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Biomedical subjects

S Radhakrishna

Publications and source records attributed to S Radhakrishna.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1971

Two controlled studies of the efficacy of isoniazid alone in preventing relapse in patients with bacteriologically quiescent pulmonary tuberculosis at the end of one year of chemotherapy.

An earlier report showed that, in patients with bacteriologically quiescent pulmonary tuberculosis at the end of 1 year of chemotherapy, isoniazid alone in a single daily dose of 150-200 mg, given as maintenance therapy in the second year, did not markedly prevent relapse over a 4-year period of follow-up in patients who had had residual cavitation (the "open-negative" syndrome) at 1 year, but was highly effective in patients who had not. As a result of these findings, two controlled studies, reported here, were undertaken.The first study was undertaken in patients with bacteriologically quiescent disease and residual cavitation at 1 year, and investigated the value of isoniazid in a higher daily dose (400 mg) throughout the second year; this is known to be the optimum therapeutic dose when isoniazid is prescribed alone for 1 year in the initial treatment of the disease. The second study was carried out in patients with bacteriologically quiescent disease and no residual cavitation at 1 year, and sought to determine the value of a shorter duration (6 months) of chemotherapy in the second year with a daily dose of 300 mg of isoniazid. Neither of the two isoniazid regimens was highly satisfactory, although both appeared to have had some effect in preventing relapse during the 4-year period of follow-up.

Clinical Trials as Topic↗
PubMed1971

Inactivation of isoniazid by condensation in a syrup preparation.

This paper reports the gross and rapid condensation of isoniazid in a commercial black-currant-flavoured syrup. In vitro studies showed that the condensation was due, at least partly, to the glucose contained in the syrup, paper chromatography having demonstrated the presence of D(+)-glucose isonicotinoyl hydrazone. Controlled studies in human beings showed that the absorption of isoniazid from the preparation was considerably impaired by this condensation.It is concluded that sugars such as glucose, fructose, and sucrose-especially glucose-should not be used in isoniazid syrup preparations, and it is suggested that sorbitol, a stable non-carbonyl compound, might be a suitable substitute.

Adult↗
PubMed1970

Attack rate of tuberculosis in a 5-year period among close family contacts of tuberculous patients under domiciliary treatment with isoniazid plus PAS or isoniazid alone.

This report from the Tuberculosis Chemotherapy Centre, Madras, considers the risk, over a 5-year period, to close family contacts of sputum-positive patients treated at home for 1 year with a standard regimen of isoniazid plus PAS or one of 3 regimens of isoniazid alone. The attack rate of tuberculosis in the contacts did not appear to be influenced by the treatment received by the patients in the first year or by the duration in the 5-year period for which the patients had (1) positive sputum smears, (2) positive cultures, or (3) isoniazid-resistant cultures. Further, over half the cases of tuberculosis developed in the first year, many of these being in the first 3 months. These findings confirm the conclusions reached from an earlier study, namely, that the major risk to the contacts is from exposure to the infectious patient before diagnosis, and that the risks from the other possible sources of infection (the patient during treatment and the urban environment of Madras) are, in comparison, small.

Ambulatory Care↗
PubMed1968

Deterioration of cycloserine in the tropics.

Gross deterioration of cycloserine during transit and storage in the tropics is reported from the Tuberculosis Chemotherapy Centre, Madras. Laboratory experiments suggest that high humidity, rather than high temperature, is the main cause of the deterioration. Further investigations undertaken at the Centre indicate that deterioration can be prevented by storing the drug in tightly closed glass bottles in an air-conditioned room (18 degrees C); if such facilities are not available, and the drug has to be stored at ambient temperature and humidity, the use of air-tight polyethylene bottles will serve to delay the deterioration. The findings also suggest that, when cycloserine is dispensed to patients, individual doses should be heat-sealed in polyethylene strips and that not more than a week's supply should be given at any one time. The authors discuss various measures that could be employed by manufacturers and by shipping and clearing agents to minimize the possibility of deterioration.

Cycloserine↗
PubMed1967

Effect of pyridoxine on vitamin B6 concentrations and glutamic-oxaloacetic transaminase activity in whole blood of tuberculous patients receiving high-dosage isoniazid.

An earlier report from the Tuberculosis Chemotherapy Centre, Madras, showed that, in tuberculous patients receiving high-dosage isoniazid (12.5-15.6 mg/kg body-weight), the concomitant administration of 6 mg of pyridoxine prevented peripheral neuropathy. In that study, biochemical determinations of B(6) concentrations and GOT activity in whole blood had been routinely undertaken on all patients on admission to treatment, and at 6, 12, 24 and 52 weeks thereafter; in addition, extra determinations were undertaken for patients who developed peripheral neuropathy. The present paper reports the findings of these investigations, which are: (a) peripheral neuropathy developed predominantly among slow inactivators of isoniazid, and was associated with a substantial reduction in GOT activity but no apparent change in B(6) concentration; (b) the reduction in GOT activity appeared to be due to deficiency of both the coenzyme (pyridoxal phosphate) and the apoenzyme; (c) the concomitant administration of pyridoxine (6 mg or 48 mg) with high-dosage isoniazid to 3 patients with peripheral neuropathy, 1 of whom had convulsions also, resulted in increased B(6) concentrations and GOT activity, and no further convulsions; and (d) the concomitant administration of pyridoxine 6 mg daily, as a prophylactic, resulted in a significant increase in B(6) concentrations and GOT activity and prevention of the neuropathy.These findings establish the existence of a definite association between the occurrence of isoniazid-induced toxicity and diminished pyridoxine function.

Aspartate Aminotransferases↗