Matrix metalloproteinase-8 regulates transforming growth factor-ß1 levels in mouse tongue wounds and fibroblasts in vitro.

Matrix metalloproteinase-8 (MMP-8)-deficient mice (Mmp8-/-) exhibit delayed dermal wound healing, but also partly contradicting results have been reported. Using the Mmp8-/- mice we investigated the role of MMP-8 in acute wound healing of the mobile tongue, and analyzed the function of tongue fibroblasts in vitro. Interestingly, in the early phase the tongue wounds of Mmp8-/- mice healed faster than those of wild type (wt) mice resulting in significant difference in wound widths (P=0.001, 6-24h). The Mmp8-/- wounds showed no change in myeloperoxidase positive myeloid cell count, but the level of transforming growth factor (TGF)-ß1 was significantly increased (P=0.007) compared to the wt tongues. Fibroblasts cultured from wt tongues expressed MMP-8 and TGF-ß1. However, higher TGF-ß1 levels were detected in Mmp8-/- fibroblasts, and MMP-8 treatment decreased phosphorylated Smad-2 levels and α-smooth muscle actin expression in these fibroblasts suggesting reduced TGF-ß1 signaling. Consistently, a degradation of recombinant TGF-ß1 by MMP-8 decreased its ability to activate the signaling cascade in fibroblasts. Moreover, collagen gels with Mmp8-/- fibroblasts reduced more in size. We conclude that MMP-8 regulates tongue wound contraction rate and TGF-ß1 levels. In vitro analyses suggest that MMP-8 may also play a role in regulating TGF-ß1 signaling of stromal fibroblasts.

A descriptive epidemiology study of cleft lip and palate in Northern Finland.

OBJECTIVE: The aim of this study was to determine the incidence of cleft lip and/or cleft palate in a population uniquely from Northern Finland. MATERIALS AND METHODS: The records of a total of 214 cleft patients treated between 1998-2011 at the Oulu Cleft Lip and Palate Center at the University of Oulu were assessed on a retrospective basis. Data regarding cleft type, sex and side of cleft was collected and analyzed. Family history of clefting was investigated. RESULTS: Cleft palate (68.7%) was most frequently found, followed by cleft lip and palate (18.7%) and cleft lip with or without alveolus (12.6%). Cleft palate occurred more frequently in females (63.3%) and cleft lip and palate was more frequently found in males (62.5%). The left side was more frequently affected in both male and female patients. Left-sided clefts were observed in 82% of patients compared to right-sided clefts in 18%. A family history of clefting was detected in 20.1% of patients. CONCLUSION: The incidence of clefts in Northern Finland is higher than the corresponding incidence in other European countries. Cleft palate was the most frequent cleft type and it was more frequent in females. In males, cleft lip and palate was more frequent. The left side was more frequently affected in both genders. One fifth of the patients had a family history of clefts.

Maxillary Arch Dimensions in 6-Year-Old Cleft Children in Northern Finland: A Cross-Sectional Study.

The aim was to cross-sectionally examine the maxillary arch dimensions in 6-year-old children with cleft lip and/or palate and to compare them with the initial cleft sizes among patients with cleft palate. The study included 89 patients with clefts treated at the Oulu University Hospital. The subjects were divided into three groups: cleft palate, cleft lip, and cleft lip and palate. Study casts were scanned, and the maxillary arch dimensions were examined using a 3D program (3Shape Orthoanalyzer, Copenhagen, Denmark). The statistical methods Student's t-test and one-way ANOVA were used to compare the means (SD) between the groups. Spearman's correlation coefficient was used to determine the correlation between cleft severity and maxillary dimensions. A significant difference was found between different initial cleft sizes in terms of distance between the second deciduous molar and the first incisor on the right side. The intermolar width showed a negative correlation with the initial cleft size. The dimensions were shorter for clefts affecting the palate and largest for clefts affecting only the lip. Larger clefts resulted in a shorter maxilla on the right side. Many dimensions became shorter when the initial cleft was larger. Clefts of the palate resulted in smaller maxillas.

Middle ear findings and need for ventilation tubes among pediatric cleft lip and palate patients in northern Finland.

