Mach number dependence of turbulent magnetic field amplification: solenoidal versus compressive flows.

We study the growth rate and saturation level of the turbulent dynamo in magnetohydrodynamical simulations of turbulence, driven with solenoidal (divergence-free) or compressive (curl-free) forcing. For models with Mach numbers ranging from 0.02 to 20, we find significantly different magnetic field geometries, amplification rates, and saturation levels, decreasing strongly at the transition from subsonic to supersonic flows, due to the development of shocks. Both extreme types of turbulent forcing drive the dynamo, but solenoidal forcing is more efficient, because it produces more vorticity.

Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d'etude des Tumeurs Endocrines.

CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) disease is an autosomal dominant syndrome that is believed to equally affect men and women. This assumption has never been confirmed. OBJECTIVE: The aims of this study were to evaluate the impact of gender on the prevalence of MEN1 lesions, on their lifetime probability of occurrence, and on the diagnosis of MEN1. DESIGN: Data regarding a study of 734 cases of MEN1 from the multicenter 'Groupe d'étude des Tumeurs Endocrines' were analyzed. RESULTS: There were 57.8% females. The prevalence and probability of pancreatic tumors were higher in males than in females (P=0.06, P=0.0004). This difference was due to gastrinomas. The prevalence and probability of developing pituitary tumors were significantly greater in females (P<0.001, P<0.0001). Thymic tumors were exclusively found in men. There were no significant gender differences in the prevalence and the probability of developing hyperparathyroidism, or adrenal and bronchial tumors, or in the proportion of positive genetic tests. A family history of MEN1 was more frequently found in men than in women at the time of diagnosis (P=0.02). In the case of pituitary tumor, the proportion of patients diagnosed with MEN1 at the time of the first lesion was lower in women (44.2%) than in men (67.3%). CONCLUSION: The phenotype expression of the MEN1 disease gene was different in males and females. In female patients, the possibility of MEN1 is not sufficiently taken into account. Any patient presenting a lesion that belongs to the MEN1 spectrum, such as a pituitary tumor, should be closely questioned about their family history and should be tested for hypercalcemia.

Prognostic factors of disease-free survival after thyroidectomy in 170 young patients with a RET germline mutation: a multicenter study of the Groupe Francais d'Etude des Tumeurs Endocrines.

BACKGROUND: In hereditary medullary thyroid carcinoma (HMTC), prophylactic surgery is the only curative option, which should be properly defined both in time and extent. OBJECTIVES: To identify and characterize prognostic factors associated with disease-free survival (DFS) in children from HMTC families. DESIGN: We conducted a retrospective analysis of a multi-center cohort of 170 patients below age 21 at surgery. Demographic, clinical, genetic, biological data [basal and pentagastrine-stimulated calcitonin (CT and CT/Pg, respectively)], and tumor node metastasis (TNM) status were collected. DFS was assessed based on basal CT levels. Kaplan-Meier curves, Cox regression, and logistic regression models were used to determine factors associated with DFS and TNM staging. RESULTS: No patients with a preoperative basal CT <31 ng/ml had persistent or recurrent disease. Medullary thyroid carcinoma defined by a diameter ≥10 mm [hazard ratio (HR): 6.0; 95% confidence interval (95% CI): 1.8-19.8] and N1 status (HR: 20.8; 95% CI: 3.9-109.8) were independently associated with DFS. Class D genotype [odds ratio (OR): 48.5, 95% CI: 10.6-225.1], preoperative basal CT >30 ng/liter (OR: 43.4, 95% CI: 5.2-359.8), and age >10 (OR: 5.5, 95% CI: 1.4-21.8) were associated with medullary thyroid carcinoma ≥10 mm. No patient with a preoperative basal CT <31 ng/ml had a N1 status. Class D genotype (OR: 48.6, 95% CI: 8.6-274.1), and age >10 (OR: 4.6, 95% CI: 1.1-19.0) were associated with N1 status. CONCLUSION: In HMTC patients, DFS is best predicted by TNM staging and preoperative basal CT level below 30 pg/ml. Basal CT, class D genotype, and age constitute key determinants to decide preoperatively timely surgery.

Addendum to "Equation of state of classical Coulomb plasma mixtures".

Recently developed analytic approximation for the equation of state of fully ionized nonideal electron-ion plasma mixtures [A. Y. Potekhin, G. Chabrier, and F. J. Rogers, Phys. Rev. E 79, 016411 (2009)], which covers the transition between the weak and strong Coulomb coupling regimes and reproduces numerical results obtained in the hypernetted-chain (HNC) approximation, is modified in order to fit the small deviations from the linear mixing in the strong-coupling regime, revealed by recent Monte Carlo simulations. In addition, a mixing rule is proposed for the regime of weak coupling, which generalizes post-Debye density corrections to the case of mixtures and numerically agrees with the HNC approximation in that regime.

