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Showing papers in "Indian Journal of Medical Research in 2010"


Journal Article
TL;DR: This work reviews the currently available bone graft and graft substitutes for the novel therapeutic approaches in clinical setting of orthopaedic surgery and suggests two new approaches that may be suitable for use in the treatment of delayed union, malunion, and nonunion.
Abstract: Treatment of delayed union, malunion, and nonunion is a challenge to the orthopaedic surgeons in veterinary and human fields. Apart from restoration of alignment and stable fixation, in many cases adjunctive measures such as bone-grafting or use of bone-graft substitutes are of paramount importance. Bone-graft materials usually have one or more components: an osteoconductive matrix, which acts as scaffold to new bone growth; osteoinductive proteins, which support mitogenesis of undifferentiated cells; and osteogenic cells, which are capable of forming bone in the appropriate environment. Autologous bone remains the "gold standard" for stimulating bone repair and regeneration, but its availability may be limited and the procedure to harvest the material is associated with complications. Bone-graft substitutes can either substitute autologous bone graft or expand an existing amount of autologous bone graft. We review the currently available bone graft and graft substitutes for the novel therapeutic approaches in clinical setting of orthopaedic surgery.

389 citations


Journal Article
TL;DR: It is suggested that adherence is a multi-factorial, complex clinical problem that requires similarly designed approaches to effectively address poor CPAP adherence in the OSA population.
Abstract: Adherence to continuous positive airway pressure (CPAP) treatment for obstructive sleep apnoea (OSA) is a critical problem. Poor adherence (30-60%) to CPAP is widely recognized as a significant limiting factor in treating OSA, reducing the overall effectiveness of the treatment and leaving many OSA patients at heightened risk for co-morbid conditions, impaired function and quality of life. The extant literature examining adherence to CPAP provides critical insight to measuring adherence outcomes, defining optimal adherence levels, and predicting CPAP adherence. This research has revealed salient factors that are associated with or predict CPAP adherence and may guide the development of interventions to promote CPAP adherence. Over the past 10 years, intervention studies to promote CPAP adherence have incorporated a multitude of strategies including education, support, cognitive behavioural approaches, and mixed strategies. This review of the current status of research on CPAP adherence will (i) synthesize the extant literature with regard to measuring, defining, and predicting CPAP adherence; (ii) review published intervention studies aimed at promoting CPAP adherence; and (iii) suggest directions for future empiric study of adherence to CPAP that will have implications for translational science. Our current understanding of CPAP adherence suggests that adherence is a multi-factorial, complex clinical problem that requires similarly designed approaches to effectively address poor CPAP adherence in the OSA population.

272 citations


Journal Article
TL;DR: In this large study of community-based sample in Kerala, high burden of NCD risk factors was observed, comparable to that in the United States, suggesting that anthropometric variables may not be useful surrogates for biochemical risk factors for population screening purposes.
Abstract: Background & objectives: Kerala State is a harbinger of what will happen in future to the rest of India in chronic non-communicable diseases (NCD). We assessed: (i) the burden of NCD risk factors; (ii) estimated the relations of behavioural risk factors to socio-demographic correlates, anthropometric risk factors with behavioural risk factors; (iii) evaluated if socio-demographic, behavioural and anthropometric risk factors predicted biochemical risk factors; and (iv) estimated awareness, treatment and adequacy of control of hypertension and diabetes, in Kerala state. Methods: A total of 7449 individuals (51% women) stratified by age group, sex and place of residence were selected and information on behavioural risk factors; tobacco use, diet, physical activity, alcohol use, measured anthropometry, blood pressure was collected. Fasting blood samples were analysed for blood glucose, total cholesterol, high density lipoprotein cholesterol and triglycerides in a sample subset. Using multiple logistic regression models the associations between socio-demographic and anthropometric variables with biochemical risk factors were estimated. Results: The burden of NCD risk factors was high in our sample. Prevalence of behavioural and each of the biochemical risk factors increased with age, adjusting for other factors including sex and the place of residence. The odds ratios relating anthropometric variables to biochemical variables were modest, suggesting that anthropometric variables may not be useful surrogates for biochemical risk factors for population screening purposes. Interpretation & conclusions: In this large study of community-based sample in Kerala, high burden of NCD risk factors was observed, comparable to that in the United States. These data may serve to propel multisectoral efforts to lower the community burden of NCD risk factors in India in general, and in Kerala, in particular.

