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Biomedical subjects

Vivek Rao

Publications and source records attributed to Vivek Rao.

At least 55 records · Page 3Linked to original sources
PubMed2004

Hypersensitivity myocarditis complicating hypertrophic cardiomyopathy heart.

The present report describes a case of eosinophilic myocarditis complicating hypertrophic cardiomyopathy. The 47-year-old female patient, known to have hypertrophic cardiomyopathy, was admitted with biventricular failure and managed aggressively with dobutamine infusion and other drugs while being assessed for heart transplantation. On transthoracic echocardiogram, she had moderate left ventricular dysfunction with regional variability and moderate mitral regurgitation. The recipient's heart showed the features of apical hypertrophic cardiomyopathy and myocarditis with abundant eosinophils. Myocarditis is rare and eosinophilic myocarditis is rarer. It is likely that the hypersensitivity (eosinophilic) myocarditis was related to dobutamine infusion therapy. Eosinophilic myocarditis has been reported with an incidence of 2.4% to 7.2% in explanted hearts and may be related to multidrug therapy.

Adrenergic beta-Agonists↗
PubMed2003

Skewing of the Th1/Th2 responses in mice due to variation in the level of expression of an antigen in a recombinant BCG system.

In spite of rapid developments in the study of mycobacteria during the last two decades, tuberculosis (TB) has maintained its status as the leading killer among all infectious diseases. Extensive evidence exists to support a central role for a T-helper type 1 (Th1) immune response for protection against TB in mice and humans. Bacille Calmette-Guerin (BCG), the only vaccine against TB, although not perfect in its ability to protect against the adult form of TB, is a strong inducer of Th1 responses and is being increasingly used as a delivery vehicle for the presentation of foreign antigens to the immune system. It has been proposed that expression of immunodominant antigens or cytokine genes in BCG can enhance the ability of BCG to induce a Th1 immune response. Since dose of the antigen is considered as one of the parameters that influence the Th cell responses, the level of expression of the candidate antigen should influence the final Th response against the recombinant BCG (rBCG). In the present study, the effect of over-expression of a candidate antigen Antigen 85B (Ag 85B) in a rBCG system, on the Th-priming ability of BCG has been investigated in the murine model. BALB/c mice were immunized with three different rBCG constructs expressing Ag 85B to various levels. Induction of Th1/Th2 responses was analyzed by measuring levels of interferon-gamma (Th1) and interleukin-10 (Th2) in antigen-stimulated splenocyte cultures and by quantifying the antigen-specific IgG2a (Th1) and IgG1 (Th2) antibody responses. By varying the level of expression of Ag 85B, specific immune responses against Ag 85B were observed to range from mixed Th1/Th2 to Th1. However, the BCG-specific immune responses in case of all rBCG-immunized animals remained predominantly Th1.

Animals↗
PubMed2003

Immunogenicity of recombinant BCG vaccine strains overexpressing components of the antigen 85 complex of Mycobacterium tuberculosis.

The components of antigen 85 complex of Mycobacterium tuberculosis (Ag 85A, Ag 85B and Ag 85C), due to their immunodominant and secretory nature, represent promising protective antigen candidates and have been used in numerous vaccine preparations. We have used recombinant Bacille Calmette Guerin (BCG) strains overexpressing Ag 85A and Ag 85C to immunize BALB/c mice to investigate the immunogenicity of these strains. Mice immunized with recombinant BCG strains exhibited an increased humoral immune response when compared to mice immunized with wild-type BCG. The recombinant BCG strain overexpressing Ag 85A also induced an increased Th1-like response, characterized by elevated levels of IFN-gamma in antigen stimulated splenocyte cultures and a strong IgG2a antibody response, when compared to wild-type BCG. Immunization with recombinant BCG strain overexpressing Ag 85C, on the other hand did not elicit increased IFN-gamma secretion on restimulation of splenocytes in vitro.

Acyltransferases↗
PubMed2003

Calcium antagonists reduce cardiovascular complications after cardiac surgery: a meta-analysis.

