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Biomedical subjects

V Rao

Publications and source records attributed to V Rao.

At least 109 records · Page 6Linked to original sources
PubMed1996

Acute myocardial infarction, reperfusion injury, and intravenous magnesium therapy: basic concepts and clinical implications.

The concept of reperfusion-induced injury has aroused special interest during the past decade as thrombolysis and direct angioplasty were introduced for early restoration of coronary blood flow in patients with acute myocardial infarction. There is experimental and clinical evidence that oxygen-derived free radicals (oxyradical hypothesis), activation of the complement system (complement hypothesis), and disturbance in calcium homeostasis (calcium hypothesis), may account for the development of reperfusion injury. Data from numerous animal experiments and clinical trials suggest that magnesium, a physiologic calcium blocker, may be efficacious for reduction of reperfusion injury. Despite encouraging results from previous clinical trials that revealed beneficial effects of intravenous magnesium therapy with respect to mortality, left ventricular function, and infarct size, a recently published large-scale trial (ISIS-4) provided conflicting data and caused major controversy. Further clinical trials, well-designed and carefully conducted, should elucidate the beneficial effects of magnesium in acute myocardial infarction, especially in conjunction with new and aggressive reperfusion techniques.

Calcium Channel Blockers↗
PubMed1996

Cardiomyocyte transplantation improves heart function.

BACKGROUND: Transplantation of cultured cardiomyocytes into myocardial scar tissue may prevent heart failure. METHODS: Scar tissue was produced in the left ventricular free wall of 15 rats (weight, 450 g) by cryoinjury. Seven animals had operation only and survived for 8 weeks (sham group). Four weeks after cryoinjury, cultured fetal rat cardiomyocytes or culture medium was injected into the scar tissue of transplantation (n = 5) and control (n = 5) animals, respectively. Five other rats were sacrificed for scar assessment. Eight weeks after cryoinjury heart function in the transplantation, control, and sham groups was measured using a Langendorff preparation. Histologic studies were performed to quantify the extent of the scar and the transplanted cells. RESULTS: Four weeks after cryoinjury, 36% +/- 4% (mean +/- 1 standard error) of the left ventricular free wall surface area was scar tissue. At 8 weeks, the scar size had increased (p < 0.01) to 55% +/- 3% in the control group. Although the scar size (43% +/- 2%) in the transplantation group at 8 weeks was not significantly different from that at 4 weeks, it was less (p < 0.05) than that in the control group. Hearts in the sham group had no scar tissue. The transplanted cardiomyocytes had formed cardiac tissue within the myocardial scar. Systolic and developed pressures in the transplantation group hearts were greater (p = 0.0001) than in the control group hearts but less (p < 0.01) than those in the sham group hearts. CONCLUSIONS: The transplanted cardiomyocytes formed cardiac tissue in the myocardial scar, limited scar expansion, and improved heart function compared with findings in the control hearts.

Animals↗
PubMed1996

Antegrade and retrograde cardioplegia: alternate or simultaneous?

UNLABELLED: Neither antegrade nor retrograde cardioplegic protection provides homogeneous distribution, and a combination may be required to avoid anaerobic metabolism and depressed postoperative ventricular function. Tepid cardioplegia (29 degrees C) avoids the delayed recovery of cardiac function and metabolism associated with cold cardioplegia (15 degrees C) and reduces the anaerobic metabolism seen with warm (37 degrees C) cardioplegia. We compared two techniques that combine antegrade and retrograde tepid cardioplegia: alternate and simultaneous. METHODS: Sixty patients undergoing elective isolated coronary artery bypass grafting were randomized to receive near continuous tepid retrograde and either intermittent antegrade cardioplegia (the alternate technique) or antegrade cardioplegia with the solution delivered concurrently through each completed vein graft (the simultaneous technique). RESULTS: Myocardial lactate extraction was greater after crossclamp release following simultaneous than alternate cardioplegia. Postoperative ventricular function was better after alternate than simultaneous cardioplegia. CONCLUSION: Both techniques permitted rapid postoperative recovery of myocardial metabolism and ventricular function. However, simultaneous cardioplegia was simpler and did not require deairing the aortic root between antegrade infusions.

Adult↗
PubMed1996

Predictors of low cardiac output syndrome after coronary artery bypass.

