Hypertension artérielle réfractaire au traitement due au syndrome d'apnées du sommeil et à la prise de médicaments [Obstructive sleep apnea and drugs as causes of treatment-resistant hypertension].

Treatment-resistant hypertension is still common despite the availability of several types of antihypertensive agents acting by different mechanisms. The existence of refractory hypertension should lead to rule out "white-coat hypertension", poor adherence to prescribed drugs as well as classical causes of secondary hypertension such as renal artery stenosis, primary aldosteronism, pheochromocytoma and renal disease. It is also important to consider the possible existence of obstructive sleep apnea or the regular intake of vasopressive drugs or substances.

Multiple non-ossifying fibromas as a cause of pathological femoral fracture in Jaffe-Campanacci syndrome.

BACKGROUND: Jaffe-Campanacci is a rare syndrome characterised by the association of café-au-lait spots, axillary freckles, multiple non-ossifying fibromas of the long bones and jaw, as well as some features of type 1 neurofibromatosis. There are less than 30 reported cases, and a genetic profile has not yet been determined. Furthermore, it has not been clarified whether it is a subtype of type 1 neurofibromatosis or a separate syndrome. The risk of pathological fracture is over 50%, due to substantial cortical thinning of the weight-bearing bones. CASE PRESENTATION: A 17-year-old female patient, known for type 1 neurofibromatosis, presented with a low-energy distal femoral fracture due to disseminated large non-ossifying fibromas. Investigations revealed all of the distinctive signs of Jaffe-Campanacci syndrome. Both her distal femurs and proximal tibias exhibited multiple non-ossifying fibromas. The fracture was treated by open reduction and internal plate fixation. Some of the bony lesions were biopsied to confirm the diagnosis. The fracture healed eventless, as did the lesions biopsied or involved in the fracture. The other ones healed after curettage and bone grafting performed at the time of plate removal. CONCLUSION: Jaffe-Campanacci is a rare syndrome having unclear interactions with type 1 neurofibromatosis, which still needs to be characterised genetically. It is associated with a high risk of pathological fracture, due to the presence of multiple large non-ossifying fibromas of the long bones, with an expected normal healing time. Curettage and bone grafting promote healing of the lesions and should be considered to prevent pathological fracture. We agree with other authors that all patients with newly-diagnosed type 1 neurofibromatosis should undergo an osseous screening to detect disseminated non-ossifying fibromas, and evaluate the inherent risk of pathological fracture.

Prevalence of the metabolic syndrome in the Seychelles according to different definitions, contribution of components, and agreement between different definitions

Background: The metabolic syndrome (MS) represents a cluster of metabolic disorders that predicts diabetes and cardiovascular disease. Several definitions exist and further descriptive and prospective data are needed to compare these definitions and their significance in different populations. Objective: We examined, in a country of the African region, i) the prevalence of MS according to three major definitions (ATP, IDF, WHO); ii) the contribution of individual MS components; and iii) the agreement between the three considered definitions. We also examined the prevalence among diabetics and non-diabetics. Methods: We conducted an examination survey in a sample representative of the general population aged 25-64 of the Seychelles (Indian Ocean, African region), attended by 1255 persons (participation rate of 80.2%). Results: The prevalence of MS was similar with either definition of MS in men (24%-25%) but differed in women (WHO: 25%, ATP: 32%; IDF: 35%). Upon exclusion of diabetic persons, the prevalence was 5-10% lower for all three MS definitions: most diabetic persons had MS although a substantial proportion of diabetic men aged 45-64 did not have MS. The following components were found most often among persons with MS: 90% had high blood pressure (HBP) and 78% had obesity (ATP); 95% had obesity and 84% had HBP (WHO), and 89% had HBP and 75% had impaired glucose regulation (IDF) -not considering impaired glucose regulation and obesity that are compulsory components of the WHO and IDF definitions, respectively. Among persons with MS based on either of the three definitions (37% of total population), less than 80% met both ATP and IDF criteria, 67% both WHO and IDF criteria, 54% both WHO and ATP criteria and only 37% met all three definitions. Conclusions. We found a fairly high prevalence of MS in an African population. However, because there was only poor agreement between the 3 MS definitions, the fairly similar proportions of MS based on ATP, IDF or WHO definitions identified, to a substantial extent, different subjects as having MS.

