Effects of TGFbeta2 on collagen synthesis in cultured normal and wounded fetal mouse palates.

OBJECTIVE: It has been demonstrated in a number of models that fetal wounds heal with little or no scar. Since collagen is an integral part of the extracellular matrix in adult scar formation, we studied the synthesis and localization of collagen in an in vitro mouse palate model for fetal wound healing. METHODS: Palates, dissected from fetal mice at 15, 16, and 17 days of gestation and from newborn mice, were cultured in medium containing serum (for 8 hours); this was followed by culture in serum-free medium (for 12 hours). One-half of the samples from each age group were wounded in the midline. All samples were placed in serum-free medium containing 20 microCi/mL 3H-proline for 8 hours. In addition, palates from 15-day gestation and from newborn mice were also incubated with transforming growth factor TGF-beta2 (10 ng/mL). Palates were washed with saline, homogenized, and radioactivity was counted. Proline uptake was calculated for each sample as counts per milligram of protein and was subjected to statistical analysis (three-way analysis of variance). Samples of the homogenate were subjected to sodium dodecyl sulfate-gel electrophoresis and Western blotting in order to determine the types of collagen that were synthesized. Immunohistochemical localization of collagen types I, III, and VI was carried out on paraffin-embedded samples from each group. RESULTS: There were no significant differences in proline uptake between wounded mouse palates and nonwounded mouse palates at any age, and there was no histological evidence of regeneration of the palate at the site of the wound. Proline uptake was significantly greater in untreated wounded palates at 15 days' gestation than it was in newborns. After treatment with TGF-beta2, proline uptake was significantly greater in both wounded and nonwounded palates in the newborn group and had no effect on collagen synthesis in palates from 15-day gestation animals. Collagen types I and III were localized in histological specimens using immunohistochemistry and on nitrocellulose using Western blotting. No type VI collagen was demonstrated by Western blotting, but it was localized around blood vessels and on basement membranes using immunohistochemistry. CONCLUSION: Treatment with TGF-beta2 significantly increased collagen synthesis, as assessed by 3H-proline uptake, in cultured palates from newborn mice as compared with palates from untreated newborn mice and from both treated and untreated palates of 15-day gestation mice. These data suggest a differential response to TGF-beta2 by mouse palates as a function of fetal development.

Muscle fiber type distribution in the normal human levator veli palatini muscle.

OBJECTIVE: This study examined the muscle fiber type distribution within the normal adult levator veli palatini muscle. METHODS: Levator veli palatini muscle tissue was harvested from the palates of 12 (seven female, five male) adult noncleft cadavers. Adjacent sections were stained for adenosine triphosphatase at pH 10.4 or 4.2. After mounting, magnifying, and photographing, Type I versus Type II fiber types were differentiated by the intensity of, or by the inhibition of, staining of matched fibers at each pH level. Type I fibers stained light at pH 10.4 and dark at pH 4.2, while Type II fibers stained light at pH 4.2 and dark at pH 10.4. MAIN OUTCOME MEASURES: The number of fibers counted for each specimen ranged from 60 to 616. The numbers of Type I and Type II stained fibers appearing in each muscle tissue sample were determined and expressed as a percentage of the total number of fibers identified. A few identified fibers could not be labelled as either Type I or Type II. RESULTS: The overall proportion of Type I fibers, averaged across all specimens, was 59.8%. Male specimens had 67.4% Type I fibers and 31.8% Type II fibers, while female specimens had 54.4% Type I fibers and 44.4% Type II fibers. CONCLUSIONS: Observed fiber type distributions were similar to those reported for other articulatory muscles, but differed slightly from previously reported distributions for normal levator veli palatini. The distributions observed in this study provide a baseline against which to relate fiber type data from the levator veli palatini of cleft palates to the functional status of the velopharyngeal mechanism.

An anatomic study of the tensor veli palatini and dilatator tubae muscles in relation to eustachian tube and velar function.

