By K. Zuben. College Misericordia.
The first group would contain genes that have never or have only rarely shown an association discount cialis extra dosage 40mg on-line erectile dysfunction treatment homeveda, generally of small effect generic cialis extra dosage 60 mg without prescription impotence guilt. There are also other genes, not reviewed here that have failed to show evidence of an association (Gomez 2006, Rajalingam 1997). Is there any way to ex- plain the difficulty in conclusively identifying the genes that determine why not all those exposed to M. Is it possible to explain why genes associated with susceptibility in some studies often fail to demonstrate an association in others? This could certainly be possible, and is consistent with data in mice (Yan 2006), but proof would likely require the technical ca- pacity to sequence hundreds of genes in hundreds or thousands of individu- als (Hill 2006). The good, the bad and the maybe, in perspective 247 While all of these explanations may be true to some extent, there are other impor- tant variables that could help account for the heterogeneity of results: exposure, strain virulence and general environment. These differences were recognized as nearly insurmountable confounding difficulties by the investigators of the early and th mid 20 century, who knew that valid associations would only be detected if all epidemiologic variables were carefully controlled. While in mouse experiments animals are infected with a uniform dose and delivery of a single strain of M. However, even if a study looking for associations were to perform molecular epi- demiology on all the strains involved, and could assign a measure of relative viru- lence to each strain, how could it evaluate the differing intensities of exposure - the number of bacilli that each subject inhaled? Could it be possible that a particular genetic make-up would be able to avoid either infection or disease after a low-dose exposure to a low-virulence strain, but succumb to the same level of exposure to a more virulent strain, or a much higher dose of the less virulent strain? While family studies should control for strain differences, the small effects of multiple genes would only be found if very large numbers of families were studied, and the most important genes may vary from family to family. To further complicate the analysis, the concor- dance rate in twin studies was, at most, about 50 % – so identical genes may not yield identical results at least half the time. Given the differences in the strain virulence and exposure within a population, and the genetic heterogeneity and apparent incomplete penetrance of the responsible genes, it should not be surprising that it is difficult to obtain clear, reproducible associations with specific alleles, even those that may have moderate effects. While documenting or quantifying exposure to the bacillus, or strain virulence, may be difficult, their roles in pathogenesis are obvious. In contrast, environmental influences are not only difficult to document and quantify (Lienhardt 2001), but their effects have not been well studied and are poorly understood. He compared two groups of infected rabbits: five animals were free to roam outdoors with ample food, while another five were kept in dark cages with minimal food. The reasons for the difference - poor nutrition (Chan 1996, Dubos 1952), crowded liv- ing conditions, or emotional stress (Stansfeld 2002) - and the mechanism of their effects on the immune system, are unclear. Before the war, in 1913, the rates were 118 and 142/100,000 for Bel- gium and the Netherlands, respectively, but by 1918, the rates had increased to 245 and 204/100,000 (Rich 1951). It may be difficult to separate these factors however, because deteriorating and traumatic social conditions are often accompanied by a collapse of the healthcare system. Given that susceptibility seems to be determined by a complex interplay of strain virulence, intensity of exposure and environmental factors, as well as human genetic composition, would it be feasible or advisable to target vaccines, prophylaxis, treatment, or control efforts based on the genetic composition of individuals, families or ethnic groups, instead of simply improving control programs (and socioeconomic status, although more difficult) for the entire population? Might it be more efficient and less costly simply to concentrate on diagnosing and effectively treating cases, and using extra funds for contact tracing? In light of the continuing presence of multi-drug resistant strains (Raviglione 2006), and the difficulties in finding and bringing new drugs and vac- cines into clinical use, further investigation in the field may be justified, despite the relatively disappointing results obtained so far. Acknowledgements: The author thanks Laurent Abel and Luis Quintana-Murci for enlight- ening discussions, Peter Taylor, Zulay Layrisse, Mercedes Fernandes, Angel Villasmil, Gustavo López, Warwick Britton, Joanne Flynn, Stewart Cole and Marisa Gonzatti for critical readings, and especially Pedro Alzari and Stewart Cole for many valuable discus- sions, as well as training, support and encouragement. Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infection in mice. No association between interferon- gamma receptor-1 gene polymorphism and pulmonary tuberculosis in a Gambian population sample. Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene. Assessment of the interleukin 1 gene cluster and other candidate gene polymorphisms in host susceptibility to tuberculosis. Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage nor tuberculosis in Africans. Toll-like receptor 2 Arg677Trp polymorphism is associated with susceptibility to tuberculosis in Tunisian pa- tients. Genetics of host resistance and susceptibility to intramacrophage patho- gens: a study of multicase families of tuberculosis, leprosy and leishmaniasis in north- eastern Brazil. Vitamin D receptor polymorphisms and susceptibility to tuberculosis in West Africa: a case-control and family study. The host resistance locus sst1 controls innate immunity to Listeria monocytogenes infection in immunodeficient mice. Tuberculosis in sub-Saharan Africa: a regional assessment of the impact of the human immunodeficiency virus and National Tuberculosis Control Program quality. Fine mapping of a putative tuberculosis- susceptibility locus on chromosome 15q11-13 in African families.
Ulceration and dissection of atherosclerotic plaques can give rise to emboli of mixed composition generic 40mg cialis extra dosage erectile dysfunction what age. Small thrombi also purchase cialis extra dosage 100 mg with visa erectile dysfunction drug samples, particularly aggregates of platelets, may break loose from the turbulent surface of atherosclerotic plaques. Fat emboli and gaseous emboli tend to produce global cerebral dysfunction rather than typical stroke because they are copious; and numerous small intraparenchymal blood vessels become occluded. Fat emboli arise from the marrow of fractured long bones, enter the venous system, and filter through the lung into the systemic circulation. Vasculitis An inflammatory process in blood vessel walls can produce infarction by swelling the wall and narrowing the lumen, by damaging the endothelial lining and inducing thrombosis, or by destroying the vessel wall (necrotizing vasculitis) giving rise to hemorrhage. Among the fungi that invade the central nervous system opportunistically, Aspergillus, Phycomyces and Candida commonly infiltrate the blood vessels; Cryptococcus does not. Hematologic Hematologic disorders affecting the coagulability, viscosity, or oxygen-carrying capacity of blood can cause, or more likely contribute to, infarction in the brain - among them the leukemias, sickle cell disease, thrombotic thrombocytopenic purpura, polycythemia, disseminated intravascular coagulation, and anticoagulant therapy. Spontaneous hemorrhages in the brain parenchyma and subarachnoid space are often a result of underlying cerebrovascular disease, although trauma can also result in hemorrhages in these sites. The most common site of rupture is one of the sizable arteries that run deep in the basal ganglia as the lenticulostriate branches of the middle cerebral artery. Less common sites of hypertensive hemorrhages are the corpus medullaris of the cerebellum and the brain stem, almost always the pons. Massive hemorrhage in the basal ganglia is attended by immediate loss of consciousness - which would be unusual in the more common stroke on the basis of infarction. The mass effect is immediate and surrounding brain swelling and pressure are more marked than with infarction. Even with optimal medical management, the most important prognostic factor remains the size of the hemorrhage. Dissection of the hemorrhage into the ventricle is incompatible with life for more than a few hours. With hypertensive hemorrhage in the cerebellum, secondary compression of vital centers in the brain stem is the main threat to survival and timely removal of the hematoma may prove effective. Pathologically, the damage from intracerebral