Sleep deprivation increases oleoylethanolamide in human cerebrospinal fluid

This study investigated the role of two fatty acid ethanolamides, the endogenous cannabinoid anandamide and its structural analog oleoylethanolamide in sleep deprivation of human volunteers. Serum and cerebrospinal fluid (CSF) samples were obtained from 20 healthy volunteers before and after a night of sleep deprivation with an interval of about 12 months. We found increased levels of oleoylethanolamide in CSF (P = 0.011) but not in serum (P = 0.068) after 24 h of sleep deprivation. Oleoylethanolamide is an endogenous lipid messenger that is released after neural injury and activates peroxisome proliferator-activated receptor-α (PPAR-α) with nanomolar potency. Exogenous PPAR-α agonists, such as hypolipidemic fibrates and oleoylethanolamide, exert both neuroprotective and neurotrophic effects. Thus, our results suggest that oleoylethanolamide release may represent an endogenous neuroprotective signal during sleep deprivation. D. Koethe, D. Schreiber and A. Giuffrida contributed equally to this study.     

Motor patterns in Parkinson's disease: A data‐driven approach

To identify patterns of motor disturbances in Parkinson's disease (PD) and evaluate their relation with other PD domains. A cohort of 399 PD patients was randomly divided into two samples. Factors within the motor section of the SPES/SCOPA were identified by exploratory factor analysis on data from the first sample and next tested by confirmatory factor analysis in the second sample. Relations with other PD domains were evaluated by regression analyses. A four factor model was found to be valid. This included a tremor, a bradykinetic‐rigid, and two axial factors. One axial factor (“rise”, “gait”, “postural instability”) was associated with age and cognition, while the other axial factor (“freezing”, “speech”, “swallowing”) was related to dopaminergic medication and complications of therapy. Both other factors showed no relevant associations with demographic and clinical characteristics. The identification of motor factors and their relation with other domains of the disease may help to elucidate the mechanisms responsible for these associations and provide an objective base for further research on subtypes in PD. © 2009 Movement Disorder Society     

Scrotal hysterectomy in a male patient with mixed gonadal dysgenesis 46,XY(75%)/45,X(25%)

We report on a 20-year-old man in whom endocrinological investigation owing to dysmorphic signs characteristic for Turner syndrome revealed mixed gonadal dysgenesis. The patient was referred to us for further diagnostic investigations on a right intrascrotal tumour. Both testes were intrascrotal and hypotrophic with normal testosterone production. Surgical investigation showed a circumscribed tumor that proved to be a rudimentary uterus without evidence of malignancy at histological examination. Biopsies from both tested showed no signs of malignant disease. After removal of the tumor, we decided not to remove the testes prophylactically because of the male phenotype and the sufficient testosterone production.     

Angular and sliding stable antegrade nailing (Targon PH) for the treatment of proximal humeral fractures

INTRODUCTION: The optimal surgical treatment for displaced proximal humeral fractures continues to be controversial. Different treatment modalities are available. Mechanical implant-related problems, however, and the preservation of the biological integrity of the humeral head remain unsolved. New implants providing angular stability are expected to maintain the intraoperative result of reduction until definitive healing. The purpose of this study was to evaluate the functional outcome and the complication rate of an angular and sliding stable antegrade interlocking nail for the treatment of displaced proximal humeral fractures. MATERIALS AND METHODS: In a prospective study, 112 consecutive patients with displaced proximal humeral fractures were treated. Complete 12 months postoperative follow-up was available for 74 patients. Fracture types were classified according to the Neer-classification. Clinical, functional and radiographic follow-up evaluations were performed 3, 6 and 12 months after surgery. The Constant Score (CS) was used to assess shoulder function. RESULTS: All fractures were united. The CS (MV +/- SD) of the injured side 3, 6 and 12 months after surgery were 42.1 +/- 15.1, 56.1 +/- 20.1 and 70.9 +/- 19.3, respectively. Patients sustaining Neer III and VI/3 fractures revealed better shoulder function (68.8 +/- 14.7, 74.9 +/- 17.6) 12 months postoperatively than those with Neer IV/4 fractures (60.7 +/- 23.2), where most complications occurred. Complications requiring surgical therapy were seen in a total of 24 patients (30%) and included backing out of screws in nails without peak inlay (20%; 2000-2003), protrusion of screws into the gleno-humeral joint (5%), loss of reduction with malunion (9%) and major tubercle displacement (7%). CONCLUSION: The treatment of displaced proximal humeral fractures with an angular and sliding stable antegrade nail (Targon-PH) led to good functional results, especially in 2- and 3-part fractures. There exists a substantial risk for postoperative complications and bad motor function in Neer IV/4 fractures. Lateral backing out of screws was abolished by implant modifications (PEEK-inlay) from 2003 onwards. Additional tension wire banding of the major tubercle may further reduce the risk of secondary displacement.     

1,4-benzodiazepines as inhibitors of respiratory syncytial virus. The identification of a clinical candidate

Respiratory syncytial virus (RSV) is the cause of one-fifth of all lower respiratory tract infections worldwide and is increasingly being recognized as representing a serious threat to patient groups with poorly functioning or immature immune systems. Racemic 1,4-benzodiazepines show potent anti-RSV activity in vitro. Anti-RSV evaluation of 3-position R- and S-benzodiazepine enantiomers and subsequent optimization of this series resulted in selection of a clinical candidate. Antiviral activity was found to reside mainly in the S-enantiomer, and the R-enantiomers were consistently less active against RSV. Analogues of 1,4-(S)-benzodiazepine were synthesized as part of the lead optimization program at Arrow and tested in the XTT assay. From this exercise, (S)-1-(2-fluorophenyl)-3-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]-diazepin-3-yl)-urea, 17b (RSV-604) was identified as a clinical candidate, exhibiting potent anti-RSV activity in the XTT assay, which was confirmed in secondary assays. Compound 17b also possessed a good pharmacokinetic profile and has now progressed into the clinic.     

