Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is the first report from Ethiopia of a case of cryptococcal meningitis in a patient with AIDS. A 20-year-old woman was admitted to Tikur Anbessa Hospital in January 1990 with complaints of generalized pruritic skin lesions of six months, and headache, fever, and poor appetite of three months duration. The headache and low-grade intermittent fever were accompanied by nausea, vomiting, anorexia, and progressive weight loss, without diarrhea. She had had multiple sex partners. Upon admission, after being bedridden for two weeks, she appeared acutely ill and restless. Her temperature was 39.5 degrees Celsius, and she had oral thrush. There was no lymphadenopathy. Widespread, irregular erythematous and whitish macular patches (3 x 5 to 8 x 10 sq. cm in size) with peripheral scaling and tiny vesicles were found on the skin, pubic and perineal regions. She had neck stiffness, but was conscious and well-oriented. Hemoglobin (Hb) was 10.5 g%; the white cell count (WBC) was 3400/cu. mm; the erythrocyte sedimentation rate (ESR) was 92 mm/hr; the platelet count was 175,000/mm; and blood films were negative for hemoparasites. Urinalysis showed 3+ albumin and many pus cells and red cells/HPF. Urine culture was negative, and the VDRL test was nonreactive. Lumbar puncture, which was performed upon arrival, showed clear cerebrospinal fluid (CSF), with normal protein and glucose levels and no cells. CSF culture showed yeast cells, and an India ink preparation was positive for Cryptococcus neoformans. Blood taken for bacterial culture grew yeast cells. Renal and liver function tests, and chest x-rays were normal. A potassium hydroxide (KOH) preparation from a skin snip showed rounded yeast cells. ELISA and Western blot tests were both positive. The patient was given supportive treatment and amphotericin B (0.6 mg/kg daily). Although the fever decreased, the patient's general condition did not improve. She complained of headache, photophobia, nausea, and vomiting. Lumbar puncture was repeated eight days after the start of treatment; CSF culture and India ink preparations were negative. Urea nitrogen (BUN) repeated two weeks later was normal. Four weeks after admission, the patient suddenly vomited massive amounts of fresh blood and died before transfusion could be given. A discussion follows regarding the clinical manifestations, diagnosis, and treatment of this disease, particularly in AIDS patients, with a review of the literature.
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PMID:Cryptococcal meningitis in a young Ethiopian woman with AIDS. 139 20

A 7-kb linear plasmid, harbored by a URA5 transformant, hybridized to all the chromosomes of Cryptococcus neoformans separated by contour-clamped homogeneous electric field electrophoresis. Its linear maintenance was determined to have been facilitated by the presence of telomere-like sequences at its free ends. Hybridization of this plasmid to AccI-digested genomic DNAs of 26 C. neoformans strains generated 21 unique DNA fingerprints. The DNA fingerprints of isolates within the same serotype were more similar to one another than to those from different serotypes. An acapsular clinical isolate, strain 602, widely used in immunological studies and previously thought to be in serotype D, showed DNA fingerprints typical of serotype A isolates. Isogenic strains of C. neoformans exhibited DNA fingerprints that were identical to one another. The DNA fingerprints were stable and reproducible in spite of repeated transfers in the laboratory on either complex (1% yeast extract, 2% Bacto Peptone, 2% glucose) or minimal (yeast nitrogen base) medium. The DNA fingerprints of isolates recovered from primary blood and cerebrospinal fluid cultures of patients for whom AIDS had been diagnosed showed that the original infection in each of these patients contained a homogeneous population of C. neoformans. The DNA fingerprints of isolates recovered from different tissues of infected mice and from patients undergoing different drug therapy regimens were also found to be very stable.
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PMID:DNA probe for strain typing of Cryptococcus neoformans. 145 66

Kaposi's sarcoma is the most common tumor found in patients with the acquired immunodeficiency syndrome. This opportunistic neoplasm has characteristics of a sexually transmitted disease. Growth factors, cytokines, immune suppression, and interaction with infectious organisms all appear to play a role in the pathogenesis of this enigmatic disorder. The manifestations of Kaposi's sarcoma are protean, and lesions may appear at any time in the course of human immunodeficiency virus disease, remain localized and asymptomatic, or spread aggressively and cause morbidity. Treatment, which must be individualized, ranges from observation, local therapy with cosmetic makeup, and cryotherapy with liquid nitrogen or local intralesional injection of agents, to radiotherapy and systemic therapy with interferon-alpha and cytotoxic chemotherapy.
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PMID:Clinical aspects of Kaposi's sarcoma. 145 2

