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Biomedical subjects

A Couturier

Publications and source records attributed to A Couturier.

At least 19 recordsLinked to original sources

Amiodarone reduces procedures and costs related to atrial fibrillation in a controlled clinical trial.

BACKGROUND: Atrial fibrillation is the most common sustained cardiac arrhythmia, and engenders significant health care costs. The impact of various treatment options for atrial fibrillation on hospital costs has not been evaluated in a randomized trial. METHODS: We analysed 1-year follow-up data on 392 patients randomized to low dose amiodarone (200 mg. day(-1)) or alternative first-line therapy (sotalol or propafenone) in a multicentre trial (Canadian Trial of Atrial Fibrillation, CTAF). RESULTS: Patients in the amiodarone group had fewer electrical cardioversions (65 vs 109 for patients in the sotalol/propafenone group, P<0.0001), and pacemaker insertions (4 vs 11, P=0.07). The average amiodarone patient spent fewer days in hospital (0.47 vs 0.97, P=0.01), and incurred lower costs ($532 vs $898, P=0.03), for admissions where atrial fibrillation was the admitting diagnosis. Average total hospital costs per patient for all admissions, as well as average combined hospital and physician costs per patient, showed wide variations within the treatment arms and were not significantly different between groups. CONCLUSION: For patients in whom antiarrhythmic drug therapy is indicated, low dose amiodarone significantly reduces atrial fibrillation-related costs by reducing the number of atrial fibrillation-related procedures.

Aged↗

Molecular and clinical characteristics in 32 families affected with familial adenomatous polyposis.

Germ-line mutations in the 5' half of the Adenomatous Polyposis Coli (APC) gene are found in about 80% of the patients affected with familial adenomatous polyposis (FAP). The vast majority of these are nonsense or frameshift mutations which result in the loss of the carboxyl terminus of the APC protein. Using an in vivo assay in yeast, we have identified pathogenic germ-line mutations in 26 of 32 (81%) unrelated Swiss families affected with FAP. Nine mutations were novel and eight families were shown to harbor two recurrent mutations. Correlations were attempted between the location of APC germ-line mutations and clinical manifestations of the disease.

Adenomatous Polyposis Coli↗

[Beating heart surgery and left ventricular dysfunction].

We report our experience with systematic coronary revascularization on the beating heart among patients with left ventricular dysfunction as defined by a left ventricular ejection fraction < or = 40%. Between September 1996 and April 2000, 500 off-pump (OPCAB) revascularizations were performed (95% of all revascularizations for the same time frame, single surgeon). Among them, 76 patients qualified as left ventricular dysfunction and were compared to a similar cohort of 237 patients operated on with cardiopulmonary bypass (CPB) during the same time frame. Age and sex distribution, average preoperative left ventricular ejection fraction and incidence of preoperative unstable angina were the same for both groups. On average, 3.04 +/- 0.89 and 2.97 +/- 0.69 grafts/patient were made in the OPCAB and CPB groups respectively (p = NS). Complete revascularization was achieved in 95% of the OPCAB group. Incidence of preoperative intra-aortic balloon assistance were higher in OPCAB (22% versus 9%, p = 0.005) whereas postoperative need for new intra-aortic balloon assistance was higher in CPB (8% versus 0%, p = 0.02). Incidence of postoperative myocardial infarction was comparable in both groups (6.5% versus 5.5%). Maximal creatinine phosphate of myocardial origin were lower in OPCAB group (beating heart: 32 +/- 52%, cardiopulmonary bypass: 45 +/- 51%, p = 0.055). Operative mortality was lower in OPCAB group although it did not reach statistical significance (beating heart: 2.6% versus cardiopulmonary bypass: 4.6%, p = 0.3). Complete coronary revascularization on the beating heart can be achieved in patients with left ventricular dysfunction with excellent outcome and low operative mortality.

Cardiac Surgical Procedures↗

Diastolic dysfunction is predictive of difficult weaning from cardiopulmonary bypass.

