Rajiva Gupta

Waist circumference cutoff points and action levels for Asian Indians for identification of abdominal obesity

Objective:To test the validity of internationally accepted waist circumference (WC) action levels for adult Asian Indians.Design:Analysis of data from multisite cross-sectional epidemiological studies in north India.Subjects:In all, 2050 adult subjects >18 years of age (883 male and 1167 female subjects).Measurements:Body mass index (BMI), WC, waist-to-hip circumference ratio, blood pressure, and fasting samples for blood glucose, total cholesterol, serum triglycerides, and high-density lipoprotein cholesterol.Results:In male subjects, a WC cutoff point of 78 cm (sensitivity 74.3%, specificity 68.0%), and in female subjects, a cutoff point of 72 cm (sensitivity 68.7%, specificity 71.8%) were appropriate in identifying those with at least one cardiovascular risk factor and for identifying those with a BMI >21 kg/m2. WC levels of ⩾90 and ⩾80 cm for men and women, respectively, identified high odds ratio for cardiovascular risk factor(s) and BMI level of ⩾25 kg/m2. The current internationally accepted WC cutoff points (102 cm in men and 88 cm in women) showed lower sensitivity and lower correct classification as compared to the WC cutoff points generated in the present study.Conclusion:We propose the following WC action levels for adult Asian Indians: action level 1: men, ⩾78 cm, women, ⩾72 cm; and action level 2: men, ⩾90 cm, women, ⩾80 cm.

Anti-Saccharomyces cerevisiae antibody does not differentiate between Crohn's disease and intestinal tuberculosis.

The clinical, morphological, and histological features of intestinal tuberculosis (IT) and Crohns disease (CD) mimic so much, that it becomes difficult to differentiate between them. The sensitivity of anti-Saccharomyces cerevisiae antibody (ASCA) IgG and ASCA IgA in CD is 60%–80%, whereas the specificity is almost 90%. There are no reports of study of ASCA in patients with IT, nor has it ever been used to differentiate CD from IT. Patients with ulcerative colitis (UC; n=25), CD (n=59), and IT (n=30) and 21 healthy controls were included in this study. The location and behavior of CD were classified according to the Modified Montreal classification. Five milliliters of blood was taken from them and serum was stored at −70°C. ASCA antibodies (both IgG and IgA) were estimated using commercially available ELISA kits (AESKU Diagnostics, Germany). Anti-neutrophilic cytoplasmic antibody was measured by indirect immunoflorescence test. ASCA IgA was positive in 4.7%, 28%, 33.9%, and 43.3% and ASCA IgG was positive in 4.7%, 24%, 50.8%, and 46.6% of healthy controls and patients with UC, CD, and IT, respectively. Either ASCA IgG or ASCA IgA was positive in 9.5%, 40%, 61% and 66.6% of healthy controls, UC, CD, and IT, respectively. ANCA was positive in 0%, 32%, 10.1%, and 6.6% of healthy controls, UC, CD, and IT, respectively. ASCA IgG was positive in a significantly higher number of patients with CD (P<0.0001) and IT (P<0.0001) in comparison to healthy controls. ASCA IgA was positive in a significantly higher number of patients with UC (P<0.04), CD (P<0.013), and IT (P<0.006) in comparison to healthy controls. In comparisons between diseases, ASCA IgG was positive in significantly more patients with CD (P<0.001) and IT (P<0.001) in comparison to UC. There was no significant difference in ASCA IgA (33.9% vs. 43.3%), ASCA IgG (50.86% vs. 46.6%), or ANCA (10.7%, 7.4%) in patients with CD and IT, respectively. There was no correlation between ASCA and duration, location and behavior of CD, and IT. We conclude that ASCA IgG and ASCA IgA do not help to differentiate between IT and CD.

