Truncating mutations on myofibrillar myopathies causing genes as prevalent molecular explanations on patients with dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. More than 40 genes have been reported to cause DCM. To provide new insights into the pathophysiology of dilated cardiomyopathy, a next-generation sequencing (NGS) workflow based on a panel of 48 cardiomyopathies-causing genes was used to analyze a cohort of 222 DCM patients. Truncating variants were detected on 63 unrelated DCM cases (28.4%). Most of them were identified, as expected, on TTN (29 DCM probands), but truncating variants were also identified on myofibrillar myopathies causing genes in 17 DCM patients (7.7% of the DCM cohort): 10 variations on FLNC and 7 variations on BAG3 . This study confirms that truncating variants on myofibrillar myopathies causing genes are frequently associated with dilated cardiomyopathies and also suggest that FLNC mutations could be considered as a common cause of dilated cardiomyopathy. Molecular approaches that would allow to detect systematically truncating variants in FLNC and BAG3 into genetic testing should significantly increase test sensitivity, thereby allowing earlier diagnosis and therapeutic intervention for many patients with dilated cardiomyopathy.

A spatialized assessment of ecosystem service relationships in a multifunctional agroforestry landscape of Senegal.

Agroforestry systems are an integral part of Sub-Saharan agricultural landscapes. Studies conducted at tree or plot scales on the supply of ecosystem services (ES) suggest that agroforestry practices are a promising way to build multifunctional agricultural landscapes. However, the current characterization and understanding of how multiple ES are associated across such heterogeneous agricultural landscapes are still limited. This study provides the first characterization of the multiple ESs supplied by a Sahelian Faidherbia albida agroforestry parkland and their relationships. Relying on field data for 11 ES indicators, recent advances in remote sensing-derived information, and blending different ES mapping approaches, we first assessed the spatial heterogeneity of the supply of each ES. We found that the majority of ES indicators remained below ES potential values over the study area by 25 % to 50 %, revealing that there is a considerable scope for increasing the ES supply in the F. albida parkland. Then, using a scoring approach, we analyzed the supply of multiple ESs. We observed a large number of hotspots and a clear effect of the proximity of F. albida trees fostering the supply of multiple ESs in their vicinity. Finally, we mapped and analyzed the dominant relationships - trade-offs, synergies or losses - between ESs from a cooccurrence spatial approach. We showed that significant trade-offs and losses (58 % of the area) between ESs can exist in the F. albida parkland. Interestingly, we also showed that synergies occurred mainly up to 10 m from the F. albida trees, suggesting that synergies need to be increased beyond this threshold. By adopting an original ES valuation framework, we provided basic insights into ESs and their relationships. The different maps and information generated can support public debates and target new policies fostering the multifunctionality of F. albida parklands as well as in various other parklands of West Africa.

Management of spontaneous coronary artery dissection: review of the literature and discussion based on a series of 12 young women with acute coronary syndrome.

Spontaneous coronary artery dissection (SCAD) is a rare pathology, principally affecting young women free of atheroma risk factors. Its physiopathology remains little understood, and the prognosis for such acute coronary syndromes is poor, as they occur suddenly. Management is often difficult, and no guidelines exist. The present single-center retrospective study concerns 12 cases of SCAD occurring between 2001 and 2008 in female patients under the age of 60. Eleven patients survived, with a favorable long-term evolution. Only 2 had conservative medical therapy, the other 10 undergoing percutaneous coronary intervention (2 procedures involving a coronary artery bypass graft). On the basis of this series and data from the literature, we suggest a strategy to improve the often dire prognosis of SCAD. Emergency angiography to confirm diagnosis is essential. Treatment should be guided by the extent of the lesions, the myocardial ischemia and the hemodynamic status. Conservative medical therapy is a reasonable approach in the case of distal dissection or conserved coronary flow. Percutaneous coronary intervention is feasible in the acute phase to restore coronary perfusion and hemodynamic stability. Surgery - emergency bypass or assisted circulation - should be restricted to cases where percutaneous coronary intervention has failed or is impossible.

[Evaluation of a dysphonic population. Interest of a therapeutic team composed by the phoniatrician and the speech therapist]. / Evaluation d'une population de dysphoniques suivis en équipe phoniatrie/orthophonie.

