Nanoindentation of the pristine and irradiated forms of a sodium borosilicate glass: Insights from molecular dynamics simulations.

We have carried out classical molecular dynamics simulations in order to get insight into the atomistic mechanisms of the deformation during nanoindentation of the pristine and irradiated forms of a sodium borosilicate glass. In terms of the glass hardness, we have found that the primary factor affecting the decrease of hardness after irradiation is depolymerization rather than free volume, and we argue that this is a general trend applicable to other borosilicate glasses with similar compositions. We have analyzed the changes of the short- and medium-range structures under deformation and found that the creation of oxygen triclusters is an important mechanism in order to describe the deformation of highly polymerized borosilicate glasses and is essential in the understanding of the folding of large rings under stress. We have equally found that the less polymerized glasses present a higher amount of relative densification, while the analysis of bond-breaking during the nanoindentation has showed that shear flow is more likely to appear around sodium atoms. The results provided in this study can be proven to be useful in the interpretation of experimental results.

Behavior of sodium borosilicate glasses under compression using molecular dynamics.

We have performed classical molecular dynamics simulations in order to study the changes under compression in the local and medium range structural properties of three sodium borosilicate glasses with varying sodium content. These glasses have been isostatically compressed up to 20 GPa and then decompressed in order to analyze the different mechanisms that affect densification, alongside with the permanent modifications of the structure after a full compression/decompression cycle. The results show that the atomic packing is the prominent characteristic that governs the amount of densification in the glass, as well as the setup of the permanent densification. During compression, the bulk modulus increases linearly up to approximately 15 GPa and more rapidly for higher pressures, a behavior which is reflected on the rate of increase of the average coordination for B and Na. Radial distribution functions at different pressures during the cycle help to quantify the amount of distortions in the elementary structural units, with a pronounced shortening of the Na-Na and Na-O bond lengths during compression. A subsequent decomposition of the glassy matrix into elementary Voronoi volumes verifies the high compressibility of Na-rich regions.

Deformation mechanisms during nanoindentation of sodium borosilicate glasses of nuclear interest.

In this paper we analyze results of Molecular Dynamics simulations of Vickers nanoindentation, performed for sodium borosilicate glasses of interest in the nuclear industry. Three glasses have been studied in their pristine form, as well as a disordered one that is analogous to the real irradiated glass. We focused in the behavior of the glass during the nanoindentation in order to reveal the mechanisms of deformation and how they are affected by microstructural characteristics. Results have shown a strong dependence on the SiO2 content of the glass, which promotes densification due to the open structure of SiO4 tetrahedra and also due to the strength of Si-O bonds. Densification for the glasses is primarily expressed by the relative decrease of the Si-O-Si and Si-O-B angles, indicating rotation of the structural units and decrease of free volume. The increase of alkali content on the other hand results to higher plasticity of the matrix and increased shear flow. The most important effect on the deformation mechanism of the disordered glasses is that of the highly depolymerized network that will also induce shear flow and, in combination with the increased free volume, will result in the decreased hardness of these glasses, as has been previously observed.

Influence of Magnesium on the Structure of Complex Multicomponent Silicates: Insights from Molecular Simulations and Neutron Scattering Experiments.

A series of multicomponent glasses containing up to five oxides are studied using classical molecular dynamics simulations and neutron scattering experiments. The focus is on the role of magnesium in determining the structural properties of these glasses and the possible mixed effect during a sodium/magnesium substitution. Calculated structure functions (pair correlation function and structure factor) rather accurately reproduce their experimental counterpart, and we show that more fine structural features are qualitatively reproduced well, despite some discrepancies in the preferential spatial distribution between sodium and magnesium to aluminum and boron, as well as the nonbridging oxygen, distribution. The simulated systems offer a solid basis to support previous experimental findings on the composition-structure relationship, allowing for further analysis and property calculation. It is confirmed that the substitution of sodium by magnesium leads to the decrease of four-fold boron and a modification of the alkali coordinations with a significant change of the network structure. Specifically, magnesium coordination extracted from numerical simulations highlights a potential dissociation from penta- to tetra- and hexahedral units with increasing MgO contents along the glass series, which could not be resolved experimentally.

