Oral appliance therapy for obstructive sleep apnea: a retrospective study in a psychiatric sleep clinic.

Objectives: We evaluated the continuity and effectiveness of oral appliances (OAs) for treating obstructive sleep apnea (OSA) in a psychiatric sleep clinic, specifically focusing on mild cases and those with psychiatric comorbidity. Methods: We retrospectively examined the medical records of 106 OSA patients treated with OA. Survival analysis was performed to assess the discontinuation of OA use. Clinical Global Impression-Improvement (CGI-I) scale were obtained from medical records. The apnea-hypopnea index (AHI), measured by polysomnography (PSG), and Epworth Sleepiness Scale (ESS) were compared between diagnosis and after post-OA treatment if a second PSG for efficacy assessment was conducted. Results: Among all 106 patients, Kaplan-Meier analysis estimated a discontinuation rate of 16.8% at 1 year. This tended to be higher for OSA patients with psychiatric comorbidity (22.7%) than those without (11.6%), though it was not statistically significant (P=0.08). The overall rate of improvement in CGI-I scale was 37.7% and was significantly lower in OSA patients with psychiatric comorbidity (25.0%) than those without (48.3%). Among the 74 patients who underwent a second PSG, AHI and ESS were significantly lower after OA treatment for the entire group and subgroups of OSA severity at diagnosis and psychiatric comorbidity, except for ESS in the moderate OSA severity subgroup. Conclusion: OA continuation was relatively good, and sleepiness was relieved by OA use, even in mild OSA patients and those with psychiatric comorbidity. However, the continuation and subjective improvement of symptoms were slightly lower in OSA patients with psychiatric comorbidity.

Importance of correcting alar base ptosis during primary cleft lip repair.

Objectives: Until 1999 at our hospital, primary cleft lip repair was performed by the straight-line method and external rhinoplasty was performed by the inverted trapezoidal suture method with bilateral reverse-U incisions for children with cleft lip and palate. Subsequently, repeated surgical corrections of the external nasal morphology became necessary during the growth period, often with unsatisfactory results because repeated external rhinoplasty results in a stronger scar contracture. From 2000 to 2004, we performed external rhinoplasty after patients had stopped growing; however, delaying surgery created a psychological burden for patients. Therefore, since 2005, we have focused on improving alar base ptosis and forming the nostril sill during the primary surgery. This study was performed to subjectively and objectively evaluate whether the current surgical method or the earlier technique produces a better treatment outcome. Methods: We subjectively and objectively evaluated alar base asymmetry after primary cleft lip repair but before bone grafting for alveolar cleft repair. For the objective evaluation, we measured the angle of alar base ptosis in frontal view photographs taken at the age of 6 or 7 years in patients who underwent repair before 1999 (Group A) and after 2005 (Group B). Results: The median angle was 2.75° in Group A and 1.50° in Group B, demonstrating a significant difference (P=0.04). Conclusions: The current surgical method, which reflects our focus on improving alar base ptosis and forming the nostril sill, subjectively and objectively improved the external nasal morphology.

Evaluation of Velopharyngeal Closure Function With 4-Dimensional Computed Tomography and Assessment of Radiation Exposure in Pediatric Patients: A Cross-Sectional Study.

OBJECTIVE: Some patients with cleft palate (CP) need secondary surgery to improve functionality. Although 4-dimensional assessment of velopharyngeal closure function (VPF) in patients with CP using computed tomography (CT) has been existed, the knowledge about quantitative evaluation and radiation exposure dose is limited. We performed a qualitative and quantitative assessment of VPF using CT and estimated the exposure doses. DESIGN: Cross-sectional. SETTING: Computed tomography images from 5 preoperative patients with submucous CP (SMCP) and 10 postoperative patients with a history of CP (8 boys and 7 girls, aged 4-7 years) were evaluated. PATIENTS: Five patients had undergone primary surgery for SMCP; 10 received secondary surgery for hypernasality. MAIN OUTCOME MEASURES: The presence of velopharyngeal insufficiency (VPI), patterns of velopharyngeal closure (VPC), and cross-sectional area (CSA) of VPI was evaluated via CT findings. Organ-absorbed radiation doses were estimated in 5 of 15 patients. The differences between cleft type and VPI, VPC patterns, and CSA of VPI were evaluated. RESULTS: All patients had VPI. The VPC patterns (SMCP/CP) were evaluated as coronal (1/4), sagittal (0/1), circular (1/2), and circular with Passavant's ridge (2/2); 2 patients (1/1) were unevaluable because of poor VPF. The CSA of VPI was statistically larger in the SMCP group (P = .0027). The organ-absorbed radiation doses were relatively lower than those previously reported. CONCLUSIONS: Four-dimensional CT can provide the detailed findings of VPF that are not possible with conventional CT, and the exposure dose was considered medically acceptable.

Odontohypophosphatasia treated with asfotase alfa enzyme replacement therapy in a toddler: a case report.

