Asthma is the most common chronic childhood disease in developed nations and its prevalence has increased in the world over the last 25 years. It is a complex disease with both genetic and environmental risk factors. Asthma is caused by multiple interacting genes, some having a protective effect and others contributing to the disease pathogenesis, with each gene having its own tendency to be influenced by the environment. This article reviews the current state of the genetics of asthma in six categories, viz. epidemiology, management, aetiology, family and twin studies, segregation and linkage studies, and candidate genes and single nucleotide polymorphisms (SNPs).

Background & objectives : Estimation of prevalence of prehypertension in a population and its association with risk factors of cardiovascular disease is important to design preventive programmes. This cross-sectional study was carried out in a healthy military population to assess the prevalence of prehypertension and its association with risk factors such as overweight, abdominal adiposity and dyslipidaemia. Methods: The study included 767 participants (130 officers and 637 from other ranks). The blood pressure, serum triglycerides and serum cholesterol (total, HDL and LDL) were assessed along with anthropometric measurements such as height, weight, waist-hip ratio in apparently healthy military personnel. Information on smoking, alcohol intake, dietary habits and physical activity was collected using pretested questionnaire. Prehypertension was defined as systolic blood pressure (SBP) 120-139 mm Hg and diastolic blood pressure (DBP) 80-89 mm Hg. Results: The overall prevalence of prehypertension was high (about 80%). The prevalence of other risk factors such as overweight (BMI>23 kg/m ² ), serum total cholesterol > 200 mg/dl, serum LDL cholesterol > 130 mg/dl, serum HDL cholesterol <40 mg/dl, serum triglyceride > 150 mg/dl in the total group was 30, 22, 22, 67, and 14 per cent, respectively. Most of the personnel undertook moderate or heavy exercise. A significantly higher proportion of individuals with prehypertension had clinical and behavioural risk factors such as overweight, dyslipidaemia and adverse dietary practices like saturated fat and added salt intake. On multivariate logistic regression analysis, prehypertension had significant positive association with BMI>23 kg/m ² (OR 1.75), age (OR 1.89), serum triglyceride >150 mg/dl (OR 2.25)and serum HDL cholesterol <40 mg/dl (OR 1.51). Interpretation & conclusions: The high prevalence of prehypertension and its association with overweight and dyslipidaemia in this young, physically active military population indicates an urgent need for targeted interventions to reduce the cardiovascular risk.

Background & objectives : Diabetic foot ulcers are the most common cause of non-traumatic lower extremity amputations in developing countries. The aim of this pilot study was to evaluate the safety of using a polyherbal formulation in healing diabetic foot ulcers in comparison with standard silver sulphadiazine cream among patients with type 2 diabetes. Methods: A total of 40 (M:F=29:14) consecutive type 2 diabetes patients with foot ulcers were enrolled in this study. They were randomly assigned to two groups of 20 each; Group 1 was treated with polyherbal formulation and group 2 with silver sulphadiazine cream. All the patients were followed up for a period of 5 months. The baseline ulcer size was noted and photograph of the wound was taken at the baseline and at each follow up visit. Number of days taken for healing of the wound was recorded. Results: The mean age of patients, duration of diabetes and HbA1c% were similar in both the study groups. The mean length and width of the ulcers was also similar in both the groups at baseline visit. There was a significant decrease in the size of the wound (length and width) in both the study groups (P<0.001). The mean time taken for the healing of the ulcer was around 43 days in both groups. Interpretation & conclusions : Diabetic wound cream prepared by using polyherbal formulation was found to be effective as well as safe in healing diabetic foot ulcers like the standard silver sulphadiazine cream.

Background & objectives : There are very few studies describing the pattern of physical activity of children in India. This study was carried out to document patterns of physical activity in south Indian school children aged 8 to 15 yr and examine changes over a one year period. Methods: Physical activity was assessed using interviewer-administered questionnaires at baseline (n=256) and at follow up (n=203) in 2006 and 2007. Frequency and duration of each activity was recorded and metabolic equivalents (MET) assigned. Sedentary activity included activities with MET < 1.5, and moderate-to- vigorous physical activity (MVPA) with >3.0. For each activity, daily duration, intensity (MET), and the product of the two (MET-minutes) were computed. Children were categorized by age group, gender and socio-economic status. Height and weight were measured. Results: At baseline, sedentary activity was higher in children aged >11 yr, while intensity of MVPA was higher in boys than girls. Over one year, physical activity at school significantly decreased (P<0.001). There was also a significant decrease in MVPA MET-min (P<0.001) with interaction effects of age group (P<0.001) and gender (P<0.001). Interpretation & conclusions : There was a significant decline in moderate-to-vigorous physical activity over a single year follow up, largely due to a decrease in physical activity at school. There appears to be a gap between State educational policies that promote physical well-being of school-going children and actual practice.