PURPOSE: To evaluate a population of dysphonic treated in rehabilitation by comparing the VHI score and GRB scale. MATERIALS AND METHODS: 300 questionnaires were completed, only 42 cases were matched before and after 15 rehabilitation sessions; that is 84 questionnaires. Patients were divided into two groups: group 1 (impaired mobility of the vocal cords), group 2 (benign mucosal lesions). All patients completed a VHI questionnaire, a questionnaire evaluating subjective voice abuse (SSVS), a GRB score. The two tests were correlated to the diagnosis of voice pathology but also used for follow up after voice therapy. The tests used for statistical studies were: comparison by pathology by unpaired series tests (theoretical deviation=0); mean tests, Wilcoxon type. RESULTS: Patients were more handicapped by impaired mobility of the vocal cord than by a nodule or a cyst. The patients' vocal handicap (VHI) was significantly lower after 15 therapy sessions, in all of its components. The perceptual evaluation GRB is also significantly better for these patients after 15 therapy sessions. We could not demonstrate a favorable evolution, that is a diminution of the SSVS before and after 15 sessions. CONCLUSION: The efficacy of speech therapy for certain vocal cord pathologies has been demonstrated both in respect of the Vocal Handicap felt by the patient as well as the Hirano scale.

Validated, stability-indicated quantitative purity test for triethylenetetramine tetrachlorhydrate by automated multiple development.

There is a monography of Triethylenetetramine dichlorhydrate (Trientine) in the United States Pharmacopeia. But neither the base nor the salts di- or tetra-chlorhydrate are in the European Pharmacopeia. Triethylène tetramine tetrachlorhydrate, used by AGEPS now as matural, is more soluble then triethylene tetramine dichlorhydrate. It is administred to patients with Wilson's disease, which results from a congenital lack of the copper metabolism. A quantitative purity test of this drug by automated multiple development high-performance thin-layer chromatography is developed and validated. The validation parameters tested are specifically characterized by retention factor, linearity, limits of detection and quantitation of several nanograms, reliability, and accuracy. To determine impurities, the monography of triethylenetetramine dichlorhydrate in the American Pharmacopeia is tested. This method in classic developing tank requires two mobile phases and is not quantitative. Assays in high-performance liquid chromatography with a different column and mobile phase did not give good results for the separation of impurities. Thus, it is not possible to perform comparative validation of the separation of the impurities. Only the assay of triethylenetetramine with potentiometer detection has been validated.

[The Williams-Beuren syndrome: reconstruction of the thoracic aorta combining surgery and endovascular treatment]. / Syndrome de Williams-Beuren: reconstruction étendue de l'aorte thoracique combinant chirurgie et traitement percutané

The Williams-Beuren syndrome is the association of elf-like facies, mental retardation with cardiovascular anomalies, the most common of which is supravalvular aortic stenosis. This lesion may be focal or associated with hypoplasia of the distal aorta. The treatment is surgical and the role of interventional cardiological treatment is poorly defined. The authors report the case of a child with typical Williams-Beuren syndrome. An initial, very localised surgical aortic repair was performed at 3 months of age for a discrete supravalvular aortic stenosis. Two months later, a second operation was required for a new stenosis of the distal anastomosis associated with marked hypoplasia of the aortic arch. The progressive constitution of an isthmic coarctation led to the percutaneous implantation of a stent followed by two balloon dilatations. Only the first two endoluminal procedures successfully reduced the transisthmic pressure gradient. An antihypertensive treatment was given and regular echocardiography allows monitoring of the adaptation of the left ventricle.

[Kawasaki disease is also a disease of adults: report of six cases]. / La maladie de Kawasaki est aussi une maladie de l'adulte: a propos de six observations.

Kawasaki disease is an inflammatory arterial disease of unknown cause usually affecting young children, the principal complication of which is coronary artery aneurysm. Early treatment with immunoglobulins and aspirin prevents this complication. The diagnosis requires expert clinical criteria and, in atypical forms, a more recent decisional diagnostic tree has to be used. The authors report 6 cases of adult Kawasaki disease. As in the other sixty or so cases in the literature, hepatic forms were the commonest (5/6). Only three of the six cases met the classical clinical criteria and the diagnosis was made by the decisional tree or after coronary complications in the oldest subject. The five treated patients progressed favourably after a course of immunoglobulins. Echocardiography detected 100% of children with coronary disease but it was more difficult in adults in whom new non-invasive methods of coronary imaging (fast CT and MRI) and stress testing should complete the investigations. The association of prolonged pyrexia, clinical criteria and a biological inflammatory syndrome should, after exclusion of the differential diagnoses, suggest a diagnosis of Kawasaki disease in the adult as in the child. The possibility of coronary disease, even though extremely rare, should be recognised by the cardiologist and lead to diagnostic and therapeutic managements as aggressive as in children.

