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A L BHATIA

Publications and source records attributed to A L BHATIA.

At least 19 recordsLinked to original sources

A COMPARISON OF THE VIRULENCE IN THE GUINEA-PIG OF TUBERCLE BACILLI FROM THAI AND BRITISH PATIENTS.

Recent work carried out at the Tuberculosis Chemotherapy Centre, Madras, and at the Postgraduate Medical School of London has shown that isoniazid-sensitive cultures of tubercle bacilli obtained before the start of chemotherapy from South Indian patients with pulmonary tuberculosis are of lower average virulence than corresponding cultures from British patients. The present paper from the Centre extends these studies to areas outside India by comparing isoniazid-sensitive cultures from 81 Thai patients and 67 British patients for their guinea-pig virulence. As assessed by the amount of disease visible at post-mortem examination six weeks after intramuscular injection of the cultures, by the mortality of the guinea-pigs and by the results of spleen culture, the Thai cultures were less virulent than the British cultures. However, a retrospective comparison with the earlier studies suggests that the Thai cultures were intermediate in their virulence between British and Indian cultures. These findings contribute to the over-all study of the geographical distribution of attenuated tubercle bacilli.

Animals↗

The course of pulmonary tuberculosis in patients excreting organisms which have acquired resistance. Response to continued treatment for a second year with isoniazid alone or with isoniazid plus PAS.

This study from the Tuberculosis Chemotherapy Centre, Madras, summarizes the progress during the second year of the patients in a concurrent comparison of four domiciliary chemotherapeutic regimens (isoniazid plus PAS and three regimens of isoniazid alone) who had bacteriologically active or bacteriologically relapsed pulmonary tuberculosis, with isoniazid-resistant organisms, at the end of the first year of treatment.Of the 57 patients who continued on the same chemotherapy during the second year, nine had attained bacteriological quiescence by the end of that year, 15 still had bacteriologically active disease and 33 had during the year had a serious radiographic deterioration necessitating a change of treatment. An association was observed between the response to treatment in the second year and both the extent of cavitation and the degree of culture-positivity at the end of the first year, but no association was found between the response to treatment in the second year and the level of isoniazid-resistance, the catalase activity, the susceptibility to hydrogen peroxide or the virulence in the guinea-pig of cultures isolated in the last months of the first year.It is concluded that persisting bacteriological positivity at the end of one year's treatment with isoniazid, either alone or in combination with PAS, is likely to lead to serious radiographic deterioration, irrespective of the level of isoniazid-resistance or of the catalase activity of the cultures of tubercle bacilli, and that, consequently, treatment of patients with bacteriologically active pulmonary tuberculosis must aim at rendering the sputum culture-negative in all instances.

4-Aminobenzoic Acid↗

Progress in the second and third years of patients with quiescent pulmonary tuberculosis after a year of chemotherapy at home or in sanatorium, and influence of further chemotherapy on the relapse rate.

A controlled comparison by the Tuberculosis Chemotherapy Centre, Madras, of the merits of home as compared with sanatorium treatment for pulmonary tuberculosis showed that, at the end of a year of chemotherapy with isoniazid plus p-aminosalicylic acid (PAS), the response of the home patients closely approached that of the sanatorium patients. The present report reviews the progress of those patients in the controlled comparison whose disease had attained bacteriological quiescence by the end of the year of combined chemotherapy. During the second year, half of the patients received further chemotherapy, with isoniazid alone, and half received a placebo, calcium gluconate. During the third year, half of those who were treated with isoniazid in the second year and whose disease remained quiescent continued to receive that drug and all the remaining patients with quiescent disease received the placebo. In the second and third years all the patients were treated at home and administered the medicaments to themselves.It has been concluded from this follow-up study that in the second and third years there was relatively little difference between the progress of the patients whose disease attained quiescence following a year of domiciliary treatment with isoniazid plus PAS and that of those whose disease attained quiescence following a year's treatment with the same drugs in sanatorium; that a second or third year of further treatment with isoniazid alone gave no better results than a year of combined chemotherapy, followed by careful observation of the patient and further chemotherapy if relapse occurred; and that the relapse rate among the patients with residual cavitation at the end of the year of combined chemotherapy was slightly higher than that among the patients with no residual cavitation at the end of the first year.

Aged↗

The virulence in the guinea-pig of tubercle bacilli isolated before treatment from South Indian patients with pulmonary tuberculosis. 2. Comparison with virulence of tubercle bacilli from British patients.

