A 3-base pair deletion,c.9711_9713del,in DMD results in intellectual disability without muscular dystrophy

We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3238, in the brain-specific isoform Dp71 of dystrophin. Linkage analysis supported causality as the mutation was present in the 7.6 cM linkage interval on Xp22.11–Xp21.1 with a maximum positive LOD score of 2.41 (MRX85 locus). Molecular modeling predicts that the p.(Leu3238del) deletion results in the destabilization of the C-terminal domain of dystrophin and hence reduces the ability to interact with β-dystroglycan. Correspondingly, Dp71 protein levels in lymphoblastoid cells from the index patient are 6.7-fold lower than those in control cell lines (P=0.08). Subsequent determination of the creatine kinase levels in blood of the index patient showed a mild but significant elevation in serum creatine kinase, which is in line with impaired dystrophin function. In conclusion, we have identified the first DMD mutation in Dp71 that results in ID without muscular dystrophy.     

Volumetric Changes in Apical Radiolucencies of Endodontically Treated Teeth Assessed by Cone-beam Computed Tomography 1 Year after Orthograde Retreatment

Introduction

Cone-beam computed tomography (CBCT) allows us to assess in 3 dimensions the location and size of periapical radiolucencies. We aimed to assess by CBCT scans the volumetric changes of periapical radiolucencies in endodontically treated teeth 1 year after orthograde retreatment.

Methods

Forty-five root-filled teeth with persistent apical periodontitis requiring endodontic orthograde retreatment from 37 individuals were included in the study. The research protocol was approved by the VU University Medical Center Amsterdam ethics committee (2007/265), and the participants signed a letter of consent. We made 2 CBCT scans for every patient, the first one before retreatment and the second one a year later. Two observers measured independently the volume of radiolucencies on CBCT images by using the AMIRA software. The intraclass correlation coefficient was used to evaluate interobserver agreement, and the Wilcoxon signed rank test was used to assess pretreatment and post-treatment volume size.

Results

The intraclass correlation coefficients were 0.994 and 0.998 for the scans before retreatment and 1 year after, respectively. The recall rate was 78% for the teeth and 73% for the patients. The volumetric change in periapical radiolucencies 1 year after retreatment was statistically significant (z = −3.112, P < .005). The volume of periapical radiolucencies reduced in 20 teeth (57%), remained unchanged in 8 (23%), and increased in 7 (20%).

Conclusions

One year after endodontic orthograde retreatment, the volume of periapical radiolucencies reduced significantly in 57% of the teeth.     

A systematic review of the results of surgery and radiotherapy on tumor control for pediatric craniopharyngioma

Objective

Craniopharyngiomas are rare tumors with bimodal incidence in the pediatric and adult age groups. Treatment strategies range from aggressive resection to planned limited resection combined with adjuvant therapies. Currently there is no consensus for standard of care for pediatric craniopharyngioma.

Materials and methods

We performed a systematic review of the published literature on pediatric craniopharyngioma. Patients were grouped based on extent of resection into gross total resection (GTR), subtotal resection (STR), and biopsy procedures. These groups were compared with respect to tumor control. Chi square was used to compare rates of recurrence. Kaplan–Meier was used to generate progression-free survival (PFS) estimates. Cox proportional hazard modeling was used to evaluate risk of progression. Each extent of resection group was also subdivided based on adjuvant therapy and compared.

Results

A total of 109 studies described extent of resection resulting in a cohort of 531 patients. Recurrence data were available for 377 patients. There was no difference in 1- or 5-year PFS between the groups who underwent GTR and STR combined with radiation (XRT; log-rank; p?=?0.76; 1-year PFS 89 vs 84 %; 5-year PFS 77 vs 73 %, respectively). One-year PFS was 84 % for STR+XRT compared to 76 % for STR alone while 5-year PFS was 73 % for STR+XRT compared to 43 % for STR alone (log-rank; p?=?0.003).

Conclusion

Although there are limitations of a systematic review of retrospective data, our results suggest that STR+XRT of pediatric craniopharyngioma is associated with similar rates of tumor control as GTR.     

Advanced Gynecologic Laparoscopy in a Fast-Track Ambulatory Surgery Center

Background/Objectives:

It has been shown that major gynecologic laparoscopy is safe in hospital ambulatory settings, but there is little data to suggest the same in freestanding ambulatory surgery centers. This study evaluates the safety and efficacy of advanced gynecologic laparoscopic surgery using a fast-track model in freestanding ambulatory surgery centers and discusses our institution protocols.

Methods:

Retrospective, multicenter review was conducted of major gynecologic surgeries from August 1^st 2010 to September 30^th 2011 in 3 surgical centers with one primary surgeon. All patients were treated for symptomatic uterine leiomyomas and/or endometriosis. Primary outcome measures were unplanned admissions and discharge within 23 hours.

Results:

One hundred and thirty-four patients underwent major laparoscopic gynecologic surgery with a total of 160 procedures: 77 stage IV endometriosis treatment including 7 disk excisions of endometriosis from the large bowel, 3 ureteroneocystostomies and 1 partial bladder resection, 38 myomectomies, and 34 hysterectomies including 12 modified radical hysterectomies. The overall unplanned admission rate was 4.5%. One hundred and thirty-one patients (97.7%) were discharged within 24 hours after surgery. Three patients (2.2%) were transferred to the hospital postoperatively: 1 patient for observation of postoperative anemia and 2 patients for postoperative fever. Three patients (2.2%) were admitted to the hospital after discharge: 1 patient for postoperative ileus, 1 patient for postoperative fever, and 1 patient with septic pelvic thrombophlebitis. These postoperative issues all resolved without complication, and all patients had an uneventful follow-up.

Conclusions:

With appropriate resources and an experienced surgeon, advanced laparoscopic surgery can be safely performed in a fast-track ambulatory surgery center with a high rate of discharge within 23 hours and low unplanned readmission rate.     

Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.     

Cone-beam Computed Tomographic Scans in Comparison with Periapical Radiographs for Root Canal Length Measurement: An In Situ Study

Introduction

The primary aim of this study was to compare the precision of root canal length determination on cone-beam computed tomographic (CBCT) scans and periapical radiographs (PAs) with the actual root canal length. The secondary aim was to examine the influence of tooth type on root canal length measurements as assessed on CBCT scans and PAs.

Methods

In total, 40 root canals of 33 teeth (molars, premolars, canines, and incisors) out of 5 dentate maxillas of human cadavers were included. Root canal length measurement was performed by a consensus panel (2 examiners) on CBCT scans (3D Accuitomo 170; J Morita, Kyoto, Japan) and digital PAs. After straight-line access opening, a #15 file was fixated in every root canal at the length measured on CBCT scans. All teeth were extracted, and the root canal containing the file was uncovered. Measurements made on images taken with a digital camera (AxioCam; Carl Zeiss, Sliedrecht, The Netherlands) linked to a stereozoom microscope (Stemi SV6, Carl Zeiss) were used as the actual root canal length.

Results

When all roots were examined together, it was not clear which method is better for all types of teeth. For root canals of anterior teeth, there was no significant difference between the 2 methods. For root canals of posterior teeth, CBCT images gave results significantly closer to the actual root canal length in comparison with PAs (t value = −1.96; critical value is 1.74 with a significance level of 0.05).

Conclusions

Root canal length measurements of posterior maxillary teeth were more accurate when assessed by CBCT images than PAs.     

Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.