Microdeletion of the entire IRF6 gene in a Subsaharian African's family with Van der Woude syndrome.

Microdeletion of the entire interferon regulatory factory 6 (IRF 6) gene is a rare cause of Van der Woude syndrome (VDW) with only few cases reported in medical literature. Its occurrence in multiple affected members of a family is exceptional. The aim of this presentation was to describe a Central African family with typical VDW phenotype carrying an IRF6 gene deletion. Here we reported phenotype features of members of a Central African family with VDW syndrome consisting of labioalveolar cleft, depressions of the lower lip with labial fistulae (lip pits), submucosal clefts and cleft palate. Mutation analysis by means of multiplex ligation-dependent probe amplification and chromosomal microarray revealed a 374.070 kb, deletion encompassing the entire IRF6 gene in four affected family members. Microdeletion of the entire IRF6 gene causes the classical VDW syndrome phenotype.

Non-syndromic cleft lip and/or cleft palate: Epidemiology and risk factors in Lubumbashi (DR Congo), a case-control study.

PURPOSE: To determine the incidence and risk factors of occurrence of non-syndromic cleft lip and/or cleft palate (NSCLP) in Lubumbashi. METHOD: A case-control study was conducted in the health district of Lubumbashi from February 2012 to December 2015. An exhaustive sampling, collecting all newborns with cleft lip and/or cleft palate (CL ± P) in maternity wards was conducted. From a total of 172 cases, 162 non-syndromic cases were recruited. For each case, one clinically normal newborn control was selected. RESULTS: NSCLP had an incidence of 1/1258 live births (0.8/1000). We found significant associations with a family history of cleft lip and palate (CLP) (x2family history = 11.5, p = 0.0007), maternal alcohol intake (OR = 19.3, 95% CI: 1.9-197.1), paternal alcohol during the periconceptional period and the first trimester of pregnancy (OR = 18.7, 95% CI: 3.9-89.2), maternal educational level lower than high school (OR = 9.5, 95% CI: 2.0-44.7), clay (Pemba) consumption during pregnancy (OR = 38.3, 95% CI: 9.3-157.0), the use of insecticides in the evening (OR = 130.3, 95% CI: 13.2-1286.9), indoor cooking with charcoal (Makala) (OR = 6.5, 95% CI: 1.22-34.5), and regular consumption of Kapolowe fish, supposedly contaminated with heavy metals (OR = 29.5, 95% CI: 7.4-116.7). CONCLUSION: Several environmental risk factors highly prevalent in Central Africa for facial clefting were found.

Wolf-Hirschhorn Syndrome: Clinical and Genetic Data from a First Case Diagnosed in Central Africa.

Wolf-Hirschhorn syndrome (WHS) is a multiple congenital anomaly-intellectual disability syndrome caused by a deletion involving chromosome 4p16.3. We report clinical and genetic findings of the first WHS patient diagnosed in central Africa. This boy who presented with cleft palate, microcephaly, severe growth delay, and intellectual disability was 12 years old. Typical craniofacial features were present, though the characteristic "Greek helmet" appearance of the nose was less evident, probably reflecting a variable expression related to the genetic background. The clinical diagnosis of WHS was confirmed by array CGH, which revealed a terminal 4p16.3 deletion of 3.47 Mb, typically associated with a milder phenotype, contributing to the long survival of this child in a developing country.

Influence of Tracheostomy on Lung Deposition in Spontaneously Breathing Patients.

BACKGROUND: Nebulized drugs are frequently administrated through tracheostomy in clinical routine. So far, the amount of drug deposited into the lung in these patients remains unknown. The aim of our pharmacokinetic study was to compare lung delivery of amikacin in the same subjects in two settings: spontaneously breathing through a tracheostomy and through the mouth. METHODS: Lung delivery was measured by amikacin urinary drug concentration in nine patients who were transitory tracheostomized for the need of a head and neck oncologic surgery. Patients performed two nebulization sessions: with a mouthpiece (MB) and through tracheostomy (TB) using a adapted jet nebulizer (Sidestream®). RESULTS AND CONCLUSION: Lung delivery was similar with the two conditions of nebulization (6.5 ± 2.5% vs. 6.3 ± 2.0% of the nominal mass of amikacin, respectively, for MB and TB; p = 0.95). Duration of nebulization was also comparable (19.7 ± 1.6 vs. 20.1 ± 1.8 min, respectively, for mouth and tracheostomy breathing; p = 0.307). The half-life and elimination rate constant were not different between the two settings. We conclude that nebulized therapy can be administered in spontaneously breathing tracheostomized adults patients, with a similar amount of drug delivered to the lung compared with spontaneously mouth breathing patients.

