Jennifer A. Lowry, MD

• Assistant Professor
• Division of Clinical Pharmacology and Medical Toxicology
• University of Missouri?Kansas City School of Medicine
• Children? Mercy Hospitals & Clinics
• Kansas City, Missouri

Other manifestations include: Increased skin pigmentation Diabetes mellitus Amenorrhea (women) Liver disease Heart failure Downloaded for Anonymous User (n/a) at Consortium Egypt - Mansoura University from ClinicalKey best treatment for shingles nerve pain cheap 500 mg azulfidine free shipping. The severity of liver disease generally correlates with the severity of hepatic iron overload pacific pain treatment center victoria bc order azulfidine with amex, 4 knee pain treatment kansas city buy azulfidine 500mg low price. The level of serum aminotransferase elevation is generally modest pain medication for pregnant dogs buy 500 mg azulfidine with visa, and serum aminotrans5 hip pain treatment options azulfidine 500mg otc. If iron depletion is achieved and maintained before the development of hepatic fibrosis or 6 treatment pain post shingles order azulfidine with paypal. It may be associated with increased plasma insulin levels, a finding that suggests peripheral insulin resistance (type 2), particularly in association with liver disease. It characteristically involves the second and third metacarpophalangeal joints; other meta- carpophalangeal joints and wrist joints are also frequently involved. Pathologic features include joint space narrowing, chondrocalcinosis, subchondral cyst formation, and osteopenia. The mechanism for the increased risk of infections is unknown but is postulated to relate to iron-mediated impairment of innate and acquired immune responses. Infections may be caused by the following uncommon bacteria: Vibrio vulnificus Yersinia enterocolitica Yersinia pseudotuberculosis Listeria monocytogenes Natural History and Prognosis 1. Liver disease is slowly progressive but is usually mild (except with concomitant viral hepati2. Some manifestations improve with iron depletion (malaise, fatigue, skin pigmentation, diabetes 7. Patients without cirrhosis or diabetes mellitus have a normal life expectancy if iron depletion is maintained. Patients with cirrhosis or diabetes mellitus have a significantly decreased life expectancy, but the prognosis is improved after iron depletion therapy. Serum ferritin is an acute phase reactant and can be elevated in inflammatory conditions 4. Circadian and postprandial variations of the transferrin saturation can be a source of labora5. Isolated elevation of the serum ferritin with a normal transferrin saturation may indicate type and other chronic liver diseases. The presence of C282Y homozygosity or C282Y/H63D compound heterozygosity confirms 3. Staining for hepatic iron is important because sampling variability can yield a low hepatic iron index. Liver biopsy for staging is important because of the following: Histopathology remains the gold standard for establishing the presence of cirrhosis in the absence of overt evidence such as portal hypertension. Magnetic resonance imaging can estimate hepatic iron quantitatively in a noninvasive fashion. Quantitative phlebotomy is useful for estimation of iron overload when liver biopsy is not required. Each phlebotomy usually removes 500 mL of blood (approximately 250 mg of iron); the need to remove 4 g or more of iron before the onset of iron-limited erythropoiesis with anemia indicates the presence of significant iron overload. Secondary iron overload can occur in the following situations: Increased red blood cell turnover. Iron-loading anemias with or without transfusion Thalassemia major Sideroblastic anemia Chronic hemolytic anemias b. Iron overload associated with chronic liver disease including Downloaded for Anonymous User (n/a) at Consortium Egypt - Mansoura University from ClinicalKey. Miscellaneous causes Porphyria cutanea tarda African iron overload Neonatal hemochromatosis Aceruloplasminemia Atransferrinemia 3. Quantitative phlebotomy demonstrates the onset of iron-limited erythropoiesis with anemia before removal of 4 g or more of iron. Sug- gested protocol for serial phlebotomy: Phlebotomy is performed, with removal of 500 mL of blood (approximately 250 mg of iron) weekly or biweekly until the serum ferritin declines to 50 to 100 g/L. The hematocrit or hemoglobin value should be checked before each session, and the serum ferritin level should be assessed every 3 months (after every 10 to 12 phlebotomies). If the hematocrit value is <32%, phlebotomy should be postponed, and the frequency should be decreased to once every 2 weeks. Once the serum ferritin level is <50 g/L, it should be tested every 3 to 4 months, with phlebotomy repeated as required to maintain the serum ferritin level at 50 to 100 g/L. The required frequency of maintenance phlebotomy depends on the rate of iron accumulation as is generally required once in 2 to 4 months. Precautions during phlebotomy: Anemia should be prevented by monitoring the hematocrit value before each phlebotomy and ensuring adequate dietary protein, vitamin B12, and folate intake. High doses of ascorbic and citric acid, as well as a diet rich in iron, should be avoided. During maintenance phlebotomy, gastric acid suppression with a proton pump inhibitor may allow a reduction in the frequency of phlebotomies, presumably by decreasing iron absorption in the duodenum. Iron chelators (deferoxamine, deferiprone, deferasirox) are less effective and more expensive than phlebotomy and associated with adverse effects. These drugs are used only in patients with anemia or those who cannot tolerate phlebotomy. Phenotypic screening (transferrin saturation) could be considered in high-risk populations, but negative results in young adults should be interpreted with caution because the transferrin saturation may become elevated with aging. Diagnosis and management of hemochromatosis: 2011 practice guidelines by the American Association for the Study of Liver Diseases. Survival after liver transplantation in patients with hepatic iron overload: the national hemochromatosis transplant registry. Approximately 1 to 2 mg of dietary copper is absorbed by the proximal small intestinal epi- thelial cells daily. Copper that is transferred into the portal circulation is bound to serum albumin and amino acids. The remaining intraepithelial copper is mostly bound to the endogenous chelating peptide metallothionein and is subsequently excreted as intestinal epithelial cells are sloughed. Dietary copper (1 to 2 mg/day) is transported into the intestinal epithelial cell, with the Menkes gene product regulating transport into the portal circulation (25% to 60%). The remaining intraepithelial copper is bound to metallothionein and is subsequently excreted in stool as the intestinal epithelial cells are sloughed. A small amount of the absorbed copper is excreted in urine, but the majority is taken up by the hepatocyte, synthesized into ceruloplasmin, and stored in the liver or excreted in bile. Only a small fraction of circulating