Distraction Osteogenesis Maxillary Expansion (DOME) for adult obstructive sleep apnea patients with narrow maxilla and nasal floor

ObjectivesThis study correlates objective and subjective measurements associated with obstructive sleep apnea (OSA) to define the efficacy of Distraction Osteogenesis Maxillary Expansion (DOME) to treat adult OSA patients with narrow maxilla and nasal floor.MethodsThis is a retrospective study reviewing cases from September 2014 through April 2018 with 75 eligible subjects. Inclusion criteria required OSA confirmed by attended polysomnography (PSG). Pre- and Post-operative clinical data were measured at the Stanford Sleep Medicine and Stanford Sleep Surgery Clinics. DOME is a two-step process starting with insertion of custom-fabricated maxillary expanders anchored to the hard palate by mini-implants followed by minimally invasive osteotomies. After maxillary expansion was complete, orthodontic treatment to restore normal occlusion was initiated. Perioperative Apnea-Hypopnea Index (AHI), Epworth Sleepiness Scale (ESS), Nasal Obstruction Symptom Evaluation (NOSE), and Oxygen Desaturation Index (ODI) were measured for 43, 72, 72, and 34 subjects respectively. Statistical analysis was performed using paired T-test with significance set at p-value < 0.05.ResultsThe mean age of test subjects was 30.5 ± 8.5 years with a gender distribution of 57 males and 18 females. There was a significant reduction in pre and post-operative NOSE score (10.94 ± 5.51 to 3.28 ± 2.89, p < 0.0001), mean ESS score (10.48 ± 5.4 to 6.69 ± 4.75, p < 0.0001), and AHI (17.65 ± 19.30 to 8.17 ± 8.47, p < 0.0001) with an increased percentage of REM sleep (14.4 ± 8.3% to 22.7 ± 6.6%, p = 0.0014). No significant adverse effects were identified.ConclusionsDOME treatment reduced the severity of OSA, refractory nasal obstruction, daytime somnolence, and increased the percentage of REM sleep in this selected cohort of adults OSA patients with narrow maxilla and nasal floor.     

Osteogénesis imperfecta. Descripción de 15 casos

Osteogenesis imperfecta (OI) is an inherited connective tissue disease. The disease has been linked to mutations in one of the type I collagen genes. The diagnosis is based on clinical and radiologic findings. The management of OI in adults is not well-established and includes physical rehabilitation, surgical procedures, the use of antiresorptive therapy and anabolic agents. The aim of the present work was to analyze the clinical and analytical characteristics of these patients in adulthood, as well as to evaluate the different treatments administered. We reviewed the cases of OI diagnosed in our center over the last 12 years (2005-2017). We describe 15 adult patients with OI.     

Noggin inhibition of mouse dentinogenesis

ObjectivesThe Bone Morphogenetic Proteins (BMPs) direct tooth development and still express in the adult tooth. We hypothesized that inhibition of BMP function would therefore disrupt dentinogenesis by differentiated odontoblasts.MethodsWe generated mice overexpressing the BMP-inhibitory protein Noggin in differentiated odontoblasts and osteocytes under control of a Dmp1 promoter-driven cre transgene. We compared the dentin phenotype in these mice with that in WT littermates and in mice with a Smad4 odontoblast/osteocyte knockout mediated by the same cre and therefore lacking all BMP and Tgfβ signaling in the same tissues.ResultsThree-month-old first molars from both Noggin-expressing and Smad4-deleted mice showed decreased dentin volume with enlarged pulp cavities, and both displayed less organized and mineralized dentinal tubules compared to WT. The Smad4-ablated phenotype was more severe. While dentin sialophosphoprotein (DSPP) and bone sialoprotein (BSP) were decreased in the dentin of both lines, dentin matrix protein 1 (DMP1) was sharply increased in Noggin-expressing teeth.ConclusionsThe phenotypes we observed in Noggin-overexpressing and Smad4-conditional knockout teeth resemble the phenotype of Dentinogenesis Imperfecta (DGI) type III. Our results show that BMPs regulate post-natal dentinogenesis and that BMP-inhibitory proteins like Noggin play a role in that regulation. The increased severity of the Smad4 phenotype indicates that Tgfβ ligands, in addition to BMPs, play a crucial role in post-developmental dentinogenesis.     

Oro-dental and cranio-facial characteristics of osteogenesis imperfecta type V

Osteogenesis imperfecta (OI) type V is an ultrarare heritable bone disorder caused by the heterozygous c.-14C > T mutation in IFITM5. The oro-dental and craniofacial phenotype has not been described in detail, which we therefore undertook to evaluate in a multicenter study (Brittle Bone Disease Consortium). Fourteen individuals with OI type V (age 3–50 years; 10 females, 4 males) underwent dental and craniofacial assessment. None of the individuals had dentinogenesis imperfecta. Six of the 9 study participants (66%) for whom panoramic radiographs were obtained had at least one missing tooth (range 1–9). Class II molar occlusion was present in 8 (57%) of the 14 study participants. The facial profile was retrusive and lower face height was decreased in 8 (57%) individuals. Cephalometry, performed in three study participants, revealed a severely retrusive maxilla and mandible, and moderately to severly retroclined incisors in a 14-year old girl, a protrusive maxilla and a retrusive mandible in a 14-year old boy. Cone beam computed tomograpy scans were obtained from two study participants and demonstrated intervertebral disc calcification at the C2-C3 level in one individual. Our study observed that OI type V is associated with missing permanent teeth, especially permanent premolar, but not with dentinogenesis imperfecta. The pattern of craniofacial abnormalities in OI type V thus differs from that in other severe OI types, such as OI type III and IV, and could be described as a bimaxillary retrusive malocclusion with reduced lower face height and multiple missing teeth.     

