Diagnostic et prise en charge de l’hyperparathyroïdie primaire

Objectif : L’hyperparathyroïdie primaire (hPTP) est définie par la production excessive et inappropriée de parathormone (PTh). Les formes asymptomatiques et modérées sont devenues de plus en plus fréquentes. Le but de ce travail est d’étudier les caractéristiques cliniques et paracliniques de l’hPTP, de préciser les indications thérapeutiques et de les discuter en comparant nos résultats avec ceux de la littérature.Matériel et méthodes: Il s’agit d’une étude rétrospective à propos de 86 patients colligés entre Janvier 2005 et Décembre 2010. Tous les patients ont bénéficié d’un examen ORL et d’un bilan biologique comportant une calcémie et un dosage de la PTh. Le bilan radiologique comportait une échographie cervicale, une scintigraphie au MIBI et/ou une IRM cervicale.Tous les patients ont été opérés sous anesthésie générale et ont eu une cervicotomie par approche classique. La surveillance a été clinique et biologique avec un recul moyen de 16 mois (4-36 mois).Résultats : La calcémie était élevée chez 77 patients (89,5%) et la PTh chez tous les patients. Une échographie cervicale a été réalisée chez 79 patients et a montré une image en faveur d’un adénome parathyroïdien chez 37 d’entre eux (46,8%). La scintigraphie au MIBI, pratiquée chez 46 patients, a montré une hyperfixation dans 31 cas (67,4%). L’IRM aété pratiquée chez 5 patients et a révélé un adénome dans 3 cas.L’exploration chirurgicale avec examen extemporané a révélé un adénome unique chez 65 patients deux adénomes chez 12 patients, et une hypertrophie des 4 PTh chez 9 autres. Une exérèse des adénomes a été ainsi réalisée chez 77 patients et une parathyroïdectomie subtotale dans 9 cas. en post-opératoire, 12 patients (14%) ont présenté une hypocalcémietransitoire. Aucune hypocalcémie définitive ni paralysie récurrentielle n’ont été notées. L’examen anatomopathologique définitif a révélé un adénome unique, un adénome double, une hyperplasie et PTh normale respectivement chez 58, 3, 24 et 1 patients. L’évolution à long terme a été marquée par l’amélioration clinique et biologique chez 81 patients  (94,2%). Une non-amélioration clinique et biologique a été notée chez 5 patients. Ils ont été réopérés et ont eu une parathyroïdectomie subtotale. L’anatomopathologie confirmait l’hyperplasie dans tous les cas.Conclusion : Le traitement de l’hPTP symptomatique est chirurgical. L’approche classique a fait preuve de son efficacité. Les progrès récents des explorations préopératoires et le dosage peropératoire de la PTh ont rendu possible une approche mini-invasive. Des controverses persistent quant à la prise en charge de l’hPTP asymptomatique dont l’indicationthérapeutique doit être bien étudiée.Mots-clés : hyperparathyroïdie primaire, adénome, glande parathyroïde, parathormone, scintigraphie, parathyroïdectomi

The Effect of Imatinib Mesylate for Newly Diagnosed Philadelphia Chromosome-Positive, Chronic-Phase Myeloid Leukemia in Sub-Saharan African Patients: The Experience of Côte d'Ivoire

Imatinib mesylate, showed encouraging activity in chronic myelogenous leukemia. However, there are few data regarding his efficacy and response monitoring in Sub-Saharan African patients. Our objective was to assess response to imatinib mesylate (Glivec) in Côte d'Ivoire patients with newly diagnosed Chronic Myeloid Leukemia (CML). From May 2005 to September 2009, we treated 42 patients (40 years; range 16–69) with Philadelphia chromosome (Ph+) positive in chronic phase CML with oral imatinib mesylate at daily doses of 400 mg. Overall survival (OS) and frequency of complete or major cytogenetic remission (CCR/MCR) were evaluated. At a median follow up of 32 (range 7.6–113) months, the CHR rate in our study group was 76%. A major CR was found in 19 patients (45%) with 17% and 29% complete and partial CR respectively. There were no significant differences in the incidence of major cytogenetic response by known prognostics factors. Median time to CHR was 8 months (range 0.4–25), and 16 months (range: 0.1–36) for CR. Projected 5-year OS rate was 72% (95%CI 42–88). We conclude that imatinib therapy sub-Saharan African CML patients is very promising and has favorably changed the prognosis for black African patients with CML

Global DNA methylation and cognitive and behavioral outcomes at 4 years of age: A cross‐sectional study

