Bo Yoon Ha, MD

• Clinical Fellow in Radiology
• Lucile Packard Children's Hospital
• Stanford, California

A wide variety of diagnostic tests are available to document and quantify portal hypertension hiv infection rates canada order amantadine overnight. In the pediatric age range over the counter antiviral cream discount generic amantadine canada, a combination of ultrasonography and flexible fiberoptic endoscopy can usually determine if portal hypertension or esophageal varices are present or absent antiviral condoms purchase amantadine canada. Ultrasonography Advances in ultrasonography antiviral drugs name amantadine 100mg otc, most specifically Doppler flow studies hiv infection no fever buy amantadine 100mg with visa, have made this the investigation of choice in children hiv infection rate in honduras generic amantadine 100mg mastercard. As with many other procedures, the information that is obtained is directly dependent on the skill and experience of the operator. An abdominal survey can yield important information, including hepatic size and echogenicity. A small liver in the setting of portal hypertension is a potentially worrisome finding. Intrahepatic bile ducts can be assessed for evidence of dilatation consistent with extrahepatic obstruction or Caroli disease. Spleen size can be easily measured and will give indirect evidence about the presence or absence of portal hypertension. Unfortunately, spleen size does not appear to correlate directly with portal pressure and is not a highly accurate predictor of the presence or absence of varices. Renal abnormalities, associated with portal vein thrombosis and congenital hepatic fibrosis/Caroli disease, can easily be detected. Finally, ascites, which may not be evident on physical examination, can be demonstrated. Doppler sonography of the hepatic and mesenteric vasculature affords an even greater amount of important information. The presence or absence of patent vessels can be determined in addition to vessel diameter, direction of blood flow in the vessel, and the presence or absence of echogenic material within the blood vessel. In children, normal non-fasting portal blood flow as assessed by Doppler examination is hepatopedal at 10 to 30 cm/s, although considerable variability exists in this measurement. Portal vein velocity decreases in severe portal hypertension as intrahepatic resistance increases. Hepatofugal flow in the left gastric, paraduodenal, or paraumbilical veins is consistent with portal hypertension, although this may be a relatively late finding. Reversal of flow in the superior mesenteric vein or splenic vein may be indicative of spontaneous mesentericocaval or splenorenal shunts, respectively. Hepatic arterial flow is often increased in portal hypertension as part of the normal compensation for diminished portal venous inflow. In selected studies in adults, careful analysis of either portal venous blood flow or superior mesenteric artery flow velocity has revealed a correlation with portal pressure. This examination is particularly useful in determining if gastrointestinal hemorrhage in a child with chronic liver disease is secondary to variceal rupture. The differential diagnosis includes gastric or duodenal ulcers, gastritis, MalloryΗeiss tears, and portal hypertensive gastropathy. In 22 children with cirrhosis and upper gastrointestinal hemorrhage, eight had gastric or duodenal ulcers [37]. In adults, the endoscopic appearance of varices can be predictive of the risk of future hemorrhage. The red wale sign and cherry-red spot are particularly associated with increased risk of hemorrhage. These findings have been systematically assessed in one group of children, those with biliary atresia. In this group, esophageal red markings and gastric varices along the cardia are predictive of an increased risk of subsequent variceal hemorrhage [4]. Intravariceal pressure can be measured by upper endoscopy, although this requires a very cooperative patient and once again has not been performed in children. Indirect variceal pressure measurement using an endoscopic pressure gauge might be more plausible for investigation in children. Capsule endoscopy can be used to look for esophageal varices, although the cost-effectiveness and feasibility of this approach with current equipment/approaches is open to question. Size issues and the ability of a young child to swallow the capsule also limits the applicability of capsule endoscopy in pediatrics. Most of these studies have not been extensively characterized in children secondary to their invasive nature. Selective angiography of the celiac axis, superior mesenteric artery, and splenic vein can be particularly useful in assessing the extrahepatic vascular anatomy. In particular, these studies are helpful in suspected portal vein thrombosis and are essential for surgical decompression of this lesion. These studies may be essential for the diagnosis and appropriate therapy of splenic vein thrombosis. Portal pressure can be directly measured by examination of splenic pulp pressure during splenoportography, although this is primarily an historical technique. A balloontipped catheter is inserted into the antecubital vein and advanced to the hepatic vein, where free and wedged hepatic vein pressures can be measured. The wedged hepatic vein pressure is usually a good index of portal vein pressure when the main lesion in the hepatic vasculature is limited to the sinusoidal area. Given the relatively invasive nature of this measurement, there is limited well-documented pediatric experience with it outside of that associated with the placement of transjugular intrahepatic portosystemic shunts. An important caveat is the unexpected finding of intrahepatic venovenous collaterals in biliary atresia, which can influence the accuracy of this measurement. Given the growing data indicating that assessment of portal pressures is predictive of both the risk of hemorrhage and the potential response to therapy, development of a practical and reliable pediatric measure is of great importance. The management of variceal hemorrhage can be divided into preprimary prophylaxis, prophylaxis (primary) of the first episode of bleeding, emergency therapy, and prophylaxis (secondary) of subsequent bleeding episodes. As with many other aspects of the science of portal hypertension, almost all of the modes of therapy are based on trials in adults. Many of these trials are controlled randomized doubleblinded studies, yielding comprehensive meta-analyses and consensus statements [39ʹ1]. The literature of the management of pediatric variceal hemorrhage is mostly descriptive or anecdotal and there are fundamental issues in the conduct of randomized trials involving children [42]. As a result, there have only been two randomized trials of therapies for portal hypertension in children [43,44]. Because of the difficulties in obtained evidenced-based approaches, expert opinions have been advanced [7]. Preprimary prophylaxis the concept of preprimary prophylaxis is that early treatment of portal hypertension has the potential to delay or prevent the development of esophageal