[Lymph node metastases from squamous cell carcinoma of unknown primary site. Is it time to change of paradigm?]. / Les adénopathies métastatiques d'un carcinome épidermoïde sans porte d'entrée. Quelle est l'attitude actuelle ?

The diagnosis of carcinoma of unknown primary (CUP) is made after exclusion of the presence of a mucosal primary. There are two mains options for the primary treatment of CUP, either a neck node dissection followed by postoperative radiotherapy or chemo-radiotherapy, or a primary radiotherapy or chemo-radiotherapy depending on the nodal stage followed in case of residual neck disease by a selective neck dissection. There is no data to suggest the superiority of one over the other. For radiotherapy, unilateral neck or bilateral neck, including the upper aerodigestive tract mucosa are possible options. There is no definite data to demonstrate the superiority of one over the other, but owing the reduced toxicity of unilateral irradiation, and the possibility of salvage treatment in case of emergence of a mucosal primary and/or a contralateral neck node development, the former may be the preferred option. Advances in radiotherapy such as intensity modulated radiation therapy have the potential to spare organs at risk and reduce late toxicity rates. A selective irradiation approach customized on "major" criteria, such as nodal stage and level, HPV and EBV status and accessory criteria, such as histological variants, is under investigation.

Pentoxifylline and tocopherol in the treatment of yearly zoledronic acid-related osteonecrosis of the jaw in a corticosteroid-induced osteoporosis.

Osteonecrosis of the jaw (ONJ) is a well-known side effect of bisphosphonate (BP) therapy. ONJ is specifically related to the intravenous form of BPs and is usually seen in combination with other risk factors, such as dental surgery, concurrent corticosteroids, chemotherapy, and tobacco use. The risk of developing ONJ in patients treated with oral BPs for osteoporosis is lower than that in patients with cancer but is still significant. Zoledronic acid is a third-generation nitrogen-containing BP. It was first used in the treatment of malignancy as a monthly infusion and then approved for the treatment of osteoporosis as a yearly infusion and is an attractive option that is more reliable than the oral form. ONJ related to the use of yearly zoledronic acid is rarely reported in the literature and is most likely underestimated. Pentoxifylline and tocopherol have been used in the treatment of osteoradionecrosis for many years, with observed lesion improvement. The authors present a case of ONJ development after 3 yearly zoledronic acid infusions for corticosteroid-induced osteoporosis. The patient was successfully managed using conservative treatment with pentoxifylline and tocopherol.

Brain plasticity and cortical correlates of osseoperception revealed by punctate mechanical stimulation of osseointegrated oral implants during fMRI.

PURPOSE: Our aim was to unveil the cortical neural correlates of osseoperception, i.e. the tactile sensation perceived when loading a bone-anchored implant, by taking oral implants as a model. This was performed in a cross-sectional observational study with 9 volunteering patients and 10 age-matched controls. For each patient, functional magnetic resonance imaging (fRMI) recordings were made during punctate mechanical stimulation of either teeth or osseointegrated implants in the maxillary incisor area. MATERIALS AND METHODS: During fMRI recordings, 1 Hz punctate tactile stimuli were applied either on a maxillary left central incisor, canine tooth or central incisor implant. A block design paradigm was used to stimulate, in 9 patients, maxillary left central incisor implants (I21-p) and maxillary left canines (T23-p). In 10 control subjects, maxillary left central incisors and canines (T21-c, T23-c) were stimulated. Random effect group analyses were performed for each stimulated site, and differences in cortical activity elicited when loading teeth or implants were examined using ANOVA. RESULTS: As a group, patients activated somatosensory area S2 bilaterally for both I21 and T23, while controls activated S1 and S2 bilaterally for T21 and T23. At an individual level, S1 was activated by 4/9 implants, mainly on the ipsilateral side. The stimulated implants activated a larger bilateral cortical network outside the somatosensory areas: in parietal, frontal and insular lobes, the main clusters being located in the inferior frontal gyri. Stimulation of T23 in patients resulted in an activation pattern intermediate between that of the implants and that of natural teeth. CONCLUSION: This study demonstrates that punctate mechanical stimulation of oral implants activates both primary and secondary cortical somatosensory areas. It also suggests that brain plasticity occurs when extracted teeth are replaced by endosseous implants. This cortical activation may represent the underlying mechanism of osseoperception.

