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Biomedical subjects

D J Girling

Publications and source records attributed to D J Girling.

At least 19 recordsLinked to original sources
PubMed1992

The early bactericidal activity of rifabutin measured by sputum viable counts in Hong Kong patients with pulmonary tuberculosis.

Previously untreated patients with smear-positive pulmonary tuberculosis were randomly allocated to treatment with 600, 300, 150 or 75 mg doses of rifabutin (LM427, ansamycin), 600, 300 or 150 mg of rifampicin, 300 mg isoniazid or to no drug daily for 2 days. The fall in viable counts of Mycobacterium tuberculosis in sputum collections during the 2 days, termed the early bactericidal activity (EBA), was estimated from counts of colony-forming units (cfu) on selective 7H-11 agar medium. The EBA for rifabutin ranged from -0.039 (an increase in counts) to 0.049 log10 cfu/ml/day whereas the EBA increased from 0.071 for 150 mg rifampicin to 0.293 log10 cfu/ml/day for 600 mg rifampicin and was 0.43 log10 cfu/ml/day for 300 mg isoniazid. The difference between the EBAs for rifabutin and rifampicin just attained significance (P = 0.05) suggesting that rifabutin was inactive or less active than rifampicin against the extracellular bacilli in pulmonary cavities. Peak plasma concentrations of rifabutin after the initial doses were found to be proportional to dose size and were approximately 7 times lower than those after the same dose size of rifampicin. The lower EBA of rifabutin as compared to rifampicin is probably due to the low plasma concentrations which are not fully compensated for by slightly greater antituberculosis activity of rifabutin in vitro.

Adolescent↗
PubMed1991

Assessment of quality of life in small-cell lung cancer using a Daily Diary Card developed by the Medical Research Council Lung Cancer Working Party.

Three hundred and sixty-nine patients in an MRC study of combination chemotherapy and radiotherapy for small-cell lung cancer of limited extent were asked to complete a Daily Diary Card which enabled an assessment of their quality of life to be made during and after treatment. The information derived from the card suggests that although cytotoxic chemotherapy has an adverse effect upon quality of life, this impairment only affects the first 2 or 3 days following each course of treatment, although there is also a small deterioration which may be associated with the 'nadir' effect of the blood counts about 10 days after each course. These results should assist physicians in counselling patients about the likely effects of treatment. Just over half of the patients (196) were subsequently randomised to either a further six courses of maintenance chemotherapy or no further chemotherapy, and it is also shown that the patients allocated to no maintenance chemotherapy experienced a gradually deteriorating quality of life, as opposed to the brief but more severe adverse effects which occurred following each course in the maintenance chemotherapy group; this supports the hypothesis of a palliative effect in this latter group. The findings demonstrate that the Daily Diary Card is a sensitive instrument capable of yielding useful information.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

A Medical Research Council phase II trial of alternating chemotherapy and radiotherapy in small-cell lung cancer. The Medical Research Council Lung Cancer Working Party.

In a non-randomised study in six centres in the UK, 24 patients with previously untreated small-cell lung cancer of limited extent were treated with a regimen of alternating chemotherapy and radiotherapy to assess response, toxicity, and the feasibility of applying such a regimen on a multicentre basis in the UK. The intention was to give six courses of chemotherapy on five consecutive days at 4-week intervals: etoposide 75 mg m-2 on days 1, 2, and 3; doxorubicin 40 mg m-2 on day 1; cisplatin 100 mg m-2 on day 2; and cyclophosphamide 300 mg m-2 on days 2, 3, 4 and 5. A dose of 20 Gy thoracic radiotherapy was to be given following the 2nd and the 3rd courses, and one of 15 Gy following the 4th course. After 12 patients had been admitted, the cisplatin dosage was reduced to 80 mg m-2 because of unacceptable toxicity. Two patients were withdrawn during treatment on review of their histology because their diagnosis was found to be incorrect. Only one patient of the 12 treated with cisplatin 100 mg m-2 was able to complete treatment, compared with five of the eligible ten given the lower dosage. Among the 22 patients with confirmed small-cell disease, a complete response was reported in 14 (64%) and a partial response in a further three (total response rate 77%). Myelosuppression was the commonest serious adverse effect. It occurred in 19 of the 24 patients and gave rise to septicaemia in five, four of whom were receiving the higher cisplatin dose. Sixteen patients required blood transfusion and ten platelet transfusion. Vomiting, oesophagitis, and peripheral neuropathy occurred in 12, four and four patients, respectively, and radiation pneumonitis developed in two. Treatment was considered a contributory cause of death in four. The working party concluded that the alternating regimen was feasible in only a small proportion of centres in the UK, and decided not to embark on a multicentre randomised trial comparing alternating with conventional scheduling.

