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This ontogenesis occurs in species whose ova are rich in yolk (fish, birds, reptilians). It is because the embryo is sup plied by the mother organism through the placenta. The embryo has provisional organs such as the amnion, chorion, yolk sack, and allantois. The embryonic development includes the following periods: prozygote, zygote, cleavage, gastrulation, tissue and organ formation. It was revealed that significant cyto plasm movement in zygotes o f Amphibia, Reptilia and Mammalia occurs. Such movements determine regions o f further organs and tissue formation (ooplasmatic segregation). Cleavage is a rapid division o f the zygote into a larger and larger number of 149 smaller and smaller cells. It can be holoblastic (symmetrical and asymmetrical) and meroblastic (discoidal and superficial) (pic 12. The symmetrical holoblastic cleavage is in isolecital eggs (in aquatic verte brates such as lancelets and agnaphants). After fertilization, the zygote divides into two cells, which are called blazoners. The asymmetrical holoblastic cleavage is typical in the telolecital eggs of Amphibia. It results in formation o f two poles: apical (poor in yolk) and vegetative (rich in yolk). Those, which are on apical pole, are smaller than those that are on vegetative pole. The cells o f the trophoblast can dissolve tissues, perhaps that the embryo can be implanted in the uterine wall. Then, trophoblast cells are separated from embryoblast (darker cells staying intemaly) and make a vesicle. The embryoblast cells are placed on the inner surface o f the trophoblasts in shape o f disc. In discoidal meroblastic cleavage, cleavage occurs only in a tiny disc o f po lar cytoplasm, called blastodisc, which fie astride the large bulk o f yolk material. It occurs in the polylecitinal eggs o f some mollusks, reptiles, birds and some fish. In spite o f different patterns o f cleavage in different organisms, all are termi nated by the formation o f a blastula. It is one o f the signs showing similar origin o f fife and parallelism in evolutionary development o f structures. There are four types o f gastrulation: invagination, immigration, epibolia and delamination. The external layer is called primary ectoderm; the internal layer is called primary entoderm. In mollusks, arthropoda, and worms it is transformed into the definitive mouth o f the adult organism. In animals having a chorda blastopore it is transformed to an anal canal, whereas the mouth is made on the opposite side as result o f complicate processes (invagination of ectoderm and fusion with primary intestine). Small cells of animal pole are divided quickly than cell o f vegetative pole, which is rich in yolk. The ways o f mesoderm formation: A - by cell migration from blastopore lips, - by cell migration from two tcloblasts; C - by mesodermal engulfs invagination: 1 - bud o f mesoblast, 2 - mesenbyme bud (by V. Mesenchyme is presented by cells immigrated from both ectoderm and endoderm layers. One is teloblastic (from Greek "thelos" - end) and second is enterocoelic (fro Greek "enteros" - internal, "koiloma" - coel).