Three-dimensional surgical guide for frontal-nasal-ethmoid-vomer disjunction in Le Fort III osteotomy.

The aim of this article was to describe the achievement and the clinical use of a new three-dimensional surgical guide for frontal-nasal-ethmoid-vomer osteotomy. The three-dimensional guide is based on a three-dimensional rapid prototyping model and provides the three-dimensional spatial orientation and depth for the frontonasal osteotome. The method was applied to a 7-year-old patient with Apert syndrome. This technique allowed a critical osteotomy path in Le Fort III surgery to be transferred in a secure, fast, and cost-effective way from the three-dimensional rapid prototyping model to the operating room.

Alveolar osseous distraction by the combined use of modified miniplates and an orthodontic appliance. A technical note.

An original alveolar osseous distraction method using a Hyrax orthodontic device connected to two miniplates modified as a skeletal orthodontic anchorage (Bollard™ type) is reported and illustrated by three cases. In all three cases with alveolar bone insufficiency, the alveolar osseous distraction allowed for dental implant positioning and fixed dental prosthetic rehabilitation.

Perceptual changes in the peri-implant soft tissues assessed by directional cutaneous kinaesthesia and graphaesthesia: a prospective study.

BACKGROUND: The innervation of skin and oral mucosa plays a major physiological role in exteroception. This innervation is also clinically relevant as sensory changes occur after neurosurgical procedures. PURPOSE: The goal of this study was to compare the perception of mechanical stimuli applied to the buccal mucosa in the vicinity of osseointegrated oral implants with that in the controlateral dentate side. The role of the previously reported increased innervation in the peri-implant soft tissues in the oral sensorimotor function was thus examined. MATERIALS AND METHODS: Seventeen subjects with 20 implants were tested. Directional cutaneous kinaesthesia (DCK) and graphesthesia (G) were performed on the buccal side of the alveolar mucosa before and at planned intervals after implant placement. The observation was pursued until 6 months after the prosthetic rehabilitation. In each subject, the contralateral mucosa served as a control to the implant sites. Average percentages of correct responses in a four-choice task for DCK and a three-choice task for G were calculated. RESULTS: Despite an intersubject variation in both the DCK and G, high intraindividual correlations were found (p < .005). The implant sites showed a significant difference toward the control sites at the four interval test for both tests. For DCK and G, the average of correct responses decreased after abutment connection (i.e., after the implant uncovering surgery) to increase afterwards to reach a level close to, but still lower than, the control sites 3 to 6 months after the prosthetic rehabilitation. CONCLUSION: The DCK and G are simple but reliable sensory tests that can be easily applied in the oral region. This prospective study indicates that tooth loss reduces tactile function compared with implant-supported prostheses. The peri-implant soft tissues could be partially involved in the osseoperception function.

Schwannoma-like pleomorphic adenoma of the parotid.

Pleomorphic adenoma is the most common benign salivary gland tumour. It can occur in any salivary gland, but is most frequently found in the parotid gland. Chondroid metaplasia is a frequent finding in pleomorphic adenoma. Other forms of metaplasia have been described, but are encountered less frequently. We report a rare case of unusual pleomorphic adenoma of the parotid gland with schwannoma-like feature.

Delivery efficacy of a vibrating mesh nebulizer and a jet nebulizer under different configurations.