Background & objectives : Receptors for the Fc fragment of immunoglobulin G (Fc γ Rs) represent the link between humoral and cellular immune responses. Polymorphisms in Fc γ Rs have been identified as genetic factors influencing susceptibility to various autoimmune diseases. This study was aimed to identify Fc γ R IIB genotypes in Indian systemic lupus erythematosus (SLE) patients and to correlate these with clinical presentation and autoantibody profile. Methods: Eighty consecutive clinically diagnosed SLE patients were included. SLE patients were classified according to the American College of Rheumatology (ACR) criteria. Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). PCR-RFLP method was used to detect Fc γ R IIB polymorphism. Results : Of the 80 SLE patients, 53 were LN and 27 were SLE without nephritis. The mean SLEDAI score at evaluation was 6.5 ± 5.8. Among SLE patients Fc γ R IIB genotype frequency was 61.2 per cent for Ile/Thr, 20.0 per cent for Thr/Thr and 18.8 per cent for Ile/Ile as compared to 65, 12.5 and 22.5 per cent respectively among normal population. There was no significant difference for Fc γ R IIB genotypes between SLE and normals. The allele frequency for Thr allele in SLE patients was slightly higher (0.51) than in normals (0.45). Thr allele frequency in LN patients was slightly higher (0.53) than in SLE patients without nephritis (0.49). Though a higher percentages of symptoms like renal manifestations (81.3%), arthritis (62.5%) and oral ulcer (56.3%) were noted in patients with Thr/Thr genotypes, no significant difference was noted when these patients were compared with Ile/Ile and Ile/Thr genotypes. Interpretation & conclusions : The findings of this study indicate towards an involvement of Thr allele with SLE disease severity and clinical presentation in Indian SLE patients. Future study on a large sample is needed to support this finding to understand the association of Fc γ R IIB 232Thr/Thr genotype as a susceptibility factor in SLE.

Background & objectives : DNA mismatch repair gene (MMR) abnormalities are seen in 95 per cent of hereditary nonpolyposis colorectal cancer (HNPCC) and 10-15 per cent of sporadic colorectal cancers. There are no data on MMR abnormalities in Malaysian colorectal cancer patients. This study was aimed to determine the frequency of abnormal MMR gene protein expression in colorectal carcinoma in Northern Peninsular Malaysia using immunohistochemistry. Methods: Clinicopathological information was obtained from 148 patients' records who underwent bowel resection for colorectal cancer (CRC) at the three hospitals in Malaysia. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins were performed on paraffin embedded tissue containing carcinoma. Results: A total of 148 subjects and 150 colorectal carcinomas of sporadic and hereditary types were assessed. Three patients had synchronous tumours. Twenty eight cancers (18.6%) from 26 subjects (17.6%) had absent immunohistochemical expression of any one of the MMR gene proteins. This comprised absent MLH1 only - 3 cancers, absent MSH2 only - 3, absent MSH6 only - 2, absent PMS2 only - 3, absent MLH1 and PMS2 - 14, absent MSH2 and MSH6 - 2 and absent MLH1, MSH6 and PMS2 - 1. There was significant association between abnormal MMR gene protein expression and proximal colon cancers, mucinous, signet ring and poorly differentiated morphology. Interpretation & conclusions : Cancers with abnormal MMR gene expression were associated with microsatellite instability-high (MSI-H) phenotype. About 15 per cent demonstrated absent MSH2, MSH6 and PMS2 protein expression in isolation or in combination with other MMR genes, which often predicts a germline mutation, synonymous with a diagnosis of HNPCC. This appears to be high frequency compared to reported data.

