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J L Georges

Publications and source records attributed to J L Georges.

At least 19 recordsLinked to original sources
PubMed2001

Interleukin-6 gene polymorphisms and susceptibility to myocardial infarction: the ECTIM study. Etude Cas-Témoin de l'Infarctus du Myocarde.

There is growing evidence that interleukin (IL) 6 plays an important role in the atherosclerotic process because of its role in mediating immune and inflammatory responses and inducing cell proliferation. The present study examined whether molecular variations at the IL-6 locus are involved in the predisposition to myocardial infarction. The entire coding region, 1,158 bp of the 5' flanking region and 237 bp of the 3' flanking region of the IL-6 gene were screened. We detected three nucleotide substitutions in the 5' region at positions -174 (G/C), -572 (G/C), and -596 (G/A) from the transcription start site, and one insertion/deletion in the 3' region at position +528 after the Stop codon. These polymorphisms were genotyped in the Etude Cas-Témoin de l'Infarctus du Myocarde study comparing male patients (n=640) and age-matched controls (n=719) from Northern Ireland and France. The IL-6/G-174C and IL-6/G-596A polymorphisms were in nearly complete association. Carriers of the IL-6/-174 C allele were more frequent in patients than in controls. The population-adjusted odds ratio for myocardial infarction associated with genotype CC+CG vs. GG was estimated as 1.34. In French patients the number of coronary arteries with greater than 50% stenosis was assessed by angiography. The IL-6/-174 C allele was more frequent in patients with two or fewer stenosed vessels than in patients with three-vessel lesions. These results suggest that genetic variation at the IL-6 locus is associated with susceptibility to myocardial infarction, especially events occurring on less extended lesions. These findings would be compatible with a lower IL-6 secretion associated with the IL-6/-174 C allele, itself or in combination with other promoter polymorphisms, leading to more unstable plaques.

Adult↗
PubMed2001

New polymorphisms in the interleukin-10 gene--relationships to myocardial infarction.

BACKGROUND: Interleukin-10 (IL-10) is a cytokine with anti-inflammatory and B-cell-stimulating activity. IL-10 is expressed in human atherosclerotic plaques and recent studies have shown the involvement of IL-10 in the atherosclerotic process. Therefore, we hypothesized that polymorphisms in the IL-10 gene might be associated with a predisposition to coronary heart disease. MATERIALS AND METHODS: To identify new polymorphisms in the human IL-10 gene, the entire coding sequence and the 3' flanking sequence of the gene were screened by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCR) followed by sequencing. The polymorphisms identified, and three others which have been previously described in the promoter region of the IL-10 gene (G-1082A, C-819T, C-592A), were then investigated in the ECTIM Study, a large population-based case-control study of myocardial infarction. RESULTS: Four new polymorphisms were identified: one in exon 1 (G+78/ex1A), which predicts a Glycine to Arginine change at position 15 in the putative signal peptide of the protein, two in the intron 3 (C+19/in3T, T+953/in3C) and one in the 3' flanking region (C+117T). All the IL-10 polymorphisms were in complete or nearly complete pairwise linkage disequilibrium. No case-control difference was found in genotype or allele frequencies for any of the polymorphisms. CONCLUSIONS: Our results suggest that IL-10 polymorphisms are not associated with an increased risk of myocardial infarction.

Adult↗
PubMed1998

New polymorphisms of the angiotensin II type 1 receptor gene and their associations with myocardial infarction and blood pressure: the ECTIM study. Etude Cas-Témoin de l'Infarctus du Myocarde.

