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Biomedical subjects

I Weller

Publications and source records attributed to I Weller.

At least 19 recordsLinked to original sources
PubMed2006

A prospective study of Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus in adults with human immunodeficiency virus-1.

Antibody titres against Kaposi's sarcoma associated herpesvirus (KSHV or human herpesvirus 8 (HHV-8)) and Epstein-Barr virus (EBV) were examined in people who subsequently developed Kaposi's sarcoma and non-Hodgkin's lymphoma, within randomised controlled trials of antiretroviral therapy in adults infected with the human immunodeficiency virus-1 (HIV). For each case of Kaposi's sarcoma (n=189) and each case of non-Hodgkin's lymphoma (n=67), which developed after randomisation, one control was randomly selected from other trial participants, after matching for age, sex, ethnicity, mode of HIV transmission, type of treatment received and period of follow-up. Using sera taken an average of two and a half years before the diagnosis of cancer, titres of antibodies against KSHV latent (LANA) and lytic (K8.1) antigens and against EBV (VCA) antigens were investigated in relation to subsequent risks of cancer by calculating odds ratios (OR) using conditional logistic regression. Latent antibodies against KSHV were detectable among 38% (72 out of 189) of Kaposi's sarcoma cases and 12% (23 out of 189) of their controls (OR=4.4, 95% confidence intervals (CI) 2.3-8.3, P<0.001). The OR for Kaposi's sarcoma increased with increasing antilatent KSHV antibody titre (chi(2)(1) for trend=32.2, P<0.001). Lytic antibodies against KSHV were detectable among 33% (61 out of 187) of Kaposi's sarcoma cases and 19% (36 out of 187) of their controls (OR=2.0, 95% CI 1.2-3.4, P=0.003) and the OR for Kaposi's sarcoma increased with increasing antilytic KSHV antibody titre (chi(2)(1) for trend=6.2, P=0.02). Virtually, all cases and controls had anti-EBV antibodies detected and the OR for non-Hodgkin's lymphoma associated with a doubling of the anti-EBV antibody titre was estimated to increase by a multiplicative factor of 1.3 (95% CI 0.9-1.7, P=0.1). Kaposi's sarcoma was not associated with antibody levels against EBV (P=0.4) and non-Hodgkin's lymphoma was not associated with antibodies against KSHV (latent P=0.3; lytic P=0.5). Adjustment for CD4 count at the time of sample collection made no material difference to any of the results. In conclusion, among human immunodeficiency virus infected people, high levels of antibodies against KSHV latent and lytic antigens are strongly associated with subsequent risk of Kaposi's sarcoma but not non-Hodgkin's lymphoma. Antibody titre to EBV does not appear to be strongly associated with subsequent risk of Kaposi's sarcoma or non-Hodgkin's lymphoma in HIV infected people.

Adult↗
PubMed2005

The effect of hospital type and surgical delay on mortality after surgery for hip fracture.

Death during the first year after hip fracture may be influenced by the type of hospital in which patients are treated as well as the time spent awaiting surgery. We studied 57,315 hip fracture patients who were admitted to hospital in Ontario, Canada. Patients treated in teaching hospitals had a decreased risk of in-hospital mortality (odds ratio (OR) 0.89; 95% confidence interval (CI) 0.83 to 0.97) compared with those treated in urban community institutions. There was a trend toward increased mortality in rural rather than urban community hospitals. In-hospital mortality increased as the surgical delay increased (OR 1.13; 95% CI 1.10 to 1.16) for a one-day delay and higher (OR 1.60; 95% CI 1.42 to 1.80) for delays of more than two days. This relationship was strongest for patients younger than 70 years of age and with no comorbidities but was independent of hospital status. Similar relationships were seen at three months and one year after surgery. This suggests that any delay to surgery for non-medical reasons is detrimental to a patient's outcome.

Aged↗
PubMed2001

Therapeutic vaccination (p24-VLP) of patients with advanced HIV-1 infection in the pre-HAART era does not alter CD4 cell decline.