Behavioral, Hormonal, Inflammatory, and Metabolic Effects Associated with FGF21-Pathway Activation in an ALS Mouse Model.

In amyotrophic lateral sclerosis (ALS), motor neuron degeneration occurs simultaneously with systemic metabolic dysfunction and neuro-inflammation. The fibroblast growth factor 21 (FGF21) plays an important role in the regulation of both phenomena and is a major hormone of energetic homeostasis. In this study, we aimed to determine the relevance of FGF21 pathway stimulation in a male mouse model of ALS (mutated SOD1-G93A mice) by using a pharmacological agonist of FGF21, R1Mab1. Mice (SOD1-WT and mutant SOD1-G93A) were treated with R1Mab1 or vehicle. Longitudinal data about clinical status (motor function, body weight) and biological parameters (including hormonal, immunological, and metabolomics profiles) were collected from the first symptoms to euthanasia at week 20. Multivariate models were performed to identify the main parameters associated with R1Mab1 treatment and to link them with clinical status, and metabolic pathways involving the discriminant metabolites were also determined. A beneficial clinical effect of R1Mab1 was revealed on slow rotarod (p = 0.032), despite a significant decrease in body weight of ALS mice (p < 0.001). We observed a decrease in serum TNF-α, MCP-1, and insulin levels (p = 0.0059, p = 0.003, and p = 0.01, respectively). At 16 weeks, metabolomics analyses revealed a clear discrimination (CV-ANOVA = 0.0086) according to the treatment and the most discriminant pathways, including sphingolipid metabolism, butanoate metabolism, pantothenate and CoA biosynthesis, and the metabolism of amino acids like tyrosine, arginine, proline, glycine, serine, alanine, aspartate, and glutamate. Mice treated with R1Mab1 had mildly higher performance on slow rotarod despite a decrease on body weight and could be linked with the anti-inflammatory effect of R1Mab1. These results indicate that FGF21 pathway is an interesting target in ALS, with a slight improvement in motor function combined with metabolic and anti-inflammatory effects.

A phase II of gemcitabine combined with pazopanib followed by pazopanib maintenance, as second-line treatment in patients with advanced leiomyosarcomas: A unicancer French Sarcoma Group study (LMS03 study).

BACKGROUND: Options in second-line therapy after doxorubicin-based chemotherapy for metastatic/advanced leiomyosarcoma include gemcitabine (G), trabectedin and pazopanib (P) monotherapy. Currently, no combination therapy is better than monotherapy. LMS03 is an open-label multicentre single-group phase II study designed to assess the efficacy and tolerance of G + P in the second-line setting. PATIENTS AND METHODS: Patients (pts), ECOG ≤2, with metastatic leiomyosarcomas (LMS) after first-line doxorubicin chemotherapy failure were eligible. Pts were treated with G 1000 mg/m2 on days 1 and 8 of each 21 days (maximum eight cycles), in combination with oral daily P (800 mg), until disease progression/toxicity. 9-month progression-free survival (PFS) rate was the primary endpoint. Inacceptable and promising 9-month PFS rates were defined, in the intent-to-treat population, as 32% and 44%. RESULTS: 106 pts were included with a mean age of 59.8 years and an ECOG 0 in 63.5%; the primary tumour site was uterus in 61%. Pts were treated with P + G for a median of 3.8 mo, and P for a median of 4.2 mo. The 9-month PFS rate was 32.1% (95% CI 23.1-41.1). After a median follow-up of 14.2 months, the PFS was 6.5 months (95% CI 5.6-8.2), and the overall survival was 22.4 months (95% CI 16.9-26.5). The best response was 23.8%. The most frequent reported grade 3-4 adverse events were haematological. CONCLUSIONS: LMS03 failed to show that second-line therapy, with gemcitabine combined with pazopanib, followed by pazopanib alone, was beneficial for advanced LMS patients. Eudract N°2011-001308-36 and NCT01442662.

Low IDL-B and high LDL-1 subfraction levels in serum of ALS patients.