BACKGROUND: Jet nebulizers coupled to spacers are frequently used to promote drug lung deposition, but their clinical efficacy has not been established. Few in vivo studies have been performed with mesh nebulizers, commonly used to nebulize antibiotics. Our study compared inhaled mass and urinary drug concentration of amikacin by using three different nebulizer delivery configuration systems: a standard unvented jet nebulizer (Sidestream(®)) used alone or coupled to a 110-mL corrugated piece of tubing and a vibrating mesh nebulizer (e-Flow rapid(®)). METHOD: The inhaled mass of amikacin was assessed using the residual gravimetric method. Delivery efficacy was evaluated by assessing amikacin urinary drug concentration in six healthy spontaneously breathing volunteers. Urinary amikacin was monitored by fluorescent polarization immunoassay then cumulative excreted amount and antibiotic elimination rate were calculated. RESULTS AND CONCLUSIONS: The total daily amount of amikacin urinary excretion (Cu) was almost twice as high with eFlow rapid(®) compared to Sidestream(®) used alone; intermediate values being observed when the device was coupled to a corrugated piece of tubing. The latter configuration was also associated with a higher total daily amount of amikacin urinary excretion. In vivo drug output rate was around threefold higher with the eFlow Rapid(®) than with the Sidestream(®) used in any configuration. These results were concordant to those obtained with in vitro analysis comparing inhaled mass of amikacin for the three nebulizers. The elimination constant (Ke) and the mass median aerodynamic diameter (MMAD) did not differ between the three devices. In conclusion, the vibrating mesh nebulizer is more efficient, promoting larger urinary drug concentration and drug output. Coupling a corrugated piece of tubing to the standard jet nebulizer favors delivery efficacy.

A manually controlled new device for punctuate mechanical stimulation of teeth during functional magnetic resonance imaging studies.

AIM: To design a simple and affordable device that could apply standardized mechanical punctuate stimuli to trigger the periodontal mechanoreceptors during functional magnetic resonance imaging (fMRI). MATERIAL AND METHODS: A new manually controlled device using von Frey monofilaments was tested on a phantom and on eight volunteers. Four block design paradigms with different timing were compared. Teeth 11, 12, 13, 21, 22, 23 and the thumb were stimulated. RESULTS: The device did not induce any artefacts in MR images. The most efficient protocol included an epoch duration of 24 s and stimuli delivered at 1 Hz. When stimulating the teeth, activations of the primary (S1) and secondary (S2) somatosensory areas were consistently obtained, either on the ipsilateral, contra-lateral or both sides. Stimulation of the thumb led to activations of the contra-lateral S1 area and either ipsilateral or contra-lateral S2 area. CONCLUSION: The use of this innovative tool should allow to perform fMRI studies aimed to unveil the neural correlates of periodontal neural receptors, and to understand their plasticity induced by tooth loss and their eventual replacement by endosseous oral implants.

Intracerebral penetration of a zygomatic dental implant and consequent therapeutic dilemmas: case report.

This case report describes a unique intracerebral penetration of a zygomatic implant inserted in the pterygoid region. A 47-year-old female patient developed severe persistent headaches immediately after two zygomatic and two standard implants were inserted under general anesthesia. However, no additional treatment or radiologic assessment was performed at that time by the treating surgeon. The maxilla was rehabilitated with an implant-supported fixed denture 3 months after the implants were placed. An episode of acute left maxillary sinusitis occurred shortly after insertion of the fixed denture. Treatment with antibiotics was insufficient, and the patient developed chronic left maxillary sinusitis. The patient presented herself to a neurologist with symptoms of chronic fatigue and severe headaches. Cerebral magnetic resonance imaging demonstrated the intracerebral penetration of a foreign body that resembled a dental implant. The authors sought to resolve the intracerebral penetration of the foreign body, along with the persistent maxillary chronic sinusitis with its concomitant risk of ascending cerebral infection. Computer-assisted preoperative planning associated with computer-assisted three-dimensional transfer should be used to avoid such a dangerous complication. Postoperative computed tomography assessment should be performed after zygomatic implant surgery. Finally, any neurologic impairment of the patient after pterygoid implantation should also be treated immediately.

Positron emission tomography with [18F]fluorodeoxyglucose improves staging and patient management in patients with head and neck squamous cell carcinoma: a multicenter prospective study.

