Pranavchand R.,Indian Statistical Institute |
Kumar A.S.,Care Hospitals |
Reddy B.M.,Indian Statistical Institute
Human Genomics | Year: 2017
Background: Genetic predisposition to the clinical categories of coronary artery disease (anatomical viz., insignificant, single, double, and triple vessel diseases and phenotypic severity categories viz., angina, acute coronary syndrome, and myocardial infarction) is poorly understood. Particularly, the apolipoprotein genes clustered at 11q23.3 chromosomal region play a vital role in cholesterol homeostasis, and a large number of SNPs identified in this region need to be explored for their association with the clinical categories of CAD. Methods: Using fluidigm SNP genotyping platform, a prioritized set of 96 SNPs of 11q23.3 chromosomal region were genotyped on 508 CAD cases and 516 ethnicity matched controls, enrolled from Hyderabad, India, and its vicinity. Results: The association analysis suggests 19 and 15 SNPs to be significantly associated (p ≤ 0.05) with at least one of the anatomical and/or phenotypic severity categories, respectively. Overall, the six SNPs rs17440396:G>A, rs6589566:A>G, rs2849165:G>A, rs10488699:G>A, rs1263163:G>A, and rs1263171:G>A were significant even after correction for multiple testing. Three of these (rs17440396:G>A, rs6589566:A>G, and rs2849165:G>A) that belong to BUD13, ZPR1, and APOA5-APOA4 intergenic regions, respectively, were found to be associated across the anatomical categories of CAD. However, no particular trend in the genotypic odds ratios with the increasing severity was apparent. The association analysis of the variants with phenotypic severity categories suggests that a high degree of phenotypic severity could be a result of more number of risk alleles. While the risk score analysis suggests high discriminative power of the variants towards the individual clinical categories of CAD, the complex network of interactions seen between the intronic variants of BUD13 and ZPR1 regulatory genes and intergenic variants of APOA5-APOA4 suggests pleiotropic effects of regulatory genes in the manifestation of these CAD categories. Conclusion: The complex network of interactions observed in the present study between the regulatory and protein-coding genes suggests their role in the manifestation of distinct clinical categories of CAD, which needs to be functionally validated. © 2017 The Author(s).
Pulido T.,Ignacio Chavez National Heart Institute |
Adzerikho I.,Republican Scientific Practical Center Cardiology |
Channick R.N.,Massachusetts General Hospital |
Delcroix M.,Gasthuisberg University Hospital |
And 19 more authors.
New England Journal of Medicine | Year: 2013
BACKGROUND: Current therapies for pulmonary arterial hypertension have been adopted on the basis of short-term trials with exercise capacity as the primary end point. We assessed the efficacy of macitentan, a new dual endothelin-receptor antagonist, using a primary end point of morbidity and mortality in a long-term trial. METHODS: We randomly assigned patients with symptomatic pulmonary arterial hypertension to receive placebo once daily, macitentan at a once-daily dose of 3 mg, or macitentan at a once-daily dose of 10 mg. Stable use of oral or inhaled therapy for pulmonary arterial hypertension, other than endothelin-receptor antagonists, was allowed at study entry. The primary end point was the time from the initiation of treatment to the first occurrence of a composite end point of death, atrial septostomy, lung transplantation, initiation of treatment with intravenous or subcutaneous prostanoids, or worsening of pulmonary arterial hypertension. RESULTS: A total of 250 patients were randomly assigned to placebo, 250 to the 3-mg macitentan dose, and 242 to the 10-mg macitentan dose. The primary end point occurred in 46.4%, 38.0%, and 31.4% of the patients in these groups, respectively. The hazard ratio for the 3-mg macitentan dose as compared with placebo was 0.70 (97.5% confidence interval [CI], 0.52 to 0.96; P = 0.01), and the hazard ratio for the 10-mg macitentan dose as compared with placebo was 0.55 (97.5% CI, 0.39 to 0.76; P<0.001). Worsening of pulmonary arterial hypertension was the most frequent primary end-point event. The effect of macitentan on this end point was observed regardless of whether the patient was receiving therapy for pulmonary arterial hypertension at baseline. Adverse events more frequently associated with macitentan than with placebo were headache, nasopharyngitis, and anemia. CONCLUSIONS: Macitentan significantly reduced morbidity and mortality among patients with pulmonary arterial hypertension in this event-driven study. Copyright © 2013 Massachusetts Medical Society.
