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Biomedical subjects

A Pozniak

Publications and source records attributed to A Pozniak.

At least 37 records · Page 2Linked to original sources
PubMed1999

ICU admission in patients infected with the human immunodeficiency virus - a multicentre survey.

We conducted a retrospective study to assess the reasons for admission to the intensive care unit, and subsequent outcome, in patients infected with the human immunodeficiency virus (HIV). Four hospitals in the south of England participated, all with specialist HIV units. Data were collected on 127 patients admitted to ICU on 133 separate occasions between June 1993 and October 1997. The mean age on admission was 38 years (range 23-60 years). Ninety-four patients (70.7%) were documented HIV-positive before admission and 36 (27%) were diagnosed HIV-positive for the first time during admission; 36.1% were admitted with Pneumocystis carinii pneumonia. Overall ICU mortality was 33%, in-hospital mortality was 56% and the eventual mortality at the end of follow-up (March 1998) was 72%. Survival was highest in those admitted with respiratory HIV-related disease or HIV-unrelated illness. Associations with poor outcome included a prior AIDS-defining illness, a CD4 cell count of less than 100 cells.ml-1 and admission secondary to sepsis.

AIDS-Related Opportunistic Infections↗
PubMed1999

Patient satisfaction with HIV service provision in NPMS hospitals: the development of a standard satisfaction questionnaire. NPMS Steering Group.

A self-completion satisfaction questionnaire evaluating the standard of care of HIV outpatient services was developed as part of the National Prospective Monitoring System on the Use, Cost and Outcome of HIV Service Provision in English Hospitals (NPMS). The questionnaire was designed in conjunction with service users and health care professionals, and piloted in three London and three non-London HIV clinics. In addition to testing alternative methods of administering the questionnaire, the pilot provided satisfaction scores on a variety of aspects of service provision for participating clinics. The questionnaire was completed by 548 respondents and was most effectively collected using a sealed box in the clinic waiting area. Mean satisfaction scores for the attitude and skills of staff members was 4.7 (95% CI 4.6-4.7) but satisfaction scores were significantly lower for the clinic environment with a mean of 4.1 (95% CI 4.1-4.2). Satisfaction scores did not differ significantly by gender, age, sexual orientation, ethnic group, employment status or severity of symptoms. London respondents were more satisfied with the clinic environment and seeing preferred members of staff than their non-London counterparts, however there were no other differences between clinics. The questionnaire functioned well in practice and provided meaningful and useful information for individual clinics as well as at aggregate level.

Acquired Immunodeficiency Syndrome↗
PubMed1998

The use and cost of HIV service provision in England in 1996. National Prospective Monitoring System (NPMS) Steering Group and NPMS Working Party on Costs.

OBJECTIVE: The aim of the study was to measure the use and estimate the cost of HIV service provision in England. DESIGN AND SETTING: Standardised activity and case-severity data were collected prospectively in 10 English HIV clinics (5 London and 5 non-London sites) for the periods 1 January 1996 to 30 June 1996 and 1 July 1996 to 31 December 1996 and linked to unit cost data. In total, 5440 patients with HIV infection attended during the first 6 months and 5708 during the second 6 months in 1996. MAIN OUTCOME MEASURES AND RESULTS: The mean number of inpatient days per patient-year for patients with AIDS was 19.7 [95% confidence interval (CI): 13.7 to 25.7] for January to June and 20.8 (95% CI: 15.3 to 26.4) for July to December 1996. The mean number of outpatient visits for asymptomatic patients with HIV infection was 14.8 (95% CI: 11.9 to 17.6) and 13.3 (95% CI: 10.8 to 15.7) for the respective periods and 16.1 (95% CI: 13.21 to 18.97) and 15.7 (95% CI: 11.2 to 20.2), respectively, for patients with symptomatic non-AIDS (i.e. symptomatic patients with HIV infection but without AIDS-defining conditions). Substantial centre-to-centre variation was observed, suggesting that many clinics can continue the shift from an inpatient- to an outpatient-based service. Cost estimates per patient-year for HIV service provision for 1996 varied from 4695 Pounds (95% CI: 3769 Pounds to 5648 Pounds) for asymptomatic patients, to 7605 Pounds (95% CI: 6273 Pounds to 8909 Pounds) for symptomatic non-AIDS patients to 20,358 Pounds (95% CI: 17,681 Pounds to 23,206 Pounds) for patients with AIDS. CONCLUSIONS: Different combinations of antiretroviral therapy affect the cost estimates of HIV service provision differently. Anticipated reduction in inpatient-related activity through the increased use of combination antiretroviral therapy will further shift service provision from an inpatient- to outpatient-based service and reduce costs per patient-year. The extent and duration of such effects are currently unknown. The long term effects of combination treatment on the morbidity and mortality patterns of individuals infected with HIV are also currently unknown, as are their implications on the use and cost of HIV service provision. Multicentre databases like the National Prospective Monitoring System (NPMS) will provide healthcare professionals with information to improve existing services and anticipate the impact of new developments.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Isolation of environmental mycobacteria from clinical specimens in south-east England: 1973-1993.

