ANO5 gene analysis in a large cohort of patients with anoctaminopathy: confirmation of male prevalence and high occurrence of the common exon 5 gene mutation.

Limb girdle muscular dystrophy type 2L or anoctaminopathy is a condition mainly characterized by adult onset proximal lower limb muscular weakness and raised CK values, due to recessive ANO5 gene mutations. An exon 5 founder mutation (c.191dupA) has been identified in most of the British and German LGMD2L patients so far reported. We aimed to further investigate the prevalence and spectrum of ANO5 gene mutations and related clinical phenotypes, by screening 205 undiagnosed patients referred to our molecular service with a clinical suspicion of anoctaminopathy. A total of 42 unrelated patients had two ANO5 mutations (21%), whereas 14 carried a single change. We identified 34 pathogenic changes, 15 of which are novel. The c.191dupA mutation represents 61% of mutated alleles and appears to be less prevalent in non-Northern European populations. Retrospective clinical analysis corroborates the prevalently proximal lower limb phenotype, the male predominance and absence of major cardiac or respiratory involvement. Identification of cases with isolated hyperCKaemia and very late symptomatic male and female subjects confirms the extension of the phenotypic spectrum of the disease. Anoctaminopathy appears to be one of the most common adult muscular dystrophies in Northern Europe, with a prevalence of about 20%-25% in unselected undiagnosed cases.

Dental implant placement in type II diabetics: a review of the literature.

Diabetes mellitus was once considered a contraindication to the use of dental implant therapy as it has been associated with comorbidities, including increased susceptibility to infection, impaired wound healing, and periodontitis. Since dental implants and techniques for controlling diabetes have evolved, dental implant therapy has become increasingly common among patients with diabetes. The rising success of dental implants, along with the realized benefits of implant therapy has shifted current trends to accommodate patients with controlled diabetes as good candidates for treatment. The literature currently suggests that successful treatment results can be attained when placing implants on carefully selected patients with glycosylated hemoglobin levels (HbA1C) less than 8 percent and with possible prophylactic antibiotic administration. This review aims to compile and critically evaluate the current literature for placement of dental implants in patients with diabetes.

Rigid internal fixation of infected mandibular fractures.

PURPOSE: To evaluate the treatment outcomes of rigid internal fixation for the management of infected mandible fractures. PATIENTS AND METHODS: A retrospective chart review of infected mandible fractures managed by a single oral and maxillofacial surgeon at a level I trauma center during a 7-year period was accomplished by independent examiners. All patients were treated with incision and drainage, culture and sensitivity testing, extraction of nonsalvageable teeth, placement of maxillomandibular fixation when possible, fracture reduction with bone debridement and decortication, rigid internal fixation of the mandible by an extraoral approach, and antibiotic therapy. The medical and social history was contributory in most patients. The analysis was stratified by the differentiation of the fractures into 2 groups: those with soft tissue infections in the fracture region versus those with hard tissue-infected fractures (biopsy-proven osteomyelitis). RESULTS: A total of 44 patients were included in this study, with an average follow-up of 18.2 months from the date of surgery (range 3 to 48). The treatment protocol was successful in all 18 patients (100%) with soft tissue infected mandibular fractures and 24 (92%) of 26 patients with hard tissue-infected fractures. CONCLUSIONS: A protocol consisting of concomitant incision and drainage, mandibular debridement, fracture reduction, and stabilization with rigid internal fixation can be effectively used for single-stage management of infected mandible fractures.

Orthognathic surgery in the young cleft patient: preliminary study on subsequent facial growth.

