Hirsutisme: que faire [Hirsutism, what can be done?]

Hirsutism is a relatively frequent condition in an ambulatory setting affecting about 4% of women. A rational clinical and biochemical diagnostic approach assures an optimal treatment directed at etiologic and pathogenetic factors. The diagnosis of hyperandrogenism is evaluated considering the pathophysiologic mechanisms responsible for excessive growth of hair. Ovarian and adrenal tumors are the most serious diseases that have to be excluded by clinical and biochemical tests. The other causes for hirsutism are treatable by a great variety of modalities, available drugs can inhibit pituitary gonadotropins, the hypothalamo-pituitary axis and the conversion of testosterone into biologically active substrate. Finally the binding of androgens to its receptor can be blocked. These possibilities for treatment and their indications for the different etiologies of hirsutism are discussed.

Three-dimensional black-blood cardiac magnetic resonance coronary vessel wall imaging detects positive arterial remodeling in patients with nonsignificant coronary artery disease.

BACKGROUND: Direct noninvasive visualization of the coronary vessel wall may enhance risk stratification by quantifying subclinical coronary atherosclerotic plaque burden. We sought to evaluate high-resolution black-blood 3D cardiovascular magnetic resonance (CMR) imaging for in vivo visualization of the proximal coronary artery vessel wall. METHODS AND RESULTS: Twelve adult subjects, including 6 clinically healthy subjects and 6 patients with nonsignificant coronary artery disease (10% to 50% x-ray angiographic diameter reduction) were studied with the use of a commercial 1.5 Tesla CMR scanner. Free-breathing 3D coronary vessel wall imaging was performed along the major axis of the right coronary artery with isotropic spatial resolution (1.0x1.0x1.0 mm(3)) with the use of a black-blood spiral image acquisition. The proximal vessel wall thickness and luminal diameter were objectively determined with an automated edge detection tool. The 3D CMR vessel wall scans allowed for visualization of the contiguous proximal right coronary artery in all subjects. Both mean vessel wall thickness (1.7+/-0.3 versus 1.0+/-0.2 mm) and wall area (25.4+/-6.9 versus 11.5+/-5.2 mm(2)) were significantly increased in the patients compared with the healthy subjects (both P<0.01). The lumen diameter (3.6+/-0.7 versus 3.4+/-0.5 mm, P=0.47) and lumen area (8.9+/-3.4 versus 7.9+/-3.5 mm(2), P=0.47) were similar in both groups. CONCLUSIONS: Free-breathing 3D black-blood coronary CMR with isotropic resolution identified an increased coronary vessel wall thickness with preservation of lumen size in patients with nonsignificant coronary artery disease, consistent with a "Glagov-type" outward arterial remodeling. This novel approach has the potential to quantify subclinical disease.

Weakening processes in thrust faults: insights from the Monte Perdido thrust fault (southern Pyrenees, Spain)

The Monte Perdido thrust fault (southern Pyrenees) consists of a 6-m-thick interval of intensely deformed clay-bearing rocks. The fault zone is affected by a pervasive pressure solution seam and numerous shear surfaces. Calcite extensional-shear veins are present along the shear surfaces. The angular relationships between the two structures indicate that shear surfaces developed at a high angle (70°) to the local principal maximum stress axis r1. Two main stages of deformation are present. The first stage corresponds to the development of calcite shear veins by a combination of shear surface reactivation and extensional mode I rupture. The second stage of deformation corresponds to chlorite precipitation along the previously reactivated shear surfaces. The pore fluid factor k computed for the two deformation episodes indicates high fluid pressures during the Monte Perdido thrust activity. During the first stage of deformation, the reactivation of the shear surface was facilitated by a suprahydrostatic fluid pressure with a pore fluid factor kv equal to 0.89. For the second stage, the fluid pressure remained still high (with a k value ranging between 0.77 and 0.84) even with the presence of weak chlorite along the shear surfaces. Furthermore, evidence of hydrostatic fluid pressure during calcite cement precipitation supports that incremental shear surface reactivations are correlated with cyclic fluid pressure fluctuations consis- tent with a fault-valve model.

Hypobaric versus normobaric hypoxia: same effects on postural stability?

