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: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Didanosine is a dideoxynucleoside analogue which undergoes intracellular conversion to the putative active triphosphate metabolite. The active metabolite appears to inhibit viral reverse transcriptase and terminate the proviral DNA, and produces virustatic inhibition of actively replicating human immunodeficiency virus (HIV) at clinically relevant concentrations. In phase I studies didanosine had beneficial effects on various surrogate markers of clinical efficacy and also improved clinical manifestations of HIV infection, with a 21-month survival rate of 80% in patients with acquired immune deficiency syndrome (AIDS) and 93% in patients with AIDS-related complex (ARC) in 1 study. Didanosine also improved CD4+ cell counts in a phase II/III trial in patients previously treated with zidovudine, whereas cell counts declined in patients continuing zidovudine therapy. However, the effects of didanosine on clinical end-points (disease progression, survival, HIV encephalopathy) remain to be established. Peripheral neuropathy and pancreatitis are the predominant dose-limiting adverse events and didanosine therapy should be withdrawn in patients developing signs or symptoms of pancreatitis and during acute treatment of Pneumocystis carinii pneumonia. However, at currently recommended clinical dosages didanosine is generally well tolerated with minimal haematological toxicity. Thus, in a therapeutic area with few treatment options, didanosine offers a welcome alternative for patients intolerant of, or resistant to, zidovudine. There are a number of clinical trials in progress evaluating didanosine alone or in combination with other antiviral agents, and these results are awaited with considerable interest.
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PMID:Didanosine. A review of its antiviral activity, pharmacokinetic properties and therapeutic potential in human immunodeficiency virus infection. 137 14

Elevated cerebrospinal fluid (CSF) levels of neopterin and beta 2-microglobulin (beta 2MG) reflect activation of the cellular immune response in the central nervous system (CNS). In 118 consecutive subjects [15 controls and 103 patients with human immunodeficiency virus (HIV) infection classified according to the Walter Reed staging system (WR)], neopterin and beta 2MG were determined in paired samples of CSF and serum. The permeability of the blood-CSF barrier and local release of neopterin and beta 2MG were taken into account: The molecular weight and diameter were used to determine filtration at the blood-CSF barrier. CSF neopterin levels were increased in all stages of HIV infection. beta 2MG levels were elevated in WR2 and later stages. Neopterin, beta 2MG, and cell counts similarly showed peaks in WR2, as did neopterin and beta 2MG also in the later stages WR5 and WR6. Neurologically asymptomatic patients exhibited higher neopterin CSF levels than did controls (12.67 +/- 11.6 vs. 2.34 +/- 1.05 nmol/l, P less than 0.001) and higher CSF beta 2MG (2.12 +/- 1.25 vs. 1.3 +/- 0.37 mg/l, P = 0.001). Patients with HIV encephalopathy had higher levels of beta 2MG (3.75 +/- 1.83 mg/l) than asymptomatic patients (P less than 0.01). CSF levels of neopterin were markedly different in patients with HIV encephalopathy and toxoplasmosis (P less than 0.01). A high quantity of local release of the markers neopterin and beta 2MG may reflect HIV infection of the CNS in early and late stages and additional release upon opportunistic infections.
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PMID:Expansion of neopterin and beta 2-microglobulin in cerebrospinal fluid reaches maximum levels early and late in the course of human immunodeficiency virus infection. 139 42

We describe the clinical and epidemiological characteristics of human immunodeficiency virus (HIV) infection in patients greater than 55 years of age at the time of diagnosis and make comparisons with younger HIV-infected patients. Patients were selected by stratification according to age (greater than 55 years and less than 40 years) from a large cohort, and information was obtained by review of charts. Three samples of younger patients were used for general comparison (sample 1), for analysis of progression to acquired immunodeficiency syndrome (AIDS) (sample 2), and for analysis of survival after AIDS (sample 3). We identified 33 patients greater than 55 years of age (30 men and 3 women). The mean age was 60.1 years (range, 55-72). Risk factors included homosexual/bisexual, 22 (67%); blood products, seven (21%); heterosexual, two (6%); and unknown risk, two (6%). HIV encephalopathy tended to be more common in the older group, while Kaposi's sarcoma was more common in younger controls. Older patients more frequently acquired HIV infection via transfusion of blood or blood products (p less than 0.005), were more likely to have AIDS at presentation (p less than 0.001), progressed to AIDS more rapidly (p less than 0.002), and had higher mortality rates (p less than 0.001). Transfusion of blood or blood products is an important mode of acquisition of HIV in patients greater than 55 years of age. HIV infection has a more rapid and aggressive course in older patients.
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PMID:HIV infection in patients over 55 years of age. 154 71

