surgical operations, including the earliest forms of plastic surgery.[6] [7] Statuette of ancient Egyptian physician Imhotep, the first physician from antiquity known by name. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Medicine 101 An ancient Greek patient gets medical treatment: this aryballos (circa 480-470 BCE, now in Pariss Louvre Museum) probably contained healing oil The Greek physician Hippocrates, the "father of medicine",[9] [10] laid the foundation for a rational approach to medicine. Hippocrates introduced the Hippocratic Oath for physicians, which is still relevant and in use today, and was the first to categorize illnesses as acute, chronic, endemic and epidemic, and use terms such as, "exacerbation, relapse, resolution, crisis, paroxysm, peak, and convalescence".[11] [12] The Greek physician Galen was also one of the greatest surgeons of the ancient world and performed many audacious operations, including brain and eye surgeries. After the fall of the Western Roman Empire and the onset of the Early The Greek physician Hippocrates Middle Ages, the Greek tradition of medicine went into decline in Western (ca. 460 BCE – ca. 370 BCE), Europe, although it continued uninterrupted in the Eastern Roman (Byzantine) considered the father of Western [8] [9] Empire. medicine. After 750 CE, the Muslim Arab world had the works of Hippocrates, Galen and Sushruta translated into Arabic, and Islamic physicians engaged in some significant medical research. Notable Islamic medical pioneers include the polymath, Avicenna, who, along with Imhotep and Hippocrates, has also been called the "father of medicine".[13] [14] He wrote The Canon of Medicine, considered one of the most famous books in the history of medicine.[15] Others include Abulcasis,[16] Avenzoar,[17] Ibn al-Nafis,[18] and Averroes.[19] Rhazes[20] was one of first to question the Greek theory of humorism, which nevertheless remained influential in both medieval Western and medieval Islamic medicine.[21] The Islamic Bimaristan hospitals were an early example of public hospitals.[22] [23] However, the fourteenth and fifteenth century Black Death was just as devastating to the Middle East as to Europe, and it has even been argued that Western Europe was generally more effective in recovering from the pandemic than the Middle East.[24] In the early modern period, important early figures in medicine and anatomy emerged in Europe, including Gabriele Falloppio and William Harvey. The major shift in medical thinking was the gradual rejection, especially during the Black Death in the 14th and 15th centuries, of what may be called the traditional authority approach to science and medicine. This was the notion that because some prominent person in the past said something must be so, then that was the way it was, and anything one observed to the contrary was an anomaly (which was paralleled by a similar shift in European society in general - see Copernicuss rejection of Ptolemys theories on astronomy). Physicians like Vesalius improved upon or Compiled and Edited by Marc Imhotep Cray , M.D.
  • Medicine 102 disproved some of the theories from the past. Andreas Vesalius was an author of one of the most influential books on human anatomy, De humani corporis fabrica.[25] French surgeon Ambroise Paré is considered as one of the fathers of surgery. Bacteria and microorganisms were first observed with a microscope by Antonie van Leeuwenhoek in 1676, initiating the scientific field microbiology.[26] Partly based on the works by the Italian surgeon and anatomist Matteo Realdo Colombo the English physician William Harvey described the circulatory system.[27] Herman Boerhaave is sometimes referred to as a "father of physiology" due to his exemplary teaching in Leiden and textbook Institutiones medicae (1708). It is said that the 17th century French physician Pierre Fauchard started dentistry science as we know it today, and he has been named "the father of modern dentistry".[28] Modern scientific biomedical research (where results are testable and reproducible) began to replace early Western traditions based on herbalism, the Greek "four humours" and other such pre-modern notions. The modern era really began with Edward Jenners discovery of the smallpox vaccine at the end of the 18th century (inspired by the method of inoculation earlier practiced in Asia), Robert Kochs discoveries around 1880 of the transmission of disease by bacteria, and then the discovery of antibiotics around 1900. The post-18th century modernity period brought more groundbreaking researchers from Europe. From Germany and Austria, doctors Rudolf Virchow, Wilhelm Conrad Röntgen, Karl Landsteiner and Otto Loewi made notable contributions. In the United Kingdom, Alexander Fleming, Joseph Lister, Francis Crick and Florence Nightingale are considered important. Spanish doctor Santiago Ramón y Cajal is considered the father of modern neuroscience. From New Zealand and Australia came Maurice Wilkins, Howard Florey, and Frank Macfarlane Burnet. In the United States, William Williams Keen, William Coley, James D. Watson, Italy (Salvador Luria), Switzerland (Alexandre Yersin), Japan (Kitasato Shibasaburō), and France (Jean-Martin Charcot, Claude Bernard, Paul Broca and others did significant work). Russian Nikolai Korotkov also did significant work, as did Sir William Osler and Harvey Cushing. As science and technology developed, medicine became more reliant upon medications. Throughout history and in Europe right until the late 18th century, not only animal and plant products were used as medicine, but also human body parts and fluids.[29] Pharmacology developed from herbalism and many drugs are still derived from plants (atropine, ephedrine, warfarin, aspirin, digoxin, vinca alkaloids, taxol, hyoscine, etc.). Vaccines were discovered by Edward Jenner and Louis Pasteur. The first antibiotic was arsphenamine / Salvarsan discovered by Paul Ehrlich in 1908 after he observed that bacteria took up toxic dyes that human cells did not. The first major class of antibiotics was the sulfa drugs, derived by French chemists originally from azo dyes. Pharmacology has become increasingly sophisticated; modern biotechnology allows drugs targeted towards specific physiological processes to be developed, sometimes designed for compatibility with the body to reduce side-effects. Genomics and knowledge of human genetics is having some influence on medicine, as the causative genes of most monogenic genetic disorders have now been identified, and the development of techniques in molecular biology and genetics are influencing medical technology, practice and decision-making. Evidence-based medicine is a contemporary movement to establish the most effective algorithms of practice (ways of doing things) through the use of systematic reviews and meta-analysis. The movement is facilitated by modern global information science, which allows as much of the available evidence as possible to be collected and analyzed according to standard protocols that are then disseminated to healthcare providers. The Cochrane Collaboration leads this movement. A 2001 review of 160 Cochrane systematic reviews revealed that, according to two readers, 21.3% of the reviews concluded insufficient evidence, 20% concluded evidence of no effect, and 22.5% concluded positive effect.[30] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Medicine 103 Clinical practice In clinical practice, doctors personally assess patients in order to diagnose, treat, and prevent disease using clinical judgment. The doctor-patient relationship typically begins an interaction with an examination of the patients medical history and medical record, followed a medical interview[31] and a physical examination. Basic diagnostic medical devices (e.g. stethoscope, tongue depressor) are typically used. After examination for signs and interviewing for symptoms, the doctor may order medical tests (e.g. blood tests), take a biopsy, or prescribe pharmaceutical drugs or other therapies. Differential diagnosis methods help to rule out conditions based on the information provided. The Doctor, by Sir Luke Fildes (1891) During the encounter, properly informing the patient of all relevant facts is an important part of the relationship and the development of trust. The medical encounter is then documented in the medical record, which is a legal document in many jurisdictions.[32] Followups may be shorter but follow the same general procedure. The components of the medical interview[31] and encounter are: • Chief complaint (cc): the reason for the current medical visit. These are the symptoms. They are in the patients own words and are recorded along with the duration of each one. Also called presenting complaint. • History of present illness / complaint (HPI): the chronological order of events of symptoms and further clarification of each symptom. • Current activity: occupation, hobbies, what the patient actually does. • Medications (Rx): what drugs the patient takes including prescribed, over-the-counter, and home remedies, as well as alternative and herbal medicines/herbal remedies. Allergies are also recorded. • Past medical history (PMH/PMHx): concurrent medical problems, past hospitalizations and operations, injuries, past infectious diseases and/or vaccinations, history of known allergies. • Social history (SH): birthplace, residences, marital history, social and economic status, habits (including diet, medications, tobacco, alcohol). • Family history (FH): listing of diseases in the family that may impact the patient. A family tree is sometimes used. • Review of systems (ROS) or systems inquiry: a set of additional questions to ask, which may be missed on HPI: a general enquiry (have you noticed any weight loss, change in sleep quality, fevers, lumps and bumps? etc.), followed by questions on the bodys main organ systems (heart, lungs, digestive tract, urinary tract, etc.). The physical examination is the examination of the patient looking for signs of disease (Symptoms are what the patient volunteers, Signs are what the healthcare provider detects by examination). The healthcare provider uses the senses of sight, hearing, touch, and sometimes smell (e.g., in infection, uremia, diabetic ketoacidosis). Taste has been made redundant by the availability of modern lab tests. Four actions are taught as the basis of physical examination: inspection, palpation (feel), percussion (tap to determine resonance characteristics), and auscultation (listen). This order may be modified depending on the main focus of the examination (e.g., a joint may be examined by simply "look, feel, move". Having this set order is an educational tool that encourages practitioners to be systematic in their approach and refrain from using tools such as the stethoscope before they have fully evaluated the other modalities. The clinical examination involves study of: Compiled and Edited by Marc Imhotep Cray , M.D.
  • Medicine 104 • Vital signs including height, weight, body temperature, blood pressure, pulse, respiration rate, hemoglobin oxygen saturation • General appearance of the patient and specific indicators of disease (nutritional status, presence of jaundice, pallor or clubbing) • Skin • Head, eye, ear, nose, and throat (HEENT) • Cardiovascular (heart and blood vessels) • Respiratory (large airways and lungs) • Abdomen and rectum • Genitalia (and pregnancy if the patient is or could be pregnant) • Musculoskeletal (including spine and extremities) • Neurological (consciousness, awareness, brain, vision, cranial nerves, spinal cord and peripheral nerves) • Psychiatric (orientation, mental state, evidence of abnormal perception or thought). It is to likely focus on areas of interest highlighted in the medical history and may not include everything listed above. Laboratory and imaging studies results may be obtained, if necessary. The medical decision-making (MDM) process involves analysis and synthesis of all the above data to come up with a list of possible diagnoses (the differential diagnoses), along with an idea of what needs to be done to obtain a definitive diagnosis that would explain the patients problem. The treatment plan may include ordering additional laboratory tests and studies, starting therapy, referral to a specialist, or watchful observation. Follow-up may be advised. This process is used by primary care providers as well as specialists. It may take only a few minutes if the problem is simple and straightforward. On the other hand, it may take weeks in a patient who has been hospitalized with bizarre symptoms or multi-system problems, with involvement by several specialists. On subsequent visits, the process may be repeated in an abbreviated manner to obtain any new history, symptoms, physical findings, and lab or imaging results or specialist consultations. Institutions Contemporary medicine is in general conducted within health care systems. Legal, credentialing and financing frameworks are established by individual governments, augmented on occasion by international organizations. The characteristics of any given health care system have significant impact on the way medical care is provided. Advanced industrial countries (with the exception of the United States)[33] [34] and many developing countries provide medical services through a system of universal health care that aims to guarantee care for all through a single-payer health care system, or compulsory private or co-operative health insurance. This is intended to ensure that the entire population has access to medical care on the basis of need rather than ability to pay. Delivery may be via private medical practices or by state-owned hospitals and clinics, or by charities, most commonly by a combination of all three. Most tribal societies, but also some capitalist countries and the United States,[33] [34] provide no guarantee of healthcare for the population as a whole. In such societies, healthcare is available to those that can afford to pay for it or have self-insured it (either directly or as part of an employment contract) or who may be covered by care financed by the government or tribe directly. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Medicine 105 Transparency of information is another factor defining a delivery system. Access to information on conditions, treatments, quality, and pricing greatly affects the choice by patients/consumers and, therefore, the incentives of medical professionals. While the US healthcare system has come under fire for lack of openness,[35] new legislation may encourage greater openness. There is a perceived tension between the need for transparency on the one hand and such issues as patient confidentiality and the possible exploitation of information for commercial gain on the other. Delivery Provision of medical care is classified into primary, secondary, and tertiary care categories. Primary care medical services are provided by physicians, physician assistants, nurse practitioners, or other health professionals who have Modern drug ampoules first contact with a patient seeking medical treatment or care. These occur in physician offices, clinics, nursing homes, schools, home visits, and other places close to patients. About 90% of medical visits can be treated by the primary care provider. These include treatment of acute and chronic illnesses, preventive care and health education for all ages and both sexes. Secondary care medical services are provided by medical specialists in their offices or clinics or at local community hospitals for a patient referred by a primary care provider who first diagnosed or treated the patient. Referrals are made for those patients who required the expertise or procedures performed by specialists. These include both ambulatory care and inpatient services, emergency rooms, intensive care medicine, surgery services, physical therapy, labor and delivery, endoscopy units, diagnostic laboratory and medical imaging services, hospice centers, etc. Some primary care providers may also take care of hospitalized patients and deliver babies in a secondary care setting. Tertiary care medical services are provided by specialist hospitals or regional centers equipped with diagnostic and treatment facilities not generally available at local hospitals. These include trauma centers, burn treatment centers, advanced neonatology unit services, organ transplants, high-risk pregnancy, radiation oncology, etc. Modern medical care also depends on information - still delivered in many health care settings on paper records, but increasingly nowadays by electronic means. Branches Working together as an interdisciplinary team, many highly trained health professionals besides medical practitioners are involved in the delivery of modern health care. Examples include: nurses, emergency medical technicians and paramedics, laboratory scientists, pharmacists, physiotherapists, respiratory therapists, speech therapists, occupational therapists, radiographers, dietitians, and bioengineers. The scope and sciences underpinning human medicine overlap many other fields. Dentistry, while a separate discipline from medicine, is considered a medical field. A patient admitted to hospital is usually under the care of a specific team based on their main presenting problem, e.g., the Cardiology team, who then may interact with other specialties, e.g., surgical, radiology, to help diagnose or treat the main problem or any subsequent complications/developments. Physicians have many specializations and subspecializations into certain branches of medicine, which are listed below. There are variations from country to country regarding which specialties certain subspecialties are in. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Medicine 106 The main branches of medicine are: • Basic sciences of medicine; this is what every physician is educated in, and some return to in biomedical research. • Medical specialties • Interdisciplinary fields, where different medical specialties are mixed to function in certain occasions. Basic sciences • Anatomy is the study of the physical structure of organisms. In contrast to macroscopic or gross anatomy, cytology and histology are concerned with microscopic structures. • Biochemistry is the study of the chemistry taking place in living organisms, especially the structure and function of their chemical components. • Biomechanics is the study of the structure and function of biological systems by means of the methods of Mechanics. • Biostatistics is the application of statistics to biological fields in the broadest sense. A knowledge of biostatistics is essential in the planning, evaluation, and interpretation of medical research. It is also fundamental to epidemiology and evidence-based medicine. • Biophysics is an interdisciplinary science that uses the methods of physics and physical chemistry to study biological systems. • Cytology is the microscopic study of individual cells. • Embryology is the study of the early development of organisms. • Endocrinology is the study of hormones and their effect throughout the body of animals. • Epidemiology is the study of the demographics of disease processes, and includes, but is not limited to, the study of epidemics. • Genetics is the study of genes, and their role in biological inheritance. • Histology is the study of the structures of biological tissues by light microscopy, electron microscopy and immunohistochemistry. • Immunology is the study of the immune system, which includes the innate and adaptive immune system in humans, for example. • Medical physics is the study of the applications of physics principles in medicine. • Microbiology is the study of microorganisms, including protozoa, bacteria, fungi, and viruses. • Molecular biology is the study of molecular underpinnings of the process of replication, transcription and translation of the genetic material. • Neuroscience includes those disciplines of science that are related to the study of the nervous system. A main focus of neuroscience is the biology and physiology of the human brain and spinal cord. Some related clinical specialties include neurology, neurosurgery and psychiatry. • Nutrition science (theoretical focus) and dietetics (practical focus) is the study of the relationship of food and drink to health and disease, especially in determining an optimal diet. Medical nutrition therapy is done by dietitians and is prescribed for diabetes, cardiovascular diseases, weight and eating disorders, allergies, malnutrition, and neoplastic diseases. • Pathology as a science is the study of disease—the causes, course, progression and resolution thereof. • Pharmacology is the study of drugs and their actions. • Photobiology is the study of the interactions between non-ionizing radiation and living organisms. • Physiology is the study of the normal functioning of the body and the underlying regulatory mechanisms. • Radiobiology is the study of the interactions between ionizing radiation and living organisms. • Toxicology is the study of hazardous effects of drugs and poisons. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Medicine 107 Specialties In the broadest meaning of "medicine", there are many different specialties. In the UK, most specialities will have their own body or college (collectively known as the Royal Colleges, although currently not all use the term "Royal"), which have their own entrance exam. The development of a speciality is often driven by new technology (such as the development of effective anaesthetics) or ways of working (e.g., emergency departments), which leads to the desire to form a unifying body of doctors and thence the prestige of administering their own exam. Within medical circles, specialities usually fit into one of two broad categories: "Medicine" and "Surgery." "Medicine" refers to the practice of non-operative medicine, and most subspecialties in this area require preliminary training in "Internal Medicine". In the UK, this would traditionally have been evidenced by obtaining the MRCP (An exam allowing Membership of the Royal College of Physicians or the equivalent college in Scotland or Ireland). "Surgery" refers to the practice of operative medicine, and most subspecialties in this area require preliminary training in "General Surgery." (In the UK: Membership of the Royal College of Surgeons of England (MRCS).)There are some specialties of medicine that at the present time do not fit easily into either of these categories, such as radiology, pathology, or anesthesia. Most of these have branched from one or other of the two camps above - for example anaesthesia developed first as a faculty of the Royal College of Surgeons (for which MRCS/FRCS would have been required) before becoming the Royal College of Anaesthetists and membership of the college is by sitting the FRCA (Fellowship of the Royal College of Anesthetists). Surgery Surgical specialties employ operative treatment. In addition, surgeons must decide when an operation is necessary, and also treat many non-surgical issues, particularly in the surgical intensive care unit (SICU), where a variety of critical issues arise. Surgeons must also manage pre-operative, post-operative, and potential surgical candidates on the hospital wards. Surgery has many sub-specialties, including general surgery, cardiovascular surgery, colorectal surgery, neurosurgery, maxillofacial surgery, orthopedic surgery, otolaryngology, plastic surgery, oncologic surgery, transplant surgery, trauma surgery, urology, vascular surgery, and pediatric surgery. In some centers, anesthesiology is part of the division of surgery (for historical and logistical reasons), although it is not a surgical discipline. Other medical specialties may employ surgical procedures, such as ophthalmology and dermatology, but are not considered surgical sub-specialties per se. Surgical training in the U.S. requires a minimum of five years of residency after medical school. Sub-specialties of surgery often require seven or more years. In addition, fellowships can last an additional one to three years. Because post-residency fellowships can be competitive, many trainees devote two additional years to research. Thus in some cases surgical training will not finish until more than a decade after medical school. Furthermore, surgical training can be very difficult and time consuming. Medicine as a specialty Internal medicine is the medical specialty concerned with the diagnosis, management and nonsurgical treatment of unusual or serious diseases, either of one particular organ system or of the body as a whole. According to some sources, an emphasis on internal structures is implied.[36] In North America, specialists in internal medicine are commonly called "internists". Elsewhere, especially in Commonwealth nations, such specialists are often called physicians.[37] These terms, internist or physician (in the narrow sense, common outside North America), generally exclude practitioners of gynecology and obstetrics, pathology, psychiatry, and especially surgery and its subspecialities. Because their patients are often seriously ill or require complex investigations, internists do much of their work in hospitals. Formerly, many internists were not subspecialized; such general physicians would see any complex nonsurgical problem; this style of practice has become much less common. In modern urban practice, most internists are subspecialists: that is, they generally limit their medical practice to problems of one organ system or to one Compiled and Edited by Marc Imhotep Cray , M.D.