In a randomized placebo controlled trial 304 HIV infected patients with CD4 cell counts below 350 cells/microL received therapeutic vaccination with: alum placebo (Group I, n = 102), p24-VLP 500 microg (Group II, n = 101) or p24-VLP 1000 microg (Group III, n = 101) p24-VLP monthly for six months. Over one year the average change in CD4 cell count did not differ significantly between groups (-32, -40 and -52 cells per microL respectively). There was also no difference between groups in progression to CDC category B or C events, or in adverse events. Therapeutic vaccination with p24-VLP does not affect CD4 cell decline in patients with advanced HIV infection.

AIDS Vaccines↗
PubMed2000

The relation between hip fracture and alzheimer's disease in the canadian national population health survey health institutions data, 1994-1995. A cross-sectional study.

PURPOSE: The purpose of this study is to examine the relation between hip fractures and Alzheimer's disease in institutionalized men and women who participated in the 1994-1995 Canadian National Population Health Survey (NPHS).METHODS: Participants in the institutional component of NPHS were randomly chosen from selected health care institutions from all provinces in Canada. A questionnaire, which assessed health, demographic and socio-economic status, risk factors, medication use, and falls, was administered by an interviewer. Proxy respondents were sought for residents who were ill or incapacitated. Logistic regression was used to examine the association between hip fractures and Alzheimer's disease in 408 men and 1105 women >/=65 years. Models were examined with either hip fracture or Alzheimer's disease as the dependent variable. Covariates that were assessed included osteoporosis, age group, sex, medications, reported falls and comorbid conditions.RESULTS: All hip fractures reported in this survey were the result of a fall, however only 3.7% of falls resulted in a hip fracture. Those who had sustained a hip fracture were more likely to have Alzheimer's disease (OR 2.0, 95% CI 1.1-3.5), osteoporosis (OR 4.3, 95% CI 2.5-7.4) and heart disease (OR 2.4, 95% CI 1.1-5.0). Respondents who had Alzheimer's disease were more likely to have sustained a hip fracture (OR 2.1 95% CI 1.2-3.6), to have osteoporosis (OR 1.9, 95% CI 1.5-2.5), and to have fallen (OR 1.4, 95% CI 1.1-1.8) and were less likely to be taking anti-psychotic medication (OR 0.4, 95% CI 0.3-0.6) than those with no diagnosis of Alzheimer's disease.CONCLUSIONS: There is an association between Alzheimer's disease and hip fractures that is independent of other covariates in this representative sample of institutionalized elderly Canadians.

Journal Article↗
PubMed1999

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Acupuncture Therapy↗
PubMed1998

The impact of excluding non-leisure energy expenditure on the relation between physical activity and mortality in women.

The purpose of this study was to examine the relation between physical activity and mortality in a 7-year follow-up of a sample of women more than 30 years of age (N = 6,620) from the Canada Fitness Survey cohort, which was initiated in 1981. Age-adjusted relative risks relating quartiles of average daily energy expenditure (kilocalories per kilogram of body weight per day) to mortality were estimated using logistic regression. Compared with the least active, the risk of all-cause mortality was 0.73 for those in the highest quartile (P for trend = 0.03). The associations were stronger for cardiovascular disease mortality (odds ratio = 0.51; P for trend = 0.01) and fatal myocardial infarction (odds ratio = 0.61; P for trend = 0.04) for those in the highest quartile. These relations were due mainly to the contribution of non-leisure (household chores) energy expenditure, which represented, on average, 82% of women's total activity. The accompanying study on the same cohort by Villeneuve et al reported estimates based on a subset of leisure-time physical activity only, which underestimates the activity of many women (Villeneuve PJ, Morrison HI, Craig CL, Schaubel DE. Physical activity, physical fitness, and risk of dying. Epidemiology 1998;9;632-635). The resulting bias illustrates the importance of including non-leisure energy expenditure in the assessment of total activity. These data support the hypothesis that physical activity is inversely associated with risk of death in women.

Adult↗
PubMed1993

Epstein-Barr virus infection of HIV-seropositive individuals is transiently suppressed by high-dose acyclovir treatment.