Background Accumulating evidence suggests that breastfeeding exclusivity and duration are positively associated with child cognition. This study investigated whether DNA methylation, an epigenetic mechanism modified by nutrient intake, may contribute to the link between breastfeeding and child cognition. The aim was to quantify the relationship between global DNA methylation and cognition and behavior at 4 years of age. Methods Child behavior and cognition were measured at age 4 years using the Wechsler Preschool and Primary Scale of Intelligence, third version (WPPSI‐III), and Child Behavior Checklist (CBC). Global DNA methylation (%5‐methylcytosines (%5mC)) was measured in buccal cells at age 4 years, using an enzyme‐linked immunosorbent assay (ELISA) commercial kit. Linear regression models were used to quantify the statistical relationships. Results Data were collected from 73 children recruited from the Women and Their Children's Health (WATCH) study. No statistically significant associations were found between global DNA methylation levels and child cognition or behavior (p > .05), though the estimates of effect were consistently negative. Global DNA methylation levels in males were significantly higher than in females (median %5mC: 1.82 vs. 1.03, males and females, respectively, (p < .05)). Conclusion No association was found between global DNA methylation and child cognition and behavior; however given the small sample, this study should be pooled with other cohorts in future meta‐analyses

Risk stratification by pre-operative cardiopulmonary exercise testing improves outcomes following elective abdominal aortic aneurysm surgery : a cohort study

Background: In 2009, the NHS evidence adoption center and National Institute for Health and Care Excellence (NICE) published a review of the use of endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs). They recommended the development of a risk-assessment tool to help identify AAA patients with greater or lesser risk of operative mortality and to contribute to mortality prediction. A low anaerobic threshold (AT), which is a reliable, objective measure of pre-operative cardiorespiratory fitness, as determined by pre-operative cardiopulmonary exercise testing (CPET) is associated with poor surgical outcomes for major abdominal surgery. We aimed to assess the impact of a CPET-based risk-stratification strategy upon perioperative mortality, length of stay and non-operative costs for elective (open and endovascular) infra-renal AAA patients. Methods: A retrospective cohort study was undertaken. Pre-operative CPET-based selection for elective surgical intervention was introduced in 2007. An anonymized cohort of 230 consecutive infra-renal AAA patients (2007 to 2011) was studied. A historical control group of 128 consecutive infra-renal AAA patients (2003 to 2007) was identified for comparison. Comparative analysis of demographic and outcome data for CPET-pass (AT ≥ 11 ml/kg/min), CPET-fail (AT < 11 ml/kg/min) and CPET-submaximal (no AT generated) subgroups with control subjects was performed. Primary outcomes included 30-day mortality, survival and length of stay (LOS); secondary outcomes were non-operative inpatient costs. Results: Of 230 subjects, 188 underwent CPET: CPET-pass n = 131, CPET-fail n = 35 and CPET-submaximal n = 22. When compared to the controls, CPET-pass patients exhibited reduced median total LOS (10 vs 13 days for open surgery, n = 74, P < 0.01 and 4 vs 6 days for EVAR, n = 29, P < 0.05), intensive therapy unit requirement (3 vs 4 days for open repair only, P < 0.001), non-operative costs (£5,387 vs £9,634 for open repair, P < 0.001) and perioperative mortality (2.7% vs 12.6% (odds ratio: 0.19) for open repair only, P < 0.05). CPET-stratified (open/endovascular) patients exhibited a mid-term survival benefit (P < 0.05). Conclusion: In this retrospective cohort study, a pre-operative AT > 11 ml/kg/min was associated with reduced perioperative mortality (open cases only), LOS, survival and inpatient costs (open and endovascular repair) for elective infra-renal AAA surgery

Effect of microneedles on transdermal permeation enhancement of amlodipine

The present study aimed to investigate the effect of microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation enhancement of amlodipine (AMLO). Two types of MN devices viz. AdminPatch® arrays (ADM) (0.6, 1.2 and 1.5 mm lengths) and laboratory-fabricated polymeric MNs (PM) of 0.6 mm length were employed. In the case of PMs, arrays were applied thrice at different places within a 1.77-cm2 skin area (PM-3) to maintain the MN density closer to 0.6 mm ADM. Scaling analyses were done using dimensionless parameters like concentration of AMLO (Ct/Cs), thickness (h/L) and surface area of the skin (Sa/L2). Microinjection moulding technique was employed to fabricate PM. Histological studies revealed that the PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 6.84- and 6.11-fold increase in the cumulative amount (48 h) of AMLO permeated was observed with 1.5 mm ADM and PM-3 treatments respectively, when compared to passive permeation amounts. Good correlations (R2 > 0.89) were observed between different dimensionless parameters with scaling analyses. The enhancement in AMLO permeation was found to be in the order of 1.5 mm ADM ≥ PM-3 > 1.2 mm ADM > 0.6 mm ADM ≥PM-1 > passive. The study suggests that MN application enhances the AMLO transdermal permeation and the geometrical parameters of MNs play an important role in the degree of such enhancement

