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Biomedical subjects

Jagdish Butany

Publications and source records attributed to Jagdish Butany.

At least 37 records · Page 2Linked to original sources
PubMed2004

Intimal thickness is not associated with wall shear stress patterns in the human right coronary artery.

OBJECTIVE: Low wall shear stress has been implicated in atherogenesis throughout the arterial tree, including the right coronary artery (RCA). The objective of this study was to determine the level of covariation of intimal thickness and wall shear stress in the human RCA. METHODS AND RESULTS: Postmortem histological measurements of intimal thickness were compared with wall shear stresses calculated from computational flow modeling in 4 human right coronary arteries. A statistically significant correlation between intimal thickness and wall shear stress was found in only 1 of the 4 arteries studied. CONCLUSIONS: Wall shear stress does not appear to be related to intimal thickness in the 4 RCAs studied.

Adult↗
PubMed2004

Direct sequencing of SARS-coronavirus S and N genes from clinical specimens shows limited variation.

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged, in November 2002, as a novel agent causing severe respiratory illness. To study sequence variation in the SARS-CoV genome, we determined the nucleic acid sequence of the S and N genes directly from clinical specimens from 10 patients--1 specimen with no matched SARS-CoV isolate, from 2 patients; multiple specimens from 3 patients; and matched clinical-specimen/cell-culture-isolate pairs from 6 patients. We identified 3 nucleotide substitutions that were most likely due to natural variation and 2 substitutions that arose after cell-culture passage of the virus. These data demonstrate the overall stability of the S and N genes of SARS-CoV over 3 months during which a minimum of 4 generations for transmission events occurred. These findings are a part of the expanding investigation of the evolution of how this virus adapts to a new host.

Amino Acid Substitution↗
PubMed2004

Beating heart catheter-based edge-to-edge mitral valve procedure in a porcine model: efficacy and healing response.

BACKGROUND: Surgical edge-to-edge repair has been used in the treatment of mitral regurgitation. We evaluated the ability of a catheter-delivered clip (Evalve, Inc) to achieve edge-to-edge mitral valve approximation without cardiopulmonary bypass and the healing response of this technique. METHODS AND RESULTS: Twenty-one pigs underwent general anesthesia and left thoracotomy. A 10F flexible delivery catheter with a clip was placed into the left atrium. With echocardiographic and fluoroscopic guidance, the clip grasped and approximated the mid portion of the anterior and posterior leaflets. After a double orifice had been confirmed, the clip was detached and the catheter withdrawn. All animals survived and had successful clip placement. Three animals were euthanized at 4 weeks, 9 at 12 weeks, 1 at 17 weeks, 7 at 24 weeks, and 1 at 52 weeks. The clip was well positioned, with leaflet approximation in all animals except 1, in which the clip separated from the posterior leaflet at 4 weeks without affecting valve function. The clip was modified and implanted in 4 pigs; all were intact at 12 to 24 weeks. Scanning electron microscopy showed clip encapsulation with complete endothelialization. Mitral stenosis and thromboembolism did not develop. Two animals developed endocarditis (1 at 12 weeks and 1 at 17 weeks). Progressive healing occurred in all other animals. CONCLUSIONS: Edge-to-edge mitral valve approximation can be successfully and reliably achieved with a catheter-delivered clip without cardiopulmonary bypass, resulting in durable healing. The success of this device supports the development of a percutaneous catheter-based system for mitral valve repair.

Animals↗
PubMed2004

The cardiac atria are chambers of active remodeling and dynamic collagen turnover during evolving heart failure.

OBJECTIVES: The role of atrial myocytes and extracellular matrix (ECM) changes in atrial chamber remodeling was studied in a canine model of heart failure (HF). BACKGROUND: Cardiac remodeling is a key process mediating the progression of HF. Studies of the structural mechanisms of cardiac remodeling have been limited to the left ventricle. The structural alterations associated with atrial chamber remodeling in evolving HF have not been studied. METHODS: Age- and weight-matched dogs were subjected to right ventricular pacing (240 beats/min) for one and three weeks to produce early and severe HF, respectively. Atrial tissues were assessed for myocyte and ECM changes. RESULTS: Right atrial and left atrial (LA) pressures were significantly increased in early and severe HF. The LA wall tension index was significantly increased at both HF stages by 116% and 443%, respectively. Atrial collagen synthesis and degradation were significantly increased in severe HF. Gelatinase activity was significantly increased at both early and severe stages of HF. Gelatin zymography showed increased matrix metalloproteinases (MMP)-9 with early HF and increased MMP-2 with severe HF. The LA wall tension index was significantly correlated with gelatinase activity and collagen synthesis. Although total atrial collagen content was not changed, disarray of collagen fibers was observed. Atrial myocyte hypertrophy without evidence of apoptosis was also present in severe HF. CONCLUSIONS: There is marked atrial chamber remodeling in canine pacing-induced HF, which is characterized by myocyte hypertrophy and dynamic collagen turnover. Atrial remodeling may contribute to the development of atrial arrhythmias and pulmonary hypertension and could offer a novel therapeutic target.

