Concorde trial of immediate versus deferred zidovudine.
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Biomedical subjects
Publications and source records attributed to A G Bird.
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A retrospective study of inoculation injuries in dental practice was conducted by means of a questionnaire distributed to 310 dental practitioners in the Lothian region of Scotland. Recent injuries were independently classified by a hospital dentist, general dental practitioner and immunologist as constituting high, moderate or low risk of transmission to the dentist. A consultant physician in infectious diseases assessed the follow-up actions. The results indicate that non-sterile inoculation injuries are a common hazard of dental practice with 56% of respondents reporting at least one such injury within the last year. A total of 30% of reported injuries constituted a moderate or high risk of transmission to the dental practitioner. Action taken following such injuries was often considered to be inadequate. While many injuries could possibly be avoided by changes in surgery design, avoidance of other injuries would probably require fundamental changes in routine dental practice. While the incidence of such injuries is high, dental practice within the UK appears to be associated with a low risk of acquiring HIV infection by occupational exposure. The increasing awareness of the importance of other blood-borne viral infections makes this a continuing issue.
The expression of markers defining functional subpopulations on the surface of CD4 and CD8 cells changes with disease. To monitor these changes in children, it is important to establish the age-related normal changes in marker expression due to maturation of the immune system. We have studied the expression of several functionally important molecules on both CD4 and CD8 cells in 168 children (aged 0-122 months) using monoclonal antibodies and flow cytometry. Our results show that the percentage of CD4 cells decreases with age, while the CD8 percentage increases, resulting in a decrease in the CD4/CD8 ratio. The expression of CD45RO and CD29 increases with age, while CD45RA expression decreases, both on CD4 and CD8 cells. The expression of HLA-DR on both CD4 and CD8 cells, and of CD11a and CD57 on CD8 cells, is less clearly age dependent. The relationships between the marker percentages and age were not straightforward; the standard deviations and the skewness, as well as their mean values, varied as a function of age. The changes were modeled for each marker and age-specific centiles are presented.
This retrospective study used a postal questionnaire to measure occupational risks and to assess infection control procedures among 310 dental practitioners. The study comprised general dental practices in the Lothian region of Scotland, Lothian Health Board Community Dental Service and Edinburgh Dental Hospital. Altogether, 217 dental practitioners responded by the due date giving recall of inoculation injuries within the previous 5 years and infection control measures employed. The study revealed that 191 practitioners (88%) had completed a course of hepatitis B vaccination but one-third of them had not been tested for post-vaccination antibody. In 1991, two thirds of dentists (66%: 137 of 207 respondents) wore the same pair of gloves, and 80% of dentists (142 of 177 respondents) wore the same mask, for dealing with more than one patient. The usual practice was to change gloves during sessions (44%: out of 71 dentists) and to change masks for each session or less often (75%: 73 out of 97 dentists). The proportion of dentists who never used gloves fell from 56% in 1981 to 1% in 1991. An autoclave was used for sterilisation by 85% of practitioners in 1991. Reported non-sterile inoculation injuries averaged 1.7 (S.D. = 3.2) injuries per dentist in the previous year with 56% of practitioners having had an injury. The average was 6.8 (S.D. = 15.9) injuries per dentist in the previous 5 years with 76% of practitioners having had an injury. Of recent non-sterile inoculation injuries described by dental practitioners, 30% constituted a moderate or high risk of transmission of infection to the practitioner (43 of 141 described injuries). Combined with HIV seroprevalance rates, probabilities of transmission and numbers of practising dentists, the mean reported number of non-sterile inoculation injuries in the previous 5 years may be used to provide estimates of expected numbers of dental practitioners occupationally infected with HIV in the previous 5 years. U.K. estimates were 0.004 dentists in Lothian region and 0.05 dentists in the Thames region occupationally infected with HIV in the previous five years. Non-sterile inoculation injuries appear to be a common hazard of dental practice. In any year, most dentists are exposed to the risk of blood-borne viral infection. Despite a high reported incidence of such injuries, dental practice within the U.K. appears to carry a low risk of acquiring HIV infection from occupational exposure.
