The effect of oxandrolone on body proportions and body composition in growth hormone‐treated girls with Turner syndrome

Objective Untreated girls with Turner syndrome (TS) have short stature, relatively broad shoulders, a broad pelvis, short legs, a high fat mass and low muscle mass. Our objective was to assess the effect of the weak androgen oxandrolone (Ox) on body proportions and composition in growth hormone (GH)‐treated girls with TS. Design/Patients 133 patients were included in a randomized, placebo‐controlled, double‐blind study. Methods Patients were treated with GH (1·33 mg/m² per day) from baseline, combined with placebo (Pl) or Ox in a low (0·03 mg/kg per day) or previously conventional (0·06 mg/kg per day) dose from the age of eight, and oestrogens from the age of twelve. Sitting height, biacromial and biiliacal distances compared with height (i.e. shape values), BMI, waist circumference, sum of 4 skinfolds (sum4skin) and upper arm muscle area (UAMA) SD scores (SDS) were assessed half‐yearly. Results Compared with GH + Pl, adult shape values on GH + Ox tended to be higher for sitting height (Ox 0·03, P = 0·2; Ox 0·06, P = 0·02) and biacromial distance (Ox 0·03, P = 0·2; Ox 0·06, P = 0·07) and lower for biiliacal distance (Ox 0·03, P = 0·004; Ox 0·06, P = 0·08). Sum4skin SDS tended to decrease more (Ox 0·03, P = 0·2; Ox 0·06, P = 0·005) while UAMA SDS increased more (Ox 0·03, P < 0·001; Ox 0·06, P < 0·001) than on GH + Pl. The increase in BMI and waist circumference SDS was comparable between the dosage groups. Conclusions In GH‐treated girls with TS, Ox 0·06 increases sitting height and tends to increase biacromial distance and decrease biiliacal distance, while Ox 0·03 significantly decreases biiliacal distance compared with height. Furthermore, Ox 0·06 reduces subcutaneous fat mass, and both Ox dosages increase muscle mass.     

Incarnation and animation: physical versus representational deficits of body integrity

Two apparently disparate phenomena of defective body integrity are reviewed. The first concerns dysmelia, characterized by the congenital absence or deformation of limbs, and the focus of the review is on phantom sensations of people with this kind of physical integrity disorder. The second phenomenon consists of non-psychotic individuals’ desire to have a healthy limb amputated, which is interpreted as a mismatch between the physical integrity of a particular limb and its representation in multimodal cortical areas of the brain. We outlined commonalities and differences between the two conditions and note the absence, in both areas of research, of a unified theory that would account for the reported phenomenology. Phantom limbs in dysmelia and the desire for limb amputation most likely are the consequence of very early developmental dissociations between physical and phenomenal body shapes. They are mirror images of one another in that the former constitutes an “animation without incarnation” and, the latter, an “incarnation without animation”.     

Differential Response of Endothelial Cells to Simvastatin When Conditioned with Steady,Non-Reversing Pulsatile or Oscillating Shear Stress

Few studies have investigated whether fluid mechanics can impair or enhance endothelial cell response to pharmacological agents such as statin drugs. We evaluated and compared Kruppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) expression in human abdominal aortic endothelial cells (HAAEC) treated with increasing simvastatin concentrations (0.1, 1 or 10 μM) under static culture and shear stress (steady, non-reversing pulsatile, and oscillating). Simvastatin, steady flow, and non-reversing pulsatile flow each separately upregulated KLF2, eNOS, and TM mRNA. At lower simvastatin concentrations (0.1 and 1 μM), the combination of statin and unidirectional steady or pulsatile flow produced an overall additive increase in mRNA levels. At higher simvastatin concentration (10 μM), a synergistic increase in eNOS and TM mRNA expression was observed. In contrast, oscillating flow impaired KLF2 and TM, but not eNOS expression by simvastatin at 1 μM. A higher simvastatin concentration of 10 μM overcame the inhibitory effect of oscillating flow. Our findings suggest that oscillating shear stress renders the endothelial cells less responsive to simvastatin than cells exposed to unidirectional steady or pulsatile flow. Consequently, the pleiotropic effects of statins in vivo may be less effective in endothelial cells exposed to atheroprone hemodynamics.     

