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.

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.

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.

[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.

The renal origin of sodium valproate-induced hyperammonemia in fasting humans.

Acute administration of 1,500 mg of sodium valproate or chronic administration of 30 mg/kg/24 hours induced a more than twofold increase of renal ammoniagenesis in fasting subjects. Hyperammonemia was moderate, as normal hepatic ammonia detoxification persisted. Renal uptake of glutamine increased simultaneously.

Increase of valproate-induced hyperammonemia in normal subjects by carbohydrate intake.

Sodium valproate-induced hyperammonemia in normal subjects is increased by the intake of carbohydrates--rapidly or slowly absorbed sugars, given by mouth or IV injection. The hyperammonemia is maximal about 3 hours after carbohydrate administration. This relation between carbohydrate and ammonia metabolism has not been described previously.

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.

Effects of 2,4-dinitrophenol on renal ammoniagenesis in the rat.

Injection of anesthetized rats with the uncoupling agent, 2,4-dinitrophenol (2,4-DNP) 10 or 20 mg/kg induced a systemic hyperammonemia unaccompanied by blood acid-base status changes and related to an increased release of ammonium from the kidney into the renal vein. Ammonium excretion into the urine did not increase. The renal uptake of circulating glutamine rose. The antiepileptic drug sodium valproate (VPA), a short-chain, branched fatty acid, had the same effects on rat and man. These findings suggest that VPA stimulates renal ammoniagenesis by the same mechanisms as 2,4-DNP.

Sodium valproate-induced hyperammonemia in the rat: role of the kidney.

The intravenous injection of sodium valproate (VPA) 200 mg/kg provoked in fasting rats a 100% increase in the arterial NH+4 concentration by the 10th min. The increase persisted at this level for at least 100 min. Simultaneous measurements of NH+4 and glutamine concentrations in the carotid artery, renal vein and suprahepatic vein showed that there were increases in the release of NH+4 and the uptake of glutamine by the kidney while the [NH+4] of suprahepatic venous blood remained stable. In binephrectomized rats injected with VPA, NH+4 levels did not change. These results suggest that the VPA-induced arterial hyperammonemia depended on the accelerated catabolism or possibly the reduced synthesis of glutamine by the kidneys. The liver of fasting rats does not seem to play a preponderant role in the VPA-induced hyperammonemia.

Decrease of valproate-induced hyperammonemia in normal subjects by lipid ingestion.

Sodium valproate (VPA), a branched short-chain fatty acid, always causes a hyperammonemia of renal origin in fasting man. The intake of medium-length, straight-chain fatty acids abolishes the VPA-induced hyperammonemia, and VPA free fraction increases concomitantly. Accordingly, fatty acids could be useful in preventing and treating hyperammonemia-accompanied stuporous states which are complications of VPA medication.

[Ultra-sensitive TSH levels: an aid in the screening for amiodarone-induced thyroid dysfunction]. / Le dosage de TSH ultra-sensible: une aide au dépistage des dysthyroïdies induites par l'amiodarone.

Amiodarone modifies thyroid hormone secretion and hypothyroidism occurs in some cases. The latter diagnosis is often difficult and is of particular importance in these patients as it may have serious consequences for the heart. Early diagnosis is therefore essential but difficult because of the induced hyperthyroxinemia with maintenance of euthyroidism and a hypotriiodothyronemia. The diagnostic performance of an ultrasensitive method of measuring TSH (TSH-U), capable of distinguishing hyper and euthyroidism were compared with standard thyroid function tests and TSH stimulation with TRH in 50 patients treated with amiodarone. Only 6 of the 14 patients with hyperthyroxinaemia had TSH-U values in the hyperthyroid range: only one of these patients had an increased triiodothyronine. In 2 cases the THS-U was low but the T4L was normal. In 4 patients, increased TSH-U allowed diagnosis of latent or patent hypothyroidism. There was a close correlation between results of the TRH stimulation test and those of the TSH-U in all cases. This test may therefore be used as an initial screening test for thyroid dysfunction in patients on amiodarone and is simple, reliable and relatively cheap to perform. It makes it unnecessary to measure all thyroid hormonal parameters and the TRH test simultaneously.

[Renal origin of hyperammonemia induced by an high-protein diet in normal rats or those with portal stricture]. / Origine rénale de l'hyperammoniémie provoquée par un régime hyperprotidique chez le rat normal ou porteur d'une stricture portale.

Hyperammonemia is observed in high protein diet fed cirrhotic and is thought to be related to an increased intestinal ammoniagenesis. We studied this problem in control rats and rats with a portal stricture and portal systemic shunts given a high protein or a standard diet. In those animals the systemic, portal and renal venous ammonemia and glutaminemia were measured. In rats with portal stricture on a high protein diet, the increase in systemic ammonemia did not significantly differ from that found in animals on a standard diet. In contrast, the control group exhibited a higher level (P less than 0.001) of systemic ammonemia after a high protein (102 +/- 7 SEM mumol/l) than after standard diet (36 +/- 1). This hyperammonemia appeared to be of renal origin since there was a significantly higher ammonia difference between renal venous and arterial blood with the high protein than with standard feeding, both in rats with a portal stricture (+ 229 +/- 32 vs. + 24 +/- 8 mumol/l; P less than 0.001). and in control rats (+ 196 +/- 23 vs. + 2 +/- 11; P less than 0.001). This increased renal ammonia release into the circulation induced by the high protein diet was associated with a high renal uptake of circulating glutamine. Moreover, a decreased ammonia passage from the digestive tract into the portal vein and disappearance of intestinal uptake of circulating glutamine was also observed with the high protein feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

[Renal glutamine metabolism in man during treatment with sodium valproate]. / Métabolisme rénal de la glutamine chez l'homme au cours des traitements par le valproate de sodium.

