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Biomedical subjects

D A Cooper

Publications and source records attributed to D A Cooper.

At least 235 records · Page 13Linked to original sources

CD4% is the best predictor of development of AIDS in a cohort of HIV-infected homosexual men.

To determine the relationships between individuals' baseline T-cell subsets, their rates of change with time, and AIDS-free survival time, data were collected at 6-monthly intervals from 379 HIV-seropositive homosexual Sydney men, of whom 31 developed AIDS during the 3-year observation period. Both CD4% and rate of change of CD4% in an individual had significant prognostic value in determining AIDS-free survival time. Compared with subjects whose CD4% remained stable, subjects whose CD4% dropped by 7% or more in a year had a relative hazard of 35.1 (95% confidence interval = 11.7-105.6, P less than 0.001) of developing AIDS. Increasing CD4% had a significant protective effect, reducing the risk of developing AIDS. CD4%, CD4 cell count and CD4: CD8 ratios showed steeper declines in subjects who were later diagnosed with AIDS than in those who remained AIDS-free. The rates of immunological change in AIDS-free seroconverters and seropositives were similar, despite indeterminate differences in durations of infections. In the multivariate Cox regression analysis, baseline CD4%, the rate of change of CD4%, and baseline lymphocyte count were associated with AIDS-free survival time. Baseline CD4% had greater prognostic value than baseline CD4 cell count. Baseline CD8%, baseline CD8 count, their rates of change and their mean square errors were not independently significant in this analysis. These findings are important for clinicians monitoring HIV infection in an individual and for entry criteria and monitoring procedures in clinical trials. They also have implications for resource-poor settings; prognosis based on CD4% can be made with a flow cytometer without a full blood count.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Zidovudine in the management of primary HIV-1 infection.

Eleven subjects who presented with a clinical illness characteristic of primary HIV-1 infection were treated with 1 g zidovudine daily for a median period of 56 days (range, 28-111 days). Primary HIV-1 infection was confirmed in each subject by seroconversion and virus isolation. The acute phase of the illness resolved a median of 4 days (range, 3-14 days) from commencement of zidovudine. Six subjects reported symptoms that may have been side-effects of zidovudine, the most common being nausea in four subjects and headache in two. Treatment was discontinued in one subject who had persistent headache and nausea. Haemoglobin, haematocrit and erythrocyte counts decreased and mean corpuscular volume increased significantly during the treatment. None of the subjects developed anaemia and none required dose modification or blood transfusion as a result of haematological side-effects. There were no significant differences in the granulocyte count or the lymphocyte count during any week of treatment when compared with baseline levels. There were no significant differences in T-cell subset numbers of the subjects during treatment compared with a group of historical controls. HIV-1 was isolated from several subjects during and after termination of zidovudine treatment. The results of this investigation indicate that zidovudine is a safe drug to administer to people with primary HIV-1 infection. There was no clear evidence, however, of any clinical benefit in terms of resolution of the acute illness and no indication that the treatment would prevent development of persistent infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

The efficacy and safety of zidovudine with or without acyclovir in the treatment of patients with AIDS-related complex. The European-Australian Collaborative Group.

