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Pain-related sensitization involves increases in signaling by non-nociceptive sensory neurons. This can allow non-nociceptive afferents to have access to nociceptive circuitry. In this study, we examine a form of synaptic potentiation in which nociceptor activity elicits increases in non-nociceptive synapses. This process involves endocannabinoids, “gating” the activation of NMDA receptors, which in turn activate CamKII and PKCζ. This study provides an important link in how nociceptive stimuli can enhance non-nociceptive signaling related to pain.

Objective Low-dose computed tomography (LDCT) lung cancer screening is endorsed by US guidelines and has recently been shown effective in a large European randomized controlled trial. Nevertheless, actual realization of a lung cancer screening program is challenging and depends on country-specific factors. This pilot study aimed to evaluate implementation, execution, and performance of LDCT lung cancer screening in Switzerland. Methods Since October 2018, asymptomatic participants aged 55–74 years with more than 30 pack-years smoking history were enrolled at a tertiary hospital in Switzerland. Participants with history of lung cancer, major (palliative) health problems or those that had a thorax CT scan 18 months prior to enrollment were excluded. First, we evaluated lung cancer risk according to NLST guidelines. Second, we estimated lung cancer risk using the PLCOm2012 model risk calculator with threshold of 5%. Lung nodules were assessed according to Lung-RADS (Version 1.1. 2019). Participants were recruited through flyers, a newspaper article and pulmonary specialists. Screening consisted of one LDCT-scan, follow-up was recommended for suspicious nodules only. LDCT assessment was performed by two radiologists, one of them a board certified chest radiologist. Enrollment and follow-up are currently ongoing. Results To date, 75 participants (25 (33%) females) with a median age of 62 years (interquartile range [IQR] 56–67 years) were included. Median number of pack years smoked was 49 (IQR 41–58 pack years). Median PLCOm2012 6-year lung cancer probability was 2.7% (IQR 2.6–2.9%), 19 (26%) participants had stopped smoking before enrollment. 6 participants required follow up imaging of suspect nodules, resulting in a recall rate of 8%. At baseline, lung cancer was found in 2 (2.7%, one squamous cell (stage IIIA) and one adenocarcinoma (stage IV)) participants. Conclusion In this Swiss LDCT lung cancer screening pilot study using modified inclusion criteria, 2.7% were diagnosed with lung cancer to date.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Zurich ACM Program is supported by generous grants from the Georg and Bertha Schwyzer-Winniker Foundation, the Baugarten Foundation, Swiss National Science Foundation, Swiss Heart Foundation and Wild Foundation. This work is also supported by a Canadian Institutes of Health Research grant (FRN: 162402) and the Labatt Heart Centre and Waugh Family Innovation Funds, Caitlin Elizabeth Morris Memorial Fund, Alex Corrance Memorial Foundation and Meredith Cartwright. BACKGROUND Arrhythmogenic right ventricular cardiomyopathy (ARVC) has several phenocopies such as cardiac sarcoidosis (CS), idiopathic outflow tract ventricular tachycardia (OT-VT) and myocarditis. Differentiation between these entities can be challenging. Recently, we have identified diagnostic anti-desmoglein-2 autoantibodies (anti-DSG2 Abs) in patients with ARVC. PURPOSE We sought to examine whether anti-DSG2 Abs are also present in clinical phenocopies of ARVC. METHODS Anti-DSG2 Abs in sera of 25, 19 and 22 patients with sarcoidosis, OT-VT and myocarditis, respectively, were assessed by western blots and ELISA. Clinical and imaging parameters, as well as conventional biomarkers were correlated to detected anti-DSG2 Ab intensity levels. RESULTS Anti-DSG2 Abs, at various intensities, were identified in 6/25 (24%) patients with sarcoidosis, all presenting with CS, but were absent in patients with OT-VT and myocarditis. Cardiac 18F- fluorodeoxyglucose positron emission tomography (18F-FDG PET) was positive in all sarcoidosis patients with positive anti-DSG2 Abs, corresponding to a median PET maximum standardized uptake value (SUVmax) of 5.65 [IQR: 5.15 – 10.9]. In sarcoidosis patients without anti-DSG2 Abs, the SUVmax values were significantly lower with a median of 0 [IQR: 0 – 4] (p = 0.011). The Pearson correlation coefficient (R) was 0.188 (p = 0.039) indicating a positive correlation between cardiac 18F-FDG uptake and anti-DSG2 Abs. No significant correlation was detected for any of the other clinical parameters and biomarkers. CONCLUSIONS In addition to being present in ARVC, anti-DSG2 Abs are also found in CS, a common phenocopy of ARVC; conversely, anti-DSG2 Abs are absent in idiopathic OT-VT and myocarditis. Anti-DSG2 Ab levels positively correlate with myocardial disease activity in CS as indicated by cardiac 18F-FDG PET scanning. Abstract Figure. Central illustration

