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Biomedical subjects

B F Buxton

Publications and source records attributed to B F Buxton.

At least 19 recordsLinked to original sources

Prediction and functional analysis of native disorder in proteins from the three kingdoms of life.

An automatic method for recognizing natively disordered regions from amino acid sequence is described and benchmarked against predictors that were assessed at the latest critical assessment of techniques for protein structure prediction (CASP) experiment. The method attains a Wilcoxon score of 90.0, which represents a statistically significant improvement on the methods evaluated on the same targets at CASP. The classifier, DISOPRED2, was used to estimate the frequency of native disorder in several representative genomes from the three kingdoms of life. Putative, long (>30 residue) disordered segments are found to occur in 2.0% of archaean, 4.2% of eubacterial and 33.0% of eukaryotic proteins. The function of proteins with long predicted regions of disorder was investigated using the gene ontology annotations supplied with the Saccharomyces genome database. The analysis of the yeast proteome suggests that proteins containing disorder are often located in the cell nucleus and are involved in the regulation of transcription and cell signalling. The results also indicate that native disorder is associated with the molecular functions of kinase activity and nucleic acid binding.

Databases, Genetic↗

Secondary structure prediction with support vector machines.

MOTIVATION: A new method that uses support vector machines (SVMs) to predict protein secondary structure is described and evaluated. The study is designed to develop a reliable prediction method using an alternative technique and to investigate the applicability of SVMs to this type of bioinformatics problem. METHODS: Binary SVMs are trained to discriminate between two structural classes. The binary classifiers are combined in several ways to predict multi-class secondary structure. RESULTS: The average three-state prediction accuracy per protein (Q(3)) is estimated by cross-validation to be 77.07 +/- 0.26% with a segment overlap (Sov) score of 73.32 +/- 0.39%. The SVM performs similarly to the 'state-of-the-art' PSIPRED prediction method on a non-homologous test set of 121 proteins despite being trained on substantially fewer examples. A simple consensus of the SVM, PSIPRED and PROFsec achieves significantly higher prediction accuracy than the individual methods.

Algorithms↗

Hemofiltration during cardiopulmonary bypass for high risk adult cardiac surgery.

AIMS: The role of hemofiltration (HF) during cardiopulmonary bypass (CPB) in adult cardiac surgery is controversial. It may be beneficial during prolonged CPB in high-risk surgery. Accordingly, we sought to compare two groups of patients undergoing high-risk cardiac surgery with or without HF. METHODS: One hundred and eighteen patients who underwent complex cardiac surgical procedures during a 12-month period were divided into two groups. Group I (n=61) comprised patients who were treated with hemofiltration during CPB. Group II (n=57) were not filtered. Estimated risk of death, standard demographic, clinical and surgical features were obtained and predetermined outcomes were studied. Statistical comparisons were made. RESULTS: Age, procedure times and mortality rates were similar in both groups. The mean volume of fluid removed in group I was 3.4 L. The preoperative mean Parsonnet score was 24.8 in group I and 22.5 in group II (ns). Postoperative serum hemoglobin, hematocrit, platelet, and albumin levels were all significantly higher in group I patients (p=0.0015) indicating hemoconcentration. Post-operative chest drainage showed a trend toward decreased post-operative bleeding in group I (p=0.065). Postoperative pleural effusions requiring chest tube drainage were significantly less in group I (9.8% vs. 29.8% 6; p = 0.0062). The incidence of lung infection was also decreased from 26.3% to 13.1% (p=0.05). Operative mortality was similar in both groups (11.4% in group 1, 10.5% in group II, ns). CONCLUSION: Hemofiltration during CPB attenuates postoperative anemia, thrombocytopenia and hypoalbuminemia, may reduce post-operative bleeding and appears to decrease post-operative pulmonary complications.

Aged↗

Anatomic and hemodynamic considerations influencing the efficiency of retrograde cardioplegia.

