Charles Oliver

Shear Wave Elastography: A New Ultrasound Imaging Mode for the Differential Diagnosis of Benign and Malignant Thyroid Nodules

CONTEXT Elastography uses ultrasound (US) to assess elasticity. Shear wave elastography (SWE) is a new technique that estimates tissue stiffness in real time and is quantitative and user independent. OBJECTIVES The aim of the study was to assess the efficiency of SWE in predicting malignancy and to compare SWE with US. DESIGN Ninety-three patients and 39 control subjects were included in the study. Predictive value of SWE was assessed by correlation between elasticity, US parameters, and histology. Elasticity index (EI) was first analyzed alone. Scores have been constructed with echographic parameters, i.e. vascularity, hypoechogenicity, and microcalcifications (Score 1=US Score), and with the same parameters plus EI (Score 2=US+SWE Score). For statistical analysis, univariate and multivariate analysis and receiver operating characteristic curves were used. RESULTS A total of 146 nodules from 93 patients were analyzed. Twenty-nine nodules (19.9%) were malignant. Mean (±sd) EI was 150±95 kPa (range, 30-356) in malignant nodules vs. 36±30 (range, 0-200) kPa in benign nodules (P<0.001, Students t test). For a positive predictive value of at least 80%, characteristics of tissue elasticity (cutoff, 65 kPa) were: sensitivity=85.2%, and specificity=93.9%. Characteristics of the US Score were: sensitivity=51.9% [95% confidence interval (CI), 33.1; 70.7], and specificity=97% (95% CI, 93.6; 1). Characteristics of the US+SWE Score were: sensitivity=81.5% (95% CI, 66.9; 96.1), and specificity=97.0% (95% CI, 93.6; 1). CONCLUSION Promising results have been obtained with SWE. This technique may be applied to multinodular goiters. Larger prospective studies are needed to confirm these results and to define the respective places of SWE, US, and FNA.

Distribution of α-melanocyte-stimulating hormone in the rat brain: Evidence that α-MSH-containing cells in the arcuate region send projections to extrahypothalamic areas

Abstract The distribution and concentration of α-MSH in the rodent brain has been determined by radioimmunoassay. The limbic system contained substantial quantities of α-MSH. Forty per cent of the α-MSH present in the brain was localized in the hypothalamus, with the highest concentration of α-MSH in the arcuate nucleus. More than 40% of the extrahypothalamic α-MSH in the brain was found in the following areas: midbrain (16%), preoptic area (13%), septum (7%), and thalamus (7%). To determine the source of the hypothalamic and extrahypothalamic α-MSH, the anterior hypothalamic preoptic area of the brain was surgically separated from more caudal diencephalic structures, and the arcuate region of the hypothalamus was surgically isolated from the remainder of the brain. Following these deafferentations, no significant reduction in hypothalamic α-MSH levels was observed; however, a significant reduction in extrahypothalamic α-MSH levels was demonstrated. This dramatic decrease of α-MSH in extrahypothalamic areas of the rodent brain strongly suggests that the bulk of the extrahypothalamic α-MSH arises from neuronal perikarya in the arcuate region. These findings are consistent with the hypothesis that a population of neuronal cell bodies producing α-MSH originate in the arcuate region of the hypothalamus and that they send axonal projections to many areas of the limbic system and brain stem.

Effect of nicotine on in vivo secretion of melanocorticotropic hormones in the rat

Abstract Corticosterone, ACTH, β-endorphin and α-MSH were measured in rat plasma by radioimmunoassay before and 2,5,15,30 minutes after an intraperitoneal injection of nicotine (500 μg/Kg b.w.). Nicotine induced an increase of plasma corticosterone (p

Influence of haloperidol on ACTH and β-endorphin secretion in the rat☆

The injection of haloperidol, a dopamine receptor blocker, was followed by a large increase of plasma ACTH and beta-endorphin-like immunoreactivity (beta-EI) in the rat. This effect was prevented when the rats were previously treated with corticosteroids. These results suggest that catecholamines inhibit ACTH and beta-endorphin secretion in the rat.

Pharmacokinetic evidence for suboptimal treatment of adrenal insufficiency with currently available hydrocortisone tablets.