SETTING: A reference centre for tuberculosis bacteriology serving South-East England. OBJECTIVE: The number of cultures of environmental mycobacteria (EM) submitted to regional and reference laboratories in the UK is increasing, and is adding considerably to the workload of these laboratories. The changing trends in the numbers and nature of EM submitted to the Dulwich Public Health Laboratory Regional Tuberculosis Centre (RTC), have been analysed to establish the nature of the increase. DESIGN: This study is based on all cultures of EM submitted to RTC between 1973 and 1993. The cultures were grouped according to year of first isolation, number of isolates and data supplied by the client laboratories, including age and human immunodeficiency virus (HIV) status of the patients and the anatomical sites from which the mycobacteria were isolated. RESULTS: A total of 9379 EM from 6668 patients was received. Single and multiple isolates were received, respectively, from 4681 and 1192 patients not known to be HIV positive and from 477 and 318 who were known to be HIV positive. The annual number of patients not known to be HIV positive with isolates of probable clinical significance increased steadily from less than 40 in 1973 to over 100 per year since 1990. Isolates of doubtful clinical significance also showed an increase over time. The annual numbers from HIV positive patients increased steeply following the first such isolates in 1984. CONCLUSIONS: The data show that the annual number of isolates of EM from both HIV positive and negative patients is increasing both absolutely and relatively to isolates of Mycobacterium tuberculosis. This trend should be considered when planning the future scope and activities of mycobacterium reference laboratories, including the introduction of new DNA-based diagnostic methods.

Body Fluids↗
PubMed1996

Abnormalities of CD45 isoform expression in HIV infection.

Using monoclonal antibodies against CD45, CD45RA, CD45RB, and CD45RO, the surface density of expression and proportions of different CD45 isoforms were analyzed on CD4+ and CD8+ T lymphocyte subsets in HIV+ patients and controls. Analysis of the relative specific fluorescence (RSF) of CD45 isoforms showed a significant reduction in expression of total CD45 and its isoforms, CD45RA, CD45RO, and CD45RB, on CD4+ and CD8+ lymphocyte subsets in HIV+ patients compared with controls. However, expression of phosphotyrosine in the cytoplasm of CD4+ and CD8+ lymphocytes did not differ significantly between HIV+ patients and controls. Percentages of "naive" CD45RA+RO- CD4+ and CD8+ lymphocytes were lower than control values in all HIV+ patients (P < 0.001). Compared with controls, HIV+ patients had similar percentages of "memory" CD45RA-RO+ CD4+ lymphocytes but significantly higher percentages of memory CD8+ lymphocytes (P < 0.001). Percentages of memory CD8+ lymphocytes were lowest in patients with AIDS (P < 0.001). The consistent reduction in surface expression of all CD45 isoforms observed in our study may be of relevance to the impaired T cell activation characteristic of HIV infection. Also, our results argue against the selective depletion of memory CD4+ lymphocytes in HIV-induced disease.

Adult↗
PubMed1996

Intestinal inflammation, ileal structure and function in HIV.