AIMS: To test the hypothesis that postural stability would be more affected during acute exposure in hypobaric (HH) than in normobaric (NH) hypoxia.¦METHODS: In separate trials, 12 subjects stood on a posturographic platform for two successive 25.6 sec tests in three conditions: eyes open (EO), eyes closed (EC), and verbal dual task (DT). Ambient pressure in O(2) was matched between HH and NH at 1700 and 3000 m, respectively.¦RESULTS: Compared to NH, the length of Centre of Pression trajectory in Y-axis was increased (p<0.05) in HH for EO at 1700 m, EC at 1700 and 3000 m, and for DT at 1700 m, whereas the variance of speed of CoP was decreased (p<0.05) in EO, EC, and DT at 1700 m. Compared to normobaric normoxia (NN; 400 m), the surface of CoP trajectory was increased (p<0.05) in HH in EO and EC at 3000 m.¦CONCLUSIONS: HH deteriorated postural stability in the antero-posterior plane, for the variance of speed and the surface of CoP in 3 conditions, whereas no difference was observed between NH and NN. These results suggest that hypobaria instead of hypoxia per se plays an important role to the altered balance classically reported in altitude.

How to improve flow during cardiopulmonary bypass in an acardia experimental model.

OBJECTIVES In extreme scenarios, such as hyperacute rejection of heart transplant, an urgent heart explantation might be necessary. The aim of this experimental study was to determine the feasibility and to improve the haemodynamics of a venoarterial cardiopulmonary bypass after cardiectomy. METHODS A venoarterial cardiopulmonary bypass was established in seven calves (56.4 ± 7 kg) by the transjugular insertion to the caval axis of a self-expanding cannula, with a carotid artery return. After baseline measurements (A), ventricular fibrillation was induced (B), great arteries were clamped (C), the heart was excised and the right and left atria remnants, containing the pulmonary veins, were sutured together leaving an atrial septal defect over the cannula in the caval axis (D). Measurements were taken with the pulmonary artery clamped and declamped. RESULTS Initial pump flow was 4.16 ± 0.75 l/min dropping to 2.9 ± 0.63 l/min (P(AB )< 0.001) 10 min after induction of ventricular fibrillation. After cardiectomy with the pulmonary artery clamped, the pump flow increased non-significantly to 3.20 ± 0.78 l/min. After declamping, the flow significantly increased close to baseline levels (3.61 ± 0.73 l/min, P(DB )= 0.009, P(DC )= 0.017), supporting the notion that full cardiopulmonary bypass in acardia is feasible only if adequate drainage of pulmonary circulation is assured to avoid pulmonary congestion and loss of volume from the left-to-right shunt of bronchial vessels.

Prothèses totales de genoux. Analyse clinique et numérique des micromouvements de l'implant tibial [Total knee prosthesis. Clinical and numerical study of micromovements of the tibial implant].

INTRODUCTION: The importance of the micromovements in the mechanism of aseptic loosening is clinically difficult to evaluate. To complete the analysis of a series of total knee arthroplasties (TKA), we used a tridimensional numerical model to study the micromovements of the tibial implant. MATERIAL AND METHODS: Fifty one patients (with 57 cemented Porous Coated Anatomic TKAs) were reviewed (mean follow-up 4.5 year). Radiolucency at the tibial bone-cement interface was sought on the AP radiographs and divided in 7 areas. The distribution of the radiolucency was then correlated with the axis of the lower limb as measured on the orthoradiograms. The tridimensional numerical model is based on the finite element method. It allowed the measurement of the cemented prosthetic tibial implant's displacements and the micromovements generated at bone-ciment interface. A total load (2000 Newton) was applied at first vertically and asymetrically on the tibial plateau, thereby simulating an axial deviation of the lower limbs. The vector's posterior inclination then permitted the addition of a tangential component to the axial load. This type of effort is generated by complex biomechanical phenomena such as knee flexion. RESULTS: 81 per cent of the 57 knees had a radiolucent line of at least 1 mm, at one or more of the tibial cement-epiphysis jonctional areas. The distribution of these lucent lines showed that they came out more frequently at the periphery of the implant. The lucent lines appeared most often under the unloaded margin of the tibial plateau, when axial deviation of lower limbs was present. Numerical simulations showed that asymetrical loading on the tibial plateau induced a subsidence of the loaded margin (0-100 microns) and lifting off at the opposite border (0-70 microns). The postero-anterior tangential component induced an anterior displacement of the tibial implant (160-220 microns), and horizontal micromovements with non homogenous distribution at the bone-ciment interface (28-54 microns). DISCUSSION: Comparison of clinical and numerical results showed a relation between the development of radiolucent lines and the unloading of the tibial implant's margin. The deleterious effect of lower limbs' axial deviation is thereby proven. The irregular distribution of lucent lines under the tibial plateau was similar of the micromovements' repartition at the bone-cement interface when tangential forces were present. A causative relation between the two phenomenaes could not however be established. Numerical simulation is a truly useful method of study; it permits to calculate micromovements which are relative, non homogenous and of very low amplitude. However, comparative clinical studies remain as essential to ensure the credibility of results.