OBJECTIVES: We sought to determine the efficacy of calcium antagonists (CAs) in reducing death, myocardial infarction (MI), ischemia, and supraventricular tachyarrhythmia (SVT) after cardiac surgery. BACKGROUND: Calcium antagonists may reduce complications after cardiac surgery-namely, death, MI, and renal failure. However, they are underused, possibly due to the results from previous observational studies. METHODS: Both MEDLINE (1966 to December 2001) and EMBASE (1980 to December 2001) were searched, with supplementation by reference list searches. No language restrictions were applied. Included studies were randomized, controlled trials (RCTs) evaluating preoperative, intraoperative, or postoperative (first 48 h) CA use (intravenous or oral) during aortocoronary bypass or valve surgery. Studies were excluded if they exclusively recruited transplant recipients, individuals <18 years old, or patients with pre-existing SVT. Two reviewers independently evaluated study quality by using the Jadad score; a minimal score of 1/5 was required. Forty-one studies, encompassing 3,327 patients, were included. No studies assessed treatment exclusively with short-acting oral nifedipine. Treatment effects were calculated using the random-effects model. Heterogeneity was assessed using the Q test. RESULTS: Calcium antagonists significantly reduced MI (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.37 to 0.91; p = 0.02) and ischemia (OR 0.53, 95% CI 0.39 to 0.72; p < 0.001). Non-dihydropyridines significantly reduced SVT (OR 0.62, 95% CI 0.41 to 0.93; p = 0.02). Calcium antagonists were associated with trends toward decreased mortality during aortocoronary bypass (OR 0.66, 95% CI 0.26 to 1.70, p = 0.4). CONCLUSIONS: Use of CAs during cardiac surgery significantly reduced rates of MI, ischemia, and SVT. Further study using large RCTs is justified.

Calcium Channel Blockers↗
PubMed2003

Cardiac cell transplantation: closer to bedside.

The current treatment for heart failure is inadequate for a large number of patients who do not qualify for heart transplantation or innovative surgical therapy. Cellular augmentation of damaged myocardium has been actively investigated in the past decade. Cells best suited for the task are skeletal myoblasts and bone morrow mesenchymal stem cells. Both cell types are autologous, abundant, and easy to harvest. The focus of early human trials will be to establish the safety of an effective cellular dose. Trials conducted with an inadequate cellular dose may discredit cell therapy because of lack of effect but, more importantly, may provide a false sense of safety because of a lack of adverse events secondary to a small inoculating dose.

Animals↗
PubMed2003

Skeletonization of bilateral internal thoracic artery grafts lowers the risk of sternal infection in patients with diabetes.

OBJECTIVE: Deep sternal wound infection is a dreaded complication of coronary artery bypass surgery, particularly in patients with diabetes. This study determines whether skeletonization of internal thoracic artery conduits compared with pedicled harvesting reduces the risk of deep sternal wound infection in patients with diabetes undergoing bilateral internal thoracic artery grafting. METHODS: We reviewed prospectively gathered data on all patients who have undergone coronary artery bypass grafting and received bilateral internal thoracic artery grafts at our institution since 1990. We compared patients with diabetes who received skeletonized (n = 79) versus conventional pedicled (n = 36) internal thoracic artery conduits. RESULTS: The proportion of patients taking insulin (19.0% vs 14.0% for skeletonized vs conventional grafts, respectively, P =.6) or oral hypoglycemic agents (68.4% vs 69.4%, P =.9), as well as the prevalence of type I diabetes (2.5% vs 8.3%, P =.18), were similar in both groups. Patients who received skeletonized grafts were more likely to receive a free rather than an in situ right internal thoracic artery graft (93.7% vs 30.6%, P <.001). The prevalence of deep sternal wound infection was significantly lower in patients who received skeletonized grafts compared with patients who received conventional grafts (1.3% vs 11.1%, P =.03). Patients in the skeletonized group were also less likely to develop any (superficial or deep) sternal wound infection postoperatively (5.1% vs 22.2%, P =.03). There was no significant difference in the prevalence of deep sternal wound infection between patients with diabetes who received skeletonized internal thoracic arteries and patients without diabetes who underwent conventional internal thoracic artery grafting (n = 578) (1.2% vs 1.6%, respectively, P =.8). CONCLUSIONS: Skeletonization of internal thoracic artery conduits lowers the risk of deep sternal wound infection in patients with diabetes undergoing bilateral internal thoracic artery grafting. We no longer consider diabetes a contraindication to bilateral internal thoracic artery grafting, provided the internal thoracic arteries are skeletonized.

Adult↗
PubMed2003

Tetrahydrobiopterin attenuates homocysteine induced endothelial dysfunction.