The purpose of this study was to identify patients at risk for the development of low cardiac output syndrome after coronary artery bypass. Low cardiac output syndrome was defined as the need for postoperative intraaortic balloon pump or inotropic support for longer than 30 minutes in the intensive care unit to maintain the systolic blood pressure greater than 90 mm Hg and the cardiac index greater than 2.2 L/min per square meter. The preoperative patient characteristics that were independent predictors of low cardiac output syndrome were identified among 4558 consecutive patients who underwent isolated coronary artery bypass at The Toronto Hospital between July 1, 1990, and December 31, 1993. The overall prevalence of low cardiac output syndrome was 9.1% (n = 412). The operative mortality rate was higher in patients in whom low cardiac output syndrome developed than in those in whom it did not develop (16.9% versus 0.9%, p < 0.001). Stepwise logistic regression analyses identified nine independent predictors of low output syndrome (percent frequency in parentheses) and calculated the factor-adjusted odds ratios associated with each predictor: (1) left ventricular ejection fraction less than 20% (27%, odds ratio 5.7); (2) repeat operation (25%, odds ratio 4.4); (3) emergency operation (27%, odds ratio 3.7); (4) female gender (16%, odds ratio 2.5); (5) diabetes (13%, odds ratio 1.6); (6) age older than 70 years (13%, odds ratio 1.5); (7) left main coronary artery stenosis (12%, odds ratio 1.4); (8) recent myocardial infarction (16%, odds ratio 1.4); and (9) triple-vessel disease (10%, odds ratio 1.3). Low cardiac output syndrome is a clinical outcome that may result from inadequate myocardial protection or perioperative ischemic injury. Patients at high risk for the development of low cardiac output syndrome should be the focus of trials of new techniques of myocardial protection to resuscitate the ischemic myocardium.

Aged↗
PubMed1996

Intragraft TGF-beta 1 mRNA: a correlate of interstitial fibrosis and chronic allograft nephropathy.

Chronic allograft nephropathy is a relentlessly progressive process and a major cause of long-term graft dysfunction and ultimate failure. Interstitial fibrosis, tubular atrophy, and glomerular and vascular lesions characterize this mechanistically unresolved disorder. Given the prominent role of TGF-beta 1 in tissue repair and in fibrosis, we have explored the hypothesis that fibrosis and chronic allograft nephropathy would be distinguished by intragraft TGF-beta 1 mRNA expression. This postulate was tested by mRNA phenotyping of RNA isolated from 127 human renal allograft biopsies. Reverse transcription assisted polymerase chain reaction was used to amplify and identify ingraft gene expression. Our investigation demonstrated a significant correlation between intragraft TGF-beta 1 mRNA display and renal allograft interstitial fibrosis and chronic allograft nephropathy. In contrast, intragraft expression of mRNA encoding immunoregulatory cytokines, IL-2, IFN-gamma, IL-4, IL-10, or cytotoxic attack molecules, granzyme B and perforin was not a correlate of interstitial fibrosis or chronic allograft nephropathy. Our studies identify, for the first time, a significant association between intragraft TGF-beta 1 mRNA expression and renal allograft interstitial fibrosis, and advance a candidate molecular mechanism for chronic allograft nephropathy.

Base Sequence↗
PubMed1996

Phenotypic changes and loss of melanoma-specific endogenous C-type retroviruses in BL6 melanoma cells transfected with the H-2Kb gene.

The murine B16 melanoma and its sublines are low or totally deficient in expression of the H-2Kb class I major histocompatibility complex (MHC) gene. In clones derived from the B16F10BL6 subline, expression of the transfected or endogenous H-2Kb gene resulted in alterations of various phenotypic properties of these melanoma cells, among which was the loss of melanoma-associated antigen (MAA) expression. Because our previous immunoelectron microscopy studies showed that MAA was associated with a C-type ecotropic retrovirus specific for melanomas of C57BL/6 origin, we examined the effect of class I H-2Kb as well as class II H-2IAk gene expression on retrovirus production in subclones of BL6 melanoma cells. Here we have shown that expression of the transfected or endogenous H-2Kb gene resulted in the loss of production of budding, MAA-specific, C-type retrovirus particles. Northern blot analysis demonstrated expression of ecotropic retroviral mRNAs in both particle-producing and non-producing BL6 melanoma clones. Southern blot analysis of high-molecular-weight cellular DNAs using an ecotropic env-specific DNA probe indicated that the parental BL6-8 melanoma cells contained the C57BL/6 endogenous ecotropic MuLV (Emv-2) and at least three additional, novel ecotropic retroviral DNAs. Restriction enzyme analysis of the proviral DNA suggests that the loss of retrovirus production in the H-2Kb-expressing melanoma clones is the result of multiple rearrangements in the novel proviral DNAs. Thus, phenotypic changes observed in the H-2Kb gene-transfected BL6 melanoma cells were associated with loss of endogenous melanoma-specific ecotropic retrovirus production.