Background Depression affects approximately 7.1% of the United States population every year and has an annual economic burden of over $210 billion dollars. Several recent studies have sought to investigate the pathophysiology of depression utilizing focused cerebrospinal fluid (CSF) and serum analysis. Inflammation and metabolic dysfunction have emerged as potential etiological factors from these studies. A dysregulation in the levels of inflammatory proteins such as IL-12, TNF, IL-6 and IFN-γ have been found to be significantly correlated with depression. Methods CSF samples were obtained from 15 patients, seven with major depressive disorder and eight age- and gender-matched non-psychiatric controls. CSF protein profiles were obtained using quantitative mass spectrometry. The data were analyzed by Progenesis QI proteomics software to identify significantly dysregulated proteins. The results were subjected to bioinformatics analysis using the Ingenuity Pathway Analysis suite to obtain unbiased mechanistic insight into biologically relevant interactions and pathways. Results Several dysregulated proteins were identified. Bioinformatics analysis indicated that the potential disorder/disease pathways include inflammatory response, metabolic disease and organismal injury. Molecular and cellular functions that were affected include cellular compromise, cell-to-cell signaling & interaction, cellular movement, protein synthesis, and cellular development. The major canonical pathway that was upregulated was acute phase response signaling. Endogenous upstream regulators that may influence dysregulation of proinflammatory molecules associated with depression are interleukin-6 (IL-6), signal transducer and activator of transcription 3 (STAT3), oncostatin M, PR domain zinc finger protein 1 (PRDM1), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A). Conclusions The proteome profiling data in this report identifies several potential biological functions that may be involved in the pathophysiology of major depressive disorder. Future research into how the differential expression of these proteins is involved in the etiology and severity of depression will be important.

Lung volume reduction surgery (LVRS) offers improvement in lung function, quality of life and even survival in well selected patients with severe emphysema. Patients with all types of emphysema morphology can profit from LVRS when certain selection criteria are present. Hyperinflation plays a key role in qualifying for the procedure. Candidate selection should be performed at high volume centers with a multidisciplinary emphysema board. Qualified thoracic surgeons together with pulmonologists and radiologists identify the suitable patient considering emphysema morphology with its target areas for resection, lung function parameters and cardiac comorbidities. This review outlines candidate selection, technique and results of LVRS to inform referring physicians how to screen und inform their patients.

Lung volume reduction surgery (LVRS) offers improvement in lung function, quality of life and even survival in well selected patients with severe emphysema. Patients with all types of emphysema morphology can profit from LVRS when certain selection criteria are present. Hyperinflation plays a key role in qualifying for the procedure. Candidate selection should be performed at high volume centers with a multidisciplinary emphysema board. Qualified thoracic surgeons together with pulmonologists and radiologists identify the suitable patient considering emphysema morphology with its target areas for resection, lung function parameters and cardiac comorbidities. This review outlines candidate selection, technique and results of LVRS to inform referring physicians how to screen und inform their patients.

Background: Dysfunction in the default mode network (DMN), a group of cortical areas more active during the resting state, has been linked to attentional deficits and symptoms associated with attention-deficit/hyperactivity disorder (ADHD). Prior imaging studies have shown decreased functional connectivity between DMN nodes in patients with ADHD, primarily between anterior and posterior regions. Using magnetoencephalography (MEG), we evaluated phase coherence (i.e., functional connectivity) among regions of the DMN in healthy controls and adults with ADHD before and after stimulant therapy. Methods: We obtained a resting-state MEG recording for all participants. Magnetoencephalography data were transformed into a ~30 node regional source model using inverse spatial filtering, in cluding regions corresponding to the DMN. We computed the zero-lag phase coherence between these regions pairwise for 5 distinct frequency bands, and we assessed group and medication effects. Results: Twelve adults with and 13 without ADHD participated in our study. Functional connectivity was stronger between particular node pairs and showed frequency-specific effects. Unmedicated patients showed reduced phase locking between posterior cingulate/precuneus regions (PCC) and right inferior parietal cortices (RIPL), and be tween medial prefrontal regions (MPFC) and the left inferior parietal region (LIPL) and the PCC. Unmedicated patients had increased phase locking between the RIPL and LIPL regions compared with controls. Administration of stimulants improved phase locking abnor malities along the MPFC‐PCC and LIPL‐RIPL pathways in patients with ADHD. Limitations: Modest sample size and lack of duration of patient treatment history may limit the generalizability of our findings. Conclusion: Adults with ADHD exhibit hyper- and hypoconnec tivity between regions of the DMN during rest, which were suppressed after stimulant medication administration.