Homocysteine is an independent risk factor for atherosclerotic vascular disease. It impairs endothelial function via increasing superoxide production and quenching nitric oxide (NO) release. Tetrahydrobiopterin (BH4) is a critical cofactor that couples nitric oxide synthase and facilitates the production of nitric oxide (vs. superoxide anions). In the first study, the effects of hyperhomocysteinemia (0.1 mM, 3 h) on endothelium-dependent vasorelaxation to ACh and A23187 were examined in isolated segments of rat aortae in the presence or absence of BH4 (0.1 mM). In the second study, the effects of hyperhomocysteinemia (24 h) on nitric oxide production and superoxide release (using lucigenin chemiluminescence) were studied in human umbilical vein endothelial cells in the absence or presence of BH4 (10 microM). Homocysteine incubation impaired receptor-dependent and -independent endothelial function to ACh and A23187. This effect was attenuated by BH4. Furthermore, homocysteine exposure increased superoxide production and impaired agonist-stimulated nitric oxide release. These effects were attenuated by BH4 (p < 0.05). Hyperhomocysteinemia impairs endothelial function, in part due to a diminished bioavailability of BH4 with resultant uncoupling of nitric oxide synthase. BH4 may represent an important target for strategies aimed at improving endothelial dysfunction secondary to hyperhomocysteinemia.

Acetylcholine↗
PubMed2003

Caveolin: a key target for modulating nitric oxide availability in health and disease.

The endothelial layer is a key component of the cardiovascular system. Recent evidence indicates that strategies aimed at preserving the endothelium may have important implications in the battle against cardiovascular disease. Nitric oxide remains the critical factor determinant of endothelial function. Understanding the regulatory components involved in nitric oxide production may elucidate novel targets for improving compromised vascular function. The caveolae/caveolin system has recently become of interest due to its ability to regulate endothelial nitric oxide synthase activity. The caveolae/caveolin system is a multifaceted structure in the plasma membrane, which plays an integral role in cellular signaling. Recognizing the potential of this specialized domain may provide the fundamental knowledge to target the endothelium in disease.

Animals↗
PubMed2003

Disruption of mptpB impairs the ability of Mycobacterium tuberculosis to survive in guinea pigs.

Protein tyrosine kinases and tyrosine phosphatases from several bacterial pathogens have been shown to act as virulence factors by modulating the phosphorylation and dephosphorylation of host proteins. The identification and characterization of two tyrosine phosphatases namely MptpA and MptpB from Mycobacterium tuberculosis has been reported earlier. MptpB is secreted by M. tuberculosis into extracellular mileu and exhibits a pH optimum of 5.6, similar to the pH of the lysosomal compartment of the cell. To determine the role of MptpB in the pathogenesis of M. tuberculosis, we constructed a mptpB mutant strain by homologous recombination and compared the ability of parent and the mutant strain to survive intracellularly. We show that disruption of the mptpB gene impairs the ability of the mutant strain to survive in activated macrophages and guinea pigs but not in resting macrophages suggesting the importance of its role in the host-pathogen interaction. Infection of guinea pigs with the mutant strain resulted in a 70-fold reduction in the bacillary load of spleens in infected animals as compared with the bacillary load in animals infected with the parental strain. Upon reintroduction of the mptpB gene into the mutant strain, the complemented strain was able to establish infection and survive in guinea pigs at rates comparable to the parental strain. These observations demonstrate a role of MptpB in the pathogenesis of M. tuberculosis.

Animals↗
PubMed2003

Revised screening scale to predict survival after insertion of a left ventricular assist device.

BACKGROUND: We previously calculated a risk factor summation score that successfully predicted survival after insertion of a left ventricular assist device. We sought to validate our previous score by using a single center's clinical experience and to determine emerging risk factors for mortality after device insertion. METHODS: The clinical records of 130 consecutive patients who received the HeartMate VE left ventricular assist device (Thoratec Corp, Pleasanton, Calif) at our institution between June 1996 and March 2001 as a bridge to transplantation were reviewed. Univariate and multivariable analyses were performed to determine the predictors of operative mortality after device insertion. Using the relative risks for each identified variable, we devised a new risk factor summation score. The new and old scores were then compared by using linear regression analyses to determine whether the revised score improved statistical accuracy. RESULTS: Overall operative mortality was 25% (n = 33). The old score successfully predicted operative mortality in the current patient population (operative mortality of 38% for score >5 vs 13% for score < or =5). However, the revised score improved risk discrimination (operative mortality of 46% for a score >5 vs 12% for a score < or = to 5). Statistical accuracy was comparable between scores, but the relationship between observed and predicted outcomes was improved with the revised score. CONCLUSIONS: The changing demographic profile and management of patients presenting for mechanical circulatory support has led to a change in the predictors of mortality after device insertion. Periodic remodeling and recalibration of risk indices helps to accurately predict outcomes in high-risk patient groups and identifies emerging risk factors for mortality.

Female↗
PubMed2003

Immunologic sensitization in recipients of left ventricular assist devices.