Animals↗
PubMed2004

Severe acute respiratory syndrome-associated coronavirus in lung tissue.

Efforts to contain severe acute respiratory syndrome (SARS) have been limited by the lack of a standardized, sensitive, and specific test for SARS-associated coronavirus (CoV). We used a standardized reverse transcription-polymerase chain reaction assay to detect SARS-CoV in lung samples obtained from well-characterized patients who died of SARS and from those who died of other reasons. SARS-CoV was detected in all 22 postmortem lung tissues (to 10(9) viral copies/g) from 11 patients with probable SARS but was not detected in any of the 23 lung control samples (sample analysis was blinded). The sensitivity and specificity (95% confidence interval) were 100% (84.6% to 100%) and 100% (85.1% to 100%), respectively. Viral loads were significantly associated with a shorter course of illness but not with the use of ribavirin or steroids. CoV was consistently identified in the lungs of all patients who died of SARS but not in control patients, supporting a primary role for CoV in deaths.

Adult↗
PubMed2004

Severe acute respiratory syndrome: overview with an emphasis on the Toronto experience.

OBJECTIVE: To provide an overview of the severe acute respiratory syndrome (SARS) outbreak in Toronto, Ontario, which experienced the largest outbreak outside Asia, and to review what has been learned during the past year. DATA SOURCES: MEDLINE search of all studies related to SARS, including review of the Centers for Disease Control and Prevention, World Health Organization (WHO), and Health Canada Web sites. DATA SYNTHESIS: During the SARS outbreak in Toronto, 438 people had been diagnosed as having suspected or probable SARS and 44 people died. Elderly people and those with comorbid illnesses were at greatest risk of complications or death. Transmission was via direct contact with respiratory secretions. The use of gloves, gowns, N95 masks, and eye protection was effective in preventing transmission. No transmission occurred before symptom onset or after recovery. Serologic tests suggest that antibodies may not appear until 28 days after illness onset. Molecular tests give their greatest yield during the second week of illness. The value of ribavirin treatment remains questionable. The combination of interferon plus corticosteroids appears to be better than corticosteroids alone. Postmortem examination revealed pulmonary edema and evidence of diffuse alveolar damage. Very few morphological changes were noted in other organs despite the presence of viral RNA as detected by polymerase chain reaction. CONCLUSION: On July 5, 2003, the WHO declared that the SARS outbreak was over. Since then, new cases of SARS have been reported in Asia. With global travel, the disease can rapidly spread throughout the world. Therefore, we must remain vigilant to prevent another pandemic.

Animals↗
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↗
PubMed2004

Constrictive pericarditis: case presentation and a review of the literature.

Constrictive pericarditis (CP) is a relatively rare entity, the result of a thickened, scarred and often calcified pericardium, adherent to the heart and limiting diastolic ventricular filling. Some reported etiologies for CP include pericardial involvement from cardiac trauma (including surgery), mediastinal irradiation, tuberculosis and other infectious diseases, neoplasms and myocardial infarction. However, the majority of CP cases are idiopathic. This report presents three cases of postoperative, tuberculous and idiopathic CP, highlighting the clinical and pathological changes seen in CP, and a review of the literature.

Adult↗
PubMed2003

The relationship between wall shear stress distributions and intimal thickening in the human abdominal aorta.

