This document discusses the etiological factors of cleft lip and palate. It begins by reviewing normal embryonic facial development. Cleft lip and palate are considered to be multifactorial, caused by both genetic and environmental factors interacting. The precise roles of each factor are difficult to determine. The document then discusses several potential pathogenic mechanisms for cleft lip and palate formation, including anatomical obstruction, interference with cell differentiation or migration, and genetic susceptibility interacting with environmental teratogens. Both genetic and environmental factors are likely involved, though more research is still needed to fully understand the etiology.
This document reviews the etiological factors of cleft lip and cleft palate, including both genetic and environmental factors. It discusses the normal embryonic development of the facial primordia and how genetic susceptibility can be influenced by multiple environmental factors to result in clefting. Both polygenic and multifactorial inheritance are mentioned as potential genetic mechanisms. The review covers cellular processes involved in palate formation and fusion, potential teratogens, and associations with other birth defects.
This document reviews the etiological factors of cleft lip and cleft palate. It discusses that cleft lip and cleft palate are multifactorial conditions influenced by both genetic and environmental factors. The development of the facial primordia and normal palate formation is explained. Factors that can interfere with development and cause clefting include genetic susceptibility, environmental teratogens, and programmed cell death during critical periods of development. Both genetic and environmental factors likely contribute to cleft lip and cleft palate, though their specific roles are still being established.
This document discusses the pathogenesis of various types of choristomas, including salivary gland, cartilaginous, osseous, lingual thyroid, sebaceous gland, glial, and gastric/respiratory mucosal choristomas. It proposes that choristomas likely arise due to embryonic developmental anomalies that result in normal cells or tissues becoming displaced and growing in abnormal locations. Specifically, theories discussed include remnants of tissues like branchial arches, thyroid gland, or gastric/respiratory tissues becoming trapped during embryogenesis. While the exact causes are unclear, most theories suggest choristomas are congenital malformations rather than neoplastic or post-traumatic in origin.
Prenatal growth and development in orthodontics /certified fixed orthodontic ...Indian dental academy
Welcome to Indian Dental Academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy has a unique training program & curriculum that provides students with exceptional clinical skills and enabling them to return to their office with high level confidence and start treating patients
Germ cells are produced through meiosis which halves the number of chromosomes from 46 to 23. Fertilization restores the diploid number when a sperm and egg fuse. Mitosis duplicates DNA before cell division so each new cell has the full chromosome number. Meiosis involves two cell divisions without DNA replication between, resulting in four haploid gametes each with 23 chromosomes. Chromosomal abnormalities can arise from errors in meiosis or mitosis, causing conditions like Down syndrome, Turner syndrome, and others with characteristic physical and dental features.
This document discusses facial growth and development from prenatal through postnatal stages. It begins with terminology for growth and development, then describes how the face develops from tissues originating in the neural crest, somites, and pharyngeal arches during prenatal development. Midface development, palate development, and common birth defects are reviewed. Postnatal growth theories including genetic, sutural, cartilaginous, functional matrix, and servosystem models are introduced. Common craniofacial anomalies associated with chromosome abnormalities or neural crest cell defects are also summarized.
The face develops between the 4th and 6th week of embryonic development from structures including the frontonasal process, mandibular arches, and maxillary processes. Between the 6th and 12th week, the palate begins to form through the fusion of the palatal shelves, separating the nasal and oral cavities. Abnormalities can occur if the fusion of structures like the medial nasal processes, mandibular arches, or palatal shelves is incomplete, leading to cleft lip, cleft palate, or other anomalies. A thorough understanding of normal facial development aids in diagnosing and treating congenital defects.
prenatal growth and development of face
GROWTH
Growth may be defined as the normal changes in the amount of a living substance – MOYER
Growth refers to an increase in size or number – PROFFIT
Growth may be defined as a developmental increase in mass i.e, it is a process that leads to an increase in the physical size of cells, tissues, organs or organisms as a whole – STEWART 1982
“Growth signifies an increase, expansion or extension of any given tissue.” - Pinkham.(1994)
Development refers to all the naturally occurring progressive, unidirectional changes in the life of an individual from its existence as a single cell to its elaboration as a multifunctional unit terminating in death. – MOYERS 1988
Development addresses the progressive evolution of a tissue PINKHAM 1994
“Development is a progress towards maturity” – Todd(1931)
This document reviews the etiological factors of cleft lip and cleft palate, including both genetic and environmental factors. It discusses the normal embryonic development of the facial primordia and how genetic susceptibility can be influenced by multiple environmental factors to result in clefting. Both polygenic and multifactorial inheritance are mentioned as potential genetic mechanisms. The review covers cellular processes involved in palate formation and fusion, potential teratogens, and associations with other birth defects.
This document reviews the etiological factors of cleft lip and cleft palate. It discusses that cleft lip and cleft palate are multifactorial conditions influenced by both genetic and environmental factors. The development of the facial primordia and normal palate formation is explained. Factors that can interfere with development and cause clefting include genetic susceptibility, environmental teratogens, and programmed cell death during critical periods of development. Both genetic and environmental factors likely contribute to cleft lip and cleft palate, though their specific roles are still being established.
This document discusses the pathogenesis of various types of choristomas, including salivary gland, cartilaginous, osseous, lingual thyroid, sebaceous gland, glial, and gastric/respiratory mucosal choristomas. It proposes that choristomas likely arise due to embryonic developmental anomalies that result in normal cells or tissues becoming displaced and growing in abnormal locations. Specifically, theories discussed include remnants of tissues like branchial arches, thyroid gland, or gastric/respiratory tissues becoming trapped during embryogenesis. While the exact causes are unclear, most theories suggest choristomas are congenital malformations rather than neoplastic or post-traumatic in origin.
Prenatal growth and development in orthodontics /certified fixed orthodontic ...Indian dental academy
Welcome to Indian Dental Academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy has a unique training program & curriculum that provides students with exceptional clinical skills and enabling them to return to their office with high level confidence and start treating patients
Germ cells are produced through meiosis which halves the number of chromosomes from 46 to 23. Fertilization restores the diploid number when a sperm and egg fuse. Mitosis duplicates DNA before cell division so each new cell has the full chromosome number. Meiosis involves two cell divisions without DNA replication between, resulting in four haploid gametes each with 23 chromosomes. Chromosomal abnormalities can arise from errors in meiosis or mitosis, causing conditions like Down syndrome, Turner syndrome, and others with characteristic physical and dental features.
This document discusses facial growth and development from prenatal through postnatal stages. It begins with terminology for growth and development, then describes how the face develops from tissues originating in the neural crest, somites, and pharyngeal arches during prenatal development. Midface development, palate development, and common birth defects are reviewed. Postnatal growth theories including genetic, sutural, cartilaginous, functional matrix, and servosystem models are introduced. Common craniofacial anomalies associated with chromosome abnormalities or neural crest cell defects are also summarized.
The face develops between the 4th and 6th week of embryonic development from structures including the frontonasal process, mandibular arches, and maxillary processes. Between the 6th and 12th week, the palate begins to form through the fusion of the palatal shelves, separating the nasal and oral cavities. Abnormalities can occur if the fusion of structures like the medial nasal processes, mandibular arches, or palatal shelves is incomplete, leading to cleft lip, cleft palate, or other anomalies. A thorough understanding of normal facial development aids in diagnosing and treating congenital defects.
prenatal growth and development of face
GROWTH
Growth may be defined as the normal changes in the amount of a living substance – MOYER
Growth refers to an increase in size or number – PROFFIT
Growth may be defined as a developmental increase in mass i.e, it is a process that leads to an increase in the physical size of cells, tissues, organs or organisms as a whole – STEWART 1982
“Growth signifies an increase, expansion or extension of any given tissue.” - Pinkham.(1994)
Development refers to all the naturally occurring progressive, unidirectional changes in the life of an individual from its existence as a single cell to its elaboration as a multifunctional unit terminating in death. – MOYERS 1988
Development addresses the progressive evolution of a tissue PINKHAM 1994
“Development is a progress towards maturity” – Todd(1931)
The document discusses human craniofacial development from conception through fetal stages. It covers the origin of the human embryo from fertilization, the formation of germ layers, development of branchial arches and clefts, and the differentiation of tissues and structures from the germ layers and arches in the lower, middle, and upper thirds of the face. Key topics include mesenchymal condensations that form the mandibular arch and maxillary processes, ossification centers of the maxilla, and cartilage contributions to mandibular growth.
The document summarizes prenatal and postnatal growth and development of the face. It describes how the face increases in size much more during the prenatal period compared to postnatal growth. It outlines the development of the face from the gestational periods and formation of the primordia. It discusses common anomalies during development and functional therapies. The craniofacial bones undergo remodeling and fusion during childhood with the skull assuming the adult shape by adolescence.
Growth & development of face/certified fixed orthodontic courses by India...Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
Prenatal growth /certified fixed orthodontic courses by Indian dental academy Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses.for details pls visit www.indiandentalacademy.com ,or call
0091-9248678078
Gastrulation in mammals establishes the basic body plan and three primary germ layers - ectoderm, mesoderm, and endoderm - through a complex series of cell movements and shape changes in the blastula. The ectoderm forms the skin, nervous system, and sense organs. The mesoderm forms the skeleton, muscles, blood vessels, heart, blood, gonads, kidneys, and skin dermis. The endoderm lines the digestive and respiratory tracts, liver, pancreas, thymus, and thyroid. Cells move during gastrulation through invagination, involution, delamination, and ingression. Gastrulation in mammals follows a similar pattern to birds, forming
This document summarizes the development of the maxilla and mandible prenatally and postnatally. Prenatally, the maxilla develops from the maxillary prominence and ossifies around 4 weeks gestation near the infraorbital nerve. The premaxilla also ossifies early and fuses with the maxilla. Palatine bones develop near the nasal capsule. Postnatally, the maxilla and palate grow through surface deposition, remodeling, and sutural growth. The mandible initially develops from Meckel's cartilage in the first pharyngeal arch and undergoes endochondral ossification through a condylar cartilage, allowing continued growth.
