Expanding the spectrum of PTH1R mutations in patients with primary failure of tooth eruption

Objectives

Primary failure of tooth eruption (PFE) is a rare autosomal-dominant disease characterized by severe lateral open bite as a consequence of incomplete eruption of posterior teeth. Heterozygous mutations in the parathyroid hormone 1 receptor (PTH1R) gene have been shown to cause PFE likely due to protein haploinsufficiency. To further expand on the mutational spectrum of PFE-associated mutations, we report here on the sequencing results of the PTH1R gene in 70 index PFE cases.

Materials and methods

Sanger sequencing of the PTH1R coding exons and their immediate flanking intronic sequences was performed with DNA samples from 70 index PFE cases.

Results

We identified a total of 30 unique variants, of which 12 were classified as pathogenic based on their deleterious consequences on PTH1R protein while 16 changes were characterized as unclassified variants with as yet unknown effects on disease pathology. The remaining two variants represent common polymorphisms.

Conclusions

Our data significantly increase the number of presently known unique PFE-causing PTH1R mutations and provide a series of variants with unclear pathogenicity which will require further in vitro assaying to determine their effects on protein structure and function.

Clinical relevance

Management of PTH1R-associated PFE is problematic, in particular when teeth are exposed to orthodontic force. Therefore, upon clinical suspicion of PFE, molecular DNA testing is indicated to support decision making for further treatment options.     

胶原-壳聚糖复合材料的制备及生物安全性检测

目的:制备胶原-壳聚糖复合细胞载体,并对该载体进行系统的生物学性能检测。方法:实验于2003-07/2006-06在天津市医药科学研究所完成。将胶原溶液和壳聚糖溶液按照一定比例(9∶1)混匀,交联后真空冷冻干燥,制成胶原-壳聚糖复合载体,对该载体进行复合材料性状及理化性能检测。并采用急性全身毒性试验、皮内刺激试验、皮肤致敏试验、溶血试验、细胞毒性试验和致突变试验进行生物学性能检测。结果:①胶原-壳聚糖复合材料具有三维立体多孔结构,适合细胞的三维生长,能为新生组织提供良好的支架。②急性全身毒性试验、皮内刺激试验均阴性,致敏率仅为6.25%,细胞毒性为0级,无诱变能力。结论:从仿生学角度出发,制备出可生物降解的胶原-壳聚糖复合材料,经过系统的生物学评价发现,胶原-壳聚糖复合材料具有良好的生物安全性,对机体无毒,不致突变,对细胞有较强的亲和作用,利于细胞生长和分化。     

EMPHYSEMATOUS PYELONEPHRITIS RESPONDING TO MEDICAL THERAPY

We describe two type 2 diabetic patients with unilateral emphysematous pyelonephritis who responded to medical treatment alone. Escherichia coli was isolated in both patients. The presence of gas was confirmed early by ultrasound and CT scan of abdomen. Following treatment, good functional recovery was demonstrable in the affected kidneys by isotope renogram. We stress the need for early diagnosis of this condition and aggressive treatment with broad spectrum antibiotics.     

Direct medical costs of adverse events in Dutch hospitals

Background  

Up to now, costs attributable to adverse events (AEs) and preventable AEs in the Netherlands were unknown. We assessed the total direct medical costs associated with AEs and preventable AEs in Dutch hospitals to gain insight in opportunities for cost savings.     

玻片法单人份免疫分型试剂盒在白血病诊断中的应用

0引言白血病免疫分型是指用已知的单克隆抗体(单抗)鉴定细胞表面或胞质内的分化抗原的方法.该方法的临床应用有利于白血病的鉴别及诊断.我们采用单人份免疫分型试剂盒对128例白血病患者进行了免疫分型.     

Histopathological changes in the oesophageal mucosa in Egyptian children with corrosive strictures: A single-centre vast experience

BACKGROUND The caustic ingestion continues to be a major problem worldwide especially in developing countries. The long-term complications include stricture and increased life time risk of oesophageal carcinoma. Patients suffered from corrosive induced oesophageal strictures have more than a 1000-fold risk of developing carcinoma of the oesophagus.AIM To determine the possibility of oesophageal mucosal dysplasia after prolonged dilatation in post corrosive stricture.METHODS This observational study was conducted at the Paediatric Endoscopy Unit in Cairo University Children's Hospital. It included children of both sexes older than 2 years of age who had an established diagnosis of post-corrosive oesophageal stricture and repeated endoscopic dilatation sessions for more than 6 mo. All patients were biopsied at the stricture site after 6 mo of endoscopic dilatation. A histopathological examination of an oesophageal mucosal biopsy was performed for the detection of chronic oesophagitis, inflammatory cellular infiltration and dysplasia.RESULTS The mean age of the enrolled children was 5.9 ± 2.6 years; 90% of the patients had ingested an alkaline corrosive substance(potash). The total number of endoscopic dilatation sessions were ranging from 16 to 100 with mean number of sessionswas 37.2 ± 14.9. Histopathological examination of the specimens showed that 85%of patients had evidence of chronic oesophagitis(group A) in the form of basal cell hyperplasia, hyperkeratosis and subepithelial fibrosis. Thirteen percent of the patients had evidence of reactive atypia(group B) in the form of severe neutrophilic intraepithelial inflammatory cellular infiltration, and 2 patients(2%)had mild squamous dysplasia(group C); we rebiopsied these two patients 6 mo after the initial pathological assessment, guided by chromoendoscopy by Lugol's iodine.CONCLUSION The histopathology of oesophageal mucosal biopsies in post-corrosive patients demonstrates evidence of chronic oesophagitis, intraepithelial inflammatory cellular infiltration and dysplasia. Dysplasia is one of the complications of postcorrosive oesophageal stricture.