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Biomedical subjects

D A Mitchison

Publications and source records attributed to D A Mitchison.

At least 127 records · Page 7Linked to original sources
PubMed1977

Comparison of strains of Mycobacterium tuberculosis from British, Ugandan and Asian immigrant patients: a study in bacteriophage typing, susceptibility to hydrogen peroxide and sensitivity to thiophen-2-carbonic acid hydrazide.

Strains of Mycobacterium tuberculosis were obtained from 65 patients with pulmonary tuberculosis resident in Uganda, and from pulmonary and extrapulmonary tuberculosis in 42 British patients of European ethnic stock and in 67 Asian immigrants, often from Uganda, resident in Britain. The bacteriophage-type patterns of the African, British and Asian strains were different. The pattern for the Asian strains resembled that found previously in patients from South India, suggesting that there has been little interchange of organisms between the Asian community and the African and British communities alongside whom they have lived. The patterns for pulmonary and extra-pulmonary tuberculosis were similar. Strains of bacteriophage type 1, mainly obtained from Asians, were characterized by a greater susceptibility to the bactericidal activity of hydrogen-peroxide and/or a greater sensitivity to thiophen-2-carbonic acid hydrazide than strains of other types.

Asia↗
PubMed1977

The relationship between nicotinamide adenine dinucleotide concentration and antibacterial activity of isoniazid in Mycobacterium tuberculosis.

The relationship between the antibacterial effect of isoniazid and the intracellular concentration of nicotinamide adenine dinucleotide (NAD) was investigated in Mycobacterium tuberculosis strain H37Rv given continuous and pulsed exposures to the drug. Depletion of NAD to a plateau value occurred rapidly during exposure, and recovery after a pulse of isoniazid was also rapid. It seemed unlikely that NAD depletion was the direct cause of the antibacterial activity because (1) insufficient depletion occurred at low isoniazid concentrations; (2) antibacterial activity, but not NAD depletion, was proportional to the product of isoniazid concentration and the exposure period; and (3) NAD depletion was not related to antibacterial activity in cultures of differing physiologic state.

Isoniazid↗
PubMed1977

Bactericidal activity of streptomycin, isoniazid, rifampin, ethambutol, and pyrazinamide alone and in combination against Mycobacterium Tuberculosis.

Log-phase cultures of Mycobacterium tuberculosis in Tween-albumin medium were exposed to streptomycin, isoniazid, rifampin, ethambutol, and pyrazinamide in concentrations in the range likely to be present in serum during treatment of patients. The bactericidal activity of the drugs was measured as the decrease in viable counts at 4 and 7 days. The activity of single drugs was highest for streptomycin and next highest for rifampin and isoniazid, but ethambutol only started to kill after 4 days. When exposed to 2 drugs, bactericidal synergism was found with streptomycin/isoniazid and isoniazid/ethambutol; additivity, with streptomycin/rifampin; indifference, with isoniazid rifampin and streptomycin/ethambutol; and antagonism, with rifampin/ethambutol and isoniazid/pyrazinamide. When cultures were exposed to the 3 drugs, isoniazid, rifampin, and ethambutol, marked antagonism was found between isoniazid and rifampin, whereas the addition of isoniazid or an increase in its concentration increased the bactericidal activity.

Drug Interactions↗
PubMed1976

Bactericidal activity in vitro and in the guinea-pig of isoniazid, rifampicin and ethambutol.

Serial viable counts on Mycobacterium tuberculosis exposed in vitro to isoniazid, rifampicin and ethambutol in Tween-albumin liquid medium showed no bactericidal synergism between isoniazid and rifampicin and no influence of ethambutol on the bactericidal activity of isoniazid or isoniazid plus rifampicin. Guinea-pigs with moderately advanced experimental tuberculosis were treated fro 11 weeks with either (1) ethambutol, (2) isoniazid, (3) isoniazid plus ethambutol, (4) isoniazid plus rifampicin, (5) isonaiazid plus rifampic in plus ethambutol, or (6) no chemotherapy. The amount of tuberculous disease was scored and the spleen cultured in groups killed at intervals from 0--7 1/2 months after the end of chemotherapy. The regimens containing rifampicin were no more bactericidal during treatment than the corresponding regimens without rifampicin, but the onset of relapse after chemotherapy was delayed for at least 2 months following the rifampicin-containing regimens. Ethambutol alone did not protect guinea-pigs, nor did it influence the response to isoniazid or to isoniazid plus rifampicin. It was concluded that rifampicin may act selectively on a small proportion of the bacterial population and that it may be unnecessary to prescribe it for long periods in short course chemotherapy in man. Ethambutol does not appear likely to contribute to the sterilizing activity of short course regimens though it may prevent the emergence of drug resistance.

Animals↗
PubMed1976

Comparison of machine and manual staining of direct smears for acid-fast bacilli by fluorescence microscopy.

Comparisons were made in Lusaka and in London between manual staining and staining in an automatic machine with auramine-phenol of direct smears of sputum and other types of specimen for acid-fast bacilli. No evidence was obtained of carry-over of acid-fast bacilli from positive to negative smears during machine staining. There was improved contrast between bacilli and the background in smears prepared with the machine.

Benzophenoneidum↗
PubMed1975

Reappraisal of the activity of morphazinamide against M. tuberculosis.

Morphazinamide was shown to have an in vitro activity similar to an equimolar concentration of pyrazinamide. This activity was not due, as had been previously assumed, to pyrazinamide formed by hydrolysis from morphazinamide, since it was demonstrated in slide cultures containing tubercle bacilli which were incubated with freshly prepared dilutions of morphazinamide in acid medium for several successive periods of only 1 hour, during which time little hydrolysis occurred. A new method was used for measuring morphazinamide and pyrazinamide separately in plasma. In man, the estimated in vitro antibacterial activity was similar after approximately equimolar oral doses of morphazinamide or pyrazinamide. However, it is uncertain whether the in vivo activity of morphazinamide is the same as its in vitro activity.

Animals↗
PubMed1975

Studies of serial plasma Isoniazid concentrations with different doses of a slow-release preparation of Isoniazid.

The suitability of a slow-release matrix preparation of isoniazid for use in once-weekly chemotherapy has been investigated in South Indian patients. Serial plasma isoniazid concentrations were determined up to 6 hours following doses of 15, 30, 45 and 60 mg/kg body-weight in rapid inactivators and up to 10 hours following doses of 15, 30 and 45 mg/kg in slow inactivators. The isoniazid levels were sustained, and the peak concentrations (per unit dose) were considerably lower than with ordinary isoniazid. It was estimated that a matrix isoniazid dose of 35 mg/kg in slow inactivators and 50 mg/kg in rapid inactivators would produce a peak similar to that attained with a non-toxic dose or ordinary isoniazid 15 mg/kg in slow inactivators. A second investigation showed that matrix isoniazid 40 mg/kg in rapid inactivators produced a coverage (with 0.2 mug/ml) and exposure similar to those attained in slow inactivators with a highly effective dose of ordinary isoniazid 15 mg/kg, while 30 mg/kg gave substantially lower values. In both investigations, disproportionately large increases in plasma isoniazid concentrations were observed in rapid inactivators with an increase in the matrix isoniazid dose. In slow inactivators, both doses of matrix isoniazid, 30 and 40 mg/gk, resulted in coverage and exposure that were substantially higher than those obtained with ordinary isoniazid 15 mg/kg.

Clinical Trials as Topic↗