Showing papers in "Bulletin De L Academie Nationale De Medecine in 2002"

The epidemiology of human cryptosporidiosis

Abstract: Cryptosporidiosis, as an emerging disease, has generated a tremendous amount of research Our purpose is a survey of the epidemiology of this disease, emphasizing: the features of the parasites and the species and genotypes that may infect Man, the most frequent of which is Cryptosporidium parvum and its two genotypes "Cattle" and "Human"; the means of dissemination of the infective stage and of human contamination; the factors that put Man at risk of catching a severe infection; the basis of a suitable control

Vitamin D and pregnancy

Abstract: During pregnancy maternal serum concentrations of 25 hydroxyvitamin D correlate with dietary vitamin D intake. Maternal serum concentrations of 1.25-dihydroxyvitamin D the hormonal circulating and active form of vitamin D are elevated, during pregnancy. 1.25-dihydoxyvitamin D is synthesized mainly by the decidual cells of the placenta and allows for increased calcium absorption. The fetus is entirely dependent on the mother for its supply of 25 (OH) D which is believed to cross easily the placenta. Vitamin D deficiency during pregnancy affects the fetus and the newborn. Birth weight is decreased, bone mineralization is impaired and neonatal hypocalcemia is frequent. In countries where dairy products are not routinely supplemented in vitamin D maternal vitamin D supplementation during pregnancy is necessary.

Trois enseignements de la première allogreffe des deux mains

Abstract: The first double hand transplantation was performed in Lyon in a 33 year-old recipient with bilateral amputation following an explosive handling accident. At 2 years, the global and the functional results were considered as very satisfactory. Three aspects are presented in this article: (1) immunosuppressive protocol was efficient and well tolerated. Only 2 skin rejection episodes on post operative days 53 and 82 were easily reversed with an increase in Prednisone doses and local applications of steroid cream; (2) successive functional magnetic resonance imaging demonstrated a global remodelling of the limb cortical map and a reversal of the functional reorganisation induced by amputation; (3) the psychological appropriation of "alien" hands improved with time. These grafts, permanently visible by the patient and others, induced a psychic defence mechanism: "denial", a lack of perception of some features of reality or a perception of reality that is immediately neglected or rejected. Denial tended to lessen as the new grafted hands gained in sensitivity and motricity.

[Localized prostatic cancer: treatment with laparoscopic radical prostatectomy: study with 841 cases]

Abstract: The authors present their experience in the technique of laparoscopic radical prostatectomy. After 841 operations done from January 1998 to april 2001. They use a trans peritoneal approach with 5 ports of 5 and 10 mm. The prostatectomy is done antegrady and the urethrovesical anastomosis is rebuilt with interrupted 3/0 resorbable sutures. Operating time is 2 hours and 40 minutes (1 h 30 to 6 h 30) Conversion rate is 0.9%, average bleeding is 330 cc and transfusion rate is 2.8%. Bladder catheter is removed between days 3 to 6. hospital stay is 5.8 days. Post-op pain is minimal (2% of antalgics at day 2). There was no death, no embolism, 0.2% of phlebitis, 1.1% of rectal injury. Anstomotic strictures occur in 0.3% of cases. 89.2% of patients are continent after 1 year and 75% of patients under 70 years old who underwent a bilateral nerve sparing procedure were potent at 6 months. Positive margins were observed in 5% of pT2a, 22.5% of pT2b, 22.7% in pT3a and 30% in PT3b. After 2 years 92.5% of patients pT2a and b have a PSA < 0.1 ng/ml. No port seeding or peritoneal invasion by cancer was observed. Laparoscopic radical prostatectomy is a safe surgical procedure which limits the risk of transfusion, of anastomotic stricture, which reduces post op pain and allows a good continence. Potency recovery is promising.

[Orthostatic tolerance after spaceflight or simulated weightlessness by head-down bed-rest].

