Volunteering for research.
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Biomedical subjects
Publications and source records attributed to B Gazzard.
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OBJECTIVE: To determine the number of deaths attributable to HIV infection among men aged 15-64 in a geographically defined population in the United Kingdom. DESIGN: Retrospective review of death certificates and linkage with local and national HIV and AIDS surveillance data. SETTING: Riverside District Health Authority, London. MAIN OUTCOME MEASURES: Numbers of deaths attributed to HIV infection in male residents of Riverside aged 15-64 and 15-44 over a six month period. Proportion of attributed deaths were (i) identified from death certificates by the Office of Population Censuses and Surveys as being due to HIV infection and (ii) reported as cases of AIDS or HIV related deaths to the Public Health Laboratory Service Communicable Disease Surveillance Centre. RESULTS: 34 of 213 (16%) deaths in men aged 15-64 and 27 of 69 (39%) deaths in men aged 15-44 were attributed to HIV infection. Six of 33 (18%) attributed deaths were identified by the Office of Population Censuses and Surveys and 32/34 (94%) were reported to the Communicable Disease Surveillance Centre. CONCLUSIONS: HIV infection was the leading cause of death in male residents of Riverside aged 15-44 and the third commonest cause of death in those aged 15-64. Most individuals dying of known HIV infection were reported to the Communicable Disease Surveillance Centre but identification of the true cause of death from the process of death certification was poor. Measures to improve the certification of HIV and AIDS or the use of AIDS surveillance information correctly to code the cause of death needs to be considered to ensure that the true impact of HIV infection is reflected in routine mortality statistics.
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To assess the hypothesis that the human immunodeficiency virus (HIV) might mimic major histocompatibility complex (MHC) allodeterminants and interact with T-cell receptors (TCRs) of alloreactive T-cells, we have done a preliminary analysis of the range of alpha beta TCR gene products in 16 HIV-1-seropositive individuals with normal CD4 counts and in 16 healthy HIV-1-negative controls. Using a panel of monoclonal antibodies with a two-colour direct immunofluorescence method, we found a significant increase in the expression of the V beta 5.3 subfamily in the HIV-positive patient group compared with controls (p less than 0.01). Selected increase in expression of V beta sequences has been described in various autoimmune conditions and our findings raise the possibility that the immunopathological damage from HIV infection may be due to the induction of autoreactivity. If HIV does mimic MHC II, the normal immune response to the virus could represent an autoimmune process similar to graft-versus-host disease.
We report a case of pneumatosis intestinalis (PI) occurring in association with cryptosporidiosis in a patient documented as being HIV-seropositive. Chest and abdominal radiographs taken 2 months previously were normal and the patient did not have any evidence of gastrointestinal infection at that time. The case was complicated by cyst rupture resulting in a pneumoretroperitoneum and pneumomediastinum. The association of pneumatosis and cryptosporidiosis has not been previously reported.
Self administered questionnaires were given to 34 midwives, who regularly counsel parturient women about the HIV antibody test, to investigate their attitudes to the test being offered in the antenatal clinic. Most of the midwives felt that testing should not be compulsory and that the test should be offered to all pregnant women who ask for it, not only those in recognized risk groups. Most also felt that women should be told the results of the test and that it should not be the midwives aim to increase the number of women having the test. Most felt that all midwives should counsel about the test but would like health advisers, GPs and obstetricians to be involved also. They also felt that they did not have sufficient knowledge in some areas to counsel particularly with regard to the practical and psychological implications of being HIV positive. This has implications in terms of the provision of adequate pre-test counselling for all pregnant women as an improvement in counselling services requires an allocation of finances, e.g. for training of midwives, which may be seen as unnecessary in areas of low seroprevalence. Further discussion and debate of these issues is required.
