A prospective, multicentric study to determine the safety and effectiveness of fixed-dose combination of camylofin dihydrochloride and nimesulide in patients presenting with acute colicky abdominal pain in India

Background:Spasmolytics and NSAIDs are a therapy of choice in colic pain. However, the tolerability and effectiveness of this combination remains unexplored. The aim of this prospective, single-arm, open label, multicenter study was to evaluate the safety and effectiveness of Anafortan-N�(fixed-dose combination of camylofin dihydrochloride 50 mg + nimesulide 100 mg) in patients with acute colicky abdominal pain.Methods: In all, 295 patients with acute colicky abdominal pain and at least one episode of colicky pain in the last 24 hours were enrolled in this study. None of the patients were hospitalized. All patients were advised Anafortan-N畉ablets twice daily orally for 5 days. The safety of Anafortan-N畐as assessed by number and percentage of patients with adverse events (AEs) and change in the severity and frequency of AEs by the end of treatment. The tolerability was determined by number and percentage of patients who hadto discontinue the treatment due to AEs. The effectiveness was evaluated as percentage change in the mean intensity of pain score (based on a 100-mm visual analog scale) from baseline to end of treatment.Results: Overall, 14 (4.7%) patients reported 14 AEs, all of which were treatment-emergent and non-serious. Of the 14 AEs, 7 AEs were mild, 6 AEs were moderate, and 1 AE was severe. No serious adverse events (SAEs) were reported. No adjustment of the study medication was required in response to any of the AEs, and none of the AEs led to discontinuation of the study treatment. At end of treatment(EOT), the pain intensity significantly (p<0.0001) reduced to 1.7�49 with a mean change of -69.9�.42 from baseline, and the daily pain intensity significantly (p<0.0001) reduced to 0.1�38 with a mean change of -3.5�77 from baseline.Conclusions: Among Indian patients presenting with acute abdominal colicky pain, twice daily treatment with a FDC of camylofin dihydrochloride 50 mg and nimesulide 100 mg (Anafortan-N�) showed significant reduction in pain intensity with very few side effects, thereby confirming its safety, tolerability, and effectiveness in acute colicky abdominal pain.

Bile salt incorporated polypyrrole thin film for ethanol sensing.

Polypyrrole (PPy)-bile salt composite was used for sensing ethanol vapor. PPy was synthesized by interface polymerization for subsequent fabrication of thin film of its composite with bile salt, by in-situ co-dispersion method and then exposed to ethanol vapour. Sensing was visualized through changes in morphological, structural and optical characterizations. The ethanol exposed film showed larger agglomeration as revealed in its surface morphology on scanning electron microscope (SEM) and greater crystallinity as seen through X-Ray diffraction (XRD). Fourier transform infra red (FTIR) and nuclear magnetic resonance spectroscopy (NMR) of the ethanol incorporated film also gave signature of the presence of bile salt and alcohol. Alcohol incorporation pattern resulted in increase in electrical conductance from 7.08539 × 10-5 mA/V to 8.0356 × 10-5 mA/V, as determined from current voltage characterizations. Average molecular weight (Mn) obtained from gel permeation chromatography changed from 6160 to 10300 on ethanol intake. Photoluminescence (PL) intensity was quenched and the PL peak shifted from 430 to 409 on ethanol exposure. Changes in morphological, structural, optical and electrical properties of the composite on ethanol exposure showed its prospective application for sensing ethanol.

Drug discovery in Tuberculosis: A molecular approach.

Summary: Despite unquestionable success of the combination drug therapy, tuberculosis (TB) very recently has drawn major attention because of the global upsurge of MDR-TB, XDR –TB and HIV-TB co-infection cases. In the last four decades, only one compound is added to the treatment regimen leaving ample opportunities to find out a new generation of TB drugs. The modern concept of drug discovery utilizes the integrated knowledge of genomics, proteomics, molecular biology and systems biology to identify more specific targets. The purpose of this review is to revisit the field of tuberculosis drug discovery based on those new concepts to identify novel targets.

A two-step genetic study on quantitative precursors of coronary artery disease in a homogeneous Indian population: Case–control association discovery and validation by transmission-disequilibrium test.

