Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with the acquired immune deficiency syndrome (AIDS) frequently develop hepatic dysfunction. Although hepatic injury may indirectly result from malnutrition, hypotension, administered medications, sepsis, or other conditions, the hepatic injury is frequently due to opportunistic hepatic infection, directly related to AIDS. Infection with Mycobacterium avium intracellulare typically occurs in patients with advanced immunocompromise and with systemic symptoms due to widely disseminated infection. In contrast, hepatic tuberculosis often occurs with less advanced immunocompromise. Cytomegaloviral infection may produce a hepatitis. Cytomegaloviral and cryptosporidial infections have been implicated as causes of acalculous cholecystitis and of a secondary sclerosing cholangitis. About 10-20% of patients with AIDS have chronic hepatitis B infection. These patients tend to develop minimal hepatic inflammation and necrosis. The clinical findings in patients with hepatic cryptococcal infection are usually due to concomitant extrahepatic infection. Hepatic histoplasmosis usually develops as part of a widely disseminated infection with systemic symptoms. Hepatic involvement by Kaposi's sarcoma is rarely documented ante mortem because an unguided liver biopsy is an insensitive diagnostic procedure. Patients with non-Hodgkin's lymphoma of the liver typically have lymphadenopathy, hepatomegaly, and systemic symptoms. As a pragmatic approach, patients with liver dysfunction and HIV-related disease should have a sonographic or computerized tomographic examination of the liver. Patients with dilated bile ducts should undergo endoscopic retrograde cholangiopancreatography because opportunistic infection may produce biliary obstruction. Patients with a focal hepatic lesion should be considered for a guided liver biopsy. Patients with a significantly elevated serum alkaline phosphatase level should be considered for a percutaneous liver biopsy. When performed for these indications, liver biopsy will demonstrate a significant disease involving the liver in about 50% of patients with AIDS and in about 25% of patients who are HIV seropositive but who are not known to have AIDS. The clinical impact of a diagnostic biopsy is blunted by a lack of efficacious therapy for many opportunistic infections.
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PMID:Hepatobiliary manifestations of the acquired immune deficiency syndrome. 198 33

Detection of a Histoplasma capsulatum polysaccharide antigen (HPA) has proved a useful approach to diagnosis of histoplasmosis. Two sandwich enzyme-linked immunosorbent assays (ELISAs) using alkaline phosphatase (AP)-or horseradish peroxidase (HRP)-conjugated antibodies were compared with solid-phase radioimmunoassay (RIA) for detection of HPA. The AP-ELISA and HRP-ELISA were each positive in 17 (89.5%) of 19 urine specimens from patients with disseminated histoplasmosis, while the RIA was positive in 18 (94.7%) of 19. Specimens from patients with nondisseminated histoplasmosis were positive by AP-ELISA in 8 of 32, by HRP-ELISA in 4 of 25, and by RIA in 12 of 25. Of control specimens from patients with other fungal infections, the AP-ELISA was negative in 22 (91.7%) of 24, the HRP-ELISA in 23 (95.8%) of 24, and the RIA in 23 (95.8%) of 24. Reproducibilities AP-ELISA and HRP-ELISA were 95.1% and 95.1%, respectively. Thus, AP-ELISA and HRP-ELISA appear less sensitive than RIA and may be falsely negative in specimens containing low levels of HPA.
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PMID:Comparison of sandwich solid-phase radioimmunoassay and two enzyme-linked immunosorbent assays for detection of Histoplasma capsulatum polysaccharide antigen. 279 60