266 citations


Journal Article
TL;DR: Intestinal absorption of curcumin was relatively higher when administered concomitantly with piperine, and it stayed significantly longer in the body tissues, compared to other two compounds.
Abstract: Maximum distribution of 24.4 per cent of administered capsaicin was seen at 1 h, while no intact capsaicin was detectable after 4 days. Absorption of capsaicin was about 94 per cent and very rapid relative to other two compounds. A maximum of 10.8 per cent of administered piperine was seen in tissues at 6 h. Absorption of the administered piperine was about 96 per cent. Curcumin concentration

236 citations


Journal Article
TL;DR: This review provides a brief account on various biomarkers for diagnosis, prognosis and therapeutic purposes, which include markers already in clinical practice as well as various upcoming biomarkers.
Abstract: In the recent years, knowledge about cancer biomarkers has increased tremendously providing great opportunities for improving the management of cancer patients by enhancing the efficiency of detection and efficacy of treatment. Recent technological advancement has enabled the examination of many potential biomarkers and renewed interest in developing new biomarkers. Biomarkers of cancer could include a broad range of biochemical entities, such as nucleic acids, proteins, sugars, lipids, and small metabolites, cytogenetic and cytokinetic parameters as well as whole tumour cells found in the body fluid. A comprehensive understanding of the relevance of each biomarker will be very important not only for diagnosing the disease reliably, but also help in the choice of multiple therapeutic alternatives currently available that is likely to benefit the patients. This review provides a brief account on various biomarkers for diagnosis, prognosis and therapeutic purposes, which include markers already in clinical practice as well as various upcoming biomarkers.

221 citations


Journal Article
TL;DR: The principle of treatment of sleep disorders is first to find cause of the sleep disturbance and vigorously treat the co-morbid conditions causing theSleep disorders are briefly described in this chapter.
Abstract: Sleep is defined on the basis of behavioural and physiological criteria dividing it into two states: non rapid eye movement (NREM) sleep which is subdivided into three stages (N1, N2, N3); and rapid eye movement (REM) sleep characterized by rapid eye movements, muscle atonia and desynchronized EEG. Circadian rhythm of sleep-wakefulness is controlled by the master clock located in the suprachiasmatic nuclei of the hypothalamus. The neuroanatomical substrates of the NREM sleep are located principally in the ventrolateral preoptic nucleus of the hypothalamus and those of REM sleep are located in pons. A variety of significant physiological changes occur in all body systems and organs during sleep as a result of functional alterations in the autonomic and somatic nervous systems. The international classification of sleep disorders (ICSD, ed 2) lists eight categories of sleep disorders along with appendix A and appendix B. The four major sleep complaints include excessive daytime sleepiness, insomnia, abnormal movements or behaviour during sleep and inability to sleep at the desired time. The most important step in assessing a patient with a sleep complaint is obtaining a detailed history including family and previous histories, medical, psychiatric, neurological, drug, alcohol and substance abuse disorders. Some important laboratory tests for investigating sleep disorders consist of an overnight polysomnography, multiple sleep latency and maintenance of wakefulness tests as well as actigraphy. General physicians should have a basic knowledge of the salient clinical features of common sleep disorders, such as insomnia, obstructive sleep apnoea syndrome, narcolepsy-cataplexy syndrome, circadian rhythm sleep disorders (e.g., jet leg, shift work disorder, etc.) and parasomnias (e.g., partial arousal disorders, REM behaviour disorder, etc.) and these are briefly described in this chapter. The principle of treatment of sleep disorders is first to find cause of the sleep disturbance and vigorously treat the co-morbid conditions causing the sleep disturbance. If a satisfactory treatment is not available for the primary condition or does not resolve the problem, the treatment should be directed at the specific sleep disturbance. Most sleep disorders, once diagnosed, can be managed with limited consultations. The treatment of primary sleep disorders, however, is best handled by a sleep specialist. An overview of sleep and sleep disorders viz., Basic science; international classification and approach; and phenomenology of common sleep disorders are presented.

194 citations


Journal Article
TL;DR: A holistic approach to tackle the childhood obesity epidemic needs a collection of activities including influencing policy makers and legislation, mobilizing communities, restructuring organizational practices, establishing coalitions and networks, empowering providers, imparting community education as well as enriching and reinforcing individual awareness and skills.
Abstract: Worldwide, obesity trends are causing serious public health concern and in many countries threatening the viability of basic health care delivery. It is an independent risk factor for cardiovascular diseases and significantly increases the risk of morbidity and mortality. The last two decades have witnessed an increase in health care costs due to obesity and related issues among children and adolescents. Childhood obesity is a global phenomenon affecting all socio-economic groups, irrespective of age, sex or ethnicity. Aetiopathogenesis of childhood obesity is multi-factorial and includes genetic, neuroendocrine, metabolic, psychological, environmental and socio-cultural factors. Many co-morbid conditions like metabolic, cardiovascular, psychological, orthopaedic, neurological, hepatic, pulmonary and renal disorders are seen in association with childhood obesity. The treatment of overweight and obesity in children and adolescents requires a multidisciplinary, multi-phase approach, which includes dietary management, physical activity enhancement, restriction of sedentary behaviour, pharmacotherapy and bariatric surgery. A holistic approach to tackle the childhood obesity epidemic needs a collection of activities including influencing policy makers and legislation, mobilizing communities, restructuring organizational practices, establishing coalitions and networks, empowering providers, imparting community education as well as enriching and reinforcing individual awareness and skills. The implications of this global phenomenon on future generations will be serious unless appropriate action is taken.

