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Biomedical subjects

A J Pinching

Publications and source records attributed to A J Pinching.

At least 37 records · Page 2Linked to original sources
PubMed1996

High resolution computed tomography in HIV patients with suspected Pneumocystis carinii pneumonia and a normal chest radiograph.

AIM: To correlate the appearances of high resolution computed tomography (HRCT) with the bronchoalveolar lavage (BAL) findings in HIV positive patients in whom there is a strong clinical suspicion of Pneumocystis carinii pneumonia (PCP) but a normal chest radiograph. PATIENTS AND METHODS: The 13 patients available for analysis fulfilled the following criteria: HIV positive, CD4 count less than 200 cells per mm3, non-productive cough or non-purulent sputum daily, documented fever above 37.5 degrees C for more than a week, dyspnoea or decreased exercise tolerance and normal chest X-ray. HRCT of the lungs was performed within 24 h of the chest radiograph, using 1 mm slice at 2 cm intervals, reconstructed using a high resolution algorithm. Bronchoalveolar lavage samples were taken for cytological examination, microscopy, culture and sensitivity. The HCRT findings were correlated with the results of BAL and clinical outcome. RESULTS: Of the 13 patients studied, four had patchy ground-glass opacities and one also had interstitial thickening. All four proved to have PCP on BAL. None of the nine patients who were negative for PCP on BAL had ground-glass opacity or abnormalities attributable to PCP. CONCLUSION: In this study HRCT showed abnormalities consistent with PCP in all four patients who had PCP on BAL before there were chest radiograph abnormalities. The use of HRCT may help avoid unnecessary delay, allow early medical intervention and, if our results are confirmed by larger series, may reduce the need for bronchoscopy.

AIDS-Related Opportunistic Infections↗
PubMed1996

The use and cost of hospital services by London AIDS patients with different AIDS defining conditions.

BACKGROUND: Contracting for HIV service provision is now an established part of the National Health Service commissioning process. AIDS is a heterogeneous condition, comprising various opportunistic illnesses which require different services and which have different resource implications. This study describes the use of hospital services and associated costs for the management of different AIDS defining conditions. METHOD: A retrospective case-notes analysis was performed, of 335 AIDS patients treated at St Mary's Hospital, London, between 1 January 1983 and 30 September 1989, as well as a costing exercise of 37 clinical departments to calculate HIV-related costs. RESULTS: Mean age at time of AIDS diagnosis for these predominantly homosexual men was 38 years. Use of services varied, as did associated costs-from 8163 pounds per patient-year for patients with Constitutional Disease to 42,124 pounds for those with Cytomegalovirus Disease Most diagnostic categories showed a shift over the study period from an in-patient- to an out-patient-based service. Patients diagnosed after 1987 had overall lower costs per patient-year compared with those diagnosed before 1987: whereas out-patient costs for most groups had increased, in-patient expenditure decreased. For most categories, in-patient care costs and out-patient drugs prescribed provided the greatest proportion of total costs. Average costs per in-patient day ranged from 334 pounds to 433 pounds, and average costs per out-patient visit ranged from 99 pounds to 411 pounds for different AIDS defining conditions. CONCLUSIONS: Different opportunistic illnesses of symptomatic HIV disease have different treatment and resource implications. Casemix will need to be taken into consideration when contracting for HIV services, including extra-contractual referrals.

AIDS-Related Opportunistic Infections↗
PubMed1996

Correlation between total and CD4 lymphocyte counts in HIV infection: not making the good an enemy of the not so perfect.

