In humans and mice, mutations in Hoxa13 cause malformation of limb and genitourinary (GU) regions. In males, one of the most common GU malformations associated with loss of Hoxa13 function is hypospadia,a condition defined by the poor growth and closure of the urethra and glans penis. By examining early signaling in the developing mouse genital tubercle,we show that Hoxa13 is essential for normal expression of Fgf8 and Bmp7 in the urethral plate epithelium. In Hoxa13GFP-mutant mice, hypospadias occur as a result of the combined loss of Fgf8 and Bmp7 expression in the urethral plate epithelium, as well as the ectopic expression of noggin(Nog) in the flanking mesenchyme. In vitro supplementation with Fgf8 restored proliferation in homozygous mutants to wild-type levels, suggesting that Fgf8 is sufficient to direct early proliferation of the developing genital tubercle. However, the closure defects of the distal urethra and glans can be attributed to a loss of apoptosis in the urethra,which is consistent with reduced Bmp7 expression in this region. Mice mutant for Hoxa13 also exhibit changes in androgen receptor expression, providing a developmental link between Hoxa13-associated hypospadias and those produced by antagonists to androgen signaling. Finally,a novel role for Hoxa13 in the vascularization of the glans penis is also identified.
Objective This case report is designed to illustrate an uncommon presentation of osteoradionecrosis (ORN) of the temporal bone and a treatment method for bloody otorrhea from a pseudoaneurysm of the internal carotid artery (ICA). Design This is a single patient case report Setting University of Missouri-Columbia Hospital and Clinics. Participants The report describes a patient with a history of hypopharyngeal squamous cell carcinoma (SCCA) who was previously treated with chemoradiation therapy and salvage bilateral neck dissections and then presented in a delayed fashion with profuse, episodic bloody otorrhea. Computed tomography (CT) was consistent with ORN of the temporal bone. The patient underwent emergent cerebral angiography. A pseudoaneurysm of the cervicopetrous ICA was confirmed to be the source of the patient's bloody otorrhea. The lesion was treated by endovascular sacrifice of the ICA using the two-catheter coiling technique. Results The patient had no neurologic sequelae or further bleeding after treatment. Conclusions Bloody otorrhea is an uncommon presentation of ORN. Sacrifice of the internal carotid can be considered as a treatment when the source is pseudoaneurysmal.
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