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Biomedical subjects

M Bertrand

Publications and source records attributed to M Bertrand.

At least 19 recordsLinked to original sources

Detection of autoantibodies against oxidized low-density lipoproteins and of IgG-bound low density lipoproteins in patients with coronary artery disease.

The role of oxidized low-density lipoprotein (ox-LDL) in the pathogenesis of atherosclerosis has been the object of intense investigation. It has been proposed that, due to the antigenic properties of ox-LDL, the anti-ox-LDL antibody titre could represent a useful index of in vivo LDL oxidation. On the other hand, LDL immune complexes (LDL-IC) have been demonstrated in patients with coronary disease and could play an atherogenic role. The goal of our study was to investigate anti-malondialdehyde (MDA)-LDL autoantibodies and LDL-IC in a cohort of patients with coronary artery disease. Seventy control subjects and 70 coronary angiographically documented patients were compared; in addition 32 healthy male non-smokers were compared with 32 healthy male smokers (> 10 cigarettes/day). All patients were matched for age and cholesterolemia. Enzyme-linked immunosorbent assay was used to measure anti-MDA-LDL autoantibodies and LDL-IC. Titres of anti-MDA-LDL autoantibodies were not larger in patients with documented coronary artery stenosis and in smokers than they were in controls and non-smokers. The titre of LDL-IC was not higher in patients with coronary artery stenosis than in controls. The results thus indicate that in populations matched for age and cholesterolemia the titres of anti-MDA-LDL autoantibodies and the titre of LDL-IC are not increased in patients suffering from coronary artery stenosis. Furthermore, cigarette smoking does not induce higher titres of anti-MDA-LDL autoantibodies in healthy patients.

Aged

Recombinant protein expression in a Drosophila cell line: comparison with the baculovirus system.

In this report, we compare two different expression systems: baculovirus/Sf9 and stable recombinant Drosophila Schneider 2 (S2) cell lines. The construction of a recombinant S2 cell line is simple and quick, and in batch fermentations the cells have a doubling time of 20 hours until reaching a plateau density of 20 million cells/ml. Protein expression is driven by the Drosophila Metallothionein promoter which is tightly regulated. When expressed in S2 cells, the extracellular domain of human VCAM, an adhesion molecule, is indistinguishable from the same protein produced by baculovirus-infected Sf9 cells. Additionally, we present data on the expression of a seven trans-membrane protein, the dopamine D4 receptor, which has been successfully expressed in both systems. The receptor integrates correctly in the S2 membrane, binds [3H]spiperone with high affinity and exhibits pharmacological characteristics identical to that of the receptor expressed in Sf9 and mammalian cells. The general implications for large scale production of recombinant proteins are discussed.

Animals

Aprotinin to decrease bleeding and intraoperative blood transfusion requirements during descending thoracic and thoracoabdominal aortic aneurysmectomy using cardiopulmonary bypass.

The purpose of this retrospective study was to assess the efficacy of aprotinin, an antifibrinolytic agent, in reducing bleeding and blood transfusion requirements in patients undergoing descending thoracic or thoracoabdominal aortic aneurysmectomy using cardiopulmonary bypass (CPB). Sixty-nine consecutive patients underwent thoracic or thoracoabdominal aneurysmectomy using CPB in a 2-year period. None of the 29 patients operated on in 1990 (group 1) received aprotinin, whereas all 40 patients operated on in 1991 (group 2) were placed on a high-dose regimen of aprotinin. There were no significant differences between the two groups. Administration of aprotinin was associated with a decrease in CPB time (p = 0.02), surgical duration (p = 0.05) and intraoperative blood loss (p = 0.008) as well as a reduction in intraoperative packed red cells (p = 0.01), Cell-Saver units (p = 0.05), fresh-frozen plasma units (p = 0.002), and platelet concentrate (p = 0.01) requirements. These data suggest that aprotinin is effective in reducing bleeding and blood transfusion requirements during descending thoracic or thoracoabdominal aortic aneurysmectomy using CPB.

Adult

Autologous blood donation before myocardial revascularization: a Holter-electrocardiographic analysis.

