The health status of children without resident permit consulting the Children's Hospital of Lausanne.

OBJECTIVE: To assess social, economic and medical data concerning children without a resident permit taken into care by the Children's Hospital of Lausanne (HEL) in order to evaluate their specific needs. METHODS: Prospective exploratory study by a questionnaire including the socio-demographic, medical and education data of 103 children without a resident permit, who consulted the HEL for the first time between August 2003 and March 2006. These children were then recalled for a second check-up one year later in order to allow a regular monitoring. RESULTS: Eighty-seven percent of the children were native of Latin America, 36% being less than two years old. This population of children lived in precarious conditions with a family income lower than the poverty level (89% of the families with less than 3100 CHF/month). Forty-five percent of the children had a health insurance. The main reasons for consultation were infectious diseases, a check-up requested by the school or a check-up concerning newborn children. Most of them were in good health and the others were affected by illnesses similar to those found in other children of the same age. At least 13% of the children were obese and 27% were overweight. All children who were of educational age went to school during the year after the first check-up and 48% were affiliated to a health insurance. CONCLUSIONS: The majority of the children from Latin America lived in very precarious conditions. Their general health status was good and most of them could benefit from regular check-ups. Prevention, focused on a healthier life style, was particularly important among this population characterised by a high incidence of overweight and obesity.

Female thyroid cancer : the role of reproductive and hormonal factors in Switzerland

We conducted a study on 91 women with thyroid cancer and 306 controls in hospital for acute nonneoplastic, non-hormone-related disorders in order to investigate the role of reproductive and hormonal factors in the etiology of epithelial thyroid cancer in the Canton of Vaud, Switzerland. Non-significant increases in cancer risk with an increasing number of full-term pregnancies (odds ratio, OR, after allowance for age and previous benign thyroid disease = 1.6, for > or = 3 vs. 0 full-term pregnancies, 95% confidence interval, CI: 0.7-3.6) and spontaneous abortions (OR = 2.0 for > or = 2 vs. 0 spontaneous abortions, 95% CI: 0.7-5.2) were seen. A significantly elevated OR (2.8, 95% CI: 1.1-7.2) was found in those women whose first pregnancy ended with an abortion. Whereas most other reproductive, menstrual and hormonal factors examined did not seem to affect the risk of thyroid cancer significantly, a clue emerged of an association between thyroid cancer and artificial menopause (OR = 6.3, for women who underwent artificial menopause vs. premenopausal women, 95% CI: 1.7-23.2). Although not necessarily causal, the relationship between the risk of epithelial thyroid cancer and the occurrence of spontaneous abortions and artificial menopause deserves attention in future studies, in the light of the high incidence of thyroid cancer in young and middle-aged women.

Estradiol levels in men with congenital hypogonadotropic hypogonadism and the effects of different modalities of hormonal treatment.

Objective: To evaluate the degree of E-2 deficiency in male congenital hypogonadotropic hypogonadism (CHH), and its response to different hormonal treatments.Design: Retrospective and prospective studies.Setting: Academic institution.Patient(s): Untreated or treated CHH, healthy men, untreated men with Klinefelter syndrome (KS). Intervention(s): Serum sex hormone-binding globulin (SHBG) and total E-2 (TE2) as well as bioavailable (BE2) and free (FE2) levels were measured and determined.Main Outcome Measure(s): Total, bioavailable, and free testosterone, TE2, BE2, FE2 were compared in normal men, untreated and treated CHH and in untreated KS.Result(s): TE2, BE2, and FE2 levels were very significantly lower in untreated patients with CHH (n = 91) than in controls (n = 63) and in patients with KS (n = 45). The TE2 correlated positively with serum total T in patients with CHH. The TE2 also correlated very positively with serum LH in the combined population of patients with CHH and healthy men, suggesting that low E-2 levels in CHH are due to severe LH-driven T deficiency. All fractions of circulating E-2 were very significantly higher in patients with CHH receiving T enanthate (n = 101) or the FSH-hCG combination (n = 88) than in untreated patients with CHH. Contrary to dihydrotestosterone (DHT), both T enanthate and combined FSH-hCGtherapy significantly and prospectively increased TE2 levels in patients with CHH.Conclusion(s): Contrary to KS, the male hypogonadism observed in CHH is associated with profound E-2 deficiency, which can be overcome by aromatizable androgen or combined gonadotropin therapy. (Fertil Steril (R) 2011; 95: 2324-29. (C) 2011 by American Society for Reproductive Medicine.)

