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Biomedical subjects

D A Cooper

Publications and source records attributed to D A Cooper.

At least 199 records · Page 11Linked to original sources
PubMed1993

Differences in time from HIV seroconversion to CD4+ lymphocyte end-points and AIDS in cohorts of homosexual men.

OBJECTIVE: To evaluate the decline in CD4+ counts in relation to the incidence of AIDS in different cohorts of homosexual men and to quantify possible consequences of laboratory variation in CD4+ measurement. METHODS: Our study includes 403 men with well documented dates of HIV seroconversion originating from five cohort studies among homosexual men. Differences in time from HIV seroconversion to the first CD4+ count dropping < 500 or 200 x 10(6)/l and to AIDS were evaluated using Kaplan-Meier survival analyses. RESULTS: We found considerable differences between cohorts in CD4+ depletion, but not in the incidence of AIDS (1987 definition). CONCLUSIONS: Variation in CD4+ depletion appears to be mainly the result of laboratory differences. Policy recommendations on a basis of CD4+ counts probably requires a calibration of measurement. The 1993 AIDS case definition leads to a site-specific shortening of the incubation time, which complicates the study of the natural history of HIV infection and of trends in the AIDS epidemic.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Increased expression of interferon-gamma in hyperplastic lymph nodes from HIV-infected patients.

Polyclonal B cell activation is characteristic of HIV infection and occurs in the presence of severe CD4+ lymphocyte depletion. In contrast, CD4+ lymphocytes are the dominant T cell in the reactive lymphoid tissues of patients not infected with HIV. In this study, lymph node biopsies from eight HIV-infected patients with persistent generalized lymphadenopathy syndrome (PGL) were assessed for IL-1 beta, IL-2, IL-4, IL-6, IL-10, interferon-gamma (IFN-gamma) and tumour necrosis factor-beta (TNF-beta) gene expression using the polymerase chain reaction (PCR). The cytokine gene expression of two cases of reactive adenopathy in patients not infected with HIV was assessed for comparison. IFN-gamma was expressed much more strongly in the PGL samples than in control reactive lymphoid tissues, whereas the other cytokines were expressed to a similar extent in both types of tissues. IFN-gamma may have an important role in maintaining the adenopathy of HIV-infected patients. Expression of cytokines such as IL-2, IL-4 and IL-10 in HIV nodes may be adequate to allow the recruitment of naive B cells to the reactive process.

AIDS-Related Complex↗
PubMed1993

In vitro cytotoxicity as a marker of hypersensitivity to sulphamethoxazole in patients with HIV.

Hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) in patients with HIV infection may be a result of either immune dysregulation, a direct cytotoxicity of the SMX-hydroxylamine metabolite (SMX-HA) (rather than SMX per se), or glutathione deficiency. We evaluated the in vitro cytotoxicity of SMX and SMX-HA to peripheral blood mononuclear cells (PBMC) of HIV-infected subjects to determine if the degree of in vitro cytotoxicity is associated with hypersensitivity, whether glutathione inhibits cytotoxicity, and whether in vitro cytotoxicity is predictive for the development of hypersensitivity. Given that fever is often a prominent feature of hypersensitivity, we also assessed whether SMX or SMX-HA could induce the in vitro production of IL-1 beta, IL-6 or tumour necrosis factor-alpha (TNF-alpha) by PBMC. The cytotoxicities of SMX and SMX-HA to PBMC were assessed in 45 HIV-infected patients with prior TMP-SMX therapy, and in eight HIV- controls. Twelve HIV-infected subjects were studied prospectively before primary Pneumocystis carinii pneumonia (PCP) therapy or rechallenge with TMP-SMX in previously hypersensitive subjects. Cytokine production was measured in four hypersensitive and two non-hypersensitive HIV-infected subjects, and three HIV-uninfected controls. The cytotoxicity of SMX-HA to PBMC was significantly greater in the 22 HIV-infected patients with prior hypersensitivity than both the 23 HIV-infected patients without hypersensitivity and the control group. Cytotoxicity was significantly reduced by glutathione only in the hypersensitive group. SMX did not induce cytotoxicity in any group. In 12 subjects studied prospectively, SMX-HA cytotoxicity was also significantly greater in those with subsequent hypersensitivity. Exposure of PBMC to SMX-HA resulted in a modest increase in the production of IL-6, IL-1 beta and TNF-alpha, although no major difference was detected between subjects with or without hypersensitivity. These data suggest that SMX-HA and glutathione deficiency are involved in the pathogenesis of hypersensitivity to TMP-SMX in HIV-infected patients, and that in vitro cytotoxicity could be useful in the diagnosis of hypersensitivity and predicting its likelihood.

