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T McManus

Publications and source records attributed to T McManus.

17 recordsLinked to original sources
PubMed2003

A therapeutic role for cyclooxygenase-2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis.

Recent studies indicate that the proinflammatory enzyme cyclooxygenase (COX)-2, an enzyme involved in inflammatory cascades but also normal neuronal activities, is elevated in the brain and spinal cord of amyotrophic lateral sclerosis (ALS) patients and ALS mouse model systems. On the basis of this evidence, we explored the impact of COX-2 inhibition on the onset and progression of ALS-like disease in the G93A human superoxide dismutase (SOD)1 mouse model of ALS. We found that prophylactic administration of nimesulide, a preferential COX-2 inhibitor, in the feed resulted in a significant delay in the onset of ALS type motor impairment. This delay of ALS symptomatology temporally overlapped with the inhibition of prostaglandin E2 elevation in the spinal cord of SOD1-G93A transgenic mice relative to untreated SOD1-G93A controls. This study strongly supports a role for COX-2 in the pathophysiology of ALS and provides the first experimental evidence that prophylactic treatment with COX-2 inhibitors can significantly delay the onset of motor dysfunction in the SOD1-G93A transgenic mouse model of ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2003

Should we offer antibiotic prophylaxis post sexual assault?

Our objective was to assess whether antibiotic prophylaxis should be offered to women post sexual assault by considering acceptability of prophylaxis, follow up attendance rates and the prevalence of sexually transmitted infections (STIs) in these women. Retrospective case notes review of female survivors of rape or sexual assault attending the Rose Clinic, Ambrose King Centre, Royal London Hospital between 1 January 1997 and 31 May 1999 was carried out. The following selection criteria were applied: age greater than 16 years; attending within two weeks of assault; having experienced vaginal and/or anal penetration. All women were screened for STI using standard investigation methods detailed below. Antibiotic prophylaxis was offered within two weeks of the assault, the antibiotic regimens used as recommended. The women were invited to attend for results at two weeks and offered a further screen at three months post assault. Bacterial vaginosis was present in 32% of the women screened, Chlamydia trachomatis was identified in 8%, none tested positive for Neisseria gonorrhoeae. Of the 25 women who were offered antibiotic prophylaxis, 88% accepted. Follow up attendances were 57% at two weeks and 30% at three months. Antibiotic prophylaxis was acceptable to women. Among recent rape victims, follow-up rates are low confirmed by our study. These factors support the use of antibiotic prophylaxis post sexual assault. There was an apparently high prevalence of STIs amongst women in this study. More research is required with respect to this aspect of the work and to consider the cost-benefit analysis of antibiotic prophylaxis.

Adolescent↗
PubMed1994

Relationship between the tumour-associated antigen 90K and cytokines in the circulation of persons infected with human immunodeficiency virus.

A tumour-associated antigen known as 90K has been found in high concentrations in the serum of patients infected with human immunodeficiency virus (HIV) even in the absence of neoplastic complications. In order to investigate the relationship between the production of 90K and soluble inflammatory mediators, we studied serum concentrations of the antigen, tumour necrosis factor-alpha (TNF-alpha), interleukin-I-alpha (IL-I-alpha), interferon-gamma (IFN-gamma), IFN-alpha, neopterin and beta 2-microglobulin (beta 2-m) in patients with non-neoplastic HIV infection at various stages of disease and in control persons. The antigen was detected in all those studied but its concentration was higher in HIV-infected patients compared with controls (P < 0.001), increasing progressively with advancing stages of disease. There was a negative correlation between concentrations of 90K and IL-I-alpha in patients in U.S.A. Centers for Disease Control groups II and III (P < 0.02) and also between that of 90K and both TNF-alpha (P < 0.01) and IL-I-alpha (P < 0.05) in control persons. The results indicate that 90K is not merely a tumour-associated antigen and that its production may be part of immune and inflammatory responses in the absence of neoplasia. The correlation between the concentrations of 90K and of some cytokines in asymptomatic patients and healthy persons suggests that 90K may be part of a network of immune and inflammatory reactants.

Adult↗
PubMed1994

Sexual behaviour of gay and bisexual men in eight European countries.

