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Biomedical subjects

B Tindall

Publications and source records attributed to B Tindall.

At least 19 recordsLinked to original sources
PubMed1998

Dehalobacter restrictus gen. nov. and sp. nov., a strictly anaerobic bacterium that reductively dechlorinates tetra- and trichloroethene in an anaerobic respiration.

The highly enriched anaerobic bacterium that couples the reductive dechlorination of tetrachloroethene to growth, previously referred to as PER-K23, was obtained in pure culture and characterized. The bacterium, which does not form spores, is a small, gram-negative rod with one lateral flagellum. It utilized only H2 as an electron donor and tetrachloroethene and trichloroethene as electron acceptors in an anaerobic respiration process; it could not grow fermentatively. Acetate served as a carbon source in a defined medium containing iron as the sole trace element, the two vitamins thiamine and cyanocobalamin, and the three amino acids arginine, histidine, and threonine. The cells contained menaquinones and b-type cytochromes. The G+C content of the DNA was 45.3 +/- 0.3 mol%. The cell wall consisted of type-A3gamma peptidoglycan with ll-diaminopimelic acid and one glycine as an interpeptide bridge. The cells are surrounded by an S-layer; an outer membrane was absent. Comparative sequence analysis of the 16S rRNA sequence showed that PER-K23 is related to gram-positive bacteria with a low G+C content of the DNA. Based on the cytological, physiological, and phylogenetic characterization, it is proposed to affiliate the isolate to a new genus, Dehalobacter, with PER-K23 as the type strain of the new species Dehalobacter restrictus.

Anaerobiosis↗
PubMed1995

A controlled trial of zidovudine in primary human immunodeficiency virus infection.

BACKGROUND: It is possible that antiretroviral treatment given early during primary infection with the human immunodeficiency virus (HIV) may reduce acute symptoms, help preserve immune function, and improve the long-term prognosis. METHODS: To assess the effect of early antiviral treatment, we conducted a multicenter, double-blind, placebo-controlled trial in which 77 patients with primary HIV infection were randomly assigned to receive either zidovudine (250 mg twice daily; n = 39) or placebo (n = 38) for six months. RESULTS: The mean time from the onset of symptoms until enrollment in the study was 25.1 days. Among the 43 patients who were still symptomatic at the time of enrollment, there was no appreciable difference in the mean (+/- SE) duration of the retroviral syndrome between the zidovudine group (15.0 +/- 4.1 days) and the placebo group (15.8 +/- 3.6 days). During a mean follow-up period of 15 months, minor opportunistic infections developed in eight patients: oral candidiasis in four, herpes zoster in two, and oral hairy leukoplakia in two. Disease progression was significantly less frequent in the zidovudine group (one opportunistic infection) than in the placebo group (seven opportunistic infections; P = 0.009 by the log-rank test). After adjustment for the base-line CD4 cell count, the patients treated with zidovudine had an average gain of 8.9 CD4 cells per cubic millimeter per month (95 percent confidence interval, -1.4 to 19.1) during the first six months of the study, whereas those receiving placebo had an average loss of 12.0 CD4 cells per cubic millimeter per month (95 percent confidence interval, 5.2 to 18.7), for a between-group difference of 20.9 CD4 cells per cubic millimeter per month (95 percent confidence interval, 8.5 to 33.2; P = 0.001). CONCLUSIONS: Antiretroviral therapy administered during primary HIV infection may improve the subsequent clinical course and increase the CD4 cell count.

AIDS-Related Opportunistic Infections↗
PubMed1995

Is the human immunodeficiency virus-related Kaposi's sarcoma epidemic coming to an end? Insights from the Tricontinental Seroconverter Study.