Recurrence of status epilepticus: Prognostic role and outcome predictors.

OBJECTIVE: Predictors of morbidity and mortality after status epilepticus (SE) have been studied extensively in hospital- and population-based cohorts. However, little attention has been directed toward SE recurrence after an incident episode. We investigated clinical and demographic characteristics of patients presenting SE recurrence and its specific prognostic role. METHODS: In this observational cohort study, we screened our prospective registry of consecutive adults with SE between April 2006 and February 2014. Demographic and clinical data were compared between incident and recurrent SE episodes; risk of SE recurrence was assessed through survival analysis, and the prognostic role of SE recurrence with multivariable logistic regressions. RESULTS: Of the incident cohort (509 patients), 68 (13%) experienced recurrent SE. The cumulative recurrence rate over 4 years was 32%. Recurrence risk was significantly reduced after an acute SE etiology (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.31-0.82; p = 0.005), and was borderline increased in women (HR 1.59, 95% CI 0.97-2.65; p = 0.06). Although recurrent SE episodes showed lower morbidity and mortality, prognosis was independently related to Status Epilepticus Severity Score (STESS) and potentially fatal etiology, but not to SE recurrence. SIGNIFICANCE: This study provides class III evidence that SE recurrence involves a significant proportion of patients, and that recurrence risk is independently associated with chronic etiology and to a lesser extent with female gender. However, contrary to underlying cause and SE severity, SE recurrence per se does not independently correlate with outcome. Early identification of patients at higher risk of SE recurrence may influence their management during follow-up.

MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status.

The methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene is an important predictive biomarker for benefit from alkylating agent therapy in glioblastoma. Recent studies in anaplastic glioma suggest a prognostic value for MGMT methylation. Investigation of pathogenetic and epigenetic features of this intriguingly distinct behavior requires accurate MGMT classification to assess high throughput molecular databases. Promoter methylation-mediated gene silencing is strongly dependent on the location of the methylated CpGs, complicating classification. Using the HumanMethylation450 (HM-450K) BeadChip interrogating 176 CpGs annotated for the MGMT gene, with 14 located in the promoter, two distinct regions in the CpG island of the promoter were identified with high importance for gene silencing and outcome prediction. A logistic regression model (MGMT-STP27) comprising probes cg1243587 and cg12981137 provided good classification properties and prognostic value (kappa = 0.85; log-rank p < 0.001) using a training-set of 63 glioblastomas from homogenously treated patients, for whom MGMT methylation was previously shown to be predictive for outcome based on classification by methylation-specific PCR. MGMT-STP27 was successfully validated in an independent cohort of chemo-radiotherapy-treated glioblastoma patients (n = 50; kappa = 0.88; outcome, log-rank p < 0.001). Lower prevalence of MGMT methylation among CpG island methylator phenotype (CIMP) positive tumors was found in glioblastomas from The Cancer Genome Atlas than in low grade and anaplastic glioma cohorts, while in CIMP-negative gliomas MGMT was classified as methylated in approximately 50 % regardless of tumor grade. The proposed MGMT-STP27 prediction model allows mining of datasets derived on the HM-450K or HM-27K BeadChip to explore effects of distinct epigenetic context of MGMT methylation suspected to modulate treatment resistance in different tumor types.

p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated limb perfusion with TNF-alpha and melphalan.

