Dengue virus belongs to family Flaviviridae, having four serotypes that spread by the bite of infected Aedes mosquitoes. It causes a wide spectrum of illness from mild asymptomatic illness to severe fatal dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Approximately 2.5 billion people live in dengue-risk regions with about 100 million new cases each year worldwide. The cumulative dengue diseases burden has attained an unprecedented proportion in recent times with sharp increase in the size of human population at risk. Dengue disease presents highly complex pathophysiological, economic and ecologic problems. In India, the first epidemic of clinical dengue-like illness was recorded in Madras (now Chennai) in 1780 and the first virologically proved epidemic of dengue fever (DF) occurred in Calcutta (now Kolkata) and Eastern Coast of India in 1963-1964. During the last 50 years a large number of physicians have treated and described dengue disease in India, but the scientific studies addressing various problems of dengue disease have been carried out at limited number of centres. Achievements of Indian scientists are considerable; however, a lot remain to be achieved for creating an impact. This paper briefly reviews the extent of work done by various groups of scientists in this country.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Surgery offers the only hope for cure. However, the potentially curable method is only possible for a small proportion of those afflicted, for the rest, palliative treatment is indicated. Despite all the treatment options when used as monotherapy, patients with HCC have a poor long term prognosis. In this setting, multimodal and combination therapy has emerged as an alternative treatment modality for HCC. Studies have looked at various forms of combination therapy, including neoadjuvant/adjuvant/downstaging therapy for surgery and the combined modality of non-operative therapies. The novel molecular targeted therapies are also being used as combination regimens for surgery or other non-operative therapies. Some forms of combination therapies, including downstaging therapy for surgery, salvage transplantation, and molecular targeted therapy have been shown to provide survival benefits for well selected patients, and need to be encouraged in the future. And others such as pre-operative bridging therapy for liver transplantation, adjuvant therapy for hepatic resection and combination of local and regional therapies have also shown some benefits in preliminary results, which need confirmation in further studies. In conclusion, multimodal and combination therapy is an encouraging treatment modality for HCC. Future research should continue to unravel the role of combination therapy with properly selected patients and appropriate end points.

Background & objectives: Several studies have reported adverse drug events ranging from 5 to 35 per cent in all age group from outpatient setting. However, adverse drug reactions (ADRs) particularly among a large sample of ambulatory elderly patients in India has not been reported. This study has attempted to identify ADRs and assessed their causality, preventability and severity, and also their risk factors in Indian ambulatory elderly patients. Methods: A 2 year long term prospective study included 4005 ambulatory elderly patients (60 yr or above; either sex) at a public teaching hospital. Suspected ADRs were assessed for causality, preventability and severity using Naranjo's probability scale, modified Schumock and Thornton's criteria, and modified Hartwig's criteria, respectively. Results: Of the total 4005 prescriptions, 406 were identified with ADRs, giving the occurrence of 10 per cent ADRs in elderly. The total number of ADRs was 422 in 406 prescriptions. Type A ADRs accounted for 46 per cent of the total ADRs. Majority of the ADRs (88.6%) were classified as 'probable'. The definitely preventable reactions were 22 per cent. The percentage of moderate reaction was 16 per cent. Only 1.6 per cent ADRs was severe in nature. The most common type of ADR was peripheral oedema. The most commonly offending class of drug was cardiovascular drugs (57.6%). Using logistic regression analysis, the risk factors which contributed to ADRs were age above 80 yr (OR=1.7), prescription of multiple drugs (OR=1.8), longer duration of treatment (OR=2.28) and multiple diagnoses (OR=1.8). Interpretation & conclusions: In this study, 10 per cent ambulatory elderly patients were found to have ADRs. This indicates that the elderly patients should be closely monitored for ADRs, to avoid clinically significant harmful consequences. The awareness of risk factors of ADRs would help physicians to identify elderly patients with greater risk of ADRs and, therefore, might benefit from ADRs monitoring and reporting programme.

