Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Therapeutic observations suggest that azidothymidine (AZT)-resistant HIV+/AIDS patients are frequently offered AZT/dideoxycytidine (DDC) or dideoxyinosine (DDI) therapy. The latter therapies have been associated with the development of acute pancreatitis. During the initial portion of this study, when patients reported limiting ethanol consumption, an increase in CD4+, a decrease in amylase, and a decrease in lipase was observed in patients on DDI monotherapy. Marinol/marijuana usage was associated with depressed CD4+ counts and elevated amylase levels within the DDI subgroup. The purpose of this study was to follow these patients over 1 year and compare clinical indicators of pancreatitis and HIV progression. After 1 year, the remaining 56 patients were reexamined in the follow-up portion for clinical indicators of HIV disease progression and pancreatoxic/hepatotoxic effects. Those in the AZT group, who remained on this therapy throughout the year, had significantly increased amylase values from 55.3 to 69.3 IU/liter (p < 0.05). In the AZT/DDC group, those who remained on combination therapy throughout the year, 4 of the 5 clinical indicators of disease progression changed. Amylase, ALT, and AST all increased significantly from 55.2 to 77.8 IU/liter (p < 0.01), from 38.0 to 92.3 IU/liter (p < 0.05), and from 55.2 to 97.0 IU/liter (p < 0.05), respectively. Lipase levels decreased significantly (106.0 to 74.6 IU/liter, p < 0.05). The most remarkable changes occurred in the AZT/DDC group (who reduced ethanol consumption), wherein clinical indicators of pancreatitis and liver dysfunction declined, including amylase (65.0 to 20.0 IU/liter, p < 0.05), ALT (350.0 to 100.0 IU/liter, p < 0.01), and AST (240.0 to 95.0 IU/liter, p < 0.01). No significant changes were noted in the DDI or AZT groups. Marinol/marijuana use was associated with declining health status in both the AZT and AZT/DDC groups. In contrast, all clinical indicators of pancreatitis improved in the DDI patients who utilized Marinol/marijuana, including amylase (-34%), lipase (-30.8%), ALT (-21.4%), and AST (-20.1%). This paired follow-up study suggests that HIV+/AIDS patients on antiretroviral therapies should restrict their ethanol consumption. In HIV+/AIDS patients with the lowest CD4+ counts (those on DDI monotherapy), utilization of Marinol/marijuana does not seem to have a deleterious impact.
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PMID:The impact of ethanol and Marinol/marijuana usage on HIV+/AIDS patients undergoing azidothymidine, azidothymidine/dideoxycytidine, or dideoxyinosine therapy. 904 84

We have studied the effects of LP-BM5 MuLV-induced murine acquired immunodeficiency syndrome (MAIDS) on concomitant murine cytomegalovirus (MCMV) infection in the livers of C57BL mice. A delayed inflammatory response in livers of mice with MAIDS (M+) on day 4 was associated with impaired clearance of MCMV-infected cells 6 days after infection. This correlated with increased levels of inflammation and serum alanine transaminase. The latter reflects enhanced hepatic necrosis, which was evident histologically. Delayed-type hypersensitivity responses to MCMV antigen were unimpaired in M+ mice and were mediated by CD8+ cells. Depletion of NK1.1+ cells from M+ mice increased MCMV replication and associated liver damage on day 6, whereas CD8+ depletion had little effect. In contrast, in the presence of CD8+ cells M- C57BL mice did not require NK1.1+ cells for control of hepatic MCMV infection, but dual NK1.1+ and CD8+ depletion dramatically potentiated hepatic MCMV replication. Our results suggest that M+ mice may acquire non-NK1.1+ and non-CD8+ cells that are able to partially control hepatic MCMV infection. These findings are discussed with reference to mortality in M+ mice after high-dose MCMV infection, as this is initially delayed but ultimately higher than in M- controls.
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PMID:Effect of a retroviral immunodeficiency syndrome on murine cytomegalovirus-induced hepatitis. 906 Aug 44