In a gross anatomic study of 20 sides in 16 human head specimens, the tensor veli palatini, the dilatator tubae, and the tensor tympani muscles were studied. The tensor veli palatini was observed to insert onto the anterior one-third of the pterygoid hamulus, whereas the dilatator tubae rounded the middle one-third of the pterygoid hamulus without an insertion. Thus, the dilatator tubae, not the tensor veli palatini, could serve to tense the anterior velum. An insertion from the superior pharyngeal constrictor muscle onto the posterior one-third of the hamulus could provide a curbing function for the dilatator tubae muscle. Adipose tissue, located at the hamulus, could provide lubrication for the tendinous fibers of the dilatator tubae as they round the hamulus. The dilatator tubae was observed to attach to the hook of the eustachian tube and is accepted as the tubal dilator. Observed on 13 of 20 sides in 11 specimens, the bulk of the dilatator tubae remained distinct from the tensor veli palatini despite a connective tissue alliance and intermingling of some muscle fibers. On 5 of 20 sides in 5 specimens, fibers of the dilatator tubae intermingled extensively with the tensor veli palatini. Of the 20 dilatator tubae muscles dissected, 2 were observed to be deficient. The tensor veli palatini was observed to be continuous with the tensor tympani. Full color versions of the figures are available at the following website: http://www.shc.uiowa.edu/papers/tensor/.

Continuity of care: University of Iowa Cleft Lip/Palate Interdisciplinary Team.

INTRODUCTION: Patient satisfaction with the continuity of care is an important aspect of care delivery that may be evaluated to assess team effectiveness. This study was conducted to evaluate the number of patients seen by each team member, and the patients' perceived importance of continued care by the same health care provider during their overall treatment. METHODS: A survey was constructed by the members of the Cleft Lip/Palate Team at the University of Iowa Hospitals and Clinics. One hundred and thirty-eight subjects were invited to participate during consecutive clinic days over a 5-month period; 101 subjects (73.1%) responded. RESULTS: The survey revealed that the percentage of patients seen by each member of the team ranged from 92.1% (93/101) for the surgeon to 24.8% (25/101) for the genetic counselor. Strong agreement with continuity of care by health professionals ranged from 85.6% (83/97) for the surgeon, 63.7% (58/91) for the orthodontist, 63% (17/27) for the psychologist, to 23.1% (19/82) for the audiologist. The percentages dropped somewhat if the patients thought that they may have to wait longer for their next appointment. CONCLUSION: There is a strong preference for continuity of health care.

Craniofacial growth after iatrogenic cleft palate repair in a fetal ovine model.

Controversy exists over the impact of scar formation on craniofacial growth after cleft palate repair. The fetal ovine model presents an opportunity to study a group of animals with little or no scar using cephalometric studies of cranio-facial growth after iatrogenic cleft palate repair. Grossly evident scar is formed in the palates of lambs repaired at 118 days or later in gestation, while those animals operated at 70 and 77 days' gestation exhibited no scar grossly and minimal scar histologically in the submucosa with normal nasal and oral mucosal surfaces. For this study, 15 lambs were studied: four were unoperated, three were operated at 70 days, one at 77 days, and seven had clefts produced and repaired at 118 to 133 days' gestation. The animals were euthanized at 1 month of age and the heads removed and frozen until analyzed. Computerized tomography of the heads was used to create voxel (volume pixel) data sets, and volume rendering and measurement software (Voxblast) was used to create a three-dimensional reconstruction of the skull. Palate measurements were obtained by selecting points on the upper deciduous premolars. A plane was set through the palate and upper deciduous premolars using standard points on the skull to maintain consistent visualization and point selection. The measurements were normalized to skull size measured by the distance between points on the right and left zygomatic bones. Using one-way analysis of variance, followed by a protected t test, no significant differences were found between the means of any measurement in the three treatment groups. Fetal palate repair, with or without scarring, resulted in normal craniofacial growth in the 1-month-old lamb.

Reduction mammaplasty: the results of avoiding nipple-areolar amputation in cases of extreme hypertrophy.

In extreme cases of breast hypertrophy, amputation of the nipple-areolar complex and transplantation during reduction mammaplasty has been advocated to avoid nipple necrosis. We report our experience with 172 patients having inferior breast pedicle reduction without amputation of the nipple-areolar complex. Mean total weight of resected tissue was 1,946 g (548 to 5,100 g), with a mean nipple-areolar transposition of 10 cm (0.5 to 23 cm). Dividing patients into four groups by weight of resection, we compared complication rates. In this series, where nipple-areola amputation was avoided, there was a 99.6% survival rate of the nipple-areolar complex with 97.1% retention of nipple sensibility. Patients with extreme breast hypertrophy (3,000 g resected tissue) experienced no increase in complications when compared to smaller reductions. In most cases of gigantomastia, amputation of the nipple can be avoided using the inferior breast pedicle technique. Size of breast resection alone should not determine the fate of the nipple.