Background & objectives: Ascent to high altitude has been reported to cause hippocampal atrophy and cognitive impairment in mountaineers. We assessed the cognitive performance and probable occurrence of mild cognitive impairment (MCI) in acclimatized lowlanders (ALL) staying at altitudes above 4,300 m for duration above 12 months and validated a multi-domain cognitive screening test (MDCST) for future demographic studies on MCI. Methods: Following evaluation of sensitivity and correlation of the newly developed MDCST battery with Mini Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) scores on a group of 28 individuals, the MDCST battery was validated on a population of 843 ALL staying at high altitude MSL >4,300 m and 862 subjects staying at MSL <230 m. EEG recordings were performed on 840 ALL staying at altitudes above 4,300 m and 743 control subjects staying at MSL <230 m. Results: Percentage prevalence of MCI was 4.18 per cent in the ALL population as assessed by MMSE while that of the LL population was <0.42 per cent. The percentage prevalence of MCI based on calculations from the MDCST scores was 12.4 per cent in the ALL population as compared to 1.19 per cent in the LL population. Decrease in alpha wave amplitude at the T3 and T4 sources in MCI subjects was observed in LL group while there was an increase in amplitude for alpha wave in these regions in the ALL groups. Domain specific MDCST showed decline in immediate recall, procedural memory and mind body co-ordination which was negligible in the LL population. Interpretation & conclusions: MDCST exhibited excellent psychometric properties in terms of sensitivity, and test-retest reliability qualifying it to be used as a more effective cognitive measure for assessment of MCI in demographic studies in comparison to traditional measures. Our findings also showed increased prevalence of MCI in ALL population staying for longer durations at high altitude which is neurophysiologically distinct from MCI leading to Alzheimer's disease.

Background & objectives: Income inequality is associated with poor health. Inequities exist in service utilization and financing for health care. Health care costs push high number of households into poverty in India. We undertook this study to ascertain inequities in health status, service utilization and out-of-pocket (OOP) health expenditures in two States in north India namely, Haryana and Punjab, and Union Territory of Chandigarh. Methods: Data from National Sample Survey 60 ^th Round on Morbidity and Health Care were analyzed by mean consumption expenditure quintiles. Indicators were devised to document inequities in the dimensions of horizontal and vertical inequity; and redistribution of public subsidy. Concentration index (CI), and equity ratio in conjunction with concentration curve were computed to measure inequity. Results: Reporting of morbidity and hospitalization rate had a pro-rich distribution in all three States indicating poor utilization of health services by low income households. Nearly 57 and 60 per cent households from poorest income quintile in Haryana and Punjab, respectively faced catastrophic OOP hospitalization expenditure at 10 per cent threshold. Lower prevalence of catastrophic expenditure was recorded in higher income groups. Public sector also incurred high costs for hospitalization in selected three States. Medicines constituted 19 to 47 per cent of hospitalization expenditure and 59 to 86 per cent OPD expenditure borne OOP by households in public sector. Public sector hospitalizations had a pro-poor distribution in Haryana, Punjab and Chandigarh. Interpretation & conclusions: Our analysis indicates that public sector health service utilization needs to be improved. OOP health care expenditures at public sector institutions should to be curtailed to improve utilization of poorer segments of population. Greater availability of medicines in public sector and regulation of their prices provide a unique opportunity to reduce public sector OOP expenditure.

Background & objectives: In view of high rate of unintended pregnancy in our country, particularly in post-partum women, there is a need for reliable, effective, long-term contraception such as intrauterine device (IUD) in post-partum women. The present study was planned to evaluate the safety and efficacy of immediate post-partum IUD insertion in women delivering vaginally or by caesarian section in a tertiary care centre facility in north India during a period of five years. Methods: The women recruited had CuT 200B insertion immediately after delivery of placenta in vaginal or caesarean delivery. Women having post-partum haemorrhage (PPH), anaemia, pre-labour rupture of membranes >18 h, obstructed labour and distorted uterine cavity by fibroid or by congenital malformation were excluded from the study. The women were followed up at 6 wk and 6 months after delivery. Results: A total of 1317 women were included in the study. Of these, 1037 (78.7%) came for first follow up. The cumulative expulsion rate at the end of 6 months was 10.68 per cent. There was no case of misplaced IUD. Interpretation & conclusions: Although the expulsion rate for immediate post-partum insertion was higher than for interval insertion, the benefits of providing highly effective contraception immediately after delivery outweigh this disadvantage, particularly in country where women have limited access to medical care.