[Implantation of mechanical pulmonary and tricuspid valve prostheses at a distance from complete repair of Tetralogy of Fallot]. / Implantation de deux prothèses mécaniques, pulmonaire et tricuspide, à distance d'une réparation complète de tétralogie de Fallot.

The authors report the case of a 39 years old woman operated for tetralogy of Fallot at the age of 6. Multiple complications due to postoperative atrioventricular block and a poor surgical result on the pulmonary outflow tract led to several reoperations. Right ventricular dysfunction with pulmonary regurgitation and mitral tricuspid valve disease in a context of endocarditis on the pacing catheter led to double pulmonary and tricuspid valve replacement with mechanical prostheses. The outcome at follow-up at 3 years is good. To the authors' knowledge, this is the first reported case of double mechanical valve replacement of the right heart after complete repair of tetralogy of Fallot.

[Idiopathic intrahepatic portosytemic shunts in 4 children]. / Anastomoses portosystémiques intrahépatiques idiopathiques: à propos de 4 observations.

Intrahepatic portosystemic anastomoses are macroscopic communications between the venous portal system and the systemic circulation and located partly in the liver. We report 4 new cases of type II shunts, which illustrate the circumstances of the diagnosis of these exceptional anomalies. For 2 children, the diagnosis was done antenataly by US and spontaneous involution in a few months was observed. In the third case the malformation was evidenced fortuitously at 3 weeks of life, and this 6-year-old child remains completely asymptomatic so far. Then, in the fourth case, a cerebral venous thrombosis was fortuitously and antenatally evidenced in an otherwise uneventful pregnancy and portosystemic shunt was demonstrated postnataly in the extensive work up of the neonate.

[Sudden transformation of pulmonary stenosis to trilogy of Fallot in a 65 year old patient]. / Transformation brutale d'un rétrécissement pulmonaire en trilogie de Fallot à 65 ans. Traitement par cathétérisme interventionnel.

The authors report the case of a 64 year old woman with typical valvular pulmonary stenosis in whom spontaneous and sudden reopening of the foramen ovale resulted in cyanosis. Transthoracic echocardiography with injection of contrast provides a complete diagnosis: valvular pulmonary stenosis with a mean pressure gradient of 83 mmHg and massive right-to-left interatrial shunt. The malformation was treated by interventional catheterisation in a two-stage procedure: pulmonary valvuloplasty followed by closure of the foramen ovale because of the persistence of a right-to-left interatrial shunt. The functional improvement was followed by the appearance of effort angina. Coronary angiography showed single vessel disease of the left anterior descending artery treated by stenting. The long-term outcome was satisfactory.

[Non infectious endocarditis: retrospective study (6 cases)]. / Endocardites non infectieuses: étude rétrospective (6 cas).

PURPOSE: If there is cardiac valve vegetation and the blood cultures are negatives we need to look for slow growing bacteria, fungi, Legionella pneumophilia, Bartonella henselae and quintana, Brucella melitensis and abortus, Coxiella burneti, Chlamydiae pneumoniae by serologic tests. The diagnosis of non- infectious endocarditis could be considered only if these results were negative. The main purpose of this study was to describe the clinical and echocardiographic signs of non-infectious endocarditis cases observed in two different wards. METHODS: This study was done retrospectively during a five-year period in a cardiology and an internal medicine wards. The selection criteria are: the proof of at least one cardiac valve vegetation, observed on echocardiography, negative blood cultures and negative serologic tests as described above. RESULTS: Six non-bacterial endocarditis were described. Four Libman-Sacks endocarditis, two associated with a primary antiphospholipid syndrome revealed by an acute ischemia of leg for one patient and by an eclampsia for another and the other two associated with a systemic lupus erythematous revealed by fever for one patient and by neurologic symptoms for the other. One fibroblastic endocarditis associated to an essential hypereosinophilia and one marastic endocarditis associated to a metastatic mucin-producing cancer. CONCLUSIONS: For these six cases, a complete physical examination, a CBC for hypereosinophylia, a dosage of antiphospholipid antibodies and a thoraco-abdominal CT-scan allowed the etiologic diagnosis of non infectious endocarditis. Libman Sacks endocarditis associated with an antiphospholipid syndrome is the main etiology for which a long-term anticoagulation treatment was not followed.