Our objective was to evaluate the efficacy and safety of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) as treatment for AIDS-related complex (ARC). A double-blind, controlled clinical trial of 6 months therapy was conducted at teaching hospital ambulatory clinics in eight European countries and Australia; 199 patients were studied. Time to development of AIDS-defining opportunistic infections (OI) and AIDS-associated neoplasms, survival, performance status, body weight and CD4+ cell counts were measured. During the study six (9%) zidovudine recipients, five (7%) combination recipients and 12 (18%) placebo recipients developed AIDS-defining OI; the probability of developing an OI was 0.23, 0.09 and 0.08 for the placebo, zidovudine and combination recipients, respectively. Four patients in the placebo group, three in the zidovudine group and one in the combination group died during the study. Patients receiving zidovudine with or without acyclovir had moderate increases in CD4+ cell counts compared with placebo recipients and serum HIV p24 antigen level decreased significantly in all those receiving zidovudine. Fourteen (21%) patients in the zidovudine group and 16 (24%) in the combination group experienced bone-marrow suppression compared with three (5%) placebo recipients. Red-cell transfusions were administered to 6, 19 and 13% of placebo, zidovudine and combination recipients, respectively. These data confirm the efficacy of zidovudine therapy after 4 weeks' treatment in the reduction of development of OI in patients with ARC and support the use of a maintenance dose of 250 mg zidovudine 6-hourly. Given the increased development of OI in the treated groups compared with placebo during the first 4 weeks of therapy, we cannot exclude an initial adverse effect of zidovudine and recommend caution in the use of a loading dose of zidovudine. At 6 months there was no apparent difference in efficacy between the combination of zidovudine and acyclovir compared with zidovudine alone. Moreover, the addition of high-dose acyclovir resulted in a minimal increase in the risk of toxicity.

AIDS-Related Complex↗

Anaerobic biodegradation of cyanide under methanogenic conditions.

Upflow, anaerobic, fixed-bed, activated charcoal biotreatment columns capable of operating at free cyanide concentrations of greater than 100 mg liter-1 with a hydraulic retention time of less than 48 h were developed. Methanogenesis was maintained under a variety of feed medium conditions which included ethanol, phenol, or methanol as the primary reduced carbon source. Under optimal conditions, greater than 70% of the inflow free cyanide was removed in the first 30% of the column height. Strongly complexed cyanides were resistant to removal. Ammonia was the nitrogen end product of cyanide transformation. In cell material removed from the charcoal columns, [14C]bicarbonate was the major carbon end product of [14C]cyanide transformation.

Anaerobiosis↗

Effects of progestagen treatment on concentrations of prostaglandins and oxytocin in plasma from the posterior vena cava of post-partum beef cows.

The role of PGF-2 alpha in determining the lifespan of corpora lutea in the post-partum beef cow was investigated. In control cows (N = 5) induced to ovulate at Day 28 to 36 post partum by injection of 1000 i.u. hCG, corpora lutea had an average lifespan of only 8 days. In cows pretreated with 6 mg implants of a progestagen (norgestomet, N = 4) for 9 days, with implant removal 2 days before injection of hCG, luteal lifespan averaged 17.5 days. Concentrations of PGF-2 alpha in 9 hourly samples of plasma collected from the posterior vena cava via indwelling catheters were higher on Days 4 through 9 after injection of hCG (P less than 0.05) in the cows with short-lived corpora lutea. Greater release of PGF-2 alpha could therefore be a major factor in premature luteal regression. Concentrations of PGFM and oxytocin did not differ between cows with corpora lutea of short or normal lifespan. In a second experiment, concentrations of PGF-2 alpha in plasma from the posterior vena cava were examined during treatment with norgestomet (N = 8) or in contemporary controls (N = 7). In progestagen-treated cows, PGF-2 alpha was higher than in control cows (P less than 0.05), beginning on Day 3 of treatment and peaking on Day 5. It is concluded that the post-partum uterus increases secretion of PGF-2 alpha very early after first exposure to endogenous or exogenous progestagen.

Animals↗

Helicobacter pylori-associated gastritis is rare in AIDS: antibiotic effect or a consequence of immunodeficiency?

Helicobacter pylori is the principal cause of type B histologic gastritis. AIDS is associated with increased susceptibility to Gram-negative enteric infections. Using a retrospective study design, we have determined the prevalence of H. pylori-associated histologic gastritis (based on gastric histopathology) in 201 patients with AIDS. These data were compared with H. pylori prevalence rates (based on serology) from healthy HIV-negative, age-matched Australian controls (n = 785) and a cohort (n = 137) of HIV-negative, dyspeptic patients undergoing panendoscopy and antral biopsy, at a community endoscopy center. Twenty-five of 201 (12.5%) patients with AIDS had histologic gastritis and, of these, six (25%) had H. pylori. The 3% (six of 201) H. pylori prevalence rate in the AIDS patients was significantly less than age-matched HIV-negative controls (22%) p = 0.001 and endoscopy center controls (59%) p = 0.009. The explanation for this unexpectedly low prevalence of H. pylori is not possible from these data. It may be a consequence of antimicrobial therapy. Other potential explanations may include specific HIV-related host factors, including hypochlorhydria or an inadequate mucosal inflammatory response, which may impair successful colonization of H. pylori.