The pathogenesis of central nervous system (CNS) disease in acquired immunodeficiency syndrome (AIDS) is poorly understood but may be related to specific effects of the immune system. Cytokines such as tumor necrosis factor and interleukin-1 may have toxic effects on CNS cells and have been postulated to contribute to the pathogenesis of the neurological complications of human immunodeficiency virus (HIV) infection. To characterize viral and immunological activity in the CNS, frozen specimens taken at autopsy from the cerebral cortex and white matter of HIV-seropositive and -seronegative individuals were stained immunocytochemically for mononuclear cells, major histocompatibility complex (MHC) antigens, HIV, astrocytes, and the cytokines interleukin-1 and -6, tumor necrosis factor-alpha and -beta, and interferon gamma. Levels of soluble CD4, CD8, and interleukin-2 receptor, as well as interferon gamma, tumor necrosis factor-alpha, beta 2-microglobulin, neopterin, and interleukin-6 and -1 beta were assayed in the cerebrospinal fluid and plasma of many of these individuals during life. The HIV-seropositive group included individuals without neurological disease, those with CNS opportunistic infections, and those with HIV encephalopathy. Perivascular cells, consisting primarily of macrophages with some CD4+ and CD8+ T cells and rare B cells, were consistently MHC class II positive. MHC class II antigen was also present on microglial cells, which were frequently positive for tumor necrosis factor-alpha. HIV p24 antigen, when present, was found on macrophages and microglia. Endothelial cells were frequently positive for interleukin-1 and interferon gamma and less frequently for tumor necrosis factor and interleukin-6. There were gliosis and significant increases in MHC class II antigen, interleukin-1, and tumor necrosis factor-alpha in HIV-positive patients compared to HIV-negative brains. Cerebrospinal fluid from most of the patients tested had increased levels of tumor necrosis factor, beta 2-microglobulin, and neopterin. There was no correlation in HIV-positive individuals between levels of cytokines and the presence or absence of CNS disease. These data indicate that there is a relative state of "immune activation" in the brains of HIV-positive compared to HIV-negative individuals, and suggest a potential role for the immune system in the pathogenesis of HIV encephalopathy.
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PMID:Cytokine expression in the brain during the acquired immunodeficiency syndrome. 158 35

To investigate the epidemiology of human immunodeficiency virus (HIV) encephalopathy, we analyzed cases of acquired immunodeficiency syndrome (AIDS) reported to the Centers for Disease Control (CDC) from September 1, 1987, through August 31, 1991. Of 144,184 persons with AIDS (PWAs), 10,553 (7.3%) were reported to have HIV encephalopathy. The proportion of PWAs with HIV encephalopathy was highest at the extremes of age: in PWAs less than 15 years old the proportion was 13%, and in PWAs greater than or equal to 15 years old the proportion progressively increased with age, from 6% in PWAs 15 to 34 years old to 19% in PWAs greater than or equal to 75 years old (p = 0.00001, chi 2 test for linear trend in proportions). The reported annual incidence of HIV encephalopathy per 100,000 population aged 20 to 59 years was 1.4 in 1988, 1.5 in 1989, and 1.9 in 1990. This analysis best provides estimates for HIV encephalopathy as the initial manifestation of AIDS because the CDC AIDS reporting system often does not ascertain diagnoses after the initial AIDS report. These data suggest that age (very young or old) is associated with the development of HIV encephalopathy and that HIV encephalopathy is a common cause of dementia in adults less than 60 years old in the United States.
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PMID:Epidemiology of human immunodeficiency virus encephalopathy in the United States. 164 Nov 38