Bohora S.,Baroda Heart Institute and Research Center |
Lokhandwala Y.,Arrhythmia Associates |
Parekh P.,CARE Hospitals |
Vasavda A.,CARE Hospitals
Journal of Cardiovascular Electrophysiology | Year: 2011
Reversal of Tachycardiomyopathy. Ivabradine has been shown to be effective in reducing sinus rate. Here we report of a case where ivabradine reduced the rate of a focal atrial tachycardia relieving patient's symptoms and reversing tachycardiomyopathy. © 2010 Wiley Periodicals, Inc.
Bouchard J.,University of Montréal |
Acharya A.,Jacobi Medical Center |
Cerda J.,Albany Medical College |
Maccariello E.R.,Quinta Dor Hospital |
And 6 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2015
Background and objectives AKI is frequent and is associated with poor outcomes. There is limited information on the epidemiology of AKI worldwide. This study compared patients with AKI in emerging and developed countries to determine the association of clinical factors and processes of care with outcomes. Design, setting, participants, & measurements This prospective observational study was conducted among intensive care unit patients from nine centers in developed countries and five centers in emerging countries. AKI was defined as an increase in creatinine of ≥0.3 mg/dl within 48 hours. Results Between 2008 and 2012, 6647 patients were screened, of whom 1275 (19.2%) developed AKI. A total of 745 (58% of those with AKI) agreed to participate and had complete data. Patients in developed countries had more sepsis (52.1% versus 38.0%) and higher Acute Physiology and Chronic Health Evaluation (APACHE) scores (mean±SD, 61.1±27.5 versus 51.1±25.2); those from emerging countries had more CKD (54.3% versus 38.3%), GN (6.3% versus 0.9%), and interstitial nephritis (7.0% versus 0.6%) (all P&0.05). Patients from developed countries were less often treated with dialysis (15.5% versus 30.2%; P&0.001) and started dialysis later after AKI diagnosis (2.0 [interquartile range, 0.75–5.0] days versus 0 [interquartile range, 0–5.0] days; P=0.02). Hospital mortality was 22.0%, and 13.3% of survivors were dialysis dependent at discharge. Independent risk factors associated with hospital mortality included older age, residence in an emerging country, use of vasopressors (emerging countries only), dialysis and mechanical ventilation, and higher APACHE score and cumulative fluid balance (developed countries only). A lower probability of renal recovery was associated with residence in an emerging country, higher APACHE score (emerging countries only) and dialysis, while mechanical ventilation was associated with renal recovery (developed countries only). Conclusions This study contrasts the clinical features and management of AKI and demonstrates worse outcomes in emerging than in developed countries. Differences in variations in caremay explain these findings and should be considered in future trials. © 2015, by the American Society of Nephrology.
Singh G.,Dayanand Medical College |
Rajshekhar V.,Christian Medical College |
Murthy J.M.K.,CARE Hospitals |
Prabhakar S.,Jawaharlal Institute of Postgraduate Medical Education & Research |
And 4 more authors.
Neurology | Year: 2010
Background: Solitary cysticercus granuloma (SCG) is one of the most common forms of presentation of neurocysticercosis (NCC). The diagnostic workup and management approach to this condition remain uncertain and controversial. Objective: To review evidence and develop a consensus approach to the diagnosis and treatment of SCG. Methods: A multidisciplinary expert group meeting was convened in order to review and discuss various aspects of management of patients with SCG. Evidence reviewed was classified and a consensus was evolved according to standard protocols. Results: SCG is commonly recognized on CT as an enhancing lesion measuring <20 mm. Further evaluation with MRI does not add much information. The use of antihelminthic agents (specifically, albendazole in combination with corticosteroids) and corticosteroids alone have been shown to improve radiologic resolution and seizure outcome in patients with SCG. However, the sizes of the effects are modest. By convention, all patients with SCG presenting with seizures are initiated on antiepileptic drugs (AEDs). Available evidence suggests that withdrawal of AEDs after complete resolution of the SCG is safe. There is a high risk of seizure relapse after AED withdrawal in patients with calcific residue following resolution of the SCG. The duration of AED prophylaxis in these individuals is unclear. Conclusions: It is desirable to have large, multicenter trials with sufficiently long follow-up, comparing outcomes with the use of antihelminthics with or without corticosteroids and corticosteroids alone in order to dissect out the benefits accrued due to each of these classes of drugs. © 2010 by AAN Enterprises, Inc.
