Intracerebral hemorhage Diagnosis and managementRamesh Babu
About ICH - Diagnosis and management, Discussed the clinical presentation, evaluation, radiological features and management including recent guidelines
Intracerebral hemorhage Diagnosis and managementRamesh Babu
About ICH - Diagnosis and management, Discussed the clinical presentation, evaluation, radiological features and management including recent guidelines
acute complication of diabetes mellitus. cardinal biochemical features for DKA. pathophysiology of DKA. clinical assesment of DKA. investigation and management for DKA. complications of DKA.
Approach to Management of Upper Gastrointestinal (GI) BleedingArun Vasireddy
Upper gastrointestinal bleeding is gastrointestinal bleeding in the upper gastrointestinal tract, commonly defined as bleeding arising from the esophagus, stomach, or duodenum. Blood may be observed in vomit (hematemesis) or in altered form in the stool (melena). Depending on the severity of the blood loss, there may be symptoms of insufficient circulating blood volume and shock. As a result, upper gastrointestinal bleeding is considered a medical emergency and typically requires hospital care for urgent diagnosis and treatment. Upper gastrointestinal bleeding can be caused by peptic ulcers, gastric erosions, esophageal varices, and some rarer causes such as gastric cancer.
The initial assessment includes measurement of the blood pressure and heart rate, as well as blood tests to determine hemoglobin concentration. In significant bleeding, fluid replacement is often required, as well as blood transfusion, before the source of bleeding can be determined by endoscopy of the upper digestive tract with an esophagogastroduodenoscopy. Depending on the source, endoscopic therapy can be applied to reduce rebleeding risk. Specific medical treatments (such as proton pump inhibitors for peptic ulcer disease) or procedures (such as TIPS for variceal hemorrhage) may be used. Recurrent or refractory bleeding may lead to need for surgery, although this has become uncommon as a result of improved endoscopic and medical treatment.
acute complication of diabetes mellitus. cardinal biochemical features for DKA. pathophysiology of DKA. clinical assesment of DKA. investigation and management for DKA. complications of DKA.
Approach to Management of Upper Gastrointestinal (GI) BleedingArun Vasireddy
Upper gastrointestinal bleeding is gastrointestinal bleeding in the upper gastrointestinal tract, commonly defined as bleeding arising from the esophagus, stomach, or duodenum. Blood may be observed in vomit (hematemesis) or in altered form in the stool (melena). Depending on the severity of the blood loss, there may be symptoms of insufficient circulating blood volume and shock. As a result, upper gastrointestinal bleeding is considered a medical emergency and typically requires hospital care for urgent diagnosis and treatment. Upper gastrointestinal bleeding can be caused by peptic ulcers, gastric erosions, esophageal varices, and some rarer causes such as gastric cancer.
The initial assessment includes measurement of the blood pressure and heart rate, as well as blood tests to determine hemoglobin concentration. In significant bleeding, fluid replacement is often required, as well as blood transfusion, before the source of bleeding can be determined by endoscopy of the upper digestive tract with an esophagogastroduodenoscopy. Depending on the source, endoscopic therapy can be applied to reduce rebleeding risk. Specific medical treatments (such as proton pump inhibitors for peptic ulcer disease) or procedures (such as TIPS for variceal hemorrhage) may be used. Recurrent or refractory bleeding may lead to need for surgery, although this has become uncommon as a result of improved endoscopic and medical treatment.
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Dr. John Millichap speaking at 2014 Denver KCNQ2 Cure summit professionals track at Children's Hospital of Colorado. More information at www.kcnq2cure.org
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
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ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
1. STATUS EPILEPTICUS
Definition and Pathophysiology
Presenter : Dr. Vamsi Krishna Koneru
DM Neurology (CMC Vellore)
PDF Epilepsy (JIPMER)
19/9/23
2. Status Epilepticus - Facts and Figures
• 10–41 per 100,000 per year .
• 4–16% of people with epilepsy will have at least one episode of status epilepticus
• Approximately half the episodes of status epilepticus occur in people with no prior history of
epilepsy.
• Status epilepticus is a risk factor in those without epilepsy for the development of chronic
epilepsy.
• Acute symptomatic SE has a three-fold risk of resulting in chronic epilepsy compared to acute
symptomatic seizures
3. Status Epilepticus - Facts and Figures
• Convulsive status epilepticus (SE) :
• Common neurological emergency
• Associated with a high mortality
• Survivors often have neurological and cognitive deficits
5. Status Epilepticus - Facts and Figures
Status Epilepticus in the Pediatric Emergency Department
Jonathan E. Kurz et al
6. • Seizure threshold in the immature brain is lower than the mature brain
• Highest synaptic density is seen at around 2 months of age
• Excitatory synapses mature earlier than inhibitory synapses
• Stimulation of GABAA receptors in the immature brain results in depolarisation
(In adult brain it causes hyperpolarisation )
7. HISTORICAL INTRODUCTION
• Historically Status epilepticus (SE) is considered
the most extreme form of a seizure
• Trousseau, 1867:
“In the status epilepticus, when the convulsive
condition is almost continuous, something
special takes place which requires an
explanation ”.