A urease-antibody conjugate was used in an enzyme-linked immunoassay (ELISA) for the detection of antibodies in blastomycosis. A Blastomyces dermatitidis immunodiffusion antigen was used as the reference antigen in a solid phase indirect ELISA procedure and the endpoints were determined visually. Urease ELISA results on serum specimens from patients with blastomycosis compared favorably (90%) with results obtained spectrophotometrically by the alkaline phosphatase enzyme system. Specificity was evaluated with assays on sera from patients with histoplasmosis (20% cross reactivity), coccidioidomycosis (0% cross reactivity) and on Histoplasma capsulatum skin-test positive individuals (0% cross reactivity). The ease of performance of the urease ELISA combined with no requirements for specialized spectrophometric equipment are factors that favor the continued development of the test as an alternative serodiagnostic method. The assay may prove to be useful and a valuable adjunct to fungal antibody screening procedures.
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PMID:Use of a urease-antibody conjugate in an enzyme immunoassay for the detection of blastomycosis. 366 59

Four patients with disseminated histoplasmosis, two of whom had late relapses after previous therapy with amphotericin B, were treated with ketoconazole 200 to 400 mg daily for 1 year. All patients improved markedly during therapy, with resolution of symptoms decreasing liver and spleen size, and weight gain; resolution of oral ulcers occurred in the two patients in whom they were present. Decrease in serum alkaline phosphatase levels correlated well with clinical improvement. One patient who was much improved while receiving ketoconazole continued to harbor Histoplasma capsulatum in an abdominal aortic aneurysm, which became symptomatic 4 months after cessation of the drug. He underwent aneurysmectomy, and H. capsulatum isolated from the resected aneurysm was susceptible in vitro to ketoconazole. No significant adverse reactions to the drug were noted despite prolonged therapy. Our results indicate that ketoconazole may have a role in the therapy of disseminated histoplasmosis in adults.
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PMID:Progressive disseminated histoplasmosis; favorable response to ketoconazole. 626 75

We have compared risk factors for cavitary histoplasmosis in 62 patients with that manifestation of the infection and in 679 patients with other forms of histoplasmosis, and we have evaluated the clinical and laboratory findings in 45 patients with cavitary histoplasmosis who were cared for at the Indiana University Medical Center hospitals during two large histoplasmosis outbreaks. Chronic obstructive lung disease and old age were the strongest risk factors for cavitary histoplasmosis but male sex, white race and immunosuppression were also important in certain patient groups. Fever, sweats, weight loss, productive cough, anemia, lymphopenia, and alkaline phosphatase elevation were common findings. The patients were occasionally incorrectly treated for presumed class 3 tuberculosis. Cultures were positive in 58% of patients, with sputum samples providing the highest yield (61%). Histoplasmal serologic tests provided useful clues to the diagnosis, positive in over 90% of cases. About one-third of patients recovered spontaneously while another 35% improved following treatment. About 4% developed chronic untreated cavitary histoplasmosis characterized by clinical and roentgenographic exacerbations and remissions. Of the deaths in four patients with untreated disease, one was caused by disseminated histoplasmosis while three died of other causes. Ketoconazole appeared effective in three of seven patients while its effect in three additional patients was uncertain. Toxicity precluded completion of ketoconazole therapy in one patient. Only amphotericin B has been proven to be effective therapy for cavitary histoplasmosis.
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PMID:Cavitary histoplasmosis occurring during two large urban outbreaks. Analysis of clinical, epidemiologic, roentgenographic, and laboratory features. 673 42

Comparative studies were performed to assess the stability and lot-to-lot variation of Blastomyces dermatitidis yeast and mycelial phase lysate antigens. Four lots were prepared from each growth phase of B. dermatitidis strain T-58 (canine isolate) during a 14-month period. Serum specimens from dogs with blastomycosis, histoplasmosis, coccidioidomycosis, cryptococcosis and aspergillosis were assayed for antibody content using an alkaline phosphatase enzyme-linked immunosorbent assay (ELISA). The four lots of the yeast phase reagents were similar with respect to sensitivity and specificity, and the absorbance readings were approximately four times greater with sera from dogs with blastomycosis than with histoplasmosis or coccidioidomycosis. Even less cross-reactivity was evidenced when the sera from dogs with cryptococcosis and aspergillosis were assayed. In contrast, the four lots of the mycelial lysate reagents were considerably less reactive and more cross-reactive than the yeast phase antigens and, as above, the four reagents retained their activity after prolonged storage. Therefore the results indicated that the lysate antigens exhibited a great deal of stability and lot-to-lot variations in activity were not observed.
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PMID:Comparative stability, sensitivity and specificity studies with different lots of Blastomyces dermatitidis yeast and mycelial lysate antigens. 789 10

