Search

Zusammenfassung Hintergrund Positive Effekte von achtsamkeitsbasierten Programmen im Kontext Schule wurden bereits vielfältig belegt. Das in dieser Studie evaluierte Konzept Achtsamkeit in der Schule (AISCHU) richtet sich an Lehrkräfte und SchülerInnen und soll deren Stresswahrnehmung und Selbstregulationsfähigkeit schulen. Im Fokus dieser explorativen Studie steht erstmals der präventive Nutzen der AISCHU-Weiterbildung für Lehrkräfte und deren psychische Gesundheit. Methodik Etablierte Messinstrumente bezüglich Stresserleben (PSQ), Burn-out-Gefährdung („Tedium measure“ (TM)), Wohlbefinden (WHO-5) und Achtsamkeit (FFA, MAAS) wurden im Prä-Post-Vergleich eingesetzt. Die Daten beziehen sich auf 36 Lehrkräfte unterschiedlicher Schulformen. Ergebnisse Es ergaben sich hinsichtlich aller untersuchten Messgrößen signifikante Verbesserungen mit z. T. großen Effektstärken. Schlussfolgerung In dieser explorativen Pilotstudie zu AISCHU für Lehrkräfte konnten erstmals vielversprechende Hinweise auf die Wirksamkeit im Sinne von Stressreduzierung, Burn-out-Risikominimierung sowie Verbesserung der Lebensqualität bei belasteten LehrerInnen beobachtet werden.

The COVID-19 pandemic challenges hospital clinicians by additional burdens. Key questions are whether hospital clinicians have experienced more stress in the care of COVID-19 patients and whether patient safety and quality of care have changed.Cross-sectional study using an online survey with clinicians in German hospitals on working conditions and quality of care during the COVID-19 pandemic, comparing clinicians with (MmK) vs. without direct contact (MoK) to COVID-19 patients.In total, 2122 clinicians participated. Most clinicians were physicians (15.4%, n = 301) or nurses (77.0%, n = 1505) working in major acute care hospitals (46.0%, n = 899). Every second respondent stated that they worked more than usual (46.4%, n = 907) and took on additional activities (47.7%, n = 932). A quarter of the participants did not receive any training or get instructions in devices (21.5%, n = 421). Only 51.5% (n = 1006) of the respondents were provided with sufficient personal protective equipment. More than 30% (32.7%, n = 639) were more satisfied than usual. The comparing clinicans with vs. without direkt contact to Covid-19 patients worked more shifts than usual ( 2 shifts: 24.1%, n = 306 vs. 13.7%, n = 63, p 0.001) and without instruction (27.9%, n = 364 vs. 17.1%), n = 57, p 0.001). In terms of patient safety, there were more deficiencies in the care, mechanical ventilation and nursing (all p 0.001).The cross-sectional study indicates an increased burden on clinicians and a restricted quality of care for patients with COVID-19. A risk to patients or clinicians cannot be excluded.HINTERGRUND: Die COVID-19-Pandemie stellt Mitarbeiter im Kontext der klinischen Versorgung stationärer Patienten vor zusätzliche Belastungen. Zentrale Fragen sind, ob Gesundheitspersonal in der Versorgung von COVID-19-Patienten mehr Belastungen erlebt und die Patientensicherheit und Versorgungsqualität sich verändert haben.Querschnittsstudie mittels einer Online-Umfrage von Ärzten, Pflegenden, Therapeuten in Krankenhäusern zu Arbeitsbedingungen und Versorgungsqualität während der COVID-19-Pandemie sowie Vergleich von Mitarbeitern mit (MmK) vs. ohne direkten Kontakt (MoK) mit infizierten COVID-19-Patienten.Insgesamt nahmen 2122 Personen an der Online-Umfrage teil. Die meisten Teilnehmer arbeiteten in Maximalversorgern (46,0 %, n = 899), waren Ärzte (15,4 %, n = 301) und Pflegende (77,0 %, n = 1505). Jeder zweite Befragte gab an, mehr als sonst gearbeitet (46,4 %, n = 907) und zusätzliche Tätigkeiten übernommen (47,7 %, n = 932) zu haben, ein Viertel ohne Einarbeitung bzw. Geräteeinweisung (21,5 %, n = 421). Lediglich 51,5 % (n = 1006) der Befragten wurde ausreichend Schutzkleidung gestellt. Ein Drittel (32,7 %, n = 639) war mehr als sonst zufrieden. Mitarbeiter mit vs. ohne direkten Kontakt mit infizierten Covid-19 Patienten gaben mehr Belastungen an, es wurde mehr ( 2 Schichten: 24,1 %, n = 306 vs. 13,7 %, n = 63, p 0,001) und ohne Einweisung (27,9 %, n = 364 vs. 17,1 %, n = 57, p 0,001) gearbeitet; in der Patientensicherheit gab es mehr Mängel in der Betreuung, Beatmung und Pflege (alle p 0,001).Die Querschnittsstudie weist auf eine erhöhte Belastung der Mitarbeiter hin, sowie auf eine eingeschränkte Versorgungsqualität von mit COVID-19 infizierten Patienten. Eine Patienten- bzw. Mitarbeitergefährdung kann nicht ausgeschlossen werden.

To evaluate a) the magnitude of the increase in caloric consumption due to early mobilisation of patients with mechanical ventilation (MV) in Intensive Care Units (ICU) as part of routine care, b) whether there are differences in caloric consumption due to active or passive mobilisation, and c) whether early mobilisation in routine care would lead to additional nutritional requirements.Prospective, observational, multi-centre study.Medical, surgical and neurological ICUs from three centres.Patients on MV in ICU who were mobilised out of bed as part of routine care.Caloric consumption was assessed in 66 patients by indirect calorimetry at six time points: (1) lying in bed 5-10 min prior to mobilisation, (2) sitting on the edge of the bed, (3) standing beside the bed, (4) sitting in a chair, (5) lying in bed 5-10 min after mobilisation, and (6) 2 h after mobilisation. Differences in caloric consumption in every mobilisation level vs. the baseline of lying in bed were measured for 5 min and found to have increased significantly by: +0.4 (Standard Deviation (SD) 0.59) kcal while sitting on the edge of the bed, +1.5 (SD 1.26) kcal while standing in front of the bed, +0.7 (SD 0.63) kcal while sitting in a chair (all p 0.001). Active vs. passive transfers showed a higher, but non-significant consumption. A typical sequence of mobilisation including sitting on edge of the bed, standing beside the bed, sitting in a chair (20 min) and transfer back into bed, would require an additional 4.56 kcal compared to caloric consumption without mobilisation.Based on this data, routine mobilisation of MV patients in ICU increases caloric consumption, especially in active mobilisation. Nevertheless, an additional caloric intake because of routine mobilisation does not seem to be necessary.

ZusammenfassungEin postoperatives Delir (POD) geht mit einem hohen Leidensdruck für die betroffenen Patienten und ihre Angehörigen und einem großen Mehraufwand für das klinische Personal einher. Darüber hinaus belasten die entstehenden Kosten erheblich das Gesundheitssystem. Der Beitrag beleuchtet die Optionen der Risikoreduktion in der postoperativen Versorgung, um ein POD und eine postoperative neurokognitive Störung zu vermeiden.

Background Anaesthesia is neurotoxic in developing primates. Retrospective clinical studies show a correlation between exposure to anaesthesia during infancy and the occurrence of learning disorders (LD). Prospective studies failed to detect any influence of a single exposure to anaesthesia on neurodevelopment. We hypothesised that some specific populations of children were electively sensitive to anaesthesia-related neurotoxicity. Methods Using a case-control design, we analysed the medical histories of children with LD, compared to those of their normally reading siblings. Interviews were conducted and medical records were reviewed. The numbers of hospitalisations and anaesthesia exposures before the age of five years were determined. Results Four hundred fourteen dyslexic children were screened over a one-year period. Two hundred and seventy patients were excluded due to confounding variables (single child, all siblings showing LD or any condition placing the neurological prognosis at risk (N = 107/414 for the latter)) or inability to accurately collect evaluation criteria. In the 144 case-control pairs studied, the mean number of hospitalisations was significantly different (N = 1.097 ± 0 .135/case versus 0.667 ± 0.097/control, p = 0.0052), as was the proportion of hospitalised patients (54.2% versus 38.9%, p = 0.0031). The mean number of anaesthesia exposures per individual was not statistically different (N = 0.958 ± 0.183/case versus 0.569 ± 0.107/control, p = 0.0732), but the proportion of children anaesthetised at least once was (43.8% (cases) versus 33.3% (controls), p = 0.0301). Discussion One or more hospitalisation(s) may reflect a health status and/or have an iatrogenic effect disrupting the normal setting up of learning abilities. Anaesthesia may play a role, but a correlation between LD and anaesthesia is of a lower magnitude than between LD and hospitalisation.