Inhaled pentamidine has become an important method of treatment and prophylaxis for Pneumocystis carinii pneumonia and we have compared nebuliser efficiency in terms of drug output and droplet sizes in four brands of jet nebuliser (Acorn-22, Inspiron, Cirrus, Respirgard II) and one brand of ultrasonic nebuliser (Fisoneb), at 2 pentamidine concentrations and 3 flow rates, using a laser particle sizer. Droplet size (which varied from 1.2 to 4.7 microns mass median diameter) was dependent in all cases, except with the Respirgard II system, on the flow rate of the gas driving the equipment and the concentration of pentamidine used. Drug output varied significantly between nebuliser brands and for a 300 mg dose of pentamidine was: 61% for the Acorn-22, 62% for the Inspiron, 49% for the Fisoneb and 43% for the Respirgard II. Both droplet size and drug output are important in determining nebuliser efficiency.
AIMS: To describe the microscopic appearance of adenovirus infection in the large bowel of human immunodeficiency virus (HIV) positive patients with diarrhoea. METHODS: Large bowel biopsy specimens from 10 HIV positive patients, eight of whom were also infected with other gastrointestinal pathogens, with diarrhoea were examined, together with six small bowel biopsy specimens from the same group of patients. Eight of the patients had AIDS. The biopsy specimens were examined by light microscopy performed on haematoxylin and eosin stained and immunoperoxidase preparations, the latter using a commercially available antibody (Serotec MCA 489). Confirmation was obtained with electron microscopy. RESULTS: The morphological appearance of cells infected with adenovirus showed characteristic nuclear and cellular changes, although the inflammatory reaction was non-specific. Immunoperoxidase staining for adenovirus was sensitive and specific, and the presence of viral inclusions consistent with adenovirus was confirmed by electron microscopy. CONCLUSIONS: The light microscopic features of adenovirus infection are distinctive and immunocytochemistry with a commercially available antibody is a sensitive and specific means of confirming the diagnosis. Further studies of the role of adenovirus in causing diarrhoea in these patients are indicated.
Four men with HIV infection who were referred to liaison psychiatry for assessment of eating disorders are described. In all four cases the eating disorder had implications for the clinical management of their HIV infection. Investigations of weight loss, dietary intervention, and compliance may all be affected by the presence of an eating disorder. The development of HIV disease may exacerbate the symptoms of an eating disorder.
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R 82913, a tetrahydroimidazobenzodiazepinthione (TIBO) derivative with potent activity against human immunodeficiency virus 1 (HIV-1) in vitro, was given to 22 patients with AIDS or AIDS-related complex in a dose-escalating pilot study. Doses of 10 to 300 mg administered daily by intravenous infusion were well tolerated for up to 50 weeks, with no haematological or biochemical evidence of toxicity. Mean OKT4 cell count rose slightly during the second month of treatment when higher steady-state plasma concentrations of the drug were achieved. Median p24 antigen concentration fell by 41% during the first month of therapy. When the rise in p24 antigen before therapy was compared to the fall during treatment, end-point analysis showed a significant difference (p less than 0.03). The combination of potent antiretroviral activity in vitro and the observed effect on HIV p24 antigen and absence of toxicity in vivo indicate that R 82913 and related TIBO derivatives merit further study in the treatment of retroviral infections.
The presentation, operative management and final diagnosis were reviewed in 28 patients with AIDS (27 men and one woman) who underwent emergency laparotomy. On clinical and radiological examination, six patients showed features of toxic megacolon, five patients had small bowel obstruction, six patients had localized peritonitis and three had perforated viscus with generalized peritonitis. The most common disease processes were acute colitis in seven patients (associated with cytomegalovirus (CMV) infection in six), intra-abdominal lymphoma in five patients, acute appendicitis in five patients (associated with CMV infection in two), and atypical mycobacterial (MAI) infection in four patients. Two perioperative deaths occurred; one in a patient with acute pancreatitis and a second with generalized peritonitis. Later deaths were due to progression of AIDS, and patient survival at 1 month, 3 months and 6 months was 89 per cent, 64 per cent and 48 per cent, respectively. Lower operative mortality than in previously reported series may be due to earlier intervention in CMV toxic megacolon. Surgery, however, conferred less benefit in patients with acute abdominal pain from MAI infection or lymphoma. With careful patient selection, emergency laparotomy may achieve worthwhile palliation in patients with AIDS.