To understand whether disease caused by the human immunodeficiency virus (HIV) affects zidovudine disposition, we compared the drug's pharmacokinetics in six healthy volunteers; six persons with the acquired immunodeficiency syndrome (AIDS) and no evidence of gastrointestinal (nausea, vomiting, diarrhea), renal (elevated blood urea nitrogen, serum creatinine), or hepatic (elevated liver function tests) disease; and three patients with AIDS and hepatic disease. After a single oral dose of zidovudine, serial blood samples were analyzed for drug concentration by radioimmunoassay. A one-compartment oral absorption model was fit to the concentration-time data. The absorption rate constant (4.05 vs 2.11 hr-1) and time to maximum concentration (0.61 vs 1.03 hr) were significantly different in healthy volunteers versus patients with AIDS without hepatic disease. Differences in half-life, oral clearance, and area under the curve were not statistically significant. In the three patients with AIDS plus hepatic disease, clearance was reduced an average of 63%, and area under the curve was increased by a factor of 2.3. These comparative pharmacokinetic data do not support profound differences between zidovudine's disposition in healthy volunteers and individuals with AIDS; however, the differences and trends that were observed may represent an effect of HIV disease. Although the presence of hepatic disease clearly indicates a need to modify individual dosages, these pharmacokinetic data may have more generalized implications for zidovudine dosing as the relationships between drug concentration and therapeutic or toxic effects are clarified.
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PMID:Comparative pharmacokinetics of zidovudine in healthy volunteers and in patients with AIDS with and without hepatic disease. 149 5

A new class of membrane-active ether lipid (EL) analogs of platelet-activating factor were studied for in vitro anti-HIV-1 activity. Human T-cell (CEM-ss) monolayers or suspension cultures were used to determine effects of structural modifications of Type A phosphorus-containing and Type B nonphosphorus EL analogs on (a) the inhibitory concentration50 (IC50) for HIV-1 syncytial plaque formation and cell growth, and, (b) virus budding at the cell plasma membrane. Results indicate that representative Type A and Type B EL inhibit HIV-1 but not herpes simplex virus type 2 plaque formation when added before or up to 2 days after viral infection. Anti-HIV-1 activity does not involve direct inactivation of virus infectivity. Type A EL (IC50 range = 0.2-1.4 microM) with alkyoxy, alkylthio, or alkyamido substitution at glycerol position 1 and ethoxy or methoxy substitution at position 2, and Type B compounds (IC50 range = 0.33-0.63 microM) with an inverse choline or nitrogen heterocyclic substitution at position 3 have selective activity against HIV-1-infected T-cells. EL treatment of HIV-1-infected cells is associated with subsequent release of reverse transcriptase activity, but infectious virus production is inhibited with time after infection. Electron microscopic examination of HIV-1-infected and EL-treated cells revealed absence of detectable budding virus at the plasma membrane but presence of intracytoplasmic vacuolar virus particles. In summary, these data suggest that EL analogs are a novel class of agents that induce defective intracytoplasmic vacuolar HIV-1 formation in T-cells. Being membrane interactive, EL are ideally suited for combination chemotherapy with DNA-interactive anti-HIV nucleoside analogs.
AIDS Res Hum Retroviruses 1990 Apr
PMID:Novel membrane-interactive ether lipid analogs that inhibit infectious HIV-1 production and induce defective virus formation. 169 29

Antibody responses to 23-valent pneumococcal vaccine were studied in 38 individuals infected with human immunodeficiency virus (HIV), including 6 with asymptomatic infection, 24 with AIDS or AIDS-related complex (ARC) receiving treatment with zidovudine, and 8 untreated AIDS/ARC patients. Antibody responses were significantly higher for asymptomatic persons (aggregate geometric mean, 972 ng of antibody nitrogen (AbN)/ml; P less than .001) and AIDS/ARC patients receiving a median of 12 weeks (range, 4-54) of zidovudine therapy (mean, 369 ng of AbN/ml; P less than .001) when compared with untreated AIDS/ARC patients. Antibody responses among zidovudine-treated AIDS/ARC patients were independent of the dose (mean, 629.2 mg/day; range, 100-1200 mg) or duration of zidovudine therapy. For zidovudine-treated AIDS/ARC patients, persistence of an aggregate antibody response 8 months after vaccination was associated with survival at 14 months after vaccination, whereas waning of response was not. Pneumococcal vaccine should be administered as early as possible in the course of HIV infection. Immunization should be delayed for at least 4 weeks for AIDS/ARC patients initiating zidovudine therapy.
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PMID:Zidovudine improves response to pneumococcal vaccine among persons with AIDS and AIDS-related complex. 189 37