hemorrhage is compounded by foci of hemorrhagic infarction surrounding the hematoma. Slowly the blood is resorbed and survivors end up with a cavity outlined by ragged walls stained by blood pigments. The initial symptoms are head pain, typically explosive, promptly followed by depression of consciousness of variable degree. It is a delayed effect, not usually seen during the first 48 hours after rupture, and it persists for days before it resolves spontaneously. The behavior of arterial spasm is unpredictable, a second bleed in short order at the site of rupture is frequent, and the ideal time at which the defect should be repaired is not an easy surgical judgment. The mechanism for the arterial spasm remains unknown and the search for pharmacologic measures that will prevent or correct it continues. Saccular aneurysms are called congenital, but they rarely occur in young children. Whether an embryologic maldevelopment underlies their appearance in later life is moot. They are located at or near arterial junctions, particularly between the posterior communicating artery and the internal carotid or the posterior cerebral artery, at the short anterior communicating artery, and at the first branching of the middle cerebral artery in the Sylvian fissure. They usually rupture near the dome, where the wall of the aneurysm is likely to be thinnest. Giant aneurysms are probably saccular aneurysms that enlarge slowly by repeated internal thrombosis and repair without hemorrhaging. Their wall becomes fairly thick, although not uniformly so, they attain a diameter of a few centimeters, and they become symptomatic as a tumor mass compressing adjacent structures. Fusiform aneurysms are segmental distensions of severely atherosclerotic arteries, notably the basilar or a vertebral artery, and are also called atherosclerotic aneurysms. Arteriovenous malformation The second major cause of spontaneous subarachnoid hemorrhage is rupture of a congenital vascular malformation of the arteriovenous type. These vessels are interconnected and shunt arterial blood directly into venous channels. The vessel walls are of uneven thickness and composition, often of ambiguous denomination, and not proportional to the caliber of the lumen. They are located mainly in the subarachnoid space, but they always extend into the cortex and sometimes into the white matter also. Blood flow through the malformation is hemodynamically abnormal, they thrombose, they leak or hemorrhage, and neuronal degeneration, foci of encephalomalacia, and astroglial reaction and fibrosis in the intervening parenchyma are the rule. Seizures, especially focal fits, and less commonly headaches, usually do not appear until adolescence or early maturity, but the lesion may be silent for decades. Small episodes of hemorrhage or ischemic parenchymal injury, as well as aging vascular changes in the malformation, are probably responsible, cumulatively, for the belated onset of symptoms. When the malformations finally hemorrhage in the subarachnoid space, the hemorrhage tends to be smaller than from a ruptured aneurysm, but malformations that are large and fed by more than one major artery are not easily corrected surgically.
A study of 78 premature and mature newborns showed that total brain tissue volume increased linearly over this period at a rate of 22 ml/week cheap cialis extra dosage 50mg online erectile dysfunction treatment ayurveda. The rapid increase in total grey matter is mainly due to a Human brain at four months (inferior surface) fourfold increase in cortical grey matter generic cialis extra dosage 50mg mastercard erectile dysfunction treatment pdf. Month 3-6 - lungs appear glandular, end month 6 alveolar cells type 2 appear and begin to secrete surfactant. Gonadal Hormones testosterone - required during fetal development for external genital development and internal genital tract in male. A teratogen (Greek, teraton = monster) is defined as any agent that causes a structural abnormality (congenital abnormalities) following fetal exposure during pregnancy. Absolute risk - the rate of occurrence of an abnormal phenotype among individuals exposed to the agent. Fetotoxicant - is a chemical that adversely affects the developing fetus, resulting in low birth weight, symptoms of poisoning at birth or stillbirth (fetus dies before it is born). Synergism - when the combined effect of exposure to more than one chemical at one time, or to a chemical in combination with other hazards (heat, radiation, infection) results in effects of such exposure to be greater than the sum of