Abstract: Cardiovascular modifications, specially orthostatic intolerance (OI) are well known after spaceflight or long duration head-down bed-rest (HDBR) There is no agreement about their mechanisms. The aim of the study was to compare OI after a 42 day HDBR (n = 7) and after a 90 to 198 day spaceflight (n = 10). The studies were made during a stand test of 10 minutes for HDBR following 10 min in supine position and 5 min in sitting position. In both groups the variables measured were blood pressure (BP by transcutaneous plethysmography, Finapres) and ECG for RR interval (RRi) determination which allowed us to calculate autonomic indexes by spectral analysis of RRi and to determine spontaneous baroreflex sensitivity. In the cosmonaut group, 1 subject experienced a vaso-vagal syncope and 2 asked to stop the test without a decrease in BP. In HDBR, 4 subjects out of 7 did not perform the whole stand test (1 vaso-vagal syncope, 1 tachycardia and 2 hypotensions). Cosmonauts or HDBR subjects had common profiles: tachycardia and a decrease in parasympathetic index and baroreflex sensitivity. Both groups have an OI (30% of the subjects). However the mechanisms are different even if they have a common postural orthostatic tachycardia syndrome (POTS). The spaceflight duration was not determinant and we have no indice to predict OI which was one of the aims of the study.

[Diagnosis and treatment of disturbances in eating behavior among adolescents: anorexia nervosa and bulimia nervosa].

Abstract: RESUME L’anorexie mentale et la boulimie nerveuse de l’adolescent representent des troubles graves des conduites alimentaires mais elles sont curables. Le medecin responsable intervient pour les traiter en etablissant un contrat. La famille doit etre rassuree parce qu’elle n’est pas responsable.

Incidence des changements climatiques planétaires sur les arboviroses transmises à l'homme par des moustiques et des tiques.

Abstract: Global warming [+0.5-0.6 degree C during the second half of the 20th century] seems a reality although climatologists did not reach a common agreement on its actual origin, and this phenomenon may still increase along the 21st century [+1.5 to 6 degrees C]. Epidemiologists are anxious at the eventual effects of the resulting climate change on the evolution of arbovirus infections transmitted to human beings by hematophagous vectors such as mosquitoes and ticks. Analysis of the literature devoted to this problem did not lead to precise conclusions and the mathematical models used seems insufficient for they take into account mainly the climatic factors and not enough the human ones. Examples of dengue, european tick-borne encephalitis and other arbovirus infections are discussed. Peculiar attention is devoted to the eventual effects of climatic changes on the hibernation process in some small mammals and the timing of bird's migrations, involved in enzootic cycles of arboviruses. It is likely that arbovirus diseases may locally extend, both in latitude and altitude, leading to outbreaks, but regressions may also occur.

[French results of enzyme replacement therapy in Gaucher's disease].

Abstract: Gaucher disease is an inborn recessive autosomal disease due to a partial deficiency of the lysosomal enzyme beta glucocerebrosidase. The deficient activity leads to accumulation of the lipid glucocerebroside in the liver, the spleen and bone marrow with concomitant anemia and thrombocytopenia. Patients with Gaucher disease have been classified in three types: type I is the more common, neurological manifestations occur in types II and III. Enzyme replacement therapy (ERT) with modified placental human glucocerebrosidase (ceredase) or recombinant glucocerebrosidase (cerezyme) is effective in most type I Gaucher disease and has become the current standard care administered to thousand of patients worldwide. ERT has obviated the need for bone marrow transplantation and virtually eliminated the need for splenectomy. We report here the French study including adults and children. ERT of 30 to 60 U/K every two weeks as starting dose was administrated to 108 patients with severe type I Gaucher disease. ERT fully reverse many of the manifestations of the disease. ERT regimen alleviated fatigue, and hematological and visceral signs and symptoms in nearly all severely-ill patients. Skeletal responses to treatment develop much more slowly than hematological or visceral responses. Studies in pediatrics show that the disease is more severe in children. These children should be treated early in the course of their disease to avoid irreparable damage. Hematological manifestation in type II cannot be reversed with enzyme replacement. In type III treatment can rarely reverse neurological deficit. Gaucher disease is also an excellent candidate for gene therapy.

Accidents and illicit drugs

Abstract: RESUME Si, depuis 1958, des efforts tres importants ont ete faits pour lutter contre la conduite sous l’emprise de l’alcool, de tres nombreuses etudes et observations ont montre que le cannabis, la cocaine, les amphetamines et les opiaces etaient, eux aussi, souvent impliques dans la survenue des accidents de la route. Parmi les milieux biologiques accessibles, la salive represente le plus adapte pour mettre en evidence un usage recent de ces substances tandis que le sang est incontestablement le seul milieu biologique utilisable pour la confirmation et la quantification. Des methodes analytiques fiables sont desormais disponibles. Tous les elements sont donc reunis pour mettre en place des actions de prevention, dont des depistages de conduite sous influence. Nos voisins de la Sarre ont donne l’exemple en effectuant des controles tres frequents, et cela s’est traduit par une baisse considerable du nombre de morts et de blesses sur les routes de cette region.