varices or other manifestations of portal hypertension. A randomized trial of timolol, a nonselective beta-blocker, on the development of varices in adults unfortunately did not show a significant effect. Consequently, at present, preprimary prophylaxis remains an interesting concept, but one that is not applicable in clinical practice. Primary prophylaxis the issue of prophylaxis of the first episode of variceal hemorrhage in children is controversial and is predicated on experience with adults, who primarily have alcoholic cirrhosis [42]. Surveillance endoscopy in children with liver disease and stigmata of portal hypertension is primarily justified if the clinician anticipates recommending a prophylactic regimen, although there may be value in surveillance for patients who live in remote areas far from medical care. Given the unpredictability of the timing of the first episode of variceal hemorrhage, primary prophylaxis regimens need to be associated with relatively low potential morbidity and mortality. The improved risk΢enefit ratio of endoscopic ligation therapy relative to sclerotherapy has led to reassessment of its role in primary prophylaxis. Uncontrolled preliminary pediatric experience with the use of propranolol in the primary prophylaxis of variceal hemorrhage has recently been reported [45,46]. The primary effect may be blockade of Therapy the therapy of portal hypertension is primarily directed at the management of its most dramatic manifestation: variceal hemorrhage. An additional important mechanism involves decreasing heart rate by 1-adrenoreceptor blockade, thus lowering cardiac output and portal perfusion. Finally, evidence exists for a specific effect of propranolol that decreases collateral circulation. Therapeutic doses in adults are expected to decrease the pulse rate by at least 25%, although these guidelines are somewhat problematic in children, where baseline and follow-up measures may be difficult. The major adverse effects associated with the use of propranolol are heart block and exacerbation of asthma. Betablockade also has the potential to interfere in the physiologic response to hypoglycemia; thus, these agents should be avoided in children with diabetes. Beta-blockers have been consistently shown to reduce the frequency of bleeding episodes, and in some trials they have improved long-term survival in patients with esophageal varices. Initial randomized trials demonstrated efficacy in patients who have had a previous bleeding episode. Subsequently, propranolol was shown to be effective in patients with varices who had never bled. In a study of 230 patients randomized to propranolol or placebo, the incidence of hemorrhage and mortality over a 14-month period was reduced by almost 50%. The successful results of numerous trials of propranolol have been summarized by meta-analyses [41]. It is clear that a goal of at least a 25% reduction in resting heart rate needs to be achieved to see these effects. Therefore combinations of beta-blockade and vasodilation therapy are now under investigation. Combination pharmacologic agents, such as carvedilol, may have enhanced efficacy [21]. Unfortunately, there is little if any prospective data on the safety or feasibility of beta-blockade in children with portal hypertension. Furthermore, there are few data indicating that beta-blockade is effective for primary prophylaxis in children. Endoscopic band ligation therapy has been used with greater frequency in adults with high-risk varices [47]. As with beta-blockade, endoscopic band ligation therapy cannot be recommended for routine use in children with varices. In fact, a small randomized trial of prophylactic endoscopic sclerotherapy in children showed no survival benefit [43]. Given the invasive nature of the technique, selected application of this approach may be appropriate only in children with apparently high-risk varices who live in remote locations. In biliary atresia, varices with red markings or those found in association with gastric varices on the cardia may be at increased risk of bleeding, although a survival benefit from primary prophylaxis of these varices has not been demonstrated [4]. Emergency therapy for variceal hemorrhage the initial management of variceal hemorrhage is stabilization of the patient. Vital signs, particularly tachycardia or hypotension, can be particularly helpful in assessing blood loss. Patients taking beta-blockers may not manifest the usual compensatory tachycardia and are at higher risk of developing hemodynamically significant hypotension. Fluid resuscitation, in the form of crystalloid initially followed by red blood cell transfusion, is critical. These fluids need to be administered carefully to avoid overfilling the intravascular space and increasing portal pressure. Optimal hemoglobin levels in adults with variceal hemorrhage are between 7 and 8 g/dL. Nasogastric tube placement is safe and may be an essential part of the management of these patients. It allows for documentation of the rate of ongoing bleeding and removal of blood, a protein source that may precipitate encephalopathy. In addition, blood in the stomach increases splanchnic blood flow and potentially could worsen portal hypertension and ongoing hemorrhage. In fact, while patient with end-stage liver disease often have abnormal prothrombin times, global assessment of clotting does not reveal a predisposition to hemorrhage apart from in severe thrombocytopenia [48]. Intravenous antibiotic therapy should be strongly considered for all patients with variceal hemorrhage in light of the high risk of potentially fatal infectious complications. Once the patient is stabilized, endoscopy should be performed to document that the hemorrhage is indeed from variceal rupture. Signs of recent hemorrhage include visualization of ongoing hemorrhage, the presence of a fresh clot, or the presence of varices with fresh blood in the stomach and no other source of bleeding. Continued hemorrhage at the time of diagnostic endoscopy is a finding that portends a poor prognosis. A significant percentage of both children and adults with chronic liver disease and gastrointestinal hemorrhage will have sources of bleeding other than varices, including duodenal or gastric ulceration [37]. As such, diagnostic endoscopy is an integral part of the emergency management of acute gastrointestinal hemorrhage in the child with portal hypertension. Pharmacotherapy of acute hemorrhage need not be withheld until endoscopy can be performed. At the time of diagnostic endoscopy, initial management in the form of sclerotherapy or ligation can commence. Unfortunately, some episodes can become life threatening and require urgent therapy. Hemorrhage that persists for more than 6 hours or requires more than one red blood cell transfusion necessitates further intervention. Documentation of their efficacy in adults is fairly convincing, whereas the data in children are scanty at best. In general, a clinical decision is made that the risk of further blood product administration and potential hemodynamic compromise outweighs the side effects associated with further therapy.