Diastolic function is receiving more attention since echocardiographic measurements were developed and have become widely available. The importance and significance of diastolic dysfunction (DD) observed before cardiac surgery and its relationship with adverse outcomes, such as difficult separation from cardiopulmonary bypass (CPB), have not been fully explored. In this study, we hypothesize that DD can be a predictor for the need of inotropic support to successfully separate from CPB. Ninety-two consecutive patients underwent surgery during the study period. Twenty-six patients were excluded. From the remaining 66 patients, 52 had coronary artery bypass grafting alone and 14 combined procedures, valvular surgery, and reoperations (redo). Systolic and diastolic function was evaluated by two experts blinded as to the clinical data except for the age. The evaluation of diastolic function was done according to published guidelines. The demographic, echocardiographic, and hemodynamic variables were entered in a logistic regression analysis to determine which variables were independent predictors of difficult separation from CPB and the need for postoperative vasoactive support. DD was present in 20 patients (30%). Patients with DD had lower weight (P = 0.046), less frequent coronary artery bypass grafting alone (P = 0.0004), more myocardial infarction before surgery (P = 0.02), higher regional wall motion score index (P = 0.0002), and larger left ventricle (P = 0.03). Total CPB time (P = 0.004) and ischemic time (P = 0.007) were longer in the DD group. Patients with DD required more frequent inotropic support at the end of surgery (P = 0.006) and up to 12 h after surgery (P = 0.003). Multivariate logistic regression identified female sex, DD, and total CPB time as predictive of difficult weaning and inotropic requirements up to 12 h after surgery.

Aged↗

Impact of residual plaque burden after balloon angioplasty in the MultiVitamins and Probucol (MVP) trial.

BACKGROUND: It has been shown in the MultiVitamins and Probucol (MVP) trial that probucol reduces angiographic lumen loss by 68% after percutaneous transluminal coronary angioplasty (PTCA). Restenosis occurred in 40% of patients not treated with probucol and in 20% of those in the probucol alone group. OBJECTIVE: To determine the morphological predictors of restenosis in patients treated with probucol. PATIENTS AND METHODS: Beginning 30 days before angioplasty, 317 patients were randomly assigned to receive probucol, multivitamins, the combined treatment or placebo. Patients were then treated for six months after angioplasty. Intravascular ultrasound (IVUS) examination was performed immediately after angioplasty and at follow-up in 94 patients (108 segments). The angioplasty operator was blinded to the IVUS results. The cross-section selected for serial analysis was the one at the angioplasty site with the smallest lumen area at follow-up. Receiver operating characteristic curves were used to determine the performance of criteria to predict angiographic restenosis at follow-up. RESULTS: In probucol-treated patients, the cross-sectional area (CSA) narrowing of 67.6% or less was the best IVUS predictor for the absence of restenosis (P=0.03). Diameter stenosis of 35% or less almost reached significance as a predictor in these patients (P=0.056). The restenosis rate when either of these predictors was met was less than 13%. Rates of repeat PTCA in patients treated with probucol were 9.7% when CSA narrowing was 67.6% or less on IVUS and 3.1% with a post-PTCA stenosis of 35% or less on quantitative coronary angiography (QCA). No predictor of the absence of restenosis in patients not treated with probucol was identified. CONCLUSIONS: The presence after balloon angioplasty of a CSA narrowing of 67.6% or less on IVUS or a diameter stenosis of 35% or less on QCA is associated, in patients treated with probucol, with extremely low rates of coronary restenosis and repeat angioplasty.

Angioplasty, Balloon, Coronary↗

Role of gender and personality on quality-of-life impairment in intermittent atrial fibrillation.

