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Biomedical subjects

P Neill

Publications and source records attributed to P Neill.

At least 19 recordsLinked to original sources

Antihypertensive effects of low doses of hydrochlorothiazide in hypertensive black Zimbabweans.

The antihypertensive effects of low doses of hydrochlorothiazide have not been examined in black African hypertensive patients although hydrochlorothiazide is commonly used as first-line therapy. The antihypertensive effects of hydrochlorothiazide in a daily dose of 6.25, 12.5, 25 and 50 mg were examined in 19 black Zimbabwean hypertensive patients in a double-blind, random order, placebo-controlled, cross-over trial. The mean systolic blood pressure on placebo was 170.2 mmHg (95% CI +/- 9.0 mmHg) and on daily doses of hydrochlorothiazide decreased to: 161.1 mmHg (95% CI + 10.0 mmHg) on 6.25 mg; 156.6 mmHg (95% CI +/- 8.6 mmHg) on 12.5 mg; 154.9 mmHg (95% CI +/- 8.5 mmHg) on 25 mg and 149.1 mmHg (95% CI +/- 9.2 mmHg) on 50 mg. The mean diastolic blood pressure on placebo was 101.4 mmHg (95% CI +/- 5.0 mmHg) and decreased to: 98.0 mmHg (95% CI +/- 5.7 mmHg) on 6.25 mg; 96.1 mmHg (95% CI +/- 4.5 mmHg) on 12.5 mg; 93.6 mmHg (95% CI +/- 5.3 mmHg) on 25 mg and 90.5 mmHg (95% CI +/- 3.9 mmHg) on 50 mg. Hydrochlorothiazide in doses of 25 mg and 50 mg decreased systolic and diastolic blood pressure and the 12.5 mg dose decreased systolic blood pressure significantly more than placebo. We conclude that in this population maximum antihypertensive effect is not seen with the lower doses of hydrochlorothiazide and 25 mg is an appropriate starting dose for most patients.

Adult

Pulmonary Kaposi's sarcoma in Africa.

BACKGROUND: A study was carried out to identify the main clinical radiological and bronchoscopic features of HIV related Kaposi's sarcoma of the lung in African patients. METHODS: Forty seven HIV positive patients with epidemic Kaposi's sarcoma who had clinical or radiological respiratory changes were investigated by simple lung function tests and fibreoptic bronchoscopy. RESULTS: The most common respiratory symptoms in the 47 patients were persistent cough in 42, haemoptysis in 23, and breathlessness in 38. A restrictive spirometric pattern was most common. The mean (SD) forced expiratory volume in one second (FEV1) was 1.88 (0.62) 1 with a forced vital capacity (FVC) of 2.66 (0.87) 1 and a FEV1/FVC% of 73.2 (7.5). On the chest radiograph 26 patients had diffuse reticulonodular shadows, 11 focal nodular shadows, seven a pleural effusion, and one a substantial increase in vascular markings; in two the radiograph was normal. At bronchoscopy characteristic discrete lesions were easily visible in 37 patients and were often bright red. Multiple nodules were seen in 11, flat or early plaque lesions in 12 (14 had both), proximal flat lesions and diffuse infiltration in three, diffuse infiltration alone in four, and masses in two; one had normal appearances at bronchoscopy. One patient had Pneumocystis carinii and two had a single bacterial pathogen cultured from the bronchoalveolar lavage fluid. Only two of 29 bronchoscopic biopsies showed classical histological Kaposi's sarcoma. After cytotoxic treatment 20 patients have died, with an overall median survival of 70 days. CONCLUSION: In this African population symptomatic pulmonary Kaposi's sarcoma was common, with lesions seen in all but one patient at bronchoscopy. Coexistent infection was uncommon. Prognosis was poor despite treatment.

Acquired Immunodeficiency Syndrome

A comparative study of the schizontocidal efficacy and safety of artemether versus chloroquine in uncomplicated malaria.

