Spinal neuroplasticity in chronic pain

Neuroplastic changes play an important role in the generation and maintenance of chronic pain syndromes. Such changes occur at all levels of the neuraxis, from the peripheral terminals of primary sensory neurons to the cerebral cortex. Changes observed in the spinal dorsal horn in particular provide a mechanistic basis for many of the characteristics of chronic pain syndromes. While facilitated synaptic transmission between nociceptive fibers and spinal projection neurons contributes to enhanced perception of noxious stimuli (hyperalgesia), diminished function of GABAergic and glycinergic interneurons not only induces hyperalgesia, but also triggers nociceptive reactions on exposure to innocuous stimuli and spontaneous pain behavior in the absence of any sensory stimulation. Spinal disinhibition thus recapitulates typical symptoms of chronic pathological pain syndromes. Studies performed by various groups over the last 10years demonstrate that such spinal disinhibition occurs naturally in response to peripheral inflammation and nerve damage. The present article summarizes current status of this researc

Detection of secretory IgA antibodies against gliadin and human tissue transglutaminase in stool to screen for coeliac disease in children: validation study

Objective To evaluate two commercial stool tests for detection of secretory IgA antibodies against gliadin and human tissue transglutaminase for diagnosis of coeliac disease in children with symptoms.Setting Tertiary care children's hospital.Participants Coded stool samples from 20 children with newly diagnosed coeliac disease and 64 controls. Six children with coeliac disease had stool tests every two weeks for three months after starting a gluten-free diet.Main outcome measures Secretory IgA antibodies against gliadin and human tissue transglutaminase in stool samples, determined in duplicate by using recommended cut-off limits.Results Sensitivity of faecal antibodies against human tissue transglutaminase was 10% (95% confidence interval 1% to 32%), and specificity was 98% (91% to 100%). For antibodies against gliadin, sensitivity was 6% (0% to 29%) and specificity was 97% (89% to 100%). Optimisation of cut-off limits by receiver operating characteristic analysis and use of results of both tests increased sensitivity to 82%, but specificity decreased to 58%. All follow-up stool tests remained negative, except for two positive anti-gliadin results in one patient, six and 10 weeks after the gluten-free diet was started.Conclusions Neither stool test was suitable for screening for coeliac disease in children with symptoms

The role of critical incident monitoring in detection and prevention of human breast milk confusions

Feeding a mother's expressed breast milk to the wrong infant is a well-known misidentification error in neonatal intermediate care units (NICU) with potential harmful consequences for the neonate. In this study, we aimed to analyze the role of critical incident monitoring on detection and prevention of human breast milk confusions. The critical incident monitoring made us aware of this misidentification error on our NICU. Despite the implementation of system changes to make breast milk application clearer and safer, we failed to reduce the incidence of breast milk confusion

Subtype-selective GABAA receptor mimetics—novel antihyperalgesic agents?

Agonists at the benzodiazepine-binding site of ionotropic γ-aminobutyric acid (GABAA) receptors are in clinical use as hypnotics, anxiolytics, and anticonvulsants since the early 1960. Analgesic effects of classical benzodiazepines have occasionally been reported in certain subgroups of patients suffering from chronic pain or after spinal delivery through intrathecal catheters. However, these drugs are generally not considered as analgesics but should in fact be avoided in patients with chronic pain. Recent evidence from genetically modified mice now indicates that agents targeting only a subset of benzodiazepine (GABAA) receptors should provide pronounced antihyperalgesic activity against inflammatory and neuropathic pain. Several such compounds have been developed recently, which exhibit significant antihyperalgesia in mice and rats and appear to be devoid of the typical side-effects of classical benzodiazepine

Lippen-Kiefer-Gaumen-Spalten: Individuelle Analyse der Lippenspalte durch 3-D-Lasertopometrie