Stress radiography and posterior pathological laxity of knee: comparison between two different techniques.

Stress radiographs have been recommended in order to obtain a better objective quantification of abnormal compartment knee motion. This tool has showed to be superior in quantifying a posterior cruciate ligament (PCL) lesion compared to clinical or arthrometer evaluation. Different radiographic techniques have been described in literature to quantify posterior pathological laxity. In this study we evaluated the total amount of posterior displacement (PTD) and side to side difference (SSD), before and after surgical reconstruction of PCL or PCL and posterolateral complex (PLC), using two different stress radiography techniques (Telos stress and kneeling view). Twenty patients were included in this study. We found a statistical significant difference about both total PTD and SSD among the two techniques preoperatively and at follow-up, with greatest values occurring using the kneeling view. Although stress radiographies has been introduced to allow an objective quantification of laxity in ligamentous injured knee, we believe that further studies on a large numbers of subjects are required to define the relationship between PTD values, measured with stress knee radiography, particularly using kneeling view, and ligamentous knee injury, in order to obtain a real useful tool in the decision making process, as well as to evaluate the outcome after ligamentous surgery.

Reversible acquired epileptic frontal syndrome and CSWS suppression in a child with congenital hemiparesis treated by hemispherotomy.

A boy with a right congenital hemiparesis due to a left pre-natal middle cerebral artery infarct developed focal epilepsy at 33 months and then an insidious and subsequently more rapid, massive cognitive and behavioural regression with a frontal syndrome between the ages of 4 and 5 years with continuous spike-waves during sleep (CSWS) on the EEG. Both the epilepsy and the CSWS were immediately suppressed by hemispherotomy at the age of 5 years and 4 months. A behavioural-cognitive follow-up prior to hemispherotomy, an per-operative EEG and corticography and serial post-operative neuropsychological assessments were performed until the age of 11 years. The spread of the epileptic activity to the "healthy" frontal region was the cause of the reversible frontal syndrome. A later gradual long-term but incomplete cognitive recovery, with moderate mental disability was documented. This outcome is probably explained by another facet of the epilepsy, namely the structural effects of prolonged epileptic discharges in rapidly developing cerebral networks which are, at the same time undergoing the reorganization imposed by a unilateral early hemispheric lesion. Group studies on the outcome of children before and after hemispherectomy using only single IQ measures, pre- and post-operatively, may miss particular epileptic cognitive dysfunctions as they are likely to be different from case to case. Such detailed and rarely available complementary clinical and EEG data obtained in a single case at different time periods in relation to the epilepsy, including per-operative electrophysiological findings, may help to understand the different cognitive deficits and recovery profiles and the limits of full cognitive recovery.

Critical evaluation of outcome scales assessment of lateral ankle ligament reconstruction

