Swallowing-like activity elicited in neonatal rat medullary slice preparation.

Swallowing is induced by a central pattern generator in the nucleus tractus solitarius (NTS). We aimed to create a medullary slice preparation to elucidate the neural architecture of the central pattern generator of swallowing (Sw-CPG) and record its neural activities. Experiments were conducted on 2-day-old Sprague-Dawley rats (n = 46). The brainstem-spinal cord was transected at the pontomedullary and cervicothoracic junctions; the medulla was sliced transversely at thicknesses of 600, 700, or 800 µm. The rostral end of the slice was 100 µm rostral to the vagus nerve. We recorded hypoglossal nerve activity and electrically stimulated the vagus nerve or microinjected bicuculline methiodide (BIC) into the NTS. The 800-µm slices generated both rhythmic respiratory activity and electrically elicited neural activity. The 700-µm slices generated only respiratory activity, while the 600-µm slices did not generate any neural activity. BIC microinjection into the NTS in 800-µm slices resulted in the typical activity that closely resembled the swallowing activity reported in other experiments. This swallowing-like activity consistently lengthened the respiratory interval. Despite complete inhibition of respiratory activity, weak swallowing-like activity was observed under bath application of a non-NMDA receptor antagonist. Contrastingly, bath application of NMDA receptor antagonists resulted in a complete loss of swallowing-like activity and no change in respiratory activity. These results suggest that the 800-µm medullary slice preparation contains both afferent and efferent neural circuits and pattern generators of swallowing activity. Additionally, NMDA receptors may be necessary for generating swallowing activity. This medullary slice preparation can therefore elucidate Sw-CPG neural networks.

Orthognathic surgery with iliac bone grafting for an interpositional gap in a patient with type III hemifacial microsomia: A case report.

Hemifacial microsomia (HFM) is characterized by uni- or bilateral microtia and hypoplasia of the mandible, orbits, facial nerve, and adjacent soft tissues. Patients with Pruzansky-Kaban type III HFM show the most severe facial deformities and often encounter difficulty obtaining treatment. In recent years, orthognathic surgery for HFM-related deformities has often been performed after the patient has stopped growing. However, few detailed reports have described the difficulties of orthognathic surgery for patients with type III HFM. This report describes the case of a patient with type III HFM who underwent three unilateral mandibular reconstructions while still growing, including autogenous reconstructions and secondary distraction osteogenesis, followed by orthognathic surgery with iliac bone grafting for an interpositional gap between the proximal and distal segments after she had stopped growing to improve facial asymmetry and malocclusion.

Labial Vestibular Flap Closure of the Cleft Palate Is Advantageous for Maxillary Development.

Objective: Using labial vestibular flap was performed to close the primary alveolar and hard palate cleft at the second stage of early 2-stage closure surgery for unilateral cleft lip and palate for minimizing the damage to the maxillary periosteum. We analyzed maxillary development to clarify the influence of cleft palate surgery. Design: Retrospective longitudinal study in 5 years after primary palatal closure. Setting: Institutional study Patients: Study subjects included 214 patients with nonsyndromic complete unilateral cleft lip and palate who were consecutively treated in our clinic. Main Outcome: We used a 3D dental model scanner to assess maxillary development in patients aged 3 months to 5 years after using either the conventional pushback method (PB) (51 cases) or 2-stage closure (Local palatal flap closure: LF [67 cases] and Labial vestibular flap closure: VF [96 cases]). Results: Comparing the measurement results, the major axis of maxilla, width, intercanine distance, and intermolar distance was significantly larger in the LF group compared to the PB group. After the age of 3, the cleft side of VF group had grown significantly to compare with LF group in width. It was also confirmed that the inserted labial mucosal flap itself grew. Enlargement of the labial mucosal flap was observed at all sites except the canine. Conclusion: Good maxillary growth occurred in the following order: VF groups > LF group > PB group. Poor growth was correlated with the extent of periosteal damage during surgery and the degree of postoperative bone surface exposure.

Maxillary Development and Dental Arch Relationships Following Early Two-Stage Palatoplasty: A Comparative Study.

