Search PubMed⌕ Search

Biomedical subjects

E Vicaut

Publications and source records attributed to E Vicaut.

At least 37 records · Page 2Linked to original sources

Meta-analysis of randomized clinical trials of colorectal surgery with or without mechanical bowel preparation.

BACKGROUND: Mechanical bowel preparation is used routinely before colorectal surgery, but some randomized clinical trials have suggested that it is of no benefit. This study assesses whether such bowel preparation may safely be omitted before elective colorectal surgery. METHODS: A search of the literature was performed; the inclusion criteria were randomized clinical trials comparing bowel preparation with no preparation in colorectal surgery. The methodological quality of included trials was assessed. The primary outcome was anastomotic leakage; secondary outcomes were other septic complications. The meta-analysis was conducted using the Peto one-step method. RESULTS: Eleven trials were retrieved, of which seven, containing 1454 patients, were included in the meta-analysis. There was no heterogeneity between the trials. Significantly more anastomotic leakage was found after mechanical bowel preparation (5.6 versus 3.2 per cent; odds ratio 1.75 (95 per cent confidence interval 1.05 to 2.90); P = 0.032). All other endpoints (wound infection, other septic complications and non-septic complications) also favoured the no-preparation regimen, but the differences were not statistically significant. Sensitivity analysis showed that these results were similar when trials of poor quality were excluded. Subgroup analysis showed that anastomotic leakage was significantly greater after bowel preparation with polyethylene glycol (PEG) compared with no preparation, but not after other types of preparation. CONCLUSION: There is good evidence to suggest that mechanical bowel preparation using PEG should be omitted before elective colorectal surgery. Other bowel preparations should be evaluated by further large randomized trials.

Colonic Diseases↗

The Coraliance study: non-compliant behavior. Results after a 6-month follow-up of patients on oral contraceptives.

OBJECTIVES: This follow-up study was planned to establish the frequency with which women miss their contraceptive pill, and to observe their behavior when they forget it. In those women who changed from a continuous cycle to an interrupted type of cycle, or vice versa, the study also aimed to evaluate the impact of this change on the pattern of omission of pills. METHODS: The longitudinal, prospective cohort study included healthy women of child-bearing age for whom a change of pill was being prescribed by their gynecologist. Data were recorded during the 6 months preceding inclusion in the study, and for the 6 months of follow-up; the women were asked to complete a diary in which they recorded the number and exact times of pill omission, and their behavior at each omission. RESULTS: A total of 617 gynecologists included 3316 women into the study; of these, a group of 2418 (73%) revisited the same gynecologist at follow-up. The groups who either visited the same or a different gynecologist were similar with respect to age, oral contraception type, omission type and frequency. A large non-compliance rate and women's difficulties in maintaining safe contraception after missing a pill were observed in the group with follow-up. Women were never risk-free when they missed a pill; they turned to numerous sources for discordant or conflicting information; 15% of 'not-forgetting' women at the pre-inclusion cycle recorded at least one omission at the last cycle of the 6-month follow-up period. Omission fluctuations during the observational period make it difficult to designate 'forgetful' or 'non-forgetful' classes of women. Administration of the pill in a continuous cycle, and probably 'study' and 'auto-questionnaire' effects, contributed to an improvement in compliance. In the group taking the continuous cycle pill, the omission number slightly decreased, particularly on the first day and week of the cycle, irrespective of the initial cycle type. CONCLUSIONS: The importance of the phenomenon of non-compliance rate is confirmed as well as women's difficulties in knowing how to maintain contraceptive safety. The continuous cycle regimen is likely to improve women's compliance during the critical period of the cycle.

Adult↗

Lower respiratory tract illness and RSV prophylaxis in very premature infants.

