Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand recent temporal trends in acquired immunodeficiency syndrome (AIDS) mortality in the era of highly active antiretroviral therapy (HAART), trends in causes of death among persons with AIDS in San Francisco who died between 1994 and 1998 were analyzed. Among 5234 deaths, the mortality rate for human immunodeficiency virus (HIV)-related or AIDS-related deaths declined after 1995 (P<.01), whereas the mortality rate for non-HIV- or non-AIDS-related deaths remained stable. The proportion of deaths of persons with AIDS associated with septicemia, non-AIDS-defining malignancy, chronic liver disease, viral hepatitis, overdose, obstructive lung disease, coronary artery disease, and pancreatitis increased (P<.05). The standardized mortality ratio was high for these causes in both pre- and post-HAART periods, except for pancreatitis, a possible complication of HAART, which demonstrated an increasing standardized mortality ratio trend after 1996. With increasing AIDS survival, prevention of chronic diseases, assessment of long-term toxicity from HAART, and surveillance for additional causes of mortality will become increasingly important.
 ...
PMID:Trends in causes of death among persons with acquired immunodeficiency syndrome in the era of highly active antiretroviral therapy, San Francisco, 1994-1998. 1223 45

A 31-year-old Japanese male was admitted to our hospital for investigation of an asymptomatic nodular lesion of the liver detected by abdominal ultrasonography (US) during a routine medical examination. Computed tomography (CT) revealed a single, hypovascular mass 35 mm in diameter, within the left lobe of the liver. The tumor demonstrated hypointensity on T1-weighted, and hyperintensity on T2-weighted magnetic resonance (MR) imaging. Hematological and biochemical investigations were normal. There were no abnormalities of the gastrointestinal or urinary tracts. A left lateral segmentectomy of the liver was performed. Pathological examination of the nodule revealed a primary leiomyoma of the liver, with positive immunohistochemical staining for vimentin and desmin antigens. Primary leiomyoma of the liver is rare, with the majority of cases associated with immunodeficiency disorders. This patient had no evidence of any underlying disease. Primary leiomyoma of the liver should be considered when a nodular lesion is found in a patient without evidence of viral hepatitis.
 ...
PMID:A case of primary leiomyoma of the liver in a patient without evidence of immunosuppression. 1224 95

Since 1998, CDC has collaborated with approximately 140 federally funded hemophilia treatment centers (HTCs) in the United States and its territories through the Universal Data Collection (UDC) surveillance project to monitor blood product safety and detect new viral hepatitis and human immunodeficiency virus (HIV) infections. This report presents findings of investigations conducted during May 1998-June 2002 of 1,149 seroconversions for hepatitis viruses identified among persons with bleeding disorders who were enrolled voluntarily in UDC; 99% of hepatitis A virus (HAV) seroconversions and 90% of hepatitis B virus (HBV) seroconversions were attributed to vaccination programs against HAV or HBV. None of these cases was attributable to blood products received during this time, which indicates that the virally inactivated blood factor concentrates used to treat bleeding disorders are unlikely to transmit viral hepatitis. Regular monitoring of patients ensures the continued safety of blood and blood products.
 ...
PMID:Blood safety monitoring among persons with bleeding disorders--United States, May 1998-June 2002. 1255 67

Human immunodeficiency virus 1 (HIV-1) protease inhibitors are important components of highly active antiretroviral therapy and have had a profound impact on the natural history of HIV and AIDS. However, in the era of highly active antiretroviral therapy (HAART), drug-induced hepatotoxicity or liver injury has emerged as an important potential complication of combination antiretroviral therapy, particularly those regimens containing protease inhibitors (PIs). Liver injury has been associated each of the six PIs currently approved by the U. S. Food and Drug Administration (FDA), most commonly with administration of full dose ritonavir (600 mg bid or 400 mg bid with saquinavir). However, this regimen has been largely replaced by the use of low-dose ritonavir (</= 200 mg bid) to pharmacologically "boost" other PI, such as lopinavir or indinavir, which has not been associated with an increased risk of hepatotoxicity compared with other PIs. Coinfection with hepatitis C virus (HCV) and B virus (HBV) remains an important risk factor for the development of HAART-associated liver injury. Although studies indicate that coinfected patients can be safely treated with PIs, such patients should be closely monitored. In addition, although unsubstantiated, some experts recommend evaluation or treatment, or both, of underlying chronic viral hepatitis prior to the initiation of antiretroviral therapy. Further research is needed to understand the etiopathogenesis of PI-associated liver injury, particularly among patients with hepatitis B or C infection.
 ...
PMID:Hepatotoxicity associated with antiretroviral therapy containing HIV-1 protease inhibitors. 1280 71