Background and ObjectiveAdrenal insufficiency is caused by primary adrenal failure or by impairment of the corticotropic axis. In both situations, cortisol secretion is deficient, and hydrocortisone is a logical replacement therapy. However, no consensus guideline for dosing has been published, and clinicians adapt the dose empirically after only a clinical evaluation. Under this regimen, some patients receiving an inappropriately high dose of cortisol feel comfortable and also have an increased risk of adverse effects. We performed a pharmacokinetic study of cortisol in patients with adrenal insufficiency to evaluate plasma concentrations when the dosing was based on clinical examination and to develop a model allowing optimization of drug dosing.Study DesignThis was a prospective, open-label study in two endocrinology departments and a clinical investigation centre (Assistance Publique Hôpitaux de Marseille, Marseille, France).MethodsFifty patients with primary (n = 20) or secondary (n = 30) adrenal insufficiency were recruited. All patients were given their usual hydrocortisone replacement regimen. Blood samples for cortisol measurements were drawn at 0600, 0800, 1000, 1200, 1400, 1600, 1800, 2000, 2200 and 0000 h. The observed values were compared with the known physiological range throughout the day (0800, 1600 and 0000 h). A population pharmacokinetic analysis was performed using nonlinear mixed-effects modelling software (NONMEM®). The final pharmacokinetic model was then used to simulate several hydrocortisone dosing scenarios.ResultsThirteen different treatment regimens for 50 patients were observed. The cortisol plasma concentrations were compared with the physiological range and showed that 79%, 55% and 45% of patients were over- or under-treated at 0800, 1600 and 2400 h, respectively. The cortisol concentrations showed wide variability and were best described using a one-compartment model with zero-order input and first-order elimination. The pharmacokinetic parameters (intersubject variability) were the following: duration of absorption 0.54 hour, volume of distribution 38.7 L (39.7%) and clearance 12.1 L/h (23.2%). The proportional residual error was 32.3%. This final model was then used to simulate 18 different dosing regimens. The regimen with the highest proportion of simulated patients within the physiological targets was 10 + 5 + 5 mg at 0730, 1200 and 1630 h, respectively. However, even with this regimen, about 54%, 44% and 32% of patients would remain over- or under-treated at 0800, 1600 and 2400 h, respectively.ConclusionsMost patients with adrenal insufficiency are imperfectly treated with hydrocortisone relative to their plasma cortisol concentrations. Using simulation, a standard dosing regimen is suggested, which increases the proportion of patients within the physiological target concentrations. However, an individualized dose adjustment would be more accurate.

Enkephalins, ACTH, α-MSH and β-endorphin in human pheochromocytomas

Abstract Three human pheochromocytomas obtained shortly after resection were analyzed for methionine- and leucine-enkephalin and enkephalin-containing proteins as well as ACTH, α-MSH, β-endorphin and catecholamines. The pheochromocytomas contained 0.8–13 nmol per gm wet weight of methionine-enkephalin, a concentration about 1000 times lower than the norepinephrine concentrations measured in the same tissues. Leucine-enkephalin levels were 9 to 33% those of methionine-enkephalin, whereas ACTH, α-MSH and β-endorphin were present in concentrations 150–2800 times lower than corresponding leucine-enkephalin levels. The human pheochromocytomas were also found to contain 14,000 and 2–5000 dalton enkephalin-containing proteins.

Immunoreactive melanocyte-stimulating hormone (α-MSH) in the brain of the frog (Rana esculenta L.)☆

Abstract MSH and ACTH levels in the hypophysis, diencephalon, telencephalon, and posterior encephalon of Rana esculenta were measured by use of sensitive and specific radioimmunoassays. Significant amounts of α-MSH-like peptide were observed in the diencephalon, telencephalon, and rhombencephalon. This component seems to be of extrahypophysial origin, since it was found in animals 8 days after hypophysectomy. Sephadex G-50 gel chromatography of tissue extracts showed that frog brain MSH behaved similarly to rat MSH and to synthetic α-MSH. Frog brain MSH was degraded by rat plasma and by liver or brain homogenates at the same velocity as rat hypophysial MSH or synthetic α-MSH. Enzymatic systems able to degrade endogenous MSH were also found in the frog telencephalon. These results provide evidence that frog brain extracts contain an α-MSH-like peptide and that a number of tissues, including rat plasma, brain, and liver, as well as frog brain, contain enzymatic mechanisms capable of degrading the α-MSH.