INTRODUCTION: Converging evidence highlights that lipid metabolism plays a key role in ALS pathophysiology. Dyslipidemia has been described in ALS patients and may be protective but peripheral lipoprotein subclasses have never been studied. MATERIAL AND METHODS: We collected sera from 30 ALS patients and 30 gender and age-matched controls. We analyzed 11 distinct lipoprotein subclasses by linear polyacrylamide gel electrophoresis (Lipoprint, Quantimetrix Corporation, USA). We also measured lipoprotein (a), apolipoprotein B, and apolipoprotein E levels. RESULTS: ALS patients had significant higher total cholesterol, HDL-cholesterol, and LDL-cholesterol levels than controls (p<0.0001, p=0.0007, and p=0.0065, respectively). The LDL-1 subfraction concentration was higher (1.03±0.41 vs. 0.71±0.28mmol/L; p=0.0006) and the IDL-B subfraction lower (6.5±2% vs. 8.0±2%; p=0.001) in ALS patients than controls. DISCUSSION: Our preliminary work confirmed the association between ALS and dyslipidemia. The low IDL-B levels may explain the hepatic steatosis frequently reported in ALS. The high levels of the cholesterol-rich LDL-1 subfraction is consistent with previously reported hypercholesterolemia. CONCLUSION: This study describes, for the first time, the distribution of serum lipoproteins in ALS patients, with low IDL-B and high LDL-1 subfraction level.

A critical appraisal of the quality of the management of infective endocarditis.

OBJECTIVES: The purpose of this study was to assess the quality of the management of infective endocarditis. BACKGROUND: Although many guidelines on the management of infective endocarditis exist, the quality of this management has not been evaluated. METHODS: We collected data on all patients (116) hospitalized with infective endocarditis over 1 year in all hospitals in the Rhône-Alpes region (France). RESULTS: Prophylactic antibiotics were not given before infective endocarditis to 8/11 cardiac patients at risk and who underwent an at risk procedure. Among the 55 cardiac patients at risk and with fever and who consulted a physician, blood cultures were not performed before antibiotic therapy was initiated for 32 patients. In-hospital antibiotic therapy was incorrect for 23 patients. The portal of entry was not treated for 16/61 patients with an accessible portal of entry. Among the 19 patients who had severe heart failure or fever persisting more than 2 weeks in spite of antibiotic therapy and who could have undergone early surgery, surgery was delayed for five, and not performed for three. Overall, the average score was 15/20. CONCLUSIONS: More information on the management of infective endocarditis should be widely disseminated to the physicians' and the dentists' communities and to the patients at risk.

Effect of a mediterranean type of diet on the rate of cardiovascular complications in patients with coronary artery disease. Insights into the cardioprotective effect of certain nutriments.

OBJECTIVES: We sought to describe the various cardiovascular complications that occurred in the Lyon Diet Heart Study (a secondary prevention trial testing the protective effects of a Mediterranean type of diet), to analyze their relations with the associated drug treatments and to gain insights into the possible mechanisms underlying the beneficial effects of certain nutriments. BACKGROUND: Dietary habits are implicated in coronary heart disease, and the traditional Mediterranean diet is thought to be cardioprotective. However, the exact mechanisms of this protection are unknown. METHODS: A total of 605 patients (303 control subjects and 302 study patients) were studied over a mean period of 27 months. Major primary end points (cardiovascular death and nonfatal acute myocardial infarction), secondary end points (including unstable angina, stroke, heart failure and embolisms) and minor end points (stable angina, need for myocardial revascularization, postangioplasty restenosis and thrombophlebitis) were analyzed separately and in combination. RESULTS: When major primary and secondary end points were combined, there were 59 events in control subjects and 14 events in the study patients, showing a risk reduction of 76% (p < 0.0001). When these end points were combined with the minor end points, there were 104 events in control subjects and 68 events in the study patients, giving a risk reduction of 37% (p < 0.005). By observational analysis, only aspirin among the medications appeared to be significantly protective (risk ratio after adjustment for prognosis factors 0.45; 95% confidence interval 0.25 to 0.80). CONCLUSIONS: These data show a protective effect of the Mediterranean diet. However, the risk reduction varied depending on the type of end point considered. Our hypothesis is that different pathogenetic mechanisms were responsible for the development of the various complications. It is likely that certain nutriments characteristic of the Mediterranean diet (omega-3 fatty acids, oleic acid antioxidant vitamins) have specific cardioprotective effects.