  • Medicine 108 particular area of medical knowledge. For example, gastroenterologists and nephrologists specialize respectively in diseases of the gut and the kidneys.[38] In Commonwealth and some other countries, specialist pediatricians and geriatricians are also described as specialist physicians (or internists) who have subspecialized by age of patient rather than by organ system. Elsewhere, especially in North America, general pediatrics is often a form of Primary care. There are many subspecialities (or subdisciplines) of internal medicine: • Cardiology • Critical care medicine • Endocrinology • Gastroenterology • Geriatrics • Haematology • Hepatology • Infectious diseases • Nephrology • Oncology • Pediatrics • Pulmonology/Pneumology/Respirology • Rheumatology • Sleep medicine Training in internal medicine (as opposed to surgical training), varies considerably across the world: see the articles on Medical education and Physician for more details. In North America, it requires at least three years of residency training after medical school, which can then be followed by a one to three year fellowship in the subspecialties listed above. In general, resident work hours in medicine are less than those in surgery, averaging about 60 hours per week in the USA. This difference does not apply in the UK where all doctors are now required by law to work less than 48 hours per week on average. Diagnostic specialties • Clinical laboratory sciences are the clinical diagnostic services that apply laboratory techniques to diagnosis and management of patients. In the United States, these services are supervised by a pathologist. The personnel that work in these medical laboratory departments are technically trained staff who do not hold medical degrees, but who usually hold an undergraduate medical technology degree, who actually perform the tests, assays, and procedures needed for providing the specific services. Subspecialties include Transfusion medicine, Cellular pathology, Clinical chemistry, Hematology, Clinical microbiology and Clinical immunology. • Pathology as a medical specialty is the branch of medicine that deals with the study of diseases and the morphologic, physiologic changes produced by them. As a diagnostic specialty, pathology can be considered the basis of modern scientific medical knowledge and plays a large role in evidence-based medicine. Many modern molecular tests such as flow cytometry, polymerase chain reaction (PCR), immunohistochemistry, cytogenetics, gene rearrangements studies and fluorescent in situ hybridization (FISH) fall within the territory of pathology. • Radiology is concerned with imaging of the human body, e.g. by x-rays, x-ray computed tomography, ultrasonography, and nuclear magnetic resonance tomography. • Nuclear medicine is concerned with studying human organ systems by administering radiolabelled substances (radiopharmaceuticals) to the body, which can then be imaged outside the body by a gamma camera or a PET scanner. Each radiopharmaceutical consists of two parts: a tracer that is specific for the function under study (e.g., neurotransmitter pathway, metabolic pathway, blood flow, or other), and a radionuclide (usually either a gamma-emitter or a positron emitter). There is a degree of overlap between nuclear medicine and radiology, as Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Medicine 109 evidenced by the emergence of combined devices such as the PET/CT scanner. • Clinical neurophysiology is concerned with testing the physiology or function of the central and peripheral aspects of the nervous system. These kinds of tests can be divided into recordings of: (1) spontaneous or continuously running electrical activity, or (2) stimulus evoked responses. Subspecialties include Electroencephalography, Electromyography, Evoked potential, Nerve conduction study and Polysomnography. Sometimes these tests are performed by techs without a medical degree, but the interpretation of these tests is done by a medical professional. Other major specialties The followings are some major medical specialties that do not directly fit into any of the above mentioned groups. • Anesthesiology (also known as anaesthetics): concerned with the perioperative management of the surgical patient. The anesthesiologists role during surgery is to prevent derangement in the vital organs (i.e. brain, heart, kidneys) functions and postoperative pain. Outside of the operating room, the anesthesiology physician also served the same function in the labor & delivery ward, and some are specialized in critical medicine. • Dermatology is concerned with the skin and its diseases. In the UK, dermatology is a subspecialty of general medicine. • Emergency medicine is concerned with the diagnosis and treatment of acute or life-threatening conditions, including trauma, surgical, medical, pediatric, and psychiatric emergencies. • Family medicine, family practice, general practice or primary care is, in many countries, the first port-of-call for patients with non-emergency medical problems. • Obstetrics and gynecology (often abbreviated as OB/GYN (American English) or Obs & Gynae (British English)) are concerned respectively with childbirth and the female reproductive and associated organs. Reproductive medicine and fertility medicine are generally practiced by gynecological specialists. • Medical Genetics is concerned with the diagnosis and management of hereditary disorders. • Neurology is concerned with diseases of the nervous system. In the UK, neurology is a subspecialty of general medicine. • Ophthalmology exclusively concerned with the eye and ocular adnexa, combining conservative and surgical therapy. • Pediatrics (AE) or paediatrics (BE) is devoted to the care of infants, children, and adolescents. Like internal medicine, there are many pediatric subspecialties for specific age ranges, organ systems, disease classes, and sites of care delivery. • Physical medicine and rehabilitation (or physiatry) is concerned with functional improvement after injury, illness, or congenital disorders. • Psychiatry is the branch of medicine concerned with the bio-psycho-social study of the etiology, diagnosis, treatment and prevention of cognitive, perceptual, emotional and behavioral disorders. Related non-medical fields include psychotherapy and clinical psychology. • Preventive medicine is the branch of medicine concerned with preventing disease. • Community health or public health is an aspect of health services concerned with threats to the overall health of a community based on population health analysis. • Occupational medicines principal role is the provision of health advice to organizations and individuals to ensure that the highest standards of health and safety at work can be achieved and maintained. • Aerospace medicine deals with medical problems related to flying and space travel. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Medicine 110 Interdisciplinary fields Some interdisciplinary sub-specialties of medicine include: • Addiction medicine deals with the treatment of addiction. • Medical ethics deals with ethical and moral principles that apply values and judgments to the practice of medicine. • Biomedical Engineering is a field dealing with the application of engineering principles to medical practice. • Clinical pharmacology is concerned with how systems of therapeutics interact with patients. • Conservation medicine studies the relationship between human and animal health, and environmental conditions. Also known as ecological medicine, environmental medicine, or medical geology. • Disaster medicine deals with medical aspects of emergency preparedness, disaster mitigation and management. • Diving medicine (or hyperbaric medicine) is the prevention and treatment of diving-related problems. • Evolutionary medicine is a perspective on medicine derived through applying evolutionary theory. • Forensic medicine deals with medical questions in legal context, such as determination of the time and cause of death. • Gender-based medicine studies the biological and physiological differences between the human sexes and how that affects differences in disease. • Hospice and Palliative Medicine is a relatively modern branch of clinical medicine that deals with pain and symptom relief and emotional support in patients with terminal illnesses including cancer and heart failure. • Hospital medicine is the general medical care of hospitalized patients. Physicians whose primary professional focus is hospital medicine are called hospitalists in the USA. • Laser medicine involves the use of lasers in the diagnostics and/or treatment of various conditions. • Medical humanities includes the humanities (literature, philosophy, ethics, history and religion), social science (anthropology, cultural studies, psychology, sociology), and the arts (literature, theater, film, and visual arts) and their application to medical education and practice. • Medical informatics, medical computer science, medical information and eHealth are relatively recent fields that deal with the application of computers and information technology to medicine. • Nosology is the classification of diseases for various purposes. • Nosokinetics is the science/subject of measuring and modelling the process of care in health and social care systems. • Pain management (also called pain medicine, or algiatry) is the medical discipline concerned with the relief of pain. • Pharmacogenomics is a form of individualized medicine. • Sexual medicine is concerned with diagnosing, assessing and treating all disorders related to sexuality. • Sports medicine deals with the treatment and preventive care of athletes, amateur and professional. The team includes specialty physicians and surgeons, athletic trainers, physical therapists, coaches, other personnel, and, of course, the athlete. • Therapeutics is the field, more commonly referenced in earlier periods of history, of the various remedies that can be used to treat disease and promote health [39]. • Travel medicine or emporiatrics deals with health problems of international travelers or travelers across highly different environments. • Urgent care focuses on delivery of unscheduled, walk-in care outside of the hospital emergency department for injuries and illnesses that are not severe enough to require care in an emergency department. In some jurisdictions this function is combined with the emergency room. • Veterinary medicine; veterinarians apply similar techniques as physicians to the care of animals. • Wilderness medicine entails the practice of medicine in the wild, where conventional medical facilities may not be available. • Many other health science fields, e.g. dietetics Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Medicine 111 Education Medical education and training varies around the world. It typically involves entry level education at a university medical school, followed by a period of supervised practice or internship, and/or residency. This can be followed by postgraduate vocational training. A variety of teaching methods have been employed in medical education, still itself a focus of active research. Many regulatory authorities require continuing medical education, since knowledge, techniques and medical technology continue to evolve at a rapid rate. Painted by Toulouse-Lautrec in the year of his own death: an examination in the Paris faculty of Legal controls medicine, 1901 In most countries, it is a legal requirement for a medical doctor to be licensed or registered. In general, this entails a medical degree from a university and accreditation by a medical board or an equivalent national organization, which may ask the applicant to pass exams. This restricts the considerable legal authority of the medical profession to physicians that are trained and qualified by national standards. It is also intended as an assurance to patients and as a safeguard against charlatans that practice inadequate medicine for personal gain. While the laws generally require medical doctors to be trained in "evidence based", Western, or Hippocratic Medicine, they are not intended to discourage different paradigms of health. Doctors who are negligent or intentionally harmful in their care of patients can face charges of medical malpractice and be subject to civil, criminal, or professional sanctions. Controversy The Catholic social theorist Ivan Illich subjected contemporary western medicine to detailed attack in his Medical Nemesis, first published in 1975. He argued that the medicalization in recent decades of so many of lifes vicissitudes — birth and death, for example — frequently caused more harm than good and rendered many people in effect lifelong patients. He marshalled a body of statistics to show what he considered the shocking extent of post-operative side-effects and drug-induced illness in advanced industrial society. He was the first to introduce to a wider public the notion of iatrogenesis.[40] Others have since voiced similar views, but none so trenchantly, perhaps, as Illich.[41] Through the course of the twentieth century, healthcare providers focused increasingly on the technology that was enabling them to make dramatic improvements in patients health. The ensuing development of a more mechanistic, detached practice, with the perception of an attendant loss of patient-focused care, known as the medical model of health, led to criticisms that medicine was neglecting a holistic model. The inability of modern medicine to properly address some common complaints continues to prompt many people to seek support from alternative medicine. Although most alternative approaches lack scientific validation, some, notably acupuncture for some conditions and certain herbs, are backed by evidence.[42] Medical errors and overmedication are also the focus of complaints and negative coverage. Practitioners of human factors engineering believe that there is much that medicine may usefully gain by emulating concepts in aviation safety, where it is recognized that it is dangerous to place too much responsibility on one "superhuman" individual and expect him or her not to make errors. Reporting systems and checking mechanisms are becoming more common in identifying sources of error and improving practice. Clinical versus statistical, algorithmic diagnostic methods were famously examined in psychiatric practice in a 1954 book by Paul E. Meehl, which found statistical methods superior.[43] A 2000 meta-analysis comparing these methods in both psychology and medicine found that statistical or "mechanical" diagnostic methods were, in general, although not always, superior.[43] Compiled and Edited by Marc Imhotep Cray , M.D.
  • Medicine 112 Disparities in quality of care given are often an additional cause of controversy.[44] For example, elderly mentally ill patients received poorer care during hospitalization in a 2008 study.[45] Rural poor African-American men were used in a study of syphilis that denied them basic medical care. Honors and awards The highest honor awarded in medicine is the Nobel Prize in Medicine, awarded since 1901 by the Royal Swedish Academy of Sciences. Patronage There is a number of patron saints for physicians, the most important of whom are Saint Luke the Evangelist the physician and disciple of Christ, Saints Cosmas and Damian (3rd-century physicians from Syria), and Saint Pantaleon (4th-century physician from Nicomedia). Archangel Raphael is also considered a patron saint of physicians. The patron saints for surgeons are Saint Luke the Evangelist, the physician and disciple of Christ, Saints Cosmas and Damian (3rd-century physicians from Syria), Saint Quentin (3rd-century saint from France), Saint Foillan (7th-century saint from Ireland), and Saint Roch (14th-century saint from France). References [1] Etymology: Latin: medicina, from ars medicina "the medical art," from medicus "physician."( Etym.Online (http:/ / www. etymonline. com/ index. php?term=medicine)) Cf. mederi "to heal," etym. "know the best course for," from PIE base *med- "to measure, limit. Cf. Greek medos "counsel, plan," Avestan vi-mad "physician") [2] "Medicine" (http:/ / www. etymonline. com/ index. php?term=medicine) Online Etymology Dictionary [3] Culliford Larry (December 2002). "Spirituality and clinical care (Editorial)". British Medical Journal 325 (7378): 1434–5. doi:10.1136/bmj.325.7378.1434. PMC 1124896. PMID 12493652. [4] Prof. Arjuna Aluvihare, "Rohal Kramaya Lovata Dhayadha Kale Sri Lankikayo" Vidhusara Science Magazine, Nov. 1993. [5] Resource Mobilization in Sri Lankas Health Sector (http:/ / www. hsph. harvard. edu/ ihsg/ publications/ pdf/ No-42. PDF) - Rannan-Eliya, Ravi P. & De Mel, Nishan, Harvard School of Public Health & Health Policy Programme, , February 1997, Page 19. Accessed 2008-02-22. [6] A. Singh and D. Sarangi (2003). "We need to think and act", Indian Journal of Plastic Surgery. [7] H. W. Longfellow (2002). "History of Plastic Surgery in India", Journal of Postgraduate Medicine. [8] Useful known and unknown views of the father of modern medicine, Hippocrates and his teacher Democritus. (http:/ / www. ncbi. nlm. nih. gov/ pubmed/ 18392218), U.S. National Library of Medicine [9] The father of modern medicine: the first research of the physical factor of tetanus (http:/ / www. blackwellpublishing. com/ eccmid16/ abstract. asp?id=50854), European Society of Clinical Microbiology and Infectious Diseases [10] Grammaticos P.C. & Diamantis A. (2008). "Useful known and unknown views of the father of modern medicine, Hippocrates and his teacher Democritus". Hell J Nucl Med 11 (1): 2–4. PMID 18392218. [11] Garrison 1966, p. 97 [12] Martí-Ibáñez 1961, p. 90 [13] Becka J (1980). "The father of medicine, Avicenna, in our science and culture: Abu Ali ibn Sina (980-1037) (Czech title: Otec lékarů Avicenna v nasí vĕdĕ a kulture)" (in Czech). Cas Lek Cesk 119 (1): 17–23. PMID 6989499. [14] Medical Practitioners (https:/ / eee. uci. edu/ clients/ bjbecker/ PlaguesandPeople/ lecture5. html) [15] ""The Canon of Medicine" (work by Avicenna)" (http:/ / www. britannica. com/ eb/ topic-92902/ The-Canon-of-Medicine). Encyclopædia Britannica. 2008. . Retrieved 2008-06-11. [16] Ahmad, Z. (St Thomas Hospital) (2007). "Al-Zahrawi - The Father of Surgery". ANZ Journal of Surgery 77 (Suppl. 1): A83. doi:10.1111/j.1445-2197.2007.04130_8.x [17] Rabie E. Abdel-Halim (2006), "Contributions of Muhadhdhab Al-Deen Al-Baghdadi to the progress of medicine and urology", Saudi Medical Journal 27 (11): 1631-1641. [18] Chairmans Reflections (2004), "Traditional Medicine Among Gulf Arabs, Part II: Blood-letting", Heart Views 5 (2): 74-85 [80]. [19] Martín-Araguz A, Bustamante-Martínez C, Fernández-Armayor Ajo V, Moreno-Martínez JM (2002-05-01—15). "Neuroscience in al-Andalus and its influence on medieval scholastic medicine" (in Spanish). Revista de neurología 34 (9): 877–892. PMID 12134355. [20] David W. Tschanz, PhD (2003), "Arab(?) Roots of European Medicine", Heart Views 4 (2). [21] On the dominance of the Greek humoral theory, which was the basis for the practice of bloodletting, in medieval Islamic medicine see Peter E. Pormann and E. Savage Smith,Medieval Islamic medicine, Georgetown University, Washington DC, 2007 p. 10, 43-45. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Medicine 113 [22] Micheau, Françoise. "The Scientific Institutions in the Medieval Near East". pp. 991–2, in (Morelon & Rashed 1996, pp. 985–1007) [23] Peter Barrett (2004), Science and Theology Since Copernicus: The Search for Understanding, p. 18, Continuum International Publishing Group, ISBN 056708969X. [24] Michael Dols has shown that the Black Death was much more commonly believed by European authorities than by Middle Eastern authorities to be contagious; as a result, flight was more commonly counseled, and in urban Italy quarantines were organized on a much wider level than in urban Egypt or Syria (The Black Death in the Middle East Princeton, 1977, p. 119; 285-290. [25] Page through a virtual copy of Vesaliuss De Humanis Corporis Fabrica (http:/ / archive. nlm. nih. gov/ proj/ ttp/ books. htm) [26] Madigan M, Martinko J (editors) (2006). Brock Biology of Microorganisms (11th ed.). Prentice Hall. ISBN 0-13-144329-1. [27] Zimmer, Carl. 2004. Soul Made Flesh: The Discovery of the Brain - and How It Changed the World. New York: Free Press. [28] " Pierre Fauchard: the Father of Modern Dentistry (http:/ / www. nature. com/ bdj/ journal/ v201/ n12/ full/ 4814350a. html)". British Dental Journal 201, 779 - 781 (2006) [29] Peter Cooper, "Medicinal properties of body parts", The Pharmaceutical Journal, 18/25 December 2004, Vol. 273 / No 7330, pp. 900-902 http:/ / www. pharmj. com/ editorial/ 20041218/ christmas/ p900bodyparts. html [30] Ezzo J, Bausell B, Moerman DE, Berman B, Hadhazy V (2001). "Reviewing the reviews. How strong is the evidence? How clear are the conclusions?". Int J Technol Assess Health Care 17 (4): 457–466. PMID 11758290. [31] Coulehan JL, Block MR (2005). The Medical Interview: Mastering Skills for Clinical Practice (5th ed.). F. A. Davis. ISBN 0-8036-1246-X. OCLC 232304023. [32] Addison K, Braden JH, Cupp JE, Emmert D, et al. (AHIMA e-HIM Work Group on the Legal Health Record) (September 2005). "Update: Guidelines for Defining the Legal Health Record for Disclosure Purposes" (http:/ / library. ahima. org/ xpedio/ groups/ public/ documents/ ahima/ bok1_027921. hcsp?dDocName=bok1_027921). Journal of AHIMA 78 (8): 64A–G. PMID 16245584. . [33] Insuring Americas Health: Principles and Recommendations (http:/ / www. iom. edu/ Reports/ 2004/ Insuring-Americas-Health-Principles-and-Recommendations. aspx), Institute of Medicine at the National Academies of Science, 2004-01-14 [34] "The Case For Single Payer, Universal Health Care For The United States" (http:/ / cthealth. server101. com/ the_case_for_universal_health_care_in_the_united_states. htm). Cthealth.server101.com. . Retrieved 2009-05-04. [35] Martin Sipkoff (January 2004). "Transparency called key to uniting cost control, quality improvement" (http:/ / www. managedcaremag. com/ archives/ 0401/ 0401. forum. html). Managed Care. . [36] " internal medicine (http:/ / www. mercksource. com/ pp/ us/ cns/ cns_hl_dorlands_split. jsp?pg=/ ppdocs/ us/ common/ dorlands/ dorland/ five/ 000063883. htm)" at Dorlands Medical Dictionary [37] H.W. Fowler. (1994). A Dictionary of Modern English Usage (Wordsworth Collection) (Wordsworth Collection). NTC/Contemporary Publishing Company. ISBN 1853263184. [38] "The Royal Australasian College of Physicians: What are Physicians?" (http:/ / web. archive. org/ web/ 20080306053048/ http:/ / www. racp. edu. au/ index. cfm?objectid=49EF1EB5-2A57-5487-D74DBAFBAE9143A3). Royal Australasian College of Physicians. Archived from the original (http:/ / www. racp. edu. au/ index. cfm?objectid=49EF1EB5-2A57-5487-D74DBAFBAE9143A3) on 2008-03-06. . Retrieved 2008-02-05. [39] http:/ / www. britannica. com/ eb/ article-9106176?query=Therapeutics& ct= [40] Illich Ivan (1974). Medical Nemesis. London: Calder & Boyars. ISBN 0714510963. OCLC 224760852. [41] Postman Neil (1992). Technopoly: The Surrender of Culture to Technology. New York: Knopf. OCLC 24694343. [42] The HealthWatch Award 2005: (http:/ / www. healthwatch-uk. org/ awardwinners/ edzardernst. html) Prof. Edzard Ernst, Complementary medicine: the good the bad and the ugly. Retrieved 5 August 2006. [43] Grove WH, Zald DH, Lebow BS, Snitz BE, Nelson C. (2000). "Clinical versus mechanical prediction: A meta-analysis" (http:/ / www. psych. umn. edu/ faculty/ grove/ 096clinicalversusmechanicalprediction. pdf) (w). Psychological Assessment 12 (1): 19–30. doi:10.1037/1040-3590.12.1.19. PMID 10752360. . [44] "Eliminating Health Disparities" (http:/ / www. ama-assn. org/ ama/ pub/ physician-resources/ public-health/ eliminating-health-disparities. shtml). American Medical Association. . [45] "Mental Disorders, Quality of Care, and Outcomes Among Older Patients Hospitalized With Heart Failure" (http:/ / archpsyc. ama-assn. org/ cgi/ content/ abstract/ 65/ 12/ 1402). . Compiled and Edited by Marc Imhotep Cray , M.D.