Die pflegerische und medizinische Versorgung wird immer komplexer. Dies gilt insbesondere fur die Intensivpflege. Die Anzahl der Intensivbetten hat sich zwischen 2002 und 2012 von 23.113 Betten auf 26.162 Betten erhoht. Gleichermasen sind in dem Zeitraum von 2002 bis 2010 die Behandlungsfalle auf Intensivstationen um 148.989 auf 2.049.888 gestiegen. Die zunehmende Komplexitat erfordert eine qualitative Weiterentwicklung pflegerischer Versorgung auf der Grundlage von Advanced Nursing Practice (ANP), die sich auch auf die Spezialisierung in der Intensivpflege (ANP–Critical Care) bezieht. Pflegeexperten auf der Grundlage von ANP definieren sich aus der Fahigkeit, komplexe gesundheitliche Versorgungssituationen in eigener Verantwortung bewaltigen zu konnen. Dies beinhaltet eigene pflegerische Entscheidungsbereiche z. B. im Beatmungs- und Weaningprozess, im Ernahrungsmanagement, im Delir‑, Wund- und Schmerzmanagement. Durch die Spezialisierung wird den Pflegeexperten ein eindeutig formulierter, eigenstandiger Kompetenz- und Aufgabenbereich zugeordnet. Wissenschaftliche Inhalte und Leitlinien gelangen somit gezielt in die Praxis und konnen direkt umgesetzt werden. Die DGF fordert in ihrem Positionspapier eine wissenschaftliche Weiterentwicklung der Intensivpflege auf Masterniveau im Sinne von ANP–Critical Care. Damit verbunden ist die Forderung nach erweiterten Kompetenzen, die die Ubertragung heilkundlicher Tatigkeiten in Orientierung an den Inhalten des internationalen Intensivpflegekompetenzrahmens der European federation of Critical Care Nursing Associations (EfCCNa) miteinschliesen.

Hygiene und Sicherheit des Patienten mussen bei der Nutzung von Smartphones im Vordergrund stehen. Die Nutzung von Smartphones und Tablets mit der dazugehorenden Software sollte daher im Unterricht thematisiert und sinnvolle und praktikable Losungen (z.B. die Nutzung der Gerate im Flugmodus) von Lernenden und Lehrenden gemeinsam vereinbart werden. Ein Verbot ist weder zeitgemas noch zielfuhrend. Die Generationen gehen unterschiedlich mit der Verwendung von personlichen Kommunikationsgeraten bei der Arbeit um und unterscheiden sich in der Einschatzung uber die Auswirkungen dieser Gerate auf die Patientenversorgung. Professionelle Verhaltenskodizes fur die Verwendung von personlichen oder vom Arbeitgeber zur Verfugung gestellten Kommunikationsgerate durch Mitarbeiter im Krankenhaus mussen entwickelt und verbindlich vereinbart werden, um die Vorteile der Verwendung von Kommunikationsgeraten zu maximieren und gleichzeitig das Potenzial einer Ablenkung und nachteilige Ergebnisse oder Risiken zu reduzieren.

Background: Skeletal muscle lacerations are a relatively common injury. Compared with nonrepaired lacerations, surgically repaired muscle lacerations regenerate faster, develop less scar tissue, have a higher return to baseline strength, and have lower incidence of hematomas. Despite the benefits of repair, the optimal repair technique is still unknown. The purpose of this study was to examine the biomechanical properties of common muscle repair techniques to determine the optimal repair. Methods: Forty-two fusiform porcine muscle specimens were dissected and used for this study. Three suture techniques were used for comparative analysis: Figure-eight, Mason Allen, and Perimeter. Each muscle was transected and then repaired using one of the 3 techniques. Fourteen muscle-tendon specimens were prepared for each group and tested for tensile failure using a material testing system. Biomechanical properties, including peak failure point and stiffness, were compared for differences between the suture groups by 1-way analysis of variance. The average time per repair technique was also recorded. Results: The Perimeter technique showed a statistically significant higher peak failure point than the Mason Allen technique ( P = .03). Both the Figure-eight ( P = .047) and Perimeter techniques ( P < .001) were significantly stiffer than the Mason Allen technique. The repair time was comparable across all 3 techniques. Conclusions: The Figure-eight and Perimeter repairs were found to be similar in peak failure point and stiffness, whereas the Mason Allen technique showed significantly lower stiffness and peak failure point. The Figure-eight was the quickest repair to perform. The Figure-eight technique may be strongly considered for muscle laceration repairs due to its simplicity and efficiency.

Die Immobilitat von Patienten auf Intensivstation kann zu nachhaltigen physischen und kognitiven Nachteilen fuhren. In den letzten Jahren wurden Masnahmenbundel zur Rehabilitation entwickelt, die u. a. auch die Fruhmobilisierung beinhalten. Die deutsche Leitlinie zur Lagerungstherapie und Fruhmobilisierung empfiehlt allgemein die Entwicklung stationsspezifischer Protokolle. Ziel dieser narrativen Ubersichtsarbeit ist es, Empfehlungen zur Entwicklung eines Best-Practice-Protokolls im eigenen Arbeitsbereich zu geben. Es wird empfohlen, a) Fruhmobilisierung als Teil eines Masnahmenbundels unter Einbeziehung von regelmasigem Screening und Management von Wachheit, Schmerz, Angst, Stress, Delir sowie der Gegenwart der Familie umzusetzen, b) spezifische Ein- und Ausschlusskriterien mithilfe eines Ampelsystems fur die zu behandelnde Populationen in einem interprofessionellen Prozess zu entwickeln, c) Checklisten zur Risikoeinschatzung und Vorbereitung der Mobilisierung zu verwenden, d) die ICU Mobility Scale zur Zielsetzung und Dokumentation der Mobilisierung zu nutzen, e) relative Sicherheitskriterien fur hamodynamische und respiratorische Veranderung sowie die Borg-Skala fur eine subjektive Evaluation zu verwenden, f) die Mobilisierung sowie Barrieren, unerwunschte Sicherheitsereignisse und andere Parameter systematisch zu dokumentieren und zu evaluieren.

Early mobilization of patients in the intensive care unit (ICU) is safe, feasible, and beneficial. However, implementation of early mobility as part of routine clinical care can be challenging. The objective of this review is to identify barriers to early mobilization and discuss strategies to overcome such barriers. Based on a literature search, we synthesize data from 40 studies reporting 28 unique barriers to early mobility, of which 14 (50%) were patient-related, 5 (18%) structural, 5 (18%) ICU cultural, and 4 (14%) process-related barriers. These barriers varied across ICUs and within disciplines, depending on the ICU patient population, setting, attitude, and ICU culture. To overcome the identified barriers, over 70 strategies were reported and are synthesized in this review, including: implementation of safety guidelines; use of mobility protocols; interprofessional training, education, and rounds; and involvement of physician champions. Systematic efforts to change ICU culture to prioritize early mobilization using an interprofessional approach and multiple targeted strategies are important components of successfully implementing early mobility in clinical practice.