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Therefore metal-backed glenoid implants could prevent these challenging situations. It is a multicentric retrospective study at a mid-term follow-up without any control group. The study period is long and our surgical technique and indications have evolved over that period of time. However it also has several strenghts, the cohort of patients is homogenous with the same indication for surgery (primary oseoarthritis) and low rate of patients lost to follow-up (7. The same kind of implant was used for all patients and the number of patients was relatively large with a clinical and radiological follow-up of minimum 3 years. The complication rate was found to be higher than what has been reported with cemented glenoid implants, however we have not observed the high rate of polyethlyne wear described in recent series (2,3). In addition, the concept of universal platform system was found to simplify revision procedures by preserving the humeral stem and the glenoid baseplate. Cemented polyethylene versus uncemented metal-backed glenoid components in total shoulder arthroplasty: a prospective, double-blind, randomized study. A ten-year radiologic comparison of two-all polyethylene glenoid component designs: a prospective trial. Mid- to long-term follow-up of total shoulder arthroplasty using a keeled glenoid in young adults with primary glenohumeral arthritis. Glenoid component insertion in total shoulder arthroplasty: comparison of three techniques for drying the glenoid before cementation. He sustained a peroperative fracture of the glenoid rim which was well stabilized thanks to the anterior winglet. Long-term survival of the glenoid components in total shoulder replacement for arthritis. Prosthetic replacement in the treatment of osteoarthritis of the shoulder: early results of 268 cases. New design of a cementless glenoid component in unconstrained shoulder arthroplasty: a prospective medium-term analysis of 143 cases. Patient self-assessment of health status and function in glenohumeral dege- nerative joint disease. Midterm Follow-Up of Metal-Backed Glenoid Components in Anatomical Total Shoulder Arthroplasties. Rates of Radiolucency and Loosening After Total Shoulder Arthroplasty with Pegged or Keeled Glenoid Components. The purpose of this study is the clinical and radiological comparison of two different stemless designs (impaction vs. In group A (n = 21) an impaction type design (Figure 1 a-f) and in group B (n = 18) a screw fixation design (Figure 2 a-f) was used. Table Comparison of the functional results between the non-revised cases (follow-up: 65months; range 36-128 months) and the revised cases (follow-up 53 months, range 36-109 months). In group A osteolysis/subscidence of the medial calcar was present in seven patients (Figure 3). We currently have two hypotheses: It might be a result of a biological reaction to a polyethylene wear of the glenoid component or impingement of the implant against the medial calcar (humeral notching). The other hypothesis is that this is the result of an uneven load distribution on the humeral bone. The screw fixation including the baseplate might distribute the load evenly leading to constant rim loading resulting in less bony resorption. The load in the impaction system is conducted through the anchor and from there to bone. Dines Professor Orthopedic Surgery Weill Cornell Medical College Co-Chief Shoulder Fellowship Hospital for Special Surgery New York, N. In the ensuing years better biomaterials and baseplate component designs have improved implant fixation. Additionally, Frankle others have demonstrated that a more lateralized glenosphere component would improve deltoid rotator cuff function and range of motion and limit scapular notching a significant complication of the original Grammont design. For this reason many of the more contemporary designs have included systems in which the Glenosphere could be lateralized based upon the design of the metallic glenosphere components.

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Three months after surgery, compensatory posterior hippocampal reorganization that occurs appears to be transient and inefficient. However, engagement of the contralateral hippocampus 12 months after surgery represented efficient reorganization in both patient groups, suggesting that the contralateral hippocampus contributes to memory outcome 12 months after surgery97. Higher homocarnosine concentrations were associated with better seizure control in both types of epilepsy119. Glutamate and glutamine Glutamate is the principal excitatory neurotransmitter in the brain and responsible for mediating excitotoxicity and initiating epileptic activity120. Glutamate is also an intermediary metabolite, and present at a concentration of 8-12 mmol/L. Aspartate, also an excitatory transmitter, is present at a concentration of 1-3 mmol/L. Discrimination between glutamate and glutamine in vivo on clinical scanners requires spectral modelling, because of the large number of coupled overlapping peaks and the limited achievable spectral resolution121. The general pattern is of localised ictal hyperperfusion, with surrounding hypoperfusion, that is followed by accentuated hypoperfusion in the region of the focus, which gradually returns to the inter-ictal state. A characteristic feature of temporal lobe seizures is an initial hyperperfusion of the temporal lobe, followed by medial temporal