Épidémiologie des infections nosocomiales après opération de la cataracte et rôle du CLIN dans la prévention

Abstract: RESUME Malgre une incidence faible (3 pour 1 000), les endophtalmies compliquant la chirurgie de la cataracte restent preoccupantes car leur pronostic est souvent grave. Le caractere nosocomial est presque toujours present, malgre une origine endogene souvent en cause ; celle-ci est liee a l’acte chirurgical a risque et a l’abondance de la flore commensale cutanee et conjonctivale. Dans ce contexte, les bacteries le plus souvent incriminees sont les staphylocoques a coagulase negative. Des micro-epidemies ont ete decrites a bacille pyocyanique, d’origine exogene. Pour prevenir ces infections nosocomiales, le role du CLIN et de l’equipe operationnelle en hygiene est important par la surveillance des nouveaux cas infectieux et de l’environnement hospitalier ainsi que par la mise en place de protocoles d’hygiene specifiques a la preparation de l’opere et a l’entretien du bloc operatoire.

Données neurobiologiques récentes sur le cannabis

Abstract: RESUME L’inquietante croissance de l’usage du cannabis suscite un regain d’interet pour les mecanismes neurobiologiques qui sous-tendent ses activites diverses et en particulier toxicomaniaques, intrinseques ou croisees avec d’autres drogues, ainsi que sur les mefaits qui en decoulent. On decrit ici les elements qui authentifient chez l’animal une dependance psychique commune a toutes les drogues, une dependance physique, laquelle servait jusqu’a maintenant a qualifier les « drogues dures », effet incitatif que parait exercer le cannabis vis-a-vis de l’usage d’autres drogues, en particulier de l’heroine. Enfin seront envisagees les relations etroites qu’entretient le cannabis avec la schizophrenie. Nombre de ces donnees recentes, loin de relativiser la toxicite psychique du cannabis, soulignent au contraire sa dangerosite potentielle.

[Annual self-assessment of perioperative complications and early success: the best way to improve the medical results in the Vascular Surgery Department].

Abstract: RESUME Malgre d’incessants progres, la chirurgie arterielle expose a des risques peri operatoires qui varient de 1 a 5 % pour les operations conventionnelles et de 0 a 2 % pour les operations endovasculaires. Si certaines complications sont dues aux caracteristiques des maladies atheromateuses et anevrysmales ou sont inherentes a certains types de reconstructions arterielles, d’autres sont equipe-dependantes, puisque leur taux varie d’un centre a un autre. A la base de la qualite des resultats se trouve l’experience d’un chirurgien et de son equipe. Depuis toujours elle est fondee sur l’analyse non quantifiee des succes et des echecs passes. Desormais il faut integrer deux autres parametres : les recommandations consensuelles et les resultats reellement obtenus par chaque equipe. Ces derniers ne sont connus precisement que s’ils sont evalues periodiquement de facon systematique. Nous rapportons ici une experience de 23 annees d’autoevaluations annuelles. Ces autoevaluations ont porte sur toutes les interventions et ont analyse toutes les complications peri-operatoires. Elles ont eu cinq impacts : l’equipe medicale et paramedicale a ete solidarisee dans la quete de l’efficacite optimale ; l’attention de tous les acteurs a ete focalisee sur les procedures a ameliorer ; elles ont ete un guide pour les indications chirurgicales ; elles ont permis d’informer les administrations, les patients et eventuellement la Justice avec des chiffres indiscutables ; enfin elles ont ete un element essentiel de formation continue. Ces autoevaluations ont un role complementaire des conferences de mortalite/morbidite ou sont periodiquement analysees les complications, cas par cas. Elles ne peuvent etre remplacees ni par les recherches scientifiques limitees a des themes particuliers, ni par le PMSI dont l’objectif est davantage economique. Les services hospitaliers publics ou prives qui n’en font pas se privent du principal moyen d’optimiser leurs resultats. Il est souhaitable que l’accreditation imposee par l’ordonnance du24 avril 1996, apres avoir dans un premier temps porte sur des controles deprocedures basiques, se concentre sur tout ce qui peut contribuer a optimiser les resultats : les conferences de mortalite/morbidite, les autoevaluations annuelles des complications peri-operatoires et les etudes de resultats a long terme. Pour des raisons medicales autant qu’economiques, la population est en droit de nous demander d’auto-evaluer nos resultats systematiquement et d’appuyer nos indications sur ces resultats. Il en va de notre credibilite.