187 citations


Journal Article
TL;DR: Sleep disturbances secondary to dementia and Parkinson's disease are usually problematic for the patient as well as the caregiver, whether in the home or in the nursing home, and proper management is beneficial in terms of delaying institutionalization and reducing nursing care costs.
Abstract: Nearly half of older adults report difficulty initiating and maintaining sleep. With age, several changes occur that can place one at risk for sleep disturbance including increased prevalence of medical conditions, increased medication use, age-related changes in various circadian rhythms, and environmental and lifestyle changes. Although sleep complaints are common among all age groups, older adults have increased prevalence of many primary sleep disorders including sleep-disordered breathing, periodic limb movements in sleep, restless legs syndrome, rapid eye movement (REM) sleep behaviour disorder, insomnia, and circadian rhythm disturbances. The present review discusses age-related changes in sleep architecture, aetiology, presentation, and treatment of sleep disorders prevalent among the elderly and other factors relevant to ageing that are likely to affect sleep quality and quantity.

165 citations


Journal Article
TL;DR: In vitro anti-tubercular activity of five medicinal plants showed that all these plants exhibited activity against MDR isolates of M. tuberculosis, and in BacT/ALERT also, extracts of these plants showed significant inhibition against M.culosis.
Abstract: Background & objectives Emergence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) strains of Mycobacterium tuberculosis has further complicated the problem of tuberculosis (TB) control. Medicinal plants offer a hope for developing alternate medicines for the treatment of TB. The present study was done to evaluate in vitro anti-tubercular activity of five medicinal plants viz., Acalypha indica, Adhatoda vasica, Allium cepa, Allium sativum and Aloe vera. Methods Aqueous extracts of leaves of A. indica, A. vasica, bulbs of A. cepa, cloves of A. sativum and pure gel of A. vera leaves, were tested in vitro for their activity against two MDR isolates (DKU-156 and JAL-1236), reference susceptible strain M. tuberculosis H37Rv as well as rapid grower mycobacterial pathogen M. fortuitum (TMC-1529) using Lowenstein Jensen (L-J) medium and colorimetric BacT/ ALERT 3D system. Activity in L-J medium was evaluated by percentage inhibition which was calculated by mean reduction in number of colonies on extract containing as compared to extract free controls. Results Extracts of all the five plants A. indica, A. vasica, A. cepa, A. sativum and A. vera exhibited anti-tuberculosis activity in L-J medium, the proportion of inhibition of these plants extract in respect mentioned above is 95, 32, 37, 72, 32 per cent, respectively for MDR isolate DKU-156 and 68, 86, 79, 72, 85 per cent, respectively for another MDR isolate JAL-1236, while for sensitive M. tuberculosis H37Rv, inhibition was found to be 68, 70, 35, 63 and 41 per cent, at 4 per cent v/v concentration in L-J medium. There was no inhibition against rapid grower M. fortuitum (TMC-1529). In BacT/ALERT also, extracts of these plants showed significant inhibition against M. tuberculosis. Interpretation & conclusion Our findings showed that all these plants exhibited activity against MDR isolates of M. tuberculosis. While the anti-TB activity of A. vera, A. vasica and A. sativum against MDR isolates confirm earlier results, activity of the extracts of A. indica and A. cepa is reported for the first time. Further studies aimed at isolation and identification of active substances from the extracts which exhibited promising activities, need to be carried out.

161 citations


Journal Article
TL;DR: The present study showed a high occurrence of NSI in HCWs with a high rate of ignorance and apathy, which need to be addressed, through appropriate education and other interventional strategies by the hospital infection control committee.
Abstract: Background & objectives: Percutaneous injuries caused by needlesticks, pose a significant risk of occupational transmission of bloodborne pathogens. Their incidence is considerably higher than current estimates, and hence a low injury rate should not be interpreted as a non existent problem. The present study was carried out to determine the occurrence of NSI among various categories of health care workers (HCWs), and the causal factors, the circumstances under which these occur and to, explore the possibilities of measures to prevent these through improvements in knowledge, attitude and practice. Methods: The study group consisted of 428 HCWs of various categories of a tertiary care hospital in New Delhi, and was carried out with the help of an anonymous, self-reporting questionnaire structured specifically to identify predictive factors associated with NSIs. Results: The commonest clinical activity to cause the NSI was blood withdrawal (55%), followed by suturing (20.3%) and vaccination (11.7%). The practice of recapping needles after use was still prevalent among HCWs (66.3%). Some HCWs also revealed that they bent the needles before discarding (11.4%). It was alarming to note that only 40 per cent of the HCWs knew about the availability of PEP services in the hospital and 75 per cent of exposed nursing students did not seek PEP. Interpretation & conclusions: The present study showed a high occurrence of NSI in HCWs with a high rate of ignorance and apathy. These issues need to be addressed, through appropriate education and other interventional strategies by the hospital infection control committee.