the individual effects of each hazard by itself. Cells exposed to a stress, drug or toxicant respond by altering the pattern of expression of genes within their chromosomes. There is also growing evidence that some effects are more subtle and relate to later life health events. The theory was therefore originally called the "Barker Hypothesis" and has recently been renamed as "fetal origins" or "programming". Glossary Links 2009 Lecture 23 From Embryology Contents Birth and Postnatal Development Introduction There are a great number of comprehensive, scientific and general, books and articles that cover Parturition, Birth or Childbirth. Birth or parturition is a critical stage in development, representing in mammals a transition from direct maternal support of fetal development, physical expulsion and establishment of the newborns own respiratory, circulatory and digestive systems. Childbirth Parturition (Latin, parturitio = "childbirth") describes expelling the fetus, placenta and fetal membranes and is probably initiated by fetus not mother. Preterm birth - Risks of preterm birth in abnormal low birth weight (intrauterine growth restriction) and high (large for gestational age) categories are 2- to 3-fold greater than the risk among appropriate- for-gestational-age infants. Respiration Lungs at birth collapsed and fluid-filled - replaced with air by powerful inspiratory movement and absorption through the alveoli Lung epithelia has to rapidly change from its prenatal secretory function to that of fluid absorbtion. Adult rib orientation is oblique (both anterior and lateral views), allows for pump-handle and bucket handle types of inspiration. The adult anatomical remnant of the umbilical vein between the umbilicus and liver is the ligamentum teres. Postnatal closure occurs initially by by smooth muscle contraction and begins at the first breath and is rapid, completed within the first day (about 15 hr after birth). Anatomical closure is much slower occuring by 2–3 weeks after birth (33% of infants), by 2 months (90% of infants) and by 1 year (99% of infants). The adult anatomical remnant of the ductus venosus is the ligamentum venosum (a dorsal fissure on the liver). In recent years there has been some controversy of the relevance and accuracy of some of the criteria used in this test, though many feel it is still an invaluable initial assessment tool particularly where medical services are limited. Different countries and medical services have different policies on not only what will be diagnostically tested, but also how long the test card will be kept following analysis. This incidence is influenced by several factors (diagnostic criteria, gender, genetic and racial factors, and age of the population). However, it is acceptable medical practice not to initiate intensive care if parents so wish, following appropriate counselling. Breech position - occurs in about 3% of fetuses when buttocks or lower limb are presented to the birth canal rather than normal cephalic (head-first) position (presentation). Associated increased - perinatal mortality, perinatal morbidity, recurrence in successive siblings Current research suggests that genetically that both men and women delivered in breech presentation at term could also contribute to an increased risk of breech delivery in their offspring. Normally this meconium is defaecated (passed) postnatally over the first 48 hours and then transitional stools from day 4. Premature discharge into the amniotic sac can lead to mixing with amniotic fluid and be reswallowed by Breech Birth the fetus. Necrotizing Enterocolitis Occurs postnatally in mainly in premature and low birth weight infants (1 in 2,000 - 4,000 births). The underdeveloped gastointestinal tract appears to be susceptible to bacteria, normally found within the tract,to spread widely to other regions where they damage the tract wall and may enter the bloodstream. Stillbirth and Perinatal Death Perinatal period is the early postnatal period relating to the birth, statistically it includes the period up to 7 days after birth. In pregnant women anywhere between 2 - 15% have birth weights of greater than 4000 grams (4 Kg, 8 lb 13 oz). Vertex Presentation (cephalic presentation) where the fetus head is the presenting part, most common and safest birth position. Each topic summary is designed for use in conjunction with the relevant didactic lecture given during the rotation. Original and Review Articles – Original, and review articles are provided for residents who seek a more comprehensive understanding of a topic.
