A Controlled Comparison of a Twice-Weekly and Three Once-Weekly Regimens in the Initial Treatment of Pulmonary Tuberculosis

value of a fully supervised twice-weekly regimen of high-dosage isoniazid plus streptomycin in the treatment of newly diagnosed tuberculous patients with drug-sensitive cultures. A logical consequence of this finding was an investigation of regimens with a longer interval between successive doses. The present report describes the findings of a controlled study of 3 once-weekly regimens and the twice-weekly regimen. The results confirm that the twice-weekly regimen is highly effective and demonstrate that its efficacy is not influenced by the rate of inactivation of isoniazid or by a reduction (by one-fourth) in the dosage of streptomycin. The results also show that once-weekly chemotherapy from the beginning, whether with high-dosage isoniazid plus streptomycin or high-dosage isoniazid plus streptomycin plus high-dosage pyrazinamide, gives unsatisfactory results. However, when an initial daily phase of 4 weeks with a moderate dosage of isoniazid plus streptomycin preceded the once-weekly phase of high-dosage isoniazid plus streptomycin, the response was highly satisfactory in slow inactivators of isoniazid (as good as with the twice-weekly regimen) but was considerably less satisfactory in rapid inactivators. These findings suggest that if a method of compensating for the insufficiency of this regimen in rapid inactivators of isoniazid can be found, the prospects for evolving a highly satisfactory once-weekly regimen are bright

A Concurrent Comparison of Intermittent (Twice-Weekly) Isoniazid plus Streptomycin and Daily Isoniazid plus PAS in the Domiciliary Treatment of Pulmonary Tuberculosis

Previous reports from the Tuberculosis Chemotherapy Centre, Madras, have established that ambulatory treatment of pulmonary tuberculosis with the combination of isoniazid and PAS, administered daily, yields satisfactory results. However, in the usage of any unsupervised regimen, reliance must be placed on the co-operation of patients in self-administering their drugs. Irregularities in drug-taking, which are not uncommon, may lead to unfavourable therapeutic results; this might be avoided by supervised administration of the drugs. Daily supervision is clearly impracticable in developing countries but regimens in which the drug is administered intermittently-say, twice a week or less frequently-are, if effective, more likely to gain general application. This paper presents the results of a controlled study of a fully supervised intermittent regimen of isoniazid (12.5-16.1 mg/kg body-weight, orally) plus streptomycin (injected in a uniform dose of I g), given together twice weekly, compared with a standard, unsupervised, daily, oral regimen of isoniazid (3.7-63 mg/kg body-weight) plus sodium PAS (0.2-0.3 g/kg body-weight), given in two doses. The intermittent regimen was at least as effective as the standard oral regimen, and although the incidence of temporary giddiness in patients receiving this regimen was rather high, this did not appear to have any long-term importance nor did it appear unduly to affect the co-operation of the patients. These encouraging findings suggest a possible change in the orientation of drug-administration for tuberculosis in developing countries

Controlled Comparison of Oral Twice-weekly and Oral Daily Isoniazid plus PAS in Newly Diagnosed Pulmonary Tuberculosis

A controlled clinical trial was undertaken in 247 patients with newly diagnosed pulmonary tuberculosis to assess the relative efficacies of a fully supervised twice-weekly oral regimen of isoniazid plus PAS (para-aminosalicylic acid) and a standard self-administered daily regimen of the same drugs following an initial intensive phase of two weeks of daily streptomycin, PAS, and isoniazid. Among patients who had isoniazid-sensitive cultures initially and who attended the clinic regularly the numbers with a favourable bacteriological response at the end of the year of chemotherapy were 79 (88%) out of 90 for the twice-weekly regimen and 72 (87%) out of 83 for the daily regimen; the numbers of patients with considerable radiographic improvement were 54 (60%) and 53 (64%) respectively. Complaints of vomiting or diarrhoea that did not require a reduction of the PAS dosage were made on one or two occasions by 23 (21 % ) out of 109 twice-weekly and 25 (23%) out of 108 daily patients, and on at least three occasions by 4 (4%) and 12 (11%) respectively. Finally, all five patients who had chemotherapy changed on account of hypersensitivity to PAS had been receiving the daily regimen, as also had one patient who died of agranulocytosis