The contribution of viral hepatitis, human immunodeficiency virus (HIV) infection and malaria to jaundice among pregnant women in Luanda, Angola, was studied. 20 pregnant women with jaundice (cases) were identified in 2 large maternity hospitals and compared with 40 pregnant women without jaundice (controls). Among the cases 6 patients died, whereas no death occurred in the control group (p < 0.001). Five spontaneous abortions and 6 stillbirths were also noted among the cases, implying foetal loss in 55% and stillbirth in 30%. One stillbirth was registered among control women. Of the cases 40% had anti-hepatitis E virus antibodies compared with 13% of the controls (p = 0.02). Plasmodium falciparum parasitaemia occurred in 47.5% and 5% of cases and controls, respectively (p < 0.001). There was no difference in the prevalence of antibodies against hepatitis C or HIV among cases and controls. The carriership of hepatitis B surface antigen was 10% in both groups. In conclusion, jaundice during pregnancy is often associated with maternal mortality in Luanda, women suffering from jaundice during pregnancy have an extremely high case fatality rate, and P. falciparum and hepatitis E are associated with jaundice in the setting studied.
 ...
PMID:Infectious aetiology of jaundice among pregnant women in Angola. 1295 53

Hepatotoxicity has been demonstrated to be associated with antiretroviral therapy. Previous studies have included small numbers of patients and, thus, were unable to produce adequate statistical comparisons. I review data analyses from the Amsterdam, CHORUS, ICONA and Target studies (5133 patients), which were conducted by a number of investigators. There were differences between the cohorts with respect to the incidence of viral hepatitis and definitions of hepatotoxicity used. However, in all cohorts, hepatotoxicity in human immunodeficiency virus type 1-infected patients was significantly associated with coinfection with viral hepatitis. In 3 cohorts, elevated baseline alanine aminotransferase levels predicted subsequent hepatotoxicity. Overall, there was a low incidence of long-term hepatotoxicity in these cohorts and no consistent association between a particular drug or drug class. Nevirapine use within the first 12 weeks after initiation of therapy with this drug and ritonavir use are associated with increased risk of antiretroviral-associated hepatotoxicity.
 ...
PMID:Liver toxicity in epidemiological cohorts. 1498 75

Human immunodeficiency virus (HIV)-infected patients frequently present with elevated levels of serum transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]). This has often been attributed to the hepatic effects of antiretroviral (ARV) drugs, including nonnucleoside reverse-transcriptase inhibitors (NNRTIs). A review of cohort studies investigating the incidence of hepatotoxicity among patients receiving ARV therapy suggests that the overall rate of ALT and/or AST elevations is similar among all ARVs. The rate of severe hepatotoxicity, ALT and/or ASTlevels >5 times the upper limit of normal (ULN), during therapy with NNRTIs is relatively low but may be significantly higher in patients with concurrent chronic viral hepatitis (hepatitis B or C). A comprehensive analysis of 17 randomized clinical trials of nevirapine demonstrated that 10% of all nevirapine-treated patients developed elevated levels of ALT and/or AST >5 times the ULN; however, almost two-thirds (6.3% of nevirapine-treated patients) of these elevations were asymptomatic. Symptomatic hepatic events were seen in 4.9% (3.2%-8.9%) of nevirapine-treated patients.
 ...
PMID:Drug-induced liver injury associated with the use of nonnucleoside reverse-transcriptase inhibitors. 1547 67