Patients with atrial fibrillation (AF) report impaired health-related quality of life (QOL). Differences between men and women with AF have not been described and personality attributes such as somatization (tendency to amplify benign bodily sensations) may mediate potential gender differences in QOL. Patients with AF (n = 264, 59% men) who participated in the Canadian Trial of Atrial Fibrillation (n = 403) completed validated QOL questionnaires at baseline, 3 months, and 12 months after antiarrhythmic drug treatment. Women were significantly older than men and a greater proportion had hypertension, but other cardiac variables did not differ between women and men. At baseline, after controlling for significant clinical and demographic factors, women reported worse physical health (p = 0.002) and functional capacity (p < 0.001), but not mental health or general well-being. Women also had more frequent and severe cardiac symptoms than men (both p < 0.001). Physical health improved significantly from baseline to 3 months for women (p = 0.002), but not for men (p = 0.066). Conversely, mental health improved for men (p = 0.007), but not for women. Cardiac symptom frequency and severity improved over time for women and men (all p < 0.001). Tendency to somatize predicted poor QOL, and women had higher scores than men (p = 0.023). However, after controlling for somatization, women still had worse physical function, functional capacity, and symptom burden than men. Independent of cardiac disease severity and age, women with AF had significantly more impaired QOL than men, specifically on domains related to physical rather than emotional functioning. Personality attributes may have a role in influencing QOL outcomes.

Age Factors↗

Outcome with high blood lactate levels during cardiopulmonary bypass in adult cardiac operation.

BACKGROUND: High blood lactate levels during cardiopulmonary bypass (CPB) are associated with tissue hypoperfusion and may contribute to postoperative complications or death. The objective of this study was to determine an association between blood lactate levels during CPB and perioperative morbidity and mortality. METHODS: We reviewed 1,376 patients who underwent cardiac operation with CPB. Patients with abnormal preoperative blood lactate levels were excluded (n = 101). Blood lactate concentration during CPB, clinical data, and perioperative events were recorded. RESULTS: Peak blood lactate levels of 4.0 mmol/L or higher during CPB were present in 227 patients (18.0%). Postoperative mortality was higher in this group than in the patients who had peak blood lactate levels of less than 4.0 mmol/L during CPB (11.0% versus 1.4%; p < 0.001, relative risk [RR] = 9.0). Postoperative hemodynamic instability occurred in 29.5% of patients with elevated levels of lactate during CPB compared with 10.9% of patients with lower lactate levels (p < 0.001, RR = 3.4). Overall, major postoperative complications occurred in 43.2% and 21.8% of patients in each group, respectively (p < 0.001, RR = 2.7). Logistic regression analysis revealed that peak blood lactate levels of 4.0 mmol/L or higher during CPB were strongly associated with postoperative mortality (p = 0.0001) and morbidity (p = 0.013). CONCLUSIONS: Blood lactate concentration of 4.0 mmol/L or higher during CPB identifies a subgroup of patients with increased risk of postoperative morbidity and mortality.

Adult↗

Systematic off-pump coronary artery revascularization in multivessel disease: experience of three hundred cases.

OBJECTIVE: We sought to report our recent experience with off-pump coronary artery revascularization in multivessel disease. METHODS: Between October 1996 and December 1998, 300 off-pump beating heart operations were performed at the Montreal Heart Institute by a single surgeon, representing 94% of all procedures undertaken during this same time frame (97% for 1998). This cohort of patients was compared with 1870 patients operated on with cardiopulmonary bypass from 1995 to 1996. RESULTS: Mean age, sex distribution, and preoperative risk factors were comparable for the two groups. On average, 2.92 +/- 0.8 and 2.84 +/- 0.6 grafts per patient were completed in the beating heart and cardiopulmonary bypass groups, respectively. A majority of patients (70%) had either a triple or quadruple bypass. Coronary anastomoses were achieved with myocardial mechanical stabilization and heart "verticalization." Ischemic time was shorter in the beating heart group (29.8 +/- 0.9 vs 45 +/- 0.4 minutes, P <.05). Similarly, the need for transfusion was significantly less in the beating heart group (beating heart operations, 34%; cardiopulmonary bypass, 66%; P <.005). Reduced use of postoperative intra-aortic counterpulsation, as well as a lower rise in creatine kinase MB isoenzyme, was observed in the beating heart group. Operative mortality rates (beating heart operations, 1. 3%; cardiopulmonary bypass, 2%) and perioperative myocardial infarction (beating heart operations, 3.6%; cardiopulmonary bypass, 4.2%) were comparable for the two groups. CONCLUSION: In a majority of patients, off-pump complete coronary artery revascularization is an acceptable alternative to conventional operations, yielding good results given progressive experience, rigorous technique, and adequate coronary artery stabilization.

