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Query: UMLS:C0019693 (HIV)
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The constellation of nephrotic proteinuria, FSGS, and rapid loss of renal function in a patient infected with HIV-1 has been sufficiently widespread and well documented to justify identification as a specific renal syndrome, HIV-associated nephropathy. The position paper of the National Kidney Foundation-National Institutes of Health task force estimated in 1990 that 10,000 to 15,000 persons will develop renal disease in association with AIDS [94]. Management of these patients is complex, and many will reach ESRD and require dialysis treatment, posing additional care problems. Greater understanding of the pathogenesis of the renal disease should lead to treatments which will forestall the development of HIVAN and possibly other forms of fibrotic renal disease. The ultimate eradication of AIDS will consign this renal syndrome to an interesting footnote in the history of nephrology. Since that time is still far in the future, nephrologists will continue to be faced with the need to diagnose and treat HIV-1-infected patients with renal involvement.
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PMID:Human immunodeficiency virus-associated glomerulosclerosis. 756 98

Hypoalbuminemia is the most powerful predictor of mortality in end-stage renal disease. Since protein-calorie malnutrition can decrease albumin synthesis it is assumed that hypoalbuminemia results principally from malnutrition in these patients, but albumin synthesis may also be decreased as part of the acute-phase response, and hypoalbuminemia can also result from redistribution of albumin pools or from albumin losses. We measured albumin synthesis, fractional catabolic rate, and distribution from the turnover of [125I] human albumin in six hemodialysis patients with plasma albumin less than 35 mg/ml and in six patients with plasma albumin greater than 40 mg/ml. Patients with liver disease, HIV, or other infection were excluded. Both groups were maintained with high-flux polysulfone dialyzers for more than three months. Kt/Vurea and PCR were measured during each dialysis (N = 12 to 18/patient). A four-day calorie and protein intake was determined by dietary history and long-term nutritional status was determined anthropometrically. Measured variables included serum urea, creatinine, transferrin, and the positive acute-phase proteins alpha 2- macroglobulin, C-reactive protein, ferritin, and IGF-1. Albumin synthesis was significantly reduced in the low albumin group. There were no differences in dietary intake, body composition, PCR, BUN, creatinine, or Kt/Vurea. Plasma albumin concentration correlated negatively with ferritin, C-reactive protein and alpha 2-macroglobulin. Albumin synthesis rate correlated negatively with both alpha 2-macroglobulin and Kt/Vurea. Both plasma albumin concentration and synthesis rate correlated positively with IGF-1, and both were independent of PCR and all other nutrition-related variables.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of hypoalbuminemia in hemodialysis patients. 756 20

We report experience from London hospitals which further illustrates the heterogeneous nature of HIV-associated nephropathy (HIVAN). Nineteen HIV-positive patients underwent renal biopsy from 1992 to 1994. Fourteen were male, five female. Eleven were Afro-Caribbean, 7 Caucasian and 1 Asian. Eleven patients had classical HIVAN with proteinuria, rapidly progressive renal failure and features of focal and segmental glomerulosclerosis (FSGS) on renal biopsy, and three of these had associated tubulo-interstitial nephritis (TIN). One further patient had TIN and tubular changes suggestive of HIVAN but no glomeruli were present in the biopsy. Other biopsy findings were of focal proliferative glomerulonephritis and TIN (1 patient), pauci-immune crescentic glomerulonephritis and TIN (1 patient), membranous nephropathy (1 patient), membranoproliferative nephropathy (1 patient) and haemolytic uraemic syndrome (2 patients). Of 11 patients with FSGS, seven died with median survival of 8 months (range 23 days-46 months) and five are still alive after median follow-up of 18 months (range 10-22 months). Of patients with glomerular disease other than FSGS, five died, with median survival of 3 months (range 1-27 months) and two have survived (10 and 27 months, respectively). Thirteen patients had renal failure, 10 of whom had FSGS. In 10 cases renal failure was acute and in two was the presenting feature of HIV infection. Thirteen patients underwent renal replacement therapy. Four received haemodialysis, and all died within one month. Nine patients received CAPD. Two were able to discontinue dialysis. Of the remaining seven, five died with median survival of 8 months (range 1.3-40 months) and two are alive 1 and 10 months after beginning dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HIV-associated renal disease in London hospitals. 758 76

