Patent Ductus Arteriosus in Infants <29 Weeks Gestation – Outcomes and Factors Affecting Closure.

Objective: To determine Patent ductus arteriosus (PDA) closure rates for extremely preterm infants in a tertiary care centre, factors affecting response to indomethacin and outcomes of these infants relative to their PDA status. Setting: Neonatal intensive care unit in tertiary-care children’s hospital. Design: Retrospective medical record review. Methods: A retrospective chart review of all infants <29 weeks gestation between 1st Jan 2003 and 30th June 2006 was carried out. Multiple courses of standard intravenous indomethacin (dose: 0.2 mg/kg 12 hourly; 3 doses) followed by a tail course (0.1 mg/kg/day; 3 doses) were used to treat PDA depending on clinical and hemodynamic status. Data on demographic characteristics, PDA status, use of indomethacin, and outcome factors such as chronic lung disease and mortality were collected. Results: A total of 166 infants were identified in the study period, of which 15 were excluded. The median gestation was 27 weeks [IQR (25, 28)] and the mean (SD) birthweight was 950 (244) grams. The remaining infants (n=151) were divided into three groups. Group1 (n=47): no or non-significant PDA, Group 2 (n=91): significant PDA closed after indomethacin treatment (≥ 1 course) and Group 3 (n=13): significant PDA not responding to indomethacin. The closure rate of PDA with indomethacin treatment (group 2) was 87%. A low gestational age < 26 weeks (OR 5.6, 95% CI 1.6-19.9) and female sex (OR 5.8, 95% CI 1.5- 22.8) was associated with poor response to indomethacin in our study population. Conclusions: Multiple indomethacin courses using the standard dosing approach result in high PDA closure rates for infants < 29 weeks gestation.

Role of C-erbB2 expression in gallbladder cancer.

Background: Gallbladder cancer (GBC) is a lethal malignancy presenting at an advanced stage. The pathogenesis is not well categorized, and surgery is the only treatment available at the early stage of the disease. There have been few reports on role of growth factor receptors in GBC. C-erbB2 is one such receptor whose over-expression is being explored in GBC as one of the factors involved in carcinogenesis and possible target for therapy. Materials and Methods: One hundred and four consecutive cases of GBC were retrospectively studied with regard to clinical features, histological type, grade and stage of tumor. Immunohistochemistry for C-erbB2 was done and expression was correlated with different clinic-pathological parameters and survival. Results: C-erbB2 overexpression was seen in 9.4% cases with complete staining and both complete and incomplete staining (2+ and 3+) was seen in 13.4% cases. Eighty percent of the C-erbB2 over-expressed cases were well differentiated and in stage II to stage IV disease. Dysplasia adjacent to carcinoma did not show any expression. No correlation was found with tumor grade, stage, gall stones, and patient survival. Xanthogranulomatous inflammation was inversely correlated with C-erbB2 over-expression. Median survival was 30 months in C-erbB2 over-expressed cases, and 12 months in C-erbB2 negative cases. Conclusion: We found complete membranous staining of C-erbB2 in 9.4% of GBC which was frequent in well differentiated and stage II to stage IV tumors. C-erbB2 tumors had longer median survival than C-erbB2 negative tumors. C-erbB2 is not involved early in the carcinogenetic process as none of the dysplasia showed expression. C-erbB2 over-expression may be considered as target for therapy in advanced stage of GBC.

Natural toxins and their therapeutic potential.

Plants have been extensively investigated for exploring their therapeutic potentials, but there are comparatively scanty reports on drugs derived from animal kingdom, except for hormones. During last decade, the toxins that are used for defense by the animals, have been isolated and found useful tools for physiological and pharmacological studies, besides giving valuable leads to drug development. Toxins with interesting results have been isolated from the venoms of snakes, scorpions, spiders, snails, lizards, frogs and fish. The present review describe about some toxins as drugs and their biological activities. Some fungal, bacterial and marine toxins have also been covered in this article.

Pyrazinamide induced hyperuricaemia presenting as severe bilateral leg cramps.