Antidepressant use and salivary cortisol in depressive and anxiety disorders

Antidepressants are an effective treatment for depressive and anxiety disorders. Those disorders are frequently accompanied by heightened cortisol levels. Antidepressants may affect hypothalamic–pituitary–adrenal axis functioning, the alteration of which could be partially responsible for treatment efficacy. The association between antidepressants and cortisol was investigated in 1526 subjects of the Netherlands Study of Depression and Anxiety who were grouped into ‘serotonin reuptake inhibitor (SSRI) users’ (n = 309), ‘tricyclic antidepressant (TCA) users’ (n = 49), ‘other antidepressant users’ (n = 100), and ‘non-users’ (n = 1068). All subjects had a current or past diagnosis of anxiety and/or depression. Subjects provided 7 saliva samples from which 3 cortisol indicators were calculated: cortisol awakening response (CAR), evening cortisol, and cortisol suppression after ingestion of 0.5 mg dexamethasone. As compared to non-users, TCA users had a flattened CAR (effect size: Cohen's d = 0.34); SSRI users had higher evening cortisol levels (d = 0.04); and SSRI users showed decreased cortisol suppression after dexamethasone ingestion (d = 0.03). These findings suggest that antidepressant subtypes are associated with distinct alterations of the HPA axis. TCA users, who showed a flattened CAR, displayed the strongest alterations of salivary cortisol.     

Dutch women's decision-making in pregnancy and labour as seen through the eyes of their midwives

OBJECTIVE: a national study of midwives' perceptions of women's decision-making in the technical interventions in the birth process. DESIGN: questionnaire survey of women and their midwives. Midwives completed a maternity record for each woman in the study after the birth, and the women completed a demographic questionnaire at to 20-24 weeks gestation. SETTING: a stratified sample of 25 Dutch midwifery practices based on rural or urban location. Each of these 25 independent practices agreed to approach 25 eligible consecutive pregnant women on a randomly assigned day. PARTICIPANTS: in total 637 women were invited and 625 participated (response rate 98%). FINDINGS AND KEY CONCLUSIONS: midwives reported that they had a large influence in the decision to refer a woman to an obstetrician, but far and far less so when it comes to decisions around taking pharmaceutical pain relief. Midwives felt women had least say in the decision around augmentation of labour and most in the decision to sweep the membranes, whilst obstetricians had most input in the decision around primary induction of labour and least in the decision to refer from primary to secondary care. Our analysis indicated that midwives saw younger women (29 and younger) as having more influence in the decision-making process than old ones. Our analysis suggests there might be a tension between midwives own professional ideology and their non-interventionist focus and women's choice, which leads to an increase in medicalisation of childbirth.     

miR-155-overexpressing monocytes resemble HLAhighISG15+ synovial tissue macrophages from patients with rheumatoid arthritis and induce polyfunctional CD4+ T-cell activation

MicroRNAs (miRs) are known to regulate pro-inflammatory effector functions of myeloid cells, and miR dysregulation is implicated in rheumatoid arthritis (RA), a condition characterized by inflammation and destruction of the joints. We showed previously that miR-155 is increased in myeloid cells in RA and induces pro-inflammatory activation of monocytes and macrophages; however, its role at the interface between innate and adaptive immunity was not defined. Here, RNA-sequencing revealed that overexpression of miR-155 in healthy donor monocytes conferred a specific gene profile which bears similarities to that of RA synovial fluid-derived CD14⁺ cells and HLA^highISG15⁺ synovial tissue macrophages, both of which are characterized by antigen-presenting pathways. In line with this, monocytes in which miR-155 was overexpressed, displayed increased expression of HLA-DR and both co-stimulatory and co-inhibitory molecules, and induced activation of polyfunctional T cells. Together, these data underpin the notion that miR-155-driven myeloid cell activation in the synovium contributes not only to inflammation but may also influence the adaptive immune response.