155 citations


Journal ArticleDOI
TL;DR: By examining similar experiences globally, this review provides the scenario of CVD in India and the need for a surveillance system and outlines the scope ofCVD surveillance in India.
Abstract: There is a rise of non-communicable diseases (NCDs) burden, which is causing increasing morbidity and premature mortality in developing countries. In 1990, cardiovascular diseases (CVD) accounted for 63 per cent of all deaths and India contributed to 17 per cent to the worldwide mortality. Several surveys conducted across the country over the past two decades have shown a rising prevalence of major risk factors for CVD in urban and rural populations. These surveys are limited by their generalisability to other parts of the country, and more was required to roll out of an action plan. There was lack of an organized national system for monitoring these risk factors over time so as to inform policy and programme for appropriate interventions. The Indian Council of Medical Research (ICMR) leveraged its research on NCD risk factor surveillance to the development of the national plan under the Integrated Disease Surveillance Project (IDSP) which will obtain State-based prevalence of selected risk factors. This review provides the scenario of CVD in India and the need for a surveillance system. By examining similar experiences globally, it outlines the scope of CVD surveillance in India.

Journal Article
TL;DR: Essential oil from the leaves of L. camara possesses adulticidal activity against different mosquito species that could be utilized for development of oil-based insecticide as supplementary to synthetic insecticides.
Abstract: Background & objectives Development of insect resistance to synthetic pesticides, high operational cost and environmental pollution have created the need for developing alternative approaches to control vector-borne diseases. In the present study we have investigated the insecticidal activity of essential oil isolated from the leaves of Lantana camara against mosquito vectors. Methods Essential oil was isolated from the leaves of L. camara using hydro-distillation method. Bioassay test was carried out by WHO method for determination of adulticidal activity against mosquitoes. Different compounds were identified by gas chromatography-mass spectrometry analysis. Results LD(50) values of the oil were 0.06, 0.05, 0.05, 0.05 and 0.06 mg/cm(2) while LD(90) values were 0.10, 0.10, 0.09, 0.09 and 0.10 mg/cm(2) against Ae. aegypti, Cx. quinquefasciatus, An. culicifacies, An. fluvialitis and An. stephensi respectively. KDT(50) of the oil were 20, 18, 15, 12, and 14 min and KDT(90) values were 35, 28 25, 18, 23 min against Ae. aegypti, Cx. quinquefasciatus, An. culicifacies, An. fluviatilis and An. stephensi, respectively on 0.208 mg/cm(2) impregnated paper. Studies on persistence of essential oil of L. camara on impregnated paper revealed that it has more adulticidal activity for longer period at low storage temperature. Gas chromatographic-mass spectrometric analysis of essential oil showed 45 peaks. Caryophyllene (16.37%), eucalyptol (10.75%), alpha-humelene (8.22%) and germacrene (7.41%) were present in major amounts and contributed 42.75 per cent of the total constituents. Interpretation & conclusions Essential oil from the leaves of L. camara possesses adulticidal activity against different mosquito species that could be utilized for development of oil-based insecticide as supplementary to synthetic insecticides.

Journal Article
TL;DR: Investigation of patients with established type 2 diabetes attending a tertiary care hospital in north India showed high prevalence of depression in patients with T2DM and the risk factors for depression were age, central obesity, diabetic complications particularly neuropathy and diabetic foot disease and increased pill burden.
Abstract: Background & objectives: Depression is common among people with diabetes and it is associated with poor outcomes. This study was carried out to investigate the prevalence and determinants of depression in patients with established type 2 diabetes (T2DM) attending a tertiary care hospital in north India. Methods: Patients with established T2DM were evaluated for depression by administering the nineitem PHQ-9 (Hindi version). Binary logistic regression model was used to examine association between predictor variables and risk of depression. Results were expressed as odds ratio and 95 per cent confidence interval. Cronbach alpha was calculated to assess internal consistency of PHQ-9. Results: Patients with T2DM (n=300) were evaluated [147(49%) male and 153(51%) female]. The median duration of diabetes (IQ) was 8(4-13) yrs. Of the study patients, 68 (23%) met the criteria for major depression, 54 (18%) for moderate depression and the remaining 178 (59%) had no clinically significant depression. Depression was strongly associated with age >54 yr (OR 1.26, 95% CI 1.02-1.67; P 4) (OR 1.27, 95%CI 1.01-1.44; P=0.035 ). However, the likelihood of depression was not significant with duration of diabetes and insulin use. Interpretation & conclusion: This study showed high prevalence of depression in patients with T2DM. The risk factors for depression were age, central obesity, diabetic complications particularly neuropathy and diabetic foot disease and increased pill burden.

Journal Article
TL;DR: There is accumulating evidence that OSA is being considered as an independent risk factor for hypertension, glucose intolerance / diabetes mellitus, cardiovascular diseases and stroke, leading to increased cardiometabolic morbidity and mortality.
Abstract: Obstructive sleep apnoea (OSA) is increasingly being recognized as an important health issue in the last two to three decades. It is characterized by frequent episodes of upper airway collapse during sleep, causing recurrent arousals, intermittent hypoxaemia, sleep fragmentation and poor sleep quality. There is accumulating evidence that OSA is being considered as an independent risk factor for hypertension, glucose intolerance / diabetes mellitus, cardiovascular diseases and stroke, leading to increased cardiometabolic morbidity and mortality. The prevalence rates of OSA have been estimated in the range of 2 to 10 per cent worldwide, and the risk factors for obstructive sleep apnoea include advanced age, male sex, obesity, family history, craniofacial abnormalities, smoking and alcohol consumption. The common clinical presenting symptoms are heavy snoring, witnessed apnoeas and daytime hypersomnolence, which would help to identify the affected individuals. With increasing awareness of this disease entity and associated complications in our society, there have been increased referrals to sleep physicians or expertise for further investigations and diagnostic evaluation. Early recognition and treatment of obstructive sleep apnoea may prevent from adverse health consequences. Some of the epidemiological aspects of obstructive sleep apnoea in adults are reviewed.