PURPOSE: The goal of this work was to determine wall shear stress (WSS) patterns in the human abdominal aorta and to compare these patterns to measurements of intimal thickness (IT) from autopsy samples. METHODS: The WSS was experimentally measured using the laser photochromic dye tracer technique in an anatomically faithful in vitro model based on CT scans of the abdominal aorta in a healthy 35-year-old subject. IT was quantified as a function of circumferential and axial position using light microscopy in ten human autopsy specimens. RESULTS: The histomorphometric analysis suggests that IT increases with age and that the distribution of intimal thickening changes with age. The lowest WSS in the flow model was found on the posterior wall inferior to the inferior mesenteric artery, and coincided with the region of most prominent IT in the autopsy samples. Local geometrical features in the flow model, such as the expansion at the inferior mesenteric artery (common in younger individuals), strongly influenced WSS patterns. The WSS was found to correlate negatively with IT (r2 = 0.3099; P = 0.0047). CONCLUSION: Low WSS in the abdominal aorta is co-localized with IT and may be related to atherogenesis. Also, rates of IT in the abdominal aorta are possibly influenced by age-related geometrical changes.

Adult↗
PubMed2003

Collagenase plaque digestion for facilitating guide wire crossing in chronic total occlusions.

BACKGROUND: Chronic total occlusions (CTOs) are associated with significant angina, impaired left ventricular function, and worse long-term outcomes. Percutaneous coronary interventions in CTO are unsuccessful in up to 50% of cases, primarily because of inability to cross the lesion with a guide wire. Collagen is the predominant component of the atherosclerotic plaque. The objective of this study was to determine the efficacy and toxicity of local delivery of a collagen-degrading enzyme to facilitate guide wire crossing in CTO. METHODS AND RESULTS: Type IA collagenase (100 or 450 microg) or placebo was locally administered to 45 CTOs in a rabbit femoral artery model. Mean occlusion duration was 16+/-5 weeks. Attempts to cross the CTO (mean length, 28+/-9 mm) with conventional guide wires were assessed at 72 hours after treatment. An additional 3 arteries per group were assessed for collagenase effects at 24 hours after treatment. Successful guide wire crossings were significantly higher in collagenase-treated arteries (13 of 21, 62%) than in placebo-treated arteries (7 of 24, 29%) (P=0.028). No adverse effects on arterial structure were observed in collagenase-treated arteries. At 24 hours, collagenase-treated arteries demonstrated increased collagenase protein, gelatinase activity, and collagen fragments. CONCLUSIONS: Local delivery of collagenase can safely facilitate guide wire crossing of CTO. This novel approach could lead to higher percutaneous coronary intervention success rates in CTO.

Angiography↗
PubMed2003

Endothelium and valvular diseases of the heart.

It has become increasingly evident that the endothelium plays a critical role in the pathogenesis of valvular heart disease. The endothelium helps regulate vascular tone, inflammation, thrombosis, and vascular remodeling. Dysfunction of the endothelial cells has been linked to many vascular disorders including atherosclerosis. Common valvular diseases such as senile degenerative valve disease, myxomatous (or floppy) valves, rheumatic valves, and infective endocarditis valves show changes in the synthetic, morphologic, and metabolic functions of the valvular endothelial cells. These diseases are active processes related to endothelial cell dysfunction. Endothelial cell dysfunction is caused by mechanical forces, bacterial infection, autoantibodies, and circulating modulators of endothelial cell function. This study reviews the role of endothelial cell dysfunction in the more common valvular diseases. Continued research on endothelial cell dysfunction is crucial to our understanding of valvular heart diseases and may elucidate novel treatment and prevention strategies.

Aged↗
PubMed2003

Decorin inhibition of PDGF-stimulated vascular smooth muscle cell function: potential mechanism for inhibition of intimal hyperplasia after balloon angioplasty.

Decorin is a small proteoglycan that binds to transforming growth factor-beta (TGF-beta) and inhibits its activity. However, its interaction with platelet-derived growth factor (PDGF), involved in arterial repair after injury, is not well characterized. The objectives of this study were to assess decorin-PDGF and decorin-PDGF receptor (PDGFR) interactions, the in vitro effects of decorin on PDGF-stimulated smooth muscle cell (SMC) functions and the in vivo effects of decorin overexpression on arterial repair in a rabbit carotid balloon-injury model. Decorin binding to PDGF was demonstrated by solid-phase binding and affinity cross-linking assays. Decorin potently inhibited PDGF-stimulated PDGFR phosphorylation. Pretreatment of rabbit aortic SMC with decorin significantly inhibited PDGF-stimulated cell migration, proliferation, and collagen synthesis. Decorin overexpression by adenoviral-mediated gene transfection in balloon-injured carotid arteries significantly decreased intimal cross-sectional area and collagen content by approximately 50% at 10 weeks compared to beta-galactosidase-transfected or balloon-injured, non-transfected controls. This study shows that decorin binds to PDGF and inhibits its stimulatory activity on SMCs by preventing PDGFR phosphorylation. Decorin overexpression reduces intimal hyperplasia and collagen content after arterial injury. Decorin may be an effective therapy for the prevention of intimal hyperplasia after balloon angioplasty.