AIMS: To determine the frequency of and the risk factors for readmissions for any lower respiratory tract illness (LRTI) and for respiratory syncytial virus (RSV) documented LRTI in children born very prematurely who had or had not received RSV prophylaxis. METHODS: Multicentre prospective longitudinal cohort study of 2813 infants, born between April 2000 and December 2000 at less than 33 weeks of gestational age, and followed until the end of the epidemic season. RESULTS: Among the 2256 children who had no bronchopulmonary dysplasia at 36 weeks of postmenstrual age and were not submitted to RSV prophylaxis, 27.4% were readmitted at least once for any reason during the epidemic season; 15.1% and 7.2% were readmitted at least once for any LRTI and RSV related LRTI, respectively. Children born at less than 31 weeks' gestation, having an intrauterine growth restriction, or living in a single mother family were at a significantly higher risk of readmission for LRTI in general as well as for RSV related LRTI. Of the 376 children submitted to prophylaxis, 28.2% were readmitted at least once for any LRTI and 6.1% for RSV related LRTI. CONCLUSION: One out of four children who had received no prophylaxis, was born very prematurely, and was without bronchopulmonary dysplasia at 36 weeks of postmenstrual age, was readmitted at least once for any reason. Roughly 50% and 20% of these readmissions were related to a LRTI and an RSV infection, respectively. Further epidemiological studies are warranted to assess the aetiology and impact of other respiratory pathogens on post-discharge readmission and respiratory morbidity in this population.

Antibiotic Prophylaxis↗

Acute release of plasminogen activator inhibitor-1 in ST-segment elevation myocardial infarction predicts mortality.

BACKGROUND: A few studies have suggested that von Willebrand factor (vWF) or plasminogen activator inhibitor-1 (PAI-1) can be associated with outcomes of acute coronary syndromes. The present study was designed to assess the acute release of these markers in ST-segment elevation myocardial infarction (STEMI) and their relations to death. METHODS AND RESULTS: In 153 consecutive patients with STEMI, vWF and PAI-1 antigens were measured on admission (H0) and 24 hours later (H24). At 30 days, the death rate was 7.2%. Heart failure (Killip stage > or =3) on admission was present in 13.7% of patients. The acute release of PAI-1 (H24-H0, in ng/mL) and of vWF (H24-H0, in %) was dramatically higher in patients who died than in those who survived (46.9+/-26.3 versus -0.6+/-2.8 ng/mL, P=0.0001 and 65.8+/-20.0% versus 10.0+/-5.1%, P=0.004 for PAI-1 and vWF, respectively) and in patients developing heart failure compared with those without (24.8+/-10.1 versus -1.1+/-3.3 ng/mL, P=0.004 and 47.3+/-11.0% versus 8.1+/-5.6%, P=0.005 for PAI-1 and vWF, respectively). The release of PAI-1 correlated weakly with the left ventricular ejection fraction (R=-0.195, P=0.01) and the peak of troponin (R=0.149, P=0.045). Postangioplasty TIMI-3 flow and the acute release of PAI-1 were the only 2 independent predictors of death at 30 days. CONCLUSIONS: The acute release of vWF and PAI-1 over the first 24 hours of STEMI is associated with death and heart failure. The acute rise of PAI-1 is also a strong independent predictor of death at 30 days.

Aged↗

Interaction between nitric oxide and prostanoids in arterioles of rat cremaster muscle in vivo.

We studied in vivo interactions of nitric oxide (NO), oxidative stress, and prostanoids derived from the cyclooxygenase pathway in the arterioles studied by intravital microscopy in peripheral muscle. Topical administration of NO synthase (NOS) inhibitor Nomega-nitro-l-arginine (l-NNA) or cyclooxygenase inhibitor mefenamic acid (MA) alone leads to vasoconstriction. We found that l-NNA after MA induced an additional constriction, whereas MA after l-NNA induced a relative dilation. Therefore, an additional constriction was found when MA was administered after l-NNA in the presence of the thromboxane A2 synthase-PGH2 (TP) receptor antagonist SQ-29548. We also found a relative dilation when the TP receptor antagonist was administered after NOS inhibition by l-NNA. In the presence of superoxide dismutase and catalase, l-NNA-induced vasoconstriction is reduced, and the dilation observed after addition of MA in presence of the reactive oxygen species is no longer present. Taken together, these results showed that NO inhibition induced a shift in the synthesis or in the effects of cyclooxygenase products, in favor of constrictor prostanoids. This effect of NO inhibition disappears when reactive oxygen species are scavenged by superoxide dismutase and catalase.