Forty-seven patients with uncomplicated falciparum malaria were randomly assigned to receive either artemether (n = 24), 9.6 mg/kg body weight intramuscularly over five days or chloroquine (n = 23), 25 mg/kg body weight orally. Patients were kept in hospital for seven days followed by review on days 14, 21 and 28. Five patients on chloroquine were withdrawn before day seven due to treatment failure. Of the remaining patients, parasite clearance time was 33.0 +/- 13.6 hours for the artemether group and 63.3 +/- 14.7 hours for patients on chloroquine (p < 0.001). No significant difference was recorded in fever clearance time between the two groups of patients. Recrudescence rate for patients on artemether was 14.3 pc compared to 57.1 pc for the chloroquine group (p < 0.05). No major adverse events were recorded for either treatment group although five patients on artemether had a transient spike of temperature after clearance of parasitaemia. In conclusion, our study has shown that no major adverse events were experienced by patients on artemether and the rate of parasite clearance for the artemether group was superior to that of patients on chloroquine.

Adolescent

Asthma paradox.

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Asthma

Comparison of the prevalence of reversible airways obstruction in rural and urban Zimbabwean children.

The prevalence of reversible airways obstruction has been assessed in children in three areas in Zimbabwe--northern Harare (high socioeconomic class urban children), southern Harare (low socio-economic class urban children), and Wedza Communal Land (rural children from peasant families). Peak expiratory flow (PEF) was measured before and after six minutes' free running in 2055 Zimbabwean primary school children aged 7-9 years. Height and weight were measured and nutritional state expressed as a percentage of the 50th centile for age (Tanner-Whitehouse standards). Reversible airways obstruction was deemed to be present when peak expiratory flow was below the 2.5th centile for height before exercise and rose by more than 15% after inhalation of salbutamol and when it fell by 15% or more after exercise and rose again after salbutamol. The prevalence of reversible airways obstruction was 5.8% (95% confidence interval 4.1-7.5%) in northern Harare (n = 726); 3.1% (1.8-4.5%) in southern Harare (n = 642), and 0.1% (0.0-0.4%) in Wedza (n = 687). In northern Harare, the only study area in which white children were found, the prevalence of reversible airways obstruction was similar in white (5.3%, 10/188) and black (5.9%, 32/538) children. Indicators of nutritional state also showed no significant differences between white and black children in northern Harare but were lower in southern Harare and lower still in Wedza. Urban living and higher material standards of living appear to be associated with a higher prevalence of reversible airways obstruction in children in Zimbabwe.

Airway Obstruction

Variation in cuff blood pressure in untreated urban outpatients with mild hypertension in Harare, Zimbabwe--implications for the diagnosis of hypertension.

Duplicate measurements of BP were recorded at six visits in 32 male urban factory workers found to have raised BP (systolic blood pressure (SBP) greater than or equal to 160 mmHg or diastolic blood pressure (DBP) greater than or equal to 90 mmHg) at the initial visit). A systematic decrease in both SBP and DBP occurred over the first three visits. The BP at visits 4-6 was not significantly different. Most of the decrease in BP occurred between the first and second visit (mean SBP decreased 8.5 mmHg and mean DBP decreased 11.1 mmHg). After 6 visits 66% of subjects could be classified into clear clinical groups (normotensive 53.5%, hypertensive 12.5%) but in 34% the variation in cuff BP precluded classification. In these subjects prolonged observation or home BP monitoring may be required before initiating lifelong treatment.

Adult

Combination of a thiazide, a vasodilator and reserpine compared with methyldopa plus hydrochlorothiazide in the treatment of hypertension in Zimbabwe.

Brinerdin (Sandoz), a combination of a diuretic (clopamide 5 mg), a vasodilator (dihydro-ergocristine 0.5 mg) and reserpine (0.1 mg) (CDR) was compared with methyldopa (MD) plus hydrochlorothiazide (HCT) for antihypertensive effect, adverse reactions, compliance and patient preference in an open cross-over trial. Eighteen patients completed both arms of the trial and 5 patients who completed the CDR arm were withdrawn while on the MD arm because of adverse effects in 4 and poor control in 1. On HCT 50 mg daily the mean baseline systolic blood pressure was 163.9 +/- 16.3 mmHg and the diastolic blood pressure was 105.9 +/- 6.7 mmHg. On CDR these were reduced to systolic blood pressure 140.3 +/- 15.1 mmHg and diastolic blood pressure 87.8 +/- 9.3 mmHg. On MD + HCT the systolic blood pressure was reduced to 138.5 +/- 16.9 mmHg and the diastolic blood pressure to 88.9 +/- 10.3 mmHg. The differences between the two treatment periods in systolic blood pressure (1.8 mmHg; 95% confidence interval (CI) - 4.1 + 7.7 mmHg) and diastolic blood pressure (1.1 mmHg; 95% CI - 4.6 + 2.4 mmHg) were not significant with P values of 0.6 and 0.7 respectively. Compliance was 98.2% for CDR and 94.7% for MD + HCT (P = 0.02). Unusual sleepiness occurred more frequently in the MD arm (P less than 0.01). Thirteen patients chose to continue on CDR, 2 on MD + HCT and 3 had no preference (P = 0.005). CDR is similar in antihypertensive effect to MD + HCT but is better tolerated with fewer withdrawals, fewer adverse effects, better compliance and has more patients electing to continue taking it.

