Impact of HSD11B1 polymorphisms on BMI and components of the metabolic syndrome in patients receiving psychotropic treatments.

BACKGROUND: Metabolic syndrome (MetS) associated with psychiatric disorders and psychotropic treatments represents a major health issue. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme that catalyzes tissue regeneration of active cortisol from cortisone. Elevated enzymatic activity of 11β-HSD1 may lead to the development of MetS. METHODS: We investigated the association between seven HSD11B1 gene (encoding 11β-HSD1) polymorphisms and BMI and MetS components in a psychiatric sample treated with potential weight gain-inducing psychotropic drugs (n=478). The polymorphisms that survived Bonferroni correction were analyzed in two independent psychiatric samples (nR1=168, nR2=188) and in several large population-based samples (n1=5338; n2=123 865; n3>100 000). RESULTS: HSD11B1 rs846910-A, rs375319-A, and rs4844488-G allele carriers were found to be associated with lower BMI, waist circumference, and diastolic blood pressure compared with the reference genotype (Pcorrected<0.05). These associations were exclusively detected in women (n=257) with more than 3.1 kg/m, 7.5 cm, and 4.2 mmHg lower BMI, waist circumference, and diastolic blood pressure, respectively, in rs846910-A, rs375319-A, and rs4844488-G allele carriers compared with noncarriers (Pcorrected<0.05). Conversely, carriers of the rs846906-T allele had significantly higher waist circumference and triglycerides and lower high-density lipoprotein-cholesterol exclusively in men (Pcorrected=0.028). The rs846906-T allele was also associated with a higher risk of MetS at 3 months of follow-up (odds ratio: 3.31, 95% confidence interval: 1.53-7.17, Pcorrected=0.014). No association was observed between HSD11B1 polymorphisms and BMI and MetS components in the population-based samples. CONCLUSIONS: Our results indicate that HSD11B1 polymorphisms may contribute toward the development of MetS in psychiatric patients treated with potential weight gain-inducing psychotropic drugs, but do not play a significant role in the general population.

Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC-C loci.

Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant condition mainly characterized by the development of mandibular keratocysts which often have their onset during the second decade of life and/or multiple basal cell carcinoma (BCC) normally arising during the third decade. Cardiac and ovarian fibromas can be found. Patients with NBCCS develop the childhood brain malignancy medulloblastoma (now often called primitive neuro-ectodermal tumor [PNET]) in 5% of cases. The risk of other malignant neoplasms is not clearly increased, although lymphoma and meningioma can occur in this condition. Wilms tumor has been mentioned in the literature four times. We describe a patient with a 10.9 Mb 9q22.3 deletion spanning 9q22.2 through 9q31.1 that includes the entire codifying sequence of the gene PTCH1, with Wilms tumor, multiple neoplasms (lung, liver, mesenteric, gastric and renal leiomyomas, lung typical carcinoid tumor, adenomatoid tumor of the pleura) and a severe clinical presentation. We propose including leiomyomas among minor criteria of the NBCCS.

New finding of Giardia intestinalis (Eukaryote, Metamonad) in Old World archaeological site using immunofluorescence and enzyme-linked immunosorbent assays

In this study, nine organic sediment samples from a medieval archaeological site at Pineuilh, France, were examined for Giardia intestinalis using two commercially available immunological kits [enzyme-linked immuno sorbent and immunofluorescence (IFA) assays]. Both techniques detected G. intestinalis in one sample, dated to 1,000 Anno Domini. This is the first time IFA was successfully used to detect protozoa in Old World archaeological samples. Such immunological techniques offer important perspectives concerning ancient protozoa detection and identification.