  • Medical history 114 Medical history The medical history or anamnesis[1] [2] (abbr. Hx) of a patient is information gained by a physician by asking specific questions, either of the patient or of other people who know the person and can give suitable information (in this case, it is sometimes called heteroanamnesis), with the aim of obtaining information useful in formulating a diagnosis and providing medical care to the patient. The medically relevant complaints reported by the patient or others familiar with the patient are referred to as symptoms, in contrast with clinical signs, which are ascertained by direct examination on the part of medical personnel. Most health encounters will result in some form of history being taken. Medical histories vary in their depth and focus. For example, an ambulance paramedic would typically limit his history to important details, such as name, history of presenting complaint, allergies, etc. In contrast, a psychiatric history is frequently lengthy and in depth, as many details about the patients life are relevant to formulating a management plan for a psychiatric illness. The information obtained in this way, together with clinical examination, enables the physician to form a diagnosis and treatment plan. If a diagnosis cannot be made, a provisional diagnosis may be formulated, and other possibilities (the differential diagnoses) may be added, listed in order of likelihood by convention. The treatment plan may then include further investigations to clarify the diagnosis. Process A practitioner typically asks questions to obtain the following information about the patient: • Identification and demographics: name, age, height, weight. • The "chief complaint (CC)" - the major health problem or concern, and its time course (e.g. chest pain for past 4 hours). • History of the present illness (HPI) - details about the complaints, enumerated in the CC. (Also often called History of presenting complaint or HPC.) • Past Medical History (PMH) (including major illnesses, any previous surgery/operations, any current ongoing illness, e.g. diabetes). • Review of systems (ROS) Systematic questioning about different organ systems • Family diseases - especially those relevant to the patients chief complaint. • Childhood diseases - this is very important in pediatrics. Example • Social history (medicine) - including living arrangements, occupation, marital status, number of children, drug use (including tobacco, alcohol, other recreational drug use), recent foreign travel, and exposure to environmental pathogens through recreational activities or pets. • Regular and acute medications (including those prescribed by doctors, and others obtained over-the-counter or alternative medicine) • Allergies - to medications, food, latex, and other environmental factors • Sexual history, obstetric/gynecological history, and so on, as appropriate. History-taking may be comprehensive history taking (a fixed and extensive set of questions are asked, as practiced only by health care students such as medical students, physician assistant students, or nurse practitioner students) or iterative hypothesis testing (questions are limited and adapted to rule in or out likely diagnoses based on information already obtained, as practiced by busy clinicians). Computerized history-taking could be an integral part of clinical Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Medical history 115 decision support systems. Review of systems Whatever system a specific condition may seem restricted to, it may be reasonable to review all the other systems in a comprehensive history. Inhibiting factors Factors that inhibit a proper medical history taking include physical inability of the patient to communicate with the physician, such as unconsciousness and communication disorders. In such cases, it may be necessary to perform a so called heteroanamnesis of other people who know the person and can give suitable information, which, however, generally is more limited than a direct anamnesis. Medical history taking may also be impaired by various factors impeding a proper doctor-patient relationship, such as transitions to physicians that are and unfamiliar to the patient. History taking of issues related to sexual or reproductive medicine may be inhibited by a reluctance of the patient to disclose intimate or uncomfortable information. Even if such an issue is on the patients mind, he or she often doesnt start talking about such an issue without the physician initiating the subject by a specific question about sexual or reproductive health.[3] Some familiarity with the doctor generally makes it easier for patients to talk about intimate issues such as sexual subjects, but for some patients, a very high degree of familiarity may make the patient reluctant to reveal such intimate issues.[3] When visiting a health provider about sexual issues, having both partners of a couple present is often necessary, and is typically a good thing, but may also prevent the disclosure of certain subjects, and, according to one report, increases the stress level.[3] References [1] Georg Klemperer (1904). The Elements of clinical diagnosis (http:/ / books. google. com/ books?vid=OCLC13821145& id=sePtO3Y5EMwC& pg=PA4& lpg=PA4& dq=anamnesis). Macmillan. . [2] Plinio Prioreschi (1998). Roman medicine (http:/ / books. google. com/ books?vid=ISBN1888456035& id=H3ZaIYAaOSQC& pg=PA489& lpg=PA489& dq=anamnesis+ "medical+ history"& sig=INJCevRz3As9iZb3jKjJz6tmvhk). 3 (reprint ed.). Horatius Press. ISBN 9781888456035. . [3] The Cringe Report (http:/ / www. medscape. com/ viewarticle/ 743689_3) By Susan Quilliam. Posted: 06/28/2011; J Fam Plann Reprod Health Care. 2011;37(2):110-112. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Chief complaint 116 Chief complaint The Chief Complaint formally known as CC in the medical field, or termed Presenting Complaint (PC) in the UK, is a concise statement describing the symptom, problem, condition, diagnosis, physician recommended return, or other factor that is the reason for a medical encounter.[1] The patients initial comments to a physician, nurse, or other health care professional help form the differential diagnosis. In some instances, the nature of a patients chief complaint may determine whether or not services are covered by medical or vision insurance.[2] Medical students are advised to use open-ended questions in order to obtain the presenting complaint.[3] Prevalence The collection of chief complaint data may be useful in addressing public health issues.[4] Certain complaints are more common in certain settings and among certain populations. Fatigue has been reported as one of the ten most common reasons for seeing a physician.[5] In acute care settings, such as emergency rooms, reports of chest pain are among the most common chief complaints.[6] The most common complaint in ERs has been reported to be abdominal pain.[7] Among nursing home residents seeking treatment at ERs, respiratory symptoms, altered mental status, gastrointestinal symptoms, and falls are the most commonly reported.[8] [9] CMS required history elements Type of history CC HPI ROS Past, family, and/or social Problem focused Required Brief N/A N/A Expanded problem focused Required Brief Problem pertinent N/A Detailed Required Extended Extended Pertinent Comprehensive Required Extended Complete Complete References [1] http:/ / www. usc. edu/ health/ uscp/ compliance/ tm6. html#6 [2] Optometric Management (http:/ / www. optometric. com/ article. aspx?article=71722) [3] sBMJ | Taking a history: Introduction and the presenting complaint (http:/ / www. studentbmj. com/ issues/ 05/ 09/ education/ 314. php) [4] http:/ / www. cdc. gov/ PHIN/ architecture/ implementation_guides/ Healthcare%20Related/ PHIN_Healthcare_Encounter_Chief_Complaint_v231. pdf [5] Nelson E, Kirk J, McHugo G, Douglass R, Ohler J, Wasson J, Zubkoff M. (Summer 1987). "Chief complaint fatigue: a longitudinal study from the patients perspective". Fam Pract Res J. 6 (4): 175–88. PMID 3455125. [6] Emergency Medicine (http:/ / www. emedmag. com/ html/ pre/ cov/ covers/ 021504. asp) [7] Graff LG 4th, Robinson D. (Feb 2001). "Abdominal pain and emergency department evaluation" (http:/ / cat. inist. fr/ ?aModele=afficheN& cpsidt=917754). Emerg Med Clin North Am. 19 (1): 123–36. doi:10.1016/S0733-8627(05)70171-1. PMID 11214394. . [8] Ackermann RJ, Kemle KA, Vogel RL, Griffin RC Jr (Jun 1998). "Emergency department use by nursing home residents". Ann Emerg Med. 31 (6): 749–57. doi:10.1016/S0196-0644(98)70235-5. PMID 9624316. [9] "www.cms.gov" (http:/ / www. cms. gov/ MLNProducts/ downloads/ eval_mgmt_serv_guide-ICN006764. pdf). . Retrieved 2011-02-27. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Chief complaint 117 External links • MedEd at Loyola ipm/comphx1/sld003.htm (http://www.meddean.luc.edu/Lumen/MedEd/ipm/comphx1/ sld003.htm) • Chief+complaint (http://www.emedicinehealth.com/script/main/srchcont_dict.asp?src=Chief+complaint) at eMedicine Dictionary History of the present illness In a medical encounter, a history of the present illness (abbreviated HPI)[1] (termed history of presenting complaint (HPC) in the UK) refers to a detailed interview prompted by the chief complaint or presenting symptom (for example, pain). Questions to include Different sources include different questions to be asked while conducting an HPI. Several acronyms have been developed to categorize the appropriate questions to include. The Centers for Medicare and Medicaid Services has published criteria for what constitutes a reimbursable HPI. A "brief HPI" constitutes one to three of these elements. A "extended HPI" includes four or more of these elements.[2] [3] CMS [4] [5] [8] [9] [10] "OPQRST" "CLEARAST" "LIQOR AAA" "SCHOLAR" [6] [7] or "PQRST" ("S" = Symptoms) location "R": Region and Radiation "L": Location "L": Location "L:" Location quality "Q": Quality of the pain "C": Character "Q": Quality "C:" Characteristics "R": Radiation "R": Radiation see above severity "S": Severity "S": Severity "I": Intensity see above duration "O": Onset "T": Time frame "O": Onset "O:" Onset "H:" History timing "T": Time see above see above see above context modifying factors "P": Provocation or Palliation "E": Exacerbation "A": Aggravating factors "A:" Aggravating factors "A": Alleviation "A": Alleviating factors "R:" Remitting factors associated signs & symptoms "A": associated symptoms "A": Associated symptoms see above Medicare definitions Compiled and Edited by Marc Imhotep Cray , M.D.
  • History of the present illness 118 [11] CMS required history elements Type of history CC HPI ROS Past, family, and/or social Problem focused Required Brief N/A N/A Expanded problem focused Required Brief Problem pertinent N/A Detailed Required Extended Extended Pertinent Comprehensive Required Extended Complete Complete References [1] Adler HM (1997). "The history of the present illness as treatment: whos listening, and why does it matter?". J Am Board Fam Pract 10 (1): 28–35. PMID 9018660. [2] Evaluation and Management Coding and Electronic Health Records (http:/ / www. emrconsultant. com/ emr_EMcoding. php) [3] http:/ / www. usc. edu/ health/ uscp/ compliance/ tm6. html#6 [4] Medical Assessment (http:/ / hopperinstitute. com/ emt_medical. html) [5] Learning To Perform a Medical Assessment – Part 1: Quick Medical Assessment (http:/ / www. alpharubicon. com/ med/ medaccesshaumanao. htm) [6] WEMSI - Assessment by PQRST (http:/ / www. wemsi. org/ pqrst. html) [7] Department of Medicine Home Page (http:/ / www. usask. ca/ medicine/ medicine/ clsc. htm) [8] Dartmouth Medicine Magazine :: Student Notebook (http:/ / dartmed. dartmouth. edu/ spring06/ html/ student_notebook. php) [9] HPI (history of present illness) (http:/ / www. aippg. net/ forum/ viewtopic. php?p=71106) [10] Buring SM, Kirby J, Conrad WF (February 2007). "A structured approach for teaching students to counsel self-care patients". Am J Pharm Educ 71 (1): 8. PMC 1847542. PMID 17429508. [11] "www.cms.gov" (http:/ / www. cms. gov/ MLNProducts/ downloads/ eval_mgmt_serv_guide-ICN006764. pdf). . Retrieved 2011-02-27. External links • Overview at medicine.ucsd.edu (http://medicine.ucsd.edu/clinicalmed/history.htm) • Overview at medinfo.ufl.edu (http://medinfo.ufl.edu/year1/bcs96/interv/hpians.html) Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Past medical history 119 Past medical history In a medical encounter, a past medical history (abbreviated PMH),[1] is the total sum of a patients health status prior to the presenting problem. Questions to include Different sources include different questions to be asked while conducting a PMH, but in general, they include the following: • General state of health: e.g. excellent, good, fair, poor. Note any significant change from previous state. • Past illnesses: e.g. cancer, heart disease, hypertension, diabetes. • Hospitalizations: including all medical, surgical, and psychiatric hospitalizations. Note the date, reason, duration for the hospitalization. • Injuries, or accidents: note the type and date of injury. • Surgeries: note the type of procedure, date, hospital, surgeon, and any complications. • Current medications: note name, dosage, frequency of any medication, including any over-the-counter medications and herbal remedies. Note whether patient is taking the medications according to the prescribed instructions. • Allergies: note any environmental, food, or drug allergies, as well as the specific type of reaction, e.g. anaphylaxis, rash, itching. • Immunizations: take a careful record of all immunizations, including tetanus, diphtheria, pertussis, polio, Hepatitis B, measles, mumps, rubella, Haemophilus influenzae type B, influenza. • Substance abuse: note any alcohol, tobacco, and illicit drug use, include type, amount, and duration, as well as any past treatment or drug rehabilitation. • Diet: ask about everything the patient has eaten the day before and for the past week. Note the type of food consumed and do a nutritional status assessment. • Sleep: a useful mnemonic for sleep patterns is BEARS, for Bedtime problems (e.g. snoring, sleep apnea, or nightmares), Excessive daytime sleepiness, Awakenings at night, Regularity and duration of sleep, Snoring.[2] • Alternative therapies: e.g. acupuncture, massage, herbal medicine, vitamins, chiropractice. • Obstetric/Gynecologic history (if female): include total number of pregnancies, whether they are full term, preterm, miscarriages, abortions, living, as well as any complications. Include menopause and date. Include sexual history and any history of sexually transmitted diseases. Acronyms Several acronyms have been developed to categorize the appropriate questions to include: • "MMASH", for Medical Illnesses, Medications, Allergies, Surgeries, Hospitalizations.[3] • "PAM HUGS FOSS",[4] for • Previous presence of the symptom (same chief complaint) • Allergies (drugs, foods, chemicals, dust, etc.) • Medicines (any drugs the patient used) • Hospitalization for any illness in the past • Urinary changes (especially if diabetic or elderly) • Gastrointestinal complains (diet changes, bowel movements, etc.) • Sleep pattern (waking up/going to sleep, etc.) • Family history (similar chief complaints/serious illness) • OB/GYN history (LMP, abortions, etc.) Compiled and Edited by Marc Imhotep Cray , M.D.
  • Past medical history 120 • Sexual habits (active/preferences/STD, etc.) • Social life (job/house/smoking/alcohol, etc.) Medicare definitions The Centers for Medicare and Medicaid Services[5] has published criteria for what constitutes a reimbursable PMH. A PMH is considered one of three elements of the "Past, Family, and Social History" (abbreviated as PFSH):[6] • Past medical history: "the patients past experiences with illnesses, operations, injuries and treatments"; • Family history: "a review of medical events in the patients family, including diseases which may be hereditary or place the patient at risk"; • Social history: "an age-appropriate review of past and current activities". A pertinent PFSH consists of at least one of the three components; a full PFSH consists of two or three components for an established patient, or all three components for a new patient visit.[7] [8] CMS required history elements Type of history CC HPI ROS Past, family, and/or social Problem focused Required Brief N/A N/A Expanded problem focused Required Brief Problem pertinent N/A Detailed Required Extended Extended Pertinent Comprehensive Required Extended Complete Complete References [1] Swartz, Mark (2002). Textbook of Physical Diagnosis: History and Examination. Philadelphia: Saunders. pp. 19–23. ISBN 1-4160-2405-0. [2] http:/ / www. sciencedaily. com/ releases/ 2004/ 09/ 040907083159. htm Science News: Enlarged Tonsils, Adenoids And Allergies May Affect A Childs Bite, Facial Appearance And/Or Behavior [3] Useful Acronyms for Facilitators and Students (http:/ / www. oucom. ohiou. edu/ FD/ Useful Acronyms for Facilitators and Students1. htm) [4] HPI (history of present illness) (http:/ / www. aippg. net/ forum/ viewtopic. php?p=71106) [5] http:/ / www. cms. hhs. gov/ [6] Evaluation and Management Coding and Electronic Health Records (http:/ / www. emrconsultant. com/ emr_EMcoding. php) [7] Evaluation and Management Coding and Electronic Health Records (http:/ / www. emrconsultant. com/ emr_EMcoding. php) [8] "www.cms.gov" (http:/ / www. cms. gov/ MLNProducts/ downloads/ eval_mgmt_serv_guide-ICN006764. pdf). . Retrieved 2011-02-27. External links • Overview at medinfo.ufl.edu (http://medinfo.ufl.edu/year1/bcs96/interv/pmh.html) • An example of Past Medical History Questionnaire (http://www.bcm.edu/breastcenter/?PMID=11131) Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Review of systems 121 Review of systems A review of systems (also called a systems enquiry) is a component of an admission note covering the organ systems, with a focus upon the subjective symptoms perceived by the patient (as opposed to the objective signs perceived by the clinician). It can be particularly useful in identifying conditions that dont have precise diagnostic tests.[1] Examples Whatever system a specific condition may seem restricted to, it may be reasonable to review all the other systems in a comprehensive history. Different sources describe slightly different systems of organizing the organ systems. However, the following are examples of what can be included: There are 14 systems recognized by the CMS:[2] System Examples Constitutional symptoms unexplained weight loss, night sweats, fatigue/malaise/lethargy, sleeping pattern, appetite, fever, itch/rash, recent (e.g., fever, weight loss) trauma, lumps/bumps/masses, unexplained falls Eyes visual changes, headache, eye pain, double vision, scotomas (blind spots), floaters or "feeling like a curtain got pulled down" (retinal hemorrhage vs amaurosis fugax) Ears, nose, mouth, and throat Runny nose, frequent nose bleeds (epistaxis), sinus pain, stuffy ears, ear pain, ringing in ears (tinnitus), gingival (ENT) bleeding, toothache, sore throat, pain with swallowing (odynophagia) Cardiovascular chest pain, shortness of breath, exercise intolerance, PND, orthopnoea, oedema, palpitations, faintness, loss of consciousness, claudication Respiratory cough, sputum, wheeze, haemoptysis, shortness of breath, exercise intolerance Gastrointestinal abdominal pain, unintentional weight loss, difficulty swallowing (solids vs liquids), indigestion, bloating, cramping, anorexia, food avoidance, nausea/vomiting, diarrhea/constipation, inability to pass gas (obstipation), vomiting blood (haematemesis), bright red blood per rectum (BRBPR, hematochezia), foul smelling dark black tarry stools (melaena), dry heaves of the bowels (tenesmus) Genitourinary Urinary: Irritative vs Obstructive symptoms: Micturition - incontinence, dysuria, haematuria, nocturia, polyuria, hesitancy, terminal dribbling, decreased force of stream Genital: Vaginal - discharge, pain, Menses - frequency, regularity, heavy or light (ask about excessive use of pads/tampons, staining of clothes, clots always indicate heavy bleeding), duration, pain, first day of last menstrual period (LMP), gravida/para/abortus, menarche, menopause, contraception (if relevant), date of last smear test and result Musculoskeletal pain, misalignment, stiffness (morning vs day long; improves/worsens with activity), joint swelling, decreased range of motion, crepitus, functional deficit, arthritis Integumentary pruritus, rashes, stria, lesions, wounds, incisions, acanthosis nigricans, nodules, tumors, eczema, excessive dryness and/or discoloration. Neurological Special senses - any changes in sight, smell, hearing and taste, seizures, faints, fits, funny turns, headache, pins and needles (paraesthesiae) or numbness, limb weakness, poor balance, speech problems, sphincter disturbance, higher mental function and psychiatric symptoms Psychiatric depression, sleep patterns, anxiety, difficult concentrating, body image, work and school performance, paranoia, ahedonia, lack of energy, episodes of mania, episodic change in personality, expansive personality, sexual or financial binges, Compiled and Edited by Marc Imhotep Cray , M.D.