Craniofacial growth in rabbits after rigid or semi-rigid fixation of the frontonasal suture.

Treatment of craniofacial dysostosis involves complex remodeling of the cranium and facial bones. Maintenance of the newly positioned segments may be achieved by rigid fixation using plates; however, there is concern that, over time, these plates may interfere with normal growth. The purpose of this study was to test a method of "semi-rigid" fixation of an osteotomy of the frontonasal suture in juvenile rabbits by comparing standardized parameters of craniofacial growth after conventional suture plating with the experimental plating method and with growth after sham operation. Forty-five, 6-week-old, weanling rabbits were divided into three groups of 15 each (12 for cephalometry, 3 for histological examination): (group 1) control, sham operated; (group 2) rigid fixation; (group 3) semi-rigid fixation. Rabbits were maintained for 14 weeks. Craniofacial growth was assessed using three-dimensional image analysis techniques. Measurements were subjected to statistical analysis (one-way analysis of variance) to compare the three treatment groups. Pairwise comparison of means between the treatment groups was done using Bonferroni's method at the 0.05 significance level. Semi-rigid fixation permitted significantly more normal growth of the developing rabbit head than rigid fixation in total snout length, total vault length, left and right midface height, and left orbital length. Both semi-rigid and rigid fixation significantly restricted growth compared with sham operated animals in left and right posterior midface height, right orbital length, right and left nasal bone length, and left parietal width. There were no significant differences in the growth of all other parameters measured.

Oral commissure burns in children.

Electrical burns of the mouth are relatively common in young children. Early intervention to prevent complications remains controversial. A chart review was conducted of 24 patients with oral commissure burns who were treated at the University of Iowa from 1975 to 1988. All of these patients were treated conservatively without splinting or early surgery. Only one patient underwent oral splinting before receiving care at the University of Iowa Hospitals and Clinics. While under our care, no patients suffered significant hemorrhage at eschar separation. Commissuroplasty and/or reconstructive lip surgery were performed at various times after the burn injury was healed and the functional or aesthetic impairment was established. Long-term follow-up was from 5 to 17 years, allowing for longitudinal evaluation of the postburn scars and their influence on facial growth. Our review revealed that (1) younger children with more severe burns have a less favorable outcome; (2) no hemorrhage was observed immediately after the burn or at eschar separation; and (3) conservative surgical treatment after scar maturation- and in some cases following steroid injections- resulted in a successful functional and esthetic outcome.

Effects of gravity on velopharyngeal muscle activity during speech.

Assessment of the role of gravitational forces in the motor control of the velopharyngeal mechanism was the focus of this study. Specifically, the effect of gravity on activation levels of the levator veli palatini and palatoglossus muscles was assessed. Nineteen volunteers repeated a CV syllable in upright and supine body positions. Overall, lower peak activation levels of levator veli palatini were observed in the supine body position. The results suggest that less muscle activity was seen in the levator veli palatini in the supine body posture, where gravitational effects worked in the same direction (i.e., toward closure). No statistically significant group effects were seen in muscle activation levels of palatoglossus across the two body postures, although clear gravity effects were observed in some subjects. The implications of these findings from a speech motor control perspective are discussed in relation to normal and disordered velopharyngeal function.

Craniofacial growth in rabbits. Effects of midfacial surgical trauma and rigid plate fixation.

OBJECTIVE: To examine the effects of soft-tissue manipulation, rigid microplate fixation, and multiple osteotomies on the growing midface in rabbits. DESIGN: Randomized, controlled experiment. SUBJECTS: Forty 6-week-old male New Zealand white rabbits. INTERVENTIONS: Group 1, exposure of the left nasofrontal and midzygomatic arch regions with periosteal elevation; group 2, osteotomies at left nasofrontal suture and midzygomatic arch; group 3, rigid plate fixation of osteotomies; and group 4, rigid plate fixation alone. Animals were killed at age 20 weeks; growth was assessed by linear and spatial measurements of craniofacial regions. RESULTS: Linear data disclosed shortening of the left nasal bone (P < .05) in groups 2 through 4. Groups 3 and 4 also had shortened left zygomatic arches and orbital diameters (P < .05). Euclidean distance matrix analysis showed significant restrictive shape alterations in groups 2 through 4 (P < .05). Significant contralateral shape alterations also were found in group 3. CONCLUSION: Rigid plate fixation does not cause more severe growth disturbance than bony trauma. Use of rigid plate fixation after bony trauma does not seem to increase the restrictive effects of trauma on growth. Furthermore, removal of rigid plate fixation may not prevent growth disturbances and may induce further harmful trauma to the growing midface.