In a number of large case series in the mid-1990s, lung volume reduction surgery (LVRS) was shown to reduce dyspnoea and improve pulmonary function and quality of life in patients with advanced pulmonary emphysema. The large randomised National Emphysema Treatment Trial (NETT) confirmed this in the early 2000s and also demonstrated that selected patients live longer after surgery. Patient selection is crucial to the success of the procedure and should be performed at a specialised experienced centre with a multidisciplinary team approach on emphysema treatment. The upper-lobe predominant heterogeneous type of emphysema is the best indication, but there are other types of emphysema morphology that are also eligible for surgery, if ideally chosen. Nowadays there is also growing evidence for positive effects after different types of bronchoscopic lung volume reduction (BLVR) with increasing quality. These methods add to the range of multimodal emphysema treatment.

In a number of large case series in the mid-1990s, lung volume reduction surgery (LVRS) was shown to reduce dyspnoea and improve pulmonary function and quality of life in patients with advanced pulmonary emphysema. The large randomised National Emphysema Treatment Trial (NETT) confirmed this in the early 2000s and also demonstrated that selected patients live longer after surgery. Patient selection is crucial to the success of the procedure and should be performed at a specialised experienced centre with a multidisciplinary team approach on emphysema treatment. The upper-lobe predominant heterogeneous type of emphysema is the best indication, but there are other types of emphysema morphology that are also eligible for surgery, if ideally chosen. Nowadays there is also growing evidence for positive effects after different types of bronchoscopic lung volume reduction (BLVR) with increasing quality. These methods add to the range of multimodal emphysema treatment.

Amphetamine-based medications robustly suppress symptoms of attention-deficit/hyperactivity disorder (ADHD), but their exact mechanisms remain poorly understood. Recent hemodynamic imaging studies have suggested that amphetamines may modulate the prefrontal and anterior cingulate brain regions, although few studies have been published and the results have not been entirely consistent. Meanwhile, several electrophysiological studies have shown that abnormal fast oscillations (in the γ range) may be closely linked to inattention and other cardinal symptoms of ADHD. In this study, we utilized magnetoencephalography to examine how amphetamines modulate high-frequency brain activity in adults with ADHD. Participants performed an auditory attention task, which required sustained attention in one block and passive listening in a separate block. Participants completed the task twice in the on-medication and off-medication states. All data were analyzed using beamforming techniques to resolve cortical regions showing event-related synchronizations and desynchronizations. Our primary findings indicated that oral administration of amphetamine decreased γ-band event-related desynchronization activity significantly in the medial prefrontal area and decreased event-related synchronization in bilateral superior parietal areas, left inferior parietal, and the left inferior frontal gyrus. These results suggest that psychostimulants strongly modulate γ activity in frontal and parietal cortical areas, which are known to be central to the brain's core attentional networks.

Die infektiose Endokarditis ist eine seltene Erkrankung mit hoher Morbiditat und Letalitat. Die Leitlinien der Europaischen Gesellschaft fur Kardiologie (ESC) dokumentieren und bewerten die vorhandene Evidenz und geben Empfehlungen zur Pravention, Diagnostik und Therapie der infektiosen Endokarditis fur den klinischen Alltag. Der vorliegende Beitrag enthalt eine von der Paul-Ehrlich-Gesellschaft fur Chemotherapie, der Deutschen Gesellschaft fur Kardiologie, Herz- und Kreislaufforschung und weiteren Deutschen Fachgesellschaften initiierte, kommentierte Zusammenfassung des im Jahr 2009 erschienen Updates der ESC-Leitlinien.