Adult↗
PubMed1993

Progression of periodontal disease in HIV seropositive patients.

Data from cross-sectional studies suggest that periodontitis in HIV-infected patients is a more destructive form of disease in contrast to the slowly progressing form of adult periodontitis in the general population. We studied prospectively over an 18-month period 30 HIV infected, but asymptomatic, patients and compared the rate of periodontal attachment loss with that of a healthy control group (n = 10) matched for age and plaque index. Every 6 months, each subject was assessed for their clinical status by a physician and CD4+ cell count determined. The proliferative response of peripheral blood lymphocytes was determined by in vitro cultures with PHA and Con A. The periodontal health status was assessed by scoring with plaque index (PI), gingival index (GI), and periodontal disease index (PDI). The control subjects were assessed for periodontal status only. Of the 30 HIV-positive patients whose data were analyzed 14 received Zidovudine (AZT) while the remaining 16 did not. There was no correlation between any clinical parameter measured and periodontal status as determined by PI or GI. However, a significant difference in the change of periodontal disease index (PDI) was observed between the HIV-infected and control groups (P = 0.005). We concluded that HIV-infected patients with pre-existing periodontitis tend to experience a greater rate of attachment loss over time compared with controls.

Adult↗
PubMed1993

The role of Epstein-Barr virus subtypes in human immunodeficiency virus-associated lymphoma.

High grade B cell non-Hodgkin's lymphoma (NHL) is an increasingly important problem in individuals infected with the human immunodeficiency virus (HIV). Fifty percent of these tumours harbour the Epstein-Barr virus (EBV) and there is an equal frequency of EBV A and B-subtypes in the tumours. This contrasts with the recent report that only A-type EBV is associated with Hodgkin's disease. Such studies are challenging the traditional models of EBV-associated lymphomagenesis and showing the way for further studies in this field. This article reviews the studies of EBV subtypes in HIV-associated NHL and uses this new knowledge to discuss the role of EBV in lymphomagenesis.

Antigens, Viral↗
PubMed1993

Factors associated with Kaposi's sarcoma in a cohort of homosexual and bisexual men.

The relationship between the occurrence of Kaposi's sarcoma (KS) and a range of factors was studied in a cohort of homosexual and bisexual men. Overall, 134 men had AIDS, including 46 for whom KS was the first AIDS-defining illness. The proportion of men diagnosed with AIDS whose first AIDS-defining illness was KS declined from 54 to 24% between 1984-85 and 1989-90 (p = 0.03 for linear trend). Kaposi's sarcoma was not associated with a history of any specific communicable disease, nor with the reported use of selected nontherapeutic drugs, at the 0.05 level of significance. No single sexual practice was significantly associated with KS, and only the relative risks for insertive oroanal contact (1.5, 95% confidence limits 0.73-2.4) and receptive fisting (1.3, 0.61-2.6) exceeded unity. Kaposi's sarcoma occurred significantly less frequently in men who reported orogenital intercourse than in those who did not (relative risk 0.47, 0.23-0.98 for receptive orogenital intercourse). History of sexual contact in the United States was associated with KS, but this association was not statistically significant. While this study provides some support for the hypothesis that Kaposi's sarcoma in people with AIDS may be caused by a sexually transmissible infectious agent, no specific sexual practice could be implicated. In particular, there was little evidence that the postulated KS agent was transmitted by fecal-oral contact.

Acquired Immunodeficiency Syndrome↗
PubMed1993

The application of capillary gas chromatography-electron capture detection in the comparative analyses of illicit cocaine samples.

