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Cleft palate formation in fetal Br mice with midfacial retrusion: tenascin, fibronectin, laminin, and type IV collagen immunolocalization.

OBJECTIVE: This study tested the hypothesis that altered craniofacial morphology does not affect the expression of extracellular matrix (ECM) molecules such as fibronectin (FN), laminin (LN), type IV collagen, and tenascin-C (TN) but is associated with failure of palatal shelf elevation and fusion concomitant with cleft palate formation. DESIGN: To test this hypothesis, a comparative immunohistological analysis of FN, LN, type IV collagen, and TN was undertaken on brachyrrhine (Br/Br) mice and normal (+/+) fetuses during secondary palate formation. Normal and Br/Br fetuses were collected at gestational days E13 and E14 (representing prefusion stages) and E15 and E18 (representing postfusion stages). Cryostat palatal sections (8 microm) were postfixed in methanol, washed, and stained with primary antibody. All sections were washed and coated with secondary antibody (swine-anti-rabbit IgG) and mounted with citifluor. RESULTS: Immunohistological analysis showed that LN and type IV collagen were located near the presumptive medial epithelial seam (MES) or edge (MEE) in +/+ or Br/Br fetuses, respectively. Fibronectin showed a homogeneous distribution at all stages in both groups of mice. In contrast, TN became localized below the presumptive MES or MEE in both groups of mice at E14. In +/+ animals at E15, TN dissipated and became confined to the oral basement membrane by E18. At E15 and E18 in cleft Br/Br mutants, TN stained beneath the MEE. CONCLUSION: Although the distributions of ECM molecules are similar during normal and cleft palatogenesis, differences in TN expression are associated with cleft palate formation.

Animals↗

Scar tissue distribution on palates and its relation to maxillary dental arch form.

OBJECTIVE: This study investigated the relationship between maxillary dental arch form and distribution of postsurgical scar tissue on previously denuded bone in isolated cleft palate patients. METHOD: The palatal blood flow of 21 Japanese isolated cleft palate patients (6 males, 15 females) was examined by laser doppler flowmetry to determine the scar tissue areas. All had undergone pushback operations for palatal repair at around 18 months of age. Tissue blood flow was examined at a time ranging from 11 years, 5 months to 19 years, 9 months of age. To evaluate the maxillary dental arch form, dental casts obtained at the start of orthodontic treatment (a mean age of 8 years, 4 months) were analyzed. RESULTS/CONCLUSIONS: Scar tissue distribution in the 21 cases was classified into five types. Characteristic features in the maxillary dental arch form were found in each of the five types according to the extent of the scar tissue. It was evident that the severity of the maxillary dental arch constriction was closely related to the scar tissue distribution on palates.

Adolescent↗

Three-dimensional analysis of cleft palate topology in newborn infants with reference to the cranial skeleton.

OBJECTIVE: To describe a method of determining the three-dimensional topology of the palatal crest relative to a reproducible anthropomorphic coordinate system in newborn infants with unilateral cleft palate. For this purpose, physical models of the maxilla and face were analyzed by computer morphometry. DESIGN: The study was limited to infants referred to the craniofacial center during the first 11 days after birth. SETTING: The study was performed at a craniofacial center servicing a large geographic area. PARTICIPANTS: The method was applied to 12 infants with unilateral cleft lip, alveolus, and palate (eight patients with left-side clefts and four with right-side clefts). MAIN OUTCOME MEASURES: The three-dimensional topology of the palatal crest referenced to an anthropometric coordinate system was the primary outcome measure. The anthropometric reference system is defined by the tragus points and the midpoint of a line connecting the endocanthia. RESULTS: The topology of the maxillary crests of the patients was characterized by considerable variability. The center of the premaxilla as defined by the attachment of the frenulum was frequently displaced by several millimeters from the midsagittal plane. The displacement was to the left in infants with right-side clefts and to the right in infants with left-side clefts. The premaxilla can be rotated by more than 30 degrees relative to the normal position. No significant retroposition of the minor segment as determined by the location of the tuber points was found. Several morphometric anomalies were found to be correlated linearly. CONCLUSIONS: We propose that the morphologic deviations are in part caused by the neuromotor activity of the tongue and of the interrupted M. orbicularis oris. The data can serve as the starting point for a longitudinal study of craniofacial development in children with cleft palate and for studies on the efficacy of different therapeutic approaches.

Alveolar Process↗

Skull base factors in relation to hearing impairment in cleft palate children.

