Pregabalin in acute treatment of anxious depression: A case series

Symptoms of anxiety are common in patients with depression. In this retrospective case series we investigated the effect of Pregabalin as an add-on medication in unipolar depressed patients with high levels of anxiety. The therapeutic effect of Pregabalin showed a fast onset and was comparable to the anxiolytic effect of benzodiazepines.     

Creating oral squamous cancer cells: a cellular model of oral-esophageal carcinogenesis

Immortalization and malignant transformation are important steps in tumor development. The ability to induce these processes from normal human epithelial cells with genetic alterations frequently found in the corresponding human cancer would significantly enhance our understanding of tumor development. Alterations in several key intracellular regulatory pathways (the pRB, p53, and mitogenic signaling pathways and the telomere maintenance system) appear to be sufficient for the neoplastic transformation of normal human cells. Nevertheless, in vitro transformation models to date depend on viral oncogenes, most prominently the simian virus 40 early region, to induce immortalization and malignant transformation of normal human epithelial cells. Here, we demonstrate a transformation model creating oral-esophageal cancer cells by using a limited set of genetic alterations frequently observed in the corresponding human cancer. In a stepwise model, cyclin D1 overexpression and p53 inactivation led to immortalization of oral keratinocytes. Additional ectopic epithelial growth factor receptor overexpression followed by c-myc overexpression as well as consecutive reactivation of telomerase induced by epithelial growth factor receptor sufficed to transform oral epithelial cells, truly recapitulating the development of the corresponding human disease.     

Emergence of racial/ethnic and socioeconomic differences in objectively measured sleep–wake patterns in early infancy: results of the Rise & SHINE study

Study ObjectivesTo characterize objectively assessed sleep–wake patterns in infants at approximately 1 month and 6 months and examine the differences among infants with different racial/ethnic backgrounds and household socioeconomic status (SES).MethodsFull-term healthy singletons wore an ankle-placed actigraph at approximately 1 month and 6 months and parents completed sleep diaries. Associations of racial/ethnic and socioeconomic indices with sleep outcomes were examined using multivariable analyses. Covariates included sex, birth weight for gestational age z-score, age at assessment, maternal education, household income, bed-sharing, and breastfeeding.ResultsThe sample included 306 infants, of whom 51% were female, 42.5% non-Hispanic white, 32.7% Hispanic, 17.3% Asian, and 7.5% black. Between 1 month and 6 months, night sleep duration increased by 65.7 minutes (95% CI: 55.4, 76.0), night awakenings decreased by 2.2 episodes (2.0, 2.4), and daytime sleep duration decreased by 73.3 minutes (66.4, 80.2). Compared to change in night sleep duration over this development period for white infants (82.3 minutes [66.5, 98.0]), night sleep increased less for Hispanic (48.9 minutes [30.8, 66.9]) and black infants (31.6 minutes [−5.9, 69.1]). Night sleep duration also increased less for infants with lower maternal education and household income. Asian infants had more frequent night awakenings. Adjustment for maternal education and household income attenuated all observed day and night sleep duration differences other than in Asians, where persistently reduced nighttime sleep at 6 months was observed.ConclusionsRacial/ethnic differences in sleep emerge in early infancy. Night and 24-hour sleep durations increase less in Hispanic and black infants compared to white infants, with differences largely explained by SES.     

Surgery for adult spondylolisthesis: a systematic review of the evidence

Surgery for isthmic and degenerative spondylolisthesis (SL) in adults is carried out very frequently in everyday practice. However, it is still unclear whether the results of surgery are better than those of conservative treatment and whether decompression alone or instrumented fusion with decompression should be recommended. In addition, the role of reduction is unclear. Four clinically relevant key questions were addressed in this study: (1) Is surgery more successful than conservative treatment in relation to pain and function in adult patients with isthmic SL? (2) Is surgery more successful than conservative treatment in relation to pain and function in adult patients with degenerative SL? (3) Is instrumented fusion with decompression more successful in relation to pain and function than decompression alone in adult patients with degenerative SL and spinal canal stenosis? (4) Is instrumented fusion with reduction more successful in relation to pain and function than instrumented fusion without reduction in adult patients with isthmic or degenerative SL? A systematic PubMed search was carried out to identify randomized and nonrandomized controlled trials on these topics. Papers were analyzed systematically in a search for the best evidence. A total of 18 studies was identified and analyzed: two for question 1, eight for question 2, four for question 3, and four for question 4. Surgery appears to be better than conservative treatment in adults with isthmic SL (poor evidence) and also in adults with degenerative SL (good evidence). Instrumented fusion with decompression appears to be more successful than decompression alone in adults with degenerative SL and spinal stenosis (poor evidence). Reduction and instrumented fusion does not appear to be more successful than instrumented fusion without reduction in adults with isthmic or degenerative SL (moderate evidence).     

