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Chacko B.,St Johns Medical College Hospital | John G.T.,Royal Brisbane and Womens Hospital
Transplant Infectious Disease | Year: 2012

Cytomegalovirus (CMV) remains a major cause of morbidity and mortality among transplant recipients, frequently engaging the clinician in a struggle to balance graft preservation with control of CMV disease. Leflunomide has been shown to have immunosuppressive activity in experimental allograft models together with antiviral activity inhibiting CMV both in vitro and in vivo. Data are emerging about its potential role in ganciclovir-sensitive and -resistant CMV, primarily by virtue of a unique mechanism inhibiting virion assembly, as opposed to inhibition of viral DNA synthesis by current agents. This review aims to put in perspective, the knowledge acquired in the last decade or so on leflunomide for CMV. Evidence suggests that it might have activity against human CMV with good oral bioavailability and, more importantly in the resource-poor setting, is economical. Although the data presented here are not from randomized trials, several relevant observations have been made that could influence future, more structured assessments of the drug. An immune suppressive compound with antiviral features and experimental activity in chronic rejection is an attractive combination for organ transplantation, and it appears that leflunomide may just fit that niche. © 2011 John Wiley & Sons A/S.


Fulcher G.R.,University of Sydney | Christiansen J.S.,Aarhus University Hospital | Bantwal G.,St Johns Medical College Hospital | Polaszewska-Muszynska M.,Bydgoszcz Diabetes and Endocrinology Center | And 3 more authors.
Diabetes Care | Year: 2014

OBJECTIVE: Insulin degludec/insulin aspart (IDegAsp) is the first combination of a basal insulin with an ultralong duration of action, and a rapid-acting insulin in a single injection. This trial compared IDegAsp with biphasic insulin aspart 30 (BIAsp 30) in adults with type 2 diabetes inadequately controlled with once-or twice-daily (OD or BID) pre-or self-mixed insulin with or without oral antidiabetic drugs. RESEARCH DESIGN AND METHODS: In this 26-week, randomized, open-label, multinational, treat-to-target trial, participants (mean age 58.7 years, duration of diabetes 13 years, BMI 29.3 kg/m2, and HbA1c 8.4% [68 mmol/mol]) were exposed (1: 1) to BID injections of IDegAsp (n = 224) or BIAsp 30 (n = 222), administered with breakfast and the main evening meal and dose titrated to a self-measured premeal plasma glucose (PG) target of 4.0-5.0 mmol/L. RESULTS: After 26 weeks, mean HbA1c was 7.1% (54 mmol/mol) for both groups, with IDegAsp achieving the prespecified noninferiority margin for mean change in HbA1c (estimated treatment difference [ETD] -0.03% points [95% CI -0.18 to 0.13]). Treatment with IDegAsp was superior in lowering fasting PG (ETD -1.14 mmol/L [95% CI -1.53 to -0.76], P < 0.001) and had a significantly lower final mean daily insulin dose (estimated rate ratio 0.89 [95% CI 0.83-0.96], P = 0.002). Fewer confirmed, nocturnal confirmed, and severe hypoglycemia episodes were reported for IDegAsp compared with BIAsp 30. CONCLUSIONS: IDegAsp BID effectively improves HbA1c and fasting PG levels with fewer hypoglycemia episodes versus BIAsp 30 in patients with uncontrolled type 2 diabetes previously treated with once-or twice-daily pre-or self-mixed insulin. © 2014 by the American Diabetes Association.


Adhyapak S.M.,St Johns Medical College Hospital | Parachuri V.R.,Narayana Hrudayalaya Institute of Medical science
European Journal of Cardio-thoracic Surgery | Year: 2011