The aim of this study was to assess the correlation and average cost of total lymphocyte count compared with CD4 count as a broad estimate of immunosuppression in HIV-1 infected individuals. Spearman's partial rank correlation were calculated between total lymphocyte count, absolute CD4 count and CD4 per cent stratified by stage of HIV-1 infection for routinely collected samples. Data were collected prospectively from a T cell-subset register combined with clinical data obtained retrospectively from case notes of HIV-infected patients managed at St Mary's Hospital, London 1982-1991. Costing data were obtained through a survey of the departments of haematology and immunology (1989/90 prices). The correlation between 1534 paired absolute lymphocyte count and CD4 lymphocyte count was found to be high (R = 0.76). When analysed by stage of HIV infection, the correlation increased from R = 0.64 for asymptomatic patients, to R = 0.72 for patients with symptomatic non-AIDS HIV infection and R = 0.73 for AIDS patients. Correlations between absolute lymphocyte count and CD4 per cent were considerably weaker: R = 0.41 all paired counts; R = 0.32 for asymptomatic patients; R = 0.25 for symptomatic non-AIDS patients; R = 0.32 for AIDS patients. Average cost was pounds 8 per full blood count compared with pounds 38 per T-cell subset analysis. The high correlation between total and CD4 lymphocyte counts, especially for patients with symptomatic HIV disease, demonstrates the suitability of the use of total lymphocyte count in the absence of CD4 counts. Given the considerably lower prices of total lymphocyte counts compared with T-cell subset analysis, this is particularly relevant for developing countries.

CD4 Lymphocyte Count↗
PubMed1996

Epidemiology of AIDS-related Kaposi's sarcoma in Europe over 10 years. AIDS in Europe Study Group.

OBJECTIVES: To determine the incidence and risk factors associated with Kaposi's sarcoma (KS) occurrence as an AIDS-defining condition or after the diagnosis of AIDS. DESIGN: Multicentre retrospective cohort study of AIDS in Europe database from 52 clinical centres in 17 European countries. METHODS: Patients' charts (n = 6546) were reviewed and collected in the database of the AIDS in Europe Study Group from 1979 to 1989. At the time of AIDS diagnosis 1394 patients had KS, whereas an additional 525 others developed KS after AIDS diagnosis. Univariate analysis and development of multivariate models determined factors associated with KS occurrence. RESULTS: Frequency of KS as an AIDS-defining condition significantly declined over time (P < 0.0001). In our cohort of patients, homo-/bisexual men from central Europe with CD4 cell counts > 150 x 10(6)/l were statistically more likely to develop KS at the time of AIDS diagnosis (P < 0.0001). For patients with an AIDS diagnosis other than KS, the probability of developing KS during the follow-up was 10 and 24% after 12 and 36 months, respectively. Variables significantly associated with a further KS development were transmission group, central European residence, previous herpes simplex infection other than ulcers, and low CD4 cells (< 150 x 10(6)/l). Previous zidovudine therapy had no influence on KS appearance. For patients who developed KS subsequent to AIDS diagnosis, there was no significant decline of the incidence over the 10-year time period. CONCLUSIONS: This large cohort study clearly shows that demographic data such as sex, transmission group and region of Europe have a major influence on KS development. It also suggests that KS as an AIDS-defining disease occurs earlier in the course of the chronic HIV infection than other opportunistic diseases. Reasons for geographical variations and its declining frequency as an initial AIDS diagnosis remain undetermined.

AIDS-Related Opportunistic Infections↗
PubMed1995

Changes in survival over time after a first episode of Pneumocystis carinii pneumonia for European patients with acquired immunodeficiency syndrome. Multicentre Study Group on AIDS in Europe.

BACKGROUND: Factors associated with improved survival over time for patients with the acquired immunodeficiency syndrome (AIDS) who have Pneumocystis carinii pneumonia at diagnosis are not clearly defined. METHODS: An inception cohort of 2533 patients with AIDS, diagnosed from 1979 to 1989, from 52 centers in 17 European countries was studied. Survival 3 months and 3 years after diagnosis was estimated by Kaplan-Meier life tables. Independent predictors of survival were analyzed by construction of Cox proportional hazards models. RESULTS: Patients in whom AIDS and P carinii pneumonia had been diagnosed before 1988 had a poorer 3-month (ie, short-term) survival, whereas the survival 1 and 2 years after P carinii pneumonia was lower only for patients whose disease was diagnosed before 1987 compared with those with more recent diagnoses. Other variables associated with poorer outcome were greater age, infection via blood transfusion, diagnosis made in south Europe, and coexisting illnesses. After controlling for these prognostic markers in multivariate analysis, improvement in survival over time was still evident. For patients who survived the P carinii pneumonia episode, both zidovudine and secondary prophylaxis for P carinii pneumonia initiated around the time of diagnosis were associated with improved survival, and, after controlling for these treatment variables, no statistically significant improvement in survival over time was observed. CONCLUSIONS: Survival after an episode of P carinii pneumonia has improved within recent years. Increased awareness of early symptoms of P carinii pneumonia and better treatment of the pneumonia may have led to improvement in short-term survival over time, whereas the introduction of zidovudine and increased use of secondary P carinii pneumonia prophylaxis may have resulted in the recent increase in survival 1 and 2 years after the diagnosis. However, 3-year survival remained unchanged over time, implying that the underlying human immunodeficiency virus infection and other complications are not effectively controlled.