  • Review of systems 122 Endocrine Hyperthyroid: prefer cold weather, mood swings, sweaty, diarrhoea, oligomenorrhoea, weight loss despite increased appetite, tremor, palpitations, visual disturbances; Hypothyroid - prefer hot weather, slow, tired, depressed, thin hair, croaky voice, heavy periods, constipation, dry skin Diabetes: polydipsia, polyuria, polyphagia (constant hunger without weight gain is more typical for a type I diabetic than type II), symptoms of hypoglycemia such as dizziness, sweating, headache,hunger, tongue dysarticulation Adrenal: difficult to treat hypertension, chronic low blood pressure, orthostatic symptoms, darkening of skin in non-sun exposed places Reproductive (female): menarche, cycle duration and frequency, vaginal bleeding irregularities, use of birth control pills Reproductive (male): difficulty with erection or sexual arousal, depression, lack of stamina/energy Hematologic/lymphatic anemia, purpura, petechia, results from routine hemolytic diseases screening, prolonged or excessive bleeding after dental extraction / injury, use of anticoagulant and antiplatelet drugs (including aspirin), family history of hemophilia, history of a blood transfusion, refused for blood donation Allergic/immunologic "Difficulty breathing" or "choking" (anaphylaxis) as a result of exposure to anything (and state what; e.g. "bee sting"). Swelling or pain at groin(s), axilla(e) or neck (swollen lymph nodes/glands), allergic response (rash/itch) to materials, foods, animals (e.g. cats); reaction to bee sting, unusual sneezing (in response to what), runny nose or itchy/teary eyes; food, medication or environmental allergy test(s) results. The questions may be asked of the patient in a "head to toe" manner.[3] Relationship to history [2] CMS required history elements Type of history CC HPI ROS Past, family, and/or social Problem focused Required Brief N/A N/A Expanded problem focused Required Brief Problem pertinent N/A Detailed Required Extended Extended Pertinent Comprehensive Required Extended Complete Complete For CMS, a "problem pertinent" ROS is limited to the problem(s) identified in the HPI; an "extended" ROS covers an additional 2 to 9 systems, and a "complete" ROS covers at least 10 additional systems.[2] References [1] Tuite PJ, Krawczewski K (April 2007). "Parkinsonism: a review-of-systems approach to diagnosis" (http:/ / www. thieme-connect. com/ DOI/ DOI?10. 1055/ s-2007-971174). Semin Neurol 27 (2): 113–22. doi:10.1055/s-2007-971174. PMID 17390256. . [2] "www.cms.gov" (http:/ / www. cms. gov/ MLNProducts/ downloads/ eval_mgmt_serv_guide-ICN006764. pdf). . Retrieved 2011-02-27. [3] Lynn S. Bickley; Peter G. Szilagyi (1 December 2008). Bates guide to physical examination and history taking (http:/ / books. google. com/ books?id=j272REejmWMC& pg=PA10). Lippincott Williams & Wilkins. pp. 10–. ISBN 9780781780582. . Retrieved 27 February 2011. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Biological system 123 Biological system In biology, a biological system (or organ system or body system) is a group of organs that work together to perform a certain task. Common systems, such as those present in mammals and other animals, seen in human anatomy, are those such as the circulatory system, the respiratory system, the nervous system, etc. A group of systems composes an organism, e.g. the human body. Human organism These specific systems are widely studied in Human anatomy. "Human" systems are also An example of a system: The nervous system. This basic diagram shows that this present in many other animals. system is made up of 4 different basic organs: the brain, the cerebellum, the spinal cord, and the nerves. • Circulatory system: pumping and channeling blood to and from the body and lungs with heart, blood and blood vessels. • Digestive system: digestion and processing food with salivary glands, esophagus, stomach, liver, gallbladder, pancreas, intestines, rectum and anus. • Endocrine system: communication within the body using hormones made by endocrine glands such as the hypothalamus, pituitary or pituitary gland, pineal body or pineal gland, thyroid, parathyroids and adrenals, i.e., adrenal glands. • Integumentary system: skin, hair, fat, and nails. • Lymphatic system: structures involved in the transfer of lymph between tissues and the blood stream, the lymph and the nodes and vessels that transport it including the Immune system: defending against disease-causing agents with leukocytes, tonsils, adenoids, thymus and spleen. • Muscular system: movement with muscles. • Nervous system: collecting, transferring and processing information with brain, spinal cord, peripheral nerves and nerves. • Reproductive system: the sex organs, such as ovaries, fallopian tubes, uterus, vagina, mammary glands, testes, vas deferens, seminal vesicles, prostate and penis. • Respiratory system: the organs used for breathing, the pharynx, larynx, trachea, bronchi, lungs and diaphragm. • Skeletal system: structural support and protection with bones, cartilage, ligaments and tendons. • Urinary system: kidneys, ureters, bladder and urethra involved in fluid balance, electrolyte balance and excretion of urine. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Biological system 124 External links • Systems Biology: An Overview [1] by Mario Jardon: A review from the Science Creative Quarterly, 2005. • Synthesis and Analysis of a Biological System [2], by Hiroyuki Kurata, 1999. • Semantic Systems Biology [3] organ system are divided into 8 parts • skeletal system • muscular system • digestive system • respiratory system • circulatory system • excretory system • nervous system • reproductive system References [1] http:/ / www. scq. ubc. ca/ ?p=253 [2] http:/ / www. genome. ad. jp/ manuscripts/ GIW99/ Poster/ GIW99P66. pdf. [3] http:/ / www. semantic-systems-biology. org Family history (medicine) In medicine, a family history consists of information about disorders from which the direct blood relatives of the patient have suffered. Genealogy typically includes very little of the medical history of the family, but the medical history could be considered a specific subset of the total history of a family. Knowledge of your family history can help identify a predisposition to develop certain illnesses, and enable you to avoid triggers in your environment. Uses Although often neglected,[1] many healthcare professionals glean information on family morbidity of particular diseases (e.g. cardiovascular diseases, autoimmune disorders, mental disorders, diabetes, cancer) to assess whether a person is at risk of developing similar problems. Family histories may be imprecise because of various possible reasons: • Adoption, fostering, illegitimacy and adultery • Lack of contact between close relatives • Uncertainty about the relatives exact diagnosis • In complex situations, a family tree or genogram may be used to organize the resulting information. Some medical conditions are carried only by the female line, and tracing female ancestors can be difficult in societies that change the womans family name when she marries. Death records often give the maiden name of the deceased, and possibly also the deceaseds mother’s maiden name. Some of the most useful records for tracing women are wills and probate records. Other medical conditions are carried only by the male line. Tracing male ancestors may be impossible if the conception is due to rape or sexual activity outside of a marriage. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Family history (medicine) 125 Consequences Not all positive family histories imply a genetic cause. If various members of the same family have been exposed to the same toxin, then they may develop similar symptoms without a genetic cause. If a patient has a strong family history of a particular disorder (or group of disorders), this will generally lead to a lower threshold for investigating symptoms. In diseases with a known hereditary component, many healthy people are now tested early to prevent the symptoms from developing. This has become accepted in cystic fibrosis, hemochromatosis and various other disorders. Definitions [2] CMS required history elements Type of history CC HPI ROS Past, family, and/or social Problem focused Required Brief N/A N/A Expanded problem focused Required Brief Problem pertinent N/A Detailed Required Extended Extended Pertinent Comprehensive Required Extended Complete Complete References [1] Rich E. C., et al. (2004) "Reconsidering the family history in primary care" in: J Gen Intern Med 2004;19:273-80. PMID 15009784. [2] "www.cms.gov" (http:/ / www. cms. gov/ MLNProducts/ downloads/ eval_mgmt_serv_guide-ICN006764. pdf). . Retrieved 2011-02-27. List of childhood diseases and disorders The term childhood disease is sometimes subjective, and does not refer to an accepted, categorical list. Nearly all the diseases in this list can also be Disability-adjusted life year for childhood-cluster diseases per 100,000 inhabitants. These include contracted by adults, and, of pertussis, poliomyelitis, diphtheria, measles, and tetanus.  no databrianna   ≤ course, all children can 25  25-50  50-100  100-200  200-300  300-400  400-500  500-750  750-1000  1000-2000  2000-3000  ≥ contract diseases not 3000 categorized as "childhood diseases". Some childhood diseases include: This list is incomplete. • Anemia • Asthma • Autism • Bronchiolitis • Candidiasis ("Thrush") • Chagas disease Compiled and Edited by Marc Imhotep Cray , M.D.
  • List of childhood diseases and disorders 126 • Chickenpox • Croup • Cystic Fibrosis • Cytomegalovirus (the virus most frequently transmitted before birth) • dental caries • Diabetes(Type 1) • Diphtheria • Downs syndrome • Duchenne muscular dystrophy • Fifth disease • Rickets • Congenital Heart Disease • Influenza • Juvenile idiopathic arthritis • Leukemia • Measles • Meningitis • Molluscum contagiosum • Mumps • Nephrotic syndrome • Osgood-Schlatter disease • Osteogenesis Imperfecta(OI) • Pneumonia • Polio • Protein energy malnutrition • Rheumatic fever • Roseola • Rubella • Severs disease • Tetanus • Tuberculosis • Whooping cough • Hepatitis A • Fever • Scarlet fever (Scarletina) • ADD • ADHD • Mono • Lyme Disease • Xerophthalmia Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Social history (medicine) 127 Social history (medicine) In medicine, a social history (abbreviated "SocHx")[1] is a portion of the Admission note addressing familial, occupational, and recreational aspects of the patients personal life that have the potential to be clinically significant. Components Components can include inquiries about: • Substances • Alcohol • Tobacco (pack years) • illicit drugs • occupation • sexual preference (increased risk of various infections among prostitutes, johns, and males engaging in anal-receptive intercourse) • prison (especially if tuberculosis needs to be ruled out) • travel Relationship to history [2] CMS required history elements Type of history CC HPI ROS Past, family, and/or social Problem focused Required Brief N/A N/A Expanded problem focused Required Brief Problem pertinent N/A Detailed Required Extended Extended Pertinent Comprehensive Required Extended Complete Complete References [1] "Medscape.com" (http:/ / www. medscape. com/ viewarticle/ 414658). . Retrieved 2009-04-10. [2] "www.cms.gov" (http:/ / www. cms. gov/ MLNProducts/ downloads/ eval_mgmt_serv_guide-ICN006764. pdf). . Retrieved 2011-02-27. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Allergy 128 Allergy Allergy Classification and external resources Hives are a common allergic symptom. ICD-10 [1] T78.4 ICD-9 [2] 995.3 DiseasesDB [3] 33481 MedlinePlus [4] 000812 eMedicine [5] med/1101 MeSH [6] D006967 Allergy is a hypersensitivity disorder of the immune system.[7] Allergic reactions occur to normally harmless environmental substances known as allergens; these reactions are acquired, predictable, and rapid. Strictly, allergy is one of four forms of hypersensitivity and is called type I (or immediate) hypersensitivity. It is characterized by excessive activation of certain white blood cells called mast cells and basophils by a type of antibody known as IgE, resulting in an extreme inflammatory response. Common allergic reactions include eczema, hives, hay fever, asthma attacks, food allergies, and reactions to the venom of stinging insects such as wasps and bees.[8] Mild allergies like hay fever are highly prevalent in the human population and cause symptoms such as allergic conjunctivitis, itchiness, and runny nose. Allergies can play a major role in conditions such as asthma. In some people, severe allergies to environmental or dietary allergens or to medication may result in life-threatening anaphylactic reactions. A variety of tests now exist to diagnose allergic conditions; these include testing the skin for responses to known allergens or analyzing the blood for the presence and levels of allergen-specific IgE. Treatments for allergies include allergen avoidance, use of anti-histamines, steroids, or other oral medications, immunotherapy to desensitize the response to allergen, and targeted therapy. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Allergy 129 Signs and symptoms Common symptoms of allergy Affected organ Symptom Nose swelling of the nasal mucosa (allergic rhinitis) Sinuses allergic sinusitis Eyes redness and itching of the conjunctiva (allergic conjunctivitis) Airways Sneezing, coughing, bronchoconstriction, wheezing and dyspnea, sometimes outright attacks of asthma, in severe cases the airway constricts due to swelling known as laryngeal edema Ears feeling of fullness, possibly pain, and impaired hearing due to the lack of eustachian tube drainage. Skin rashes, such as eczema and hives (urticaria) Gastrointestinal abdominal pain, bloating, vomiting, diarrhea tract Many allergens such as dust or pollen are airborne particles. In these cases, symptoms arise in areas in contact with air, such as eyes, nose, and lungs. For instance, allergic rhinitis, also known as hay fever, causes irritation of the nose, sneezing, itching, and redness of the eyes.[9] Inhaled allergens can also lead to asthmatic symptoms, caused by narrowing of the airways (bronchoconstriction) and increased production of mucus in the lungs, shortness of breath (dyspnea), coughing and wheezing.[10] Aside from these ambient allergens, allergic reactions can result from foods, insect stings, and reactions to medications like aspirin and antibiotics such as penicillin. Symptoms of food allergy include abdominal pain, bloating, vomiting, diarrhea, itchy skin, and swelling of the skin during hives. Food allergies rarely cause respiratory (asthmatic) reactions, or rhinitis.[11] Insect stings, antibiotics, and certain medicines produce a systemic allergic response that is also called anaphylaxis; multiple organ systems can be affected, including the digestive system, the respiratory system, and the circulatory system.[12] [13] [14] Depending on the rate of severity, it can cause cutaneous reactions, bronchoconstriction, edema, hypotension, coma, and even death. This type of reaction can be triggered suddenly, or the onset can be delayed. The severity of this type of allergic response often requires injections of epinephrine, sometimes through a device known as the EpiPen or Twinject auto-injector. The nature of anaphylaxis is such that the reaction can seem to be subsiding, but may recur throughout a prolonged period of time.[14] Substances that come into contact with the skin, such as latex, are also common causes of allergic reactions, known as contact dermatitis or eczema.[15] Skin allergies frequently cause rashes, or swelling and inflammation within the skin, in what is known as a "wheal and flare" reaction characteristic of hives and angioedema.[16] Cause Risk factors for allergy can be placed in two general categories, namely host and environmental factors.[17] Host factors include heredity, gender, race, and age, with heredity being by far the most significant. However, there have been recent increases in the incidence of allergic disorders that cannot be explained by genetic factors alone. Four major environmental candidates are alterations in exposure to infectious diseases during early childhood, environmental pollution, allergen levels, and dietary changes.[18] Compiled and Edited by Marc Imhotep Cray , M.D.
  • Allergy 130 Foods One of the most common food allergies is a sensitivity to peanuts. Peanut allergies may be extremely severe, but can sometimes be outgrown by children school-age.[19] Tree nuts, including pecans, pistachios, pine nuts, and walnuts, are another common allergen. Sufferers may be sensitive to one, or many, tree nuts.[20] Also seeds, including sesame seeds and poppy seeds, contain oils where protein is present, which may elicit an allergic reaction.[20] Egg allergies affect one to two percent of children but are outgrown by about two-thirds of children by the age of 5.[21] The sensitivity is usually to proteins in the white rather than the yolk.[20] Milk, from cows, goats, or sheep, is another common allergy-causing food, and many sufferers are also unable to tolerate dairy products such as cheese. Lactose intolerance, a common reaction to milk, is not in fact a form of allergy. A small portion of children with a milk allergy, roughly ten percent, will have a reaction to beef. Beef contains a small amount of protein that is present in cows milk.[22] Other foods containing allergenic proteins include soy, wheat, fish, shellfish, fruits, vegetables, spices, synthetic and natural colors, chicken, and chemical additives. Non-food proteins Latex can trigger an IgE-mediated cutaneous, respiratory, and systemic reaction. The prevalence of latex allergy in the general population is believed to be less than one percent. In a hospital study, one in 800 surgical patients (0.125 percent) report latex sensitivity, although the sensitivity among healthcare workers is higher, between seven and ten percent. Researchers attribute this higher level to the exposure of healthcare workers to areas with significant airborne latex allergens, such as operating rooms, intensive-care units, and dental suites. These latex-rich environments may sensitize healthcare workers who regularly inhale allergenic proteins.[23] The most prevalent response to latex is an allergic contact dermatitis, a delayed hypersensitive reaction appearing as dry, crusted lesions. This reaction usually lasts 48 to 96 hours. Sweating or rubbing the area under the glove aggravates the lesions, possibly leading to ulcerations.[23] Anaphylactic reactions occur most often in sensitive patients, who have been exposed to the surgeons latex gloves during abdominal surgery, but other mucosal exposures, such as dental procedures, can also produce systemic reactions.[23] Latex and banana sensitivity may cross-react; furthermore, patients with latex allergy may also have sensitivities to avocado, kiwifruit, and chestnut.[24] These patients often have perioral itching and local urticaria. Only occasionally have these food-induced allergies induced systemic responses. Researchers suspect that the cross-reactivity of latex with banana, avocado, kiwifruit, and chestnut occurs because latex proteins are structurally homologous with some plant proteins.[23] Toxins interacting with proteins Another non-food protein reaction, urushiol-induced contact dermatitis, originates after contact with poison ivy, eastern poison oak, western poison oak, or poison sumac. Urushiol, which is not itself a protein, acts as a hapten and chemically reacts with, binds to, and changes the shape of integral membrane proteins on exposed skin cells. The immune system does not recognize the affected cells as normal parts of the body, causing a T-cell-mediated immune response.[25] Of these poisonous plants, sumac is the most virulent.[26] The resulting dermatological response to the reaction between urushiol and membrane proteins includes redness, swelling, papules, vesicles, blisters, and streaking.[27] Estimates vary on the percentage of the population that will have an immune system response. Approximately 25 percent of the population will have a strong allergic response to urushiol. In general, approximately 80 percent to 90 percent of adults will develop a rash if they are exposed to .0050 milligrams (7.7×10−5 gr) of purified urushiol, but some people are so sensitive that it takes only a molecular trace on the skin to initiate an allergic reaction.[28] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Allergy 131 Genetic basis Allergic diseases are strongly familial: identical twins are likely to have the same allergic diseases about 70% of the time; the same allergy occurs about 40% of the time in non-identical twins.[29] Allergic parents are more likely to have allergic children,[30] and their allergies are likely to be more severe than those from non-allergic parents. Some allergies, however, are not consistent along genealogies; parents who are allergic to peanuts may have children who are allergic to ragweed. It seems that the likelihood of developing allergies is inherited and related to an irregularity in the immune system, but the specific allergen is not.[30] The risk of allergic sensitization and the development of allergies varies with age, with young children most at risk.[31] Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years.[31] The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10.[32] Overall, boys have a higher risk of developing allergy than girls,[30] although for some diseases, namely asthma in young adults, females are more likely to be affected.[33] Sex differences tend to decrease in adulthood.[30] Ethnicity may play a role in some allergies; however, racial factors have been difficult to separate from environmental influences and changes due to migration.[30] It has been suggested that different genetic loci are responsible for asthma, to be specific, in people of European, Hispanic, Asian, and African origins.[34] Hygiene hypothesis Allergic diseases are caused by inappropriate immunological responses to harmless antigens driven by a TH2-mediated immune response. Many bacteria and viruses elicit a TH1-mediated immune response, which down-regulates TH2 responses. The first proposed mechanism of action of the hygiene hypothesis stated that insufficient stimulation of the TH1 arm of the immune system lead to an overactive TH2 arm, which in turn led to allergic disease.[35] In other words, individuals living in too sterile an environment are not exposed to enough pathogens to keep the immune system busy. Since our bodies evolved to deal with a certain level of such pathogens, when it is not exposed to this level, the immune system will attack harmless antigens and thus normally benign microbial objects — like pollen — will trigger an immune response.[36] The hygiene hypothesis was developed to explain the observation that hay fever and eczema, both allergic diseases, were less common in children from larger families, which were, it is presumed, exposed to more infectious agents through their siblings, than in children from families with only one child. The hygiene hypothesis has been extensively investigated by immunologists and epidemiologists and has become an important theoretical framework for the study of allergic disorders. It is used to explain the increase in allergic diseases that have been seen since industrialization, and the higher incidence of allergic diseases in more developed countries. The hygiene hypothesis has now expanded to include exposure to symbiotic bacteria and parasites as important modulators of immune system development, along with infectious agents. Epidemiological data support the hygiene hypothesis. Studies have shown that various immunological and autoimmune diseases are much less common in the developing world than the industrialized world and that immigrants to the industrialized world from the developing world increasingly develop immunological disorders in relation to the length of time since arrival in the industrialized world.[37] Longitudinal studies in the third world demonstrate an increase in immunological disorders as a country grows more affluent and, it is presumed, cleaner.[38] The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases.[39] The use of antibacterial cleaning products has also been associated with higher incidence of asthma, as has birth by Caesarean section rather than vaginal birth.[40] [41] Compiled and Edited by Marc Imhotep Cray , M.D.
  • Allergy 132 Other environmental factors International differences have been associated with the number of individuals within a population that suffer from allergy. Allergic diseases are more common in industrialized countries than in countries that are more traditional or agricultural, and there is a higher rate of allergic disease in urban populations versus rural populations, although these differences are becoming less defined.[42] Exposure to allergens, especially in early life, is an important risk factor for allergy. Alterations in exposure to microorganisms is another plausible explanation, at present, for the increase in atopic allergy.[18] Endotoxin exposure reduces release of inflammatory cytokines such as TNF-α, IFNγ, interleukin-10, and interleukin-12 from white blood cells (leukocytes) that circulate in the blood.[43] Certain microbe-sensing proteins, known as Toll-like receptors, found on the surface of cells in the body are also thought to be involved in these processes.[44] Gutworms and similar parasites are present in untreated drinking water in developing countries, and were present in the water of developed countries until the routine chlorination and purification of drinking water supplies.[45] Recent research has shown that some common parasites, such as intestinal worms (e.g., hookworms), secrete chemicals into the gut wall (and, hence, the bloodstream) that suppress the immune system and prevent the body from attacking the parasite.[46] This gives rise to a new slant on the hygiene hypothesis theory — that co-evolution of man and parasites has led to an immune system that functions correctly only in the presence of the parasites. Without them, the immune system becomes unbalanced and oversensitive.[47] In particular, research suggests that allergies may coincide with the delayed establishment of gut flora in infants.[48] However, the research to support this theory is conflicting, with some studies performed in China and Ethiopia showing an increase in allergy in people infected with intestinal worms.[42] Clinical trials have been initiated to test the effectiveness of certain worms in treating some allergies.[49] It may be that the term parasite could turn out to be inappropriate, and in fact a hitherto unsuspected symbiosis is at work.[49] For more information on this topic, see Helminthic therapy. Acute response In the early stages of allergy, a type I hypersensitivity reaction against an allergen encountered for the first time and presented by a professional Antigen-Presenting Cell causes a response in a type of immune cell called a TH2 lymphocyte, which belongs to a subset of T cells that produce a cytokine called interleukin-4 (IL-4). These TH2 cells interact with other lymphocytes called B cells, whose role is production of antibodies. Coupled with signals provided by IL-4, this interaction stimulates the B cell to begin production of a large amount of a particular type of antibody known as IgE. Secreted IgE circulates Degranulation process in allergy. Second in the blood and binds to an IgE-specific receptor (a kind of Fc exposure to allergen.1 - antigen; 2 - IgE antibody; receptor called FcεRI) on the surface of other kinds of immune cells 3 - FcεRI receptor; 4 - preformed mediators called mast cells and basophils, which are both involved in the acute (histamine, proteases, chemokines, heparine); 5 - inflammatory response. The IgE-coated cells, at this stage are granules; 6 - mast cell; 7 - newly formed mediators (prostaglandins, leukotrienes, sensitized to the allergen.[18] thromboxanes, PAF) If later exposure to the same allergen occurs, the allergen can bind to the IgE molecules held on the surface of the mast cells or basophils. Cross-linking of the IgE and Fc receptors occurs when more than one IgE-receptor complex interacts with the same allergenic molecule, and activates the sensitized cell. Activated mast cells and basophils undergo a process called degranulation, during which they release histamine and other inflammatory chemical mediators (cytokines, interleukins, leukotrienes, and prostaglandins) from their granules into the surrounding tissue causing several systemic effects, such as vasodilation, mucous secretion, nerve Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Allergy 133 stimulation, and smooth muscle contraction. This results in rhinorrhea, itchiness, dyspnea, and anaphylaxis. Depending on the individual, allergen, and mode of introduction, the symptoms can be system-wide (classical anaphylaxis), or localized to particular body systems; asthma is localized to the respiratory system and eczema is localized to the dermis.[18] Late-phase response After the chemical mediators of the acute response subside, late phase responses can often occur. This is due to the migration of other leukocytes such as neutrophils, lymphocytes, eosinophils and macrophages to the initial site. The reaction is usually seen 2–24 hours after the original reaction.[50] Cytokines from mast cells may also play a role in the persistence of long-term effects. Late phase responses seen in asthma are slightly different from those seen in other allergic responses, although they are still caused by release of mediators from eosinophils, and are still dependent on activity of TH2 cells.[51] Diagnosis Before a diagnosis of allergic disease can be confirmed, the other possible causes of the presenting symptoms should be carefully considered.[52] Vasomotor rhinitis, for example, is one of many maladies that shares symptoms with allergic rhinitis, underscoring the need for professional differential diagnosis.[53] Once a diagnosis of asthma, rhinitis, anaphylaxis, or other allergic disease has been made, there are several methods for discovering the causative agent of that allergy. An allergy testing machine being operated in the diagnostic immunology lab at Lackland Air Force Base Compiled and Edited by Marc Imhotep Cray , M.D.