1. The document discusses prenatal facial growth, which can be divided into three periods: the period of the ovum, embryo, and fetus.
2. During the period of the embryo (1-7 weeks), the major development of the facial and cranial regions occurs, including the formation of the branchial arches which give rise to structures of the face, neck, and throat.
3. In the period of the fetus, accelerated growth of craniofacial structures occurs resulting in increased size and changes in proportions, and the prenatal growth of structures such as the cranial base, maxilla, mandible, palate, and mandible are described.
This document discusses embryogenesis and prenatal face formation. It covers early embryonic development from fertilization through the fetal period. Key points include:
- Embryogenesis occurs in three main periods: preimplantation, embryonic, and fetal.
- The pharyngeal arches play an important role in face development, with each arch contributing muscles, nerves, and blood vessels.
- Organ systems like the cardiovascular, digestive, and nervous systems undergo differentiation during the somite period from 3-4 weeks.
- The postsomite period from 5-8 weeks sees formation of external features and digit development. The embryo is now termed a fetus.
The document summarizes the process of gastrulation in humans. It discusses how the embryo develops two germ layers, the epiblast and hypoblast, just before implantation. It describes the formation of the primitive streak around day 15, which defines the body axes. Cells migrate through the primitive streak during gastrulation to form the definitive endoderm, intraembryonic mesoderm, and ectoderm. Key cellular processes in gastrulation include epithelial-to-mesenchymal transition and convergent extension.
Face develops in humans between 4th – 10th week of intrauterine life.
prenatal growth of the maxilla
DEVELOPMENT OF UPPER LIP
Development of lower lip
Development of nose
hare lip
OBLIQUE FACIAL CLEFT
macrostomia
lateral facial cleft
microstomia
Course in facial development for European Course in Neuroradiology in Tarragona, Spain, on 12 octobre 2008. For questions, e-mail to etchevers at free dot fr. Download to play the animations (especially as some pictures are covered by others)
This document discusses cell movement during amphibian gastrulation. It begins by introducing gastrulation and how it establishes the three germ layers and body plan. There are a few basic types of cell movement during gastrulation: invagination, involution, ingression, delamination, and epiboly. The document then focuses on amphibian gastrulation, noting that bottle cells first sink in and the blastopore forms opposite the sperm entry point. Involution begins dorsally and the mesoderm enters through the expanding blastopore lip through the end of gastrulation.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
Spermatogenesis is the process by which germ cells differentiate into spermatozoa. It occurs within the seminiferous tubules of the testis and can be divided into three main phases: proliferation of spermatogonia, meiotic reduction division producing spermatocytes, and differentiation of spermatids into spermatozoa. Spermatogenesis progresses through cycles of the seminiferous epithelium, where each stage is defined by the association of germ cells at a specific developmental phase. Repeated cycles ensure continuous production of spermatozoa.
Mammalian development begins with fertilization inside the female's body. The zygote then undergoes cleavage divisions that are slower than in other animals. Around the 8-cell stage, the cells compact together and later form two distinct cell types - the inner cell mass and trophoblast cells. The trophoblast cells go on to form the blastocyst, with an inner cell mass surrounded by trophoblast cells. The blastocyst hatches from the zona pellucida and implants in the uterus, where the trophoblast cells invade the uterine tissue and the inner cell mass forms the embryo.
1. The cranial end of the embryo folds first due to the rapid growth of the brain, forming the primitive oral cavity and stomatodeum.
2. The face develops from five mesodermal elevations called processes that are augmented by neural crest cells and lined with ectoderm. These include the frontonasal process, two maxillary processes, and two mandibular processes.
3. The frontonasal process forms the forehead and nose. The maxillary processes form parts of the upper lip, cheek, and palate. The mandibular processes merge to form the lower lip and chin.
This document discusses the development of the face and oral cavity from early embryogenesis through postnatal growth. It describes how the fertilized ovum undergoes cell division and differentiation to form the three germ layers (ectoderm, endoderm, and mesoderm) which give rise to the tissues of the body. It also discusses the formation of structures like the branchial arches and pouches which contribute to development of the face and neck. Prenatal growth involves formation of the oral cavity and differentiation of tissues, while postnatal growth occurs through growth spurts in a cephalocaudal direction with variability between individuals.
The document discusses the development of the face and palate in humans. It describes how the face develops from structures around the stomatodeum, including the frontonasal process and first pharyngeal arch. The lips, nose, cheeks, eyes, and ears develop through the growth and fusion of these structures between 4-8 weeks. The palate develops from the primary and secondary palate, which grow towards each other and fuse between 6-12 weeks. Possible developmental anomalies that can occur if this process is disrupted include cleft lip, cleft palate, and abnormalities in the size and position of facial features.
EXTRACTION AND IMMEDIATE IMPLANT PLACEMENT USING A COMBINED PRF, AND PROVISIO...Abu-Hussein Muhamad
This document discusses immediate implant placement using platelet-rich fibrin (PRF) and provisionalization. It describes a case where a fenestration defect around an implant was treated using PRF, a bone graft, and guided tissue regeneration membrane. PRF is a simple, natural, and inexpensive concentrate that helps healing by stimulating osteoblastic activity, angiogenesis, and growth factor release. The document reviews literature supporting the use of PRF and immediate implant placement techniques.
This article discusses the genetics of non-syndromic cleft lip and palate. It begins by providing background on cleft lip and palate, noting that they are common birth defects caused by both genetic and environmental factors. The article then reviews the various genetic approaches that have been used to study the genetics of cleft lip and palate, including linkage analysis, genome-wide association studies, and sequencing of candidate genes. It discusses several genes that have been implicated in cleft lip and palate development, including IRF6, MTHFR, and MSX1. The article concludes that while several genes have been identified, the genetic basis of non-syndromic cleft lip and palate remains unclear due
The document discusses human craniofacial development from conception through fetal stages. It covers the origin of the human embryo from fertilization, the formation of germ layers, development of branchial arches and clefts, and the differentiation of tissues and structures from the germ layers and arches in the lower, middle, and upper thirds of the face. Key topics include mesenchymal condensations that form the mandibular arch and maxillary processes, ossification centers of the maxilla, and cartilage contributions to mandibular growth.
The document summarizes prenatal and postnatal growth and development of the face. It describes how the face increases in size much more during the prenatal period compared to postnatal growth. It outlines the development of the face from the gestational periods and formation of the primordia. It discusses common anomalies during development and functional therapies. The craniofacial bones undergo remodeling and fusion during childhood with the skull assuming the adult shape by adolescence.
Growth & development of face/certified fixed orthodontic courses by India...Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
Prenatal growth /certified fixed orthodontic courses by Indian dental academy Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses.for details pls visit www.indiandentalacademy.com ,or call
0091-9248678078
Gastrulation in mammals establishes the basic body plan and three primary germ layers - ectoderm, mesoderm, and endoderm - through a complex series of cell movements and shape changes in the blastula. The ectoderm forms the skin, nervous system, and sense organs. The mesoderm forms the skeleton, muscles, blood vessels, heart, blood, gonads, kidneys, and skin dermis. The endoderm lines the digestive and respiratory tracts, liver, pancreas, thymus, and thyroid. Cells move during gastrulation through invagination, involution, delamination, and ingression. Gastrulation in mammals follows a similar pattern to birds, forming
This document summarizes the development of the maxilla and mandible prenatally and postnatally. Prenatally, the maxilla develops from the maxillary prominence and ossifies around 4 weeks gestation near the infraorbital nerve. The premaxilla also ossifies early and fuses with the maxilla. Palatine bones develop near the nasal capsule. Postnatally, the maxilla and palate grow through surface deposition, remodeling, and sutural growth. The mandible initially develops from Meckel's cartilage in the first pharyngeal arch and undergoes endochondral ossification through a condylar cartilage, allowing continued growth.
1. The document discusses prenatal facial growth, which can be divided into three periods: the period of the ovum, embryo, and fetus.
2. During the period of the embryo (1-7 weeks), the major development of the facial and cranial regions occurs, including the formation of the branchial arches which give rise to structures of the face, neck, and throat.
3. In the period of the fetus, accelerated growth of craniofacial structures occurs resulting in increased size and changes in proportions, and the prenatal growth of structures such as the cranial base, maxilla, mandible, palate, and mandible are described.
This document discusses embryogenesis and prenatal face formation. It covers early embryonic development from fertilization through the fetal period. Key points include:
- Embryogenesis occurs in three main periods: preimplantation, embryonic, and fetal.
- The pharyngeal arches play an important role in face development, with each arch contributing muscles, nerves, and blood vessels.
- Organ systems like the cardiovascular, digestive, and nervous systems undergo differentiation during the somite period from 3-4 weeks.
- The postsomite period from 5-8 weeks sees formation of external features and digit development. The embryo is now termed a fetus.
The document summarizes the process of gastrulation in humans. It discusses how the embryo develops two germ layers, the epiblast and hypoblast, just before implantation. It describes the formation of the primitive streak around day 15, which defines the body axes. Cells migrate through the primitive streak during gastrulation to form the definitive endoderm, intraembryonic mesoderm, and ectoderm. Key cellular processes in gastrulation include epithelial-to-mesenchymal transition and convergent extension.