In spite of its strong familiality, gene identification for coronary artery disease (CAD) has not yielded a consistent picture. One major reason for this is that families or cases and controls were not recruited from a homogeneous population. We, therefore, attempted to map genes underlying 10 quantitative traits (QTs) that are known precursors of CAD in a homogeneous population (Marwari) of India. The QTs are apolipoprotein B (ApoB), C-reactive protein (CRP), fibrinogen (FBG), homocysteine (HCY), lipoprotein (a) (LPA), cholesterol – total (CHOL-T), cholesterol – HDL (CHOL-H), cholesterol – LDL (CHOL-L), cholesterol – VLDL (CHOL-V) and triglyceride (TG). We assayed 209 SNPs in 31 genes among members of Marwari families. After log-transformation and covariate-adjustment of the QTs, a two-step analysis was performed. In Step-1, data on unrelated individuals were analysed for association with the SNPs. In Step-2, for validation of Step-1 results, a quantitative transmission-disequilibrium test on parent– offspring data was performed for each SNP found to be significantly associated with a QT in Step-1 on an independent sample set drawn from the same population. Statistically significant results found for the various QTs and SNPs were: rs3774933, rs230528, rs230521, rs1005819 and rs1609798 (intronic, NFKB1) with APOB; rs5361 (Missense, R>S, SELE) and rs4648004 (Intronic, NFKB1) with FBG; rs4220 (Missense, K>R, FGB) with HCY; and rs3025035 (Intronic, VEGFA) with CHOL-H. SNPs in SELE, VEGFA, FGB and NFKB1 genes impact significantly on levels of quantitative precursors of CAD in Marwaris.

The posterior reversible encephalopathy syndrome.

The posterior/potentially reversible encephalopathy syndrome is a unique syndrome encountered commonly in hypertensive encephalopathy. A 13-year-old boy presented with of intermittent high grade fever, throbbing headache and non-projective vomiting for 5 days. The patient had a blood pressure of 120/80 mmHg but fundoscopy documented grade 3 hypertensive retinopathy. The patient improved symptomatically following conservative management. However, on the 5(th) post-admission day headache reappeared, and blood pressure measured at that time was 240/120 mmHg. Neuroimaging suggested white matter abnormalities. Search for the etiology of secondary hypertension led to the diagnosis of pheochromocytoma. Repeated MRI after successful surgical excision of the tumor patient showed reversal of white matter abnormalities. Reversible leucoencephalopathy due to pheochromocytoma have not been documented in literature previously.

Patterns of nucleotide sequence variation in ICAM1 and TNF genes in twelve ethnic groups of India: roles of demographic history and natural selection.

We have studied DNA sequence variation in and around the genes ICAM1 and TNF, which play functional and correlated roles in inflammatory processes and immune cell responses, in 12 diverse ethnic groups of India, with a view to investigating the relative roles of demographic history and natural selection in shaping the observed patterns of variation. The total numbers of single nucleotide polymorphisms (SNPs) detected at the ICAM1 and TNF loci were 29 and 12, respectively. Haplotype and allele frequencies differed significantly across populations. The site frequency spectra at these loci were significantly different from those expected under neutrality, and showed an excess of intermediate-frequency variants consistent with balancing selection. However, as expected under balancing selection, there was no significant reduction of F(ST) values compared to neutral autosomal loci. Mismatch distributions were consistent with population expansion for both loci. On the other hand, the phylogenetic network among haplotypes for the TNF locus was similar to expectations under population expansion, while that for the ICAM1 was as expected under balancing selection. Nucleotide diversity at the ICAM1 locus was an order of magnitude lower in the promoter region, compared to the introns or exons, but no such difference was noted for the TNF gene. Thus, we conclude that the pattern of nucleotide variation in these genes has been modulated by both demographic history and selection. This is not surprising in view of the known allelic associations of several polymorphisms in these genes with various diseases, both infectious and noninfectious.

Knowledge about heart attack and hypertension among individuals attending a cardiac camp in Pokhara city.

OBJECTIVES: Previous studies in other countries had shown lacunae in patients' and general publics' understanding of cardiovascular diseases. Such studies are lacking in Nepal. Hence the present study was carried out to: a) note the respondent's knowledge regarding myocardial infarction and hypertension and b) note the association, if any, of the knowledge with demographic and personal characteristics. MATERIALS AND METHODS: Respondents attending a cardiac camp organized in the Manipal Teaching hospital during September 2002 were interviewed by previously briefed seventh semester students using a structured questionnaire. Basic demographic information and knowledge about myocardial infarction and hypertension was collected. The median score was calculated. Differences in scores among different subgroups of respondents were noted using appropriate statistical tests (p<0.05). RESULTS: Sixty-six respondents were interviewed; 44 were male. The knowledge scores for heart attack and hypertension were 6 (maximum score 8) and 11 (maximum score 14) respectively. The scores were significantly lower among respondents with a monthly family income below 2000 rupees and was higher among respondents/family members suffering from cardiovascular disease. CONCLUSION: The respondents were aware of the basic facts regarding myocardial infarction and hypertension. However, lacunae in knowledge were noted. Further studies are required.