The gas chromatographic detection of manufacturing impurities in illicit cocaine can be enhanced by chemical derivatization and the use of an electron-capture detector. After derivatization of illicit cocaine hydrochloride samples with heptafluorobutyric anhydride, the isolated heptafluorobutyryl derivatives of the cocaine impurities were subjected to capillary gas chromatography-electron capture detection analysis. The on-column detection of cocaine impurities at low picogram levels was possible for compounds such as N-norcocaine and other N-demethylated impurities, amidic by-products, including N-benzoylnorecgonine methyl ester and tertiary amines possessing hydroxy functions. The latter compounds include the so-called hydroxycocaine impurities, believed to be new coca leaf alkaloids. This methodology is especially suited for sample comparison analyses.

Cocaine↗
PubMed1993

HIV and malignancy.

Although a number of tumors in patients infected with the human immunodeficiency virus have been reported, Kaposi's sarcoma and non-Hodgkin's lymphoma remain the two principal malignancies. This article provides an Australian perspective of the recent advances in research into malignancy in HIV-infected persons.

Australia↗
PubMed1993

Prophylaxis of opportunistic infections in patients with HIV infection.

Prophylaxis of opportunistic infections in patients with human immunodeficiency virus (HIV) infection has been one of the major factors responsible for increasing patient survival. Secondary prophylaxis of most opportunistic infections is warranted, although in most instances the optimal therapy remains to be determined. Primary prophylaxis of opportunistic infections is an attractive concept, as the majority of opportunistic infections are reactivations of latent infections. Primary prophylaxis against Pneumocystis carinii pneumonia is both effective and necessary, but the role for primary prophylaxis against other infections is as yet unclear. Use of prophylactic agents requires careful study for determining the most effective and least toxic forms of prophylaxis that will allow for adequate concurrent antiretroviral therapy but will not induce resistant organisms.

AIDS-Related Opportunistic Infections↗
PubMed1993

Current status of clinical trials in HIV disease in Australia.

Clinical trials in Australia in diseases related to human immunodeficiency virus (HIV) have steadily expanded from the earliest national study of zidovudine to a range of trials either actively recruiting or being activated that cover a wide spectrum of primary viral, opportunistic infection and opportunistic malignant diseases. From its earliest establishment as the National Health and Medical Research Council special unit to its current role as the clinical trials unit of the National Centre in HIV, this central group has organized a coordinated approach to the conduct of clinical trials that has been a hallmark of Australia's response to the treatment of HIV-related disease. The original local trials were in the form of collaboration in multicenter trials, initiated by the pharmaceutical industry, with the participation of only a few major treatment centers. This has now evolved to a network of more than 20 hospital and ambulatory care centers and a group of enthusiastic and committed general practitioners who have contributed data to a number of major studies. These include the national zidovudine study that generated data on the use of surrogate markers such as CD4 and p24 antigen as predictors of survival, studies of the combination of acyclovir and zidovudine that have indicated a new direction in combination antiretroviral therapy, placebo-controlled studies of zidovudine in asymptomatic individuals that may alter the timing of introduction of therapy, and the MRC/INSERM study of didanosine in advanced disease that will give the clearest indication of its activity yet to be reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiviral Agents↗
PubMed1992

Long-term symptomless HIV-1 infection in recipients of blood products from a single donor.

There have been reported cases of long-term symptomless human immunodeficiency virus type 1 (HIV-1) infection, but it is not clear whether the benign course of infection was due to host, viral, or other unknown factors. During follow-up of subjects with transfusion-acquired HIV-1 infection in New South Wales, Australia, we identified a group of 6 subjects who had been infected through a single common donor. We were therefore able to study the contributions of various factors to the course of infection. Throughout follow-up (range 6.8-10.1 years after infection), 5 of the recipients and the donor (last follow-up 10.2 years after infection of the first recipient) remained clinically free of symptoms, with normal CD4 cell counts and no p24 antigenaemia. HIV-1 was isolated from only 1 recipient; the isolate did not induce syncytia in a SUPT1 co-culture assay and had a limited in-vitro host range. 1 infected recipient (who had received extensive immunosuppressive treatment for systemic lupus erythematosus) developed Pneumocystis carinii pneumonia and died 4.3 years after infection. The frequency of progression to AIDS or a CD4 cell count below 0.50 x 10(9)/l was significantly lower among the 6 subjects with a common donor (1/6) than among 101 other HIV-infected transfusion recipients for whom data from 7 years of follow-up were available (94/101; p less than 0.0001). These findings suggest that the subjects were infected by a less virulent strain of HIV-1. The identification of this group of subjects should stimulate a search for other similar groups, which will provide important information on the immunopathogenesis of HIV-1 disease.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Low-dose trimethoprim-sulfamethoxazole prophylaxis for toxoplasmic encephalitis in patients with AIDS.