Activities of Daily Living↗
PubMed1990

Serodiagnosis of tuberculosis using an ELISA with antigen 5 and a hemagglutination assay with glycolipid antigens. Results in patients with newly diagnosed pulmonary tuberculosis ranging in extent of disease from minimal to extensive.

Hemagglutination tests with three glycolipid antigens, A1, B1, and C, and ELISA with antigen 5 were done on serum from Chinese patients with pulmonary tuberculosis and from normal subjects in Hong Kong. Tests with all four antigens were of similar efficiency, giving positive results in 30 to 52% of 88 smear-positive patients, in 16 to 22% of 37 smear-negative, culture-positive patients, in 5 to 13% of 76 culture-negative patients with radiologically active disease, in 5 to 11% of 217 culture-negative patients with inactive disease, and in 1 to 4% of 140 normal subjects. If tests were combined so that an overall positive was scored when all tests were positive, there was worse discrimination between patients and normal subjects; however, as suggested by the poor correlation between the results with pairs of the tests, better discrimination was obtained if an overall positive was scored when any of the tests was positive. A positive result in any of the four tests was found in 22% of all cases, including 58% of smear-positive patients, 32% of smear-negative, culture-positive patients, and 0.7% of normal subjects.

Antigens, Bacterial↗
PubMed1988

Controlled clinical trial of complete open surgical drainage and of prednisolone in treatment of tuberculous pericardial effusion in Transkei.

240 patients with active tuberculous pericardial effusion received a 4-drug daily antituberculosis regimen for 6 months and have been studied for 24 months or longer. Those willing were randomly allocated to open pericardial biopsy and complete drainage of pericardial fluid on admission or percutaneous pericardiocentesis as required. All patients were randomly allocated to prednisolone or matching placebo for the first 11 weeks, on a double-blind basis. Complete open drainage on admission abolished the need for pericardiocentesis (p less than 0.01) but did not influence the need for pericardiectomy for subsequent constriction or the risk of death. Among patients who did not have open drainage on admission, 2 (3%) of 76 given prednisolone compared with 10 (14%) of 74 given placebo died of pericarditis (p less than 0.05), 6 (8%) and 9 (12%) respectively required pericardiectomy, 7 (9%) and 17 (23%) repeat pericardiocentesis (p less than 0.05), and 3 (4%) and 7 (9%) open surgical drainage. By 24 months, apart from the 16 who died from pericarditis, all but 3 patients (2%) had a favourable status.

Adolescent↗
PubMed1988

HLA typing in the Hong Kong Chest Service/British Medical Research Council study of factors associated with the breakdown to active tuberculosis of inactive pulmonary lesions.

As part of a multifactorial study of the causes of breakdown to active tuberculosis of inactive pulmonary lesions, HLA-A, -B, and -DR typing was performed on 256 Hong Kong Chinese patients and 100 healthy control subjects. Patients were classified into those with smear-positive, active pulmonary tuberculosis (n = 103), those with inactive disease (n = 113), and those with breakdown to active disease after 6 months or more of inactivity (n = 40). Separately, 21 multiple-case families comprising 38 available parents and 93 offspring were examined for HLA haplotype segregation in relation to infection. Results of both studies indicate that among Hong Kong Chinese there is no statistically significant association between HLA and susceptibility to pulmonary tuberculosis.

Adolescent↗
PubMed1987

Controlled trial of prednisolone as adjuvant in treatment of tuberculous constrictive pericarditis in Transkei.

In Transkei, 143 patients with active tuberculous constrictive pericarditis without significant pericardial effusion all received the same daily 6-month antituberculosis regimen of streptomycin, isoniazid, rifampicin, and pyrazinamide for 14 weeks followed by isoniazid and rifampicin. They were randomly allocated to receive in addition either prednisolone or placebo for the first 11 weeks; the comparison was double-blind throughout treatment and follow-up. In the 114 patients assessable up to 24 months, improvement was significantly more rapid in the prednisolone group, as shown by the rate of fall in the mean pulse rate and the rate at which jugular venous pressure and level of physical activity became normal. During follow-up, 2 (4%) of the 53 prednisolone and 7 (11%) of the 61 placebo patients died from pericarditis, and 11 (21%) and 18 (30%), respectively, required pericardiectomy. By 24 months 50 (94%) prednisolone and 52 (85%) placebo patients had a favourable status. 3 patients (1 prednisolone, 2 placebo) were normally active but were classified as not having achieved a favourable status. It is recommended that, in the absence of a specific contraindication, antituberculosis chemotherapy should be initially supplemented by steroids.

Adolescent↗
PubMed1986

The bioavailability of isoniazid, rifampin, and pyrazinamide in two commercially available combined formulations designed for use in the short-course treatment of tuberculosis.