Hot Exoplanet Atmospheres Resolved with Transit Spectroscopy (HEARTS) VIII. Nondetection of sodium in the atmosphere of the aligned planet KELT-10b

We searched for potential atmospheric species in KELT-10b, focusing on sodium doublet lines (Na i; 589 nm) and the Balmer alpha line (H $\alpha$; 656 nm) in the transmission spectrum. Furthermore, we measured the planet-orbital alignment with the spin of its host star. We used the Rossiter-McLaughlin Revolutions technique to analyze the local stellar lines occulted by the planet during its transit. We used the standard transmission spectroscopy method to probe the planetary atmosphere, including the correction for telluric lines and the Rossiter-McLaughlin effect on the spectra. We analyzed two new light curves jointly with the public photometry observations. We do not detect signals in the Na i and H $\alpha$ lines within the uncertainty of our measurements. We derive the 3-sigma upper limit of excess absorption due to the planetary atmosphere corresponding to equivalent height Rp to 1.8Rp (Na i) and 1.9Rp (H $\alpha$). The analysis of the Rossiter-McLaughlin effect yields the sky-projected spin-orbit angle of the system $\lambda$ = -5.2 $\pm$ 3.4 and the stellar projected equatorial velocity $v_{eq} \sin{i_\star}$ = 2.58 $\pm$ 0.12 km/s. Photometry results are compatible within 1 -sigma with previous studies. We found no evidence of Na i and H $\alpha$, within the precision of our data, in the atmosphere of KELT-10b. Our detection limits allow us to rule out the presence of neutral sodium or excited hydrogen in an escaping extended atmosphere around KELT-10b. We cannot confirm the previous detection of Na i at lower altitudes with VLT/UVES. We note, however, that the Rossiter-McLaughlin effect impacts the transmission spectrum on a smaller scale than the previous detection with UVES. Analysis of the planet-occulted stellar lines shows the sky-projected alignment of the system, which is likely truly aligned due to tidal interactions of the planet with its cool (Teff < 6250 K) host star.Comment: Accepted in A&

TOI-858 B b: A hot Jupiter on a polar orbit in a loose binary

We report the discovery of a hot Jupiter on a 3.28-day orbit around a 1.08 M$_{Sun}$ G0 star that is the secondary component in a loose binary system. Based on follow-up radial velocity observations of TOI-858 B with CORALIE on the Swiss 1.2 m telescope and CHIRON on the 1.5 m telescope at the Cerro Tololo Inter-American Observatory (CTIO), we measured the planet mass to be $1.10\pm 0.08$ M$_{J}$ . Two transits were further observed with CORALIE to determine the alignment of TOI-858 B b with respect to its host star. Analysis of the Rossiter-McLaughlin signal from the planet shows that the sky-projected obliquity is $\lambda = 99.3\pm 3.8$. Numerical simulations show that the neighbour star TOI-858 A is too distant to have trapped the planet in a Kozai-Lidov resonance, suggesting a different dynamical evolution or a primordial origin to explain this misalignment. The 1.15 Msun primary F9 star of the system (TYC 8501-01597-1, at $\rho$ ~11") was also observed with CORALIE in order to provide upper limits for the presence of a planetary companion orbiting that star.Comment: Accepted for publication in A&

Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome

Statistical methodology for the analysis of dye-switch microarray experiments

<p>Abstract</p> <p>Background</p> <p>In individually dye-balanced microarray designs, each biological sample is hybridized on two different slides, once with <it>Cy3 </it>and once with <it>Cy5</it>. While this strategy ensures an automatic correction of the gene-specific labelling bias, it also induces dependencies between log-ratio measurements that must be taken into account in the statistical analysis.</p> <p>Results</p> <p>We present two original statistical procedures for the statistical analysis of individually balanced designs. These procedures are compared with the usual ML and REML mixed model procedures proposed in most statistical toolboxes, on both simulated and real data.</p> <p>Conclusion</p> <p>The UP procedure we propose as an alternative to usual mixed model procedures is more efficient and significantly faster to compute. This result provides some useful guidelines for the analysis of complex designs.</p