Cerebellar contributions to cognitive functions: A progress report after two decades of research

Accumulating evidence from both human lesion and functional neuroimaging studies appears to support the hypothesis that the cerebellum contributes to non-motor functions. Along similar lines, cognitive, affective and behavioural changes in psychiatric disorders, such as autism, schizophrenia and dyslexia, have been linked to structural cerebellar abnormalities. The aim of this special issue was to evaluate the current knowledge base after more than 20 years of controversial discussion. The contributions of the special issue cover the most important cognitive domains, i.e., attention, memory and learning, executive control, language and visuospatial function. The available empirical evidence suggests that cognitive changes in patients with cerebellar dysfunction are mild and clearly less severe than the impairments observed after lesions to neocortical areas to which the cerebellum is closely connected via different cerebro-cerebellar loops. Frequently cited early findings, e.g., with respect to a specific cerebellar involvement in attention, have not been replicated or might be confounded by motor or working memory demands of the respective attention task. On the other hand, there is now convincing evidence for a cerebellar involvement in the mediation of a range of cognitive domains, most notably verbal working memory. Verbal working memory problems may partly underlie the compromised performance of cerebellar lesion patients on at least some complex cognitive tasks. Although investigations have moved from anecdotical case reports to hypothesis-driven controlled clinical group studies based on sound methods which are complemented by state-of-the-art functional neuroimaging studies, the empirical evidence available so far does not yet allow a convincing theory of the mechanisms of a cerebellar involvement in cognitive function. Future studies are clearly needed to further elucidate the nature of the processes linked to cerebellar mediation of cognitive processes and their possible link to motor theories of cerebellar function, e.g., its role in prediction and/or timing.     

The role of the cerebellum for predictive control of grasping

Predictive control of grasping forces when manipulating objects in the environment is suggested to reflect internal models that capture the causal relationship between actions and their consequences. The anatomical correlate of predictive control of grasping within the central nervous system is not completely understood. One structure which has been related to the neural representation of internal models is the cerebellum. Given its stereotyped cytoarchitecture, the widespread connections with cortical and subcortical sensory-motor structures and the neural activity of cerebellar Purkinje cells during sensory-motor tasks, the cerebellum has long been considered to play a major role in the establishment and maintenance of sensory-motor representations related to voluntary movement. Such representations are necessary to predict the consequences of our own movements. Here we review theoretical concepts, electrophysiological, imaging and behavioural data suggesting the cerebellum to be the anatomical and functional correlate of internal models relevant for predictive control of grasping.     

Digital X-ray radiogrammetry better identifies osteoarthritis patients with a low bone mineral density than quantitative ultrasound

This study assessed the ability of quantitative ultrasound (QUS) and digital X-ray radiogrammetry (DXR) to identify osteopenia and osteoporosis in patients with knee osteoarthritis (OA). One hundred and sixty-one patients with painful knee OA (81 men, 80 women; age 62.6±9.2 years, range 40–82 years) were included in this cross-sectional study and underwent dual-energy X-ray absorptiometry (DXA) of both hips and the lumbar spine, QUS of the phalanges and calcanei of both hands and heels, and DXR using radiographs of both hands. Unpaired t-test, Mann-Whitney U test, ROC analysis and Spearman’s rank correlation were used for comparisons and correlation of methods. Using DXA as the reference standard, we defined a low bone mineral density (BMD) as a T-score ≤−1.0 at the lumbar spine or proximal femur. In contrast to phalangeal or calcaneal QUS, DXR was able to discriminate patients with a low BMD at the lumbar spine (p<0.0001) or hips (p<0.0001). ROC analysis showed that DXR had an acceptable predictive power in identifying OA patients a low hip BMD (sensitivity 70%, specificity 71%). Therefore, DXR used as a screening tool could help in identifying patients with knee OA for DXA.     

Medically appropriate use of helicopter EMS: the mission acceptance/triage process

INTRODUCTION: Appropriate use of helicopter emergency medical services (HEMS) ensures the maximum impact of a limited resource on improved health outcomes. Overtriage increases real and opportunity costs and may unjustifiably expose the program to small but inherent safety risks. The purpose of this study is to describe the mission acceptance process for an integrated, provincially based HEMS program and determine its utilization patterns. METHODS: This is a retrospective review of patient care and administrative databases. All missions were reviewed to determine whether they were medically appropriate. "Appropriateness" was defined a priori as requiring admission to a critical care unit, death during transportation or in first 24 hours, or in the case of trauma, an injury severity scale (ISS) score > or = 12. Overtriage was defined as not meeting these a priori definitions. RESULTS: Five hundred eighty-four missions were reviewed from March 31, 2003 through December 31, 2004. Our mission acceptance process consists of three distinct but complementary phases: ongoing outreach education, scanning by dispatchers in an integrated dispatch center, and a clinician to online physician discussion about each case. The overall overtriage rate was 13.1%. CONCLUSION: The rate of medically appropriate missions in this system is relatively high. Prospective research is required to improve HEMS triage systems.