Human immunodeficiency virus associated nephropathy (Hivan) is a distinct renal disease described in patients infected with the human immunodeficiency virus (HIV). Hivan is characterized by a nephrotic syndrome, enlarged kidneys, a histologic finding of focal and segmental glomerulosclerosis, and a very rapid progression to end-stage renal disease (ESRD). No therapeutic intervention has been shown, in a prospective evaluation, to either alter the course of established Hivan or to influence the emergence of Hivan in HIV-infected patients. We conducted a prospective study on 23 consecutively selected patients seen between 1989 and 1992 who were infected with the HIV, 14 (61%) of whom had significant proteinuria (> or = 2+). Percutaneous kidney biopsy was performed in 5 (36%) of the 14 subjects who had significant proteinuria, and histologic examination of the kidney tissue revealed focal and segmental glomerulosclerosis in all 5 cases. Of the 14 subjects with proteinuria, 8 (57%) also had azotemia (serum creatinine level > or = 1.3 mg/dl). Nine (39%) of 23 subjects admitted intravenous drug use, while 9 (39%) of 23 subjects have had an opportunistic infection before enrollment in the study. The known duration of HIV infection before initiation of zidovudine therapy was 10.3 +/- (SD) 8 months. The mean CD4 count before zidovudine therapy was 195.9 +/- 117 (range 21-654) cells/mm3. The mean dose of zidovudine administered was 543 +/- 117 (range 400-800) mg daily for a period of 20.4 +/- 11 (range 6-38) months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Zidovudine is beneficial in human immunodeficiency virus associated nephropathy. 761 46

Focal segmental glomerulosclerosis associated with human immunodeficiency virus nephropathy (HIVFGS) involves glomeruli, tubules, and interstitium. Its pathogenesis is unknown, but HIV peptides may be critical in its development. Human immunodeficiency virus peptides and peptide-antibody complexes are immunomodulatory, and are associated with apoptosis in lymphoid cells. To determine whether apoptosis is present in HIVFGS, renal biopsy specimens of eight patients with HIVFGS were compared with those of 10 patients with idiopathic focal glomerulosclerosis (FGS) using the Apoptag kit (Oncor, Gaithersburg, MD), which detects single cell apoptosis in formalin-fixed tissue by staining 3' nucleosome fragments with digoxigenin-labeled nucleotides after terminal deoxynucleotidyl transferase enzyme treatment. Apoptosis was scored per glomerulus, in total renal tissue sectioned, and in tubules and interstitium per square millimeter using a computerized digital image analyzer. There was no difference between the number of apoptotic cells per glomerulus or per square millimeter of interstitium in patients with FGS and HIVFGS. There were greater numbers of tubular apoptotic cells per square millimeter (2.1 +/- 0.9 v 0.15 +/- 0.08; P = 0.03) in HIVFGS compared with idiopathic FGS. The difference between apoptotic cells per total square millimeter of renal tissue (2.8 +/- 1.2 v 0.7 +/- 0.3) approached significance (P = 0.066). Apoptosis may be associated with the pathogenesis of HIV nephropathy and may be an important determinant of the tubular disease in HIVFGS.
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PMID:Apoptosis in human immunodeficiency virus-associated nephropathy. 764 32