A series of studies has been undertaken by the Tuberculosis Chemotherapy Centre Madras, with the ultimate object of finding out whether differences in the virulence of the tubercle bacilli isolated from Indian tuberculous patients before the start of chemotherapy are related to the severity of the patients' disease and to the subsequent response to treatment. This paper-the second in the series-presents the results of a comparative investigation of the virulence in the guinea-pig of tubercle bacilli obtained from Indian and from British tuberculous patients before treatment. In this investigation, which was carried out at the Centre and at the Microbiological Research Establishment, Porton, England, the virulence of the Indian and the British cultures was assessed by guinea-pig mortality, by the "root-index of virulence" (based on the post-mortem tuberculous disease score and the survival period of the animal), and by the results of spleen culture. The Indian cultures were found, on the average, to be less virulent and to show a w der range of virulence than the British cultures, both in the Porton and in the Madras series of experiments. A further indication of the heterogeneity of the Indian tubercle bacilli was provided by the results of tuberculin tests: whereas the British cultures appeared to be homogeneous in their ability to induce tuberculin allergy in the guinea-pig, the Indian cultures showed considerable variation in this respect.

Animals↗

Response of patients infected with isoniazid-resistant tubercle bacilli to treatment with isoniazid plus PAS or isoniazid alone.

This study from the Tuberculosis Chemotherapy Centre, Madras, compares patients infected with isoniazid-resistant tubercle bacilli ("R" patients) with those infected with isoniazid-sensitive tubercle bacilli ("S" patients) as regards, first, their pretreatment status and, secondly, their response to a year's chemotherapy, either with isoniazid plus p-aminosalicylic acid (PAS) or with isoniazid alone. With regard to the first comparison, there was, on admission to treatment, little difference between the R and S patients in terms of the extent of the radiographic lesion, the extent of cavitation or the bacterial content of the sputum, but there were major differences in the age and sex distributions, the R patients showing a greater preponderance of young males than the S patients. As to the second comparison, statistically significant differences in the bacteriological response to treatment of the S and the R patients were observed in both the isoniazid-plus-PAS and the isoniazid-alone series, the response of the S patients being much better than that of the R patients. When the response to treatment was assessed in terms of radiographic progress and weight changes, however, hardly any difference was observed between the progress of the S and the R patients. The reasons for the response in the R patients are discussed.

Bacillus↗

Rate of inactivation of isoniazid in South Indian patients with pulmonary tuberculosis.

Since isoniazid is metabolized in man to several derivatives with little or no specific activity against the tubercle bacillus, its rate of inactivation in the body may have an important bearing on its efficacy as an antituberculosis drug. The inactivation rate, though constant in any one person, is known to vary from individual to individual and from race to race. A series of studies on the rate of inactivation of isoniazid in Indian patients with pulmonary tuberculosis has recently been undertaken at the Tuberculosis Chemotherapy Centre, Madras. The present paper describes the first of these studies, in which the concentration of isoniazid in the serum of patients admitted to a controlled comparison of four domiciliary chemotherapeutic regimens was determined by microbiological assay four-and-a-half hours after administration of a standard dose of isoniazid (3 mg/kg body-weight). Patients with serum levels of 0.58 mug/ml or more were classified as slow inactivators of isoniazid and those with levels below 0.58 mug/ml as rapid inactivators. By this definition, 195 (61%) of the 321 patients studied were found to be slow inactivators and 126 (39%) rapid inactivators. A relationship was shown between sex and the rate of inactivation, there being a significantly higher proportion of rapid inactivators among the females than among the males. The observed estimates of the error of the microbiological assay procedure are discussed and possible ways of reducing the error suggested.

Antitubercular Agents↗

The virulence in the guinea-pig of isoniazid-sensitive tubercle bacilli isolated from South Indian patients before treatment and after three months of chemotherapy.

In order to find out whether chemotherapy with isoniazid affects the virulence in the guinea-pig of tubercle bacilli that do not develop resistance to the drug, virulence tests were carried out on isoniazid-sensitive cultures obtained from 20 South Indian tuberculous patients before treatment and after three months of chemotherapy with isoniazid. No significant difference in virulence was observed between the cultures obtained on admission to treatment and those obtained after three months of chemotherapy. This is a finding with important implications for large-scale surveys of the distribution of attenuated strains of tubercle bacilli from untreated patients in India and other countries. Detailed and repeated inquiries as to previous chemotherapy are not important in such surveys, provided that sensitivity tests are done on all the cultures.

Bacillus↗

The virulence in the guinea-pig of tubercle bacilli isolated before treatment from South Indian patients with pulmonary tuberculosis. I. Homogeneity of the investigation and a critique of the virulence test.