Objective: Surgical ventricular restoration has been the bailout therapy for end-stage heart failure due to ischemic cardiomyopathy in patients not suitable for cardiac transplantation. The recently concluded STICH trial has stated that surgical restoration of the left ventricle does not benefit this subgroup of patients clinically as compared with revascularization alone. The reasons for failure of this trial are multifactorial. The technique of surgical ventricular restoration employed in the STICH trial was circular endoventricular patch plasty. The various drawbacks related to this technique can be offset by a modification based on a mathematical hypothesis, which should result in a more physiological ventricular geometry, with consequent late reverse remodeling and improved left-ventricular performance. Methods: A total of 54 consecutive patients out of 102 patients with post-infarction left-ventricular aneurysms were studied before and 2 years after surgical ventricular restoration by linear endoventricular patch plasty using two-dimensional (2D) echocardiography and contrast ventriculography. Results: Linear endoventricular patch plasty resulted in a decrease in end-diastolic volume (EDV) of 40.2. ml (95% confidence interval (CI): 33.6, 46.7) and stroke volume (SV) of 10.0. ml (95% CI: 6.6, 13.5) and increase in ejection fraction (EF) of 6.7% (95% CI: 5.5, 7.9). There was a further 14% decrease in EDV and SV (30%) at 2 years with increase in EF (20%). There was a persistent significant improvement in sphericity index. The changes in EDV and SV were linearly related (r= 0.72, p< 0.001) and persisted at 2 years following surgery. The change in EDV was linearly related to the EF (r= 0.35, p= 0.02). The left-ventricular shape analysis showed improvements in the anterior and anterolateral segments (effect size = 1.1, p< 0.001) with nonsignificant changes in the inferior segments, conforming to an ellipsoid geometry. Conclusions: Linear endoventricular patch plasty restored a physiological elliptical ventricular geometry with persistent late reverse remodeling. The decreases in EDVs following surgery were significantly linearly proportional to the decreases in SVs at rest, which conforms to the normal left-ventricular geometry. © 2010 European Association for Cardio-Thoracic Surgery.


Devarbhavi H.,St Johns Medical College Hospital | Andrade R.J.,Hospital Universitario Virgen Of La Victoria | Andrade R.J.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas
Seminars in Liver Disease | Year: 2014

Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity. Copyright © 2014 by Thieme Medical Publishers, Inc.


Indumathi C.K.,St Johns Medical College Hospital
The Indian journal of chest diseases & allied sciences | Year: 2012

Lipoid pneumonia in children follows mineral oil aspiration and may result in acute respiratory failure. Majority of the patients recover without long-term morbidity, though a few may be left with residual damage to the lungs. We report a case of a two-and-a-half-year-old child with persistent lipoid pneumonia following accidental inhalation of machine oil, who was successfully treated with steroids.


Manohari S.M.,St Johns Medical College Hospital
Journal of Indian Association for Child and Adolescent Mental Health | Year: 2013

The Vineland Adaptive Behavior Scales - II Edition 2005 (Vineland-II) is useful in assessing abilities in autism spectrum disorder, where an accurate assessment of intelligence using standardized tools is difficult both due to the unique social and communication difficulties that these children present with and the behavioral issues that occur as co morbidity. We describe the scale and our experience in using the scale. Difficulties in administration of the scale to Indian children are illustrated. The main reasons for these difficulties center on cultural differences in gender roles and differences in the way some self care tasks are performed.


Adhyapak S.M.,St Johns Medical College Hospital
Preventive Cardiology | Year: 2010

The relationship of right ventricular function and pulmonary systolic pressure in patients with congestive heart failure was evaluated to risk-stratify them. The study included 147 consecutive patients with symptomatic heart failure who underwent clinical and laboratory examination and echocardiography including Doppler tissue echocardiography. They were followed for a mean of 11.2±6.4 months. During follow-up, 16 patients died and 45 patients had nonfatal cardiac events. There were 60 readmissions for heart failure. Pulmonary artery systolic pressure and right ventricular systolic function were inversely related (r2=0.66, P<001). On Cox multivariate survival analysis, early worsening of pulmonary arterial pressures was an independent prognostic predictor (hazard ratio, 0.44; confidence interval, 0.28-0.91, P=024). The patients with pulmonary hypertension and right ventricular systolic dysfunction had the worst prognosis. The assessments of right ventricular function help to risk-stratify patients with heart failure. The early worsening of pulmonary hypertension is a powerful predictor of worse prognosis. © 2009 Wiley Periodicals, Inc.