Effects of dietary supplementation with alpha-tocopherol on myocardial infarct size and ventricular arrhythmias in a dog model of ischemia-reperfusion.

OBJECTIVES: We investigated whether dietary supplementation with the antioxidant vitamin alpha-tocopherol (500 mg daily) might reduce lethal ventricular arrhythmias and infarct size. BACKGROUND: Previous studies suggested that dietary supplementation with alpha-tocopherol may be associated with a reduced risk of ischemic heart disease. However, the mechanism of this protection remains unknown. METHODS: Beagle dogs were randomized to either a supplemented or a control group. Because of the low mortality rate in the supplemented group, five dogs were added to the control group. After 2 months, dogs were anesthetized and underwent a 2-h coronary artery occlusion and 6-h reperfusion. Plasma vitamin E, retinol and malondialdehyde concentrations were assessed in all dogs. RESULTS: Fourteen dogs (11 of 25 control vs. 3 of 19 supplemented dogs, p < 0.05) developed ventricular fibrillation during either ischemia or reperfusion. Malondialdehyde concentrations were higher in dogs that subsequently developed arrhythmias (2.7 +/- 0.2 mumol/liter, mean +/- SEM) compared with dogs that did not (2.1 +/- 0.2 mumol/liter, p = 0.03). Among survivors with significant ischemia, infarct size was larger in supplemented (n = 12, 58.5 +/- 3.3% of area at risk) than in control (n = 11, 41.9 +/- 6.5%, p < 0.04) dogs. In addition, for a given collateral flow, supplemented dogs (n = 16) developed larger infarct size than control dogs (n = 15, p < 0.001, analysis of covariance). CONCLUSIONS: The data suggest that dietary alpha-tocopherol supplementation prevented lethal ventricular arrhythmias associated with ischemia and reperfusion. However, its influence on infarct size and long-term prognosis warrants further investigation.

Regional myocardial energetics during brief periods of coronary occlusion and reperfusion: Comparison with S-T segment changes.

In open-chest dogs transient occlusion of the left anterior descending coronary artery induced an immediate decline in the creatine phosphate content of the ischaemic area, a lesser decline of the ATP and total adenine nucleotide contents and a rise in S-T segments. Reperfusion after 15 min restored creatine phosphate level and intramyocardial electrograms to normal whereas ATP and total adenine nucleotide levels stayed down. None of these parameters were modified in the nonischaemic area during the experiments. This study shows that there is no close relationship between electrical and biochemical events during either ischaemia or reflow.

Cretan Mediterranean diet for prevention of coronary heart disease.

As a result of the Seven Countries Study, the Mediterranean diet has been popularized as a healthy diet. Nevertheless, it has not replaced the prudent diet commonly prescribed to coronary patients. Recently, we completed a secondary, randomized, prospective prevention trial in 605 patients recovering from myocardial infarction in which we compared an adaptation of the Cretan Mediterranean diet with the usual prescribed diet. After a mean follow-up period of 27 mo, recurrent myocardial infarction, all cardiovascular events, and cardiac and total death were significantly decreased by > 70% in the group consuming the Mediterranean diet. These protective effects were not related to serum concentrations of total, low-density-lipoprotein (LDL), or high-density-lipoprotein (HDL) cholesterol. In contrast, protective effects were related to changes observed in plasma fatty acids: an increase in n-3 fatty acids and oleic acid and a decrease in linoleic acid that resulted from higher intakes of linolenic and oleic acids, but lower intakes of saturated fatty acids and linoleic acid. In addition, higher plasma concentrations of antioxidant vitamins C and E were observed. We conclude that a Cretan Mediterranean diet adapted to a Western population protected against coronary heart disease much more efficiently than did the prudent diet. Thus, it appears that the favorable life expectancy of the Cretans could be largely due to their diet.

Thiopurine S-methyltransferase gene polymorphism is predictive of azathioprine-induced myelosuppression in heart transplant recipients.