The influence of preoperative autologous blood donation on myocardial ischemia and arrhythmias was evaluated in 24 patients scheduled for coronary artery bypass grafting (CABG). All had a Holter recorder placed 24 hours before predonation (day 1), the cassette was changed prior to donation, and the recording continued for 24 hours thereafter (day 2). Each patient served as his or her own control, and observations made on day 2 were compared with those of day 1. Ischemia was quantitated by calculating the duration (C.Dur.) and the area (C. Area) of ischemic ST segment depressions, and ventricular premature beats (VPB) were classified according to the Lown grading system. Twenty-one men and 3 women were monitored. On day 1, 9 patients had 20 ischemic events, 3 being symptomatic. Nine patients demonstrated ischemia on day 2, representing a total of 3 symptomatic and 26 silent events. When comparing the two monitoring periods, 7 patients had longer or more severe ST segment depression whereas 6 other patients presented with more severe VPBs on day 2. Three patients had less ischemia on day 2, one remained stable, and 13 had no ischemia throughout the study. Silent ischemia was significantly more prolonged (C.Dur.Sil 316 v 152 sec, P < 0.05) and more intense (C. Area Sil 8 v 3.8 mm.min, P < 0.05) on day 2. Moreover, on top of a normal circadian distribution of ischemic events in the morning and in the evening, 40% of events were related to the donation or to a trip to the hospital. No preoperative characteristic helped to detect patients at risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Wiktor stent implantation in patients with restenosis following balloon angioplasty of a native coronary artery.

Intracoronary stenting has been introduced as an adjunct to balloon angioplasty aimed at overcoming its limitations, namely acute vessel closure and late restenosis. This study reports the first experience with the Wiktor stent implanted in the first 50 consecutive patients. All patients had restenosis of a native coronary artery lesion after prior balloon angioplasty. The target coronary artery was the left anterior descending artery in 26 patients, the circumflex artery in 7 patients and the right coronary artery in 17 patients. The implantation success rate was 98% (49 of 50 patients). There were no procedural deaths. Acute or subacute thrombotic stent occlusion occurred in 5 patients (10%). All 5 patients sustained a nonfatal acute myocardial infarction. Four of these patients underwent recanalization by means of balloon angioplasty; the remaining patient was referred for bypass surgery. A major bleeding complication occurred in 11 patients (22%): groin bleeding necessitating blood transfusion in 6, gastrointestinal bleeding in 3 and hematuria in 2. Repeat angiography was performed at a mean of 5.6 +/- 1.1 months in all but 1 patient undergoing implantation. Restenosis, defined by a reduction of greater than or equal to 0.72 mm in the minimal luminal diameter or a change in diameter stenosis from less than to greater than or equal to 50%, occurred in 20 (45%) and 13 (29%) patients, respectively. In this first experience, the easiness and high technical success rate of Wiktor stent implantation are overshadowed by a high incidence of subacute stent occlusion and bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary

The relation between triglyceride synthesis in peripheral tissues and postprandial plasma triglyceride levels: preliminary evidence of a role for acylation stimulating protein.

The present study examines the hypothesis that the rate at which peripheral tissues synthesize triglycerides is a key determinant of the rate at which they are removed from plasma. The cells of greatest interest in this regard would, of course, be the adipocytes. However, serial sampling of this tissue is not possible in man. We have approached the question indirectly, by studying triglyceride synthesis in human mononuclear cells before and after an oral fat load. In addition, plasma levels of Acylation Stimulating Protein (ASP) were measured after an overnight fast and 4 h after ingestion of the oral fat load. Similar measurements were made in the same subjects after fasting overnight and with the fast extended for 4 additional hours. With the extended fast, no parameter measured changed significantly. However, after the oral fat load, the following changes were found to be significant: plasma triglycerides increased (63.6 +/- 31.1 vs 101.5 +/- 43 mg/dl, p less than 0.005) as did d less than 1.006 g/ml triglycerides (42.3 +/- 22.8 vs 78.0 +/- 39.7 mg/dl, p less than 0.005) and plasma ASP (10.4 +/- 2.2 vs 14.7 +/- 2.3 mg/dl, p less than 0.005). In addition, the rate of triglyceride synthesis in the mononuclear cells increased significantly (1.22 +/- 0.3 vs 1.52 +/- 0.3 nmol oleate/mg cell protein per h, p less than 0.005). There was also a significant inverse relation between the increase in the d less than 1.006 triglycerides between 0 and 4 h and the increase in triglyceride synthesis in the mononuclear cells (r = 0.91, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Acylation

Morphologic change in coronary artery stenosis with the Medtronic Wiktor stent: initial results from the core laboratory for quantitative angiography.