hyperperfusion and lateral temporal hypoperfusion129. Varying patterns have been seen in patients with autosomal dominant frontal lobe epilepsy131. This technique enhances objectivity and the accuracy of data interpretation133,134. Further, spread to other areas of the brain, such as the contralateral temporal lobe, may occur within seconds of seizure onset and so an image of cerebral blood flow distribution 1-2 minutes after the onset of a seizure may indicate other than the site of onset. This allows the labelled tracer to be prepared in advance and injected into a patient at any time over the subsequent six hours. The advantage of this development is that the interval between seizure onset and tracer delivery to the brain can be significantly reduced. The interval between seizure onset and injection may also be shortened by the use of an automated injection device that may be activated by the patient when they detect the beginning of a seizure138,139. Extratemporal seizures may be very brief, increasing the need for injection of blood flow tracer as soon as possible after the start of a seizure. With the inevitable interval between injection and fixation of the tracer in the brain, however, it may not be possible to obtain true ictal studies. In addition, quantitative analysis of data, with correction for partial volume effects add a further useful dimension to the analysis, and this is facilitated by the use of a template to objectively delineate multiple volumes of interest53. An epileptogenic focus, studied inter-ictally, is associated with an area of reduced glucose metabolism, and reduced blood flow that is usually considerably larger than the pathological abnormality. The results of comparative studies depend critically on the relative sophistication of the techniques used. Absence of unilateral temporal hypometabolism does not preclude a good result from surgery149. Bilateral temporal hypometabolism was associated with a poor prognosis for seizure remission after surgery150. Patients with mesiobasal tumours generally had only a slight reduction of glucose uptake in the temporal lobe. Emotional symptoms correlated with hypometabolism in the anterior part of the ipsilateral insular cortex, whereas somaesthetic symptoms correlated with hypometabolism in the posterior part. Insula hypometabolism, however, did not affect the outcome from temporal lobe resection152. In other hippocampal subregions, loss of receptors paralleled loss of neurones and increases in affinity were noted in the subiculum, hilus and dentate gyrus169. There have been few studies of newly diagnosed patients; only 20% of children with new onset epilepsy had focal hypometablism155. In 90% of those with a hypometabolic area, structural imaging shows a relevant underlying abnormality. The area of reduced metabolism in frontal lobe epilepsy may be much larger than the pathological abnormality. In contrast, however, the hypometabolic area may be restricted to the underlying lesion156. There have been three main patterns of hypometabolism described in patients with frontal lobe epilepsy: no abnormality; a discrete focal area of hypometabolism; diffuse widespread hypometabolism. Conclusion There have been significant advances in brain imaging that have revolutionised epilepsy management and particularly surgery.

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The molecular weights were determined from the obtained retention times via an external calibration curve using polystyrene standards (1. The contact Designer Descemet Membranes 143 angle for each sample was determined as the average during the first 30 seconds. Transparency of the membranes coated on glass-plates was measured using a custom made set up consisting of a broadband halogen light source (Avantes Avalight-Hal) which was guided towards the sample holder using an optical fiber. The transmitted light was transferred to a broadband spectrum analyzer (Avantes Avaspec ­ 2048). In this way transmission at all wavelengths was measured simultaneously after performing a baseline correction. Furthermore, during the measurement the sample holder was covered with a black case to remove influence of stray light. Transmission of all coated glass slides was compared relative to a glass slide with a gelatin A coating. For the hydrated samples, a droplet of deionized water (300 µL) was placed on each sample, and they were allowed to reach equilibrium swelling during 90 min prior to the measurement. The thickness was then measured from the glass to the top of the coating using depth profilometry. To this end, a 10 w/v% glucose solution in double distilled water was prepared with 0. The setup is built up out of 2 diffusion cells, each diffusion cell is supplied with a stirring bar and kept at a constant 37°C. The acceptor cell is periodically emptied inside a mass tube and then refilled with 2. The collected fractions of the acceptor cell are then diluted 100 times and 144 Chapter Seven analysed using a glucose oxidase assay. The glass coverslips were first methacrylated to ensure covalent attachment between the gelatin derivatives and the glass coverslips. In brief, the spincoated samples on glass coverslips (diameter 12 mm) were secured into a 24 well tissue culture plate using the cellcrown insert (Scaffdex, Tampere, Finland). To sterilize the samples, they were incubated in a range from 30 % - 70% ethanol solution with a 10% increment every 30 min. Next, the nuclei were counterstained