Human immunodeficiency virus-associated nephropathy (HI-VAN) is a common form of nephropathy present in HIV-infected individuals that clinically presents with proteinuria that is frequently in the nephrotic range, less often with hematuria, and with a course that may evolve to irreversible azotemia ultimately resulting in renal failure. Pediatric and adult HIV-positive patients both experience HIVAN morphologically after displaying focal segmental glomerulosclerosis, diffuse mesangial hyperplasia, microcystic tubular dilatation, interstitial inflammation, edema, and fibrosis. There is minimal information regarding the interstitial inflammatory cell infiltrate, despite the possibility that these cells may play an important role in the etiology of HIVAN. This study was designed to characterize and compare several morphological and immunopathological features of clearly established HIVAN, particularly the hematopoietic cell markers present on the interstitial inflammatory cells and the state of T-lymphocyte activation (ie, class II expression). Quantitative grading of HIVAN kidneys showed that CD4-positive and CD8-positive T cells comprised the major cell populations in the interstitium, often with CD4-positive T cells exceeding or being equivalent in number to CD8-positive T cells. B cells and macrophages were negligible components of the infiltrate. Human leukocyte antigen-DR class II molecules were found to be increased on the interstitial T cells as well as on all glomerular cells and endothelial cells. There was no significant relationship established between the immunophenotype of the interstitial inflammatory cells and other morphological, ultrastructural, immunofluorescent, or clinical features. These data imply that the inflammatory infiltrate in HIVAN is largely composed of activated T cells. At this point the role of these interstitial T cells in HIVAN is undetermined, although it can be speculated that they may be participating as antiviral or autoreactive immune effector cells imparting renal injury in this entity.
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PMID:Immunopathological characteristics of in situ T-cell subpopulations in human immunodeficiency virus-associated nephropathy. 770 20

Rheumatoid arthritis (RA) once a rarity in Africa, is now reported in large numbers from many parts of Africa. Although epidemiological surveys have shown that the prevalence in urban populations is similar to Western communities, it is less common in rural areas. Further epidemiological studies are needed to confirm these findings in other parts of Africa and identify factors contributing to this difference to provide a better understanding for the emergence of RA in Africa. Earlier reports suggested that in African blacks RA was a mild disease, severe radiographic changes were uncommon, deformities were rare and extra-articular features were unusual and only symptomatic therapy was necessary to control symptoms in most patients. Recent experience shows that severe disease with deformities and radiographic changes are seen and a wide spectrum of extra-articular features are noted although they may be less common than in Caucasians. African blacks with RA may have a younger age of onset and the genetic association with HLA DR4 has been confirmed. Systemic lupus erythematosus (SLE) is also recognized more often in African blacks who have a younger age of onset. SLE is also recognized less often in males. Features such as photosensitivity and serositis are less common while renal disease is more common. A reported short-term mortality of about 30% emphasizes the need for urgent efforts to improve the prognosis in SLE. The infrequent occurrence of localized systemic sclerosis and the absence of anti-centromere antibodies in blacks was noted in a recent large series of patients with systemic sclerosis. The other connective tissue diseases and systemic vasculitides are reported much less frequently and will probably be detected more often in future. Anti-cardiolipin antibodies are detected frequently in association with infections, including HIV infection. The spectrum of diseases associated with ANCA includes a variety of connective tissue diseases and infections such as HIV infection and invasive amoebiasis must be added.
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PMID:Rheumatoid arthritis and connective tissue disorders: sub-Saharan Africa. 772 86

The non-taxonomic term microsporidia relates to a group of organisms belonging to the order Microsporida of the phylum Microspora. Microsporidia are obligate intracellular spore-forming protozoa and have no metabolically active stages outside the host cell. Their host range is extensive and includes most invertebrates and all 5 classes of vertebrates. More than 100 microsporidial genera and almost 1000 species have now been identified. 5 genera (Enterocytozoon, Encephalitozoon, Septata, Pleistophora and Nosema) and unclassified microsporidia have been associated with human disease. Only 10 cases of microsporidiosis have been described among persons not infected with HIV. In contrast, microsporidia have gained increasing attention as important opportunistic pathogens in the evolving pandemic of HIV infection. Diagnosis depends on morphological demonstration of the organisms themselves. The potential sources and modes of transmission of human microsporidial infections are uncertain. The clinical manifestations of microsporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease. Preliminary observations of the possible utility of albendazole for infections due to Septata intestinalis and Encephalitozoon sp. have been reported. The success of therapy for intestinal Enterocytozoon bieneusi infection has been limited. Cyclospora sp. are recently described protozoa capable of causing diarrhea in immunocompetent and immunodeficient patients. Groups at risk for infection are children in the developing world, travellers and HIV-infected patients. Diagnosis depends on light-microscopic detection of oocysts in stool smears stained with acid-fast stains. Diarrhea is usually self-limiting. Diarrhea, however, may often last weeks to months, causing significant morbidity. Cotrimoxazole appears to be the drug of choice for treatment of Cyclospora infection.
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PMID:[New parasitic diseases in man: infections caused by Microsporida and Cyclospora species]. 777 Jul 52