Multiorgan involvement due to cytomegalovirus infection in AIDS

Cytomegalovirus (CMV) infection is a relatively late complication of AIDS. Like other viruses contributing to co-morbidity of HIV infection, cytomegalovirus has the propensity to cause multiorgan involvement. We report the case of a 34-year-old seropositive man who presented with bilateral lower limb weakness and symptomatic pallor. He was already on antiretroviral drugs for a month prior to presentation. Detailed clinical examination and laboratory investigations revealed cytomegalovirus polyradiculoneuropathy associated with bone marrow dysplasia. Dysplasia of haematopoeitic cell lines occurs in 30 percent to 70 percent of HIV infected patients, and is often indistinguishable from myelodysplastic syndrome. However, in our case, the bone marrow picture reverted back to normal with treatment of the CMV infection, pointing to a possible role of CMV as the causative agent of bone marrow dysplasia. Moreover, CMV has been incriminated as a pathogen producing the immune reconstitution inflammatory syndrome. The onset of the disease in our case one month after initiation of HAART strongly raises the possibility of this being a case of CMV related IRIS. This is the first reported case where IRIS has presented with CMV polyradiculoneuropathy and bone marrow dysplasia. We would like to highlight that in today's era of HIV care, clinicians should be aware of the possibility of multiorgan involvement by CMV, for appropriate management of this disease in the background of AIDS.

High prevalence of metabolic syndrome and its correlates in two tribal populations of India and the impact of urbanization.

BACKGROUND AND OBJECTIVES: Metabolic syndrome is one of the major causes of morbidity and mortality in the world. The prevalence of this syndrome is high among Asians, including Indians, and is rising, particularly with the adoption of a modernized life style. Whether traditional societies in India have a low prevalence and the extent to which a transition to a modern life style contributes to the increase in prevalence are unknown. To examine the role of environmental and genetic factors in metabolic syndrome we conducted a study in two sub-Himalayan tribal populations with shared ancestry (Toto and Bhutia). The Toto live exclusively in a rural area, whereas a section of the Bhutia has adopted a modern life style. METHODS: Fasting (12 h) blood samples of Toto (n=258); rural Bhutia (n=75) and urban Bhutia (n=230) were collected, with written informed consent. Lipid profile, blood pressures, body fat and other anthropometric parameters were assessed. Criteria suggested by National Cholesterol Education Programme (NCEP) Adult Treatment Panel III (2001) were used for assessment of metabolic syndrome. RESULTS: The prevalence of metabolic syndrome was high (about 30-50%) among the Bhutia, with no significant rural-urban difference. Among the Toto, though the prevalence of metabolic syndrome was low (about 4-9%), their lipid levels were alarmingly adverse (about 37-67% had low HDLcholesterol or high triglyceride levels). There was an additional adverse impact of adoption of urban life-styles (perhaps primarily mediated through dietary changes) on cardiovascular risk factors. INTERPRETATION AND CONCLUSION: Our study suggested that metabolic syndrome and its correlates could be a major health problem even in traditional societies, indicating that this syndrome was not necessarily a result of modernization. Further, our study indicates that genetic factors that adversely affect the levels of such variables have long antiquities in Indian ethnic groups.

Intensive care unit drug utilization in a teaching hospital in Nepal.

OBJECTIVES: The intensive care unit (ICU) is a setting where a large number of drugs are administered to patients and the costs of hospitalization and drug treatment are high. Information on drug utilization in intensive care units (ICUs) are lacking in western Nepal. The present study was carried out to obtain information on the basic demographic pattern of the respondents, drug utilization during the study period, the antibiotic sensitivity patterns of isolated microorganisms and measure drug consumption in defined daily dose (DDD)/ 100 bed-days. METHODS: A retrospective analysis of patients admitted to the ICU of the Manipal Teaching hospital, Pokhara, Nepal during the time period from 01/02/2002 to 31/05/2002 was carried out. The ICU mortality rate, length of stay greater than 7 days and median length of stay were calculated. RESULTS: A total of 259 individuals were admitted. The ICU mortality rate was 15.4%; median length of stay was 4 days. E.coli, H.influenzae, K.pneumoniae, S.aureus and P.aeruginosa were the common organisms isolated and were found to be resistant to some of the commonly used antibiotics. Mean +/- SD number of drugs and cost of drugs were 5.1 +/- 2.7 and 1958.5 +/- 1267.8 Nepalese rupees (25.1 +/- 16.2 US dollars). Total drug consumption was 356.4 DDD/100 bed-days. Consumption of intravenous fluids was 25.8 litres/100 bed-days. CONCLUSIONS: An antibiotic use policy should be framed. Formation of a multidisciplinary team to oversee drug use and periodically review microbial sensitivity patterns will be helpful. Longitudinal surveillance of ICU drug use should be carried out.

A comparison of two popular statistical methods for estimating the time to most recent common ancestor (TMRCA) from a sample of DNA sequences.

We have compared two statistical methods of estimating the time to most recent common ancestor (TMRCA) from a sample of DNA sequences, which have been proposed by Templeton (1993) and Bandelt et al. (1995). Monte-Carlo simulations were used for generating DNA sequence data. Different evolutionary scenarios were simulated and the estimation procedures were evaluated. We have found that for both methods (i) the estimates are insensitive to demographic parameters and (ii) the standard deviations of the estimates are too high for these methods to be reliably used in practice.