Cardiopulmonary Bypass↗

Value of exercise electrocardiography in the detection of restenosis after coronary angioplasty in patients with one-vessel disease.

Exercise treadmill testing (ETT) is considered an unreliable method for detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA). The studies on which this belief is based have used quantitative coronary angiography (QCA) as a reference. The inherent limitations of angiography have been demonstrated by intravascular ultrasound (IVUS). To determine the value of ETT for detecting restenosis when IVUS criteria are used to define restenosis, we studied 29 patients with angiographically documented 1-vessel coronary disease (<35% stenosis in all nondilated segments) who underwent angioplasty. ETT was performed < or =2 weeks before follow-up angiography and IVUS imaging. Only patients without any abnormalities precluding an accurate reading of the ST segment during ETT were included. Restenosis was defined as a > or =50% diameter stenosis by QCA criteria and as a cross-sectional area narrowing of > or =75% by IVUS. The ETT was positive in 12 patients and restenosis was documented by QCA and IVUS in 38% and 48% of cases, respectively. Sensitivity, specificity, and positive and negative predictive values of ETT when QCA was used as a reference were 55%, 67%, 50%, and 71%, respectively. This corresponded to an accuracy of 62% when compared with QCA. Sensitivity, specificity, and positive and negative predictive values were 79%, 93%, 92%, and 82% when ETT was compared with IVUS, with an accuracy of 86% (p = 0.002). Thus, ETT is a reliable noninvasive method for detecting the presence of restenosis after PTCA in patients with 1-vessel coronary artery disease. The presence of > or =75% cross-sectional narrowing shown by IVUS is well correlated with > or =1-mm ST-segment depression at follow-up ETT after PTCA.

Aged↗

A new three allele polymorphism at distal 21q22.3, a region relatively devoid of polymorphic markers. Mutations in brief no. 212. Online.

We amplified 305bp of the 3'UT region of COL18A1 from 62 healthy chromosomes from Caucasian individuals. SSCP analysis of these PCR products allowed us to identify 3 alleles which were confirmed through sequencing analysis and ASO. The heterozigosity found for this polymorphic region is 74.2%, and mendelian inheritance was demonstrated in 5 two/three generation families. This polymorphism, located in a region relatively devoid of microsatellites, will be very useful for linkage analysis, particularly for narrowing down candidate regions for genes mapped in this area.

3' Untranslated Regions↗

Cell surface expression of HLA-E: interaction with human beta2-microglobulin and allelic differences.

The formation of a trimeric complex composed of MHC class I heavy chain, beta2-microglobulin (beta2m) and peptide ligand is a prerequisite for its efficient transport to the cell surface. We have previously demonstrated impaired intracellular transport of the human class Ib molecule HLA-E in mouse myeloma X63 cells cotransfected with the genes for HLA-E and human beta2m (hbeta2m), which is most likely attributable to inefficient intracellular peptide loading of the HLA-E molecule. Here we demonstrate that cell surface expression of HLA-E in mouse cells strictly depends on the coexpression of hbeta2m and that soluble empty complexes of HLA-E and hbeta2m display a low degree of thermostability. Both observations imply that low affinity interaction of HLA-E with beta2m accounts to a considerable extent for the observed low degree of peptide uptake in the endoplasmic reticulum. Moreover, we show that the only allelic variation present in the caucasoid population located at amino acid position 107 (Gly or Arg) greatly affects intracellular transport and cell surface expression upon transfection of the respective alleles into mouse cells. No obvious difference was found with regard to the sequence of the peptide ligand.