Animals↗
PubMed1996

Loss of intracisternal A-type retroviral particles in BL6 melanoma cells transfected with MHC class I genes.

Electron microscopy of B16 melanoma and its sublines revealed that these cells produce numerous intracisternal A-type retroviral particles (IAPs). To identify and sequence the melanoma-associated IAPs of C57BL/6 mice, a cDNA library was constructed from IAP-producing BL6.8 cell RNA and screened using MIA14 IAP DNA as a probe. A 6-8 kb mRNA was identified that represents the full-length message for a new subfamily of IAP, termed MeIAP. The melanoma-derived IAP cDNA showed high similarity to MIA14 with major differences in the LTR. A nine base motif of the R region showed that this IAP differs from other previously sequenced IAPs. Analysis of the individual clones from BL6 melanoma revealed that IAPs were produced only in the clones that failed to express H-2Kb molecules. No IAPs were found in the melanoma clones that expressed endogenous H-2Kb. To analyse further the association between MHC class I genes and IAP production, the H-2Kb-negative clones of BL6 melanoma were transfected with various H-2 genes. Transfection of the H-2Kb or H-2Kd, but not H-2Dd or H-2Ld genes resulted in the elimination of IAPs. Northern blot analysis revealed that loss of IAPs in the H-2K gene-transfected BL6 melanoma cells was due to lack of IAP transcripts. Elimination of IAPs in the H-2Kb-positive BL6 melanoma cells was also accompanied by alterations in expression of various cellular genes and changes of their phenotypic properties.

Animals↗
PubMed1996

Primary malignant melanoma of the sinonasal cavity: MR imaging evaluation.

To evaluate the magnetic resonance (MR) imaging characteristics of primary malignant melanoma of the sinonasal cavity, T1- and T2-weighted MR images of 12 patients with primary sinonasal melanoma were retrospectively reviewed. Gadolinium-enhanced imaging was performed in seven cases. The MR images were compared with histopathologic results. There were seven melanotic melanomas and five amelanotic melanomas; hemorrhage was present in three melanotic and two amelanotic melanomas. The seven melanotic melanomas were hyperintense to gray matter on T1-weighted images (whether hemorrhage was present or not), consistent with the paramagnetic effect of melanin. Four of the five amelanotic melanomas had intermediate signal intensity on T1-weighted images; one was not detected. On T2-weighted images, all of the melanomas detected had intermediate though variable signal intensity compared with that of gray matter. On gadolinium-enhanced images, all cases demonstrated mild to moderate enhancement. The signal intensity of sinonasal melanoma appears to vary according to the histopathologic components of the tumor. High signal intensity within the lesion on T1-weighted images suggests the presence of melanin.

Aged↗
PubMed1996

Vitellogenin induction and reduced serum testosterone concentrations in feral male carp (Cyprinus carpio) captured near a major metropolitan sewage treatment plant.

Endocrine disrupting chemicals can potentially alter the reproductive physiology of fishes. To test this hypothesis, serum was collected from common carp (Cyprinus carpio) at five riverine locations in Minnesota. Male fish collected from an effluent channel below the St. Paul metropolitan sewage treatment plant had significantly elevated serum egg protein (vitellogenin) concentrations and significantly decreased serum testosterone concentrations compared to male carp collected from the St. Croix River, classified as a National Wild and Scenic River. Carp collected from the Minnesota River, which receives significant agricultural runoff, also exhibited depressed serum testosterone concentrations, but no serum vitellogenin was apparent. These data suggest that North American rivers are receiving estrogenic chemicals that are biologically active, as has been reported in Great Britain.

Animals↗
PubMed1996

Results of combined pulmonary resection and cardiac operation.