Animals↗

Evaluation of a new non-mydriatic digital camera for detection of diabetic retinopathy.

AIMS: To compare the results of fundus photography using a new non-mydriatic digital camera with the results of reference standard of Early Treatment Diabetic Retinopathy Study (ETDRS) retinal photographs, for the detection of diabetic retinopathy (DR). METHODS: Fundus colour photographs were taken with a Topcon non-mydriatic camera of 147 eyes of 74 diabetic patients, without pupillary dilation (five overlapping fields of 45 degrees; posterior pole, nasal, temporal, superior and inferior). Three retinal specialists classified the photographs in a masked fashion, as showing no DR or mild non-proliferative DR (NPDR) not requiring referral, moderate or more severe NPDR and/or macular oedema, or as non-gradable image requiring referral. ETDRS 35-mm colour slides served as reference images for DR detection. RESULTS: For moderately severe to severe DR, the sensitivities of detection reported by the three observers were 92, 100 and 92%, respectively, and the specificities, 87, 85, and 88%. For four levels of DR severity (none or mild NPDR, moderate NPDR, severe NPDR and proliferative DR), the percentages of exact agreement between the three observers on the retinopathy grades assigned to the non-mydriatic photographs and to the ETDRS reference slides were 94.6, 93 and 87.6%, respectively (kappa 0.60-0.80). Sixteen eyes of nine patients (11%) were judged ungradable by at least one observer. In a second series of 110 patients, evaluated in the setting of a screening procedure, fewer photographs were ungradable (< 6%). CONCLUSION: These results suggest that fundus photographs taken by the Topcon TRC-NW6S non-mydriatic camera, without pupillary dilation, are suitable for DR screening.

Adult↗

Hypertension and the microcirculation.

A large part of the changes in peripheral resistances associated with hypertension involves changes in the microvascular network. From the brief review presented here, it appears that arterioles' functional characteristics are largely modified in hypertension. Sensitivity to numerous vasoconstrictive substances is increased. Local angiotensin-converting enzyme activity is considerably higher. Endothelium-dependent dilation is reduced. Myogenic responses are also amplified by mechanisms dependent on both prostanoids and endothelin. Oxidative stress has been recently demonstrated to be an important pathophysiological mechanism of these alterations. Changes also affect the structure of the microvascular network. Morphological alterations in the arteriolar wall are not observed for all types of hypertension. Conversely, arteriolar and capillary rarefaction appears to be the changes affecting the structure of the microvascular network which are most often found. This led us to consider that the microvascular network should not only be considered as one of the putative mechanisms responsible for increased blood pressure but also as a key target for hypertension. Consequently, hypotensive drugs should also be tested and differentiated as regards their efficiency to prevent or to reverse the microcirculatory damage associated with hypertension.

Antihypertensive Agents↗

Polymorphonuclear leukocyte activation induces cerebral hypoperfusion in rats in the absence of previous ischemia-reperfusion damage.

We determined if activation of circulating neutrophils could influence local cerebral blood flow (lCBF) and cerebrovascular reactivity without previous ischemic endothelial activation. After intracarotid infusion of phorbol myristate acetate (PMA, twice in 30 min), Laser-Doppler measurements of lCBF in the parietal cortex of anesthetised rats showed a fall of 34% (P<0.05) at 30 min, but not in the vehicle group nor the group predepleted in polymorphonuclear leukocytes (PMNLs). Blood gases or arterial pressure did not change significantly in any group. The PMNL count fell by 78% at 30 min and reactivity to systemic hypercapnia by 58% at 30-60 min post infusion in the PMA group. These results show that activated PMNLs reduce lCBF and vasoreactivity in the absence of previous cerebral ischemia.

Animals↗

The fetal mandible: a 2D and 3D sonographic approach to the diagnosis of retrognathia and micrognathia.

