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D A MITCHISON

Publications and source records attributed to D A MITCHISON.

At least 19 recordsLinked to original sources
PubMed1964

A VERTICAL DIFFUSION METHOD FOR THE MICROBIOLOGICAL ASSAY OF ISONIAZID.

A method is described for the assay of isoniazid in serum and other fluids by diffusion along slopes of Löwenstein-Jensen medium inoculated with tubercle bacilli. The method is convenient, rapid and robust, but is less accurate than diffusion systems for the assay of some other substances.

Biological Assay↗
PubMed1964

THE EMERGENCE OF ISONIAZID-RESISTANT CULTURES IN PATIENTS WITH PULMONARY TUBERCULOSIS DURING TREATMENT WITH ISONIAZID ALONE OR ISONIAZID PLUS PAS.

Previous reports from the Tuberculosis Chemotherapy Centre, Madras, have described a comparison of four regimens (three of isoniazid alone and one of isoniazid plus PAS) in the treatment of pulmonary tuberculosis and an investigation of the serum isoniazid levels in the patients concerned. The present report studies the emergence of isoniazid-resistant organisms in these patients during treatment. All patients with an unsatisfactory response to treatment yielded resistant cultures, showing that the isoniazid dosage was never too low to inhibit sensitive organisms. From the degree of resistance of the first resistant cultures and of the six-month cultures from the patients treated with isoniazid alone it was concluded that resistance emerged in two stages. In the first stage, very earlyin treatment, highly resistant mutant bacilli grew freely whatever the isoniazid dosage, but mutants of lower resistance were prevented from growing to an extent dependent on the peak isoniazid concentration in the serum. Consequently, when the isoniazid dosage was increased the proportion of patients with resistant organisms decreased, since fewer low-resistance strains were able to develop. In the second stage, organisms with relatively low resistance continued to multiply, though still partially inhibited by isoniazid, and became more resistant, particularly in slow inactivators. The first-stage events determined the results of treatment since, once resistance had emerged, its extent was unrelated to the patient's eventual progress. These findings emphasize the importance of early intensive chemotherapy and adjustment of the isoniazid dosage according to peak serum concentrations rather than concentrations measured three or six hours after the dose. Concomitant administration of PAS prevented emergence of isoniazid resistance in many patients and in others delayed its emergence and reduced its degree, possibly because growth in the second stage was slow.

Aminosalicylic Acid↗
PubMed1963

MYCOBACTERIA: LABORATORY METHODS FOR TESTING DRUG SENSITIVITY AND RESISTANCE.

In its seventh report, published in 1960, the WHO Expert Committee on Tuberculosis "noted the need for international standards for the definition and determination of drug resistance which will permit comparisons to be made from one area to another, and recommended that the World Health Organization take appropriate steps to establish such standards".(10) Acting on this recommendation, WHO took the first step towards standardization by convening in Geneva, in December 1961, an informal international meeting of specialists in the bacteriology of tuberculosis. At this meeting an attempt was made to formulate prerequisites for reliable sensitivity tests and to specify the technical procedures for them.The first part of the present paper is a joint contribution by the participants in the meeting, summarizing the general conclusions reached and recommendations made with regard to tests of sensitivity to the three main antituberculosis drugs-isoniazid, streptomycin and p-aminosalicylic acid. The other three parts describe, in turn, three different tests for determining drug sensitivity-the absolute-concentration method, the resistance-ratio method and the proportion method-that are generally considered to give reasonably accurate results.

Aminosalicylic Acid↗
PubMed1961

The virulence in the guinea-pig of tubercle bacilli isolated before treatment from South Indian patients with pulmonary tuberculosis. 2. Comparison with virulence of tubercle bacilli from British patients.

A series of studies has been undertaken by the Tuberculosis Chemotherapy Centre Madras, with the ultimate object of finding out whether differences in the virulence of the tubercle bacilli isolated from Indian tuberculous patients before the start of chemotherapy are related to the severity of the patients' disease and to the subsequent response to treatment. This paper-the second in the series-presents the results of a comparative investigation of the virulence in the guinea-pig of tubercle bacilli obtained from Indian and from British tuberculous patients before treatment. In this investigation, which was carried out at the Centre and at the Microbiological Research Establishment, Porton, England, the virulence of the Indian and the British cultures was assessed by guinea-pig mortality, by the "root-index of virulence" (based on the post-mortem tuberculous disease score and the survival period of the animal), and by the results of spleen culture. The Indian cultures were found, on the average, to be less virulent and to show a w der range of virulence than the British cultures, both in the Porton and in the Madras series of experiments. A further indication of the heterogeneity of the Indian tubercle bacilli was provided by the results of tuberculin tests: whereas the British cultures appeared to be homogeneous in their ability to induce tuberculin allergy in the guinea-pig, the Indian cultures showed considerable variation in this respect.

Animals↗