The purpose of this study was to assess the early changes in stenosis geometry after implantation of the Medtronic Wiktor stent in human coronary arteries. Morphologic changes were evaluated by quantitative coronary angiography using automated edge detection. The hemodynamic significance of the morphologic changes were assessed by the calculation of the theoretical pressure drop across the dilated and stented stenosis derived from the Poiseuile and turbulent resistances assuming a coronary blood flow of either 0.5, 1, or 3 ml/sec. Fifty patients were studied before and immediately after stent implantation. The stented coronary artery was the left anterior descending artery in 26 patients, the circumflex artery in eight patients, and the right coronary artery in 16 patients. Stent implantation resulted in an additional increase in the minimal luminal cross-sectional area and minimal luminal diameter of the dilated vessel without changing the curvature of the stenosis. Furthermore, there was a significant reduction of the "plaque area." This was associated with a normalization of the calculated resistances to flow and pressure drop across the stenosis. To a minimal extent, recoil (0.1 +/- 0.36 mm) was observed after stent implantation.

Adult

A new radioimmunoassay for the determination of the angiotensin-converting enzyme inhibitor perindopril and its active metabolite in plasma and urine: advantages of a lysine derivative as immunogen to improve the assay specificity.

A new radioimmunoassay (RIA) was developed for the direct measurement of perindoprilate (PT), the active metabolite (diacid) of Perindopril (P), an angiotensin-converting enzyme (ACE) inhibitor. Antibodies were raised in rabbits against the lysine derivative of PT conjugated to bovine serum albumin. The p-hydroxyphenyl derivative of the lysine analogue was used for preparation of the radioligand by iodination (125I). Cross-reactivities for the glucuronide metabolites of P and PT are low (0.25 and 3.5%, respectively). The theoretical limit of detection is 0.2 nM, the sensitivity attainable with random samples is about 0.5 nM. Within- and between-assay variabilities observed were 4.2-6.7 and 2.8-5.9%, respectively (concentration range 2.1-41.7 nM). Serial dilution of plasma and urine samples showed excellent parallelism (r greater than 0.95; P less than 0.001). Recoveries of PT spiked to urine and plasma samples were 90-120%. The prodrug P can be measured in the same sample (plasma/urine) after chromatographic separation on a Dowex AG 1 x 2 anion-exchange column and quantitative alkaline hydrolysis of the P-containing fraction. It is concluded that the specificity and sensitivity of this assay are amply sufficient for pharmacokinetic studies and in patient monitoring.

Angiotensin-Converting Enzyme Inhibitors

Combined epidural and general anesthesia versus general anesthesia for abdominal aortic surgery.

The goal of this randomized study of high-risk surgical patients was to determine whether intraoperative thoracic epidural anesthesia in combination with light general anesthesia alters postoperative morbidity when compared to a standard technique of "balanced" general anesthesia. A total of 173 patients scheduled for abdominal aortic reconstruction were admitted to the study; 86 were to receive "balanced" general anesthesia (group 1) and 87 thoracic epidural anesthesia in combination with light general anesthesia (group 2). Preoperative evaluation included standard clinical tools, dipyridamole thallium gammatomography, and radionuclide angiography. In these patients, all of whom had peripheral artery disease, there were no significant differences in associated coronary artery disease, hypertension, and cardiovascular treatment. The distribution of left ventricular ejection fraction and the number of patients with thallium redistribution were not statistically different between the two groups. During the postoperative period, group 1 received analgesia of subcutaneous morphine (n = 35), epidural fentanyl (n = 30), or epidural bupivacaine (n = 21). In group 2, 6 patients with a nonfunctioning epidural catheter due to technical failure received a balanced general anesthesia and were eliminated from the study. During the postoperative period, group 2 received analgesia of subcutaneous morphine (n = 26), epidural fentanyl (n = 25), or epidural bupivacaine (n = 30). Cardiovascular morbidity did not differ between the two groups: 22 patients in group 1 and 19 patients in group 2 had a major postoperative cardiac event.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

An experimental study in electrical impedance tomography using backprojection reconstruction.

This paper reports on experiments designed to evaluate the performance of the equipotentials backprojection method under conditions modeling those of proposed applications of electrical impedance tomography. Small spherical targets were placed inside a saline-filled tank with dimensions similar to a human torso. Data were acquired with a computer-based instrument that applies current to pairs of electrodes located on two horizontal planes and records potential differences between electrodes of a third plane. The relative contrast produced by nonconducting spheres in a uniform saline background was measured on the reconstructed images and used to determine system sensitivity to target volume and to the radial and vertical positions of single spheres. Results show that for radial positions within a critical radius sensitivity is always maximum when the spheres center is on the recording plane and decreases gradually when the target is moved outside this plane. Localization of simple targets in 3-D, with data acquired from multiple recording planes, appears feasible. The results provide guidelines for the interpretation of images with complex 3-D conductivity distributions.