Zusammenfassung: Hintergrund: Mit Gipsmodellen und Fotografien ist die dreidimensionale Analyse einer Lippen-Kiefer-Gaumen-Spalte meist nur unzureichend möglich. Ziel der vorliegenden Studie war es daher, die 3-D-Lasertopometrie auf ihre Anwendbarkeit zur dreidimensionalen Weichgewebserfassung bei Patienten mit Lippen-Kiefer-Gaumen-Spalten zu testen. Patienten und Methode: Bei 20 Patienten (3-35 Jahre), die eine einseitige, nicht operierte Lippen-, Lippen-Kiefer- oder Lippen-Kiefer-Gaumen-Spalte aufwiesen, wurde mit einem 3-D-Laserscanner die Gesichtsoberfläche prä- und postoperativ dreidimensional erfasst. Die dabei erzeugten digitalen Datensätze wurden in einer virtuellen Umgebung metrisch analysiert und anhand von Quotienten größenunabhängig wiedergegeben. Sie dienten der Auswahl der Operationstechnik und der Beurteilung des Operationsergebnisses. Ergebnisse: Mit dem 3-D-Laserscanner wurden 3-D-Oberflächen guter Qualität erstellt, die sich im Millimeterbereich ausmessen ließen. Die dreidimensionale Spaltmorphologie konnte in den Datensätzen reproduzierbar mit Landmarks versehen und vermessen werden. Auch die postoperative Symmetrie ließ sich so kontrollieren und objektivieren. Als nachteilig erwiesen sich die relativ lange Messzeit und die Notwendigkeit zur Kombination mehrerer Ansichten. Schlussfolgerung: Das vorgestellte 3-D-Laserverfahren ermöglicht eine präzise dreidimensionale Weichteilanalyse der Lippen- und Nasenregion bei Spaltpatienten. Es eignet sich jedoch nur bedingt für lebhafte Säuglinge und unkooperative Patiente

Natural history of a medulloblastoma: 30months of wait and see in a child with a cerebellar incidentaloma

Introduction: With the increasing use of neuroimaging studies, the discovery of incidental neoplastic lesions is becoming more frequent. However, standard procedures are lacking, and little is known about their optimal management. Case Report: We here present the case of a boy with a cerebellar mass incidentally discovered on a CT scan performed after head trauma. In another scan performed after another incident of head trauma 14months earlier, the lesion could be seen after retrospective examination. In view of the asymptomatic clinical and stable radiological status and the presumed diagnosis of a low-grade glioma, a watch-and-wait strategy was elected. After clinical and radiological progression was observed, the tumour was resected, 2½ years after the initial imaging study. Histological evaluation revealed a WNT pathway-activated classical medulloblastoma. Discussion: To our knowledge, this is the first description of such a long natural history and pre-symptomatic period of a medulloblastoma. The long period of stability followed by a period of accelerated tumour growth is compatible with increasing biological aggressiveness, possibly related to the stepwise accumulation of genetic change

Synthesis, biological evaluation, and SAR studies of 14β-phenylacetyl substituted 17-cyclopropylmethyl-7, 8-dihydronoroxymorphinones derivatives : Ligands with mixed NOP and opioid receptor profile

© 2018 Kumar, Polgar, Cami-Kobeci, Thomas, Khroyan, Toll and Husbands.A series of 14β-acyl substituted 17-cyclopropylmethyl-7,8-dihydronoroxymorphinone compounds has been synthesized and evaluated for affinity and efficacy for mu (MOP), kappa (KOP), and delta (DOP) opioid receptors and nociceptin/orphanin FQ peptide (NOP) receptors. The majority of the new ligands displayed high binding affinities for the three opioid receptors, and moderate affinity for NOP receptors. The affinities for NOP receptors are of particular interest as most classical opioid ligands do not bind to NOP receptors. The predominant activity in the [35S]GTPγS assay was partial agonism at each receptor. The results are consistent with our prediction that an appropriate 14β side chain would access a binding site within the NOP receptor and result in substantially higher affinity than displayed by the parent compound naltrexone. Molecular modeling studies, utilizing the recently reported structure of the NOP receptor, are also consistent with this interpretation.Peer reviewedFinal Published versio