Granulomatous hepatitis (GH) is an uncommon histopathologic diagnosis in dogs. On the basis of clinical reports, fungal infections appear to be the most common cause of GH in dogs, but many other potential causes have been identified. The medical records and histopathologic findings for 9 dogs with GH were reviewed to identify additional specific causes of GH in dogs. Diseases associated with GH included intestinal lymphangiectasia (n = 2), lymphosarcoma (n = 1), histiocytosis (n = 1), dirofilariasis (n = 1), and histoplasmosis (n = 1). In 1 dog, no other disease process was identified. Of the remaining 2 dogs, 1 had concurrent granulomatous pneumonitis of unknown cause, and the other had periportal hepatitis and temporal muscle wasting. All 9 dogs with GH had clinical evidence of liver disease, such as hepatomegaly, icterus, and ascites, or had high serum alkaline phosphatase and alanine aminotransferase activity. Because of the wide variety of potential causes of GH in dogs, an accurate diagnosis should be sought so that appropriate treatment can be chosen and an accurate prognosis given.
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PMID:Granulomatous hepatitis in dogs: nine cases (1987-1990). 840 37

51 cases of granulomatous hepatitis were seen among 1234 liver biopsies over a 10 year period. Tuberculosis was the commonest cause seen in 55 percent of cases. Other causes included leprosy, sarcoidosis, histoplasmosis, brucellosis, amoebic liver abscess, lymphoma and malignant granuloma. 12 percent of cases remained undiagnosed. Clinically these patients presented with pyrexia and hepatosplenomegaly. Jaundice was uncommon. Many showed elevated alkaline phosphatase levels, anaemia and raised ESR Granulomatous hepatitis of unknown aetiology with FUO was seen in 6 percent cases only.
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PMID:Granulomatous hepatitis: a retrospective study. 972 54

We report factors associated with severe manifestations of histoplasmosis (such as shock, respiratory failure, and death) in patients with AIDS during an outbreak. Severe disease was present in 28 of 155 patients (17.9%). The following factors were associated with severe disease: black race (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.2-6.2); hemoglobin level <9.5 g/dL (OR, 2.7; 95% CI, 1.2-6.4), partial thromboplastin time >45 s (OR, 3.1; 95% CI, 1.1-9.3); alkaline phosphatase level >2.5 times normal (OR, 3.4; 95% CI, 1.3-8.7); aspartate aminotransferase level >2.5 times normal (OR, 4.2; 95% CI, 1.7-10.0); bilirubin level concentration >1.5 mg/dL (OR, 9.2; 95% CI, 2.5-34.3); creatinine concentration >2.1 mg/dL (OR, 8.3; 95% CI, 2.2-31.9); and albumin concentration <3.5 g/dL (OR, 4.6; 95% CI, 1.3-16.4). Zidovudine use was associated with decreased risk of severe disease (OR, 0.3; 95% CI, 0.1-0.7). Multivariate analysis showed that a creatinine value >2.1 mg/dL (OR, 9.5; 95% CI, 1.7-52) and an albumin value <3.5 g/dL (OR, 4.8; 95% CI, 1.0-22) were associated with an increased risk of severe disease, and zidovudine therapy remained associated with a decreased risk (OR, 0.2; 95% CI, 0.1-0.6). Findings associated with severe histoplasmosis should be recognized early and the cases managed aggressively.
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PMID:Factors associated with severe manifestations of histoplasmosis in AIDS. 1085 63