  • Allergy 134 Skin testing For assessing the presence of allergen-specific IgE antibodies, allergy skin testing is preferred over blood allergy tests because it is more sensitive and specific, simpler to use, and less expensive.[54] Skin testing is also known as "puncture testing" and "prick testing" due to the series of tiny puncture or pricks made into the patients skin. Small amounts of suspected allergens and/or their extracts (pollen, grass, mite proteins, peanut extract, etc.) are introduced to sites on the skin marked with pen or dye (the ink/dye should be carefully selected, lest it cause an allergic response itself). A small plastic or metal device is used to Skin testing on arm puncture or prick the skin. Sometimes, the allergens are injected "intradermally" into the patients skin, with a needle and syringe. Common areas for testing include the inside forearm and the back. If the patient is allergic to the substance, then a visible inflammatory reaction will usually occur within 30 minutes. This response will range from slight reddening of the skin to a full-blown hive (called "wheal and flare") in more sensitive patients similar to a mosquito bite. Interpretation of the results of the skin prick test is normally done by allergists on a scale of severity, with +/- meaning borderline reactivity, and 4+ being a large reaction. Increasingly, allergists are measuring and recording the diameter of the wheal and flare reaction. Skin testing on back Interpretation by well-trained allergists is often guided by relevant literature.[55] Some patients may believe they have determined their own allergic sensitivity from observation, but a skin test has been shown to be much better than patient observation to detect allergy.[56] If a serious life threatening anaphylactic reaction has brought a patient in for evaluation, some allergists will prefer an initial blood test prior to performing the skin prick test. Skin tests may not be an option if the patient has widespread skin disease or has taken antihistamines sometime the last several days. Blood testing Various blood allergy testing methods are also available for detecting allergy to specific substances. This kind of testing measures a "total IgE level" - an estimate of IgE contained within the patients serum. This can be determined through the use of radiometric and colormetric immunoassays. Radiometric assays include the radioallergosorbent test (RAST) test method, which uses IgE-binding (anti-IgE) antibodies labeled with radioactive isotopes for quantifying the levels of IgE antibody in the blood.[54] Other newer methods use colorimetric or fluorometric technology in the place of radioactive isotopes. Some "screening" test methods are intended to provide qualitative test results, giving a "yes" or "no" answer in patients with suspected allergic sensitization. One such method has a sensitivity of about 70.8% and a positive predictive value of 72.6% according to a large study.[57] A low total IgE level is not adequate to rule out sensitization to commonly inhaled allergens.[58] Statistical methods, such as ROC curves, predictive value calculations, and likelihood ratios have been used to examine the relationship of various testing methods to each other. These methods have shown that patients with a high total IgE have a high probability of allergic sensitization, but further investigation with specific allergy tests for a carefully chosen allergens is often warranted. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Allergy 135 Other Challenge testing: Challenge testing is when small amounts of a suspected allergen are introduced to the body orally, through inhalation, or other routes. Except for testing food and medication allergies, challenges are rarely performed. When this type of testing is chosen, it must be closely supervised by an allergist. Elimination/Challenge tests: This testing method is utilized most often with foods or medicines. A patient with a particular suspected allergen is instructed to modify his/her diet to totally avoid that allergen for determined period of time. If the patient experiences significant improvement, he/she may then be “challenged” by reintroducing the allergen to see if symptoms can be reproduced. Patch testing: Patch testing is used to help ascertain the cause of skin contact allergy, or contact dermatitis. Adhesive patches, usually treated with a number of different commonly allergic chemicals or skin sensitizers, are applied to the back. The skin is then examined for possible local reactions at least twice, usually at 48 hours after application of the patch, and again two or three days later. Unreliable tests: There are other types of allergy testing methods that the American Academy of Allergy, Asthma, and Immunology considers to be unacceptable. These unreliable allergy testing methods are: Applied kinesiology (allergy testing through muscle relaxation), Cytotoxicity testing, Urine autoinjection, Skin titration (Rinkel method), and Provocative and neutralization (subcutaneous) testing or sublingual provocation[59] Treatment In recent times, there have been enormous improvements in the medical practices used to treat allergic conditions. With respect to anaphylaxis and hypersensitivity reactions to foods, drugs, and insects and in allergic skin diseases, advances have included the identification of food proteins to which IgE binding is associated with severe reactions and development of low-allergen foods, improvements in skin prick test predictions; evaluation of the atopy patch test; in wasp sting outcomes predictions and a rapidly disintegrating epinephrine tablet, and anti-IL-5 for eosinophilic diseases.[60] Traditional treatment and management of allergies consisted simply of avoiding the allergen in question or otherwise reducing exposure. For instance, people with cat allergies were encouraged to avoid them. However, while avoidance of allergens may reduce symptoms and avoid life-threatening anaphylaxis, it is difficult to achieve for those with pollen or similar air-borne allergies. Nonetheless, strict avoidance of allergens is still considered a useful treatment method, and is often used in managing food allergies. New technology approaches to decreasing 1gE overproduction, and regulating histimine release in allergic individuals have demonstrated statisitically significant reduction on Total Nasel Symptom Scores.[61] [62] Pharmacotherapy Several antagonistic drugs are used to block the action of allergic mediators, or to prevent activation of cells and degranulation processes. These include antihistamines, glucocorticoids, epinephrine (adrenaline), theophylline and cromolyn sodium. Anti-leukotrienes, such as Montelukast (Singulair) or Zafirlukast (Accolate), are FDA approved for treatment of allergic diseases. Anti-cholinergics, decongestants, mast cell stabilizers, and other compounds thought to impair eosinophil chemotaxis, are also commonly used. These drugs help to alleviate the symptoms of allergy, and are imperative in the recovery of acute anaphylaxis, but play little role in chronic treatment of allergic disorders. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Allergy 136 Immunotherapy Desensitization or hyposensitization is a treatment in which the patient is gradually vaccinated with progressively larger doses of the allergen in question. This can either reduce the severity or eliminate hypersensitivity altogether. It relies on the progressive skewing of IgG antibody production, to block excessive IgE production seen in atopys. In a sense, the person builds up immunity to increasing amounts of the allergen in question. Studies have demonstrated the long-term efficacy and the preventive effect of immunotherapy in reducing the development of new allergy.[63] Meta-analyses have also confirmed efficacy of the treatment in allergic rhinitis in children and in asthma. A review by the Mayo Clinic in Rochester confirmed the safety and efficacy of allergen immunotherapy for allergic rhinitis and conjunctivitis, allergic forms of asthma, and stinging insect based on numerous well-designed scientific studies.[64] In addition, national and international guidelines confirm the clinical efficacy of injection immunotherapy in rhinitis and asthma, as well as the safety, provided that recommendations are followed.[65] A second form of immunotherapy involves the intravenous injection of monoclonal anti-IgE antibodies. These bind to free and B-cell associated IgE; signalling their destruction. They do not bind to IgE already bound to the Fc receptor on basophils and mast cells, as this would stimulate the allergic inflammatory response. The first agent of this class is Omalizumab. While this form of immunotherapy is very effective in treating several types of atopy, it should not be used in treating the majority of people with food allergies. A third type, Sublingual immunotherapy, is an orally-administered therapy that takes advantage of oral immune tolerance to non-pathogenic antigens such as foods and resident bacteria. This therapy currently accounts for 40 percent of allergy treatment in Europe. In the United States, sublingual immunotherapy is gaining support among traditional allergists and is endorsed by doctors treating allergy. Allergy shot treatment is the closest thing to a ‘cure’ for allergic symptoms. This therapy requires a long-term commitment. Unproven and ineffective treatments An experimental treatment, enzyme potentiated desensitization (EPD), has been tried for decades but is not generally accepted as effective.[66] EPD uses dilutions of allergen and an enzyme, beta-glucuronidase, to which T-regulatory lymphocytes are supposed to respond by favouring desensitization, or down-regulation, rather than sensitization. EPD has also been tried for the treatment of autoimmune diseases but is not approved by the U.S. Food and Drug Administration or of proven effectiveness.[66] Systematic literature searches conducted by the Mayo Clinic through 2006, involving hundreds of articles studying multiple conditions, including asthma and upper respiratory tract infection, showed no effectiveness of homeopathic treatments and no difference compared with placebo. The authors concluded that, based on rigorous clinical trials of all types of homeopathy for childhood and adolescence ailments, there is no convincing evidence that supports the use of homeopathic treatments.[67] Epidemiology Many diseases related to inflammation such as type 1 diabetes, rheumatoid arthritis, and allergic diseases — hay fever and asthma — have increased in the Western world over the past 2-3 decades.[68] Rapid increases in allergic asthma and other atopic disorders in industrialized nations, it is estimated, began in the 1960s and 1970s, with further increases occurring during the 1980s and 1990s,[69] although some suggest that a steady rise in sensitization has been occurring since the 1920s.[70] The incidence of atopy in developing countries has, in general, remained much lower.[69] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Allergy 137 Allergic conditions: Statistics and Epidemiology Allergy type United States [71] United Kingdom Allergic rhinitis [72] [73] [74] 35.9 million (about 11% of the population ) 3.3 million (about 5.5% of the population ) Asthma 10 million suffer from allergic asthma (about 3% of the 5.7 million (about 9.4%). In six and seven population). The prevalence of asthma increased 75% year olds asthma increased from 18.4% to from 1980-1994. Asthma prevalence is 39% higher in 20.9% over five years, during the same time [75] the rate decreased from 31% to 24.7% in 13 African Americans than in Europeans. to 14 year olds. Atopic eczema About 9% of the population. Between 1960 and 1990 5.8 million (about 1% severe). prevalence has increased from 3% to 10% in [76] children. Anaphylaxis At least 40 deaths per year due to insect venom. About Between 1999 and 2006, 48 deaths occurred 400 deaths due to penicillin anaphylaxis. About 220 in people ranging from five months to 85 cases of anaphylaxis and 3 deaths per year are due to years old. [77] latex allergy. An estimated 150 people die annually [78] from anaphylaxis due to food allergy. Insect venom Around 15% of adults have mild, localized allergic Unknown reactions. Systemic reactions occur in 3% of adults and [79] less than 1% of children. Drug allergies Anaphylactic reactions to penicillin cause 400 deaths Unknown per year. Food allergies About 6% of US children under age 3 and 3.5-4% of the 5-7% of infants and 1-2% of adults. A overall US population. Peanut and/or tree nut (e.g. 117.3% increase in peanut allergies was walnut) allergy affects about three million Americans, or observed from 2001 to 2005, an estimated [78] 25,700 people in England are affected. 1.1% of the population. Multiple allergies Unknown 2.3 million (about 3.7%), prevalence has (Asthma, eczema and increased by 48.9% between 2001 and allergic rhinitis together) [80] 2005. Although genetic factors fundamentally govern susceptibility to atopic disease, increases in atopy have occurred within too short a time frame to be explained by a genetic change in the population, thus pointing to environmental or lifestyle changes.[81] Several hypotheses have been identified to explain this increased prevalence; increased exposure to perennial allergens due to housing changes and increasing time spent indoors, and changes in cleanliness or hygiene that have resulted in the decreased activation of a common immune control mechanism, coupled with dietary changes, obesity and decline in physical exercise.[68] The hygiene hypothesis maintains[82] that high living standards and hygienic conditions exposes children to fewer infections. It is thought that reduced bacterial and viral infections early in life direct the maturing immune system away from TH1 type responses, leading to unrestrained TH2 responses that allow for an increase in allergy.[47] [83] Changes in rates and types of infection alone however, have been unable to explain the observed increase in allergic disease, and recent evidence has focused attention on the importance of the gastrointestinal microbial environment. Evidence has shown that exposure to food and fecal-oral pathogens, such as hepatitis A, Toxoplasma gondii, and Helicobacter pylori (which also tend to be more prevalent in developing countries), can reduce the overall risk of atopy by more than 60%,[84] and an increased prevalence of parasitic infections has been associated with a decreased prevalence of asthma.[85] It is speculated that these infections exert their effect by critically altering TH1/TH2 regulation.[86] Important elements of newer hygiene hypotheses also include exposure to endotoxins, exposure to pets and growing up on a farm.[86] Compiled and Edited by Marc Imhotep Cray , M.D.
  • Allergy 138 History The concept of "allergy" was originally introduced in 1906 by the Viennese pediatrician Clemens von Pirquet, after he noted that some of his patients were hypersensitive to normally innocuous entities such as dust, pollen, or certain foods.[87] Pirquet called this phenomenon "allergy" from the Ancient Greek words ἄλλος allos meaning "other" and ἔργον ergon meaning "work".[88] All forms of hypersensitivity used to be classified as allergies, and all were thought to be caused by an improper activation of the immune system. Later, it became clear that several different disease mechanisms were implicated, with the common link to a disordered activation of the immune system. In 1963, a new classification scheme was designed by Philip Gell and Robin Coombs that described four types of hypersensitivity reactions, known as Type I to Type IV hypersensitivity.[89] With this new classification, the word "allergy" was restricted to type I hypersensitivities (also called immediate hypersensitivity), which are characterized as rapidly developing reactions. A major breakthrough in understanding the mechanisms of allergy was the discovery of the antibody class labeled immunoglobulin E (IgE) - Kimishige Ishizaka and co-workers were the first to isolate and describe IgE in the 1960s.[90] Medical specialty An allergist is a physician specially trained to manage and treat allergies, asthma and the other allergic diseases. In the United States physicians holding certification by the American Board of Allergy and Immunology (ABAI) have successfully completed an accredited educational program and an evaluation process, including a secure, proctored examination to demonstrate the knowledge, skills, and experience to the provision of patient care in allergy and immunology.[91] Becoming an allergist/immunologist requires completion of at least nine years of training. After completing medical school and graduating with a medical degree, a physician will then undergo three years of training in internal medicine (to become an internist) or pediatrics (to become a pediatrician). Once physicians have finished training in one of these specialties, they must pass the exam of either the American Board of Pediatrics (ABP) or the American Board of Internal Medicine (ABIM). Internists or pediatricians wishing to focus on the sub-specialty of allergy-immunology then complete at least an additional two years of study, called a fellowship, in an allergy/immunology training program. Allergist/immunologists listed as ABAI-certified have successfully passed the certifying examination of the American Board of Allergy and Immunology (ABAI), following their fellowship.[92] In the United Kingdom, allergy is a subspecialty of general medicine or pediatrics. After obtaining postgraduate exams (MRCP or MRCPCH respectively), a doctor works for several years as a specialist registrar before qualifying for the General Medical Council specialist register. Allergy services may also be delivered by immunologists. A 2003 Royal College of Physicians report presented a case for improvement of what were felt to be inadequate allergy services in the UK.[93] In 2006, the House of Lords convened a subcommittee that reported in 2007. It concluded likewise that allergy services were insufficient to deal with what the Lords referred to as an "allergy epidemic" and its social cost; it made several other recommendations.[94] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
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[84] Matricardi PM, Rosmini F, Riondino S, et al (2000). "Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study". BMJ 320 (7232): 412–7. doi:10.1136/bmj.320.7232.412. PMC 27285. PMID 10669445. [85] Masters S, Barrett-Connor E (1985). "Parasites and asthma—redictive or protective?". Epidemiol Rev 7: 49–58. PMID 4054238. [86] Sheikh A, Strachan DP (2004). "The hygiene theory: fact or fiction?". Curr Opin Otolaryngol Head Neck Surg 12 (3): 232–6. doi:10.1097/01.moo.0000122311.13359.30. PMID 15167035. [87] Clemens Peter Pirquet von Cesenatico (http:/ / www. whonamedit. com/ Doctor. cfm/ 2382. html) at Who Named It? [88] Von Pirquet C (1906). "Allergie". Munch Med Wochenschr 53 (5): 1457. PMID 20273584. [89] Gell PGH, Coombs RRA. (1963). Clinical Aspects of Immunology. London: Blackwell. [90] Ishizaka K, Ishizaka T, Hornbrook MM (1966). "Physico-chemical properties of human reaginic antibody. IV. Presence of a unique immunoglobulin as a carrier of reaginic activity". J. Immunol. 97 (1): 75–85. PMID 4162440. [91] "ABAI: American Board of Allergy and Immunology" (http:/ / www. abai. org/ training. asp). Archived (http:/ / www. webcitation. org/ 5uHp4Xiak) from the original on 2010-11-16. . Retrieved 2007-08-05. [92] "AAAAI - What is an Allergist?" (http:/ / www. aaaai. org/ media/ resources/ allergist. asp). Archived (http:/ / www. webcitation. org/ 5uHp3JDDM) from the original on 2010-11-16. . Retrieved 2007-08-05. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Allergy 142 [93] Royal College of Physicians (2003). Allergy: the unmet need. London, UK: Royal College of Physicians. ISBN 978-1-86016-183-4. PDF version (http:/ / www. rcplondon. ac. uk/ pubs/ contents/ 81e384d6-0328-4653-9cc2-2aa7baa3c56a. pdf)PDF (1.03 MB) [94] House of Lords - Science and Technology Committee (2007). Allergy - HL 166-I, 6th Report of Session 2006-07 - Volume 1: Report (http:/ / www. publications. parliament. uk/ pa/ ld200607/ ldselect/ ldsctech/ 166/ 16602. htm). London, UK: TSO (The Stationery Office). ISBN 978-0-10-401149-2. . External links • American Academy of Allergy, Asthma & Immunology (http://www.aaaai.org) • Allergy & Asthma Network Mothers of Asthmatics (http://www.aanma.org) Doctor-patient relationship The doctor-patient relationship is central to the practice of healthcare and is essential for the delivery of high-quality health care in the diagnosis and treatment of disease. The doctor-patient relationship forms one of the foundations of contemporary medical ethics. Most universities teach students from the beginning, even before they set foot in hospitals, to maintain a professional rapport with patients, uphold patients’ dignity, and respect their privacy. Importance A patient must have confidence in the competence of their physician and must feel that they can confide in him or her. For most physicians, the establishment of good rapport with a patient is important. Some medical specialties, such as psychiatry and family medicine, emphasize the physician-patient relationship more than others, such as pathology or radiology. The quality of the patient-physician relationship is important to both parties. The better the relationship in terms of mutual respect, knowledge, trust, shared values and perspectives about disease and life, and time available, the better will be the amount and quality of information about the patients disease transferred in both directions, enhancing accuracy of diagnosis and increasing the patients knowledge about the disease. Where such a relationship is poor the physicians ability to make a full assessment is compromised and the patient is more likely to distrust the diagnosis and proposed treatment, causing decreased compliance to actually follow the medical advice. In these circumstances and also in cases where there is genuine divergence of medical opinions, a second opinion from another physician may be sought or the patient may choose to go to another physician. Michael Balint pioneered the study of the physician patient relationship in the UK with his wife Enid Balint resulting in the publication of the seminal book "The Doctor, His Patient and the Illness." Balints work is continued by The American Balint Society [1] in the United States, The International Balint Federation [2] and other national Balint societies in other countries. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Doctor-patient relationship 143 Issues The following issues may complicate or negatively affect the doctor-patient relationship if not taken properly into consideration. Physician superiority The physician may be viewed as superior to the patient, because the physician has the knowledge and credentials, and is most often the one that is on home ground. The physician-patient relationship is also complicated by the patients suffering (patient derives from the Latin patior, "suffer") and limited ability to relieve it on his/her own, potentially resulting in a state of desperation and dependency on the physician. A physician should at least be aware of these disparities in order to establish rapport and optimize communication with the patient. It may be further beneficial for the doctor-patient relationship to have a form of shared care with patient empowerment to take a major degree of responsibility for her or his care. Benefiting or pleasing A dilemma may arise in situations where determining the most efficient treatment, or encountering avoidance of treatment, creates a disagreement between the physician and the patient, for any number of reasons. In such cases, the physician needs strategies for presenting unfavorable treatment options or unwelcome information in such a way that minimizes strain on the doctor-patient relationship while benefiting the patients overall physical health and best interests. Formal or casual There may be differences in opinion between the doctor and patient in how formal or casual the doctor-patient relationship should be. For instance, according to a Scottish study,[3] patients want to be addressed by their first name more often than is currently the case. In this study, most of the patients either liked (223) or did not mind (175) being called by their first names. Only 77 disliked it, most of whom were aged over 65.[3] On the other hand, most patients dont want to call the doctor by his or her first name.[3] Some familiarity with the doctor generally makes it easier for patients to talk about intimate issues such as sexual subjects, but for some patients, a very high degree of familiarity may make the patient reluctant to reveal such intimate issues.[4] Transitional care Transitions of patients between health care practitioners may decrease the quality of care in the time it takes to reestablish proper doctor-patient relationships. Generally, the doctor-patient relationship is facilitated by continuity of care in regard to attending personnel. Special strategies of integrated care may be required where multiple health care providers are involved, including horizontal integration (linking similar levels of care, e.g. multiprofessional teams) and vertical integration (linking different levels of care, e.g. primary, secondary and tertiary care).[5] Compiled and Edited by Marc Imhotep Cray , M.D.