Les conséquences des violences conjugales sur la santé des femmes et leur prise en charge en médecine de premier recours

Abstract: RESUME Les violences conjugales faites aux femmes, par leur frequence et leurs consequences sur la sante des victimes, interessent la sante publique. Troubles psychiques et psychosomatiques, traumatiques et gynecologiques, ou encore complications de grossesses desirees ou non en sont les principales consequences, parfois a long terme. Les professionnels de sante, en particulier les generalistes, les urgentistes, les gynecologues, les obstetriciens et les sagefemmes sont en premiere ligne pour depister et prendre en charge ces violences. Pour ce faire, leur information est necessaire, de meme que l’adoption de pratiques professionnelles en partenariat avec les autres intervenants specialises dans la prise en charge des femmes victimes.

Evaluation of the effect of magnetic fields on the secretion of melatonin in humans and rats. Circadian study

Abstract: The consequences of electromagnetic exposure on human health are receiving increasing scientific attention and have become the subject of a vigorous public debate. In the present study we evaluated the effects of magnetic field on pineal function in man and rat. Two groups of Wistar male rats were exposed to 50-Hz magnetic fields of either 1, 10 or 100 microT. The first group was exposed for 12 hours and the second for 30 days (18 hours per day). Short-term exposure depressed both pineal NAT activity and nocturnal serum melatonin concentration but only with the highest intensity used (100 microT). Long-term exposure to a magnetic field significantly depressed the nighttime peak of serum melatonin concentration and pineal NAT activity with 10 and 100 microT. Our results show that sinusoidal magnetic fields altered the production of melatonin through an inhibition of pineal NAT activity. Both duration and intensity of exposure played an important role in this effect. In the second step of this study, thirty-two young men (20-30 years old) were divided into two groups (control group, i.e., sham-exposed: 16 subjects; exposed group: 16 subjects). The subjects were exposed to the magnetic field from 23 h to 08 h (i.e. for 9 h) while lying down. In one experiment the exposure was continuous, in the second one, the magnetic field was intermittent. No significant differences were observed between sham-exposed (control) and exposed men for serum melatonin and 6-sulfatoxymelatonin. In our last and more recent study, we looked for the circadian rhythm of melatonin in 15 men exposed chronically and daily for a period of 1-20 years, in the workplace and at home, to a 50 Hz (exposure 0.1 to > 0.3 microT) magnetic field. The results are compared to those for 15 unexposed men who served as controls. Blood samples were taken hourly from 2000 to 0800. Nighttime urine was also collected and analyzed. This work shows that subjects exposed over a long period (up to 20 years) and on a daily basis to magnetic fields experienced no changes in their plasma melatonin level, their urinary 6-sulfatoxymelatonin level, or the circadian rhythm of melatonin. It thus clearly rebuts the "melatonin hypothesis" that a decrease in plasma melatonin concentration--or a disruption in its secretion--explains the occurrence of, clinical disorders or cancers possibly related to magnetic fields.

[Heart re-synchronization with biventricular stimulation: new treatment for refractory heart failure].

