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Biomedical subjects

D A Mitchison

Publications and source records attributed to D A Mitchison.

At least 109 records · Page 6Linked to original sources
PubMed1981

Experimental models to explain the high sterilizing activity of rifampin in the chemotherapy of tuberculosis.

Model systems were set up in vitro to explore the reasons why rifampin is a better sterilizing drug than isoniazid in short-course chemotherapy of tuberculosis. When the growth rate of Mycobacterium tuberculosis strain H37Rv was reduced uniformly by lowering the incubation temperature or the pH of the culture medium, the bactericidal activity of rifampin and isoniazid decreased to a similar extent. However, when a culture was maintained at 8 degrees C and incubated for daily periods of 1 or 6 h at 37 degrees C, rifampin killed more rapidly than isoniazid. Maintenance of control cultures without antimicrobials at 8 degrees C with or without periods at 37 degrees C, had little or no effect on their viability, ability to commence logarithmic growth at 37 degrees C, or to incorporate [14C]uridine. Old cultures left undisturbed or to which small additions of fresh culture medium were regularly added were killed more rapidly by rifampin than by isoniazid. These experiments supported the view that the special part of the bacterial population that is killed more rapidly by rifampin than by isoniazid during short-course chemotherapy consists of bacilli dormant much of the time but occasionally metabolising for short periods.

Culture Media↗
PubMed1981

Hemagglutination tests for tuberculosis with mycobacterial glycolipid antigens. Results in patients with active pulmonary tuberculosis before and during chemotherapy and in healthy tuberculosis contacts.

Hemagglutination tests using three serologically active mycobacterial glycolipids as antigens were carried out on serum specimens from patients with pulmonary tuberculosis and from healthy family contacts of patients with tuberculosis in Singapore. A positive response to any of the three antigens was found in 82.5% of 211 patients with newly diagnosed disease and in 21% of 100 contacts. The much higher proportion of positive results in the contacts than in other groups of healthy subjects previously reported might have been due to subclinical infection with tubercle bacilli or with other environmental mycobacteria. The use of rules derived from discriminant analysis improved discrimination between patients and contacts, so that a positive result was obtained in 72% of patients and 5% of contacts. Serial positive titers during 1 yr of chemotherapy showed an initial slight increase during the first month and then a slow decrease, although conversion from a serologically positive result to a negative result was uncommon. The occurrence of widely variable patterns of response to the three antigens in different patients emphasizes the importance of using a battery of tests, each with a separate antigen.

Adolescent↗
PubMed1981

The contribution of hydrogen peroxide resistance to virulence of Mycobacterium tuberculosis during the first six days after intravenous infection of normal and BCG-vaccinated guinea-pigs.

The course of infection with Mycobacterium tuberculosis strains H37Rv, H37Ra and their isoniazid-resistant, hydrogen peroxide-susceptible mutants in guinea-pig spleen and lung were assessed by measuring changes in number of viable bacteria during the first and second 3-day intervals after i.v. infection of normal and BCG-vaccinated animals. Vaccination had no effect on bacterial survival in the first 3 days of infection. The peroxide-susceptible mutants were killed or inhibited more than their parent strains; in normal animals this enhanced susceptibility was expressed equally during the first and second 3-day intervals while in vaccinated animals the effect was greater in the second 3-day interval. The results suggest that hydrogen peroxide is generated in significant amounts in the environment of tubercle bacilli lodged in normal tissues and in enhanced amounts when acquired immunity becomes expressed after a few days' lodgement in the tissues of vaccinated animals. Thus hydrogen peroxide resistance may contribute to virulence by protecting against both normal resident and immunologically activated macrophages.

Animals↗
PubMed1980

Quality control in tuberculosis bacteriology. 1. Laboratory studies on isolated positive cultures and the efficiency of direct smear examination.

