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D A MITCHISON

Publications and source records attributed to D A MITCHISON.

At least 37 records · Page 2Linked to original sources

Response of patients infected with isoniazid-resistant tubercle bacilli to treatment with isoniazid plus PAS or isoniazid alone.

This study from the Tuberculosis Chemotherapy Centre, Madras, compares patients infected with isoniazid-resistant tubercle bacilli ("R" patients) with those infected with isoniazid-sensitive tubercle bacilli ("S" patients) as regards, first, their pretreatment status and, secondly, their response to a year's chemotherapy, either with isoniazid plus p-aminosalicylic acid (PAS) or with isoniazid alone. With regard to the first comparison, there was, on admission to treatment, little difference between the R and S patients in terms of the extent of the radiographic lesion, the extent of cavitation or the bacterial content of the sputum, but there were major differences in the age and sex distributions, the R patients showing a greater preponderance of young males than the S patients. As to the second comparison, statistically significant differences in the bacteriological response to treatment of the S and the R patients were observed in both the isoniazid-plus-PAS and the isoniazid-alone series, the response of the S patients being much better than that of the R patients. When the response to treatment was assessed in terms of radiographic progress and weight changes, however, hardly any difference was observed between the progress of the S and the R patients. The reasons for the response in the R patients are discussed.

Bacillus↗

The virulence in the guinea-pig of isoniazid-sensitive tubercle bacilli isolated from South Indian patients before treatment and after three months of chemotherapy.

In order to find out whether chemotherapy with isoniazid affects the virulence in the guinea-pig of tubercle bacilli that do not develop resistance to the drug, virulence tests were carried out on isoniazid-sensitive cultures obtained from 20 South Indian tuberculous patients before treatment and after three months of chemotherapy with isoniazid. No significant difference in virulence was observed between the cultures obtained on admission to treatment and those obtained after three months of chemotherapy. This is a finding with important implications for large-scale surveys of the distribution of attenuated strains of tubercle bacilli from untreated patients in India and other countries. Detailed and repeated inquiries as to previous chemotherapy are not important in such surveys, provided that sensitivity tests are done on all the cultures.

Bacillus↗

The virulence in the guinea-pig of tubercle bacilli isolated before treatment from South Indian patients with pulmonary tuberculosis. I. Homogeneity of the investigation and a critique of the virulence test.

A series of studies on the virulence in the guinea-pig of tubercle bacilli isolated before treatment from Indian tuberculous patients admitted to a controlled comparison of different regimens of domiciliary chemotherapy has recently been undertaken by the Tuberculosis Chemotherapy Centre, Madras. The main object of these studies was to determine whether the differences in virulence of the tubercle bacilli obtained from Indian patients before the start of chemotherapy were related to the severity or type of the patients' disease at that time and to the subsequent response to treatment. Before these relationships could be investigated, however, it was necessary to find out whether the results of the virulence tests, which were carried out over a period of two-and-a-half years at the Centre and at the Microbiological Research Establishment, Porton, England, could be considered as a unified whole-that is, as if they had all been done on the same day in the same laboratory.A proportion of the cultures was stored at - 20 degrees C for 44-78 weeks, but this did not affect their virulence. Inter-experimental variation was found to be small in the Porton series of tests and undetectable in the Madras series, and the results in the latter series could be successfully adjusted to those in the former by allowing for differences in the means and standard deviations of the distributions for the two series. The measure of virulence used was found to be reasonably acceptable for the analysis of variance technique. Suggestions are made as to ways of improving the efficiency of the experimental design in future studies.

Bacillus↗

The virulence in the guinea-pig of tubercle bacilli isolated before treatment from South Indian patients with pulmonary tuberculosis. 3. Virulence related to pretreatment status of disease and to response to chemotherapy.

This is the last of a series of three reports from the Tuberculosis Chemotherapy Centre Madras, on a study undertaken with the object of finding out whether differences in the virulence in the guinea-pig of tubercle bacilli isolated from South Indian tuberculous patients before the start of chemotherapy are related to the severity of the patients' disease on admission to treatment and to the subsequent response to chemotherapy. The 281 patients in this study were drawn from the patients admitted to a 1-year comparison of four domiciliary chemotherapeutic regimens: (a) 3.9-5.5 mg/kg isoniazid plus 0.2-0.3 g/kg sodium PAS daily, divided into two doses (PH series); (b) 7.8-9.6 mg/kg isoniazid alone daily in one dose (HI-1 series); (c) 7.8-9.6 mg/kg isoniazid alone daily, divided into two doses (HI-2 series); (d) 3.9-5.5 mg/kg isoniazid alone daily, divided into two doses (H series).No evidence was found of an association between the virulence of the organisms and any pretreatment condition of known prognostic importance. There was no association between pretreatment virulence and progress during treatment in the PH series (the most effective regimen). In the other series, however, the progress was more satisfactory in patients infected with organisms of low virulence than in those infected with organisms of high virulence, the association between virulence and progress attaining statistical significance in the combined HI-2 and H series (the least effective regimens) and only just failing to do so in the smaller HI-1 series.Possible explanations are put forward both for the absence of an association between virulence and severity of disease on admission and for the presence of an association between virulence and response in the patients treated with isoniazid alone.

Aged↗

A comparison of the sensitivity to p-aminosalicylic acid of tubercle bacilli from South Indian and British patients.

In a comparison of home and sanatorium treatment for tuberculous patients in India, pretreatment cultures of tubercle bacilli showed a higher average level of resistance to p-aminosalicyclic acid (PAS) than pretreatment cultures from a representative sample of patients in Great Britain. The investigation described in the present paper was therefore undertaken to find out the nature of the difference in the PAS sensitivity of cultures from Indian and British patients. In this investigation, carried out jointly at the Tuberculosis Chemotherapy Centre, Madras, and the Postgraduate Medical School of London, sputum specimens from 147 Indian and 93 British patients were cultured and subjected to sensitivity tests. The tests were set up on slopes containing various concentrations of PAS and inoculated with 10(5) viable units of the cultures, and the minimal concentrations of PAS inhibiting the growth of 20, 50 and 100 colonies were determined. According to the 20-colony end-point-the one commonly used in routine sensitivity tests-the Indian strains were significantly more resistant than the British strains. This difference in sensitivity was not apparent, however, in either the 50-colony or the 100-colony results. The presence of a small proportion of resistant organisms was found to be a general characteristic of the Indian strains, but did not appear to be related to any special tendency for the patient to fail to respond to treatment with PAS. Since a chance increase in the inoculum size might well affect the 20-colony results, the authors recommend a tenfold decrease in the size of the inoculum used in routine PAS-sensitivity tests on Indian patients.

Aminosalicylic Acid↗