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OBJECTIVE: To examine changes in lymphocyte subpopulations in early pregnancy using a methodologically appropriate study design that addresses previous sources of bias. METHODS: Thirty-seven healthy women without risk factors for human immunodeficiency virus (HIV) were reviewed when less than 9 weeks pregnant (median 51 days, range 44-61) and again at least 4 weeks following termination of pregnancy. No woman took the oral contraceptive pill. Blood was taken on each occasion at the same time of day under the same conditions of rest and food intake, transported immediately to the laboratory, and directly prepared for analysis. Lymphocyte surface markers were determined by staining with dual-colored, isotype-matched monoclonal antibody fluorescent conjugates, followed by whole blood lysis and subsequent flow cytometric analysis. RESULTS: Pregnancy was associated with a significant reduction in total lymphocytes (P < .0001) and also in CD4+ cells, whether expressed as a percentage of lymphocytes (P = .004), an absolute count (P = .0006), or a ratio (P = .01). Change was independent of the basal level except for lymphocytes, and almost all indices had significant correlations between pregnant and nonpregnant values. CONCLUSIONS: In this study design, each woman served as her own control and all factors remained constant except the pregnancy state. Early pregnancy causes a reduction in total lymphocytes of about 6% expressed as a percentage of total white cell count, and in CD4+ cells by 3% as a percentage of lymphocytes, or 100/mm3. We believe this fall can be accepted as definitive.
HIV-specific cytotoxic T lymphocytes (CTL) are thought to play a major role in viral control in HIV-infected adults. Changes in the relative proportions of CD8 lymphocyte subpopulations are also thought to be associated with disease progression. Less is known about the relative effectiveness of CTL against different HIV targets, or about the relationship, if any, between CTL activity and CD8 subpopulations. We have measured CTL activity against four HIV gene products (gag, tat, pol and env) and expression of CD45RO, CD45RA, HLA-DR, CD29, S6F1, and CD57 surface markers on CD8 cells from nine HIV-infected and 11 HIV-uninfected children. Of nine HIV-infected children, six showed antigen-specific CTL activity on at least one occasion: 4/6 directed against tat, 6/6 against pol, 1/6 against env, and 1/6 against gag. However, the specificity of the CTL activity varied between children and within individual children with time. Furthermore, two uninfected children showed CTL activity, one to HIV-gag, -pol and -tat, and the other to HIV-pol. All the HIV-infected and two uninfected children had abnormal proportions of CD8 subpopulations in whole blood compared with age-matched controls. There was no correlation between CTL activity and CD8 subsets in whole blood. Five children changed from CTL-positive to CTL-negative (or vice versa) during the study. In these, the occasions when CTL activity was detected coincided with an increase in CD8 cells, an expansion of HLA-DR+ CD8 cells and a loss of CD45RA+ CD8 cells.
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OBJECTIVES: To estimate the prevalence of infection with HIV in young offenders in Scotland and to obtain information about related risk factors and previous tests for HIV. DESIGN: Voluntary anonymous study with subjects giving saliva samples for testing for HIV and completing questionnaires about risk factors. SETTING: Polmont Young Offenders' Institution near Falkirk, Scotland. SUBJECTS: 421 of 424 available male prisoners in Polmont. The questionnaires of 17 of the prisoners were excluded because of inaccuracies. MAIN OUTCOME MEASURES: Prevalence of infection with HIV and related risk behaviour. RESULTS: 68 (17%) of prisoners admitted misuse of intravenous drugs, of whom 17 (25%) admitted having injected drugs while in prison. Three subjects admitted having anal intercourse while in prison. Prevalence of misuse of intravenous drugs varied geographically: 28% (33/120) of prisoners from Glasgow compared with 9% (7/81) of those from Edinburgh and Fife. A high level of heterosexual activity was reported, with 36% (142/397) of prisoners claiming to have had six or more female sexual partners in the year before they were imprisoned. Altogether 8% (32/389) of prisoners had previously taken a personal test for HIV: 50% (9/18) of those who had started misusing intravenous drugs before 1989, 18% (9/49) of those who started misuse later, and only 4% (14/322) of those who had not misused intravenous drugs. No saliva sample tested positive for antibodies to HIV, but 96 prisoners requested a confidential personal test for HIV as a result of heightened awareness generated by the study. CONCLUSIONS: Voluntary, anonymous HIV surveys can achieve excellent compliance in prisons, and the interest generated by the study suggests that prisons may be suitable sites for providing education and drug rehabilitation for a young male population at high risk of future infection with HIV.
