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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of exclusionary techniques in the procurement of donors for bone allografts greatly reduces chances for disease transmission. Furthermore, treatment of HIV with either chemical agents or strong acids will effectively inactivate the AIDS virus. These data are taken as indirect proof that the risk of obtaining AIDS from a freeze-dried bone allograft is highly remote. The purpose of this study is to obtain direct evidence that the processing of a demineralized freeze-dried bone allograft would render the allograft safe for human use. In Part I, human cortical bone was obtained from a cadaveric source and tested to be free of HIV contamination. The bone was spiked with 5.26 x 10(9) viral particles. This corresponded to 148 micrograms of total viral protein. In Part II, cortical bone was procured from a donor who died of AIDS. In both Parts I and II, the cortical bone was ground to yield particle sizes of 90 to 500 microns. Test samples were treated with a virucidal agent and demineralized in HCl. Control samples were left untreated. All samples were cocultivated with stimulated peripheral blood lymphocytes and assayed for p24 core protein, reverse transcriptase, and viral gag gene by polymerase chain reaction (PCR). In Part I, the HIV spiking experiment, untreated virus infected particulate bone was positive for HIV replication. Treated samples were negative when assayed for HIV. Bone samples in Part II, HIV infected bone, were positive by PCR. Replication of viable HIV could not be demonstrated after treatment. It was concluded that demineralization and treatment with a virucidal agent inactivates HIV in spiked and infected bone.
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PMID:HIV inactivation in a bone allograft. 128 53

Human immunodeficiency virus (HIV)-infected cells induce acid-labile interferon-alpha (al-IFN-alpha) in cultures of mononuclear cells from peripheral human blood. We have investigated the physiochemical properties of such preparations to elucidate the reasons for acid-lability of this IFN. Al-IFN-alpha is a mixture of both glycosylated and unglycosylated molecules as shown by separation on Concanavalin-A Sepharose. Acid-lability is associated only with glycosylated molecules. Upon chromatography of the glycosylated fraction on Sepharose coupled to IFN-alpha-specific antibody, the portion of the IFN that is retained and eluted with guanidine-HCl is acid-stable, whereas the excluded antiviral activity is acid-labile, and is partially neutralized by antibodies to either IFN-alpha or IFN-gamma. Also, upon further purification of the unglycosylated fraction on the same antibody column, all antiviral activity remains indistinguishable from conventional IFN-alpha. Reconstitution experiments showed that glycosylated material excluded from the anti-IFN-alpha column potentiates antiviral activity of the IFN that is specifically retained by the column. This potentiation is abolished by acid treatment. Similar results are obtained with al-IFN-alpha from the serum of acquired immunodeficiency syndrome (AIDS) patients, indicating that its acid-lability is also the consequence of an acid-labile component that is capable of enhancing the antiviral activity. The potentiation of antiviral activity obtained by combining recombinant preparations of IFN-alpha and IFN-gamma suggests that the cooperating molecule is IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acid lability is not an intrinsic property of interferon-alpha induced by HIV-infected cells. 128 11

Various nucleoside analogues are being used or are being considered for use as therapeutic drugs to inhibit replication of the HTLV-III/LAV virus in infected human cells. Here, the ability of seven nucleoside analogues, a combination of two analogues, and two other therapeutic compounds to induce genotoxic and cytotoxic damage in vivo was evaluated in the mouse bone marrow micronucleus test. Using a 3-consecutive-day oral treatment protocol, almost all of the test chemicals induced a significant increase in the frequency of micronucleated polychromatic erythrocytes (MN-PCE) in male B6C3F1 mice, ranked in decreasing potency as 6-thioguanine greater than Cytarabine HCl greater than 3'-azido-3'-deoxythymidine (AZT)/2',3'-dideoxycytidine combination = AZT greater than Ribavirin = 2',3'-didehydro-3'-deoxythymidine greater than 2',3'-dideoxyadenosine = 2',3'-dideoxycytidine. The frequency of MN-PCE was not increased significantly by treatment with 2',3-dideoxyinosine (DDI) or pentamidine isethionate (PI). The differential ability of AZT and DDI to induce MN in mouse bone marrow was verified from peripheral blood smears prepared from subchronic (90 day) oral studies. The lack of genotoxic activity by DDI was route-specific since, when tested by intraperitoneal injection, a small but significant increase in MN-PCE was observed. A number of these chemicals induced a significant depression in erythropoiesis. However, there was not a significant correlation between the increase in MN-PCE and the depression in the percentage of PCE. This lack of a correlation suggests that factors other than DNA damage may contribute to the inhibition in the rate of erythropoiesis. The presence of increased levels of micronuclei in bone marrow PCE following treatment with various nucleoside analogues suggests that intrinsic genotoxic activity in mammalian cells should be one factor considered during drug selection for AIDS therapy.
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PMID:Induction of micronuclei in mouse bone marrow cells: an evaluation of nucleoside analogues used in the treatment of AIDS. 191 12