Background & objectives : Intravenous device (IVD) associated nosocomial blood stream infections due to staphylococci are major cause of morbidity and mortality. The present study was carried out to assess the frequency of staphylococcal IVD associated infections in a paediatric ward of a tertiary case hospital. Prevalence of resistance to commonly used antimicrobials in hospital acquired staphylococcal isolates was also tested. Methods: Children admitted in paediatric wards with IVD for more than 48 h were enrolled. Blood, IVD tip at the time of removal, skin swab at the site of insertion of IVD and nasal swab were collected and cultured by standard protocol. All staphylococcal isolates from any source were analyzed for antimicrobial susceptibility by disk diffusion method. Genotyping matching of those staphylococcal isolates was done which were isolated from different sites of the same patient, but were phonotypically similar. Genotype of blood isolate was compared with genotype of isolate from nose/IVD/skin. Results: Staphylococcus aureus was the most frequent blood isolate (8.7%) followed by Candida (2.9%), coagulase negative staphylococci (CoNS 2.6%), Pseudomonas spp. (0.4%), Klebsiella spp. (0.3%) and Escherichia coli (0.1%). Isolation of microorganisms from blood was significantly higher in patients whose skin, IVD and nose were colonized by same microorganism (P<0.001). None of the staphylococcal isolate was found to be resistant to glycopeptides (vancomycin and teicoplanin). High penicillin and oxacillin resistance was present in both S. aureus (penicillin resistance; 76.8%, oxacillin resistance; 66.7%) and CoNS (penicillin resistance; 73.3%, oxacillin resistance; 60.0%). Among CoNS biotypes, S. haemolyticus was commonest blood isolate while S. epidermidis was commonest isolate from Skin/nose. Only 33.3 per cent of S. aureus blood stream infections and most of S. epidermidis and S. haemolyticus blood infections were IVD associated. Interpretation & conclusions : Staphylococci were the major causative agent of nosocomial blood stream infections. All episodes of septicaemia due to S. epidermidis and S. haemolyticus were IVD associated while only 1/3 of S. aureus septicaemia was IVD associated.

Background & objectives : Hepatitis C virus (HCV) induces an immune response of the host, manifested by the formation of anti-HCV antibodies mediated by adaptive and innate immunity. Toll-like receptors (TLRs) play a pivotal role in innate immunity system. This study was aimed to investigate the promoter region polymorphism and expression of TLR3 gene in patients with chronic HCV infection. Methods: Patients with chronic HCV infection (N=180) and an equal number of age-sex matched controls were included in the study. Patients positive for HCV-RNA were subjected to analysis of TLR3 polymorphism by direct sequencing of PCR products verified by comparing with the sequences reported in the National Centre for Biotechnology Information (NCBI) database (accession number: NT 022792). Expression of TLR3 gene was analyzed by semiquantitative RT-PCR using housekeeping β-actin gene as the internal control. Results : Polymorphisms at position -288G/A and -705A/G were identified. The results were significant in -705 allele (P=0.004) OR 2.79(1.46-5.42) and were associated with high risk of HCV infection. In silico sequence analysis showed the presence of ectropic viral integration site 1 encoded factor, in which G at -705 results in the loss of this site. The -7C/A polymorphism was not seen in our study cohort. The expression of TLR3 was upregulated in chronic HCV patients compared to healthy controls. Interpretation & conclusions : Polymorphism in the -705A/G allele at the promoter region of the TLR3 gene may predispose individual to HCV infection. However association of TLR3 expression with polymorphism of TLR3 promoter was not found.

Background & objectives : Catheter associated urinary tract infections are the second most common nosocomial infections and Pseudomonas aeruginosa is the third most common organism responsible for these infections. In this study P. aeruginosa isolates from catheterized urinary tract infection patients were screened and profiled for the presence of different type of quorum sensing (QS) signal molecules. Methods: Screening and quantitation of AHLs was done by using cross feeding assay and by determining β-galactosidase activity respectively using Escherichia coli MG4 as reporter strain. Further, AHL profiles were determined by separating AHLs on TLC coupled with their detection using Chromobacterium violaceum CV026 and Agrobacterium tumifaciens A136 biosensor strains. Results: All uroisolates from catheterized patients having urinary tract infections were found to be producers of QS signal molecules. There were differences in amounts and type of AHL produced amongst uroisolates of P. aeruginosa. Several AHLs belonging to C4-HSL, C6-HSL, oxo-C6-HSL, C8-HSL, C10-HSL and C12-HSL were determined in these strains. Interpretation & conclusions : Simultaneous use of more than one reporter strain and assay method proved useful in determining the AHLs profile in uroisolates of P. aeruginosa. Observed differences in the amounts and types of AHLs may reflect differences in virulence potential of P. aeruginosa to cause UTIs which can be further confirmed by employing animal model system. The present study speculates that production of QS signal molecules may act as a new virulence marker of P. aeruginosa responsible for causing catheter associated UTIs and can be considered as futuristic potential drug targets towards treatment of UTIs.