8. HISTORICAL INTRODUCTION
• In 1876, Bourneville defined status epilepticus as more or less incessant seizures.
• In 1903 Clark and Prout described the natural course of status epilepticus
• They recognised three phases:
• Early pseudostatus phase,
• Convulsive status and
• Stuporous status
9. HISTORICAL INTRODUCTION
• First ILAE definition of status epilepticus (1970) :
• Seizure that persists for a sufficient length of time or is repeated
frequently enough to produce a fixed and enduring condition
10. HISTORICAL INTRODUCTION
• 1981 Revision of ILAE status epilepticus definition:
• Seizure that persists for a sufficient length of time or is repeated
frequently enough that recovery between attacks does not occur
11. HISTORICAL INTRODUCTION
• Observations from the work by Meldrum et al :
• Led to the definition for SE duration of 30 min.
• Experimental evidence from baboons
• Rationale : Irreversible neuronal injury may occur after 30 min of ongoing seizure
activity
13. HISTORICAL INTRODUCTION
• As the prognosis of SE worsens
with increasing duration
• Clinicians have rightfully argued
for earlier initiation of
treatment
14. HISTORICAL INTRODUCTION
• Review article by Bleck (1991) :
• Status epilepticus : continuous or repeated
seizures lasting >20 min
• Veterans Affairs status epilepticus cooperative study
group:
• Duration of 10 min as inclusion criterion for
status epilepticus
15. HISTORICAL INTRODUCTION
• Generalized convulsive SE in adults and children older than 5 years was operationally
defined as :
• “ ≥5 min of continuous seizure or two or more discrete seizures between which
there is incomplete recovery of consciousness”
16. 2015 ILAE DEFINITION OF STATUS EPILEPTICUS
• Status epilepticus is a condition resulting either from :
• Failure of the mechanisms responsible for seizure termination or
• Initiation of mechanisms, which lead to abnormally, prolonged
seizures (after time point t1).
• It is a condition, which can have long-term consequences (after time
point t2), including neuronal death, neuronal injury, and alteration of
neuronal networks, depending on the type and duration of seizures.
17. 2015 ILAE DEFINITION OF STATUS EPILEPTICUS
• This definition is conceptual, with two operational dimensions:
• Time point (t1) : beyond which the seizure should be regarded as
“continuous seizure activity.”
• Time point (t2) : time of ongoing seizure activity after which there is
a risk of long-term consequences
18. 2015 ILAE DEFINITION OF STATUS EPILEPTICUS
• Time points of convulsive (tonic–clonic) SE :
• T1 : 5 min
• T2 : 30 min
• Based on animal experiments and clinical research
• This evidence is incomplete
• There is considerable variation
• Should be considered as the best estimates currently available
20. DEFINITION OF ELECTRICAL STATUS EPILEPTICUS
• ELECTRICAL STATUS EPILEPTICUS :
• More than or equal to 10 minutes
(or)
• 20% of the record
21. Refractory & Super Refractory SE
• Refractory status epilepticus :
• seizures that continue despite first- and second line treatments
• Super Refractory Status Epilepticus :
• Status epilepticus that continues or recurs 24 hours or more after
the onset of anesthetic therapy, including those cases where status
epilepticus recurs on the reduction or withdrawal of anesthesia
22. ILAE classification of SE
• The ILAE classification of SE consists of 4 axes, as follows:
• Semiology - including those with or without prominent motor findings
• Etiology - known and unknown causes
• EEG correlates - description of the EEG
• Age - neonatal, infancy, childhood, adolescent, adult, and elderly
27. Paroxysmal Depolarizing Shift
• It is a sudden large depolarization of the resting membrane potential
• Magnitude of voltage change is in the range of 20 - 40 mV and lasts 50 - 200 ms
• At its peak triggers a flurry of action potentials with a frequency of several
hundred Hz.
• Paroxysmal depolarizing shift is followed by prolonged hyperpolarization
34. • HYPEREXCITABILITY + HYPERSYNCHRONY + LOSS OF SURROUND
INHIBITION
• Leads to spread of seizure activity:
• Contiguous areas via local cortical connections,
• Distant areas via long association pathways such as the CC
35. Pathophysiology Of Status Epilepticus
• For seizure termination, different biological processes have been proposed :
• Neurotransmitter depletion
• ATP depletion
• Ionic changes
• Increased GABA-ergic drive
• Release of adenosine
• Release of peptides (e.g. Inhibitory Neuropeptide Y etc.)