OBJECTIVE: To define parameters that enable the objective diagnosis of anomalies of the position and/or size of the fetal mandible in utero. DESIGN: Fetuses at 18-28 gestational weeks were examined by two- and three-dimensional ultrasound. The study included normal fetuses and fetuses with syndromes associated with known mandible pathology: Pierre Robin sequence or complex (n = 8); hemifacial microsomia (Treacher-Collins syndrome, n = 3); postaxial acrofacial dysostosis (n = 1). Fetuses with Down syndrome (n = 8) and cleft lip and palate without Pierre Robin sequence or complex (n = 18) were also studied. Retrognathia was assessed through the measurement of the inferior facial angle, defined on a mid-sagittal view, by the crossing of: 1) the line orthogonal to the vertical part of the forehead at the level of the synostosis of the nasal bones (reference line); 2) the line joining the tip of the mentum and the anterior border of the more protruding lip (profile line). Micrognathia was assessed through the calculation of the mandible width/maxilla width ratio on axial views obtained at the alveolar level. Mandible and maxilla widths were measured 10 mm posteriorly to the anterior osteous border. RESULTS: In normal fetuses, the inferior facial angle was constant over the time span studied. The mean (standard deviation) value of the inferior facial angle was 65.5 (8.13) degree. Consequently, an inferior facial angle value below 49.2 degree (mean - 2 standard deviations) defined retrognathism. All the fetuses with syndromes associated with mandible pathology had inferior facial angle values below the cut-off value. Using 49.2 degree or the rounded-up value of 50 degree as a cut-off point, the inferior facial angle had a sensitivity of 1.0, a specificity of 0.989, a positive predictive value of 0.750 and a negative predictive value of 1.0 to predict retrognathia. In normal fetuses, the mandible width/maxilla width ratio was constant over the time interval studied. The mean (standard deviation) value was 1.017 (0.116). Consequently, a mandible width/maxilla width ratio < 0.785 defined micrognathism. Mandible width/maxilla width ratio values were below this cut-off point in eight and in the normal range in four fetuses with syndromes associated with mandible pathology. CONCLUSIONS: Retrognathia and micrognathia are conditions that can be separately assessed. The use of inferior facial angle and mandible width/maxilla width ratio should help sonographic recognition and characterization of fetal retrognathic and micrognathic mandibles in utero.

Cephalometry↗

Role of nitric oxide and cyclooxygenase pathways in the coronary vascular effects of halothane, isoflurane and desflurane in red blood cell-perfused isolated rabbit hearts.

BACKGROUND: The coronary vascular endothelium could mediate some of the coronary effects of halogenated anaesthetic agents. The role of the endothelial vasodilator substances nitric oxide (NO) and prostaglandins (PGs) in the coronary effects of halothane and isoflurane remains to be determined and has not been investigated for desflurane. In this study, the roles of NO and cyclooxygenase pathways in the coronary effects of halothane, isoflurane and desflurane were studied in isolated red blood cell-perfused rabbit hearts. METHODS: Rabbit hearts were perfused by a Langendorf technique with red blood cells mixed with modified Krebs-Henseleit buffer. Coronary blood flow (CBF), oxygen consumption and myocardial performance were evaluated during exposure to 0.5, 1 and 2 rabbit minimum alveolar concentrations of halothane, desflurane and isoflurane. Thereafter, the same protocol was applied with the addition of N(G)-nitro-L-arginine (L-NNA), indomethacin or a combination of both inhibitors. RESULTS: Similar and significant increases in CBF were observed with increasing concentrations of isoflurane and desflurane. In contrast, CBF did not change with halothane. The combination of the two antagonists abolished desflurane-induced vasodilation, whereas it did not change the isoflurane-mediated increase in CBF. Halothane-induced vasoconstriction was observed in the presence of a combination of indomethacin with L-NNA. CONCLUSIONS: Halothane and desflurane induce the release of vasodilating prostaglandins and NO in rabbit coronary arteries. In contrast, these mediators are not involved in the coronary vasodilating properties of isoflurane.

Anesthetics, Inhalation↗

Oral contraception: patterns of non-compliance. The Coraliance study.