Background & objectives: The aetiology of mental retardation is varied and difficult to establish. Reports from India on the spectrum of underlying causative conditions are lacking. This retrospective study was conducted to establish the various aetiologies of mental retardation (MR) and developmental delay (DD) in patients attending a medical genetics centre in north India and to assess the contribution of genetic disorders. Methods: This retrospective study was conducted at a tertiary care centre in north India. All patients attending the centre with MR or DD from January 2007 to December 2009 were included. The aetiology of MR/DD was ascertained after clinical assessment and targeted laboratory evaluation. The spectrum of causative conditions and contribution of genetic disorders was established. Results: A total of 338 patients were included in the study, of whom definite diagnosis was established in 253 (74.8%). The various aetiological categories were: chromosomal disorders in 112 (33.1%), non chromosomal syndromes in 32 (9.5%), neurometabolic disorders in 34 (10.1%), central nervous system structural defects in 25 (7.4%), cerebral palsy in 43 (12.7%) and environmental insults in 7 (2%). Eighty five patients (25.2%) had idiopathic mental retardation. A total of 196 (58%) patients had a genetic disorder as the cause of MR/DD. Interpretation & conclusions: The aetiology of MR/DD is varied and difficult to establish in a significant proportion of patients. Chromosomal and various monogenic disorders contribute to a large number of MR/DD cases and hence a genetic work up is essential for all such patients.

Background & objectives: Hydroxyethyl starches (HES) 130/0.4 (Voluven;) and 130/0.42 (Venofundin;) impair coagulation less than older HES solutions with higher molecular weight and molar substitution. Thus, these may be used in high doses up to 50 ml/kg/day. The aim of this study was to investigate and compare the effects of HES 130/0.4 versus HES 130/0.42 on coagulation after the intraoperative infusion of 30 ml/kg in patients undergoing major abdominal surgery. Methods: Fifty two patients scheduled for elective major abdominal surgery were randomized to receive 30 ml/kg of HES 130/0.4 or HES 130/0.42 intraoperatively. Coagulation variables were assessed before and after infusion of the colloid solution using thrombelastography. Results: Data from 49 patients, 25 patients in the HES 130/0.4 and 24 in the HES 130/0.42 group, were analyzed. Measurements of reaction time, kinetic time, α-angle, maximum amplitude and coagulation index before and after colloid infusion did not differ between the groups. Within each group, after colloid infusion, reaction time did not change significantly, while α-angle, maximum amplitude and coagulation index values were significantly decreased (P <0.01, P<0.001 and P<0.001, respectively in HES 130/0.4 group and P<0.01, P<0.001 and P<0.01, respectively in HES 130/0.42 group). Kinetic time was significantly increased (P<0.001) in both the groups. In both groups, all thrombelastographic measurements after colloid infusion were found within normal limits. Interpretation & conclusions: HES 130/0.4 and HES 130/0.42 showed similar, not clinically significant effects on coagulation, as assessed by thrombelastography, when a dose of 30 ml/kg was administered in patients undergoing major abdominal surgery.

Background & objectives: Aetiology of malabsorption syndrome (MAS) differs in tropical and temperate countries over time; clinical and laboratory parameters may differentiate between various causes. This study was undertaken to investigate the spectrum of MAS among Indian adults and to find out the features that may help to differentiate between TM and celiac disease. Methods: Causes of MAS, and factors differentiating tropical malabsorption (TM) from celiac disease (CD) were determined in 275 patients. Results: Using standard criteria, causes in 275 patients [age 37.5+13.2 yr, 170, (61.5%) male] were, TM 101 (37%), CD 53 (19%), small intestinal bacterial overgrowth 28 (10%), AIDS 15 (5.4%), giardiasis 13 (5%), hypogammaglobulinemia 12 (4%), intestinal tuberculosis 7 (2.5%), strongyloidiasis 6 (2%), immunoproliferative small intestinal disease 5 (2%), Crohn's disease 6 (2%), amyloidosis 4 (1.5%), intestinal lymphangiectasia 3 (1%) and unknown 22 (8%). On univariate analysis, patients with CD were younger than TM (30.6+12 vs. 39.3+12.6 yr, P<0.001), had lower body weight (41.3+11.8 vs. 49.9+11.2 kg, P<0.001), longer diarrhoea duration (median 36 inter-quartile range 17.8-120 vs. 24-months, 8-48, P<0.01), lower stool frequency (6/day, 5-8 vs. 8, 5-10, P<0.05), lower haemoglobin (9.4+3.2 vs. 10.4+2.7 g/dl, P<0.05), higher platelet count (2,58,000, range 1,35,500-3,23,500 vs. 1,60,000, 1,26,000-2,58,000/mm ³ , P<0.05), and more often had hepatomegaly (9/53, 17% vs. 4/101, 4%, P<0.01), and subtotal or partial villous atrophy (36/50, 72% vs. 28/87, 32%, P<0.001). Younger age (<35 yr), longer diarrhoea duration, higher platelet count and villous atrophy were significant on multivariate analysis. Interpretation & conclusions: TM and CD are common causes of MAS among Indian adults. Younger age (<35 yr), longer diarrhoea duration, higher platelet count and villous atrophy were found to be associated with CD.

