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Biomedical subjects

Jagdish Butany

Publications and source records attributed to Jagdish Butany.

At least 19 recordsLinked to original sources

Ex vivo imaging of chronic total occlusions using forward-looking optical coherence tomography.

BACKGROUND AND OBJECTIVES: Percutaneous coronary interventions (PCI) of chronic total occlusions (CTOs) of arteries are more challenging lesions to treat with angioplasty and stenting than stenotic vessels due primarily to the difficulty in guiding the wire across the lesion. Angiography alone is unable to differentiate between the occluded lumen and the vessel wall and to characterize the content of the occlusion. New technologies to aid in interventional guidance are therefore highly desirable. We sought to evaluate tissue characterization in arterial (CTOs) by imaging ex vivo peripheral arterial samples with optical coherence tomography (OCT). STUDY DESIGN/MATERIALS AND METHODS: Ex vivo arterial samples were obtained from patients undergoing peripheral limb amputation. Samples were imaged in an enface orientation using an OCT system, enabling sequential acquisition of longitudinal images and volumetric reconstruction of cross-sectional views of the occluded arteries. Histology was performed for comparison. RESULTS: OCT imaging reliably differentiated between the occluded lumen and the underlying arterial wall in peripheral CTOs. OCT correctly identified tissue composition within the CTO, such as the presence of collagen and calcium and was also able to identify intraluminal microchannels. CONCLUSIONS: OCT imaging of CTO anatomy and tissue characteristics may potentially lead to substantial improvements in PCI interventions by providing novel guiding capabilities.

Angiography↗

Fatty lesions of the atria and interatrial septum.

Lipomatous lesions of the heart involving the atria and interatrial septum are not well known. Most such lesions do not become clinically significant; however, intractable arrhythmias, blood flow obstruction, and valvular disruption may result from extensive fatty infiltration of the atrial wall or from the mass effect of benign or malignant lipomatous tumors. Some fatty lesions may be difficult to characterize radiologically, and misdiagnosis may lead to unnecessary surgical interventions. We describe the pathology of the most common fatty lesions and underscore some of the radiographic and surgical issues pertaining to the diagnosis and management of these masses.

Adipose Tissue↗

Effects of cocaine intoxication on the threshold for stun gun induction of ventricular fibrillation.

OBJECTIVES: This study sought to assess cocaine's effects on Taser-induced ventricular fibrillation (VF) threshold in a pig model. BACKGROUND: Stun guns are increasingly used by law enforcement officials to restrain violent subjects, who are frequently intoxicated with cocaine and other drugs of abuse. The interaction of cocaine and the stun gun on VF induction is unknown. METHODS: We tested five adult pigs using a custom device built to deliver multiples of standard neuromuscular incapacitating (NMI) discharge that matched the waveform of a commercially available electrical stun gun (Taser X-26, Taser International, Scottsdale, Arizona). The NMI discharges were applied in a step-up and step-down fashion at 5 body locations. End points included determination of maximum safe multiple, minimum VF-inducing multiple, and ventricular fibrillation threshold (VFT) before and after cocaine infusion. RESULTS: Standard NMI discharges (x1) did not cause VF at any of the 5 locations before or after cocaine infusion. The maximum safe multiple, minimum VF-inducing multiple, and VFT of NMI application increased with increasing electrode distance from the heart. There was a 1.5- to 2-fold increase in these values at each position after cocaine infusion, suggesting decreased cardiac vulnerability for VF. Cocaine increased the required strength of NMI discharge that caused 2:1 or 3:1 ventricular capture ratios at all of the positions. No significant changes in creatine kinase-MB and troponin-I were seen. CONCLUSIONS: Cocaine increased the VFT of NMI discharges at all dart locations tested and reduced cardiac vulnerability to VF. The application of cocaine increased the safety margin by 50% to 100% above the baseline safety margin.

Animals↗

Time course and cellular localization of SARS-CoV nucleoprotein and RNA in lungs from fatal cases of SARS.