Comparison of ultrasound biomicroscopic parameters after laser iridotomy in eyes with primary angle closure and primary angle closure glaucoma

PurposeTo study changes in anterior segment morphology after laser peripheral iridotomy (LPI) in primary angle closure (PAC) and primary angle closure glaucoma (PACG) using ultrasound biomicroscopy (UBM).MethodsNinety-three eyes of 93 patients underwent anterior segment evaluation including gonioscopy, disc evaluation with + 90D lens, applanation intraocular pressure, and standard achromatic perimetry. UBM was performed before and 2 weeks after Nd:YAG LPI to measure the trabecular-iris angle (TIA), the angle-opening distance (AOD 250/500), and the central anterior chamber depth (ACD).ResultsThe superior TIA widened from a mean of 7.54±3.15 to 15.66±6.69° (P=0.0001), the inferior TIA increased from a mean of 9.0±4.7 to 15.9±6.8° (P=0.0001) after LPI in PAC. In PACG, the mean superior angle changed from 4.55±2.5 to 6.12±3.8° (P=0.4) and the inferior angle increased from 4.75±2.0 to 7.9±3.7° (P=0.1). The mean ACD increased from 2.19±0.36 to 2.30±0.36 mm in PAC group (P=0.0003), with no significant change seen in the PACG group (1.79±0.32 vs1.82±0.33 mm, P=0.13).ConclusionLPI leads to a widening of the anterior chamber angle and a deepening of the anterior chamber in eyes with PAC. It does not significantly change any anterior segment parameters in eyes with PACG.

Caucasian and Asian Specific Rheumatoid Arthritis Risk Loci Reveal Limited Replication and Apparent Allelic Heterogeneity in North Indians

Genome-wide association studies and meta-analysis indicate that several genes/loci are consistently associated with rheumatoid arthritis (RA) in European and Asian populations. To evaluate the transferability status of these findings to an ethnically diverse north Indian population, we performed a replication analysis. We investigated the association of 47 single-nucleotide polymorphisms (SNPs) at 43 of these genes/loci with RA in a north Indian cohort comprising 983 RA cases and 1007 age and gender matched controls. Genotyping was done using Infinium human 660w-quad. Association analysis by chi-square test implemented in plink was carried out in two steps. Firstly, association of the index or surrogate SNP (r2>0.8, calculated from reference GIH Hap-Map population) was tested. In the second step, evidence for allelic/locus heterogeneity at aforementioned genes/loci was assessed for by testing additional flanking SNPs in linkage equilibrium with index/surrogate marker. Of the 44 European specific index SNPs, neither index nor surrogate SNPs were present for nine SNPs in the genotyping array. Of the remaining 35, associations were replicated at seven genes namely PTPN22 (rs1217407, p = 3×10−3); IL2–21 (rs13119723, p = 0.008); HLA-DRB1 (rs660895, p = 2.56×10−5; rs6457617, p = 1.6×10−09; rs13192471, p = 6.7×10−16); TNFA1P3 (rs9321637, p = 0.03); CCL21 (rs13293020, p = 0.01); IL2RA (rs2104286, p = 1.9×10−4) and ZEB1 (rs2793108, p = 0.006). Of the three Asian specific loci tested, rs2977227 in PADI4 showed modest association (p<0.02). Further, of the 140 SNPs (in LE with index/surrogate variant) tested, association was observed at 11 additional genes: PTPRC, AFF3, CD28, CTLA4, PXK, ANKRD55, TAGAP, CCR6, BLK, CD40 and IL2RB. This study indicates limited replication of European and Asian index SNPs and apparent allelic heterogeneity in RA etiology among north Indians warranting independent GWAS in this population. However, replicated associations of HLA-DRB1, PTPN22 (which confer ∼50% of the heritable risk to RA) and IL2RA suggest that cross-ethnicity fine mapping of such loci is apposite for identification of causal variants.

Genome-wide analysis of methotrexate pharmacogenomics in rheumatoid arthritis shows multiple novel risk variants and leads for TYMS regulation.