Background & objectives: Our previous study showed that cow ghee relative to soybean oil had a protective effect against carcinogen induced mammary cancer in rats. The objective of this study was to elucidate its biochemical mechanism. Methods: Two groups of 21 day old rats (20 each) were fed for 44 wk diet containing cow ghee or soybean oil (10%). Five animals from each group were sacrificed at 0 day and at 5, 21 and 44 wk for analysis of phase I and phase II pathways enzymes of carcinogen metabolism. Results: Dietary cow ghee relative to soybean oil decreased the activities of cytochrome P450 (CYP) enzymes, CYP1A1, CYP1A2, CYP1B1 and CYP2B1, responsible for activation of carcinogen in liver. Carcinogen detoxification activities of uridinediphospho-glucuronosyl transferase (UDPGT) and quinone reductase (QR) in liver, and γ-glutamyltranspeptidase (GGTP) and QR in mammary tissue were significantly higher in cow ghee fed rats than in soybean oil fed rats. The hepatic GGTP activity decreased on soybean oil diet; while in cow ghee group it remained unaffected. Interpretation & conclusions: Our findings show that dietary cow ghee compared to soybean oil downregulates the enzyme activities responsible for carcinogen activation in liver and upregulates carcinogen detoxification activities in liver and mammary tissues.

Background & objectives: The steroidal estrogen 17α-ethynyl estradiol (EE) is an orally bio-active estrogen used in almost all modern formulations of estrogen-progestin combination preparations of oral contraceptives. Contrasting effects of treatment with combined oral contraceptives on bone mineral density of pre-, peri-, and post-menopausal women have been reported, and it has been suggested that the estrogen dose and the type of progestogen may be the main contributing factors for these contrasting results. The objective of this study was to evaluate the effects of EE on osteoprecursor cells. Methods: The effects of single component of oral contraceptive, EE, were tested to see the relationship between EE and osteoblast proliferation, differentiation and mineralization. Tests used included a cell viability test, alkaline phosphatase (ALP) test, alizarin red-S staining, and a Western blot analysis. The effect on cell viability was determined by MTT assay. Differentiation and mineralization were examined using an ALP test and alizarin red-S staining. Protein expressions related to bone formation, such as estrogen receptor-alpha (ER-α), estrogen receptor-beta (ER-β), bone morphogenetic protein-2 (BMP-2), osteocalcin (OCN), and osteopontin (OPN) were evaluated by using a Western blot analysis. Results: Cultures growing in the absence of EE presented the lowest value for the MTT value. However, there were no significant changes in viability/proliferation when EE was added in the medium. Cultures growing in the absence of EE presented the highest value for the ALP activity, and the additional presence of EE resulted in dose-dependent decrease concerning ALP activity. Interpretation & conclusions: Our finding showed that EE in tested dosage within MC3T3-E1 cells seem to affect the proliferation and differentiation; however, significant differences are achieved in ALP activity in early differentiation phase and further studies are needed to elucidate the mechanisms of EE on bone.

Background & objectives: In congestive heart failure (CHF), increased concentrations of several cytokines including cardiotrophin-1 (CT-1) and immunactivation are found. This study was performed to evaluate whether CT-1 can induce in vitro cytokines in monocytes and CD4 ⁺ T-lymphocytes of healthy volunteers. Methods: The study was performed in vitro to see whether CT-1 can modulate monocyte or CD4 ⁺ T-lymphocyte interleukin (IL)-1β, -2, -4, -5, -10, interferon γ (IFNγ), and tumour necrosis factor α (TNFα) expression by flow cytometry following stimulation with CT-1 alone or together with lipopolysaccharide (LPS) or phorbol myristate acetate (PMA)/ionomycine (iono). Results: CT-1 increased the number of TNFα and IL-1β positive monocytes. LPS induced IL-10, TNFα, and IL-1β in monocytes but only IL-2 in CD4⁺ T-lymphocytes, whereas PMA/iono induced all cytokines besides IL-5 in monocytes and IL-1β in CD4⁺ T-lymphocytes. In LPS activated monocytes, CT-1 induced a concentration-dependent reduction in the number of TNFα positive monocytes. After LPS activation, CT-1 decreased the number of CD4⁺ lymphocytes positive for IL-2, IL-4, and IL-5. In addition, following PMA/iono stimulation, CT-1 initiated a concentration-dependent decrease of CD4 ⁺ T-lymphocytes positive for TNFα, IL-4, IL-5, and IL-10. Interpretation & conclusions: The present data show that in vitro CT-1 can activate monocytes and modulate cytokine production of activated CD4 ⁺ T-lymphocytes. We speculate that CT-1 may at least be partly responsible for immunactivation in CHF.

