Influence of transdermal scopolamine on motion sickness during 7 days' exposure to heavy seas

We conducted a double-blind, placebo-controlled study to evaluate the efficacy and tolerability of transdermal scopolamine in the prevention of motion sickness (MS) aboard a frigate during 7 days of continuously moderate or heavy seas. Forty-nine healthy sailors with a previous history of MS were randomly assigned to receive a transdermal therapeutic system of scopolamine (TTS-S) or transdermal placebo (TD-P). Patches were placed behind the ears at least 4 hours before departure and were removed 72 hours later. Subjects were observed on days 1 to 4 and 6. In the TTS-S group, both subjective feeling of MS and the incidence of nausea were reduced during the first 2 days. Because of adaptation, differences in signs and symptoms of MS between subjects receiving TTS-S and TD-P disappeared after the second day. During the first 3 days, vomiting occurred less often in the TTS-S group. On day 6, 3 days after removal of the patch, vomiting occurred in 23% of the TTS-S group, probably due to delay in adaptation, but none of the subjects in the TD-P group vomited. Concentration was not adversely influenced, since the ability to work increased in the TTS-S group. During prolonged continuous exposure to heavy and moderate seas, 2.5 cm2 TTS-S discs proved to be efficacious in preventing MS, with xerostomia as a tolerable side effect and no significant ocular side effects.     

Signal peptide mutations in RANK prevent downstream activation of NF‐κB

Familial expansile osteolysis and related disorders are caused by heterozygous tandem duplication mutations in the signal peptide region of the gene encoding receptor activator of NF‐κB (RANK), a receptor critical for osteoclast formation and function. Previous studies have shown that overexpression of these mutant proteins causes constitutive activation of NF‐κB signaling in vitro, and it has been assumed that this accounts for the focal osteolytic lesions that are seen in vivo. We show here that constitutive activation of NF‐κB occurred in HEK293 cells overexpressing wild‐type or mutant RANK but not in stably transfected cell lines expressing low levels of each RANK gene. Importantly, only cells expressing wild‐type RANK demonstrated ligand‐dependent activation of NF‐κB. When overexpressed, mutant RANK did not localize to the plasma membrane but localized to extensive areas of organized smooth endoplasmic reticulum, whereas, as expected, wild‐type RANK was detected at the plasma membrane and in the Golgi apparatus. This intracellular accumulation of the mutant proteins is probably the result of lack of signal peptide cleavage because, using two in vitro translation systems, we demonstrate that the mutations in RANK prevent cleavage of the signal peptide. In conclusion, signal peptide mutations lead to accumulation of RANK in the endoplasmic reticulum and prevent direct activation by RANK ligand. These results strongly suggest that the increased osteoclast formation/activity caused by these mutations cannot be explained by studying the homozygous phenotype alone but requires further detailed investigation of the heterozygous expression of the mutant RANK proteins. © 2011 American Society for Bone and Mineral Research     

Clinical Trials Do Not Use Random Samples Anymore

Current clinical trials do not use random samples, but, instead, convenience samples. This raises the risk of non-normal data.

The aim of this paper is to review and describe for a non-mathematical readership common methods for testing the normal property, as well as methods for analyzing the data in case of non-normality.

With slight departures from the normal distribution, normality tests can be used even so. They include, among other tests, the normal-, t-, chi-square- tests, analysis of variance, and regression analyses. They should not be used if the chi-square goodness of fit is significant. Rank-testing is, then, an alternative, but, sometimes, distributions do not allow for this approach either. This can be checked by the Kolmogorov-Smirnov test. If the latter test is also positive, rank-testing is not warranted, and confidence intervals can be derived from the data without prior assumption about the type of frequency distribution. This can be done by calculating the range within which 95% of all possible outcomes lie. Another popular method for this purpose is bootstrapping, which resamples at random from the study's own data. This paper reviews methods to assess data for compliance with normality, and summarizes solutions for the analysis of non-normal data. We strongly believe that normality statistics, although the mainstay of statistical analysis for centuries, will rapidly be replaced with non-normal testing as the awareness of non-normal sampling distributions grows, and we hope that the paper will strengthen this awareness and affect the design and analysis of future clinical trials.     