Objective Methotrexate (MTX) is the drug of first choice for the treatment of rheumatoid arthritis (RA), but is effective only in around 60% of the patients. Identification of genetic markers to predict response is essential for effective treatment within a critical window period of 6 months after diagnosis, but have been hitherto elusive. In this study, we used genome-wide genotype data to identify the potential risk variants associated with MTX (poor)response in a north Indian RA cohort. Materials and methods Genome-wide genotyping data for a total of 457 RA patients [297 good (DAS28-3⩽3.2) and 160 poor (DAS28-3≥5.1) responders] on MTX monotherapy were tested for association using an additive model. Support vector machine and genome-wide pathway analysis were used to identify additional risk variants and pathways. All risk loci were imputed to fine-map the association signals and identify causal variant(s) of therapeutic/diagnostic relevance. Results Seven novel suggestive loci from genome-wide (P⩽5×10−5) and three from support vector machine analysis were associated with MTX (poor)response. The associations of published candidate genes namely DHFR (P=0.014), FPGS (P=0.035), and TYMS (P=0.005) and purine and nucleotide metabolism pathways were reconfirmed. Imputation, followed by bioinformatic analysis indicated possible interaction between two reversely oriented overlapping genes namely ENOSF1 and TYMS at the post-transcriptional level. Conclusion In this first ever genome-wide analysis on MTX treatment response in RA patients, 10 new risk loci were identified. These preliminary findings warrant replication in independent studies. Further, TYMS expression at the post-transcriptional level seems to be probably regulated through an antisense-RNA involving the 6-bp ins/del marker in the overlapping segment at 3′UTR of TYMS-ENOSF1, a finding with impending pharmacogenetic applications.

An Unusual Cause of Paraparesis in a Patient on Chronic Steroid Therapy

Abstract Background/Objective: Spinal epidural lipomatosis is the excessive deposition of unencapsulated fat in the epidural space. This is a rare disorder often associated with high levels of endogenous steroids or the administration of exogenous steroids. Case Description: A 32-year-old man with congenital kyphosis treated with prednisolone daily for 5 months for interstitial lung disease developed compressive myelopathy. Findings: Magnetic resonance imaging showed congenital kyphosis along with epidural lipomatosis compressing the cord. Cessation of steroid therapy was associated with improvement in the symptoms. Conclusions: Spinal epidural lipomatosis is a rare side effect of chronic steroid therapy that may occur with relatively short-term, low-dose regimens. In patients with congenital vertebral anomalies, spinal fat deposition may worsen the neurological status in an already compromised cord. Discontinuation of steroid therapy is beneficial; some patients may require surgical intervention for decompression.

A Genome‐Wide Association Study Reveals ARL15, a Novel Non‐HLA Susceptibility Gene for Rheumatoid Arthritis in North Indians

OBJECTIVE Genome-wide association studies (GWAS) and their subsequent meta-analyses have changed the landscape of genetics in rheumatoid arthritis (RA) by uncovering several novel genes. Such studies are heavily weighted by samples from Caucasian populations, but they explain only a small proportion of total heritability. Our previous studies in genetically distinct North Indian RA cohorts have demonstrated apparent allelic/genetic heterogeneity between North Indian and Western populations, warranting GWAS in non-European populations. We undertook this study to detect additional disease-associated loci that may be collectively important in the presence or absence of genes with a major effect. METHODS High-quality genotypes for >600,000 single-nucleotide polymorphisms (SNPs) in 706 RA patients and 761 controls from North India were generated in the discovery stage. Twelve SNPs showing suggestive association (P < 5 × 10(-5)) were then tested in an independent cohort of 927 RA patients and 1,148 controls. Additional disease-associated loci were determined using support vector machine (SVM) analyses. Fine-mapping of novel loci was performed by using imputation. RESULTS In addition to the expected association of the HLA locus with RA, we identified association with a novel intronic SNP of ARL15 (rs255758) on chromosome 5 (Pcombined = 6.57 × 10(-6); odds ratio 1.42). Genotype-phenotype correlation by assaying adiponectin levels demonstrated the functional significance of this novel gene in disease pathogenesis. SVM analysis confirmed this association along with that of a few more replication stage genes. CONCLUSION In this first GWAS of RA among North Indians, ARL15 emerged as a novel genetic risk factor in addition to the classic HLA locus, which suggests that population-specific genetic loci as well as those shared between Asian and European populations contribute to RA etiology. Furthermore, our study reveals the potential of machine learning methods in unraveling gene-gene interactions using GWAS data.

