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Biomedical subjects

B S Goldman

Publications and source records attributed to B S Goldman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Coronary bypass with arterial conduits.

To assess the efficacy of arterial revascularization 368 patients were studied who underwent myocardial revascularization with two or more arterial conduits (group M) and compared with 2092 patients in whom a single internal mammary artery +/- veins (group S), and to a third group in which only saphenous vein conduits (group V, n = 602) were used. Group M patients were younger (aged 54.0(9.5) years; 4.1% aged > 70 years) than either group V (67.6(8.9) years, 40.7% > 70 years, P < 0.0001) or group S patients (62.0(8.5) years, 15.7% > 70 years, P < 0.0001). Furthermore, this cohort group had the lowest percentage of females (8.4%), of urgent cases (21.7%), of preoperative myocardial infarction (6.0%), and of redo surgery (0.8%). In contrast, patients who received only saphenous vein conduits had the highest proportion of female patients (29.2%), of urgent cases (47.4%), of preoperative myocardial infarction (16.5%), and of redo surgery (5.5%). By multivariate logistic regression analysis (odds ratio in parentheses), redo surgery (6.06, P = 0.0001), preoperative intra-aortic balloon pump assist (6.11, P = 0.0001), diabetes (1.97, P = 0.03), urgent surgery (1.80, P = 0.05), and advanced age (2.14, P = 0.01) were all predictors of operative mortality. In contrast, while choice of conduit appeared to influence outcome by univariate analysis (4.2% mortality in group V, P < 0.001), it was not found to be a predictor of either mortality or morbidity by regression analysis. The present results indicate that, in carefully selected patients, despite increased technical demands with longer periods of aortic occlusion and longer pump times, multi-arterial grafting (compared with conventional revascularization) is a safe and efficacious procedure. Whether or not this approach to revascularization will increase long-term survival and freedom from reoperation will require further study.

Aged↗
PubMed1998

The development of sinoatrial dysfunction in pacemaker patients with isolated atrioventricular block.

The purpose of this paper is the assessment of sinus node competence over time in patients with isolated atrioventricular block (AV block). Patients implanted with AV synchronous pacemakers for isolated AV block between December 1993 and June 1995 were prospectively evaluated at predischarge, 6 weeks, and subsequent 6 months follow-up with respect to atrial rate monitors/24-hour Holter and modified exercise test. Patients unable to maintain AV synchronous pacing or complete a modified exercise test were excluded. Sinus node competency is interpreted as: (1) absence of atrial brady- or tachyarrhythmia, (2) ability to achieve a minimum heart rate of 100 beats/min with modified exercise test or during daily activities. There were 58 patients (22 women), mean age 71.0 +/- 13.8 with an average follow-up of 30.4 months (11-40). Three patients did not complete a modified exercise test, 4 patients were lost to follow-up, and 2 patients were unable to maintain AV synchronous pacing. Of the remaining 49 patients, 3 developed chronic or paroxysmal atrial fibrillation. No patient developed significant bradyarrhythmias. All patients achieved a heart rate of > or = 100 beats/min modified exercise test. In our group of patients with isolated AV block within a moderate follow-up period, development of sinoatrial dysfunction was rare (6%). A longer follow-up is required to delineate the natural history of sinoatrial dysfunction in patients with isolated AV block.

Aged↗
PubMed1998

Early results using an ePTFE membrane for pericardial closure following coronary bypass grafting.

A prospective randomized trial was conducted to evaluate the early efficacy and safety of the Gortex surgical membrane. Three hundred two patients (265 males, 37 females) undergoing isolated coronary bypass surgery were randomized to receive a Gortex membrane (GM = 138) or have the pericardium left open (complication [C] = 164). The groups did not differ in age, gender, urgency of procedure, length of procedure, or use of arterial grafts. Two deaths occurred in each group giving an overall mortality of 1.3%. Fifty-three (17%) patients experienced some complication (C = 34, 21%), GM = 19 (14%). Although the combined complication rate was higher in the control group, this was not statistically significant (chi2 = 2.51, p = 0.11). Postoperative ischemic events (C = 8, GM = 4) observed between the groups were not significant (chi2 = 0.05, p = 0.8), and no statistically significant difference was observed between the incidences of infections (C = 7, GM = 5) or mediastinal complications (C = 3, GM = 3). The Gortex surgical membrane can be used safely without increasing the risk of infection or mediastinal complications. The incidence of recurrent myocardial ischemia, a possible indicator of graft compression, was not higher following membrane implantation. Efficacy at injury prevention will need to be determined by a longitudinal follow-up study presently underway.

Adult↗
PubMed1998

Cardiac pacing in Canada in 1998: working towards optimal pacing therapy. Canadian Working Group on Cardiac Pacing.