OBJECTIVE: In an earlier report, we suggested that a polymorphism located in the 3' untranslated region of the angiotensin II type 1 receptor gene (AT1R+1166 A/C) might interact with the angiotensin I converting enzyme (ACE) insertion/deletion (I/D) polymorphism to increase the risk of myocardial infarction. Since the AT1R+1166 A/C polymorphism does not appear to be functional, we postulated that it might be in linkage disequilibrium with an unidentified functional variant which would affect the regulation of the gene in response to angiotensin II. The present study was conducted to identify new polymorphisms of the AT1R gene that might be responsible for this interaction. METHODS: The first four exons, which are untranslated, and 2.2 kb in the 5' flanking region of the AT1R gene were explored by polymerase chain reaction/single-strand conformation polymorphism. Seven polymorphisms were detected in the 5' region at positions -1424, -810, -713, -521, -214, -213 and -153 upstream from the start of transcription. The genotypes of the -810, -713, -214, -213 and -153 polymorphisms were completely concordant. One substitution was detected at the 55th nucleotide of exon 4. These polymorphisms, together with the +1166 A/C polymorphism and a previously described T/C substitution at the 573th nucleotide of exon 5, were genotyped in the Etude Cas-Témoin de l'Infarctus du Myocarde (ECTIM) study, a multicentre study comparing 651 patients who had survived a myocardial infarction and 728 controls from Belfast (United Kingdom) and Lille, Strasbourg and Toulouse (France). RESULTS: The newly identified polymorphisms were not in linkage disequilibrium with the +1166 A/C polymorphism and therefore could not explain the interaction observed with ACE I/D. None of the polymorphisms was associated with blood pressure levels in control subjects. In the four populations, the A allele of the -810 polymorphism was associated with a lower risk of myocardial infarction (population-adjusted odds ratio of 0.80, confidence interval 0.65-0.97, P< 0.05). CONCLUSIONS: None of the newly identified polymorphisms could account for the previously described interaction between the AT1R+1166 A/C and the ACE I/D polymorphisms affecting the risk of myocardial infarction. However, the present study suggests that AT1R-810 T/A, or other polymorphisms which are in complete association with it, might be associated with the risk of myocardial infarction. Further studies are required to confirm this finding and to identify the functional variants.

Adult↗
PubMed1996

Time course of troponin I, myoglobulin, and cardiac enzyme release after electrical cardioversion.

The results of this study, conducted in 25 patients without myocardial infarction, showed that all the biologic markers of myocardial infarction, except the highly cardiospecific cardiac troponin I, increased in some patients after electrical cardioversion. These results allow us to conclude that electrical cardioversion, even preceded by a mechanical resuscitation of short duration, does not result in myocardial damage, and that cardiac troponin I is more accurate than creatine kinase-MB activity and creatine kinase-MB mass determination for the diagnosis of myocardial damage in patients who have undergone electrical cardioversion.

Aged↗
PubMed1996

Family study of lipoprotein lipase gene polymorphisms and plasma triglyceride levels.

To better characterize the role of the lipoprotein lipase (LPL) gene in the determination of triglyceride levels in healthy subjects, a study was performed in 193 nuclear families (384 parents, means age = 42.0 +/- 5.2 years; 399 offspring, mean age = 14.6 +/- 4.3 years) volunteering to have a free health checkup examination. The pattern of familial resemblance was compatible with a zero correlation between spouses, a weak father-offspring correlation (0.099 +/- 0.054; P < 0.07), and significant mother-offspring (0.235 +/- 0.053; P < 10(-4)) and sib-sib (0.294 +/- 0.064; P < 10(-4)) correlations. Associations of triglyceride levels with the LPL HindIII and PvuII polymorphisms were investigated by a familial measured genotype analysis, specifying sex- and age-dependent polymorphism effects. The effects associated with both polymorphisms were significant only in fathers, the H+ and P+ alleles being associated with raised triglyceride levels. The HindIII and PvuII polymorphisms explained 3.5% and 3%, respectively, of the variability of triglycerides in fathers. The relationship was weakened after prior adjustment on body mass index, but remained significant for PvuII. Because of the lack of effect in mothers and offspring, the polymorphisms did not contribute to the covariance of triglyceride levels in relatives. In conclusion, this family study showed a weak relationship of the HindIII and PvuII polymorphisms to plasma triglyceride levels in young healthy male subjects. The effects detectable only in fathers suggest a possible modulation of the LPL expression by hormonal or lifestyle factors.

Adolescent↗
PubMed1996

[Treatment of refractory unstable angina by transluminal coronary angioplasty].