In contrast hiv infection rate oral cheap 100mg amantadine amex, females have undersaturated bile before puberty antiviral herbs discount 100 mg amantadine fast delivery, which becomes supersaturated after puberty [53] hiv infection map 100 mg amantadine fast delivery. Enhanced cholesterol secretion may be observed with certain drugs (estrogens effect of hiv infection on menstrual cycle length discount 100mg amantadine visa, clofibrate) hiv infection gas pumps purchase amantadine 100mg without a prescription. Most adults with gallstones have a combination of both reduced bile salt secretion and enhanced biliary cholesterol secretion anti viral apps buy amantadine pills in toronto. Conditions predisposing to cholesterol gallstone formation Obesity Obese adults have a prevalence of cholesterol gallstones that is almost twice that of the non-obese population. Evidence has accumulated that the biliary secretion of cholesterol is increased relative to bile acid and phospholipid secretion in obese subjects. As a consequence, bile is supersaturated with cholesterol, predisposing to stone formation. Supersaturated bile may develop at puberty in women and is often associated with obesity. Little, if anything, is known about the risk of cholesterol gallstone formation in children with obesity; however, obesity appears to predispose to stone formation in adolescent females. Findings from a German study suggest that the prevalence of gallstones could be as high as 2% in obese children and adolescents. Fasting and residual gallbladder volumes are increased in patients with cystic fibrosis who do not have microgallbladders. This finding, coupled with abnormalities of mucus, may predispose patients to stasis and nidus formation in the gallbladder. Pregnancy Women have a higher frequency of gallstones than men at all ages from puberty to menopause [17,19,22]. This suggests that hormonal influences in women may play an important role in the pathogenesis of cholesterol gallstones. Women have a smaller total bile acid pool and enhanced biliary cholesterol secretion compared with men, resulting in increased biliary cholesterol saturation. Pregnancy and the use of oral contraceptives accentuate these sex-related differences. During pregnancy, the total bile acid pool expands but there is enhanced sequestration of the pool in the intestine. Consequently, there is no change or a decline in the biliary bile acid secretion rate. Increases in gallbladder residual volume and fasting volumes, and reductions in gallbladder contractility and rate of emptying, make pregnant women and those receiving oral contraceptives particularly susceptible to gallstone formation. In two series of adolescent girls aged 14Ͳ0 years, strong associations were found between the presence of gallstones and parity and obesity; a weak, statistically non-significant association was found between oral contraceptive use and gallstones [55,56]. Miscellaneous conditions Gallstones have been identified in at least one child with familial hypobetalipoproteinemia who presented with obstructive jaundice. In this rare condition, stones may form because of increased biliary cholesterol secretion. Genome-wide association studies of patients from Germany and Chile and linkage studies of affected sib pairs from Germany and Romania have shown a reported odds ratio for gallstone disease of 2. These results have been replicated in Chinese patients and Swedish twin pairs [61,62]. Mutations affecting hepatocyte enzymes and membrane transporters important to bile acid and bilirubin biology also appear to be associated with risk for gallstone disease. Clinical features of gallstones In adults, gallstones may remain asymptomatic for years. Gracie and Ransohoff [66] evaluated the outcome of gallstones in 123 male university faculty members identified 24 years earlier on pre-employment oral cholecystograms. In 16 subjects identified with asymptomatic or silent gallstones, symptoms developed that were heralded by the appearance of biliary tract pain; 3 of 13 developed biliary tract complications, 2 with acute cholecystitis and 1 with pancreatitis. If complications occurred, they were likely to follow previous episodes of biliary colic. Based on this study, it appears that the risk of serious complications associated with silent gallstones is small. Non-elective cholecystectomy is necessary in less than 5% of patients with identified silent gallstones. No studies of this type have been performed in infants and children; however, there is no reason to believe that the risk of complications with silent stones would be higher in children than adults. Non-specific dyspepsia, fatty food intolerance, and vague epigastric or right upper quadrant discomfort are common in adults with and without gallstones. In children, only recurrent right upper quadrant pain or epigastric pain would suggest gallstone disease. Typically, biliary colic is episodic and characterized by pain that is steady and lasts 1ͳ hours, rather than colicky or crampy in nature. Although pain is commonly localized to Genetic predisposition to gallstones the importance of heredity to risk for gallstone disease is becoming increasingly clear. In more than 43 000 Swedish twin pairs, the concordance rate for symptomatic gallstone disease was significantly higher in monozygotic than in dizygotic twins. In a model derived from these data, it was proposed that genetic factors were responsible for 25% of the phenotypic variation among the twins [57]. Efforts to determine the specific gene(s) involved in risk for gallstone disease are ongoing. Pregnane X receptor is a nuclear receptor that is highly produced in the liver and is activated by bile acids and bile acid precursors. Radiation of pain to the umbilicus may suggest the presence of acute appendicitis. Episodes of pain may occur irregularly over years, and the severity of attacks may vary. Pressure in the gallbladder increases in an attempt to contract against the obstruction. In one-third of patients, inflammation leads to necrosis with either perforation or empyema of the gallbladder. In a small fraction of patients, there is transient mild elevation of serum bilirubin, aminotransferases, and alkaline phosphatase. If a gallbladder can be identified by ultrasound, the stone discovery rate is as high as 98% of expected. Plain abdominal radiography identifies only stones that have a high calcium content (usually about 15% of all stones). Oral cholecystography may be helpful in identifying non-calculous causes of gallbladder disease and evaluating function. Cholescintigraphy, using one of the technetium-99m-labeled acetanilide aminodiacetic acid derivatives, is currently the most accurate method for evaluating the patient with acute cholecystitis. In general, ultrasound is the method of choice for identifying gallstones in children and adolescents complaining of recurrent epigastric or right abdominal pain. Chronic cholecystitis or cholelithiasis Generally, some inflammation accompanies cholelithiasis. In some patients, chronic