Ischemic conditioning is defined as a transient and subcritical period of ischemia integrated in an experimental paradigm that involves a stimulus of injurious ischemia, activating endogenous tissue repair mechanisms that lead to cellular protection under pathological conditions like stroke. Whereas ischemic pre-conditioning is irrelevant for stroke treatment, ischemic post-conditioning, and especially non-invasive remote ischemic post-conditioning (rPostC) is an innovative and potential strategy for stroke treatment. Although rPostC has been shown to induce neuroprotection in stroke models before, resulting in some clinical trials on the way, fundamental questions with regard to its therapeutic time frame and its underlying mechanisms remain elusive. Hence, we herein used a model of non-invasive rPostC of hind limbs after cerebral ischemia in male C57BL6 mice, studying the optimal timing for the application of rPostC and its underlying mechanisms for up to 3 months. Mice undergoing rPostC underwent three different paradigms, starting with the first cycle of rPostC 12 h, 24 h, or 5 days after stroke induction, which is a very delayed time point of rPostC that has not been studied elsewhere. rPostC as applied within 24 h post-stroke induces reduction of infarct volume on day three. On the contrary, very delayed rPostC does not yield reduction of infarct volume on day seven when first applied on day five, albeit long-term brain injury is significantly reduced. Likewise, very delayed rPostC yields sustained neurological recovery, whereas early rPostC (i.e.

Levamisole-contaminated cocaine toxicity is a serious emerging public health concern, and providers should be aware of its presentation and management. Most cases of levamisole-induced vasculitis/vasculopathy (LIV) are associated with high antineutrophil cytoplasmic antibodies (ANCA). We describe a unique case of a cocaine user who presented with an acute purpuric eruption and negative ANCA laboratory findings. A brief clinical overview of LIV, spanning from patient presentation to treatment, is provided. In addition, we present a summary of all cases of ANCA-negative vasculitis identified via a PubMed literature review.

Supplemental Digital Content is available in the text., Background and Purpose— Poststroke, neuronal excitability is tonically reduced in peri-infarct tissue via inhibitory influences of extrasynaptic GABAA receptors. We hypothesized that GABAA α5 blockade by the competitive antagonist S44819 enhances postischemic neurological recovery, brain remodeling, and neuroplasticity. Methods— In an explorative study followed by a confirmation study, male C57Bl6/j mice were exposed to transient intraluminal middle cerebral artery occlusion. Starting 72 hours poststroke, vehicle or S44819 (3 or 10 mg/kg, BID) was delivered orally for 28 days. Neurological recovery, perilesional tissue remodeling, and contralesional pyramidal tract plasticity were evaluated for 42 days, that is, 14 days after completion of S44819 delivery. Results— S44819, delivered at 10 but not 3 mg/kg, persistently improved motor coordination and spatial memory in both studies. Striatal atrophy was reduced by 10 mg/kg S44819 at 42 days post-treatment onset, and neuronal long-term survival in the peri-infarct striatum was increased. Delayed neuroprotection was associated with reduced peri-infarct astrogliosis, increased peri-infarct brain capillary density, and increased neural precursor cell proliferation and differentiation in proximity to the ipsilesional subventricular zone. Contralesional pyramidal tract plasticity, evaluated by anterograde tract tracing at the level of the red nucleus, was not influenced by S44819. Concentrations of neurotrophic (brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor) and angiogenic (vascular endothelial growth factor and basic fibroblast growth factor) growth factors were elevated by 10 mg/kg S44819 in peri-infarct but not contralesional brain tissue. Conclusions— Our data demonstrate that S44819 enhances neurological recovery and peri-infarct brain remodeling in the postacute stroke phase.

Intensivmedizinische Versorgungsprozesse sind durch ein hohes Mas an Komplexitat gekennzeichnet und erfordern eine transparente Kommunikationskultur und engagierte Zusammenarbeit auf interdisziplinarer und multiprofessioneller Ebene. Um in diesem Umfeld qualitativ hochwertig zu arbeiten und Fehler bestmoglich zu vermeiden, sind ein proaktives Qualitats- und Fehlermanagement und eine strukturierte Qualitatssicherung von unverzichtbarer Bedeutung. Seit den fruhen 1990er-Jahren wurden Konzepte zum Qualitatsmanagement und zur Qualitatssicherung in der Intensivmedizin entwickelt. Zielsetzung von gegrundeten Netzwerken ist es, unterstutzend evidenzbasierte Erkenntnisse in den klinischen Alltag zu implementieren, um die medizinische Ergebnisqualitat, Effektivitat und Effizienz in der Intensivmedizin zu steigern. Zu den aktuellen Instrumenten und Konzepten der Qualitatssicherung in der Intensivmedizin in Deutschland zahlen der Kerndatensatz Intensivmedizin mit dem Datenregister DIVI-REVERSI, intensivmedizinische Qualitatsindikatoren, Peer Review in der Intensivmedizin, IQM Peer Review und unterschiedliche Zertifizierungsverfahren, die inzwischen auch ein speziell fur die Intensivmedizin ausgerichtetes Verfahren umfassen. Eine erste Version der intensivmedizinischen Qualitatsindikatoren fur Deutschland wurde bereits im Jahr 2010 von einer interdisziplinaren und interprofessionellen Expertenkommission publiziert. Mithilfe von Kennzahlen, Indikatoren und nationalen Benchmarks soll die Qualitat von Strukturen, Prozessen und Ergebnissen in der intensivmedizinischen Versorgung beschrieben werden. Insgesamt haben sich viele dieser Qualitatssicherungssysteme in der klinischen Versorgungspraxis bewahrt, auch wenn die flachendeckende Umsetzung noch verbessert werden kann.

Background Early mobilization is an evident, interprofessional concept to improve the outcome of intensive care patients. It reduces psychocognitive deficits and delirium and attenuates a general deconditioning, including atrophy of the respiratory pump and skeletal muscles. In this regard the interdisciplinary approach of early mobilization, taking into account different levels of mobilization, appears to be beneficial. The purpose of this study was to explore opinions on collaboration and tasks between different professional groups. Method During the 25th Bremen Conference on Intensive Medicine and Nursing on 20 February 2015, a questionnaire survey was carried out among the 120 participants of the German Early Mobilization Network meeting. Results In all, 102 questionnaires were analyzed. Most participants reported on the interdisciplinarity of the approach, but none of the tasks and responsibilities concerning early mobilization can be assigned to a single professional group. The practical implementation of mobilizing orally intubated patients may require two registered nurses as well as a physical therapist. Implementation in daily practice seems to be heterogeneous. Conclusions There is no consensus regarding collaboration, competencies, and responsibilities with respect to early mobilization of intensive care patients. The approach to date has been characterized by a lack of interprofessional communication, which may lead to an inefficient use of the broad and varied base of knowledge and experienceof the different professions.

Objective Polycystic ovary syndrome (PCOS) is a complex disease, the aetiology of which is not well understood. Alterations in potential candidate genes involved in the biosynthesis and metabolism of androgens, folliculogenesis and insulin and glucose metabolism have been suggested as possible aetiologies. Dipeptidyl peptidase-4 (DPP4) plays a key role in glucose homoeostasis and, thus, in the regulation of insulin secretion. The aim of our study was to analyse the DPP4 activity and concentrations in the serum of PCOS and non-PCOS patients and, additionally, study the activation of the DPP4 promoter by androgens in vitro. Design, patients and measurements Serum samples were obtained from 288 female patients treated at the Center for Reproductive Medicine and Andrology (154 non-PCOS and 134 patients with PCOS). DPP4 activity was measured by the conversion of the DPP4 substrate Gly-Pro p-nitroanilide hydrochloride and DPP4 concentration with a commercial ELISA. Luciferase reporter assays, qPCR and Western Blot analyses were performed for the in vitro evaluation of the activation of the DPP4 promoter by androgens. Results DPP4 serum activity was increased in women with PCOS, regardless of which Rotterdam criteria led to the PCOS diagnosis. Furthermore, DPP4 serum levels were strongly correlated with the anti-Mullerian hormone (AMH) serum level. In vitro, the DPP4 promoter was stimulated by androgens in luciferase reporter assays, and DPP4 mRNA expression was increased in KGN granulosa carcinoma cells after androgen treatment. Conclusions The results suggested that a deregulation of DPP4 serum levels could be an additional characteristic of the metabolic imbalances associated with PCOS.