OBJECTIVE: To assess whether oral acyclovir can eliminate persistent Epstein-Barr virus (EBV) infection and thereby prevent EBV-associated lymphoma development in HIV-seropositive homosexual men. METHOD: Persistent EBV infection was examined in a group of 21 HIV-seropositive homosexual men before, during and after treatment with oral acyclovir at a dose of 800 mg every 6 h (10 individuals) or with a placebo (11 individuals). RESULTS: In 13 individuals, EBV was isolated from the oropharynx before and after treatment (seven cases from the acyclovir-treated group and six from the placebo-treated group). A significant reduction in virus isolation occurred during treatment in the acyclovir-treated group, but not in the placebo-treated group. In seven cases in whom EBV shedding was detected before and after treatment, the EBV strain isolated was identical throughout the study, even when acyclovir had abolished detectable shedding for the duration of the treatment. In two other cases more than one strain was detected. On examination of the EBV type present, 89% of a group of 18 patients consistently shed type A virus, 5.5% type B virus and 5.5% showed evidence of co-infection with both virus types. This compares with figures of 100, 0 and 0%, respectively, in a control group of HIV-seronegative individuals. CONCLUSIONS: High-dose acyclovir therapy does not eliminate persistent EBV infection from the oropharynx of healthy HIV-seropositive individuals and therefore would not necessarily prevent lymphoma development. Our results suggest that infection by type B EBV, and co-infections of both A and B type, are more common in HIV-seropositives than HIV-seronegatives.

Acyclovir↗
PubMed1993

Mood and psychiatric disturbance in HIV and AIDS: changes over time.

A sample of 26 HIV seronegative, 59 HIV seropositive asymptomatic and 7 HIV seropositive symptomatic homosexual and bisexual men were assessed over two visits, a mean of 11 months apart, using the BDI, STAI, and CIS. Significant differences emerged between the symptomatic group and the other two groups. Past psychiatric history and the somatic items in the assessments accounted for some of these differences. The seropositive asymptomatic and the seronegative groups did not differ on any of the mood or psychiatric assessments, suggesting minimal effect on psychological well-being of seroconversion in the absence of symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Risk of Kaposi's sarcoma and sexual practices associated with faecal contact in homosexual or bisexual men with AIDS.

The causal agent of Kaposi's sarcoma is unknown. That the disorder is ten times more common in homosexual or bisexual men with the acquired immunodeficiency syndrome (AIDS) than in other human immunodeficiency virus (HIV) transmission groups suggests that a certain aspect of their behaviour exposes them to the agent or facilitates its spread. We therefore assessed social and demographic characteristics, including sexual behaviour, of 65 homosexual or bisexual men with AIDS from London. Sexual practices in which there was contact with partner's faeces before AIDS developed were the main determinants of Kaposi's sarcoma risk. Risk increased with frequency of insertive "rimming" (oral-anal contact): Kaposi's sarcoma developed in 18% of the men with AIDS who reported never having practised insertive rimming compared with 50% who practised it less than once a month, 73% between once a week and once a month, and 75% or more once a week (two-sided exact p-value for trend less than 0.001). 45 men had been interviewed about their sexual practices before AIDS developed, and 20 were interviewed at the time the syndrome developed. The findings were similar and statistically significant when each group was analysed separately. The men with Kaposi's sarcoma also tended to be more sexually active and were more likely to engage in other sexual activities that entailed contact with faeces than were the men who had other features of AIDS only. Other behaviours and exposures, including the use of "poppers" (nitrite inhalants), were not related to Kaposi's sarcoma risk, after taking into account whether the subjects had practised insertive rimming. The data suggest that faecal-oral contact is the main route of transmission of the agent of Kaposi's sarcoma in homosexual or bisexual men with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Direct measurement of viraemia in patients infected with HIV-1 and its relationship to disease progression and zidovudine therapy.

Cell-free human immunodeficiency virus type-1 (HIV-1) was precipitated from archival serum with polyethylene glycol (PEG), and HIV-1 RNA was detected and quantified by reverse transcription and amplification in a nested polymerase chain reaction (PCR). The assay of end-point dilutions cDNA in nested PCRs allowed an estimation of the minimum RNA copies per unit volume of serum. RNA titres correlated with the classification of HIV-1 infection by CDC disease groups (30 patients). The geometric mean titres of HIV-1 serum RNA from patients grouped by disease stage gave minimum estimates of 340 and 400 virions per millilitre of serum in CDC groups II and III (n = 6 and 10, respectively) and 4,240 virions per millilitre in CDC group IV (n = 14). An overall fall in viral titre measured in this way was observed in 3 patients during zidovudine treatment. HIV-1 titres increased in a further 4 patients when therapy was interrupted, stopped, or complicated by secondary infection.