Matsa L.S.,Osmania University |
Sagurthi S.R.,Osmania University |
Ananthapur V.,Institute of Genetics and Hospital for Genetic Diseases |
Nalla S.,CARE Hospitals |
Nallari P.,Osmania University
Gene | Year: 2014
Dilated cardiomyopathy (DCM) is a myocardial disease of unknown etiology with left ventricular dilatation and impaired myocardial contractility leading to heart failure. It is considered to be a multifactorial disorder with the interplay of both genetic and environmental factors. One of the possible genes implicated in DCM is endothelin 1 (EDN1). The genetic variants of EDN1 may be involved in the pathophysiology of DCM hence the entire EDN1 gene was screened to examine for the possible genotypic associations with DCM. A total of 115 DCM patients and 250 control subjects were included in the present study. PCR based SSCP analysis was carried out followed by commercial sequencing. Screening of EDN1 revealed two common and two rare polymorphisms. Allelic and genotypic frequencies were estimated in patient and control groups by appropriate statistical tests. The heterozygotes of insertion variation (+. 138A) were found to exhibit four-fold increase risk to DCM (OR=4.12, 95% CI 2.10-8.08; p=0.0001). The two rare variants (G>A transition (rs150035515) at c.90 and C>T transition (rs149399492) at c.119) observed in the present study were found to be unique in DCM. The secondary mRNA structures of these variations were found to have less free energy than wild type. The haplotype analysis revealed 4A-T to be risk haplotype for DCM (OR 5.90, 95% CI 2.29-15.25, p=0.0001). In conclusion, EDN1 polymorphisms (+. 138A, A30A, T40I) appear to play a significant role in the pathogenesis of DCM, as they influence the stability of protein. The increased EDN1 production may lead to constriction of coronary arteries, reducing coronary blood flow which may in turn increase the load on left ventricle, impairing contractility of the heart resulting in a DCM phenotype, an end stage of heart failure. © 2014 Elsevier B.V.
Vadapalli S.,Osmania University |
Surekha Rani H.,Osmania University |
Sastry B.K.S.,CARE Hospitals |
Nallari P.,Osmania University
International Journal of Molecular Epidemiology and Genetics | Year: 2010
Idiopathic Pulmonary arterial hypertension (IPAH) is a debilitating disease associated with very poor prognosis. The disease is characterised by endothelial dysfunction, smooth muscle proliferation and insitu thrombosis in the pulmonary artery, eventually leading to right ventricular failure. Two of the key endothelial mediators implicated in the pathogenesis of IPAH are endothelin-1 (EDN1) and nitric oxide (NO). EDN1 is a potent endogenous vasoconstrictor whereas NO is a vasodilator. In the present study screening of the EDN1 gene (EDN1) and NOS3 polymorphisms was taken up, to evaluate their association with IPAH. A significant association of EDN1 3A/4A polymorphism (+138 A; rs10478694) (OR-3.485; CI-1.254, 9.999; p=0.013) and EDN1 Lys198Asn polymorphism (G/T, rs5370) (OR-3.378, CI-1.104, 10.582; p=0.03) with IPAH was observed. Our results indicate that EDN1 polymorphisms in interaction with other genetic markers may play a significant role in individual's susceptibility to the disease and its clinical progression.