To compare the sexual behaviour and HIV risk reduction strategies of gay and bisexual men in Europe, a survey, disseminated via the gay press and gay associations, was conducted amongst gay and bisexual men in Austria, Switzerland, Germany, Denmark, France, Great Britain, Italy and the Netherlands during the autumn and winter of 1991. By end March of 1992, 12,347 completed questionnaires had been obtained. A preliminary analysis shows striking similarities in patterns of sexual behaviour of gay men in the 8 European countries but indicates that strategies of risk management concerning HIV and AIDS vary widely. While the majority of gay men have multiple partners, and intercourse is more common with stable partners than with causal partners. The proportion of men who, during the past 12 months, engaged in unprotected anal intercourse with a partner with different or unknown HIV-status ranged from 1/3 in East Germany to 1/6 in UK. However, reported incidence over the past 12 months of STDs, other than HIV infection, was similar in all countries (2%-3%). The reported HIV antibody prevalence varied from less than 7% in East Germany, Italy and the United Kingdom to 15% in Denmark and 17% in France. HIV risk reduction strategies appear to be most common in those countries where the gay community had been included in targeted prevention campaigns during the early phase of the AIDS epidemic. Considering the high proportion of gay men engaging in high risk activities it is imperative that prevention efforts are sustained and improved.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Prospective analysis of patterns of weight change in stage IV human immunodeficiency virus infection.

Weight loss is a major manifestation of infection with the human immunodeficiency virus (HIV). Prospective analysis of weight change was performed in 30 male subjects with stage IV HIV infection over a period of 9-49 mo and weight change events (> 4 kg) related to contemporaneous clinical events. Two distinct patterns of weight loss were observed: episodes of acute severe weight loss and episodes of chronic unremitting progressive weight loss. Thirty-three acute episodes (median 9.1 kg in 1.7 mo) and 23 chronic episodes (13.2 kg in 9.5 mo) were identified. Twenty-seven of 33 (82%) acute weight-loss episodes were associated with nongastrointestinal opportunistic infections and 15 of 23 (65%) chronic episodes with gastrointestinal disease (P < 0.01). Weight loss was neither inevitable nor unremitting. Periods of weight stability (> 4 mo) occurred in 13 individuals (43%); 35 episodes of weight gain were identified, mostly related to recovery from opportunistic infection. These findings have important implications for our understanding of the natural history of weight loss in HIV infection.

Adult↗
PubMed1992

Detection of HIV in haemopoietic progenitors.

Peripheral blood cytopenias present a major problem in the management of patients with HIV infection. Their pathophysiology is likely to be multifactorial, although there is controversy as to whether haemopoietic progenitors are a target for HIV. In order to investigate the haemopoietic defect in HIV infection, we looked at bone marrow culture characteristics of marrow from eight HIV+ patients compared to normal controls. We performed long-term liquid culture (LTC) and colony forming assays for granulocyte-macrophage (CFU-GM) and granulocyte, erythroid, megakaryocyte, macrophage (CFU-GEMM). In LTC we found normal stromal appearance and haemopoietic focus formation. There was no difference in colony assays of CFU-GM and CFU-GEMM between HIV+ and normal controls. Colonies taken from CFU-GM and CFU-GEMM were analysed for HIV DNA sequences, and we were able to detect HIV DNA in colonies from all HIV+ patients. Our results indicate that despite infection of haemopoietic progenitor cells by HIV, bone marrow function is preserved. This suggests that HIV-related cytopenias may be due to alternative mechanisms not present in our in vitro system.

Adult↗
PubMed1992

Hepatitis B and delta virus infection among "at risk" populations in south east London.

STUDY OBJECTIVE: The hepatitis delta virus (HDV) contributes significantly to the morbidity and mortality of hepatitis B virus (HBV) infection, which is particularly prevalent among intravenous drug users and male homosexuals. A recent report has indicated that HDV first appeared in the South East London intravenous drug using population in 1982. The aim of the present study was to assess the prevalence of HDV in these two groups at risk of HBV infection in South East London. DESIGN: The study was a cohort analysis of HBV and delta virus serum markers, stratified temporally and with respect to intravenous drug use and sexual practice. SETTING: This was a population study of 372 consecutive intravenous drug users attending a local drug rehabilitation centre and 1481 subjects seen at a sexually transmitted disease clinic in the same area, during the years 1979 to 1988. MEASUREMENTS AND MAIN RESULTS: Of 372 intravenous drug users, 195 (52.4%) had evidence of current or past infection with HBV, of whom 17 had chronic HBV infection--a carriage rate of 8.7%. Twelve (70.6%) of these 17 also had chronic HDV infection--the first cases being identified in 1984. By comparison, 406 (27.4%) of the sexually transmitted disease clinic patients had been been exposed to HBV, 32 having chronic HBV: a carriage rate of 7.9% (7.5% v 9.4% among male homosexuals v male heterosexuals). Ten had been exposed to HDV (the first case in 1980) but only two (who did not admit to intravenous drug use) had chronic HDV infections (p less than 0.0005 v the rehabilitation centre patients). CONCLUSIONS: Although the HBV carriage rate is very similar in these two populations, chronic HDV infections were mainly confined to intravenous drug users. However, reports from the USA and France indicate spread of delta virus to the male homosexual community and, since there is clearly a pool of HDV in SE London, vaccination against HBV in these risk groups in likely to be cost-effective and should be actively encouraged.

Female↗
PubMed1990

Activation of the complement system in human immunodeficiency virus infection: relevance of the classical pathway to pathogenesis and disease severity.

In vitro studies implicate classical and alternative complement pathway activation in the pathogenesis of human immunodeficiency virus (HIV) infection. To ascertain their importance in vivo, activation fragments of the classical (C4d), alternative (Ba), and common (C3d) pathways were measured and fragment to parent molecule ratios derived in 74 HIV-infected individuals and related to circulating immune complex (CIC) levels, Centers for Disease Control (CDC) stage, and beta 2-microglobulin, neopterin, and CD4-positive (CD4+) lymphocyte levels. All fragments and ratios were significantly higher in patients (P less than .01) than controls. C4 conversion indices (C4d and C4d to C4) increased linearly with increasing CDC stage (P less than .001), while CD4+ lymphocytes decreased linearly (P less than .001). C4d, C3d, C4d to C4, and C3d to C3 correlated with increasing CIC and beta 2-microglobulin, and C4d and C4d to C4 correlated with decreasing CD4+ lymphocytes (P less than .05). The relationship of classical complement pathway activation to disease progression and CD4+ lymphocytes suggests its involvement in the pathogenesis of HIV infection.

Adult↗
PubMed1986

Three-year prospective study of HTLV-III/LAV infection in homosexual men.

170 symptom-free homosexual men were recruited in London in 1982-83 and 133 were evaluable in 1983-85. Of the 33 who were seropositive to HTLV-III/LAV at entry, 4 (12%) progressed to AIDS, 16 (48%) progressed to persistent generalised lymphadenopathy (PGL), and 13 (40%) remained symptom-free. A further 15 men seroconverted during the study (7% per annum), of whom 8 progressed to PGL. Serial estimations of T lymphocyte subsets showed progressive reduction in T4 numbers in the seropositive groups, but these indices also varied widely in the seronegative group. Counts of T4 and T8 cells or T4/T8 ratio at entry were not of prognostic value. Seronegative subjects were as likely as seropositives to have abnormal immunological tests. Serial measurement of T lymphocyte subsets seems to be of little prognostic or clinical value in the monitoring of populations infected with the HTLV-III/LAV virus. The strongest association with prognosis was an episode of sexually transmitted disease in the six months before entry to the study. This supports the hypothesis that intercurrent infection may be an important co-factor in the acquisition of HTLV-III/LAV infection, and in subsequent disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Conventional tissue culture compared with rapid immunofluorescence for identifying Chlamydia trachomatis in specimens from patients attending a genitourinary clinic.

Specimens collected from 182 patients with histories suggesting chlamydial disease were examined by conventional culture and direct immunofluorescence techniques. Chlamydia trachomatis was identified by both methods in 57% of all patients. There was no significant difference between the two methods in detecting C trachomatis. Where a tissue culture service is not already established, cost analysis in individual departments may justify the use of the immunofluorescence method.

Bacteriological Techniques↗