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Biomedical subjects

G A Ellard

Publications and source records attributed to G A Ellard.

At least 55 records · Page 3Linked to original sources
PubMed1984

Lack of relationship between hepatic toxicity and acetylator phenotype in three thousand South Indian patients during treatment with isoniazid for tuberculosis.

The results are presented of a retrospective analysis of the incidence of jaundice among 3,000 patients with pulmonary tuberculosis and of the activities of serum aspartate aminotransferase among 850 according to their isoniazid acetylator phenotype. The patients had been treated with a variety of isoniazid-containing regimens in a series of controlled clinical trials in South India. The results show that rapid acetylators are no more prone to develop isoniazid-induced hepatic toxicity than are slow acetylators.

Acetylation↗
PubMed1984

[The potential clinical significance of the isoniazid acetylator phenotype in the treatment of pulmonary tuberculosis].

The most important factor determining the speed with which isoniazid is eliminated from the body is the rate of its acetylation in the liver. There are large differences between individuals in the rates at which isoniazid is acetylated. Over 98% of subjects can be clearly characterized as being either rapid of slow acetylators. Among the many satisfactory procedures for determining the acetylator phenotype of subjects, the simple sulphamethazine method is probably the most convenient. The proportions of rapid acetylators among different populations vary from about 40% among those of European and South Indian descent to over 85% among Japanese and Eskimos. The isoniazid acetylator phenotype of tuberculosis patients treated with isoniazid-containing regimens is without prognostic significance when treatment is given daily and only of doubtful importance when weak twice-weekly regimens are employed. However if treatment is given on a once-weekly basis, the response of rapid acetylators is generally much less satisfactory than that of slow acetylators. Since isoniazid is eliminated from the body predominantly by metabolism its clearance is not greatly diminished in the event of renal failure. As a consequence there are no grounds for reducing the dosage of isoniazid given to patients with impaired renal function. The incidence of the commonly encountered asymptomatic increases in serum transaminases associated with isoniazid treatment is similar in rapid and slow acetylators. Clinically important hepatic toxicity manifested by jaundice only occurs in 1-2% of patients treated with isoniazid-containing regimens. Despite earlier suggestions to the contrary, it is no more common in rapid than among slow acetylators. Since all patients can be treated effectively and safely with standard isoniazid dosages, determining patients' isoniazid serum/plasma levels or acetylator phenotype is hardly ever worthwhile. By contrast, since poor patient compliance is a major cause of therapeutic failure, monitoring the regularity with which patients self-administer their prescribed isoniazid treatment using simple urine-test methods can be of considerable value.

Acetylation↗
PubMed1982

The nose in lepromatous leprosy; bacteriological and histopathological studies of patients treated with dapsone monotherapy for varying periods of time.

A clinical, bacteriological and histopathological investigation of 62 patients with lepromatous leprosy attending a hospital in South India is reported, with particular emphasis on the activity of the disease in the nose. Twelve of the patients were from a group of 34 new patients who had been originally examined 5 years previously, and subsequently treated with dapsone (DDS) monotherapy. A further 50 lepromatous patients were also examined, who had been treated for periods ranging from 3 months to 10 years. With a few exceptions, there was good correlation between the clinical and histopathological findings in the skin and nose. Evidence of disease activity was demonstrated among three-quarters of the patients who had been treated for over a year. Failure to achieve quiescence was explained in most of the patients by failure to collect their dapsone treatment or to ingest it regularly as demonstrated by the determination of DDS/creatinine ratios on urine samples collected at the time of their visit to the clinic. Although the compliance of most patients was relatively satisfactory during the first 12 months of treatment, thereafter it deteriorated markedly. In contrast to the clinical, bacteriological, and histopathological evidence of disease activity in the skin and nose of most patients, in only one of the patients treated for more than a year was a positive nose-blow encountered. This suggests that the infectivity of DDS-treated lepromatous patients within this time and this diminished infectivity often persists despite poor drug compliance and continuing disease activity.

Dapsone↗
PubMed1981

Serum uric acid concentrations and arthralgia among patients treated with pyrazinamide-containing regimens in Hong Kong and Singapore.

The serum uric acid concentrations of patients being treated in Hong Kong and Singapore with a daily regimen consisting of streptomycin, isoniazid, rifampicin and pyrazinamide or a control regimen of daily streptomycin, p-amino-salicylic acid (PAS) and isoniazid were determined by the phosphotungstate method. Arthralgia and elevated serum uric acid levels were encountered only during the period that patients were being treated with pyrazinamide. Although daily treatment with pyrazinamide increased serum uric acid concentrations approximately 2.5-fold, the concentrations of the 6 patients who developed arthralgia were closely similar to those of matched controls without arthralgia. This fails to confirm a previous suggestion that patients with arthralgia might have higher values. Rifampicin appeared not to influence the hyperuricaemic effect of pyrazinamide.

Humans↗
PubMed1980

An evaluation of the potential use of isoniazid, acetylisoniazid and isonicotinic acid for monitoring the self-administration of drugs.

1. The possibility of using minute doses of the antituberculosis drug isoniazid (INH) or of its metabolites acetylisoniazid (AcINH) or isonicotinic acid (INA) as innocuous markers for monitoring patient compliance has been investigated. 2. The ingestion of these colourless and tasteless compounds can readily be demonstrated using a sensitive and specific colorimetric method for detecting INA and its metabolite isonicotinylglycine (INAG) in the urine that is rapid and simple to perform. 3. Studies on the kinetics of the urinary elimination of INA and INAG after the ingestion of 6 mg doses of either INH, AcINH or INA by small groups of volunteers indicated the potential suitability of INH or AcINH for monitoring daily or twice-daily self-medication and the appropriateness of INA as a marker for investigating the compliance of drugs prescribed for thrice-daily ingestion. 4. More extensive studies showed that over 99% of the urine samples collected within 18h of dosage with 6 mg INH would give positive results when tested for the presence of INA and INAG, and that doses of 2-6 mg INH could readily by incorporated into capsules or tablets and used as markers for monitoring the ingestion of the antituberculosis or antileprosy drugs dapsone, thiacetazone, ethionamide or prothionamide, or the antihypertensive oxprenolol. Such doses are less than a fiftieth of the normal therapeutic INH dose used in the treatment of tuberculosis. 5. Evidence is presented that INH, AcINH and INA possess most of the characteristics that one would hope to find in a marker for monitoring compliance including very limited inter-individual variability in the rates at which they are converted to the compounds being detected in the urine.

Glycine↗