A Concurrent Comparison of Isoniazid plus PAS with Three Regimens of Isoniazid Alone in the Domiciliary Treatment of Pulmonary Tuberculosis in South India

Recent studies have shown that treatment of pulmonary tuberculosis with isoniazid plus p-aminosalicylic acid (PAS) at home is, in the majority of cases, as satisfactory as treatment with the same combination of drugs in sanatorium and does not appear to expose the patient’s contacts to any special risk. Before mass domiciliary chemotherapy can be introduced, however, a question that has to be decided is what drug or drugs and what dosage and rhythm of administration will be most effective. This paper presents the results of a controlled comparison of four chemotherapeutic regimens : (a) 3.9-5.5 mglkg body-weight of isoniazid plus 0.2-0.3 g/kg body-weight of PAS (sodium salt) daily in two doses (the standard combined chemotherapy) ; (b) 7.8-9.6 mglkg body-weight of isoniazid alone daily in one dose ; (c) 7.8-9.6 mg/kg body-weight of isoniazid alone daily in two doses ; (d) 3.9-5.5 mg/kg body-weight of isoniazid alone daily in two doses. Isoniazid plus PAS proved to be the most satisfactory regimen; it was clinically effective and there were very few toxic manifestations

Isoniazid plus Thioacetazone * compared with Two Regimens of Isoniazid plus PAS in the Domiciliary Treatment of Pulmonary Tuberculosis in South Indian Patients

Previous reports from the Tuberculosis Chemotherapy Centre, Madras, have established that ambulatory treatment of pulmonary tuberculosis with a standard daily regimen of isoniazid plus PAS for one year yields satisfactory results. However, this regimen may be unsuitable for large-scale use in many developing countries, because PAS is expensive, bulky and unpleasant to take, and has poor keeping qualities, especially in tropical countries. It might be possible to overcome these disadvantages, by substituting for the PAS a drug which is equally effective but less expensive and more acceptable, or by reducing the daily dosage of PAS and the period for which it is prescribed. This paper presents the results over a II-month period of a controlled comparison of (a) the standard regimen of isoniazid (average 4.5 mg/kg body-weight) plus sodium PAS (average 0.22 g/kg), daily in two divided doses ; (b) a regimen of isoniazid (average 6.9 mg/kg) plus thioacetazone (average 3.4 mg/kg), daily in one dose ; and (c) a 2-phase regimen of isoniazid (average 5.5 mg/kg) plus sodium PAS (average 0.17 g/kg), daily in one dose for 6 months, followed by isoniazid alone (average 6.8 mg/kg), daily in one dose for the second 6 months. The regimen of isoniazid plus thioacetazone was found to be therapeutically as effective as the standard regimen of isoniazid plus PAS ; however, it was associated with a higher incidence of minor side-effects, and three cases of exfoliative dermatitis. The 2-phase regimen of isoniazid plus PAS followed by isoniazid alone was less effective. These findings are encouraging for the large-scale use in developing countries of the relatively inexpensive regimen of isoniazid plus thioacetazone ; however, any such step should be preceded by carefully planned studies to investigate, under local conditions, the toxicity and the efficacy of the regimen

Effects of neo-adjuvant chemotherapy for oesophago-gastric cancer on neuro-muscular gastric function