BACKGROUND: Recombinant tumor necrosis factor-alpha (TNF-alpha) combined to melphalan is clinically administered through isolated limb perfusion (ILP) for regionally advanced soft tissue sarcomas of the limbs. In preclinical studies, wild-type p53 gene is involved in the regulation of cytotoxic action of TNF-alpha and loss of p53 function contributes to the resistance of tumour cells to TNF-alpha. The relationship between p53 status and response to TNF-alpha and melphalan in patients undergoing ILP is unknown. PATIENTS AND METHODS: We studied 110 cases of unresectable limbs sarcomas treated by ILP. Immunohistochemistry was carried out using DO7mAb, which reacts with an antigenic determinant from the N-terminal region of both the wild-type and mutant forms of the p53 protein, and PAb1620mAb, which reacts with the 1620 epitope characteristic of the wild-type native conformation of the p53 protein. The immunohistochemistry data were then correlated with various clinical parameters. RESULTS: P53DO7 was found expressed at high levels in 28 patients, whereas PAb1620 was negative in 20. The tumours with poor histological response to ILP with TNF-alpha and melphalan showed significantly higher levels of p53-mutated protein. CONCLUSIONS: Our results might be a clue to a role of p53 protein status in TNF-alpha and melphalan response in clinical use.

Taxonomic status of Hylomys parvus and Hylomys suillus (Insectivora: Erinaceidae): biochemical and morphological analyses

The genus Hylomys was thought to be represented by a single widespread species. Biochemical and morphometric analyses of several Southeast Asian populations reveal that Sumatra is inhabited by two distinct species, the dwarf gymnure (H. parvus) and the lesser gymnure (H. suillus). The absence of interbreeding between these two groups along with their relatively ancient common origins are documented by several diagnostic loci and a large Nei's genetic distance (D = 0.353 +/- 0.035). The dwarf gymnure has been reported only from the slopes of the Mt. Kerinci volcano in Sumatra, where the species lives at higher elevations than its potential competitor, the lesser gymnure. Other populations of Hylomys from Java, Borneo, and Malaysia are more closely related to the Sumatran sample of H. suillus, but they exhibit strong interpopulational genetic differentiation (D = 0.165 +/- 0.040) that may be accounted for by their isolated montane habitat. In addition, a principal-components analysis based on 16 measurements of the skull clearly separates adult specimens of both species. There is little overlap in the measurements between H. suillus (which is larger) and H. parvus. On Sumatra where both species may be sympatric, the notched space between premaxillary tips, soft texture of the fur, and more delicate skull and dentition are diagnostic of H. parvus.

The peroxisome proliferator-activated receptors at the cross-road of diet and hormonal signalling.

The peroxisome proliferator-activated receptors (PPARs) are members of the steroid/thyroid nuclear receptor superfamily of ligand-activated transcription factors. To date, three isotypes have been identified, alpha, beta and gamma, encoded by three different genes. The alpha isotype is expressed at high levels in the liver where it has a role in lipid oxidation. Its expression and activity follow a diurnal rhythm that parallels the circulating levels of corticosterone in the bloodstream. The gamma isotype on the other hand, is mainly expressed in adipose tissue and has a critical role in adipocyte differentiation and lipid storage. The function of the ubiquitously expressed isotype, PPAR beta, remains to be determined. Besides fulfilling different roles in lipid metabolism, the different PPAR isotypes also have different ligand specificities. A new approach to identify ligands was developed based on the ligand-dependent interaction of PPAR with the recently characterized co-activator SRC-1. This so-called CARLA assay has allowed the identification of fatty acids and eicosanoids as PPAR ligands. Although the evidence clearly links PPAR isotypes to distinct functions, the molecular basis for this isotype-specificity is still unclear. All three isotypes are able to bind the same consensus response element, formed by a direct repeat of two AGGTCA hexamers separated by one base, though with different affinities. We recently demonstrated that besides the core DR-1 element, the 5' flanking sequence should be included in the definition of a PPRE. Interestingly, the presence of this flanking sequence is of particular importance in the context of PPAR alpha binding. Moreover, it reflects the polarity of the PPAR-RXR heterodimer on DNA, with PPAR binding to the 5' half-site and RXR binding to the 3' half-site. This unusual polarity may confer unique properties to the bound heterodimer with respect to ligand binding and interaction with co-activators and corepressors.