Association of malignant insulinoma and type 2 diabetes mellitus: a case report.

We report a case of recurrent hypoglycemia due to malignant insulinoma in a type 2 diabetic patient correctly controlled for years with the same doses of oral antidiabetic agents. A 79-year-old woman was admitted for recurrent severe hypoglycemia. She had a history of type 2 diabetes since 2000. HbA1c was 7.8% when she reported mild hypoglycemia and 5.8% when recurrent hypoglycemia appeared despite progressive diminution of glicazide. Severe hypoglycemia continued despite interrupting diabetes medications. At admission, results showed inappropriately elevated insulin, C-peptide and proinsulin levels despite significant hypoglycemia. CT scan showed "cystic" nodes in the pancreas and in the liver. Liver biopsy found a well-differentiated neuroendocrine carcinoma with positive staining for chromogranin A and negative staining for insulin. Hypoglycemia improved with diazoxide, lanreotide and dextrose infusion. Liver chemoembolization was planned. Severe edema, dyspnea, hyponatremia, and hypo-osmolarity occurred. The patient's clinical status deteriorated rapidly with severe cardiac, renal and hepatic failure. She died in a few days. Association of diabetes mellitus and insulinoma is extremely rare. Malignant insulinoma survival is less than two years, shorter when hepatic localizations are present at diagnosis. Association of diabetes with insulinoma delays the diagnosis, but does not alter prognosis or favor carcinoma frequency. Lanreotide was inefficient in our patient despite good responses described in the literature. Heart, respiratory and renal failures have been described with diazoxide independently of the doses; this may in part explain the rapid death. Insulinoma should be considered as a cause of unusual and recurrent hypoglycemia in a diabetic patient especially if it persists after interrupting antidiabetic agents.

Efficacy of short term continuous subcutaneous insulin lispro versus continuous intravenous regular insulin in poorly controlled, hospitalized, type 2 diabetic patients.

UNLABELLED: Intravenous insulin infusion (IVII) is rapidly effective in improving glycaemia in uncontrolled hospitalized diabetic patients. This significantly improves their morbidity and mortality. Intravenous insulin infusion may lead to IV infusion complications and is a heavy burden for caregivers. AIM: The aim of our work was to compare the efficacy of IV regular insulin versus lispro Continuous Subcutaneous Insulin Infusion (CSII), in improving glycaemia in patients hospitalized for uncontrolled type 2 diabetes, the efficacy being assessed on the average blood glucose level observed. METHODS: The study was designed as a prospective randomized study. Thirty-three type 2 diabetic patients, hospitalized for uncontrolled diabetes by their usual practitioner were included. After acceptation, patients were randomly assigned to lispro CSII (group 1, n=20) or IVII regular insulin (group 2, n=13) for 5 days. Ten capillary blood glucose/day were performed. Pre-meal blood glucose targets were 4.4-6.6 mmol/l. Mann Whitney, Wilcoxon and Fischer exact tests were used. RESULTS: BG levels decreased significantly (-3.4+/-0.55 mmol/l in group 1 and -3.60+/-0.55 mmol/l in group 2, P<0.01) during the first 12 hours. Mean daily blood glucose at day 5 was statistically improved in both groups compared to day 1 (P<0.05 Wilcoxon) and comparable between the 2 groups. No severe hypoglycaemia was reported. No catheter complications occurred in group 1, 7 occurred in group 2. CONCLUSION: CSII and IVII infusion were comparable in rapidly improving hyperglycaemia in uncontrolled type 2 diabetic patients. CSII, being more convenient, could be preferred in medical and surgical settings.

Insulin initiation in type 2 diabetic patients admitted in hospital in France and follow-up at 1 year.

OBJECTIVES AND METHODS: The IDAHO 2 epidemiological survey was conducted in departments of diabetology in insulin-naïve type 2 diabetics for whom insulin was initiated. The objective was to assess the patients' profile, the treatments proposed during hospital stay and after one year. RESULTS: 797 patients were analysed. Their characteristics were: age 64+/-12 years, 49% males, weight: 78+/-17 kg, BMI: 29+/-6 kg/m2, diabetes duration 11 years, prevalence of complications: 68%, fasting blood glucose 13+/-6 mmol/l, HbA1c: 10+/-2.2%; treatment prior to insulin comprised: at least 2 OHA: 71% of cases, one: 21%, no OAD: 8%. At hospital discharge, 54% of the patients used basal insulin. After 1 year, 670 continued on insulin. The insulin initiation was accompanied by a decrease in the FBG level (baseline: 13+/-6 mmol/l; final: 8.5+/-2.75 mmol/l; P<0.0001) and a HbA1c improvement (baseline: 10+/-2.2%; final: 7.9+/-1.4%; P<0.0001). This was observed du-ring the first 6 months (HbA1c: 7.8%, P<0.0001 versus baseline). 80% of the patients remained on the same insulin regimen after 1 year: 35% had 1 injection/day, 44% had 2, 12% had 3 and 9% had a complex regimen. The weight gain, the final daily dose and hypoglycaemias increased with the number of injections. The mean daily insulin dose was 33 U/day (24 U with 1 injection/day). CONCLUSION: The IDAHO study shows that insulin is effective in type 2 diabetics however, management is inadequate with insulin therapy being initiated too late and at doses which are low after one year.