AIDS-Related Opportunistic Infections↗
PubMed1995

Safety and activity of saquinavir in HIV infection.

We evaluated saquinavir, an orally active, selective inhibitor of HIV proteinase, in a randomised, double-blind, dose-ranging study in 49 zidovudine-naive HIV-positive patients with few or no symptoms and CD4 cell counts of 500 or less. The study was designed to assess the antiviral activity and tolerability of saquinavir. Patients were randomised to receive 25, 75, 200, or 600 mg of saquinavir three times daily for 16 weeks. No serious adverse events occurred. CD4 cell counts showed a trend indicative of a dose response in favour of the 600 mg dosage, the maximum increase being seen around week 4. In none of the 8 patients with positive plasma viraemia at baseline did cultures become negative after treatment; peripheral blood mononuclear cell and plasma-viral load by culture and DNA and RNA PCR all showed a trend towards reduction at higher doses of saquinovir. Saquinavir was well tolerated in this group of previously untreated patients with few or no symptoms; this study shows that an HIV-proteinase inhibitor is active in HIV-infected patients.

CD4 Lymphocyte Count↗
PubMed1995

Presence of CD3+CD8+Bcl-2(low) lymphocytes undergoing apoptosis and activated macrophages in lymph nodes of HIV-1+ patients.

Infection with human immunodeficiency virus 1 causes profound changes in the lymph nodes of infected patients. In particular, large numbers of CD8+CD45RO+ T cells infiltrate both the paracortex and the germinal centers. These cells contained the cytotoxic granule-associated protein TIA-1 but showed no detectable levels of perforin and shared the same characteristics of the expanded, activated, short-lived CD8+ population found during acute viral infections. These cells expressed low levels of Bcl-2 and are likely to be short-lived in vivo as evidenced by the direct observation of CD8+ apoptotic cells in the paracortical areas of the infected nodes. Changes in the paracortical nonlymphoid populations were also seen. There were reactive changes in the blood vessels, and the macrophage population was expanded and activated. Furthermore, apoptotic bodies were seen in the cytoplasm of the activated CD68+RFD-7+RFD-1+ macrophages pointing to the phagocytic capacity of these cells and their role in the clearance of the apoptotic cells from the tissues. These observations suggest that the persistance of CD8+ population in human immunodeficiency virus 1 infection is not a result of the presence of an abnormal CD8+ population but rather a result of an inappropriate over-stimulation of the CD8+ cells.

Adult↗
PubMed1995

Screening for cytomegalovirus retinitis in HIV-positive and AIDS patients.

The ability of physicians to screen for AIDS-related cytomegalovirus retinitis (CMVR) was studied at a London AIDS centre. Patients had undergone direct ophthalmoscopy as part of their general examination by the physicians and were referred if fundal abnormalities were found, if a focus of extra-ocular CMVR was present or if the patient complained of visual symptoms. The provisional diagnoses of the physicians were compared with the final diagnoses of the ophthalmologists. Of 348 consecutive patients referred for an ophthalmic opinion, the physicians made the correct diagnosis in 69% of those referred with a provisional diagnosis of CMVR, in 66% of those with normal fundi and in 81% of those with toxoplasma chorioretinitis. Those cases of CMVR which were misdiagnosed by the physicians were usually mistaken for other retinal pathology which would warrant a specialist referral. Screening for CMVR in HIV-positive and AIDS patients may safely be undertaken by physicians familiar with the ocular manifestations of HIV-related disease.

