Search PubMed⌕ Search

Biomedical subjects

D A Cooper

Publications and source records attributed to D A Cooper.

At least 163 records · Page 9Linked to original sources
PubMed1995

Effects of primary HIV-1 infection on subsets of CD4+ and CD8+ T lymphocytes.

OBJECTIVE: To analyse changes in T-lymphocyte subsets in patients with primary HIV infection and to determine their specificity (and therefore their diagnostic utility) by comparing these changes with those seen in other acute illnesses as well as in HIV-uninfected patients. METHODS: T-lymphocyte subsets were analysed by two- and three-colour flow cytometry, and compared between HIV seroconverters (n = 16), HIV-infected (n = 18) and uninfected (n = 33) controls, patients with infectious mononucleosis (n = 7), and patients suspected clinically of having primary HIV infection but who were later found to be uninfected (referred to as HIV non-converters; n = 17). RESULTS: CD4+ lymphocyte counts were significantly lower in HIV seroconverters (mean, 444 x 10(6)/l) than in the HIV non-converters (793 x 10(6)/l; P = 0.003), HIV-seronegative controls (888 x 10(6)/l; P < 0.0001) and, to a lesser extent, those with mononucleosis (694 x 10(6)/l; P = 0.045). The reduction in CD4+ lymphocytes occurred in both the CD45RA+ (55%) and CD45R0+ (33%) subsets. CD8+ lymphocyte counts were significantly higher in HIV seroconverters (942 x 10(6)/l) than in HIV non-converters (570 x 10(6)/l; P = 0.003) and seronegative controls (467 x 10(6)/l; P < 0.0001), but significantly lower than in the mononucleosis group (3682 x 10(6)/l; P = 0.004). The CD8+ cells in the HIV seroconverters had increased coexpression of CD45R0, human leukocyte antigen (HLA)-DR, CD38 and CD11a/CD18. The mean CD4: CD8 ratio in the HIV seroconverters was 0.49, versus 1.52 in the non-converters (P < 0.0001), 2.08 in the seronegative patients (P < 0.0001) and 0.37 in the mononucleosis patients (P > 0.2). CONCLUSIONS: Primary HIV infection is characterized by a depletion of CD4+ lymphocytes, especially of the CD45RA+ phenotype, and by an increase in CD8+ lymphocytes with an activated phenotype; the latter was also seen in patients with infectious mononucleosis but not in HIV non-converters or HIV-seronegative patients. Patients suspected clinically of having primary HIV infection but with normal T-cell phenotype are less likely to have primary HIV infection. These phenotypic changes, as well as an inverted CD4: CD8 ratio, can readily distinguish patients with primary HIV infection from HIV-uninfected patients except those with infectious mononucleosis. Therefore, T-cell-subset enumeration may be useful in the diagnosis of primary HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Quinolinic acid production is related to macrophage tropic isolates of HIV-1.

We sought to determine whether the neurotoxin quinolinic acid (QUIN) was produced by macrophages or lymphocytes infected with isolates of HIV-1 with varying degrees of macrophage tropism derived from patients with varying stages of AIDS dementia complex (ADC). Highly macrophage tropic isolates and minimally macrophage tropic isolates were used to inoculate macrophages and QUIN production was measured. Similarly, QUIN production from macrophages was monitored using a purified cell free highly macrophage tropic isolate and laboratory isolates SF33 and SF2. Each of these experiments was also performed with lymphocytes. We found that macrophages infected with macrophage tropic isolates of HIV-1 led to QUIN production while lymphocytes did not produce QUIN. The ability of the HIV-1 infected macrophages to produce QUIN was related to the viral inoculum and the degree of macrophage tropism of the isolate. The severity of ADC in the patient from whom a particular isolate was derived was not per se a determining factor for QUIN production. Purified cell free ADC isolates also led to QUIN production by macrophages thereby suggesting that HIV-1 infection alone is capable of inducing QUIN production.

AIDS Dementia Complex↗
PubMed1995

Novel chlorinated tropanes derived from the treatment of cocaine with sodium hypochlorite.