  • Doctor-patient relationship 144 Other people present An example of where other people present in a doctor-patient encounter may influence their communication is one or more parents present at a minors visit to a doctor. These may provide psychological support for the patient, but in some cases it may compromise the doctor-patient confidentiality and inhibit the patient from disclosing uncomfortable or intimate subjects. When visiting a health provider about sexual issues, having both partners of a couple present is often necessary, and is typically a good thing, but may also prevent the disclosure of certain subjects, and, according to one report, increases the stress level.[4] Bedside manner A good bedside manner is typically one that reassures and comforts the patient while remaining honest about a diagnosis. Vocal tones, body language, openness, presence, and concealment of attitude may all affect bedside manner. Poor bedside manner leaves the patient feeling unsatisfied, worried, frightened, or alone. Bedside manner becomes difficult when a healthcare professional must explain an unfavorable diagnosis to the patient, while keeping the patient from being alarmed. An example of how body language affects patient perception of care is that the time spent with the patient in the emergency department is perceived as longer if the doctor sits down during the encounter.[6] Examples in fiction • Dr. Gregory House (of the show House) has a caustic, callous bedside manner. However, this is an extension of his normal personality. • In Greys Anatomy, Dr. Burke compliments Dr. George OMalleys ability to care for Dr. Baileys baby by saying "it speaks to a good bedside manner." • Doc Martin from the Doc Martin British TV series is a good example of a doctor with a poor bedside manner. • In Lost, Hurley tells Jack Shephard that his bedside manner "sucks". Later in the episode, Jack is told by his father to put more hope into his sayings, which he does when operating on his future wife. The comments continue in other episodes of the series with Benjamin Linus sarcastically telling Jack that his "bedside manner leaves something to be desired" after Jack gives him a harsh negative diagnosis. • In Closer, Larry, the doctor tells Anna when they first meet that he is famed for his bedside manner. • In Scrubs, J.D is a good example of a doctor with great bedside manner, while Elliot Reid is a doctor with poor or non-existent bedside manner. Dr. Cox is an interesting subversion, in that his manner is gruff and intense while still inspiring patients to do their own best to aid in the healing process, akin to a drill sergeant. It is also remarked on this show that the most amount of time that a doctor needs to be in the presence of the patient before he finds out everything he needs to know is 18 seconds approx. • In Star Trek: Voyager, the Doctor often compliments himself on the charming bedside manner he developed with the help of Kes. • In M*A*S*H, Hawkeye Pierce, Trapper John McIntyre, B.J. Hunnicutt, and Sherman Potter all possess a caring and humorous bedside manner meant to help patients cope with traumatic injuries. Charles Winchester initially possesses no real bedside manner, acting with detached professionalism, until the rigors of his job help him develop a sense of compassion for his patients. Frank Burns has a poor bedside manner, constantly minimizing the seriousness of his patients injuries, accusing them of cowardice and goading them to return to the front lines. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Doctor-patient relationship 145 References [1] http:/ / www. americanbalintsociety. org [2] http:/ / www. balintinternational. com [3] McKinstry B (October 1990). "Should general practitioners call patients by their first names?". BMJ 301 (6755): 795–6. doi:10.1136/bmj.301.6755.795. PMC 1663948. PMID 2224269. [4] The Cringe Report (http:/ / www. medscape. com/ viewarticle/ 743689_3) By Susan Quilliam. Posted: 06/28/2011; J Fam Plann Reprod Health Care. 2011;37(2):110-112. [5] Gröne, O & Garcia-Barbero, M (2002): Trends in Integrated Care – Reflections on Conceptual Issues. World Health Organization, Copenhagen, 2002, EUR/02/5037864 [6] Simple Tips to Improve Patient Satisfaction (http:/ / www. medscape. com/ viewarticle/ 743875?src=mp& spon=25) By Michael Pulia. American Academy of Emergency Medicine. 2011;18(1):18-19. Further information • Alexander GC, Casalino LP, Meltzer DO (August 2003). "Patient-physician communication about out-of-pocket costs". JAMA 290 (7): 953–8. doi:10.1001/jama.290.7.953. PMID 12928475. • Alexander GC, Casalino LP, Tseng CW, McFadden D, Meltzer DO (August 2004). "Barriers to patient-physician communication about out-of-pocket costs". J Gen Intern Med 19 (8): 856–60. doi:10.1111/j.1525-1497.2004.30249.x. PMC 1492500. PMID 15242471. • Alexander GC, Casalino LP, Meltzer DO (March 2005). "Physician strategies to reduce patients out-of-pocket prescription costs". Arch. Intern. Med. 165 (6): 633–6. doi:10.1001/archinte.165.6.633. PMID 15795338. • Alexander GC, Lantos JD (2006). "The doctor-patient relationship in the post-managed care era". Am J Bioeth 6 (1): 29–32. doi:10.1080/15265160500394556. PMID 16423784. • Pham HH, Alexander GC, OMalley AS (April 2007). "Physician consideration of patients out-of-pocket costs in making common clinical decisions". Arch. Intern. Med. 167 (7): 663–8. doi:10.1001/archinte.167.7.663. PMID 17420424. External links • Report of a large summit of patients and physicians, where the ideal patient-physician relationship in the 21st century was discussed. (http://www.patient-physician.com/docs/PatientPhysician.pdf) Organised by Johns Hopkins and American Healthways in 2003 • Time Magazine article: "When the patient is a Googler" (http://www.time.com/time/health/article/ 0,8599,1681838,00.html) - Mary Shomons response I (http://thyroid.about.com/b/2007/11/13/ my-letter-to-the-editor-of-time-magazine-re-dr-haig-and-his-googler-article.htm) II (http://thyroid.about.com/ b/2007/11/13/time-magazines-dr-scott-haig-proves-that-patients-need-to-be-googlers.htm) - Trisha Torreys response (http://patients.about.com/b/2007/11/24/cnntime-dr-haigs-own-misdiagnosis.htm) Compiled and Edited by Marc Imhotep Cray , M.D.
  • Differential diagnosis 146 Differential diagnosis Differential diagnosis Intervention MeSH [1] D003937 A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a systematic method used to identify unknowns. This method, essentially a process of elimination, is used by taxonomists to identify living organisms, and by physicians, nurse practitioners, physician assistants, and other trained medical professionals to diagnose the specific disease in a patient. Not all medical diagnoses are differential ones: some diagnoses merely name a set of signs and symptoms that may have more than one possible cause, and some diagnoses are based on intuition or estimations of likelihood. Process Differential diagnosis often involves first making a list of possible diagnoses, then attempting to remove diagnoses from the list until one diagnosis remains. In some cases, there will remain no diagnosis; this suggests the physician has made an error, or that the true diagnosis is unknown to medicine. Removing diagnoses from the list is done by making observations and using tests that should have different results, depending on which diagnosis is correct. Many mnemonics are routinely taught to medical students (for example VINDICATE) to ensure that all possible pathological processes are considered. Medicine In medicine, differential diagnosis is the process whereby a given condition or circumstance, called the presenting problem or chief complaint, is examined in terms of underlying causal factors and concurrent phenomena as discerned by appropriate disciplinary perspectives and according to several theoretical paradigms or frames of reference, and compared to known categories of pathology or exceptionality. Differential diagnosis allows the physician to: • more clearly understand the condition or circumstance • assess reasonable prognosis • eliminate any imminently life-threatening conditions • plan treatment or intervention for the condition or circumstance • enable the patient and the family to integrate the condition or circumstance into their lives, until the condition or circumstance may be ameliorated, if possible. If the patients condition does not improve as anticipated when the treatment or therapy for the disease or disorder has been applied, the diagnosis must be reassessed. The method of differential diagnosis was first suggested for use in the diagnosis of mental disorders by Emil Kraepelin. It is more systematic than the old-fashioned method of diagnosis by gestalt (impression). The method of differential diagnosis is based on the idea that one begins by first considering the most common diagnosis first: a head cold versus meningitis, for example. As a reminder, medical students are taught the adage, "When you hear hoofbeats, look for horses, not zebras," which means look for the simplest, most common explanation first. Only after the simplest diagnosis has been ruled out should the clinician consider more complex or exotic diagnoses. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Differential diagnosis 147 At one time doctors ordered only particular blood tests, but now a full blood chemistry profile is standard, which can speed up the process of diagnosis as well as uncover sub-clinical conditions. With the advent of better radiological studies like MRI and the wider use of nuclear medicine, it has become more likely that unexpected findings will emerge and will be further studied, though such findings may not be supported by further investigation. Such findings are a valuable tool but not infallible; often it still takes a physician or medical team to track down either a more common illness with a rare presentation or a rare illness with symptoms suggestive of many other conditions. Sometimes a definitive diagnosis might take years. Differential diagnosis also refers simply to a list of the most common causes of a given symptom, to a list of disorders similar to a given disorder, or to such lists when they are annotated with advice on how to narrow the list down (the book Frenchs Index of Differential Diagnosis ISBN 0340810475 is an example). Thus, a differential diagnosis in this sense is medical information specially organized to aid in diagnosis. The professional Merck Manual of Diagnosis and Therapy has 11 index entries describing the topic as differential diagnosis. The topic is mentioned within the body of 125 other separate articles on various medical conditions. Machine differential diagnosis Machine differential diagnosis is the use of computer software to partly or fully make a differential diagnosis. It may be regarded as an application of artificial intelligence. Many studies demonstrate improvement of quality of care and reduction of medical errors by using such decision support systems. Some of these systems are designed for a specific medical problem such as schizophrenia,[2] Lyme disease[3] or ventilator-associated pneumonia.[4] Others such as Iliad, QMR, DiagnosisPro,[5] and VisualDx [6] are designed to cover all major clinical and diagnostic findings to assist physicians with faster and more accurate diagnosis. However, these tools all still require advanced medical skills in order to rate the symptoms and choose additional tests to deduce the probabilities of different diagnoses. Thus, non-professionals still need to see a health care provider in order to get a proper diagnosis. References [1] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?field=uid& term=D003937 [2] Razzouk D, Mari JJ, Shirakawa I, Wainer J, Sigulem D (January 2006). "Decision support system for the diagnosis of schizophrenia disorders". Brazilian Journal of Medical and Biological Research 39 (1): 119–28. doi:/S0100-879X2006000100014. PMID 16400472. [3] Hejlesen OK, Olesen KG, Dessau R, Beltoft I, Trangeled M (2005). "Decision support for diagnosis of lyme disease" (http:/ / booksonline. iospress. nl/ Extern/ EnterMedLine. aspx?ISSN=0926-9630& Volume=116& SPage=205). Studies in Health Technology and Informatics 116: 205–10. PMID 16160260. . [4] "Evaluation of a Computer Assisted Decision Support System (DSS) for Diagnosis and Treatment of Ventilator Associated Pneumonia (VAP) in Intensive Care Unit (ICU)." (http:/ / gateway. nlm. nih. gov/ MeetingAbstracts/ ma?f=102248792. html). nih.gov. . Retrieved 2008-10-03. [5] "DiagnosisPro differential diagnosis reminder tool" (http:/ / en. diagnosispro. com/ ). diagnosispro.com. . Retrieved 2008-10-03. [6] http:/ / www. visualdx. com Compiled and Edited by Marc Imhotep Cray , M.D.
  • Symptom 148 Symptom A symptom (from Greek σύμπτωμα, "accident, misfortune, that which befalls"[1] , from συμπίπτω, "I befall", from συν- "together, with" + πίπτω, "I fall") is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality. A symptom is subjective,[2] observed by the patient,[3] and not measured.[4] A symptom may not be a malady, for example symptoms of pregnancy. One could debate, however, that this is an example of common misuse of a word, as the majority of symptoms and the history of the word are related to malady. The proper word for such situations would be "indication" or "suggestion" or simply "sign" Types Symptoms may be chronic, relapsing or remitting. They also may progressively worsen or progressively become better (convalescence). Conditions may also be classified as symptomatic (present and demonstrating symptoms) or asymptomatic (present but without symptoms). Asymptomatic conditions and asymptomatic infections can exist for many years undiagnosed and may only be found upon medical testing (such as high blood pressure). Constitutional or general symptoms are those that are related to the systemic effects of a disease (e.g., fever, malaise, anorexia, weight loss). They affect the entire body rather than a specific organ or location. The terms "chief complaint", "presenting symptom", or "presenting complaint" are used to describe the initial concern which brings a patient to a doctor. The symptom that ultimately leads to a diagnosis is called a "cardinal symptom". Non-specific symptoms are those self-reported symptoms that do not indicate a specific disease process or involve an isolated body system. For example, fatigue is a feature of an enormous number of medical conditions, and is a documented feature of both acute and chronic medical conditions, both physical and mental disorders, and as both a primary and secondary symptom. Fatigue is also a normal, healthy condition when experienced after exertion or at the end of a day. Positive and negative symptoms In describing mental disorders,[5] [6] especially schizophrenia, symptoms can be divided into positive and negative symptoms.[7] • Positive symptoms are symptoms that most individuals do not normally experience but are present in the disorder. Examples are hallucinations, delusions, and bizarre behavior.[5] • Negative symptoms are symptoms that are not present or that are diminished in the affected persons but are normally found in healthy persons. Examples are social withdrawal, apathy, inability to experience pleasure and defects in attention control.[6] Possible causes Some symptoms occur in a wide range of disease processes, whereas other symptoms are fairly specific for a narrow range of illnesses. For example, a sudden loss of sight in one eye has a significantly smaller number of possible causes than nausea does. Some symptoms can be misleading to the patient or the medical practitioner caring for them. For example, inflammation of the gallbladder often gives rise to pain in the right shoulder, which may understandably lead the patient to attribute the pain to a non-abdominal cause such as muscle strain. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Symptom 149 Symptom versus sign A symptom can more simply be defined as any feature which is noticed by the patient. A sign is noticed by other people. It is not necessarily the nature of the sign or symptom which defines it, but who observes it. A feature might be sign or a symptom, or both, depending on the observer(s). For example, a skin rash may be noticed by either a healthcare professional as a sign, or by the patient as a symptom. When it is noticed by both, then the feature is both a sign and a symptom. Some features, such as pain, can only be symptoms, because they cannot be directly observed by other people. Other features can only be signs, such as a blood cell count measured in a medical laboratory. References [1] Sumptoma, Henry George Liddell, Robert Scott, A Greek-English Lexicon, at Pursues (http:/ / www. perseus. tufts. edu/ cgi-bin/ ptext?doc=Perseus:text:1999. 04. 0057:entry=#98870) [2] Pathology - Glossary (http:/ / www. uwo. ca/ pathol/ glossary. html#S) [3] eMedicine/Stedman Medical Dictionary Lookup! (http:/ / www. emedicine. com/ asp/ dictionary. asp?keyword=symptom) [4] Devroede G (1992). "Constipation--a sign of a disease to be treated surgically, or a symptom to be deciphered as nonverbal communication?". J. Clin. Gastroenterol. 15 (3): 189–91. doi:10.1097/00004836-199210000-00003. PMID 1479160. [5] Encyclopedia of Mental Disorders: positive symptom (http:/ / www. minddisorders. com/ Ob-Ps/ Positive-symptoms. html) [6] [http://www.minddisorders.com/Kau-Nu/Negative-symptoms.html Encyclopedia of Mental Disorders: negative symptom [7] Mental Health: a Report from the Surgeon General (http:/ / www. surgeongeneral. gov/ library/ mentalhealth/ chapter2/ sec2. html) Medical sign A medical sign is an objective[1] indication of some medical fact or characteristic that may be detected by a physician during a physical examination of a patient.[2] Signs may have no meaning for, and can even go unnoticed by, the patient, but may be full of meaning for the healthcare provider, and are often significant in assisting a healthcare provider in diagnosis of medical condition(s) responsible for the patients symptoms. Examples include elevated blood pressure, a clubbing of the fingers (which may be a sign of lung disease, or many other things), and arcus senilis. The term sign is not to be confused with the term indication, which denotes a valid reason for using some treatment. Signs and semiotics The art of interpreting clinical signs was originally called semiotics (a term now used for the study of sign communication in general) in English. This term, then written semeiotics (derived from the Greek adjective σημειοτικός: semeiotikos, "to do with signs"), was first used in English in 1670 by Henry Stubbes (1631–1676), to denote the branch of medical science relating to the interpretation of signs: …nor is there any thing to be relied upon in Physick, but an exact knowledge of medicinal phisiology (founded on observation, not principles), semeiotics, method of curing, and tried (not excogitated, not commanding) medicines…[3] Compiled and Edited by Marc Imhotep Cray , M.D.