AIDS-Related Opportunistic Infections↗
PubMed1994

Dendritic cells from HIV-1 infected individuals show reduced capacity to stimulate autologous T-cell proliferation.

Dendritic cells (DC) exposed for a short period of time (1 day) in vitro to HIV infection caused stimulation of autologous T-cells, but those exposed for a longer period (3 days) before addition to T-cells stimulate little or no proliferation [1]. Since a proportion of DC from patients who are HIV-1 seropositive is infected with HIV-1 [2] we used the same culture system to test the level of ongoing stimulation of autologous T-cells by DC. The DC from patients with HIV-1 infection showed no enhanced stimulation of autologous T-cells; they produced significantly lower levels of proliferation than those induced by DC from normal controls or from high risk seronegative individuals. However, DC stimulated production of antibodies to gp120 and p24 in cultures containing autologous B plus T-cell in the absence of any added exogenous antigens as previously described [3]. DC in asymptomatic individuals thus appear to be fuelling antibody production but not T-cell proliferation. The results suggest that a failure by DC to stimulate T-cell proliferation either to HIV-1 or to other environmental antigens may be involved in the failure of cell-mediated responses in HIV infection.

Cells, Cultured↗
PubMed1994

Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi's sarcoma in AIDS.

The objective of this study was to assess the efficacy and toxicity of a novel Stealth liposomal encapsulated formulation of doxorubicin (Doxil). A Phase I/II dose escalation study was carried out in a specialist HIV oncology unit in a teaching hospital (predominantly in an outpatient department). Fifteen patients with HIV related, biopsy confirmed, cutaneous Kaposi's sarcoma, with or without visceral involvement of sufficient severity to require systemic chemotherapy, were treated. Most patients had poor prognosis disease as assessed by the Tumour/Immune status/Systemic symptoms (TIS) system and Karnofsky indices; six patients had previously received combination chemotherapy. Primary treatment consisted of a dose of Doxil 10 mg/m2, repeated after 2 weeks. If the Kaposi's sarcoma (KS) responded and the treatment was tolerated, the patient began maintenance therapy at the same dose every 2 weeks. If there was no clinical response, the dose was increased to 20 mg/m2 for the further two cycles, before proceeding to maintenance therapy. Treatment continued until other intercurrent disease, lack of further response, patient preference, or toxicity precluded further treatment. Tumour response was assessed 2 weeks after completion of at least two cycles of chemotherapy. Toxicity was assessed for each cycle. Doxil was well tolerated, and toxicity was manageable, the principal toxicity being haematological. A partial response rate of 11/15 (73%) was achieved, with disease stabilization in the remaining patients. We conclude that Doxil is an effective palliative treatment for epidemic KS in a patient group with a poor predicted outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1994

Changing use of hospital services and costs at a London AIDS referral centre, 1983-1989.

OBJECTIVE: To describe the use of hospital-based services and associated costs over time for HIV-infected individuals by disease stage and year of treatment. METHODS: Data on service use were abstracted from inpatient and outpatient case-notes of 459 HIV-infected patients (121 asymptomatic and 338 AIDS patients) treated at St Mary's Hospital, London between 1983 and 1989. Cost estimates were derived from a survey of the 37 departments involved with HIV-related care. The number and type of admissions and outpatient visits, referral and discharge venues, number and type of tests and procedures performed, drugs prescribed and associated costs for the study period were the outcome measures used. RESULTS: Most patients were homosexual men. At the time of first HIV-related visit, 80.7% lived in London. Most day cases and planned admissions were organized through the outpatient clinic; 31% of emergency admissions were initiated by patients themselves. For people with AIDS the number of day case admissions increased while planned admissions decreased. There was a marked reduction in the duration of inpatient stays, especially for AIDS patients. Costs associated with inpatient care decreased concomitantly. The number of outpatient visits for patients with symptomatic disease increased, resulting in increased outpatient expenditure. Asymptomatic patients had fewer inpatient tests, while outpatient tests did not change over time; costs followed similar patterns. Mean inpatient and outpatient drug-days prescribed did not change nor did average inpatient drug-costs although outpatient drug-costs increased. Inpatient tests performed on symptomatic non-AIDS patients decreased, while mean outpatient tests increased; average costs followed similar patterns. Inpatient drug-days prescribed and costs remained the same, while outpatient drug-days and average drug-costs increased during the study period. For AIDS patients, the number of inpatient tests performed and their average costs decreased but outpatient tests performed increased, though their average costs remained the same. Mean inpatient drug-days prescribed and average drug-costs decreased, while number of outpatient drug-days prescribed and average drug-costs increased markedly over time. For each disease category, expenditure on admissions and related tests decreased over time, while expenditure on outpatient visits and drug-costs increased. CONCLUSIONS: The shift from an inpatient- to an outpatient-based service has resulted in fewer patients being investigated and treated in hospital and more as outpatients. This has resulted in a reduction of inpatient-related costs, while outpatient-related costs have increased. The overall contribution of drug-costs to the total cost has increased greatly over time. With the anticipated advent of new antiviral compounds, the importance of ascertaining their effectiveness as well as their efficacy will become crucial.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Changing presentation and survival, service utilization and costs for AIDS patients: insights from a London referral centre.