Changes in sleeping and basal energy expenditure and substrate oxidation induced by short term thyroxin administration in man.

The present study was designed to explore the thermogenic effect of thyroid hormone administration and the resulting changes in nitrogen homeostasis. Normal male volunteers (n = 7) received thyroxin during 6 weeks. The first 3-week period served to suppress endogenous thyroid secretion (180 micrograms T4/day). This dose was doubled for the next 3 weeks. Sleeping energy expenditure (respiratory chamber) and BMR (hood) were measured by indirect calorimetry, under standardized conditions. Sleeping heart rate was continuously recorded and urine was collected during this 12-hour period to assess nitrogen excretion. The changes in energy expenditure, heart rate and nitrogen balance were then related to the excess thyroxin administered. After 3 weeks of treatment, serum TSH level fell to 0.15 mU/L, indicating an almost complete inhibition of the pituitary-thyroid axis. During this phase of treatment there was an increase in sleeping EE and sleeping heart rate, which increased further by doubling the T4 dose (delta EE: +8.5 +/- 2.3%, delta heart rate +16.1 +/- 2.2%). The T4 dose, which is currently used as a substitutive dose, lead to a borderline hyperthyroid state, with an increase in EE and heart rate. Exogenous T4 administration provoked a significant increase in urinary nitrogen excretion averaging 40%. It is concluded that T4 provokes an important stimulation of EE, which is mostly mediated by an excess protein oxidation.

Importance of a three-dimensional measure of humeral head subluxation in osteoarthritic shoulders.

HYPOTHESIS: During total shoulder arthroplasty (TSA), humeral head subluxation may be difficult to manage. Furthermore, there is a risk for postoperative recurrence of subluxation, affecting the outcome of TSA. An accurate evaluation of the subluxation is necessary to evaluate this risk. Currently, subluxation is measured in 2 dimensions (2D), usually relative to the glenoid face. The goal of this study was to extend this measure to 3 dimensions (3D) to compare glenohumeral and scapulohumeral subluxation and to evaluate the association of subluxation with the glenoid version. MATERIALS AND METHODS: The study analyzed 112 computed tomography scans of osteoarthritic shoulders. We extended the usual 2D definition of glenohumeral subluxation, scapulohumeral subluxation, and glenoid version by measuring their orientation in 3D relative to the scapular plane and the scapular axis. We evaluated statistical associations between subluxation and version in 2D and 3D. RESULTS: Orientation of subluxation and version covered all sectors of the glenoid surface. Scapulohumeral subluxation and glenoid version were highly correlated in amplitude (R(2) = 0.71; P < .01) and in orientation (R(2) = 0.86; P < .01). Approximately every degree of glenoid version induced 1% of scapulohumeral subluxation in the same orientation of the version. Conversely, glenohumeral subluxation was not correlated to glenoid version in 2D or in 3D. CONCLUSIONS: Orientation of the humeral subluxation is rarely within the arbitrary computed tomography plane and should therefore be measured in 3D to detect out-of-plane subluxation. Scapulohumeral subluxation and glenoid version measured in 3D could bring valuable information for decision making during TSA.

Laparoscopic surgery for coeliac artery compression syndrome: current management and technical aspects.

Objectives: The study aims to assess the feasibility and midterm outcome of trans-peritoneal laparoscopy for coeliac artery compression syndrome (CACS).Design: Retrospective chart review involving four European vascular surgery departments and two surgical teams.Materials and methods: charts for patients who underwent laparoscopy for symptomatic CACS between December 2003 and November 2009 were reviewed. Preoperative computed tomography (CT) angiography and postoperative duplex scan and/or CT angiography were performed.Results: Eleven consecutive patients (nine women) with a median age of 52 years (interquartile range: 42.5-59 years) underwent trans-peritoneal laparoscopy for CACS. All patients had a history of postprandial abdominal pain; weight loss exceeded 10% of the body mass in eight cases. Preoperative CT angiography revealed coeliac trunk stenosis >70% in all cases. One patient had additional aortitis and inferior mesenteric artery occlusion, while another patient presented with an occluded superior mesenteric artery. Two conversions occurred (one difficult dissection and one aorto-hepatic bypass needed for incomplete release of CACS). The median blood loss was 195 ml (range: 50-900 ml) and median operative time was 80 min (interquartile range: 65-162.5 years). Symptoms improved immediately in 10/11 patients (no residual stenosis) while one remained unchanged despite a residual stenosis treated by a percutaneous angioplasty. Symptoms reappeared in one patient due to coeliac axis occlusion. The mean follow-up period was 35 +/- 23 months (range: 12-78 months).Conclusion: Our study demonstrates that trans-peritoneal laparoscopy for treating median arcuate ligament syndrome is safe and feasible. Additional patients and a longer follow-up are needed for long-term assessment of this laparoscopic technique. (C) 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