BACKGROUND: Cellular localization of severe acute respiratory syndrome coronavirus (SARS-CoV) in the lungs of patients with SARS is important in confirming the etiological association of the virus with disease as well as in understanding the pathogenesis of the disease. To our knowledge, there have been no comprehensive studies investigating viral infection at the cellular level in humans. METHODS AND FINDINGS: We collected the largest series of fatal cases of SARS with autopsy material to date by merging the pathological material from two regions involved in the 2003 worldwide SARS outbreak in Hong Kong, China, and Toronto, Canada. We developed a monoclonal antibody against the SARS-CoV nucleoprotein and used it together with in situ hybridization (ISH) to analyze the autopsy lung tissues of 32 patients with SARS from Hong Kong and Toronto. We compared the results of these assays with the pulmonary pathologies and the clinical course of illness for each patient. SARS-CoV nucleoprotein and RNA were detected by immunohistochemistry and ISH, respectively, primarily in alveolar pneumocytes and, less frequently, in macrophages. Such localization was detected in four of the seven patients who died within two weeks of illness onset, and in none of the 25 patients who died later than two weeks after symptom onset. CONCLUSIONS: The pulmonary alveolar epithelium is the chief target of SARS-CoV, with macrophages infected subsequently. Viral replication appears to be limited to the first two weeks after symptom onset, with little evidence of continued widespread replication after this period. If antiviral therapy is considered for future treatment, it should be focused on this two-week period of acute clinical disease.

Antibodies, Monoclonal↗

Stent thrombosis following the STAR technique in a complex RCA chronic total occlusion.

Four drug-eluting stents were deployed in the right coronary artery (RCA) of a symptomatic young woman who presented with a chronic total occlusion (CTO) of the RCA. The occlusion was successfully crossed using the recently described STAR technique. However, the patient died suddenly 15 hr later. Autopsy demonstrated a long segment of subintimal stenting in the proximal and mid RCA that was intraluminal in the distal vessel. Acute stent thrombosis in the subintimal stents was responsible for sudden death. This case highlights the potential risk of performing extensive subintimal stenting for CTO.

Angioplasty, Balloon, Coronary↗

Morphological findings in 192 surgically excised native mitral valves.

INTRODUCTION: Mitral valve disease (MVD) is a significant clinical problem that is becoming more common in the 21st century. The pathogenesis of MVD seems to be changing and is not well understood. PATIENTS AND METHODS: The present study details the morphological findings in 192 native mitral valves excised over a one-year period at the Toronto General Hospital, Toronto, Ontario. The mean patient age was 59.7+/-12.3 years at operation. RESULTS: There were 106 men (55.2%) and 86 women (44.8%) in the present study. The most frequent changes in the surgically excised valvular leaflets were fibrosis (78.6%) and thickening (66.2%). Fusion (32.3%) and calcification (25.2%) were common changes at the commissures. Chordae tendineae most often showed evidence of thickening (47.9%) and fibrosis (37.0%). In total, 110 valves showed mitral incompetence (57.3%), 72 showed mitral stenosis (37.5%), and 10 showed a combination of stenosis and incompetence (5.2%). CONCLUSIONS: In the present series, MVD was most frequently caused by postinflammatory (rheumatic) valve disease (RVD) (35.9%), followed by myxomatous degeneration (33.3%). Patients with RVD were usually female (66.7%), while those with myxomatous degeneration were more likely to be male (76.6%). RVD remains a significant problem even though the incidence of acute rheumatic fever with cardiac involvement has declined in Canada. This most likely reflects the current sociodemographic composition of the referral population.

Adolescent↗

Fetal pericardial teratoma: presentation of two cases and review of literature.

We present the fetal ultrasound and echocardiographic findings and clinical outcome of two fetuses with intrapericardial teratoma encountered in our institution. In the first (diagnosed at 19 weeks of gestation) case there was elective termination of pregnancy; in the second case (diagnosed at 24 weeks), a pericardio-amniotic shunt was placed after reaccumulation of fluid following pericardiocentesis. We review the published experience of intrapericardial teratomas, focusing on the diagnosis, fetal echocardiographic findings, and outcome with and without prenatal intervention.

Adult↗

Murine hepatitis virus strain 1 produces a clinically relevant model of severe acute respiratory syndrome in A/J mice.