BACKGROUND: Concomitant lesions of the heart and lung are uncommon, but when present they pose a therapeutic challenge for thoracic surgeons. A combined procedure avoids the need for a second major thoracic procedure and may improve outcomes and provide economic benefit. However, cardiopulmonary bypass may adversely affect the natural history of pulmonary malignancies. METHODS: The clinical records of 30 patients were reviewed who underwent simultaneous lung resection and cardiac operations between January 1982 and July 1995. Follow-up was obtained on all 30 patients (mean follow-up, 22 months; range, 1 to 100 months). RESULTS: Twenty-four patients underwent coronary artery bypass grafting in conjunction with pulmonary resection. Six patients underwent aortic (n = 4) or mitral (n = 2) valve replacement. The pulmonary resections consisted of pneumonectomy (n = 3), lobectomy (n = 14), wedge excision (n = 12), and tracheal resection (n = 1). Twenty-one patients had pathologic findings that confirmed adenocarcinoma (n = 10), squamous cell carcinoma (n = 5), small cell carcinoma (n = 2), or other malignancy (n = 4). Tumor stage of primary lung cancers was stage I, n = 12; stage II, n = 3; and stage IIIa, n = 2. Pathologic examination revealed benign disease in 9 patients. There were two operative deaths, one due to aspiration and one due to stroke. There were three late deaths, two cardiac and one of metastatic disease. Overall late survival was 85% +/- 7% and 73% +/- 16% at 1 and 5 years, respectively. Actuarial survival for patients with malignant disease was 64% at 5 years. CONCLUSIONS: Simultaneous cardiac operation and lung resection was not associated with increased early or late morbidity or mortality. Cardiopulmonary bypass does not adversely affect survival in patients with malignant disease. Cardiac valve replacement can be performed safely in conjunction with pulmonary resection.

Actuarial Analysis↗
PubMed1995

Crystal structure of endo-beta-N-acetylglucosaminidase H at 1.9 A resolution: active-site geometry and substrate recognition.

BACKGROUND: Endo-beta-N-acetylglucosaminidase H (Endo H), an endoglycosidase secreted by Streptomyces plicatus, hydrolyzes the glycosidic bond between the core N-acetyglucosamine residues of asparagine-linked high-mannose oligosaccharides. Endo H is a commonly used reagent in glycobiology research, including the characterization of oligosaccharides in glycoproteins. On-going crystallographic studies of Endo H and related endoglycosidases are aimed at identifying the molecular features that determine the different substrate specificities of these enzymes. RESULTS: The three-dimensional structure of Endo H has been determined to 1.9 A resolution. The overall fold of the enzyme is that of an irregular (alpha/beta)8-barrel comprising eight beta-strand/loop/alpha-helix units. Units 5 and 6 have very short loop sections at the top of the molecule and their alpha-helices are replaced by sections of extended geometry. The loop of unit 2 includes a small two-stranded antiparallel beta-sheet. A shallow curved cleft runs across the surface of the molecule from the area of units 5 and 6, over the core of the beta-barrel to the area of the beta-sheet of loop 2. This cleft contains the putative catalytic residues Asp130 and Glu132 above the core of the beta-barrel. These residues are surrounded by several aromatic residues. The loop 2 area of the cleft is formed by neutral polar residues, mostly asparagines. CONCLUSIONS: The structure of Endo H is very similar to that of Endo F1, a closely related endoglycosidase secreted by Flavobacterium meningosepticum. Detailed comparison of the structures of Endo H and Endo F1 supports the model previously proposed for substate binding and recognition, in which the area of loop 2 determines the substrate specificity and the alpha-helices of units 5 and 6 are missing to accommodate the protein moiety of the substrate.

Bacterial Proteins↗
PubMed1995

Myocardial protection for coronary bypass grafting: the Toronto Hospital perspective.

BACKGROUND: The contemporary results of coronary artery bypass grafting using a variety of myocardial preservation techniques are excellent. In recent years, the number of "high-risk" patients referred for operation has increased, thus necessitating continued advances in surgical myocardial protection. METHODS: In this article, we review recent advances in clinical myocardial protective techniques and emphasize studies conducted at The Toronto Hospital. Further, on the basis of promising current research, we speculate on future prospects for myocardial protection. RESULTS: At The Toronto Hospital, we converted from crystalloid to intermittent cold blood cardioplegia in 1985. We demonstrated that "continuous" cardioplegic strategies may help resuscitate the ischemic myocardium and reduce operative complications in high-risk patients. Further improvements in myocardial protection will require refinements in cardioplegic solution temperature, direction of delivery, and additives to "precondition" the myocardium against ischemic damage. CONCLUSIONS: Major advances that meet the requirements of an increasingly high risk patient population have been made in surgical myocardial protection in recent years. The future is bright for continued progress in this area.

Blood↗
PubMed1995

Exercise oximetry versus spirometry in the assessment of risk prior to lung resection.