Emotional effects of plastic surgery on the adolescent with a cleft.

Issues related to the emotional effects of surgery on the adolescent are reviewed in this paper. Psychological aspects of the preoperative preparation of the adolescent and family are discussed. Caution is suggested regarding overgeneralizations from the sometimes conflicting data in the literature, reviewed here, on social aspects of physical appearance. An outline of a plan for the work-up of an adolescent undergoing appearance changing surgery is presented. The importance of communication and patience in approaching the adolescent is stressed.

Management of the adopted child in the craniofacial clinic.

Because of the decrease in the number of children available for adoption, there has been an increase in frequency of parents who are willing to adopt children of different ethnic and racial groups, children from other countries, older children, and children with special needs. More of these children, particularly those with special needs such as cleft lip and palate, are being seen in cleft palate or craniofacial clinics. It is important that medical care providers understand some of the potential special considerations surrounding their care. Legal status, history, medical history, genetic history, development, emotional and behavioral concerns, and the need for counseling are management issues that need to be considered in the overall multidisciplinary management of these children.

Augmentation of oral tissues in rabbit using autogenous fat.

Patients with mild velopharyngeal incompetence (VPI) may have speech disorders, which are not sufficiently severe to warrant extensive surgical intervention, yet may not be amenable to correction by speech therapy alone. Augmentation of the posterior pharyngeal wall to aid in closure of the velopharyngeal sphincter may be beneficial in establishing better speech patterns, especially when combined with speech therapy. A variety of materials and techniques have been used in the past for this purpose. In this setting, autogenous fat may be transplanted without the risks incurred by augmentation with synthetic materials and involves very little donor site morbidity. The literature is somewhat contradictory, however, regarding the stability of the augmentation achieved using autogenous fat and there are no histologic studies describing the fate of fat injected into tissues of the oral cavity. Prior to introduction of this technique into clinical practice, this study was designed to investigate the fate of autogenous fat injected submucosally in the oropharyngeal region. Autogenous fat was injected into the anterior soft palate using the rabbit as a model. Histologic and gross inspections were performed at 2 days, 1, 2, and 4 weeks after injections. At the end of 4 weeks, at least 50% of the injection sites had visible evidence of augmentation, and 90% had histologic evidence of submucosal fat. In some instances most of the fat was resorbed; however, there were no instances of clinical infection or necrosis of the injection site. We conclude that submucosal injection of autogenous fat is a feasible alternative to using synthetic or other biologic materials for augmentation in the oral cavity.

Complication outcomes based on preoperative admission and length of stay for primary palatoplasty and cleft lip/palate revision in children aged 1 to 6 years.

With increasing focus on outcome studies, there is continued need for data about whether same-day admission and reduced hospital stay have adverse effects on surgical treatment, including that for cleft lip and palate. In this study, medical records were inspected for all cleft lip and palate patients, aged 1 to 6 years, who had primary palatoplasty or cleft lip/palate revision in this treatment center between 1978 and 1992 (N = 329). Length of stay for 251 (96.5%) of the 260 subjects admitted the day before surgery was from 4 to 7 days; 9 remained in the hospital longer than 8 days. Length of stay for 67 (97.1%) of 69 patients admitted the day of surgery was from 2 to 3 days; 2 were in the hospital for 7 days, and none for 8 or more days. Thirty-seven instances of surgical complications were reported for the 260 patients admitted the day before surgery (14.2%). Twelve complications (17.4%) were recorded for the 69 patients admitted the day of surgery. There was no significant difference in the number of complications between the two groups of patients (Fisher's exact test, p = 0.5682). There was no significant difference in the types of complications observed between the two groups (Fisher's exact test). Surgery was performed at age 1 year for 61 of the 69 patients admitted on the day of surgery (88.4%). The mean age of this group was significantly younger than that of patients operated on earlier than 1989 and admitted on the day before surgery (Wilcoxon's test, p = .0001, Z = 4.48).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of nasal obstruction in rhinoplasty.

