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Biomedical subjects

V Rao

Publications and source records attributed to V Rao.

At least 19 recordsLinked to original sources

Spondyloepimetaphyseal dysplasia and abnormal dentition in siblings: a new autosomal recessive syndrome.

The clinical and radiological features are described in male and female siblings with a unique form of spondyloepimetaphyseal dysplasia. In addition to generalized platyspondyly with epiphyseal and metaphyseal involvement, these children also have thin tapering fingers with accentuated palmar creases and abnormal dentition with oligodontia and pointed incisors. Parental consanguinity suggests that this is an autosomal recessive disorder.

Adolescent

Changing pattern of valve surgery.

BACKGROUND: Advances in surgical technique and perioperative myocardial protection have reduced the risk of aortic and mitral valve surgery. Improved methods of valve repair have reduced the proportion of patients who require valve replacement. However, patients who require valve replacement often have advanced disease and/or extensive calcification and may therefore be at increased risk for perioperative morbidity and mortality. METHODS AND RESULTS: We reviewed the results of 2898 patients who underwent aortic (AVR) or mitral (MVR) valve replacement at the Toronto Hospital. We compared patients who underwent surgery between January 1982 and December 1986 (early group) with those who were operated on between January 1989 and December 1993 (late group). The univariable and multivariable predictors of postoperative low-output syndrome (LOS) and operative mortality (OM) were determined for each time period. A total of 1779 patients underwent AVR (late, n = 997; early, n = 782). Multivariable analyses revealed that the late group had significantly more patients with independent pre-epidemiology operative risk factors for both OM and LOS. Despite the greater proportion of high risk patients, the incidence of postoperative LOS was lower in the late group (10% versus early, 14%; P = .012). There was no difference in OM between the two groups (late, 3.4% versus early, 3.7%; P = .732). A Total of 1119 patients underwent MVR (late, n = 493; early, n = 626). Compared with the early group, the late group had significantly more patients with preoperative multivariable risk factors for OM and LOS. There was no difference in postoperative LOS (late, 19% versus early, 21%; P = .361) or OM between the two groups (late, 5.8% versus early, 6.9%; P = .432). CONCLUSIONS: Despite an increase in high-risk patients, there was no significant increase in mortality or morbidity associated with aortic or mitral valve surgery.

Adult

Preconditioning to improve myocardial protection.

Major advances in the composition and delivery of cardioplegia have helped to reduce the morbidity and mortality associated with coronary bypass surgery. The discovery of the preconditioning response should facilitate the development of more powerful myocardial protective agents. These new agents may act to directly stimulate the preconditioning response or may act in a supplementary fashion to either augment the response or provide protection from alternate pathways. As new techniques of myocardial protection continue to be developed, the risk-to-benefit ratio of coronary bypass surgery will continue to improve. As a result of these improvements, surgeons will be able to offer surgery to an increasingly high risk patient population without increasing the morbidity or mortality currently associated with coronary bypass.

Animals

Structure in Thin and Ultrathin Spin-Cast Polymer Films

The molecular organization in ultrathin polymer films (thicknesses less than 1000 angstroms) and thin polymer films (thicknesses between 1000 and 10,000 angstroms) may differ substantially from that of bulk polymers, which can lead to important differences in resulting thermophysical properties. Such constrained geometry films have been fabricated from amorphous poly(3-methyl-4-hydroxy styrene) (PMHS) and semicrystalline poly(di-n-hexyl silane) (PD6S) by means of spin-casting. The residual solvent content is substantially greater in ultrathin PMHS films, which suggests a higher glass transition temperature that results from a stronger hydrogen-bonded network as compared with that in thicker films. Crystallization of PD6S is substantially hindered in ultrathin films, in which a critical thickness of 150 angstroms is needed for crystalline morphology to exist and in which the rate of crystallization is initially slow but increases rapidly as the film approaches 500 angstroms in thickness.

Journal Article

Activation of glycosylasparaginase. Formation of active N-terminal threonine by intramolecular autoproteolysis.

