Validity and reliability of clinical prediction rules used to screen for cervical spine injury in alert low-risk patients with blunt trauma to the neck: part 2. A systematic review from the Cervical Assessment and Diagnosis Research Evaluation (CADRE) Collaboration.

PURPOSE: To update findings of the 2000-2010 Bone and Joint Decade Task Force on Neck Pain and its Associated Disorders (Neck Pain Task Force) on the validity and reliability of clinical prediction rules used to screen for cervical spine injury in alert low-risk adult patients with blunt trauma to the neck. METHODS: We searched four databases from 2005 to 2015. Pairs of independent reviewers critically appraised eligible studies using the modified QUADAS-2 and QAREL criteria. We synthesized low risk of bias studies following best evidence synthesis principles. RESULTS: We screened 679 citations; five had a low risk of bias and were included in our synthesis. The sensitivity of the Canadian C-spine rule ranged from 0.90 to 1.00 with negative predictive values ranging from 99 to 100%. Inter-rater reliability of the Canadian C-spine rule varied from k = 0.60 between nurses and physicians to k = 0.93 among paramedics. The inter-rater reliability of the Nexus Low-Risk Criteria was k = 0.53 between resident physicians and faculty physicians. CONCLUSIONS: Our review adds new evidence to the Neck Pain Task Force and supports the use of clinical prediction rules in emergency care settings to screen for cervical spine injury in alert low-risk adult patients with blunt trauma to the neck. The Canadian C-spine rule consistently demonstrated excellent sensitivity and negative predictive values. Our review, however, suggests that the reproducibility of the clinical predictions rules varies depending on the examiners level of training and experience.

Do we need retarded delivery of bone growth factors in facial bone repair? An experimental study in rats.

The aim of the present study was to evaluate the effect of different dosages of retarded vs. rapid release of bone morphogenic protein 2 (BMP2) at different recipient sites. Porous composite poly(D,L-lactic acid) (PDLLA)/CaCO3 scaffolds were loaded with three different dosages of rhBMP2 (24 µg, 48 µg and 96 µg) and implanted, together with blank controls, both into non-healing defects of the mandibles and into the gluteal muscles of 24 adult male Wistar rats. After 26 weeks, bone formation and expression of bone specific markers [alkaline phosphatase (AP) and Runx2] were evaluated by histomorphometry and immunohistochemistry. Results showed that the mode of delivery had no quantitative effect on bone formation in mandibular sites. Expression of AP and Runx2 showed significant differences among the three dosage groups. There were significant correlations between the expression of both AP and Runx2 as well as the extent of bone formation, with both retarded and rapid release of rhBMP2. In ectopic sites, retarded release significantly enhanced bone formation in the low and medium dosage groups, compared to rapid release. Expression of AP was significantly higher and Runx2 significantly lower in ectopic sites, compared to mandibular sites. Significant correlations between the expression of bone specific markers and bone formation occurred only in the retarded delivery groups, but not in the rapid release groups. Within the limitations of the experimental model, it was concluded that retarded delivery of BMP2 was effective, preferably in sites with low or non-existing pristine osteogenic activity. Expression of bone specific markers indicated that osteogenic pathways might be different in mandibular vs. ectopic sites.

[School re-integration after child brain dislocation : The trauma surgeon's role]. / Schulische Reintegration nach kindlicher Gehirnerschütterung : Die Rolle des Unfallchirurgen.

Concussion injury of the brain is still a frequently underestimated injury, which can be associated with long-lasting consequences. Compared to adults, the recovery phase is often prolonged in childhood. Primary treatment consists of symptom-dependent physical and mental activities. Re-integration into daily life is crucial. In childhood, the primary focus is therefore on returning to school. New symptoms, or an increased presence of symptoms must be detected, to avoid prolonged recovery courses. School restrictions have to be minimized. Corresponding concepts are already implemented in North America. Comparable concepts are not established in Germany. In addition to well-known standard return-to-play protocols for sport re-integration, it is urgently recommended to integrate gradual return-to-learn protocols.Thus, academic adaptations and support must be established as well as symptom-oriented organizational and teaching modules.