Effects of caffeine on carotid sinus nerve chemosensory discharge in kittens and cats.

Caffeine (C) decreases apneic episodes in premature infants and is thought to stimulate breathing mainly by a central mechanism. While the methylxanthines theophylline and aminophylline are known to alter the carotid chemoreceptor activity, there are little data on C. The aim of the study was to examine the effects of C on the carotid sinus nerve discharge (CSND) in developing animals. Nine kittens 17-21 days old and six adult cats that were anesthetized and artificially ventilated were studied. They received four consecutive doses of C, each of 10 mg/kg, administered at intervals of 20 min either as intravenous bolus injection (6 kittens, 3 cats) or continuous infusion (3 kittens, 3 cats). Bolus injections of C invariably induced a prompt but transient increase in the CSND from 4.1 +/- 0.6 to 8.1 +/- 1.0 (SE) impulses/s in kittens (P = 0.01) and form 3.9 +/- 0.1 to 7.9 to 1.0 impulses/s in cats (after the first injection). This response was associated with a significant decrease in arterial blood pressure. Continuous infusion of C did not induce any early change in either CSND or blood pressure in kittens or cats. Fifteen minutes after C injection or infusion was begun, CSND values in air, 8% O2-balance N2, or 100% O2 were not significantly different from control. Haloperidol administered at the end of the experiment in four cats and four kittens significantly increased CSND and did not suppress the early response to C injection. It is concluded that caffeine administered by bolus in the kitten induces a transient stimulation of the CSND that is associated with a decrease in the arterial blood pressure and is independent of the dopaminergic mechanisms in the carotid body. The lack of sustained effect implies the main mechanism to the ventilatory stimulation by C must be central.

Expression of dopamine D1-receptor mRNA in the carotid body of adult rabbits, cats and rats.

Dopamine is a major neurotransmitter in the carotid body of several animal species and its functional role at the level of peripheral arterial chemoreflex pathway is attributed to the presence of the dopamine D2-receptors. We present evidence that the dopamine D1-receptor mRNA is also expressed in the carotid body of adult rabbits, cats and rats. A DNA fragment of 611 bp of this receptor was first isolated from rabbit. The nucleic acid sequence of this fragment was found to be 84.5% identical to that of rat. This specific 611 bp fragment was used as a probe to detect, either by Northern analysis or by the reverse transcription-polymerase chain reaction, the dopamine D1-receptor mRNA. The results revealed the presence of dopamine D1-receptor transcript in the carotid body as well as in the petrosal ganglion and the superior cervical ganglion from the three animal models studied here. The physiological significance of dopamine D1-receptor expression in the carotid body is discussed.

Non-infectious interstitial alveolitis and foreign body pulmonary vasculitis in a child treated for acute lymphoblastic leukemia.

We report a case of a 14-month-old girl who was treated for acute lymphoblastic leukemia but died from interstitial alveolitis associated with foreign body vasculitis. This respiratory complication arose 3 months after an allogenic bone marrow transplant. No infectious agents (bacteria, virus, or parasite) were isolated from bronchial or lung tissue samples. Respiratory complications after chemotherapy are reviewed as well as the potential origin of the intravascular foreign body.

A new spectrofluorimetric microdetermination of nitrite in water after derivatization with 4-methyl-7-aminocoumarin.

A method for analysing traces of nitrites is described. The method is based on the diazotization of a heteroaromatic primary amine-4-methyl-7-aminocoumarin (Coumarin 120((R)))-by nitrite ions in acidic medium. A large excess of Coumarin 120((R)) is mandatory for a quantitative reaction. The corresponding in-situ-produced diazonium salt is stable at room temperature and can be selectively isolated in the aqueous layer by extraction of the excess of unreacted Coumarin 120((R)) with ethyl acetate. The hydrolysis of the diazonium salt at 100 degrees C yields a fluorescent product, 4-methyl-7-hydroxycoumarin (4-methylumbelliferone), which is measured by direct spectrofluorimetry (lambda(ex) = 325 nm; lambda(em) = 380 nm). In this way levels of nitrites in water samples as low as 10 mug 1(-1) can be easily quantified.