Severe acute respiratory syndrome (SARS) is a life-threatening infectious disease which has been difficult to study and treat because of the lack of a readily available animal model. Intranasal infection of A/J mice with the coronavirus murine hepatitis virus strain 1 (MHV-1) produced pulmonary pathological features of SARS. All MHV-1-infected A/J mice developed progressive interstitial pneumonitis, including dense macrophage infiltrates, giant cells, and hyaline membranes, resulting in death of all animals. In contrast, other mouse strains developed only mild transitory disease. Infected A/J mice had significantly higher cytokine levels, particularly macrophage chemoattractant protein 1 (MCP-1/CCL-2), gamma interferon, and tumor necrosis factor alpha. Furthermore, FGL2/fibroleukin mRNA transcripts and protein and fibrin deposits were markedly increased in the lungs of infected A/J mice. These animals developed a less robust type I interferon response to MHV-1 infection than resistant C57BL/6J mice, and treatment with recombinant beta interferon improved survival. This study describes a potentially useful small animal model of human SARS, defines its pathogenesis, and suggests treatment strategies.

Animals↗

True versus false left ventricular aneurysm: differentiation with MR imaging--initial experience.

PURPOSE: To assess the usefulness of cardiac magnetic resonance (MR) imaging for differentiation of true from false left ventricular aneurysm in patients after myocardial infarction. MATERIALS AND METHODS: Cardiac MR images obtained in 22 sequential patients (20 men, two women; mean age, 63 years; age range, 45-75 years) with pathologically proved left ventricular true aneurysm (n = 18) or false aneurysm (n = 4) after myocardial infarction were retrospectively analyzed. The MR imaging protocol included steady-state cine imaging followed by perfusion measurement and delayed contrast-enhanced imaging with delays of 15 and 20 minutes. Differences between true and false aneurysms with regard to maximal internal width of orifice, maximal parallel internal diameter, ratio of maximal orifice to maximal internal diameter, presence of mural thrombus and delayed enhancement of pericardium, left ventricular end-diastolic volume, and left ventricular ejection fraction were analyzed by using the Mann-Whitney U test or Fisher exact test, as appropriate. RESULTS: Inferior wall location was noted in two of four patients with false aneurysm and in none of 18 patients with true aneurysm (P = .03). The remaining aneurysms were apicoanterior (two false, 10 true) or apical (eight true). False aneurysms had a ratio of maximal internal width of the orifice to maximal parallel internal diameter that was significantly lower than that of true aneurysms (0.73 vs 1.00, P < .001) and had a significantly higher left ventricular end-diastolic volume (median, 202 vs 136 mL/m(2); P = .001), as well as a nonsignificant tendency toward lower left ventricular ejection fraction (17% vs 28%, P = .15). Mural thrombus was identified in all four patients with false aneurysm and in seven of 18 patients with true aneurysm (P = .09). Delayed enhancement of pericardium was noted in all four patients with false aneurysm and in three of 18 patients with true aneurysm. Resultant sensitivity of MR imaging for the detection of false left ventricular aneurysm was four of four, specificity was 15 of 18, accuracy was 19 of 22, and positive and negative predictive values were four of seven and 15 of 15 patients, respectively. CONCLUSION: Initial experience with a small number of patients suggests that marked delayed enhancement of the pericardium is a characteristic feature of false aneurysm. Study with a larger patient sample is required to further assess this feature.

Aged↗

Human saphenous vein coronary artery bypass graft morphology, geometry and hemodynamics.

Coronary artery bypass graft (CABG) failure has been linked to graft hemodynamics, in particular wall shear stress. This study characterizes the morphology, geometry and wall shear stress patterns in human CABGs. The intimal thickness (IT) in 49 human saphenous vein CABGs was measured by digital light microscopy. The geometry of six saphenous vein CABGs was replicated by post-mortem infusion of Batson's #17 anatomical corrosion casting compound. Graft hemodynamics were evaluated in two flow models, fabricated from the casts, under steady (Re = 110) and pulsatile flow (Re = 110, alpha = 2) conditions. Saphenous vein CABGs in situ for more than 2 months had, on average, the greatest IT on the hood and suture sites of the distal anastomosis. Floor thickening was highly variable and significantly less than IT at the hood, suture site and graft body. All casts showed an indentation along the floor and 5/6 casts displayed a sharp local curvature on the hood. In both flow models, a large increase in wall shear rate occurred on the hood, just proximal to the toe. The local geometry of the hood created this large spatial gradient in wall shear stress which is a likely factor in hood intimal hyperplasia.

Aged↗

Cardiac tumours: diagnosis and management.