Journal Article
TL;DR: Older age, poor nutritional status including baseline hypoalbuminaemia were independent predictors of occurrence of anti-TB DIH and Clinicians should be vigilant for occurrence of hepatotoxicity in this high risk group.
Abstract: Background & objectives: Antituberculosis (anti-TB) drug induced hepatotoxicity (DIH) is the most common side effect leading to interruption of therapy. Wide variations have been found in the reported incidence of hepatotoxicity during short-course chemotherapy. Several risk factors for hepatotoxicity have been suggested in previous studies. We undertook a prospective case-control study to assess the role of these putative risk factors in the development of DIH in patients receiving anti-TB treatment. Methods: One hundred and seventy five consecutive cases with a diagnosis of anti-TB DIH were compared with 428 consecutive controls who took anti-TB drugs for the full duration of chemotherapy without clinical or biochemical evidence of hepatitis. Cases positive for markers of acute viral hepatitis were carefully excluded. Cases and controls were compared with respect to age, sex, site of tuberculosis, radiological extent of disease on chest radiograph, body mass index (BMI), mid-arm circumference (MAC) and liver function at baseline which included serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum total protein and serum albumin. Results: Univariate logistic regression revealed that the risk of developing DIH was greater in older patients. Significantly greater percentage of cases had extrapulmonary tuberculosis (TB) ( P 35 yr, MAC <20 cm and hypoalbuminaemia (albumin <3.5 g/dl).

Journal Article
TL;DR: Comprehensive hypertension management focuses on reducing overall cardiovascular risk by lifestyle measures, BP lowering and lipid management and should be the preferred initial treatment approach.
Abstract: High blood pressure (BP) is a major public health problem in India and its prevalence is rapidly increasing among urban and rural populations. Reducing systolic and diastolic BP can decrease cardiovascular risk and this can be achieved by non-pharmacological (lifestyle measures) as well as pharmacological means. Lifestyle changes should be the initial approach to hypertension management and include dietary interventions (reducing salt, increasing potassium, alcohol avoidance, and multifactorial diet control), weight reduction, tobacco cessation, physical exercise, and stress management. A number of pharmaceutical agents, well evidenced by large randomized clinical trials, are available for initial treatment of high BP. These include older molecules such as thiazide diuretics and beta-blocking agents and newer molecules, dihydropyridine calcium channel blockers (CCB), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARB). In view of the recent clinical trials data, some international guidelines suggest that CCB, ACE inhibitors or ARB and not beta-blockers or diuretics should be the initial therapy in hypertension management. Comprehensive hypertension management focuses on reducing overall cardiovascular risk by lifestyle measures, BP lowering and lipid management and should be the preferred initial treatment approach.

Journal Article
TL;DR: The present review provides an insight into the research conducted on animals as well as on human subjects for providing the concept that zinc deficiency is an important factor in the development and progression of malignancy and that zinc could be efficacious in the prevention and treatment of several cancers.
Abstract: Proper intake of dietary nutrients is considered crucial for preventing the initiation of events leading to the development of carcinoma. Many dietary compounds have been considered to contribute in cancer prevention including zinc, which plays a pivotal role in host defense against the initiation and promotion of several malignancies. Zinc is an essential element that is integral to many proteins and transcription factors which regulate key cellular functions such as the response to oxidative stress, DNA replication, DNA damage repair, cell cycle progression, and apoptosis. Zinc has been ascribed roles in the metabolism and interaction of malignant cells, particularly in apoptosis. Zinc is involved in structural stabilization and activation of the p53 that appears to be an important component of the apoptotic process and also in activation of certain members of the caspase family of proteases. Zinc exerts a positive beneficial effect against chemically induced preneoplastic progression in rats and provides an effective dietary chemopreventive approach to disease in vulnerable section of population with family history of carcinoma. The present review provides an insight into the research conducted on animals as well as on human subjects for providing the concept that zinc deficiency is an important factor in the development and progression of malignancy and that zinc could be efficacious in the prevention and treatment of several cancers viz., colon, pancreas, oesophageal and head and neck. However, it needs further exploration with regard to other definitive bioassays including protein expression and documentation of specific molecular markers to establish the exact mechanism for zinc-mediated cancer chemoprevention. Preclinical trials need to investigate the genetic and epigenetic pathways of chemoprevention by zinc.