with NucLight Rapid Red Reagent 1:2000 (Sartorius, Gцttingen, Germany) and imaged every 2 hours. Using the built-in software, custom masking algorithms were generated to quantify cellular growth expressed as #nuclei/mm2 as a function of time. Additionally, derivatives with a different number of crosslinkable groups Designer Descemet Membranes 147 were compared. These derivatives were obtained via the reaction of the primary amines present in the (hydroxy)lysine and ornithine amino acids with 1 or 2. To compare the different reactivities of the applied derivatives, photo-rheological measurements were performed on 10 w/v% solutions in the presence of 2 mol% (in respect to the amount of incorporated crosslinkable functionalities) Irgacure 2959 as photoinitiator, and 0. Irgacure 2959 was selected as photoinitiator, due to its known biocompatible behavior. We compared the gel points of the different materials as an indication of reactivity thereby providing information about the minimally required irradiation time. Here, the drastic increase in reactivity for norbornene derivatives over the more conventional systems is apparent (Figure 2; right panel). Secondly, the photoinitiator is added in a 2 mol% ratio relative to the number of crosslinkable groups present. However, this also increases the probability of termination which can hamper the reactivity. On the other hand, due to the presence of more crosslinkable functionalities, the probability of termination will again be lower as the formed radicals will have a higher chance to encounter unpolymerized methacryloyl functionalities rather than recombining with another radical. C Figure 3 ­ (A) the principle of spin coating (B) the final composition of the obtained membranes. First, a layer of unmodified gelatin A was applied on a supporting glass Designer Descemet Membranes 151 substrate, as sacrificial layer to enable dissolution in a final step after incubation in water at 40°C to enable membrane harvesting. To this end an amorphous poly(D,L-lactide) with a molecular weight of 150 kg/mol and a polydispersity of 1.

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He concluded that schizo caused or contributed by cannabis use may be more severe than schizo cases in general Patients + cannabis history seem to have more severe and more persistent history of schizo as indicated by duration of first vist, total duration of hosp days, nos of readmissions 2013 April, Morgan et al found that: `Anandamide is a ligand of the endocannabinoid system. Higher levels of anandamide are associated with a lower risk of psychotic symptoms following cannabis use. Performance on critical tracking and divided attention tasks was assessed on 19 male daily chronic cannabis users. Psychomotor performance moderately improved over the 3 weeks of sustained abstinence but did not recover to equivalent control group performance. However: the smokers and controls were not matched for education, social economic status, life style and race. Another one of the listed disorders, called cannabis use disorder, combines the diagnoses of two conditions-cannabis abuse and cannabis dependence-formerly included as separate mental health issues in previous edition of the Diagnostic and Statistical Manual. Cannabis Intoxication People affected by cannabis intoxication have typically smoked or ingested marijuana or hashish within roughly two hours of the onset of their symptoms. Specific symptoms that indicate the presence of intoxication include a significant spike in the normal heart rate, mouth dryness, appetite elevation and unusual fluid accumulation in the eyelids (a condition known as conjunctival injection). In addition to at least two of these cannabis-related alterations, all diagnosed individuals must experience substantial psychological or behavioral impairments as a result of marijuana or hashish use. They must also lack other conditions that provide a more reasonable basis for their mental/physical state. Examples of problems that qualified as significant include a frequent inability to meet any essential duties or responsibilities, frequent participation in dangerous activities while under the influence of cannabis, and an insistence on continuing cannabis use despite its known harmful life impact. However, modern scientific thinking indicates that the difference between substance abuse and substance dependence is rarely cut-and-dried. In reality, doctors and researchers can find no consistently sensible way to address abuse and dependence as separate issues. This means that cannabis abuse and cannabis dependence are now addressed together under the cannabis use disorder heading. Cannabis Withdrawal According to the guidelines established by the American Psychiatric Association, substance withdrawal qualifies as a mental health concern when it produces symptoms that significantly degrade participation in a functional routine or trigger troublesome states of mind. The "other" cannabis-induced disorders category was created in order to provide doctors with the freedom to specify exactly which issues they uncover in their cannabis-using patients. Raver et al 2013 investigated whether adolescent cannabinoid exposure alters cortical oscillations in adults. Cortical oscillations are integral for cognitive processes and are abnormal in people with schizophrenia. The endocannabinoid system on which marijuana acts is a neuromodulatory system which actively develops cortical oscillations. They