Primary cardiac tumours are rare, with an autopsy incidence ranging from 0.001% to 0.030%. Three-quarters of these tumours are benign and nearly half of the benign tumours are myxomas. Metastases to the heart are far more common than primary cardiac tumours. Primary cardiac tumours present with one or more of the symptoms of the classic triad of: cardiac symptoms and signs resulting from intracardiac obstruction; signs of systemic embolisation; and systemic or constitutional symptoms. They are diagnosed by use of transthoracic and transoesophageal echocardiograms, MRI, and CT scan. Whereas surgery is indicated in patients with benign tumours, systemic chemotherapy is indicated in those who have widespread or unresectable malignant disease, and chemotherapy and radiotherapy are usually combined in treatment of patients with primary cardiac lymphomas. The prognosis after surgery is usually excellent in the case of benign tumours but is unfortunately still limited in localised malignant diseases. Patients with sarcomas live for a mean of 3 months to 1 year, and those with lymphomas live up to 5 years if treated, but usually die within 1 month if untreated.

Echocardiography↗

Pulmonary pathology of severe acute respiratory syndrome in Toronto.

The severe acute respiratory syndrome (SARS) pandemic in Toronto resulted in a large number of autopsies on its victims. We describe the pulmonary pathology of patients who died in the 2003 Toronto outbreak. Autopsy material from the lungs of 20 patients who died between March and July 2003 were characterized by histology, molecular biology, and immunohistochemistry for cytokeratins, thyroid transcription factor-1, CD68, Epstein-Barr virus, cytomegalovirus, and human herpes simplex viruses. Matched controls were obtained from patients who died of other causes over the same interval. The mean duration of illness was 27 days (range 5-108 days). Post-mortem lung tissues from 19 of 20 patients with probable SARS were positive for SARS-associated coronavirus by RT-PCR. Histologically, all patients showed varying degrees of exudative and proliferative phase acute lung injury, evidenced in conventional and immunohistochemical stains by edema, inflammatory infiltrate, pneumocyte hyperplasia, fibrinous exudates, and organization. Eight of 20 patients showed predominantly a diffuse alveolar damage pattern of acute lung injury, six showed predominantly an acute fibrinous and organizing pneumonia pattern, and the remainder showed an admixture of the two patterns. Squamous metaplasia and scattered multinucleate giant cells were present in most cases. Vascular fibrin thrombi were a common finding and were often associated with pulmonary infarcts. Special stains demonstrated vascular endothelial damage of both small- and mid-sized pulmonary vessels. Two cases were complicated by invasive fungal disease consistent with Aspergillosis, and another by coinfection with cytomegalovirus. Our findings indicate that the lungs of patients who die of SARS are almost always positive for the SARS-associated coronavirus by RT-PCR, and may show features of both diffuse alveolar damage and acute fibrinous and organizing pneumonia patterns of acute injury. Cases of SARS may be complicated by coexistent infections and therapy-related lung injury.

Adult↗

Microvessels in chronic total occlusions: pathways for successful guidewire crossing?

Arterial chronic total occlusions (CTO) are a common and clinically relevant problem in patients with coronary artery disease. Percutaneous coronary intervention (PCI) success rates in a wide range of CTO are low, primarily due to inability of guidewire crossing. The pathophysiology of CTO is poorly understood and limits our ability to introduce innovative therapies. Recent studies from our laboratory have suggested that microvessel formation within arterial CTO is a complex process with temporal and regional differences. Moreover, there is evidence from pilot studies that the presence of either microvessels or the particular extracellular matrix environment in the adjacent perivascular tissue can facilitate guidewire crossing and successful PCI. Currently, studies are underway in our experimental CTO model to delineate the pathophysiology of microvessel formation in CTO and its potential role in PCI.

Animals↗

Bicuspid aortic valve disease: recent insights in pathophysiology and treatment.

Bicuspid aortic valve is a common congenital cardiac malformation with a broad spectrum of clinical outcomes. Bicuspid aortic valve may go undetected throughout an individual's lifetime or, alternatively, they may have devastating clinical consequences, resulting in death. Both clinicians and medical scientists have taken a renewed interest in the development, pathophysiology and treatment options for this subtle but often substantial clinical entity. Evidence is mounting to suggest that an underlying disease of the aorta is inherited with bicuspid aortic valve, although considerable controversy surrounds this theory. Novel molecular mechanisms underlying the valve and vascular pathologies, as well as new surgical therapies for these patients have been proposed in the past 10 years.