PURPOSE: This study evaluated the long-term effects of orthognathic surgery on subsequent growth of the maxillomandibular complex in the young cleft patient. PATIENTS AND METHODS: We evaluated 12 young cleft patients (9 male and 3 female patients), with a mean age of 12 years 6 months (range, 9 years 8 months to 15 years 4 months), who underwent Le Fort I osteotomies, with maxillary advancement, expansion, and/or downgrafting, by use of autogenous bone or hydroxyapatite grafts, when indicated, for maxillary stabilization. Five patients had concomitant osteotomies of the mandibular ramus. All patients had presurgical and postsurgical orthodontic treatment to control the occlusion. Radiographs taken at initial evaluation (T1) and presurgery (T2) were compared to establish the facial growth vector before surgery, whereas radiographs taken immediately postsurgery (T3) and at longest follow-up (T4) were used to determine postsurgical growth. Each patient's lateral cephalograms were traced, and 16 landmarks were identified and used to compute 11 measurements describing presurgical and postsurgical growth. RESULTS: Before surgery, all patients had relatively normal growth. After surgery, cephalograms showed statistically significant growth changes from T3 to T4, with the maxillary depth decreasing by -3.3 degrees +/- 1.8 degrees , Sella-nasion-point A by -3.3 degrees +/- 1.8 degrees, and point A-nasion-point B by -3.6 degrees +/- 2.8 degrees. The angulation of the maxillary incisors increased by 9.2 degrees +/- 11.7 degrees. Of 12 patients, 11 showed disproportionate postsurgical jaw growth. Maxillary growth occurred predominantly in a vertical vector with no anteroposterior growth, even though most patients had shown anteroposterior growth before surgery. The distance increased in the linear measurement from nasion to gnathion by 10.3 +/- 7.9 mm. Four of 5 patients operated on during the mixed dentition phase had teeth that erupted through the cleft area. A variable impairment of postoperative growth was seen with the 2 types of grafting material used. No significant difference was noted in the effect on growth in patients with unilateral clefts versus those with bilateral clefts. The presence of a pharyngeal flap was noted to adversely affect growth, whereas simultaneous mandibular surgery did not. After surgery, 11 of 12 patients tended toward a Class III end-on occlusal relation. CONCLUSIONS: Orthognathic surgery may be performed on growing cleft patients when mandated by psychological and/or functional concerns. The surgeon must be cognizant of the adverse postsurgical growth outcomes when performing orthognathic surgery on growing cleft patients with the possibility for further surgery requirements. Performing maxillary osteotomies on cleft patients would be more predictable after completion of facial growth.

Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis (ACTiMuS): study protocol for a randomised controlled trial.

BACKGROUND: We have recently completed an evaluation of the safety and feasibility of intravenous delivery of autologous bone marrow in patients with progressive multiple sclerosis (MS). The possibility of repair was suggested by improvement in the neurophysiological secondary outcome measure seen in all participants. The current study will examine the efficacy of intravenous delivery of autologous marrow in progressive MS. Laboratory studies performed in parallel with the clinical trial will further investigate the biology of bone marrow-derived stem cell infusion in MS, including mechanisms underlying repair. METHODS/DESIGN: A prospective, randomised, double-blind, placebo-controlled, stepped wedge design will be employed at a single centre (Bristol, UK). Eighty patients with progressive MS will be recruited; 60 will have secondary progressive disease (SPMS) but a subset (n = 20) will have primary progressive disease (PPMS). Participants will be randomised to either early or late (1 year) intravenous infusion of autologous, unfractionated bone marrow. The placebo intervention is infusion of autologous blood. The primary outcome measure is global evoked potential derived from multimodal evoked potentials. Secondary outcome measures include adverse event reporting, clinical (EDSS and MSFC) and self-assessment (MSIS-29) rating scales, optical coherence tomography (OCT) as well as brain and spine MRI. Participants will be followed up for a further year following the final intervention. Outcomes will be analysed on an intention-to-treat basis. DISCUSSION: Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis (ACTiMuS) is the first randomised, placebo-controlled trial of non-myeloablative autologous bone marrow-derived stem cell therapy in MS. It will determine whether bone marrow cell therapy can, as was suggested by the phase I safety study, improve conduction in multiple central nervous system pathways affected in progressive MS. Furthermore, laboratory studies performed in parallel with the clinical trial will inform our understanding of the cellular pharmacodynamics of bone marrow infusion in MS patients and the mechanisms underlying cell therapy. TRIAL REGISTRATION: ISRCTN27232902 Registration date 11/09/2012. NCT01815632 Registration date 19/03/2013.