The aim of this retrospective study was to assess the value of percutaneous transluminal coronary angioplasty (PTCA) in unstable angina refractory to maximal medical therapy. The results of this procedure in these patients were compared with the results in unstable angina controlled by medication before angioplasty. Between january 1987 and january 1993, 30 patients underwent emergency PTCA for refractory unstable angina (group I). The clinical and angiographic features were compared with these of 30 patients with medically controlled unstable angina, paired for age and dilated artery (group II). The left ventricular ejection fraction was compared in the two groups (58 and 57%). The morphology of the coronary lesions according to the Ambrose classification, TIMI grading, number of lesions, degree of stenosis and severity of coronary calcification were comparable in the two groups. However, in group I, there was a significantly higher number of filling defects (30% compared with 10%, p = 0.05) and a greater number of per-PTCA complications, especially acute occlusions (23 compared with 13%, NS) with 3 deaths and 2 myocardial infarctions (compared with 1 death and 2 myocardial infarctions in group II). At long term, the restenosis, myocardial infarction and secondary death rates were comparable in the two groups with an average follow-up of 27 +/- 18 months. The poor prognosis of refractory unstable angina is therefore related to morbidity in the hospital period. These results confirm the physiopathological importance of the thrombotic process in unstable angina; the presence of "filling defect" is a poor prognostic factor associated with resistance to medical therapy. Coronary angioplasty is a valuable technique in this context but carries a higher risk of acute complications which can be reduced by an optimal platelet antiaggregant and anticoagulant therapy and in future by the use of new antithrombotic agents.

Angina, Unstable↗
PubMed1996

[Tolerance of amlodipine in left ventricular dysfunction of ischemic origin].

The aim of this study was to assess the effects of amlodipine on left ventricular function at rest and on effort, at least 30 days after myocardial infarction. The 30 patients included in the study had resting isotopic ejection fractions of 40 to 60%. At inclusion and after 15 days treatment with 10 mg of amlodipine, the patients underwent exercise stress testing with a standard Bruce protocol and resting and exercise isotopic left ventricular ejection fractions were measured. The association of betablockers was allowed but vasodilator therapy was prohibited. During the second exercise stress test, the duration of exercise increased (437 +/- 167 to 518 +/- 154 s; p < 0.002) and the work level rose from 140 +/- 56 to 169 +/- 60 Watts; p < 0.04. The number of electrically positive tests did not change significantly (33 vs 26.7%; NS). The resting ejection fraction did not increase after 15 days treatment with amlodipine (47.4 +/- 6.7 vs 48.3 +/- 8.9%; NS). Similar results were observed with respect to the exercise ejection fraction (51.4 +/- 10.4 vs 52.6 +/- 8.6%; NS). These patients may however be divided into two subgroups. In the first subgroup of 10 patients, the resting ejection fraction rose by more than 5% with amlodipine whereas the exercise ejection fraction remained unchanged (54.4 +/- 7.7% vs 54.5 +/- 7.5% with amlodipine). In the second subgroup of 20 patients, the resting ejection fraction decreased slightly with amlodipine (48 +/- 6.9% vs 45.3 +/- 8%; p = 0.04) but increased significantly on exercise (45.3 +/- 8% vs 51.7 +/- 9.1%; p < 0.0002). Therefore, amlodipine, a new generation calcium antagonist, does not induce any deleterious effect after myocardial infarction with mild left ventricular dysfunction.

Adult↗
PubMed1995

[Favorable outcome of orbital nasal sinus mucormycosis complicating the induction treatment of acute lymphoblastic leukemia].