inflammation leads to the development of a fibrotic and shrunken gallbladder. With fibrosis, visualization of the gallbladder and its contents may be difficult with ultrasound. As with acute cholecystitis, nuclear imaging techniques may prove helpful in diagnosing chronic cholecystitis. Failure of gallbladder visualization should suggest the presence of chronic cholecystitis. Treatment of cholelithiasis and acute and chronic cholecystitis Cholecystectomy is the definitive treatment for symptomatic stones. The only treatment questions that arise focus on the timing of surgery and the operative approach. In a study in which patients with gallstones were monitored carefully, 112 patients were followed who had experienced biliary pain in the previous 12 months: 60% developed recurrent pain within 2 years, and 6% required cholecystectomy [67]. Those with recurrent pain are more likely to develop significant complications and should have elective cholecystectomy without prolonged waiting. With acute cholecystitis, emergency cholecystectomy might be warranted if complications supervene; in most patients, however, cholecystectomy can be delayed safely for between a few days and 2ͳ months. The only exception to the use of cholecystectomy for treatment of gallstones might be in patients whose medical conditions make operative cholecystectomy dangerous. In chronically ill children with high-risk conditions such as severe pulmonary compromise in cystic fibrosis, cholecystotomy might be a reasonable therapeutic alternative to cholecystectomy. Experience with laparoscopic cholecystectomy has demonstrated its advantage over conventional forms of operative cholecystectomy. Indications for this technique in children are the same as for open cholecystectomy, and the gallbladder should be surgically removed from patients with symptomatic cholelithiasis or children with a hemoglobinopathy and asymptomatic cholelithiasis. Several studies have demonstrated the efficacy of this technique in children with cholelithiasis caused by familial hyperlipidemia, hereditary spherocytosis, glucose-6-phosphatase deficiency, thalassemia, glycogen storage disease, and sickle cell anemia. Pediatric laparoscopic cholecystectomy has been modified from the adult procedure because the operating area is considerably smaller and children have a higher risk of having an umbilical hernia adhering to the peritoneal lining. Intraoperative cholangiography is important to exclude common bile duct stones or congenital biliary anomalies. Laparoscopic cholecystectomy allows a short postoperative recovery and is unlikely to have surgical complications. It is believed that approximately 80% of adults requiring cholecystectomy are suitable for the laparoscopic technique. In about 5% of patients, the surgeon must perform an open cholecystectomy because of anatomic problems or adhesions. Patients with acute cholecystitis, pancreatitis, or a high probability of upper abdominal adhesions are not considered candidates for this procedure. In a report of a 5-year experience from three institutions, including 110 children aged 1ͱ6 years, there were no fatalities and the complication rate was 15. As experience has gained at most major pediatric centers, laparoscopic cholecystectomy has become the treatment of choice for elective cholecystectomies [68,69]. In adults with cholesterol stones, alternative non-surgical therapies have been suggested, including dissolution with chenodeoxycholic or ursodeoxycholic acids or combinations of these agents, extracorporal shock-wave lithotripsy with continued dissolution of fragments with oral bile acids, or direct instillation of cholesterol solvents into the gallbladder. The efficacies of bile acid, chenodeoxycholic acid, and ursodeoxycholic acid are similar. Because of dose-related side effects associated with the use of chenodeoxycholic acid (diarrhea, increased serum aminotransferases, and modest hypercholesterolemia), it is not used at all for gallstone dissolution. If drug therapy is used, ursodeoxycholic acid is the drug of choice for oral gallstone dissolution. Dissolution of stones can be achieved in 60% of selected patients with small gallstones. Unfortunately, cessation of therapy is associated with a recurrence rate of 10% per year. Oral therapy is a reasonable treatment option only for patients who are at a high surgical risk, including children. Lithotripsy using shock waves has been used in the past to disintegrate stones after several hundred to several thousand shocks. Currently few, if any, centers use lithotripsy for stone dissolution and any discussion is only of historical interest. Varying results have been obtained, depending on the number and size of gallstones found in the gallbladder. Large solitary stones of 2ͳ cm may be dissolved in up to 90% of all patients after 13 to 18 months. The efficacy is reduced with multiple smaller stones, even though the total stone mass may be smaller than with solitary stones. Without concomitant oral bile acid therapy, gallstone recurrence rate was very high [70]. The management of asymptomatic adults with so-called silent gallstones found incidentally has changed over several decades. Silent stones do not require surgery or medical therapy because their natural history is benign. Non-surgical approaches to therapy, including oral bile acid therapy or lithotripsy, should not be considered for individuals with silent gallstones. In children, available evidence supports deferring therapy for asymptomatic stones. A review of 382 Canadian children with gallstones reported complications attributable to gallstone disease in less than 5% of the asymptomatic children, and approximately 20% of the asymptomatic children demonstrated eventual resolution of their gallstones [71]. Among the infants in the study, there was a similarly low rate of complications (8. With this in mind, expectant management would appear appropriate particularly for otherwise healthy infants and children with stones that are <2 cm. For patients with smaller stones, serial ultrasound examinations appear warranted to monitor for spontaneous disappearance of stones. Gallstones may play a role in the development of carcinoma of the gallbladder, with larger stones (>2 cm) carrying a greater risk than small ones. Because larger stones are unlikely to disappear spontaneously, there is a reasonable argument for removing the gallbladder in an otherwise asymptomatic child because of the inherent enhanced risk of gallbladder carcinoma caused by the presence of a stone in the gallbladder over several decades. In infants and children with known hemolytic disease, pigment stone formation will only worsen with increasing age, and cholecystectomy at time of identification of stones (even though they may be silent) appears warranted. Specifically in patients with sickle cell disease, once stones are identified the gallbladder should be removed. With increasing age, it is clear that gallstone formation and the risk of cholecystitis and attendant adhesions increases.

