Long-term evolution of endocrine disorders and effect of GH therapy in 35 patients with pituitary stalk interruption syndrome

We report long-term evolution of endocrine functions and the results of GH treatment in 35 patients (26 male and 9 female) with pituitary stalk interruption. At diagnosis, mean chronological age was 4.8 +/- 2.7 years, mean SDS for height -3.1 +/- 0.8 with a bone age retardation of 2.3 +/- 1.3 years and a mean SDS for growth velocity of -0.5 +/- 1.1; 80% presented complete GH deficiency (GHD) and 20% partial GHD; thyroid deficiency was present in 47.1% of children with complete GHD but absent in all partial GHD. Diagnosis was made during the first months of life in only 2 patients while 23% presented with severe neonatal distress; neonatal signs were only observed in the group with pituitary height below 2 mm (45.7% of patients). GHD was isolated in 40.6% of patients below 10 years while multiple hormone deficiencies was consistent at completion of growth in all patients. Height gain was significantly higher in patients who started GH treatment before 4 years (p = 0.002). GH treatment is very effective: in 13 patients, final height was -0.4 +/- 1.0, total height gain 3.2 +/- 1.2 and distance to target height -0.3 +/- 1.6 SDS.     

Impaired Frontal-Basal Ganglia Connectivity in Male Adolescents with Conduct Disorder

Alack of inhibition control has been found in subjects with conduct disorder (CD), but the underlying neuropathophysiology remains poorly understood. The current study investigated the different mechanism of inhibition control in adolescent-onset CD males (n = 29) and well-matched healthy controls (HCs) (n = 40) when performing a GoStop task by functional magnetic resonance images. Effective connectivity (EC) within the inhibition control network was analyzed using a stochastic dynamic causality model. We found that EC within the inhibition control network was significantly different in the CD group when compared to the HCs. Exploratory relationship analysis revealed significant negative associations between EC between the IFG and striatum and behavioral scale scores in the CD group. These results suggest for the first time that the failure of inhibition control in subjects with CD might be associated with aberrant connectivity of the frontal–basal ganglia pathways, especially between the IFG and striatum.     

Effect of low body temperature on gastric secretory activity in the guinea pig under urethane general anaesthesia

Effect of low body temperature on gastric secretory activity in the guinea pig under urethane general anaesthesia. Acta Physiol. Pol., 1978, 29 (1): 61-66. The effect of low body temperature on spontaneous and histamine (H) stimulated or Nalpha Nalpha-dimethylhistamine (NDMH)-stimulated gastric secretion was investigated in the guinea pig under general anaesthesia with urethane. In normothermia NDMH had a stronger stimulatory action on acid secretion In hypothermia (30 degrees C and 25 degrees C) only NDMH showed some stimulating effect. The obtained results point to the necessity of strict controlling of body temperature in the experiments performed on animals under general anaesthesia and suggest that the lack of effect at low temperature may be connected with an inhibition of the processes of H side-chain methylation when the rate of metabolic processes in the organism has fallen.     

Extracellular Norepinephrine Clearance by the Norepinephrine Transporter Is Required for Skeletal Homeostasis

Changes in bone remodeling induced by pharmacological and genetic manipulation of β-adrenergic receptor (βAR) signaling in osteoblasts support a role of sympathetic nerves in the regulation of bone remodeling. However, the contribution of endogenous sympathetic outflow and nerve-derived norepinephrine (NE) to bone remodeling under pathophysiological conditions remains unclear. We show here that differentiated osteoblasts, like neurons, express the norepinephrine transporter (NET), exhibit specific NE uptake activity via NET and can catabolize, but not generate, NE. Pharmacological blockade of NE transport by reboxetine induced bone loss in WT mice. Similarly, lack of NE reuptake in norepinephrine transporter (Net)-deficient mice led to reduced bone formation and increased bone resorption, resulting in suboptimal peak bone mass and mechanical properties associated with low sympathetic outflow and high plasma NE levels. Last, daily sympathetic activation induced by mild chronic stress was unable to induce bone loss, unless NET activity was blocked. These findings indicate that the control of endogenous NE release and reuptake by presynaptic neurons and osteoblasts is an important component of the complex homeostatic machinery by which the sympathetic nervous system controls bone remodeling. These findings also suggest that drugs antagonizing NET activity, used for the treatment of hyperactivity disorders, may have deleterious effects on bone accrual.     

Common denominators in the etiology and pathology of visceral lesions of cystic fibrosis and Keshan disease

The common denominator of a unique disseminated multi-focal milliary myocardial hyaline necrosis and fibrosis in Keshan disease (KSD) and cystic fibrosis (CF) and a commonality of the affected age groups of fetuses and preschool children led to the review of existing KSD autopsy material to search for pancreatic and hepatic lesions considered pathognomonic for CF. Pancreatic lesions considered pathognomonic for CF were found in 595, or 35% of 1700 documented cases of KSD. The pancreatic lesions were limited to tissues of fetuses and preschool children. Adults dying of KSD had diagnostic lesions limited to the cardiovascular system, liver, and skeletal muscle. Varying degrees of focal biliary cirrhosis were identified in 850, or 50% of the KSD autopsies, and 85, or 5% developed severe lobular cirrhosis. The common denominator in CF and KSD appears to be a primary or induced secondary selenium deficiency in age-susceptable humans, prenatally at or around 22 wk of fetal life, during early postnatal life, or during the rapid-growth preschool years. The basic difference between the natural history of CF and KSD is that the selenium deficiency is totally environmental in KSD and appears to be the result of a maternal malabsorptive syndrome or an abnormality of selenium transfer in CF.