Usefulness of anti -CCP antibodies in rheumatic diseases in Indian patients.

BACKGROUND The usefulness of anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) to identify rheumatic arthritis (RA) from other rheumatic diseases presenting with joint pain is not well studied. AIMS We aimed to determine the sensitivity and specificity of anti-CCP antibodies in Indian RA patients with respect to non-RA rheumatic diseases and to study the relationship of anti-CCP antibodies and IgG, IgM and IgA rheumatoid factor in RA. SETTINGS AND DESIGN Case-control cross-sectional study carried out in the rheumatology division of All India Institute of Medical Sciences. MATERIALS AND METHODS Sixty-three patients with rheumatoid arthritis (RA) and 51 patients with non-RA rheumatic diseases having joint pain were included in the study. Sera were tested for anti-CCP antibodies (IgG) and IgA, IgM, IgG rheumatoid factor, using a commercially available enzyme-linked immunosorbent assay. STATISTICAL ANALYSIS Statistical analysis was performed using SPSS statistical software version 11.5. RESULTS Fifty-four of 63 RA patients (85.71%) were positive for anti-CCP antibodies. In the non-RA group, anti-CCP antibody was positive in only 5 of 51 patients (9.8%). Our study found a sensitivity of 85% and a specificity of 90.19% with regard to the use of anti-CCP antibodies assay in patients with joint pain to correctly identify RA. Anti-CCP antibodies positive patients did not have more erosive disease. IgM-RF-positive patients had more erosion when compared to the IgM-RF-negative group. Thirty-two of 57 (56.1%) IgM-RF-positive patients had erosions, while no patient (0/6 patients) had erosions in the IgM-RF-negative group (P=0.01) CONCLUSION Anti-CCP antibodies have high sensitivity and specificity for diagnosis of RA, in Indian patients. Anti-CCP antibodies positive patients did not have more erosive disease in our study.

Fibrous dysplasia localized to spine: a diagnostic dilemma

Fibrous dysplasia of the spine is uncommon, especially in monostotic form. Isolated vertebral involvement in polyostotic form is very rare. We report a case of polyostotic fibrous dysplasia with lesions localized to dorso-lumbar spine in a 45-year-old rheumatoid arthritis patient. No associated appendicular lesions, cutaneous manifestations or endocrinopathies were seen. The extreme rarity of this type of lesion can pose a diagnostic dilemma, and biopsy is required for diagnosis. The association with rheumatoid arthritis in our case seems to be a chance occurrence.

Lemierre's syndrome due to community-acquired meticillin-resistant Staphylococcus aureus infection and presenting with orbital cellulitis: A case report

IntroductionLemierres syndrome is septic thrombophlebitis of the internal jugular vein leading to metastatic septic complications following an oropharyngeal infection. It is usually caused by the anaerobe, Fusobacterium necrophorum. Of late, meticillin-resistant Staphylococcus aureus is increasingly being recognised as a cause of community-acquired skin and soft tissue infections. We report a rare case of Lemierres syndrome caused by community-acquired meticillin-resistant Staphylococcus aureus infection.Case presentationA previously healthy 16-year-old girl presented with fever of 13 days duration, painful swelling around the right eye and diplopia followed by the appearance of pulmonary infiltrates. Imaging studies confirmed the clinical suspicion of bilateral jugular venous thrombosis with septic pulmonary embolism. Meticillin-resistant Staphylococcus aureus was isolated on blood cultures. The hospital course was complicated by massive haemoptysis and pulmonary aspiration necessitating mechanical ventilation. The patient subsequently made a complete recovery.ConclusionLemierres syndrome, although rare, is a potentially lethal but treatable complication of head and neck sepsis. Early clinical recognition of Lemierres syndrome and appropriate antibiotic treatment can be life-saving. One should consider the possibility of community-acquired meticillin-resistant Staphylococcus aureus infection in patients with suspected Lemierres syndrome.