Since their introduction, hepatotoxicity has been associated with the use of human immunodeficiency virus (HIV)-1 protease inhibitors (PIs). However, the complexity of the HIV-infected patient and the combinations of medications used to treat HIV complicate the understanding of the independent effects of PIs in the development of drug-induced liver injury (DILI). I discuss the current understanding of PI-associated hepatotoxicity. Of the PI regimens studied, the greatest risk of DILI has been observed among patients receiving full-dose ritonavir. Similarly, hepatitis B and/or C virus coinfection has been associated with a greater risk of DILI, compared with those with no hepatitis. Although the specific mechanism by which viral hepatitis increases this risk is not known, patients with cirrhosis may have decreased cytochrome P450 activity, leading to increased PI exposure. Clearly, further research is needed to define the interaction of PIs and chronic viral hepatitis in the development of DILI.
 ...
PMID:Drug-induced liver injury associated with antiretroviral therapy that includes HIV-1 protease inhibitors. 1498 80

Spontaneous hepatobiliary tumors in non-human primates are uncommon. Here we report a case of hepatic carcinoma and a case of hepatic focal nodular hyperplasia (FNH) and myelolipoma in two captive chimpanzees. A 16-year-old male chimpanzee (4X0392) died after an 8-month history of hepatic amyloidosis and low-grade anemia. Necropsy findings included a hepatic neoplasm with highly pleomorphic hepatocytes arranged into irregular thickened trabeculae. The diagnosis was high-grade hepatocellular carcinoma. A second male chimpanzee (4X0080), 23 years of age, died suddenly of heart failure secondary to cardiomyopathy. An incidental finding at necropsy was a liver mass characterized by multinodularity, prominent fibrous septa, and biliary hyperplasia. These features were consistent with FNH. While 4X0392 had no history of experimental viral exposure, 4X0080 was vaccinated with inactivated hepatitis B virus, an attenuated hepatitis A virus, and was experimentally infected with hepatitis C virus and human immunodeficiency virus. A survey of the literature revealed 68 reported cases of hepatobiliary tumors in non-human primates, including 12 hepatocellular adenomas, eight cholangiocellular adenomas/cystadenomas, 22 hepatocellular carcinomas, seven cholangiocarcinomas, and seven gallbladder adenocarcinomas. The majority of reported cases have been in prosimians and Old World monkeys. Hepatic neoplasia is rare in chimpanzees. Only four hepatic neoplasms have been reported in chimpanzees, three of which were associated with viral hepatitis. FNH has not been previously described in any non-human primate.
 ...
PMID:A case report of hepatocellular carcinoma and focal nodular hyperplasia with a myelolipoma in two chimpanzees and a review of spontaneous hepatobiliary tumors in non-human primates. 1506 32

The toxicity of nucleoside reverse transcriptase inhibitors (NRTIs) is linked to altered mitochondrial DNA (mtDNA) replication and subsequent disruption of cellular energetics. This manifests clinically as elevated concentrations of lactate in plasma. The mechanism(s) underlying how the changes in mtDNA replication lead to lactic acidosis remains unclear. It is hypothesized that mitochondrial oxidative stress links the changes in mtDNA replication to mitochondrial dysfunction and ensuing NRTIs toxicity. To test this hypothesis, changes in mitochondrial function, mtDNA amplification efficiency, and oxidative stress were assessed in HepG2-cultured human hepatoblasts treated with the NRTI stavudine (2',3'-didehydro-2',3'-deoxythymidine or d4T) for 48 h. d4T produced significant mitochondrial dysfunction with a 1.5-fold increase in cellular lactate to pyruvate ratios. In addition, d4T caused a dose-dependent decrease in mtDNA amplification and a correlative increase in abundance of markers of mitochondrial oxidative stress. Manganese (III) meso-tetrakis (4-benzoic acid) porphyrin, MnTBAP, a catalytic antioxidant, ameliorated or reversed d4T-induced changes in cell injury, energetics, mtDNA amplification, and mitochondrial oxidative stress. In conclusion, d4T treatment elevates mitochondrial reactive oxygen species (ROS), enhances mitochondrial oxidative stress, and contributes mechanistically to NRTI-induced toxicity. These deleterious events may be potentiated in acquired immunodeficiency syndrome (AIDS) by human immunodeficiency virus (HIV) infection itself, coinfection (e.g., viral hepatitis), aging, substance, and alcohol use.
 ...
PMID:Mitochondrial oxidative stress in human hepatoma cells exposed to stavudine. 1528 86


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>