To assess the response and toxicity of liquid nitrogen cryotherapy for cutaneous lesions of Kaposi's sarcoma (KS) associated with AIDS, we evaluated 20 subjects with biopsy-proven KS in a phase II clinical trial. Subjects had two to four cutaneous KS indicator lesions treated with liquid nitrogen cyrotherapy. Treatment was repeated at 3 week intervals, allowing adequate healing time. On average, subjects received three treatments per lesion with a mean follow-up time of 11 weeks (range of 6-25 weeks). One treatment consisted of two freeze-thaw cycles, with thaw times ranging from 11 to 60 s per cycle. A complete response was observed in 80% of treated KS lesions and lasted a minimum of 6 weeks following the completion of therapy. Greater than 50% cosmetic improvement of KS was observed. Histopathology of treated lesions correlated poorly with cosmetic improvement. Response was not predicted by tolerance to zidovudine therapy, CD4+ cell count, presence of B symptoms, or previous chemotherapy. Subjects without prior history of opportunistic infection (OI) were more likely to have a better response than those with a prior history of OI. Subjects tolerated cryotherapy well. Blistering occurred frequently, but local pain was limited and relieved by acetaminophen. Secondary infection did not occur. Based on this study, we recommend cryotherapy to subjects with cutaneous KS lesions. Liquid nitrogen cryotherapy is easily applied as a primary therapy, and may also have a role in the treatment of cutaneous KS lesions that respond slowly or show incomplete cosmetic improvement with systemic therapies.
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PMID:Cryotherapy for cutaneous Kaposi's sarcoma (KS) associated with acquired immune deficiency syndrome (AIDS): a phase II trial. 189 4

Pneumocystis carinii was obtained in high yield from the lungs of immunosuppressed rats by rupturing mammalian host cells, washing away the soluble mammalian dihydrofolate reductase, and harvesting intact organisms in association with the mammalian plasma membranes. P. carinii dihydrofolate reductase, measured in the 100,000 x g supernatant from sonicated organisms, was obtained in yields ranging up to 62 IU per rat. The enzyme prepared in the presence of protease inhibitors was stable when frozen in liquid nitrogen. P. carinii dihydrofolate reductase differed from the mammalian enzyme in that the former was slightly inhibited by 150 mM KCl, whereas the latter was stimulated over twofold by 150 mM KCl. The standard assay for P. carinii dihydrofolate reductase contained 0.12 mM NADPH and 92 microM dihydrofolic acid. Under these conditions, the 50% inhibitory concentrations of the known inhibitors trimethoprim, trimetrexate, and pyrimethamine were 12 microM, 42 nM, and 3.8 microM, respectively. These standard compounds were also tested against dihydrofolate reductase from rat liver to allow an assessment of the selectivity of the drugs. Although it was the least potent, trimethoprim was the most selective. Pyrimethamine was more potent but was nonselective. Trimetrexate was extremely potent but was selective for mammalian dihydrofolate reductase. A series of experimental compounds was obtained from the National Cancer Institute and other sources through the Developmental Therapeutics Branch of the Division of AIDS at the National Institute of Allergy and Infectious Diseases. Among the first 87 compounds tested, 11 had 50% inhibitory concentrations below that of trimetrexate and 3 were more selective than trimethoprim. The most promising compounds in this original group were chemically related to methotrexate.
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PMID:Pneumocystis carinii dihydrofolate reductase used to screen potential antipneumocystis drugs. 192 92

Malnutrition occurs commonly in patients with acquired immunodeficiency syndrome (AIDS). The efficacy of nutritional support is unknown. A prospective, longitudinal study was conducted to determine the effect of prolonged total parenteral nutrition on body composition in 12 AIDS patients. Five patients were malnourished because of problems with food intake or absorption, while seven had systemic infections, with or without a malabsorption syndrome. The AIDS patients gained body weight and body fat content in response to total parenteral nutrition, while mean body cell mass, estimated as total body potassium content, was unchanged. However, all five patients with altered intake or absorption had significant repletion of body cell mass which was significantly different from the patients with systemic infections. Calorie and nitrogen intake did not differ between the two groups. It is concluded that body mass repletion is possible in AIDS patients in whom malabsorption is the major pathogenetic factor in producing malnutrition and is less successful in patients with serious ongoing systemic diseases. Thus, the response to nutritional support is dependent on the particular clinical circumstances.
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PMID:Effect of home total parenteral nutrition on body composition in patients with acquired immunodeficiency syndrome. 212 17

Antibody responses to pneumococcal vaccine were studied in asymptomatic heterosexual partners of persons with AIDS and intravenous drug users seropositive for human immunodeficiency virus (HIV). Serum antibodies to 12 pneumococcal capsular antigens were measured by radioimmunoassay. Eleven intravenous drug users seropositive for HIV, 13 seronegative intravenous drug users, and 10 each seropositive and seronegative sexual partners received 23-valent pneumococcal vaccine. Additional unvaccinated matched seropositives served as controls. Antibody responses were significantly lower among subjects seropositive for HIV (P less than .05). Fourteen (88%) of 16 seropositive subjects with baseline type-specific antibodies to one or more pneumococcal antigens less than 300 ng of antibody nitrogen/ml (ngAbN/ml) demonstrated a rise in one or more of these antibodies to greater than 400 ngAbN/ml. No clinical deterioration or decrease in T4 cells attributable to vaccination was found. Although antibody responses to pneumococcal vaccine among HIV-infected subjects were impaired, most with antibody levels less than 300 ngAbN/ml developed titers of one or more type-specific antibodies to levels greater than 400 ngAbN/ml without notable adverse effects.
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PMID:Response to pneumococcal vaccine among asymptomatic heterosexual partners of persons with AIDS and intravenous drug users infected with human immunodeficiency virus. 257 50


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