Face develops in humans between 4th – 10th week of intrauterine life.
prenatal growth of the maxilla
DEVELOPMENT OF UPPER LIP
Development of lower lip
Development of nose
hare lip
OBLIQUE FACIAL CLEFT
macrostomia
lateral facial cleft
microstomia
Course in facial development for European Course in Neuroradiology in Tarragona, Spain, on 12 octobre 2008. For questions, e-mail to etchevers at free dot fr. Download to play the animations (especially as some pictures are covered by others)
This document discusses cell movement during amphibian gastrulation. It begins by introducing gastrulation and how it establishes the three germ layers and body plan. There are a few basic types of cell movement during gastrulation: invagination, involution, ingression, delamination, and epiboly. The document then focuses on amphibian gastrulation, noting that bottle cells first sink in and the blastopore forms opposite the sperm entry point. Involution begins dorsally and the mesoderm enters through the expanding blastopore lip through the end of gastrulation.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
Spermatogenesis is the process by which germ cells differentiate into spermatozoa. It occurs within the seminiferous tubules of the testis and can be divided into three main phases: proliferation of spermatogonia, meiotic reduction division producing spermatocytes, and differentiation of spermatids into spermatozoa. Spermatogenesis progresses through cycles of the seminiferous epithelium, where each stage is defined by the association of germ cells at a specific developmental phase. Repeated cycles ensure continuous production of spermatozoa.
Mammalian development begins with fertilization inside the female's body. The zygote then undergoes cleavage divisions that are slower than in other animals. Around the 8-cell stage, the cells compact together and later form two distinct cell types - the inner cell mass and trophoblast cells. The trophoblast cells go on to form the blastocyst, with an inner cell mass surrounded by trophoblast cells. The blastocyst hatches from the zona pellucida and implants in the uterus, where the trophoblast cells invade the uterine tissue and the inner cell mass forms the embryo.
1. The cranial end of the embryo folds first due to the rapid growth of the brain, forming the primitive oral cavity and stomatodeum.
2. The face develops from five mesodermal elevations called processes that are augmented by neural crest cells and lined with ectoderm. These include the frontonasal process, two maxillary processes, and two mandibular processes.
3. The frontonasal process forms the forehead and nose. The maxillary processes form parts of the upper lip, cheek, and palate. The mandibular processes merge to form the lower lip and chin.
This document discusses the development of the face and oral cavity from early embryogenesis through postnatal growth. It describes how the fertilized ovum undergoes cell division and differentiation to form the three germ layers (ectoderm, endoderm, and mesoderm) which give rise to the tissues of the body. It also discusses the formation of structures like the branchial arches and pouches which contribute to development of the face and neck. Prenatal growth involves formation of the oral cavity and differentiation of tissues, while postnatal growth occurs through growth spurts in a cephalocaudal direction with variability between individuals.
The document discusses the development of the face and palate in humans. It describes how the face develops from structures around the stomatodeum, including the frontonasal process and first pharyngeal arch. The lips, nose, cheeks, eyes, and ears develop through the growth and fusion of these structures between 4-8 weeks. The palate develops from the primary and secondary palate, which grow towards each other and fuse between 6-12 weeks. Possible developmental anomalies that can occur if this process is disrupted include cleft lip, cleft palate, and abnormalities in the size and position of facial features.
EXTRACTION AND IMMEDIATE IMPLANT PLACEMENT USING A COMBINED PRF, AND PROVISIO...Abu-Hussein Muhamad
This document discusses immediate implant placement using platelet-rich fibrin (PRF) and provisionalization. It describes a case where a fenestration defect around an implant was treated using PRF, a bone graft, and guided tissue regeneration membrane. PRF is a simple, natural, and inexpensive concentrate that helps healing by stimulating osteoblastic activity, angiogenesis, and growth factor release. The document reviews literature supporting the use of PRF and immediate implant placement techniques.
This article discusses the genetics of non-syndromic cleft lip and palate. It begins by providing background on cleft lip and palate, noting that they are common birth defects caused by both genetic and environmental factors. The article then reviews the various genetic approaches that have been used to study the genetics of cleft lip and palate, including linkage analysis, genome-wide association studies, and sequencing of candidate genes. It discusses several genes that have been implicated in cleft lip and palate development, including IRF6, MTHFR, and MSX1. The article concludes that while several genes have been identified, the genetic basis of non-syndromic cleft lip and palate remains unclear due
Replantation of Avulsed Permanent Anterior Teeth: A Case Report.Abu-Hussein Muhamad
Tooth avulsion in the permanent dentition constitutes a dental emergency. Replantation of the avulsed tooth restores aesthetics and occlusal function shortly after the injury. This article describes the management of a 12-year old male with four avulsed anterior maxillary permanent teeth. The avulsed teeth were replanted and root canal treatment carried out after a short fixation. The result obtained was very satisfactory and the teeth remain in good functional status one year after replantation. Early treatment and regular attendance to clinic following replantation is an important factor for good result.
This document summarizes a literature review on the color of primary teeth. It finds that primary teeth appear to be much more important for esthetics than traditionally thought. The review examines factors that influence tooth color perception and different color notation systems. It also analyzes studies on measuring the color of primary teeth and finding they are generally lighter than permanent teeth. The review concludes more research is needed to improve restorations for primary teeth and account for color variations between individuals.
This article discusses the genetics of non-syndromic cleft lip and palate. It begins by providing background on cleft lip and palate, noting that they are common birth defects caused by both genetic and environmental factors. The article then reviews the various genetic approaches that have been used to study the genetics of cleft lip and palate, including linkage analysis, genome-wide association studies, and sequencing of candidate genes. It discusses several genes that have been implicated in cleft lip and palate development, including IRF6, MTHFR, and MSX1. The article concludes that while several genes have been identified, the genetic basis of non-syndromic cleft lip and palate remains unclear due
IMMEDIATE IMPLANT PLACEMENT WITH ONE YEAR FOLLOW-UP: A CASE REPORTAbu-Hussein Muhamad
This case report describes the immediate placement of a dental implant into the extraction socket of a fractured maxillary central incisor tooth. The tooth was extracted atraumatically without flap reflection to preserve hard and soft tissues. A dental implant was immediately placed into the prepared socket. Four months later, an impression was taken and a definitive restoration was placed. The patient exhibited no clinical or radiographic complications over 12 months of follow-up after loading. Immediate implant placement and provisional restoration provided esthetics, function, and tissue preservation for the patient.
This case report describes the use of mineral trioxide aggregate (MTA) in apexification of two immature permanent teeth with open apices and periapical lesions in a 14-year old patient. After cleaning and shaping the root canals, MTA was used to create an apical plug in each canal. Follow up radiographs at 6 and 12 months showed periapical healing and apical closure of the teeth. MTA is described as a promising alternative to traditional calcium hydroxide treatment for apexification due to its superior biocompatibility and ability to stimulate hard tissue formation.
This document summarizes several articles from The Journal of Implant & Advanced Clinical Dentistry. The first article discusses zygomatic implants and reviews their use for supporting dental prostheses in patients with severe maxillary atrophy. The second article describes a safer technique for lateral sinus augmentation. The third article presents a case report of loading two mandibular implants with a locator attachment for final restoration.
This document provides an overview of pediatric facial trauma, including epidemiology, examination considerations, management of specific injuries like nasal fractures and mandible fractures, and differences from adult facial trauma. Some key points:
- Facial fractures account for about 5% of all pediatric injuries, most commonly mandible and nasal fractures. Treatment differs from adults due to facial growth.
- Examination is more difficult in children and sedation should only be used as a last resort. Soft tissue injuries require careful repair to prevent scarring.
- Rigid fixation is controversial in children due to potential effects on growth, but may be used if necessary for accurate reduction.
- Nasal fractures are rare in children due to soft
The multifactorial factors influencing cleft Lip-literature reviewAbu-Hussein Muhamad
This document summarizes the genetic and environmental factors that influence cleft lip and cleft palate. It discusses that cleft lip and palate are considered multifactorial issues influenced by both genetic susceptibility and multiple environmental factors. The document reviews normal facial development and the pathogenesis of clefts, including the role of cell death. It discusses evidence that cleft lip with or without cleft palate may have a polygenic basis while cleft palate alone could have different etiology. The role of both polygenic and single-gene inheritance is examined based on family and pedigree studies.
The multifactorial factors influenc cleft Lip-literature review Abu-Hussein Muhamad
Congenital cleft-Lip and cleft palate have been the subject of many genetic
studies, but until recently there has been no consensus as to their modes of
inheritance. In fact, claims have been made for just about every genetic
mechanism one can think of. Recently, however, evidence has been
accumulating that favors a multifactorial basis for these malformations. The
purpose of the present paper is to present the etiology of cleft lip and cleft palate
both the genetic and the environmental factors. It is suggested that the genetic
basis for diverse kinds of common or uncommon congenital malformations may
very well be homogeneous, whilst, at the same, the environmental basis is
heterogeneous.
This document provides a review of the etiology of cleft lip and palate. It discusses that cleft lip and palate have a multifactorial etiology involving both genetic and environmental factors. Several genes have been discovered that can cause syndromic cleft lip and palate. The etiology is complex, and both genetic and environmental factors contribute, but have not been fully elucidated. Normal facial development and the pathogenesis of cleft lip and cleft palate are also reviewed.
This document discusses the development of the face and oral cavity from early embryogenesis through formation of structures. It covers the formation of the three germ layers and how they give rise to different tissues. Pharyngeal arches form and contribute to structures including muscles and cartilages. The oral cavity develops from the stomatodeum and foregut. Facial prominences including the frontonasal, maxillary and mandibular processes form the lips, nose, and palate as they grow and fuse. Structures such as the eyes also develop during this period of facial development.