[New guidelines for cervical cancer screening in young patients: what impact? ]. / Nouvelles recommandations dans le dépistage du cancer du cot chez les jeunes patientes: quel impact?

The publication in 2009 of the new recom- mandations by the American College of Obstetricians and Gynaecologists (ACOG) about the screening of cervical cancer enabled us to optimize the treatment, especially in young patients. The aim of these modifications is to decrease overtreatment of low grade lesions and thereby the risk of obstetrical complica- tions. The objective of our article is to briefly recall these new guidelines together with a study conducted in our Department of Obstetrics and Gynaecology which aim is to confirm that our practice follows these instructions and to check that these procedures are safe for the future of these young patients.

[Prevention as a pension insurance task: innovative models complementing proven concepts]. / Prävention als Aufgabe der Rentenversicherung: Innovative Modelle ergänzen bewährte Konzepte.

Health-related strategies aimed at ensuring long-term participation in working life are gaining increasing importance against a background of longer working lives and demographic change. Medical and vocational rehabilitation under the German statutory pension insurance scheme are among these strategies. For a long time already, preventive concepts have been taken into account in rehabilitation so that the pension insurance's prevention approach is mainly based on the experience gained with preventive-modules in rehabilitation and follow-up care. Having so far only been able to offer in-patient prevention benefits, the statutory pension insurance scheme now can offer out-patient prevention measures, given the amendment it initiated to change Section 31 (1) no. 2 of Book 6 of the German Social Code which came into effect on January 1, 2009. The common guidelines of the statutory pension insurance institutions directed at ensuring continued working capacity were revised relative to the preventive benefits contained and were supplemented by recommendations for their use. The changing occupational demands in modern service society have thus been taken into account, and prevention benefits can be implemented in a more flexible manner following successful trials. The concept of out-patient prevention measures following along at the workplace and during leisure time is intended to enhance sustainability of acquired health-promoting behaviours in every day (working) life. At present this new concept is being tried out in various circumscribed pilot projects by several pension insurance institutions, partly in combination with in-patient components. On account of their specific know-how and their regional networks with enterprises, rehabilitation facilities are destined as locations for carrying out pension insurance prevention benefits.

A new approach in three dimensions to define pre- and intraoperative condyle-fossa relationships in orthognathic surgery - is there an effect of general anaesthesia on condylar position?

Incorrect registration of the condylar position in orthognathic surgery is supposed to cause postoperative relapse, condylar resorption and temporomandibular disorders. The aim of this prospective study was to evaluate the influence of general anaesthesia on centric relation (CR). Therefore, CR registered preoperatively in the awake patient and CR registered intraoperatively under general anaesthesia were recorded in 30 patients (14 men, 16 women) undergoing orthognathic surgery (skeletal class I: n=3, II: n=13, III: n=14; symmetric: n=20; asymmetric: n=10). CR records were digitized and, through superimposition on the preoperative cone beam computed tomography of the patient's skull, the superior, anterior and posterior joint space and the volumetric congruence of 120 condyles were analysed. The linear measurements of joint spaces did not demonstrate any clinically relevant discrepancy between the CR measured in the awake and anaesthetized patient. In contrast, volumetric analysis revealed statistically significant differences between both states, with an intraoperative condylar sag predominantly in the posterior-inferior direction. The patient's skeletal class or symmetry had no significant influence on the intraoperative condylar displacement. Thus, the risk of fixing the condyle in an unphysiological position supports the idea of using intraoperative condylar positioning devices to achieve predictable and stable outcomes.

Influence of tumour necrosis factor alpha on epithelial-mesenchymal transition of oral cancer cells in co-culture with mesenchymal stromal cells.