BACKGROUND: Most cases of mucormycosis occur in immunosuppressed children. Intracranial extension is lethal and must be prevented with early specific treatment. CASE REPORT: A 42 month-old boy was admitted suffering from acute lymphoblastic leukemia. Edema of the left eyelid developed on the sixth day of induction chemotherapy. Mucormycosis was suspected because of gradual extension of infection to nasal ala and periorbital area with fever, edema of nasal turbinates and nasal black secretions. Chemotherapy was discontinued and the patient was given intravenous amphotericin B (1.0 mg/kg/day) and heparin associated with G.CSF. Improvement was only temporary and scan examination performed on day 17 showed involvement of the orbit, eye and wall of the maxillary sinus; cultures of secretions were positive for staphylococcus and Absidia corymbifera. Remission of leukemia was obtained a few days later permitting surgical resection of involved tissues on day 30. A relapse of mucormycosis was observed six weeks later despite prolonged administration of amphotericin B requiring extended resection of necrotic areas and replacement of amphotericin B by its liposomal form (Ambisome). Bone marrow relapse of leukemia required further chemotherapy. The patient is in good condition 30 months after the initial symptoms. CONCLUSION: Our patient seems to be the first with prolonged remission of facial mucormycosis and acute leukemia despite relapse of both diseases. This favorable outcome could be due to the use of Ambisome.

Amphotericin B↗
PubMed1995

Bioprosthetic valve replacement in the elderly.

One hundred and ten patients aged more than 65 years (mean, 73.4; range, 65-82) underwent successful bioprosthetic valve replacement (aortic, n = 71; mitral, n = 32; both, n = 7) from 1979 to 1985. The valve was pericardial in 39 cases and porcine in 78. The mean follow-up was 75 months (total, 688 patient-years; range, 2 months to 12 years). Actuarial patient survival was 79.4% at 5 years and 55.2% at 10 years. Thirty-seven patients died: 18 from valve-related causes and 19 from other causes. Eight patients have been reoperated on for valve-related complications (1.17% per patient-year): five primary deteriorations, two paravalvular leaks and one case of endocarditis. One surgical death occurred (12.5%). Twenty-five percent of the patients were receiving anticoagulants because of atrial fibrillation, and 5.4% developed severe bleeding (3.8% patient-year). Mid-term follow-up of these patients aged more than 65 years and undergoing bioprosthetic valve replacement surgery revealed a low rate of documented primary structural deterioration (0.9% per patient-year), a low mortality rate on reoperation (12.5%) and a high mortality rate due to non valve-related causes (51.4%).

Aged↗
PubMed1994

Coronary angioplasty in patients 75 years and older; comparison with coronary bypass surgery.

From November 1988 to May 1992, 108 patients (79 men, 29 women) 75 years or older (mean 78 +/- 3, range 75-90 years) underwent coronary angioplasty (group I: n = 62) or coronary bypass surgery (group II: n = 46). Group II patients were younger (76 +/- 2 vs 79 +/- 4, P = 0.002) and had a higher proportion of multivessel disease. The two groups were comparable with regard to the presence of unstable angina, left ventricular ejection fraction and Q wave infarction. In-hospital mortality was similar in the two groups (6.4% vs 4.3%). Complete revascularization (72% vs 47%, P < 0.05) and left anterior descending artery revascularization (100% vs 45%, P < 0.01) were more frequent in group II. Two-year infarction-free survival was similar (group I: 76 +/- 6%; group II: 79 +/- 6%) but recurrent class III or IV angina (36% vs 9%, P < 0.05) and repeat procedures (26% vs 0%, P < 0.05) were more frequent in group I.

Aged↗
PubMed1994

Usefulness of radionuclide ventriculography during transesophageal atrial pacing in the diagnosis of coronary artery disease.

Radionuclide ventriculography before, during, and after atrial transesophageal pacing was carried out in 15 patients with suspected coronary artery disease (CAD) and without myocardial infarction. All patients underwent coronary angiography. Ten patients (group 1) had a coronary lesion > 50% on at least one of the main coronary arteries. Five patients (group 2) had normal coronary arteries. Radionuclide left ventricular ejection fraction (LVEF) before pacing was 56 +/- 3% in group 1 and 59 +/- 3% in group 2 (NS). Radionuclide ventriculography during pacing was 45 +/- 4% in group 1 (P < 0.0001 vs basal in group 1) and 45 +/- 6% in group 2 (P < 0.01 vs basal in group 2, NS vs group 1 during pacing). Immediate postpacing ejection fraction did not differ in the two groups and was identical to the prepacing value. A quantitative regional wall motion analysis was performed in 105 segments. Regional radionuclide ventriculography was calculated in each segment as follows: end-diastolic counts-end-systolic counts/end-diastolic counts. The relative decrease in regional LVEF during pacing was more important in the 39 segments related to a narrowed vessel than in the 66 segments related to normal coronary artery (32 +/- 13% vs 13 +/- 10%, P < 0.0001). A more than 20% relative decrease in at least one segment during pacing occurred in 10 patients in group 1 (sensitivity 100%) and in 2 patients in group 2 (specificity 60%). In conclusion, global radionuclide ventriculography during transesophageal atrial pacing decreases in patients with and without CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Evaluation of a new commercial kit for emergency determination of serum myoglobin].