Hypophosphatasia (HPP) is a rare skeletal disorder caused by loss-of-function mutations in Alkaline Phosphatase, Biomineralization associated (ALPL) gene that encodes tissue-nonspecific alkaline phosphatase. Odontohypophosphatasia (odonto-HPP), a mild form of HPP, is characterized only by oral manifestations including premature exfoliation of deciduous teeth. Enzyme replacement therapy (ERT) is effective in severe HPP cases; however, information about its efficacy for odonto-HPP is limited. A 2-yr-old girl was referred to our hospital for mobility of her deciduous teeth with low serum alkaline phosphatase (ALP) level of 253 U/L (reference range: 410-1,150 U/L) and high urine phosphoethanolamine level of 1,419.9 µmol/g·Cre (7-70 µmol/g·Cre). She had no history of bone fractures; however, several members of her family had low serum ALP levels with a history of pathological fractures. She had a novel heterozygous missense mutation (c.1183A>T, p.Ile395Phe) in ALPL, and therefore, was diagnosed with odonto-HPP. After she was provided ERT to prevent premature exfoliation, no tooth mobility was observed. However, two deciduous teeth exfoliated two months after starting ERT, which was possibly triggered by a bout of common cold. Starting ERT following tooth mobility might be relatively late. Previous studies on experimental mice showed that starting ERT at birth may be effective in preventing premature exfoliation of deciduous teeth.

Clinical and genetic aspects of mild hypophosphatasia in Japanese patients.

BACKGROUND: Hypophosphatasia (HPP) is a rare inborn error of metabolism that results from a dysfunctional tissue non-specific alkaline phosphatase enzyme (TNSALP). Although genotype-phenotype correlations have been described in HPP patients, only sparse information is currently available on the genetics of mild type HPP. METHODS: We investigated 5 Japanese patients from 3 families with mild HPP (patients 1 and 2 are siblings; patient 4 is a daughter of patient 5) who were referred to Fujita Health University due to the premature loss of deciduous teeth. Physical and dental examinations, and blood, urine and bone density tests were conducted. Genetic analysis of the ALPL gene was performed in all patients with their informed consent. RESULTS: After a detailed interview and examination, we found characteristic symptoms of HPP in some of the study cases. Mobile teeth or the loss of permanent teeth were observed in 2 patients, and 3 out of 5 patients had a history of asthma. The serum ALP levels of all patients were 30% below the lower limit of the age equivalent normal range. ALPL gene analysis revealed compound heterozygous mutations, including Ile395Val and Leu520Argfs in family 1, Val95Met and Gly491Arg in family 2, and a dominant missense mutation (Gly456Arg) in family 3. The 3D-modeling of human TNSALP revealed three mutations (Val95Met, Ile395Val and Gly456Arg) at the homodimer interface. Severe collisions between the side chains were predicted for the Gly456Arg variant. DISCUSSION: One of the characteristic findings of this present study was a high prevalence of coexisting asthma and a high level serum IgE level. These characteristics may account for the fragility of tracheal tissues and a predisposition to asthma in patients with mild HPP. The genotypes of the five mild HPP patients in our present study series included 1) compound heterozygous for severe and hypomorphic mutations, and 2) dominant-negative mutations. All of these mutations were at the homodimer interface, but only the dominant-negative mutation was predicted to cause a severe collision effect between the side chains. This may account for varying mechanisms leading to different effects on TNSALP function.

Intestinal secretion of indoxyl sulfate as a possible compensatory excretion pathway in chronic kidney disease.

Indoxyl sulfate (IS) is a protein-bound uremic toxin that progressively accumulates in plasma during chronic kidney disease (CKD), and its accumulation is associated with the progression of CKD. This study examined the intestinal secretion of IS using in situ single-pass intestinal perfusion in a rat model of renal insufficiency, MRP2- and BCRP-overexpressing Sf9 membrane vesicles, and Caco-2 cell monolayers. An in situ single-pass perfusion study in CKD model rats demonstrated that a small amount of IS is secreted into intestinal lumen after iv administration of IS, and the clearance increased AUC-dependently. An excess amount of IS (3 mm) partially inhibited the MRP2- and BCRP-mediated uptake of specific fluorescent substrates, CDCF and Lucifer yellow, respectively, into the membrane vesicles, although IS was not taken up at a physiological concentration, 10 µm. In the Caco-2 cell monolayers, the IS transport was higher in the absorptive direction than in the secretory direction (p < 0.05). p-Aminohippuric acid (PAH) strongly inhibited IS transport in both directions (absorptive, p = 0.142; secretory, p < 0.01). Given that the blood IS levels are much higher than those in the intestinal lumen, it is possible that this unknown PAH-sensitive system contributes to the intestinal IS secretion. Although in situ inhibition study is needed to confirm that this unknown transporter mediates the in vivo intestinal secretion of IS, we speculate that this unknown active efflux system works as a compensatory excretion pathway for excess organic anions such as IS especially in end-stage renal disease.