Introduction: Les résultats d'une chirurgie du pied et de la cheville peuvent être évalués par des scores spécifiques à la région anatomique ainsi que par des scores spécifiques à la pathologie. Beaucoup de scores existent rendant la comparaison entre les études difficile. La présente étude se focalise sur une pathologie fréquente du pied et de la cheville et compare les résultats obtenu par deux scores spécifiques à la région et deux scores spécifiques à la pathologie. Méthode: Nous avons revu 41 patients ayant bénéficié d'une plastie ligamentaire externe de la cheville. Quatre scores ont été administrés simultanément: the Cumberland Ankle Instability Tool (CAIT) et the Chronic Ankle Instability Scale (CAIS), spécifiques à la pathologie, the American Orthopedic Foot & Ankle Society (AOFAS) hindfoot scale et the Foot and Ankle Ability Measure comprenant deux parties (FAAM1 et FAAM2), spécifiques à la région anatomique. Le degré de corrélation entre les scores a été évalué par le coefficient de corrélation de Pearson. L'analyse graphique des variances a été utilisée pour le choix de tests paramétriques versus non paramétriques. Des tests non paramétriques, le Kruskal-Wallis pour éliminer l'hypothèse nulle et le Mann-Whitney pour la comparaison entre les scores deux à deux, ont été utilisés. Résultats: Une différence significative (p<.005) a été démontrée entre le CAIS et l'AOFAS (p=.0002), entre le CAIS et le FAAM1 (p=.0001) et entre le CAIT et l'AOFAS (p=.0003) Conclusions: Cette étude compare les performances de quatre scores dont deux spécifiques à la région anatomique et deux spécifiques à la pathologie. Nous avons démontré une bonne corrélation entre les scores ainsi que des différences significatives entre les résultats obtenus par chacun d'eux. Les résultats obtenus par les scores spécifiques à la pathologie semblent être plus précis que ceux obtenus par les scores spécifiques à la région anatomique. De plus, nous avons mis en évidence une forte corrélation entre l'AOFAS et les autres scores. Le FAAM semble être un bon compromis car il offre la possibilité, du fait de ses deux parties, d'évaluer le résultat en fonction de la demande fonctionnelle du patient. Perspectives: Un algorithme est proposé qui permet d'évaluer la littérature spécifique de manière plus critique et peut s'adapter également à la recherche et à la clinique relative à d'autres pathologies du pied et de la cheville

Therapy of acute massive pulmonary embolism associated with Klippel-Trenaunay syndrome.

Acute massive pulmonary embolism (PE) is a life-threatening event. Before the era of cardiopulmonary bypass, acute pulmonary embolectomy had been historically attempted in patients with severe hemodynamic compromise. The Klippel-Trenaunay syndrome (KTS) represents a significant life-long risk for major thromboembolic events. We present two young patients with Klippel-Trenaunay syndrome who survived surgical embolectomy after massive PE and cardiopulmonary resuscitation, with good postoperative recovery. Even though the role of surgical embolectomy in massive PE is not clearly defined, with current technology it can be life saving and can lead to a complete recovery, especially in young patients as described in this study.

Dietary and lifestyle interventions in the management of the metabolic syndrome: present status and future perspective.

OBJECTIVE: To review the mechanisms underlying the metabolic syndrome, or syndrome X, in humans, and to delineate dietary and environmental strategies for its prevention. DESIGN: Review of selected papers of the literature. RESULTS: Hyperinsulinemia and insulin resistance play a key role in the development of the metabolic syndrome. Strategies aimed at reducing insulin resistance may be effective in improving the metabolic syndrome. They include low saturated fat intake, consumption of low-glycemic-index foods, physical exercise and prevention of obesity. CONCLUSIONS: Future research, in particular the genetic basis of the metabolic syndrome and the interorgan interactions responsible for insulin resistance, is needed to improve therapeutic strategies for the metabolic syndrome.

Fraser syndrome: epidemiological study in a European population.

Fraser syndrome is a rare autosomal recessive disorder characterized by cryptophthalmos, cutaneous syndactyly, laryngeal, and urogenital malformations. We present a population-based epidemiological study using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network of birth defect registries. Between January 1990 and December 2008, we identified 26 cases of Fraser syndrome in the monitored population of 12,886,464 births (minimal estimated prevalence of 0.20 per 100,000 or 1:495,633 births). Most cases (18/26; 69%) were registered in the western part of Europe, where the mean prevalence is 1 in 230,695 births, compared to the prevalence 1 in 1,091,175 for the rest of Europe (P = 0.0003). Consanguinity was present in 7/26 (27%) families. Ten (38%) cases were liveborn, 14 (54%) pregnancies were terminated following prenatal detection of a serious anomaly, and 2 (8%) were stillborn. Eye anomalies were found in 20/24 (83%), syndactyly in 14/24 (58%), and laryngeal anomalies in 5/24 (21%) patients. Ambiguous genitalia were observed in 3/24 (13%) cases. Bilateral renal agenesis was present in 12/24 (50%) and unilateral in 4/24 (17%) cases. The frequency of anorectal anomalies was particularly high (42%). Most cases of Fraser syndrome (85%) are suspected prenatally, often due to the presence of the association of renal agenesis and cryptophthalmos. In the European population, a high proportion (82%) of pregnancies is terminated, thus reducing the live birth prevalence to a third of the total prevalence rate.