In 1974, the existence of hepatitis serologically distinct from hepatitis A and B was recognized. They were tentatively designated non-A non-B. They accounted for 90% of post-transfusional hepatitis. During 15 years numerous studies failed to identify agent(s) responsible for these hepatitis. In 1989 the virus responsible for parenteral non-A non-B hepatitis was identified and named hepatitis C virus. Shortly after, the virus responsible for enteral non-A, non-B was also discovered (hepatitis E virus). During these 15 years, a 60% reduction of post-transfusional hepatitis was obtained both by the measures instituted to prevent AIDS transmission and by the introduction of surrogate assays (ALT levels and anti-HBc antibody).
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PMID:[From non-A non-B hepatitis to hepatitis C]. 926 87

Ganciclovir therapy was given intravenously to 20 children with cytomegalovirus (CMV)-associated liver disease, of whom 6 were immunocompetent and 14 were immunocompromised (9 had AIDS and 5 had solid tumors). Immunocompetent children had isolated liver disease diagnosed at birth (4 children), or systemic congenital CMV infection including liver disease (2 children). Ganciclovir was used following two regimens: A) 5 mg/kg twice daily for 8 to 86 days (mean 21); B) 7.5 mg/kg twice daily for 14 days followed by 10 mg/kg three times weekly for three months. CMV infection was diagnosed by viral isolation, detection of viral antigens, and/or CMV DNA from blood and urine. All immunocompetent children had negative CMV culture and CMV DNA detection from blood and/or urine after 14 weeks of treatment. However, the three children who were treated with regimen B showed normal ALT levels at the end of the maintenance course, whereas the children who received ganciclovir with regimen A had normal ALT levels only after about 1 year. All children with tumors initiated regimen B, but only three, who had negative CMV detection and markedly decreased ALT levels, received full treatment; of the remaining two children, one recovered after only an initial course, and the other had therapy interrupted because of hepatic failure and died 9 days later. In contrast, the children with AIDS received several ganciclovir courses for different periods at the lower dosage: they generally improved during treatment but did not recover completely, and five children died with active CMV infections. Based on our study, CMV-associated liver disease can be efficiently treated with ganciclovir both in immunocompetent and immunodeficient children. However, a single ganciclovir course including a higher dosage and prolonged therapy appeared to be more effective than several courses with lower dosages.
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PMID:Ganciclovir therapy for cytomegalovirus-associated liver disease in immunocompetent or immunocompromised children. 934 3

The usefulness of the direct virus detection by polymerase chain reaction (PCR) and reverse transcription/polymerase chain reaction (RT PCR) for blood donor screening was investigated, including the following viruses: cytomegalovirus (CMV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency type 1 virus (HIV1). Hepatitis C viraemia was detected by RT PCR in 97% of anti-HCV-positive haemophiliacs, in 48% of anti-HCV-positive hepatitis patients, in only 21% of anti-HCV-positive blood donors from North-West Germany, and not at all in 945 blood donors with elevated serum ALT. In order to compare HIV1 detection by PCR and by p24 antigen determination, we tested 34 anti-HIV1-positive AIDS patients for p24 antigen, HIV1 RNA and HIV1 provirus DNA. 97% had HIV1 provirus DNA, 35% had HIV RNA, but only 30% had p24 antigen. A multiplex PCR specific for HBV, HCV and HIV1 (RNA and DNA) was developed for the investigation of a blood donor population from Namibia, where HBV and HIV1 infections occur more frequently than in German blood donors. The prevalence of anti-HIV1 antibodies in this population was 0.6%. HIV1 RNA was never detected in the plasma of 2,569 anti-HIV1-negative donors. HIV1 provirus DNA was present in 75% of the 16 anti-HIV1-positive individuals. None of these anti-HIV1-positive blood donors was also positive for p24 antigen. CMV infections and reactivations in 130 immunocompromised heart transplant patients and in 420 healthy anti-CMV-positive blood donors were monitored using cytochemical detection of CMV early antigen, and PCR. CMV DNA was neither detected in the plasma nor in the leucocytes of any anti-CMV-positive blood donor. During the course of CMV reactivation in immunocompromised heart transplant patients, CMV DNA was always detectable first in granulocytes and afterwards in the plasma. The cytochemical demonstration of CMV early antigen was typically delayed by several days and was observed in only 11% of those blood samples which contained CMV DNA in leucocytes. The determination of CMV DNA in leucocytes proved to be the most sensitive method to detect viraemia. Thus, CMV detection in leucocytes is the method of choice for the monitoring of transplant patients. This method is also promising for blood donor screening. The sensitive routine monitoring of blood donations for virus infections by multiplex PCR is practicable. However, nucleic acid must be extracted both from the plasma and from the cellular compartments of blood in order to detect HIV and CMV provirus DNA. Lysate from EDTA blood is a suitable material for this purpose. The determination of the surrogate marker serum ALT activity is of no use in hepatitis C screening, and determination of p24 antigen is not required in HIV1 screening.
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PMID:[Molecular biological screening of viruses important to transfusion medicine]. 948 64