The activation mechanism of glycosylasparaginase of Flavobacterium meningosepticum has been analyzed by site-directed mutagenesis and activation of purified precursors in vitro. Mutation of Thr-152 to Ser or Cys leads to gene products that are not activated in vivo but are activated in vitro because processing of the mutant precursors is inhibited by certain amino acids in the cell. Kinetic studies reveal that activation is an intramolecular autoproteolytic process. The involvement of His-150 and Thr/Ser/Cys-152 in activation suggests that autoproteolysis resembles proteolysis by serine/cysteine proteases. Multiple functions of the highly conserved active threonine residue are implicated.

Amino Acid Sequence

Can patients with left main stenosis wait for coronary artery bypass grafting?

BACKGROUND: The economic impact of health care reforms may result in waiting lists for coronary artery bypass grafting. This study was designed to examine the clinical results of patients with left main stenosis who were placed on a triaged wait list for operation. METHODS: Data were collected prospectively on 2,145 patients undergoing isolated coronary artery bypass grafting between 1989 and 1994. Critical left main stenosis (LMS, 50% or more stenosis) was present in 281 patients, and 1,864 patients had no left main disease, or a left main stenosis of less than 50% (no LMS). RESULTS: The average time from angiography to operation was shorter in patients with LMS (LMS 38 +/- 46 days versus no LMS 84 +/- 71 days; p = 0.0001). Two patients in the LMS group died; they had declined operation. Four patients suffered non-Q wave myocardial infarctions, all of whom subsequently underwent operation with no perioperative complications. The presence of LMS did not influence operative mortality (LMS 2.8% versus no LMS 1.3%), the incidence of low output syndrome (LMS 8.3% versus no LMS 5.4%), or the incidence of perioperative myocardial infarction (LMS 3.8% versus no LMS 4.2%). To examine the effect of waiting time on outcomes, patients with LMS were divided into early (operation 10 days or less after angiography) and late revascularization groups (more than 10 days). Operative mortality, low output syndrome, and myocardial infarction were similar in the early and late groups. Patients in the early group were more likely to have New York Heart Association functional class IV symptoms (64% versus late 22%; p < 0.0001), unstable angina (87% versus late 65%; p < 0.0001), or a recent preoperative myocardial infarction (17% versus late 2%; p < 0.0001). CONCLUSIONS: Carefully selected patients with significant left main stenosis can safely wait for operation with a low risk of complications. Early surgical intervention is allocated to patients with severe symptoms or recent preoperative myocardial infarction.

Aged

Randomized study of right ventricular function with intermittent warm or cold cardioplegia.

BACKGROUND: Transient right ventricular dysfunction has been previously documented after bypass operations despite adequate myocardial protection with intermittent antegrade cold blood cardioplegia. Recently warm blood cardioplegia has been interrupted during construction of distal anastomoses to improve visualization. The effects of intermittent antegrade warm blood cardioplegia, and the resultant periods of right ventricular normothermic ischemia, on postoperative right ventricular function are unknown. METHODS: To assess the effects of cardioplegia on right ventricular protection, 52 patients undergoing isolated bypass grafting were randomized to intermittent warm or cold blood cardioplegia. The two groups were similar with respect to age, sex, ventricular function, and right coronary stenoses. Cross-clamp times were similar (warm, 64 +/- 22 minutes; cold, 63 +/- 15 minutes; not significant). The cumulative time of cardioplegia interruption was longer in the cold group (42 +/- 8 minutes) than in the warm group (31 +/- 14 minutes; p < 0.002). A rapid-response thermodilution catheter was employed to assess postoperative right ventricular ejection fraction and end-diastolic and end-systolic volume indices. RESULTS: The right ventricular ejection fraction was greater in the warm group at 6 hours (warm, 0.46 +/- 0.06; cold, 0.37 +/- 0.08; p < 0.05) and 8 hours (warm, 0.43 +/- 0.08; cold, 0.37 +/- 0.08; p < 0.05) postoperatively. The right ventricular end-diastolic volume index was less in the warm group 8 hours postoperatively (warm, 83 +/- 11 mL/m2; cold, 94 +/- 16 mL/m2; p < 0.05). There were no differences in pulmonary arterial pressures or right ventricular stroke work index. CONCLUSIONS: Despite intermittent normothermic ischemia of half the cross-clamp time, patients receiving warm cardioplegia maintained right ventricular hemodynamics after bypass grafting.