[How to prescribe physical activity in clinical practice?]. / Comment prescrire l'activité physique en pratique médicale?

Accumulating scientific evidence indicates that regular physical activity confers significant health benefits. Besides its preventive interest, its promotion is an effective approach of several health problems, including obesity and type 2 diabetes. Its clinical prescription is based on two complementary approaches aimed to decrease sedentary behaviours and/or to promote an active lifestyle with long-term objectives. Physicians can play a key role in motivating patients by advising them regarding their physical limitations, their goals, their concerns, and the barriers to exercise. Assessment of the patient's attitudes and motivation towards physical activity is a key element for the success. Objectives, clearly defined, should be evaluated and adapted on a regular basis, with the patient and taking into account the familial and social environment.

Familial medullary thyroid carcinoma with noncysteine ret mutations: phenotype-genotype relationship in a large series of patients.

Familial medullary thyroid carcinoma only is related to germline mutations in the protooncogene RET, mainly in exons 10, whereas noncysteine mutations (exons 13-15) are considered infrequent. We analyzed 148 patients from 47 familial medullary thyroid carcinoma only families, and we found noncysteine RET mutations in 59.5% of these families. Of the index cases with noncysteine mutations, 43.4% presented with a multinodular goiter and high basal calcitonin; they were older at diagnosis than those with mutation in exon 10 and had more multifocal medullary thyroid carcinoma, but no difference in size, bilaterality, presence of C cell hyperplasia, or nodal metastases was found. Gene carriers with noncysteine RET mutations had a lower incidence of medullary thyroid carcinoma (78.2% vs. 94.1%) than those with mutation in exon 10; 20.2% had C cell hyperplasia only, although thyroidectomized at an older age. In conclusion, familial medullary thyroid carcinoma with noncysteine RET mutations are not infrequent and are overrepresented in presumed sporadic medullary thyroid carcinoma, suggesting that RET analysis should routinely be extended to exons 13, 14, and 15. The phenotype is characterized by a late onset of the disease, suggesting a delayed appearance of C cell disease rather than a less aggressive form. In familial medullary thyroid carcinoma gene carriers, the optimal timing for thyroidectomy remains controversial. Based on these data, we propose that surgery should be performed before elevation of the basal calcitonin level, potentially as soon as the pentagastrin test becomes abnormal.

Pheochromocytoma in multiple endocrine neoplasia type 2: a prospective study.

OBJECTIVE: The aim of this prospective study is to update our knowledge of the chronology of pheochromocytoma occurrence in multiple endocrine neoplasia type 2 (MEN 2), and to better manage MEN 2 patients after the genetic diagnosis. DESIGN: Eighty-seven non-index gene carrier MEN 2 patients were included in this prospective study: 84 patients with MEN 2A (from 52 families) and 3 with MEN 2B (from 3 families). METHODS: Medullary thyroid carcinoma (MTC) was diagnosed by measuring plasma calcitonin in basal conditions or after pentagastrin stimulation. The search for pheochromocytoma consisted of clinical evaluation, 24 h determination of urinary catecholamines and adrenal imaging. The mean age at genetic diagnosis of MEN 2 was 14.0+/-7.0 years, the mean duration for the follow-up was 7.6+/-2.8 years. RESULTS: All 87 patients had a MTC detected at the same time as the genetic diagnosis was made. Urinary catecholamine measurements led to the diagnosis of pheochromocytoma and a combination of imaging techniques enabled the correct localization of both unilateral or bilateral adrenal involvement. Pheochromocytoma was detected simultaneously with MTC in only seven patients, and seven others were detected throughout the follow-up. Of the 14 patients with pheochromocytoma, 11 had bilateral involvement: nine were initially bilateral and two became so during follow-up. CONCLUSION: This study demonstrates that in MEN 2, MTC is the lesion which appears earliest. Pheochromocytoma develops later during the evolution of the disease, and necessitates regular clinical and biological monitoring throughout follow-up. Determination of urinary and/or plasma catecholamines and metanephrines should be performed to detect pheochromocytoma. Imaging techniques lead to the detection of both unilateral and bilateral pheochromocytoma, thus making video-assisted laparoscopic adrenalectomy possible.