The aim of this study was to describe blood recipients and blood components transfused during the first 24 hours in 13 French hospitals. We included all blood recipients who had not had any blood transfusion within the past six months. Recipients were screened for red cell alloantibodies, the alanine aminotransferase activity and specific viral markers (hepatitis B and C, Human Immunodeficiency Virus). Eligible patients represented 47% of the all transfused. Among the 371 patients included, 57% were males and 71% were transfused in a surgical unit. Alloantibodies, non specific and specific viral markers were detected in 3%, 19% and 2% respectively. Among the patients included, 42 received 172 autologous units. In total, 1056 allogeneic units (an average of 3 units per patient) were transfused; blood products were leucocyte-depleted (49%) or leucocyte-poor (20%); 54% of red cell units were matched for antigens Rh and Kell. Neoplasms were the most frequently reported disease for which patients were transfused. This study provides baseline blood transfusion information on recipients and blood utilization for a specific period in French hospitals. Following this study, a national study will allow the clarification of the characteristics, for instance the surgical procedures requiring transfusion.
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PMID:[Pilot study of the characteristics of transfused patients and utilized labile blood products]. 952 18

Viral load has emerged recently as a reliable marker of disease progression and therapeutic efficacy in chronic infections, including AIDS and hepatitis C. The clinical management of type B hepatitis could also be improved by monitoring viremia levels in patients with chronic liver disease undergoing anti-viral treatment. To address this question we evaluated the performance of a newly developed, quantitative PCR assay (Amplicor HBV Monitor test, Roche Diagnostic Systems) in the assessment of viremia changes over time in a group of 45 patients with chronic active hepatitis (CAH) who received interferon treatment. Of the 45 patients, 14 were HBsAg and anti-HBeAg positive and 31 HBsAg, HBeAg positive. Follow-up extended up to 24 months. An average of ten samples per patient were analyzed for levels of ALT, IgM anti-HBc (Abbott Laboratories), HBV DNA by in-house dot-blot hybridization and hybridization-capture assays (HBV-DNA hybrid capture kit, Murex Diagnostics) and by Amplicor HBV Monitor. A sustained biochemical response was observed at the end of treatment in 12 HBeAg-positive and in seven anti-HBeAg positive patients. This was accompanied by the disappearance of HBeAg and of HBV DNA (hybridization assays) in all cases and by the clearance of IgM anti-HBc in 70% of the cases. Viremia (quantitative PCR assay) became undetectable only in 25-30% of cases and was associated with the loss of HBsAg. A good correlation was observed between the time course of IgM anti-HBc, quantitative PCR and dot-blot hybridization although the latter missed 33% of viremic samples. Together, these results indicate that the Amplicor HBV Monitor test is a robust and standardized assay for quantifying HBV viremia levels in the range from 10(2) to 10(7) copies/ml. Compared to other current markers, viral load may provide additional clinical information by predicting long term virologic response and HBsAg clearance in patients with normal ALT at the end of interferon therapy.
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PMID:Clinical evaluation and applications of the Amplicor HBV Monitor test, a quantitative HBV DNA PCR assay. 977 15