Pyrazinamide is one of the first line drugs used for the treatment of tuberculosis. Hepatotoxicity and hyperuricaemia are important and common untoward effects seen after administration of pyrazinamide. The drug inhibits elimination of urates resulting in hyperuricaemia, the presenting features of which are arthralgia, arthritis or even gout. A-case of bilateral leg cramps due to hyperuricaemia following pyrazinamide therapy is reported here.

Results of letrozole in postmenopausal women after tamoxifen treatment for advanced breast cancer.

AIM: To analyze overall and progression-free survival after letrozole in postmenopausal women with advanced breast cancer who failed after tamoxifen therapy. MATERIALS AND METHODS: This is a retrospective analysis of 95 patients with breast cancer who were postmenopausal and had failed after tamoxifen therapy. Dose of letrozole was 2.5 mg daily until disease progressed. Patients had estrogen receptor- and/or progesterone receptor-positive tumors or both receptors were unknown. One complete course of (6 cycles) chemotherapy for metastatic disease was allowed. The primary end point was time to progression (TTP). Secondary end points included overall objective response rate (ORR), its duration, time to treatment failure (TTF), overall survival and tolerability. RESULTS: Median TTP was 10 months. ORR was 21% with complete response rate of 9%. Nine patients died of disease during treatment. Median overall survival was 36 months. Median time to response was three months and median duration of response was 13 months. Time to chemotherapy was 13.5 months and TTF was 9.3 months. Treatment failure was seen in 76% of patients. Disease progression was the main cause for treatment failure. Treatment was well-tolerated by all patients. CONCLUSION: This retrospective analysis shows that letrozole is quite effective as second line therapy in postmenopausal patients with advanced breast cancer who had failed after tamoxifen therapy.

Degradation kinetics of Metronidazole and its Mutual Prodrug with Ciprofloxacin : a Calorimetric Analysis

Calorimetric technique has aroused considerable interest as a versatile tool in pharmaceutical industry and academia to provide useful information about thermodynamic and kinetic aspects of drug molecules. The present paper utilizes this technique to monitor the hydrolytic degradation of metronidazole and its prodrug with ciprofloxacin; i.e. 2-(2-methyl-5-nitroimidazol-1-yl)ethyl-1-cyclopropyl-6-fluoro-1;4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylate. The synthesis of the present mutual prodrug was envisaged to combine the antiprotozoal and anaerobic antibacterial effects of metronidazole with antibacterial effects of ciprofloxacin. Heat flux microcalorimeter was used to determine the rate of heat evolved during the degradation of the drug and prodrug as a function of concentration; pH and temperature. In terms of enthalpy of hydrolysis the response is exothermic both for drug and prodrug. However; the absolute value of the enthalpy of reaction (?rH0) is low for the prodrug. The degradation followed pseudo first order kinetics; showed marked stability at pH 3-7 followed by accelerated hydrolysis at higher pH; characteristic of general acid-base catalysis. The catalytic rate constant for hydrogen ion (kH) and hydroxyl ion (kOH) were found to be 0.413 and 526.1 M-1h-1; respectively; at 318.15 K. The hydrolysis of the prodrug was found to be approximately 50-60 times faster than that of the drug. This may be attributed to the fact that hydrolysis of ester group in prodrug is assisted by keto group on the ciprofloxacin. However; there is no effect of protonation of nitrogen in piperazine ring in ciprofloxacin on the hydrolysis due to the distance from the ester moiety

Cholecystectomy in patients with asymptomatic gallstones to prevent gall bladder cancer--the case against.

Gallstones (GS) are common in northern India. GS are the most important risk factor for gall bladder cancer (GBC). Data from the West, however, indicate that the risk of GBC in persons with asymptomatic GS is very small and does not warrant prophylactic cholecystectomy. Can these recommendations be applied to northern India where incidence rates of GBC are one of the highest in the world? Not all persons with asymptomatic GS require cholecystectomy. There may, however, be a case for offering cholecystectomy to a young woman in northern India with a large GS or a gall bladder packed with GS, though there is no evidence to support this recommendation. Type of stone, tumor markers and genetic markers need to be investigated to identify those with asymptomatic GS who are at the highest risk of developing GBC so that they can selectively be offered pre-emptive cholecystectomy to prevent GBC.