A decline in the proportion of Kaposi's sarcoma among AIDS cases since the 1980s has been attributed to changes in sexual behavior among homosexual men and a decreasing exposure to a hypothesized Kaposi's sarcoma cofactor. Recent studies have shown that the incidence rate of Kaposi's sarcoma has remained relatively stable, which seems to argue against the hypothesis of a declining exposure to the putative cofactor. To examine this paradox, we evaluated the incidence of Kaposi's sarcoma, using Cox proportional hazard analyses, and performed a simulation to compare incidences of different AIDS outcomes among 407 homosexual men with documented dates of seroconversion. Our data show that men who seroconverted early in the epidemic did not progress faster to Kaposi's sarcoma than men who seroconverted more recently. A lower incidence rate of Kaposi's sarcoma would be expected among the latter group if exposure to the hypothesized cofactor is decreasing over time. The percentage of Kaposi's sarcoma among incident AIDS cases decreased over the years following seroconversion, but not over calendar time. This study demonstrates that the decline in the proportion of Kaposi's sarcoma among AIDS cases should not be interpreted as a decline in the incidence of Kaposi's sarcoma and that there is no evidence that a hypothesized Kaposi's sarcoma cofactor is declining over calendar time.

Acquired Immunodeficiency Syndrome↗
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

Structure elucidation and biosynthesis of 31-methylhopanoids from Acetobacter europaeus. Studies on a new series of bacterial triterpenoids.

Apart from a mixture of bacteriohopanetetrols already found in other Acetobacter species, four new 3 beta-methylhopanoids have been isolated from Acetobacter europaeus. All of them present an ether linkage between a bacteriohopanetetrol or a bacteriohopanepentol and a carbapseudopentose moiety often found in bacterial hopanoids. Three of these ethers were shown by comparison with synthetic reference hopanoids to posess a supplementary methyl group at C31. This novel series of methylhopanoids may be the precursor of yet unidentified molecular fossils found in sediments. [methyl-2H3]Methionine was efficiently incorporated into the 31-methylhopanoids with retention of all three deuterium atoms in the transferred methyl group. This labelling pattern might be consistent with a rather rarely found methylation reaction of an enol.

Acetobacter↗
PubMed1994

Estimation of time since infection using longitudinal disease-marker data.

We propose a method to estimate the usually unknown time since infection for individuals infected with human immunodeficiency virus type 1 (HIV-1). If we assume the time since infection has an exponential prior distribution, then under the model the conditional distribution of time since infection, given the CD4 level at the time of the first positive HIV-1 antibody test, is a truncated normal density. We applied the method to prevalent cohort data both from intravenous drug users and from homosexual/bisexual men. For the intravenous drug users the estimated mean time since infection was 15.0 months from infection at a presumed mean CD4 level of 1060 cells/ml to first positive antibody test at a CD4 level of 597 cells/ml, which was the average CD4 at enrollment for infected subjects. For the homosexual/bisexual men the estimated mean time since infection was 16.7 months from infection at a presumed mean CD4 level of 699 cells/ml to first positive antibody test at an average CD4 level of 577 cells/ml. We performed a validation study using initially seronegative subjects in these cohorts who seroconverted to HIV-1-positive antibody status during the follow-up period. For the intravenous drug users, data were too few to provide definitive verification of the method. In the cohort of homosexual/bisexual men, however, there was a total of 70 seroconverters with relevant data. Among them, the median absolute difference between the midpoint of the known seroconversion interval and the estimated mean infection date was 4.6 months, conditional on CD4-lymphocyte measurements taken approximately 18 months subsequent to infection. Conditional on CD4 approximately 30 months after infection, this median difference increased modestly to 8.2 months. Our analysis suggested that the underlying mathematical model tends to overestimate short times since infection and underestimate long times since infection. We consider potential corrective modifications to the model.

Bias↗
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

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

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↗
PubMed1994

Increasing age is associated with faster progression to neoplasms but not opportunistic infections in HIV-infected homosexual men.

