Glucocorticoid receptor (GR) recycles between an inactive form complexed with heat shock proteins (hsps) and localized to the cytoplasm and a free liganded form that regulates specific gene transcription in the nucleus. We report here that, contrary to previous assumptions, association of GR into hsp-containing complexes is not sufficient to prevent the shuttling or trafficking of the GR across the nuclear membrane. Following the withdrawal of treatment with cortisol or the hormone antagonist RU486, GRs recycled rapidly into hsp-associated, hormone-responsive complexes. However, cortisolwithdrawn receptors redistributed to the cytoplasm very slowly (t1 ⁄2 ؍ 8 -9 h) and RU486-withdrawn receptors not at all. Persistent localization of these GRs to the nucleus was not due to a gross defect in export, since in both instances the complexed nuclear GRs transferred efficiently between heterokaryon nuclei. Moreover, the addition of a nuclear retention signal to the N terminus of GR induced the transfer of naive receptor to the nucleus in the absence of steroid. These results suggest that the localization of GR to the cytoplasm is determined by fine control of the rates of transfer of GR across the nuclear membrane and/or by active retention that occurs independently from the association of GR with hsps.
This study demonstrates that innervation of free TRAM flaps used for breast reconstruction not only improves sensibility but also has a positive effect on patient-rated quality of life.
Goals of a successful cleft palate repair include separation of the oral and nasal components without fistula, achieving sufficient velar length, and creating functional transverse orientation of the levator muscle sling. A number of techniques have been described to achieve these goals, but they all have the following technical details in common: elevation of oral mucosal flaps based on the greater palatine arteries, tension free nasal lining mobilization, and functional intervelar muscle dissection. After palate repair, speech evaluation needs to be performed by an objective interdisciplinary team following a standardized protocol. Identification of velopharyngeal insufficiency secondary to an incompetent nasopharyngeal port will necessitate secondary speech surgery. These secondary techniques include pharyngeal flaps, soft palate lengthening, or pharyngeal sphincters, which should be tailored to optimize speech, while minimizing the risk of obstructive sleep apnea.
Internationally adopted children with clefts have unique treatment challenges. Children with unrepaired clefts undergo surgery late, and children with prior repairs frequently undergo revision. Compared with nonadoptees, adoptees require more revisions and have a higher fistula rate. Further detailed study is important to optimize care.
Experts are reliably able to subjectively rank patients according to the degree of nasal deformity. Measures of the columellar angle and the nostril width ratio vary in a linear fashion with the perceived deformity and may serve as independent and objective indicators of presurgical severity of unilateral cleft lip nasal deformity.
In spite of established indications for early operative repair of orbital floor fractures 7-10% of patients treated nonoperatively develop enophthalmos. Clearly further indications for repair are required to prevent these post-injury complications. Rounding of the inferior rectus muscle on coronal computerized tomography (CT) scan results from a loss of soft tissue and bony support and may therefore be predictive of late enophthalmos.A four-year institutional review was conducted to identify patients with orbital floor fractures that had been treated nonoperatively. Patients were recruited for late clinical follow-up (mean 30 months) where clinically significant enophthalmos and diplopia were measured. Clinical results were correlated with measurements of the height-to-width ratio of the inferior rectus muscle on CT scans by a blinded examiner. Eighteen of 78 patients were available for late follow-up. Sixteen patients had no enophthalmos whereas 2 patients had enophthalmos. The inferior rectus height-to-width ratios measured in the unaffected orbits were statistically similar between the two groups. There was a significantly increased height-to-width ratio exceeding 1.00 in the affected orbit when the enophthalmos group was compared to the no enophthalmos group.A height-to-width ratio of the inferior rectus muscle on coronal CT scan of greater than or equal to 1.00 is predictive of late enophthalmos.
Management of cleft lip and palate requires a unique understanding of the various dimensions of care to optimize outcomes of surgery. The breadth of treatment spans multiple disciplines and the length of treatment spans infancy to adulthood. Although the focus of reconstruction is on form and function, changes occur with growth and development. This review focuses on the surgical management of the primary cleft lip and nasal deformity. In addition to surgical treatment, the anatomy, clinical spectrum, preoperative care, and postoperative care are discussed. Principles of surgery are emphasized and controversies are highlighted.
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