Abstract: Despite continuous progress in drug therapy, many patients are still progressing into advanced heart failure, a very poor condition in terms of quality of life and prognosis. Therapeutic resources are quite limited at that end-stage. Heart transplantation may only be proposed to a small minority of patients. New non-pharmacological alternatives like cellular cardiomyo-plasty or left ventricular (LV) implantable assist device are still under evaluation. So simpler and cheaper approaches have imperatively to be developed for treating this highly invalidated and rapidly growing and ageing population. Cardiac resynchronization therapy (CRT) with multisite biventricular pacing has been initiated in France in early 90's. The aim of CRT is to try and correct the electromechanical abnormalities that result from antrioventricular and intraventricular conduction delay (IVCD), a very common observation (30-50%) in patients with chronic heart failure (CHF). IVCD worsens progressively overtime and is responsible for discoordinated interventricular and left-intraventricular contraction-relaxation which in turn enhances the hemodynamic consequences of the baseline LV systolic dysfunction. This new therapeutic concept was first assessed in acute hemodynamic studies with temporary pacing, then in pilot studies with permanent transvenous biventricular pacing. Several controlled studies (MUSTIC, MIRACLE, CONTAKCD...) were conducted afterwards and demonstrated that CRT might improve significantly symptoms, quality of life and exercise tolerance in patients with severe heart failure (NYHA class III -- IV) under optimized drug treatment, low ejection fraction and significant IVCD as indicated by an intrinsic QRS duration QRS> 150 MS. The rehospitalization rate was also significantly reduced with CRT. The clinical benefit was preserved over at least 1 year follow-up. The first validation stem is now completed. There are however several important questions yet to be answered. Which is the impact of CRT on all-cause mortality and sudden cardiac death? Two large-scale studies, CARE-HF in Europe and COMPANION in USA, are ongoing to try and answer this question. Which type of implantable devices has to be developed preferentially: multisite pacemakers or multisite pacemaker-defibrillators? May CRT induce LV reverse remodelling and thus help at preventing heart failure progression? Which cost-effectiveness ratio for heart faulure management? How to better select potential responders?... The whole validation process of CRT should be completed on 2004-2005.

Génétique et hypertension artérielle : trois approches pour décrypter une maladie complexe

Abstract: Human arterial hypertension is a complex trait, partly determined by genetic factors. From the analysis of familial studies, it has been estimated that approximately 30% of the blood pressure variance within a population was of genetic origin. Three main types of human studies have been undertaken to try to identify susceptibility genes to hypertension. The first one corresponds to the systematic analysis of the so-called candidate genes, i.e. genes encoding proteins, enzymes, receptors, which are known to belong to pathways controlling blood pressure. Up to now, the most interesting results have been obtained on genes encoding the renin angiotensin system, the a adducin, the G protein subunit beta 3, and adrenergic receptors. The genome wide scan approach corresponds to a systematic analysis of evenly spaced markers throughout the genome in sibling pairs or in more complex families. This second strategy has shown that there was not a single locus that was regularly found by several studies, but rather several possible loci which most often have not been replicated from one study to another one. Among those, the long arm of the human chromosome 17 (17q12-q21) is in synteny with a blood pressure locus found in spontaneously hypertensive rats. The third approach, up to now the most successful, corresponds to the identification of major genes involved in rare Mendelian forms of hypertension. For example, genes responsible for Liddle syndrome, glucocorticoid remediable aldosteronism, apparent mineralocorticoid excess have been characterized and have demonstrated the importance of sodium and water homeostasis in blood pressure control.

[Pathogenesis of pre-eclampsia: role of gamma PPAR in trophoblast invasion].

Abstract: Pre-eclampsia is a major complication of human pregnancy. Its trigger is from placental origin and may involve an abnormal placentation characterized by a defect of trophoblast invasion and an absence of remodelling of the maternal spiral arteries. In this study, we have characterized and developed a model of culture of extravillous trophoblast cells involved in human implantation. We showed that these cells expressed high levels of PPAR gamma by immunocytochemistry and real-time quantitative PCR. We showed that different natural ligands potentially present at the feto-maternal interface, such as oxidised low density lipoproteins, inhibited in vitro in a concentration dependent manner extravillous cytotrophoblast invasion. These results point to a key role of PPAR gamma in the pathology of pre-eclampsia.

[Alpha-1-antitrypsin deficiency. Role in skin disorders].

Abstract: Alpha1 antitrypsin (AAT) deficiency is an autosomic codominant inherited disorder characterized by inefficient or non-functional serum AAT. The principal clinical manifestations are panlobular emphysema and cirrhoses. Among cutaneous aspects, about 30 cases of panniculitis have been reported in the literature, likewise rare clinical cases: pemphigus herpetiformis, Muir Torre syndrome, urticaria and angioedema, cutis laxa and Marshall syndrome, lupus erythematosus, psoriasis, vasculitis. Probably because of it's high frequency, numerous others diseases have been reported described in association. Acting on several factors of inflammation, AAT deficiency seems product or modify the expression of some, notably cutaneous diseases.