The usefulness of a nephelometric-based serum myoglobin assay kit in the early diagnosis of acute myocardial infarction was assessed in 92 consecutive patients admitted within 24 hours of the onset of spontaneous chest pain lasting > or = 20 minutes. The discharge diagnosis was acute myocardial infarction in 37 patients (40.2%), myocardial infarction lasting > or = 6 hours in 10, and no myocardial infarction in 45 (48.9%). The characteristic curve showed that the best differential diagnostic value was a serum myoglobin > or = 130 micrograms/l (sensitivity, 75.6%; specificity, 91.7%; positive-predictive value, 88%; negative-predictive value, 82%). The initial diagnosis was doubtful in 33 patients (36%) because of an inconclusive electrocardiogram. A serum myoglobin value of > or = 130 micrograms/l would have identified 9 of the 13 patients with acute myocardial infarction and all of the 20 patients without myocardial infarction, giving an accuracy of 84.8%. These results suggest that this new rapid, quantitative serum myoglobin assay would be useful in the evaluation of suspected myocardial infarction, especially in patients with an inconclusive electrocardiogram.

Aged↗
PubMed1993

Prognostic value of thallium-201 myocardial scintigraphy after atrial transoesophageal pacing in patients with suspected coronary artery disease.

Fifty-five patients with suspected coronary artery disease underwent planar thallium-201 myocardial scintigraphy after atrial transoesophageal pacing. Coronary angiography was carried out in all patients. Eighteen patients had no myocardial infarction, but a greater than 50% narrowing of at least one main vessel: initial hypoperfusion with redistribution at 4 h occurred in 16 patients (sensitivity 89%). Twenty-one patients had had a previous myocardial infarction: a reversible thallium defect was observed in 12 patients and an irreversible defect in the nine remaining patients. Sixteen patients had normal coronary arteries: a reversible thallium defect was observed in three patients (specificity 81%). After a mean follow-up of 22 +/- 13 months (range 6 to 40), 23 cardiac events occurred: cardiac death in one patient, unstable angina in three, and revascularization procedures for recurrent angina despite medical therapy in 19 (coronary artery bypass surgery in 7 and coronary angioplasty in 12). By univariate analysis, the predictors of future cardiac events were a history of previous myocardial infarction (odds ratio 5.5, P < 0.02), multivessel coronary artery disease (odds ratio 9.6, P < 0.0002), angina during atrial pacing (odds ratio 5.1, P < 0.05), abnormal scintigraphy (odds ratio 17.1, P < 0.001) and reversible perfusion defect after pacing (odds ratio 7.9, P < 0.002). By multivariate analysis, multivessel disease (P < 0.004) and reversible perfusion defect after pacing (P < 0.02) were the only independent predictors of future cardiac events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Mid-term results of bioprosthesis in patients over 65 years].