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They usually cause severe burning pain at the site of the bite hiv infection no antibodies order amantadine with a visa, but in severe cases can cause systemic envenoming with tachycardia antivirus windows vista buy online amantadine, hypertension statistics hiv infection rates nsw 100 mg amantadine free shipping, sweating and priapism hiv new infection rates purchase amantadine online. Funnel-web spider Bites by funnel web spiders in Australia may cause systemic envenoming with autonomic effects on the cardiovascular system and neurological symptoms new hiv infection symptoms quality 100mg amantadine. Marine envenoming Venomous fish Many different venomous fish hiv infection of the brain buy amantadine, for example stonefish, can sting patients if they are stood on or touched. Regional nerve blocks and local infiltration of lidocaine may be effective, but most marine venoms are heat labile. Care should be taken to avoid scalding; the envenomed limb may have abnormal sensation. Asking the patient to also immerse the non-bitten limb may help to avoid scalding. Pain and wheals are the usual effects but, rarely, systemic envenoming can be life-threatening. Many of the nematocysts remain undischarged on tentacles that adhere to the victim and rubbing the area of the sting causes further discharge and worsens envenoming. In box jellyfish stings, pouring vinegar over the sting prevents the discharge of nematocysts. For most other jellyfish, seawater should be poured over the stings and adherent tentacles gently removed. Ice may be useful for pain relief and hot water is effective in reducing pain for some species. Mortality patterns these are often difficult to determine in tropical countries because of diagnostic difficulties, problems of enumerating deaths outside hospital, and variable and mobile populations. Thus, coronary artery disease is the most important form of cardiac disease in developed countries, but in many areas of the tropics the most important is rheumatic heart disease. Overall mortality caused by infectious disease is falling; and even in poor countries life expectancy is slowly increasing. Increased vehicle use and social unrest are also Tropical Medicine Lecture Notes, Seventh edition. In Africa, obesity is an especial problem in women, and in some areas up to 40% of adult urban women are significantly obese, compared with less than 5% in rural environments. Tackling this problem is especially difficult as in a number of areas of Africa, it is regarded as culturally advantageous to be overweight or obese. Not surprisingly, its mortality is high: 20 years ago a study from Zimbabwe showed that 6 years after diagnosis, nearly 50% of diabetic patients had died predominantly from metabolic problems (hypoglycaemia, ketoacidosis and other glycaemic states) or infections. There have been relatively few studies since, but what information there is suggests that there have been only modest improvements. However, in some communities renal failure (as a result of diabetic nephropathy) and cardiovascular disease are emerging causes of mortality. Diabetes outcome everywhere is highly dependent on local medical services, patient education and the availability of insulin and other appropriate medication. Obesity is a major Diagnosis All type 1 diabetes, and much type 2 diabetes, present no diagnostic challenges, as patients present with classical symptoms (thirst, polyuria, weight loss, etc. Some type 2 diabetic patients, however, have borderline values (particularly those who may be found accidentally). Note that glycated haemoglobin (HbA1c) has recently been accepted for diagnostic purposes in type 2 diabetes (cut off >6. HbA1c as a diagnostic test for type 2 diabetes is unlikely at present to become widely used in the tropics, as it is an expensive test and not widely available. Type 1 diabetes in sub-Saharan Africa also appears to have a later age of onset than in Western countries (early twenties, rather than early teens). Thus, in the late 1980s, a group of Africans from a famine area in northern Ethiopia were moved to Israel and within 4 years type 2 diabetes prevalence had risen from 0. It is seen in certain geographical areas of the tropics, and its exact cause is unknown though it appears related to past or present malnutrition. Sometimes there is obvious generalized pancreatic destruction, with fibrosis or calcification, and steatorrhoea. This has been described particularly in West Africans, or migrants from this area. After appropriate insulin treatment, however, the disease often remits, and patients can be controlled on oral agents or even diet. The basal and 2-h cut-off levels are the same as for the fasting and random levels above. It should be remembered that although most European and North American laboratories have standardized to plasma glucose levels, many tropical laboratories still measure blood glucose. Prevalence Fifty years ago diabetes was thought to be rare or even non-existent in tropical countries. In the last decade, type 2 diabetes in particular has reached epidemic rates all over the world, and the rate of expansion appears to be faster in developing as compared to developed countries. Global world prevalence was estimated as 6% in 2007, but some areas of the Caribbean have rates of 10ͱ5%, and of the Middle East over 20%. These lead to increased body weight and reduced exercise, both of which are potent causes of insulin resistance, which is the hallmark of type 2 diabetes. Type 1 diabetes appears less common than in Western countries, and contributes usually less than 10% of the total diabetic population. The incidence in Africa is about 3͵ per 100 000 per year (compared to about 15Ͳ0 per 100 000 per year in Europe). Antiretroviral treatment (particularly with protease inhibitors or nucleoside reverse transcriptase inhibitors) can cause central obesity, with insulin resistance, glucose intolerance and potentially type 2 diabetes. Nevertheless, even in resource-poor situations, simple but firm advice should be offered. Oral agents Metformin should be used for obese and overweight patients inadequately controlled on diet alone, and sulphonylureas for the non-obese with similarly inadequate control. All sulphonylurea drugs can cause hypoglycaemia, but glibenclamide and chlorpropamide are the most problematic. Oral hypoglycaemic agents should be started in low doses, and then increased as necessary. Combination treatment (metformin plus sulphonylureas) can be used if control is poor on maximal doses of one drug, but beyond this insulin may be needed. Hypoglycaemia is not infrequently caused by sulphonylurea drugs; the commonly used glibenclamide is long-acting and may cause severe and prolonged hypoglycaemia. Chronic complications