  • Medical sign 150 Eponymous signs Historically, medical signs were named after the physicians who first described them.[4] Signs versus symptoms Signs are different from symptoms, the subjective experiences, such as fatigue, that patients might report to their examining physician. For convenience, signs are commonly distinguished from symptoms as follows: Both are something abnormal, relevant to a potential medical condition, but a symptom is experienced and reported by the patient, while a sign is discovered by the physician during examination of the patient.[5] :75 A slightly different definition views signs as any indication of a medical condition that can be objectively observed (i.e., by someone other than the patient), whereas a symptom is merely any manifestation of a condition that is apparent to the patient (i.e., something consciously affecting the patient). From this definition, it can be said that an asymptomatic patient is uninhibited by disease. However, a doctor may discover the sign hypertension in an asymptomatic patient, who does not experience "dis-ease", and the sign indicates a disease state that poses a hazard to the patient. With this set of definitions, there is some overlap – certain things may qualify as both a sign and a symptom (e.g., a bloody nose). Lester S. King, author of Medical Thinking, argues that an "essential feature" of a sign is that there is both a sign [or "signifier"] and a "thing signified". And, because "the essence of a sign is to convey information", it can only be a sign, properly speaking, if it has meaning. Therefore, "a sign ceases to be a sign when you cannot read it".[5] :73–74 A person, who has and exercises the knowledge required to understand the significance or indication or meaning of the sign, is necessary for something to be a complete sign. A physical phenomenon that is not actually interpreted as a sign pointing to something else is, in medicine, merely a symptom. Thus, King rejects "these present-day views [distinguishing signs from symptoms based on patient-subjective versus clinician-objective], however widely accepted, as quite faulty, at variance not only with ordinary usage but with the entire history of medicine."[5] :77 Types of signs Medical signs may be classified by the type of inference that may be made from their presence,[5] :80–81 for example: • Prognostic signs (from progignṓskein, προγιγνώσκειν, "to know beforehand"): signs that indicate the outcome of the current bodily state of the patient (i.e., rather than indicating the name of the disease). Prognostic signs always point to the future. Perhaps the most famous prognostic sign is the facies Hippocratica: "[If the patients facial] appearance may be described thus: the nose sharp, the eyes sunken, the temples fallen in, the ears cold and drawn in and their lobes distorted, the skin of the face hard, stretched and dry, and the colour of the face pale or dusky.… and if there is no improvement within [a prescribed period of time], it must be realized that this sign portends death."[6] • Anamnestic signs (from anamnēstikós, ἀναμνηστικός, "able to recall to mind"): signs that (taking into account the current state of a patients body), indicate the past existence of a certain disease or condition. Anamnestic signs always point to the past. (Whenever we see a man walking with a particular gait, with one arm paralysed in a particular way, we say "This man has had a stroke"; and, if we see a woman in her late 50s with one arm distorted in a particular way, we say "She had polio as a child".) • Diagnostic signs (from diagnōstikós, διαγνωστικός, "able to distinguish"): signs that lead to the recognition and identification of a disease (i.e., they indicate the name of the disease). • Pathognomonic signs (from pathognomonikós, παθογνωμονικός, "skilled in diagnosis", derived from páthos, πάθος, "suffering, disease", and gnṓmon, γνώμον, "judge, indicator"): the particular signs whose presence means, beyond any doubt, that a particular disease is present. They represent a marked intensification of a diagnostic Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Medical sign 151 sign. (An example would be the palmar xanthomata seen on the hands of people suffering from hyperlipoproteinaemia.) Singular pathognomonic signs are relatively uncommon. "[Thus] a symptom is a phenomenon, caused by an illness and observable directly in experience. We may speak of it as a manifestation of illness. When the observer reflects on that phenomenon and uses it as a base for further inferences, then that symptom is transformed into a sign. As a sign it points beyond itself — perhaps to the present illness, or to the past or to the future. That to which a sign points is part of its meaning, which may be rich and complex, or scanty, or any gradation in between. In medicine, then, a sign is thus a phenomenon from which we may get a message, a message that tells us something about the patient or the disease. A phenomenon or observation that does not convey a message is not a sign. The distinction between signs and symptom rests on the meaning, and this is not perceived but inferred."[5] :81 Technological development creating signs detectable only by physicians Prior to the nineteenth century there was little difference in the powers of observation between physician and patient. Most medical practice was conducted as a joint co-operative interaction between the physician and the patient as equals.[7] [8] Whilst each noticed much the same things, the physician had a more informed interpretation of those things: "the physicians knew what the findings meant and the layman did not".[5] :82 Advances in the 19th century However, the patient was gradually removed from the medical interaction[7] [8] [9] due to significant technological advances such as: • The 1808 introduction of the percussion technique: “ ” "The process through which "the physician can assess the state of the underlying lung by sensing the character of vibrations by gentle taps on the chest wall [something which] greatly facilitated the diagnosis of pneumonia and other respiratory diseases" [10] The techniques, which had been first described by the Viennese physician Leopold Auenbrugger (1722–1809) in 1761, became far more widely known following the publication of Jean-Nicolas Corvisarts translation of Auenbruggers work in 1808. • The 1819 introduction by René Laënnec (1781–1826) of the technique of auscultation (using a stethoscope to listen to the circulatory and respiratory functions of the body). Laënnecs publication was translated into English, 1821–1834, by John Forbes. • The 1846 introduction by surgeon John Hutchinson (1811–1861) of the spirometer, an apparatus for assessing the mechanical properties of the lungs via measurements of forced exhalation and forced inhalation. (The recorded lung volumes and air flow rates are used to distinguish between restrictive disease (in which the lung volumes are decreased: e.g., cystic fibrosis) and obstructive diseases (in which the lung volume is normal but the air flow rate is impeded; e.g., emphysema).) • The 1851 invention by Hermann von Helmholtz (1821–1894) of the ophthalmoscope, which allowed physicians to examine the inside of the human eye. • The 1895 clinical use of X-rays which began almost immediately after they had been discovered that year by Wilhelm Conrad Röntgen (1845–1923). • The 1896 introduction of the sphygmomanometer, designed by Scipione Riva-Rocci (1863–1937), to measure blood pressure. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Medical sign 152 Alteration of the relationship between physician and patient The introduction of the techniques of percussion and auscultation into medical practice altered the relationship between physician and patient in a very significant way, specifically because these techniques relied almost entirely upon the physician listening. Not only did this greatly reduce the patients capacity to observe and contribute to the process of diagnosis, it also meant that the patient was often instructed to stop talking, and remain silent. As these sorts of evolutionary changes continued to take place in medical practice, it was increasingly necessary to uniquely identify data that was accessible only to the physician, and to be able to differentiate those observations from others that were also available to the patient, and it just seemed natural to use "signs" for the class of physician-specific data, and "symptoms" for the class of observations available to the patient. King proposes a more advanced notion; namely, that a sign is something that has meaning, regardless of whether it is observed by the physician or reported by the patient: The belief that a symptom is a subjective report of the patient, while a sign is something that the physician elicits, is a 20th-century product that contravenes the usage of two thousand years of medicine. In practice, now as always, the physician makes his judgments from the information that he gathers. The modern usage of signs and symptoms emphasizes merely the source of the information, which is not really too important. Far more important is the use that the information serves. If the data, however derived, lead to some inferences and go beyond themselves, those data are signs. If, however, the data remain as mere observations without interpretation, they are symptoms, regardless of their source. Symptoms become signs when they lead to an interpretation. The distinction between information and inference underlies all medical thinking and should be preserved.[5] :89 Signs as tests In some senses, the process of diagnosis is always a matter of assessing the likelihood that a given condition is present in the patient. In a patient who presents with haemoptysis (coughing up blood), the haemoptysis is very much more likely to be caused by respiratory disease than by the patient having broken their toe. Each question in the history taking allows the medical practitioner to narrow down their view of the cause of the symptom, testing and building up their hypotheses as they go along. Examination, which is essentially looking for clinical signs, allows the medical practitioner to see if there is evidence in the patients body to support their hypotheses about the disease that might be present. A patient who has given a good story to support a diagnosis of tuberculosis might be found, on examination, to show signs that lead the practitioner away from that diagnosis and more towards sarcoidosis, for example. Examination for signs tests the practitioners hypotheses, and each time a sign is found that supports a given diagnosis, that diagnosis becomes more likely. Special tests (blood tests, radiology, scans, a biopsy, etc.) also allow a hypothesis to be tested. These special tests are also said to show signs in a clinical sense. Again, a test can be considered pathognonomic for a given disease, but in that case the test is generally said to be "diagnostic" of that disease rather than pathognonomic. An example would be a history of a fall from a height, followed by a lot of pain in the leg. The signs (a swollen, tender, distorted lower leg) are only very strongly suggestive of a fracture; it might not actually be broken, and even if it is, the particular kind of fracture and its degree of dislocation need to be known, so the practitioner orders an x-ray. The x-ray film shows a fractured tibia, so the film is said to be diagnostic of the fracture. Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Medical sign 153 Examples of signs • Ascites (fluid in the abdomen) • Gynecomastia (excessive breast tissue in males) • Cachexia (loss of weight, muscle atrophy) • Hemoptysis (blood-stained sputum) • Caput medusae (dilated umbilical veins) • Hepatosplenomegaly (enlarged liver and spleen) • Clubbing (deformed nails) • Icterus ("jaundice") • Cough • Lymphadenopathy (swollen lymph nodes) • Death rattle (last moments of life in a person/animal) • Palmar erythema (reddening of hands) • Fever • Splenomegaly (enlarged spleen) References [1] eMedicine/Stedman Medical Dictionary Lookup! (http:/ / www. emedicine. com/ asp/ dictionary. asp?keyword=sign) [2] Definition (http:/ / www. uwo. ca/ pathol/ glossary. html#S) at University of Western Ontario [3] Stubbe, H. (Henry Stubbes), The Plus Ultra reduced to a Non Plus: Or, A Specimen of some Animadversions upon the Plus Ultra of Mr. Glanvill, wherein sundry Errors of some Virtuosi are discovered, the Credit of the Aristotelians in part Re-advanced; and Enquiries made..., (London), 1670, p. 75 [4] See list of eponymous medical signs, and "Who Named It?" (http:/ / www. whonamedit. com/ azeponyms. cfm) for more information on eponymous signs. [5] King, Lester S. (1982). Medical Thinking: A Historical Preface. Princeton, NJ: Princeton University Press. ISBN 0691082979. [6] Chadwick, J. & Mann, W.N.(trans.) (1978). Hippocratic writings. Harmondsworth, UK: Penguin. pp. 170–171. ISBN 0-14-044451-3. [7] Jewson, N. D., " Medical Knowledge and the Patronage System in 18th Century England (http:/ / soc. sagepub. com/ cgi/ content/ abstract/ 8/ 3/ 369)", Sociology, Vol.8, No.3, (1974), pp. 369–385. [8] Jewson, N. D., " The Disappearance of the Sick Man from Medical Cosmology, 1770–1870 (http:/ / soc. sagepub. com/ cgi/ content/ abstract/ 10/ 2/ 225)", Sociology, Vol.10, No.2, (1976), pp. 225–244. [9] Tsouyopoulos N (1988). "The mind-body problem in medicine (the crisis of medical anthropology and its historical preconditions)". Hist Philos Life Sci 10 Suppl: 55–74. PMID 3413276. [10] Weatherall, D. (1996). Science and the Quiet Art: The Role of Medical Research in Health Care. New York: W. W. Norton & Company. pp. 46. ISBN 0-393-31564-9. External links • Who Named It? (http://www.whonamedit.com/azeponyms.cfm): eponymous signs. Compiled and Edited by Marc Imhotep Cray , M.D.
  • Physical examination 154 Physical examination Physical examination Intervention Examination room in Washington, DC, period of WWI. ICD-9-CM [1] 89.7 MeSH [2] D010808 Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient. Together with the medical history, the physical examination aids in determining the correct diagnosis and devising the treatment plan. This data then becomes part of the medical record. Uses of physical examinations A physical examination may be provided under health insurance cover, required of new insurance customers, or stipulated as a condition of employment. In the United States, physicals are also marketed to patients as a one-stop health review, avoiding the inconvenience of attending multiple appointments with different healthcare providers.[3] [4] Comprehensive physical exams of this type are also known as executive physicals, and typically include laboratory tests, chest x-rays, pulmonary function testing, audiograms, full body CAT scanning, EKGs, heart stress tests, vascular age tests, urinalysis, and mammograms or prostate exams depending on gender.[5] [6] The executive physical format was developed from the 1970s by the Mayo Clinic and is now offered by other health providers, including Johns Hopkins University, EliteHealth and Mount Sinai in New York City. While elective physical exams have become more elaborate, in routine use physical exams have become less complete. This has led to editorials in medical journals about the importance of an adequate physical examination. [7] [8] Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Physical examination 155 Process During a physical examination, a doctor may check both male and female reproductive organs to make sure there is not a hernia. For a male, the doctor places his hands on the testes and asks the patient to cough. For females, the doctor will do a "fingering" sort of process that will test the females reproductive organs. Format and interpretation Although providers have varying approaches as to the sequence of body parts, a systematic examination generally starts at the head and finishes at the extremities. After the main organ systems have been investigated by inspection, palpation, percussion, and auscultation, specific tests may follow (such as a neurological investigation, orthopedic examination) or specific tests when a particular disease is suspected (e.g. eliciting Trousseaus sign in hypocalcemia). With the clues obtained during the history and physical examination the healthcare provider can now formulate a Auscultation of a man in Vietnam differential diagnosis, a list of potential causes of the symptoms. Specific diagnostic tests (or occasionally empirical therapy) generally confirm the cause, or shed light on other, previously overlooked, causes. While the format of examination as listed below is largely as taught and expected of students, a specialist will focus on their particular field and the nature of the problem described by the patient. Hence a cardiologist will not in routine practice undertake neurological parts of the examination other than noting that the patient is able to use all four limbs on entering the consultation room and during the consultation become aware of their hearing, eyesight and speech. Likewise an Orthopaedic surgeon will examine the affected joint, but may only briefly check the heart sounds and chest to ensure that there is not likely to be any contraindication to surgery raised by the anaesthetist. Non-specialists generally examine the genitals only upon request of the patient. A complete physical examination includes evaluation of general patient appearance and specific organ systems. It is recorded in the medical record in a standard layout which facilitates others later reading the notes. In practice the vital signs of temperature examination, pulse and blood pressure are usually measured first. Example Section Sample text Comments General "Patient in NAD. VS: WNL" May be split on two lines. "WNL" = "within normal limits". HEENT: "NC/AT. PERRLA, EOMI. No cervical "Neck" is sometimes split out from "Head". "Good dentition" may be noted. LAD, no thyromegaly, no bruit, no pallor, fundus WNL, oropharynx WNL, tympanic membrane WNL, neck supple" Resp or "Nontender, CTA bilat" More detailed examinations can include rales, rhonchi, wheezing ("no r/r/w"), and rubs. "Chest" Other phrases may include "no cyanosis or clubbing" (if section is labeled "Resp" and not "Chest"), "fremitus WNL", and "no dullnes to percussion". CV or "+S1, +S2, RRR, no m/r/g" If "CV" is used instead of "heart", peripheral pulses are sometimes included in this "Heart" section (otherwise, they may be in the extremities section) Compiled and Edited by Marc Imhotep Cray , M.D.
  • Physical examination 156 Abd "Soft, nontender, nondistended, no If lower back pain is involved, then the "Back" may become a primary section. hepatosplenomegaly, NBS" Costovertebral angle tenderness may be included in the abdominal section if there is no back section. More detailed examinations may report "+psoas sign, +Rovsings sign, +obturator sign". If tenderness was present, it might be reported as "Direct and rebound RLQ tenderness". "NBS" stands for "normal bowel sounds"; alternatives might include "hypoactive BS" or "hyperactive BS". Ext "No clubbing, cyanosis, edema" Checking the fingers for clubbing and cyanosis is sometimes considered part of the pulmonary exam, because it closely involves oxygenation. Examinations of the knee may involve the McMurray test, Lachman test, and drawer test. Neuro "A&Ox3, CN II-XII grossly intact, Sensation may be expanded to include dull, sharp, vibration, temperature, and position Sensation intact in all four extremities (dull sense. A mental status exam may be reported at the beginning of the neurologic exam, or and sharp), DTR 2+ bilat, Romberg under a distinct "Psych" section. negative, cerebellar reflexes WNL, normal gait" Depending upon the chief complaint, additional sections may be included. For example, hearing may be evaluated with a specific Weber test and Rinne test, or it may be more briefly addressed in a cranial nerve exam. Vital signs The primary vital signs are: • Temperature recording • Blood pressure • Pulse • Respiratory rate References [1] http:/ / icd9cm. chrisendres. com/ index. php?srchtype=procs& srchtext=89. 7& Submit=Search& action=search [2] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?field=uid& term=D010808 [3] Brink, Susan (18 February 2008). "$2,000 physicals for busy execs" (http:/ / articles. latimes. com/ 2008/ feb/ 18/ health/ he-exec18). Los Angeles Times. . Retrieved 16 July 2009. [4] Armour, Lawrence A. (21 July 1997). "2,500 executives flock to Rochester, Minn., for a deluxe, soup-to-nuts physical at the Mayo clinic. Our man went for a tune-up to find out why" (http:/ / money. cnn. com/ magazines/ fortune/ fortune_archive/ 1997/ 07/ 21/ 229208/ index. htm). CNN.com. . Retrieved 16 July 2009. [5] "EliteHealth Executive Physical Exam" (http:/ / www. elitehealth. com/ executive_physical_exams. php). . [6] "John Hopkins Executive Health Program" (http:/ / www. hopkinsmedicine. org/ gim/ clinical/ executive_health/ personalized. html#standard). . [7] Flegel KM (November 1999). "Does the physical examination have a future?". Canadian Medical Association Journal 161 (9): 1117–8. PMC 1230732. PMID 10569087. [8] McAlister FA, Straus SE, Sackett DL (February 2000). "High marks for the physical exam". Canadian Medical Association Journal 162 (4): 493. PMC 1231165. PMID 10701381. External links • Video Resource: General Practitioner examination videos by a consultant orthopaedic surgeon (http://tenease. com/videos) • Connecticut Tutorials Physical Examination Video (http://www.conntutorials.com/) • Physical examination of respiratory system video (http://medicaleducator.co.uk/ medicalstudent-practical-video-guides/) • The Journal of Clinical Examination - A useful online source for evidence-based guidance on physical examination (http://www.thejce.com/) Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Article Sources and Contributors 157 Article Sources and Contributors Anatomy  Source: http://en.wikipedia.org/w/index.php?oldid=444364443  Contributors: 168..., 1Dot11, 203.109.250.xxx, =Benjamin=, A J Hay, A Macedonian, APH, Abdjibawi, AdAdAdAd, Adolphus79, Ahoerstemeier, Airplaneman, Akanemoto, Alex43223, Ams80, AnatomyArcade, Andre Engels, Andy Smith, AnemoneProjectors, Angela, Ap, Arkuat, Art LaPella, Aryeh, Astral, Baa, Basharh, Bcooper1210, Bejnar, Ben-Zin, Benjaminkuitenbrouwer, Biblioanatomica, Blackjack48, Blackwell79, Bmicomp, Bobo192, Bodnotbod, Bogdangiusca, Bornintheguz, Brandmeister (old), Brian Crawford, Brian0918, Bryan Derksen, Burner0718, Cant sleep, clown will eat me, Cdc, Ceranthor, Chrisch, Cliff smith, CloudNine, Cobi, Conleylm, Conversion script, Courcelles, Crusio, Cyde, DARTH SIDIOUS 2, DBishop1984, DOCtraind, DSRH, Danaman5, Dantel50, Dany4175, Dar-Ape, Davehi1, Dcljr, DeadEyeArrow, Demonfox7, Derwig, Devapriya, Diberri, Dimmes, Discospinster, Doctorbruno, Docu, Dori, Dracontes, Dramatic, Dubliner, Dullhunk, Dwayne Reed, Ebricca, Ec5618, Edward321, Ehwills, El C, Eleassar777, Enchanter, Epbr123, Erik Zachte, EugeneZelenko, Evercat, Fastilysock, Fatimahaider, FernandoAires, Feydey, FrancoGG, Fribbler, Funandtrvl, Funguyinfection, Furkaocean, Galoubet, GameKeeper, Garion96, Gaseous Snake, Gdoggy111, Gekosart, Gerry Ashton, Giftlite, Gilliam, Git2010, Glenn, Gracenotes, GraemeL, Graham87, Grunt, Gsdlova, Gurch, Guy Peters, Hadal, Haham hanuka, Harps21, Hashar, Hbackman, HeikoEvermann, Henrik, Herakles01, Herk1955, Homie727, Hopiakuta, Hu, Hypoglossal00, Hysbys, Ian Pitchford, Iridescent, Irishguy, Itselectric, JNW, Jaania, Jagged 85, Jaknouse, Jcbutler, Jfdwolff, Jhenderson777, Jim Flint, JimVC3, Jimothytrotter, Jiy, Jnyanydts, JoanneB, Joe de Coy, Joehall45, John254, Johnuniq, Jonathanlund, Jonkerz, Jpgordon, Jrockley, Jyril, KHAAAAAAAAAAN, KVDP, Kakofonous, Katalaveno, Keilana, Kelly Martin, Kenny sh, Kim Bruning, Kingpin13, Kipala, Kirt, Kmab, Knutux, Kosebamse, Kpjas, LC, Landskull 12, Leonard G., Lexor, Lightmouse, LilacPhonograph, Linforest, Lir, Livin.la.vi.da.loca, Mac, Mace, Machn, Magioladitis, Magnus Manske, Majorly, Malcolm Farmer, Man vyi, Mandarax, Marnanel, MarylandArtLover, Matdrodes, Materialscientist, Mattie2465, Maurreen, Mav, Mayumashu, Mboverload, Medicineman28, Messerup, Mgiganteus1, Michal Nebyla, Mikdawg15, Minna Sora no Shita, Mitch Ames, Mkraft9650, Mnfiero, Moh man742, Mokele, Mortotron 77777, Mr.DH, Mschel, Mxn, Myanw, NAKEDRICKY, Nafile, Nakon, NatureA16, NawlinWiki, NellieBly, Neurolysis, Nevlow, Newt Winkler, Nick, Nikai, Nishanthb, Nivix, Nk, No Mu, Noldoaran, Non-dropframe, NonNobisSolum, Notinasnaid, NuclearWarfare, Odysses, Ohnoitsjamie, OnardFMA, Optimale, Ortonmc, OttoMäkelä, Paleorthid, Patrick, Persian Poet Gal, Philip Trueman, Piano non troppo, Pinethicket, Plastinacion, Pmlineditor, Poopoogenius, Possum, Poul818, Qst, Quiddity, Quintote, Qwertying, RMFan1, Radon210, 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  • Article Sources and Contributors 159 Endocrinology  Source: http://en.wikipedia.org/w/index.php?oldid=445034250  Contributors: 213.76.2.xxx, APH, Abel.alfonso, Alsandro, Alteripse, Animum, Anna19025, Anypodetos, Aranel, Arcadian, Atchernev, Avicennasis, Ben-Zin, Bernfarr, BlastOButter42, Blurpeace, BrettAllen, Brighterorange, Bryan Derksen, Bryce, CDN99, Ceyockey, Charm, Christian15213, Conversion script, Corinne68, Crkey, Cybergoth, Cícero, Danierrr, Davewild, Deathphoenix, DerHexer, DoctorJohn12345, Domino42, DrFO.Jr.Tn, Drguttler, Drmies, EBMdoc, Earle Martin, Earthdirt, Edgar181, Edward, Ekem, El C, Emperorbma, Eras-mus, Everyking, Evolauxia, Fiquem, Flowanda, Fortdj33, Fvasconcellos, Gabbe, Gadfium, Gaius Cornelius, Gioto, Gleng, Gobonobo, Grieret, Gtrmp, HamburgerRadio, Helon, Hu12, Ian Pitchford, Ianmc, Ilc808, Immunize, Interpretre, Ioan-Mihai Gale I, Iokseng, Iushad, IvanLanin, J.delanoy, JWSchmidt, Jagged 85, Jan11989, Janibul, Jbacharach, Jfdwolff, JorgeGG, Kaobear, Kpjas, Kstrojwas, Lampica, Lando5, LeadSongDog, Lshanahan, Malcolm Farmer, Marumari, Mav, Merlinsorca, Mig11, Mikhail Ryazanov, Mineralogy, Mktgguest1, Mmxx, MrOllie, Mushin, Nirmos, Nono64, OrbitSoldier, Orioane, PFHLai, Palladius, Patxi lurra, Pearlls sun, Plindenbaum, Poindexter Propellerhead, Puchiko, Quadricode, RDBrown, Rewster, Rich Farmbrough, Riskiebiz, Rjwilmsi, RoyBoy, Samarat, Sgall, Shrimp wong, Singinglemon, Sirmelle, Steve Rawlinson, Takk hx3, Teles, Template namespace initialisation script, Themfromspace, Think outside the box, ThomasPusch, Tide rolls, Tobby72, TreasuryTag, TrojanMan, Velvetron, Versageek, Waggers, Wikij2, Will Beback Auto, Wolfkeeper, Wolfmankurd, Wowanda 88, Wrp103, Yintan, Åkebråke, 221 anonymous edits General pathology  Source: http://en.wikipedia.org/w/index.php?oldid=434864752  Contributors: Emmanuelm, Frietjes, Geometry guy, Meercat96, PigFlu Oink, Rror, Yobmod Immunology  Source: http://en.wikipedia.org/w/index.php?oldid=444489076  Contributors: APH, AbinoamJr, Adavallou, Aetkin, Alansohn, Andreadb, Andres, Andries, Antigrandiose, Arcadian, Argon233, Ariedartin, ArmadilloFromHell, Art LaPella, AxelBoldt, Bact, Blueboy96, Bratsche, Brtlabs, Caltas, Celefin, Cforrester101, Christian List, Cinik, Connelly, Conversion script, Crashdoom, Current Protocols, DGG, DO11.10, Dave Nelson, Delfino2009, Dicklyon, Djcam, Dono, Dreadstar, ESkog, Ebmat, Edward Gordon Gey, Eleassar777, Emesee, Espoo, Evershine, Everyking, Fasach Nua, Flowanda, Franamax, Gaius Cornelius, Gcm, Giftlite, Gilliam, GrahamColm, Haham hanuka, Hopping, Hparnell, Hughbl, Ilc808, IvanLanin, J.delanoy, Jachis07, Jan11989, Jethero, Jfdwolff, Jfurr1981, Johnuniq, JonHarder, JosephBarillari, Jwy, KVDP, Kanei22, Kappa, Karol Langner, Kpjas, Kubra, Lampica, Latka, LeaveSleaves, Leptictidium, Lightmouse, Magnus Manske, Medrise, MichaelJanich, Mikael Häggström, Mktgguest1, Mlaffs, MrOllie, NameIsRon, NawlinWiki, NewEnglandYankee, Nicolas guyot, Oo64eva, Orange Suede Sofa, Osteoimm, Otets, Ozmaweezer, Pascal.Tesson, Pejhman, Pinethicket, Pjvpjv, Quantumobserver, R. 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B., Alansohn, Alphabeta123, Andres, AndrewHowse, Andy M. Wang, Andy.we, Andycjp, Arcadian, B7T, Ballista, Barticus88, BillC, Brinerustle, Bryan Derksen, Brz7, COMPFUNK2, Caco de vidro, Cgingold, Conti, CrackDragon, Dacoutts, Danny, DeadEyeArrow, Diberri, Dougweller, Dr. Cornelius OLochlan, Drrem, EdBever, Ellywa, Erich gasboy, Ettrig, Excirial, FF2010, Fred Condo, Gilliam, GraemeL, Greetings, Earthling, Harionlad, Hede2000, Henrik, Hintgergedani, ImperfectlyInformed, Innerfire, Isoxyl, J.delanoy, Jannex, Jclemens, Jfdwolff, Jim62sch, JoaoMenezes, JoergenB, JoeyluvMary, Jonkerz, Karada, Kd4ttc, Compiled and Edited by Marc Imhotep Cray , M.D.