Dental findings associated with the malformations of CHARGE.

The acronym CHARGE refers to a non-random clustering of congenital malformations whose cause remains unknown. To date, the dental features of CHARGE association are not well known. A brief review of the literature and a case in a 10-year old boy with the CHARGE association are presented. The patient had multiple dental anomalies including congenital absence of teeth, ectopic eruption, submergence of primary molars and an odontogenic fibroma associated with an impacted permanent molar.

Alveolar distraction osteogenesis for implant site development.

Alveolar distraction osteogenesis can be a valuable tool for implant site development. Simultaneous regeneration of hard and soft tissue and an overall decrease in treatment time compared with other methods of site preparation can be an advantage. The authors advocate the concept of "prosthetically driven alveolar distraction." Surgical planning should begin with visualization of the final restoration to determine the volume and position of the soft and hard tissue deficiency. Surgical guides will help the surgeon determine the vector of distraction. Adherence to surgical principles to avoid damage to adjacent vital structures and maintain vascular supply to the transport segment is necessary for success. Bone grafting may be necessary before or after distraction to increase the surgical success of the procedure. Close follow-up is needed to verify the appropriate distraction vector and volume. Patient management and acceptance should be considered in distractor design and placement.

Does natalizumab treatment increase the risk of herpes simplex encephalitis in multiple sclerosis? Case and discussion.

This report presents the 4th documented case worldwide of herpes simplex encephalitis in multiple sclerosis (MS) patients treated with natalizumab and the first case in the UK. Natalizumab is licensed for relapsing remitting multiple sclerosis in patients with high disease activity despite treatment with interferon-beta and patients with rapidly evolving severe, multiple sclerosis. Natalizumab is a monoclonal antibody targeted against alpha-4 integrin. Its proposed mechanism is attenuation of the migration of immune cells into the central nervous system. Reactivation of the JC virus causing progressive multifocal leucoencephalopathy (PML) and its association with natalizumab is well documented. This case adds support to the suggestion that natalizumab also increases the reactivation risk of CNS herpes simplex infection. A 34 year old woman was admitted with a generalized tonic-clonic seizure, fever and confusion following her 40th infusion of natalizumab. MRI demonstrated increased signal in the medial temporal lobes and EEG showed focal sharp waves over the temporal lobe. CSF PCR later confirmed herpes simplex virus. The patient made an eventual excellent recovery following 21 days of intravenous acyclovir therapy followed by 14 days of oral treatment.

Referral patterns of general dental practitioners for oral surgical procedures.

PURPOSE: The health maintenance organizations (HMOs) in the United States continue to be a powerful force in the field of medicine. Their infiltration into dentistry has placed an emphasis on having the primary care provider (general practitioner [GP]) function as the central orchestrator from which patient care cascades. The purpose of this study is to determine the self-perceived threshold and referral tendencies for the GP to a specialist for oral surgical needs. MATERIALS AND METHODS: Six hundred dentists were randomly selected to receive a questionnaire containing 16 clinical cases. These randomly arranged cases consisted of a brief case history and appropriate radiographs. Each case differed in complexity and was grouped according to surgical difficulty as follows: group I--simple dentoalveolar surgery, group II--complex dentoalveolar surgery (including any third molar case), group III--cases requiring placement of an implant, group IV--simple surgery for a medically compromised patient, and group V--complex surgery for a medically compromised patient. RESULTS: Differences in the referral patterns of cases were noted comparing age, gender, and years of practice of the GP. A higher referral rate to the specialist was also observed in patients with remarkable medical conditions. Most general dentists referred the complex dentoalveolar surgery cases. There exists a gender difference in the referral patterns of female dentists compared to their male counter parts in similar age groups and years of clinical practice. Most dentists referred the implants procedures to oral and maxillofacial surgeons or periodontists. Referrals for simple and complex surgical procedures were most often made because of inadequate surgical experience. CONCLUSIONS: When designing dental health policy with regard to exodontia, dentoalveolar surgery and management of the medically compromised patient, insurance companies and public health administrators should consider the existing competencies and level of comfort of the GP.