these include the classic specific complications of retinopathy, neuropathy and nephropathy, as well as the non-specific large vessel complications caused by atherosclerosis of the lower limb, coronary and cerebral arteries. Diabetic complications in particular those caused by small vessel disease are strongly related to the degree of glycaemic control and the duration of disease. In some poorly resourced areas, the occurrence of diabetic complications may appear low; however, this may be because of inadequate surveillance or patients simply dying prematurely before complications have time to appear. Insulin All type 1 diabetic patients obviously require insulin for survival, but many type 2 patients ideally require insulin for control. If insulin is in short supply, it may need to be reserved for type 1 patients only. The potential benefits of insulin in type 2 diabetes also need to be weighed against hypoglycaemic risks (especially if patient self blood glucose monitoring is not available). A common misconception is that patients need a refrigerator to store their insulin. Insulin is relatively stable in all but the hottest conditions, and storage in a cool and shady area of the home is sufficient. Infection Infections are more common and more severe in diabetic patients, particularly those with poor control. Infective complications can be dramatic in the tropics caused both by high blood glucose levels and delayed presentation. However, such systems often require equipment not available in developing countries. Management Diet Diet and exercise are the prime treatments for type 2 diabetes, particularly when associated with obesity. This should be delivered to patients by local nurses or other health workers, often at primary health centre level. Organization of care Although the skilled use of individual drugs and insulin is important, the real challenge of diabetes management in the tropics is of delivery of care in difficult circumstances. Monitoring Ideal diabetes monitoring is with self-glucose testing (for those on insulin), and regular HbA1c tests in clinic. Urine glucose testing is often used as an alternative, but it is insensitive and of doubtful value. Symptom surveillance can be surprisingly effective for example, in type 2 diabetes nocturia is a sensitive indicator of glycaemic status. It is an expensive drug in developing countries, and supplies are often poor and erratic. With all these problems, the aims of treatment may need to be compromised, with relief of symptoms and avoidance of hypoglycaemia the main aims. The major factors in setting up a district diabetic service in Non-communicable diseases 339 Box 59. Obviously, the list will need to be adapted to the geographical situation, resources available and particular clinical problems present. Nurse-led care of type 2 diabetic patients in primary health care units is especially appropriate, and has been shown to be highly successful. It assumes metformin and glibenclamide are the available drugs, but obviously must be adapted to local conditions. Effective treatment of hypertension lowers risk by at least 40%, and such treatment can involve relatively simple and inexpensive drugs. Sadly, however, much hypertension remains undiagnosed, and of those cases diagnosed many are inadequately controlled. Diagnostic 340 Non-communicable diseases essential hypertension, rather than actual causes. There is, however, evidence that in certain high-risk groups (notably those with diabetes) the cut-off level should be lower probably 130/80 mmHg. However, the use of such equipment is declining, as a number of countries are restricting their use because of concerns over mercury toxicity. Aneroid models are a reasonable compromise, although they can read slightly lower than other systems. Reduced activity and central obesity leads to insulin resistance, and this is strongly associated with hypertension, as well as diabetes. Increased salt intake is probably a major feature of tropical urbanization, and some individuals may be particularly prone to the potential hypertensive effect of increased dietary salt. Complications the long-term result of uncontrolled hypertension can be a variety of complications resulting from endorgan damage. In some poor rural areas of the tropics, where obesity is rare, rates of well below 5% are found. Conversely, in many urban areas of sub-Saharan Africa, where obesity is very common, hypertension may be found in 40͵0% of the population or more. Most tropical doctors will find themselves working in areas with hypertension prevalence rates of 10Ͳ0% at least. It should always be remembered that the prevalence of known hypertension (those on antihypertensive medication) always considerably underestimates the total hypertension prevalence often by about one-half. In view of this, and the essentially asymptomatic nature of the disease, opportunist hypertension screening should be undertaken whenever possible. It is more useful to think in terms of risk factors for Of these, stroke is by far the most important, with hypertension leading to an excess risk of up to 10 times that in non-hypertensive subjects. Stroke in hypertensive patients can be caused by cerebral thrombosis as well as cerebral haemorrhage. Left ventricular hypertrophy is also a serious complication, which may lead to hypertensive heart failure. Hypertensive renal disease is one of the most common causes of chronic renal failure. Management Principles of treatment Treatment of hypertension should follow a logical pathway, bearing in mind the important basic principles of management below. A simple, but often surprisingly effective treatment is simply to give methyldopa orally, 1 gm stat and then 500 mg 4-hourly. All these drugs are relatively expensive and often unavailable in resource-limited tropical countries. In developing countries, the choice will usually be dependent on cost and availability. Simple and cheap drugs such as thiazides and methyldopa may be appropriate and effective. It has already been mentioned that only about half of hypertensive patients are detected. Organization of care As with type 2 diabetes, routine hypertension management is ideally suited to primary health clinic care by suitably trained nurses. In most areas, there are large numbers of hypertensive patients, and such a system will allow medical staff to concentrate on more difficult cases. Again, as with diabetes, the protocol needs to be adapted to local needs and drug supplies. Special situations There are specific clinical situations where the standard progression of treatment (first-line, second-line, etc. Beta-blockers should be avoided in asthma, but they are good first-line drugs in the presence of angina. Secondly, the nature and importance of hypertension should be carefully explained.