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Bronchial narrowing is the major side effect of inhaled nebulised pentamidine isethionate, used for the prophylaxis and treatment of Pneumocystis carinii pneumonia. Several agents and delivery systems were assessed for prophylaxis of bronchial narrowing in HIV-positive males receiving regular nebulised pentamidine isethionate. In a previous study we found the mean maximum fall in FEV1 with nebulised pentamidine alone to be 21%. FEV1 was measured before and after inhaling nebulised pentamidine, preceded by one of the following bronchodilator/immunoregulatory agents: Terbutaline metered dose inhaler (500 micrograms), nebulised salbutamol (5 mg), nebulised ipratropium bromide (500 micrograms), nebulised sodium cromoglycate (20 mg), and nedocromil sodium metered dose inhaler (4 mg). Each agent was administered once only to ten different subjects. Nebulised salbutamol gave most effective prophylaxis against bronchial narrowing induced by nebulised pentamidine (mean maximum fall in FEV1 = 5% vs. 21%, P less than 0.001). Terbutaline given by metered dose inhaler was significantly less effective than high dose terbutaline (10 mg) given by nebuliser, demonstrated in the previous study (mean maximum fall in FEV1 = 14% vs. 6%, P less than 0.05). Mean maximum falls in FEV1 for ipratropium bromide, sodium cromoglycate and nedocromil sodium were 16, 17 and 16%, respectively. High dose beta 2-agonists administered by nebuliser give more effective prophylaxis against nebulised pentamidine-induced bronchial narrowing than either lower doses given by metered dose inhaler, anticholinergics or immunoregulatory drugs.
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Ten bronchoscopes that had been used on patients with the acquired immunodeficiency syndrome were sampled to determine the nature and extent of microbial contamination. Samples were taken by irrigating the suction biopsy channel with modified viral transport medium and by swabbing the insertion tube. Sampling was repeated after they had been cleaned in detergent and after two minutes' disinfection in 2% alkaline glutaraldehyde. Before being cleaned the seven bronchoscopes tested by polymerase chain reaction were contaminated with the human immunodeficiency virus, though infectivity and antigen assays gave negative results. Other organisms identified were hepatitis B virus (1), commensal bacteria (9), and Pneumocystis carinii (4). Mean bacterial contamination was 2.27 log colony forming organisms per millilitre. Cleaning the bronchoscope before disinfection removed all detectable contaminants with a reduction in bacterial growth of up to 8 log colony forming units/ml.
Pneumocystis carinii pneumonia (PCP) is seen in people with a defect in cell-mediated immunity. Today the most common cause for this is the Acquired Immunodeficiency Syndrome (AIDS). There have been some remarkable advances recently in the development of new drug regimens to combat this otherwise fatal infection. Although cotrimoxazole (trimethoprim-sulfamethoxazole) is still the drug of first choice it cannot be tolerated by a significant proportion of patients, and therapies such as pentamidine (pentamidine-isethionate) [intravenous or nebulised], dapsone-trimethoprim, eflornithine (DFMO; difluoromethylornithine), trimetrexate, and clindamycin-primaquine are finding therapeutic niches. The major advantage in these other agents is not improved efficacy but different toxicity profiles, enabling therapy to be most appropriately tailored to individual patients' conditions. Although the majority of patients should now survive an attack of PCP, relapses will occur if prophylaxis is not used. There is also the capacity to predict accurately which patients are at risk for this pneumonia and prevent it through the use of chemoprophylaxis. These advances in the treatment and prevention of PCP, together with anti-retroviral therapy, mean that this is an area of AIDS management that has resulted in improved long term survival.