copper (<50 g/24 hours) is normally excreted by the 4. In the hepatocyte, copper is complexed with and detoxified by metallothionein or glutathione and is used as a cofactor for specific cellular enzymes, incorporated into ceruloplasmin that is excreted into the circulation, or excreted into bile. The site of hepatocellular copper incorporation into ceruloplasmin is the trans-Golgi apparatus. The delivery of cytosolic copper to specific intracellular locations is mediated by small proteins termed copper chaperones. A secondary route for biliary copper excretion of hepatocellular copper is via transport of copper-glutathione. In addition, some intracellular copper transports back across the hepatocyte basolateral plasma membrane into the circulation. Systemic circulation Cu-metallothionein kidney; most is taken up by hepatocytes, and excess is excreted into bile. Copper (Cu) is taken up by the hepatocytes, where it interacts with glutathione and metallothionein. It is postulated that copper is also routed from the trans-Golgi apparatus to a vesicular compartment in lysosomes for subsequent excretion in bile. Comparatively few patients are homozygous for the same mutation; however, most are compound heterozygotes. Maintenance of normal copper homeostasis depends on a balance between gastrointestinal 2. Morphologic abnormalities from oxidant damage have been identified, particularly in mitochondria. Hepatic copper accumulation and hepatocellular injury lead to increased circulating nonceruloplasmin-bound copper, which is responsible for extrahepatic copper accumulation. Affected organs, in particular the central nervous system, invariably exhibit elevated copper levels. Pathologic copper deposition in the brain, mostly in the caudate nucleus and the putamen of the basal ganglia, results in the neurologic and psychiatric manifestations of the disease. Patients may be asymptomatic, although most present with hepatic or neurologic manifesta- tions. Less commonly, patients present with renal, skeletal, cardiac, ophthalmologic, endocrinologic, or dermatologic symptoms. Clinical symptoms are rarely observed before age 3 to 5 years, and most untreated patients become symptomatic by the age of 40 years. Hepatic symptoms usually are present in the second or third decade of life, and neurologic in the third and fourth decades. In a large series, the initial clinical manifestations were hepatic in 42%, neurologic in 34%, psychiatric in 10%, and hematologic in 12%. Hepatic manifestations tend to occur at a younger age (mean, 10 to 12 years) than neu- rologic manifestations. Patients with asymptomatic disease typically have abnormalities of liver biochemical tests that correlate histologically with hepatic steatosis and inflammation. Young patients may present with features that are indistinguishable from chronic viral or autoimmune hepatitis. Ongoing inflammation leads to progression of fibrosis and eventual cirrhosis with progressive hepatic insufficiency and liver failure. Patients tend to be young, in their second decade of life, and the clinical picture may be indistinguishable from that of viral-induced massive hepatic necrosis. Although serum aminotransferase levels are only mildly to moderately elevated, there is marked elevation of the serum bilirubin, a low serum alkaline phosphatase level, and evidence of Coombs-negative hemolytic anemia. Liver biopsy, if performed (generally via a transjugular route due to coagulopathy), demonstrates an elevated hepatic copper content and usually advanced fibrosis or cirrhosis with severe hepatocellular injury. Common early neurologic symptoms are dysarthria, clumsiness, tremor, drooling, gait 3. Athetosis (involuntary writhing movements) or a more severe movement disorder may be present. Autonomic dysfunction may be present, most commonly in association with other advanced neurologic findings. Cognitive ability usually remains normal but may be impaired in patients with severe neurologic impairment. Early symptoms in teenagers may be limited to subtle behavioral changes and deterioration of academic and work performance. Patients may present later with personality changes, lability of mood, emotionalism, impulsive and antisocial behavior, depression, and increased sexual preoccupation. Electron-dense granules rich in copper and sulfur are deposited in the Descemet membrane 2. The ring eventually becomes circumferential, and the width of the ring increases in untreated patients. Findings include proximal renal tubular acidosis or features of Fanconi syndrome in patients 2. Hematuria, mostly microscopic, may be caused by nephrolithiasis or glomerular disease. Symptomatic arthropathy occurs in 25% to 50% of patients; this degenerative joint disease 3. Osteochondritis dissecans, chondromalacia patellae, and chondrocalcinosis have also been osteoporosis, or both. An episode of acute intravascular hemolysis may be the presenting feature in up to 15% of 2. The frequency of cardiac involvement was underestimated in the past; electrocardiographic 3. Azure lunulae (bluish discoloration of the lunules [bases] of fingernails) are an uncommon but 4. Ceruloplasmin Normal serum concentration is 20 to 40 mg/dL (consult the local laboratory for reference ranges, as minor variations are common). Nonceruloplasmin serum copper In unaffected patients copper in ceruloplasmin accounts for approximately 90% of the total serum copper. An estimate of the "free" (nonceruloplasmin) serum copper concentration can be calculated by subtracting the amount of ceruloplasmin copper (0. The nonceruloplasmin serum copper concentration is useful for monitoring the adequacy of chelation therapy during maintenance treatment. The proportion of nonceruloplasmin copper is reduced in treated patients, and levels are typically 5 to 15 g/dL. Newer assays for "exchangeable copper" measure nonceruloplasmin copper directly from plasma samples and may in the future be useful for monitoring treatment. Elevated levels may be seen in other hepatic disorders, such as primary biliary cholangitis and chronic hepatitis, and in severe proteinuria from ceruloplasmin loss in urine. Early features may include glycogen inclusions in the nuclei of periportal hepatocytes (glycogenated nuclei) and moderate fatty infiltration that may be both microsteatotic and macrosteatotic. In severe acute hepatitis and chronic hepatitis, submassive necrosis with Mallory hyaline, (Mallory-Denk bodies) and cirrhosis or advanced fibrosis is seen. Histochemical staining of liver biopsy specimens for copper using rhodanine or rubeanic acid is of limited value unless results are positive, because during the initial stages of hepatocellular copper accumulation the metal is distributed diffusely in the cytosol and does not stain histochemically by these methods. Timm sulfide staining can detect cytosolic copper binding protein, but this test in not routinely performed. In older reusable needles that may be made of brass, such as a Klatskin or Menghini needle, recommendations were to wash the needle in 0.