Endoscopy-assisted sural nerve harvest in infants

A minimally invasive method of endoscopy-assisted sural nerve (SN) harvest in infants with obstetric brachial plexus lesions requiring nerve grafting procedures was applied to reduce the skin incision size and scarring at the donor site. Endoscopic visualization was achieved using a flexible and steerable Neuroview neuronavigational endoscope (Promedics, NL) 2.3 mm in diameter and 12 or 18 cm long in a peelaway sheath (700-9F) attached to a video camera. Through three 1.5-cm skin incisions the SN could be dissected free using a 2.5-mm-diameter nerve stripper, pituitary curette or pituitary scissors under endoscopic vision from the opposite direction. To prevent any central nociceptive pain behavior the sural nerve was blocked by lidocaine, and sectioned first proximally in the popliteal fossa then distally at the lateral malleolus. Received: 30 September 1998     

有症状门诊病人深静脉血栓形成的诊断,临床评价和D-二聚体分析可能减少对影像学诊断的需要

深静脉血栓形成(DVT)的年发病率为48-182／10万,一般估计为1／1000。DVT病死率为1%-5%,发病率和病死率与年龄密切相关。慢性疼痛、肿胀、偶尔腿部皮肤溃疡等血栓后综合征见于1／3发生过DVT的患者。血栓后综合征可出现较早,也可迟至10年才出现,总的发病率为2年23%,5年28%。患者如使用弹力加压袜至少2年以上,腿部病变的发生率可     

纤维蛋白原检测的指南

英国血液学界通常通过纤维蛋白原的测定来判断纤维蛋白量的降低和质的异常,评估出血危险性。纤维蛋白原的升高通常预示各种缺血性事件的存在,建议进行纤维蛋白原检测就是基于这种观点。 纤维蛋白原的测定方法有多种,其中Clauss检测法(以凝血酶时间为基础)是英国医院最常采用的,它可选用多种检测试剂和测定方法。许多实验室配置了自动凝集仪,其中许多是根据光散射变化的差异或凝血酶原时问(PT-Fg)检测时光密度的变化来计算纤维蛋白原的量。PT-Fg法检测中还存在一系列的问题,     

Monitoring of neoadjuvant chemotherapy using multiparametric, <Superscript>23</Superscript>Na sodium MR,and multimodality (PET/CT/MRI) imaging in locally advanced breast cancer

We prospectively investigated using advanced magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) to identify radiological biomarkers for treatment response in patients receiving preoperative systemic therapy (PST) for locally advanced breast cancer. Patients with a stage II or III breast cancer receiving PST were selected and underwent positron emission tomography (PET), magnetic resonance imaging (MRI), and breast biopsies at baseline and after the first cycle of PST (days 7–8) during the full course of treatment. PET/CT was acquired after injection of 2-deoxy-2-[18F]-fluoro-d-glucose (¹⁸FDG, 0.22 mCi/kg) and quantified with standardized uptake value assessment (SUV). Diagnostic breast MRI and sodium (²³Na) was acquired at 1.5 T. Total tissue sodium concentration (TSC), response criteria in solid tumors (RECIST), and volumes were quantified. Treatment response was determined by pathological assessment at surgery. Immunohistochemistry values of the proliferative index (Ki-67) were performed on biopsy specimens. Six of nineteen eligible women (43 ± 11 years) who received PST underwent radiological imaging of ¹⁸FDG-PET/CT and MRI for at least two cycles of treatment. Five patients had a pathological partial response (pPR) and one had pathological non-response (pNR). TSC decreased 21% in responders with increases in the non-responder (P = 0.03). Greater reduction in SUV was observed in responders (38%) compared to the non-responder (22%; P = 0.03). MRI volumes decreased after cycle 1 by 42% (responders) and 35% (non-responder; P = 0.11). Proliferation index Ki-67 declined in responders in the first cycle (median = 47%, range = 29–20%), but increased (4%) in the non-responder. Significant decreases in TSC, SUV, and Ki-67 were observed in responders with increases in TSC and Ki-67 in non-responders. Our results demonstrate the feasibility of using multi-modality proton, ²³Na MRI, and PET/CT metrics as radiological biomarkers for monitoring response to PST in patients with operable breast cancer.     

Surgical morbidity and mortality of pediatric brain tumors: a single center audit

Objectives  

The primary aim of this study is to perform an internal quality control of pediatric brain tumor surgery in the neurosurgical department of the VU University Medical Center Amsterdam (The Netherlands). Secondly, this study aims to contribute to the accumulating data concerning outcome in pediatric neurosurgery, in order to establish institutional practice benchmarks.     

Recommendations on management of EGFR inhibitor-induced skin toxicity: a systematic review

Epidermal growth factor receptor (EGFR) inhibitors, such as the monoclonal antibodies cetuximab and panitumumab, have proven efficacy in various types of cancer. However, these agents frequently result in skin toxicity, due to the expression of the EGFR in the skin. A correlation between the occurrence of skin toxicity and anti-tumor activity has been suggested in several phase III studies. However, since skin toxicity may impair the quality of life, and severe skin toxicity requires dose reduction or interruption, adequate and timely management of skin toxicity is important to maximize the anti-tumor efficacy of the EGFR inhibitor, as well as maintaining the patient's quality of life. Due to the small number of randomized controlled trials conducted in the field of EGFR inhibitor-induced skin toxicity so far, it is not possible yet to generate evidence based guidelines on its management. Here, we review and discuss available trials and case studies reporting on the management of EGFR inhibitor-induced skin toxicity.