Adult

Pneumocystis carinii pneumonia in patients with AIDS in Central Africa.

Over a period of 11 months, 37 patients infected with the Human Immunodeficiency Virus (HIV) presenting with symptoms of bronchopulmonary disease were investigated. Patients presented with cough, weight loss, fever and dyspnoea. Investigations included fibreoptic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. In eight patients (22%) Pneumocystis carinii was found. Pulmonary infiltrates were found on chest radiographs of six patients, while in the remaining two patients chest radiographs showed clear lung fields. P. carinii was found in two patients with pulmonary Kaposi's sarcoma. Infection with P. carinii often occurred with other pathogens: Streptococcus pneumoniae was found in four patients, Staphylococcus aureus in two and tuberculosis in two. P. carinii pneumonia does occur in patients with HIV infection in Africa and the diagnosis is relatively simple to make provided that transbronchial biopsy and bronchoalveolar lavage are carried out through a fibreoptic bronchoscope and specimens examined after appropriate staining. However, the prevalence of P. carinii in patients with HIV infection in Africa appears to be lower than that found in patients with HIV infection in Europe and North America.

Acquired Immunodeficiency Syndrome

A comparison of inhaled beclomethasone dipropionate and nedocromil sodium as additional therapy in asthma.

We have compared the effects of inhaled beclomethasone dipropionate (BDP) 400 micrograms day-1 with inhaled nedocromil sodium (NDS) 16 mg day-1 as additional therapy in adults with asthma not fully controlled by regular beta-2-agonist inhalers with, or without, oral theophyllines. Seventeen subjects were entered into a 2-week baseline phase, and subsequently in a double-blind crossover fashion into two 8-week phases of daily BDP or NDS. Subjects recorded daily peak expiratory flow rates, morning and evening (PEF am and pm), symptom scores and beta-2-agonist inhaler use. Thirteen subjects completed the study and the last 2 weeks of each phase were analysed. Compared to baseline, both BDP and NDS caused a significant improvement in PEF am (P less than 0.05), PEF pm (P less than 0.05) and the 'amplitude % mean' (P less than 0.001). Both drugs gave a highly significant improvement in all symptom scores. There was no significant difference between BDP and NDS for PEF am, PEF pm, amplitude % mean, cough and daytime asthma score. However, beta-2-agonist inhaler use and scores for nocturnal asthma and morning tightness were all significantly better in the BDP phase, and may have contributed to its better overall subjective performance. Thus, both NDS and BDP resulted in a significant improvement in asthma control in the subjects studied, and both drugs caused a similar improvement in PEF.

Administration, Inhalation

Case discussion in clinical pharmacology: application of small group teaching methods to a large group.

Problem-oriented case discussion is a valuable teaching tool in clinical pharmacology. Small groups are ideal for discussion but attempts to extend this to large groups often magnify the problems seen with small group discussion to an unacceptable extent. We describe a format which overcomes many of the problems encountered. The class is divided into groups of six students. Cases for discussion are distributed a week before discussion. Individual groups meet, research, discuss, form a consensus opinion and appoint a chairperson for each topic. The class meets and two groups are randomly chosen to discuss the first topic. The chairperson of the first group briefly presents the group's analysis of the problem. The chairperson of the second group then acts as an 'interrogator', questioning statements of fact, application of knowledge or logic, and offers alternative opinions. After discussion between the two groups the rest of the class join the discussion. Two new groups are chosen for the second case. This format facilitates self-directed learning, well-prepared participants and worthwhile discussion.

Group Processes

Therapeutic review: antibiotic prophylaxis for bacterial endocarditis.