OBJECTIVE: This investigation was performed to determine if an easily measurable, reproducible, bony parameter could be identified that might predict hearing loss in cleft palate children. SUBJECTS: In this prospective study performed at the Sheffield Children's Hospital (U.K.), 34 children with successfully repaired cleft palate who responded to a postal request for volunteers were assessed clinically, audiologically, and by lateral soft tissue neck radiography. Six children were excluded because of previous otologic surgery or poor quality radiographs. Twenty-six children who had the same series of investigations were randomly selected from routine otolaryngological outpatient clinics and acted as controls. METHODS: The sphenopalatine angle (SPA), which relates the facial and cranial components of the skull, was measured on each child's radiograph. RESULTS: The median SPA in the cleft palate group was significantly greater than in the control group (p = 0.01). In those cleft palate children with a hearing loss the sphenopalatine angle was smaller than in their normal hearing counterparts (p = 0.01). No significant difference was found in the SPA between the hearing loss and normal hearing controls. There was no significant difference in age ranges between the hearing and hearing loss subgroups in each of the two primary groups. CONCLUSIONS: In this study, those cleft palate children with a smaller SPA have a greater incidence of hearing loss.

Case-Control Studies↗

The effects of lactation education and a prosthetic obturator appliance on feeding efficiency in infants with cleft lip and palate.

OBJECTIVE: This prospective study examined the effect of lactation instruction and palatal obturation in decreasing time to feed, increasing intake, and on growth in eight breast milk bottle-fed newborn infants with cleft lip, cleft palate, or both. DESIGN: An A, B1, C1, B2, and C2 reversal design was used with eight mothers. In A, baseline data on minutes fed by breast were recorded. In B1, baseline on minutes fed with a Haberman bottle was recorded. In C1, minutes fed following lactation education and palatal obturation were documented. Lactation education was information given to mothers to recognize infant feeding cues and to have infant-led feedings. The palatal obturator was a passive molding appliance. In B2, the obturator was removed and minutes fed noted. In C2, the obturator was returned and lactation support provided. Mothers kept feeding logs, satisfaction was assessed, and infant breast milk intake and flow rate were recorded during each study phase. Routine nutrition evaluation of weight, height, weight for height, and feed volume was completed by a registered dietitian during and following completion of the study. RESULTS: Feeding times decreased with all infants, volume consumed increased with seven of eight infants, and flow rate increased with all infants. Mean feeding times during B1 and B2 phases (Haberman bottle only) were 34.4 and 32.3 minutes, respectively. Mean feeding times during C1 and C2 phases (obturation and lactation education) were 15.1 and 15.6 minutes. Volume of milk consumed during B1 and B2 feedings averaged 36.5 and 37 mL, compared with 67 mL and 76 mL during C1 and C2 phases. Growth as measured by height, weight gain, and weight for height during the study and the first 2 years of life compared favorably with that of children born without clefts. CONCLUSIONS: The combined use of a palatal obturator and lactation education reduced feeding time and increased volume intake and was associated with good growth. Mothers who had desired to breast-feed elected to use the obturator to support high-volume intake, decrease infant fatigue, and provide breast milk for nutrition.

Analysis of Variance↗

A comparison of three methods of repairing the hard palate.

OBJECTIVE: To compare growth, speech, and nasal symmetry outcomes of three methods of hard palate repair. PATIENTS: Consecutive available records of children born with unilateral bony complete cleft lip and palate over the period 1972 to 1992. INTERVENTIONS: Identical management of lip, nose, alveolus, and soft palate. Hard palate repair by Cuthbert Veau (CV) from 1972 to 1981, von Langenbeck (vL) from 1982 to 1989, or medial Langenbeck (ML) from 1989 to 1991. OUTCOME MEASURES: For growth: GOSLON yardstick or 5-year model index. For speech: articulation test. Nasal anemometry. For nasal symmetry: Coghlan computer-based assessment. All these measures were developed during the period of data collection but not for this project. RESULTS: There was a strong trend toward more favorable anteroposterior maxillary growth with the change from CV to vL to ML techniques. This fell short of statistical significance because of the small sample size. There was a significant reduction in cleft-related articulation faults (p =.01) considered to be related to improved arch form. In the absence of improved rates of velopharyngeal insufficiency or nasal symmetry, increased surgical experience was discounted as a significant contribution to improved growth and articulation outcomes. CONCLUSIONS: Reduced periosteal undermining and residual exposed palatal shelf from CV to vL to ML improved incisor relationships and articulation.