Electric Conductivity

Relation of arteriographically defined coronary artery disease to serum lipoprotein particles mapped with monoclonal antibodies.

BACKGROUND: This study was designed to investigate the relation of a molecular analysis of apolipoprotein B (apoB)-containing atherogenic lipoprotein particles to coronary artery disease (CAD) in middle-aged men. METHODS AND RESULTS: Two groups of men were studied. The first consisted of 97 patients with angiographically documented CAD (greater than 50% stenosis of at least one coronary artery). The second group consisted of 145 subjects without symptomatic CAD, who served as controls. In both groups, measurements were obtained for total cholesterol level, triglyceride level, cholesterol contents in apoB- and nonapoB-containing particles (LpB, LpnonB), total apoB and apolipoprotein AI (apoAI levels), lipoprotein particles recognized by monoclonal antibodies anti-apoB (LpBL3, LpBL5, LpBL7) and anti-apoAI (LpAI-2GII). Taking into account age, body mass index, hypertension, diabetes, smoking habits, and drug consumption, the analysis showed that the mean levels of cholesterol were identical in both groups but differed when cholesterol content in LpB and LpnonB subfractions were assessed, thus reflecting an increase in the low density fraction and a decrease in the high density fraction, respectively. This was confirmed by an increase in total apoB and a decrease in total apoAI. Measurements of LpBL3, LpBL5, LpBL7, and LpAI-2GII particles also discriminated between the two groups. After adjustment for cholesterol content in LpnonB particles, a difference in total apoB was no longer significant between groups, whereas LpBL3, LpBL5, and LpBL7 levels remained significantly higher in CAD patients. CONCLUSIONS: The measurement of separate concentrations of apoB in different particles may permit a more-accurate assessment of CAD risk than measurements of total apoB levels.

Adult

[Torsades de pointes and prolongation of the duration of QT interval after injection of droperidol].

Following a case of torsades de pointe (TDP) after the injection of droperidol (D), the authors studied the electrocardiographic variations caused by the drug. Fifty five unselected patients under the same conditions (general anesthesia) were given D (0.25 mg/kg IV). Significant prolongation of the QT interval was seen in 70% of cases by the end of the first minute. QT interval and the ratio of QTm (measured) over QTt increased from 387 +/- 34 ms to 423 +/- 37 ms (p less than 0.0001) and from 1.06 +/- 0.08 to 1.28 +/- 0.1 (p less than 0.001) respectively. These changes could favourise the onset of TDP. Although exceptional in terms of the extensive use of the neuroleptic in question, this possibility indicates the need for monitoring of the duration of QT before and during treatment with droperidol and for prescription of the drug to be avoided in circumstances known to be propitious to this arrhythmia (bradycardia, hypokalemia, anti-arrhythmic drugs).

Adult

[Vasomotor activity and coronary insufficiency].

Provocative testing has provided a method of evaluating the important role of vasomotor tone in coronary artery disease. The most sensitive test is the ergonovine (Methergin) test. This is a specific and reliable method of defining the clinical situations in which coronary spasm is common: --focal coronary artery spasm is mainly observed in resting angina alone or in association with effort angina. The prognosis of spasm is excellent with calcium antagonist therapy provided there is no other associated pathology such as left ventricular failure or triple vessel disease; --in the six weeks following myocardial infarction, focal coronary artery spasm is a common event: 20% of coronary angiographies. After six weeks, spasm is much less frequent. It does not influence the prognosis. This type of spasm is probably related to the scarring process; --coronary artery spasm is frequently associated with restenosis after coronary angioplasty, a process which is histologically related to proliferation of smooth muscle; --diffuse increase in coronary vasomotor tone is a much rarer pathology, perhaps related to global changes in vascular tone as its association with the Raynaud syndrome and with migraine would suggest. It presents clinically with resting angina and sometimes by typical Prinzmetal angina; --finally, vosomotor tone plays an important role in the daily life of coronary patients. Holter recordings for the detection of silent myocardial ischemia have shown episodes of myocardial ischemia at lower myocardial oxygen consumption levels than those usually recorded during exercise stress testing, which suggests a reduction in oxygen supply, that is to say coronary vasoconstriction. Changes in coronary vasomotor tone can modify the diameter of healthy coronary arteries by 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease

Comparison of isoflurane with sodium nitroprusside for controlling hypertension during thoracic aortic cross-clamping.