Sputum specimens unlikely to contain M. tuberculosis or specimens artificially created as methylcellulose/egg solution were autoclaved and distributed in batches together with sputum specimens containing viable M. tuberculosis marked with an unusual drug-sensitivity pattern. These specimens were prepared in 1 East African laboratory, divided into aliquots and examined by direct smear and culture in 3 East African laboratories. Independent batches were also prepared and cultured in London. Scanty colonies of M. tuberculosis, always with the characteristic marker sensitivity pattern, were obtained from a proportion of the autoclaved specimens, ranging from 0% of 825 specimens in London to 1.3% of 2165 specimens in Kampala. Transfer of bacilli from positive to negative specimens could therefore account for some of the isolated positive cultures that occur in clinical trials. The occurrence of transfer seemed to be related more to the quality of the technician than to the detail of the technical methods. The African laboratories could be graded in their overall efficiency in smear and culture examination.

Africa, Eastern↗
PubMed1980

Quality control in tuberculosis bacteriology. 2. The origin of isolated positive cultures from the sputum of patients in four studies of short course chemotherapy in Africa.

During intensive bacteriological follow-up of 2123 patients who had received short course chemotherapy regimens in 4 controlled clinical trials in Africa and had not had a bacteriological relapse, 405 isolated positive cultures were obtained from 37 429 sputum specimens in 3 East African laboratories. These cultures might have arisen as a result of clerical error, of transfer of bacilli from positive to negative specimens in the laboratory or from the lesions of the patients. Clerical error in the labelling of specimens or the recording of results did not seem a frequent cause, since isolated positive cultures contained many fewer colonies than cultures from other positive specimens being processed at the same time. Several of evidence suggested that some isolated positive cultures arose from the lesions of patients: a decrease in their incidence occurred in successive time periods after chemotherapy; the number of isolated positives per patient departed significantly from the Poisson distribution; they were more often drug resistant than other cultures processed at the time; positive cultures were obtained less frequently from known autoclaved specimens inserted among the the study specimens than from the study specimens themselves; no association was found between the incidence of isolated positive and of specimens containing numerous viable M. tuberculosis being processed at the same time. Nevertheless some of these cultures probably arose by transfer in the laboratory, since the rates at which transfer were known to occur differed in the 3 laboratories and corresponded to the rates of obtaining isolated positive cultures.

Africa, Eastern↗
PubMed1978

The correlation of bacteriophage types of Mycobacterium tuberculosis with guinea-pig virulence and in vitro-indicators of virulence.

Among 58 isoniazid-sensitive strains of Mycobacterium tuberculosis from India, Burma and East Africa, 23 were of phage type A, 31 of type I (intermediate), 4 of type B and none of type C. Type I strains differed from type A strains in being attenuated in the guinea-pig, susceptible to H2O2, sensitive to thiophen-2-carboxylic acid hydrazide and resistant to thiacetazone and p-aminosalicylic acid; the content of strongly acidic lipids and of sulphatide lipids was low and the attenuation indicator lipid was present. The pattern of results with the type B strains did not correspond to the patterns for types A or I. Strains of type I appear to be a distinct group within the species M. tuberculosis.

Aminosalicylic Acid↗
PubMed1978

A computer-assisted bacteriology reporting and information system.

A computer system for reporting and recording all specimens processed by the routine bacteriology laboratory at the Royal Postgraduate Medical School is described. Features of interest are the method of input using a mixture of 3-character alphanumeric codes and numbers, cumulative reporting to the wards, and selective listing of relevant previous results for the patient, which is available to technical and supervisory staff during processing of the specimen. The relative value to the wards and the laboratory of each type of information transfer has been assessed. Overall the use of a computer has resulted in higher quality bench work and more accurate reporting. It seems little more expensive than a previous manual system, although it has transferred work from the technical to the clerical staff.

Bacteriology↗
PubMed1977

Evaluation of a serological test for tuberculosis.

The agglutination test of Nicholls was found to be ineffective in diagnosing active tuberculosis. A positive result (titre of 1/125 or more) was found in the serum of 74 (70%) out of 105 patients with newly diagnosed, smear-positive pulmonary tuberculosis; 61 (62%) out of 98 healthy family contacts; and 19 (63%) out of 30 patients with non-tuberculous conditions. These findings were not due to faulty technique since the results obtained at Hammersmith were similar to those obtained by Nicholls's laboratory in the same serum samples. Twenty-seven of the tuberculous patients who had a negative result before treatment were retested two months after the start of chemotherapy but showed no evidence of a rising titre.

Agglutination Tests↗