OBJECTIVE: To examine skeletal morphology and dental arch relationships at 8 years of age following early 2-stage palatoplasty, which consists of soft palate plasty at 1 year of age and hard palate closure at 1.5 years of age, and to compare the results with those of conventional pushback palatoplasty. DESIGN: Retrospective. SETTING: Single institutional study. PATIENTS: Eighty-six patients with nonsyndromic complete unilateral cleft lip and palate (UCLP) were selected. INTERVENTION: The subjects were divided into 2 groups according to the palatoplasty protocols, as follows: 45 patients, who underwent early 2-stage palatoplasty (ETS group), and 41 patients, who underwent 1-stage pushback palatoplasty (PB group). MAIN OUTCOME MEASURES: Skeletal morphology was assessed using lateral cephalometric analysis, and dental arch relationships were examined using the GOSLON yardstick. RESULTS: Cephalometric analysis revealed that the anterior-posterior length of the maxilla, measured by PTM-A and PTM-ANS, both projected to the nasal floor (NF) plane, was longer in the ETS group than in the PB group (PTM-A/NF, p = .04; PTM-ANS/NF, p = .03, unpaired t-test), although no significant difference was observed in SNA (p = .09, unpaired t-test). Upper posterior facial height was shorter in the ETS group than in the PB group (p = .02, unpaired t). Assessments with the GOSLON yardstick showed that the ETS group presented better dental arch relationships than the PB group (p = 0.04, Mann-Whitney's U-test). CONCLUSIONS: The present results suggested that the ETS protocol reduced the negative effects of palatal surgery on facial development and dental arch relationships in patients with complete UCLP at 8 years of age.

Dental Arch Relationship Outcomes Following 2-Stage Palatoplasty for Japanese Patients With Complete Unilateral Cleft Lip and Palate: A 3-Center Study.

OBJECTIVE: To compare dental arch relationship outcomes following 3 different 2-stage palatal repair protocols. DESIGN: Retrospective, cross sectional. SETTING: Three cleft palate centers (A, B, C) in Japan. PATIENTS: Ninety (A: 39, B: 26, C: 25) consecutively treated Japanese patients with complete unilateral cleft lip and palate. INTERVENTIONS: In A, the soft palate and the posterior half of the hard palate were repaired at a mean age of 1 year 7 months. In B, the soft palate and hard palate were closed separately at a mean age of 1 year 6 months and 5 years 8 months, respectively. In C, the soft palate and hard palate were closed at a mean age of 1 year and 1 year 5 months, respectively. MAIN OUTCOME MEASURES: Dental arch relationships were assessed using the 5-Year-Olds' (5-Y) index by 5 raters and the Huddart/Bodenham (HB) index by 2 raters. RESULTS: Intra- and inter-rater reliabilities showed substantial or almost perfect agreement for the 5-Y and HB ratings. No significant differences in mean values and distributions of 5-Y scores were found among the 3 centers. The mean HB index scores of molars on the minor segment were significantly smaller in C than those in A and B (P < .05). CONCLUSIONS: There were no significant differences in dental arch relationships at 5 years among the times and techniques of hard palate closure. However, further analysis of the possible influence of infant cleft size as a covariable on a larger sample size is needed.

Long-term Morphological Changes of the Velum and the Nasopharynx in Patients With Cleft Palate.

OBJECTIVE: To investigate long-term morphological changes in the soft palate length and nasopharynx in patients with cleft palate. We hypothesized that there would be differences in the morphological development of the soft palate and nasopharynx between patients with and without cleft palate and that these developmental changes would negatively affect the soft palate length to pharyngeal depth ratio involved in velopharyngeal closure for patients with cleft palate. DESIGN: Retrospective, case-control study. SETTING: Institutional practice. PATIENTS: Ninety-two patients (Group F) with unilateral cleft lip, alveolus, and palate and 67 patients (Group CLA) with unilateral cleft lip and alveolus not requiring palatoplasty were included. MAIN OUTCOME MEASURES: The soft palate length, nasopharyngeal size, and soft palate length to pharyngeal depth ratio were measured via lateral cephalograms obtained at three different periods. RESULTS: Group F showed a shorter soft palate length and smaller nasopharyngeal size than Group CLA at all periods. Both these parameters increased with age, but the increase in amount was significantly less in Group F compared with that in Group CLA. The soft palate length to pharyngeal depth ratio in Group F decreased with age. CONCLUSIONS: In patients with cleft palate, the soft palate length to pharyngeal depth ratio, which is involved in velopharyngeal closure, can change with age. Less soft palate length growth and unfavorable relationship between the soft palate and nasopharynx may be masked in early childhood but can manifest later on with age.