  • Article Sources and Contributors 162 Kjkolb, Kpjas, Levineps, Lindsay658, LittleHow, Lova Falk, Lugnuts, MER-C, MONGO, Maha ts, Mani1, Marasmusine, Mark.murphy, Mendalus, Michael Hardy, MichaelBillington, Mikael Häggström, Mike2vil, Minority Report, Misza13, Modulatum, Ncurrier, Nguyen Thanh Quang, NickGorton, Nono64, Nposs, Pasi, Pit, Quarkfactor, RJP, RShnike, Ranveig, Rasa ponomarenko, Richard0612, RoyBoy, Rramir16, Ryanjc559, SD5, Sakkout, Samsubhash, Senator Palpatine, Sherybatta, Sietse Snel, SiobhanHansa, Someone else, Somethingironic, Stoa, Tdolphin, The Thing That Should Not Be, TheBearPaw, TheEgyptian, Trixt, Vegetator, Versageek, WLU, WereSpielChequers, WhatamIdoing, Wiki alf, Woohookitty, Yidisheryid, 124 anonymous edits Medical sign  Source: http://en.wikipedia.org/w/index.php?oldid=443418173  Contributors: Akane700, AlanS1951, Alansohn, Alex.tan, Andthu, Antifamilymang, Antono, Arcadian, Bryan Derksen, Calypso Joe, Cmh, D6, DabMachine, Darrel francis, Dr Oldekop, Eequor, Eleassar777, Ellywa, FirstPrinciples, Fluoborate, Fredrik, Hairy Dude, Hcx0331, J04n, Jfdwolff, John Vandenberg, KathrynLybarger, Kavadi carrier, Kjkolb, Levineps, Lindsay658, Marilyn.hanson, Mendalus, Michael Hardy, Mike2vil, Minority Report, Neelix, Nephron, Noetica, Oldekop, PsychoticSock, Rkomatsu, SMcCandlish, Seforadev, Shirt58, Tamfang, Tdolphin, Tenorcnj, Tmonzenet, Una Smith, Velella, Vogon77, Wojder, Xanzzibar, Пёс-призраг, 31 anonymous edits Physical examination  Source: http://en.wikipedia.org/w/index.php?oldid=445523498  Contributors: AED, Abbas73, Aeon1006, Afr77, Amisme, Andrewr47, Anonymaus, Arcadian, Ayman Qasrawi, Az1568, Blueboy96, Burhan Ahmed, CDN99, Ciumtt, CopperKettle, Csweatjr, Cynique86, D.G.S.V.D. Gajasinghe, Datongli, Daughter of Mímir, Davepape, Davidruben, Dekimasu, Delta759, Deville, Difu Wu, Digfarenough, Dolphin51, E2e3v6, Edgar181, El T, Eleassar, Eleassar777, Fiziker, Gaius Cornelius, Gary King, Gene Nygaard, George100, Goga312, Gogo Dodo, Gonzonoir, Graham87, Headbomb, Hiberniantears, High Contrast, ITasteLikePaint, Iatrogenic, Imaginaryoctopus, Insanity Incarnate, Isnow, J.delanoy, J04n, JD554, Janibul, Jfdwolff, Jgatesy, Jkuo3, Jlittlet, Joechao, Karada, Kauczuk, Kilfoylea, Kilroggftw, Kmccoy, Ksheka, Lowellian, Master1228, Mayfare, Medicine786, Mel Etitis, Mikael Häggström, MrOllie, NawlinWiki, Nephron, Nerdroid, Notinasnaid, NuvieK, Ohnoitsjamie, Owain.davies, PeeKoo, Petersam, Pkubin, Porchcorpter, Pyllis, Qajar, RnB, Rewster, Rsage, Saladjohn316, SchuminWeb, Scott1965, Sillyfolkboy, Steven J. Anderson, Stevenfruitsmaak, THB, Tdolphin, TheListener, Theanphibian, Tony Sidaway, Una Smith, Uncle G, WLU, Wattly, Wouterstomp, Zodon, Zoe Buchanan, 135 anonymous edits Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer
  • Image Sources, Licenses and Contributors 163 Image Sources, Licenses and Contributors File:COLLECTIE TROPENMUSEUM Anatomische les op de dokter Djawaschool in Weltevreden Batavia Java TMnr 10002345.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:COLLECTIE_TROPENMUSEUM_Anatomische_les_op_de_dokter_Djawaschool_in_Weltevreden_Batavia_Java_TMnr_10002345.jpg  License: unknown  Contributors: Docu, Humboldt File:Structural.gif  Source: http://en.wikipedia.org/w/index.php?title=File:Structural.gif  License: Creative Commons Attribution-Sharealike 3.0  Contributors: Dwayne Reed (talk) Original uploader was Dwayne Reed at en.wikipedia File:Chest.png  Source: http://en.wikipedia.org/w/index.php?title=File:Chest.png  License: Creative Commons Attribution-ShareAlike 3.0 Unported  Contributors: Bryan, Chikumaya, Juiced lemon, Lipothymia, O File:Heart-and-lungs.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Heart-and-lungs.jpg  License: Public Domain  Contributors: Grays Anatomy File:Blastulation.png  Source: http://en.wikipedia.org/w/index.php?title=File:Blastulation.png  License: Public Domain  Contributors: Pidalka44 File:Gastrulation.png  Source: http://en.wikipedia.org/w/index.php?title=File:Gastrulation.png  License: Public Domain  Contributors: Mithril, Pidalka44 File:6 weeks pregnant.png  Source: http://en.wikipedia.org/w/index.php?title=File:6_weeks_pregnant.png  License: Creative Commons Attribution-Sharealike 2.5  Contributors: Escondites, Ipankonin, 5 anonymous edits File:10dayMouseEmb.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:10dayMouseEmb.jpg  License: Creative Commons Attribution-ShareAlike 3.0 Unported  Contributors: Bo Li File:Beetle larvae filtered sw.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Beetle_larvae_filtered_sw.jpg  License: Public Domain  Contributors: C.G.Calwer, 1876 Image:Sucrose-inkscape.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Sucrose-inkscape.svg  License: GNU Free Documentation License  Contributors: Don A. 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 Source: http://en.wikipedia.org/w/index.php?title=File:Cellulose-2D-skeletal.png  License: Public Domain  Contributors: Benjah-bmm27, Edgar181, Slashme Image:1GZX Haemoglobin.png  Source: http://en.wikipedia.org/w/index.php?title=File:1GZX_Haemoglobin.png  License: GNU Free Documentation License  Contributors: Original uploader was Zephyris at en.wikipedia Image:Amino acids 1.png  Source: http://en.wikipedia.org/w/index.php?title=File:Amino_acids_1.png  License: GNU Free Documentation License  Contributors: Arria Belli, CommonsDelinker, CommonsDelinkerHelper, Edgar181, Karelj, Matanya (usurped), OsamaK, 1 anonymous edits Image:Schematic relationship between biochemistry, genetics and molecular biology.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Schematic_relationship_between_biochemistry,_genetics_and_molecular_biology.svg  License: Creative Commons Attribution-ShareAlike 3.0 Unported  Contributors: OldakQuill, PatríciaR File:Microscope with stained slide.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Microscope_with_stained_slide.jpg  License: GNU Free Documentation License  Contributors: Every1blowz File:Emphysema H and E.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Emphysema_H_and_E.jpg  License: Creative Commons Attribution 2.0  Contributors: Cwbm (commons), Snek01, 1 anonymous edits Image:Snow-cholera-map.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Snow-cholera-map.jpg  License: Public Domain  Contributors: Corso, DO11.10, Editor at Large, Lenildo, Oxyman, Warburg, Wouterhagens, 10 anonymous edits Image:DNA Overview2.png  Source: http://en.wikipedia.org/w/index.php?title=File:DNA_Overview2.png  License: GNU Free Documentation License  Contributors: Uploaders work on original work by mstroeck Image:Sexlinked inheritance white.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Sexlinked_inheritance_white.jpg  License: Public Domain  Contributors: Electric goat Image:Punnett square mendel 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Price Ball at en.wikipedia Image:Genetic code.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Genetic_code.svg  License: Creative Commons Attribution-Sharealike 2.5  Contributors: Madprime Image:Sickle cell hemoglobin shortened.png  Source: http://en.wikipedia.org/w/index.php?title=File:Sickle_cell_hemoglobin_shortened.png  License: Public Domain  Contributors: Madeleine Price Ball, Materialscientist, 1 anonymous edits File:Niobe050905-Siamese Cat.jpeg  Source: http://en.wikipedia.org/w/index.php?title=File:Niobe050905-Siamese_Cat.jpeg  License: Creative Commons Attribution-Sharealike 2.5  Contributors: en:User:TrinnyTrue Image:Zinc finger DNA complex.png  Source: http://en.wikipedia.org/w/index.php?title=File:Zinc_finger_DNA_complex.png  License: GNU Free Documentation License  Contributors: Thomas Splettstoesser Image:Gene-duplication.png  Source: http://en.wikipedia.org/w/index.php?title=File:Gene-duplication.png  License: Public Domain  Contributors: Courtesy: National Human Genome Research Institute Image:Eukaryote tree.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Eukaryote_tree.svg  License: Creative Commons Attribution-ShareAlike 3.0 Unported  Contributors: Madprime Image:Drosophila melanogaster - side (aka).jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Drosophila_melanogaster_-_side_(aka).jpg  License: Creative Commons Attribution-Sharealike 2.5  Contributors: André Karwath aka Aka Image:Ecoli colonies.png  Source: http://en.wikipedia.org/w/index.php?title=File:Ecoli_colonies.png  License: Creative Commons Attribution-ShareAlike 3.0 Unported  Contributors: Madprime Image:NIEHScell.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:NIEHScell.jpg  License: Public Domain  Contributors: US Government Image:FluorescentCells.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:FluorescentCells.jpg  License: Public Domain  Contributors: Amada44, DO11.10, Emijrp, Hannes Röst, NEON ja, Origamiemensch, Splette, Tolanor, 7 anonymous edits Image:Electronmicroscopynhlbi.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Electronmicroscopynhlbi.jpg  License: Public Domain  Contributors: U. S. government Image:Drosophila m oogenesis.png  Source: http://en.wikipedia.org/w/index.php?title=File:Drosophila_m_oogenesis.png  License: GNU Free Documentation License  Contributors: Dysmachus, Mindmatrix, Superborsuk Image:PD-icon.svg  Source: http://en.wikipedia.org/w/index.php?title=File:PD-icon.svg  License: Public Domain  Contributors: Various. See log. (Original SVG was based on File:PD-icon.png by Duesentrieb, which was based on Image:Red copyright.png by Rfl.) Image:Blood cell crossing vascular sinus wall - TEM.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Blood_cell_crossing_vascular_sinus_wall_-_TEM.jpg  License: Public Domain  Contributors: Louisa Howard, Roy Fava File:Monocyte.png  Source: http://en.wikipedia.org/w/index.php?title=File:Monocyte.png  License: GNU Free Documentation License  Contributors: Arcadian, Bobjgalindo, Joey-das-WBF, Marek M, Tano4595 Compiled and Edited by Marc Imhotep Cray , M.D.
  • Image Sources, Licenses and Contributors 164 File:Increase2.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Increase2.svg  License: unknown  Contributors: Sarang Image:Agar plate with colonies.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Agar_plate_with_colonies.jpg  License: Public Domain  Contributors: Ies, Phyzome, Roomba, Wickey-nl, Wst Image:Anton van Leeuwenhoek.png  Source: http://en.wikipedia.org/w/index.php?title=File:Anton_van_Leeuwenhoek.png  License: Public Domain  Contributors: Jan Verkolje (1650—1693) Image:Samadams2.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Samadams2.jpg  License: GNU Free Documentation License  Contributors: Original uploader was Kafziel at en.wikipedia Image:Renal Cell Carcinoma.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Renal_Cell_Carcinoma.jpg  License: Public Domain  Contributors: Nehrams2020, Rustavo, 2 anonymous edits File:UNDmicroscope.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:UNDmicroscope.jpg  License: Creative Commons Attribution-Share Alike  Contributors: Bobjgalindo Image:Konelab60i.png  Source: http://en.wikipedia.org/w/index.php?title=File:Konelab60i.png  License: GNU Free Documentation License  Contributors: User Soaj on fi.wikipedia File:Acute leukemia-ALL.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Acute_leukemia-ALL.jpg  License: GNU Free Documentation License  Contributors: Original uploader was VashiDonsk at en.wikipedia File:Birth defect03.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Birth_defect03.jpg  License: GNU Free Documentation License  Contributors: Kolossos File:Powdery mildew.JPG  Source: http://en.wikipedia.org/w/index.php?title=File:Powdery_mildew.JPG  License: GNU Free Documentation License  Contributors: Ejdzej, Pedros, Romanm, 1 anonymous edits Image:Infiltrating ductal carcinoma of the breast.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Infiltrating_ductal_carcinoma_of_the_breast.jpg  License: Public Domain  Contributors: DO11.10, Ephraim33, Patho File:PurkinjeCell.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:PurkinjeCell.jpg  License: Public Domain  Contributors: Chrislb, Feezil, Hystrix, Interpretix, SriMesh File:Gray739.png  Source: http://en.wikipedia.org/w/index.php?title=File:Gray739.png  License: Public Domain  Contributors: Arcadian, Lipothymia, Magnus Manske Image:GolgiStainedPyramidalCell.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:GolgiStainedPyramidalCell.jpg  License: Creative Commons Attribution-Sharealike 2.5  Contributors: Original uploader was Cahass at en.wikipedia Image:neuron colored.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Neuron_colored.jpg  License: GNU Free Documentation License  Contributors: Xpanzion, 1 anonymous edits Image:Structural.gif  Source: http://en.wikipedia.org/w/index.php?title=File:Structural.gif  License: Creative Commons Attribution-Sharealike 3.0  Contributors: Dwayne Reed (talk) Original uploader was Dwayne Reed at en.wikipedia Image:Pharmacologyprism.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Pharmacologyprism.jpg  License: Public domain  Contributors: Original uploader was Miserlou at en.wikipedia File:Mathieu Joseph Bonaventure Orfila.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Mathieu_Joseph_Bonaventure_Orfila.jpg  License: Public Domain  Contributors: Litograph by Alexandre Collette (1814-1876). Original uploader was User Magnus Manske on en.wikipedia File:Asklepios.3.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Asklepios.3.jpg  License: GNU Free Documentation License  Contributors: Nina Aldin Thune Image:Imhotep-Louvre.JPG  Source: http://en.wikipedia.org/w/index.php?title=File:Imhotep-Louvre.JPG  License: Creative Commons Attribution-ShareAlike 3.0 Unported  Contributors: User:Hu Totya Image:Medicine aryballos Louvre CA1989-2183.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Medicine_aryballos_Louvre_CA1989-2183.jpg  License: Public Domain  Contributors: User:Bibi Saint-Pol Image:Hippocrates.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Hippocrates.jpg  License: Public Domain  Contributors: G.dallorto, Knutux, Matt314 File:The Doctor Luke Fildes crop.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:The_Doctor_Luke_Fildes_crop.jpg  License: Public Domain  Contributors: Beyond My Ken Image:Drug ampoule JPN.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Drug_ampoule_JPN.jpg  License: Creative Commons Attribution-ShareAlike 3.0 Unported  Contributors: Calvero, Cwbm (commons), Ignis, Simplesse, Vantey Image:Get lautrec 1901 examination at faculty of medicine.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Get_lautrec_1901_examination_at_faculty_of_medicine.jpg  License: Public Domain  Contributors: AndreasPraefcke, Mattes, Petrusbarbygere, Sandik, TwoWings, Yareite, 1 anonymous edits file:Hx in PEDz.pdf  Source: http://en.wikipedia.org/w/index.php?title=File:Hx_in_PEDz.pdf  License: Creative Commons Attribution-Sharealike 3.0  Contributors: madhero88 Image:SystemExample.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:SystemExample.jpg  License: GNU Free Documentation License  Contributors: Original uploader was TomasBat at en.wikipedia Image:Childhood-cluster diseases world map - DALY - WHO2002.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Childhood-cluster_diseases_world_map_-_DALY_-_WHO2002.svg  License: Creative Commons Attribution-Sharealike 2.5  Contributors: Lokal_Profil File:Hives2010.JPG  Source: http://en.wikipedia.org/w/index.php?title=File:Hives2010.JPG  License: Creative Commons Attribution-Sharealike 3.0  Contributors: James Heilman, MD File:Allergy degranulation processes 01.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Allergy_degranulation_processes_01.svg  License: Creative Commons Attribution-ShareAlike 3.0 Unported  Contributors: Paweł Kuźniar (Jojo_1, Jojo) File:Allergy testing machine.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Allergy_testing_machine.jpg  License: Public Domain  Contributors: U.S. Air Force photo/Senior Airman Erin M. 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  • License 165 License Creative Commons Attribution-Share Alike 3.0 Unported http:/ / creativecommons. org/ licenses/ by-sa/ 3. 0/ Compiled and Edited by Marc Imhotep Cray , M.D.