A series of studies on the virulence in the guinea-pig of tubercle bacilli isolated before treatment from Indian tuberculous patients admitted to a controlled comparison of different regimens of domiciliary chemotherapy has recently been undertaken by the Tuberculosis Chemotherapy Centre, Madras. The main object of these studies was to determine whether the differences in virulence of the tubercle bacilli obtained from Indian patients before the start of chemotherapy were related to the severity or type of the patients' disease at that time and to the subsequent response to treatment. Before these relationships could be investigated, however, it was necessary to find out whether the results of the virulence tests, which were carried out over a period of two-and-a-half years at the Centre and at the Microbiological Research Establishment, Porton, England, could be considered as a unified whole-that is, as if they had all been done on the same day in the same laboratory.A proportion of the cultures was stored at - 20 degrees C for 44-78 weeks, but this did not affect their virulence. Inter-experimental variation was found to be small in the Porton series of tests and undetectable in the Madras series, and the results in the latter series could be successfully adjusted to those in the former by allowing for differences in the means and standard deviations of the distributions for the two series. The measure of virulence used was found to be reasonably acceptable for the analysis of variance technique. Suggestions are made as to ways of improving the efficiency of the experimental design in future studies.

Bacillus↗

The virulence in the guinea-pig of tubercle bacilli isolated before treatment from South Indian patients with pulmonary tuberculosis. 3. Virulence related to pretreatment status of disease and to response to chemotherapy.

This is the last of a series of three reports from the Tuberculosis Chemotherapy Centre Madras, on a study undertaken with the object of finding out whether differences in the virulence in the guinea-pig of tubercle bacilli isolated from South Indian tuberculous patients before the start of chemotherapy are related to the severity of the patients' disease on admission to treatment and to the subsequent response to chemotherapy. The 281 patients in this study were drawn from the patients admitted to a 1-year comparison of four domiciliary chemotherapeutic regimens: (a) 3.9-5.5 mg/kg isoniazid plus 0.2-0.3 g/kg sodium PAS daily, divided into two doses (PH series); (b) 7.8-9.6 mg/kg isoniazid alone daily in one dose (HI-1 series); (c) 7.8-9.6 mg/kg isoniazid alone daily, divided into two doses (HI-2 series); (d) 3.9-5.5 mg/kg isoniazid alone daily, divided into two doses (H series).No evidence was found of an association between the virulence of the organisms and any pretreatment condition of known prognostic importance. There was no association between pretreatment virulence and progress during treatment in the PH series (the most effective regimen). In the other series, however, the progress was more satisfactory in patients infected with organisms of low virulence than in those infected with organisms of high virulence, the association between virulence and progress attaining statistical significance in the combined HI-2 and H series (the least effective regimens) and only just failing to do so in the smaller HI-1 series.Possible explanations are put forward both for the absence of an association between virulence and severity of disease on admission and for the presence of an association between virulence and response in the patients treated with isoniazid alone.

Aged↗

A comparison of the sensitivity to p-aminosalicylic acid of tubercle bacilli from South Indian and British patients.

In a comparison of home and sanatorium treatment for tuberculous patients in India, pretreatment cultures of tubercle bacilli showed a higher average level of resistance to p-aminosalicyclic acid (PAS) than pretreatment cultures from a representative sample of patients in Great Britain. The investigation described in the present paper was therefore undertaken to find out the nature of the difference in the PAS sensitivity of cultures from Indian and British patients. In this investigation, carried out jointly at the Tuberculosis Chemotherapy Centre, Madras, and the Postgraduate Medical School of London, sputum specimens from 147 Indian and 93 British patients were cultured and subjected to sensitivity tests. The tests were set up on slopes containing various concentrations of PAS and inoculated with 10(5) viable units of the cultures, and the minimal concentrations of PAS inhibiting the growth of 20, 50 and 100 colonies were determined. According to the 20-colony end-point-the one commonly used in routine sensitivity tests-the Indian strains were significantly more resistant than the British strains. This difference in sensitivity was not apparent, however, in either the 50-colony or the 100-colony results. The presence of a small proportion of resistant organisms was found to be a general characteristic of the Indian strains, but did not appear to be related to any special tendency for the patient to fail to respond to treatment with PAS. Since a chance increase in the inoculum size might well affect the 20-colony results, the authors recommend a tenfold decrease in the size of the inoculum used in routine PAS-sensitivity tests on Indian patients.

Aminosalicylic Acid↗