In light of the lack of any prior systematic evaluations of the prevalence and types of pain syndromes and treatments found in patients with AIDS, a chart review study was undertaken to evaluate this issue. Fifty-two of 96 charts reviewed (54%) had at least one note on nonprocedural pain or analgesic prescription. Although chest pain was the most prevalent pain location (22%), presumably because of the high incidence of Pneumocystis carinii pneumonia, other possible AIDS-related entities, such as peripheral neuropathy and thrombophlebitis, were also found. No specific AIDS syndromes could be identified that were related to a higher incidence of pain. Nearly one-third of patients with pain received codeine (31%), others received acetaminophen (27%), and 17% of patients received acetaminophen and oxycodone HCl. Specific pain management interventions must be evaluated and applied to control the nontrivial occurrence of pain in patients who have AIDS symptoms that may be overlooked by the physician given the overwhelming disease process.
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PMID:The prevalence and management of pain in patients with AIDS: a review of 134 cases. 252 Apr 10

The authors investigated 19 cases of Kaposi's sarcoma (KS) obtained from patients with the acquired immune deficiency syndrome (AIDS) for their expression of Factor VIII-related antigen (FVIIIRAg), HLA-DR (Ia) antigens, OKM1, and three distinctive vascular, but not lymphatic, endothelial-cell-associated antigens, E92, OKM5, and HCl. Antigen expression was demonstrated by immunoperoxidase staining of cryostat sections. FVIIIRAg is strongly expressed by the cells lining the vascular spaces (VCs) but is absent, weakly or focally, and variably expressed by the spindle cell (SC) component of KS. The VC component of each KS lesion examined strongly expressed E92, moderately expressed HCl, and weakly expressed OKM5. In contrast, the entire SC component of each KS lesion studied strongly expressed E92 and OKM5 and weakly expressed HCl. Neither the VCs nor the SCs expressed OKM1. These studies provide strong and compelling evidence for the vascular endothelial cell histogenesis of both the vascular and spindle cell components of KS, demonstrate the intertumor and intratumor phenotypic heterogeneity of KS, and suggest that monoclonal antibodies OKM5 and anti-E92 are the best currently available immunohistochemical markers for identifying the spindle cell component of AIDS-associated KS in cryostat sections.
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PMID:The expression of endothelial cell surface antigens by AIDS-associated Kaposi's sarcoma. Evidence for a vascular endothelial cell origin. 395 72

The reverse transcriptase (RT) of the human immunodeficiency virus type 1 (HIV-1) is the major target for antiretroviral therapy of the acquired immunodeficiency syndrome (AIDS). While some inhibitors exhibit activity against most retroviral RTs, others are specific for the HIV-1 enzyme. To develop an animal model for the therapy of the HIV-1 infection with RT inhibitors, the RT of the simian immunodeficiency virus (SIV) was replaced by the RT of HIV-1. Macaques infected with this SIV/HIV-1 hybrid virus developed AIDS-like symptoms and pathology. The HIV-1-specific RT inhibitor LY300046.HCl, but not zidovudine [3'-azido-3'-deoxythymidine (AZT)] delayed the appearance of plasma antigenemia in macaques infected with a high dose of the chimeric virus. Infection of macaques with the chimeric virus seems to be a valuable model to study the in vivo efficacy of new RT inhibitors, the emergence and reversal of drug resistance, the therapy of infections with drug-resistant viruses, and the efficacy of combination therapy.
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PMID:Animal model for the therapy of acquired immunodeficiency syndrome with reverse transcriptase inhibitors. 754 97

Phenylethylthiazolylthiourea (PETT) derivatives have been identified as a new series of non-nucleoside inhibitors of HIV-1 RT. Structure-activity relationship studies of this class of compounds resulted in the identification of N-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea hydrochloride (trovirdine; LY300046.HCl) as a highly potent anti-HIV-1 agent. Trovirdine is currently in phase one clinical trials for potential use in the treatment of AIDS. Extension of these structure-activity relationship studies to identify additional compounds in this series with improved properties is ongoing. A part of this work is described here. Replacement of the two aromatic moieties of the PETT compounds by various substituted or unsubstituted heteroaromatic rings was investigated. In addition, the effects of multiple substitution in the phenyl ring were also studied. The antiviral activities were determined on wild-type and constructed mutants of HIV-1 RT and on wild-type HIV-1 and mutant viruses derived thereof, Ile100 and Cys181, in cell culture assays. Some selected compounds were determined on double-mutant viruses, HIV-1 (Ile 100/Asn103) and HIV-1 (Ile100/Cys181). A number of highly potent analogs were synthesized. These compounds displayed IC50's against wild-type RT between 0.6 and 5 nM. In cell culture, these agents inhibited wild-type HIV-1 with ED50's between 1 and 5 nM in MT-4 cells. In addition, these derivatives inhibited mutant HIV-1 RT (Ile 100) with IC50's between 20 and 50 nM and mutant HIV-1 RT (Cys 181) with IC50's between 4 and 10 nM, and in cell culture they inhibited mutant HIV-1 (Ile100) with ED50's between 9 and 100 nM and mutant HIV-1 (Cys181) with ED50's between 3 and 20 nM.
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PMID:Phenethylthiazolylthiourea (PETT) compounds as a new class of HIV-1 reverse transcriptase inhibitors. 2. Synthesis and further structure-activity relationship studies of PETT analogs. 886 4