Between 1979 and 1985, 79 patients over 65 years of age (mean 70.8; range 65-82 years) underwent valvular replacement with a bioprosthesis (aortic: 48, mitral: 26, aortic and mitral: 5). Of the 84 valves implanted, 56 were porcine and 28 were pericardial bioprostheses. The average follow-up was 66 months (total: 434 patient-years; range: 2 months-12 years). Twenty-three patients (29%) died; 13 of these deaths were related to the prosthesis and 10 were not formally related to the bioprosthesis. Of the latter 10 deaths, 7 were caused by malignant disease. Seven patients were reoperated for a complication due to the prosthesis (1.6% per patient-year): 5 primary tissue failure, 1 endocarditis, 1 perivalvular leak. Sixteen patients (20.3%) received oral anti-coagulants for atrial fibrillation; 6 of them (7.6%) had severe haemorrhagic complications (3 deaths). The actuarial survival was 76.2% at 5 years and 53.4% at 10 years. Actuarial survival without reoperation was 76% at 5 years and 42% at 10 years. Analysis of survival with respect to the type of bioprosthesis (porcine of pericardial), the valve orifice (mitral or aortic) and age (under or over 70 years) did not show any significant differences. Follow-up of patients over 65 years of age showed a high rate of haemorrhagic complications related to oral anticoagulant therapy for atrial fibrillation (6.8% per patient-year), a low rate of primary tissue failure (1.1% per patient-year) and a low reoperative mortality (1 death for 7 reoperations).

4-Hydroxycoumarins↗
PubMed1993

[Reperfusion-induced arrhythmia and oxidative stress].

Although recognized and reproduced in numerous animal models, reperfusion arrhythmias were not studied extensively in humans until the advent of methods of coronary reperfusion during the acute phase of myocardial infarction. Usually of ventricular origin, these arrhythmias are polymorphic and constitute imperfect but useful markers of coronary reperfusion. Their electrophysiologic mechanisms are complex and their molecular mechanisms unelucidated. Predisposing conditions are the duration and severity of the ischemia, biochemical modifications such as heterogeneous uptake of extracellular potassium, magnesium deficit, intracellular calcium overload and release of arrhythmogenic lipid metabolites or prostaglandins. The autonomic nervous system also plays a part by an increase in the number and response of alpha-adrenoceptors. Furthermore, experimental studies provide theoretical and pharmacologic arguments for the participation of free oxygen radicals (superoxide anion (02.-, hydroxyl radical OH.) in reperfusion arrhythmias in the animal. By its complexity, human myocardial infarction differs markedly from the animal models studied; it probably involves, apart from the free oxygen radicals, multiple thrombotic, humoral and nervous factors whose respective role in the production of reperfusion arrhythmias remains to be established. Some enlightenment should be obtained by analysis of rhythmic events during proposed controlled studies using anti-free radical agents to prevent these post-myocardial infarct acute events.

Arrhythmias, Cardiac↗
PubMed1992

Treatment of severe mitral regurgitation caused by ischemic papillary muscle dysfunction: indications for coronary angioplasty.

The aim of this study was to evaluate the prognosis and functional outcome of mitral regurgitation caused by ischemic papillary muscle dysfunction with respect to treatment, and to determine the role of coronary angioplasty in this context. Thirty patients with severe ischemic mitral regurgitation were followed up for 33 +/- 3 months. Thirteen patients were treated medically (group I) and 17 patients underwent surgery or angioplasty (group II). The 3-year survival was 59.5% (45.6% in group I and 70.2% in group II). Angioplasty was only used in paroxysmal mitral regurgitation caused by papillary muscle ischemia. This technique resulted in spectacular immediate results in three patients with pulmonary edema caused by mitral regurgitation during myocardial ischemia. Surgical correction of mitral regurgitation should be considered without delay if angioplasty is not feasible or if the regurgitation is permanent or severe. Widening the indications of surgery or angioplasty should result in an improvement of the prognosis of these high-risk patients.

Acute Disease↗
PubMed1992

Life-threatening thyrotoxicosis induced by amiodarone in patients with benign heart disease.

We report four cases of life-threatening amiodarone iodine-induced thyrotoxicosis. Two patients died of a thyroid storm, and the other two patients developed severe thyrocardiac disease unresponsive to 6 months intensive antithyroid and steroid therapy. One of these latter patients died 1 month after thyroidectomy. Euthyroidism was achieved in the last patient by treatment with potassium perchlorate. The course could not be explained by the prior thyroid or cardiac status in any of the four cases.

Aged↗