A recent survey of antibiotic prophylaxis found that local practice often differed from that recommended by authoritative bodies such as the British Society for Antimicrobial Chemotherapy (BSAC) and the American Heart Association (AHA). Practitioners found the subject confusing and requested guidance. For these reasons we present current recommendations. Unfortunately all recommendations are based on animal studies and an understanding of the pathogenesis of bacterial endocarditis in humans. There are no controlled trials in humans on which to base guidelines, so rigidity is inappropriate. It is also important to realise that optimal prophylaxis will not eliminate bacterial endocarditis. In developed countries it has been estimated that only 10% of cases of endocarditis are theoretically preventable.

Anti-Bacterial Agents

Effects of two pulmonary tuberculosis drug treatments and acetylator status on liver function in a Zimbabwean population.

In Zimbabwe patients with pulmonary tuberculosis who are acid-fast bacilli (AFB) negative in the sputum are treated in the two month intensive phase with isoniazid, thiacetazone pyrazinamide and streptomycin (regimen A). Sputum positive patients receive regimen A plus rifampicin (regimen B). Both groups continue treatment with isoniazid and thiacetazone. 21 patients on regimen A and 19 on regimen B had clinical assessment and liver function tests performed at weeks 0, 2, 4, 8, and 12 weeks of treatment (during and four weeks after, the intensive phase of 8 weeks). Acetylator status was also assessed, no significant difference was found between patients on regimen A or B (41 per cent and 45 per cent fast acetylators respectively). Liver function tests results (alanine aminotransferase and alkaline phosphatase) showed a persisting rise during the intensive phase on both regimens, and further rise after four weeks in the continuation phase, this further rise reaching statistical significance in regimen B. These results are unexpected when compared to other studies but the regimens under investigation are not used elsewhere. The significant rise after stopping intensive therapy in regimen B suggests some protective effect of rifampicin against the hepatotoxicity of the regimen, possibly the isoniazid/thiacetazone component. Acetylator status did not influence the degree of hepatotoxicity.

Alanine Transaminase

Carcinoma of the bronchus in tobacco farm workers. An unrecognised high risk group.

A case-control study of 47 patients with bronchoscopically diagnosed carcinoma of the lung revealed that 12 were tobacco farm workers. This is significantly (p less than 0.001) greater than the number of tobacco farm workers in a healthy control group (1 out of 46). All of the tobacco farm workers smoked and 11 had smoked more than 10 pack-years of cigarettes. All of the tobacco farm workers admitted to smoking unprocessed tobacco, as did 28 of the other 35 carcinoma patients, but none of the control group. It was not possible to quantify the effect of working with tobacco or the effect of other atmosphere pollutants on a tobacco farm as possible risk factors for developing carcinoma, but this risk is unlikely to be significant compared to that from cigarette smoking.

Agricultural Workers' Diseases

Lack of effect of paracetamol on the pharmacokinetics of chloramphenicol.

The effect of oral paracetamol (1 g) on the pharmacokinetics of oral chloramphenicol (500 mg) was examined in five adult male Zimbabwean patients with normal hepatic and renal function. No significant alteration of half-life, area under the concentration-time curve or peak concentration of chloramphenicol was observed. The previously reported, potentially serious interaction between chloramphenicol and paracetamol administered intravenously was not observed with the more commonly used oral preparations.

Acetaminophen

Sputum levels of fluconazole in humans.

We measured fluconazole levels in sputum samples obtained from 11 bronchiectatic volunteers at 4 and 24 h after a single oral dose of 150 mg of fluconazole. Levels in sputum were similar to levels in plasma at both times.

Aged

Nocardiosis: a neglected chronic lung disease in Africa?

Nocardia organisms were cultured from the sputum of 11 patients at the central hospitals in Harare, Zimbabwe, over a 12 month period. Pulmonary nocardiosis was diagnosed in one further patient on the basis of direct microscopy. Among the nine patients available for follow up, pulmonary nocardiosis was considered to be the major clinical problem in six. The patients usually presented with a chronic pulmonary infection with fever and cough without evidence of dissemination of underlying systemic disease. The chest radiograph showed consolidation in any part of the lung, and this was seen to extend slowly over several months. Prolonged diagnostic delay was a frequent problem. Haemoptysis, alcohol abuse, and empirical treatment for tuberculosis commonly featured in the history. Treatment with sulphonamides was generally successful in those patients who complied. Nocardiosis is a treatable lung disease that may be more common in developing countries than is currently recognised.

Adult