Child↗

Gingival necrosis in relation to palatal expansion appliance: an unwanted sequelae.

A palatal expansion appliance is frequently used for the expansion of the palatal arch. The expansion can be rapid or slow. The degree of turn given to the screw of the appliance determines the rapidity and amount of expansion achieved. This report describes a case of necrosis of the palatal gingiva as a result of an attempt to expand the palatal arch rapidly and is of great importance to the pediatric dentist as palatal expansion is done more often in pediatric patients.

Adult↗

Diagnosis of induced cleft palate in rats from defective patterns of differentiation of isoenzymes.

Cleft palate was induced in 420 embryos of Sprague-Dawley rats with a single oral dose of 600 mg/kg beta-aminoproprionitrile (BAPN) on embryonal day 15, 7 hours. The cleft palate was accompanied by a pathological differentiation pattern of various isoenzymes in palatal shelves. These isoenzymes could be detected in amniotic fluid from the 16th to the 20th days of pregnancy when they also had a pathological differentiation pattern. We conclude that teratogenically induced cleft palate in rats is accompanied by a pathological differentiation pattern that can be traced by determination of isoenzymes in the palatal shelves as well as in amniotic fluid.

Abnormalities, Drug-Induced↗

[Maxillary growth following tissue engineered oral mucosal implantation on mucoperiosteal denudated palate process in young rat].

OBJECTIVE: To observe the effectiveness of prevention and cure for maxillary growth deformity following tissue engineered oral mucosa implantation on mucoperiosteal denuded palate process in young rat. METHODS: Hard palate mucoperiosteum of a SD baby rat were excised and oral keratinocytes were isolated and cultured. Tissue engineered oral mucosa was fabricated with the cultured oral keratinocytes and the membrane made of sodium alginate (SA). 80 female three-week-old SD rats were used as subjects in this study. The animals were divided randomly into a normal control group and 3 experimental groups, each group included 20 rats. Normal control group (NG) were not operated. Hard palate mucoperiosteum on left side in all experimental groups were excised, exposed bone were not treated in denuded group (DG), but repaired with membrane in material group (MG) and repaired with the tissue engineered oral mucosa in mucosal group (MUG). All the animals were sacrificed at 9th week postoperatively (12 weeks old), and the clean widths of right and left hard palatal were measured under a dissection microscope. The difference between palatal widths of two sides and the asymmetry ratio between the different groups were compared and analyzed. RESULTS: No significant difference in asymmetry was discovered between the DG and the MG, but the asymmetry in MUG was less than DG or MG. CONCLUSION: Tissue engineered oral mucosal implantation in palatoplasty is an effective method in preventing and curing secondary maxilla deformity by repairing denuded bone wound.

Animals↗

[Long-term effects and influence on facial structure of palatal distraction].

OBJECTIVE: The purpose of this study was to evaluate a new palatoplasty with persistent elastic distraction osteogenesis. METHODS: Twenty mongrel dog aged in 6 month were divided into two groups: the control (n = 10) and the experimental group (n = 10). The cleft palate model was made surgically in experimental dogs. The hard palate clefts were repaired with persistent elastic distraction osteogenesis. Then the animals were observed for an additional 12 weeks before sacrifice. Direct measurements was taken on dry skulls of the dogs and the data were analyzed statistically. RESULTS: For all experimental dogs, the clefts were closed after gradual distraction. No relapse and airway blocking occurred in observational period. There were no significant differences in the variables of facial length, height and width between the two groups (P > 0.05). The length of horizontal portion of hard palate in experimental group was significantly longer than that in the control (P < 0.01). CONCLUSION: There was no complication and disturbance on maxillofacial structure in repairing cleft palate with persistent elastic distraction osteogenesis. It is an effective and safe technique for repairing cleft palate in animal model.

Animals↗

[Effects of dexamethasone and vitamin B12 on EGF, TGFalpha, and TGFbeta1 gene expressions of A/J mouse palatal cells in vitro].

OBJECTIVE: To investigate the molecular mechanism of congenital cleft palate induced by Dexamethasone (DEX) and the counteractive effect of Vitamin B12. METHODS: The RT-PCR was used to detect the independent and joint effects of DEX and Vitamin B12 on the gene expressions of A/J embryonic mouse palatal cells. RESULTS: DEX stimulated the gene expressions of EGF and TGFbeta1, while the expression of TGFalpha left unchanged in the palatal cells. Vitamin B12 had no direct effects on the gene expressions of EGF, TGFalpha, and TGFbeta1; however, it counteracted the effects of DEX on the palate cells. CONCLUSION: DEX induces cleft palate through increasing some gene expressions of growth factors, which can be inhibited by Vitamin B12.