La place de la dopamine dans les processus de dépendance aux drogues

Abstract: RESUME Des donnees recentes neurobiologiques ont permis de montrer que tous les produits qui declenchent une dependance chez l’homme (amphetamine, cocaine, morphine, heroine, cannabis...) augmentent la liberation de dopamine dans une structure sous-corticale, le noyau accumbens. Ce noyau fait partie d’un ensemble de structures cerebrales, denomme « circuit de la recompense » qui definit a chaque instant l’etat physique et psychique dans lequel se trouve l’individu. Les drogues, en modifiant la cinetique et l’amplitude de la production de dopamine, induisent une sensation de satisfaction. Cette deregulation conduit le toxicomane a memoriser artificiellement les evenements associes a la prise de produit et a en devenir dependant.

Role of dopamine in drug dependence processes

Abstract: Recent neurobiological data have indicated that almost all drugs of abuse (amphetamine, cocaine, morphine, heroin, cannabis...) increase dopamine release in a sub-cortical structure, the nucleus accumbens. This nucleus is part of different cerebral structures, named "reward system" which constantly defines physical and mental states of an individual. Development of addiction would be due to the modification, by drugs of abuse, of the kinetic and the amplitude of dopamine release. Such a dysregulation would induce the addict to artificially memorize any event linked to the product consumption.

[Transfusion medicine in the 2000s, on a reform].

Abstract: RESUME La creation de l’Etablissement francais du sang (EFS) a ete inscrite dans la loi du 1er juillet 1998 relative a la securite sanitaire. L’EFS est un operateur unique de la transfusion sanguine, structure juridique unique, place sous la tutelle du ministre charge de la sante. L’EFS organise sur l’ensemble du territoire les activites de la chaine transfusionnelle, favorise les activites de recherche et participe a la cooperation scientifique internationale. Il peut exercer des activites de biologie medicale et des activites de therapie cellulaire et tissulaire. Dans le cadre du nouveau schema territorial 2000–2004 de la transfusion, l’EFS dispose d’un reseau de 18 etablissements, 14 en metropole, 4 dans les departements d’Outre-Mer (43 dans le precedent schema), qui comprend 18 plateaux techniques de qualification biologique des produits sanguins et 27 de preparation/transformation/stockage. Pour les activites de prelevement et de distribution et dans le respect du principe de proximite vis-a-vis du donneur et du malade, il existe 220 sites sur l’ensemble du territoire. Dans les axes strategiques pour le futur, retenus par l’EFS, il y a la reduction des risques infectieux residuels (apport de la biologie moleculaire), la prevention des risques immunologiques, l’elaboration d’un projet pedagogique pour enseigner autrement la medecine transfusionnelle. Malgre les progres des biotechnologies il faudra attendre encore longtemps pour disposer de produits de substitution a la transfusion sanguine. L’EFS souhaite soutenir 3 poles d’activite: la medecine transfusionnelle, la biologie medicale et l’ingenierie cellulaire. L’EFS avec 18 etablissements et 8 200 personnes doit relever le defi des annees 2000 en s’appuyant sur les progres des biotechnologies.

Dysfonction de la voie du monoxyde d’azote au cours de la régénération de l’endothélium coronarien

Abstract: RESUME Des experiences sur culture de cellules endotheliales d’arteres coronaires de porc ont ete effectuees afin de determiner si le vieillissement per se ou la densite cellulaire affecte l’activite de la NO-synthase endotheliale (eNOS), et explique la diminution de la relaxation endothelium-dependante a la bradykinine observee au cours du processus de regeneration apres denudation endotheliale. La presente etude demontre que des cellules endotheliales mises en culture a partir d’endothelium regenere preleve huit jours apres la denudation possedent une capacite basale de production de GMP cyclique (GMPc) intacte mais reagissent deja plus faiblement a une stimulation receptorielle (bradykinine) ou intracellulaire (ionophore calcique). En fonction de passages cellulaires multiples, employes pour mimer le phenomene de vieillissement, la production basale de GMPc reste stable pendant plusieurs passages (semaines), pour diminuer au bout d’un mois. En revanche, la reponse a la stimulation receptorielle (bradykinine) faiblit deja au bout de la seconde semaine pour rester stable au cours des passages suivants. Dans des cultures de cellules endotheliales aortiques, l’augmentation de la densite cellulaire s’accompagne d’une diminution de sites actifs de la eNOS, ainsi que d’une production de NO plus faible en reponse a la bradykinine et au A23187. Ces resultats suggerent qu’aussi bien l’augmentation de la densite cellulaire que le vieillissement des cellules participent a la dysfonction endotheliale au cours du processus de regeneration. Ils permettent de mieux comprendre l’evolution de la reactivite vasculaire apres denudation endotheliale et ses consequences physiopathologiques.