Secondary bacterial infections resulting from infiltration and suppression of reticuloendothelial cell function include pneumonia pain treatment with heat buy discount azulfidine 500mg on line, pneumococcal infection pain treatment for liver cancer buy azulfidine 500 mg otc, and tuberculosis and are important causes of mortality pain treatment satisfaction questionnaire azulfidine 500 mg on-line. Physical findings include often massive hepatomegaly dfw pain treatment center buy azulfidine 500 mg overnight delivery, soft and nontender splenomegaly pain treatment center of arizona 500mg azulfidine mastercard, jaundice natural pain treatment for shingles discount 500mg azulfidine otc, or ascites in severe disease as well as generalized lymphadenopathy, and muscle wasting. Cutaneous gray hyperpigmentation, which prompted the name kalaazar ("black fever"), is characteristically seen in India. Oral and nasopharyngeal nodules resulting from granuloma formation can be seen in Africa. Histopathology Organisms are found in macrophages of the liver and spleen, bone marrow, and lymph nodes. Healing is accompanied by fibrous deposition similar to that seen in congenital syphilis, and occasionally the liver looks cirrhotic (Rogers cirrhosis); complications of cirrhosis are rare. Diagnosis this is based on history, physical examination, and demonstration of tissue amastigotes. The highest yield comes from aspiration of the spleen, with parasites seen in 95% of cases. Liver aspiration is safer and has 70% to 85% a similar sensitivity, as does bone marrow aspiration. The leishmanin skin test (Montenegro test) is typically negative and unhelpful in acute visceral disease. Treatment of secondary bacterial infections is essential, and specific antileishmanial chemotherapy should be initiated promptly. Liposomal amphotericin B administered intravenously is the treatment of choice for visceral leishmaniasis. Alternative agents include oral meglumine antimoniate, paromomycin, and miltefosine. Life cycle Cats are the definitive hosts; humans and other animals are incidental hosts that become infected by ingestion of oocysts in soil, water, or contaminated meat. The oocysts mature in the intestinal tract of humans to become sporozoites, which penetrate the intestinal mucosa, become tachyzoites, and circulate systemically, thus invading a wide array of cell types. They can form tissue cysts, containing many bradyzoites, which are responsible for latent infection. Clinical features Acquired toxoplasmosis can manifest as a mononucleosis-like illness with fever, chills, headache, and lymphadenopathy. Uncommonly, hepatomegaly, splenomegaly, and minimal elevations of serum aminotransferase levels are present. Infection of immunocompromised hosts can result in encephalitis, chorioretinitis, pneumonitis, myocarditis, and, uncommonly, hepatitis. Atypical lymphocytosis, an otherwise unusual feature of parasitic disease, may occur. Treatment Antibiotic therapy with pyrimethamine and sulfadiazine, plus folinic acid to minimize hematologic toxicity, for 2 to 6 weeks (depending on patient characteristics), should be administered to immunocompetent persons with severe infection and immunocompromised or pregnant patients. Ascariasis Ascaris lumbricoides is estimated to infect 819 million people worldwide, especially in tropical countries and areas with poor sanitation practices. Life cycle Humans are infected by ingesting embryonated eggs, usually in raw vegetables. The larvae hatch in the duodenum and migrate to the cecum, where they penetrate the mucosa, enter the portal circulation, and reach the liver, pulmonary artery, and lungs. The larvae grow in the alveolar spaces, are regurgitated and swallowed, and become mature adults in the intestine 2 to 3 months after ingestion, eventually reaching 15 to 35 cm, whereupon the cycle repeats itself. Clinical features Most infected persons are asymptomatic or minimally symptomatic during larval migration. Chronic infection is more frequently characterized by episodic epigastric or periumbilical pain. If the worm burden is particularly heavy, small bowel obstruction, intussusception, volvulus, perforation, or appendicitis may occur. Fragments of disintegrating worms within the biliary tract can serve as a nidus for biliary calculus formation. Preexisting disease of the biliary tract or pancreatic duct can predispose to worm migration into the bile ducts, with resulting obstructive jaundice, cholangitis, cholecystitis, pancreatitis, or pylephlebitis and intrahepatic abscesses. Diagnosis In the absence of a history of worm passage or regurgitation, the diagnosis is made definitively by identification of characteristic eggs in stool specimens. In patients with intestinal obstruction, piperazine citrate may be used (75 mg/kg for 2 days to a maximum of 3. Intestinal or biliary obstruction may require surgical or endoscopic intervention and removal of the worm. In the absence of intestinal perforation or ischemia, conservative management may be attempted first for up to 24 hours. The eggs hatch in the small intestine and release larvae, which penetrate the intestinal wall, enter the portal circulation, and reach the liver and systemic circulation. The immature worms bore through the vessel walls and migrate through the tissues, thereby leading to secondary inflammatory responses. They do not return to the intestinal lumen; therefore, neither eggs nor larvae appear in the feces. When larvae become trapped in tissue, they provoke granuloma formation with a predominance of eosinophils. Findings include fever, hepatomegaly, urticaria, and leukocytosis with persistent eosinophilia, hypergammaglobulinemia, and elevated blood group isohemagglutinins. Stool studies are not useful because the larvae do not mature to produce eggs in humans and do not remain in the gastrointestinal tract. A definitive diagnosis is made by identification of the larvae in affected tissues, although blind biopsies have a low yield and are not routinely recommended. Ultrasound-guided liver biopsy may be necessary to differentiate visceral larva migrans from hepatic capillariasis. More severe cases require antihelminthic treatment with albendazole 400 mg twice daily for 5 days or mebendazole 100 to 200 mg twice daily for 5 days. Significant pulmonary, cardiac, ophthalmologic, or neurologic manifestations may warrant the use of systemic glucocorticoids. Hepatic capillariasis Infection with Capillaria hepatica is acquired by ingestion of eggs in contaminated soil, food, or water, especially by children under poor hygienic conditions. Life cycle Larvae released in the cecum penetrate the intestinal mucosa, enter the portal venous circulation, and become lodged in the liver, where adult worms develop within 3 weeks to a size of 20 mm. As the female worm dies, it releases eggs into the hepatic parenchyma and produces an intense granulomatous and fibrosing reaction. Clinical features the features may be similar to those of visceral larva migrans, but it manifests as acute or subacute hepatitis. Patients may have tender hepatomegaly and, occasionally, splenomegaly, prominent eosinophilia, mild elevations of serum aminotransferase, alkaline phosphatase, and bilirubin levels, anemia, and an elevated erythrocyte sedimentation rate. Diagnosis Adult worms or eggs can be detected in liver biopsy or autopsy specimens. Associated histologic findings in the liver