OBJECTIVES: To determine the number of times women failed to take their oral contraceptive medication and their behavior in response to a missed pill. Another objective was to determine the potential benefit provided by a continuously administered oral contraceptive compared with an oral contraceptive involving a pill-free interval during a 6-month period. METHODS: Healthy women were enrolled in a cohort study; their contraceptive practices were followed by their gynecologists. Data were collected at inclusion using cross-sectional method with retrospective data collection for the previous 6 months and, more specifically, on their previous or their current menstrual cycle. Women on the pill were asked to specify the number of times and precise time at which they missed one or more pills and what they did in response to missing a pill. RESULTS: A total of 617 gynecologists enrolled and followed 3316 patients from six geographic areas throughout France. The mean age of patients was 30 years. Duration of oral contraceptive use was 8 years. During their previous cycle, 23% of women (n = 737) missed a pill at least once. Among women on the pill involving a treatment-free interval, 42% of instances of missing a pill occurred during the first week following the treatment-free interval. In response to missing a pill, patients read the product information leaflet (39%) or asked someone's advice (28%), mainly their gynecologist (63%) or their family physician (18%). Almost one-third of women did not take any specific measures. CONCLUSIONS: Patients on a discontinuous oral contraceptive regimen tended to miss a pill during the first week of treatment. Prescription of a continuous regimen without a treatment-free interval may improve compliance.

Adolescent↗

Microcirculation in intestinal villi: a comparison between hemorrhagic and endotoxin shock.

Using intravital microscopy, we studied the effects of hemorrhagic and endotoxin (ETX) shock on the velocity of erythrocytes (red blood cells [RBC]) and the density of perfused villi in mouse small intestine. The mice were divided into four groups: control, normotensive sepsis (a low ETX group, 1.5 mg/kg intravenously), hypotensive sepsis (a high ETX group, 10 mg/kg intravenously), and a hemorrhagic group. One hour after endotoxemia or hemorrhage was induced, mean arterial pressure significantly decreased in the high ETX and hemorrhagic groups (72.5 +/- 1.0 mm Hg in the control group, 71.0 +/- 2.4 in the low ETX group, 42.7 +/- 1.8 in the high ETX group, 43.0 +/- 1.4 in the hemorrhagic group, respectively). We found significant decreases in RBC velocities in the villous tip and capillaries in both ETX groups but not in the hemorrhagic group (in villus tip arteriole, 1.25 +/- 0.02 mm/s, 0.80 +/- 0.02, 0.15 +/- 0.01, 1.20 +/- 0.08; in villus capillaries, 0.55 +/- 0.02, 0.38 +/- 0.02, 0.10 +/- 0.01, 0.61 +/- 0.02, for control, low ETX, high ETX, and hemorrhagic groups, respectively). We also found a significant decrease in the density of RBC-perfused villi in the high ETX and hemorrhagic groups but not in the low ETX or control groups. However, the change in the hemorrhagic group was much less than in the high ETX group (100.0 %, 95.2 +/- 1.6, 32.5 +/- 1.9, 87.3 +/- 3.4, for control, low ETX, high ETX, and hemorrhagic groups, respectively). We concluded that ETX induces a significant decrease in mucosal perfusion characterized by a diminution in RBC velocity and flux in villi found even in a normotensive situation. At a high dose of ETX, these changes are associated with a significant decrease in the number of perfused villi. In addition, we found that at the same level of hypotension, hemodynamics and mucosal perfusion disorders are considerably larger in ETX-induced hypotension than in hemorrhagic hypotension.

Animals↗

The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel.