Aged

Results of represervation of the chordae tendineae during redo mitral valve replacement.

BACKGROUND: Previous studies have shown that preservation of the chordae tendineae improves early and late postoperative left ventricular function after mitral valve replacement. This report describes the results of represervation of the chordae tendineae during redo mitral valve replacement in patients who had their chordae tendineae preserved during their initial operation. METHODS: Fifty-four patients undergoing reoperative mitral valve replacement with preservation of their chordal annular attachments (chordae group) were compared with 187 patients who had redo mitral valve replacement without preservation of the chordae (nonchordae group). The interval between the initial operation and the reoperation was 8.7 +/- 4.4 years in the chordae group and 8.6 +/- 4.9 years in the nonchordae group (p = 0.315). Seventy-three patients underwent aortic valve replacement during their redo mitral valve replacement compared with 168 patients who had mitral valve replacement alone. There were 15 patients who had their chordal attachments represerved during redo double-valve replacement. RESULTS: In the chordae group, intraoperative assessment revealed excellent chordal connection between the preserved papillary muscles and the mitral annulus in all patients. One patient had adhesions between the preserved chordae and the stent of the tissue valve. The chordal attachments were preserved during insertion of the second valve in all patients. The incidence of low output syndrome and operative mortality in the chordae group was 16.7% and 7.4%, respectively. In the nonchordae group, the incidence of low output syndrome was 27.3% (p = 0.112 compared with the chordae group) and the operative mortality was 13.4% (p = 0.236 compared with the chordae group). In patients with double-valve replacement, represervation of the chordae was associated with a reduction in low output syndrome (0% versus 24%; p = 0.034) and mortality (6.7% versus 15.5%; p = 0.374). CONCLUSIONS: Preservation of the chordal attachments between the papillary muscles and the mitral annulus can be accomplished during reoperative mitral valve replacement. Represervation of the chordae tendineae may reduce postoperative low output syndrome, especially in high-risk patients undergoing redo double-valve replacement.

Aortic Valve

Does the internal thoracic artery graft delay the recovery of myocardial metabolism?

BACKGROUND: The left internal thoracic artery (LITA) bypass graft to the left anterior descending artery has greater long-term patency than a saphenous vein graft. However, surgeons may be reluctant to use the LITA graft in some patients because they are unable to deliver cardioplegia to the left anterior descending artery territory. METHODS: We compared the myocardial levels of high-energy phosphates and their metabolites in patients who received an LITA graft with those in patients who received a saphenous vein graft to the left anterior descending artery territory during elective coronary artery bypass grafting. Right and left ventricular biopsy specimens were obtained at three times: before aortic cross-clamping, after cross-clamp removal, and after 10 minutes of reperfusion. RESULTS: No differences were found between the LITA graft group and the saphenous vein graft group in any right ventricular metabolites. There was an improvement in myocardial protection over time and a higher proportion of LITA graft patients in the late time period (early group, 63% versus late group, 80%; p < 0.01). Within each time period, there were no differences between the LITA and saphenous vein graft groups. Among patients receiving cold antegrade cardioplegia, the myocardial levels of high-energy phosphates were better preserved in those receiving an LITA graft. CONCLUSIONS: Advances in myocardial protection have led to improved preservation of high-energy phosphate levels after cardioplegic arrest. In patients undergoing elective coronary artery bypass grafting, the use of an LITA graft does not adversely affect myocardial metabolism. Further investigations are required to determine the effects of the use of the LITA during urgent or emergent procedures.

Adenine Nucleotides

Left ventricular mass regression early after aortic valve replacement.