Alleles↗

[Systemic coronary surgery in the beating heart. Experience in 250 cases].

OBJECT: To report our recent experience with off-pump coronary artery revascularization in multi-vessel disease. METHODS: Between October 1996 and August 1998, 250 off-pump (OP) procedures were completed at the Montreal Heart Institute, representing more than 90% of all procedures done during the same time frame (97% for 1998). These patients have been compared to 1870 patients operated upon under cardiopulmonary bypass during the years 1995-1996 (CPB). RESULTS: Mean age, sexe distribution, and preoperative risk factors were comparable for both groups. On average 2.89 +/- 0.8 and 2.84 +/- 0.6 grafts/patient were completed in OP and CPB groups respectively. A majority (70%) of patients had either a triple or quadruple bypass. Coronary anastomoses were achieved with myocardial mechanical stabilization and heart "verticalization". Ischemic time was shorter in the OP group (29.8 +/- 0.9 vs 45 +/- 0.4 min, p < 0.05). Similarly, need for transfusion was significantly less (OP: 34 vs CPB: 66%, p < 0.005). Use of postoperative intra-aortic counterpulsation as well as the raise of CK-MB were lesser in the OP group. Operative mortality (OP: 1.6%, vs CPB: 2%, p = ns) and perioperative myocardial infarction rate (OP: 3.6% vs CPB: 4.2) were comparable for both groups. CONCLUSION: Off-pump complete coronary artery revascularization is an acceptable alternative to conventional surgery in a majority of patients with good results given progressive experience, rigorous technique, and adequate coronary artery stabilization.

Aged↗

[Left main coronary artery stenosis and revascularization in the beating heart. Short- and long-term experience].

OBJECT: To determine the safety of surgical revascularization without cardiopulmonary bypass in left main coronary artery stenosis. METHODS: Between October 1996 and October 1998, 67 patients with a left main stem stenosis (LMS) (> 50%) underwent revascularization on beating heart surgery (BHS) and were compared to a cohort of 192 patients with LMS disease that were operated on under cardiopulmonary bypass (CPB) during 1996. RESULTS: Mean age and sex distribution and prevalence of preoperative risk factors were the same in both groups as well as the average number of grafts per patient was 3.1 +/- 0.7 and 2.9 +/- 0.7 in BHS and CPB groups respectively. Perioperative infarction rate (defined arbitrarily as a CK-MB > 100 IUL) was 2.9% in BHS group and 3.1% in CPB group. Postoperative blood transfusion requirements were less in BHS group (38%) compared to CPB group (64%), p < 0.05. Inotropic requirements postoperatively were similar in both groups. Hospital stay was shorter in BHS group (6.8 days) compared to CPB group (7.6 days) although not significant. There was no operative mortality in BHS group whereas 4.7% died postoperatively in CPB group. CONCLUSION: Our experience suggests that non-bypass surgical revascularization is a feasible and safe alternative to conventional cardiopulmonary bypass.

Aged↗

Excess of hMLH1 germline mutations in Swiss families with hereditary non-polyposis colorectal cancer.

Lynch syndrome, or hereditary non-polyposis colorectal cancer (HNPCC), is a consequence of a dominantly inherited susceptibility to accumulate somatic mutations. The disorder is manifested as a familial aggregation of colorectal cancers diagnosed at an early age and, to a lesser degree, of cancers of the endometrium, ovary, urinary tract, and organs of the gastrointestinal tract other than the colon. In more than half of the HNPCC families investigated, the cancer predisposition has been linked to germline mutations in one of the 2 genes hMLHI or hMSH2, involved in post-replicative DNA-mismatch repair. Twenty-four Swiss families affected with colorectal cancer were screened for germline mutations in these 2 genes, and pathogenic mutations were identified in over 70% of the families fulfilling the Amsterdam criteria (AC), but in only 10% of the families not completely fulfilling these criteria. One of the reported mutations, discovered in an extended HNPCC kindred from the Swiss Alps, is shown to be a founding mutation. Unexpectedly, all the mutations identified are in the hMLHI gene, where all but one are novel sequence alterations. Our data suggest that an unusually high proportion of Swiss HNPCC patients may harbour a germline mutation in the hMLHI gene.