The ventricular area at the level of the foramen of Monro was measured from axial x-ray computed tomography (CT) scans obtained prior to and 6 months after the initiation of continuous infusion of zidovudine (ZDV) in eight children with human immunodeficiency virus-induced encephalopathy. Evidence of moderate to severe central atrophy was present on initial CT scans (p less than 0.05). Ventricular area and ventricular brain area ratio (VBR) decreased after ZDV therapy in seven of eight children (mean decrease of 21.5 and 20%, respectively, p less than 0.05). The degree of decrease in VBR correlated with reductions in cerebrospinal fluid (CSF) protein concentration (r = 0.93, p less than 0.01), but not lymphocyte T4 or T8 counts. Intelligence quotients (IQs) improved in all seven children tested (mean improvement of 17.7%, p less than 0.01) and correlated significantly with reductions in CSF protein concentration (r = -0.85, p = 0.003). The magnitude of IQ changes was not significantly correlated with the magnitude of changes in ventricular area. We conclude that the cognitive improvement of HIV encephalopathy seen after 6 months of continuous infusion of ZDV is accompanied by reduction in brain atrophy and decreased CSF protein, suggesting an ameliorating effect of ZDV on the pathogenesis of AIDS encephalopathy in children.
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PMID:Brain growth and cognitive improvement in children with human immunodeficiency virus-induced encephalopathy after 6 months of continuous infusion zidovudine therapy. 167 12

The authors examined the autopsy brain samples of nine children infected with human immunodeficiency virus (HIV) at birth by histology, immunologic staining, and in situ hybridization. Surprisingly, although seven of these children presented with typical AIDS encephalopathy, the authors could detect a multifocal HIV infection in the brains of only three of these patients. The authors could not detect any significant HIV replication in the brain of four other children despite severe neurologic disease. However, HIV DNA was detected by polymerase chain reaction (PCR) in the central nervous system (CNS) of all patients. In addition, the authors found associated lesions in the brains of three of these four patients. This study shows that severe AIDS encephalopathy exists in children and therefore might exist in adults with few signs or without any signs of HIV replication or inflammation in the CNS. Understanding the pathogenesis of this neurologic disease and the kinetics of HIV replication in brain tissue of children with AIDS encephalopathy is essential to determine the best therapeutic strategy.
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PMID:Low levels of human immunodeficiency virus replication in the brain tissue of children with severe acquired immunodeficiency syndrome encephalopathy. 173 20

The nucleotide sequence of the gp41 transmembrane protein coding region of human immunodeficiency virus type 1 (HIV-1) proviral DNA obtained from blood and cerebrospinal fluid (CSF) from 6 individuals was determined by direct sequencing of polymerase chain reaction (PCR)-amplified DNA. The direct sequencing approach was performed to avoid errors introduced by Taq polymerase during the amplification reaction. In 3 of 6 paired samples distinct sequence differences between proviral DNA from blood and CSF, ranging from 0.64% to 1.73%, were detected. The greatest diversity (4.2% different amino acids) was found between paired samples of a patient suffering from AIDS encephalopathy, with most of the differences clustering near the carboxy-terminal end of gp41. The results demonstrate that genetically different populations of HIV-1 may be present in different biological compartments and specific neurotropic HIV variants may exist.
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PMID:Distinct populations of human immunodeficiency virus type 1 in blood and cerebrospinal fluid. 173 40

Although the human immunodeficiency virus type 1 (HIV-1) is frequently isolated from the cerebrospinal fluid of infected patients, only a small percentage of patients are found to have clinical dementia or neuropathies (or both). The reasons for this remain unclear. In our study, serum neutralizing antibody titers against the human T cell leukemia virus-IIIB isolate of HIV-1 were tested in 10 patients with acquired immunodeficiency syndrome (AIDS) with neurologic complications and 20 patients with HIV infection without neurologic complications. Titers were significantly lower in the neuro-AIDS group, suggesting that impaired neutralizing antibody responses in this subpopulation of patients may be involved in the immunopathogenesis of AIDS encephalopathy.
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PMID:Neutralizing antibody responses in patients with AIDS with neurologic complications. 174 7

Fifty-two patients at various stages of human immunodeficiency virus (HIV) infection who had one or several epileptic seizures in the course of that disease were retrospectively studied from 1985 to 1990. Thirty-five percent of these patients were in overt clinical AIDS at the time of the seizure(s). AIDS was revealed by a seizure in 2 cases. Generalized seizures were observed in 71 percent of the patients, and partial seizures in 29 percent. Electroencephalograms showed signs of brain irritation in only 19 percent of the cases. The cause of epileptic seizure(s) could be determined in 36 patients: cerebral toxoplasmosis in 23 cases; progressive multifocal leucoencephalitis in 2 cases; HIV encephalopathy in 3 cases; iatrogenic cause in 4 cases; meningoencephalitis in 3 cases and neurosyphilis in 1 case. No cause other than HIV infection was found in 16 patients. These findings confirm those of previous studies. In about one-third of AIDS patients epileptic seizures are the only clinical manifestation of viral central nervous system infection.
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PMID:[Epilepsy seizures in HIV infection. 52 cases]. 183 61


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