Aortic Valve↗

A 30-year analysis of cardiac neoplasms at autopsy.

INTRODUCTION: Cardiac neoplasms are rare and the vast majority are metastatic in origin. Symptoms of cardiac neoplasms (primary or metastatic) usually appear late in the course of the disease and are often ignored because of the more severe effects of the primary malignant disorder or its therapy. Consequently, cardiac neoplasms, especially metastatic ones, are often not discovered until autopsy. OBJECTIVES: To assess the incidence of cardiac neoplasms at autopsy and to determine the sites of origins of metastatic cardiac neoplasms. METHODS: The pathology records from consecutive autopsies performed at the University Health Network, Toronto, Ontario, from January 1973 to May 2004 were reviewed. They showed 266 cases of neoplasms involving the heart among 11,432 consecutive autopsies. These cases were then categorized based on their system of origin and further subclassified into specific primary site categories. As well, the type of cardiac tissue affected was noted in 193 cases (72.6%). RESULTS: The 266 autopsy cases involving cardiac neoplasms represented 2.33% of the total number of autopsies. Among the 266 cases, two neoplasms were primaries, while 264 were metastatic in origin. Metastatic cardiac neoplasms most frequently metastasized from the respiratory system, followed (in order of decreasing frequency) by the hematopoietic, gastrointestinal, breast and genitourinary systems. A minority of metastatic cardiac neoplasms were found to have spread from other systems. Cardiac neoplasms most frequently involved the pericardium, followed (in order of decreasing frequency) by the myocardium, epicardium and endocardium. CONCLUSIONS: There were 132 times more metastatic cardiac neoplasms than primary cardiac neoplasms found in the present study. The most common sites of metastatic origin were the lungs, bone marrow (leukemia/multiple myeloma), breasts and lymph nodes (lymphoma). Leukemias were more prevalent in the present study than in previous studies. The pericardium was the tissue that was most frequently affected by metastatic cardiac neoplasms.

Adolescent↗

Morphological and clinical findings in 247 surgically excised native aortic valves.

Aortic valve disease is an increasingly common medical problem in the 20th century; however, its pathogenesis is poorly understood. The present paper reviews 247 cases of aortic valves surgically excised over a one-year period, with special attention to the morphological and histological changes observed in surgically excised aortic valves, and to how those changes relate to the mechanisms of valve failure. Patient age ranged from 17 to 86 years, with a mean of 64.1 +/-13.4 years, and there were 156 men (63.2%) and 91 women (36.8%). A total of 172 valves (69.6%) were tricuspid and 75 valves (30.4%) were congenitally abnormal, of which 67 valves (27.1%) were congenitally bicuspid, six valves (2.4%) were congenitally unicommissural and one valve (0.4%) was quadricuspid; the status of one valve could not be determined. Almost 70% of patients had features of aortic stenosis. Calcification was seen in the large majority of cases, with almost 70% of the valves showing either grade 3 or grade 4 calcification. Ulceration of calcific nodules was present in 42.0% of cases and in the majority of the valves with grade 4 calcification. A total of 15% of the valves showed evidence of postinflammatory changes consistent with rheumatic disease. Neovascularization was present in two-thirds of all valves, while one-half showed inflammatory cell infiltrates. Inflammatory cells were composed mainly of lymphocytes and macrophages, and were located primarily near areas of neovascularization. There was no significant difference in the pathological findings between men and women.

Adolescent↗

Fatal severe acute respiratory syndrome is associated with multiorgan involvement by coronavirus.

Severe acute respiratory syndrome (SARS) is characterized by pulmonary compromise; however, patients often have evidence of other organ dysfunction that may reflect extrapulmonary dissemination of SARS coronavirus (SARS-CoV). We report on the distribution and viral load of SARS-CoV in multiple organ samples from patients who died of SARS during the Toronto outbreak. SARS-CoV was detected in lung (100%), bowel (73%), liver (41%), and kidney (38%) in 19 patients who died of SARS, with the highest viral loads observed in lung (1.0 x 10(10) copies/g) and bowel (2.7 x 10(9) copies/g). Fatal SARS was associated with multiorgan viral dissemination in a distribution that has implications for disease manifestation, viral shedding, and transmission.

Coronavirus↗