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

Rapport de synthèse : Cette thèse a étudié en détail le cas d'un enfant souffrant d'une hémiplégie congénitale sur un infarctus prénatal étendu qui a développé une forme particulière d'épilepsie, le syndrome des pointes ondes continues du sommeil (POCS), associé à une régression mentale massive. Les caractéristiques de cette détérioration pointaient vers un dysfonctionnement de type frontal. Une chirurgie de l'épilepsie (hémisphérotomie) a, non seulement, permis la guérison de l'épilepsie mais une récupération rapide sur le plan comportemental et cognitif, suivie d'une reprise plus lente du développement, avec finalement à l'âge de 11 ans un niveau de déficience intellectuelle modérée. L'intérêt de cette étude réside dans le fait que l'enfant a pu être suivi prospectivement entre l'âge de 4.5 ans et 11 ans par des enregistrements électro-encéphalographiques (EEG) ainsi que des tests neuropsychologiques et des questionnaires de comportements sériés, permettant de comparer les périodes pré-, péri- et postopératoires, ce qui est rarement réalisable. Un enregistrement EEG de surface a même pu être effectué durant l'opération sur l'hémisphère non lésé, permettant de documenter l'arrêt des décharges épileptiformes généralisées dès la fin de l'intervention. L'hypothèse que nous avons- souhaité démontrer est que la régression comportementale et cognitive présentée par l'enfant après une période de développement précoce presque normale (retard de langage) était de nature épileptique : nous l'expliquons par la propagation de l'activité électrique anormale à partir de la lésion de l'hémisphère gauche vers les régions préservées, en particulier frontales bilatérales. L'hémisphérotomie a permis une récupération rapide en déconnectant l'hémisphère gauche lésé et épileptogène de l'hémisphère sain, qui a ainsi pu reprendre les fonctions cognitives les plus importantes. Les progrès plus lents par la suite et l'absence de rattrapage au delà d'un niveau de déficience mentale modérée sont plus difficiles à expliquer: on postule ici un effet de l'épilepsie sur le développement de réseaux neuronaux de l'hémisphère initialement non lésé, réseaux qui sont à la fois à un stade précoce de leur maturation et en cours de réorganisation suite à la lésion prénatale. La littérature sur les déficits cognitifs avant et après hemisphérotomie s'est surtout préoccupée du langage et de sa récupération possible. À notre connaissance, notre étude est la première à documenter la réversibilité d'une détérioration mentale avec les caractéristiques d'un syndrome frontal après hémisphérotomie. La chirurgie de l'épilepsie a offert ici une occasion unique de documenter le rôle de l'activité épileptique dans la régression cognitive puisqu'en interrompant brusquement la propagation de l'activité électrique anormale, on a pu comparer la dynamique du développement avant et après l'intervention. La mise en relation des multiples examens cliniques et EEG pratiqués chez un seul enfant sur plusieurs années a permis d'obtenir des informations importantes dans la compréhension des troubles cognitifs et du comportement associés aux épilepsies focales réfractaires. ABSTRACT : 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 4months. A behavioural-cognitive follow-up prior to hemispheratomy, 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. T9ris outcome is probably explained by another facet of the epilepsy, namely the structural effects of prolonged epileptic dischazges 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 postoperatively, 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 peroperative electrophysiological findings, may help to understand the different cognitive deficits and recovery profiles and the limits of full cognitive recovery.

Leukemic cluster growth in culture is an independent risk factor for acute myeloid leukemia and short survival in patients with myelodysplastic syndrome.

In patients with myelodysplastic syndrome (MDS) precursor cell cultures (colony-forming unit cells, CFU-C) can provide an insight into the growth potential of malignant myeloid cells. In a retrospective single-center study of 73 untreated MDS patients we assessed whether CFU-C growth patterns were of prognostic value in addition to established criteria. Abnormalities were classified as qualitative (i.e. leukemic cluster growth) or quantitative (i.e. strongly reduced/absent growth). Thirty-nine patients (53%) showed leukemic growth, 26 patients (36%) had strongly reduced/absent colony growth, and 12 patients showed both. In a univariate analysis the presence of leukemic growth was associated with strongly reduced survival (at 10 years 4 vs. 34%, p = 0.004), and a high incidence of transformation to AML (76 vs. 32%, p = 0.01). Multivariate analysis identified leukemic growth as a strong and independent predictor of early death (relative risk 2.12, p = 0.03) and transformation to AML (relative risk 2.63, p = 0.04). Quantitative abnormalities had no significant impact on the disease course. CFU-C assays have a significant predictive value in addition to established prognostic factors in MDS. Leukemic growth identifies a subpopulation of MDS patients with poor prognosis.

Selective acquired long QT syndrome (saLQTS) upon risperidone treatment.