It is a common clinical perception that alcohol intoxication systematically lowers Glasgow Coma Scale (GCS) scores when evaluating traumatic brain injury (TBI). However, the research findings in this area do not uniformly support this notion. The purpose of this study is to examine the effects of blood alcohol level (BAL) on GCS scores following TBI.Participants were 475 patients (64% male) who presented to a Level 1 trauma centre following a TBI. Patients were selected if they were injured in a motor vehicle accident and had an available day-of-injury GCS, BAL and Computed Tomography (CT) brain scan.Overall, acute alcohol intoxication did not significantly affect GCS scores, even in patients with BALs of 200 mg dl(-1) or higher. When controlling for the effects of injury severity, acute alcohol intoxication affected GCS scores only in those patients with BALs greater than 200 mg dl(-1) who also had intracranial abnormalities detected on CT scan.These findings suggest that GCS scores can be interpreted at face value in the vast majority of patients who are intoxicated. However, GCS scores will likely over-estimate the severity of brain injury in patients with abnormal head CT scans and BALs greater than 200 mg dl(-1).

The literature pertaining to intelligence assessment reveals an ongoing discussion about the areas of intelligence captured by nonverbal tests. To date, few studies have investigated the criterion validity of the Test of Nonverbal Intelligence, Third Edition (TONI-3). The present study investigates the concurrent validity of the TONI-3 in a sample of children at an outpatient medical facility. Scores from the TONI-3 are moderately positively correlated with the Full Scale IQ of the Wechsler Intelligence Scale for Children—Fourth Edition (WISC-IV). The TONI-3 demonstrates a strong positive correlation with the Matrix Reasoning subtest of the WISC-IV. The results indicate positive relationships between the TONI-3 and measures that tap into other areas of intelligence, such as verbal abilities and processing speed. Relationships among the variables are not distinct enough to suggest specificity in terms of testing a particular ability area. Limitations and implications for intelligence assessment are discussed.

Biochemical combinatorial techniques such as phage display, RNA display and oligonucleotide aptamers have proven to be reliable methods for generation of ligands to protein targets. Adapting these techniques to small synthetic molecules has been a long-sought goal. We report the synthesis and interrogation of an 800-million-member DNA-encoded library in which small molecules are covalently attached to an encoding oligonucleotide. The library was assembled by a combination of chemical and enzymatic synthesis, and interrogated by affinity selection. We describe methods for the selection and deconvolution of the chemical display library, and the discovery of inhibitors for two enzymes: Aurora A kinase and p38 MAP kinase.

Background Despite the stabilization of match rates, negative perceptions toward general surgery are still rife among medical students. The aim of this study was to describe the attitudes of fourth-year medical students towards general surgery at a regional level. Method All fourth-year medical students in the state of Nebraska were invited to complete an online survey about their perceptions of the field of general surgery and the factors that influenced their residency choice. Results Of the 145 respondents, 10% were interested in general surgery; this result is slightly higher than the national average. The main reasons cited by those who are choosing general surgery were personal factors; the perceived adverse external factors did not influence their career choice. In contrast, students who chose nonsurgical careers did so because of external factors, such as poor lifestyle and perceptions of an unfriendly environment. Conclusions The results of this study suggested regional variations in the level of interest toward general surgery and that interest in the field among medical students in Nebraska may be higher than what has been reported nationally. Students who chose general surgery did so for personal reasons, which were independent of external factors. Recruitment efforts into the field should be focused on those students who choose non-general surgery careers and on rectifying the negative influences that steered them away from the field.

Although aphids are among the most injurious of all agronomic insect pests, much remains unknown about how their feeding alters plant physiology. Two experiments were conducted to examine the physiological responses of wheat, Triticum aestivum L. and barley, Hordeum vulgare L. to injury by Diuraphis noxia (Mordvilko) and Rhopalosiphum padi (L.) (Hemiptera: Aphididae). Gas-exchange parameters, chlorophyll fluorescence, and chlorophyll content were examined at 3, 6, and 9 days post-infestation on control and aphid (D. noxia and R. padi) infested treatments. In general, chlorophyll content and chlorophyll fluorescence parameters (non-variable minimal fluorescence, maximal fluorescence, and variable fluorescence) were not significantly affected by either aphid species. Photochemical and non-photochemical quenching coefficients were significantly impacted by both aphid species, suggesting that aphid feeding may influence the photoprotective xanthophyll cycle altering the thylakoid membrane pH gradient. Feeding by both aphid species resulted in an increase in electron transport rate, but at different time periods. Wheat plants infested with D. noxia had accelerated declines in photosynthetic capacity when compared to R. padi-infested and control plants. These plants exhibited decreased values for Amax, which was accompanied by decreased values for Vcmax and Jmax Neither aphid species negatively affected the photosynthetic capacity of the barley plants until day 9. At this time, aphid-infested plants had decreased values for Amax which was accompanied by decreased values in Jmax. Although R. padi feeding does not typically result in visual damage symptoms as previously demonstrated, clearly this aphid does have an impact on the gas-exchange and chlorophyll fluorescence of its host plants.