WOS: 000409039000026 PubMed ID: 27699598 In view of the failure of pharmacological therapies, alternative strategies promoting post-stroke brain repair are needed. Post-conditioning is a potentially promising therapeutic strategy, which induces acute neuroprotection against ischemic injury. To elucidate longer lasting actions of ischemic post-conditioning, mice were exposed to a 60-min stroke and post-conditioning by an additional 10-min stroke that was induced 10 min after reperfusion onset. Animals were sacrificed 24 h or 28 days post-stroke. Post-conditioning reduced infarct volume and neurological deficits 24 h poststroke, enhancing blood-brain barrier integrity, reducing brain leukocyte infiltration, and reducing oxidative stress. On the molecular level, post-conditioning yielded increased Hsp70 expression, whereas nuclear factor (NF)-kappa B and proteasome activities were decreased. Reduced infarct volume and proteasome inhibition were reversed by Hsp70 knockdown, suggesting a critical role of the Hsp70 proteasome pathway in ischemic post-conditioning. The survival-promoting effects of ischemic post-conditioning, however, were not sustainable as neuroprotection and neurological recovery were lost 28 days post-stroke. Although angioneurogenesis was not increased by post-conditioning, the favorable extracellular milieu facilitated intracerebral transplantation of neural progenitor cells 6 h post-stroke, resulting in persisted neuroprotection and neurological recovery. Thus, post-conditioning might support brain repair processes, but in view of its transient, neuroprotection is unlikely useful as stroke therapy in its current form. TUBITAK [2221] The study was supported by TUBITAK (grant no. 2221 to TRD).

WOS: 000394964100059 PubMed ID: 26860410 Adult neural progenitor cells (NPCs) induce post-ischemic long-term neuroprotection and brain remodeling by releasing of survival- and plasticity-promoting mediators. To evaluate whether secreted factors may mimic neuroprotective and restorative effects of NPCs, we exposed male C57BL6 mice to focal cerebral ischemia and intravenously applied conditioned medium (CM) derived from subventricular zone NPCs. CM dose-dependently reduced infarct volume and brain leukocyte infiltration after 48 h when delivered up to 12 h after focal cerebral ischemia. Neuroprotection persisted in the post-acute stroke phase yielding enhanced neurological recovery that lasted throughout the 28-day observation period. Increased Bcl-2, phosphorylated Akt and phosphorylated STAT-3 abundance, and reduced caspase-3 activity and Bax abundance were noted in ischemic brains of CM-treated mice at 48 h post-stroke, indicative of enhanced cell survival signaling. Long-term neuroprotection was associated with increased brain glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF) concentrations at 28 days resulting in increased neurogenesis and angiogenesis. The observation that NPC-derived CM induces sustained neuroprotection and neurological recovery suggests that cell transplantation may be dispensable when secreted factors are instead administered. TUBITAK [2221]; German Research Council [HE3173/2-2, HE3173/3-1] The present study was supported by TUBITAK (#2221; to TRD) and the German Research Council (HE3173/2-2 and HE3173/3-1; to DMH).

Background The pectoralis major typically is manipulated for implant coverage and pocket design in subpectoral breast augmentation. An understanding of its anatomy can guide successful creation of the implant pocket. Objectives The authors evaluated the anatomy of the sternal origin of the pectoralis major to inform surgical planning, help establish a technique for subpectoral augmentation mammaplasty, and identify the most common locations of perforators. Methods The sternal origins of 24 pectoralis major muscles were dissected and examined in 15 female cadavers to determine the structure and width of the pectoralis major sternal origin and its relationship to the locations of internal mammary perforators. Results The average width of the sternal origin of the pectoralis major was 7.1 mm (range, 3 mm-1.8 cm). This width decreased slightly from the second rib to the second intercostal space and then increased progressively in the caudal direction toward the fifth rib. The sternal origin terminated an average of 5.4 mm (range, 1-16 mm) from the midline, with the greatest distance at the fifth rib and large variability throughout. A row of perforators from the internal mammary artery traversed the subpectoral space an average of 2.7 cm from the midline (range, 1-3.7 cm). Conclusions The sternal origin of the pectoralis major was thin and highly variable, suggesting that its partial release for implant medialization during subpectoral augmentation is unsafe.

Bei Intensivpatienten mit Stuhlinkontinenz besteht ein hohes Infektionsrisiko fur Haut, Weichteile, Harnwege sowie fur allgemein nosokomiale Infektionen. Dabei hat sich die Behandlung und Pflege inzwischen grundlegend geandert. Warum traditionelle Versorgungsmasnahmen nicht mehr empfohlen werden und welche Strategien heute geeignet sind.

In der klinischen Praxis der Intensivtherapie in Deutschland werden unterschiedliche Strategien zur Sicherung, Fixierung und Pflege des peroralen Endotrachealtubus und der Mundpflege bei beatmeten Patienten angewandt. Es fehlen national verbindliche und allgemein konsentierte Leitlinien oder Empfehlungen hierzu. In einer Umfrage unter Intensivpflegenden wurden die am meisten verbreiteten Vorgehensweisen und Pflegemasnahmen erfasst. Gemas Auswertung der Umfrage und der zur Verfugung stehenden internationalen Literatur werden aktuell angewandte Strategien diskutiert. In der Folge dieser Arbeit entstanden Empfehlungen zur Verbesserung der Pflegepraxis unter Berucksichtigung aller Moglichkeiten, der patientenseitigen Notwendigkeiten und der gefundenen Evidenz dazu. Berucksichtigt wurden auch Aspekte der Medizinproduktzweckbestimmung, der Patientensicherheit und der Komplikationsvermeidung sowie Grundlagen qualitatsorientierter Pflegepraxis im Kontext limitierter Pflegeressourcen.

PTSD can develop in the aftermath of traumatic incidents like combat, sexual abuse, or life threatening accidents. Unfortunately, there are still no biomarkers for this debilitating anxiety disorder in clinical use. Anyhow, there are numerous studies describing potential PTSD biomarkers, some of which might progress to the point of practical use in the future. Here, we outline and comment on some of the most prominent findings on potential imaging, psychological, endocrine, and molecular PTSD biomarkers and classify them into risk, disease, and therapy markers. Since for most of these potential PTSD markers a causal role in PTSD has been demonstrated or at least postulated, this review also gives an overview on the current state of research on PTSD pathobiology.

Decreased β-amyloid (Aβ) clearance from the brain has been suggested to contribute to cerebral Aβ accumulation in Alzheimer’s disease. Based on the idea of a dynamic Aβ equilibrium in different body compartments, plasma Aβ levels have been investigated as biomarker candidates for preclinical Alzheimer’s pathology, yet with inconsistent results. Since the kidneys are involved in Aβ elimination from the blood, we evaluated how chronic kidney disease (CKD) affects the association between plasma Aβ and cognitive deficits and cognitive decline. In 28 CKD patients, stages 3–5D, and 26 control subjects with comparable vascular risk profile from the New Tools for the Prevention of Cardiovascular Disease in Chronic Kidney Disease (NTCVD) cohort, plasma total Aβ was determined with a highly sensitive electrochemiluminescence immunoassay. Cognition was evaluated using a comprehensive battery of ten neuropsychological tests at baseline and 2-year follow-up. Subjects with high plasma Aβ level (above median) demonstrated a significantly worse baseline cognitive performance than subjects exhibiting low Aβ level (summary score of global cognitive performance at baseline z = −0.46 ± 0.76 vs z = −0.08 ± 0.57, p = 0.045). Cognitive performance moderately decreased over the 2-year follow-up in subjects with high plasma Aβ level (Δz = −0.13 ± 0.51), but increased in subjects with low plasma Aβ level (Δz = 0.16 ± 0.41, p = 0.023). In linear regression analyses, baseline plasma Aβ was significantly associated with cognitive decline both in unadjusted analyses (β = −0.28, 95% CI = −0.55 to −0.01) and analyses adjusted for age (β = −0.27, 95% CI = −0.54 to −0.01). Our results suggest the utility of plasma Aβ level in predicting cognitive decline in patients suffering from CKD.

