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Biomedical subjects

R Brettle

Publications and source records attributed to R Brettle.

18 recordsLinked to original sources
PubMed2002

Changes in the cause of death among HIV positive subjects across Europe: results from the EuroSIDA study.

OBJECTIVES: The causes of death among HIV-positive patients may have changed since the introduction of highly active antiretroviral therapy (HAART). We investigated these changes, patients who died without an AIDS diagnosis and factors relating to pre-AIDS deaths. METHODS: Analyses of 1826 deaths among EuroSIDA patients, an observational study of 8556 patients. Incidence rates of pre-AIDS deaths were compared to overall rates. Factors relating to pre-AIDS deaths were identified using Cox regression. RESULTS: Death rates declined from 15.6 to 2.7 per 100 person-years of follow-up (PYFU) between 1994 and 2001. Pre-AIDS incidence declined from 2.4 to 1.1 per 100 PYFU. The ratio of overall to pre-AIDS deaths peaked in 1996 at 8.4 and dropped to < 3 after 1998. The adjusted odds of dying following one AIDS defining event (ADE) increased yearly (odds ratio, 1.53; P < 0.001), conversely the odds of dying following three or more ADE decreased yearly (odds ratio, 0.79; P < 0.001). The proportion of deaths that followed an HIV-related disease decreased by 23% annually; in contrast there was a 32% yearly increase in the proportion of deaths due to known causes other than HIV-related or suicides. Injecting drug users (IDU) were significantly more likely to die before an ADE than homosexuals (relative hazard, 2.97; P < 0.0001) and patients from northern/eastern Europe (relative hazard, 2.01; P < 0.0001) were more likely to die pre-AIDS than southern patients. CONCLUSIONS: The proportion of pre-AIDS deaths increased from 1994 to 2001; however, the incidence of pre-AIDS deaths and deaths overall declined. IDU and subjects from northern/eastern Europe had an increased risk of pre-AIDS death. HIV-positive patients live longer therefore it is essential to continue to monitor all causes of mortality to identify changes.

Cause of Death↗
PubMed1997

Features and outcome of Pneumocystis carinii pneumonia according to risk category for HIV infection.

A retrospective study of Pneumocystis carinii pneumonia (PCP) was undertaken to examine differences between the presentation and outcome of PCP in AIDS patients from different risk categories for HIV infection. There were 176 PCP episodes recorded in 126 patients from the following risk categories: 69 intravenous drug misusers (IDMs), 36 homosexually infected men and 21 heterosexually infected patients. Most clinical features did not differ significantly between the 3 groups but hypercapnia was almost exclusively seen in IDMs and, if recorded, was associated with a poorer survival. Pneumothorax was more likely to complicate PCP in IDMs and, although present in all groups, concomitant bacterial respiratory infections were more common in IDMs. Recovery from PCP and the incidence of adverse events during treatment did not differ according to risk category. Subsequent survival time was shorter amongst IDMs, but the uptake of antiretrovirals in this group was significantly lower. We conclude that there are few differences in the presentation of PCP between IDMs and other risk categories for HIV infection and that these do not influence the outcomes of illness. The lower post-PCP survival in IDMs can be accounted for by a reduced uptake of antiretroviral drugs by this group.

AIDS-Related Opportunistic Infections↗
PubMed1993

Diagnosis of Pneumocystis carinii pneumonia in a population of HIV-positive drug users, with particular reference to sputum induction and fluorescent antibody techniques.

Between June 1990 and May 1991, 200 sputum inductions were examined by a fluorescent antibody test (FAT) for Pneumocystis carinii (PC). A total of 164 specimens were negative, 36 were positive and a further 20 inductions were unsuccessful. All patients with a positive result, seven of whom had normal chest X-rays and blood gas analyses, were treated for Pneumocystis carinii pneumonia (PCP) with symptomatic response. Two additional patients were diagnosed as PCP during the study period. No patient with a negative or unsuccessful result developed clinical PCP during that admission, although six did develop 10 episodes of PCP (FAT positive for PC on induced sputum samples) within 3 months of a negative result. Sputum induction was well tolerated by patients and not associated with adverse events. Sensitivity of FAT for PC was 95% and specificity was 100%. These results may in part be because most of the patients were injection drug users (IDUs) who often suffer from chronic productive cough, and also because sputum induction in all cases was supervised by an experienced physiotherapist.

