The FKBP-12-binding ligand FK506 has been successfully used to stimulate nerve regeneration and prevent the rejection of peripheral nerve allografts. The immunosuppressant rapamycin, another FKBP-12-binding ligand, stimulates axonal regeneration in vitro, but its influence on nerve regeneration in peripheral nerve isografts or allografts has not been studied. Sixty female inbred BALB/cJ mice were randomized into six tibial nerve transplant groups, including three isograft and three allograft (C57BL/6J) groups. Grafts were left untreated (groups I and II), treated with FK506 (groups III and IV), or treated with rapamycin (groups V and VI). Nerve regeneration was quantified in terms of histomorphometry and functional recovery, and immunosuppression was confirmed with mixed lymphocyte reactivity assays. Animals treated with FK506 and rapamycin were immunosuppressed and demonstrated significantly less immune cell proliferation relative to untreated recipient animals. Although every animal demonstrated some functional recovery during the study, animals receiving an untreated peripheral nerve allograft were slowest to recover. Isografts treated with FK506 but not rapamycin demonstrated significantly increased nerve regeneration. Nerve allografts in animals treated with FK506, and to a lesser extent rapamycin, however, both demonstrated significantly more nerve regeneration and increased nerve fiber widths relative to untreated controls. The authors suggest that rapamycin can facilitate regeneration through peripheral nerve allografts, but it is not a neuroregenerative agent in this in vivo model. Nerve regeneration in FK506-treated peripheral nerve isografts and allografts was superior to that found in rapamycin-treated animals. Rapamycin may have a role in the treatment of peripheral nerve allografts when used in combination with other medications, or in the setting of renal failure that often precludes the use of calcineurin inhibitors such as FK506.
The sphincter pharyngoplasty is a surgical procedure designed to correct velopharyngeal dysfunction. Its advocates cite the theoretical advantage of its induction of dynamic activity of the neovelopharyngeal port, but this dynamic activity has yet to be quantitatively demonstrated in the literature. The purpose of this study was to quantify postoperative velopharyngeal dynamism and to document the results of intervention outcome on sphincteric excursion measurements from minimal-to-maximal orifice closure. We conducted a 7-year retrospective review of speech videofluoroscopy evaluations in patients who had undergone sphincter pharyngoplasty in our center. Between 1989 and 1994, there were 58 patients so treated for postpalatoplasty velopharyngeal dysfunction by two surgeons using the same operative technique. Patients for whom sphincter pharyngoplasty was recommended fulfilled both of the following criteria: (1) velopharyngeal dysfunction caused by an anatomic, myoneural, or combined deficiency of the velopharyngeal sphincter that would not be expected to be managed by speech therapy alone, and (2) preoperative videonasendoscopy and speech videofluoroscopic studies that demonstrated large-gap coronal, circular, or bow-tie closure patterns or velopharyngeal hypodynamism. Of the original 58 patients, 24 underwent postoperative speech videofluoroscopic evaluations with basal views. Of these, 20 of the evaluations (83 percent) were of adequate quality to be included in a research study. Still images showing maximum and minimum excursion of the sphincter in basal view were obtained. To test for observer reliability, the speech videofluoroscopic studies were randomized and presented for measurement to the same individual on two occasions, each session separated by a 1-month time interval. Topographic imaging software was used to obtain maximum and minimum measurements to within 0.1 mm. Partitioning the variance of the data showed that measurement variability was a very small portion of the total, and that difference between the minimum and maximum values was the largest source of variability. Of the total variability in the data, 64.0 percent originated in the minimum/maximum difference, 34.3 percent came from patient variability, and only 1.7 percent resulted from original or repeat measurements. The patient variability may be exaggerated because of variability in the scale of measurement. Results of this study indicate a quantifiable and statistically significant difference in maximum-to-minimum excursion of sphincteric closure. Sphincter pharyngoplasty appears to be dynamic in the majority of cases.
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