Young female subjects are known to have the highest baseline menstrual hormone levels of any female age group. Studies have found an association between hormone levels and wound healing. This has been researched in the orthopedic, gynecologic, and dermatologic literature, and more recently, in young patients undergoing augmentation mammaplasty. The purpose of this study was to determine whether the timing of surgery relative to the menstrual cycle plays a role in surgical complications following bilateral reduction mammaplasty.All female patients aged 25 years or younger with a documented last menstrual cycle undergoing a bilateral reduction mammaplasty from 2005 to 2013 were reviewed. Surgical timing and postoperative complications relative to the last menstrual cycle were recorded. The preovulatory phase referred to days 1 to 14 after the patient's last menstrual cycle, whereas the postovulatory phase referred to days 15 to 28.Forty-nine patients met inclusion criteria. Undergoing bilateral reduction mammaplasty during the postovulatory phase was associated with development of wound dehiscence and hypertrophic scarring (p0.005), which were the most common postoperative complications. Surgery in the preovulatory or postovulatory phase did not affect hematoma, seroma, wound infection, or nipple-areolar complex necrosis rates (p0.05). Age, race/ethnicity, body mass index, large resection mass, and medical comorbidities did not affect wound dehiscence or scar hypertrophy rates (p0.05).Young patients undergoing bilateral reduction mammaplasty during the postovulatory phase of the menstrual cycle have an increased risk of wound healing issues and poor scarring. This may be attributable to hormonal fluxes occurring during this phase and the already high hormone levels in this population.

Disturbed brain-to-blood elimination of β-amyloid (Aβ) promotes cerebral Aβ accumulation in Alzheimer’s disease. Considering that the kidneys are involved in Aβ elimination from the blood, we evaluated how chronic kidney disease (CKD) affects plasma Aβ. In 106 CKD patients stages 3–5 (including 19 patients on hemodialysis and 15 kidney recipients), 53 control subjects with comparable vascular risk profile and 10 kidney donors, plasma Aβ was determined using electrochemiluminescence immunoassay and gel electrophoresis followed by Western blotting. Plasma Aβ increased with CKD stage (control = 182.98 ± 76.73 pg/ml; CKD3A = 248.34 ± 103.77 pg/ml; CKD3B = 259.25 ± 97.74 pg/ml; CKD4 = 489.16 ± 154.16 pg/ml; CKD5 = 721.19 ± 291.69 pg/ml) and was not influenced by hemodialysis (CKD5D = 697.97 ± 265.91 pg/ml). Renal transplantation reduced plasma Aβ (332.57 ± 162.82 pg/ml), whereas kidney donation increased it (251.51 ± 34.34 pg/ml). Gel electrophoresis confirmed stage-dependent elevation namely of Aβ1-40, the most abundant Aβ peptide. In a multivariable regression including age, sex, estimated glomerular filtration rate (eGFR), potassium, hemoglobin, urine urea, and urine total protein, the factors eGFR (β = −0.42, p

Manganese-enhanced MRI has recently become a valuable tool for the assessment of in vivo functional cerebral activity in animal models. As a result of the toxicity of manganese at higher dosages, fractionated application schemes have been proposed to reduce the toxic side effects by using lower concentrations per injection. Here, we present data on regional-specific manganese accumulation during a fractionated application scheme over 8 days of 30 mg/kg MnCl2 , as well as on the clearance of manganese chloride over the course of several weeks after the termination of the whole application protocol supplying an accumulative dose of 240 mg/kg MnCl2 . Our data show most rapid accumulation in the superior and inferior colliculi, amygdala, bed nucleus of the stria terminalis, cornu ammonis of the hippocampus and globus pallidus. The data suggest that no ceiling effects occur in any region using the proposed application protocol. Therefore, a comparison of basal neuronal activity differences in different animal groups based on locally specific manganese accumulation is possible using fractionated application. Half-life times of manganese clearance varied between 5 and 7 days, and were longest in the periaqueductal gray, amygdala and entorhinal cortex. As the hippocampal formation shows one of the highest T1 -weighted signal intensities after manganese application, and manganese-induced memory impairment has been suggested, we assessed hippocampus-dependent learning as well as possible manganese-induced atrophy of the hippocampal volume. No interference of manganese application on learning was detected after 4 days of Mn(2+) application or 2 weeks after the application protocol. In addition, no volumetric changes induced by manganese application were found for the hippocampus at any of the measured time points. For longitudinal measurements (i.e. repeated manganese applications), a minimum of at least 8 weeks should be considered using the proposed protocol to allow for sufficient clearance of the paramagnetic ion from cerebral tissue.

Patients suffering from major depression have repeatedly been reported to have dysregulations in hypothalamus-pituitary-adrenal (HPA) axis activity along with deficits in cognitive processes related to hippocampal and prefrontal cortex (PFC) malfunction. Here, we utilized three mouse lines selectively bred for high (HR), intermediate, or low (LR) stress reactivity, determined by the corticosterone response to a psychological stressor, probing the behavioral and functional consequences of increased vs. decreased HPA axis reactivity on the hippocampus and PFC. We assessed performance in hippocampus- and PFC-dependent tasks and determined the volume, basal activity, and neuronal integrity of the hippocampus and PFC using in vivo manganese-enhanced magnetic resonance imaging and proton magnetic resonance spectroscopy. The hippocampal proteomes of HR and LR mice were also compared using two-dimensional gel electrophoresis and mass spectrometry. HR mice were found to have deficits in the performance of hippocampus- and PFC-dependent tests and showed decreased N-acetylaspartate levels in the right dorsal hippocampus and PFC. In addition, the basal activity of the hippocampus, as assessed by manganese-enhanced magnetic resonance imaging, was reduced in HR mice. The three mouse lines, however, did not differ in hippocampal volume. Proteomic analysis identified several proteins that were differentially expressed in HR and LR mice. In accordance with the notion that N-acetylaspartate levels, in part, reflect dysfunctional mitochondrial metabolism, these proteins were found to be involved in energy metabolism pathways. Thus, our results provide further support for the involvement of a dysregulated HPA axis and mitochondrial dysfunction in the etiology and pathophysiology of affective disorders.

Purpose There is evidence that multifocal visual evoked potentials (VEPs) can be used as an objective tool to detect visual field loss. The aim of this study was to correlate multifocal VEP amplitudes with standard perimetry data and retinal nerve fibre layer (RNFL) thickness. Method Multifocal VEP recordings were performed with a four-channel electrode array using 58 stimulus fields (pattern reversal dartboard). For each field, the recording from the channel with maximal signal-to-noise ratio (SNR) was retained, resulting in an SNR optimised virtual recording. Correlation with RNFL thickness, measured with spectral domain optical coherence tomography and with standard perimetry, was performed for nerve fibre bundle related areas. Results The mean amplitudes in nerve fibre related areas were smaller in glaucoma patients than in normal subjects. The differences between both groups were most significant in mid-peripheral areas. Amplitudes in these areas were significantly correlated with corresponding RNFL thickness (Spearman R=0.76) and with standard perimetry (R=0.71). Conclusion The multifocal VEP amplitude was correlated with perimetric visual field data and the RNFL thickness of the corresponding regions. This method of SNR optimisation is useful for extracting data from recordings and may be appropriate for objective assessment of visual function at different locations. Trial registration number This study has been registered at http://www.clinicaltrials.gov (NCT00494923).