Swamy T.L.,Care Hospitals
The Indian journal of chest diseases & allied sciences | Year: 2010
A young man presented with infrequent haemoptysis spanning over 10 years. Chest radiograph was normal. However, the computed tomography (CT) of the chest had shown endotracheal wall changes. The diagnosis of tracheopathia osteoplastica was suggested on fiberoptic bronchoscopy and confirmed histologically.
Kiran V.R.,Care Hospitals |
Zhu T.Y.,Fudan University |
Yip T.,Tung Wah Hospital |
Lui S.L.,Tung Wah Hospital |
Lo W.K.,Tung Wah Hospital
Peritoneal Dialysis International | Year: 2014
⧫ Background: Obesity increases mortality in the general population, but improves survivalin hemodialysis patients. In peritoneal dialysis (PD) patients, the reported effect is controversial. We investigated the effect of body mass index (BMI) on patient survival in Asian PD patients. ⧫ Methods: The survival of incident Asian PD patients from 2001 to 2008 in a single center in Hong Kong was analyzed retrospectively. Baseline demographic and clinical data were collected from patient records. Patients who had a total Kt/V below 1.7 or who died within 6 months were excluded. The BMI was categorized using the World Health Organization recommendation for Asian populations. ⧫ Results: In the 274 study patients [154 men (56%); 138 with diabetes (50.4%); mean age: 63.4 ± 14.6 years; mean BMI: 21.97 ±3.23 kg/m2; 37 underweight (13.5%); 35 obese (12.8%)], the relative risk (RR) for mortality [adjusted for age, diabetes status, and cardiovascular disease (CVD)] was similar for the normal and overweight groups, but higher for the underweight (RR: 1.909; p = 0.028) and obese groups (RR: 1.799; p = 0.048).The increased mortality in obese patients was more prominent in patients with diabetes (RR: 1.9 vs 1.19 in patients without diabetes; p = 0.074 and 0.76 respectively), and in patients with CVD (RR: 8.895 vs 1.642 in patients without CVD; p = 0.012 and 0.122 respectively). ⧫ Conclusions: In Asian PD patients, the relationship between BMI and mortality was U-shaped, with higher mortality in the underweight and obese patients. The negative impact of obesity was more prominent in patients with diabetes and CVD. Pent DialInt 2014; 34(4):390-398 www.PDIConnect.com epub ahead of print: 04 Feb 2014 doi:10.3747/pdi.2013.00055 © 2014 International Society for Peritoneal Dialysis
Lingappa L.,Rainbow Hospital for Women and Children |
Varma R.D.,Care Hospitals |
Siddaiahgari S.,Rainbow Hospital for Women and Children |
Konanki R.,Rainbow Hospital for Women and Children
Developmental Medicine and Child Neurology | Year: 2014
Aims: The objective of this study was to describe a cohort of infants with basal ganglia stroke associated with mineralization in the lenticulostriate arteries and their clinical outcomes. Method: Subcortical strokes occurring in infants during the study period were categorized as arterial ischaemic, venous, or haemorrhagic. A cohort of infants with basal ganglia infarcts and associated mineralization of lenticulostriate arteries were identified. This group was analysed for possible aetiological factors, clinical course, and recurrence rate of the stroke. Results: Of 23 infants with basal ganglia arterial ischaemic stroke, 22 (16 males, six females; mean age 11mo [±SD 4.8mo]) were found to have lenticulostriate artery mineralization. Twenty infants presented with hemiparesis and two presented with recurrent episodes of hemidystonia. Eighteen infants had a history of minor trauma before onset of stroke. No other predisposing factors were identified in this cohort. There were no demonstrable causes for vascular and soft tissue calcification. The mean follow-up was 11 months, during which five infants experienced stroke recurrence. Of the 17 infants who did not experience a recurrent stroke, eight exhibited complete neurological recovery, and nine had mild residual hemiparesis. Interpretation: Acute basal ganglia stroke after minor trauma associated with mineralization of lenticulostriate arteries in infants is a distinct clinicoradiological entity. Investigations for prothrombotic states and vasculopathies are normal. Although neurological outcomes in most children are good, trauma is a risk factor for recurrence of stroke. This article is commented on by deVeber on pages 9-10 of this issue. © 2013 Mac Keith Press.