PURPOSE To address the impact of positron emission tomography with [(18)F]fluorodeoxyglucose (PET-FDG) on the initial staging and management of patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS This multicenter, prospective study included 233 patients with newly diagnosed and untreated HNSCC. TNM stage and therapeutic decision were first determined based on the conventional work-up (including physical examination, computed tomography [CT]/magnetic resonance imaging of the head and neck region, and thoracic CT) and sealed in envelope 1. Whole-body PET-FDG was then performed, and subsequent TNM stage and therapeutic decision were written in envelope 2. Changes in TNM stages and in patient management as a result of PET-FDG imaging were recorded. Clinical outcome and histopathology were used as gold standards to validate the TNM stage. Conventional and PET stages were compared using the McNemar test. Results Conventional and PET stage were discordant in 100 (43%) of 233 patients. PET proved to be accurate in 47 patients and inaccurate in 13 patients. TNM status was left unconfirmed in 40 patients because no therapeutic change was expected from the stage difference. Conventional + PET TNM classification (envelope 2) was significantly more accurate than conventional classification (envelope 1; P < .0001, McNemar test). PET-FDG altered the therapeutic plan in 32 (13.7%) of 233 patients. CONCLUSION Adding whole-body PET-FDG to the pretherapeutic conventional staging of HNSCC improved the TNM classification of the disease and altered the management of 13.7% of patients. These findings support the implementation of PET-FDG in the routine imaging work-up of HNSCC.

Reproducibility of osseous landmarks used for computed tomography based three-dimensional cephalometric analyses.

PURPOSE: The aim of this paper was to measure the reproducibility of osseous landmark identification from two recently described three-dimensional (3D) cephalometric analyses: 3D-ACRO and 3D-Swennen analyses. The study population consisted of 13 patients examined with spiral 3D computed tomography (CT). We used a previously validated low-dose CT protocol. For each analysis, 22 cephalometric reference landmarks were identified on 3D CT surface renderings. Forty-four reference landmarks were identified per patient. Two series of identifications were performed by two independent observers. In total, 3432 imaging measurements were completed. The intra-observer reconstructed mean log was 1.210+/-1.042mm for the 3D-ACRO analysis, and 1.311+/-1.042mm for 3D-Swennen analysis (comparison: p=0.17 NS). The inter-observer reconstructed mean log was 1.799+/-1.037mm for the 3D-ACRO analysis, and 2.465+/-1.036mm for 3D-Swennen analysis (comparison: p=0.000000002). The difference between the intra- and inter-observer reconstructed mean logs were 1.486+/-1.057mm for 3D-ACRO and 1.880+/-1.056mm for 3D-Swennen analysis. In conclusions: 3D-ACRO analysis was significantly more reproducible than 3D-Swennen analysis (p=0.0027) due to the use of a majority of highly reproducible cephalometric landmarks. Finally, we propose a classification scheme and exclusion criteria for reference landmarks used in 3D cephalometrics, based on inter-observer reproducibility and anatomical reality.

Oxygen isotope fractionation between human phosphate and water revisited.

The oxygen isotope composition of human phosphatic tissues (delta18OP) has great potential for reconstructing climate and population migration, but this technique has not been applied to early human evolution. To facilitate this application we analyzed delta18OP values of modern human teeth collected at 12 sites located at latitudes ranging from 4 degrees N to 70 degrees N together with the corresponding oxygen composition of tap waters (delta18OW) from these areas. In addition, the delta18O of some raw and boiled foods were determined and simple mass balance calculations were performed to investigate the impact of solid food consumption on the oxygen isotope composition of the total ingested water (drinking water+solid food water). The results, along with those from three, smaller published data sets, can be considered as random estimates of a unique delta18OW/delta18OP linear relationship: delta18OW=1.54(+/-0.09)xdelta18OP-33.72(+/-1.51)(R2=0.87: p [H0:R2=0]=2x10(-19)). The delta18O of cooked food is higher than that of the drinking water. As a consequence, in a modern diet the delta18O of ingested water is +1.05 to 1.2 per thousand higher than that of drinking water in the area. In meat-dominated and cereal-free diets, which may have been the diets of some of our early ancestors, the shift is a little higher and the application of the regression equation would slightly overestimate delta18OW in these cases.