Azathioprine (AZA) is metabolized via the cytosolic enzyme thiopurine S-methyltransferase (TPMT). TPMT activity exhibits genetic polymorphism with four prevalent (75%) mutant alleles TPMT*2 (G238C) and TPMT*3 (A719G and/or G460A) and a wild-type allele TPMT*1. To test the hypothesis that presence of these mutations is associated with greater toxicity of AZA in heart transplant recipients, 30 consecutive patients treated with AZA were followed up for the first month after heart transplant. Mutation of TPMT gene (mutation-specific polymerase chain reaction-based methods) was observed in four patients (A719G: n = 2; A719G plus G460: n = 2). Agranulocytosis did not occur in patients with the wild genotype. It occurred in the two patients with mutation A719G and there was a 40% drop in neutrophils in the two other patients. Discontinuation of AZA in the four mutant patients corrected for the drop. Presence of TPMT mutations is associated with a greater likelihood of agranulocytosis. Determination of these mutations could reduce the risk for hematological side-effects.

Quantitation of reperfused myocardial infarction by Gd-DOTA-enhanced magnetic resonance imaging. An experimental study.

Because there is evidence that myocardial infarct size is modified by coronary artery reperfusion, an ex vivo experimental model of myocardial infarction was developed to determine the influence of the timing of gadolinium-tetraazacyclododecane tetraacetic acid (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) on the accuracy of infarct size quantitation. Eighteen dogs underwent a 2-hour coronary occlusion followed by 1 (n = 6), 6 (n = 6), or 48 (n = 6) hours of reperfusion. Gd-DOTA was injected 10 minutes before the dogs were killed. T1 (SE 250/26) and T2 (SE 1500/78) weighted images were performed on excised hearts. Gd-DOTA concentration was measured in myocardium by atomic emission spectrometry, and correlated with myocardial blood flow evaluated by radioactive microspheres. All dogs presented with myocardial infarction (mean size 20.4% +/- 3.1% of the left ventricle), and a corresponding area of increased signal intensity on T1-weighted MR images. In none of the three groups did the area of high signal intensity correlate with the ischemic area. By contrast, after 6 and 48 hours of reperfusion, the high signal intensity area (17.9% +/- 2.4%) closely matched the area of nonreversible jeopardized tissue (16.4% +/- 2.5%), as determined on tetrazolium-stained heart slices. Although a noreflow phenomenon was observed in the jeopardized tissue, Gd-DOTA concentration was higher in the subendocardial central ischemic zone than in normally perfused myocardium. Gd-DOTA imaging enhancement seems to be the consequence of a delayed clearance of the agent from the injured tissue. Gd-DOTA-enhanced MRI accurately quantitates the size of reperfused myocardial infarction on the ex vivo heart for more than 6 hours after the beginning of reperfusion. It remains to be determined whether the in vitro results obtained here can be applied to assess the myocardial infarct size in vivo.

Effect of dietary cholesterol on low density lipoprotein-receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, and low density lipoprotein receptor-related protein mRNA expression in healthy humans.

We investigated the possibility that dietary cholesterol downregulates the expression of low density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase genes of circulating mononuclear cells in vivo in healthy humans. We also studied the variations of the LDL receptor-related protein (LRP) gene in the same conditions. Dieters (n = 5) were submitted to a 4-d fat restriction (mean cholesterol intake: 6+/-4 mg/d), followed by a 7-d cholesterol (a mean of 791+/-150 mg/d) supplementation. Controls (n = 3) did not change their diet. During fat restriction, serum total and LDL cholesterol decreased significantly (P < 0.05), and LDL receptor and HMG-CoA reductase mRNA copy numbers in mononuclear cells increased by 57 and 147%, respectively (P < 0.05). After reintroducing cholesterol, serum cholesterol was stable whereas LDL receptor and HMG-CoA reductase mRNA decreased by 46 and 72% (P < 0.05) and LRP mRNA increased by 59% (P < 0.005). The changes in LDL receptor and HMG-CoA reductase mRNA abundance were correlated (r = +0.79, P = 0.02) during cholesterol reintroduction as were LDL receptor and LRP mRNA levels, but negatively (r = -0.70, P = 0.05). Also, 70% of the variability in LRP mRNA (P < 0.005) was explained by dietary cholesterol. Thus, the basic mechanisms regulating cellular cholesterol content, the coordinate feedback repression of genes governing the synthesis and uptake of cholesterol, are operating in vivo in humans. However, serum cholesterol did not increase in response to dietary cholesterol, suggesting that these mechanisms may not play as predominant a role as previously believed in the short-term control of serum cholesterol in vivo in humans. A new finding is that LRP gene is also sensitive to dietary cholesterol, suggesting that it may participate in the control of serum cholesterol. Further in vivo studies in humans are warranted to explore the molecular mechanisms of the physiological response to dietary cholesterol in humans.