ABSTRACT: BACKGROUND: Numerous structurally unrelated drugs, including antipsychotics, can prolong QT interval and trigger the acquired long QT syndrome (aLQTS). All of them are thought to act at the level of KCNH2, a subunit of the potassium channel. Although the QT-prolonging drugs are proscribed in the subjects with aLQTS, the individual response to diverse QT-prolonging drugs may vary substantially. CASE PRESENTATION: We report here a case of aLQTS in response to small doses of risperidone that was confirmed at three independent drug challenges in the absence of other QT-prolonging drugs. On the other hand, the patient did not respond with QT prolongation to some other antipsychotics. In particular, the administration of clozapine, known to be associated with higher QT-prolongation risk than risperidone, had no effect on QT-length. A detailed genetic analysis revealed no mutations or polymorphisms in KCNH2, KCNE1, KCNE2, SCN5A and KCNQ1 genes. CONCLUSIONS: Our observation suggests that some patients may display a selective aLQTS to a single antipsychotic, without a potassium channel-related genetic substrate. Contrasting with the idea of a common target of the aLQTS-triggerring drugs, our data suggests existence of an alternative target protein, which unlike the KCNH2 would be drug-selective.

Factors associated with improvement in disability-adjusted life years in patients with HIV/AIDS

Background The epidemic of HIV/AIDS and treatments that have emerged to alleviate, have brought about a shift in the burden of disease from death to quality of life/disability. The aim was to determine which factors are associated with improvements in the level of health of male and female patients with HIV/AIDS in Andalusia, in terms of disability-adjusted life years. Methods Descriptive study based on a sample group of 8800 people on the Andalusian AIDS register between 1983 and 2004. Dependent variables: Life lost due to premature mortality (YLL), years lost due to disability (YLD) and disability-adjusted life years (DALY). Independent variables: vital state, sex, age at the time of diagnosis, age at the time of death, transmission category, province of residence, AIDS-indicator disease and the period of diagnosis. A bivariate analysis was carried out to find out if the health level variables changed in accordance with the independent variables. Using the independent variables which had a statistically significant link with the level of health variables, a multivariate linear regression model, disaggregated by gender, was constructed. Results Amongst the women, we found a model which explained the level of health of 64.9%: a link was found between a higher level of health (lower DALYs) and not intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Amongst the men, we found a model which explained the level of health of 64.4%: a link was found between a higher level of health (lower DALYs) and intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Conclusion A higher level of health (lower DALY) amongst both men and women was found to be linked to not be intravenous drug user, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis.

Cytokine levels in bronchoalveolar lavage and serum in 3 patients with 2009 influenza A(H1N1)v severe pneumonia.

Introduction: Pandemic Influenza A (H1N1)v pneumonia has led to a notable increase of admissions to intensive care units. A cytokine-mediated inflammatory response has been well documented in pneumonia and acute respiratory distress syndrome. However, few studies have focused on the role of these inflammatory mediators in infections caused by the Influenza A (H1N1)v. In this study, we assess the inflammatory response mediated by cytokines at the local and systemic levels in three cases of severe pneumonia caused by Influenza A (H1N1) virus. Methodology: Serum and bronchoalveolar lavage samples were obtained from three mechanically ventilated patients diagnosed with Influenza A (H1N1) virus pneumonia by bronchoscopic bronchoalveolar lavage. Levels of interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrosis factor alpha (TNFα) and interleukin 1 beta (IL-1ß) were meassured in these samples by enzyme-linked immunosorbent assay (ELISA). Results: High levels of C Reactive Protein, Procalcitonin below 1 ng/ml and absence of leukocytosis were common findings in all patients. TNF α and IL-1ß were not detected in the serum. IL-6 levels in serum were (94, pg/ml, 77 pg/ml and 84 pg/ml) respectively in the three patients, while IL-8 levels were (30,2 pg/ml, 128 pg/ml and 40,5 pg/ml). In the BAL samples, only one of the analysed cytokines, IL-1ß was present at detectable levels in two patients (21 pg/ml and 11 pg/ml respectively). Conclusions: Our results support previous findings which suggest that high levels of IL-6 and IL-8 in serum somehow participate in the inflammatory response in severe cases of pandemic influenza pneumonia.

