A Randomized, Controlled, Phase III Clinical Trial to Evaluate the Efficacy and Tolerability of Risorine with Conventional Rifampicin in the Treatment of Newly Diagnosed Pulmonary Tuberculosis Patients.

BACKGROUND: The overall goals for treatment of Tuberculosis (TB) are to cure individual patient and to minimize the transmission of Mycobacterium tuberculosis. At the time of study conduction, the standard treatment for newly diagnosed tuberculosis patients consisted of an intensive phase for two months with four drugs (HRZE), followed by continuation phase for four months with two drugs (HR). Rifampicin, which is very effective against Mycobacterium tuberculosis, in both the phases of treatment, has certain concerns, which includes, decreased bioavailability with chronic use and hepatotoxicity. To overcome these concerns a new boosted formulation of Rifampicin (Risorine) with bio-enhancer Piperine was developed. Piperine has been found to increase bioavailability of several drugs including Amoxicillin, Cefotaxime, Theophylline and Propranolol. Risorine is a fixed dose combination that contains Rifampicin 200 mg + Isoniazid 300 mg + Piperine 10 mg. AIM AND OBJECTIVE: The aim of the present study was to validate the therapeutic efficacy and tolerability of Risorine formulation containing regimen with a conventional regimen in the management of patients with newly diagnosed pulmonary tuberculosis. METHODS: Total 216 patients with sputum positive and treatment naïve pulmonary tuberculosis were enrolled in the study after fulfillment of inclusion / exclusion criteria. These patients were randomized to receive either a conventional anti-TB therapy (n = 117) or a similar regimen containing Risorine (n = 99) for 6 months. During the study period, symptomatic improvement, sputum conversion and radiological improvement were monitored at regular intervals. RESULTS: Of the 216 enrolled patients, 75% in the Risorine group and 79% in the control group completed the study. At 4 weeks the sputum conversion rate was significantly superior in Risorine group (93%) than the control group (84%), which was consistence throughout the study. Cure rate at the end of 24 weeks, was higher in Risorine group (92%) than in the control group (82%). Elevation of liver enzymes were observed in 3 patients in the Risorine group and in 9 patients in control group. CONCLUSIONS: Risorine, a novel formulation of low dose Rifampicin (200 mg), a bio enhancer Piperine (10 mg) and standard dose Isoniazid (300 mg) when given along with Ethambutol and Pyrazinamide was comparable in efficacy with standard WHO therapy using conventional formulation. Risorine provides more Rifampicin in blood compare to GI tract as well as maintaining higher blood levels on chronic therapy compared to conventional Rifampicin with better safety profile. Risorine gives higher sputum conversion rate during the Intensive Phase which is maintained till the end of study. Further a trend was also noticed towards better tolerability with newer formulation, Risorine. H = Isoniazid, R = Rifampicin, Z = Pyrazinamide and E = Ethambutol.

A prospective randomized study comparing concurrent chemoradiation with weekly and 3 weekly cisplatin in locally advanced oropharyngeal carcinoma.

INTRODUCTION: The chemotherapy schedules with cytotoxic dose or weekly regimes are still challenging, weighing the benefits versus toxicities. This prospective randomized study is an attempt to assess the efficacy of two schedules of cisplatin in management of locally advanced HNSCC. OBJECTIVES: The objectives of this study was to evaluate tolerance, tumour response and toxicities of concurrent chemoradiation with cisplatin in weekly and three weekly regimes. METHODS: Locally advanced oropharyngeal squamous cell carcinoma patients fit for concurrent chemoradiation with cisplatin 40 mg/m2 (weekly) and 100 mg/m2 (3 weekly) were randomized to Arm A and B concurrently with radiotherapy of 70Gy/35frs/7 weeks. STATISTICAL ANALYSIS: Chi-square/ Fisher Exact test has been used to find the significance of study parameters on categorical scale between the groups. The statistical software SPSS 15.0 was used. RESULTS: Between December 2010 and January 2013, 60 patients were enrolled. The median cycles of cisplatin in Arm-A was 5 and 2 in Arm-B. The complete response of 80.9% vs 75% and partial response of 14.3% vs 12.5% was observed in both arms respectively. There was no statistical difference in acute radiation and hematological toxicities between the two groups. With median follow up of 28 months, the 2 and 5 years overall survival was 55% and 58%; 41.6% and 32.3% in arms A and B respectively. CONCLUSION: In our study of locally advanced oropharyngeal carcinoma treated with radical radiotherapy comparing concurrent chemotherapy with cisplatin weekly vs 3 weekly had no significant difference in overall response, complete response and acute toxicities.

Neopterin as a marker for cell-mediated immunity in patients with pulmonary tuberculosis.