Assessing the goodness of fit of personal risk models

We describe a flexible family of tests for evaluating the goodness of fit (calibration) of a pre‐specified personal risk model to the outcomes observed in a longitudinal cohort. Such evaluation involves using the risk model to assign each subject an absolute risk of developing the outcome within a given time from cohort entry and comparing subjects’ assigned risks with their observed outcomes. This comparison involves several issues. For example, subjects followed only for part of the risk period have unknown outcomes. Moreover, existing tests do not reveal the reasons for poor model fit when it occurs, which can reflect misspecification of the model's hazards for the competing risks of outcome development and death. To address these issues, we extend the model‐specified hazards for outcome and death, and use score statistics to test the null hypothesis that the extensions are unnecessary. Simulated cohort data applied to risk models whose outcome and mortality hazards agreed and disagreed with those generating the data show that the tests are sensitive to poor model fit, provide insight into the reasons for poor fit, and accommodate a wide range of model misspecification. We illustrate the methods by examining the calibration of two breast cancer risk models as applied to a cohort of participants in the Breast Cancer Family Registry. The methods can be implemented using the Risk Model Assessment Program, an R package freely available at http://stanford.edu/~ggong/rmap/ . Copyright © 2014 John Wiley & Sons, Ltd.     

Vergleichende Untersuchungen der Ototoxicität verschiedener antibiotischer Substanzen bei lokaler Applikation am Innenohr des Meerschweinchens

Ohne Zusammenfassung     

Sensory reinnervation of myocutaneous flaps revealed by infrared laser evoked sensations and brain potentials

The aim of this study was to examine the recovery of sensory function in myocutaneous flaps comparing 2 test methods. Eight flaps in 7 patients were examined by using clinical neurological test procedures (CNT) in comparison with psychophysics and evoked brain potentials (LEP) following infrared laser stimuli. The authors found that only 3 out of 8 flaps in 7 patients exhibited signs of reinnervation when tested with CNT. Three grades of reinnervation appeared in 7 flaps when tested with the laser. Grade 1 indicated the recovery of unmyelinated C-fiber function in 7 flaps accounting for the ability to discriminate laser intensities by different degrees of warmth. Grade 2 appeared in 3 of these flaps and was characterized by the additional ability to sense pinprick pain and the elicitation of late components of LEP mediated by thinly myelinated A delta-nociceptors. Grade 3 involved the additional sensibility for superficial touch indicating the recovery of thickly myelinated A beta-fibers noted in 2 of these flaps. The authors conclude that the LEP method is more sensitive than standard neurological test procedures to objectively document early signs of reinnervation after reconstructive flap surgery. This result is promising to investigate greater patient populations comparing different surgical techniques in future studies.     

Laser-evoked potentials: prognostic relevance of pain pathway defects in patients with acute radiculopathy

The radicular pain syndrome is a major problem in public health care that can lead to chronic back and leg pain in 30%. Ischalgia and back pain are the most prominent signs of dorsal root affection. Until now, no clinical or neurophysiological test procedure exists that evaluates the function of the dorsal root and predicts the prognosis of patients suffering from RPS. We have recently demonstrated that laser-evoked potentials (LEP) are able to demonstrate dorsal root damage. With this study, we investigated 54 patients with acute radicular symptoms and compared LEP parameters (side to side difference of latency and amplitude, transformed to a z-score) with their state of health after 3 months to calculate their predictive value for outcome prognosis. Most significantly, the latency difference between the LEP of the affected dermatome relative to the contralateral healthy dermatome was able to predict the prognosis. Latency z score above two demonstrates a 91% specificity (33% sensitivity) for a poor outcome at 3 months. A significant relation between amplitude changes and the main outcome measure could not be shown. Only extreme changes (z score >10) in amplitude show a high specificity for the persistence of ischialgia in particular (specificity 0.94; sensitivity 0.35). All other parameters, such as clinical scores or other LEP parameters, were not able to predict the outcome of patients. We propose that clinical testing using LEP with latency analysis is a useful tool for estimating the course of disease, so that patients with poor predictive parameters can be treated more invasively at early disease stages to avoid persistence of radiculopathy.