demonstrated that chronic adolescent but not adult cannabinoid exposure suppresses pharmacologically evoked cortical oscillations and impairs working memory performance in adults. They concluded that `Cannabis use patterns, childhood adversity and the use of other substances are similar in dependent and non-dependent frequent cannabis uses. With the exception of more externalizing disorders, the mental health condition of non-dependent frequent cannabis users is similar to that of the general population, whereas it is worse in dependent frequent cannabis users. She became intrigued by the fact that people with schizophrenia predominantly experience their first episode of psychosis early in adulthood. She found that `adolescence is not too late in terms of learning, training and intervention. Patients with a history of cannabis use presented with their first episode at a younger age than those who had never used cannabis. Subjects who had been using the high potency cannabis (skunk) every day, had the earliest onset, on average 6 years earlier than non-users. Poulton, looking at the results of the Dunedin Study (running now 40 years and involving over 1,000 subjects) said that chronic cannabis use in early adolescence makes some people up to 11 times more likely to develop schizophrenia. For people who used cannabis heavily before the age of 18, the risk of schizophrenia went up 10. He also said that for certain people with a specific gene combination the risk increased about 11 fold, and that a quarter of the population carries this combination.

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Matured male and female parasites mate after which fertilized eggs passed through the feces. Once the eggs have been deposited on the ground it usually takes three weeks before they are matured enough to be infective. Humans through eating uncooked vegetables consume infective eggs, or other foods that have been contaminated after cooking or by placing contaminated hands and other objects in the mouth. The male and female of this worm also mate and the fertilized eggs are passed out with the feces and mature on the ground. After maturation the eggs in the soil hatch and the newly emerged larvae undergo further development for another one to two weeks. Once mature enough to be infective they penetrate bare footed person and travel to the intestine via the blood stream, lungs, trachea, gullet and stomach. It is transmitted to the healthy person by ingesting raw meat that has been infected by the disease. The infected person will pass the feces with eggs on to the ground where cows graze. The eggs deposited with the feces in the grass are eaten up by the cow and hatch in the intestine after which larvae emerge. The larvae bore into the intestinal walls, enter the blood stream and become lodged in the muscle tissues where they develop a hard protective capsule. When a person eats raw meat the capsule is digested and a new tapeworm is set free in the intestine. They then appear as cysts in the active muscles of the animal Starting from the day that the eggs are swallowed it takes two to three months for the parasite to produce ripe segments that lay eggs. Sanitation related illnesses also depletes national economies: When people miss school or can not work; When tourism are affected; When agricultural products are suspected to be contaminated; When highly infectious disease such as cholera outbreak is reported. In addition creating awareness on the part of the public on hand washing after visiting toilets; proper maintenance of the latrine so that flies will be discouraged and utilization will be maximized. Stongyloides Stercoralis Strongyloides is a helminthic infection of the duodenum and upper jejunum. It is more common in warm and wet areas where the eggs of the infective organism survive easily. Obviously, this parasitic infection is common in Ethiopia because of the poor sanitation condition of our neighborhood. The infection is common among children who play in dirty and infected environment. Life Cycle of Strongyloides Stericoralis Infective larvae, which are, called filariform and that which has developed in feces or moist soil in the environment enters by penetrating the skin. Once in the body of the person it enters into the venous circulation and is carried to the lungs. It travels through when infected person defecates indiscriminately complicated routes trespassing capillary walls, entering alveoli, ascending to the trachea and descends the digestive tract to reach its final destination- the small intestine. In the small intestine the adult development of the adult female parasite takes place. The eggs hatch and ultimately are liberated through feces and develop into infective parasite of the same person or other new host or live freely in the soil. It is also a disease that is common in areas where sanitation is very poor and where people commonly defecate in the open. The eggs are not immediately infective but will mature in the soil in approximately 2-3 weeks. The infective embroynated eggs are ingested with food when people with contaminated hand eat with out washing properly or not washing at all. The larvae that have hatched in the intestine will attach itself to the mucosa of the cecumand proximal colon and develop into mature worms. Eggs appear in the feces 90 days after infection of the eggs and the cycle continues so long as the unsanitary disposal of feces continues in that community.