The Canadian Working Group on Cardiac Pacing (CWGCP) was formed in 1996 with the primary goal of promoting optimal pacing therapy in Canada. In 1997, the CWGCP conducted a survey of pacing practices across Canada. Ninety-two of 125 implanting programs (74%) responded. Implant rates vary by province--from 39 per 100,00 population in Ontario to 63 per 100,000 population in Nova Scotia and Prince Edward Island. Variations in regional implant rates persist even after correcting for the age of the population. Physiological pacing was used for 35% of all implants in Canada in 1996/97. There were marked differences across Canada in the mode of pacing selected. In western Canada, 39.5% of pacing systems implanted were physiological compared with 18.2% in Atlantic Canada and 29% in Quebec. There were also differences in follow-up practices. Approximately 40% of centres follow patients with single chamber pacemakers annually, whereas most other centres still follow these patients every six months. Economic constraints, the size of pacing programs and the involvement of committed pacing physicians are factors that may influence the regional differences in cardiac pacing across Canada.

Canada↗
PubMed1997

Coronary artery bypass grafting in patients with non-dialysis-dependent renal insufficiency.

BACKGROUND: Preoperative renal failure increases the morbidity and mortality of coronary artery bypass graft (CABG) surgery. The results of CABG in patients with non-dialysis-dependent, mild renal insufficiency are unknown. METHODS: From a population of 2978 consecutive patients undergoing isolated CABG from 1990 to 1996, 38 patients with preoperative renal insufficiency (Renal group; serum creatinine >150 micromol/L) were identified and matched on six prognostic variables to a cohort of 152 control patients (Control group). Two patients with preoperative dialysis-dependent renal failure were excluded from analysis. RESULTS: Compared to the overall population, the Renal group were more likely to be over age 70, diabetic, hypertensive, and suffer from peripheral vascular disease and left ventricular dysfunction. Compared to the Control group, the Renal group were more likely to require perioperative blood transfusions (P<.001) and had a greater requirement for postoperative dialysis (P<.01). The Renal group had longer ventilation times, intensive care unit stay, and postoperative hospital stay. Mild renal insufficiency was found to be an independent predictor of postoperative low output syndrome (odds ratio=3.6). CONCLUSIONS: Mild renal insufficiency, even in the absence of dialysis, increases the risk of blood transfusion, low output syndrome and prolonged the length of intensive care unit and postoperative stay for patients undergoing CABG.

Aged↗
PubMed1997

Early experience with stentless versus stented valves.

BACKGROUND: The Toronto stentless porcine valve (SPV) was designed to improve hemodynamics after aortic valve replacement by maximizing available flow area in comparison to stented valves (STD). METHODS: To assess possible hemodynamic differences between STD and SPV, 59 patients undergoing isolated aortic valve replacement (+/-coronary artery bypass graft) were prospectively evaluated by preoperative and 3- to 6-month postoperative echocardiography. Among these, 23 patients received a STD, whereas 36 received the Toronto SPV. RESULTS: The mean size (mm) of SPV implanted was larger (SPV, 26.6+/-2.1; STD, 24.0+/-2.9; P=0.0002). Patients receiving STD valves were older and had a higher prevalence of coronary artery disease and congestive heart failure. There were no preoperative differences in left ventricular mass index (g/mo2), peak or mean pressure gradients (mmHg), effective orifice area (cm2), extent of fractional shortening (%), or velocity of circumferential shortening (cf/sec). ANOVA demonstrated a significant reduction in left ventricular mass index at 3 to 6 months (P=.0001) but no differences in left ventricular mass index regression between groups (STD, -28.8+/-37.5; SPV, -31.2+/-32.4; P=.36). Effective orafice area was increased postoperatively (P=.0001), particularly among SPV cases (STD, 1.5+/-0.4; SPV, 1.9+/-0.7; P=.01). Postoperative left ventricular mass index and mean pressure gradient were reduced (P=.0001) but did not differ between groups. Fractional shortening and velocity of circumferential shortening were greater in the SPV patients at 3 to 6 months after aortic valve replacement (P=.0004 and .0001, respectively), and an interactive effect was seen between time and prosthetic group (P=.0028 and .032, respectively). CONCLUSIONS: In a consecutive series of patients, we identified no hemodynamic differences between STD and SPV, although ventricular function improved after SPV. Because of the nonrandomized nature of the study, selection bias may have accounted for some of the observed results. A prospective, randomized trial is necessary to determine the hemodynamic advantages, if any, of the SPV valve.

Aged↗
PubMed1997

A thioreduction pathway tethered to the membrane for periplasmic cytochromes c biogenesis; in vitro and in vivo studies.