Tumour progression in head and neck squamous cell carcinoma (HNSCC) is influenced by the surrounding stroma and inflammatory cytokines such as tumour necrosis factor alpha (TNF-α). The aim of this study was to test the hypothesis that TNF-α modulates the interactions of HNSCC cell line PCI-13 and bone marrow mesenchymal stromal cells (BMSCs) and influences markers of epithelial-mesenchymal transition (EMT). Following induction with TNF-α, mono- and co-cultures of BMSCs and the established HNSCC cell line PCI-13 were analyzed; protein expression of E-cadherin and vimentin and qRT-PCR expression of Snail, Twist, MMP14, vimentin, E-cadherin, and ß-catenin were examined, and changes in cellular AKT signalling were analyzed. TNF-α induced a significant decrease in E-cadherin (64.5±6.0%, P=0.002) and vimentin (10.4±3.5%, P=0.04) protein expression in co-cultured PCI-13, while qRT-PCR showed a significant increase in ß-catenin (BMSCs P<0.0001; PCI-13 P=0.0005) and Snail (BMSCs P=0.009; PCI-13 P=0.01). TNF-α also resulted in a down-regulation of AKT downstream targets S6 (38.7±20.9%, P=0.01), p70S6 (16.7±12%, P=0.05), RSK1 (23.6±28.8%, P=0.02), and mTOR (27.4±17.5%, P=0.004) in BMSC co-cultures. In summary, while reducing the expression of vimentin and AKT-signalling in PCI-13 and BMSC, respectively, TNF-α introduced an inflammatory-driven tumour-stroma transition, marked by an increased expression of markers of EMT.

Traditional face-bow transfer versus three-dimensional virtual reconstruction in orthognathic surgery.

Face-bow transfer is an essential step in articulator-based orthognathic surgery planning. However, it can be a source of inaccuracy. Virtual computer-based planning avoids this error through the use of direct patient-related three-dimensional imaging data. The aim of this prospective observational study was to determine the error of face-bow transfer three-dimensionally and correlate it to the different types of malocclusion. Orthognathic surgery performed on 38 patients (10 male, 28 female; mean (standard deviation) age 24.7 (6.9) years) was planned twice: first articulator-based with plaster models and second computer-based with surgery planning software. Both models were digitized and compared regarding the angle between the Frankfort horizontal plane and the occlusal plane. In most cases, the angle in the sagittal dimension was higher in the articulator-based model than in the computer-based model. The angle in the transverse dimension was as often under- as over-represented. The type of malocclusion, i.e. skeletal class, vertical relationship, and degree of asymmetry, had no significant impact on the amount of error. In conclusion, this study indicates that computer-based planning should be considered as an advantageous alternative in orthognathic surgery planning.

Continuous delivery of rhBMP2 and rhVEGF165 at a certain ratio enhances bone formation in mandibular defects over the delivery of rhBMP2 alone--An experimental study in rats.

The aim of the present study was to test the hypothesis that different amounts of vascular endothelial growth factor and bone morphogenic protein differentially affect bone formation when applied for repair of non-healing defects in the rat mandible. Porous composite PDLLA/CaCO3 carriers were fabricated as slow release carriers and loaded with rhBMP2 and rhVEGF165 in 10 different dosage combinations using gas foaming with supercritical carbon dioxide. They were implanted in non-healing defects of the mandibles of 132 adult Wistar rats with additional lateral augmentation. Bone formation was assessed both radiographically (bone volume) and by histomorphometry (bone density). The use of carriers with a ratio of delivery of VEGF/BMP between 0.7 and 1.2 was significantly related to the occurrence of significant increases in radiographic bone volume and/or histologic bone density compared to the use of carriers with a ratio of delivery of ≤ 0.5 when all intervals and all outcome parameters were considered. Moreover, simultaneous delivery at this ratio helped to "save" rhBMP2 as both bone volume and bone density after 13 weeks were reached/surpassed using half the dosage required for rhBMP2 alone. It is concluded, that the combined delivery of rhVEGF165 and rhBMP2 for repair of critical size mandibular defects can significantly enhance volume and density of bone formation over delivery of rhBMP2 alone. It appears from the present results that continuous simultaneous delivery of rhVEGF165 and rhBMP2 at a ratio of approximately 1 is favourable for the enhancement of bone formation.

Classical Alzheimer features and cholinergic dysfunction: towards a unifying hypothesis?