[The risk of coronary angiography in unstable angina. Survey by the working group of "Functional cardiovascular tests" of the French Society of Cardiology]. / Le risque de la coronarographie dans l'angor instable. Enquête du groupe de travail "Explorations fonctionnelles cardiovasculaires" de la Société française de cardiologie.

Coronary angiography has become a current cardiological investigation in acute coronary insufficiency. A multicentre study was performed by the French Cardiac Society's work group (Pierre Calazel) to define the risk of this investigation. The investigation was performed on 581 patients with unstable angina and the following complications were observed at coronary angiography or during the 48 hours which followed: --16 myocardial infarcts (2,75%); --8 deaths (1,37%), 2 by severe arrhythmias and 6 complicating acute myocardial infarction considered as induced by the coronary angiography. The risk of coronary angiography is higher in unstable angina than in stable angina. The highest risk group are patients with unstable angina after recent infarction. The incidence seems to be related to the severity of the coronary lesions especially those on the main left coronary artery. On the other hand, other factors, such as the period between the onset of pain and coronary angiography and the function of the left ventricle, do not seem to play an important part.

[Oxygen requirements of the myocardium]. / Les besoins en oxygène du myocarde.

Myocardial oxygen consumption (MVO2) is defined by the equation: MVO2 = coronary blood flow x arteriovenous difference in O2 content. The average value for a heart of 300 g is 30 to 35 ml/min. In the absence of physiological variations in the arteriovenous difference in O2 content, MVO2 is related to coronary blood flow and the typical anti-anginal agent is one which prevents or reduces increases in MVO2. MVO2 depends on several factors: 1. intraparietal tension, which depends on intraventricular pressure and volume and in which the oxygen demands of pressure overload are much higher than those of volume overload; 2. contractility or myocardial inotropism: 50 per cent increase in the velocity of left ventricular contraction increases MVO2 by 40 per cent; 3. heart rate; 4. external cardiac work--the work accomplished during the ejection phase; this represents about 15 per cent of the MVO2; 5. the energy of electrical activation; this represents about 0,5 per cent of the MVO2; 6. the oxygen requirements of basal myocardial metabolism which represent about 20 per cent of the MVO2; 7. ventricular relaxation: is a factor to be added to those described above; this consumes about 15 per cent of the total energy of a cardiac beat; it may be increased with Isoproterenol or decreased by increasing the calcium concentration. This mechanism may explain the physiopathological impact of calcium inhibitors in effort angina or angina due to increased MVO2.

[Current etiology of organic mitral insufficiency in adults]. / Etiologies actuelles de l'insuffisance mitrale organique de l'adulte.

Between 1976 and 1981, 173 patients with severe symptomatic mitral incompetence were referred for preoperative assessment. The etiological diagnosis was based on echocardiography, catheterisation, angiography, and, in the 71 patients operated on, the surgical findings. Rheumatic valvular disease was demonstrated in 40 cases (23,1 p. 100), bacterial endocarditis in II cases (6,3 p. 100), myocardial disease in 30 cases (17,3 p. 100) including 19 cases of mitral incompetence during cardiomyopathy with dilatation, and II cases of mitral incompetence during hypertrophic obstructive cardiomyopathy: ischemic heart disease was the underlying cause in 27 patients (15,6 p. 100), congenital heart disease in 9 patients (5,3 p. 100); dystrophic valvular disease (mitral valve prolapse with or without chordal rupture) was detected in 56 cases (32,3 p. 100). These results show a continuing reduction in the incidence of rheumatic fever and an increase in the number of cases of dystrophic mitral valve disease in patients of 50 to 70 years of age, a condition often rapidly progressive with hemodynamic characteristics very similar to those of mitral incompetence observed in ischemic heart diseases.