The personality profile of borderline personality disordered patients using the five-factor model of personality

The purpose of this ex post facto study is to analyze the personality profile of outpatients who met criteria for borderline personality disorder according to the Five-Factor Model of personality. All patients (N = 52) completed the International Personality Disorder Examination (IPDE) Screening Questionnaire, the Big Five Questionnaire (BFQ), the Beck Depression Inventory (BDI), and the Beck Hopelessness Scale (BHS). The results show a high comorbidity with other DSM-IV-TR Axis II disorders, in particular with those from Cluster C. The BFQ average score indicates that the outpatients who met borderline criteria score lower than controls on all five dimensions, and especially on emotional stability. Correlations were computed between the BFQ and the IPDE scales in our sample. These results suggest that specific personality profile are linked to different comorbidity patterns. More than a half of our sample has clinically significant scores on Beck's scales. Surprisingly, depression and hopelessness are neither correlated with the borderline scale, nor have an effect in the relationship between personality and personality disorders.

Chemokine receptor trio: CXCR3, CXCR4 and CXCR7 crosstalk via CXCL11 and CXCL12.

Although chemokines are well established to function in immunity and endothelial cell activation and proliferation, a rapidly growing literature suggests that CXC Chemokine receptors CXCR3, CXCR4 and CXCR7 are critical in the development and progression of solid tumors. The effect of these chemokine receptors in tumorigenesis is mediated via interactions with shared ligands I-TAC (CXCL11) and SDF-1 (CXCL12). Over the last decade, CXCR4 has been extensively reported to be overexpressed in most human solid tumors and has earned considerable attention toward elucidating its role in cancer metastasis. To enrich the existing armamentarium of anti-cancerous agents, many inhibitors of CXCL12-CXCR4 axis have emerged as additional or alternative agents for neo-adjuvant treatments and even many of them are in preclinical and clinical stages of their development. However, the discovery of CXCR7 as another receptor for CXCL12 with rather high binding affinity and recent reports about its involvement in cancer progression, has questioned the potential of "selective blockade" of CXCR4 as cancer chemotherapeutics. Interestingly, CXCR7 can also bind another chemokine CXCL11, which is an established ligand for CXCR3. Recent reports have documented that CXCR3 and their ligands are overexpressed in different solid tumors and regulate tumor growth and metastasis. Therefore, it is important to consider the interactions and crosstalk between these three chemokine receptors and their ligand mediated signaling cascades for the development of effective anti-cancer therapies. Emerging evidence also indicates that these receptors are differentially expressed in tumor endothelial cells as well as in cancer stem cells, suggesting their direct role in regulating tumor angiogenesis and metastasis. In this review, we will focus on the signals mediated by this receptor trio via their shared ligands and their role in tumor growth and progression.

Immune and stress responses covary with melanin-based coloration in the barn swallow

Eumelanin and pheomelanin are the main endogenous pigments in animals and melanin-based coloration has multiple functions. Melanization is associated with major life-history traits, including immune and stress response, possibly because of pleiotropic effects of genes that control melanogenesis. The net effects on pheo- versus eumelanization and other life-history traits may depend on the antagonistic effects of the genes that trigger the biosynthesis of either melanin form. Covariation between melanin-based pigmentation and fitness traits enforced by pleiotropic genes has major evolutionary implications particularly for socio-sexual communication. However, evidence from non-model organisms in the wild is limited to very few species. Here, we tested the hypothesis that melanin-based coloration of barn swallow (Hirundo rustica) throat and belly feathers covaries with acquired immunity and activation of the hypothalamic-pituitary-adrenal (HPA) axis, as gauged by corticosterone plasma levels. Individuals of both sexes with darker brownish belly feathers had weaker humoral immune response, while darker males had higher circulating corticosterone levels only when parental workload was experimentally reduced. Because color of belly feathers depends on both eu- and pheomelanin, and its darkness decreases with an increase in the concentration of eu- relative to pheomelanin, these results are consistent with our expectation that relatively more eu- than pheomelanized individuals have better immune response and smaller activation of the HPA-axis. Covariation of immune and stress response arose for belly but not throat feather color, suggesting that any function of color as a signal of individual quality or of alternative life-history strategies depends on plumage region.