Cloning, characterization and immunolocalization of human ameloblastin

Amelogenesis imperfecta is a broad classification of hereditary enamel defects, exhibiting both genetic and clinical diversity. Most amelogenesis imperfecta cases are autosomal dominant disorders, yet only the local hypoplastic form has been mapped to human chromosome 4q between D4S242 1 and the albumin gene. An enamel protein cDNA, termed ameloblastin (also known as amelin and sheathlin), has been isolated from rat, mouse and pig. Its human homolog has been mapped to chromosome 4q21 between markers D4S409 and D4S400, flanking the local hypoplastic amelogenesis imperfecta critical region. Therefore, ameloblastin is a strong candidate gene for this form of amelogenesis imperfecta. To facilitate genetic studies related to this dental disease, we isolated and characterized a human ameloblastin cDNA. A human third molar cDNA library was screened and two ameloblastin clones identified. Nucleotide sequencing of these cDNAs indicated alternative splicing of the putative open reading frame, use of different polyadenylation signals, and a high degree of similarity to reported rat, mouse and porcine cDNAs. Immunohistochemistry studies on embryonic human teeth using an antibody to recombinant ameloblastin indicated ameloblastin expression by ameloblasts with localization in the enamel matrix associated with the sheath structures.     

Enamelin maps to human chromosome 4q21 within the autosomal dominant amelogenesis imperfecta locus

Amelogenesis imperfecta is a group of hereditary enamel defects. Of the autosomal dominant forms, only the local hypoplastic type has been mapped to human chromosome 4q 13-4q21. Enamelin is a large enamel matrix protein secreted by ameloblasts. The purpose of this study was to determine the human chromosomal localization of enamelin to establish an association with various forms of amelogenesis imperfecta. Chromosomal mapping was performed by polymerase chain reaction (PCR) amplification using somatic hybrid and deletion/derivation cell line panels with an enamelin primer set based on 100% conserved regions between pig and mouse cDNAs. Sequence-tagged site content mapping using eight markers within the critical local hypoplastic amelogenesis imperfecta region was then performed using an isolated human enamelin genomic BAC clone. The human enamelin amplicon was confirmed by DNA sequence analysis, revealing 81% and 73% identity to pig and mouse cDNAs, respectively. PCR amplification using a somatic cell hybrid panel placed enamelin on chromosome 4 with analysis of a regional chromosome 4 mapping panel refining the localization to 4q 13.1-q21.23. An identified human enamelin BAC genomic clone was shown to contain markers D4S2604 and D4S2670, as well as the first exon of the human ameloblastin gene, placing enamelin in the critical amelogenesis imperfecta locus between markers HIS1 and D4S2604 at 4q21. Our results suggest that enamelin is a strong candidate gene for this disease. Furthermore, human 4q21 may contain a second cluster of enamel matrix genes located proximally to the identified cluster of dentin and bone genes.     

Mutational analysis of candidate genes in 24 amelogenesis imperfecta families

Amelogenesis imperfecta (AI) is a heterogeneous group of inherited defects in dental enamel formation. The malformed enamel can be unusually thin, soft, rough and stained. The strict definition of AI includes only those cases where enamel defects occur in the absence of other symptoms. Currently, there are seven candidate genes for AI: amelogenin, enamelin, ameloblastin, tuftelin, distal-less homeobox 3, enamelysin, and kallikrein 4. To identify sequence variations in AI candidate genes in patients with isolated enamel defects, and to deduce the likely effect of each sequence variation on protein expression and structure, families with isolated enamel defects were recruited. The coding exons and nearby intron sequences were amplified for each of the AI candidate genes by using genomic DNA from the proband as template. The amplification products for the proband were sequenced. Then, other family members were tested to determine their genotype with respect to each sequence variation. All subjects received an oral examination, and intraoral photographs and dental radiographs were obtained. Out of 24 families with isolated enamel defects, only six disease-causing mutations were identified in the AI candidate genes. This finding suggests that many additional genes potentially contribute to the etiology of AI.     

雌激素对原代成骨细胞骨形成的影响

了解雌激素对培养的原代成骨细胞骨形成的影响。观察添加雌激素后直接对成骨细胞骨形成的作用，并用VOnKossa免疫染色法定量表示骨形成。结果显示：雌激素对该原代成骨细胞无促进骨形成作用。     

记忆合金牵引器弹力输出及对牵引成骨的影响

目的：了解记忆合金牵引器弹力输出特点，以及对牵引速度和新骨再生结果的影响。方法：设计不同记忆合金牵引器，生物力学检测仪测量绘制其弹力输出曲线，制作bi—focal牵引成骨重建一侧下颌骨3．5～4cm节段缺失的杂种犬动物模型，观察不同牵引器牵引成骨速度和长度。结果：记忆合金牵引器可输出稳定柔和的超弹性弹力，牵引速度超过传统的每天1mm，骨再生结果稳定，再生骨节段长度与牵引器外形设计和弹力强度相关。结论：记忆合金牵引器设计制作简便，弹力输出可控，可稳定成骨，具有深入研究价值。