Growth hormone therapy for children with KBG syndrome: A case report and review of literature.

BACKGROUND: The incidence of short stature in KBG syndrome is relatively high. Data on the therapeutic effects of growth hormone (GH) on children with KBG syndrome accompanied by short stature in the previous literature has not been summarized. CASE SUMMARY: Here we studied a girl with KBG syndrome and collected the data of children with KBG syndrome accompanied by short stature from previous studies before and after GH therapy. The girl was referred to our department because of short stature. Physical examination revealed mild dysmorphic features. The peak GH responses to arginine and clonidine were 6.22 and 5.40 ng/mL, respectively. The level of insulin-like growth factor 1 (IGF-1) was 42.0 ng/mL. Genetic analysis showed a c.2635 dupG (p.Glu879fs) mutation in the ANKRD11 gene. She received GH therapy. During the first year of GH therapy, her height increased by 0.92 standard deviation score (SDS). Her height increased from -1.95 SDS to -0.70 SDS after two years of GH therapy. There were ten children with KBG syndrome accompanied by short stature who received GH therapy in reported cases. Height SDS was improved in nine (9/10) of them. The mean height SDS in five children with KBG syndrome accompanied by short stature increased from -2.72 ± 0.44 to -1.95 ± 0.57 after the first year of GH therapy (P = 0.001). There were no adverse reactions reported after GH treatment. CONCLUSION: GH treatment is effective in our girl and most children with KBG syndrome accompanied by short stature during the first year of therapy.

Endoplasmic reticulum stress pathway mediates isoflurane-induced neuroapoptosis and cognitive impairments in aged rats.

Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important clinical syndrome. Although it has been documented that volatile anesthetics induce neuronal apoptosis and cognitive deficits in several aged animal models, the underlying mechanisms are not well understood. Endoplasmic reticulum stress (ERS) is considered as an initial or early response of cells under stress and linked to neuronal death in various neurodegenerative diseases. The study was designed to explore the possible role of ERS pathway in isoflurane-induced neuroapoptosis and cognitive impairments. In the present study, twenty-month-old rats were exposed to 1.3% isoflurane for 4h. Two weeks later, the rats were subjected to behavioral study. Protein and mRNA expressions of ERS markers were evaluated. Meanwhile, hippocampal neuronal apoptosis was also detected. We found that isoflurane triggered ERS as evidenced by increased phosphorylation of eukaryotic initiation factor (EIF) 2α, and increased expression of 78-kDa glucose-regulated protein (GRP78), activating transcription factor (ATF) 4 and C/EBP homologous protein (CHOP). Furthermore, the level of apoptosis in the hippocampus was significantly up-regulated after isoflurane exposure, and salubrinal (ERS inhibitor) treatment attenuated the increase. More importantly, cognitive impairments caused by isoflurane were also effectively alleviated by salubrinal pretreatment. These results indicate that ERS-mediated apoptotic pathway is involved in isoflurane neurotoxicity in aged rats. Inhibition of ERS overactivation contributes to the relief of isoflurane-induced neurohistopathologic changes.

Characteristics of girls with pituitary hyperplasia and sexual precocity secondary to primary hypothyroidism.

AIM: To investigate the different characteristics of girls with pituitary hyperplasia secondary to primary hypothyroidism (PPH), with and without sexual precocity. METHODS: Pituitary hyperplasia secondary to primary hypothyroidism girls were divided into two groups: group A, with sexual precocity (n = 8), and group B, without sexual precocity (n = 14). The following values were measured before and after 3 months levothyroxine therapy: free triiodothyronine (FT3 ), free thyroxine (FT4 ), thyrotropin (TSH), follicle-stimulating hormone (FSH), luteinising hormone (LH), prolactin (PRL), estradiol (E2 ), testosterone (T), pituitary height, uterine volume (UV), ovarian volume (OV) and follicular diameter (FD). RESULTS: Thyrotropin, FSH, PRL, E2 , T, pituitary height, UV, OV and FD were higher in group A than group B (all p < 0.05); FT3 , FT4 and LH levels were not different (all p > 0.05). In all of the PPH girls, pituitary height was correlated with FT3 , FT4 and PRL (r = -0.545, p = 0.009, r = -0.567, p = 0.006 and r = 0.666, p = 0.001, respectively). PRL was positively correlated with UV, FD and FSH (r = 0.581, p = 0.005, r = 0.482, p = 0.031 and r = 0.667, p = 0.001, respectively), and FSH was positively correlated with OV (r = 0.522, p = 0.013). These abnormalities regressed after therapy. CONCLUSION: Pituitary hyperplasia secondary to primary hypothyroidism girls with sexual precocity have increased plasma TSH, FSH, PRL, E2 and T levels, pituitary height and uterine, ovarian and follicular size.

Fetal exposure to high isoflurane concentration induces postnatal memory and learning deficits in rats.

We developed a maternal fetal rat model to study the effects of isoflurane-induced neurotoxicity on the fetuses of pregnant rats exposed in utero. Pregnant rats at gestational day 14 were exposed to 1.3 or 3% isoflurane for 1h. At postnatal day 28, spatial learning and memory of the offspring were examined using the Morris Water Maze. The apoptosis was evaluated by caspase-3 immunohistochemistry in the hippocampal CA1 region. Simultaneously, the ultrastructure changes of synapse in the hippocampal CA1 and dentate gyrus region were observed by transmission electron microscopy (TEM). The 3% isoflurane treatment group showed significantly longer escape latency, less time spent in the third quadrant and fewer original platform crossings in the Morris Water Maze test, significantly increased number and optical densities of caspase-3 neurons. This treatment also produced remarkable changes in synaptic ultrastructure compared with the control and the 1.3% isoflurane groups. There were no differences in the Morris Water Maze test, densities of caspase-3 positive cells, or synaptic ultrastructure between the control and 1.3% isoflurane groups. High isoflurane concentration (3%) exposure during pregnancy caused spatial memory and learning impairments and more neurodegeneration in the offspring rats compared with control or lower isoflurane concentrations.