Treatment recommendations must be tailored to the individual on a case-by-case basis with an understanding of the expertise of the treating center and physicians graphs on hiv infection rates purchase amantadine with visa. Accumulating reports of the success of mesentericoportal (meso Rex) bypass surgery needs to be incorporated into the clinical decision making in the management of individuals with portal vein thrombosis [31] antiviral soap buy amantadine 100mg on line. The physiologic restoration Biliary atresia is the leading cause of significant pediatric liver disease and the single most common indication for liver transplantation in children [32] stages of hiv infection graph cheap amantadine amex. Unlike portal vein obstruction hiv infection personal stories safe 100mg amantadine, this is an example of a disease where portal hypertension is associated with ongoing and progressive liver disease hiv infection and aids an overview order amantadine online from canada. Biliary atresia is universally fatal in early childhood unless operative intervention is undertaken hiv infection rate dubai quality amantadine 100mg. At the time of portoenterostomy, portal hypertension has been documented, and its subsequent natural history is complicated by the variable results of portoenterostomy [33]. In general, the complications of portal hypertension are more prevalent in patients with poor biliary drainage or postoperative cholangitis [33]. Variceal hemorrhage is a common problem in children with biliary atresia and can occur as early as the first year of life [15,34,35]. The importance of bile flow, as manifest by total serum bilirubin, in the prognosis after variceal hemorrhage is reflected in reported experiences from Denver and Hong Kong [15,35]. Survival without liver transplantation after first variceal hemorrhage is significantly greater in children with total serum bilirubin <4 mg/dL [15]. In most circumstances, variceal bleeding appears to be life threatening and recurrent unless some intervention is undertaken. Variceal hemorrhage in these patients requires intervention, which must be tempered with the prospect of possible liver transplantation in the future. Given the progressive nature of portal hypertension associated with biliary atresia, the effects of interventions, both medical and surgical, are more easily discerned. Diagnostic evaluation Portal hypertension should be suspected in any child with significant gastrointestinal hemorrhage or unexplained splenomegaly. Physical examination should be directed at assessing for evidence of chronic liver disease. Care should be taken to look for growth failure or cutaneous lesions consistent with chronic liver disease. The combination of gastrointestinal hemorrhage and splenomegaly is highly suggestive of portal hypertension until proven otherwise. In addition, white blood cell and platelet counts may give evidence of hypersplenism. Thrombocytopenia in the setting of clinically suspected portal hypertension is a reasonable predictor of the potential for the presence of esophageal varices [6]. In children with portal vein thrombosis or Budd Chiari syndrome, investigation of thrombophilia or myeloproliferative disease is potentially indicated. As in children in general, the most benign therapies are frequently the most favorable initial modalities of treatment. Our own unpublished experience and the published experience in other pediatric centers indicates that intravenous octreotide appears to be relatively well tolerated by sick infants and children [50]. There is a critical need for better safety and efficacy data on these agents in infants and children. Emergency endoscopic therapy As noted above, approximately 15% of children will have persistent hemorrhage despite conservative management plus some form of splanchnic vasoconstriction. The most commonly used second approach is endoscopic sclerotherapy or endoscopic band ligation. This therapy is very effective in controlling bleeding, although it may be technically challenging in the individual with rapid hemorrhage. An extensive experience with emergency sclerotherapy exists in children, and it is rare for additional therapy to be required [13]. A variety of methods are used that chemically cause the varices to clot off and fibrose. Sclerosants, chemically irritating compounds such as ethanolamine or tetradecyl sulfate, are injected either intra- or paravariceally, until bleeding has stopped. Sclerotherapy is associated with a series of complications of its own, which will be discussed below. In the setting of emergency sclerotherapy, it is important to be aware of the significant incidence of associated bacteremia and to consider prophylaxis in nearly all patients. The major drawback of an endoscopic approach to treating acute hemorrhage is that the bloody field that is frequently encountered makes the procedure technically challenging. Endoscopic band ligation of varices may be a preferable approach because it is easier and safer to perform in an obscured field. A randomized trial of ligation versus sclerotherapy in adults demonstrated similar control of active bleeding and recurrence of hemorrhage, with significantly lower overall complications and mortality in the patients treated with endoscopic ligation. A potential concern in the application of this technique in small children, where the esophageal wall is thinner than in adults, is entrapment of the full thickness of the esophageal wall by the rubber band and subsequent ischemic necrosis and perforation. In addition, there may be technical difficulties in performing band ligation in children younger than 2 years of age because of difficulties in passing the endoscope. In most cases, a combination of conservative management, splanchnic vasoconstriction, and endoscopic sclerotherapy or band ligation will stop acute variceal hemorrhage. Emergency pharmacologic therapy the pharmacologic therapy of acute variceal bleeding typically consists of the use of terlipressin, vasopressin, or somatostatin (or their respective analogues). Vasopressin has the longest history of usage and acts by increasing splanchnic vascular tone and thus decreasing portal blood flow. Its use is often limited by the side effects of this vasoconstriction, which include left ventricular failure, bowel ischemia, angina, and chest and abdominal pain. Only a limited number of studies have compared vasopressin therapy with supportive care alone. In these studies, vasopressin leads to more rapid control of gastrointestinal hemorrhage, but no significant effect on mortality was seen. Of 215 children with acute variceal hemorrhage, 184 had bleeding arrested by the combined use of fluid support and vasopressin [49]. Vasopressin has a half-life of 30 minutes and is usually administered as a bolus followed by a continuous infusion. These recommendations are apparently empiric, based on clinical practice and most likely derived from extrapolation of adult dosages. Terlipressin, a long-acting synthetic analogue of vasopressin, has shown similar effects and does not require continuous infusion. A potential significant advantage of terlipressin is its favorable effect on both control of hemorrhage and mortality. Alternatives to vasopressin