Female↗
PubMed1993

The effects of indomethacin and naproxen on zidovudine pharmacokinetics.

The effects of indomethacin and naproxen on zidovudine (ZDV) pharmacokinetics were studied in six patients with the acquired immunodeficiency syndrome (AIDS), AIDS related complex (ARC) or asymptomatic HIV disease using a placebo-controlled crossover design. Indomethacin 25 mg twice daily or naproxen 250 mg twice daily did not alter ZDV pharmacokinetics compared with placebo. The mean AUC value for the glucuronidated metabolite, GZDV, was reduced from 26.6 +/- 11.7 mumol l-1 h in the presence of placebo to 20.9 +/- 8.3 mumol l-1 h (95% C.I. of the difference 1.39-9.98; P < 0.05) following treatment with naproxen 250 mg twice daily for 3 days. The small decrease in plasma GZDV in the naproxen phase reflects an increase in clearance of ZDV to other metabolites and/or a decrease in the formation clearance to GZDV and/or an increase in the clearance of GZDV. A decrease in formation clearance to GZDV would be consistent with the results of in vitro studies reported previously. No significant increase in ZDV concentration in the presence of naproxen may reflect a lower sensitivity of parent drug measurements to selective inhibition of parallel pathways of metabolism. The clinical significance of these findings is unknown but toxicity may be increased if a decreased formation of GZDV is accompanied by shunting of metabolism to 3'-amino-3'-deoxythymidine which is alleged to be cytotoxic.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Changing patterns of malaria in south-east Scotland: implications for practitioner awareness and prophylactic advice.

The medical records of all 229 patients with malaria admitted to the Edinburgh City Hospital between 1969 and 1988 were studied retrospectively. A total of 137 were from Africa, 44 from the Indian subcontinent, 19 from the Far East, 18 from New Guinea, 5 from the Middle East and 3 from South America. The number of yearly admissions rose markedly after 1983, mainly due to an increase in Plasmodium falciparum cases. Ninety-four cases (15 with severe parasitaemia) mainly from Kenya and Nigeria were due to P. falciparum infection and 99 to P. vivax. There were no deaths. A seasonal distribution of onset of fever in patients with P. vivax infections originating from the Indian subcontinent showed that most patients presented during the summer. Prophylaxis had generally been irregular or non-existent but many compliant patients may have been receiving an inadequate dose of chloroquine on a mg/kg body weight basis. General practitioners are likely to see at least one case of malaria every 4 years. They are encouraged to seek advice from a specialist unit whenever necessary whether before or after their patient travels abroad. Travellers, in particular to Kenya and Nigeria, and Asian immigrants to the UK returning on holiday to their country of origin should be strongly advised to take regular prophylaxis including on return to the UK.

Adolescent↗
PubMed1990

The polymerase chain reaction in the diagnosis of vertically transmitted HIV infection.

The presence of HIV-1 DNA sequences in DNA from peripheral blood mononuclear cells (PBMCs) was investigated in a two-stage polymerase chain reaction ('double' PCR) using four sets of nested primers. The PBMCs tested were obtained from 46 children born to HIV-seropositive mothers, seven 'control' children born to HIV-seronegative mothers and seropositive fathers, and 45 healthy adult blood donors who were HIV seronegative. Nine of the children had symptomatic HIV infection and other laboratory features characteristic of HIV infection: all nine were PCR-positive with each set of primers in each of their 22 blood samples tested. The remaining 44 children had no clinical or laboratory evidence of HIV infection, and each of their 50 samples was PCR-negative with each set of primers, as were all blood donor samples. PCR-positive samples were tested in more detail using two of the sets of primers, which spanned hypervariable regions in the env gene. Polyacrylamide gel electrophoresis of DNA amplified from these regions yielded patterns of amplified DNA length variation which were characteristic for each child, and which changed little with time (in serial samples obtained over periods of 3-7 months). This excluded contamination as a cause of PCR positivity. This is the first report of the use of a double PCR for the diagnosis of HIV infection. The results demonstrate the specificity of this PCR method in diagnosis, with failure to reveal in this cohort any cases of vertically transmitted HIV-1 infection in addition to those already confirmed by conventional laboratory techniques.