SETTING: Cell-mediated immunity (CMI) involves macrophage activation and T cell proliferation. These two parameters are compared in this study. OBJECTIVE: To ascertain the role of neopterin as a biochemical marker for CMI in patients with pulmonary tuberculosis. DESIGN: We measured neopterin levels in serum and the culture supernatants of peripheral blood mononuclear cells (MNC) after stimulation with purified protein derivative (PPD) in 11 patients with pulmonary tuberculosis and 10 healthy individuals. Lymphocyte proliferative response to PPD was carried out in these two groups. RESULTS: The mean concentration of serum neopterin was significantly higher in patients than in controls (P < 0.01). The spontaneous release of neopterin was significantly higher in culture supernatants of MNC from patients when compared with those of healthy controls (P < 0.05). Release of neopterin from MNC stimulated with PPD, however, was similar in both groups. The neopterin release and the stimulation index (SI) in lymphocyte proliferation assay were not comparable, suggesting that these two parameters do not run in parallel for measuring the status of CMI. However, serum concentration of neopterin was inversely related to the SI in a large proportion of subjects (66%). CONCLUSION: Measurement of neopterin, a soluble product of immune cells (macrophage), may provide information on the state of CMI.

Intraoperative fine needle aspiration cytology of pancreas: a study of 97 cases.

Intraoperative fine needle aspiration cytology (FNAC) for pancreatic and ampullary lesions was carried out under direct vision using transduodenal approach in 97 patients. Cytological findings were classified as follows: positive for malignancy, suspicious for malignancy, benign (normal) cells from duodenum or pancreas, inflammatory and non-representative smears. Suboptimal smears (non-representative, suspicious and inflammatory) were excluded for calculating decision analysis values. Sensitivity for malignancy was 90.5% and specificity 100%. Positive and negative predictive values were 100% and 50% respectively. We conclude that intraoperative FNAC is useful in diagnosing malignant lesions of the pancreas.

Brief communication: rapid culture of tubercle bacilli.

One of the biggest obstacles to the correct diagnosis and efficient treatment of tuberculosis is the absence of a rapid technique for culturing tubercle bacilli and for testing their susceptibility to antituberculosis drugs. Current procedures typically take 6-10 weeks to perform. This article describes a simple, rapid, reliable and cheap method of culturing tubercle bacilli using a liquid medium consisting of a mixture of coconut water, horse serum, glycerol and benzylpenicillin. Addition of specific concentrations of antituberculosis drugs to the medium, permits information on the drug susceptibility of tubercle bacilli to be obtained in only 6 days. The procedure requires no special instruments or technical skill and can therefore be carried out routinely in the average laboratory in developing countries.

A cold staining method for acid-fast bacilli.

The Ziehl-Neelsen method is probably the best known and most frequently used procedure for staining tubercle bacilli. The method requires controlled heating for its success. However, in developing countries, such as India, where most laboratories rely mainly on spirit lamps as a source of heat, the Ziehl-Neelsen method often cannot be carried out because rectified spirit is difficult to obtain. The study describes a cold staining technique that uses the same staining solutions as the conventional Ziehl-Neelsen method. For direct smears, the correlation of results of the cold staining procedure with those of the Ziehl-Neelsen method was 97% and for concentrated smears was 99%. The method described is suitable for use in basically equipped laboratories.

Detection of HIV infection in pulmonary tuberculosis patients.

Well documented 112 pulmonary tuberculosis patients were studied for the prevalence of human immunodeficiency virus (HIV) seropositivity by using two antibody screening tests along with western blot test. Nineteen of the pulmonary tuberculosis patients were HIV seropositive, 12 were acid-fast bacillus smear positive; 12 patients were tuberculin skin test positive and 15 patients were culture positive. As the incidence of HIV infection is increasing in India, it is observed that patients co-infected with HIV and TB are also on the rise. Recognition of the dual infection and taking adequate steps to deal with this epidemic are needed.

PIP: Infection with HIV depresses cell-mediated immunity by selectively depleting the CD4 T cells. That process increases the HIV-infected individual's susceptibility to other infections such as Myco tuberculosis. The World Health Organization estimates that more than 4 million people worldwide have been infected with HIV and Myco tuberculosis. 35 patients newly diagnosed with pulmonary tuberculosis (TB) at the Government Thiruvotteswarar Hospital of Thoracic Medicine in Madras and 77 at the Institute of Thoracic Medicine were tested for infection with HIV using particle agglutination, ELISA, and Western blot. 19 were HIV positive, 12 were acid-fast bacillus smear positive, 12 were tuberculin skin test positive, and 15 were culture positive. As the incidence of HIV infection increases in India, so does the number of patients coinfected with HIV and TB. Health personnel need to recognize such dual infection and take the proper steps to manage the epidemic.