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OBJECTIVE: To establish whether various accepted and proposed AIDS definitions have clinical and biological validity: because the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) reclassifications of AIDS are important not only for describing the epidemiology of HIV disease but also to individual patients. SETTING: Regional Infectious Diseases Unit, City Hospital, Edinburgh, Scotland, UK. PATIENTS: We analysed the disease progression of 532 HIV-seropositive individuals seen at the City Hospital, Edinburgh, up to the end of July 1991. MAIN OUTCOME MEASURES: Annual numbers of potentially reportable cases from the Edinburgh City Hospital Cohort according to three proposed AIDS case definitions based on: (1) first lymphocyte count < or = 1000 x 10(6)/l; (2) first CD4 cell count < or = 200 x 10(6)/l; or (3) first of two consecutive CD4 cell counts < or = 200 x 10(6)/l. Lifetables to death (irrespective of cause) from month of satisfying the above case definitions, and proportion of patients who satisfied each definition in their calendar year of enrollment in the cohort are reported. RESULTS: There is a threefold increase in patients in the Edinburgh City Hospital Cohort defined as having AIDS under the 1987 and the proposed 1992 CDC definitions--a substantial change for patients and epidemiologists alike. That they are describing different immunodeficiency states is clear from lifetable analysis, which reveals median survivals of 20 and 50 months under the 1987 and the proposed 1992 AIDS definitions, respectively. For epidemiological purposes, redefinitions based on the WHO proposed classification of HIV disease using either a lymphocyte count < or = 1000 x 10(6)/l or a CD4 cell count < or = 200 x 10(6)/l are broadly interchangeable. They are not equally effective for monitoring individual progression (CD4 cell count is superior). Both, for different reasons, lack biological plausibility. CONCLUSIONS: We therefore suggest that the stricter, biologically more plausible, case definition used in Scotland of two consecutive CD4 cell counts of < or = 200 x 10(6)/l [CD4(200) (x 2)] should be adopted--not as a new definition of AIDS, but as an additional important state of severe HIV-related immunodeficiency (SHRID). Median survival under the CD4(200) (x 2) case definition was 40 months in the Edinburgh cohort. We have illustrated differences in CD4(200) case ascertainment between injecting drug users and other HIV-infected patients in the Edinburgh City Hospital Cohort. We recommend that surveillance centres should ascertain date of first immunological monitoring as well as date of SHRID diagnosis in order to identify differential case ascertainment.
The CD8+ T cell population is believed to play an important role in the control of viral infection, both for suppression of viral replication and for cytotoxic activity against viral infected cells. Elevated numbers of CD8+ T cells have been demonstrated in HIV infection, and CD8+ cytotoxic T cell (CTL) activity is associated with the early, asymptomatic stage of disease. We investigated the phenotypic characteristics of the CD8 population, in whole blood, in HIV disease and determined the predominant CD8+ subpopulation involved in anti-HIV CTL activity. We found that CD8+ T cells co-expressing markers of activation (HLA-DR), memory (CD45RO, CD29), and cytotoxic activity (S6F1) were significantly elevated in the early stages of disease, while the numbers of naive (CD45RA) cells remained unchanged. Progression to AIDS resulted in an overall loss of absolute CD8+ T cells, though the percentages of CD8+ HLA-DR+ and CD8+ S6F1+ remained elevated. In contrast to patients in the late stages of disease, anti-HIVgag CTL activity, following in vitro stimulation, was present in most HIV+ asymptomatic subjects and was associated with an expansion of CD8+ HLA-DR+ and CD8+ CD45RO+ cells. The absence of CTL activity was associated with a reduced ability of these populations to expand in vitro and with a significant loss of peripheral CD4+ T cells, independent of clinical stage. We suggest that CD8+ expressing HLA-DR+ CD45RO+ and S6F1+ play an important role in anti-HIV cytotoxicity.
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