Child, Preschool↗
PubMed1989

Transmission of HIV to heterosexual partners of infected men and women.

Future heterosexual spread of HIV will in part depend on the efficiency of transmission from men to women and from women to men. We studied seventy-eight female sexual partners of men infected with HIV and 18 male sexual partners of infected women. Participants were interviewed concerning sexual practices, use of contraception and other risk factors for HIV infection. Fifteen out of 78 (19.2%) female partners and one out of eighteen (5.5%) male partners were seropositive for HIV antibody. All couples had practised vaginal intercourse. Seropositive female partners did not differ significantly from seronegative partners with regard to length of relationship, number of acts of vaginal intercourse, other sexual practices, stage of clinical disease in the index case, or numbers of other sexual partners in the last five years. In two women, seroconversion was documented after one act of unprotected sexual intercourse. The majority of infected female partners (eight out of 15) had sexual relationships with men who were asymptomatic and did not practice anal intercourse. Biological factors such as variability in infectivity of the index case and susceptibility of the contact, as well as behavioural variables may be important in determining transmission.

Adolescent↗
PubMedDate not supplied

Cytomegalovirus retinitis and AIDS in Edinburgh.

The medical records, retinal drawings and fundus photographs of all patients with cytomegalovirus retinitis (CMVR) and AIDS in Edinburgh between 1986-1992 were reviewed to determine the efficacy of treatment in preserving vision. Ophthalmoscopic features of CMVR were observed in 32 eyes of 24 patients with AIDS, 19 males and 5 females. HIV transmission in this group was by homo/bisexual contact (16), injection drug use (7) and blood transfusion (1). Unilateral blurring was the commonest visual symptom although 9 (38%) patients had no visual symptoms. All patients presented with a corrected visual acuity of 6/12 or better in at least one eye. Following treatment with systemic ganciclovir or foscarnet 16 patients (66%) developed toxic side-effects of therapy and 13 (54%) experienced a recurrence of CMVR. Four (17%) patients developed a retinal detachment in one eye. The mean survival was 8.3 months after the diagnosis of CMVR. At final follow-up, between 2-26 months after the diagnosis of CMVR, 21 (87.5%) patients retained useful vision (6/18 or better) although 3 (12.5%) were effectively blind (less than 6/60). We conclude that with prompt diagnosis and treatment of CMVR vision can be preserved in the majority of cases.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

A comparison of AIDS-defining events and subsequent CDC stage IV events in IDUs and gay men.

The two major risk groups for acquisition of HIV in the UK are gay men and IDUs. Individuals from these risk groups vary in a number of respects in their life-style, which have the potential to affect the course of their HIV disease. This study compares gay men and IDUs from the Lothian Region of Scotland with respect to their AIDS defining diagnosis and subsequent CDC (Centers for Disease Control) stage IV events. Comparisons were made between the two risk groups for their AIDS defining diagnosis by performing chi square tests, Mann-Whitney tests and logistic regression. Subsequent CDC stage IV events were analysed using ordinal logistic regression and Cox regression. 89 IDUs and 56 gay men were included in the analysis. Oesophageal candida was a commoner AIDS-defining diagnosis in IDUs than gay men and Kaposi's sarcoma was diagnosed more frequently in gay men than IDUs. Subsequently oesophageal candida was also commoner in IDUs and CMV retinitis was seen more frequently in gay men. The role of prophylaxis and differences in diet are discussed as possible causes of the observed differences in the incidence of oesophageal candida. The higher incidence of CMV retinitis in gay men probably reflects the high level of sexual acquisition of CMV.

AIDS-Related Complex↗