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Fetal cleft lip repair in rabbits: A preliminary report
Abstract Session V RECONSTRUCTION Friday, September 22 2:00-5:00 p.m. Moderator: Lionel Gold, DDS, Cherry Hill, NJ Reactor Panel: James D. Ruskin, DMD, MD, Omaha, NE Jack E. Gotcher, DMD, PhD, Knoxville, TN
Fetal Cleft Lip Repair in Rabbits: A Preliminary Report Leonard B. Kaban, DMD, MD, Department of Oral and Maxillofacial Surgery and Surgery, University of California-San Francisco, 5 13 Parnassus, S-738, San Francisco, CA 94143 (Dodson, T.B., Eckhart, A., Longaker, M., Harrison, M.) Post-nasal cleft lip repair is available and very effective. However, progressive scarring from multiple surgical procedures leads to midfacial growth retardation. In contrast, fetal wound healing occurs without inflammation and scar formation. We hypothesize that cleft lip repaired in utero will heal by regeneration of oral mucosa, muscle and skin. Without scar, secondary maxillary growth deficiency will not occur. In this investigation, we developed a model to study fetal cleft repair in rabbits. Time-dated pregnant rabbits, in mid-third trimester (24/3 1 days gestation), were anesthetized with halothane/ oxygen by mask. A sterile midline laparotomy was performed and one fetus on each side of the bicornate uterus was used. Control fetuses were exposed and returned without operation. Under 6X loupe magnification, the others had a lmm paramedian section of lip and maxillary alveolus removed. The defects were repaired with 8-O nylon sutures or left unrepaired. Fetuses were sacrificed at 1,2,3,4 and 7 (at birth) days postoperatively and examined for maxillary width, length, nasal and lip morphology. Fetuses delivered spontaneously were similarly examined at birth, 4 and 12 days post natally. Horizontal sections through the lip, maxilla and nose were examined histologically at the same time points. We operated on 50 fetuses in 25 pregnant does and 36150 fetuses survived (72%): 14 with repaired cleft lip, 12 unrepaired and 10 controls. Both repaired and unrepaired fetuses had decreased maxillary length and width and an asymmetric nose at 4,7 (birth), 11 and 19 days (12 days post natal) postoperatively. However, the repaired group had milder deformity at all time points and was improving with growth. Histologically, at 1 through 4 days postoperatively, there were no inflammatory cells and no scar in the wounds of both the repaired and unrepaired fetuses. In the repaired group however, there was regeneration of epithelium and mucosa across the cleft by 4 days postoperatively. By 7 days postoperatively, the nasal cartilage 102
defect seemed to have regenerated and there were bundles of living muscle cells in the repaired cleft area. However, up to 12 days post-natally (19 days postoperatively) there had not been complete regeneration of muscle across the cleft despite the fact that the repaired animals had only minimal facial asymmetry. The results of this study indicate that the fetal cleft lip model is technically feasible with acceptable survival. There was no inflammation and no scar in the fetal wounds. In the repaired fetuses there was epithelial and mucosal regeneration but incomplete muscle regeneration. References Harrison, M.R., Golbus, MS., Filly, R.A.: The Inborn Patient. Orlando, Grune and Stratton, 1984 Longaker, M.T., Harrison, M.R., Kaban, L.B.: Concepts of fetal surgery-Applications in craniofacial surgery, In: Pediatric Oral and Maxillofacial Surgery. L.B. Kaban (ed), W.B. Saunders Co., Chapter 19. Philadelphia, 1989 Funding provided by ICSF-OMS Dept. Research Fund
Trigeminal Ganglion Response to Immediate and Delayed Peripheral Nerve Injury and Repair John R. Zuniga, DMD, MS, PhD, Univ. of North Carolina, Dept. of OMS, School of Dentistry, CB #7450, Chapel Hill, NC 27599-7450 (Pate, J.L., Hegtvedt, A.K.) The consequence of transection of a peripheral nerve requires surgical coaptation techniques designed to realign proximal axons and their cell bodies with distal axons and receptor endings to re-establish function. Very few studies have examined the anatomic and functional connections of first-order cells with distal nerves following microneuroanastomosis (1,2). As a result of these deficiencies, a two-stage double-label (DL) method was used to determine the regenerative capabilities of trigeminal ganglion cells after mandibular nerve transection and repair in the adult rat. Moreover, the benefits of immediate versus delayed repair was investigated in this study. Twenty-four ganglia from 12 male adult SpraugueDawley rats were analyzed in the following paradigm:
Fetal Cleft Lip Repair in Rabbits: A Preliminary Report Leonard B. Kaban, DMD, MD, Department of Oral and Maxillofacial Surgery and Surgery, University of California-San Francisco, 5 13 Parnassus, S-738, San Francisco, CA 94143 (Dodson, T.B., Eckhart, A., Longaker, M., Harrison, M.) Post-nasal cleft lip repair is available and very effective. However, progressive scarring from multiple surgical procedures leads to midfacial growth retardation. In contrast, fetal wound healing occurs without inflammation and scar formation. We hypothesize that cleft lip repaired in utero will heal by regeneration of oral mucosa, muscle and skin. Without scar, secondary maxillary growth deficiency will not occur. In this investigation, we developed a model to study fetal cleft repair in rabbits. Time-dated pregnant rabbits, in mid-third trimester (24/3 1 days gestation), were anesthetized with halothane/ oxygen by mask. A sterile midline laparotomy was performed and one fetus on each side of the bicornate uterus was used. Control fetuses were exposed and returned without operation. Under 6X loupe magnification, the others had a lmm paramedian section of lip and maxillary alveolus removed. The defects were repaired with 8-O nylon sutures or left unrepaired. Fetuses were sacrificed at 1,2,3,4 and 7 (at birth) days postoperatively and examined for maxillary width, length, nasal and lip morphology. Fetuses delivered spontaneously were similarly examined at birth, 4 and 12 days post natally. Horizontal sections through the lip, maxilla and nose were examined histologically at the same time points. We operated on 50 fetuses in 25 pregnant does and 36150 fetuses survived (72%): 14 with repaired cleft lip, 12 unrepaired and 10 controls. Both repaired and unrepaired fetuses had decreased maxillary length and width and an asymmetric nose at 4,7 (birth), 11 and 19 days (12 days post natal) postoperatively. However, the repaired group had milder deformity at all time points and was improving with growth. Histologically, at 1 through 4 days postoperatively, there were no inflammatory cells and no scar in the wounds of both the repaired and unrepaired fetuses. In the repaired group however, there was regeneration of epithelium and mucosa across the cleft by 4 days postoperatively. By 7 days postoperatively, the nasal cartilage 102
defect seemed to have regenerated and there were bundles of living muscle cells in the repaired cleft area. However, up to 12 days post-natally (19 days postoperatively) there had not been complete regeneration of muscle across the cleft despite the fact that the repaired animals had only minimal facial asymmetry. The results of this study indicate that the fetal cleft lip model is technically feasible with acceptable survival. There was no inflammation and no scar in the fetal wounds. In the repaired fetuses there was epithelial and mucosal regeneration but incomplete muscle regeneration. References Harrison, M.R., Golbus, MS., Filly, R.A.: The Inborn Patient. Orlando, Grune and Stratton, 1984 Longaker, M.T., Harrison, M.R., Kaban, L.B.: Concepts of fetal surgery-Applications in craniofacial surgery, In: Pediatric Oral and Maxillofacial Surgery. L.B. Kaban (ed), W.B. Saunders Co., Chapter 19. Philadelphia, 1989 Funding provided by ICSF-OMS Dept. Research Fund
Trigeminal Ganglion Response to Immediate and Delayed Peripheral Nerve Injury and Repair John R. Zuniga, DMD, MS, PhD, Univ. of North Carolina, Dept. of OMS, School of Dentistry, CB #7450, Chapel Hill, NC 27599-7450 (Pate, J.L., Hegtvedt, A.K.) The consequence of transection of a peripheral nerve requires surgical coaptation techniques designed to realign proximal axons and their cell bodies with distal axons and receptor endings to re-establish function. Very few studies have examined the anatomic and functional connections of first-order cells with distal nerves following microneuroanastomosis (1,2). As a result of these deficiencies, a two-stage double-label (DL) method was used to determine the regenerative capabilities of trigeminal ganglion cells after mandibular nerve transection and repair in the adult rat. Moreover, the benefits of immediate versus delayed repair was investigated in this study. Twenty-four ganglia from 12 male adult SpraugueDawley rats were analyzed in the following paradigm: