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Biomedical subjects

T McManus

Publications and source records attributed to T McManus.

6 recordsLinked to original sources

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

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

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

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

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