Transforming growth factor alpha treatment alters intracellular calcium levels in hair cells and protects them from ototoxic damage in vitro

To determine if transforming growth factor alpha (TGFα) pretreatment protects hair cells from aminoglycoside induced injury by modifying their intracellular calcium concentration, we assayed hair cell calcium levels in organ of Corti explants both before and after aminoglycoside (i.e. neomycin, 10⁻³M) exposure either with or without growth factor pretreatment. After TGFα (500ng/ml) treatment, the intracellular calcium level of hair cells showed a five-fold increase as compared to the levels observed in the hair cells of control cultures. After ototoxin exposure, calcium levels in hair cells of control explants showed an increase relative to their baseline levels, while in the presence of growth factors pretreatment, hair cells showed a relative reduction in calcium levels. Pretreatment of organ of Corti explants afforded significant protection of hair cell stereocilia bundle morphology from ototoxic damage when compared to explants exposed to ototoxin alone. This study correlates a rise in hair cell calcium levels with the otoprotection of hair cells by TGFα in organ of Corti explants.     

Hirschsprung's disease: associated abnormalities and demography.

We here examine the demographic parameters of patients with Hirschsprung's disease. The study population includes all patients with histologically confirmed disease treated at the Children's Hospital Medical Center of Boston over the 25-year period extending from 1961 through the first quarter of 1986. There were 179 cases. Overall, children with Hirschsprung's disease were found less likely to be first born (P less than .01). This relationship was seen to persist irrespective of maternal age, maternal race, or type of disease. The implications of this finding are discussed. Overall, 22% of these children had one or more associated abnormalities involving the neurological, cardiovascular, urological, and gastrointestinal systems. Many of the disorders appeared to be related to neurocrestopathies. Frequent associations included Down's syndrome, defects in cardiac septation, tetralogy of Fallot, and Dandy-Walker syndrome. These conditions occurred more frequently than would have been predicted through chance alone. This study found no association between an increased maternal age and the occurrence of Hirschsprung's disease. This study also found that approximately 7% of the affected children had been born prematurely.     

Multiple myxomata of soft tissue associated with polyostotic fibrous dysplasia. A case report

Polyostotic fibrous dysplasia with associated myxomata of soft tissue has been reported rarely. In most cases, the patient appears first with fibrous dysplasia and many years later presents with soft-tissue tumors. This is a report of a 57-year-old woman--an unusual case of soft-tissue myxomas with fibrous dysplasia. This case suggests that a patient developing myxomatous tumors of the soft tissues might be evaluated for the possibility of associated fibrous dysplasia.     

Revascularization of a thrombosed aortopulmonary shunt with the use of the AngioJet thrombectomy system.

We report the use of the AngioJet F140 rheolytic catheter to recannalize an acutely thrombosed aortopulmonary shunt in a 21-year-old female with palliated, complex congenital heart disease. After extracting the thrombus that filled the entire length of the shunt, three stents were placed at sites where the lumen was compromised by distortion or thrombus. Unobstructed flow was restored to the left pulmonary artery that persisted at 1-year follow-up.     

WAIS-R verbal-performance IQ discrepancies in persons with lateralized lesions: utility of a seven subtest short form.

WAIS-R Verbal-Performance IQ difference scores for Ward's (1990) seven subtest short form and the complete WAIS-R were examined in patients with lateralized and diffuse lesions. For both versions, the expected Performance > Verbal pattern was observed in the right hemisphere lesion group, while no summary score differences were seen in the left hemisphere group. Verbal-Performance IQ discrepancies for the short form fell within +/- 5 points of the WAIS-R discrepancy scores in about 75%of the cases, regardless of lesion location. Statistically reliable IQ differences between the complete and abbreviated WAIS-R attained 66%, 91%, and 89% agreement for the left, right, and diffuse groups, respectively. The results support the clinical utility of the seven subtest short form.     

Effects of clonidine and tricyclic antidepressants on gastric smooth muscle contractility

To determine if and how clonidine and tricyclic antidepressants affect gastric contractility. Guinea pig fundic and antral circular muscle strips were studied in vitro. The effects of clonidine or amitriptyline added in graded concentrations on contractions to electric field stimulation (EFS), acetylcholine (ACh), and SP in the presence of N(epsilon)-nitro-l-arginine methyl ester (l-NAME) were studied. EFS produced frequency dependent contractions of fundic and antral muscle that were abolished by atropine or tetrodotoxin (TTX). ACh contractions were abolished by atropine but not TTX. Clonidine reduced contractile response to EFS but had no effect on ACh contractions. The threshold concentration of clonidine to inhibit EFS contractions was lower in the fundus than in the antrum. Amitriptyline reduced contractions to both EFS and ACh but not to SP. The threshold concentration of amitriptyline to inhibit EFS contractions was lower in the antrum than in the fundus. Both clonidine and amitriptyline affect gastric contractility. At threshold concentrations, clonidine affects fundic contractility whereas amitriptyline affects antral contractility. Clonidine affects gastric contractility in response to EFS but not to ACh, suggesting alpha-2 receptors on cholinergic nerves that reduce ACh release. Amitriptyline inhibits gastric contractility to EFS and ACh suggesting an inhibitory muscle effect.     

Mutational analysis of familial and sporadic hyperekplexia

Hyperekplexia is a rare, autosomal dominant neurological disorder characterized by hypertonia, especially in infancy, and by an exaggerated startle response. This disorder is caused by mutations in the ?1 subunit of the inhibitory glycine receptor (GLRA1). We previously reported two GLRA1 point mutations detected in 4 unrelated hyperekplexia families; both mutations were at nucleotide 1192 and resulted in the replacement of Arg²⁷¹ by a glutamine (R271Q) in one case and a leucine (R271L) in the other. Here, 5 additional hyperekplexia families are shown to have the most common G-to-A transition mutation at nucleotide 1192. Haplotype analysis using polymorphisms within and close to the GLRA1 locus suggests that this mutation has arisen at least twice (and possibly four times). In 2 additional families, a third mutation is also presented that changes a tyrosine at amino acid 279 to a cysteine (Y279C). Five patients with atypical clinical features and equivocal or absent family history of hyperekplexia and 1 patient with a classical presentation but no family history are presented in whom a mutation in the GLRA1 gene was not detected. Thus, only clinically typical hyperekplexia appears to be consistently associated with GLRA1 mutations, and these affect a specific extracellular domain of the protein.