Animals↗

[Mechanical force distribution on cleft maxillary finite-element models after alveolar and hard palate bone graft].

OBJECTIVE: To investigate the biomechanical force distribution of three different cleft maxillary finite-element models pre- and post-bone graft with specified load to certain area of the models. METHODS: Developing a cleft palate bony model from a 15-year cleft palate male CT scan DICOM data and generating alveolar bone-grafted, alveolopalatal bone-grafted cleft maxillary finite-element model was set up through gluing the graft model. Also the pre-grafted model as compared, vector lip force on the anterior and anteriolateral face of the alveolar ridge was applied, and studied the press distribution properties and localized area. RESULTS: The press principal spread along the alveolar ridge and focused on anterior wall of maxillary prior to graft. But the press tended to be evenly distributed after bone grafted, whether alveolar or/and hard palate bone grafted. The grafted bone could resisted the medially deformation of alveolar crest and decreased the shear press to the nasal base bony structure. The map showed no significant differences along with alveolar or/and hard palate bone graft. CONCLUSION: The postoperative lip pressure plays an important role for the deformation and deviation of alveolar ridge. Alveolar bone graft could even the distribution of the stresses and should be emphasized. But the grafted bony palatal appears superior to but no significant mapping and anti-deformation difference with alveolar bone graft.

Alveolar Process↗

[Consideration to the experimental study on the rapid palatal expansion in the rat].

The purpose of this study is to clarify the most suitable position and method to investigate bone formation in the mid-palatal suture after rapid palatal expansion in the rat. 10 of 8 week-old Wistar rats were employed to observe the structure of the normal mid-palatal suture at the line connecting the incisors, the anterior end of the anterior palatine foramen, the line bisecting the anterior palatine foramina, and the line of the 1st molars. A mid-palatal suture of 8 week-old Wistar rats was expanded laterally for 6 days by means of maxillary incisor expansion apparatus with a spring of 60 g load. After beheading, soft X-ray picture of the skull was taken to observe the suture. The maxilla was removed and decalcified sections (frontal section) were prepared. They were stained with hematoxylin and eosin for microscopy. The mid-palatal suture was observed at 4 levels to the lines drawn as follows; the line running through the centers of incisors (A), the line running the anterior ends of the anterior palatine foramen (B), the line running through the center of the anterior palatine foramen (C), and the line running through the centers of the 1st molars (D). At the opposing margins of A and B, the suture was composed of two layers; the layer of osteoblasts and the layer of interconnecting Sharpey's fibers. At C, the suture was curved and the layer of Sharpey's fibers were made up with longitudinal as well as transverse fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pathogenesis of cleft palate in Treacher Collins, Nager, and Miller syndromes.

Abnormalities of the secondary palate were studied in an animal model in which features of Treacher Collins syndrome (TCS) and Nager or Miller syndromes (both of which are facially similar to Treacher Collins, but include limb malformations) were induced by acute maternal exposure to 13-cis-retinoic acid (13-cis-RA, isotretinoin, Accutane). Previous work in our laboratory has illustrated that excessive cell death in the proximal aspect of the maxillary and mandibular prominences of the first visceral arch and in the apical ectodermal ridge of the limb bud probably accounts for the characteristic craniofacial and limb abnormalities observed (Sulik et al, 1987; Sulik and Dehart, 1988). The current study shows that maternal treatment with 400 mg per kilogram 13-cis-RA at 8 days 14 hours (8d14hr) or 9d6hr post fertilization results in abnormalities of the secondary palate that vary in incidence and severity. Following the earlier treatment time, 82 percent (68 of 74) of the 18d fetuses were affected, with, severely hypoplastic, unfused palatal shelves present in 34 percent (25 of 74). The less severely affected fetuses had malformations that involved primarily the posterior aspect of the palatal shelves. This malformation (foreshortening of the posterior portion of the palate) constituted the major developmental alteration that resulted from treatment at the later time, at which time a 52 percent (26 of 50) malformation incidence was seen. The change in pattern of malformations with treatment time is consistent with the changing pattern of programmed cell death, which was observed to occur in the first visceral arch.

Animals↗

Elongated pharyngeal flap in extensive clefts of the hard and soft palate.