One of the major issues raised by cardiac surgical procedures requiring cardiopulmonary bypass is the question of myocardial protection. The preferred route for the administration of cardioplegia is controversial. A number of studies show the beneficial effects of retrograde cardioplegia but some demonstrate only partial or poor myocardial protection. This paper reviews the anatomy and anatomic variations of the coronary sinus, the coronary sinus orifice and cardiac veins, and the major systemic venous drainage, all of which may affect the distribution of retrograde cardioplegia.

Cardiopulmonary Bypass↗

Early and intensive continuous hemofiltration for severe renal failure after cardiac surgery.

BACKGROUND: The aim of this study was to test whether early and intensive use of continuous venovenous hemofiltration (CVVH) achieved a better than predicted outcome in patients with severe acute renal failure undergoing cardiac operations, and whether a simple and yet accurate model could be developed to predict their outcome before starting CVVH. METHODS: Medical record analysis with collection of demographic, clinical, and outcome information was used. RESULTS: Sixty-five consecutive patients were treated with early and intensive CVVH (mean operation to CVVH time, 2.38 days; pump-controlled ultrafiltration rate, 2 L/h) after coronary artery bypass grafting (56.9%), single valve procedure (16.9%), or combined operations (26.2%). In 32.3% of patients, intraaortic balloon counterpulsation was required and 20% of patients were emergencies. Sustained hypotension despite inotropic and vasopressor support occurred in 40% of patients and prolonged mechanical ventilation in 58.5%. Using an outcome prediction score specific for acute renal failure, the predicted risk of death was 66%. Actual mortality was 40% (p = 0.003). Using multivariate logistic regression analysis and neural network analysis, patient outcome could be predicted with good levels of accuracy (receiver operating characteristic 0.89 and 0.9, respectively). CONCLUSIONS: Early and aggressive CVVH is associated with better than predicted survival in severe acute renal failure after cardiac operations. Using readily available clinical data, the outcome of such patients can be predicted before the implementation of CVVH.

Acute Kidney Injury↗

An extracorporeal membrane oxygenation-based approach to cardiogenic shock in an older population.

BACKGROUND: We investigated the efficacy of an integrated system of advanced supportive care based on extracorporeal membrane oxygenation (ECMO) in older patients with an estimated mortality of more than 90% to establish whether its use is justifiable. METHODS: Treatment was provided by cardiac surgeons and critical care physicians and included the following key elements: (1) ECMO, (2) early application of continuous venovenous hemofiltration, (3) inhaled nitric oxide, (4) maintenance of perfusion pressure with norepinephrine, (5) maintenance of pulmonary blood flow by ventricular filling with intravenous colloids, (6) avoidance of early postoperative anticoagulation, (7) frequent use of transesophageal echocardiography, and (8) low tidal volume ventilation. Demographic features, intraoperative details, postoperative course, ECMO weaning rate, morbidity, survival to hospital discharge, and the quality of life of survivors were recorded. RESULTS: Seventeen consecutive patients (median age, 69 years) with refractory cardiogenic shock were studied. The median duration of ECMO was 86 hours (20 to 201 hours). Eleven patients (65%) were successfully weaned from ECMO. Seven patients (41%) survived to discharge. The major causes of morbidity were bleeding and leg ischemia. All patients who survived to discharge were alive and well at follow-up (median, 21 months) and reported a satisfactory quality of life. CONCLUSIONS: An ECMO-based approach can be used with acceptable results in the treatment of refractory cardiogenic shock, even in older patients.

Aged↗

High lactate predicts the failure of intraaortic balloon pumping after cardiac surgery.

BACKGROUND: Despite the use of intraaortic balloon pump (IABP) support in complex cardiac surgical patients, morbidity and mortality rates are high. More advanced mechanical cardiovascular support should be considered in those patients who are highly likely to die despite IABP support. We sought to identify early, readily available prognostic markers for patients receiving IABP support. METHODS: A retrospective analysis was performed on 39 patients requiring IABP support following cardiac surgery for more than 2 years. The accuracy and predictive ability of multiple potential markers of mortality were statistically assessed. RESULTS: Sixty-seven percent of the patients were successfully weaned from IABP support and 46% survived to hospital discharge. Serious complications occurred in 13% of patients. Serum lactate more than 10 mmol/L in the first 8 hours of IABP support predicted a 100% mortality. Base deficit more than 10 mmol/L, mean arterial pressure less than 60 mm Hg, urine output less than 30 mls/h for 2 hours, and dose of epinephrine or norepinephrine more than 10 microg/min were other highly predictive prognostic markers. CONCLUSIONS: Morbidity and mortality rates remain high despite IABP support following cardiac surgery. Mortality can be predicted by the presence of elevated serum lactate, elevated base deficit, hypotension, oliguria and large vasopressor doses, any of which should prompt appropriate consideration as to other mechanical cardiovascular support.