include necrosis, fibrosis, eosinophilic infiltrate, and granuloma formation. Case studies have reported success with dithiazanine iodide, sodium stibogluconate, albendazole, and thiabendazole. Strongyloidiasis Strongyloides stercoralis is prevalent in the tropics and subtropics, southern and eastern Europe, and the United States. Life cycle Humans are infected by the filariform larvae, which penetrate intact skin, are carried to the lungs, migrate through the alveoli, and are swallowed to reach the intestine, where maturation ensues. Autoinfection can occur if the rhabditiform larvae transform into infective filariform larvae in the intestine, thereby causing persistent infection even decades after exposure; reinfection occurs by penetration of the bowel wall or perianal skin and entry into the portal circulation and then the liver. Diagnosis the diagnosis should be considered in persons with a history of pica, exposure to dogs Downloaded for Anonymous User (n/a) at Consortium Egypt - Mansoura University from ClinicalKey. A hyperinfection syndrome may result from dissemination of filariform larvae into any organ, including the liver, lung, and brain, which is not ordinarily in the life cycle of the nematode. Clinical features As with other helminthic infections, acute infection can lead to a pruritic eruption followed by fever, cough, wheezing, abdominal pain, diarrhea, and eosinophilia. When the liver is affected, cholestatic liver biochemical abnormalities can be seen. Liver biopsy specimens may show periportal inflammation, and larvae may be observed in intrahepatic bile canaliculi, lymphatic vessels, and small branches of the portal vein. The presence of an obstructive hepatobiliary picture in a person with established strongyloidiasis suggests possible dissemination. Treatment For acute infection, the drug of choice is ivermectin 200 g/kg daily for 2 days; alternatively albendazole can be used. Retreatment with a second course may be necessary in immunocompromised patients or those with disseminated disease. Treatment options are limited following dissemination, and mortality rates are as high as 85%. Life cycle Humans may be infected with Trichinella spiralis by consuming raw or undercooked pork bearing larvae, which are released in the upper gastrointestinal tract, enter the small intestine, penetrate the mucosa, and disseminate through the systemic circulation. In the small bowel, the larvae develop into adult worms, which release larvae that migrate to striated muscle, where they become encapsulated. Clinical features Clinical manifestations occur when the worm burden is high and include diarrhea, fever, myalgias, periorbital and facial edema, conjunctivitis, and leukocytosis with marked eosinophilia. Severe complications include myocarditis, central nervous system involvement, and pneumonitis. Diagnosis Suggested by fever associated with eosinophilia Serologic studies for antibody to Trichinella may not be helpful in the acute phase of infection and false positives exist. Rarely, hepatic histologic examination may demonstrate invasion of hepatic sinusoids by larvae. Treatment Glucocorticoids are used to relieve allergic symptoms, followed by antihelminthic treatment with albendazole 400 mg twice daily for 8 to 14 days or, alternatively, mebendazole 200 to 400 mg three times a day for 3 days, followed by 400 to 500 mg three times a day for 10 days. Schistosomiasis Schistosomiasis (bilharziasis) is caused by trematodes (blood flukes) of the genus Schistosoma. Approximately 200 million persons are infected worldwide, with approximately 200,000 deaths annually. An estimated 400,000 people, mostly immigrants from endemic areas, are infected in the United States. Within 24 hours, the cercariae reach the peripheral venules and lymphatics and the pulmonary vessels. They pass through the lungs and reach the liver, where they lodge, develop into adults 1 to 2 cm long, and mate. Mated adult worms then migrate to their ultimate destinations in the inferior mesenteric venules (Schistosoma mansoni), superior mesenteric venules (S. These locations correlate with the clinical complications associated with each species. The eggs are deposited in the terminal venules and eventually migrate into the lumen of the involved organ, after which they are excreted in the stool or urine. Excreted eggs hatch immediately in fresh water and liberate early intermediate miracidia, which infect their snail hosts. The miracidia transform into cercariae within the snails and are then released into the water, from which they may again infect humans. Clinical features the severity of clinical symptoms is related to the total worm burden in the host and possibly genetic susceptibility factors and is caused by the host reaction to the schistosomes. Water Skin Human Cercaria Sporocysts Schistosomula Worms grow and mate in portal vein Aquatic snail Reach pulmonary veins and eventually portal circulation Worms migrate Eggs reach liver via portal to intestinal circulation where they elicit venous plexus granulomatous response and deposit eggs S. Manifestations include headache, fever, chills, cough, diarrhea, myalgia, arthralgia, tender hepatomegaly, splenomegaly, and eosinophilia. Untreated acute schistosomiasis invariably progresses to chronic disease over many years. Mesenteric infection leads to hepatic complications, including periportal fibrosis, presinusoidal occlusion, and, ultimately, presinusoidal portal hypertension, as a result of the inflammatory reaction to eggs deposited in the liver. With severe schistosomal infection, portal hypertension becomes progressive, leading to ascites, gastroesophageal varices, and splenomegaly. Chronic schistosomal infection may be complicated by increased susceptibility to Salmonella infections. Hepatitis B and C virus infections are also common in persons living in endemic areas and may accelerate the progression of liver disease and the development of hepatocellular carcinoma. Laboratory findings in chronic schistosomiasis include anemia from recurrent gastrointestinal bleeding or hypersplenism, eosinophilia, an elevated erythrocyte sedimentation rate, and increased serum IgE levels. Diagnosis the diagnosis of acute schistosomiasis should be considered in a patient with an exposure history to fresh water who has abdominal pain, diarrhea, and fever. Multiple stool examinations for ova using the Kato-Katz thick smear may be required to confirm the diagnosis, because results are frequently negative in the early phases of disease. Sigmoidoscopy or colonoscopy may reveal rectosigmoid or transverse colonic involvement and may be useful in chronic disease when few eggs pass in the feces. Ultrasonography and liver biopsy are useful for demonstrating periportal (or "pipestem") fibrosis but not for diagnosing acute infection. Treatment Praziquantel 40 mg/kg given for 1 day in two divided doses is the treatment of choice for infection caused by S. Treatment of acute toxemic schistosomiasis requires praziquantel 75 mg/kg for 1 day in three divided doses and, in some cases, prednisone for the prior 2 to 3 days to suppress immune-mediated helminthicidal or drug reactions. Periodic treatment of patients in endemic areas will keep the burden of infection low and will minimize chronic complications. Noncirrhotic, presinusoidal portal hypertension may lead to variceal bleeding requiring band ligation or sclerotherapy.