PURPOSE: Middle ear problems are common in cleft patients. This study aimed to determine the need for ventilation tubes (VTs) and complications such as tympanic perforation and cholesteatoma. MATERIAL AND METHODS: Data of 156 children with clefts managed in northern Finland spanning 15 years from 1997 to 2011 were collected from 6 hospitals. The following were recorded: birth date, gender, cleft type, surgery timing, surgery type, number of tube insertions, tube material, middle ear findings, and tube placement timing. Clefts were divided into 4 groups: cleft palate (CP), cleft lip and palate (CLP), cleft lip (CL), and submucous cleft palate. The prevalence of middle ear findings was reported. RESULTS: Mucous secretion was noted in 96.8% of CLP patients, 69.2% of CP patients, and 13.0% of CL patients. In all, 82.7% of study group had 1 or more VTs placed during follow-up. All CLP patients required more than 1 VT placement. A total of 94.5% of CP patients required VTs compared to 13.0% of CL patients. In the presence of residual oral nasal fistula, the mean number of tube insertions was 5.3. The prevalence of tympanic perforations in clefts was 35.9% and cholesteatoma in 2.6% of patients. CONCLUSIONS: CLP and isolated CP patients have frequent middle ear infections requiring multiple VT placements.

The association of cleft severity and cleft palate repair technique on hearing outcomes in children in northern Finland.

BACKGROUND: The consequences of cleft lip and palate include scaring, dental malformations, tooth misalignment, speech problems, and hearing loss. Otitis media with effusion causing hearing loss is a problem for many cleft palate patients. METHODS: This study examines the association among cleft severity, palate repair technique, and hearing outcomes in children from northern Finland with clefts, aged 3-9 years. The study included 90 cleft patients who were treated at the Oulu University Hospital Cleft Lip and Palate Center between 1998 and 2011. The severity of the cleft, the surgical technique used to repair the palate, audiogram configuration data, and the need for ventilation tube placement were determined retrospectively from patient records. RESULTS: Only 3.3% of cleft patients had an abnormal pure tone average hearing threshold representing abnormal hearing. Neither the surgical technique used to repair the cleft palate nor the severity of the cleft was a significant factor related to hearing loss or to the number of ventilation tubes required. Hearing improved significantly with increasing age over a span of 6 years. CONCLUSIONS: Continuous follow-up with proactive placement of ventilation tubes before or at the time of palatoplasty results in hearing outcomes in cleft children that are similar to those reported in non-cleft children.

Incidence of palatal fistula formation after primary palatoplasty in northern Finland.

OBJECTIVE: The purpose of this retrospective study was to determine the incidence of palatal fistulas after primary cleft palate repair. STUDY DESIGN: The study included 136 patients who were treated at the Oulu University Hospital cleft lip and palate center between 1998 and 2011. All patients were treated by the same surgeons with 1-stage palatoplasty closing the hard and soft palate concurrently. RESULTS: The overall frequency of postoperative fistula was 9.6% of patients. Patients with cleft lip and palate (20.0%) were more likely to develop postoperative palatal fistulas than patients with cleft palate (6.6%). Surgical technique and cleft severity were not significant factors for the development of palatal fistulas. CONCLUSIONS: The majority of patients undergoing primary palatal repair do not develop palatal fistulas.

Frequency of pharyngoplasty after primary repair of cleft palate in northern Finland.

OBJECTIVE: One measure of primary cleft palate repair success is the subsequent need for secondary pharyngoplasty due to velopharyngeal insufficiency. This study aimed to assess primary palatoplasty outcomes and frequency of secondary pharyngoplasty. STUDY DESIGN: A total of 138 patients underwent palatoplasty between 1998 and 2011. All patients were treated with 1-stage palatoplasty closing the hard and soft palate concurrently. RESULTS: Overall frequency of pharyngoplasty after palatoplasty was 21% of patients. The rate of secondary surgery was significantly higher for girls (27%) than for boys (13%). Patients with cleft lip and palate were more likely to require secondary pharyngoplasty (24%) than the patients with soft and hard cleft palate (20%). Surgical technique and cleft severity were significant factors for secondary surgery. Pharyngoplasty was least common in patients whose palatal clefts were treated at 9 to 12 months of age. CONCLUSIONS: The majority of patients undergoing primary palatal repair do not need secondary pharyngoplasty.