Transient nephrogenic diabetes insipidus caused by fetal exposure to haloperidol

Haloperidol is commonly used in the treatment of psychiatric disorders. Data from animal experiments indicate haloperidol is not teratogenic, but is embryotoxic in high doses. For the first time, we report a neonate with transient nephrogenic diabetes insipidus (DI) caused by fetal exposure to haloperidol. The magnitude of risk associated with the use of haloperidol during pregnancy appears to be small, but nephrogenic DI secondary to haloperidol is a serious condition with the risk of hypernatremic dehydration. Haloperidol can have adverse effects on the fetus and newborn infant, that’s why one should prevent the use of haloperidol during pregnancy and lactation.     

17-Hydroxyprogesterone Response to Standard Dose Synacthen Stimulation Test in CYP21A2 Heterozygous Carriers and Non-carriers in Symptomatic and Asymptomatic Groups: Meta-analyses

Objective:Standard dose synacthen stimulation test (SDSST) is a gold standard screening test for evaluating adrenal gland function. Despite studies using SDSST to identify heterozygosity in CYP21A2, the reliability of the test for this purpose is still controversial. Therefore, the meta-analyses were performed to determine the differences in 17-hydroxyprogesterone (17-OHP) responses to standard dose (0.25 mg) SDSST in the diagnosis of CYP21A2 heterozygous individuals, with or without clinical signs of androgen excess disorders.Methods:PubMed and MEDLINE databases were searched. A total of 1215 subjects (heterozygous carriers n=669, mutation-free controls n=546) were included in the meta-analyses.Results:Basal 17-OHP median/mean levels were 4.156 (3.05-10.5)/5.241 (±2.59) nmol/L and 3.90 (2.20-9.74)/4.67 (±2.62) nmol/L in symptomatic heterozygous carriers and symptomatic mutation-free controls, respectively. Stimulated 17-OHP median/mean levels were 17.29 (14.22-37.2)/19.51 (±7.63) nmol/L and 9.27 (7.32-15.9)/10.77 (±3.48) nmol/L in symptomatic heterozygous carriers and symptomatic mutation-free controls, respectively. Basal 17-OHP median/mean levels were 3.21 (2.64-4.78)/3.33 (±0.84) nmol/L and 3.12 (1.82-3.6)/2.83 (±0.71) nmol/L in asymptomatic heterozygous carriers and asymptomatic mutation-free healthy controls, respectively. Stimulated 17-OHP median/mean levels were 14.16 (12.73-16.37)/14.16 (±1.37) nmol/L and 6.26 (4.9-8.23)/6.48 (±1.2) nmol/L in asymptomatic heterozygous carriers and asymptomatic mutation-free healthy controls, respectively. The cut-off levels for stimulated 17-OHP were 10.48 nmol/L and 13.48 nmol/L for asymptomatic heterozygous and symptomatic heterozygous, respectively.Conclusion:The meta-analyses support the idea that stimulated 17-OHP level has potential for use in identifying CYP21A2 carriers. Besides, considering differences in the basal and stimulated 17-OHP levels in symptomatic heterozygous individuals compared to those who were asymptomatic heterozygous could increase the accuracy of the test.     

Frontal and occipital perfusion changes in dissociative identity disorder

There is some evidence that emotional reactivity to daily life stress is related to a genetic or familial liability to develop schizophrenia. However, it is unclear whether the emotional distress is elevated in schizophrenia patients with positive compared to negative family history. The aim of the study was to test the hypothesis that a persistent higher level of emotional distress in schizophrenia subjects is associated with a positive family history of schizophrenia. This study used the Talbieh Brief Distress Inventory (TBDI), the Positive and Negative Syndrome Scale (PANSS; including dysphoric mood, positive and negative subscales), Montgomery-Asberg Depression Rating Scale (MADRS), and the Distress Scale for Adverse Symptoms (DSAS) to investigate the difference in the magnitude of emotional distress scores between schizophrenia subjects with and without a positive family history of schizophrenia over time. Data were recorded for 69 multiplex family and 79 singleton patients at admission and about 16 months thereafter. No between-group differences were obtained in PANSS and DSAS scores. With regard to the TBDI: (a) both group of patients had no significant differences in emotional distress scores at admission; (b) patients with negative family history reported improvement in distress severity and depression severity (MADRS) 16 months after admission, while those with positive family history experienced persistent elevated emotional distress, mainly, on obsessiveness, and depression subscales; and (c) both groups of patients are characterized by elevated emotional distress at follow-up examination compared to healthy subjects. Thus, it appears that there is a strong association between positive family history and persistent elevated emotional distress. Because patients with positive and negative family history are likely to differ in genetic risk, our results suggest that long-term elevated levels of emotional distress may be related to a familial (environmental)/genetic vulnerability to schizophrenia.     