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Placement of laser tubes is routine low back pain treatment video discount azulfidine online amex, although care should be taken to prevent traumatizing the laryngeal lesion as the laser tube is passed through the glottis and into the trachea pain wrist treatment discount 500mg azulfidine overnight delivery. After the laser tube is in position and the cuff inflated pain treatment for dogs with cancer cheap azulfidine 500mg on line, there is protection of the lower airway from blood and secretions pain treatment center winnipeg buy cheap azulfidine 500mg. Routine control of the airway and ventilation are established milwaukee pain treatment center milwaukee wi purchase genuine azulfidine line, and because the system is closed pain medication for dog injury discount azulfidine 500mg line, there is little danger of pollution of oxygen or volatile agents unless the cuff is compromised. Appreciate immediately any cuff compromise as a result of laser strike because it causes oxygen and volatile agent leaks around the laser tube, increasing the fire risk. All laser tubes have a greater outer diameter for any given internal diameter because of their laser-resistant coverings, and this may limit surgical access and visualization of laryngeal lesions. Because the surgeon requires adequate exposure, small laser tubes are usually placed, which can lead to higher inflation pressures. Spontaneous Ventilation and Insufflation Techniques Open systems can be used during anesthesia for laser procedures on the vocal cords, with spontaneous ventilation techniques being used in adults and in children. Spontaneous ventilation techniques with insufflation are particularly suitable for infants and children in whom it is not possible to pass a tube past a lesion or when a laser tube obscures the lesion. Spontaneous ventilation and insufflation techniques are useful in the removal of foreign bodies, evaluation of airway dynamics. The technique requires a spontaneously breathing patient and provides a clear view of an unobstructed glottis. Insufflation of anesthetic gases and agents can be achieved by several routes: a small catheter introduced into the nasopharynx and placed immediately above the laryngeal opening; a tracheal tube cut short and placed through the nasopharynx, emerging just beyond the soft palate; a nasopharyngeal airway; and the side arm or channel of a laryngoscope or bronchoscope. However, great care must be taken to prevent the catheter or nasopharyngeal airway from getting very close to or entering the larynx. This would provide a fuel source that could easily cause an airway fire if struck by a laser beam. If the catheter is inadvertently inserted too far, it may enter the esophagus, causing marked gastric distention and possible regurgitation. At a suitable depth of anesthesia, as assessed by clinical observations of the rate and depth of respiration, pupil size, eye reflexes, blood pressure, and heart rate changes, laryngoscopy is undertaken and topical lidocaine administered Anesthesia Management for Laryngeal Laser Surgery Many laryngeal lesions are resected and removed with the aid of a laser, including papillomas, vocal cord cysts, vocal cord polyps, Reinke edema, vocal cord granulomas, vocal cord microwebs, and scar tissue after intubation. For most of these lesions, airway obstruction is not significant, and several anesthesia techniques are appropriate. The preoperative assessment should identify the type and size of laryngeal lesion to establish the extent of airway compromise and establish the general medical status of the patient. The exact anesthesia technique chosen is determined by the experience of the anesthesiologist, surgical preference and access, equipment available, type of laser used, duration of the procedure, type and vascularity of the lesion, and protection against airway soiling from blood and secretions. Two approaches are used: closed systems, in which a cuffed laser tracheal tube is used, and open systems, in which a cuffed laser tracheal tube is absent. The technique chosen for a procedure is not absolute and may have to change as surgical and anesthesia requirements change. One hundred percent oxygen is administered by face mask with spontaneous ventilation and anesthesia continued with inhalational (insufflation) or an intravenous route (propofol infusion). At a suitable depth of anesthesia assessed by clinical observations, the surgeon undertakes rigid laryngoscopy or bronchoscopy. Movements of the vocal cords are usually minimal with a spontaneously breathing technique, provided an adequate level of anesthesia is maintained. If the depth of anesthesia is too light, the vocal cords may move, the patient may cough, or laryngospasm may occur. If the depth of anesthesia is too great, the patient may become apneic with cardiovascular instability. Careful observation throughout the procedure, observing movements, respiratory rate and depth, cardiovascular stability, and unobstructed breathing, is vital, with the concentration of the volatile anesthetic adjusted accordingly. The insufflation technique requires close cooperation between the anesthesiologist and the surgeon. The limitations of spontaneous ventilation or insufflation techniques include the lack of control over ventilation and the potential for airway soiling. Insufflation techniques may not be suitable for large, soft, floppy lesions, particularly in the supraglottic or glottis regions, which may obstruct the airway after the onset of general anesthesia with spontaneous ventilation. Rita and associates concluded that although the insufflation technique is potentially hazardous, if it is done correctly, it provides an appropriate anesthetic technique for surgery on the larynx of infants. A suspension laryngoscope and microscope, which provided excellent visualization of the larynx, were used in these cases so that endotracheal intubation could be readily accomplished without moving the laryngoscope. The apneic technique removes all the flammable material from the larynx during laser actuation and is thought to greatly decrease the possibility of an airway fire. Weisberger and Miner stated that the apneic period should be shortened for small children because of their decreased functional residual capacity. Jet Ventilation Techniques Jet ventilation techniques are suitable for ventilation during laser surgery of most adult vocal cord lesions. The main limitation for their use is the experience of the anesthesiologist and the absence of suitable equipment. Jet ventilation techniques involve the intermittent administration of high-pressure jets of air, oxygen, or oxygen-air mixtures that entrain room air and lower the delivered pressures. The risk of life-threatening barotrauma is the most serious complication, and it occurs when entrainment of room air is absent. The frequency of ventilation and the location of the jet cannula should be selected according to the degree of airway obstruction and the location of the lesion. Specially designed catheters, laryngoscopes, bronchoscopes, and ventilators are available for the clinician to choose from. Many techniques have been described, claiming different advantages over the other methods. There is no clear consensus about the ideal ventilation modes or the laser techniques. Selection must be done based on a thorough understanding of the pathophysiology of airway obstruction and individual experience with use of these devices. If mucosal disruption is noticed, the jetting catheter should be positioned away from the mucosal opening because pressure drops rapidly with the distance from the jetting orifice. During a 2-year period, 51 procedures were performed by the investigators on nine patients who had juvenile laryngeal papillomatosis. After induction of general anesthesia, the patients were paralyzed