Several novel chlorinated tropanes were produced when cocaine was treated with aqueous sodium hypochlorite. Two of these, 2'- and 3'-chlorobenzoyloxy-2-carbomethoxypseudotropine (that is, ortho- and meta-chlorococaine), were characterized by synthesis and gas chromatography/mass spectrometry. Four other new chlorinated tropanes (endo-6- and 7-chlorococaine, exo-6- or 7-chlorococaine and N-chlorobenzoylnorecgonine methyl ester) were also tentatively identified via their gas chromatography retention data and mass spectra. The results are of potential use in cocaine signature and comparative analysis.

Chlorine↗
PubMed1994

Determinants of HIV disease progression among homosexual men registered in the Tricontinental Seroconverter Study.

Data on 403 homosexual/bisexual men with documented dates of human immunodeficiency virus (HIV) seroconversion were merged. All subjects originated from cohort studies that started between 1982 and 1984 in Amsterdam, The Netherlands; San Francisco, California; Sydney, Australia; and Vancouver, British Columbia, Canada. With respect to the four geographic locations, no statistically significant differences in progression time from HIV seroconversion to acquired immunodeficiency syndrome (AIDS) and death as well as in AIDS diagnoses patterns could be demonstrated. The median time from HIV seroconversion to AIDS was 8.3 years, that from HIV seroconversion to death was 8.9 years, and that from AIDS to death was 17 months. The authors evaluated HIV disease progression with respect to demographic, clinical, and behavioral cofactors. Younger age and use of prophylaxis against Pneumocystis carinii pneumonia were significantly related to slower progression from seroconversion to death. In addition, an association between slower progression and earlier dates of seroconversion was found. No relation of sexual behavior; history of sexually transmitted diseases; or use of alcohol, tobacco, and recreational drugs with rates of disease progression could be demonstrated.

AIDS Serodiagnosis↗
PubMed1994

Determination and in-depth chromatographic analyses of alkaloids in South American and greenhouse-cultivated coca leaves.

Methodology is described for the detection and/or determination of cocaine and minor alkaloids in South American coca as well as in greenhouse- and tropical-cultivated field coca of known taxonomy. Coca leaf from Bolivia, Peru, Ecuador and Colombia were subjected to the determination of cocaine, cis- and trans-cinnamoylcocaine, tropacocaine, hygrine, cuscohygrine and the isomeric truxillines. The greenhouse samples were cocaine-bearing leaves of the genus Erythroxylum and included E. coca var. coca, E. novogranatense var. novogranatense and E. novogranatense var. truxillense, and the alkaloids determined were cocaine, ecgonine methyl ester, cuscohygrine, tropacocaine and the cinnamoylcocaines. The tropical-cultivated coca were E. novogranatense var. novogranatense and E. coca var. coca. Cocaine and minor alkaloids were isolated from basified powdered leaf samples using a toluene extractant, followed by acid-Celite column chromatography. The isolated alkaloids were determined by capillary gas chromatography with flame ionization or electron-capture detection. Methodology is also presented for the isolation and mass spectral analysis of numerous trace-level coca alkaloids of unknown structure.

Alkaloids↗
PubMed1994

Effects of two formats of informed consent on knowledge amongst persons with advanced HIV disease in a clinical trial of didanosine.

To determine subjects' perception of the purpose of informed consent, 113 subjects were recruited from a dose-controlled clinical trial of didanosine (ddI). Subjects were surveyed regarding how they made decisions regarding their medical care in general, about how they obtained information about this trial in particular, and several aspects of the informed consent procedure. Subjects were then randomly allocated to receive information about the trial by either a written only format or a written and verbal format 1 week before commencement of the trial. An eight-item instrument assessed knowledge of ddI prior to and subsequent to receiving information. Most subjects obtained information about HIV-related issues from their specialist (70%) or general (51%) medical practitioner. A large proportion of subjects (88%) reported that they believed their specialist medical practitioner always acted in their best interest. The majority of subjects (79%) believed that subjects should be allowed the choice between participating in the clinical trial and receiving the drug outside the trial mechanism. Of the subjects, 96% believed that informed consent was necessary in clinical trials; however, their opinions of the purpose of informed consent varied widely. Although they signed the informed consent, 44% of the subjects stated that they did not understand 'all' of the information that was provided. We found that the provision of information by written mode alone, or written and verbal modes were both associated with significant increases in knowledge levels and that there was a significant interaction in the degree of change between the two methods, with the written plus verbal method showing the most improvement over time. There was an interaction between degree of improvement in knowledge of didanosine in subjects who received written information versus those who received written and verbal knowledge and time (pre- versus post-consent) and a significant main effect for time. All subjects were relatively well-informed about the drug and stated that specialist and general medical practitioners were their major source of knowledge for all aspects of their HIV health care.