have been investigated because of its poor side effect profile. Somatostatin and its synthetic homologue octreotide have also been shown to decrease splanchnic blood flow. This effect is presumably mediated by blockade of secretion of vasoactive peptides by the intestine. Its effects on acute variceal hemorrhage appear to be similar to those of vasopressin, with fewer side effects. Like vasopressin, Emergency mechanical therapy the Sengstaken΂lakemore tube was designed to stop hemorrhage by mechanically compressing esophageal and gastric varices. The endoscopic tip is positioned over a variceal column in the distal esophagus (upper left). Suction is applied to draw the esophageal mucosa and varix up into the dead space with the ligating device (upper right). The tripwire is pulled and the O-ring slipped around the aspirated tissue (lower left). It is passed into the stomach where the first balloon is inflated and pulled up snug against the gastroesophageal junction. Once the tube is secured in place, the second balloon is inflated in the esophagus at a pressure (60ͷ0 mmHg) that compresses the varices without necrosing the esophagus. A channel in the rubber tube allows gastric contents to be sampled for evidence of bleeding. Unfortunately, it is associated with a significant number of complications and a high incidence of rebleeding when the tube is removed. Most patients find this treatment uncomfortable, and its use in children requires significant sedation. Obstruction of the esophagus by the apparatus increases the risk of aspiration pneumonia, which can be a devastating complication in an individual with liver failure. Given these problems, the Sengstaken΂lakemore tube is reserved for severe uncontrollable hemorrhage and generally serves as a temporizing measure until a more definitive procedure can be performed. Intubation and heavy sedation is typically recommended for children requiring this approach. In summary, the approach to acute variceal hemorrhage in the pediatric patient is a stepwise progression from least invasive to most invasive. An adequate trial of conservative medical management is recommended, although evidence of significant bleeding. Endoscopic band ligation is generally effective in those few patients who remain unresponsive and/or should be implemented soon after control of bleeding as part of secondary prophylaxis (see below). The ultimate long-term prognosis for the patient and the particular strengths of the team caring for the patient are key factors in choosing the particular approach for a given patient in a given institution. Emergency surgical and interventional radiology Surgical therapy is usually a last resort for acute variceal hemorrhage. Many of the patients with recalcitrant hemorrhage will be found to have gastric varices. The reluctance to perform emergency surgery partly stems from its associated high mortality but also from concerns of increased incidence of encephalopathy and greater difficulty of subsequent liver transplantation. The variety of surgical procedures that have been performed for intractable hemorrhage can be divided into transection, devascularization, and portosystemic shunting. The techniques of esophageal transection and devascularization are rarely used and work by interrupting blood flow through the esophagus. Liver transplantation can be an effective means of treating esophageal varix hemorrhage, if an acceptable organ can be procured quickly enough. Esophageal varix embolization via a percutaneous transhepatic or trans-splenic approach has been advocated by some as another method of controlling acute hemorrhage. It does not require surgery or puncture of an organ that is predisposed to hemorrhage. The experience Secondary prophylaxis the decision making in the long-term management of the patient with portal hypertension and a previous episode of variceal hemorrhage is very complex. The first level of consideration involves the natural history of portal hypertension and more importantly the natural history of the underlying liver disease. As discussed above, there are significant differences in the natural history of portal hypertension in the setting of minimal and inactive versus active and progressive hepatic disease. As a result, certain individuals might have the possibility to outgrow their portal hypertension through the development of spontaneous portosystemic shunts, whereas others might be expected to develop end-stage liver disease and ultimately be candidates for liver transplant. Another important issue relates to the presence or absence of systemic manifestations of the underlying disease. Decision making in cystic fibrosis and congenital hepatic fibrosis/autosomal recessive polycystic kidney disease need to incorporate the prognosis of the pulmonary and renal diseases, respectively [53,54]. Sclerotherapy can be administered with a wide variety of sclerosing agents and by two different techniques (intra- or paravariceal). Endoscopic band ligation offers an important and generally safer alternative to sclerotherapy. A catheter is inserted into the jugular vein and is advanced into the hepatic vein, where a needle is used to form a tract between the portal vein and the hepatic vein. This tract is expanded with a balloon angioplasty catheter, and a stent is then placed, forming the permanent portosystemic shunt. A final level of complexity results from the varying results of randomized and nonrandomized trials in adults. The trials are difficult enough to compare in adults and cannot necessarily be extrapolated to children, in whom alcoholic liver disease and end-stage hepatitis C are rare. Given these complex issues, the major modalities of long-term secondary prophylactic therapy of portal hypertension will be reviewed: endoscopic therapy, portosystemic shunting, and liver transplantation. The rationale for beta-blockade has been discussed as possible primary prophylaxis. It may also be used for secondary prophylaxis or as an adjunctive approach to endoscopic therapy. In particular, the rationale, effectiveness, and complications of these treatments will be stressed. Secondary prophylaxis: sclerotherapy and ligation therapy Sclerotherapy and band ligation therapy work by physical obliteration of esophageal varices. Hemorrhage may occur during the several weeks required to complete the obliteration, and there is a tendency for the vessels to recanalize. Most importantly, the principal problem of portal hypertension is not addressed, and there is the risk of bleeding from varices elsewhere in the gastrointestinal tract, notably the stomach. Despite these problems, endoscopic therapy has been a mainstay of the treatment of esophageal varices. In addition, there is a significant amount of clinical experience with these approaches in children [13,43,44,55,56]. The effectiveness of sclerotherapy has been studied for prevention of initial bleeding and for subsequent bleeding episodes. Sclerotherpy, which has in general been supplanted by band ligation, is reviewed here for completeness. In addition, in very young children, band ligation therapy may not be feasible and sclerotherapy may be required. Intravariceal, paravariceal, and some combination injection protocols have been used.