Journal Article
TL;DR: Current status of efforts in addressing daunting tasks and challenges in developing therapeutics against chronic and rapidly changing hepatitis C virus is dealt with.
Abstract: Hepatitis C virus (HCV) is a small (approximately 55 to 65 nm), spherical, enveloped, hepatotropic RNA virus that causes acute and chronic hepatitis in humans. Persistent virus infection with HCV often leads to cirrhosis and hepatocellular carcinoma (HCC). At present there is neither a selective antiviral therapy nor a preventive vaccine. The only available treatment option is a long-acting pegylated-interferon-alpha, given in combination with nucleoside analog ribavirin, which is not very effective. Molecular studies of HCV began with the successful cloning of its genome in 1989. For many years, research to develop therapeutics was stalled by the inability to grow virus in tissue culture. A major milestone was achieved with the recent development of a robust cell culture system for HCV propagation. HCV proteins assemble and form replication complexes on modified host membranes, called as membranous webs. Even though HCV is detected and targeted by host immune mechanisms, it establishes and maintains a life-long persistent infection. HCV has evolved multiple strategies to survive and persist in hostile cellular environments; and the viral population is known to rapidly change during the course of a natural infection thereby escaping immune surveillance. Rapid mutations also help virus to survive by selecting for the variants which are resistant to antiviral drugs. Although precise mechanisms regulating HCV entry into hepatic cells via receptors remain unknown, HCV also has the capability of direct cell-to-cell transmission. The extremely complex and incompletely understood nature of the HCV lifecycle has complicated the discovery of new therapies. A complete understanding of the functional roles played by the HCV proteins during HCV lifecycle is vital for developing a successful cure. This review deals with current status of efforts in addressing these daunting tasks and challenges in developing therapeutics against chronic and rapidly changing hepatitis C virus.

Journal Article
TL;DR: Paediatric UTI was common in children with male gender, age<1 yr, and in children suffering from VUR and PUV, with a preponderance of nosocomial multi-drug resistant pathogens.
Abstract: Results: Significant bacteriuria was found in 558 children (28.3%). Male gender (25.6%), age < 1 yr (77.5%), vesicoureteric reflux disease (VUR) (19.9%) and posterior urethral valve (PUV) (27.6%) were common risk factors in children suffering from UTI. Pyuria was detected in 53.6 per cent of infections. Common uropathogens isolated were Escherichia coli (47.1%), Klebsiella spp. (15.6%), Enterococcus fecalis (8.7%), members of tribe Proteae (5.9%), Pseudomonas aeruginosa (5.9%) and Candida spp. (5.5%). Against lactose fermenting Enterobacteriaceae, in-vitro resistance was least against amikacin (32.5%), nitrofurantoin (26.7%) and imipenem (3.7%). Among enterococci, vancomycin resistant enterococci constituted 12 per cent of the strains. 93.4 per cent of the UTI detected was nosocomial. Interpretation & conclusion: Paediatric UTI was common in children with male gender, age < 1 yr, and in children suffering from VUR and PUV. Spectrum of pathogens causing paediatric UTI in our center had a preponderance of nosocomial multi-drug resistant pathogens.

Journal Article
TL;DR: RFLP yielded homogeneous band pattern, suggesting that there may be a point source or a common evolutionary origin for all the ESBL isolates, which were initially screened by phenotypic method.
Abstract: Background & objectives Extended spectrum beta lactamases (ESBLs) have been observed in virtually all the species of family Enterobacteriaceae. The enzymes are predominantly plasmid mediated and are derived from broad-spectrum beta lactamase TEM-1, TEM-2 or SHV-1 by a limited number of mutations. This study was undertaken to characterize ESBL producers among Escherichia coli and Klebsiella pneumoniae by PCR-RFLP, which were initially screened by phenotypic method. Methods A total of 100 isolates of each species (E. coli and K. pneumoniae) were screened for ESBL production. PCR analysis for β-lactamase genes of the family TEM and SHV was also carried out. PCR products of TEM and SHV genes were subjected to digest with three different restriction enzymes. The digested products were run on 1.5 per cent agarose gel, stained and examined for DNA bands. Results PCR carried out on plasmid DNA alone detected 30 per cent ESBL positive isolates using TEM primer and 38 per cent using SHV primer, whereas PCR for both plasmid and chromosomal DNA showed 56 per cent positivity for TEM and 60 per cent positivity for SHV. Interpretation & conclusion RFLP yielded homogeneous band pattern, suggesting that there may be a point source or a common evolutionary origin for all the ESBL isolates.