A 52-year-old man had a generalized seizure resulting in fracture of two vertebrae 10 years after excision of a superficially spreading melanoma (Clark level III) on the left flank. Additional to pain on pressure over the right upper abdomen, the erythrocyte sedimentation rate was increased (41 mm) and the activity of the liver enzymes was raised. Neurological examination indicated a loss of short-term memory, signs of meningeal irritation, unsteady gait and falling tendency. Cerebrospinal fluid showed mild pleocytosis and cells suspicious of tumour. Upper abdominal ultrasonography revealed an enlarged gallbladder with contents of soft-tissue density. Magnetic resonance imaging showed numerous round lesions in the brain which looked nodular after contrast-medium injection. Cholecystectomy revealed metastases of a malignant melanoma. It was likely that the cerebral lesions also represented metastases. The confusional state increased in severity. Neither cytostatic drugs nor radiotherapy were administered, because of the poor prognosis. The patient, now fully disoriented, died 54 days after hospital admission.

Some researchers have found that day-of-injury alcohol intoxication is associated with worse outcome following traumatic brain injury (TBI). The purpose of this study is to examine the effects of day-of-injury intoxication on the acute neuropsychological outcome from TBI. Participants were 36 patients with TBI (18 sober, 18 intoxicated) matched on injury severity characteristics and demographic variables. A larger group of 146 patients (112 sober, 36 intoxicated) with TBI was also selected for analyses; not matched on injury severity or demographic variables. Patients had no history of pre-injury alcoholism and were assessed within 10 days post-injury on 13 cognitive measures. Unexpectedly, patients who were sober at the time of injury performed lower on many of the cognitive measures compared to those who were intoxicated. In contrast to the research literature, these results suggest that individuals who were intoxicated at the time of injury performed similarly, and in some cases, better than those who were sober at the time of injury.

HISTORY AND CLINICAL FINDINGS A 31-year-old female with known type 1 diabetes mellitus was referred because of symptomatic hyperglycemia. On admission she was delirious and impressed with marked Kussmaul breathing. All other vital signs were normal. INVESTIGATIONS Blood serum glucose concentration was 26.4 mmol/l. Arterial blood gas analysis revealed massive metabolic acidosis (pH 6.80) with an elevated anion gap (21 mmol/l) and a marginally increased osmolar gap (21,5 mOsm/l). TREATMENT AND COURSE Despite normalization of the serum glucose and acidemia after administration of normal saline, insulin and bicarbonate, the delirium persisted, and the possibility of an additional intoxication had to be considered. Serum headspace analysis for intoxication with solvents (gas chromatography) finally detected a "ghost peak", which could not be assigned to any established substance. The same peak was, however, found in a healthy subject's serum and was found to be a "toluene peak". Toluene is contained as "contaminator" in gels in blood collection tubes. The patient gradually regained consciousness and "merely" suffered from diabetic ketoacidosis associated with cocaine use. CONCLUSION The differential diagnosis of high anion gap metabolic acidosis includes among other reasons intoxications with different kinds of solvents. When looking for solvents in the serum when poisoning is suspected (headspace analysis), only blood collection tubes without gel (EDTA plasma) should be used, because all gels contain solvents (in this case toluene).

The impact of Blissus occiduus Barber feeding on resistant ('Prestige') and susceptible ('378') buffalograsses, Buchloe dactyloides (Nuttall) Engelmann, was evaluated through measurement of carbon exchange rate, light and carbon assimilation (A-C(i)) curves, chlorophyll a fluorescence, and nonstructural carbohydrates. No significant differences in carbon exchange rates were observed between infested and control plants for 378 at 5 and 10 d after infestation; however, at 20 d after chinch bug introduction, significant differences in carbon exchange rates between infested and control 378 plants were detected. Carbon exchange rates were similar between infested and control Prestige plants at 5,10, and 20 d after infestation, suggesting that resistant plants can allocate energy for recovery from chinch bug injury. Significant differences in the photochemical efficiency of photosystem II (PSII) and the apparent photosynthetic electron transport ratio were observed between infested and control 378 plants, whereas, no significant differences in the photochemical efficiency of PSII and the electron transport ratio were detected between control and infested Prestige plants. Blissus occiduus-infested 378 and Prestige plants consistently had similar or higher levels of nonstructural carbohydrates compared with their respective control plants. These data suggest that both resistant and susceptible buffalograsses increase levels of nonstructural carbohydrates in response to B. occiduus feeding. This research also suggests compensatory photosynthesis takes place in Prestige but not in 378.