Effects of Fexofenadine, Cetirizine and Diphenhydramine on Psychomotor Performance in Adult Healthy Volunteer

The present study was conducted to assess and compare the cognitive and psychomotor effects of fexofenadine, a newer second generation antihistamine with cetirizine, diphenhydramine and placebo in 10 healthy adult volunteers in a double blind, randomized cross over study. Following single dose of each drug, the volunteers were subjected to perform a series of tests of cognitive and psychomotor performance at 1, 3 and 6 hours post dose. The test battery consisted of both subjective and objective tests which were further grouped into instrumental and non-instrumental. Instrumental tests included – Simple reaction time (SRT), Multiple Choice ReactionTime Task (MCRT) and Critical Flicker Fusion frequency threshold (CFFT). The tests used in the non instrumental group were- Stanford Sleepiness Scale (SSS), Digit Cancellation Task (DCT), Digit Symbol Substitution Task (DSST) and mental arithmetic tests. Fexofenadine at doses of 120 mg was not significantly different from placebo in any of the tests used. However, as expected for a verum, all the measures were significantly disrupted by diphenhydramine 25 mg upto 6 hours post dose. Cetirizine 10 mg has produced significant subjective somnolence at 3 & 6 hours post dose but without any impairment of objective tests. These results allow the conclusion that fexofenadine at its recommended therapeutic dose of 120 mg is free from impairment effects on aspects of psychomotor function and hence can be used safely. Cetirizine is mildly sedating though it did not impair any of the objective psychometric tests.

Gallbladder cancer: an 'Indian' disease.

The prevalence of gallbladder cancer, the commonest biliary malignancy, shows geographical and racial variations. It is reported to be rare in India. However, the incidence of gallbladder cancer in north and central India is very high--it is the commonest gastrointestinal cancer in women. Even Indian migrants to different countries have a higher risk of having gallbladder cancer as compared to the respective native populations. The incidence of gallbladder cancer parallels the prevalence of gall stone disease; large and long-standing gall stones being associated with a higher risk of gallbladder cancer. Gall stone disease is common in north India and occurs at a younger age than in the western populations. Moreover, patients with gall stone disease present for treatment a long time after the onset of symptoms. Both these factors result in prolonged exposure of the gallbladder to stones. Besides gall stone disease, various other factors may also play a role in the causation of gallbladder cancer which is an (north) Indian disease.

Surgical management of complicated hydatid cysts of the liver.

AIMS: To review the clinical presentation and surgical management of complicated hydatid cysts of the liver. METHODS: Forty-three patients with hydatid disease of the liver were managed surgically between 1991 and 1998. There were 14 men and 29 women with a median age of 34 years. An abdominal ultrasound, computed tomography and serology established diagnosis. Preoperative endoscopic retrograde cholangiography was performed in patients with associated jaundice and high suspicion of intrabiliary rupture. Eleven (26%) patients had complicated cysts and formed the basis for our study. RESULTS: Infection (n = 5, 11%) and intrabiliary rupture (n = 4, 9%) were the common complications. Intrathoracic rupture and intraperitoneal rupture were encountered in one patient each. All patients with infected cysts presented with pain and fever (n = 5, 100%) while those with intrabiliary rupture had jaundice (n = 4, 100%), pain and fever (n = 3, 75%). Surgical procedures performed in complicated cysts were-infection: omentoplasty (n = 2) and external drainage (n = 3); intrabiliary rupture: omentoplasty (n = 2) and internal drainage (n = 2). Patient with intrathoracic and intraperitoneal rupture underwent external drainage. There was no mortality. Postoperative morbidity was encountered in 14 patients and was more in complicated cysts (n = 6/11; 55%) compared to uncomplicated cysts (n = 8/32; 25%). CONCLUSION: Hydatid disease in not an uncommon problem. Around a fourth of patients, present with complications such as infection or intrabiliary rupture. The site, size, number of cysts and presence of complications govern the choice of surgical procedure. Complicated cysts can be successfully managed surgically with good long-term results.