This document outlines a course on developmental biology and teratology. It discusses how pattern formation during embryogenesis is genetically controlled and involves cells responding to morphogen gradients and cell signaling pathways to develop spatial patterns. Key genes involved in pattern formation are homeobox genes, which help specify where anatomical structures will develop. In particular, Hox genes are organized in clusters and control patterning along the anteroposterior body axis. Mutations in genes of pattern formation can lead to various clinical congenital malformations and anomalies.
This document discusses congenital craniofacial malformations. It describes the embryological development of the face, which involves contributions from the ectoderm, neural crest, and paraxial mesoderm. Precise signaling between these tissues is required for normal patterning and growth. Malformations can result from disruptions to molecular signals like hedgehogs, fibroblast growth factors, and retinoic acid during crucial developmental windows. The palate, nasal cavities, and facial skeleton all develop through complex interactions between mesodermal and ectodermal tissues guided by these molecular signals.
Management of cleft lip and palate 1. /certified fixed orthodontic courses ...Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses.for details pls visit www.indiandentalacademy.com ,or call
00919248678078
Indian Dental Academy: will be one of the most relevant and exciting training center with best faculty and flexible training programs for dental professionals who wish to advance in their dental practice,Offers certified courses in Dental implants,Orthodontics,Endodontics,Cosmetic Dentistry, Prosthetic Dentistry, Periodontics and General Dentistry.
Developmental biology is the study of how organisms grow and develop. It involves processes like gametogenesis, fertilization, growth, differentiation, pattern formation and morphogenesis. Gametogenesis refers to the formation of gametes or sex cells through meiosis. In spermatogenesis, spermatogonia undergo mitosis and meiosis to form spermatids that then differentiate into spermatozoa. In oogenesis, oogonia undergo mitosis and meiosis to form a secondary oocyte and first polar body, with the secondary oocyte then undergoing a second meiotic division. Fertilization occurs when a sperm fuses with an ovum, forming a zygote. Development then progresses through
Inheritance and malocclusion / /certified fixed orthodontic courses by India...Indian dental academy
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Tooth development proceeds with reciprocal inductive interactions between stomadeum ectoderm and underlying ectomesenchymal cells in a strictly controlled temporal and spatial order.
Well studied at the molecular biologic level, over 300 genes and 100 growth and differentiation factors are implicated in the control of cellular differentiation and crosstalk in dental development that result in structures containing combination of mineralized tissues (enamel, dentine, cementum), soft connective tissues (dental pulp, periodontal ligament), blood vessels, nerves and lymphatics
This document discusses genetics and its application to orthodontics. It covers several key topics:
1. Principles of genetic transmission including dominant and recessive inheritance.
2. The role of genetics in craniofacial development and conditions like malocclusion. Twin studies help determine hereditary influences.
3. Genetic syndromes that can cause dentofacial disturbances and their inheritance patterns. Conditions discussed include cleft lip/palate and Angle's Class II malocclusions.
4. The concepts of homeobox genes and how they control tooth and facial development. Mutations in genes can also cause diseases of enamel and dentin formation.
Embryology of head and neck - arun omfspptxRishiKodali2
1. The document discusses the embryology of the head and neck, covering topics like gametogenesis, fertilization, cleavage, blastulation, implantation, and the development of structures in the head and neck region like the skull, face, palate, and teeth.
2. It describes the three main phases of prenatal development - the preimplantation, embryonic, and fetal periods - and the key processes during each like formation of the germ layers and organogenesis.
3. Various congenital abnormalities are discussed, especially chromosomal abnormalities like Down syndrome, and the effects of teratogens on development.
Anomalies of the first and second branchial archesDr Medical
https://userupload.net/8n9v7tg9jkl1
Anomalies of the branchial arches are the second most common congenital lesions of the head and neck in children [1]. They may present as cysts, sinus tracts, fistulae or cartilaginous remnants and present with typical clinical and radiological patterns dependent on which arch is involved. The course of a particular branchial anomaly is caudal to the structures derived from the corresponding arch and dorsal to the structures that develop from the following arch. Branchial anomalies are further typed into cysts, sinuses, and fistulas.
Many evidences that CSCs also play a central role in the pathogenesis and progression of carcinomas of the head and neck (HNSCC), including OSCC,have been found.
Early tissue culture studies showed that only a subpopulation of OSCC cells can form expanding tumor colonies, suggesting that human OSCC may contain some form of stem cells and it was subsequently shown that only a small subpopulation of the cells in OSCC corresponds to tumor-initiating cells.
These finding are in accordance with CSCs concept (17,34) that the tumor mass is a mixture of (a) CSCs dividing themselves to feed the tumor's growth, b) transient amplifying cells that divide themselves a few times before maturing into (c) differentiated tumor cells that do not contribute to tumor growth (4).
The isolation of CSCs from oral cancers has mainly been performed with the CD44 marker that was initially used to isolate breast cancer CSCs.
Many evidences that CSCs also play a central role in the pathogenesis and progression of carcinomas of the head and neck (HNSCC), including OSCC,have been found.
Early tissue culture studies showed that only a subpopulation of OSCC cells can form expanding tumor colonies, suggesting that human OSCC may contain some form of stem cells and it was subsequently shown that only a small subpopulation of the cells in OSCC corresponds to tumor-initiating cells.
These finding are in accordance with CSCs concept (17,34) that the tumor mass is a mixture of (a) CSCs dividing themselves to feed the tumor's growth, b) transient amplifying cells that divide themselves a few times before maturing into (c) differentiated tumor cells that do not contribute to tumor growth (4).
The isolation of CSCs from oral cancers has mainly been performed with the CD44 marker that was initially used to isolate breast cancer CSCs.
- Epigenetic modifications like DNA methylation and histone modifications play an important role in regulating gene expression and cell differentiation.
- Certain transcription factors are asymmetrically distributed during early cell divisions, leading to new patterns of gene expression over generations in response to cellular signaling.
- While epigenetic changes are not always heritable, some studies have found evidence that epigenetic switches can be transmitted from parents to offspring, though these effects may be reversible. This has implications for the inheritance of acquired traits.
Tooth development proceeds with reciprocal inductive interactions between stomadeum ectoderm and underlying ectomesenchymal cells in a strictly controlled temporal and spatial order.
Well studied at the molecular biologic level, over 300 genes and 100 growth and differentiation factors are implicated in the control of cellular differentiation and crosstalk in dental development that result in structures containing combination of mineralized tissues (enamel, dentine, cementum), soft connective tissues (dental pulp, periodontal ligament), blood vessels, nerves and lymphatics.
Congenital absence of maxillary lateral incisors is a frequent clinical challenge which must be solved by a multidisciplinary approach in order to obtain an
esthetic and functional restorative treatment. . Fixed prosthodontic and removable prostheses, resin bonded retainers, orthodontic movement of maxillary
canine to the lateral incisor site and single tooth implants represent the available treatment modalities to replace congenitally missing teeth. This case report
demonstrates the team approach in prosthetic and surgical considerations and techniques for managing the lack of lateral incisors. The aims of this case
report of replacement of bilaterally congenitally missing maxillary lateral incisors with dental implants.
Aesthetic Management of Fractured Anteriors: A Case ReportAbu-Hussein Muhamad
Introduction: Coronal fracture of anterior teeth is an important topic for esthetic dentistry. Such fractures may jeopardize esthetics, function, tissue biology
and occlusal physiology, thus endangering tooth vitality and integrity. Coronal fractures resulting from dental trauma most frequently occur to the maxillary
anterior teeth of adolescents and less frequently to mandibular teeth. Adult teeth may also suffer traumatic fracture, although less frequently than for
adolescents.
Case Report: In our case, an economical and time-saving novel technique has been described for direct composite restoration in a young patient with
uncomplicated fractured maxillary anterior tooth.
Conclusion: As restoring a fractured tooth is a complex procedure, this technique can prove as a simple, effective and appropriate technique that will fulfill all
the requirements of dental personnel. This technique can also prove to be easy for inexperienced beginner clinicians without requiring special skills in
providing the patients with direct composite restorations.
Impacted Maxillary Central Incisors: Surgical Exposure and Orthodontic Treat...Abu-Hussein Muhamad
The maxillary permanent central incisor develops early in life and forms part of an aesthetic smile. Disruption of the formation or eruption of the permanent
central incisor has multiple etiological factors. Treatment options depend to some extent on the cause of failure of eruption of the central incisor. Generally,
the earlier treatment is provided, the higher the likelihood of success and the less the complexity. Our results suggest that close monitoring and interdisciplinary
cooperation during the treatment phases led to a successful esthetic result, with good periodontal health and functional occlusion.
Excess of space in the dental arch is diagnosed as a
generalised spacing or a local divergence, often
observed in the maxillary anterior region, as a median
diastema, traumatic loss of central incisors, or
congenital absence of lateral incisors. Furthermore,
spacing is observed in aging individuals, due to
pathological migration of teeth caused by
periodontitis. Finally, adult individuals with partial
edentulous jaws demand pre-prosthetic orthodontic
treatment from functional aspects. Thus, indication for
orthodontic treatment in subjects with spacing of teeth
exists for aesthetic reasons, but also for facilitating
prosthetic restorations with optimal occlusalstability.
Dental implants represent one of the most successful treatment modalities in dentistry.
However, failures do occur in the range from 5 to 8% for routine procedures and up to 20% in major grafting
cases after at least 5 years of function . The majority of implant losses may be explained as biomechanically
induced failures, since low primary implant stability, low bone density, short implants and overload have been
identified as risk factors . Hence, achievement and maintenance of implant stability are pre-conditions for a
successful clinical outcome with dental implants.