The bioavailability of isoniazid, rifampin, and pyrazinamide in 2 combined formulations of the 3 drugs (Rifater) for use primarily in the short-course chemotherapy of tuberculosis has been studied in Chinese patients in Singapore and Hong Kong. One formulation, containing 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide per tablet is suitable for daily use, whereas the other, containing higher proportions of isoniazid and pyrazinamide, is designed for intermittent treatment, each tablet containing 125 mg isoniazid, 100 mg rifampin, and 375 mg pyrazinamide. Appropriate dosages for the Chinese patients, whose average weight was approximately 50 kg, were 5 and 6 tablets, respectively. Plasma concentrations of the 3 drugs after giving such dosages of the 2 combined formulations were compared in 16 patients, 8 in Singapore and 8 in Hong Kong, by means of a crossover study, with the concentrations obtained when identical doses of the 3 drugs were given using standard separate drug formulations. The concomitant urinary excretions of the drugs and their major metabolites were also estimated. Very similar results were obtained whether the drugs were given as the combined preparations or in their standard separate formulations, demonstrating the excellent bioavailability of all 3 drugs in each of the 2 combined formulations.

Acetylation↗
PubMed1985

Fifteen-year follow-up of all patients in a study of post-operative chemotherapy for bronchial carcinoma.

The 15-year findings are presented of a double-blind, randomised study planned in 1964 in which cytotoxic chemotherapy with either busulphan or cyclophosphamide prescribed to be given daily for 2 years as an adjuvant to surgery was compared with placebo in the treatment of 726 patients with carcinoma of the bronchus. The two cytotoxic agents administered in this way did not influence survival. At 15y, 8% of the 243 patients allocated busulphan, 9% of the 234 cyclophosphamide, and 10% of the 249 placebo were alive, these being 10% of the patients who had had epidermoid cancers, 12% large-cell, 5% small-cell, 5% adenocarcinomas, and 8% other histological types. The study provides data on long-term results in a large group of patients who were, in effect, treated by surgery alone. Survival was significantly shorter in patients with histological involvement of the resected intrathoracic nodes (log-rank test P much less than 0.001). A finding of particular interest is that the histological type of the tumour did not influence survival in the 390 patients whose nodes were not involved, although, as expected, it did in the 336 whose nodes were involved, the 226 with epidermoid cancers surviving longer than the 57 with small cell carcinoma, the 31 with adenocarcinoma and all 110 with non-epidermoid carcinomas (P much less than 0.001 in each comparison).

Aged↗
PubMed1983

Amikacin in the treatment of pulmonary tuberculosis.

Sensitivity tests on strains from 11 patients with pulmonary tuberculosis, previously treated with kanamycin and/or capreomycin, showed incomplete cross-resistance between amikacin and capreomycin but complete cross-resistance between amikacin and kanamycin. Treatment with amikacin of 4 patients with multiply resistant strains resulted in no response as assessed by sputum smears and cultures, but resistance emerged to amikacin, kanamycin and capreomycin. Amikacin has no role in the treatment of tuberculosis as it cannot be given as an alternative to kanamycin, has no advantages over it and is more expensive.

Adult↗
PubMed1979

The symptoms of newly diagnosed pulmonary tuberculosis and patients' attitudes to the disease and to its treatment in Hong Kong.

A questionnaire was applied by Government Health Visitors in Hong Kong to 201 consecutive patients with smear-positive, and 199 with smear-negative pulmonary tuberculosis who were attending one of the 7 full-time Government chest clinics for the first time on account of their current illness. Information was obtained about the symptoms of the disease and its diagnosis and management outside the Government service, and about patients' knowledge and attitudes towards the Government service. Among the 343 patients who sought treatment because of respiratory symptoms, the first symptom for the great majority (81 %) was cough, 15 % having sputum and 27 % haemoptysis as well. However, treatment was sought by only 15 % because of cough alone, compared with 40 % because of haemoptysis. Most patients (76 %) attended their first source of treatment or investigation within a month of the onset of symptoms, but some allowed long delays, and only 35 % attended a Government chest clinic within a month (whether this was the first source of treatment or not). The first source attended was a private practitioner for 53 % of the patients, another private medical establishment for 4 %, a Government chest clinic for only 11 % and another Government medical establishment for 17 %, 9 % went first to a herbalist and 5 % went to a drug store or treated themselves. The delays between the patients' first attendance at a source of treatment and their first attendance at a Government clinic were important, because outside the Government chest clinics only 49 % were investigated by chest radiograph and only 7 % by sputum bacteriology. Only 33 % were even suspected of having pulmonary tuberculosis, and many were correspondingly inadequately treated. The patients were, in general, ill informed about the Government chest clinic service; 52 % did not know, before their current illness, of the existence of the service, only 9 % knew that it was free, and only 12 % that it specialised in the management of tuberculosis. This study thus revealed a need to educate the public about the symptoms of tuberculosis, and about the possibility of their being investigated and treated, free, in a Government chest clinic.

Adolescent↗