Release of immunoreactive α-MSH by synaptosome-enriched fractions of homogenates of hypothalami

Immunoreactive alpha-melanocyte-stimulating hormone (alpha-MSH) was found to be concentrated in a synaptosome-enriched fraction prepared by differential centrifugation of rat hypothalamic homogenates. The release of the hormone from this preparation was investigated. After incubation, the synaptosomes were isolated by ultrafiltration and alpha-MSH in the ultrafiltrate was determined by radioimmunoassay. Particle-bound alpha-MSH, recovered by extraction with acid ethanol, and alpha-MSH released from the synaptosome preparation, were immunologically similar to synthetic alpha-MSH and had an accompanying melanotropic activity. Less than 10% of the particle-bound alpha-MSH was released during incubation in 0.32 M sucrose. However, in the presence of 2 mM Ca2+, alpha-MSH release increased with increasing concentrations (30-150 mM) of K+. The stimulatory effect of 60 mM K+ was complete within 2 min and was potentiated by increasing Ca2+ concentrations over the range of 0 to 2 mM. K+-induced release of alpha-MSH was independent of temperature from 1 to 30 degrees C, and neither glucose (10 mM) nor dopamine (10(-10)-10(-2) M) had any effect on the release of the peptide. It is concluded that a synaptosome-enriched fraction from the hypothalamus contains a releasable pool of immunoreactive alpha-MSH that is mobilized by depolarizing concentrations of K+ in a Ca2+-dependent manner.

Refinement of genetic localization of the Alström syndrome on chromosome 2p12-13 by linkage analysis in a North African family

Alström syndrome is a rare autosomal recessive disorder characterized by retinal pigment degeneration, neurogenic deafness, infantile obesity, hyperlipidemia, and non-insulin-dependent diabetes mellitus. While the disease-related gene remains unknown, studies of the genetic isolate of French Acadians provisionally locate the Alström syndrome on chromosome 2p12-13 within a 14.9-cM interval. To confirm this finding in another ethnic population and refine the candidate region we investigated by linkage analysis a consanguineous family of North African origin, in which three of seven siblings displayed all major neurological and metabolic features of Alström syndrome. Genotyping was performed on an ABI377 DNA automatic sequencer and LOD scores were obtained with the Fastlink program. Five markers previously investigated in French Acadians confirmed the involvement of the candidate region, although pairwise LOD scores were of poor significance (Zmax=2.9). To further confirm homogeneity and refine the candidate region, 20 additional markers were investigated. Haplotype analysis and allele segregation revealed that affected children shared a single haplotype and were homozygous for the eight most centromeric markers (D2S291–D2S2114), over a 6.1-cM interval. Significative multipoint LOD scores (Zmax=3.96) were obtained between markers D2S2110/145 and D2S286. Two clusters of known genes are present in this refined region of chromosome 2p, the most attractive candidate being the hexokinase II gene. However, except for several known polymorphisms, no mutations were detected in the coding region of this gene. In conclusion, the location of Alström syndrome on chromosome 2p12-13 is confirmed, reducing the genetic interval to 6.1 cM.

Obésité: où en sommes-nous ?

Points essentiels Le surpoids et l’obesite correspondent a un exces de masse grasse, defini et evalue, en pratique clinique, par l’indice de masse corporelle (IMC – rapport du poids, en kilogrammes, sur le carre de la taille, en metre). Les consequences de l’obesite sur la sante sont nombreuses: complications metaboliques, cardiovasculaires et mecaniques, predisposition a certains cancers mais egalement repercussions psychosociales. En France, en 2003, 30% des adultes etaient en surpoids et 11% etaient obeses. L’augmentation des reserves adipeuses caracterisant l’obesite resulte d’un desequilibre de la balance energetique. Ce desequilibre releve d’interactions complexes, expliquant l’heterogeneite clinique et biologique de l’obesite humaine. L’espoir de voir l’epidemie maitrisee dans les annees a venir repose sans doute plus sur la mise en place d’actions coordonnees entre divers acteurs de la societe que sur l’attente d’un medicament specifique.