In human immunodeficiency virus type 1 (HIV)-1-infected Black people, the circulating p24 antigen is hidden frequently in immune complexes, because of high titers of serum anti-p24 antibodies. In order to evaluate the prognostic values for progression of free and dissociated serum p24 antigen in Black people, sera from 45 HIV-1-infected Black patients, all at non-AIDS stages, were evaluated prospectively for p24 antigen by several assays; circulating free p24 antigen was measured by immunocapture ELISA only (method 1) and with ELAST amplification (method 2), and dissociated p24 antigen determined after glycine-HCl pretreatment of serum, by immunocapture ELISA only (method 3) and with ELAST amplification (method 4). Serum CD4 and CD8 cell counts, beta 2-microglobulin, and total IgA were determined also at least twice a year. Clinical events for AIDS were those included in the 1986 CDC classification for HIV infection. At entry, p24 antigen was found in 3 (6.7%) patients by method 1, in 7 (15.6%) by method 2, in 14 (31.1%) by method 3, and in 22 (48.9%) by method 4. Methods 3 and 4 were more sensitive than method 1 (P < 0.001) and method 2 (P < 0.001). The mean follow-up was 30 months. The free symptom survival times (mean +/- SD months) were significantly lower in patients being p24 antigen positive by method 1 [(+) 33 +/- 27 vs. (-) 61 +/- 15, P = 0.03), but they were similar in patients positive and in those negative for p24 antigen determined by method 2 [(+) 71 +/- 17 vs. (-) 74 +/- 9, P = 0.54], method 3 [(+) 76 +/- 12 vs. (-) 69 +/- 13.2, P = 0.80], and method 4 [(+) 79 +/- 9 vs. (-) 63 +/- 7, P = 0.71]. At 24 months, p24 antigen positivity did not correlate either with CD4 or CD4/CD8 slops, nor with beta 2-microglobulin or IgA variations. By contrast, a CD4 cell count below 200/mm3 at entry was significantly associated with disease progression. In conclusion, dissociated p24 antigenemia does not appear as a useful surrogate marker for progression in HIV-1-infected Black people.
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PMID:Lack of predictive value for progression of dissociated circulating P24 antigen in human immunodeficiency virus type 1-infected black patients. 891 85

The Food and Drug Administration (FDA) approved injectable doxorubicin HCl liposome (DOXIL) for treatment of Kaposi's sarcoma (KS) in AIDS patients. DOXIL's major benefit is that its reported circulating half-life is fifty hours, compared to ten minutes for free (non-liposome) doxorubicin.
AIDS Alert 1996 Jan
PMID:FDA approves KS drug. Food and Drug Administration. Florida Department of Health and Rehabilitation Services. 1136 27

Over time, the spectrum of the acquired immune deficiency syndrome (AIDS) epidemic has changed, especially with the advent of highly active antiretroviral therapy (HAART). The goal of this article is to delineate changes occurring in the incidence and management of lymphoma over the course of the AIDS epidemic. Lymphoma usually occurs rather late in the course of human immunodeficiency virus (HIV) infection and is the cause of death in up to 20% of HIV-infected individuals. It is seen in all population groups at risk for HIV and is more common in men than in women. It is usually diagnosed in patients with markedly decreased CD4 cell counts, consistent with prolonged periods of HIV infection and subsequent immunosuppression. Recent data from several large series have demonstrated a substantial decline in the median CD4 cell count among patients with newly diagnosed AIDS-related lymphoma despite the recent widespread use of HAART. While still somewhat controversial, use of HAART has generally not produced a significant decline in the incidence of AIDS-related lymphoma. Patients treated with low-dose vs standard-dose chemotherapy for AIDS-related lymphoma have achieved similar response and survival rates, although standard-dose therapy is associated with greater toxicity. Adapting therapy to prognostic factors has not produced a significant improvement in survival. Use of antiretroviral therapy along with chemotherapy appears safe, and may be associated with longer survival. An infusional regimen called EPOCH (etoposide, prednisone, vincristine [Oncovin], cyclophosphamide, doxorubicin HCl) shows promise in the future management of AIDS-related lymphoma. No regimen is currently considered the standard of therapy for patients with relapsed AIDS-related lymphoma, and survival is short in this setting.
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PMID:Incidence and management of AIDS-related lymphoma. 1139 57


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