[Congenital aortic stenosis in the adult]. / Rétrécissement aortique congénital de l'adulte.

Congenital aortic stenosis is a common pathology in adults. The valvular lesion, usually secondary to a bicuspid valve, is dominant. Dilatation of the ascending aorta, the result of a jet lesion or structural wall abnormalities, is often observed in association with the valvular stenosis. Subvalvular stenosis is progressive and may only present late, after surgery of another congenital lesion. Supravalvular stenosis is much less common and is usually diagnosed in a dysgenetic context. Echocardiography is usually diagnostic and enables quantification of the stenosis and evaluation of secondary left ventricular changes. Exercise stress testing is decisional in asymptomatic severe stenosis. Percutaneous valvuloplasty is a good palliative procedure. Other surgical techniques comprise valvular commissurotomy, supravalvular valvuloplasty, valvular replacement (autograft, homo- or heterograft or mechanical prostheses). The indications depend on the quantification of the stenosis, symptoms, the results of exercise testing, the valvular lesion secondary to subaortic stenosis and the progression of the aneurysm of the ascending aorta.

[Ventricular septal defect of the neonate]. / Communication interventriculaire du nourrisson.

Ventricular septal defect is the commonest congenital cardiac lesion and represents 30-40% of all congenital heart disease with a prevalence of 1.8 to 6.5 per 1000 births. The aim of this study was to evaluate the outcome of neonates with ventricular septal defects and to deduce from the echocardiographic appearances in the first year of life a relationship between the initial anatomy and the outcome. Between January 2001 and July 2003, 89 children from the Auvergne region were followed up prospectively for an average period of 7.6 months. The study showed that the majority of muscular ventricular septal defects with a diameter of 3 mm and less progress to a reduction in size and spontaneous closure more commonly and at an earlier stage than perimembranous ventricular septal defects.

[Double aortic and mitral valve replacement in an 18 year old patient with Hunter's disease]. / Double remplacement valvulaire aortique et mitral chez un patient de 18 ans atteint d'une maladie de Hunter.

Hunter's disease, a type II mucoplysaccharidosis, a disease of lysosomal overload, may cause cardiovascular disease. This mainly affects the valves of the left heart which are infiltrated, and results in regurgitation rather than stenosis of the aortic and mitral valves. The general context of this disease explains the fact that only one case of mitral valve replacement was found in a review of the literature. The authors report the case of a young patient who was very symptomatic because of mitral and aortic regurgitation and who underwent double valve replacement of the aortic and mitral valves with mechanical prostheses at 18 years of age. The skeletal involvement and respiratory function led to much discussion before surgical referral but the indication was finally retained in view of the patient's practically normal intellectual functions. Seven years later, the patient is asymptomatic from the cardiac point of view and has been included in a protocol of enzyme therapy.

[Evaluation of a new stress echocardiography technique combining exercise and dobutamine in the detection of coronary disease]. / Evaluation d'une nouvelle technique d'échocardiographie de stress couplant effort et dobutamine dans la détection de la maladie coronaire.

Dobutamine stress echocardiography (DSE) and exercise stress echocardiography (ESE) are widely used for diagnosis of coronary artery disease. Each of these methods has limitations: secondary effects of Dobutamine, poor imaging quality, difficulty in attaining the maximal heart rate. The authors evaluated a test associating pedalling exercise at a constant low load (30-60 watts) with Dobutamine infusion (10-20-30-40 j/Kg/min +/- Atropine) (DES + E) in 42 patients referred for suspected coronary artery disease. All patients underwent coronary angiography on Day 1. There was significant coronary disease (> 50% stenosis) in 19 of the 42 patients. Sensitivity, specificity, negative predictive value, positive predictive value and overall diagnosis value were respectively 84, 87, 84, 87 and 86%. In the first 20 patients, the DES + E was compared directly with DES: There was only one undesirable side effect (hypertension) with DES + E compared with 5 with DES alone. The target heart rate was attained with lower doses of Dobutamine with DES + E (32.35 vs 39.42 j/Kg/min, p = 0.05). DES + E therefore seems to be a promising technique which is better tolerated than DES alone with very satisfactory diagnostic performances. However, these results require further confirmation in larger numbers of patients.