The aims of this randomized study were (1) to determine if isoflurane is effective in controlling blood pressure during thoracic aortic cross-clamping, and (2) to compare its effects on hemodynamics and oxygen transport to those of sodium nitroprusside. Sodium nitroprusside (SNP group, n = 10) or isoflurane (ISO group, n = 10) was started 2 minutes before cross-clamping and was adjusted to maintain systolic arterial pressure as near as possible to preinduction values. The duration of thoracic aortic cross-clamping was 26 +/- 4 minutes in the SNP group and 30 +/- 4 minutes in the ISO group. Administration of isoflurance and sodium nitroprusside was stopped 2 minutes before unclamping. The same anesthetic technique using fentanyl, 6 micrograms/kg, flunitrazepam, 0.02 mg/kg, pancuronium, 0.1 mg/kg, and 50% N2O was used for all patients. At the time of clamping, either isoflurance (maximal expired concentration, 2.5% +/- 0.3%) or sodium nitroprusside (cumulative dose, 11.1 +/- 1.0 mg) was effective in maintaining the systolic blood pressure below 160 mm Hg, whereas the pulmonary capillary wedge pressure did not change. However, only SNP was able to bring the arterial pressure above the cross-clamp back to postinduction levels. During clamping, stroke index values were similar in both groups, but cardiac index increased only in patients receiving SNP. In both groups, at clamping and unclamping, PvO2 was higher than postinduction values, indicating that throughout the study the oxygen needs of the perfused area were adequately met. There was no evidence of acute left ventricular decompensation because pulmonary capillary wedge pressures did not abruptly increase, nor did pulmonary edema occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta, Abdominal

[Venous catheterization and congenital abnormalities of the superior vena cava].

Persistent left superior vena cava is encountered in about 0.3 to 0.4% of human beings. It derives from remnants of the left cardinal vein system. This results in either a duplication of the superior vena cava or in a single left vena cava. The diagnosis is easy in case of associated cardiovascular anomalies. Two cases of single left vena cava and one case of duplication of the superior vena cava are described. All were identified owing to repeatedly aberrant courses of central venous catheters. Diagnosis was easily provided by angiography. Clinical course was uneventful. Despite its usual good tolerance, the persistence of a left vena cava, as an isolated anomaly, must not be neglected as it carries many practical implications which are reviewed.

Adult

Prospective randomized comparison of fluorouracil versus fluorouracil and high-dose continuous infusion leucovorin calcium for the treatment of advanced measurable colorectal cancer in patients previously unexposed to chemotherapy.

Seventy-nine patients with advanced, measurable, metastatic colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either fluorouracil (FUra) administered intravenously at a dose of 370 mg/m2/d for 5 days or the combination of FUra in the same dose and schedule with high-dose continuous infusion leucovorin calcium (500 mg/m2/d) beginning 24 hours before the first dose of FUra and continuing for 12 hours after the completion of FUra therapy. Patients whose disease progressed on treatment with FUra alone were, if eligible, crossed over to receive leucovorin and FUra. Three patients on the FUra plus leucovorin arm of the study were excluded from the analysis because they did not meet eligibility requirements. The treatment arms were well balanced for prognostic criteria including performance status, age, prior radiotherapy, distribution of metastatic sites, and on-study carcinoembryonic antigen (CEA), lactic dehydrogenase, and serum albumin. FUra plus leucovorin was superior to FUra alone for response (P = .0019) and for time to progression or death (log-rank, P = .045). Response rates were 16 of 36 (44%) versus five of 40 (13%), and median time to progression or death was 164 versus 120 days in the two arms of the trial, respectively. Overall survival, however, while longer in the FUra and leucovorin arm was not significantly so. An analysis of the toxicities experienced by the patients in the two treatment groups showed that, except for significantly more stomatitis in the leucovorin arm of the study, the side effects experienced by patients treated with either regimen were comparable. These results suggest that the efficacy of FUra in patients with advanced, measurable, metastatic colorectal cancer can be enhanced significantly by administration of a continuous high-dose infusion of leucovorin calcium.

Adenocarcinoma