Zusammenfassung Die Relevanz pflegerischer Interventionen bei Patienten mit Stuhlinkontinenz/Defäkationsstörungen in der Intensivmedizin ist ein häufig unterschätzter Aspekt. Stuhlinkontinenz kann als Erkrankungssymptom, Begleiterkrankung oder auch Primärerkrankung vorkommen. Die Stuhlinkontinenz beeinträchtigt die betroffenen Intensivpatienten stark in der Selbstpflegefähigkeit. Stuhlinkontinenz besteht häufig im Zusammenhang mit Diarrhö und stark eingeschränkter eigenständiger Mobilität. Zudem beeinträchtigt eine pflegerisch nicht adäquat versorgte Stuhlinkontinenz, gleich welcher Genese oder Ausprägung, das Patientenoutcome negativ. Die unversorgte Stuhlinkontinenz kann Infektionen verursachen (z. B. gestörte Hautschutzfunktion, vorhandene Kathetereinstichstellen), Sekundärheilungen verzögern (von z. B. Dekubitalgeschwüren, Wunden im Rücken oder Leisten-/Intimbereich) und unerwünschte Umgebungskontaminationen auslösen (z. B. intestinale Infektionskrankheiten). In der Vergangenheit wurden verschiedene improvisierte Techniken und Materialien zur Stuhlableitung bei immobilisierten und/oder kritisch erkrankten Patienten mit temporärer oder persistierender Stuhlinkontinenz eingesetzt. Die kontinuierliche und sichere Stuhldrainage stellte ein häufiges Problem dar. Es existierte keinerlei Ansatz eines einheitlichen, empfohlenen und/oder überprüfbaren pflegerischen Versorgungskonzepts. Aktuell befinden sich verschiedene vorgefertigte Stuhldrainagesysteme zur kontinuierlichen Stuhlableitung in der Markteinführung. Verschiedenste Indikationen und Anwendungsbereiche werden zum Einsatz dieser kontinuierlichen Stuhldrainagesysteme (KSS) empfohlen. Diese Arbeit stellt Stärken und Schwächen der KSS dar, erläutert die jeweiligen Funktionen und setzt diese in einen Zusammenhang zu möglichen Indikationen und Kontraindikationen. Einsatzoptionen und -grenzen werden zusammengefasst und resümieren in einem Algorithmus als praktische Entscheidungsfindungshilfe.

The anaemia of chronic disease is a concomitant phenomenon of various chronic intectious, neoplastic and autoimmune diseases. Whenever possible, the treatment of the underlying disease is the treatment of choice. When this is not feasible at present blood transfusion, iron therapy and the use of erythropoietic agents are further treatment options. Blood transfusions are reserved for the short-term use in the case of life-threatening anaemia (Hb 100 μg/L) without functional iron deficiency should not be treated with iron. The erythropoietic stimulation with the currently available agents epoetin alfa, epoetin beta and darbepoetin can result in a nearly 100% therapeutic response provided the individual iron requirements are considered. Using erythropoietin in combination with iron in patients with RA und ACD, it has been shown that besides the correction of the haemoglobin deficit also disease activity as well as health-related quality of life could be approved. The risk-benefit ratio of the treatment of ACD regarding the underlying disease has, however, not been fully evaluated so far. This is also true for the use of iron and erythropoietin in the treatment of ACD. Further therapeutic options such as the use of iron chelating agents or other agents with an influence on the regulation of the cellular iron metabolism are in preclinical evaluation. It can, however, already be stated with regard to an appropriate management of patients with rheumatic diseases, regardless of the underlying disease, that ACD can be treated effectively.

A psoriatic osteoarthropathy localized in the left quadrant of a male patient is described. Diagnosis was made on the basis of bone scintigraphy (specific distribution pattern) and histological evaluation of a bone biopsy. There is no indication of psoriasis in the patient's family. Nor is there an association to psoriasis-typical HLA markers. Psoriasis of the skin has not been found. Environmental factors, including a Köbner phenomenon on the skeleton resulting from a trauma 13 years ago (hallux rigidus operation), are discussed in connection with this manifestation. The genetic aspects of this unusual localization are considered.

Bio-availability and therapeutic efficacy of two oral ferrous preparations in the form of effervescent tablets (A and A*) were compared. In a randomly controlled trial, postabsorption rise of serum iron was compared intraindividually after oral intake of the effervescent tablets and of an optimally bio-available ferrous ascorbate standard solution (80.5 mg). Afterwards the therapeutic efficacy of both preparations (161 mg daily) was compared with a proprietary iron preparation (B: 150 mg daily) for three months. The trial was conducted on 24 male subjects (aged 20-38 years) who underwent weekly phlebotomies of 500 ml until exhaustion of body iron reserves and development of a mild iron-deficiency anaemia (standard phlebotomy protocol). Relative bioavailability, related to the standard iron solution, was 89% and 104%, respectively, for tablets A and A*. The rise in haemoglobin and ferritin during the three-months treatment was relatively the same for all three preparations: the average daily haemoglobin rise (means +/- SD) was 1.4 +/- 0.5 g/l (A), 1.5 +/- 0.4 g/l (A*) and 1.2 +/- 0.5 g/l (B), respectively, the differences not being statistically significant.

Major depression is a serious side effect of interferon-α (IFN-α), which is used in the therapy of hepatitis C virus (HCV) infection. Due to the lack of reproducible animal models, the mechanisms underlying IFN-α-related depression are largely unknown. We herein established a mouse model, in which murine IFN-α (250 IU/day) and polyinosinic/polycytidylic acid (poly(I:C); 1 μg/day), a toll-like receptor-3 (TLR3) agonist that mimics the effect of HCV double-strand RNA, were continuously infused into the lateral ventricle via miniosmotic pumps over up to 14 days. The delivery of IFN-α and poly(I:C), but not of IFN-α or poly(I:C) alone, resulted in a reproducible depression-like state that was characterized by reduced exploration behavior in open-field tests, increased immobility in tail suspension and forced swimming tests, and a moderate loss of body weight. In the hippocampus and prefrontal cortex, the pro-inflammatory genes TNF-α, IL-6, tissue inhibitor of metalloproteinases-1 (Timp-1), CXC motif ligand-1 (Cxcl1), Cxcl10, and CC motif ligand-5 (Ccl5) were synergistically induced by IFN-α and poly(I:C), most pronounced after 14-day exposure. In comparison, the interferon-inducible genes of signal transducer and activator of transcription-1 (Stat1), guanylate binding protein-1 (Gbp1), proteasome subunit-β type-9 (Psmb9), ubiquitin-conjugating enzyme E2L-6 (Ube2l6), receptor transporter protein-4 (Rtp4), and GTP cyclohydrolase-1 (Gch1), which had previously been elevated in the blood of IFN-α-treated patients developing depression, in the brains of suicidal individuals, and in primary neurons exposed to IFN-α and poly(I:C), were induced even earlier, reaching maximum levels mostly after 24 hours. We propose that interferon-inducible genes might be useful markers of imminent depression.

Background: The incidence of anaemia is high in many chronic conditions, yet it often receives little attention. Scope/methods: A panel of international experts with experience in haematology, nephrology, oncology, rheumatology and pharmacy was convened to prepare strategic guidelines. A focused literature search was conducted after key issues had been identified. A series of recommendations was agreed, backed, wherever possible, by published evidence which is included in the annotations. Recommendations: Anaemia is a critical issue for patients with chronic diseases. Healthcare professionals need to recognise that anaemia is a frequent companion of cancer and chronic conditions such as rheumatoid arthritis and heart failure. It reduces patients' quality of life and can increase morbidity and mortality. Anaemia should be considered as a disordered process in which the rate of red cell production fails to match the rate of destruction which leads eventually to a reduction in haemoglobin concentration; this process is common to all chronic anaemias. The aim of anaemia management should be to restore patient functionality and quality of life by restoring effective red cell production. Blood transfusion can elevate haemoglobin concentration in the short term but does nothing to address the underlying disorder; red cell transfusion is, therefore, not an appropriate treatment for chronic anaemia. Patients with anaemia of chronic disease may benefit from iron therapy and/or erythropoiesis stimulating agents (ESAs). Intravenous iron should be considered since this can be given safely to patients with chronic diseases while intramuscular iron causes unacceptable adverse effects and oral iron has limited efficacy in chronic anaemia. Conclusion: The management of anaemia calls for the development of a specialist service together with education of all healthcare professionals and transfer of skills from areas of good practice. Improvement in the management of anaemia requires a fundamental change of attitude from healthcare professionals. Read More: http://informahealthcare.com/doi/abs/10.1185/030079906x100096

To examine the economic consequences of effective antihypertensive treatment using the novel vasodilating beta1-adrenoceptor antagonist nebivolol (Nebilet) from the perspective of the healthcare provider.The evaluation was based on a postmarketing surveillance study in Germany involving 8682 moderately hypertensive patients. Using the Framingham Risk Model, the antihypertensive effectiveness of nebivolol after 6 weeks of treatment was extrapolated to estimate the reductions in 10-year risks of cardiovascular events. Data sources included direct costs for medical and invasive cardiovascular interventions in Germany, costs of therapy in the US and the UK, and estimates on the prevalence of cardiovascular events issued by the American Heart Association.Six-week antihypertensive treatment resulted in a DBP reduction of 13.7 mm Hg. The rate of responders, defined as those patients achieving DBP90 mm Hg, was 70%. SBP was reduced by 26.1 mm Hg. According to the Framingham Risk Model, 313 deaths would be avoided. Coronary heart disease (CHD) could be reduced by 94 cases (from 1339 to 1245 events) and 150 strokes would be avoided (from 518 to 368 events) in a 10-year period. This reduction of 244 cardiovascular events among the 8682 patients investigated corresponded to cost savings of between Euro 250,000 and Euro 2.5 million, depending on the healthcare environment and the intervention applied.Treatment of moderately hypertensive patients with nebivolol can be considered cost effective. Nebivolol has the potential to decrease the overall long-term costs of medical care for patients with hypertension.