The purpose of this study was to examine the clinical application of traditional time scores and various derived indices from the Trail Making Test (TMT) in a sample of 571 patients with acute traumatic brain injury (TBI). Participants were classified into four injury severity groups. A clear linear relation between injury severity and TMT performance was demonstrated, with the more severely brain injured patients performing more poorly on most measures. Hierarchical logistic regression analysis of TMT time scores across binary extreme groups based on injury severity resulted in high classification rates for patients with very mild TBI (93.0% correctly classified) and low classification rates for patients with moderate to severe TBI (50.0% correctly classified). However, TMT derived indices did not provide a unique contribution to test interpretation beyond what is already available from Part A and B separately.

In order to promote the care of patients with COPD in Germany a national guideline clearing project was initiated jointly by autonomous corporate bodies of the German health care system. Following a systematic search of literature data bases between 1992 and 2002, 20 guidelines were identified that met the inclusion criteria and were evaluated with the German Checklist for Methodological Guideline Appraisal. Following this, a multidisciplinary expert group appointed by the German Guideline Clearinghouse (Leitlinien-Clearingstelle im Arztlichen Zentrum fur Qualitat in der Medizin, AZQ) reviewed the suitability of these guidelines for the use in the German health care system. Referring to methodological aspects, criteria were best met by the guideline of the Veteran's Health Administration/Department of Defense (US), followed by the one of the Deutsche Atemwegsliga and the Deutsche Gesellschaft fur Pneumologie. Aiming at the production respectivly a revision of a German national guideline for COPD the expert group agreed on recommendations organized in 19 chapters. Among others these strengthened the role of a precise definition of COPD based primarily on the pathogenesis, of a subtle description of all diagnostic and therapeutic tools and of a detailed description of quality assurance and quality management. The feasability of recommendations were demonstrated by examples chosen from the evaluated guidelines. Additionally the presented findings may be used as steering tools in the German Health care system.

Hintergrund und Zielsetzung: Zur Qualitatsforderung von zukunftigen Leitlinien zum Thema „Asthma bronchiale” wurde in den Jahren 2000 - 2001 ein Leitlinien-Clearingverfahren durchgefuhrt. Ziel des Verfahrens war es, die Qualitat verfugbarer Leitlinien nach den Kriterien der evidenzbasierten Medizin auf internationalem Standard zu bewerten. Die nachfolgende Darstellung fasst die inhaltliche Bewertung des Clearingverfahrens und die daraus resultierenden Eckpunkte fur Leitlinien zusammen. Erganzend wird auf methodische Aspekte verwiesen, die bei der Erstellung einer Leitlinie Beachtung finden sollten. Die zur Erstellung des Clearingberichtes benutzten Methoden wurden bereits gesondert veroffentlicht 6. Ergebnisse des Clearingverfahrens: Der Clearingbericht dient als Quelle fur eine umfassende und national gultige Leitlinie. Er kann daruber hinaus auch als Basis fur die Erstellung von regional oder lokal gultigen Leitlinien genutzt werden und bietet somit Leitlinienautoren auf allen Versorgungsebenen eine Sammlung wichtiger Informationen. Der Clearingbericht „Asthma bronchiale” fasst eine methodische und inhaltliche Analyse der zum Zeitpunkt des Verfahrens vorliegenden methodisch besten Leitlinien zusammen. Er ist Basis fur die Uberarbeitung oder Neuentwicklung von Leitlinien. Die definierten Inhalte erstrecken sich uber: (1) Ziele und Anwendungsbereich, (2) Definition des Asthma bronchiale, (3) Krankheitsursachen, (4) Formen des Asthma bronchiale, (5) Schweregrade, (6) Diagnostik/Differenzialdiagnostik, (7) Therapieziele und Grundsatze der Behandlungsstrategie, (8) Pravention, (9) Medikamentose Therapie, (10) Nicht-medikamentose Verfahren (11) Therapiekontrolle und Compliance, (12) Notfalltherapie, (13) Rehabilitation, (14) Komorbiditat, (15) Spezielle Aspekte, (16) Versorgungskoordination, (17) Qualitat der Versorgung (Qualitatsmanagement, Hinweise zur wirtschaftlichen Versorgung), (18) Implementierung. Eine deutsche Asthma bronchiale-Leitlinie, die den Qualitatskriterien des Clearingverfahrens entspricht, kann aus bestehenden Leitlinien abgeleitet werden. Background: In order to promote the quality of asthma management in Germany, a national asthma guidelines clearing project was initiated in 2000 by the German Guidelines Clearinghouse (Sponsors: German Medical Association (GMA), National Association of the Statutory Health Insurance Physicians (NASHIP), German Hospital Federation, Federal Association of the Statutory Sickness Funds. This Part shows the key topics which should be dealt with in a German guideline on bronchial asthma. Summary points: For quality promotion of bronchial asthma management in Germany, the development of a national evidence-based guideline, using the internationally accepted quality criteria for clinical practice guidelines, was recommended by an expert group of the German Guideline Clearinghouse. The experts identified and peer-reviewed 16 out of 54 guidelines, which might be useful as benchmarks and examples for a German asthma guideline. From the peer review results, the expert group identified 18 key topics for a national asthma guideline.