OBJECTIVES: This study examines small intestinal absorption-permeability, intestinal inflammation and ileal structure and function in HIV-positive male homosexuals. METHODS: Thirty HIV-seropositive male homosexuals at various stages of disease underwent intestinal absorption permeability and 111indium leukocyte studies (for quantification of intestinal inflammation). Twenty-six men with AIDS had a dual radioisotopic ileal function test (whole body retention of tauro 23-[75Se]-selena 25-homocholic acid and 58cobalt-labelled cyanocobalamine), and 17 underwent ileocolonoscopy with terminal ileal biopsy. RESULTS: Well, HIV-infected, subjects had normal intestinal absorption-permeability, but both functions were impaired upon the development of AIDS. The median faecal excretion of 111indium in well patients (0.66%) did not differ significantly (P > 0.5) from controls (0.46%), but subjects with AIDS who were well or who had diarrhoea had significant (P < 0.005) intestinal inflammation (1.33% and 2.18%, respectively). The median 7-day retention of tauro 23-[75Se]-selena 25-homocholic acid in well patients with AIDS (38.9%) did not differ significantly (P > 0.2) from controls (39.3%), whereas the absorption of 58cobalt-labelled cyanocobalamine was significantly (P < 0.05) lower than controls (32.1% and 59.4%). Patients with AIDS-diarrhoea had significant (P < 0.001) malabsorption of both the bile acid (7.7%) and vitamin B12 (8.9%) which was more severe than in Crohn's ileitis (14.2% and 30.3%, respectively). Morphometric analyses of ileal biopsies were unremarkable in AIDS. CONCLUSIONS: These studies demonstrate a low-grade enteropathy in patients with AIDS, severe ileal malabsorption in patients with AIDS diarrhoea and relatively minor ileal morphologic changes. Malabsorption of bile acids may play a pathogenic role in patients with AIDS and diarrhoea.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Summary of track B: clinical science.

AIM: To review Track B on clinical science. Major topics covered were quantitative HIV-1 plasma RNA measurement, combination antiretroviral therapy, protease inhibitors, treatment of primary HIV-1 infection, HIV-1 drug resistance, future use of antiretroviral drugs, paediatric HIV-1 infection, opportunistic infections and HIV/AIDS in developing countries. QUANTITATIVE HIV-1 PLASMA RNA MEASUREMENT: Quantification of HIV-1 RNA is a predictor of progression of immune deficiency and death in HIV-infected adults and children, and is useful in monitoring response to antiretroviral therapy. THERAPY: Combination antiretroviral therapy is now the standard of care, although questions about optimal starting time and the best initial regimen remain unresolved. Protease inhibitors are a powerful new class of antiretroviral agents which in combination with other drugs can produce profound reductions in plasma HIV-1 RNA levels. Trials are in progress of combination antiretroviral therapy, including protease inhibitors, in persons recently infected with HIV-1 to assess the feasibility of permanent suppression or eradication of HIV-1. Adherence to therapy and drug resistance will become increasingly important subjects. CONCLUSIONS: The genuine improvements in patient management are out of reach to the majority of the world's HIV-infected persons, a conclusion with implications which dampened the optimism generated by the conference.

Adult↗
PubMed1995

Markers of immune cell activation and disease progression. Cell activation in HIV disease.