HIV caregivers face many challenges following initiation of ART. The development of jaundice is uncommon but worrisome. In this case, two distinct and contrasting episodes of jaundice were observed. In the first instance, isolated elevation of the indirect bilirubin without elevation of the alkaline phosphatase was noted. The normal PT and serum aminotransferase levels indicate the absence of intrinsic liver dysfunction. Elevations in the indirect bilirubin may result from either impaired uptake/conjugation or excess production. The latter, usually from acquired hemolysis, may be a complication of an occult NHL. A work-up for this AIDS-related malignancy was not initiated since the caregivers recognized jaundice as a complication of IDV, which inhibits UDP-glucuronyl transferase and produces a Gilbert's-like syndrome. Physicians can expect to encounter this syndrome even more frequently with ATV. Experienced patients given RTV-boosted ATV have experienced elevations of unconjugated hyper-bilirubinemia in up to 45 percent of cases in clinical trials. However, such elevations do not reflect liver dysfunction and symptomatic jaundice requiring dosage reduction that occurred infrequently (7 to 8 percent of study patients). Counseling patients about this syndrome may promote adherence and prevent self-directed interruptions of ATV that compromise efficacy. The second case of jaundice provides a more formidable diagnostic challenge. The triad of LFT abnormalities (mild elevation of aminotransferases, normal PT, and marked cholestatic jaundice) implies an acute process that is mildly toxic to hepatocytes without affecting their synthetic function. The subacute nature of the patient's cholestatic jaundice suggests either intrahepatic infiltrative disease of the liver or extrahepatic obstruction of the biliary tree, most likely due to the patient's relatively modest level of pain and lack of fever. Despite LFT abnormalities occurring 17 months after a switch in his ART, cumulative drug-related toxicities must still be considered. Ritonavir can produce significant elevations in the AST/ALT, especially with pre-existing chronic liver disease as with hepatitis C virus coinfection. The NRTIs can produce hepatic steatosis, a result of mitochondrial toxicity and impaired fatty acid oxidation. However, jaundice and cholestasis are not typical of the latter syndrome. With a negative contrast CT that excludes parenchymal liver disease, investigation of the biliary tree to assess the presence of AIDS-related cholangitis was the next step. Performing a sphincterotomy or stent placement, and obtaining brushings or biopsy specimens to determine the extent of extrahepatic obstruction may help define a pathogen and be life-saving. The negative results of the ERCP justify the final diagnostic step, a liver biopsy to evaluate microscopic infiltrative disease that might not have been detected on contrast abdominal CT. Examples might include granulomatous disease (MAC), fungal etiologies (histoplasmosis), carcinomatosis (lymphoma, hepatoma, cholangiocarcinoma), and microvascular disease (bacillary angiomatosis). The failure to observe granulomatous inflammation in the liver does not exclude MAC infection, as MAC may involve other peri-aortic or mesenteric lymph nodes. This form of IRIS is unlikely given the abdominal CT findings, lack of systemic complaints, and extended persistence of liver aminotransferases. The nonspecific results of the liver biopsy are a common outcome in advanced AIDS patients with elevated alkaline phosphatase levels. Despite not having identified a pathogen, the biopsy establishes chronic liver disease and prompts re-evaluation and change of treatment to NFV. The subsequent normalization of the patient's aminotransferase levels suggests a prior adverse effect of LPV/r in the setting of unexplained, chronic liver disease. Most importantly, this case highlights the importance of HIV caregivers to review ART for safety when noting chronic liver dysfunction. Patients need to be counseled to minimize acetaminophen use, to consume alcohol in moderation, and to avoid behavior with risk for hepatitis C. Finally, all HIV patients should receive appropriate vaccination against hepatitis A and B if serology shows lack of protective immunity.
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PMID:Clinical vignette in antiretroviral therapy: jaundice. 1498 14


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