Morphological Correlations in Nasolabial Formation After Primary Lip Repair for Unilateral Cleft Lip.

PURPOSE: We aim to reveal postoperative morphological correlations between the nasolabial components in patients with unilateral cleft lip (UCL). The hypothetical correlations are first, a correlation between the vertical height of the cleft-side alar base and the length of the cleft-side red lip, and second, a correlation between the length of the cleft-side red lip and the vertical position of the cleft-side oral commissure. We explain how these morphological balances are controlled by surgery. METHODS: Three-dimensional bilateral measurements of the length of the red lip, vertical height of the nasal alar base, and vertical height of the oral commissure were conducted retrospectively on 31 patients with UCL and palate (complete UCL: 26; incomplete UCL: 5) who underwent primary lip plasty at Osaka Women's and Children's Hospital from 2017 to 2019. RESULTS: We found a statistically significant correlation between the vertical height of the cleft-side alar base and cleft-side red lip length (P = .012, r = 0.45); thus, the longer the red lip, the lower was the nasal alar base. The correlation between the cleft-side red lip length and the vertical height of the cleft-side oral commissure also showed a statistical significance (P = .00074, r = 0.57); thus, the shorter the red lip, the higher was the oral commissure. CONCLUSIONS: The present results provided objective evidence showing basic morphological relationships between the postoperative nasolabial features of patients with UCL. The results lead to a reasonable approach to define the proposed peak of the Cupid's bow, an unsettled major controversy in cleft lip surgery.

Occlusion at 5 Years of Age Following Hard Palate Closure With Vestibular Flap.

OBJECTIVE: This study aims to assess occlusal relationships and frequency of oronasal fistula at 5 years of age following 2 hard palate closure techniques and to compare results. DESIGN: Retrospective longitudinal study. SETTING: Institutional study. PATIENTS: Study patients included 57 patients with nonsyndromic complete unilateral cleft lip and palate who were consecutively treated. All patients underwent our early 2-stage protocol for palatoplasty, which consisted of soft palate plasty at 1 year of age and hard palate closure at 1.5 years of age. Twenty-nine patients underwent hard palate closure using vestibular flap (VF group) technique (2009-2011) and 28 patients underwent conventional hard palate closure with local palatal flap (LPF group) technique (2006-2008). MAIN OUTCOME MEASURES: Occlusal relationships were assessed with 5-year-olds' index, and frequency of oronasal fistula was investigated. RESULTS: Average 5-year-olds' index scores for VF and LPF groups were 3.11 and 3.57, respectively (P < .001). Oronasal fistula occurred in approximately 7% of patients in the VF group and in 18% of patients in the LPF group. CONCLUSION: Hard palate closure with VF technique may provide better occlusal relationships at 5 years of age than does conventional local closure with the LPF.

Clinical outcomes of ex utero intrapartum treatment for fetal airway obstruction.

PURPOSE: The aim of this study was to evaluate the indications and the clinical outcomes of the fetuses managed with ex utero intrapartum treatment (EXIT) procedures. METHODS: We retrospectively reviewed the medical records of all fetuses who underwent EXIT procedures between 2003 and 2018. RESULTS: EXIT procedures were performed in nine cases. The prenatal diagnosis of the neonates was congenital high airway obstruction syndrome in four cases, the neck masse in five cases. Although the airway management under the EXIT procedure was successful in eight cases, the airway management failed in one case. During the EXIT procedures, the airway was managed by endotracheal intubation in two cases, whereas six cases underwent tracheostomy. Six cases with fetal airway obstruction survived to discharge, whereas three cases died due to airway management failure or complications of the underlying disease. A case with a cervical teratoma underwent tumor resection the day after birth due to rapid enlargement of the neck mass. Long-term survival was achieved in five cases. CONCLUSIONS: We concluded that the EXIT procedure was effective and could be performed safely in the airway management of fetuses with suspected airway obstruction. The treatment strategy for the neck masses should be planned before birth.