Acquired Immunodeficiency Syndrome↗

Update on HIV infection.

With more effective therapies and prophylaxis for HIV infection and its sequelae, survival is steadily improving. This article outlines some of these recent advances in therapy as well as the epidemiology, transmission and natural history of the infection. Prolonged survival and the trend towards earlier intervention have resulted in an increasing role for the primary physician. Clinical and laboratory monitoring of the 'asymptomatic' patient are discussed, with emphasis on selection of the most appropriate times for various medical interventions.

Acquired Immunodeficiency Syndrome↗

Prevalence of maternal HIV infection based on anonymous testing of neonates, Sydney 1989.

The presence of antibody to human immunodeficiency virus (HIV) in post-partum women may be inferred by screening the blood of their newborn babies, since maternal IgG antibodies freely cross the placenta. We tested a sample of 10,217 newborns from 10 hospitals covering three areas in Sydney and other metropolitan centres in New South Wales from April to July, 1989. None of the specimens gave a positive test for antibody to HIV. Thus, the prevalence of HIV positive serology in this sample of newborns was found to be zero. It was estimated that the seroprevalence of antibody to HIV among all neonates in the study area was between zero and 0.045% (99% confidence interval). Because newborns are an accessible group for the study of HIV, and can act as surrogates for their mothers, anonymous testing of this sentinel group will remove some of the limitations generalizing the information in the present database of HIV infection in Australia. This study provides baseline data and suggests that there is not a widespread epidemic of HIV infection among heterosexual persons in Australia at the present time and that routine antenatal testing of women for antibody to HIV may not be cost-effective. However, it will be important to repeat this study at regular intervals to detect any increase in HIV seroprevalence.

Adult↗

Predicting the course of AIDS in Australia.

There have been urgent demands for knowledge about the epidemic of the acquired immunodeficiency syndrome (AIDS) in Australia. Accurate predictions are important for efficient allocation and planning of limited health-care resources. Ideal data for this purpose would be reliable knowledge of the past and present incidence of human immunodeficiency virus (HIV) infection. However, since the incidence of the infection is unknown predictions can only be based on historical data of the incidence of AIDS. In this article, we show the limitations of such predictions by examining a broad range of mathematical models that successfully track the observed data (1187 cases diagnosed to December 31, 1988). In addition, we describe a simple method for prediction in subgroups where the numbers of cases observed so far are small. Four models representing different forms of departure from the simple exponential model provide the best fits to the Australian AIDS data. Regional variability and a possible effect resulting from the introduction of zidovudine were incorporated into the models. Significant regional variability in the course of the epidemic was observed between New South Wales, Victoria and the rest of the country. For Australia as a whole, the doubling time changed from less than one year before mid 1987 to more than two years after this time. Model fits were improved by fitting the models to just the four years of data from 1985. The models give comparable predictions for the first year (1989) of around 600 new cases. However, by 1993 the predictions vary considerably, ranging from 500 to 2300 new cases. It is predicted that between 3100 and 6700 cases are likely to be diagnosed in Australia between 1989 and 1993. The results from the subgroup prediction demonstrate that when the observed number of cases is small, then the range of predictions for a future time interval is very wide. For reliable long-term predictions that are necessary for public health planning, basic information on the past and present incidence of HIV infection is urgently needed.

Acquired Immunodeficiency Syndrome↗

Effect of zidovudine on survival of patients with AIDS in Australia.