The administration of 1500 mg sodium valproate to 20 patients provoked in the kidney an increased glutamine uptake correlated with an increased ammonia release, as shown by the changes of the renal arterial-venous concentration differences of glutamine and ammonia. VPA's action on the renal cell may perhaps constitute a valid model for elucidating the effects of this drug on neurons.

[Role of hyperammonemia in stuporous states induced by sodium valproate]. / Rôle de l'hyperammoniémie dans les états stuporeux induits par le valproate de sodium.

Stuporous states induced by sodium valproate (VPA) are accompanied by an isolated marked hyperammonemia. In reality, hyperammonemia occurs after administration of VPA even in the absence of neurological complications. The hyperammonemia is of purely renal origin and results from modifications in glutamine metabolism, this compound being the main precursor of amino acid neurotransmitters. Combined administration of VPA and phenobarbitone increases the level of hyperammonemia due to lack of detoxification by the liver of the excess of ammonia produced by the kidneys. The anatomical site of origin of the ammoniogenesis, and its intensity, were studied in two patients with a history of stuporous states during combined VPA-phenobarbitone treatment. A single injection of VPA at a later date when they were being treated by combined phenobarbitone-carbamazepine therapy, induced disturbances in ammonia metabolism which did not differ qualitatively from those observed when intolerance to VPA is lacking. It is therefore not possible to rely on simple biological tests to detect patients at risk. Correlation is also lacking between the degree of hyperammonemia and disorders of vigilance. Ammonia does not therefore appear to be the only factor responsible for neurological complications and the role of other factors must be investigated. These include: disturbances of metabolism of inhibitory and excitatory aminoacid neurotransmitters, the condition of the cerebral parenchyma, and the excitatory effect of sodium valproate which could act to varying degrees in synergy with the hyperammonemia to provoke a stuporous state.

[Hyperthyroidism and immune hemolytic anemia following amiodarone therapy]. / Hyperthyroïdie et anémie hémolytique immune après traitement par amiodarone.

We report the cases of two patients who, after prolonged amiodarone therapy developed hyperthyroidism and immune haemolytic anaemia. Antibodies were of the IgG type and non-specific at elution. A search for other causes of haemolytic anaemia with positive Coombs' test gave negative results. Antiamiodarone antibodies have recently been discovered; they reflect an immunological disturbance due to this drug and might be responsible for some of the undersirable effects of amiodarone. In our patients, hyperthyroidism and haemolytic anaemia were induced by a dual mechanism: accumulation of amiodarone and induction of an effect of this drug on the immune system.

[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.

[Effects of subcutaneous administration of sandostatine (SMS 201.995) in 18 cases of thyroid medullary cancer]. / Effets de l'administration sous cutanée de la sandostatine (SMS 201.995) en sous cutané dans 18 cas de cancer médullaire du corps thyroïde.

Recent studies have suggested that somatostatin could reduce calcitonin plasma levels (CT) in normal subjects and in medullary thyroid carcinoma (MTC). The aim of this study was to examine the usefulness of the somatostatin analog, sandostatine (SMS 201.995) in MTC with elevated residual CT levels post-thyroidectomy with or without metastases. 18 patients (17-64 years, 12 men and 8 women) with CT greater than 850 pg/ml (N less than 150 pg/ml) and with metastases in 12 cases, were studied. MTC was sporadic in 11 cases, familial in 4 cases and of undefined form in 3. Initial posology was 300 micrograms/d of sandostatin (3 injections/day). It was then increased by 300 micrograms/d every 9 day till a maximum of 1500 micrograms/d. Treatment duration was 37 days in 11 cases and 60 days in 7 cases. Plasma CT and carcinoembryonic antigen levels (CEA) were measured before treatment and at the end of each dosage plateau. Morphologic evaluation of metastases was done at 0, 30, 60 days. 7/18 patients were reevaluated 2 to 8 months after with drawal of sandostatine. Treatment was well tolerated. Flushes improved in 4 out of 5 cases but diarrhea in only 2 out of 9 patients. Sandostatine was without any effect on plasma CEA. Heterogenous responses were observed for plasma CT levels (CT decreases greater than 20% in 8/18 patients when 900 to 1500 micrograms/day were administered). Patients were subdivised into 3 groups according to CEA levels and presence or absence of metastases. Group A (n = 9) had elevated CEA levels (greater than 10 mg/ml) and metastases.(ABSTRACT TRUNCATED AT 250 WORDS)