OBJECTIVE: To characterize the associations of age and progression rates to AIDS-defining neoplasms and opportunistic infections (OI) in HIV-infected homosexual men. METHODS: Data from 407 homosexual men with documented dates of HIV seroconversion participating in cohort studies from four geographic locations were merged. Kaplan-Meier and Cox proportional hazards analyses were conducted with respect to the association of age with time from seroconversion to the first AIDS-defining neoplasm and OI. RESULTS: Among the 407 participants, 139 (34%) were diagnosed with AIDS; 45 (11%) with neoplasms and 90 (22%) with OI. Older age at seroconversion was significantly associated with faster progression to neoplasms, but not to OI. For each 10-year increase in age the risk for neoplasms increased 1.65-fold [95% confidence interval (CI), 1.12-2.43], after adjustment for clinical treatments. For OI this risk estimate was 0.98 (95% CI, 0.72-1.34). CONCLUSIONS: Increasing age is associated with faster progression to AIDS-defining neoplasms, but not with progression to OI. This has not been previously reported and may explain conflicting results in other studies among homosexual men that considered AIDS as a single entity. Our findings suggest that age and AIDS manifestations should be considered, particularly in the context of natural history studies, clinical trials and mathematical modelling.

AIDS-Related Opportunistic Infections↗
PubMed1993

Subtypes of Epstein-Barr virus (EBV) in Hodgkin's disease: association between B-type EBV and immunocompromise.

Epstein-Barr virus (EBV) has been associated with Hodgkin's disease (HD) in up to 50% of cases, but the subtype of EBV involved has only recently been studied. In this report, biopsy samples from 30 patients with HD were assessed for EBV sequences using both the polymerase chain reaction (PCR) and in situ hybridization (ISH). EBV sequences were localized to the malignant Reed-Sternberg cells and their mononuclear variants (Hodgkin's cells) in 9 of the 30 cases, with 7 demonstrating A-type and 2 B-type EBV sequences. Both of the patients with B-type EBV-associated HD had features to suggest pre-existing immune compromise: one was infected with human immunodeficiency virus (HIV) and had severe CD4+ T-lymphocyte depletion; the other was a debilitated elderly patient with dementia. A previous study suggested that A-type EBV alone is associated with HD and the finding of predominantly A-type EBV in the present series is in keeping with this report. The presence of B-type EBV in the HD of patients with pre-existing immunodeficiency, taken together with the recent report that B-type EBV occurs in HIV-associated non-Hodgkin's lymphoma, suggests that B-type EBV may be an important human pathogen in immunocompromised patients.

Actins↗
PubMed1993

HIV seroconversion illness.

HIV seroconversion is associated with characteristic clinical findings which reflect the first interaction of HIV with the host immune system. Recognition of the characteristic clinical illness associated with HIV seroconversion helps to establish an early diagnosis and obviates the need for further investigation or empiric therapy. It may also afford a unique opportunity to institute counselling to prevent the further spread of HIV in the community.

Adult↗
PubMed1993

Development of AIDS in people with transfusion-acquired HIV infection.

OBJECTIVE: To determine the rate of development of AIDS, and the demographic and clinical cofactors for development of AIDS in a group of 117 people with transfusion-acquired HIV infection, who were infected between 1980 and 1985 in New South Wales, Australia. RESULTS: By December 1991, 67 (57%, 95% CI 48-66%) of the study subjects had developed AIDS. The estimated median time to development of AIDS was 7.2 years from the date of infection. There was no significant difference in median age at infection or sex between individuals who did and did not develop AIDS. The median time to development of AIDS was shorter in older individuals (median time to AIDS for age groups 13-39, 40-59 and > 59 was 7.8, 7.1 and 5.4 years, respectively; P = 0.20). A significantly greater proportion of individuals who had never received treatment with zidovudine developed AIDS compared with individuals who had (P = 0.04). But in a statistical analysis which took account of the changing availability of zidovudine over time, there was no significant association between the development of AIDS and treatment with zidovudine (P = 0.44). CONCLUSION: Consistent with other studies, age appeared to increase the rate of progression to AIDS, although not significantly so in this study.

Acquired Immunodeficiency Syndrome↗
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

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↗