In some cases of extensive palatal defects surgical closure may be regarded as unfeasible, and the condition treated with an obturator prosthesis. In such a case the cleft can be closed in one operation by means of a pharyngeal flap elongated through a pharyngotomy according to Bengt Johanson (1966). Eleven patients who had used obturators were operated on between 1957 and 1978. The mean age of the patients was 39 years. All patients were cleft lip and palate or cleft palate cases; two unilateral, five bilateral, and four with an isolated cleft palate. In most of these patients a temporary tracheostomy was performed after which the pharynx was opened through a neck incision. A flap was created which reached the alveolar ridge. For oral closure, mucoperiosteal flaps were used. Anterior palatal fistulas developed in two cases; one closed spontaneously and the other remained as a 3-mm fistula behind the alveolar ridge. Three patients had postoperative transient dysphagia. Phoniatric evaluation showed that two patients had better speech after operation than before with an obturator. Gross speech improvement at this late age should not be expected and is not the primary goal of the procedure. The aim of surgical closure with an elongated pharyngeal flap is to replace the obturator.

Adolescent↗

Analysis of the size variability of the human normal and cleft palate fetal nasal capsule by means of three-dimensional computer reconstruction of histologic preparations.

As part of an ongoing study of cleft palate fetal morphology, normal and dysmorphic development of the human fetal nasal capsule was studied in a cross-sectional sample of 29 human fetuses (20 "normal" and 9 cleft), ranging in age from 8 to 21 postmenstrual weeks. The specimens were celloidin embedded, sectioned at 20 microns, and every tenth section stained with hematoxylin and eosin. A computer reconstruction technique was applied to produce three-dimensional representations of the nasal capsule, nasal septal cartilage, and nasal airway. Qualitatively, the cleft palate nasal capsule exhibited gross abnormalities including cartilaginous nasal septum deformities, abnormal septal volume and hypertrophy, reduced nasal airway and capsule volumes, and abnormal spatial relationships between the nasal capsule components. These results suggest that the reduced nasal airways, noted clinically in cleft perinates, may be a function of an interaction of nasal capsule deficiency and nasal septum hypertrophy. However, when lengths and volumes were plotted against fetal postmenstrual age, producing fetal "growth" curves, no significant differences (p greater than 0.05) were noted for growth rates (slopes) or nasal capsule size between the normal and cleft palate fetal samples. Curvilinear regression analysis revealed that both normal and cleft palate nasal capsule and septum lengths changed in a sigmoidal fashion, with the steepest increases from 13 to 17 weeks. In contrast, nasal capsule, airway, and septum volumes changed curvilinearly, showing slow relative growth rates from 8 to 17 weeks, which increased sharply from 18 to 21 weeks. Results suggest that from 8 to 21 weeks prenatally, normal and cleft palate specimens exhibited a similar pattern of fetal nasal capsule development that was characterized by an initial anteroposterior elongation followed by circumferential (i.e., volumetric) growth.

Cleft Palate↗

Liability to cleft palate in trisomy 19 mouse embryos.

A mouse model is available which permits both the measurement of the underlying liability for cleft palate and the induction of trisomic states. By using this model the palate development has been investigated and compared in normal and trisomic embryos. These studies indicate that palate development of trisomy 19 embryos is significantly delayed compared to that of their normal littermates. Furthermore, the delay in palate development observed in trisomy 19 embryos is in direct relationship with the observed pattern of palate development in normal littermates. This suggests that the increased expression of major congenital malformations associated with aneuploidy is due to a change in their underlying liability.

Animals↗

Observations about the normal and abnormal embryogenesis of the canine lip and palate.

Twenty-three puppies with cranofacial and limb abnormalities from a family of Australian shepherd dogs were studied anatomically. Limb abnormalities included lumbar scoliosis, short malformed tibias and fibulas, and polydactyly. Craniofacial abnormalities consisted of retronathia, cleft palate, and cleft lip. The clefts can be separated into three categories: group I, cleft of the secondary palate associated with a midline cleft lip; group II, unilateral cleft of the lip and primary and secondary palate; and group III, complete bilateral cleft of the lip and primary and secondary palate. Comparing human clefts with the canine clefts suggests that the development of the secondary palate is similar whereas the development of the upper lip is different. In the dog, the maxillary processes fuse in the midline to produce the majority of the upper lip, whereas in the human the upper lip is composed of fused maxillary and medial nasal processes.

Animals↗