Vasopressin-stimulated CFTR Cl- currents are increased in the renal collecting duct cells of a mouse model of Liddle's syndrome.

Liddle's syndrome is a genetic form of hypertension linked to Na(+) retention caused by activating mutations in the COOH terminus of the beta or gamma subunit of the epithelial sodium channel (ENaC). In this study, we used the short-circuit current (I(sc)) method to investigate the effects of deamino-8-d-arginine vasopressin (dDAVP) on Na(+) and Cl(-) fluxes in primary cultures of cortical collecting ducts (CCDs) microdissected from the kidneys of mice with Liddle's syndrome carrying a stop codon mutation, corresponding to the beta-ENaC R(566) stop mutation (L) found in the original pedigree. Compared to wild-type (+/+) CCD cells, untreated L/+ and L/L CCD cells exhibited 2.7- and 4.2-fold increases, respectively, in amiloride-sensitive (Ams) I(sc), reflecting ENaC-dependent Na(+) absorption. Short-term incubation with dDAVP caused a rapid and significant increase (approximately 2-fold) in Ams I(sc) in +/+, but not in L/+ or L/L CCD cells. In sharp contrast, dDAVP induced a greater increase in 5-nitro-2-(3-phenylpropamino)benzoate (NPPB)-inhibited apical Cl(-) currents in amiloride-treated L/L and L/+ cells than in their +/+ counterparts. I(sc) recordings performed under apical ion substituted conditions revealed that the dDAVP-stimulated apical secretion of Cl(-), which was absent in cultured CCDs lacking CFTR, was 1.8-fold greater in L/+ and 3.7-fold greater in L/L CCD cells than in their +/+ CCD counterparts. After the basal membrane had been permeabilized with nystatin and a basal-to-apical Cl(-) gradient had been imposed, dDAVP also stimulated larger Cl(-) currents across L/L and L/+ CCD layers than +/+ CCD layers. These findings demonstrate that vasopressin stimulates greater apical CFTR Cl(-) conductance in the renal CCD cells of mice with Liddle's syndrome than in wild-type mice. This effect could contribute to the enhanced NaCl reabsorption observed in the distal nephron of patients with Liddle's syndrome.

Acquired auditory agnosia in childhood and normal sleep electroencephalography subsequently diagnosed as Landau-Kleffner syndrome: a report of three cases.

Aim  We report three cases of Landau-Kleffner syndrome (LKS) in children (two females, one male) in whom diagnosis was delayed because the sleep electroencephalography (EEG) was initially normal. Method  Case histories including EEG, positron emission tomography findings, and long-term outcome were reviewed. Results  Auditory agnosia occurred between the age of 2 years and 3 years 6 months, after a period of normal language development. Initial awake and sleep EEG, recorded weeks to months after the onset of language regression, during a nap period in two cases and during a full night of sleep in the third case, was normal. Repeat EEG between 2 months and 2 years later showed epileptiform discharges during wakefulness and strongly activated by sleep, with a pattern of continuous spike-waves during slow-wave sleep in two patients. Patients were diagnosed with LKS and treated with various antiepileptic regimens, including corticosteroids. One patient in whom EEG became normal on hydrocortisone is making significant recovery. The other two patients did not exhibit a sustained response to treatment and remained severely impaired. Interpretation  Sleep EEG may be normal in the early phase of acquired auditory agnosia. EEG should be repeated frequently in individuals in whom a firm clinical diagnosis is made to facilitate early treatment.