The review focuses on different methods used to assess implant stability and recent advances in this field.
This document provides guidance on how to write and publish a scientific paper in 3 steps:
1. Plan adequate time for writing a high-quality paper that will be accepted for publication. Previous studies show lack of time is the top reason papers are not published.
2. Carefully review the instructions for authors on the target journal's website and adhere strictly to formatting requirements. Ignoring guidelines is a common reason for rejection.
3. The paper should have key sections - an informative abstract, introduction establishing the study's purpose and novelty, thorough methods section, clear results, and conclusions tying it all together. Following best practices increases the chances of successful publication.
Aesthetic Management of Fractured Anteriors: A Case ReportAbu-Hussein Muhamad
Introduction: Coronal fracture of anterior teeth is an important topic for esthetic dentistry. Such fractures may jeopardize esthetics, function, tissue biology
and occlusal physiology, thus endangering tooth vitality and integrity. Coronal fractures resulting from dental trauma most frequently occur to the maxillary
anterior teeth of adolescents and less frequently to mandibular teeth. Adult teeth may also suffer traumatic fracture, although less frequently than for
adolescents.
Case Report: In our case, an economical and time-saving novel technique has been described for direct composite restoration in a young patient with
uncomplicated fractured maxillary anterior tooth.
Conclusion: As restoring a fractured tooth is a complex procedure, this technique can prove as a simple, effective and appropriate technique that will fulfill all
the requirements of dental personnel. This technique can also prove to be easy for inexperienced beginner clinicians without requiring special skills in
providing the patients with direct composite restorations
Orthodontic tooth movement is basically a biologic response towards a mechanical force. Osteoclast and osteoblast cells mediate bone resorption and apposition, which eventually produces tooth movement. Researches showed that the rate of orthodontic tooth movement can be altered by certain drugs locally or systemically. The Objective of this article is to discuss the current data concerning the effect of drugs on orthodontic tooth movement.
Multidisciplinary Approach in the Rehabilitation of Congenitally Maxillary C...Abu-Hussein Muhamad
Objective: This case report describes the multidisciplinary
approach to treat a congenitally missed maxillary canine, how to
improve patient’s smile using orthodontic fixed appliance, endosseous
dental implant, and porcelain veneer to achieve the treatment results of
function and esthetic.
Materials and procedures: Unilateral agenesis of the permanent
maxillary canines in healthy individuals is extremely rare. This
paper presents the case of a female patient diagnosed with congenital
unilateral agenesis of the permanent maxillary canines as well as
occlusal abnormalities in the form of left-side crossbite. To restore the
proper aesthetics and function, interdisciplinary therapeutic treatment
was implemented. In the case presented in this paper, the aim of
oral rehabilitation was to restore a functional balance by obtaining
proper skeletal relationships, creating optimal occlusal conditions and
obtaining arch continuity.
Conclusion: Interdisciplinary treatment combined of orthodontics,
implant surgery, and prosthodontics was useful to treat a nonsyndromic
oligodontia patient. Especially, with the new strategy, implantanchored
orthodontics, which can facilitate the treatmentand make it
more simply with greater predictability.
Dental implants represent one of the most successful treatment modalities in dentistry.
However, failures do occur in the range from 5 to 8% for routine procedures and up to 20% in major grafting cases after at least 5 years of function . The majority of implant losses may be explained as biomechanically induced failures, since low primary implant stability, low bone density, short implants and overload have been identified as risk factors . Hence, achievement and maintenance of implant stability are pre-conditions for a successful clinical outcome with dental implants.
The review focuses on different methods used to assess implant stability and recent advances in this field
Over time, progressively shorter implants have been placed such that short implants are now available that are less than 6 mm in length. The viability and high success rates seen with short implants can be explained by osseointegration, the macro geometric design of the implant, as well as physics and the distribution of forces. This paper was aimed to review the stability and survival rate of short implants under functional loads. Numerical and clinical studies were reviewed. Keywords: Short dental implants, sinus augmentation, factors affecting bone regeneration in dental implantology
Porcelain laminate veneers are among the most esthetic means of creating a more pleasing and beautiful smile. Porcelain veneers within reason allow for the alteration of tooth position, shape, size and color. They require a minimal amount of tooth preparation, approximately 0.5 mm to 0.7mm of surface enamel reduction. This study describes the use of ceramic veneers without tooth wear, reinforcing the concept that minimally invasive porcelain laminate veneers could become versatile and conservative allies in the fi eld of esthetic dentistry. Keywords: Ceramics, dentin-bonding agents, esthetics
Immediate Restoration of Single Implants Replacing Lateral Incisor Compromis...Abu-Hussein Muhamad
Today, the diagnosis of internal root resorption is significantly improved by the three-dimensional imaging. Furthermore, the CBCT’s superior diagnosis accuracy resulted in an improved management of the resorptive defects and a better outcome of Implant therapy of teeth with internal resorption.Implant has become a wide option to maintain periodontal architecture. Diagnosis and treatment planning is the key factors in achieving the successful outcomes after placing and restoring implants placed immediately after tooth extraction. The purpose of this clinical update is to report on the success and survival of Immediate restoration of single implants replacing right lateral incisor compromised by internal resorption.
Immediate Implant Placement And Restoration With Natural Tooth In The Maxilla...Abu-Hussein Muhamad
Anterior tooth loss and restoration in the esthetic zone is a common challenge in dentistry today. The prominent visibility of the area can be especially distressing to the patient and requires a timely and esthetically pleasing solution. Immediate single-tooth implantation followed by immediate provisionalization is becoming an increasingly desirable treatment that offers numerous benefits over conventional delayed loading. Provisionalization for immediately-placed implants using the patient’s existing tooth can enhance the final aesthetic outcome if certain steps are
followed. If the natural tooth is intact and can be used as a provisional, the emergence profile can be very similar to the preoperative condition. This article outlines a technique to use the patient’s natural tooth after extraction to provisionalize an implant.
Clinical Management of Bilateral Impacted Maxillary CaninesAbu-Hussein Muhamad
Introduction: Impaction of maxillary canines is a frequently encountered clinical problem in orthodontic therapy. When a preventive
approach fails, treatment involves surgical exposure of the impacted tooth, followed by orthodontic traction to guide and align it into the
dental arch. The aim of the present report was to demonstrate by case reports of an adult patient with bilateral impacted maxillary canines
treated with surgical exposure and orthodontic treatment.
Material and Methods: A 15year-old female with various degrees of bilateral palatal impaction of maxillary canines were managed
by the described technique.
Results and Discussion: Autonomous eruption of the impacted canines after surgical uncovering was witnessed in all patients
without the need for application of a vertical orthodontic force for their extrusion.
Conclusion: The described method of surgical uncovering and autonomous eruption created conditions for biological eruption of the
palatally impacted canines into the oral cavity and facilitated considerably the subsequent orthodontic treatment for their proper alignment
in the dental arch.
Keywords: Impacted canines; Surgical; Tooth exposure; Orthodontic treatment
“One-Piece” Immediate-Load Post-Extraction Implant In Maxillary Central IncisorAbu-Hussein Muhamad
Abstract: This case report describes extraction of a fractured left maxillary central incisor tooth, followed by immediate placement of an one-piece implant in the prepared socket and temporization by a bonded restoration.
Materials And Methods: The tooth was extracted with minimal hard and soft tissue trauma and without flap reflection. The socket was prepared to the required depth and a Implant was inserted.
Results: The atraumatic operating technique and the immediate insertion of the one-piece Implant resulted in the preservation of the hard and soft tissues at the extraction site.
Conclusion: The “One-piece” dental implant and provisional restoration provided the patient with immediate esthetics, function, comfort and most importantly preservation of tissues. The one-piece implant design resulted in a high cumulative implant survival rate and beneficial marginal bone levels.
Single Visit Replacement of Central Maxillary Using Fiber-Reinforced Composi...Abu-Hussein Muhamad
Fiber reinforced composites are high strength filling materials composed of conventional composites and glass fibres. They exhibit extensive applications in different fields of dentistry. This clinical report present a case where FRC technology was successfully used to restore central maxillary incisor edentulous area in terms of esthetic-cosmetic values and functionality.
Zirconium Dental Implants And Crown for Congenitally Missing Maxillary Latera...Abu-Hussein Muhamad
Zirconia implants were familiarized into dental implantology. Zirconia appears
to be an appropriate implant material due to its low plaque affinity, tooth like color, biocompatibility and mechanical properties. The following a case presentations will show how the acid-etched zirconia Implant can be used to functionally and aesthetically replace congenitally missing left lateral incisor tooth germ in the maxilla, and achieve optimal soft tissues and health.
Surgery of Labially Impacted Canine & Orthodontic Management – A Case ReportAbu-Hussein Muhamad
Maxillary canines are one of the most common teeth that are impacted among patients seeking orthodontic treatment. Depending on the position of these impacted teeth, various surgical techniques have been employed for their exposure. His primary goal of surgical phase is to provide the means for correct position of orthodontic anchorage. Additionally, the technique used must ensure favorable tissue anatomy that will permit long-term maintenance of periodontal health. In the present case, a labially impacted maxillary left canine was surgically exposed using an apically positioned flap. Orthodontic extrusion was carried out further.
Travel Clinic Cardiff: Health Advice for International TravelersNX Healthcare
Travel Clinic Cardiff offers comprehensive travel health services, including vaccinations, travel advice, and preventive care for international travelers. Our expert team ensures you are well-prepared and protected for your journey, providing personalized consultations tailored to your destination. Conveniently located in Cardiff, we help you travel with confidence and peace of mind. Visit us: www.nxhealthcare.co.uk
Breast cancer: Post menopausal endocrine therapyDr. Sumit KUMAR
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Summer is a time for fun in the sun, but the heat and humidity can also wreak havoc on your skin. From itchy rashes to unwanted pigmentation, several skin conditions become more prevalent during these warmer months.