Improved Quality of Life for Children With Beckwith-Wiedemann Syndrome Following Tongue Reduction Surgery.

Macroglossia is observed in the majority of patients with Beckwith-Wiedemann syndrome (BWS), a congenital condition with characteristic anomalies. In addition, sleep disordered breathing (SDB) associated with macroglossia has occasionally been noted in BWS patients, for which tongue reduction surgery is generally performed. However, macroglossia is related to various health problems, such as eating and articulation disorders, attention deficit disorder, enuresis, and thorax deformation, as well as aesthetic issues. Therefore, in addition to treating airway obstruction, tongue reduction surgery can also exert favorable effects on the overall quality of life (QOL) of patients. However, surgical indications for tongue reduction have yet to be established and reports on QOL assessments after surgery are rare. The OSA-18 questionnaire is used for screening SDB and is also useful for assessing the effect of tongue reduction surgery on QOL. We report a patient whose QOL was improved by tongue reduction surgery. On the basis of our patient's results, we recommend tongue reduction surgery in early childhood not only to treat SDB but also to improve QOL.

Kinetic properties of persistent Na+ current orchestrate oscillatory bursting in respiratory neurons.

The rhythmic pattern of breathing depends on the pre-Bötzinger complex (preBötC) in the brainstem, a vital circuit that contains a population of neurons with intrinsic oscillatory bursting behavior. Here, we investigate the specific kinetic properties that enable voltage-gated sodium channels to establish oscillatory bursting in preBötC inspiratory neurons, which exhibit an unusually large persistent Na+ current (INaP). We first characterize the kinetics of INaP in neonatal rat brainstem slices in vitro, using whole-cell patch-clamp and computational modeling, and then test the contribution of INaP to rhythmic bursting in live neurons, using the dynamic clamp technique. We provide evidence that subthreshold activation, persistence at suprathreshold potentials, slow inactivation, and slow recovery from inactivation are kinetic features of INaP that regulate all aspects of intrinsic rhythmic bursting in preBötC neurons. The slow and cumulative inactivation of INaP during the burst active phase controls burst duration and termination, while the slow recovery from inactivation controls the duration of the interburst interval. To demonstrate this mechanism, we develop a Markov state model of INaP that explains a comprehensive set of voltage clamp data. By adding or subtracting a computer-generated INaP from a live neuron via dynamic clamp, we are able to convert nonbursters into intrinsic bursters, and vice versa. As a control, we test a model with inactivation features removed. Adding noninactivating INaP into nonbursters results in a pattern of random transitions between sustained firing and quiescence. The relative amplitude of INaP is the key factor that separates intrinsic bursters from nonbursters and can change the fraction of intrinsic bursters in the preBötC. INaP could thus be an important target for regulating network rhythmogenic properties.

Development of resurgent and persistent sodium currents in mesencephalic trigeminal neurons.

Sodium channels play multiple roles in the formation of neural membrane properties in mesencephalic trigeminal (Mes V) neurons and in other neural systems. Mes V neurons exhibit conditional robust high-frequency spike discharges. As previously reported, resurgent and persistent sodium currents (INaR and INaP , respectively) may carry small currents at subthreshold voltages that contribute to generation of spike firing. These currents play an important role in maintaining and allowing high-frequency spike discharge during a burst. In the present study, we investigated the developmental changes in tetrodotoxin-sensitive INaR and INaP underlying high-frequency spike discharges in Mes V neurons. Whole-cell patch-clamp recordings showed that both current densities increased one and a half times from postnatal day (P) 0-6 neurons to P7-14 neurons. Although these neurons do not exhibit subthreshold oscillations or burst discharges with high-frequency firing, INaR and INaP do exist in Mes V neurons at P0-6. When the spike frequency at rheobase was examined in firing Mes V neurons, the developmental change in firing frequency among P7-14 neurons was significant. INaR and INaP density at -40 mV also increased significantly among P7-14 neurons. The change to an increase in excitability in the P7-14 group could result from this quantitative change in INaP. In neurons older than P7 that exhibit repetitive firing, quantitative increases in INaR and INaP density may be major factors that facilitate and promote high-frequency firing as a function of age in Mes V neurons.