The c-type cytochromes are distinguished from other heme proteins by the covalent ligation of two heme vinyl groups to two cysteine residues on the apoprotein (at a CXXCH domain). The present study was undertaken to elucidate the roles and topological locations of two of the proteins necessary for cytochrome c biogenesis, the HelX and Ccl2 proteins in the Gram-negative bacteria Rhodobacter capsulatus. From their primary sequence, each of these proteins has a CXXC motif that could be involved in the reduction of the cysteine residues of the apocytochromes c, a prerequisite for covalent ligation to the heme. Results of site-directed mutagenesis of HelX and Ccl2 demonstrate that each cysteine residue is required for the in vivo function of the protein. We demonstrate that the native HelX in R. capsulatus is tethered to the cytoplasmic membrane via its uncleaved signal sequence. Ccl2 is tethered by a single transmembrane domain present in the C terminus with the N-terminal two-thirds of the protein in the periplasm. Thus, both CXXC motifs are exposed to the periplasm. The complete HelX protein and the soluble N-terminal portion of Ccl2 (called Ccl2*) were overproduced and purified from periplasmic fractions. The Ccl2* signal sequence is efficiently processed. In vitro studies with these purified proteins indicate that although neither can reduce insulin, HelX can reduce the Ccl2 cysteine residues and the Ccl2 cysteine residues are oxidized by an apocytochrome c peptide containing the CXXCH domain. Revertants of an helX deletion mutant were isolated that regain the ability to make c-type cytochromes (and thus grow photosynthetically); some of these suppressor strains are enhanced for photosynthetic growth by the addition of thio-reducing agents. In contrast, revertants of a ccl2 deletion strain could not be isolated under any condition. These results suggest that the HelX and Ccl2 proteins form a thioreduction pathway (HelX-->Ccl2-->apocytochrome c) whereby Ccl2 function may be highly specific for apocytochromes c while HelX may act as a more general reductant of proteins with vicinal cysteines.

Amino Acid Sequence↗
PubMed1997

Molecular and immunological analysis of an ABC transporter complex required for cytochrome c biogenesis.

The helABC genes are predicted to encode an ATP-binding cassette (ABC) transporter necessary for heme export for ligation in bacterial cytochrome c biogenesis. The recent discoveries of homologs of the helB and helC genes in plant mitochondrial genomes suggest this is a highly conserved transporter in prokaryotes and some eukaryotes with the HelB and HelC proteins comprising the transmembrane components. Molecular genetic analysis in the Gram-negative bacterium Rhodobacter capsulatus was used to show that the helABC and helDX genes are part of an operon linked to the secDF genes. To facilitate analysis of this transporter, strains with non-polar deletions in each gene, epitope and reporter-tagged HelABCD proteins, and antisera specific to the HelA and HelX proteins were generated. We directly demonstrate that this transporter is present in the cytoplasmic membrane as an HelABCD complex. The HelB and HelC but not HelD proteins are necessary for the binding and stability of the HelA protein, the cytoplasmic subunit containing the ATP-binding region. In addition we show that the HelA protein co-immunoprecipitates with either the HelC or HelD proteins. Thus, the HelABCD heme export complex is distinguished by the presence of four membrane-associated subunits and represents a unique subfamily of ABC transporters.

ATP-Binding Cassette Transporters↗
PubMed1997

Technique for reconstruction of the sinotubular junction.

Correct geometric relationships between the annulus and sinotubular junction during stentless valve implantation are critical to minimize the development of insufficiency. Some patients with aortic valve disease have dilatation of the sinotubular junction and are unable to have a stentless valve placed by standard techniques. We recently encountered such a patient and reconstructed the sinotubular junction by aortic crenation. Multiple interrupted plicating sutures were used to reduce the aorta from a diameter of 42 mm to 28 mm. This method allows tailoring of the aorta to appropriate size by varying the number of crenating sutures.

Aged↗
PubMed1997

Is this the natural history of the retention wire? A case report.

We report on a 71-year-old man who had a dual chamber pacemaker implanted in 1991. A Class IV fracture of the Telectronics Accufix 330-801 atrial lead was observed on a chest X ray in December 1993. Serial chest X ray and fluoroscopy documented stable position of the migrated fractured J wire. The patient remained asymptomatic and a decision for conservative monitoring was made. A subsequent finding of a right atrial mass on echocardiography and evidence of pulmonary embolism on lung scan prompted a change of strategy. The patient underwent atriotomy, and a right atrial thrombus was discovered associated with the fractured J retention wire, both of which were extracted uneventfully. This case is illustrative that despite apparent stability of a Class IV fracture, it may result in endothelial injury with a thrombogenic nidus and resultant complications.

Aged↗
PubMed1997

Differential levels of specific cytochrome c biogenesis proteins in response to oxygen: analysis of the ccl operon in Rhodobacter capsulatus.