OBJECTIVE: Our autopsy studies show possible links between classical Alzheimer pathology and decreased expression of nicotinic acetylcholine receptors. For further elucidation we are now using in vitro models. We report preliminary evidence for the impact of beta-amyloid on nicotinic receptor expression in hippocampal dissociation culture. METHODS: Cultures (E18 rats) were grown in a serum-free medium and incubated at 8 days in vitro for 3 days with 1 microM Abeta1-42. Expression of alpha4, alpha7, and beta2 nicotinic receptor subunit protein was assessed immunohistochemically and rated semiquantitatively. RESULTS: Abeta1-42 incubation resulted in a massive reduction of alpha4 protein-expressing neurons, this effect was less pronounced for the alpha7 and beta2 subunit protein. CONCLUSION: These findings provide first evidence for a direct impact of classical Alzheimer pathology features on nicotinic receptor expression in vitro. Our model will be useful for testing the potential of drugs to stop or reverse these effects.

What is hypopnea, anyway?

Quantitation of apneas and hypopneas is routinely included in studies of epidemiology, diagnosis, and treatment of sleep-disordered breathing (SDB). The definition of apnea appears clear-cut in the sleep literature. In contrast, the literature contains remarkable variety in both recording techniques and definitions of hypopnea. The purpose of this study was to characterize the variety in the definitions and techniques used to identify hypopnea in clinical sleep laboratories. One hundred surveys were mailed to 100 accredited sleep laboratories. Each laboratory was asked to provide its criteria and equipment used to define hypopnea. Forty-five surveys (45 percent) were returned. No two laboratories used the same definition and measures of hypopnea. We conclude that there is no consensus about either recording techniques or definitions of hypopnea. Thus, epidemiologic studies and reports of interventions on SDB that do not include precise definitions of hypopnea must be interpreted with caution.

Parvalbumin-containing interneurons of the human cerebral cortex express nicotinic acetylcholine receptor proteins.

Cholinergic fibers from the basal forebrain are known to contact cholinoceptive cortical pyramidal neurons. Recent electrophysiological studies have revealed that nicotinic acetylcholine receptors are also present in human cerebrocortical interneurons. A direct visualization of nicotinic receptor subunits in cortical interneurons has, however, not yet been performed. We have applied double-immunofluorescence using antibodies against parvalbumin --a marker for the Chandelier and basket cell subpopulation of interneurons--and to the alpha4 and alpha7 subunit proteins of the nicotinic acetylcholine receptor. The vast majority of the parvalbuminergic interneurons was immunoreactive for the alpha4 and the alpha7 nicotinic acetylcholine receptor. Provided these receptors would be functional--as suggested by recent electrophysiological findings--the connectivity pattern of cholinergic afferents appears much more complex than thought before. Not only direct cholinergic impact on cortical projection neurons but also the indirect modulation of these by cholinergic corticopetal fibers contacting intrinsic cortical cells would be possible.

Expression of nicotinic acetylcholine receptors in Alzheimer's disease: postmortem investigations and experimental approaches.

Nicotinic ligand binding studies have shown rather early that the cholinoceptive system is affected in Alzheimer's disease (AD). Today, molecular histochemistry enables one to study the nicotinic acetylcholine receptor (nAChR) subunit expression on the cellular level in human autopsy brains, in animal models and in in vitro approaches, thus deciphering the distribution of nAChRs and their role as potential therapeutic targets. The studies on the nAChR expression in the frontal and temporal cortex of AD patients and age-matched controls could demonstrate that both, the numbers of alpha4- and alpha7-immunoreactive neurons and the quantitative amount, in particular of the alpha4 protein, were markedly decreased in AD. Because the number of the corresponding mRNA expressing neurons was unchanged these findings point to a translational/posttranslational rather than a transcriptional event as an underlying cause. This assumption is supported by direct mutation screening of the CHRNA4 gene which showed no functionally important mutations. To get more insight into the underlying mechanisms, two model systems organotypic culture and primary hippocampal culture - have been established, both allowing to mimic nAChR expression in vitro. In ongoing studies the possible impact of beta-amyloid (Abeta) on nAChR expression is tested. Preliminary results obtained from primary cultures point to an impaired nAChR expression following Abeta exposure.

Expression of the alpha4 isoform of the nicotinic acetylcholine receptor in the fetal human cerebral cortex.

