Ectopic Hedgehog Signaling Causes Cleft Palate and Defective Osteogenesis.

Cleft palate is a common birth defect that frequently occurs in human congenital malformations caused by mutations in components of the Sonic Hedgehog (S HH) signaling cascade. Shh is expressed in dynamic, spatiotemporal domains within epithelial rugae and plays a key role in driving epithelial-mesenchymal interactions that are central to development of the secondary palate. However, the gene regulatory networks downstream of Hedgehog (Hh) signaling are incompletely characterized. Here, we show that ectopic Hh signaling in the palatal mesenchyme disrupts oral-nasal patterning of the neural crest cell-derived ectomesenchyme of the palatal shelves, leading to defective palatine bone formation and fully penetrant cleft palate. We show that a series of Fox transcription factors, including the novel direct target Foxl1, function downstream of Hh signaling in the secondary palate. Furthermore, we demonstrate that Wnt/bone morphogenetic protein (BMP) antagonists, in particular Sostdc1, are positively regulated by Hh signaling, concomitant with downregulation of key regulators of osteogenesis and BMP signaling effectors. Our data demonstrate that ectopic Hh-Smo signaling downregulates Wnt/BMP pathways, at least in part by upregulating Sostdc1, resulting in cleft palate and defective osteogenesis.

The role of epineurotomy in the operative treatment of carpal tunnel syndrome.

We conducted a prospective, randomized study to evaluate the effect of epineurotomy on the outcome of operative treatment of established median-nerve compression in the carpal canal. Fifty hands (forty-four patients) were randomized into two groups: one group had a release of the transverse carpal ligament alone, and the other had a release and adjuvant epineurotomy of the median nerve. The groups were similar with regard to age, gender, duration of symptoms, and preoperative physical findings. All patients had electrophysiological evidence of sensory delays and fibrillations on preoperative testing. All of the operative procedures were performed by the same surgeon. The patients were evaluated preoperatively and at one year postoperatively. The follow-up examination revealed no detectable differences between the two groups with regard to symptoms, objective findings, or electrophysiological findings. This suggests that epineurotomy of the median nerve offers no benefit compared with sectioning of the transverse carpal ligament alone.

Counseling issues with gay and lesbian adolescents.

Few resources have been available to counselors working with lesbian and gay adolescents. This article seeks to bridge the gulf between the life experiences of these teens and those of the counselor by providing information on sexual identity formation, increased mental health risk factors for gay and lesbian youth, "coming out" issues, and barriers to supportive intervention given the hidden nature of much of this population within the schools and the world at large. Specific suggestions regarding how mental health counselors can assist these adolescents are provided.

Pelvic displacement osteotomy for chronic hip dislocation in myelodysplasia.

Twelve children with lumbar-level myelodysplasia (average age, eight and three-quarter years) underwent twenty-one pelvic displacement osteotomies for subluxated or dislocated hips. Nineteen of the twenty-one hips remained reduced on three-year follow-up. Gains in gait pattern, ease of bracing, and reduced pelvic obliquity were noted. Active function about the hips was not improved, nor was there a decrease in the amount of bracing needed following the osteotomy. Pelvic displacement osteotomy can be utilized in selected cases as part of the over-all management of chronic hip dislocation in myelodysplasia.