Since the first case of AIDS in Australia was diagnosed in December 1982, there have been substantial improvements in the treatment of AIDS-related conditions. In particular, zidovudine was widely introduced into clinical practice in Australia in June 1987. In order to evaluate its effect, we compared the survival of patients diagnosed before and after July 31, 1987 using data available in early 1989. Survival distributions were compared by means of Kaplan-Meier curves and by fitting exponential survival models incorporating a special feature of the data. Before August 1, 1987 the overall distribution of survival times for patients with AIDS in Australia is well described by an exponential distribution with a mean of 1.04 years. The corresponding median survival time for this period was 8.8 months. For patients diagnosed with AIDS after July 31, 1987 the median survival time had not been attained by December 31, 1988. However, the estimated mean survival time increased to 2.7 years. Survival times were found to be remarkably stable over the different regions of Australia. We have shown that substantial improvements in survival of patients diagnosed with AIDS in Australia are associated with the widespread availability of zidovudine from mid 1987. To the best of our knowledge this study is the first of its kind to show a major shift in the distribution of survival associated with the introduction of antiviral therapy.

Acquired Immunodeficiency Syndrome↗

Development of AIDS in a cohort of HIV-seropositive homosexual men in Australia.

The Sydney AIDS Prospective Study is a cohort study of 1057 homosexual men enrolled between February 1984 and January 1985. By June 30, 1989, 111 (26.8%) of the 414 men who were seropositive for antibodies to human immunodeficiency virus (HIV) at enrollment had developed the acquired immunodeficiency syndrome (AIDS). On univariate analysis the following baseline factors were significantly associated with subsequent development of AIDS: splenomegaly; a lymphocyte count less than 1500 x 10(6)/L; a percentage of CD4+ cells less than 20% of the total lymphocyte count; an absolute number of CD4+ cells less than 200 x 10(6)/L; and a CD4+: CD8+ ratio less than 1.00. In a proportional hazards model the following factors retained significance: a lymphocyte count less than 1500 x 10(6)/L; an absolute number of CD4+ cells less than 200 x 10(6)/L; and a CD4+: CD8+ ratio less than 1.00. A CD4+ cell count less than 200 x 10(6)/L carried the greatest relative risk (3.99) for the development of AIDS. This study has confirmed that the appreciable rates of progression to AIDS demonstrated in overseas cohorts of HIV-infected persons also apply in the Australian context. A number of laboratory variables was found to be predictive for the subsequent development of AIDS. As we were not able to determine accurately whether subjects were receiving antiretroviral treatment or prophylaxis for opportunistic infections the observed rates in this study should be seen as minimum estimates. These findings have important implications for HIV-infected persons and for public health planning, and emphasise the need for regular clinical monitoring and T-cell subset enumeration in HIV-infected persons.

Acquired Immunodeficiency Syndrome↗

Voluntary HIV antibody testing among STD clinic patients: a pilot study.

A pilot study was conducted with the aim of measuring the acceptability of voluntary testing for human immunodeficiency virus (HIV) antibody among patients attending sexually transmissible disease (STD) clinics. Three STD clinics, two public and one private, participated in the study which was conducted over a three-month period beginning in November 1988. For each patient attending the clinics, sex, date of birth, HIV transmission category and previous HIV test result were recorded. Patients who did not request the HIV antibody test were offered testing. Of the 2356 patients who were included in the analyses, 784 (34%) requested testing. For almost all patients (97%) who requested testing, a serum sample was collected and testing completed. Approximately half (55%) of those patients who were offered the test accepted testing. Overall, 70% of patients completed HIV antibody testing. Of the major transmission categories, the acceptance rate for those offered the test was lowest among homosexual men (45%), who also had the highest rate of HIV antibody seropositivity (11%) among those tested. Of patients who reported themselves to be HIV antibody seronegative prior to the pilot study, 78% were retested during the study and seven had a positive test for HIV antibody. We conclude that voluntary HIV antibody testing is acceptable in both public and private STD clinic settings, although a substantial amount of additional resources would need to be allocated to counselling if voluntary testing is to be introduced on a routine basis.

Acquired Immunodeficiency Syndrome↗