Journal ArticleDOI
TL;DR: The evidence from INTERHEART provides rationale for developing treatment algorithms and treatment guidelines for CHD at various levels of health care and answer for the quest for a single reliable biomarker, Apo B/ApoA 1 ratio, that can predict the future CHD risk among individuals.
Abstract: Coronary heart diseases (CHD) have reached epidemic proportions among Indians. The recently concluded INTERHEART study emphasizes the role of behavioural and conventional risk factors in the prediction of CHD risk among Indians. These findings have implication for the health care providers and policy makers in the country due to the fact that all these conventional risk factors are potentially modifiable and are good starting points for prevention. The policy measures by means of legislation and regulatory approaches on agriculture and food industry or tobacco or physical activity will have large impact on CHD risk factor reduction in the population. In addition, the health system needs to focus on: (i) providing information for increasing awareness and an enabling environment for adoption of healthy living habits by the community; (ii) early detection of persons with risk factors and cost-effective interventions for reducing risk; and (iii) early detection of persons with clinical disease and cost-effective secondary prevention measures to prevent complications. The evidence from INTERHEART provides rationale for developing treatment algorithms and treatment guidelines for CHD at various levels of health care. In addition, INTERHEART provides answer for the quest for a single reliable biomarker, Apo B/ApoA 1 ratio that can predict the future CHD risk among individuals. Further to this, the INTERHEART study also opens up several unanswered questions on the pathobiology of the premature onset of myocardial infarction among Indians and calls for the need to developing capacity in clinical research in CHD in India.

Journal Article
TL;DR: The lacunae along with the current status of molecular events underlying insulin resistance and the contribution of insulin signaling pathway genes in pathogenesis of PCOS are described along with future researchable areas.
Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of unknown etiology. Insulin resistance is very common and plays a central pathogenic role in PCOS. During last decade several studies have been conducted to understand the mechanisms contributing to the state of insulin resistance and insulin-induced hyperandrogenemia in PCOS. Insulin signaling pathways have been dissected in different insulin responsive tissues such as skeletal muscles, adipose tissues, fibroblasts as well as ovaries to elucidate the mechanism. These studies suggest a post receptor signaling defect where metabolic action of insulin is affected but not the steroidogenic and mitogenic actions. Despite advancement in these studies gaps exist in our understanding of the mechanism of insulin resistance as well as insulin- induced steroidogenesis in PCOS. The syndrome is now considered as a complex multigenic disorder. Efforts are ongoing to dissect the variants of genes from multiple logical pathways which are involved in pathophysiology of the syndrome. But still today no gene has been emerged as universally accepted susceptibility gene for PCOS. This review briefly describes the lacunae along with the current status of molecular events underlying insulin resistance and the contribution of insulin signaling pathway genes in pathogenesis of PCOS along with future researchable areas.

Journal Article
TL;DR: Sleep-disordered breathing in children is a spectrum that combines obstructive sleep apnoea syndrome and the upper airway resistance syndrome and studies that do not take into account this spectrum may misclassify symptomatic patients as 'primary snorers'.
Abstract: Sleep disordered breathing (SDB) is increasingly being recognised as a cause of morbidity even in young children. With an estimated prevalence of 1 to 4 per cent, SDB results from having a structurally narrow airway combined with reduced neuromuscular tone and increased airway collapsibility. SDB in children differs from adults in a number of ways, including presenting symptoms and treatment. Presentation may differ according to the age of the child. Children have a more varied presentation from snoring and frequent arousals to enuresis to hyperactivity. Those with Down syndrome, midface hypoplasia or neuromuscular disorders are at higher risk for developing SDB. First line definitive treatment in children involves tonsillectomy and adenoidectomy. Rapid maxillary expansion, allergy treatment and continuous positive airway pressure (CPAP) are other options. As untreated SDB results in complications as learning difficulties, memory loss and a long term increase in risk of hypertension, depression and poor growth, it is important to diagnose SDB.

Journal ArticleDOI
TL;DR: An overview of the role of social determinants of CVD and its possible conceptual pathways with special focus on acute coronary syndrome (ACS) outcomes among Indians is provided.
Abstract: Cardiovascular diseases (CVD) are the leading cause of death and disability in both developed and developing countries. In developed countries socio-economic mortality differentials have been studied extensively showing that the low socio-economic group suffers the highest mortality. As the epidemiological transition is taking place against a background of economic globalization, CVD risk factors among the urban poor and middle class are rapidly increasing in India. Recent evidences from India also suggest reversal of social gradient with excess burden of CVD morbidity in the low socio-economic group. Understanding the social determinants of environmental and behavioural exposures, in determining the risk factors for cardiovascular disease is an important challenge for public health professionals as well as communities. Socio-economic disadvantage is not simply a proxy for poor cardiovascular risk factor status, but also an indication of the likely trajectory that an individual or a community may follow in the course of their life. The paucity of intervention research seeking to address the role of social determinants in shaping lifestyle practices among individuals in culturally and socially diverse population groups within India is definitely a measure of inadequacy in public health research. This review article provides an overview of the role of social determinants of CVD and its possible conceptual pathways with special focus on acute coronary syndrome (ACS) outcomes among Indians.

Journal Article
TL;DR: This paper seeks to sort through unwieldy evidence, keeping these findings in perspective, to deliver a clearer message for the context of South Asia and cardio-metabolic risk management.
Abstract: Coronary heart disease (CHD) is currently the leading cause of death worldwide and together with diabetes, poses a serious health threat, particularly in the Indian Asian population. Risk factor management has evolved considerably with the continued emergence of new and thought-provoking evidence. The stream of laboratory- and population-based research findings as well as unresolved controversies may pose dilemmas and conflicting impulses in most clinicians, and even in our more well-informed patients. As results of the most recent clinical trials on glycaemic control for macrovascular risk reduction are woven into concrete clinical practice guidelines, this paper seeks to sort through unwieldy evidence, keeping these findings in perspective, to deliver a clearer message for the context of South Asia and cardio-metabolic risk management.