• Suppression or failure of these processes may promote STATUS EPILEPTICUS
36. Pathophysiology of status epilepticus
• Much of the pathophysiology of status epilepticus :
• Poorly understood
• Animal models
• Fundamental principle :
• Failure of endogenous mechanisms to terminate a seizure
• Initiation of mechanisms leading to abnormally prolonged seizures
37. Important changes leading to status epilepticus
• GABA A receptor internalisation
• NMDA receptor increased expression
• AMPA receptors lose their GLUA 2 subunit
• Presynaptic adenosine A1 receptor is decreased
• Presynaptic GABA(B) receptor expression is decreased
• Increase in Substance P
• Decrease in Neuro-peptide Y
• Decrease in other inhibitory Neuro-peptides like Galanin, Dynorphin, Somatostatin
41. • Ability of diazepam to stop seizures progressively decreased from :
• 6 of 6 rats when administered early
• (mean: 7.3 minutes since seizure onset)
• 1 of 6 rats when administered late
• (mean: 36.7 minutes since seizure onset)
42. • A rat model of SE based on electrical stimulation of the hippocampus :
• Phenobarbital (70 mg/kg) administered :
• 15 min after stimulation , controlled seizures in 66% of animals(n= 6).
• 60 min after stimulation , controlled seizures in 25% of animals (n = 4)
• Ketamine (100 mg/kg) administered :
• 15 min after stimulation did not control seizures in any animal (n = 4)
• One hour after stimulation , controlled seizures in all animals (n = 4).
43. AMPA RECEPTOR
The essential role of AMPA receptor GluA2 subunit RNA editing in the normal and
diseased brain. Amanda Wright, Bryce Vissel. Frontiers Neurology
44.
45. • During SE, there is rapid, ongoing plasticity of AMPARs
• Expression of GluA2-lacking AMPARs.
• They provide another source of Ca2+ entry into the principal neurons.
• Benzodiazepam-refractory SE can be terminated by AMPAR antagonism.
• The data identifies AMPARs as potential therapeutic target for the treatment of
SE
46. Role of GABAB RECEPTORS
Keeping the Balance: GABAB Receptors in the
Developing Brain and Beyond. Brain Sci. 2022
47. Role of Adenosine A1 Receptor
Adenosine A1 Receptor and Epilepsy.
https://doi.org/10.3390/ijms22010320
48. Role of Substance P
• Binding of SP to the NK-1 receptor will result in :
• Reduces inward rectifying K+ currents
• Increases the intracellular Ca2+concentration
• Removal of Mg2+ blockade and increased glutamate sensitivity
• Promotes protein kinase c-dependent phosphorylation of the NMDA
receptor
• All the above processes contribute to the maintenance phase of self-
sustaining status epilepticus
49. Role of Substance P
• SSSE results in a rapid and dramatic increase in the expression of Preprotachykinin A (a
precursor of Substance P) mRNA and SP in principal neurons in CA3, CA1, and the dentate
gyrus and in hippocampal mossy fibers
Substance P is expressed in hippocampal principal neurons during
status epilepticus and plays a critical role in the maintenance of status
epilepticus
https://doi.org/10.1073/pnas.96.9.5286
50. Role of Neuro-peptide Y
• Neuro-peptide Y exerts
• Potent anticonvulsive action
• Through presynaptic Y2 receptors
• By suppressing Glutamate release
• It’s level increases towards the end of the seizure
• However in SE, there will be insufficient replacement
52. Net effect
• GABA A receptor internalisation
• NMDA receptor increased expression
• AMPA receptors lose their GLUA 2 subunit
• Presynaptic adenosine A1 receptor is decreased
• Presynaptic GABA(B) receptor expression is decreased
• Increase in Substance P
• Decrease in Neuro-peptide Y
• Decrease in other inhibitory Neuro-peptides like Galanin, Dynorphin, Somatostatin
54. Pathophysiology of status epilepticus
• Neuronal death and dysfunction
• Specific groups of neurons seem to be more susceptible
• CA3 and CA1 regions
• Reason
• Physiological compromise including hypotension, hypoxia, hypoglycemia and acidosis
• Seizure itself
• Enzymes activated by intracellular calcium accumulation (Apoptosis through activation of
caspase 3)
• Mitochondrial dysfunction
• Reactive oxygen species
55. Pathophysiology of status epilepticus
• Seizure-induced re-modeling of neuronal networks
Neuronal loss and damage
Neurogenesis
Axonal sprouting
Reduced dendritic branching and spine loss Gliosis
Majak and Pitkänen, Epil Behav 2004
Mitochondria are one of the main buffers of cytosolic calcium, taking up calcium predominantly through the mitochondrial calcium uniporter[75]. Calcium uptake by mitochondria activates mitochondrial respiratory chain function and can increase mitochondrial ATP (and free radical) production through activation of calcium-dependent NADH dehydrogenases[75]. However, excessive mitochondrial calcium accumulation has two main detrimental effects. First, calcium accumulation can result in mitochondrial membrane depolarization[60]. Since the mitochondrial membrane potential is necessary for ATP production, this can result in decreased ATP production and consequently cellular energy failure[60]. Energy failure results in a decrease in the cell’s ability to maintain ionic gradients, and so results in cellular depolarization, hyperexcitability and eventually cell death