Nano-gold for Cancer Therapy chemistry investigatory projectSIVAVINAYAKPK
chemistry investigatory project
The development of nanogold-based cancer therapy could revolutionize oncology by providing a more targeted, less invasive treatment option. This project contributes to the growing body of research aimed at harnessing nanotechnology for medical applications, paving the way for future clinical trials and potential commercial applications.
Cancer remains one of the leading causes of death worldwide, prompting the need for innovative treatment methods. Nanotechnology offers promising new approaches, including the use of gold nanoparticles (nanogold) for targeted cancer therapy. Nanogold particles possess unique physical and chemical properties that make them suitable for drug delivery, imaging, and photothermal therapy.
Are you looking for a long-lasting solution to your missing tooth?
Dental implants are the most common type of method for replacing the missing tooth. Unlike dentures or bridges, implants are surgically placed in the jawbone. In layman’s terms, a dental implant is similar to the natural root of the tooth. It offers a stable foundation for the artificial tooth giving it the look, feel, and function similar to the natural tooth.
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
How to Control Your Asthma Tips by gokuldas hospital.Gokuldas Hospital
Respiratory issues like asthma are the most sensitive issue that is affecting millions worldwide. It hampers the daily activities leaving the body tired and breathless.
The key to a good grip on asthma is proper knowledge and management strategies. Understanding the patient-specific symptoms and carving out an effective treatment likewise is the best way to keep asthma under control.
2. 150 M. Abu-Hussein
so the palatal mesenchymal cells are themselves In human embryos, palatal shelves elevate simul-
contractile and secrete various neurotransmit- taneously on day 43 (22–24 mm CRL), and the palate
ters that effect both mesenchymal cell contractili- is closed by day 55 (33–37 mm CRL). Mesenchymal
ty and glycosaminoglycan dehydration and there- fusion is complete by day 60 (45–46 mm CRL).
fore play a role in palate morphogenesis [1].
At this precise developmental stage, the shelves
rapidly elevate to a horizontal position above the Pathogenesis of CL and CP
dorsum of the tongue. Self elevation probably oc-
curs within minutes or hours. The medial edge In studying different types of orofacial mal-
epithelia of the approximating palatal shelves fuse formation, animal specimens have been proved to
with each other, developing cell adhesion mole- be especially helpful because they permit observa-
cules and desmosomes to form a midline epithelial tion of embryological and fetal stages that lead to
seam. The epithelial seam starts to thin by expan- malformations found at birth.
sion in palatal height and epithelial cell migration The majority of congenital craniofacial mal-
onto the oral and nasal aspects of the palate [1] and formations occur during the first 5–12 weeks
then degenerates, establishing mesenchyme conti- of fetal development [2]. The embryonic period
nuity across the intact horizontal palate. Medial (from 3–9 weeks) is the most sensitive period dur-
edge epithelial cells cease DNA synthesis 24–36 hrs ing which teratogens can be particularly damag-
prior to shelf contact and this is referred to as pro- ing. This is especially true for midline morpholog-
grammed cell death (PCD). The basement mem- ic disorders such as cleft lip and palate. They are
brane on each side of the epithelial seam remains considered to be a polygenic multifactorial prob-
intact even when it has completely thinned. Epi- lem in which genetic susceptibility is influenced
thelial-mesenchymal recombination experiments by multiple and probably cumulative environmen-
have demonstrated that epithelial differentiation tal factors, interacting altogether to shift the com-
is specified by the mesenchyme and that medial plex process of morphogenesis of the primary and
edge epithelial cell death is rather a “murder” by secondary palates, toward a threshold of abnor-
the underlying mesenchyme than an intrinsic ep- mality at which clefting may occur (multifactori-
ithelial suicide (rev by Ferguson, 1988). The ways al/threshold model). Both the genetic and the en-
in which mesenchyme could signal epithelial dif- vironmental factors have not yet been established.
ferentiation is either through extracellular matrix Cell death is a normal phenomenon seen in
molecules (i.e. collagen molecules), through solu- the developing embryo (PCD). It is also a common
ble factors (i.e. growth factors), direct cell-to cell feature seen in embryos after exposure to a variety
contact, or a combinations of all the above. The ac- of teratogens that induce craniofacial malforma-
tual period of fusion of the mesenchymal shelves tions. There are three distinct types of PCD (rev
may be just a matter of minutes, but complications by Sulik, 1988). Type 1 is characterized by cellu-
in events leading up to and during fusion will re- lar condensation, fragmentation, phagocytosis
sult in a palatal clefting of varying severity. and finally lysosomal degradation. Type 2 is char-
Also, seam disruption occurs by migration of acterized primarily by the appearance of large ly-
a large number of epithelial seam cells (perhaps sosomes which initiate cellular degradation. Type
50%) into the palatal mesenchyme (rev by Fergu- 3 occurs without the involvement of lysosomes
son, 1988). These fragments very quickly become and without apparent phagocytosis.
undistinguishable from other palatal mesenchyme The sites of cell death vary depending up-
cells. The epithelia on the nasal aspect of the pal- on the teratogen (or genetic insult) and the expo-
ate differentiate into pseudo-stratified ciliated co- sure time (i.e. developmental stage of the embryo).
lumnar cells while on the oral aspect of the palate There seems to be a selective sensitivity of cells;
they differentiate into stratified squamous non-ke- tissues with high proliferative activity are more
ratinized cells. Osteogenic blastemata for the pala- likely to show cell death than tissues that prolif-
tal processes of the maxillary and palatine bones erate more slowly. Other factors may also been in-
differentiate in the mesenchyme of the hard pal- volved, i.e. the state of cellular differentiation, dif-
ate while several myogenic blastemata develop in ferential drug distribution or other specific cel-
the soft palate. lular characteristics. Both the disappearance and
During the period of shelf elevation, there expansion of areas of PCD may have a role in tera-
is almost no growth in head width but constant togenesis (rev by Sulik, 1988).
growth in head height. This establishes a conduc- Pathogenesis is probably caused by one of the
tive orofacial environment that permits the ex- following mechanisms:
panding palatal shelves to occupy a position above 1) Anatomic obstruction, i.e. the tongue ob-
the dorsum of the tongue. struction hypothesis – only when associated with
3. Cleft Lip and Palate 151
mandibular underdevelopment [4]. In cases where an embryo to the disturbance of lip formation.
the chin is compressed against the sternum, the Where the size of the facial processes is reduced
tongue may interpose in the space between the as- and they are not in tight apposition, there is an in-
cending shelves. The resultant palatal deficiency is creased probability of cleft lip. Experimental sup-
U-shaped not V-shaped by disturbance in growth port of the previous is found in the work of Trasler,
potential not tissues that may have been affected 1968 and Brown, Hetzel, Harne & Long, 1985, re-
by disturbances of ecto-mesenchyme or other phe- viewed by Poswillo, 1988, where the spontaneous
nomena at the cellular level [5]; development of cleft lip and palate in A strain mice
2) Interference with cell differentiation or mi- is attributable to the pointed facial processes that
gration, either through hormonal defect, biochem- prevent wide areas of contact. On the other hand,
ical defect, or extrinsic biochemical interference. in the C57 black strain of mouse, the larger facial
Numerous studies have substantiated the associa- processes facilitate wider contact of the processes
tion between teratogens and clefting. Such terato- and therefore clefting doesn’t develop.
gens may be individually operative in a subgroup While anatomical variation is one potential
of individuals that is genetically and biologically predisposing factor in the development of cleft lip
susceptible. Conversely, several different terato- and palate, other factors also exist. It is well es-
gens may act together on a single mechanism con- tablished that at the time of consolidation of the
trolled by only a few genes. At present our knowl- facial processes, there is a concurrent program of
edge of the teratogens that are associated with spontaneous cell death (PCD). It is involved in the
clefting is very limited. Only a few substances such removal of the epithelial debris from the devel-
as retinoic acid (used in the treatment of acne and oping nasal placode. When this PCD is more ex-
psoriasis), have been confirmed as teratogens with tensive than necessary and repair of mesenchyme
direct effect on facial morphogenesis. is disturbed, a weakness develops in the forming
Several other factors that may influence genet- lip and alveolus. The continued action of growth
ic behavior and early morphogenesis have received traction forces may further disrupt the association
attention in the investigation of the etiology of CL of the facial processes with the lip margins being
and CP (rev by Amaratunga, 1989). pulled apart. Resultant clefts of the lip may vary
A seasonal variation in the incidence of CLP from a simple groove in the muscle to a complete
has been reported by several authors while oth- cleft that includes the nasal floor [7].
ers have reported the opposite. This phenomenon In regards to submucous cleft palate and bi-
has not been satisfactorily explained. One possible fid uvula, both can be considered microforms of
reason is viral infection, which may have a season- isolated palatal clefting. Probably, the disturbanc-
al trend. However, a correlation between clefts and es in the local mesenchyme occurred at the time
viral infections has not clearly been established. of the ossification of the palatal bridge and merg-
Also, some authors report that the instance of ing of the margins of the soft palate. These phe-
CLP is higher in earlier born children (in terms nomena occur between 7–10 weeks of human de-
of birth order) while others conclude the opposite. velopment [8].