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These associations remained significant after adjustment for background characteristics (nonmedical opioid use: adjusted odds ratio=2. Among adults with pain at wave 1, cannabis use was also associated with increased incident nonmedical opioid use (adjusted odds ratio=2. Among adults with nonmedical opioid use at wave 1, cannabis use was also associated with an increase in nonmedical opioid use (adjusted odds ratio=3. Cannabis use appears to increase rather than decrease the risk of developing nonmedical prescription opioid use and opioid use disorder. One-year treatment retention was the primary outcome of interest and was measured for patients who did and did not have a cannabis positive urine sample in their first month of treatment, and as a function of the proportion of cannabis-positive urine samples throughout treatment. Our cohort consisted of 644 patients, 328 of which were considered baseline cannabis users and 256 considered heavy users. Patients with baseline cannabis use and heavy cannabis use were at increased risk of dropout (38. When evaluating these trends by gender, only female baseline users and male heavy users are at increased risk of premature dropout. Both baseline and heavy cannabis use are predictive of decreased treatment retention, and differences do exist between genders. With cannabis being legalized in the near future, physicians should closely monitor cannabis-using patients and provide education surrounding the potential harms of using cannabis while receiving treatment for opioid use disorder. Abstract: medical cannabis refers to the use of cannabis or cannabinoids as medical therapy to treat disease or alleviate symptoms. Within the European Union, medicinal cannabis laws and praxis vary wildly between Countries. The aim was to provide evidence for benefits and harms of cannabis (including extracts and tinctures) treatment for adults in the following indications: control of spasticity and pain in patients with multiple sclerosis; control of pain in patients with chronic neuropathic pain; control of nausea and vomiting in adults with cancer receiving chemotherapy. Three authors independently evaluated the titles and abstracts of studies identified in the literature searches for their eligibility. The included studies were published between 1975 and 2015, and the majority of them were conducted in Europe. The large majority (80%) of the comparisons were with placebo; only 8 studies included patients with cancer receiving chemotherapy comparing cannabis with other antiemetic drugs. Concerning the efficacy of cannabis (compared with placebo) in patients with multiple sclerosis, confidence in the estimate was high in favour of cannabis for spasticity (numerical rating scale and visual analogue scale, but not the Ashworth scale) and pain. For chronic and neuropathic pain (compared with placebo), there was evidence of a small effect; however, confidence in the estimate is low and these results could not be considered conclusive. There is uncertainty whether cannabis, including extracts and tinctures, compared with placebo or other antiemetic drugs reduces nausea and vomiting in patients with cancer requiring chemotherapy, although the confidence in the estimate of the effect was low or very low. In the included studies, many adverse events were reported and none of the studies assessed the development of abuse or dependence. There is incomplete evidence of the efficacy and safety of medical use of cannabis in the clinical contexts considered in this review. Furthermore, for many of the outcomes considered, the confidence in the estimate of the effect was again low or very low. To give conclusive answers to the efficacy and safety of cannabis used for medical purposes in the clinical contexts considered, further studies are needed, with higher quality, larger sample sizes, and possibly using the same diagnostic tools for evaluating outcomes of interest. Analyses tested associations among these classifications, cannabis growing, and edible use and procurement. Permitting home cultivation contributes to a greater likelihood of growing cannabis. Those who grow cannabis economize the plant by creating homemade edible cannabis products. Conversely, permitting dispensaries increases the likelihood of purchasing edibles. The psychoactive effects of edibles with unknown and variable cannabinoid content will be unpredictable. Therefore, it is important for anesthesiologists to know about the most common illicit drugs being used, their clinical presentation and side effects, and the anesthetic options that are beneficial or detrimental to these patients. The most frequently used illicit substances, apart from alcohol and tobacco, are cannabis, cocaine, heroin, prescription opioids, methamphetamine, and hallucinogens. Adults and adolescents increasingly view cannabis as harmless, and some can use cannabis without harm.