OBJECTIVE: To determine the efficacy of low-dose trimethoprim-sulfamethoxazole (trimethoprim, 160 mg plus sulfamethoxazole, 800 mg; one tablet twice daily, 2 days per week) as primary prophylaxis against toxoplasmic encephalitis in patients with human immunodeficiency virus (HIV) infection and previous Pneumocystis carinii pneumonia. DESIGN: A retrospective study. SETTING: Tertiary referral teaching hospital. PATIENTS: During a 3-year period after primary episodes of P. carinii pneumonia, 60 patients received trimethoprim-sulfamethoxazole, and 95 patients received pentamidine (aerosolized in 78 patients and intravenous in 17 patients) as secondary prophylaxis. RESULTS: No patient in the trimethoprim-sulfamethoxazole group and no patient seronegative for Toxoplasma gondii developed toxoplasmic encephalitis, compared with 12 of 36 (33%; 95% Cl, 19% to 51%) seropositive patients in the pentamidine group (trimethoprim-sulfamethoxazole compared with pentamidine, P = 0.008). A significant difference was seen in the time to development of toxoplasmic encephalitis between the trimethoprim-sulfamethoxazole group (no case at 1153 days) and the pentamidine group (median time, 460 days) (P = 0.004). Neither the CD4+ lymphocyte count at the start of prophylaxis nor zidovudine therapy during the period of prophylaxis influenced the rate of toxoplasmic encephalitis in any group. CONCLUSIONS: Low-dose trimethoprim-sulfamethoxazole (four tablets per week) appears to be effective prophylaxis against toxoplasmic encephalitis in HIV-infected patients with previous P. carinii pneumonia. A prospective, randomized, controlled study is needed to further evaluate these findings.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Chronic colitis associated with human immunodeficiency virus infection.

OBJECTIVE: A clinical and pathological description of chronic colitis associated with human immunodeficiency virus (HIV) infection. DESIGN: A retrospective case review. SETTING: Tertiary referral institution and specialist gastroenterology practice. PATIENTS: A series of six patients with human immunodeficiency virus infection and chronic colitis observed for up to four years. RESULTS: The six patients had chronic diarrhoea for longer than six months, rectal bleeding, abdominal pain and stool leukocytosis. The mucosal pattern on colonoscopy showed diffuse proctocolitis, consisting of contact bleeding, superficial ulcerations, exudates, and/or loss of vascular pattern. Colonic biopsies showed a persisting diffuse colitis characterised principally by a mixed inflammatory cell infiltrate (mononuclear cells and neutrophils) and essentially preserved crypt architecture after six to 39 months of histological follow-up. The histopathology over this time frame was not typical of ulcerative colitis or Crohn's disease, nor of the conventionally described forms of infective colitis. HIV nucleic acid was identified by insitu hybridisation in colonic biopsies from four patients. In two of three patients tested, the presence of HIV DNA was confirmed by Southern blot analysis. No other microbial agent could be demonstrated as the cause of diarrhoea. At presentation all patients had CD4+ lymphocyte counts greater than 265 x 10(6)/L and none had the acquired immunodeficiency syndrome. Four patients have gone into remission, the other two patients were not in remission at four and a half to five years after onset. CONCLUSION: We suggest that chronic colitis may represent a new entity related to infection of the colon with human immunodeficiency virus.

Acquired Immunodeficiency Syndrome↗