Protein kinase A regulates the long-term potentiation of intrinsic excitability in neonatal trigeminal motoneurons.

Although much is known about neuronal plasticity in the mammalian hippocampus and other cortical neurons, the subcellular mechanisms underlying plasticity at the level of motor pools are less well characterized. Protein kinase A (PKA) activation plays an essential role in long-term potentiation of intrinsic excitability (LTP-IE) in layer V (LV) visual cortical neurons and may be involved in other systems as well. Trigeminal motoneurons (TMNs) participate in rhythmical motor behaviors, such as suckling, chewing, and swallowing. Using the whole-cell patch clamp method and various kinase inhibitors and activators, we investigated the mechanism of LTP-IE in neonatal rat TMNs. Ca(2+) depletion using ACSF with 0mM Ca(2+) or the Ca(2+) chelator bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) blocked the long-lasting increase in intrinsic excitability in TMNs, showing that intracellular Ca(2+) during the induction protocol is necessary for the induction of LTP-IE. We next used specific inhibitors of PKA, protein kinase C, and calcium/calmodulin-dependent protein kinase II during the induction protocol. Only the PKA inhibitor H-89 blocked the increase in the firing rate induced by the induction protocol. In addition, forskolin, which activates PKA, induced a long-lasting increase in excitability that resembled the excitability produced by the induction protocol. Thus, we conclude that LTP-IE in TMNs is calcium-dependent, and PKA is the primary regulator of this process.

Role of endothelin receptor signalling in squamous cell carcinoma.

Endothelin plays important roles in various physiological functions including vascular constriction. Recent studies reported that the endothelin receptors ETA and ETB are highly expressed in lung and skin tumor tissues. In contrast, there are few reports on endothelin signalling in the proliferation of head and neck cancer. We found that both ETA and ETB endothelin receptors were overexpressed in tumor cells of tongue cancer samples by immunohistochemistry. ETA and ETB were expressed in cultured lingual and esophageal squamous cell carcinoma (SCCs) cell lines. When both cultured cell lines were treated with an ETA selective antagonist (BQ123) or an ETB selective antagonist (BQ788), inhibition of cell growth was observed. Similar results were observed when SCCs were treated with specific siRNA for the suppression of ETA or ETB. Furthermore, inhibition of the mitogen-activated protein (MAP) kinase pathway by the treatments with ET receptor antagonists and siRNA was also observed. These results indicate that endothelin signalling may, in part, play important roles in cell growth in SCCs through the MAP kinase pathway.

Early two-stage double opposing Z-plasty or one-stage push-back palatoplasty?: comparisons in maxillary development and speech outcome at 4 years of age.

Determining the optimal timing and procedure of palatal surgery for children with cleft lip and palate has long raised a major controversy. An early two-stage palatoplasty protocol has been a recent trend in an attempt to obtain preferable maxillary growth without compromising adequate speech development. In this study, we aim to address whether the resulting maxillofacial growth and speech development obtained by an early 2-stage palatoplasty protocol are better than those obtained by conventional 1-stage push-back palatoplasty. Seventy-two nonsyndromic children with complete unilateral cleft lip and palate were enrolled in this study. They were divided into 2 groups: 30 children, who were treated with early 2-stage palatoplasty, in which soft palate closure was performed using a modified Furlow's procedure at 12 months of age and hard palate closure was performed at 18 months of age (Early Tow Stage [ETS] group: 22 boys, 8 girls), and 42 children, who underwent 1-stage Wardill-Kilner push-back palatoplasty at 12 months of age (Push Back [PB] group: 31 boys, 11 girls). Cephalometric analysis for maxillofacial growth and assessments of speech development were performed for each child at 4 years of age. The ETS group showed a lager maxillary length than the PB group [anterior nasal spine (ANS)-ptm': ETS, 46.7 ± 2.0 mm; PB, 43.6 ± 2.3 mm]. The ANS in the ETS group was positioned more anteriorly than that in the PB group (N'-ANS: ETS, 2.5 ± 1.8 mm; PB, 0.26 ± 2.5 mm), whereas the posterior edge of the maxilla positioned anteroposteiorly was comparable between the 2 groups. The anterior facial height was significantly greater in the ETS group than in the PB group (N-N': ETS, 43.3 ± 2.9 mm; PB, 40.1 ± 2.3 mm, S-S': ETS, 29.7 ± 3.2 mm; PB, 31.0 ± 3.2 mm). No statistically significant differences were observed in the incidence of either velopharyngeal incompetence or articulation errors between the 2 groups at 4 years of age. Our results show that the early 2-stage protocol is advantageous with regard to maxillary growth compared with 1-stage push-back palatoplasty without compromising speech development as evaluated for all children at 4 years of age.