Objective. Current treatment options for psoriatic arthritis (PsA) are limited. Leflunomide, an oral pyrimidine synthesis inhibitor, is highly effective in the treatment of rheumatoid arthritis, and small studies have suggested similar efficacy in PsA. We undertook this double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of leflunomide in patients with PsA and psoriasis. Methods. One hundred ninety patients with active PsA and psoriasis (at least 3% skin involvement) were randomized to receive leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally) or placebo for 24 weeks. The primary efficacy end point was the proportion of patients classified as responders by the Psoriatic Arthritis Response Criteria (PsARC). Additional efficacy (joint and skin involvement), safety, and quality-of-life assessments were performed. Results. At 24 weeks, 56 of 95 leflunomide-treated patients (58.9%; 95% confidence interval [95% CI] 48.4-68.9) and 27 of 91 placebo-treated patients (29.7% [95% CI 20.6-40.2]) were classified as responders by the PsARC (P < 0.0001). Significant differences in favor of leflunomide were also observed in the proportions of patients achieving modified American College of Rheumatology 20% improvement criteria, improvement in the designated psoriasis target lesion, and mean changes from baseline in Psoriasis Area and Severity Index scores and quality-of-life assessments. Diarrhea and alanine aminotransferase increases occurred at higher rates in the leflunomide group. No cases of serious liver toxicity were observed. Conclusion. Leftunomide is an effective treatment for PsA and psoriasis, providing a safe and convenient alternative to current therapies.

Immunosuppression with antithymocyte globulin, (methyl)prednisolone, and cyclosporin A is considered the treatment of choice for the patient with aplastic anemia without a donor for standard-risk stem cell transplantation. This consensus is supported by the results of several series, including a randomized German trial. Here we report 11-year results of the latter trial. With stringent response criteria and 4 months as the time to evaluate responses, this analysis confirms the superiority of the cyclosporine regimen regarding the response rate in all patients treated (70% vs 41%, with or without cyclosporine; P = .015) and in patients with severe aplastic anemia (65% vs 31%; P = .011). Patients responded more rapidly after treatment with cyclosporine (median, 60 vs 82 days; P = .019). Most patients treated with cyclosporine needed only one course of immunosuppression, whereas many patients treated without cyclosporine required repeated immunosuppressive treatment. Because of the efficacy of salvage treatment, overall survival was not different between the 2 treatment groups. However, failure-free survival favored the cyclosporine regimen (39% vs 24%; P = .04). The relapse rate, projected at 38% after 11.3 years, was similar between the 2 treatment groups. Remissions were cyclosporine dependent in 26% of the patients responding to a regimen that included cyclosporine. Clonal or malignant diseases developed in 25% of the patients. These data demonstrate that antithymocyte globulin, methylprednisolone, and cyclosporin A are an effective regimen for the treatment of aplastic anemia. However, remissions are unstable, and secondary diseases are common. In contrast to the results of stem cell transplantation, most patients are not cured.

Objective.To determine the prevalence of and independent factors associated with joint involvement in a large population of patients with systemic sclerosis (SSc).Methods.This study was cross-sectional, based on data collected on patients included in the European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) registry. We queried this database to extract data regarding global evaluation of patients with SSc and the presence of any clinical articular involvement: synovitis (tender and swollen joints), tendon friction rubs (rubbing sensation detected as the tendon was moved), and joint contracture (stiffness of the joints that decreased their range of motion). Overall joint involvement was defined by the occurrence of synovitis and/or joint contracture and/or tendon friction rubs.Results.We recruited 7286 patients with SSc; their mean age was 56 ± 14 years, disease duration 10 ± 9 years, and 4210 (58%) had a limited cutaneous disease subset. Frequencies of synovitis, tendon friction rubs, and joint contractures were 16%, 11%, and 31%, respectively. Synovitis, tendon friction rubs, and joint contracture were more prevalent in patients with the diffuse cutaneous subset and were associated together and with severe vascular, muscular, renal, and interstitial lung involvement. Moreover, synovitis had the highest strength of association with elevated acute-phase reactants taken as the dependent variable.Conclusion.Our results highlight the striking level of articular involvement in SSc, as evaluated by systematic examination in a large cohort of patients with SSc. Our data also show that synovitis, joint contracture, and tendon friction rubs are associated with a more severe disease and with systemic inflammation.

Objective: To compare the three year safety and efficacy of cyclosporin and parenteral gold in the treatment of early, active, severe rheumatoid arthritis (RA), and to study the reversibility of cyclosporin associated renal dysfunction in patients who discontinued cyclosporin treatment. Methods: The patients continued to receive cyclosporin or parenteral gold in an 18 month open extension to an 18 month randomised, parallel group study. The main efficacy variable was blinded evaluation of radiographic progression of joint damage. Safety variables included serum creatinine, calculated creatinine clearance, and blood pressure. Results: Radiographic progression during follow up was similar in both groups. About 60% of the patients in the intention to treat groups (n=272) and about half of the patients in the completer groups (n=114) had definite radiographic progression in joint damage (increases >6 in the Larsen-Dale score), and about one in three also had substantial progression (>18 increase in Larsen-Dale score). Both systolic and diastolic blood pressure were significantly increased in the cyclosporin group compared with the gold group, and 12/139 (9%) versus 3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine increased by 28% at the treatment end point in the cyclosporin group as compared with 7% in the gold group. The mean calculated creatinine clearance was reduced by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at the end of the study. At the final follow up visit after discontinuation of cyclosporin (at least three months after treatment was stopped) the mean serum creatinine was increased by 15% and creatinine clearance reduced by 16%. Sustained increases in serum creatinine at this post-treatment end point were mostly seen in patients with a raised serum creatinine during treatment of at least 50%. Conclusion: Three year changes in radiographic damage during cyclosporin and parenteral gold were similar in patients with early, active RA. Abnormal renal function and raised blood pressure were often seen in the cyclosporin treated patients.