Aged↗

Geometric endo-ventricular patch repair of inferior left ventricular scars improves mitral regurgitation and clinical outcome.

BACKGROUND: The surgical reconstruction of inferior left ventricular (LV) aneurysms and scars has been considered a difficult procedure and there has been little material published about this treatment option. In this study we report on our experience with reconstruction of the inferior wall and compare it to the outcome of anterior LV reconstructions. METHODS: Seventeen patients (group 1) underwent geometric endo-ventricular patch repair (GER) of inferior LV aneurysms and dyskinetic scars between January 1998 and December 2000. In addition to poor LV function, 5 of these patients had severe mitral valve regurgitation (MR), 8 had moderate MR, and 4 had mild MR preoperatively. These patients also underwent coronary artery bypass graft surgery or valve surgery. The perioperative course, survival, and clinical status were evaluated in this group and was compared to those of 86 patients (group 2) undergoing anterior GER during the same period. RESULTS: There was 1 early death in group 1 (5.8%) and 6 in group 2 (7%) (p = ns). At the conclusion of the operative procedure, all patients in group 1 were weaned off cardiopulmonary bypass with trivial to mild MR. There was 1 late death in group 1 (6.2%) and 2 in group 2 (2.8%) (p = ns). Eleven patients (73%) in group 1 were in New York Heart Association class 1 compared to 60 in group 2 (77%) (p = ns). Follow-up echocardiography showed that 80% of patients in group 1 had trivial MR. CONCLUSIONS: The surgical reconstruction of inferior LV aneurysms and scars can be performed safely with the expectation of a reasonable early outcome similar to that achieved with anterior LV scars. When used in this setting GER improves MR, reducing the likelihood of heart failure decompensation.

Bioprosthesis↗

Metabolic changes and myocardial injury during cardioplegia: a pilot study.

BACKGROUND: The timing, nature, and severity of both increased cardiac troponin I (cTn-I) levels and myocardial injury during ischemic arrest with cardioplegia are unknown. To define them more accurately, we studied myocardial metabolic activity and the release of markers of myocardial cell injury into the coronary sinus before, during, and after cardioplegia. METHODS: We simultaneously measured creatine kinase, creatine kinase-MB, cTn-I, lactate, phosphate, and blood gases in coronary sinus and systemic arterial blood from 12 patients before cardiopulmonary bypass, after removal of the aortic cross-clamp, and after discontinuation of cardiopulmonary bypass. We also measured coronary sinus flow and transmyocardial fluxes of all analytes and calculated myocardial oxygen consumption, myocardial carbon dioxide production, and myocardial energy expenditure. RESULTS: Myocardial lactate release increased 10-fold after removal of the aortic cross-clamp (p = 0.012) and was accompanied by a surge in myocardial phosphate uptake (p = 0.056). These events were associated with only partial cardioplegia-induced suppression of myocardial oxygen consumption (p = 0.0047), myocardial carbon dioxide production (p = 0.0022), and myocardial energy expenditure (p = 0.0029). Simultaneously, coronary sinus cTn-I levels increased from a mean of 0.76 to 2.43 ng/mL after removal of the aortic cross-clamp, and 2.51 ng/mL after cardiopulmonary bypass (p = 0.014), leading to an increase in arterial cTn-I concentration from 0.18 to 0.98 and 3.01 ng/mL (p = 0.0002). Thus, cTn-I release across the myocardium was absent at baseline, became detectable (p = 0.012) after removal of the aortic cross-clamp, and correlated with cross-clamp and pump times. Similar changes occurred with creatine kinase-MB. CONCLUSIONS: Metabolic myocardial stress occurs during ischemic arrest with cardioplegia and is associated with inadequate suppression of metabolism and with a surge in cTn-I and creatine kinase-MB release, which is maximal after removal of the aortic cross-clamp. These changes are likely to represent structural myocardial cell injury.

