PBX-WNT-P63-IRF6 pathway in nonsyndromic cleft lip and palate.

Nonsyndromic cleft lip and palate (NSCLP) is one of the most common craniofacial anomalies in humans, affecting more than 135,000 newborns worldwide. NSCLP has a multifactorial etiology with more than 50 genes postulated to play an etiologic role. The genetic pathway comprised of Pbx-Wnt-p63-Irf6 genes was shown to control facial morphogenesis in mice and proposed as a regulatory pathway for NSCLP. Based on these findings, we investigated whether variation in PBX1, PBX2, and TP63, and their proposed interactions were associated with NSCLP. Fourteen single nucleotide variants (SNVs) in/nearby PBX1, PBX2, and TP63 were genotyped in 780 NSCLP families of nonHispanic white (NHW) and Hispanic ethnicities. Family-based association tests were performed for individual SNVs stratified by ethnicity and family history of NSCLP. Gene-gene interactions were also tested. A significant association was found for PBX2 rs3131300 and NSCLP in combined Hispanic families (p = .003) while nominal association was found for TP63 rs9332461 in multiplex Hispanic families (p = .005). Significant haplotype associations were observed for PBX2 in NHW (p = .0002) and Hispanic families (p = .003), and for TP63 in multiplex Hispanic families (.003). An independent case-control group was used to validate findings, and significant associations were found with PBX1 rs6426870 (p = .007) and TP63 rs9332461 (p = .03). Gene-gene interactions were detected between PBX1/PBX2/TP63 with IRF6 in NHW families, and between PBX1 with WNT9B in both NHW and Hispanic families (p < .0018). This study provides the first evidence for a role of PBX1 and PBX2, additional evidence for the role of TP63, and support for the proposed PBX-WNT-TP63-IRF6 regulatory pathway in the etiology of NSCLP.

Association of IFT88 gene variants with nonsyndromic cleft lip with or without cleft palate.

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with multifactorial etiology. Genetic studies have identified numerous gene variants in association with NSCLP. IFT88 (intraflagellar transport 88) has been suggested to play a major role in craniofacial development, as Ift88 mutant mice exhibit cleft palate and mutations in IFT88 were identified in individuals with NSCLP. OBJECTIVE: To investigate the association of IFT88 single nucleotide gene variants (SNVs) with NSCLP in a large family data set consisting of non-Hispanic white (NHW) and Hispanic families. METHODS: Nine SNVs in/nearby IFT88 were genotyped in 482 NHW families and 301 Hispanic NSCLP families. Genotyping was performed using TaqMan® chemistry. Single- and pairwise-SNV association analyses were performed for all families stratified by ethnicity and family history of NSCLP using the family-based association test (FBAT), and association in the presence of linkage (APL). Bonferroni correction was used to adjust for multiple testing and p values ≤.0055 were considered statistically significant. RESULTS: Significant association was found between IFT88 rs9509311 and rs2497490 and NSCLP in NHW all families (p = .004 and .005, respectively), while nominal associations were found for rs7998361 and rs9509307 (p < .05). Pairwise association analyses also showed nominal associations between NSCLP in both NHW and Hispanic data sets (p < .05). No association was found between individual variants in IFT88 and NSCLP in Hispanics. CONCLUSIONS: Our results suggest that variation in IFT88 may contribute to NSCLP risk, particularly in multiplex families from a non-Hispanic white population.

Dexmedetomidine Decreases Postoperative Pain and Narcotic Use in Children Undergoing Alveolar Bone Graft Surgery.

OBJECTIVE: Dexmedetomidine is a parenteral agent that combines the benefits of cooperative sedation, anxiolysis, and analgesia without the risks of respiratory depression. Off-label use has been reported in children. We have introduced dexmedetomidine for use in patients having undergone alveolar bone graft (ABG). The objective is to demonstrate the value and safety of postoperative dexmedetomidine infusion in a non-ICU setting following ABG. DESIGN: A retrospective review was performed on patients who underwent ABG by the senior author. Patients were divided into 2 groups: those who received postoperative dexmedetomidine and those who received patient-controlled anesthesia. MAIN OUTCOME MEASURE(S): The primary study outcome measures included patient demographics, adverse events, length of stay, pain scores, and doses of narcotics during admission were collected. RESULTS: Inclusion criteria were met by 54 patients; 39 received dexmedetomidine whereas 15 did not. There were no significant differences between groups in age, gender, and length of stay. The patients who received dexmedetomidine used oral narcotics less often ( P = .01). In addition, more patients reported no pain after surgery ( P = .05) and at the time of discharge if they received dexmedetomidine ( P < .01). There were no reported adverse effects. CONCLUSIONS: Dexmedetomidine provided superior pain control after surgery and at the time of discharge, as well as a significant decrease in the use of oral narcotics. In our institution, it has since replaced the PCA as a postoperative pain control modality. Absent the risk for respiratory depression, dexmedetomidine has demonstrated a safe option for postoperative pain control in our focused group of pediatric patients.