Evaluation of an enzyme-linked immunoelectrotransfer blot test for the confirmatory serodiagnosis of human toxocariasis

To improve the serodiagnosis of human toxocariasis, a sensitive and specific enzyme-linked immunoelectrotransfer blot (EITB-IgG) test was developed and evaluated using Toxocara canislarvae excretory-secretory antigens for detecting anti-Toxocara IgG antibodies. The EITB-IgG profile of toxocariasis was characterized by comparing 27 sera from patients with toxocariasis, 110 sera from healthy subjects and 186 sera from patients with other helminth diseases (ascariasis, ancylostomiasis, trichuriasis, enterobiasis, strongyloidiasis, hymenolepiasis, diphyllobothriasis, taeniasis, cysticercosis, hydatidosis and fascioliasis). Antigenic bands of 24, 28, 30, 35, 56, 117, 136 and 152 kDa were predominantly recognized in sera from all patients with toxocariasis. However, only bands of 24-35 kDa were highly specific for Toxocara infection (98.3%), whereas other antigenic bands observed displayed cross-reactivity. Additionally, when the results of the EITB-IgG test were compared to those of the ELISA-IgG test, a 100% concordance was observed for positive results in human toxocariasis cases. The concordance for negative results between the two tests for healthy subjects and patients with other helminth diseases were 96.3% and 53.7%, respectively, showing that the EITB-IgG test has a higher specificity than ELISA. In conclusion, the EITB-IgG test is a very useful tool to confirm the serological diagnosis of human toxocariasis.

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.

Homozygosity for a novel truncating mutation confirms TBX15 deficiency as the cause of Cousin syndrome.

Cousin syndrome, also called pelviscapular dysplasia (OMIM 260660), is characterized by short stature, craniofacial dysmorphism, and multiple skeletal anomalies. Following its description in two sibs in 1982, no new cases have been observed until the observation of two unrelated cases in 2008 who were homozygous for frameshift mutations in TBX15. We investigated an adult individual with short stature, a complex craniofacial dysmorphism, malformed and rotated ears, short neck, elbow contractures, hypoacusis, and hypoplasia of scapula and pelvis on radiographs. We identified homozygosity for a novel nonsense mutation (c.841C>T) in TBX15 predicted to cause a premature stop (p.Arg281*) with truncation of the protein. This observation confirms that Cousin syndrome is a consistent and clinically recognizable phenotype caused by loss of function of TBX15.

The effect of post-discharge educational intervention on patients in achieving objectives in modifiable risk factors six months after discharge following an episode of acute coronary syndrome, (CAM-2 Project): a randomized controlled trial

We investigated whether an intervention mainly consisting of a signed agreement between patient and physician on the objectives to be reached, improves reaching these secondary prevention objectives in modifiable cardiovascular risk factors six-months after discharge following an acute coronary syndrome. BACKGROUND: There is room to improve mid-term adherence to clinical guidelines' recommendations in coronary heart disease secondary prevention, specially non-pharmacological ones, often neglected. METHODS: In CAM-2, patients discharged after an acute coronary syndrome were randomly assigned to the intervention or the usual care group. The primary outcome was reaching therapeutic objectives in various secondary prevention variables: smoking, obesity, blood lipids, blood pressure control, exercise and taking of medication. RESULTS: 1757 patients were recruited in 64 hospitals and 1510 (762 in the intervention and 748 in the control group) attended the six-months follow-up visit. After adjustment for potentially important variables, there were, between the intervention and control group, differences in the mean reduction of body mass index (0.5 vs. 0.2; p < 0.001) and waist circumference (1.6 cm vs. 0.6 cm; p = 0.05), proportion of patients who exercise regularly and those with total cholesterol below 175 mg/dl (64.7% vs. 56.5%; p = 0.001). The reported intake of medications was high in both groups for all the drugs considered with no differences except for statins (98.1% vs. 95.9%; p = 0.029). CONCLUSIONS: At least in the short term, lifestyle changes among coronary heart disease patients are achievable by intensifying the responsibility of the patient himself by means of a simple and feasible intervention.