Aged↗

The radial artery in coronary re-operations.

OBJECTIVES: Vein graft (VG) failure often leads to coronary re-operation (re-do coronary artery bypass grafting (CABG)). As the internal thoracic artery (ITA(s)) and VG have often already been used and as the VG has usually failed, the radial artery (RA) is ideally suited for use in re-do CABG. We evaluated our experience where the RA(s) was a key conduit in re-do CABG to determine the safety and efficacy and compared this to re-operations where the RA was not used. METHODS: Three hundred and fifty-two consecutive patients who had re-do CABG using the RA(s) from July 1995 to March 1999 were studied: mean age 67.3 years, 209 (60%) angina Class III or IV, past acute myocardial infarction (AMI) in 201 (57%), left ventricular ejection fraction <50% in 109 (31%). Five hundred and thirty-two RAs were used (bilateral in 180 (51%) patients). Additionally, 232 new left ITAs (66% of patients) and 71 new right ITAs (20% of patients) were placed. A total of 1022 distal anastomoses were performed (mean of 2.9 per patient). Follow-up was at 1 month, 3 months, and yearly. The results were also compared to 730 patients having re-do CABG without an RA (January 1990 to June 1995) using identical operative and myocardial protection techniques. RESULTS: RA spasm was noted intra-operatively in four (1.1%) patients, operative mortality was noted in 14 (3.9%) patients, peri-operative myocardial infarction was noted in ten (2.8%) patients, intra-aortic balloon pump was used in nine (2.6%) patients, stroke was noted in six (1.7%) patients, deep sternal infection was noted in two (0.6%) patients, and re-operation for haemorrhage was performed in seven (2.0%) patients. There was only one (0.3%) forearm infection, and two (0.6%) forearm haematomas required drainage. There was no hand ischaemia. When compared to 730 re-do CABG patients without RA, there were significant differences in arterial grafts used (2.6 vs. 1.2, P=0.01), in deep sternal infection (0.6% vs. 2.6%, P=0.01) and donor site infection (0.3% vs. 2.7%, P=0.005) favouring the RA group. Three-year actuarial survival was 89.2% in the RA group and 88.5% in the non-RA group (P=1.0). CONCLUSIONS: Use of the RA in re-do CABG is safe, effective, allows additional conduit choice, reduces donor site and sternal infections, and may avoid further late VG failure.

Aged↗

Developing performance indicators for cardiac surgery: a demonstration project in Victoria.

Six Victorian cardiac surgical units pooled data in order to undertake a demonstration project aimed at developing performance indicators to assess outcomes following cardiac surgery. The outcome of the project was an indicative report for the purpose of monitoring surgical performance indicators in a format suitable for: (i) the general public; (ii) the Victorian State Government; and (iii) the participating units and surgeons. Each participating cardiac surgical unit had an existing database used for recording information from each procedure. A request was made to each unit to extract a subset of data from all cases entered over the past 5 years. The proposed list of performance indicators included surgical mortality (within the period of admission for surgery), complication rates (including sternal infection, postoperative myocardial infarction, postoperative stroke, haemorrhage requiring return to theatre), and length of hospital stay. A model was developed from the data and used to provide risk-adjusted measures of hospital performance. Cases from five cardiac surgical units (n = 10 715) were included in the final analysis. A risk-adjusted model (including age, sex, diabetes, hypertension, smoking, procedure type, urgency of procedure) was developed for surgical mortality. Performance indicators for coronary artery bypass graft surgery, including mortality, sternal infection rate and length of hospital stay are presented. From the available data, performance indicators for cardiac surgery in Victorian hospitals compared favourably with international benchmarks. This project has demonstrated that prospective data collection using a standardised system could readily produce local risk-adjustment models for cardiac surgery to aid in developing appropriate performance indicators.

