A novel gene delivery method transduces porcine pancreatic duct epithelial cells.

Gene therapy offers the possibility to treat pancreatic disease in cystic fibrosis (CF), caused by mutations in the CF transmembrane conductance regulator (CFTR) gene; however, gene transfer to the pancreas is untested in humans. The pancreatic disease phenotype is very similar between humans and pigs with CF; thus, CF pigs create an excellent opportunity to study gene transfer to the pancreas. There are no studies showing efficient transduction of pig pancreas with gene-transfer vectors. Our objective is to develop a safe and efficient method to transduce wild-type (WT) porcine pancreatic ducts that express CFTR. We catheterized the umbilical artery of WT newborn pigs and delivered an adeno-associated virus serotype 9 vector expressing green-fluorescent protein (AAV9CMV.sceGFP) or vehicle to the celiac artery, the vessel that supplies major branches to the pancreas. This technique resulted in stable and dose-dependent transduction of pancreatic duct epithelial cells that expressed CFTR. Intravenous (IV) injection of AAV9CMV.sceGFP did not transduce the pancreas. Our technique offers an opportunity to deliver the CFTR gene to the pancreas of CF pigs. The celiac artery can be accessed via the umbilical artery in newborns and via the femoral artery at older ages--delivery approaches that can be translated to humans.

Linear and rotational changes in large mandibular advancements using three or four fixation screws.

Forty-one patients who underwent bilateral sagittal ramus osteotomy for large mandibular advancements were evaluated by retrospective cephalometric analysis for rotational and linear stability of the proximal and distal segments of the mandible. The patients were grouped by the number of screws used in fixation (three versus four 2-mm bicortical screws) and matched for the amount of advancement measured from changes in mandibular body length. The group with four fixation screws did receive significantly larger advancements relative to the cranial base than did the group with three screws. However, the pattern of postoperative change was similar for the two groups. There was no higher rate of relapse seen in those patients with high mandibular plane angles, genioplasties, mandibular constriction with a symphyseal osteotomy, or open bites preoperatively, nor did the number of screws used in fixation affect changes seen in those patients. Factors associated with both relapse and continued postoperative movement in the direction of advancement independent of the screw fixation group were identified.

Perceptions of facial profile and their influence on the decision to undergo orthognathic surgery.

Eighty patients, who had previously been evaluated by an oral surgeon and an orthodontist as requiring orthognathic surgery, completed questionnaires rating their perceptions of their own profiles. Half of the patients had decided to undergo surgical correction of their jaw deformities, while the other half had decided against surgical treatment. In addition, booklets containing pretreatment photographs of all 80 patients were mailed to 37 oral surgeons, 46 orthodontists, and 43 lay persons. These three groups of evaluators rated the patients' profiles, using the same rating scales that the patients had used. Cephalometrically, the two patient groups were statistically the same in all skeletal and soft-tissue measures except for ANB (mean difference = 1.8 degrees) and soft-tissue AN-pogonion (mean difference = 2.4 degrees). Differences in these dimensions were considered in subsequent data analyses. Results of this study support the following conclusions: In spite of the fact that surgical treatment may be recommended by dental specialists and indicated by cephalometric measurements, self-perceptions of profile are more important in the patient's decision to elect surgical correction; the perception by others that the profiles of patients deciding against surgery are closer to ideal may have some influence on their decision against surgical correction of their jaw deformities; oral surgeons and orthodontists evaluate facial profiles similarly, but surgeons are more likely to recommend surgical correction; lay persons are more likely to rate an individual's profile as being normal than are dental specialists in orthodontics and oral surgery; in contrast, individuals perceive their own profiles differently than orthodontists, oral surgeons, and lay persons, particularly with respect to the mandibular and dentoalveolar dimensions.