Background & objectives: Hepatitis E virus (HEV) causes acute viral hepatitis. Majority of the documented studies on hepatitis E have been focused on the incidence of this disease in northern and south central India. Limited data are available on HEV infection among acute sporadic hepatitis cases in north western India. The present study was undertaken to investigate the contribution of hepatitis E virus infection in sporadic hepatitis cases in Rajasthan and neighbouring States. Methods: Seven hundred and thirty six patients suspected to have viral hepatitis were screened for the hepatotropic viral markers, hepatitis A, B, C and E by using commercial enzyme immunoassay kits with a high sensitivity and specificity. The acute nature of HEV infection was also confirmed by the detection of HEV RNA by nested RT-PCR. Results: Hepatitis E was found to be the major cause of acute sporadic viral hepatitis (49.7%) in this region of India. Mixed infections of HEV-HAV (1.2%), HEV-HBV (6.1%), and HEV-HCV (1.7%) were also detected. No viral marker was detected in 32 per cent cases. Interpretation & conclusion: HEV was found as the major aetiological agent of acute sporadic viral hepatitis in Rajasthan (north western India). It is important to screen primarily for all the common enterically and parenterally transmitted hepatotropic viral markers in acute sporadic viral hepatitis. There is a need to do additional serological and molecular tests to identify the aetiological agent in the cases of acute hepatitis.

Background & objectives: The discrimination between the Staphylococcus epidermidis colonizing the deep seated indwelling devices and those which are mere commensals has always been a challenge for the clinical microbiologist. This study was aimed to characterize the S. epidermidis isolates obtained from device related infection for their phenotypic and molecular markers of virulence and to see whether these markers can be used to differentiate the pathogenic S. epidermidis from the commensals. Methods: Fifty five S. epidermidis isolates from various device related infections such as endophthalmitis following intra-ocular lens (IOL) implantation, intravascular (IV) catheter related sepsis and orthopaedic implant infections, were studied for slime production, biotyping, antibiotic sensitivity; and mec A and ica positivity by the recommended procedures. Results: Twenty three (41.8%) isolates were multi-drug resistant, 26 (65.2%) were slime producers, 30 (54.5%) were adherent, 23 (41.8%) possessed the intercellular adhesin (ica) gene, and 28 (50.9%) harboured the mec A gene. Biotypes I and III were the commonest, most members of which were multi- drug resistant. Twenty two (73.3%) of the 30 adherent bacteria were slime producers as opposed to only 4 (16%) of the 25 non-adherent bacteria (P<0.001). A vast majority i.e. 21 (91.3%) of the 23 ica positive organisms were adherent to artificial surfaces in contrast to only 9 (28.1%) of the 32 non-ica positive organisms (P<0.001). Twenty (86.9%) of the 23 ica positive bacteria were slime producers, as opposed to only 6 (18.7%) of the 32 ica negative bacteria (P<0.001). Of the 23 multi-drug resistant isolates, 19 (82.6%) carried the mec A gene. Interpretation & conclusions: The present findings showed that ica AB and mec A were the two important virulence markers of S. epidermidis in implant infections and slime was responsible for the sessile mode of attachment on the devices.

Background & objectives: Dengue is an important arboviral disease. All four dengue virus serotypes are reported to be circulating in India. It is also known that different serotypes, genotypes and clades of genotype determine outbreak severity. Dengue affected children are known to have serious disease outcome. We carried out this study to give reliable diagnosis of dengue infection in children and to detect circulating serotype in central India. Methods: Samples collected from paediatric patients suspected to have dengue fever were subjected to IgM and IgG ELISA to determine dengue virus infection. Samples collected within 0-5 days of onset of illness and positive by IgM ELISA were tested by nested reverse transcription polymerase chain reaction (nRT-PCR). The PCR products were sequenced and analyzed. Results: Of the 89 samples tested, 18 and 7 were positive for dengue IgM and IgG, respectively. Dengue activity was observed in both Jabalpur city and adjoining rural settings. One sample found positive by nRT-PCR was further sequenced to confirm dengue virus 4 as aetiological agent. Interpretation & conclusions: Our findings demonstrated dengue virus infection in children and adolescent in central India. Because of continuous changing epidemiology, it is important to monitor dengue virus activity at both serological and molecular level in this part of the country for better patient care and management.