BACKGROUND: Familial hemiplegic migraine, an autosomal dominant disorder characterized by attacks of transient hemiparesis followed by a migraine headache, is classically divided into pure familial hemiplegic migraine (affecting 80 percent of families) and familial hemiplegic migraine with permanent cerebellar signs (affecting 20 percent of families). Mutations in CACNA1A, which encodes a neuronal calcium channel, are present in 50 percent of families with hemiplegic migraine, including all those with cerebellar signs. We studied the various clinical manifestations associated with mutations in CACNA1A in families with hemiplegic migraine with and without cerebellar signs. METHODS: CACNA1A was analyzed and nine mutations were detected in 15 of 16 probands of families affected by hemiplegic migraine and cerebellar signs, in 2 of 3 subjects with sporadic hemiplegic migraine and cerebellar signs, and in 4 of 12 probands of families affected by pure hemiplegic migraine. Genotyping of probands and relatives identified a total of 117 subjects with mutations whose clinical manifestations were assessed in detail. RESULTS: Eighty-nine percent of the subjects with mutations had attacks of hemiplegic migraine. One third had severe attacks with coma, prolonged hemiplegia, or both, with full recovery. All nine mutations, including five newly identified ones, were missense mutations. Six mutations were associated with hemiplegic migraine and cerebellar signs, and 83 percent of the subjects with these six mutations had nystagmus, ataxia, or both. Three mutations were associated with pure hemiplegic migraine. CONCLUSIONS: Hemiplegic migraine in subjects with mutations in CACNA1A has a broad clinical spectrum. This clinical variability is partially associated with the various types of mutations.

Age of Onset↗

Analysis of retinal and choroidal circulation during central retinal vein occlusion using indocyanine green videoangiography.

OBJECTIVE: To explore the hemodynamic changes and their correlation with clinical presentation during central retinal vein occlusion. MATERIALS AND METHODS: Retrospective, 2-center study. The medical records of 27 patients with central retinal vein occlusion were reviewed. For each patient, the plasma transit in central retinal vessels and in peripapillary choroidal vessels was analyzed using indocyanine green videoangiography. RESULTS: The incidence of alteration in retinal plasma transit, ie, pulsatile filling of arteries and/or veins and increased arteriovenous filling time, was inversely correlated to duration from the onset but not to funduscopic features. Among the 14 patients with less than 1 month's duration of symptoms, 3 developed chronic macular edema, and impairment of arterial flow preceded its onset. Among the 10 patients with opticociliary circulation, choroidal drainage routes were identified in 5 cases, with pulsatile filling in 3. CONCLUSIONS: Early in the course of central retinal vein occlusion, arterial and/or venous flow alterations are present, irrespective of visual acuity, vein dilation, or fundus hemorrhages. These alterations are less frequent in chronic than in recent-onset central retinal vein occlusion. The mechanisms of these alterations remain uncertain but may involve arterial constriction and/or intermittent venous compression. The relationship between these alterations in retinal flow and the secondary onset of macular edema or capillary nonperfusion deserves further investigation.

Adult↗

Reproducibility of retinal mapping using optical coherence tomography.

OBJECTIVE: To assess the reproducibility of retinal thickness measurement using commercially available mapping software of optical coherence tomography (OCT). METHODS: Six radial scans, 6 mm long and centered on the fixation point, were performed on 10 eyes of 10 healthy volunteers and 10 eyes of 10 diabetic patients with clinically significant macular edema. Retinal thickness was measured automatically using the mapping software of OCT in the 9 macular Early Treatment Diabetic Retinopathy Study areas and in a central area 500 microm in diameter. Measurement reproducibility was tested by means of 3 series of scans performed by 2 different observers on 2 different days. Results were assessed by their repeatability and intraclass correlation coefficients (ICCs). RESULTS: In healthy subjects, intraobserver, interobserver, and intervisit reproducibility of retinal thickness measurements were excellent, with a repeatability coefficient of less than 7 microm and ICCs of greater than 0.89. In diabetic patients, the repeatability coefficient was less than 21 microm in all areas of the macula except one, with an ICC of greater than 0.98. Relative variations in measurements were small in both healthy and diabetic subjects, with reproducibilities of +/- 5% and +/- 6%, respectively. CONCLUSION: Retinal mapping software of OCT allows reproducible measurement of retinal thickness in both healthy subjects and diabetic patients with macular edema.

Adult↗

Nonlinear analysis of arterial oscillated flow in experimental stenosis and microsurgical anastomosis.