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Upright chest radiograph: Can detect presence of free air under the diaphragm and thus possible bowel perforation. Findings: Transition zone, with dilation of bowel proximally and decompression of the bowel distally, no contrast present distal to transition point, and paucity of gas and fluid in colon. Monitor electrolytes for signs of hypokalemia, base deficit/metabolic acidosis (signs of ischemia). Patients with suspected strangulation need to be resuscitated with fluids prior to surgery. If the patient fails conservative management (24 hrs without improvement, abdominal tenderness worsens, fever, other signs of clinical deterioration), then laparotomy should be performed. Hernias should be reduced and repaired or, if contents of sac are strangulated, needs intestinal resection. Whatever the cause, the entire small bowel should be examined, and nonviable intestine should be resected. Primary anastomosis should be performed in hemodynamically stable patients who have had small segments of bowel resected. The inflammation is discontinuous, resulting in skip lesions, and often leads to fibrosis and ultimately obstruction, as well as to the formation of fistulae. Diagnosis most common between ages 15 and 40, although there is a second peak between 50 and 80 years of age (bimodal distribution). Perianal disease including skin tags, anal fissures, perirectal abscesses, and anorectal fistulae. Colonoscopy (with biopsy), visualization of the terminal ileum may reveal focal ulcerations adjacent to areas of normal mucosa along with a cobblestone appearance to the intestinal mucosa. Imaging (small bowel contrast studies) is helpful in characterizing length of involvement and areas of stricture, especially in parts of small bowel that are inaccessible via colonoscopy. Radiographic appearance: Mucosal nodularity, narrowed lumen, ulceration, string sign, presence of abscesses and fistulae. Many patients require surgery to relieve symptoms that do not respond to drugs, or to treat complications such as obstruction, abscesses, fistulae, perforation, perianal disease, or cancer. Surgical procedure depends on indication: One third of patients require surgery to relieve intestinal obstruction by strictures, either via segmental small bowel resection or stricturoplasty (Figures 9-3 and 9-4). Ten to twenty percent of patients experience prolonged remission after initial presentation. Total colectomy with ileostomy has 10% recurrence rate over 10 years in remaining small bowel. It can be caused by either narrowing of the small bowel lumen or secondary to intussusception, with the neoplasm serving as the lead point. Intermittent obstruction: Crampy abdominal pain, distention, nausea, and vomiting. Enteroclysis: Test of choice; high sensitivity; used to detect tumors in distal small intestine. Majority of patients: Small bowel series with follow-through followed by enteroclysis. Tumors located in proximal duodenum, even asymptomatic lesions, should be removed either endoscopically (< 1 cm) or surgically (> 2 cm). Tumors in second portion of duodenum, near ampulla, may require pancreaticoduodenectomy (Whipple procedure). Malignant Neoplasms of Small Intestine Enteroclysis is a doublecontrast study that involves passing a tube into the proximal small intestine and injecting barium and methylcellulose. Extended small bowel enteroscopy (Sonde enteroscopy) is much like push enteroscopy, but involves advancement of the enteroscope by peristalsis. It visualizes up to 70% of the small bowel mucosa and detects tumors missed by enteroclysis. For adenocarcinomas, wide local excision of the intestine with its accompanying mesentery is performed along with regional lymph nodes. Localized lymphoma is treated with segmental resection of the intestine, and neighboring mesentery. Diffuse lymphoma is the only situation where chemotherapy, rather than surgical resection, should be the primary therapy. Small bowel is frequently affected by metastasis or invasion from cancers originating in other organs, particularly melanoma.