Nicotinic acetylcholine receptors are likely to play an important role in neuronal migration during development. Furthermore, the alpha4 receptor subunit gene is related to a hereditary juvenile form of epilepsy. Only little information is available, however, on the expression of cerebrocortical nicotinic acetylcholine receptors during human fetal development. Using non-isotopic in situ hybridization and immunohistochemistry, we have studied the distribution of the alpha4 subunit of the nicotinic acetylcholine receptor mRNA and protein in the human frontal cortex at middle (17-24 weeks of gestation) and late (34-42 weeks of gestation) fetal stages. Both, alpha4 receptor mRNA and alpha4 receptor protein were observed beginning during week 17-18 of gestation. At this time of development, a few weakly labeled mRNA-containing cells were present mainly in the ventricular zone, the subplate and the cortical plate. A similar distribution pattern was found for the receptor protein. Around week 38 of gestation, the distribution in the cerebral cortex of alpha4 subunit-containing cells was similar to that of adult human cortices with the highest densities of labeled neurons found in layers II/III, followed by layers V and VI. Nicotinic acetylcholine receptor-containing neurons appear rather early in human fetal development. Given functional maturity, they may interact during cortical development with acetylcholine released from corticopetal fibers or other yet unknown sources subserving the process of neuronal migration and pathfinding.

A synthetic model for microsurgical training: a surgical contribution to reduce the number of animal experiments.

Microsurgery has grown to be an essential technique in pediatric surgery. Thus, there is an increasing need for basic training and skills maintenance, which require a continuous laboratory training. As an alternative to microsurgical exercises on living animals, a model including a simulation vein, artery and nerve is being introduced. It provides an opportunity to practice microsurgical technique with optimal availability at any time at fairly low cost. Its potentials and limits in the training of microsurgical dissection, anastomosis and quality control are being compared to experiments on anesthetized animals. Although a few exercises on living animals are mandatory to close the gap between the laboratory and the patient, a synthetic model is a valuable tool in microsurgical training and helps to reduce animal experiments.

Muscle biopsy for malignant hyperthermia screening in children.

Malignant Hyperthermia (MH) remains a life-threatening event in anaesthetic practice. In paediatric patients, triggering agents such as volatile anaesthetics and other succinylcholine are widely used. For children with a positive family history or previous clinical signs of MH, muscle biopsy for the halothane and caffeine in vitro muscle contracture tests is the only reliable procedure for diagnosis of MH susceptibility. Here we investigated outcome and compliance of patients and parents involved in the test. Twenty-four children between 6 and 14 yrs of age were admitted to hospital for biopsy. Muscle withdrawal was performed at the upper leg from lateral vastus muscle using regional or trigger-free general anaesthesia. Outcome and compliance were controlled by a telephone interview or direct physical re-evaluation. Seventeen patients out of 24 were diagnosed as clinically MH-susceptible according to the protocol of the European MH Group. Seven children were excluded as MH-negative by the test. Twenty-one children were evaluated postoperatively. Minor side effects of wound healing occurred, but none of the patients showed any abnormalities of muscle contracture or movement performance. Considering the high risk of fatal complications in the presence of MH-susceptibility, muscle biopsy of the upper leg for in-vitro diagnosis is a justified procedure that is acceptable to children and their parents.

[A new method for treating the Kirner deformity with the SM-Fix phalangeal distractor]. / Eine neue Behandlungsmethode der Kirner-Deformität mit dem SM-Fix-Phalangendistraktor.

The Kirner deformity belongs to the rare bony deformities of the small finger. The present treatments range from hemiepiphysiodesis to osteotomy with bone-grafting. We present a ten-year-old girl with a unilateral Kirner deformity treated in a new fashion. Through a distal phalanx osteotomy and the use of a SM-Fix-phalangeal distractor, bridging the distal interphalangeal joint, the axis was corrected. After four to five weeks the defect was filled by callus distraction. The advantage of this method is not only the minimal traumatisation of the juvenile distal phalanx but also the functional and cosmetic results.

The use and abuse of prescription medication to facilitate or enhance sexual behavior among adolescents.

Adolescents naturally experience an increased interest in sexual behavior, but they usually lack much experience. Thus, any prescription medication that holds the potential to ease or facilitate sexual matters holds a unique allure. Widespread cultural awareness of medications to treat erectile dysfunction (ED) has combined with a recent trend toward increased adolescent prescription drug abuse to create unique challenges for industry, clinicians, and researchers.