OBJECTIVE: To describe the use of services and associated costs for HIV-infected patients by stage of infection in the context of changing patterns of presentation and survival. METHODS: A retrospective analysis of inpatient and outpatient case-notes of 335 AIDS patients and a survey of HIV-related care provided by 37 departments at St Mary's Hospital, London. Survival from time of diagnosis of AIDS, time from diagnosis of HIV infection to AIDS, and use and costs of services per patient-year were outcome measures. RESULTS: During the study period 1 January 1982 to 30 September 1989, 152 AIDS patients were diagnosed before 1987 (group 1) and 183 since 1987 (group 2), most of whom were homosexual men. The median interval of first HIV-related visit to diagnosis of AIDS increased from 0 (group 1) to 264 days (group 2; P < 0.0001). Median survival from AIDS diagnosis increased from 14.6 (group 1) to 21.0 months (group 2; P < 0.02). Group 2 patients used fewer inpatient services than group 1 patients irrespective of disease stage. Symptomatic patients in group 2 used more outpatient services than group 1 patients. Total HIV-related expenditure was lower for patients without AIDS in group 2 than in group 1, while expenditure for AIDS patients remained similar. CONCLUSION: Earlier patient presentation, a shift from inpatient- to outpatient-based clinical care and increased survival from time of AIDS diagnosis has occurred. Increased drug expenditure was offset by reduced inpatient expenditure. Total expenditure per patient-year was stable; increased survival and introduction of new drugs will increase future lifetime use of resources.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Dendritic cells persistently stimulate antibody responses to HIV in seropositive individuals.

OBJECTIVES: B-cell hyperactivity and hypergammaglobulinaemia with high levels of HIV-1-specific antibody occur during HIV-1 infection. We investigated the role played by antigen-presenting cells (APC) in the ongoing production of antibody. METHODS: Adherent monocytes and non-adherent low density dendritic cells were enriched from peripheral blood of patients at different stages of HIV-1 infection (Centers for Disease Control and Prevention categories II, III and IV) and from control subjects at high or low risk of HIV infection. Different concentrations of lymphocytes were cultured in 20 ml hanging drops in the presence or absence of autologous dendritic cells or monocytes. Antibodies to p24 and gp120 were assessed by enzyme-linked immunosorbent assay. RESULTS: Lymphocytes taken from asymptomatic HIV-1-seropositive subjects and depleted of APC produced low or moderate levels of antibody to gp120 or p24 in vitro. However, adding back autologous dendritic cells significantly enhanced antibody production, although fewer samples showed responses to p24 than to gp120. Less antibody production was stimulated using cells from patients with persistent generalized lymphadenopathy, or if monocytes rather than dendritic cells were added back. Little or no antibody was produced by cells from patients with AIDS and no antibody was detected in cultures of cells from seronegative individuals with low or high risk for infection. CONCLUSIONS: The evidence suggests that ongoing humoral responses to HIV-1 are fuelled by dendritic cells. Thus, the dominance of humoral over cell-mediated responses in HIV-1 infection may depend upon signalling via dendritic cells. Changes in signalling by dendritic cells could be central to the immunologic features of HIV-1 infection.

Antibody Formation↗