Corneal Opacities in Trisomy 8 Mosaic Syndrome : Clinical, Histologic and Genetic Features

Purpose: To describe the clinical, histologic and genetic findings of corneal opacities in the trisomy 8 mosaic syndrome. Methods: 3 children aged 8 years (Patients A), 6 years (Patients B) and 1 month (Patients C) respectively, were referred with corneal opacities for ophthalmologic evaluation. The 2 older patients had been previously diagnosed with trisomy 8 mosaicism, while the third was diagnosed after the ocular examination. Automated lamellar keratoplasty (ALTK) was performed on the most amblyopic eye. Histopathologic analysis with immunohistochemical markers and cytogenetic studies by FISH using haploid probes for chromosome 8 and chromosome 16 (control) were performed on the excised corneal lesion. Results: All patients presented vascularized corneal opacities involving the superficial stroma, and amblyopia with a bilateral involvement in two of them (Patients A and B). Post-operative follow-up (range 6-20 months) was satisfactory, with the graft remaining clear and improved visual acuity, allowing iso-acuity and stereoscopy in the one month old child (Patients C). The clinically observed corneal opacities corresponded histopathologically to the replacement of the normal anterior corneal stroma by a choristomatous loose richly vascularized connective tissue containing mucopolysacharides. Bowman's membrane was absent. There were no adnexal structures. The overlaying epithelium expressed keratin 3 in all three cases. Keratin 19 was found in the suprabasal epithelial cells in one case but was absent in the other cases. There were no expression of keratin 7 and 1 as well as MUC5AC in the epithelial cells. FISH analysis from 100 interphase cells of the affected tissue and normal conjontival probe revealed normal diploid cells. Conclusions: In this series, the corneal opacities associated with trisomy 8 mosaic syndrome share a common clinical, histopathological and genetic features. ALTK should be considered at diagnosis to prevent amblyopia in these children.

Regulatory T cell defects are associated with autoimmunity in Wiskott-Aldrich Syndrome protein deficient mice

Abstract : The Wiskott-Aldrich Syndrome (WAS) is an X-linked recessive human primary immunodeficiency. It is caused by mutations in the gene encoding the hermatopoietic specific regulator of the actin cytoskeleton Wiskott-Aldrich Syndrome Protein (WASP). Importantly, a majority of affected patients develop autoimmunity including an inflammatory bowel disease (IBD)-like disease. WASP deficient mice share many similarities with the human WAS. One of these similarities is the spontaneous development of colitis. I have focused my dissertation studies on the pathogenesis of colitis in WASP deficient mice. Prior work from our laboratory had shown that lymphocytes were required and that CD4+ T cells sufficient for colitis development. This colitis was associated with a predominant Th2-cytokine skewing. I have contributed in exploring whether the Th2 cytokine IL-4 plays a role in disease maintenance. Using two approaches to neutralize IL-4, we found that this cytokine plays a role in disease maintenance. Natural CD4*CD25*Foxp3* regulatory T cells (nTreg cells) have been implicated in the pathogenesis of several autoimmune disorders. We found that WASP deficient mice have reduced nTreg cell numbers in peripheral lymphoid organs. This was associated with functional defects in suppressing T cell proliferation and preventing colitis induced by transfer of naïve T cells into SCID recipient, which lack lymphocytes. WASP deficiency affected homing of nTreg cells to lymphoid compartments, IL-2-mediated activation and secretion of the immunomodulatory cytokine IL-10. Finally, we could prevent colitis onset via adoptive transfer of WT nTreg cells prior to colitis development. This suggests that nTreg cells dysfunction is one of the mechanisms underlying colitis development in WASP deficient mice. Future directions will aim at deciphering the role of other immune cell types, the bacterial flora, and various cytokines in colitis development in this murine model of colitis. In addition, we believe that colitis in WASP deficient mice could serve as a useful tool to evaluate nTreg cells manipulation as novel therapeutic approach for IBD.