The aim of this study was to assess the natural history of patients after transfusion and the acceptability of a standardized biological follow-up. In 1995, during 1 month, in 13 French hospitals, a follow-up at 3 and 6 months after blood transfusion was proposed to all blood recipients who had not received any blood transfusion within the past 6 months (eligible patients): screening for red cell antibodies, alanine aminotransferase (ALT) activity and specific viral markers of hepatitis B (hepatitis B surface antigen and antibody to hepatitis virus core antigen), of hepatitis C (antibodies) and of Human Immunodeficiency Virus (antibodies). At the beginning of the study, 296 patients were followed for 6 months. A complete follow-up was available at 3 months for 183 patients (62%), at 6 months for 168 (57%) and after 6 months, 198 patients (67%) have been once followed. Of eligible patients, 76% were alive at six months. After transfusion, the incidence of red cell alloantibodies and elevated ALT concentration were respectively 4% and 17%. At 6 months, one patient had Hepatitis B surface antigen; the responsibility of blood transfusion was excluded. Within the first 24 hours, 68 patients (23%) required another blood transfusion and 42% of units were transfused to patients with malignant disease. Our study quantifies in real conditions the difficulty of a biological follow-up in a transfused population, mostly composed of patients that could not be followed in the hospital where they were transfused.
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PMID:[Feasibility of following up transfused patients]. 978 66

We analysed the time from the date CD4+ cell counts fell below 200 x 10(6) L-1, defined as ti, to the onset of clinical AIDS, according to the 1987 Centers for Disease Control and Prevention case definition, in 129 Japanese haemophilia patients infected with HIV-1. The cumulative onset of clinical AIDS was analysed by the Kaplan-Meier method and proportional hazard model. Incorporated covariates were age of each patient at time ti, as well as CD4+ and CD8+ cell counts, serum levels of IgG, IgA, IgM, GOT and GPT at ti. The time of antiretroviral treatment initiation was also considered. The 50% AIDS-free interval after ti was 3.00 years (95% confidence interval (CI), range 0.49-5.51) and 1.71 years (95% CI, range 0.66-2.76) for the patients at CDC stage II and stage III, respectively (significantly different, P = 0.0013). Among the patients at CDC stage II at ti, higher levels of IgA were tightly associated with a shorter period from ti to onset of clinical AIDS (P < 0.0001), and relative hazard was 1.35 (95% CI, 1.11-1.64) with increase of IgA level by 1.0 g L-1. Thus there is a broad distribution in the time to onset of clinical AIDS in Japanese haemophiliacs even after CD4+ cell counts fall below 200 x 10(6) L-1. This should be taken into consideration in deciding upon the therapy and care of HIV-1 infected people.
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PMID:Analysis of clinical AIDS-free interval after CD4+ cell counts fall below 200 x 10(6) L-1 in Japanese haemophiliacs infected with HIV-1. 987 64

Zidovudine is known to be responsible for a mitochondrial myopathy with ragged-red fibres and mitochondrial DNA depletion in muscle. Lactic acidosis alone or associated with hepatic abnormalities has also been reported. A single report mentioned the concomitant occurrence of muscular and hepatic disturbances and lactic acidosis in a patient receiving zidovudine, but muscle and liver tissues were not studied. A 57-year-old man with AIDS, who had been treated with zidovudine for 3 years, developed fatigue and weight loss. Serum creatine kinase and hepatic enzyme levels were high. Lactic acidosis was present. Liver biopsy showed diffuse macrovacuolar and microvacuolar steatosis. After withdrawal of zidovudine, creatine kinase, aspartate aminotransferase, and alanine aminotransferase levels normalised within 5 days, and lactacidaemia decreased. Acidosis persisted. The patient became confused and febrile and died 8 days after detection of high blood lactic acid. A muscle sample obtained at autopsy showed mitochondrial abnormalities with ragged-red fibres and lipid droplet accumulation. Southern blot analysis showed depletion of mitochondrial DNA, affecting skeletal muscle and liver tissue. No depletion was found in myocardium and kidney. This case emphasises that zidovudine treatment can induce mitochondrial multisystem disease, as revealed in our case by myopathy, liver steatosis and lactic acidosis.
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PMID:Zidovudine-induced mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion. 1070 83


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