Journal Article↗

Left ventricular aneurysm repair in rats: structural, functional, and molecular consequences.

OBJECTIVES: This study examined the effects of aneurysm repair in a rat model of myocardial infarction on functional indices and on the spatiotemporal distribution of cardiac contractile protein and natriuretic peptide messenger RNA. METHODS: In a rat infarct model, expanded left ventricular aneurysms were plicated 4 weeks after infarction. At 30 weeks, transverse heart sections were taken at 4 levels (apex [level 1] through base [level 4]) and assessed by in situ hybridization histochemistry to determine regional messenger RNA levels of pre-pro-atrial natriuretic peptide, cardiac alpha-actin, skeletal alpha-actin, myosin light chain-2v, and beta-myosin heavy chain. RESULTS: Rats with plicated left ventricular aneurysms had reduced left ventricular endocardial circumference (19%, P <.005), lower heart weight ratio (31%, P <.05), left ventricular end-diastolic pressures (51%, P <.05), and increased +/-dP/dt (34%-38%, P <.05). Cardiac messenger RNA levels of pre-pro-atrial natriuretic peptide were reduced in the septum (levels 2 and 3), and skeletal alpha-actin levels were reduced in the septum and left ventricular free wall of plicated rats (level 3). beta-Myosin heavy chain levels were markedly reduced in peri-infarct regions of the left ventricular free wall, septum, and right ventricle in plicated rats at level 4, whereas myosin light chain-2v levels were reduced at levels 2 and 4 in the left ventricular free wall and at level 4 in the right ventricle. CONCLUSIONS: Plication of left ventricular aneurysm after infarction in the rat significantly reduced cardiac hypertrophy, improved cardiac function, and reduced the upregulation of pre-pro-atrial natriuretic peptide and both fetal and adult contractile protein isoforms associated with cardiac hypertrophy.

Actins↗

Preoperative assessment of hand circulation by means of Doppler ultrasonography and the modified Allen test.

OBJECTIVE: The aims of this study were as follows: (1) to evaluate Doppler ultrasonography in assessing hand collateral circulation; (2) to define the criteria for an abnormal Doppler ultrasonography dynamic test result; and (3) to validate the modified Allen test. METHODS: The hand circulation of 71 patients scheduled for coronary artery bypass grafting was assessed by means of the Allen test and Doppler ultrasonography. The flow in the superficial palmar branch of the radial artery, the ulnar artery, and the dorsal digital thumb artery with and without radial artery compression were recorded. Flow patterns in the superficial palmar branch of the radial artery, the ulnar artery, and the dorsal digital thumb artery with radial artery compression were categorized into 4 groups: (1) no flow; (2) decreased flow; (3) reversed flow; and (4) increased flow. RESULTS: Among the 71 hands, 4 (5.6%) had an abnormal Allen test result (>10 seconds). Seven (10.6%) of 66 superficial palmar branches of the radial artery, 3 (4.2%) of 71 ulnar arteries, and 2 (2.8%) of 71 dorsal digital thumb arteries showed no flow with radial artery compression, as measured by Doppler ultrasonography. There were significant differences among the 4 groups (superficial palmar branch of the radial artery: F = 7.0, P <.001; ulnar artery: F = 13.1, P <.001; and dorsal digital thumb artery: F = 8.4, P <.001) for the Allen test. Pairwise comparisons showed that when subjected to an Allen test, category 1 patients (no flow) had significantly longer recovery times compared with the other groups (P <.02 in all cases) for the superficial palmar branch of the radial artery, the ulnar artery, and the dorsal digital thumb artery. CONCLUSION: Absence of flow in the dorsal digital thumb artery with radial artery compression is considered an absolute contraindication to radial artery harvesting. An increased recovery time with the modified Allen test predicts absence of flow in the dorsal digital thumb artery in Doppler ultrasonographic flow patterns. This demonstrates the validity of the modified Allen test for primary screening.

Aged↗

Surgical implications of variations in hand collateral circulation: anatomy revisited.