OBJECTIVE: Left ventricular assist device implantation is associated with an increased risk of development of circulating anti-HLA class I and II antibodies (sensitization). We investigated the impact of sensitization on posttransplantation outcomes in 105 consecutive left ventricular assist device recipients. METHODS: Five hundred twenty-one consecutive adult cardiac allograft recipients between 1992 and 1999 were retrospectively studied. Of these, 105 were supported with a left ventricular assist device. Pretransplantation and posttransplantation antibody production, time to transplantation after listing, rejection, freedom from transplant coronary artery disease, and survival were evaluated by Kaplan-Meier analysis. Among sensitized left ventricular assist device recipients, 26 were treated with a pretransplantation immunomodulatory regimen consisting of intravenous immunoglobulin and cyclophosphamide. RESULTS: There were no significant differences between left ventricular assist device recipients and nonbridged recipients with respect to pretransplantation demographic characteristics and ABO and HLA matching. Among left ventricular assist device recipients, 66% (69/105) were sensitized before transplantation; in contrast, only 6% (24/399) of nonbridged recipients were sensitized (P <.001). Sensitized untreated left ventricular assist device recipients had both a prolongation of waiting time to transplantation and an increased risk of acute rejection. Pretransplantation immunomodulatory therapy reduced both the increased waiting time and the increased risk of acute rejection. However, sensitization or the use of immunomodulatory therapy in left ventricular assist device-bridged recipients did not influence posttransplantation survival relative to nonbridged recipients. CONCLUSIONS: Left ventricular assist device recipients have survival outcomes similar to those of nonbridged recipients after cardiac transplantation, despite their significantly higher immunologic risk. The reduced rate of transplantation and the increased incidence of rejection observed in sensitized left ventricular assist device recipients are prevented by immunomodulatory therapy. Sensitization will remain an important issue with increased use of left ventricular assist devices, and improved understanding of this is essential to achieve better outcomes in the management of patients with end-stage heart failure.

Actuarial Analysis↗
PubMed2003

Evaluating surrogate measures of renal dysfunction after cardiac surgery.

UNLABELLED: Renal insufficiency after cardiac surgery is associated with increased mortality, morbidity, and length of intensive care unit stay. A convenient surrogate measure would facilitate the evaluation of renal-protective therapies. We evaluated two measures: the 72-h change in serum creatinine (Cr) (DeltaCr(72h)) and the percentage 72-h change in calculated (Cockcroft-Gault equation) Cr clearance (%DeltaCrCl(72h)). We randomly selected 2000 individuals who underwent aortocoronary bypass, valve surgery, or both at the Toronto General Hospital between May 1999 and August 2000. The variables were analyzed with frequency histograms and normal probability plots. Their association with dialysis, mortality, and prolonged intensive care unit stay was determined by using receiver operating characteristic (ROC) curves. DeltaCr(72h) was skewed to the right, whereas %DeltaCrCl(72h) was normally distributed. ROC curve areas showed DeltaCr(72h) to be a good predictor of dialysis (0.98), death (0.83), and prolonged hospitalization (0.74). %DeltaCrCl(72h) had similar ROC curve areas for predicting dialysis (0.97), death (0.82), and prolonged hospitalization (0.74). ROC curve areas did not differ significantly with respect to mortality (P = 0.89), dialysis (P = 0.49), or prolonged hospitalization (P = 0.85). Both variables were correlated with patient-relevant outcomes. Mathematical transformation of DeltaCr(72h) to %DeltaCrCl(72h) results in a normal distribution that is amenable to parametric statistical tests. DeltaCr(72h) and %DeltaCrCl(72h) may be used as surrogate outcomes in future trials. IMPLICATIONS: A convenient surrogate measure of renal function is needed for evaluating renal-protective therapies in cardiac surgery. We evaluated the performance of serum creatinine concentration and calculated creatinine clearance for predicting dialysis, mortality, and prolonged hospitalization. Both measures were correlated with clinical outcomes. Creatinine clearance had the advantage of a distribution suitable for parametric statistical tests.

Age Factors↗
PubMed2003

An incidental calcified right atrial mass.

A 58-year-old man presented to his family physician with a mild cough. A routine chest x-ray revealed a 4 cm 'ring opacity' in the right atrium. A transthoracic echocardiogram revealed a 41 mm x 33 mm mass in the right atrium. The patient underwent urgent cardiac surgery, where a firm to hard 4 cm x 3 cm mass was excised. Pathology revealed an old, largely infarcted and calcified right atrial myxoma. A review of the published literature shows that this case is the first to demonstrate an almost completely infarcted atrial myxoma with only a few clusters of viable cells identified histologically.

Calcinosis↗