Hernia and hydrocele: Transillumination has been advocated as a means of distinguishing between the presence of a sac filled with fluid in the scrotum (hydrocele) and the presence of bowel in the scrotal sac cheap cialis extra dosage 200mg visa erectile dysfunction walmart. However buy cialis extra dosage 50mg without prescription erectile dysfunction 2, in cases of inguinal hernia incarceration, transillumination may not be beneficial because any viscera that are distended and fluid-filled in the scrotum of a young infant may also transilluminate. It is indicated when presentation and examination suggest a diagnosis other than hernia or hydrocele. Laparoscopy: Diagnostic laparoscopy may rarely be required for determining the presence of an inguinal hernia. It is used only in the following: a) assessment of contralateral hernia when one is being operated upon, and b) recurrent hernia after previous surgery. Inguinal hernias do not spontaneously heal and must be surgically repaired because of the ever-present risk of incarceration. Repair is usually planned as an elective procedure as soon as possible after diagnosis. If successful, the operation is performed after 24-48 hours to allow local oedema to settle down. If reduction is unsuccessful, or if there is clinical evidence of inflammation (as evidenced by pain, redness, edema of skin on hernia) emergency exploration and hernia repair is necessary. Hydroceles without hernia in neonates: This is the only exception in which surgical treatment may be delayed. Repair of hydroceles in neonates without the presence of hernia is typically delayed for 12 months because the connection with the peritoneal cavity (via the processus vaginalis) may be very small and may have already closed or be in the process of closing. If the hydorcoele persists after this observation period, operative repair is indicated and appropriate. Postpone the operation in the event of upper respiratory tract infection,otitis media, or significant rash in the groin. After that time, the patient is allowed to participate in physical activities (eg, sports, swimming, running). Children younger than 5 years are likely to recover extremely quickly from surgery; they are typically capable of returning to their normal level of activities within 24-48 hours of surgery. Inguinal hernia: Treatment is surgery -herniotomy operation that aims at ligating the patent processus vaginalis at the internal ring after reduction of contents into the abdomen nd b. Congenital hydrocoele: Treatment is deferred until the 2 birthday as there is a 80% chance of spontaneous closure. Surgery is indicated if hydrocoele persists nd beyond the 2 year and if it is rapidly growing is size. All children with comorbid problems-cardiac, respiratory or others, need inpatient care after surgery b Out Patient criteria same as above c. Doctor makes a clinical diagnosis, counsels the family and plans surgery- a pediatric surgeon performs the surgery b. Nurse: assists surgeon in care of child during pre, intra and post operative course of the baby c. Technician: assists medical and nursing teams in care of child during intra and post-operative periods. Quantity to also be specified) Situation Human Resources Drugs & Consumables Equipment 1 Pediatric I. Zameer K Both from Department of Pediatric Surgery Narayana Hrudayalaya,Bangalore I. Introduction: Neonatal cholestatis is a pathological condition in the newborn where in bile flow from the liver is reduced. Most of these disorders have linkage with insults during antenatal, natal and postnatal periods. Mothers must be informed about the need to seek medical attention if jaundice persists beyond two weeks of birth and / or baby passes pale stools and high coloured urine. If the previous sibling has had liver disease antenatal counselling and referral for further evaluation may be necessary. Clinical: Neonate with jaundice persistent beyond 2 weeks, dark colour urine and/or pale stool 2. Screening Biochemistry: Serum bilirubin direct and indirect Any child that meets with the clinical and /or biochemical criteria needs investigation, treatment and referral. Initiation of antibiotics: if there is clinical or laboratory evidence of infection or sepsis a. Out Patient : Baby who is clinically well, feeding well and has no evidence of hypoglycemia or coagulopathy can be investigated as an outpatient 50 c. None of the biochemical tests are of deciding value and at best reflect the degree of damage to liver. Role of Hida Scan Hepatobiliary scintigraphy, after a 5 day priming with phenobarbitone,is useful. However, the converse is not true and absence of gut excretion of radiotracer requires further evaluation. Carbamazepine Liver Transplantation This may remain the only option for infants with decompensated liver disease (ascites and /or encephalopathy) or failed portoenterostomy. Failure of Kasai operation Evidence of liver cirrhosis in biopsy Jaundice not cleared by 2 months after surgery 4.
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