Characterization of the nasal, sublingual, and oropharyngeal mucosa microbiota in cleft lip and palate individuals before and after surgical repair.

OBJECTIVE: To delineate inherent differences in the microbial milieu in cleft palate patients compared with cleft lip patients and to document changes in microbial flora before and after cleft lip and palate repair. DESIGN: A prospective study of preoperative and postoperative culture results from the nasal, sublingual, and oropharyngeal surfaces of patients undergoing primary cleft lip repair and palate closure. SETTING: Shriners Hospitals for Children, Galveston, Texas, and University of Texas Medical Branch, Galveston, Texas. PATIENTS: Seventy-nine patients were included in a 3-year period. Ten patients with isolated cleft lip underwent primary lip repair. Twenty-five patients with cleft lip and palate underwent primary lip repair, and 44 patients underwent palatoplasty. RESULTS: Cleft palate patients had a significantly higher rate of colonization by staphylococcal species, but not methicillin-resistant Staphylococcus aureus , when compared to cleft lip patients (p=.0298; chi-square test). Closure of the palatal cleft coincided with significant decline in the prevalence of Klebsiella and Enterobacter species (p<.05; McNemar test). The only major complication, palatal dehiscence, was believed to be directly related to infection with group A beta-hemolytic streptococci. CONCLUSIONS: Despite a high prevalence of potential pathogenic and enteric flora preoperatively in primary palate repair, postoperative wound infection is rare in the prospective study population. However, the presence of beta-hemolytic streptococci was associated with a higher risk of repair dehiscence; therefore, screening for Streptococci prior to surgery should be performed routinely.

Cross-chest lipoplasty and surgical excision for gynecomastia: a 10-year experience.

BACKGROUND: Gynocomastia is a relatively common condition in men, with a reported overall incidence of 32% to 36% and as high as 65% among adolescent males in some series. OBJECTIVE: We reviewed the senior surgeon's experience over the past decade in the surgical treatment of gynecomastia using suction-assisted lipoplasty (SAL) with a cross-chest tunneling technique, performed alone or in combination with direct excision. METHODS: Thirty-four patients with gynecomastia were evaluated and treated surgically at the University of Texas Medical Branch in the past 10 years. Twelve were treated with cross-chest SAL alone, 16 with cross-chest SAL and direct excision, and 6 with direct excision. Infusion of wetting solution was performed with the use of a 2.0-mm cannula, through an access site at the medial border of the contralateral nipple-areolar complex. Next, a 4.0-mm Mercedes-tip (Byron/Mentor Corp., Santa Barbara, CA) cannula was tunneled across the sternum to liposuction the contralateral prepectoral fatty breast. Patients with composite fatty and glandular tissue first underwent SAL, then direct excision through a periareolar incision; those with only retroareolar glandular tissue underwent direct excision alone. RESULTS: All patients who underwent SAL alone or SAL combined with excision had satisfactory aesthetic results and no reported postoperative complications. In one patient who underwent excision alone, a hematoma developed. CONCLUSIONS: Despite newer technologies, traditional SAL performed with a cross-chest technique and direct excision as indicated is a valuable approach that yields predictable success. This approach avoids scarring and offers a sculpted reduction of the retroareolar glandular and fatty elements, resulting in a natural, smooth breast contour.

Facial fracture approaches with landmark ratios to predict the location of the infraorbital and supraorbital nerves: an anatomic study.

In exposing facial fractures for reduction and fixation with coronal, subciliary, subtarsal, and upper buccal sulcus approaches, the supraorbital and infraorbital nerves are susceptible to injury. The location of the supraorbital and infraorbital nerves can be predicted by palpating for the supraorbital notch. Significant edema as seen with facial fractures can make these prominent bony landmarks difficult to palpate, however. The purpose of this study was to determine a method to predict the location of the supraorbital and infraorbital nerves in the face of frontal and periorbital edema when the supraorbital and infraorbital nerves are not palpable. The supraorbital and infraorbital nerves were identified in 14 cadaver heads. The orbital width from the medial to lateral canthus was measured. The distance of the vertical vector of the supraorbital and infraorbital nerves from the medial canthus was measured along this horizontal vector of the orbit. The distance of the infraorbital nerve from the infraorbital rim was measured. The orbital width measured 42.2 +/- 1.6 mm from the medial to lateral canthus. The vertical vector of the supraorbital nerve measured 15.9 +/- 1.1 mm from the medial canthus along the horizontal vector of the orbit. The vertical vector of the infraorbital verve measured 16.8 +/- 1.4 mm from the medial canthus along the horizontal vector of the orbit. The infraorbital nerve measured 9.8 +/- 1.0 mm inferior to the infraorbital rim. The medial one third of the orbit measured 14.1 mm. Therefore, the supraorbital and infraorbital nerves are located approximately along the medial third of the orbit, with the upper bound of 95% confidence at 3.1 mm. The location of the supraorbital and infraorbital nerves can be predicted by the previous landmark ratio to within 3 mm.