with atracurium or vecuronium and anesthesia maintained with halothane or enflurane in 100% oxygen. This resulted in a rapid rise in the oxygen saturation so that repeated extubations and surgery could continue. The median number of apneic episodes required for each procedure was two, with a range of one to five. Supraglottic jet ventilation techniques allow a clear, unobstructed view for the surgeon with no risk of a laser airway fire. However, if the surgeon places surgical swabs into the operating field, there is a risk of an airway fire with the swab acting as a fuel source. Subglottic Jet Ventilation Elective transtracheal catheter placement under local anesthesia in individuals with significant airway pathology or under general anesthesia for elective laryngeal surgery has been described. Other potential problems include blockage, kinking, infection, bleeding, and failure to site the catheter. None of the commercially available transtracheal catheters is specifically designed for laser use, and transtracheal jet ventilation techniques for endoscopic laser surgery of the larynx require a careful evaluation of the potential risks and benefits. Jet Ventilation Frequency Low-Frequency Jet Ventilation Subglottic jet ventilation involves placing a small (2- to 3-mm external diameter) catheter or specifically designed tubes. This means a fuel source is present within the airway, and care must be taken during laser airway surgery. Many of the subglottic catheters that are commercially available have some laser-resistant properties, but if their tolerance is exceeded, the catheters can degrade and fracture. If after a fracture of the catheter and after a laser strike, jet ventilation is resumed, the distal fragment may be forced into the distal airways. Subglottic jet ventilation is more efficient than supraglottic jet ventilation and results in reduced driving pressures, minimal vocal cord movements, a good surgical field, and no time constraints for the surgeon in the placement of the rigid laryngoscope. Low-frequency ventilation typically describes ventilatory rates of less than 60 breaths per minute (1 Hz), and in practice, most lowfrequency ventilation is accomplished by a manual Sanders-type device at rates of 15 to 25 breaths per minute. With sufficient driving pressures, this leads to near-normal tidal volumes, visible chest inflation, and passive chest deflation. The green basket of the Hunsaker catheter reduces catheter tip movement within the trachea. To prevent barotrauma, a reducing valve and a pressure regulator should be in line so that the oxygen pressure is limited to 50 psi for adults. The anesthesiologist should start with much lower values and gradually increase the pressure while observing the chest movements. Holding down the handheld lever controls the duration and frequency of the jet of oxygen. The actual delivered tidal volume, concentration of oxygen, and inspiratory pressures depend on the amount of air entrainment by the jet, length of the cannula and its alignment to the trachea, size of the laryngoscope, and lung compliance. These factors are hard to measure in a clinical situation with any great precision and are at best estimates. Adequate ventilation is accomplished in most patients who are anesthetized and given muscle relaxants. The minimal possible pressure that can provide adequate ventilation should be used. The Venturi jet must be kept in perfect alignment with the trachea to achieve streaming of the flow into the lungs. Anesthesiologists should be watchful after any readjustment of the operating laryngoscope to which the jet is clamped, which may impair ventilation of the lungs. Oxygen saturation must be constantly monitored and chest movement continually observed. During supraglottic jet ventilation, there is considerable movement of the laryngeal structures, and the timing of each breath can be coordinated with the surgeon operating the laser. Short-acting muscle relaxants are used to prevent movements of the patient that can be dangerous during a laser operation. Gastric distention with possible regurgitation may occur with a misaligned cannula,139 and a nasogastric tube may be required. Adequate fluids are given intraoperatively, and gases may be humidified in the postoperative period to prevent mucosal drying. Air trapping and stacking of breaths are inherent problems in high-frequency ventilation because of short expiratory times. Obstruction to gas outflow can easily occur because of the tumor and because of the presence of surgical instruments, bleeding, and mucosal edema. Light anesthesia or inadequate muscle relaxation can cause laryngospasm, closing the glottis and further obstructing the airflow. In this method using combined (superimposed) frequencies of ventilation, the location of the gas inflow in the airway seems to influence the efficiency of jet ventilation. Supraglottic, combined-frequency ventilation seems to be superior to subglottic, monofrequent jet ventilation in providing an unobstructed view and access to glottis. High-frequency ventilation should be reserved for patients with severe airway obstruction or severe pulmonary dysfunction. Most cases do well with a variety of simpler techniques that are well established. They include ventilation with a laser-resistant tube or microlaryngoscopy tube, supraglottic jet ventilation with a jet needle, and subglottic jet ventilation with a catheter. Complications have been associated with various ventilation techniques in laser resections (Table 39. This is an effective ventilation method that provides adequate gas exchange with excellent views and access to the surgical site. To-and-fro movements of the major airways that are invariably present during normal respiratory excursions are not present. Because a small tidal volume is used, there is less movement of the larynx, trachea, and lungs. Ventilators should initially be set at the lowest possible driving pressures and increased incrementally while carefully observing chest movements. Anesthetic Management for Tracheobronchial Tree Laser Surgery Laser resection is the preferred method for removal of obstructive lesions from the trachea and bronchus. With more than 4000 published interventions, the safety and efficacy of laser bronchoscopy have been well established. Maintaining unhampered views of the operative field, gaining free and safe access to the laser, and supplying adequate ventilation are essential in choosing a method of anesthetic management, and these are not easy measures to provide for patients with an obstructed airway. The challenge is to preserve adequate gas exchange while maintaining good visualization and surgical access to the lesion. Prolongedmasksupport(10) Prolongedendotracheal intubation(5) Laryngospasm(5) Prolongedsleeporparalysis(2) the primary advantage of using a laser for recurrent benign tumors is that multiple resections can be safely performed in outpatients. In cancer patients, endoscopic palliation helps in evaluation and staging of malignant tumors. These treatments reduce morbidity during chemotherapy without increasing surgical complications. Often, mechanical ventilation is successfully discontinued and death from suffocation postponed. Good communication and cooperation are important, and development of a team approach is necessary for successful results. Mechanical issues deal with attaining good surgical access while simultaneously providing adequate gas exchange and anesthesia. Distal lesions pose a greater challenge because they can cause complete airway obstruction and are difficult to reach with laser treatment. An ideal treatment modality for endoscopic ablation provides secure airway protection, excellent visualization of the lesion, and delivery of safe and effective method of treatment. First decide on the type of laser therapy, type of scope, and technique of ventilation.