BACKGROUND: Thrombotic vascular occlusion is one of the main complications that can occur during microsurgical anastomosis and is frequent when the blood becomes turbulent. The aim of this ex vivo study was to test the use of nonlinear mathematical tools to detect turbulence flow upstream and downstream of an arterial stenosis and of a microsurgical anastomosis technique in arteries with diameters in the range of microsurgical practice. MATERIALS AND METHODS: Rat carotid arteries (0.8 to 1.2 mm diameter) were transferred to a flow chamber and perfused with Krebs solution. An oscillated vascular flow was initiated with a peristaltic pump and a transit time flowmeter was used to measure flow with two probes. An arterial stenosis was created by a ligature and progressively increased ranging from 0 to 95%. For each flow signal three nonlinear analytical procedures were applied: time-delayed procedures, correlation dimension, and computing of the largest Lyapunov exponent. RESULTS: Our results indicated that the level of turbulence flow is correlated with the area reduction stenosis. In the range of 60-95% area reduction stenosis, we noted an experimental increase of turbulence flow. We also founded that a classical end-to-end anastomosis technique induced an increase of the turbulence flow in comparison with a control artery. CONCLUSIONS: Thus nonlinear analysis can be useful in characterizing the complexity of an oscillated flow in small arteries submitted to stenosis or microsurgical anastomosis and may have clinical uses in detecting high level turbulent flow after microsurgery.

Anastomosis, Surgical↗

Ambulatory heart failure management in private practice in France.

UNLABELLED: Management of ambulatory heart failure was assessed in a group of 600 patients, mean age 73, 64% males, NYHA I: 9%; II: 52%; III: 33%; IV: 6%; followed up by a representative sample of private cardiologists. Fifty-two percent of patients had been previously hospitalised for worsening heart failure with a mean duration of stay of 13.1 days, for those hospitalised in the year preceding the survey (26%). First diagnosis of heart failure had been performed by a cardiologist (57%), a general practitioner (37%) or another category of physician (6%). Seventy percent of patients received three or more different classes of heart failure medications. Diuretics were prescribed to 71%, angiotensin converting enzyme inhibitors to 54% and digitalis to 35% of the population. Beta-blockers were given to only 14% of the patients. In patients aged over 80 years, only 45% received angiotensin converting enzyme inhibitors. CONCLUSION: This survey of ambulatory heart failure patients confirms that the disease is predominantly observed in elderly patients, and associated with prolonged and recurrent hospitalisations. The underuse of recommended therapeutic classes including angiotensin converting enzyme inhibitors and beta-blockers deserves further investigation.

Age Distribution↗

Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide.

Tumor necrosis factor (TNF)-alpha increases mitochondrial reactive oxygen species (ROS) production in tumor cells and hepatocytes. However, whether TNF-alpha stimulates mitochondrial ROS production in endothelial cells (EC) has not yet been reported. We studied the effect of TNF-alpha on mitochondrial ROS generation in EC and the signaling pathways involved. Cultured human umbilical vein EC (HUVEC) were studied by fluorescence microscopy, using dichlorodihydrofluorescein diacetate (DCFH-DA) as a marker of ROS production and propidium iodide uptake for cell viability. TNF-alpha increased DCFH oxidation in HUVEC dose-dependently. To determine the source of ROS, the mitochondrial respiratory chain inhibitors rotenone + thenoyltrifluoroacetone (TTFA), which inhibit electron entry to ubiquinone, and antimycin A (AA), a blocker of ubisemiquinone, were used. Rotenone and TTFA inhibited (n = 7, P < 0.05), whereas AA increased (118% in 3 min; n = 4, P < 0.01) ROS generation in HUVEC. In contrast, ROS production was not abolished by the nicotinamide adenine dinucleotide phosphate-dependent oxidase inhibitor diphenylene iodonium, by the xanthine oxidase inhibitor allopurinol, nor by the nitric oxide and cyclooxygenase pathway inhibitors N(omega)-nitro-L-arginine and mefenamic acid. In addition, TNF-alpha-induced ROS production was inhibited by the acidic sphingomyelinase inhibitor desipramine (5 microM; -80%, n = 4, P < 0.01) and totally blocked by the ceramide-activated protein kinase (CAPK) inhibitor dimethylaminopurine (1 mM; n = 6, P < 0.05). Thus, TNF-alpha induces mitochondrial ROS production in HUVEC that primarily occurs at the ubisemiquinone site and is mediated by ceramide-dependent signaling pathways involving CAPK.

Ceramides↗