Background & objectives : Diverse mechanisms have been identified in enteric bacteria for their adaptation and survival against multiple classes of antimicrobial agents. Resistance of bacteria to the most effective fluoroquinolones have increasingly been reported in many countries. We have identified that most of the enterotoxigenic Escherichia coli (ETEC) were resistant to several antimicrobials in a diarrhoea outbreak at Ahmedabad during 2000. The present study was done to identify several genes responsible for antimicrobial resistance and mobile genetic elements in the ETEC strains. Methods: Seventeen ETEC strains isolated from diarrhoeal patients were included in this study. The antimicrobial resistance was confirmed by conventional disc diffusion method. PCR and DNA sequencing were performed for the identification of mutation in the quinolone resistance-determining regions (QRDRs). Efflux pump was tested by inhibiting the proton-motive force. DNA hybridization assay was made for the detection of integrase genes and the resistance gene cassettes were identified by direct sequencing of the PCR amplicons. Results: Majority of the ETEC had GyrA mutations at codons 83 and 87 and in ParC at codon 80. Six strains had an additional mutation in ParC at codon 108 and two had at position 84. Plasmid-borne qnr gene alleles that encode quinolone resistance were not detected but the newly described aac(6')-Ib-cr gene encoding a fluoroquinolne-modifying enzyme was detected in 64.7 per cent of the ETEC. Class 1 (intI1) and class 2 (intI2) integrons were detected in six (35.3%) and three (17.6%) strains, respectively. Four strains (23.5%) had both the classes of integrons. Sequence analysis revealed presence of dfrA17, aadA1, aadA5 in class 1, and dfrA1, sat1, aadA1 in class 2 integrons. In addition, the other resistance genes such as tet gene alleles (94.1%), catAI (70.6%), strA (58.8%), bla _TEM-1 (35.2%), and aphA1-Ia (29.4%) were detected in most of the strains. Interpretation & conclusions : Innate gene mutations and acquisition of multidrug resistance genes through mobile genetic elements might have contributed to the emergence of multidrug resistance (MDR) in ETEC. This study reinforces the necessity of utilizing molecular techniques in the epidemiological studies to understand the nature of resistance responsible for antimicrobial resistance in different species of pathogenic bacteria.

Background & objectives : Despite routine iron supplementation and promotion of diet modification, iron deficiency anaemia (IDA) remains widely prevalent in our antenatal population. Recent studies in pediatric population have highlighted the role of Helicobacter pylori infection in IDA. This study was undertaken to study the effect of eradication therapy in H. pylori infected pregnant women with IDA. Methods: Randomized placebo-controlled double blind clinical trial was done on 40 antenatal women between 14-30 wk gestation, with mild to moderate IDA and having H. pylori infection, as detected by stool antigen test. These women were randomly divided into group I (n=20): H. pylori treatment group (amoxicillin, clarithromycin, omeprazole for 2 wk) and group II (n=20): placebo group. Both groups received therapeutic doses of iron and folic acid. Outcome measures were improvement in haematological parameters and serum iron profile after 6 wk of oral iron therapy. Results: The prevalence of iron deficiency in pregnant women with mild to moderate anaemia was 39.8 per cent (95% CI 35.7, 44.3); and 62.5 per cent (95% CI 52, 73) of these pregnant women with IDA were infected with H. pylori. After 6 wk of therapeutic oral iron and folic acid supplementation, the rise in haemoglobin, packed cell volume, serum iron and percentage transferrin saturation was significantly (P<0.05) higher in the group given H. pylori eradication therapy as compared to the placebo group. Interpretation & conclusions : Our results showed a high occurrence of H. pylori infection in pregnant women with IDA. Eradication therapy resulted in significantly better response to oral iron supplementation among H. pylori infected pregnant women with IDA.