[Surgery for obesity]. / La chirurgie de l'obésité.

With the development of new surgical techniques (laparoscopic procedure, adjustable gastric banding) bariatric surgery is still increasing. In France about 10,000 adjustable gastric banding have been performed during the last year, as well as a thousand of gastric operations and approximately fifty gastric by-pass. The surgical approach has a real efficacy on weight loss and is associated with a reduction in comorbid conditions. However its long-term efficacy, its effects on quality of life, its nutritional consequences and the surgical-linked complication incidence are only poorly evaluated, especially for adjustable gastric banding. Therefore bariatric surgery indications should be thoroughly examined. As recommended by the experts, surgical treatment for obesity should be restricted to patients presenting morbid obesity, and this despite a multidisciplinary medical treatment. Long-term post-surgical follow-up is necessary and may be an important determinant of long-term efficacy. Considering the growing number of this type of intervention outside of any evaluation, a national register is recommended.

Equation of state of fully ionized electron-ion plasmas. II. Extension To relativistic densities and to the solid phase

The analytic equation of state of nonideal Coulomb plasmas consisting of pointlike ions immersed in a polarizable electron background [G. Chabrier and A. Y. Potekhin, Phys. Rev. E 58, 4941 (1998)] is improved, and its applicability range is considerably extended. First, the fit of the electron screening contribution in the free energy of the Coulomb liquid is refined at high densities where the electrons are relativistic. Second, we calculate the screening contribution for the Coulomb solid (bcc and fcc) and derive an analytic fitting expression. Third, we propose a simple approximation to the internal and free energy of the liquid one-component plasma of ions, accurate within the numerical errors of the most recent Monte Carlo simulations. We obtain an updated value of the coupling parameter at the solid-liquid phase transition for the one-component plasma: Gamma(m)=175.0+/-0.4(1sigma).

Partially ionized hydrogen plasma in strong magnetic fields.

We study the thermodynamic properties of a partially ionized hydrogen plasma in strong magnetic fields, B approximately 10(12)-10(13) G, typical of neutron stars. The properties of the plasma depend significantly on the quantum-mechanical sizes and binding energies of the atoms, which are strongly modified by thermal motion across the field. We use new fitting formulas for the atomic binding energies and sizes, based on accurate numerical calculations and valid for any state of motion of the atom. In particular, we take into account decentered atomic states, neglected in previous studies of thermodynamics of magnetized plasmas. We also employ analytic fits for the thermodynamic functions of nonideal fully ionized electron-ion Coulomb plasmas. This enables us to construct an analytic model of the free energy. An ionization equilibrium equation is derived, taking into account the strong magnetic field effects and the nonideality effects. This equation is solved by an iteration technique. Ionization degrees, occupancies, and the equation of state are calculated.

Sertoli cell barrier dysfunction and spermatogenetic cycle breakdown in the human testis: a lanthanum tracer investigation.

The introduction of nitrate of lanthanum in fixative solutions for testicular biopsies improves ultrastructural observations of the blood-testis barrier. In complete (normal) spermatogenesis, junctional specializations impede the diffusion of lanthanum into the adluminal compartment. They clearly exhibit a three-storied disposition in orthogonal sections. In maturation arrest, lanthanum passes easily through the junctional specializations surrounding the germ cells and up to the lumen. In irregular hypospermatogenesis, the Sertoli cell barrier is permeable, but diffusion of the tracer is less significant and variable. Unexpectedly, in germ cell aplasia, the barrier remains efficient

RET mutations in exons 13 and 14 of FMTC patients.

RET is a receptor tyrosine kinase gene which is responsible for three different inherited cancer syndromes namely multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC) as well as for Hirschsprung disease (HSCR), a congenital disorder affecting the intestinal motility. Germ-line mutations in the RET exons 10 and 11 were demonstrated in the majority of the MEN 2A and FMTC patients. On the other hand, one codon of RET exon 16 is preferentially changed in MEN 2B patients. Recently, a germ-line mutation in the exon 13 was described in one FMTC family as well as in four sporadic MTCs. In the present study, we observed the same exon 13 mutation in two FMTC families. In addition, we identified a previously unreported substitution of RET exon 14 in two unrelated FMTC families. Both mutations segregate with the disease in these four FMTC families and involve the tyrosine kinase domain of RET. Haplotype analysis using polymorphic markers tightly linked to the RET gene indicates that in each pedigree the mutation arose as an independent event.