Adult↗
PubMed1994

Neuropsychological function in asymptomatic HIV-1 infection: methodological issues.

There have been conflicting reports as to whether significant neuropsychological deterioration occurs in asymptomatic HIV-1 infection. Comparisons among studies have been hindered by substantial variations in sample size, statistical methods, definitions of neuropsychological abnormality, and attention to potential confounding factors. In this study, the neuropsychological performance of 44 subjects with asymptomatic HIV-1 infection and 41 seronegative (SN) controls was compared using analysis of variance models. Rates of abnormality were also determined using commonly employed impairment criteria. The seropositive (SP) subjects performed comparably to SN controls once differences in full scale IQ were taken into account. Rates of abnormality for HIV-1 SP subjects were estimated at 10%, 17.5%, and 67.5% by three different criteria, and were not significantly different from the rates of the control group. The findings indicated that both premorbid characteristics, and the validity and biases of definitions of impairment should be examined and incorporated into the interpretation of study findings.

Adult↗
PubMed1994

Neutralizing antibodies against sequential autologous human immunodeficiency virus type 1 isolates after seroconversion.

The emergence of human immunodeficiency virus type 1 (HIV-1) variants with different sensitivities to serum neutralization and biologic phenotype was studied for 2-5 years after primary HIV-1 infection in 5 subjects. In 3 subjects, the initial virus isolate from seroconversion could be neutralized by autologous serum, but isolates obtained at two subsequent times exhibited reduced sensitivity to serum neutralization, decreased replication in primary macrophages, and increased ability to induce syncytia. Two of these 3 subjects progressed to AIDS and died. Sequential virus isolates from the other 2 subjects showed variability in sensitivity to serum neutralization or biologic features. These patients remained relatively stable in clinical status. Thus, viruses isolated at seroconversion appear to be either non-syncytium-inducing, strong macrophage-tropic, serum neutralization-sensitive phenotypes with stable clinical status or to have escaped neutralization by autologous sera over time, have reduced macrophage tropism and increased syncytia formation, and be associated with disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Zidovudine twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study. The European-Australian Collaborative Group (Study 017)

OBJECTIVE: To evaluate the efficacy of zidovudine given twice daily in subjects with asymptomatic HIV-1 infection and a high risk of progression to AIDS. DESIGN: Randomized, double-blind placebo-controlled trial. SETTING: Multicentre study in five European countries and Australia. PATIENTS: Asymptomatic subjects (n = 329) with CD4 cell counts between 200 and 400 x 10(6)/l, or if > 400 x 10(6)/l, subjects with HIV p24 antigenaemia (> 10 pg/ml). INTERVENTION: Patients were randomly assigned to receive zidovudine 500 mg or placebo twice daily for 104 weeks, following a 250 mg four times daily dose regimen for the first 4 weeks. MAIN OUTCOME MEASURES: The primary end-point was the development of AIDS or severe AIDS-related complex (ARC). Before unblinding the study other end-points were defined: the development of Centers for Disease Control and Prevention (CDC) group IV disease (AIDS, severe ARC and other CDC stage IV disease) and the development of symptomatic HIV disease (AIDS, severe ARC, other CDC stage IV disease and minor HIV disease). Changes in CD4+ cell counts, p24 antigenaemia and toxicity were also reviewed. RESULTS: Median treatment duration was 57 weeks for the placebo and 60 weeks for the zidovudine group, respectively. Progression to AIDS or severe ARC occurred in 17 placebo and 12 zidovudine recipients (log-rank P = 0.26). However, in the first of the 2 study years the rate of progression to AIDS or severe ARC was significantly higher in the placebo than in the zidovudine group. Zidovudine delayed progression to symptomatic HIV disease (P = 0.01); a trend in a delay in progression to CDC stage IV disease was observed (P = 0.08). Zidovudine recipients maintained CD4+ cell counts at or above baseline levels for longer than placebo recipients (P = 0.04). HIV p24-antigen levels decreased in the zidovudine group and returned to pretreatment levels by week 36. Substantial toxicity was not observed. CONCLUSIONS: Zidovudine twice daily is effective in delaying progression to symptomatic HIV disease in high-risk, asymptomatic HIV-infected subjects. Modified definitions of clinical end-points may be useful for evaluating Phase III trials in comparable patient groups in the light of changes in the definition of AIDS and the increasing use of primary prophylaxis against opportunistic infections.