Geographic information systems and logistic regression for high-resolution malaria risk mapping in a rural settlement of the southern Brazilian Amazon

BACKGROUND: In Brazil, 99% of the cases of malaria are concentrated in the Amazon region, with high level of transmission. The objectives of the study were to use geographic information systems (GIS) analysis and logistic regression as a tool to identify and analyse the relative likelihood and its socio-environmental determinants of malaria infection in the Vale do Amanhecer rural settlement, Brazil. METHODS: A GIS database of georeferenced malaria cases, recorded in 2005, and multiple explanatory data layers was built, based on a multispectral Landsat 5 TM image, digital map of the settlement blocks and a SRTM digital elevation model. Satellite imagery was used to map the spatial patterns of land use and cover (LUC) and to derive spectral indices of vegetation density (NDVI) and soil/vegetation humidity (VSHI). An Euclidian distance operator was applied to measure proximity of domiciles to potential mosquito breeding habitats and gold mining areas. The malaria risk model was generated by multiple logistic regression, in which environmental factors were considered as independent variables and the number of cases, binarized by a threshold value was the dependent variable. RESULTS: Out of a total of 336 cases of malaria, 133 positive slides were from inhabitants at Road 08, which corresponds to 37.60% of the notifications. The southern region of the settlement presented 276 cases and a greater number of domiciles in which more than ten cases/home were notified. From these, 102 (30.36%) cases were caused by Plasmodium falciparum and 174 (51.79%) cases by Plasmodium vivax. Malaria risk is the highest in the south of the settlement, associated with proximity to gold mining sites, intense land use, high levels of soil/vegetation humidity and low vegetation density. CONCLUSIONS: Mid-resolution, remote sensing data and GIS-derived distance measures can be successfully combined with digital maps of the housing location of (non-) infected inhabitants to predict relative likelihood of disease infection through the analysis by logistic regression. Obtained findings on the relation between malaria cases and environmental factors should be applied in the future for land use planning in rural settlements in the Southern Amazon to minimize risks of disease transmission

3D Surface Measurement for Medical Application—Technical Comparison of Two Established Industrial Surface Scanning Systems

In 3D mapping of flexible surfaces (e.g. human faces) measurement errors due to movement or positioning occur. Aggravated by equipment- or researcher-caused mistakes considerable deviations can result. Therefore first the appliances' precision handling and reliability in clinical environment must be established. Aim of this study was to investigate accuracy and precision of two contact-free 3D measurement systems (white light vs. laser). Standard specimens of known diameter for sphere deviation, touch deviation and plane deviation were tested. Both systems are appropriate for medical application acquiring solid data (<mm). The more complex white-light system shows better accuracy at 0.2s measuring time. The laser system is superior concerning robustness, while accuracy is poorer and input time (1.5-2.5s) longer. Due to the clinical demand the white-light system is superior in a laboratory environment, while the laser system is easier to handle under non-laboratory condition

Three-dimensional cephalometric evaluation of maxillary growth following in utero repair of cleft lip and alveolar-like defects in the mid-gestational sheep model

Objective: To evaluate maxillary growth following in utero repair of surgically created cleft lip and alveolar (CLA)-like defects by means of three-dimensional (3D) computer tomographic (CT) cephalometric analysis in the mid-gestational sheep model. Methods: In 12 sheep fetuses a unilateral CLA-like defect was created in utero (untreated control group: 4 fetuses). Four different bone grafts were used for the alveolar defect closure. After euthanasia, CT scans of the skulls of the fetuses, 3D re-constructions, and a 3D-CT cephalometric analysis were performed. Results: The comparisons between the operated and nonoperated skull sides as well as of the maxillary asymmetry among the experimental groups revealed no statistically significant differences of the 12 variables used. Conclusions: None of the surgical approaches used for the in utero correction of CLA-like defects seem to affect significantly postsurgical maxillary growth; however, when bone graft healing takes place, a tendency for almost normal maxillary growth can be observed. Copyright (c) 2006 S. Karger AG, Basel