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Phenytoin Phenytoin is now a last resort option for focal and tonic-clonic seizures in view of its chronic toxicity and kinetic profile. Accordingly, at higher levels a moderate increment in dose can produce an unexpectedly large rise in the level with accompanying neurotoxicity. Conversely, levels can fall precipitously when the dose is reduced modestly, resulting sometimes in unexpected deterioration in seizure control. The dosage producing the same levels, therefore, varies substantially among different individuals. Phenytoin can produce a range of dose-related and idiosyncratic adverse effects including rash, hepatotoxicity and blood dyscrasias. Reversible cosmetic changes (gum hyperplasia, acne, hirsutism, facial coarsening), although often mild, can be troublesome. Symptoms of neurotoxicity (drowsiness, dysarthria, tremor, ataxia, cognitive difficulties) become increasingly likely with higher levels but the diagnosis of phenytoin toxicity should be made on clinical grounds and not assumed from a high level. The person may complain of mental slowing and unsteadiness, and neurological examination may show cerebellar signs. Permanent cerebellar damage may be a consequence of chronic toxicity, so it is important to examine regularly the person taking it. In some of these people, cerebellar atrophy will be apparent on brain imaging, although hard evidence for cause and effect is not readily available. A paradoxical increase in seizure frequency may also occur with marked phenytoin toxicity. It can accelerate the metabolism of a number of lipid-soluble drugs, including carbamazepine, sodium valproate, ethosuximide, anticoagulants, steroids and cyclosporin. Due to its saturable metabolism, phenytoin provides a target for drugs such as allopurinol, amiodarone, cimetidine, imipramine and some sulphonamides. Phenobarbital Phenobarbital is an established treatment for focal and tonic-clonic seizures but is seldom currently used in developed countries due to its potential to cause neurotoxicity. To minimise sedation, a low dose should be started (30 mg in adolescents and adults), which can be increased gradually (15-30 mg incremental steps) according to clinical requirements. The value of measuring its levels is limited, as concentration associated with seizure control varies considerably. The major problem in the clinical use of phenobarbital is its effect on cognition, mood and behaviour. It can produce fatigue, listlessness and tiredness in adults and insomnia, hyperactivity and aggression in children (and sometimes in the elderly). Tolerance develops to the deleterious cognitive effects of the drug but also to its efficacy in some people. Phenobarbital is an enzyme inducer and can accelerate the metabolism of many lipid-soluble drugs and has an impact on bone health. Piracetam Piracetam is only indicated as an adjunctive treatment in refractory myoclonus. Effective doses are usually between 12 and 24 g/day and this bulk is one of the limiting factors of the use of this drug. Primidone Primidone is metabolised to phenobarbital and its efficacy is similar to that of phenobarbital, but it is not as well tolerated. There is therefore nothing to recommend it over phenobarbital for people in whom treatment with a barbiturate is contemplated. It use in women of childbearing potential, however, is problematic in view of its potential teratogenicity. The starting dose of sodium valproate for adults and adolescents should be 500 mg/day for one or two weeks, increasing in most people to 500 mg twice daily. Since the drug can take several weeks to become fully effective, frequent dosage adjustments shortly after initiating therapy may be unwarranted. As valproate does not exhibit a clear-cut concentration-effect-toxicity relationship and the daily variation in the level at a given dose is wide, routine monitoring is not helpful unless used as a check of adherence to therapy. Side effects of sodium valproate include dose-related tremor, weight gain due to appetite stimulation, thinning or loss of hair (usually temporary), and menstrual irregularities including amenorrhoea.

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References:

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