[Prognosis of primary non-obstructive cardiomyopathies]. / Etude pronostique des myocardiopathies primitives non obstructives.

The prognosis of congestive cardiomyopathy was studied in 132 consecutive patients (110 male, 22 female, average age 45 +/- 11 years) in whom a thorough clinical evaluation had excluded a secondary cause. The patients presented with left ventricular failure, a history of systemic embolism, syncope or radiological cardiomegaly. Right (100 p. 100) and left (81 p. 100) heart catheterisation was performed and left ventricular endiastolic volumes (202 +/- 77 ml/m2) and ejection fractions (31 +/- 12 p. 100) calculated from angiography in the 30 degrees right anterior oblique projection. Regional abnormalities of contraction were observed in 32 patients. The average follow up period was 40,4 +/- 23,8 months. At the end of the study 48 patients (37 p. 100) had died and 2 had been lost to follow up. Survival rates were calculated by actuarial methods. Age, sex, the period they had been symptomatic, alcoholic intoxication and the degree of cardiac dilatation were not significant prognostic factors. Patients in Class IV NYHA had the worst prognosis: 63 p. 100 2 year mortality. Atrioventricular conduction defects were observed in 56 patients and were associated with a significantly increased mortality rate (43 p. 100 compared with 23 p. 100, p < 0.001). Atrial fibrillation (32 patients) was a better prognostic factor than the persistence of sinus rhythm; 2 year mortality 11,1 p. 100 compared to 37,6 p. 100 (p < 0.001). Increased left ventricular end diastolic pressures greater than 20 mmHg were related with a mortality of 51,5 p. 100. Also, the patients with a ejection fraction of 30 p. 100 and a 2 year mortality rate of 44 p. 100 compared to 17,5 p. 100 when the ejection fraction was greater than 30 p. 100 (p < 0,001). In conclusion : 1. Regional abnormalities of left ventricular contraction are not rare in primary cardiomyopathy. 2. The prognosis is directly related to the degree of cardiac failure and the extent of left ventricular dysfunction.

[Treatment with angiotension converting enzyme inhibitors]. / Traitement par les inhibiteurs de l'enzyme de conversion.

Eight randomised clinical trials of angiotensin converting enzyme (ACE) inhibitors versus placebo in myocardial infarction have been published in three years, including over 100,000 patients. High risk myocardial infarction carries a poor prognosis with a 25% death rate at 42 months in SAVE, 23% at 15 months in AIRE and 42% at 37 months in TRACE. This form of myocardial infarction benefits the most from treatment with ACE inhibitors: the relative reductions in risk for the previously mentioned trials were 19%, 27% and 22% respectively, and the absolute reductions in risk of death were 4% at 42 months, 6% at 15 months and 8% at 37 months, respectively. Studies including all forms of myocardial infarction involve populations at lower risk. The effects of ACE inhibitors on mortality are then less obvious: from 7.7% to 7.2% at 5 weeks in ISIS-4, from 7.1% to 6.3% at 6 weeks in GISSI-3, from 9.6% to 9.0% at 4 weeks in CCS-1, corresponding to relative reductions in the risk of death of 7%, 12% and 3% respectively and absolute reductions of the risk of death of 0.5% at 5 weeks, 0.8% at 6 weeks and 0.6% at 4 weeks, respectively. Who should be treated? All patients for 4 to 6 weeks or only high risk patients. When should treatment be started? Some investigators institute treatment from the first day but others think it prudent to wait until the second day. For how long? Four to 6 weeks would be sufficient to counteract ventricular remodelling while the benefits are sustained in the long term. But treatment should be continued long term in high risk patients. Which molecule, which dose and how many times, should it be taken per day? The logical answer is molecules with proven efficacy at the dose given in the clinical trials respecting the number of times indicated per day.