The biogenic origin of needle fibre calcite

Needle fibre calcite is one of the most ubiquitous habits of calcite in vadose environments (caves deposits, soil pores, etc.). Its origin, either through inorganic, indirect or direct biological processes, has long been debated. In this study, investigations at 11 sites in Europe, Africa and Central America support arguments for its biogenic origin. The wide range of needle morphologies is the result of a gradual evolution of the simplest type, a rod. This rod is the elementary brick which, by aggregation and welding, builds more complex needles. The absence of cross-welded needles implies that they are welded in a mould, or under a longitudinal and unidirectional constraint, before being released inside the soil pores. The difference between the lengthening of the needles and the c axis can be explained by the existence of needles observed under a scanning electron microscope in organic sleeves, which can act as a mould during rod growth. Complex morphologies with epitaxial outgrowths on straight rods cannot have grown entirely inside organic microtubes; they must result from soil diagenesis after the release of straight rods in a soil-free medium. Whisker crystals are interpreted as the result of growth and coalescence of euhedral crystals on a rod. Rhomb chains are considered to be the consequence of successive epitaxial growth steps on a needle during variations in growth conditions. Isotopic signatures for needle fibre calcite vary from -16.63[per mille] to +1.10[per mille] and from -8.63[per mille] to -2.25[per mille] for Delta13C and Delta18O, respectively. The absence of high Delta18O values for needle fibre calcite precludes a purely physicochemical origin (evaporative) for this particular habit of calcite. As epitaxial growth cannot precipitate in the same conditions as initial needles, needle fibre calcite stable isotopic signatures should be used with caution as a proxy for palaeoenvironmental reconstructions. In addition, it is suggested that the term needle fibre calcite should be kept for the original biogenic form. The other habit should be referred to as epitaxial forms of needle fibre calcite.

A genetic basis for functional hypothalamic amenorrhea.

Background: Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition of the reproductive axis by such stressors, but it is unknown whether this variability reflects a genetic predisposition to hypothalamic amenorrhea. We hypothesized that mutations in genes involved in idiopathic hypogonadotropic hypogonadism, a congenital form of GnRH deficiency, are associated with hypothalamic amenorrhea. Methods: We analyzed the coding sequence of genes associated with idiopathic hypogonadotropic hypogonadism in 55 women with hypothalamic amenorrhea and performed in vitro studies of the identified mutations. Results: Six heterozygous mutations were identified in 7 of the 55 patients with hypothalamic amenorrhea: two variants in the fibroblast growth factor receptor 1 gene FGFR1 (G260E and R756H), two in the prokineticin receptor 2 gene PROKR2 (R85H and L173R), one in the GnRH receptor gene GNRHR (R262Q), and one in the Kallmann syndrome 1 sequence gene KAL1 (V371I). No mutations were found in a cohort of 422 controls with normal menstrual cycles. In vitro studies showed that FGFR1 G260E, FGFR1 R756H, and PROKR2 R85H are loss-of-function mutations, as has been previously shown for PROKR2 L173R and GNRHR R262Q. Conclusions: Rare variants in genes associated with idiopathic hypogonadotropic hypogonadism are found in women with hypothalamic amenorrhea, suggesting that these mutations may contribute to the variable susceptibility of women to the functional changes in GnRH secretion that characterize hypothalamic amenorrhea. Our observations provide evidence for the role of rare variants in common multifactorial disease. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00494169.)

Nervous glucose sensing regulates postnatal β cell proliferation and glucose homeostasis.

How glucose sensing by the nervous system impacts the regulation of β cell mass and function during postnatal development and throughout adulthood is incompletely understood. Here, we studied mice with inactivation of glucose transporter 2 (Glut2) in the nervous system (NG2KO mice). These mice displayed normal energy homeostasis but developed late-onset glucose intolerance due to reduced insulin secretion, which was precipitated by high-fat diet feeding. The β cell mass of adult NG2KO mice was reduced compared with that of WT mice due to lower β cell proliferation rates in NG2KO mice during the early postnatal period. The difference in proliferation between NG2KO and control islets was abolished by ganglionic blockade or by weaning the mice on a carbohydrate-free diet. In adult NG2KO mice, first-phase insulin secretion was lost, and these glucose-intolerant mice developed impaired glucagon secretion when fed a high-fat diet. Electrophysiological recordings showed reduced parasympathetic nerve activity in the basal state and no stimulation by glucose. Furthermore, sympathetic activity was also insensitive to glucose. Collectively, our data show that GLUT2-dependent control of parasympathetic activity defines a nervous system/endocrine pancreas axis that is critical for β cell mass establishment in the postnatal period and for long-term maintenance of β cell function.