The photosynthetic bacterium Rhodobacter capsulatus synthesizes c-type cytochromes under a variety of growth conditions. For example, under aerobic growth, c-type cytochromes are synthesized as part of an electron transport pathway, using oxygen as the terminal electron acceptor. Anaerobically in the light, R. capsulatus requires cytochrome bc1 and other c-type cytochromes for the photosynthetic electron transport pathway. It is shown here that the ccl1 and ccl2 genes of R. capsulatus are required for the synthesis of all c-type cytochromes, including the cytochrome c' protein of unknown function but of structural similarity to cytochrome b562. Polar and nonpolar mutations constructed in each gene demonstrated that the ccl12 genes form an operon. Expression of the ccl12 genes was examined by using lacZ and phoA fusions as translational reporters. Primer extension analysis was used to determine transcriptional control and the start site of the ccl12 promoter. Finally, antiserum to the Ccl2 protein was used to quantitate levels of Ccl2 under six different growth conditions. The Ccl2 protein is present at 20-fold-higher levels under conditions where oxygen is present. In contrast, other cytochromes c biogenesis proteins, HelA and HelX, previously shown to be part of an helABCDX operon, are at relatively similar levels under these six growth conditions. This discovery is discussed in terms of the physiology and evolution of cytochromes c biogenesis, with particular attention to oxidative environments.

Aerobiosis↗
PubMed1997

Comparison of the bacterial HelA protein to the F508 region of the cystic fibrosis transmembrane regulator.

The HelA protein of Rhodobacter capsulatus is the ATP-binding-cassette subunit of an exporter complex required for cytochrome c biogenesis. By primary sequence comparisons the F88 residue of HelA is similar to the F508 residue of the cystic fibrosis transmembrane regulator (CFTR) protein. Previous studies have established that CFTR F508delta or F508R proteins are defective but F508C is functional. Our results demonstrate that the HelA F88 mutants functionally mimic the phenotypes of known CFTR F508 mutants. The phenotypes of additional HelA mutants and the in vivo steady-state levels of these proteins are also reported.

ATP-Binding Cassette Transporters↗
PubMed1996

Phase 1 human trial of adenosine-potassium cardioplegia.

BACKGROUND: The cardioprotective role of adenosine in various models of ischemia-reperfusion, including adenosine supplementation to cardioplegic formulations, has been studied extensively. The appropriate dose of adenosine in humans is uncertain and could be limited by systemic hypotension or AV block. METHODS AND RESULTS: An open-label, nonrandomized phase 1 adenosine dose-ranging study was performed. Patients scheduled for primary isolated coronary bypass surgery were eligible for the study. Antegrade warm blood potassium cardioplegia (ratio, 4:1, blood to crystalloid) was administered in the routine fashion, with adenosine added to the initial 1000-mL dose and final 500-mL dose. Patients were studied in blocks of 4 per concentration. An escalating adenosine dosage schedule was planned to produce blood cardioplegia concentrations from 0 to 250 mumol/L, and the blocks were tested sequentially. Stopping rules were defined for systemic hypotension (phenylephrine dose during cardiopulmonary bypass > or = 5.0 mg; phenylephrine dose during cardioplegic induction > or = 800 micrograms) and AV block (permanent pacemaker insertion; temporary pacing dependency for > 90 minutes after cardiopulmonary bypass). Doses of 1, 2.5, 5, 10, and 25 mumol/L were well tolerated. With 50 mumol/L, systemic hypotension occurred during cardioplegic induction in 3 of 4 patients versus 1 of 24 (P < .005) at all lower concentrations (880 +/- 217 versus 297 +/- 286 micrograms phenylephrine per patient). The studies were repeated with an 8:1 blood-to-crystalloid cardioplegia delivery system. Adenosine concentrations of 0 (n = 4), 15 (n = 12), 20 (n = 8), and 25 mumol/L (n = 4) were tested. Hypotension during cardioplegic induction was more prevalent (P = .05) with the higher doses (15 mumol/L, 394 +/- 189 micrograms, 1 of 12 patients; 20 mumol/L, 360 +/- 355 micrograms, 2 of 8 patients; 25 mumol/L, 600 +/- 478 micrograms, 2 of 4 patients). There were no differences with respect to systemic hypotension during cardiopulmonary bypass or for pacing > 90 minutes after discontinuation of cardiopulmonary bypass, and no patient required permanent pacing. There have been no deaths, Q-wave myocardial infarctions, intra-aortic balloon pump insertions, or cerebral infarctions in the total sample of 56 patients. CONCLUSIONS: Our initial investigations have shown that adenosine can be safely administered during cardiopulmonary bypass. The authors recommend that further studies are warranted using adenosine 15 to 25 mumol/L, depending on the delivery system.

Adenosine↗
PubMed1996

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↗
PubMed1996

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↗