Mild-to-moderate elevations of serum bilirubin and aminotransferase levels are common in typhoid fever pain medication for dogs spayed order azulfidine now. Hepatic damage appears to be mediated by bacterial endotoxin back pain treatment options order 500mg azulfidine, which can produce nonspecific reactions homeopathic treatment for shingles pain discount azulfidine 500 mg with visa, such as sinusoidal and portal inflammation pain buttocks treatment buy azulfidine with american express, necrosis myofascial pain treatment vancouver buy discount azulfidine on-line, hypertrophy of Kupffer cells pain medication for dogs with osteosarcoma cheap 500 mg azulfidine with mastercard, and nonnecrotizing granulomas. First-line treatment is with a fluoroquinolone, although resistance is increasing in some areas. Patients with hepatic involvement have underlying comorbidities such as diabetes mellitus, cirrhosis, or hemochromatosis; excess tissue iron appears to be a predisposing factor. Aminoglycosides or tetracyclines are first-line treatment, although fluoroquinolones may also be effective. Hepatic involvement, predominantly as jaundice, is frequent in multiorgan Rocky Mountain spotted fever; pathologic examination reveals portal perivascular inflammation and vasculitis. Cervicofacial infection is the most frequent manifestation of actinomycosis, and gastrointestinal involvement is common (13% to 60% of cases). Hepatic involvement is present in 15% of abdominal actinomycosis cases, most often as abscesses and is thought to result from metastatic spread from other abdominal sites through the portal vein. The course is more indolent than that of other causes of pyogenic hepatic abscess (see Chapter 30). The diagnosis is based on aspiration of an abscess cavity and visualization of characteristic "sulfur granules" or a positive anaerobic culture. The treatment of choice is a prolonged course of intravenous penicillin; alternative options include tetracycline or clindamycin. An acute febrile illness is accompanied by jaundice, hemolysis, hepatosplenomegaly, and lymphadenopathy. Mortality rates resulting from sepsis or hemolysis approach 40%, but prompt treatment with chloramphenicol, fluoroquinolones, or tetracycline prevents fatal complications. The infection manifests as an acute febrile illness with arthralgias, headaches, and malaise or as a subacute or chronic disease. Hepatomegaly and abnormal liver biochemical test levels are common; jaundice may be present in severe cases. Typically, liver histologic examination shows multiple noncaseating granulomas and, less often, focal portal tract infiltration or fibrosis. The diagnosis is confirmed by serologic testing in combination with an animal exposure history. Leptospirosis is among the most common zoonoses in the world, with a wide range of do- 2. Human-to-human transmission is uncommon; rather, transmission occurs via contaminated urine, soil, water, or animal tissue. Up to 80% of the population has been exposed in some tropical countries; it is uncommon in the United States. Human disease can occur as one of two syndromes: Anicteric leptospirosis and Weil disease. Anicteric leptospirosis accounts for more than 90% of cases and is characterized by a selflimited biphasic course. A few patients have elevated serum aminotransferase and bilirubin levels with hepatomegaly. The second, or immune, phase, lasting 4 to 30 days, follows 1 to 3 days of improvement and is characterized by myalgias, nausea, vomiting, abdominal tenderness, and aseptic meningitis in up to 80% of patients. Weil disease is a severe icteric form of leptospirosis and constitutes 5% to 10% of all cases. During the second phase, fever may be high, and hepatic and renal manifestations predominate. Aminotransferase levels usually do not exceed five times the upper limit of normal, and thrombocytopenia is common. Acute tubular necrosis, which can lead to renal failure, cardiac arrhythmias, and hemorrhagic pneumonitis, are common. Liver histologic examination reveals individual hepatocyte damage and canalicular cholestasis with mild portal inflammation. Doxycycline 200 mg per day is given in mild cases (effective only if given early) and as prophylaxis. Severe cases require intravenous penicillin, with the risk of a Jarisch-Herxheimer reaction. Congenital syphilis Liver involvement may result from immunologic mechanisms and is worsened by penicil- lin treatment. Newborns have characteristic mucocutaneous lesions and osteochondritis, as well as hepatosplenomegaly and jaundice. Liver histologic examination reveals diffuse hepatitis with spirochetes seen mostly in the spaces of Disse. Secondary syphilis Liver involvement is characteristic (up to 50% of cases) and usually manifests with non- specific symptoms. Biochemical testing generally reveals low-grade elevations of serum aminotransferase and bilirubin levels, with a disproportionate elevation of the serum alkaline phosphatase level. Liver histologic examination reveals focal necrosis, especially in the periportal and centrilobular regions, or granulomas and portal vasculitis. Liver dysfunction may be worsened by the Jarisch-Herxheimer reaction as a response to treatment, which can occur with treatment of all spirochete infections. Occasionally, tender hepatomegaly and nodularity may raise the suspicion of metastatic cancer (hepar lobatum). If hepatic involvement is unrecognized, hepatocellular dysfunction and complications of portal hypertension can ensue. Characteristic lesions are single or multiple gummas with central necrosis, often surrounded by granulation tissue consisting of a lymphoplasmacytic infiltrate with endarteritis obliterans. Predominant manifestations are dermatologic, cardiac, neurologic, and musculoskeletal. Hepatic involvement occurs in 20% to 40% of affected patients and usually manifests as hepatomegaly with increased serum aminotransferase and lactate dehydrogenase levels. In early stages, spirochetes disseminate hematogenously from the skin and multiply in the organs of the reticuloendothelial system, including the liver. The clinical picture is suggestive of acute hepatitis and often accompanies erythema chronicum migrans, the sentinel rash. Liver histologic examination reveals hepatocyte ballooning, marked mitotic activity, microvesicular fat, hyperplasia of Kupffer cells, a mixed sinusoidal infiltrate, and intraparenchymal and sinusoidal spirochetes on Warthin-Starry stain. The diagnosis is confirmed by serologic testing in a patient with a typical clinical history. Hepatic involvement does not appear to affect the overall outcome, which is excellent in primary disease after antibiotic treatment with doxycycline or penicillin. Chloroquine and primaquine (chloroquinesensitive) or mefloquine and primaquine (chloroquineresistant) (eliminate exoerythrocytic forms)b Endemic Areas Predisposing Pathophy Factors siology Manifesta tions Diagnosis Treatmenta Malaria Africa, (Plasmodium Asia, South falciparum, America P. Malarial sporozoites injected by an infected female Anopheles mosquito circulate to the liver, enter hepatocytes, and mature to schizonts. When the schizont ruptures, merozoites are released into the bloodstream and invade erythrocytes. The four major species of Plasmodium responsible for malaria differ with respect to the number of merozoites released and the maturation times. Unconjugated hyperbilirubinemia is most commonly seen as a result of hemolysis, but