Delayed gastric emptying symptoms are often reported after chemotherapy. This study aims to characterise the effects of chemotherapy on gastric neuro-muscular function. Patients undergoing elective surgery for oesophago-gastric cancer were recruited. Acetylcholinesterase, nNOS, ghrelin receptor and motilin expressions were studied in gastric sections from patients receiving no chemotherapy (n = 3) or oesophageal (n = 2) or gastric (n = 2) chemotherapy. A scoring system quantified staining intensity (0–3; no staining to strong). Stomach sections were separately suspended in tissue baths for electrical field stimulation (EFS) and exposure to erythromycin or carbachol; three patients had no chemotherapy; four completed cisplatin-based chemotherapy within 6 weeks prior to surgery. AChE expression was markedly decreased after chemotherapy (scores 2.3 ± 0.7, 0.5 ± 0.2 and 0 ± 0 in non-chemotherapy, oesophageal- and gastric-chemotherapy groups (p < 0.03 each) respectively. Ghrelin receptor and motilin expression tended to increase (ghrelin: 0.7 ± 0.4 vs 2.0 ± 0.4 and 1.2 ± 0.2 respectively; p = 0.04 and p = 0.2; motilin: 0.7 ± 0.5 vs 2.2 ± 0.5 and 2.0 ± 0.7; p = 0.06 and p = 0.16). Maximal contraction to carbachol was 3.7 ± 0.7 g and 1.9 ± 0.8 g (longitudinal muscle) and 3.4 ± 0.4 g and 1.6 ± 0.6 (circular) in non-chemotherapy and chemotherapy tissues respectively (p < 0.05 each). There were loss of AChE and reduction in contractility to carbachol. The tendency for ghrelin receptors to increase suggests an attempt to upregulate compensating systems. Our study offers a mechanism by which chemotherapy markedly alters neuro-muscular gastric function

Use of accelerometry to investigate physical activity in dogs receiving chemotherapy

Objectives: To perform a preliminary study to assess whether single-agent palliative or adjuvant chemotherapy has an impact on objectively measured physical activity in dogs. Methods: Fifteen dogs with neoplasia (treatment group) wore ActiGraph™ accelerometers for 5-day periods before, during and after receiving single-agent adjuvant or palliative chemotherapy. Mean 5-day total physical activity and time spent in three different intensities of activity (sedentary, light-moderate and vigorous) before, during and after receiving chemotherapy were compared to a group of 15 healthy dogs (control group). Results were also compared within the treatment group across time. Results: Prior to chemotherapy, treated dogs tended to be less active than control dogs. Treatment group dogs were slightly more active at restaging than they were prior to treatment but had similar activity levels to control dogs. Marked effects of chemotherapy on physical activity were not detected. Physical activity was slightly lower in treated dogs during chemotherapy when compared to control dogs but there was a slight increase in physical activity of treated dogs during chemotherapy when compared with pretreatment recordings. There was little change in the mean 5-day total physical activity between treated dogs during chemotherapy and at restaging but a mild decrease in time spent sedentary and increase in time spent in light-moderate activity at this comparison of time points. Clinical Significance: Single-agent adjuvant or palliative chemotherapy had minimal impact on physical activity levels in dogs with neoplasia

Breast cancer: Monitoring response to neoadjuvant chemotherapy using Tc-99m sestamibi scintimammography

Background: Aim of the study was to assess the value of scintimammography using Tc-99m sestamibi in the evaluation of tumor response to neoadjuvant chemotherapy. Material and Methods: Results were calculated for 9 patients undergoing neoadjuvant chemotherapy. Scintimammography using 740 MBq Tc-99m sestamibi was performed before, during and after chemotherapy, and sestamibi uptake was scored visually and semiquantitatively to evaluate tumor response. Results: In the case of complete response (n = 3) sestamibi uptake decreased 8 days after beginning neoadjuvant chemotherapy and normalized in the following course. Focal uptake decreased more slowly in patients with partial response (n = 3), who showed clear, persisting tracer accumulation after therapy. The patients without response (n = 3) showed a persisting high tumor activity even after chemotherapy was completed. Conclusions: The preliminary data suggest that in contrast to other imaging modalities scintimammography appears to yield early information regarding tumor response to neoadjuvant chemotherapy

Perceived Cognitive Changes with Chemotherapy for Breast Cancer: A Pilot Study

Purpose The purpose of this study was to determine perceived cognitive functioning, fatigue, depression and general well-being among women before and after the initiation of chemotherapy for breast cancer compared to a sample of healthy women. Method This descriptive, repeated measures study compared women receiving chemotherapy and healthy women. Women completed measures of quality of life, fatigue, cognitive changes and depression. Results Before chemotherapy, women with cancer reported more fatigue and depression than healthy women. After chemotherapy, women with cancer reported decreased cognitive functioning accompanied by more fatigue and depressive symptoms than healthy women. Conclusion This study is one of the first to use multiple symptom measures before and after starting chemotherapy. Understanding cognitive changes and related symptoms that occur before and during chemotherapy for breast cancer is the first step toward helping women cope with changes that occur with breast cancer treatment