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M M Hodgkin

Publications and source records attributed to M M Hodgkin.

At least 19 recordsLinked to original sources
PubMed1983

Conventional and radiometric drug susceptibility testing of Mycobacterium tuberculosis complex.

A recently developed method of drug susceptibility testing of Mycobacterium tuberculosis which measures the evolution of labeled CO2 from [1-14C]palmitic acid (BACTEC 460 system) was compared to three conventional methods. The proportion method of drug susceptibility testing was the standard against which all test results were compared. Indirect drug susceptibility to isoniazid, streptomycin, rifampin, and ethambutol of 245 isolates belonging to the M. tuberculosis complex was determined. In 95% of the cases, results obtained by the radiometric method were available within 1 week, as opposed to 3 to 6 weeks needed in conventional methodology. Overall agreement was 96.4%. Specificity values ranged from 0.98 to 1.0; sensitivity values of 1.0 for rifampin, 0.96 for streptomycin, 0.91 for isoniazid, and 0.18 for ethambutol were obtained. The specificity of the absolute concentration and resistance ratio drug susceptibility testing methods were 0.99 and 1.0, respectively. The sensitivity of the former was higher than that of the radiometric method (0.99 verus 0.92), whereas that of the latter was lower (0.88 verus 0.96). Further testing indicated that the low sensitivity determined for ethambutol may be due to the choice of the critical concentration used, rather than to a shortcoming of the procedure. The radiometric method thus does not significantly differ in reliability from conventional methods of drug susceptibility testing of M. tuberculosis.

Antitubercular Agents↗
PubMed1981

Risk factors for isoniazid (NIH)-induced liver dysfunction.

We examined prospectively risk factors which might contribute to INH-induced liver damage in 113 patients taking preventive INH for at least 8 weeks. Twelve who had abnormal initial liver tests did not get worse with INH, while 19/101 with normal initial tests developed significant liver dysfunction, mostly hepatocellular, three having overt hepatitis. When 12 other patients who drank alcohol were excluded from analysis, there were still 15/89 with significant liver dysfunction, 12 of whom were slow acetylators (p less than 0.05). The only other risk factor was age. By combining acetylator phenotype with age, but excluding alcohol, we calculated the risk of INH-induced liver enzyme elevation as follows: under 35 years--fast acetylators, 3.7%, slow acetylators, 13%; over 35--fast acetylators, 13.2%, slow acetylators, 37% (p less than 0.02). Fast acetylation is thus not a risk factor for developing INH-induced liver dysfunction; indeed, the contrary seems to be the case.

Acetylation↗
PubMed1979

Isoniazid phenotyping of black as well as white patients.

The isoniazid phenotyping in black patients from Birmingham (Alabama) as well as from South Africa yielded a higher frequency of fast inactivation than that in the Canadian and U.S. white participants. Following an oral test dose of 10 mg isoniazid per kilogram, the incidence of fast acetylation was 58.7 and 60.3% in South African and Birmingham blacks, respectively. In the Canadian and Birmingham Caucasians the rate was 41.9 and 41.0%, respectively.

Black People↗
PubMed1979

Phenotyping of South African black tuberculosis patients for inactivation of isoniazid.

Studies of isoniazid inactivation rates in black tuberculosis patients from South Africa and Birmingham, Alabama, showed a higher frequency of fast inactivation than those of North American Caucasian patients. After an oral test dose of 10 mg/kg isoniazid the percentage of fast inactivators in black patients of South Africa and Alabama was close to 60% while in North American white participants (Canadian and Birmingham Caucasians), the frequency of fast inactivation was approximately 40%.

Administration, Oral↗
PubMed1979

Evaluation of various isoniazid slow releasing matrix preparations for intermittent chemotherapy of tuberculosis.

The blood level achieved with 15 mg/kg ordinary isoniazid (INH) was compared with that obtained with INH slow releasing Matrix preparation. Three brands of INH Matrix preparation were compared namely: the product of ICN Canada Ltd, utilized by Laboratory Centre for Disease Control, the preparation of Smith and Nephew, Britain employed by the Tuberculosis unit of the British Medical Research Council and Tebesium, the product of Hefa-Frenon Arzneimittel, Germany studied by the Tuberculosis Unit of South African Medical Research Council. The results of this study showed that pharmacogenetic principle have to be taken into account, it is not possible to produce INH slow releasing Matrix preparate equally applicable for slow and fast acetylators of INH.

Acetylation↗
PubMed1979

Comparison of isoniazid phenotyping of black and white patients with emphasis on South African blacks.

Black tuberculosis patients from South Africa (S. A.) as well as from Birmingham, Alabama, U.S.A., showed a higher percentage of fast inactivators of isoniazid (INH) than that found in the North American white population, simultaneously sampled. In S. A. blacks, the frequency of fast inactivation was 57.9--59.6%, while in American blacks of Birmingham it amounted to 60.3%; in comparison to the above groups the rate of fast acetylators in Canadian Caucasians was 41.9% and in the USA white population 41.0%. For phenotyping of isoniazid inactivators a urine test was used. In this method the concentrations of INH (including isoniazidhydrazones) as well as acetylisoniazid were determined in the specimens collected 6--8 hrs following a test dose of 10 mg/kg INH.

Administration, Oral↗
PubMed1978

Isoniazid overdose.

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Antitubercular Agents↗
PubMed1975

A new isoniazid preparation designed for moderately fast and "fast" metabolizers of the drug.

The bioavailability of a new isoniazid preparation consisting of 37% ordinary isoniazid (INH) and 63% matrix component was investigated in 11 slow, 8 moderately fast, and 9 "fast" acetylators of the drug. Initially, a 15 mg/kg dose of normal INH was administered to all the participants. In addition, the two groups of fast metabolizers received 30 and 45 mg INH-matrix/kg, respectively, with a one-week interval between the test doses. These high dosages of the INH-matrix could be given without encountering toxic reactions because of the delayed absorption of the matrix formulation. In moderately fast acetylators, with a triple dose of matrix isoniazid, it was possible to mimic the blood levels produced by 15 mg ordinary INH/kg in slow inactivators. However, in "fast" acetylators the blood concentrations achieved with the 45 mg/kg dose of INH-matrix were somewhat lower. This study also showed that a large input rate is essential to procure the required, high blood levels in fast metabolizers. The therapeutic implications of the results of this bioavailability trial are discussed.

Acetylation↗
PubMed1974

Screening of isoniazid inactivators by dilution test.

A modification of the screening test for the phenotyping of isoniazid inactivators is described. As this simple dilution technique does not require expensive equipment or even electricity, it can be used in poorly equipped laboratories.

Acetylation↗
PubMed1973

Screening of isoniazid inactivators.

A method is described for phenotyping of isoniazid inactivators. After a test dose of isoniazid, free isoniazid and its acetyl derivative are estimated in urine by the same colorimetric reaction.

Acetylation↗
PubMed1973

Simplification of isoniazid phenotyping procedure to promote its application in the chemotherapy of tuberculosis.

In this investigation a simple urine test for phenotyping isoniazid inactivators is evaluated. In the new method, isoniazid is artificially acetylated in urine and determined by the same colour reaction as that used for acetylisoniazid. Comparative studies showed that the test is reliable and can be performed with accuracy and ease even in poorly equipped laboratories. In contrast to other urine tests, it does not require an expensive spectrophotometer, tedious hydrolysis processing of the samples, or standard curves. The results can be read on a plain colorimeter, or even without any instrument.

Acetates↗