Kinetic properties and functional dynamics of sodium channels during repetitive spiking in a slow pacemaker neuron.

We examined the kinetic properties of voltage-gated Na(+) channels and their contribution to the repetitive spiking activity of medullary raphé neurons, which exhibit slow pacemaking and strong spiking adaptation. The study is based on a combination of whole-cell patch-clamp, modeling and real-time computation. Na(+) currents were recorded from neurons in brain slices obtained from male and female neonatal rats, using voltage-clamp protocols designed to reduce space-clamp artifacts and to emphasize functionally relevant kinetic features. A detailed kinetic model was formulated to explain the broad range of transient and stationary voltage-dependent properties exhibited by Na(+) currents. The model was tested by injecting via dynamic clamp a model-based current as a substitute for the native TTX-sensitive Na(+) currents, which were pharmacologically blocked. The model-based current reproduced well the native spike shape and spiking frequency. The dynamics of Na(+) channels during repetitive spiking were indirectly examined through this model. By comparing the spiking activities generated with different kinetic models in dynamic-clamp experiments, we determined that state-dependent slow inactivation contributes significantly to spiking adaptation. Through real-time manipulation of the model-based current, we established that suprathreshold Na(+) current mainly controls spike shape, whereas subthreshold Na(+) current modulates spiking frequency and contributes to the pacemaking mechanism. Since the model-based current was injected in the soma, the results also suggest that somatic Na(+) channels are sufficient to establish the essential spiking properties of raphé neurons in vitro.

TASK channels contribute to the K+-dominated leak current regulating respiratory rhythm generation in vitro.

Leak channels regulate neuronal activity and excitability. Determining which leak channels exist in neurons and how they control electrophysiological behavior is fundamental. Here we investigated TASK channels, members of the two-pore domain K(+) channel family, as a component of the K(+)-dominated leak conductance that controls and modulates rhythm generation at cellular and network levels in the mammalian pre-Bötzinger complex (pre-BötC), an excitatory network of neurons in the medulla critically involved in respiratory rhythmogenesis. By voltage-clamp analyses of pre-BötC neuronal current-voltage (I-V) relations in neonatal rat medullary slices in vitro, we demonstrated that pre-BötC inspiratory neurons have a weakly outward-rectifying total leak conductance with reversal potential that was depolarized by approximately 4 mV from the K(+) equilibrium potential, indicating that background K(+) channels are dominant contributors to leak. This K(+) channel component had I-V relations described by constant field theory, and the conductance was reduced by acid and was augmented by the volatile anesthetic halothane, which are all hallmarks of TASK. We established by single-cell RT-PCR that pre-BötC inspiratory neurons express TASK-1 and in some cases also TASK-3 mRNA. Furthermore, acid depolarized and augmented bursting frequency of pre-BötC inspiratory neurons with intrinsic bursting properties. Microinfusion of acidified solutions into the rhythmically active pre-BötC network increased network bursting frequency, halothane decreased bursting frequency, and acid reversed the depressant effects of halothane, consistent with modulation of network activity by TASK channels. We conclude that TASK-like channels play a major functional role in chemosensory modulation of respiratory rhythm generation in the pre-Bötzinger complex in vitro.

Early two-stage palatoplasty using modified Furlow's veloplasty.