Apart from serologic markers structural changes of bronchi and adjacent lung tissue are key factors determining the diagnosis and course of allergic bronchopulmonary aspergillosis (ABPA). Due to problems relating to procedural hazards and radiation exposure using bronchography and computerized tomography we evaluated the efficacy of magnetic resonance imaging of the lung in ABPA. Direct comparison of high resolution computerized tomography (HR-CT) and magnetic resonance imaging (MR) in 5 patients with ABPA revealed that image resolution and data acquisition of present MR technique are insufficient to accurately delineate the extent and activity of structural damage of bronchi and adjacent lung tissue. Although major bronchiectasis may be identified, MR was unable to demonstrate even extensive patchy infiltrates seen in high resolution computerized tomography. At present, magnetic resonance imaging cannot be recommended for determining diagnosis or course of ABPA.

Background In order to promote quality of asthma management in Germany, a national asthma guidelines clearing project was initiated in 2000 by the German Guidelines Clearinghouse (Sponsors: German Medical Association (GMA), National Association of the Statutory Health Insurance Physicians (NASHIP), German Hospital Federation, Federal Association of the Statutory Sickness Funds. Part 1 of this article shows the methodology and the results of the appraisal, part 2 (to be published) shows the key topics which should be dealt with in a german guideline on bronchial asthma. Objectives To identify and compare evidence-based, high-quality German- and English language asthma guidelines as benchmarks for ongoing guideline development and implementation programmes. To disseminate information about asthma guidelines developed in accordance with current methodological know-how. To identify and consent key topics for a national evidence-based guideline for Germany. Methods Search procedure, formal appraisal: Systematic search using literature databases (XMED, incl. Medline and Embase) and English-/German-language guideline databases (via www. leitlinien.de), published between January 1990 and March 2000. Abstract screening of the search results according to the inclusion criteria (n = 54 of a total of 502 hits). Methodological guideline evaluation of 16 guidelines using the German checklist for methodological guideline appraisal. Appraisal of guidelines' contents: Peer review of guidelines with the following inclusion criteria: Bronchial Asthma-general, German and English language, based in references published later than 1994, new guideline or actual update. Peer review was performed by a multidisciplinary focus group of EBM experts (clinical and ambulatory settings). No expert was involved in guideline production during the review period. Results Methodological appraisal: 16 out of guidelines were in accordance with the formal minimal standard with a wide range within the following domains: "description of the development process", "declaration of authors' independence", "explicit link between recommendations and the supporting evidence", "management options", "tools for implementation". The focus group recommended for future national asthma guidelines to rely on the following procedures: (1) to formulate the recommendations using standardized, clearly described consensus methods basing on evidence retrieved and selected in a systematic way (2) to prove links between recommendations and supporting evidence (3) to develop guideline versions for health care professionals as well as for consumer/patients (4) to develop guideline-based education tools (5) to ensure periodical updates of the asthma guideline (6) to consider the methodological recommendations and to give reasons for deviations from the methodological recommendations. APPRAISAL OF GUIDELINES CONTENT: None of the guidelines identified comprised information about all of the following key topics considered to be relevant for a German national guideline by the focus group: (1) intended guideline users/goals, (2) definition (3) cause of disease, (4) form of disease, (5) severity, (6) diagnosis, (7) therapeutic goals, (8) prevention, (9) pharmacotherapy, (10) non-pharmacotherapy, (11) therapy control and compliance, (12) emergency treatment, (13) rehabilitation, (14) comorbidity, (15) special aspects, (16) coordination of care, (17) quality assurance/quality management, (18) implementation. Summary points For quality promotion of bronchial asthma management in Germany, the development of a national evidence-based guideline, using the internationally accepted quality criteria for clinical practice guidelines, was recommended by an expert group of the German Guideline Clearinghouse. The experts identified and peer-reviewed 16 out of 54 guidelines, which might be useful as benchmarks and examples for a German asthma guideline. From the peer review results, the expert group identified 18 key topics for a national asthma guideline.