When birth rank is raised, maternal age could also An association between clefts of the lip and
be raised. Mutations of genes can occur with ad- cleft palate has been observed. Animal stud-
vanced parental age. ies suggest that “following the failure of lip clo-
Monozygous twins discordant for clefting are sure there is an overgrowth of the prolabial tissues
interesting. Examinations of the developing fe- which then divert the tongue into the nasal cavity.
tus using ultrasound have shown that there are al- The mesenchymal obstruction of the tongue can
tered rates of fetal growth, both of the whole body delay the movement of one or both palatal shelves,
and of its parts, so that at any one time, twins may so that opportunities for palatal fusion are lost”
exhibit different stages of development. There- (rev by Poswillo, 1988).
fore the variable expression of clefting could re- Lip and palate formation lasts over 15 days in
sult from the same factor acting on both twins at humans. Therefore in many syndromes, cleft lip
the same time, but at relatively different stages of and palate may be accompanied by anomalies of
their early growth. different parts of the body. Many developing sys-
With regards to lip clefting, it seems that the tems can be disturbed simultaneously by terato-
crucial stage of lip formation is the moment when genic influences which operate over a long period
medial and lateral nasal processes contact each of morphodifferentiation. But despite the fact that
other and fuse. there are over 150 recognized disorders in which
Anatomical variations (differences in the size, CL, CP or both may represent one feature, it is
shape or position of the facial processes), possibly widely believed that the majority of affected indi-
based on ethnic or other factors, may predispose viduals are otherwise structurally normal (rev by
4. 152 M. Abu-Hussein
Jones, 1988). Recent studies [10] have emphasized well as for many common disorders, e.g. congeni-
the fact that a significant portion of children with tal malformations.
clefts have the cleft as one feature of a broader pat- The normal rate of development can be
tern of malformation. It is important to recognize thought of as a continuous distribution in which,
that structural defects are not, for the most part, if it is disturbed, a serious malformation may oc-
randomly associated. The presence of other ma- cur. This has been described as the multifactori-
jor and minor malformations in association with al/threshold model and several human congenital
a cleft implies that a single etiologic factor – ge- malformations reveal family patterns that fit this
netic, chromosomal or teratogenic – produced the model. CL with or without CP and CP alone are
pattern as a whole. included in this category.
Although CL is frequently associated with CP, CL with or without CP shows both geographi-
CL with or without CP and CP alone are distinctly cal and racial variations which means that it could
different in etiology. Subsequent studies have con- be explained by the multifactorial/threshold mod-
sistently confirmed that these two conditions indeed el. In contrast CP alone shows little variation in
differ in etiology and also in incidence, sex predis- different racial groups. This may mean that isolat-
position and their relationship to associated birth ed CP will not fit the purely multifactorial model.
defects. CL results from the non-fusion of the up- To date, there have been three pedigrees re-
per lip and the anterior part of the maxilla at the ported in which CP is clearly inherited as a single-
5–7 week of gestation and is observed in approxi- gene X-linked disorder [13–15].
mately 1/1000 births [11]. Isolated CP results from One of these pedigrees is described to a large
a failure of the mesenchymal masses of the palatine Icelandic family (293 individuals) that shows Men-
processes to fuse during weeks 7–12 and has an av- delian inheritance of X-linked secondary cleft palate
erage incidence of 0.7/1000 births. The incidence of and ankyloglossia [15]. Family analysis has shown
CL with or without CP varies from 2.1/1000 in Ja- that the frequency of CP among all the members of
pan to 0.4/1000 in Nigeria (rev by Moore, 1988), with this family was much higher among the male than
the geographical variation being less important than among the female CP probands. There was no in-
ethnic differences. In contrast, the incidence of CP cidence of male to male transmission in this large
alone shows little variation in different racial groups. family. The X-linked mode of inheritance of CP is
This may mean that CP alone will not fit the purely indicated by the family distribution. Also the large
multifactorial model which includes genetic and en- number of members of this family together with
vironmental factors that would increase the varia- the availability of many X-chromosome probes has
tion in incidence both geographically and to some made it possible to localize the defect subchromo-
extent racially. Generally CL with or without CP is somally (using RFLP-restriction fragment length
more frequent in males, whereas CP alone is more polymorphism studies for linkage) to the q13-q21.1
frequent in females. Therefore, due to both genetic region of the X chromosome [16]. Finer mapping
and environmental evidence, it seems that CL with and the use of cell lines from patients with dele-
or without CP and CP alone are separate entities. tions of the X chromosome have further localized
the defect to Xq21.31-q21.33 [17].
In the case of CL with or without CP, Melnick
Genetic Factors et al, 1980 [18] reviewed worldwide CL/P recur-
rence risk data and found that both a multifactori-
Polygenic inheritance refers to conditions de- al-threshold model and a monogenic with random
termined by a large number of genes. Each of them environment component model fitted poorly.
has a small effect, but they act additively (i.e. hair Farrall and Holder, 1992 [19] refer to the work
color) [12]. of several investigators. According to their report:
Multifactorial inheritance refers to conditions Marazita, 1984, in his analysis of a subset of Dan-
determined by a combination of factors each with ish CL/P families, found no support for a MF/T
a minor but additive effect (i.e. blood pressure) [11] model but suggested the possibility of a major gene.
and has been developed to describe the observed Also Marazita et al, 1986, have reported an anal-
non-Mendelian recurrences of common birth de- ysis of ten English multigenerational CL/P fami-
fects. It includes both polygenic origin and un- lies collected by Carter, 1982. They were able to re-
defined environmental factors that will increase ject an MF/T model and demonstrated that a ma-
the variation in incidence depending on race and jor locus acting on a multifactorial background
geographic region. The multifactorial inheritance (mixed-model) gave a reasonable fit. Chung, 1986,
pattern is more difficult to analyze than any oth- analyzed a series of Danish and Japanese CL/P
er type of inheritance but it is thought to account families and concluded that the best fitting model
for much of the normal variation in families, as predicted a recessive major gene acting on a multi-
5. Cleft Lip and Palate 153
factorial background (mixed-model). Chung et al, Vitamin A
1989, analyzed Hawaiian families from several ra-
cial groups and found that the data was consistent By introducing human teratogenic agents (e.g.
with a major-gene/multifactorial model (mixed excess vitamin A) into the maternal diet of A strain
model). Ardinger, 1988, has provided additional mice, it has been observed that 100% of offspring
evidence for an association between the locus for are born with the expected deformity [7]. Renewed
transforming growth factor alpha (TGFA) and the interest in retinoic teratogenicity has followed the
CL/P locus. TGFA is believed to be the embryon- introduction of 13-cis-retinoic acid as an effective
ic form of epidermal growth factor, which is be- treatment for severe cystic acne. Inadvertent use
lieved to regulate the proliferation and differenti- of 13-cis-retinoic acid during the first trimester of
ation of palatal epithelial cells both in vitro and human pregnancy has been reported to result in
in vivo. Hecht et al, 1991, analyzed mid-western a spectrum of malformations termed retinoic ac-
U.S. Caucasian families and showed consisten- id embryopathy (RAE) [20] and includes microtia
cy with a major-locus model. He found that the or anotia, micrognathia and in some cases CP. The
dominant or codommant models with decreased induction of CP following administration of excess
penetrance fitted the best. Both the MF/T mod- vitamin A to pregnant laboratory animals is well
el and the mixed model with a dominant major documented [21]. Most of the early animal stud-
gene effect were found to provide an explanation ies involved exposure to forms of vitamin A that
for the familiar clustering pattern. Marazita et al, are stored in the maternal liver and that, therefore,
1992, analyzed almost 2000 Shanghai families and have a relatively long half-life; they also involved
found that the best fitting model was that of an au- multiple administrations of the drug or examined
tosomal recessive major locus. the developmental end-point only, thereby exclud-
Farrall and Holder [19], in their own analysis, ing study of the developmental changes that lead
have shown that “the extensive published recur- to CP.
rence risk data, which have been interpreted to be A study by Kochhar and Johnson, 1965, re-
consistent with an MF/T pattern of inheritance, viewed by Sulik, 1989, describes palatal clefts for
are equally compatible with an oligogenic model which the shelves were very small or entirely ab-
with perhaps as few as four genes.” sent; these resulted from insufficient maxillary
In conclusion, the extensive recurrence risk prominence mesenchyme. These investigators al-
data, which has been widely interpreted as pro- so found that size reduction of the palatal shelves
viding evidence of a polygenic multifactorial trait, occurred only posteriorly in most cases.
are now thought to be consistent with a mod- The use of all-trans-retinoic acid, which is of
el with a major-gene effect contributing to about short half-life, has shown that incidence of cleft
1/3 of CL/P and acting on a multifactorial back- palate peaks at more than one developmental stage
ground. For CL/P, the observed decline in risk in both hamsters and mice (Kochhar, 1973, rev by
with decreasing relatedness to the proband is in- Sulik, 1989).
compatible with any generalized single-major-lo- The changing incidence and severity of sec-
cus (gSML) model of inheritance and is suggestive ondary palatal malformations that may be in-
of multilocus inheritance. duced within a narrow window of time (over
a 16 hour period) appear to be related to a cor-
responding change in the pattern of PCD in the
Teratogenes first visceral arch. It has been shown that 13-cis-
-retinoic acid increases the amount of cell death in
Palatal shelf elevation and fusion depends on regions of PCD in C57B1/6J mice, a strain which
fetal neuromuscular activity, growth of the crani- is particularly prone to spontaneous craniofacial
al base and mandible, production of extracellu- malformations [3, 22]. The distribution of exces-
lar matrix and contractile elements in the palatal sive cell death in regions of PCD provides a basis
shelves, shelf adhesion, PCD of the midline epithe- for understanding the composition of syndromes
lial seam and fusion of the ectomesenchyme be- in which malformation appears to be unrelated by
tween one shelf and another. All these phenomena tissue type or location [22].