Angioplasty, Balloon↗
PubMed2003

Vascular matrix remodeling in patients with bicuspid aortic valve malformations: implications for aortic dilatation.

BACKGROUND: Patients with bicuspid aortic valve malformations are at an increased risk of aortic dilatation, aneurysm formation, and dissection. Vascular tissues with deficient fibrillin-1 microfibrils release matrix metalloproteinases, enzymes that weaken the vessel wall by degrading elastic matrix components. In bicuspid aortic valve disease a deficiency of fibrillin-1 and increased matrix metalloproteinase matrix degradation might result in aortic degeneration and dilatation. METHODS: Samples of the pulmonary artery and aorta were obtained from surgical patients with bicuspid aortic valves (n = 21) and tricuspid aortic valves (n = 16). RESULTS: Fibrillin-1 content was reduced in bicuspid aortic valve aortas compared with that seen in tricuspid aortic valve aortas (P =.001), whereas the associated matrix components, elastin and collagen, were unchanged (P =.51 and P =.21). Reductions of aortic fibrillin-1 content were independent of valve function and patient age. Compared with tricuspid aortic valve aorta, matrix metalloproteinase 2 activity was increased more than 2-fold in bicuspid aortic valve aortas (P =.04) and correlated positively with aortic diameter (r = 0.74, P =.05). Matrix metalloproteinase 9 activity was not significantly different. Fibrillin-1 content was also reduced in the pulmonary arteries of patients with bicuspid aortic valves (P =.06), suggesting a systemic deficiency of fibrillin-1. Promatrix metalloproteinase 2 was increased (P =.04), reflecting an increased production of matrix metalloproteinase 2 in these fibrillin-1-deficient tissues, whereas active matrix metalloproteinase 2 and matrix metalloproteinase 9 species were unchanged, and correspondingly, the pulmonary arteries were not dilated. CONCLUSIONS: Deficient fibrillin-1 content in the vasculature of patients with bicuspid aortic valves might trigger matrix metalloproteinase production, leading to matrix disruption and dilatation. This process of vascular matrix remodeling in patients with bicuspid aortic valves offers novel therapeutic targets to prevent the aortic degeneration and dilatation characteristic of this disease.

Adult↗
PubMed2003

Tropheryma whippelii as a cause of afebrile culture-negative endocarditis: the evolving spectrum of Whipple's disease.

With the advent of molecular diagnostics culture-negative endocarditis caused by the organism Tropheryma whippelii is an increasingly described entity. We describe two patients with afebrile, culture-negative endocarditis caused by T. whippelii who had neither the gastrointestinal nor arthritic manifestations of Whipple's disease. Whipple's disease is a systemic illness caused by the organism Tropheryma whippelii and is typically characterized by diarrhea, weight loss, and arthropathy [Clin. Microbiol. Rev. 2001;14:561-583; Medicine (Baltimore) 1997;76:170-184]. Whipple's endocarditis is relatively common in autopsy studies [Can. J. Cardiol. 1996;12:831-834] but has rarely been diagnosed before death. With the advent of molecular diagnostic tools such as the polymerase chain reaction (PCR), Tropheryma whippelii as a cause of culture-negative endocarditis has become increasingly recognized [Clin. Infect. Dis. 2001;33:1309-1316; Ann. Intern. Med. 1999;131:112-116; Infection 2001;29:44-47; Ann. Intern. Med. 2000;132:595]. With this increased recognition has come the realization that Whipple's endocarditis can occur without other common manifestations of Whipple's disease [Ann. Intern. Med. 1999;131:112-116; Infection 2001;29:44-47; Ann. Intern. Med. 2000;132:595]. We report here two cases of Whipple's endocarditis without discrete febrile illness, gastrointestinal manifestations, or arthritic manifestations, diagnosed by PCR of resected valvular material.

Aged↗