occasional hepatocyte dysfunction can be seen, leading to conjugated hyperbilirubinemia as well as a prolonged prothrombin time. Reversible reductions of portal venous blood flow during the acute phase of falciparum malaria may be a consequence of micro-occlusion of portal venous branches by parasitized erythrocytes. Histopathology In an acute attack of falciparum malaria, large quantities of malarial pigment, hemozoin (an iron porphyrin protein complex resulting from hemoglobin degradation by the parasite) accumulates in Kupffer cells, which hypertrophy and phagocytose erythrocytes. Tender hepatomegaly and splenomegaly, as well as jaundice caused by hemolysis, are common in adults, especially with heavy infection by P. Hepatic failure is generally seen only in association with concomitant viral hepatitis or with severe P. Diagnosis the differential diagnosis includes hepatotropic and nonhepatotropic viral hepatitis, gastroenteritis, amebic liver abscess, yellow fever, typhoid fever, tuberculosis, leptospirosis, and brucellosis. The diagnosis of acute malaria rests on clinical history, physical examination, and identification of parasites on peripheral thick or thin blood smears. Because the number of parasites in the blood may be small, repeated smear examinations should be performed when the index of suspicion is high. Several rapid antigen detection assays now exist with sufficient sensitivity and specificity to be clinically useful in endemic regions. Treatment Treatment depends on the species and the pattern of chloroquine resistance for falciparum infection. Hyperreactive malarial splenomegaly (tropical splenomegaly syndrome) Repeated exposure to malaria may lead to an aberrant immunologic response with overproduction of immunoglobulin M (IgM) malarial antibody and high levels of IgM aggregates, dense hepatic sinusoidal lymphocytosis (similar to that seen in Felty syndrome), hyperplasia of Kupffer cells, and massive splenomegaly. Severe anemia resulting from hypersplenism, especially in women of childbearing age, can result; variceal bleeding is uncommon. Treatment consists of lifelong antimalarial therapy and supportive care of anemia with blood transfusions. Babesiosis Babesiosis is caused by Babesia species and transmitted by the deer tick Ixodes scapularis (also known as I. It is a malaria-like illness endemic to the Northeast and Midwest of the United States, most often between May and September. Patients present with fever, anemia, hepatosplenomegaly, and abnormal liver biochemical test levels. Combination therapy with atovaquone 750 mg twice daily and azithromycin 500 mg followed by 250 mg once daily or with clindamycin 600 mg three times daily and quinine 650 mg three to four times daily for 7 days is recommended. Clinical features Only the erythrocytic stage of malaria is associated with clinical illness. Symptoms Downloaded for Anonymous User (n/a) at Consortium Egypt - Mansoura University from ClinicalKey. Life cycle the parasite multiplies in the gut of the female sandfly as a flagellated promastigote and migrates to the pharynx. Following injection into the human host, promastigotes are phagocytosed by macrophages in the reticuloendothelial system, where they multiply as amastigotes and are taken up with the next blood meal of the sandfly. Visceral infection begins with a papular or ulcerative skin lesion at the site of the sandfly bite (similar to the cutaneous form of the disease). Following an incubation period of 2 to 6 months, twice daily fevers, weight loss, diarrhea (of bacillary, amebic, or leishmanial origin), and progressive painful hepatosplenomegaly develop, often accompanied by pancytopenia and a polyclonal hypergammaglobulinemia. Advanced chronic schistosomal liver disease can be managed with a distal splenorenal shunt with or without splenopancreatic disconnection or esophagogastric devascularization with splenectomy. Since the advent of praziquantel, complicated schistosomal liver disease has become uncommon. Fascioliasis Fascioliasis, caused by the sheep liver fluke Fasciola hepatica, is endemic in many areas of Europe and Latin America, North Africa, Asia, the Western Pacific, and some parts of the United States, and it causes >2 million infections worldwide. Hosts become infected when they consume plants bearing the encysted organisms, which bore into the intestinal wall, enter the abdominal cavity, penetrate the hepatic capsule, and settle in the bile ducts, where they develop into adults within 3 to 4 months and reach a length of 20 to 30 mm. Clinical features Fascioliasis is divided into three phases corresponding to three syndromes. Urticaria with dermatographia and nonspecific gastrointestinal symptoms are common. Affected persons are mostly asymptomatic but may experience vague gastrointestinal symptoms. This phase may be marked by recurrent biliary pain, cholangitis, cholelithiasis, and biliary obstruction. Blood loss may result from epithelial injury, and rare cases of overt hemobilia have been described. Long-term infection may lead to biliary cirrhosis and secondary sclerosing cholangitis, but no convincing association with malignancies of the liver or biliary tract exists. In the latent and chronic phases, the diagnosis is made definitively by detection of eggs in stool, duodenal aspirates, or bile. Hepatic histologic findings include necrosis and granuloma formation with eosinophilic infiltrates and Charcot-Leyden crystals. Eosinophilic abscesses, epithelial hyperplasia of the bile ducts, and periportal fibrosis may also be seen. Treatment Unlike other liver fluke infections, praziquantel is not effective for fascioliasis. Treatment is a single dose of triclabendazole 10 mg/kg once or twice; alternatively, nitazoxanide or bithionol may be effective. Clonorchiasis and opisthorchiasis Clonorchis sinensis, Opisthorchis viverrini, and O. Life cycle All species require two intermediate hosts-an aquatic snail and freshwater fish. Eggs are passed in the feces into fresh water, are consumed by snails, and hatch as free-swimming cercariae, which seek and penetrate fish or crayfish and encyst in skin or muscle as metacercariae. The metacercariae excyst in the small bowel and migrate into the ampulla of Vater and bile ducts, where they mature into 10- to 20-mm adult flukes. Clinical features Infection is clinically silent or associated with nonspecific features, with fever, abdominal pain, and diarrhea. Chronic manifestations correlate with the fluke burden and are dominated by fever, right upper quadrant pain, tender hepatomegaly, and eosinophilia. With a heavy worm burden in the bile ducts, chronic or intermittent biliary obstruction can ensue, with frequent development of cholelithiasis, cholecystitis, jaundice, and, ultimately, recurrent pyogenic cholangitis (see Chapter 35). Serum alkaline phosphatase and bilirubin levels are elevated, and mild to moderate elevations of serum aminotransferase levels are also seen. Long-standing untreated infection leads to exuberant inflammation resulting in periportal fibrosis, marked biliary epithelial hyperplasia and dysplasia, and a substantially increased risk of cholangiocarcinoma. Cholangiocarcinoma resulting from clonorchiasis or opisthorchiasis tends to be multicentric and arises in the secondary biliary radicles of the hilum of the liver. The diagnosis should be suspected in infected persons with weight loss, jaundice, epigastric pain, or an abdominal mass.