Adaptor Proteins, Signal Transducing↗

Cloning of STK13, a third human protein kinase related to Drosophila aurora and budding yeast Ipl1 that maps on chromosome 19q13.3-ter.

This report describes the identification of a cDNA encoding STK13, a third human protein kinase related to the Drosophila Aurora and the budding yeast Ipl1 kinases. After screening of a human placental cDNA library with a Xenopus laevis cDNA encoding the pEg2 protein kinase and 5' RACE on testis mRNA, a full-length cDNA was isolated. The chromosomal localization of STK13 on 19q13.3-ter between the markers D19S210 and D19S218 was established by a combination of somatic cell and radiation hybrid panel PCR screening. The localization of STK13 on human chromosome 19 was confirmed by fluorescence in situ hybridization (FISH) using a genomic clone containing STK13 as a probe.

Amino Acid Sequence↗

Physiological role of human placental growth hormone.

Placental growth hormone (PGH) is the product of the GH-V gene specifically expressed in the syncytiotrophoblast layer of the human placenta. PGH differs from pituitary growth hormone by 13 amino acids. It has high somatogenic and low lactogenic activities. Assays of PGH by specific monoclonal antibodies reveal that in the maternal circulation from 15-20 weeks up to term, PGH gradually replaces pituitary growth hormone which becomes undetectable. It is secreted by the placenta in a non-pulsatile manner. This continuous secretion appears to have important implications for physiological adjustment to gestation and especially in the control of maternal IGF1 levels. PGH secretion is inhibited by glucose in vitro and in vivo, and is significantly decreased in the maternal circulation in cases of pregnancies with intrauterine growth retardation. PGH does not appear to have a direct effect on fetal growth, as this hormone is not detectable in the fetal circulation. However the physiological role of PGH might also include a direct influence on placental development via an autocrine or paracrine mechanism as suggested by the presence of specific GH receptors in this tissue.

Cell Differentiation↗

The Xenopus protein kinase pEg2 associates with the centrosome in a cell cycle-dependent manner, binds to the spindle microtubules and is involved in bipolar mitotic spindle assembly.

By differential screening of a Xenopus laevis egg cDNA library, we have isolated a 2,111 bp cDNA which corresponds to a maternal mRNA specifically deadenylated after fertilisation. This cDNA, called Eg2, encodes a 407 amino acid protein kinase. The pEg2 sequence shows significant identity with members of a new protein kinase sub-family which includes Aurora from Drosophila and Ipl1 (increase in ploidy-1) from budding yeast, enzymes involved in centrosome migration and chromosome segregation, respectively. A single 46 kDa polypeptide, which corresponds to the deduced molecular mass of pEg2, is immunodetected in Xenopus oocyte and egg extracts, as well as in lysates of Xenopus XL2 cultured cells. In XL2 cells, pEg2 is immunodetected only in S, G2 and M phases of the cell cycle, where it always localises to the centrosomal region of the cell. In addition, pEg2 'invades' the microtubules at the poles of the mitotic spindle in metaphase and anaphase. Immunoelectron microscopy experiments show that pEg2 is located precisely around the pericentriolar material in prophase and on the spindle microtubules in anaphase. We also demonstrate that pEg2 binds directly to taxol stabilised microtubules in vitro. In addition, we show that the presence of microtubules during mitosis is not necessary for an association between pEg2 and the centrosome. Finally we show that a catalytically inactive pEg2 kinase stops the assembly of bipolar mitotic spindles in Xenopus egg extracts.

Amino Acid Sequence↗