Primary objective: Post-concussion syndrome (PCS) is a controversial diagnosis, in part because many symptoms may be present in other conditions, such as chronic pain (CP). However, direct comparisons between people with CP and mild traumatic brain injury (MTBI) are limited. The purpose of this study was to compare people with CP and MTBI on a measure of PCS symptoms. Design: Group comparison between patients with CP and MTBI on the Rivermead Post-Concussion Questionnaire (RPCQ). Methods: Sixty-three patients with CP and 32 with MTBI were evaluated at the authors' institutions. Patients completed the RPCQ as part of their initial evaluation. Results: No group differences were found for total RPCQ scores. There were some differences in the proportion of patients endorsing specific symptoms. However, most people with CP endorsed symptoms consistent with PCS. Conclusions: PCS symptoms are not unique to MTBI, and may be seen in conditions such as CP.

Molecular biomarkers are becoming increasingly significant in the workup of lung carcinoma patients. They assist in diagnosis, selecting the most adequate therapy and determining prognosis. Obtaining blood based biomarkers or volatile markers in exhaled breath may provide a less invasive method in the future. For the time being, bronchoscopy is still the method of choice to obtain specimen and assess tissue based biomarkers. The techniques how specimen are collected and processed for analysis are of paramount importance.

The ability to attend to particular stimuli while ignoring others is crucial in goal-directed activities and has been linked with prefrontal cortical regions, including the dorsolateral prefrontal cortex (DLPFC). Both hyper- and hypo-activation in the DLPFC has been reported in patients with attention-deficit/hyperactivity disorder (ADHD) during many different cognitive tasks, but the network-level effects of such aberrant activity remain largely unknown. Using magnetoencephalography (MEG), we examined functional connectivity between regions of the DLPFC and the modality-specific auditory cortices during an auditory attention task in medicated and un-medicated adults with ADHD, and those without ADHD. Participants completed an attention task in two separate sessions (medicated/un-medicated), and each session consisted of two blocks (attend and no-attend). All MEG data were coregistered to structural MRI, corrected for head motion, and projected into source space. Subsequently, we computed the phase coherence (i.e., functional connectivity) between DLPFC regions and the auditory cortices. We found that un-medicated adults with ADHD exhibited greater phase coherence in the beta (14–30 Hz) and gamma frequency (30–56 Hz) range in attend and no-attend conditions compared to controls. Stimulant medication attenuated these differences, but did not fully eliminate them. These results suggest that aberrant bottom-up processing may engulf executive resources in ADHD.

Über einen ungeklärten Mechanismus blockiert Bupropion im Zentralnervensystem Nikotinsucht und deren Abhängigkeitserscheinungen. In einer offenen Studie unterzogen sich 20 männliche und weibliche Patienten mit langjährigem Nikotinkonsum einer Raucherentwöhnung mit Bupropion über 4-8 Wochen. Eine initale Aufgabe des Nikotinkonsums gelang bei allen 20 Probanden. Nach 3 Tagen wurde eine Patientin und nach 8 Wochen wurde ein Patient rückfällig (10%). Nach insgesamt 6 Monaten waren 10 Probanden weiter komplette Nicht-Raucher geblieben. Unter Berücksichtigung amerikanischer Studien lässt auch diese Untersuchung vermuten, dass Bupropion einen viel versprechenden Ansatz in der Raucherentwöhnung darstellt.

Short forms of the Wisconsin Card Sorting Test (WCST) have been developed and studied in adult populations, however studies addressing their use in children are lacking. This study compared the full WCST to two short forms in a sample of 174 school-age children who were referred for neuropsychological evaluation. Multiple regression was used to predict standard scores (SSs) on the full WCST. Percent scores were obtained, and normative data from the WCST manual was then used to obtain SSs. We found that scores from the short forms were significantly correlated with corresponding scores on the full WCST, however a high proportion of children obtained short form SSs, which differed significantly from the SSs obtained on the full WCST. It is recommended that clinicians use the full WCST with children, unless at least four categories are reached in the first deck.