The superimposition of human immunodeficiency virus (HIV) infection, associated opportunistic infections, and anti-retroviral therapy further worsens the severity of anemia in patients also suffering from end-stage renal disease. A major cause of anemia in renal failure is a deficiency of erythropoietin. The causes of anemia in HIV disease include direct and indirect stem cell inhibition by the virus, increased peripheral destruction of red blood cells, and bone marrow suppression by various opportunistic infections and therapeutic drugs, particularly zidovudine. We compared the efficacy of recombinant human erythropoietin (rHuEPO) therapy in improving the anemia in HIV-infected end-stage renal disease patients (group I) with that in nondiabetic (group II) and diabetic (group III) hemodialysis patients without HIV infection. All three groups of patients were comparable in dialysis prescription and serum iron studies. Iron supplementation was prescribed to all patients, and none received blood transfusions. After 8 weeks of rHuEPO therapy (administered intravenously in a dose of 100 U/kg body weight thrice weekly), the mean increase in hematocrit was similar in all responders (5.8% increase in hematocrit in 23 of 30 HIV patients and 6.7% increase in 24 of 30 non-HIV patients). Response in hematocrit was noted in HIV patients despite the presence of opportunistic infections in 15 and zidovudine administration in 11. Seven HIV-positive patients and six non-HIV patients failed to respond to rHuEPO. Irrespective of the HIV status, the baseline serum EPO levels in patients responding to rHuEPO were significantly lower than those in nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The efficacy of erythropoietin in human immunodeficiency virus-infected end-stage renal disease patients treated by maintenance hemodialysis. 777 87

Transgenic technology has been very successful at providing insights into possible processes involved in HIV-induced pathogenesis. The availability of these small animal models for the study of HIV-related syndromes including KS, epidermal proliferative lesions, HIV-associated nephropathy, AIDS-related growth failure and cachexia may well facilitate the development of novel therapies for these complications. Other phenotypes created in mice, such as cataracts and hepatic cancer [59], may not have human analogies but may still provide insight into pathogenesis. Thus, transgenic models have already provided resources to study many manifestations of AIDS and others are likely to be developed. The optimal strategy for designing future transgenic animals, however, is less clear. No transgenic mouse model has been generated to date that will provide an avenue for vaccine development. This advance awaits the further discovery of the host factors that facilitate the virus replicative cycle in humans and a better understanding of these pathways in the mouse. For the development of molecular-based therapy, however, the currently available models may well be adequate to test molecular inhibitors of transcription [7,60,61] and post-transcriptional processing of viral mRNA [62]. Whether single or multigenic constructs under the control of the LTR are better or worse for this purpose is a debatable issue. Transgenic technology may yet make an additional contribution to the development of molecular therapy for AIDS. The best method of demonstrating that a gene therapeutic strategy is safe to administer to patients has not been determined. By introducing potentially therapeutic constructs into mice as transgenes, their safety can be assessed in many different cell types in vivo, analogous to toxicological testing in rodents for systemically administered drugs. Thus, transgenic technology has already provided insights into the pathogenesis of HIV-1. While it has not yet proven its utility for vaccine development, transgenic technology holds the promise of being an active participant in the development of both safe and effective gene therapy approaches for the treatment of AIDS.
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PMID:Transgenic models of HIV-1. 779 36


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