Die Untersuchung der Synovialflussigkeit hat in den letzten Jahren in der rheumatologischen Praxis an Akzeptanz verloren. Fragestellung Welche diagnostische Wertigkeit besitzen quantitative Komplement- (C′3c und C′4) und Immunglobulin-Isotyp-Bestimmungen (IgG, IgA und IgM) in der Synovialflussigkeit fur die Arthritis-Differentialdiagnostik unter Berucksichtigung pathophysiologischer Zusammenhange und der derzeit gultigen Klassifikationskriterien der rheumatoiden Arthritis und Spondylarthropathie? Methodik Untersuchung von 22 nach den ACR-Kriterien klassifizierten Patienten mit rheumatoider Arthritis (RA), 18 Patienten mit seronegativer Spondylarthropathie (SpA) entsprechend den Klassifikationskriterien der ESSG und 16 Gelenkpunktaten von Patienten mit Gonarthrose/Osteoarthritis (OA). Nephelometrische Bestimmung von IgG, IgA, IgM, C′3c und C′4 in Serum und Synovialflussigkeit. Vergleich der Krankheitsgruppen und lineare Regressionsanalysen zur Ermittlung statistischer Zusammenhange zwischen einzelnen Parametern. Schrittweise logistische Regressionsanalyse zur Bestimmung der diagnostischen Wertigkeit einzelner und miteinander verknupfter Parameter. Ergebnisse SF-IgA, SF-IgG und SF-IgM Konzentrationen hangen in erster Linie von den korrespondierenden Serumwerten ab (p

Systemic transplantation of neural progenitor cells (NPCs) in rodents reduces functional impairment after cerebral ischemia. In light of upcoming stroke trials regarding safety and feasibility of NPC transplantation, experimental studies have to successfully analyze the extent of NPC-induced neurorestoration on the functional level. However, appropriate behavioral tests for analysis of post-stroke motor coordination deficits and cognitive impairment after NPC grafting are not fully established. We therefore exposed male C57BL6 mice to either 45 min (mild) or 90 min (severe) of cerebral ischemia, using the thread occlusion model followed by intravenous injection of PBS or NPCs 6 h post-stroke with an observation period of three months. Post-stroke motor coordination was assessed by means of the rota rod, tight rope, corner turn, inclined plane, grip strength, foot fault, adhesive removal, pole test and balance beam test, whereas cognitive impairment was analyzed using the water maze, the open field and the passive avoidance test. Significant motor coordination differences after both mild and severe cerebral ischemia in favor of NPC-treated mice were observed for each motor coordination test except for the inclined plane and the grip strength test, which only showed significant differences after severe cerebral ischemia. Cognitive impairment after mild cerebral ischemia was successfully assessed using the water maze test, the open field and the passive avoidance test. On the contrary, the water maze test was not suitable in the severe cerebral ischemia paradigm, as it too much depends on motor coordination capabilities of test mice. In terms of both reliability and cost-effectiveness considerations, we thus recommend the corner turn, foot fault, balance beam, and open field test, which do not depend on durations of cerebral ischemia. peerReviewed

Gene variations of HFE, a HLA-class I like molecule, are highly associated with hereditary haemochromatosis (HH). Functional as well as molecular studies of the HFE protein have indicated that the molecule is involved in iron metabolism and that the HFE gene variations observed among HH patients affect its interaction with the transferrin receptor (TfR). In the present study, we have therefore analysed the relationship between the HFE gene variants, C282Y and H63D, and body iron status among 85 German HH patients. In addition, two TfR gene polymorphism, TfR-Hin6I and TfR-BanI, were typed that have been reported to define ethnically distinct haplotypes. As controls we used 251/159 healthy German blood donors. Seventy-eight (92%) patients were C292Y homozygous, the H63D mutation was present in five (6%) patients with none of the patients being H63D homozygous. Serum transferrin, transferrin saturation and liver iron content were determined prior to therapeutic intervention. Among C282Y homozygous patients serum ferritin levels (2294 +/- 3174 vs. 463 +/- 224 microg L-1, P < 0.0001) and transferrin saturation (86 +/- 18% vs. 62 +/- 25%, P = 0.048) were elevated significantly compared with C282Y and/or H63D heterozygous patients. In addition, the liver iron content (291 +/- 165 vs. 138 +/- 95 micromol g-1, P = 0.028) and liver iron index (6.4 +/- 2.8 vs. 3.2 +/- 2.3, P = 0.019) were increased among C282Y homozygotes compared with C282Y heterozygotes. In contrast, no difference was observed between patients and controls regarding the distribution of TfR-Hin6I and TfR-BanI alleles. These data indicate that the iron intake is higher among C282Y homozygous patients compared with C282Y heterozygous or C282Y/H63D compound heterozygous individuals and supports the functional role of the HFE protein in iron metabolism whereas the TfR gene variants seem to have no influence on iron uptake.

Objective To compare the clinical efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis (RA). Methods In this multicentre, double-blind trial, 999 subjects with active RA were randomized to leflunomide (n = 501; loading dose 100 mg/day for 3 days, maintenance dose 20 mg/day) or methotrexate (n = 498; 10-15 mg/week) for 52 weeks. After 1 yr the subjects could choose to stay for a second year of double-blind treatment. The primary end-points were tender and swollen joint counts and overall physician and patient assessments. Analyses were of the intent-to-treat group. Results After 1 yr, the mean changes in the leflunomide and methotrexate groups, respectively, were -8.3 and -9.7 for tender joint count; -6.8 and -9.0 for swollen joint count; -0.9 and -1.2 for physician global assessment; -0.9 and -1.2 for patient global assessment; -14.4 and -28.2 for erythrocyte sedimentation rate. Improvements seen with methotrexate were significantly greater than those with leflunomide. No further improvement occurred after the second year of treatment and the distinction between the two treatments in terms of tender joint count and patient global assessment was lost. During the first year of treatment, a small and equivalent degree of radiographically assessed disease progression was seen with both drugs. After 2 yr, disease progression was significantly less with methotrexate. The most common treatment-related adverse events in both groups were diarrhoea, nausea, alopecia, rash, headache, and elevated plasma liver enzyme levels. Over 2 yr, 21 subjects receiving methotrexate were withdrawn due to elevated plasma liver enzymes vs eight subjects taking leflunomide. Two drug-related deaths from pulmonary causes were recorded with methotrexate vs no drug-related deaths among the subjects receiving leflunomide. Conclusions Both leflunomide and methotrexate are efficacious for prolonged treatment of RA. At the doses used, some clinical benefit of methotrexate over leflunomide was observed in the first year of treatment. This benefit must be weighed against the potential toxicity of this drug when used without folate supplementation.

Objective: To determine the expression and localization of the arylhydrocarbon (dioxin) receptor in human endometrium throughout the normal menstrual cycle. Design: Retrospective immunohistochemical and in situ hybridization study. Setting: Academic research unit. Patient(s): Premenopausal women (n = 86), aged 25 to 45 years, with histologically normal endometrium undergoing curettage or hysterectomy. Intervention(s): Endometrial samples were collected from days 3 to 26 of the cycle by superficial scrapings of the uterine cavity or by hysterectomy. Main Outcome Measure(s): Expression of arylhydrocarbon receptor mRNA and protein. Result(s): Arylhydrocarbon receptor was expressed in 43% of the endometria studied and was correlated with the day of the cycle. The maximum of immunopositive endometria was found around the time of ovulation. Immunostaining decreased with increasing age of the patients. The receptor protein was localized exclusively in the apical part of the cytoplasm in the epithelial cells of the endometrial glands. In women positive for arylhydrocarbon receptor, arylhydrocarbon receptor mRNA was expressed in the cytoplasm of endometrial epithelial cells. Conclusion(s): Our results describe the expression of the arylhydrocarbon receptor in human endometrium and indicate a possible involvement of this transcription factor in endometrial function in women during the reproductive phase.

In the present study we have analysed the effect of HLA-DRB1 and -DQB1 alleles on disease progression and genetic predisposition among 201 RA patients. We clearly confirm the association of RA with HLA class II alleles sharing the (Q)R/KRAA amino acid (AA) cassette in the third hypervariable region (HVR3) of the DRSS-chain. The HVR3 (Q)R/KRAA motif was significantly overrepresented among RA patients (79% vs. 40%, P < 0.001), with one third of the patients homozygous (28% vs. 6.7%, P < 10 -9 ) and the number of rheumatoid factor positive (RF +) patients was significantly increased among HVR3 (Q)R/KRAA homozygous in comparison to HVR3 (Q)R/KRAA negative individuals. Erosive disease defined by the Larsen Score and personal disability determined using the Health Assessment Questionnaire (HAQ) was significantly increased among patients positive for the HVR3 motif with the worst outcome among HVR3 (Q)R/KRAA homozygous patients. In contrast, there was no association of the shared HVR3 AA cassette and disease severity in the majority of patients presenting systemic (extraarticular) disease. Homozygosity for the shared HVR3 motif was only marginally increased among patients presenting 'severe' extraarticular disease in comparison to patients with articular disease (33% vs. 43%, P = ns). Similarly, patients with nodular disease were not more often homozygous for the HVR3 (Q)R/KRAA motif.