must act in perfect harmony over a short period What has been described as vitamin A cell ne-
of time in order to produce normal palatogene- crosis is consistent with type-2 cell death (rev by
sis. Factors that interfere with any of these events Sulik, 1988). On the other hand, it has been not-
could lead to a cleft. ed that not all lysosomal membranes of all cells
lyse. Only those membranes that are at a particu-
lar stage of differentiation or which have been per-
turbed in some other way lyse. Membrane destabi-
6. 154 M. Abu-Hussein
lization by the retinoids may interfere with many ethanol when the embryos have approximate-
cellular functions. For example, blebbing of the ly 7–10 somites results in a pattern of malforma-
neural crest cell membrane was noticed follow- tion that is consistent with the DiGeorge sequence
ing retinoic exposure. This may interfere with the (midline clefts in the nose and cleft palate are fea-
migratory ability of these cells. Recovery follows tures of this sequence. The DiGeorge sequence has
removal of the retinoic acid in vitro. In vivo, re- been described in the offspring of alcoholic moth-
covery from a brief interference with cell migra- ers.
tion might also be expected but sufficient recovery Among the cellular effects of ethanol are in-
probably does not follow the excessive cell death of creased peroxidase activity, interference with cy-
progenitor cells. toskeletal components, diminished DNA synthe-
Treatment of female C57B1/6J with 13-cis-ret- sis and suppressed rates of cell division, direct ef-
inoic acid at the early stage of pregnancy (8d14hr fects on membranes resulting in excessive fluidity
to 9d0hr) has a more severe effect on the second- (reviewed by Sulik, 1988). Recent investigations il-
ary palate [22]. 12 hours after the 8d14hr treatment lustrate excessive cell death within 12hr follow-
time, embryos have 13 to 20 somites. Extensive ex- ing maternal treatment. The rates of cell death are
pansion of cell death at this time would be expect- similar to the normal rates of cell death seen in
ed to have a major effect on almost the entire sec- PCD, but the areas of cell death are expanded. The
ondary palatal shelf complex, thereby resulting reason for this excessive cell death is not yet clear.
in severe hypoplasia and clefting. Minor effects One possible explanation is that exposure to etha-
would be expected to involve only the posterior nol results in lipid peroxidase/formation that leads
portion of the maxillary prominences, thereby re- to rupture of lysosomal membranes and release of
sulting in deficiency in the posterior aspect of the hydrolytic enzymes (type-2 cell death).
secondary palate.
12 hours after the 9d6hr treatment time (late
treatment), embryos have approximately 30 to
Hyperthermia
34 somites. Expansion of cell death in embryos Hyperthermia has teratogenic effects and the
at this stage of development results primarily in facial malformations induced include, among oth-
foreshortening of the secondary palate, which oc- ers, cleft lip and/or cleft palate. CNS is particular-
curs at the expense of its posterior portion. Ma- ly sensitive to hyperthermia. Facial abnormalities
jor effects on the entire palatal shelves would not have been associated with human maternal hyper-
be expected at this treatment time. Later treatment thermia at 4–7 weeks (rev by Sulik, 1988). The type
times are mostly associated with induction of limb and extent of damage depend on the duration of
malformations [23]. temperature elevation and the extent of elevation.
Also, low sustained temperature elevations appear
to be as damaging as repeated spikes of higher ele-
Phenytoin vation. Elevations of 1.5–2.5 degrees Celsius above
Also, “under the influence of teratogenic dos- normal body temperatures represent the threshold
es of phenytoin, the lateral nasal process fails to for teratogenesis in humans. Such elevations can
expand to the size necessary for tight tissue con- result from excessive exercise, the use of hot baths
tact with the medial nasal process” (rev by Poswil- and saunas and febrile episodes.
lo, 1988). Abnormal differentiation of the cellular Again in the case of heat-induced teratogen-
processes of the ectomesenchymal cells is probably esis, cell death is considered to play a major role,
associated with this condition, where the lip and with the mitotic cells being the most susceptible.
primary palate form. The pathogenesis of heat-induced malformations
in areas other than the CNS have not been studied
yet. It has been suggested though that hyperther-
Ethanol mia could result in intra and extracellular leakage
Ethanol (alcohol) is an important human te- of lysosomal enzymes which could lead to type-2
ratogen. IT is estimated to severely affect 1.1/1000 cell death.
live births and have lesser effects in 3–4/1000 chil-
dren born. Its abuse during pregnancy results in fe-
tal alcohol syndrome (FAS) which involves a wide
Ionizing Radiation
variety of malformations in many organs. Abnor- Ionizing radiation acts as a direct insult to the
malities that are not diagnostic of FAS, but are as- embryo. The malformations induced are similar to
sociated with maternal ethanol abuse are termed those noted following exposure to ethanol, retino-
fetal alcohol effects (FAE) (rev by Sulik, 1988). ic acid or hyperthermia. The cellular mechanisms
Treatment of C57BL/6J female pregnant mice with of radiation-induced teratogenesis are not com-
7. Cleft Lip and Palate 155
pleted understood. They vary from sublethal in- The fiber diameters were also found to be much
juries affecting differentiation and cellular inter- smaller. NADH stain and electron microscopy re-
actions, to effects on rates of proliferation and cell vealed a large accumulation of mitochondria at the
death (rev by Sulik, 1988). Response of the cells to central portion of the fiber, giving a star shaped
the radiation is dependant on cell cycle. Also, in appearance to the fiber. The mitochondria are
some instances cell death is linked to chromosom- more variable in shape than normal, and the cris-
al damage. Some studies have shown that irradia- tae are more densely packed than expected.
tion results in altered permeability of intracellular These abnormalities in mitochondrial size, lo-
structures and enzyme release, i.e. rupture of ly- cation, cristae and number suggest a form of met-
sosomal membranes, and suggest that this results abolic defect that could underlie cleft lip deformi-
from lipid peroxide formation. ties. The suggested explanation is that a defect in
energy production could result in insufficient cel-
lular migration and proliferation and thus be the
Hypoxia pathophysiological basis for cleft lip. As mentioned,
Of particular interest is hypoxia-induced cleft in addition to the mitochondria, the cleft lip mus-
lip. Hypoxia in the human embryo may result cles were found to be abnormal. However, no signs
from cigarette smoking, reduced atmospheric ox- of group denervation or reinnervation were found
ygen levels and also placental insufficiency. Pre- and the motor end plate structure appeared nor-
vious studies had shown size reduction and ab- mal. These findings argue against denervation or
normal apposition of the facial prominences as abnormal innervation as a cause of the abnormal-
possible pathogenetic mechanisms. The presence ities. Since the innervation was normal, the mus-
of cellular debris resulting from cell death in the cle atrophy was attributed to an inability of these
deepest aspects of the invaginating nasal placodes, muscles to function properly, which was further-
as well as overall growth retardation of the facial more attributed to the mitochondrial energy pro-
prominences, leads to inability of the facial prom- duction abnormality or to the lack of normal fiber
inences to contact and fuse (rev by Sulik, 1988). orientation. If the causative factor is the fiber ori-
There are also direct effects suggested of oxygen entation, one would expect this to improve follow-
deficiency on the cells which lead to glycolysis fol- ing adequate surgical reconstruction of the muscle
lowed by acidification of intercapillary spaces and at the time of lip repair. On the other hand, chang-
subsequent necrosis resulting from intra and ex- es secondary to cellular energy problems would
tracellular leakage of lysosomal enzymes. It is in- not be expected to improve following surgery.
teresting to note that chemicals that interfere with In general, a common target for some terato-
oxidative enzymes such as phenytoin induce cleft genes (i.e. cells in regions of PCD that represent
lip in mice. a developmental weak point) provides reason to
expect interactive effects. Repeated exposure of
teratogenes in subthreshold doses of more than
Antimetabolites one agent could result in potentiation. Potentia-
Methotrexate and aminopterin are two un- tion indeed occurs after repeated exposures to vi-
common antimetabolites that can induce crani- tamin A and hyperthermia.
al dysplasia and cleft palate in humans. Their ac-
tion is inhibitory of DNA synthesis through com-
petitive folic acid antagonism. The pathogenesis Conclusions
of methotexate involves fluid imbalance, result-
ing perhaps from interference with osmoregulato- At present, our knowledge of the teratogenes
ry cells in extraembryonic capillary beds, which is that are associated with clefts is not very exten-
partially responsible for the malformation. sive. Some of these substances (such as retinoic ac-
id) have been confirmed to have direct effects on
facial morphogenesis but many more await iden-
Metabolic Disorders tification.
Metabolic disorders, inherited or not, may
An interesting finding associated with lip play a role in the pathogenesis of clefting.
clefting was that of mitochondrial myopathy of Our knowledge of cell biology is increasing
cleft muscles [24]. Facial muscle specimens from rapidly and may eventually lead to the under-
the cleft site were characterized by disorganized fi- standing and possibly prevention of clefts of the
bers, going in many different directions. The num- lip and palate. This can particularly apply in cas-
ber of fibers appeared to be decreased and there is es with monogenic etiology and in chromosom-
more connective tissue between the muscle fibers. al disorders.
8. 156 M. Abu-Hussein
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Address for correspondence:
Muhamad Abu-Hussein
Pediatric Dentistry
123 Argus Street
10441 Athens
Greece
E-mail: muham001@otenet.gr
Received: 23.03.2012
Accepted: 16.04.2012
Praca wpłynęła do Redakcji: 23.03.2012 r.
Zaakceptowano do druku: 16.04.2012 r.