Immune cell activation is a feature of infection with the human immunodeficiency virus (HIV). Here we report our studies on a cohort of over 400 patients with HIV infection studied cross-sectionally and longitudinally to examine the relationship between markers of immune cell activation and disease progression. To examine disease progression, 340 patients with HIV infection but without AIDS were followed for a total of 574 patient years, during which 56 developed AIDS. In our first study, 157 patients in CDC groups II-IV were examined cross-sectionally for in vivo expression of the activation markers HLA-DR and CD25 on CD3, CD4 and CD8 T cells. Levels of CD3+ HLA-DR+ T cells are high in HIV infection and show a significant negative correlation with CD4 counts (r = 0.52; p < 0.001). The appearance of HLA-DR+ CD3+ T cells is an early feature of asymptomatic HIV+ patients, with a greater proportion (82%) showing abnormally high levels of these than abnormally low levels of CD4 (52%; p < 0.001). Examining activation of the CD4 subset specifically is likely to be of greater interest, given that this cell is the viral target. Indeed, we found that in the cross-sectional study, levels of HLA-DR+ and CD25+ CD4 lymphocytes show a step-wise linear increase with increasing disease severity (significant test for linear trend; p < 0.001). In our previous studies, only declining CD4 count has shown such a significant linear trend. These data suggest that measuring activated CD4+ T cells in the periphery may be a powerful predictive tool. In our second study, we examined the expression of other markers acquired (CD45R0) and lost (CD45RA) following activation of naïve T cells. Examining expression of these on CD4 and CD8 cells cross-sectionally in 71 HIV+ patients, we found abnormalities in percentage levels of CD45RA+ and CD45R0+ populations, none of which showed any relationship to disease severity. Intriguingly, however, we noted that the surface density of both CD45RA and CD45R0 molecules on CD4 and CD8 cells was markedly and significantly reduced at all stages of HIV infection (eg relative specific fluorescence reduced by up to 50%; p < 0.001). This abnormality was confirmed in studies using antibodies to a common epitope on all CD45 isoforms (pan-CD45) and to the CD45RB isoform. Finally, returning to the question of immune cell markers of activation and disease progression, we have examined some of the best documented markers in our longitudinal study.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Circulating levels of mannose binding protein in human immunodeficiency virus infection.

Mannose binding protein (MBP) is a serum lectin which, upon binding to a carbohydrate extremity, acquires the ability to activate the classical complement pathway. MBP binds human immunodeficiency virus (HIV) in vitro via glycans on gp120 and thus, it may play a defensive role in HIV infection and contribute to virus clearance through the activation of complement associated with this condition. We measured serum MBP and activation indices of the classical complement pathway (plasma C4d and C3d) in HIV-seropositive patients at different stages of disease severity, and in normal subjects. MBP was higher in HIV patients as a whole and in each Centers for Disease Control (CDC) group than controls (P<0.01). MBP was not significantly different between CDC groups and and did not significantly correlate either with CD4-positive lymphocytes, neopterin or beta2-microglobulin or with C4d and C3d. The possibility that MBP plays a defensive role in HIV infection cannot be excluded, but, it it is, it does not appear to act by recruiting complement for vital elimination.

Adult↗
PubMed1995

Cell cycling in HIV infection: analysis of in vivo activated lymphocytes.

Infection with HIV results in increased circulating levels of T lymphocytes expressing phenotypic markers of immune activation. In the present study, using three-colour immunofluorescence, we examined the cell cycle status of these activated cells. Activated (HLA-DR+, CD25+ and CD38+) CD4+ and CD8+ T lymphocytes in peripheral blood were analysed for DNA content in 15 HIV+ patients and 10 healthy age- and sex-matched control subjects. As expected, all HIV+ patients had elevated percentage levels of activated CD4+ HLA-DR+, CD4+ CD25+, CD8+ HLA-DR+, CD8+ CD25+ and CD8+ CD38+ T lymphocytes compared with control subjects (P < 0.001 for all). Percentage levels of CD4+ HLA-DR+ and CD8+ HLA-DR+T lymphocytes in the 'proliferative' (S-G2M) phase of the cell cycle were also higher in the HIV+ patients compared with controls (P < 0.001 for both). The percentage levels of proliferative CD4+ CD25+, CD8+ CD25+ and CD8+ CD38+ lymphocytes were, however, similar in HIV+ patients and controls, indicating that the proliferative fraction of cells in vivo was confined to the HLA-DR+ subset and absent from the CD25+ and CD38+ populations. Four HIV+ patients had grossly elevated levels of CD8+ lymphocytes which were CD38+ (> 95%) and confined to the pre-G0-G1 phase of the cell cycle, suggesting these may be cells committed to apoptosis. These observations indicate an increase in the proliferative capacity of HLA-DR+ T lymphocytes in HIV infection in vivo. The reduced DNA content in other populations (e.g. CD38+ CD8+ lymphocytes) of some patients with advanced HIV disease suggests that these cells are apoptotic. Thus our results define both proliferative and apoptotic processes as a spectrum of activation-related events in HIV infection.

ADP-ribosyl Cyclase↗