BACKGROUND: Spirometry remains a standard method of assessing patient risk prior to lung resection despite its poor sensitivity and specificity. This study compares the relative ability of standardized exercise oximetry and spirometry--forced expiratory volume in the first second--to predict morbidity and mortality after lung resection. METHODS: The study comprised a retrospective review of 396 consecutive patients of whom 299 underwent both oximetry and spirometry. Oximetry was undertaken during standard exercise under the supervision of a single physical therapist. Spirometry identified 46 patients with a forced expiratory volume in the first second of less than 1.5 L who were considered to be high risk. Exercise oximetry was used to identify patients with arterial oxygen desaturation at rest, while walking on level ground, or while climbing two flights of stairs (n = 65). RESULTS: Compared with spirometry, exercise oximetry more reliably predicted home oxygen requirements (p < 0.001), need of admission to the intensive care unit (p < 0.05), prolonged hospital stay (p < 0.001), and respiratory failure (p < 0.05). Oximetry identified 50% of the patients who died, all of whom had a forced expiratory volume in the first second of greater than 1.5 L. Despite its superior predictive value, the sensitivity of oximetry remained low. CONCLUSIONS: We conclude that standardized exercise oximetry is a superior screen of the high-risk patient than spirometry (forced expiratory volume in the first second) prior to pulmonary resection when there are no other risk factors noted on initial history and physical examination. A prospective, randomized trial is required to substantiate this conclusion.

Critical Care↗
PubMed1995

Is body size the cause for poor outcomes of coronary artery bypass operations in women?

Although small body size and coronary artery diameter are recognized as major contributors to the increased risk of coronary artery bypass grafting in women, few studies have established the independent influence of body size and gender on outcome. We studied 7025 consecutive patients (5694 men, 1331 women) undergoing isolated coronary artery bypass grafting between 1990 and 1994. Women were older, had higher preoperative prevalences of urgent operation because of unstable angina, diabetes, peripheral vascular disease, hypertension, and single-vessel coronary artery disease (p < 0.0001), and a lower prevalence of left ventricular ejection fraction 40% or less (p < 0.0001). The prevalences of operative mortality (men, 1.8%; women, 3.5%), low-output syndrome (men, 6.6%; women, 14.8%), and myocardial infarction (men, 2.8%; women, 5.5%) were higher in women (p < 0.0001). Patients were divided into quartiles for body surface area, weight, height, and body mass index. For both men and women, there was no difference in operative mortality between the highest and lowest quartiles of body size. Women, however, had a higher prevalence of operative mortality than men in the lower quartiles of body surface area, height, and weight and in the higher quartiles of body mass index. Among men, the prevalence of low-output syndrome increased (p < 0.0001) with decreasing body surface area, weight, and body mass index, suggesting that body size did influence the prevalence of low-output syndrome. However, women had a higher prevalence of low-output syndrome than men in every category and quartile of body size (p < 0.0001). Multivariable analysis identified gender as a significant determinant of operative mortality (odds ratio 1.83, 95% confidence interval 1.27 to 2.64) and low-output syndrome (odds ratio 2.52, 95% confidence interval 2.05 to 3.11). When multivariable adjustments were made for body size and preoperative risk factors, gender remained a predictor of both operative mortality and low-output syndrome. Multivariable assessment of risk for men and women separately identified that urgent operation was a predictor of operative mortality (odds ratio 2.52, 95% confidence interval 1.32 to 5.61) and low-output syndrome (odds ratio 1.57, 95% confidence interval 1.14 to 2.17) in women but not men. In conclusion, the increased risk of coronary artery bypass grafting in women may be explained in part by dramatic differences in preoperative risk factors between men and women. In both men and women, small body size did not increase the risk of operative mortality, but may have contributed to the risk of low-output syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1995

Intragraft expression of IL-10 messenger RNA: a novel correlate of renal allograft rejection.

A major conceptual advance is the formulation that type I cytokines (such as IL-2 and IFN-gamma) enhance cellular immunity and are host-protective, and that type II cytokines (such as IL-4 and IL-10) dampen cellular immunity and facilitate the progression of infection. We have explored the intragraft expression of type I and type II cytokines during human renal allograft rejection. RNA was isolated from 98 allograft biopsies, and reverse transcription-PCR was used to amplify and identify intragraft expression of mRNA encoding IL-2, IFN-gamma, IL-4, or IL-10. Intragraft expression of IL-7 mRNA and TGF-beta 1 mRNA was also investigated. Our investigation demonstrated that: (a) intragraft expression of IL-10 mRNA and IL-2 mRNA are significant correlates of acute rejection; (b) IL-4, IL-7, IFN-gamma and TGF-beta 1 mRNA expression do not correlate with acute rejection; and (c) IL-10 does not prevent in vivo expression of IFN-gamma, IL-2, IL-7, or TGF-beta 1. Our studies identify, for the first time, a significant association between intragraft IL-10 mRNA expression and acute rejection, and suggest that treatment strategies capable of constraining IL-10 expression might be of value in the prevention of acute rejection.

Base Sequence↗