AIDS-Related Complex↗
PubMed1994

Acetylation phenotype and cutaneous hypersensitivity to trimethoprim-sulphamethoxazole in HIV-infected patients.

OBJECTIVE: Hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) is more common in patients with HIV infection. In non-infected patients, TMP-SMX hypersensitivity is more common in those with a slow acetylator phenotype. This study was conducted to determine whether the slow acetylation phenotype is associated with an increased risk of hypersensitivity to TMP-SMX in patients with HIV infection. METHODS: Acetylation phenotype was determined in 28 HIV-infected subjects, of whom 16 had prior TMP-SMX hypersensitivity and 12 had received long-term TMP-SMX therapy without hypersensitivity, as well as in 29 healthy controls. Acetylation phenotype was determined by measuring the ratio of two urinary caffeine metabolites, 5-acetylamino-6-amino-3-methyl uracil (AAMU) and 1-methylxanthine (1-MX), after ingestion of a single 200 mg dose of caffeine. RESULTS: Of the 28 HIV-infected subjects, 20 (71%) expressed a slow acetylation phenotype and eight (29%) a fast phenotype. By comparison, of the 29 healthy controls, 15 (52%) expressed a slow phenotype (P = 0.11). Of the 16 HIV-infected subjects with prior TMP-SMX hypersensitivity, 15 (94%) had a slow acetylation phenotype, whereas only five out of 12 (42%) non-hypersensitive subjects had a slow acetylation phenotype (P < 0.01). CONCLUSIONS: A slow acetylation phenotype is a risk factor for hypersensitivity to TMP-SMX in HIV-infected subjects.

Acetylation↗
PubMed1994

Efficacy of zidovudine treatment in homosexual men with AIDS-related complex: factors influencing development of AIDS, survival and drug intolerance. Australian Zidovudine Study Group.

OBJECTIVES: To investigate (1) the efficacy and safety of zidovudine treatment in homo-/bisexual men with AIDS-related complex (ARC) and (2) factors associated with development of intolerance to zidovudine. DESIGN: A multicentre open-label study. SETTING: Australian public hospital system. SUBJECTS: A total of 235 homo-/bisexual men with ARC were enrolled. INTERVENTIONS: All subjects received 1200 mg zidovudine daily. MAIN OUTCOME MEASURES: Survival, incidence and time to development of AIDS and to development of haematological and clinical side-effects. RESULTS: Median time to development of AIDS was 61 weeks, significantly longer (P < 0.03) than the median of 22 weeks in a small control group of 12 untreated ARC subjects. Median survival from development of AIDS was 48 weeks, marginally longer than the 44 weeks in untreated historical AIDS controls. Anaemia requiring transfusion occurred in 113 subjects (48%). Significant differences in time to development of AIDS were found in favour of subjects not requiring transfusions (P < 0.001) with no weight loss (P = 0.004), and who received the full zidovudine dose (1200 mg) during the first 52 weeks of treatment (P = 0.021). Significantly longer median survival times from commencement of zidovudine were found in subjects with a baseline Karnofsky score > or = 90, baseline Hb > or = 13 g/dl, baseline CD4+ cell count > or = 50 x 10(6)/l, no weight loss during first year of treatment, and no or not more than one blood transfusion during treatment. The ability to tolerate full-dose zidovudine was best predicted by a baseline Hb > or = 13 g/dl. Zidovudine-intolerant subjects (defined as the development of either anaemia requiring transfusions, WCC 1000 x 10(6)/l or zidovudine-related myopathy) had a significantly shorter time to development of AIDS than zidovudine-tolerant subjects (P = 0.002). CONCLUSIONS: Zidovudine may benefit people with ARC by significantly postponing the development of AIDS. This benefit appears to be greater in those who do not develop clinical intolerance whilst receiving zidovudine. However, administration of zidovudine to subjects with ARC does not appear to contribute to improved survival after the development of AIDS. People with ARC who develop AIDS while receiving zidovudine, or who develop intolerance to zidovudine, should be considered immediately eligible for other antiretroviral therapies.

AIDS-Related Complex↗