OBJECTIVE: To achieve sufficient velopharyngeal function and maxillary growth for patients with unilateral cleft lip and palate (UCLP), the authors have designed a new treatment protocol for palate closure involving early two-stage palatoplasty with modified Furlow veloplasty. Details of the surgical protocol and the outcomes of the dental occlusion of patients at 4 years of age are presented. DESIGN AND SETTING: This was an institutional retrospective study. PATIENTS: Seventy-two UCLP patients were divided into two groups based on their treatment protocols: patients treated using the early two-stage palatoplasty protocol (ETS group; n = 30) and patients treated using Wardill-Kilner pushback palatoplasty performed at 1 year of age (PB group; n = 42). INTERVENTIONS: The features of the ETS protocol are as follows: The soft palate is repaired at 12 months of age using a modified Furlow technique. The residual cleft in the hard palate is closed at 18 months of age.Lip repair is carried out at 3 months of age with a modified Millard technique for all subjects. RESULTS: The ETS group showed a significantly better occlusal condition than the PB group.The incidence of normal occlusion at the non-cleft side central incisor was 7.1% in the PB group; whereas, it was 66.7% in the ETS group. CONCLUSION: The results indicate that the early two-stage protocol is advantageous for UCLP children in attaining better dental occlusion at 4 years of age.

Effect on maxillary arch development of early 2-stage palatoplasty by modified furlow technique and conventional 1-stage palatoplasty in children with complete unilateral cleft lip and palate.

PURPOSE: The purpose of this study was to evaluate the palatal morphology of patients with complete unilateral cleft lip and palate after early 2-stage palatoplasty (ETS) consisting of soft palate closure by a modified Furlow palatoplasty at 12 months of age and hard palate closure at 18 months of age. We compared the result with the palatal morphology obtained by Wardill-Kilner push-back palatoplasty (PB) at 12 months of age with that of children with noncleft palate. In the present study we investigated whether ETS can result in better palatal development than conventional PB. MATERIALS AND METHODS: Thirty subjects were treated by ETS and 42 underwent PB. We also included cross-sectional data obtained from 66 children with noncleft palate as control. We measured the arch length, width, and cleft width using dental cast models that were consecutively taken at 3 months to 4 yrs of age and compared the results among the 3 groups. RESULTS: At 4 years of age, the anteroposterior palatal length of ETS was significantly longer than that of PB by 9.8%, and the transversal palatal width of ETS was also markedly wider than that of PB at every point measured. Furthermore, ETS showed potential catch-up growth in the anteroposterior palatal length from 12 months to 4 years of age. CONCLUSION: These results demonstrate that ETS has a considerable benefit for the palatal development of patients with complete unilateral cleft lip and palate compared with PB.

Raphé neurons stimulate respiratory circuit activity by multiple mechanisms via endogenously released serotonin and substance P.

Brainstem serotonin (5-HT) neurons modulate activity of many neural circuits in the mammalian brain, but in many cases endogenous mechanisms have not been resolved. Here, we analyzed actions of raphé 5-HT neurons on respiratory network activity including at the level of the pre-Bötzinger complex (pre-BötC) in neonatal rat medullary slices in vitro, and in the more intact nervous system of juvenile rats in arterially perfused brainstem-spinal cord preparations in situ. At basal levels of activity, excitation of the respiratory network via simultaneous release of 5-HT and substance P (SP), acting at 5-HT(2A/2C), 5-HT(4), and/or neurokinin-1 receptors, was required to maintain inspiratory motor output in both the neonatal and juvenile systems. The midline raphé obscurus contained spontaneously active 5-HT neurons, some of which projected to the pre-BötC and hypoglossal motoneurons, colocalized 5-HT and SP, and received reciprocal excitatory connections from the pre-BötC. Experimentally augmenting raphé obscurus activity increased motor output by simultaneously exciting pre-BötC and motor neurons. Biophysical analyses in vitro demonstrated that 5-HT and SP modulated background cation conductances in pre-BötC and motor neurons, including a nonselective cation leak current that contributed to the resting potential, which explains the neuronal depolarization that augmented motor output. Furthermore, we found that 5-HT, but not SP, can transform the electrophysiological phenotype of some pre-BötC neurons to intrinsic bursters, providing 5-HT with an additional role in promoting rhythm generation. We conclude that raphé 5-HT neurons excite key circuit components required for generation of respiratory motor output.