New insights about immunopathology of lipoid nephrosis

Abstract: Clinical and experimental observations suggest that Lipoid Nephrosis (Minimal change nephrotic syndrome) results from T cell dysfunction due to still unknown mechanisms. By subtractive screening library, we identified 84 transcripts, of which twelve match with proteins of yet unknown function and thirty are unknown clones. Among the 42 known transcripts, at least 18 are closely involved in the TCR-mediated complex signaling cascade. This includes genes encoding components of the T cell receptor and proteins associated with the cytoskeleton scaffold, as well as transcription factors such as NF-kappa B and c-maf. During the relapse phase, we have found significant alterations of the NF-kappa B/I kappa Ba regulatory pathway, whereas very low levels of IL12R beta 2 mRNA were detected suggesting that T cell activation evolves toward a Th2 phenotype. We have shown that c-maf is highly induced, shuttling between nuclear and cytoplasmic compartment during the relapse and the remission phases, respectively. Contrasting with the nuclear expression of c-maf, low IL4 levels were detected in relapse. This suggests that the downstream target gene of c-maf in Lipoid Nephrosis, is not IL4 and provides new directions in research leading to identify the target gene, possibly an unknown Th2 cytokine, which might play a critical role in the pathophysiology of this disease. Thus, the combination of subtractive cloning and differential screening constitutes an efficient approach to identify genes likely to be involved in the pathophysiology of MCNS.

[Heart failure with preserved left ventricular function: clinical, echocardiographic, and clinical course features. Prognostic factors]

Abstract: Heart failure is clinically associated with inadequate myocardial contraction, a significant reduction of left ventricular systolic function and ejection fraction and a cardiac enlargement. Some studies have reported that patients with symptomatic heart failure may have an impaired left ventricular filling with a normal or preserved left ventricular systolic function and an ejection fraction > 45%. These patients have a "diastolic heart failure" often neglected or misdiagnosed. The aims of our study is to describe clinical, echocardiographic and hemodynamic characteristics of 64 patients hospitalized for symptomatic heart failure, to determine possible variables with prognosis relevance, and for evaluating the severity of this diastolic left ventricular dysfunction. All patients were assessed by physical and radiographic examination, 12 leads electrocardiogram, and usual laboratory tests. The internal diameter of left atrium and left ventricular end diastolic and tele-systolic diameter were measured following the recommendations of the American Society of Echocardiography, Ejection fraction was determined following Simpson's method. Left ventricular filling patterns were evaluated by pulsed Doppler mitral or venous pulmonary flow. The following parameters were assessed: maximum velocity of E and A waves, E/A ratio, E wave deceleration time and isovolumic relaxation time. The patients were studied following Appleton's classification. 45 patients were submitted to left heart catheterization and coronary angiography. All subjects were routinely followed by cardiologic examinations and the mean follow up is 18 +/- 4, 5 months. 29 women (45.3%) and 35 men with a mean age of 72.5 +/- 3.2 years were included in this study. Left ventricular ejection fraction was in mean 48.5 +/- 4.2%. 65% of patients had ischemic cardiomyopathy with severe coronary stenosis > 50%, often associated with hypertension. 52% of patients had hypertensive heart disease and 38% were diabetics. 34 patients were re-hospitalized for recurrent heart failure despite medical treatment with diuretics, ACE inhibitors (90% of patients), beta-blockers, (37%) or nitrates (36%). 24 patients have been treated by coronary angioplasty. In hospital mortality was 6.2% and during the follow up at 18 months the mortality reaches 18.7%. The factors of poor prognosis are age > 75 years, left ventricular restrictive pattern at doppler diastolic trans mitral flow evaluation, (p 150 micromoles (p = 0.002). In conclusion heart failure with preserved left systolic ventricular function is frequent in women with hypertensive heart disease. The prognosis at mean term is better that prognosis of patients with systolic dysfunction but despite medical treatment there is a high morbidity with numerous re hospitalizations. Restrictive left ventricular filling pattern is significantly related to the occurrence of events and mortality.