Base Sequence↗
PubMed1991

T cell responses to peptides covering the gag p24 region of HIV-1 occur in HIV-1 seronegative individuals.

We demonstrate that peptides (16 amino acids long) covering the sequence of the HIV-1 core protein p24 induce significant proliferation in peripheral blood mononuclear cells (PBMC) of several (greater than 50%) healthy seronegative volunteers as well as seronegative homosexual men. The nature of this response was characterized and compared with those of HIV-infected patients. Several peptides induced responses; however, the most frequent responses in both seropositive and seronegative individuals were noted to the following peptides: 1 and 2 (aa 133-157); 6 and 7 (aa 183-207); 15 (aa 273-287); and 17 and 18 (aa 293-317). The response pattern was related to the disease stage of the patients; seronegative individuals as well as asymptomatic seropositive individuals (CDC II/III) responded to low concentrations of several peptides, but symptomatic patients (CDC IV) only responded to high concentrations of a few peptides. Cell separation studies of PBMC from healthy volunteers showed that the responding cells were CD4+ and expressed the CD45RO differentiation antigen. Furthermore, cord-blood mononuclear cells with less than 5% of CD45RO T cells did not proliferative to any of the peptides. Finally, CD4+ T cell lines specific for both peptides and p24 protein were successfully established from the PBMC of seronegative individuals confirming the data obtained with freshly isolated cells. These studies therefore suggest that the CD4+ cell response to p24 is not strictly disease related, instead, the response may be due to priming of the host with cross-reactive antigens.

Amino Acid Sequence↗
PubMed1991

Altered production of tumour necrosis factors alpha and beta and interferon gamma by HIV-infected individuals.

In vitro studies shows that recombinant tumour necrosis factor (TNF) alpha and beta, and interferon-gamma (IFN-gamma) can enhance HIV replication, and peripheral blood mononuclear cells (PBMC) infected with HIV in vitro secrete high levels of the same cytokines. As T cells secrete all three mediators, the capacity of T cell activation signals to trigger cytokine production in PBMC from HIV-infected individuals was investigated as such patients may be immunocompromised. We demonstrate that asymptomatic seropositives in CDC group II/III as well as patients who have progressed to CDC group IV of the disease proliferate efficiently to anti-CD3 antibody, recombinant interleukin-2 (rIL-2), phytohaemagglutinin (PHA), PHA plus phorbol 12,13 dibutyrate (PMA) but secrete significantly (P less than 0.05) higher amounts of TNF-alpha, TNF-beta and IFN-gamma compared with controls in response to the same stimulants. We also show a difference between group II/III and group IV patients with the latter secreting more TNF-alpha and IFN-gamma. The kinetics of TNF-alpha and -beta, and IFN-gamma production was stimulus dependent with overall levels varying in time for each stimulus. Furthermore, the kinetics of the response to all three stimulants were altered in seropositives; CDC group II/III and group IV patients secreted higher levels of cytokines over several time points compared to controls. The altered production of these mediators by HIV-infected patients may contribute to disease progression and to the pathogenesis of AIDS.

HIV Infections↗
PubMed1987

Human immunodeficiency virus infection in two cohorts of homosexual men: neutralising sera and association of anti-gag antibody with prognosis.

Sequential sera from 48 subjects infected with human immunodeficiency virus type I (HIV-I) were examined over 36 months for the presence of neutralising antibodies, and for specific anti-gag (p24) and anti-env (gp41) antibodies to HIV-I. Results were interpreted in terms of clinical outcome during the period 1982/3 to 1985/6. HIV-I-infected subjects who remained symptom-free, by comparison with those who manifested AIDS or AIDS-related complex (ARC), had a significantly higher titre of anti-p24 antibodies throughout the 3 years, as measured by competitive enzyme-linked immunosorbent assay and radioimmunoprecipitation. The symptomless subjects also showed a trend towards an increasing neutralising antibody titre with time. There was no relation between anti-gp41 titre and clinical outcome, nor an independent relation between anti-p24 and neutralising titre. A lower or falling titre of anti-p24 antibody was associated significantly with clinical progression, up to 27 months before development of AIDS/ARC.

AIDS-Related Complex↗