Devarbhavi H.,St Johns Medical College Hospital
Journal of Clinical and Experimental Hepatology | Year: 2012

Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. No age is exempt although adults and the elderly are at increased risk. DILI spans the entire spectrum ranging from asymptomatic elevation in transaminases to severe disease such as acute hepatitis leading to acute liver failure. The liver specific Roussel Uclaf Causality Assessment Method is the most validated and extensively used for determining the likelihood that an implicated drug caused DILI. Asymptomatic elevation in liver tests must be differentiated from adaptation. Drugs producing DILI have a signature pattern although no single pattern is characteristic. Antimicrobial and central nervous system agents including antiepileptic drugs are the leading causes of DILI worldwide. In the absence of a diagnostic test or a biomarker, the diagnosis rests on the evidence of absence of competing causes such as acute viral hepatitis, autoimmune hepatitis and others. Recent studies show that antituberculosis drugs given for active or latent disease are still a major cause of drug-induced liver injury in India and the West respectively. Presence of jaundice signifies a severe disease and entails a worse outcome. The pathogenesis is unclear and is due to a mix of host, drug metabolite and environmental factors. Research has evolved from incriminating candidate genes to genome wide analysis studies. Immediate cessation of the drug is key to prevent or minimize progressive damage. Treatment is largely supportive. N-acetylcysteine is the antidote for paracetamol toxicity. Carnitine has been tried in valproate injury whereas steroids and ursodeoxycholic acid may be used in DILI associated with hypersensitivity or cholestatic features respectively. This article provides an overview of the epidemiology, the patterns of hepatotoxicity, the pathogenesis and associated risk factors besides its clinical management. © 2012 INASL.


Chacko B.,St Johns Medical College Hospital
Clinical Transplantation | Year: 2012

Long-term renal graft survival is hampered by allograft dysfunction and cardiovascular disease resulting from calcineurin inhibitors (CNIs). This has led to the development of immunosuppressive regimens involving mammalian target of rapamaycin (mTOR) inhibitors, sirolimus and everolimus. They seem to provide long-term benefits for kidney function in transplant patients because of their anti-proliferation and anti-tumor properties and absence of nephrotoxicity. Their use has been evaluated in therapeutic regimens aimed at reducing the nephrotoxicity associated with CNIs. Both proactive and reactive strategies have been used. Whether existing strategies of using mTORi in renal transplantation is applicable for Indian patient's remains to be seen. Data on side effect profile, economic viability and the impact of these drugs on infections, particularly in India, are worth documenting. After briefly reviewing available data from India, this article explores the indications, patient populations; timing and practical aspects as well as the safety and efficacy of mTORi-based regimens for renal transplantation and suggests a framework which could allow transplant physicians to tailor its use to their own practice with particular reference to the Indian subcontinent. © 2011 John Wiley & Sons A/S.


Devarbhavi H.,St Johns Medical College Hospital
Tropical gastroenterology : official journal of the Digestive Diseases Foundation | Year: 2011

Drug-induced liver injury (DILI) is a minor but significant cause of liver injury across all regions. Antituberculosis drug-induced liver injury (TB DILI) is a leading cause of DILI and drug-induced acute liver failure (DIALF) in India and much of the developing world. Single center registries of DILI continue to highlight the high incidence of DILI and DIALF, much of it due to diagnostic errors and inappropriate prescriptions. The clinical spectrum includes asymptomatic elevation in liver tests to acute hepatitis and acute liver failure. TB DILI can occur across all age groups including children with significant morbidity and mortality. Although TB DILI develops more commonly in males, ALF is noted to be commoner in females with a worse prognosis. Contrasting reports on the role of genetic and environmental factors continue to be published. Since DILI is a diagnosis of exclusion, acute viral hepatitis particularly hepatitis E needs to be excluded in such cases. The presence of jaundice, hypoalbuminemia, ascites, encephalopathy and high prothrombin time are poor prognostic markers. Recent reports of the beneficial role of N-acetylcysteine in DIALF and in preventing TB DILI in elderly individuals needs further investigation. Reintroduction of antitubercular therapy must be balanced with the knowledge of adaptation a common occurrence with antituberculosis drugs. Although monitoring and rechallenge practices vary greatly, the importance of early clinical symptoms cannot be underestimated. Simultaneous rechallenge with combination drugs or sequential treatment have similar incidence of DILI, although increasing reports about the role of pyrazinamide in DILI and on rechallenge warrants its careful use. The combined affliction of HIV or chronic hepatitis B or C and tuberculosis poses multiple challenges including the greatly increased risks of DILI.

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