Nasal obstruction is commonly due to septal deviation, enlarged turbinate mucosa, enlarged bony turbinates, nasal valving or, occasionally, a ptotic nasal tip. Correct preoperative diagnosis using the algorithm presented will lead to the appropriate selection of treatment for the patient groups discussed. The same diagnostic system will help the surgeon avoid patients who are likely not to be helped by operative intervention.

Effects of argon beam coagulation on split thickness skin graft survival in the swine model.

Argon beam coagulation (ABC) uses argon gas to evacuate blood in an operative field and simultaneously to transport a coagulating electric current to bleeding sites. This allows a 'no touch' method of coagulation which is faster, more precise, and less destructive than conventional electrocautery. The technique has been used to reduce blood loss in liver surgery, trauma surgery and neck dissections. In this study, the effect of ABC treatment of the recipient graft beds on the survival of split thickness skin grafts was assessed in pigs, testing the hypothesis that ABC treatment of the recipient bed would have no adverse effect on skin graft survival. Nine 20 kg mixed breed pigs had split thickness skin grafts raised on each side of the paraspinous area. The graft beds on one side were prepared using ABC and the contralateral side served as controls. The percentage of graft survival on the ABC treated sides was compared to control graft survival on the other side at 12 days postsurgery. Our results confirm the hypothesis that treatment of the recipient bed with ABC does not adversely affect the survival of split thickness skin grafts.

The effects of tretinoin on random skin flap survival in the swine model.

Tretinoin is currently marketed for topical treatment of acne vulgaris and has also been used in the rejuvenation of aging skin. After topical application, it has been shown to stimulate mitotic activity and increase vascularity in skin. In this study a porcine model was used to test the hypothesis that presurgical treatment with topical tretinoin would increase the surviving area of random full-thickness skin flaps. Four hybrid barrows, 40 to 60 lb, were treated with tretinoin and 4 similar animals were treated with placebo (carrier vehicle) for 2 weeks before raising four dorsally based full-thickness skin flaps (4 x 12 cm) on each animal. Biopsies were taken from tretinoin-treated, placebo-treated, and untreated skin at the time the flaps were initially raised and 1 week later before killing the animals. All tissue was processed for light and electron microscopy. One week after surgery, the pigs were killed. Photographs were taken at the termination of the experiment and the negatives were digitized and analyzed using a high-speed graphics workstation supported by SGITrace software. The percentage of skin flap survival was determined using this method of image analysis. Using repeated-measures analysis of variance, there was no significant difference in the mean flap survival between the tretinoin (mean = 46.75; SEM = 7.05) and placebo (mean = 65.80; SEM = 7.05) treated groups at the 0.05 significance level. Pretreatment with tretinoin did not enhance skin flap survival under the conditions of this study. Rationale for this finding and possible modifications of future studies are discussed.

In utero cleft palate repair in the ovine model.

Cleft lip and palate defects assume many forms from mild to severe, but all may be associated with abnormal craniofacial development. Even the most expert and sophisticated methods of surgical repair are followed by scar contraction and fibrosis, which result in skeletal defects, dental abnormalities, cosmetic disfigurement, and speech impairment. Recent clinical and experimental observations that fetal cutaneous wounds heal without scarring are of great potential interest in the management of cleft lip and palate. The objective of this study was to investigate the effect of prenatal repair of iatrogenically produced cleft palate on scar formation in the fetal lamb model. Ten ewes were operated on ranging in gestation from 70 to 133 days. Fifteen lambs were studied (nine cleft palates produced and repaired in utero; one cleft produced in utero and not repaired, four normal, unoperated palates; and one cleft palate produced and repaired 1 week postnatally). The lambs were delivered normally at 145 to 147 days gestation and maintained with the ewe until 1 month of age. The lambs were euthanized, and the surgical area of the palates studied grossly and histologically. Animals operated at 112 days or later in gestation exhibited scars both clinically and histologically. The animals that had cleft palate produced and repaired at 70 days gestation did not have a visible palatal scar at 1 month of age. Histologically, there was evidence of minimal scarring without disruption of normal architecture. Studies are underway to determine the impact of reduced scarring on craniofacial growth after palatal repair during mid gestation in the ovine model.