OBJECTIVES: One of the risks associated with harvesting the radial artery is hand ischemia. Accordingly, this study investigated the variations of the hand collateral circulation. METHODS: Fifty hands of cadavers were examined. Variations of the palmar arches were recorded. A classic superficial palmar arch was defined as direct continuity between the ulnar artery and the superficial palmar branch of the radial artery. A classic complete deep palmar arch was defined as direct continuity between the radial artery and the deep branch of the ulnar artery. RESULTS: A classic superficial palmar arch was found in 10% (5/50) of hands, and a classic complete deep palmar arch was found in 90% (45/50) of hands. The superficial palmar branch of the ulnar artery supplied blood to all fingers in 66% (33/50) of hands. Although the superficial palmar branch of the ulnar artery was continuous with the radial artery in only 34% (17/50) of hands (including the classic type of superficial palmar arch), every hand had at least one major branch connecting the radial and ulnar arteries. CONCLUSIONS: Variations in the terminations of the radial and ulnar arteries are common. Although the classic type of superficial palmar arch occurs relatively infrequently, there is always a significant anastomosis between the radial and the ulnar artery in the hand. This anatomic study confirms the presence of a collateral supply in the hand. In the absence of vascular disease, harvesting the radial artery should be regarded as a safe procedure.

Arteries↗

The mid-term results of ventricular containment (ACORN WRAP) for end-stage ischemic cardiomyopathy.

The acorn cardiac support device (ACSD) is a device designed to treat heart failure by containing the heart to prevent further dilation. Six patients with symptomatic heart failure due to ischemic cardiomyopathy were treated surgically with ACSD. All patients simultaneously underwent coronary artery bypass grafting. Ventricular reconstruction was also performed in 5 of the 6 patients. We followed up the patients for 12 months postoperatively, monitoring the left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), mitral regurgitation, and NYHA classification. Both the LVEDD and LVESD were significantly improved one month postoperatively (from 63.2 to 50.6 mm, p=0.004, and from 51.6 to 39.5 mm, p=0.025, respectively). These dimensions did not change significantly over the next 11 months. NYHA functional class improved significantly from a mean of 3 to 1.4 at 12 months (p=0.012). Mitral regurgitation improved from a mean of 2.7 preoperatively to 1.4 at 12 months and the average LVEF also improved from 27% preoperatively to 35.9% at 12 months after surgery. However these latter two results were not statistically significant. There were no late deaths and no readmissions for heart failure. Repeat coronary angiography at 6 months revealed patent grafts in all patients. The mid-term results of ACSD for patients with symptomatic heart failure suggest that ventricular containment may be useful for preventing further cardiac dilation in patients with ischemic cardiomyopathy. Randomized, long-term studies are needed to assess the efficacy and possible role of ASCD in the future management of heart failure.

Aged↗

Outcome of geometric endoventricular repair in impaired left ventricular function.

BACKGROUND: Traditionally, repair of left ventricular aneurysms has been limited to patients with large localized ventricular aneurysms. Repair of dyskinetic segments in the setting of poor left ventricular function is still contentious. METHODS: Forty patients underwent geometric endoventricular repair, a new technique of ventricular aneurysm repair, over a 2-year period. Two groups of patients undergoing coronary artery bypass grafting (CABG) for left ventricular dysfunction in the same time period were reviewed. Group 1 comprised 23 consecutive patients who underwent geometric endo-ventricular repair along with CABGs, whereas group II consisted of 22 patients who underwent CABG alone. RESULTS: The early mortality was 9.1% in group I (1 cardiac, 1 noncardiac) and 0 in group II (NS). New York Heart Association class was remarkably improved from 3.4 to 1.4 (p < 0.05) in group I and to a lesser extent in group II (3.7+/-0.5 versus 2.3+/-0.5). Diastolic dimension of left ventricle was significantly reduced from 5.6 cm to 4.4 cm (p < 0.05) in group I and virtually unchanged in group II. There was one late death in each of the groups. CONCLUSIONS: This technique of geometric left ventricular aneurysm repair is useful in patients with dyskinetic segments and may help in reducing cardiac size.

Aged↗