Journal Article
TL;DR: The present review focuses on both warfare potential and medical uses of botulinum neurotoxin, the first biological toxin which is licensed for treatment of human diseases, as a military or terrorist weapon.
Abstract: Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle associated proteins responsible for acetylcholine release into the neuromuscular junction. As a military or terrorist weapon, botulinum toxin could be disseminated via aerosol or by contamination of water or food supplies, causing widespread casualties. A fascinating aspect of botulinum toxin research in recent years has been development of the most potent toxin into a molecule of significant therapeutic utility . It is the first biological toxin which is licensed for treatment of human diseases. In the late 1980s, Canada approved use of the toxin to treat strabismus, in 2001 in the removal of facial wrinkles and in 2002, the FDA in the United States followed suit. The present review focuses on both warfare potential and medical uses of botulinum neurotoxin.

Journal Article
S Sreeja1, V S Anju
TL;DR: The study provided the evidence for estrogenic activities of fenugreek seeds in breast cancer cells and could demonstrate its suitability as an alternative to hormone replacement therapy (HRT).
Abstract: Background & objectives: Trigonella foenum graecum commonly known as fenugreek, has been widely cultivated in Asia, Africa and Mediterranean countries for the edible and medicinal values of its seeds. Earlier reports show that fenugreek seeds provide a mastogenic effect resulting in enhanced breast size. However, very little is known about its estrogenic effect. The present study investigated the effect of chloroform extracts of fenugreek seeds (FCE) in breast cancer cells for its estrogenic effect, and to assess its capacity as an alternative to hormone replacement therapy (HRT). Methods: The effect of FCE on cell proliferation of estrogen receptor (ER) positive breast cancer cells, MCF-7 was studied by MTT assay at a concentration range of 20 to 320 µg/ml. The competitive ER binding assay (HAP assay) was done to find out the ER binding capacity of the extract. Transfection and reporter assay (DLR assay), and RT- PCR with an estrogen responsive gene pS2 were done to find out the transcriptional regulatory activity of FCE. Results: FCE stimulated the proliferation of MCF-7 cells, showed binding to ER (IC 50 = 185.6 ± 32.8 µg/ ml) and acted as an agonist for ER mediated transcription via ERE. It also induced the expression of estrogen responsive gene pS2 in MCF-7 cells. Interpretation & conclusion: Our study provided the evidence for estrogenic activities of fenugreek seeds. Further in vitro and in vivo studies could demonstrate its suitability as an alternative to HRT.

Journal Article
TL;DR: In non-diabetic Asian Indians, visceral, but not subcutaneous component of abdominal fat is associated with insulin resistance, cardiovascular risk factors and metabolic syndrome.
Abstract: 2=0.457, β= 0.34; P=0.006), HDL cholesterol (R 2 =0.430, β= -0.051; P=0.018) and ISI-Matsuda (R 2 =0.437, β= -0.05; P=0.039) after adjusting for age, gender and BMI. Visceral fat showed significant association with metabolic syndrome (OR: 1.013, 95% CI: 1.001- 1.025; P=0.041) even after adjusting for age, gender, body mass index and glycated haemoglobin whereas subcutaneous fat did not show such an association. Interpretation & conclusions: These results indicate that in non-diabetic Asian Indians, visceral, but not subcutaneous component of abdominal fat is associated with insulin resistance, cardiovascular risk factors and metabolic syndrome.

Journal Article
TL;DR: High incidence of ZDV induced anaemia seen in this study indicates regular monitoring of patients, particularly women on ZDDV based antiretroviral regimens is needed.
Abstract: Results: Two hundred three (16.2%) patients on ZDV regimen developed anaemia (<8 g%); 7.9 per cent (n=100) of these developed severe anaemia (<6.5 g%). Females were more prone to develop anaemia (P=0.026). Age, weight, WHO clinical stage and CD4 counts had no relation to development of anaemia. Interpretation & conclusion: High incidence of ZDV induced anaemia seen in this study indicates regular monitoring of patients, particularly women on ZDV based antiretroviral regimens.

Journal Article
TL;DR: Both sedative-hypnotic and cognitivebehavioural interventions exist for insomnia and each type of intervention have substantial levels of empirical support for their efficacy.
Abstract: Insomnia is a highly prevalent sleep disorder that frequently occurs in its acute form and occurs at a rate of approximately 10 per cent in its chronic form in many countries. There is a high prevalence of insomnia in a variety of medical and psychiatric conditions for which insomnia often serves as a risk factor. The aetiology and pathophysiology of insomnia is such that several factors may predispose individuals for or precipitate and/or perpetuate the condition. Both sedative-hypnotic and cognitivebehavioural interventions exist for insomnia and each type of intervention have substantial levels of empirical support for their efficacy.