Connective tissue growth factor does not affect transforming growth factor-beta 1-induced Smad3 phosphorylation and T lymphocyte proliferation inhibition

Transforming growth factor-beta 1 (TGF-beta(1)) is a key regulator of immune tolerance. TGF-beta(1) controls T lymphocyte activation and is involved in the immunosuppressive function and generation of regulatory T lymphocytes. Connective tissue growth factor (CTGF) has an essential role in the formation of connective tissue and blood vessels. CTGF expression is induced by TGF-beta(1) in several cell types and CTGF mediates several of the downstream actions of TGF-beta(1). Since little is known about the potential synergy between CTGF and TGF-beta(1) in T lymphocyte biology, the purpose of the present study was to determine whether CTGF can modulate TGF-beta(1)-mediated effects on human CD4+ T lymphocytes. Human recombinant CTGF was expressed in HEK293 cells. rCTGF was biologically active demonstrated by induction of proliferation in the endothelial cell line EA hy 926. rCTGF alone did not potentiate or diminish anti-CD3-induced CD4+ T lymphocyte proliferation and did not activate the Smad signaling pathway in CD4+ T lymphocytes. Furthermore, rCTGF did not attenuate TGF-beta(1)-mediated inhibition of CD4+ T lymphocyte proliferation and TGF-beta(1)-induced Smad signaling in CD4+ T lymphocytes. These results indicate that rCTGF had no detectable effects of its own on human CD4+ T lymphocytes and did not potentiate the effects of low amounts of TGF-beta(1) on human CD4+ T lymphocytes. Overall, these data support the hypothesis that CTGF does not act on CD4+ T lymphocytes.     

Type 1 diabetes mellitus in a 3 1/2 year-old girl with Turner's syndrome

Turner's syndrome is associated with autoimmune disorders. Autoimmune endocrinopathy in Turner's syndrome seems to be limited to autoimmune thyroiditis. A small number of patients with Turner's syndrome has also been associated with celiac disease, inflammatory bowel disease and juvenile rheumatoid arthritis. Type 1 diabetes mellitus in Turner's syndrome has been rarely reported. We present here the youngest patient with Turner's syndrome who developed type 1 diabetes mellitus. At the age of 3.5 years she was hospitalized with diabetic ketoacidosis. Anti-islet cell and anti-insulin antibodies were positive and C-peptide level was low. When she was investigated for recurrent urinary tract infections, horseshoe kidney was detected by ultrasonography. Karyotype analysis revealed 45,XO. She has been followed for 2 years with an insulin dose of 0.9 U/kg per day. The prevalence of type 1 diabetes mellitus associated with Turner's syndrome is still unknown.     

Mutations in the lipoma HMGIC fusion partner-like 5 (LHFPL5) gene cause autosomal recessive nonsyndromic hearing loss

In two large Turkish consanguineous families, a locus for autosomal recessive nonsyndromic hearing loss (ARNSHL) was mapped to chromosome 6p21.3 by genome-wide linkage analysis in an interval overlapping with the loci DFNB53 (COL11A2), DFNB66, and DFNB67. Fine mapping excluded DFNB53 and subsequently homozygous mutations were identified in the lipoma HMGIC fusion partner-like 5 (LHFPL5) gene, also named tetraspan membrane protein of hair cell stereocilia (TMHS) gene, which was recently shown to be mutated in the "hurry scurry" mouse and in two DFNB67-linked families from Pakistan. In one family, we found a homozygous one-base pair deletion, c.649delG (p.Glu216ArgfsX26) and in the other family we identified a homozygous transition c.494C>T (p.Thr165Met). Further screening of index patients from 96 Turkish ARNSHL families and 90 Dutch ARNSHL patients identified one additional Turkish family carrying the c.649delG mutation. Haplotype analysis revealed that the c.649delG mutation was located on a common haplotype in both families. Mutation screening of the LHFPL5 homologs LHFPL3 and LHFPL4 did not reveal any disease causing mutation. Our findings indicate that LHFPL5 is essential for normal function of the human cochlea.