BACKGROUND: Regression of left ventricular hypertrophy is an important and well-recognized salutary effect of aortic valve replacement. The earliest evidence of left ventricular mass regression after aortic valve replacement and the influence of prosthesis type are not well known, and were the focus of this study. METHODS: Transthoracic echocardiography was used to measure left ventricular mass index preoperatively and before discharge in 57 consecutive patients undergoing isolated aortic valve replacement (with or without coronary artery bypass grafting). RESULTS: Three patients were excluded from the study because of inability to obtain accurate M-mode echocardiographic images for left ventricular mass measurement preoperatively (1) or postoperatively (2). Of the remaining 54 patients, mechanical bileaflet valves were used in 19, stented tissue bioprostheses were implanted in 15, and a stentless porcine bioprosthesis was chosen for 20. Postoperative echocardiograms were obtained 4.9 +/- 2.3 days after aortic valve replacement (range, 2 to 9 days). A two-way repeated-measures analysis of variance demonstrated a significant reduction of left ventricular mass index before discharge (preoperative 141.4 +/- 45.2 g/m2, postoperative 127.5 +/- 32.8 g/m2; p = 0.0005) but no differences between prostheses. CONCLUSIONS: Left ventricular mass regression begins early after aortic valve replacement, probably because of reduction of transvalvular gradients and left ventricular wall stress. At least in the very early postoperative period, the type of prosthesis does not influence the extent of mass regression.

Aged

Cost-effective provision of cardiac services in a fixed-dollar environment.

In the Canadian single-payer system, all hospital payments, including payments for cardiac operations, are negotiated with the government annually. Each hospital is required to remain within 50 cases of its negotiated surgical target. Physicians are paid on a capitated basis and are subject to penalties if negotiated targets are exceeded. There is a computerized waiting list for cardiac operation, with patients classified by an urgency rating scale and objectives set for the maximum period for any given urgency category. Experience has shown that many patients are delayed in the queue, waiting longer than expected for surgical procedures. Waiting times are not influenced by age, sex, or reoperative status, but are influenced by factors such as the presence of multiple risk factors, the number of diseased vessels, stability or unstability of angina, left main coronary artery disease, and recent angioplasty. Waiting time has not been shown to affect operative mortality, the incidence of postoperative low-output syndrome, or length of hospital stay. Canada's 30-year experience with the provision of cardiac services under managed care may provide useful information to hospitals and physicians in the United States currently confronting capitation. The following overview focuses on two critical issues: negotiation of costs and management of patient waiting lists.

Canada

Impact of preoperative risk and perioperative morbidity on ICU stay following coronary bypass surgery.

Prolonged intensive care unit treatment (> 3 days) contributes to increased health costs and resource utilization. In order to devise strategies to limit intensive care unit stay, and provide cost-effective medical care, it is necessary to identify the pre- and perioperative risk factors of prolonged treatment. Over 100 potential risk variables were collected prospectively in 889 consecutive patients undergoing isolated coronary bypass surgery between 1990 and 1992. The incidence of intensive care unit therapy lasting > 3 days was 6.8%. Univariate statistics identified 23 pre- and perioperative variables that were potential contributors to prolonged intensive care unit therapy. However, multivariate analysis of preoperative risk variables identified only recent myocardial infarction (within 30 days of surgery) and continued preoperative smoking (within 30 days of surgery) to be independent risk factors. Only 6.3% of patients without preoperative myocardial infarction and 6.1% of non-smokers required prolonged intensive care unit treatment, compared with 14.8% of patients with preoperative myocardial infarction (P = 0.01) and 10.1% of smokers (P = 0.07). When multivariate analysis was repeated with both pre- and perioperative variables, only ischemic morbidity (inotropes, myocardial infarction and low-output syndrome; 138 patients) and non-ischemic morbidity (infection, stroke or bleeding; 37 patients) predicted prolonged intensive care unit treatment. Intensive care unit treatment for > 3 days occurred in 26.8% of patients with ischemic morbidity compared with 3.2% of patients without ischemic morbidity (P = 0.001). Prolonged intensive care stay occurred in 32.4% of patients who suffered non-ischemic complications compared with 5.7% of patients who did not suffer these complications. The multiple logistic regression analysis odds ratio for ischemic morbidity was 7.4 (95% c.i. 4.0-13.4) compared with 4.8 (95% c.i. 1.9-10.1) for non-ischemic morbidity. Strategies designed to reduce the incidence of prolonged intensive care unit treatment should include prevention of stroke, infection and bleeding. However, the greatest reduction of intensive care unit utilization would be mediated by prevention of ventricular dysfunction secondary to myocardial ischemia or inadequate myocardial preservation.

Adult

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

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

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

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

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

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