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A survey on worries of pregnant women - testing the German version of the Cambridge Worry Scale
(2009)
Background: Pregnancy is a transition period in a woman's life characterized by increased worries and anxiety. The Cambridge Worry Scale (CWS) was developed to assess the content and extent of maternal worries in pregnancy. It has been increasingly used in studies over recent years. However, a German version has not yet been developed and validated. The aim of this study was (1) to assess the extent and content of worries in pregnancy on a sample of women in Germany using a translated and adapted version of the Cambridge Worry Scale, and (2) to evaluate the psychometric properties of the German version. Methods: We conducted a cross-sectional study and enrolled 344 pregnant women in the federal state of Baden-Wurttemberg, Germany. Women filled out structured questionnaires that contained the CWS, the Spielberger-State-Trait-Anxiety Inventory (STAI), as well as questions on their obstetric history. Antenatal records were also analyzed. Results: The CWS was well understood and easy to fill in. The major worries referred to the process of giving birth (CWS mean value 2.26) and the possibility that something might be wrong with the baby (1.99), followed by coping with the new baby (1.57), going to hospital (1.29) and the possibility of going into labour too early (1.28). The internal consistency of the scale (0.80) was satisfactory, and we found a four-factor structure, similar to previous studies. Tests of convergent validity showed that the German CWS represents a different construct compared with state and trait anxiety but has the desired overlap. Conclusions: The German CWS has satisfactory psychometric properties. It represents a valuable tool for use in scientific studies and is likely to be useful also to clinicians.
It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and beta-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-µm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V–VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I–II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers.
Background: Wnt signaling controls the balance between stem cell proliferation and differentiation and body patterning throughout development. Previous data demonstrated that non-canonical Wnts (Wnt5a, Wnt11) increased cardiac gene expression of circulating endothelial progenitor cells (EPC) and bone marrow-derived stem cells cultured in vitro. Since previous studies suggested a contribution of the protein kinase C (PKC) family to the Wnt5a-induced signalling, we investigated which PKC isoforms are activated by non-canonical Wnt5a in human EPC. Methodology/Principal Findings: Immunoblot experiments demonstrated that Wnt5a selectively activated the novel PKC isoform, PKC delta, as evidenced by phosphorylation and translocation. In contrast, the classical Ca2+-dependent PKC isoforms, PKC alpha and beta2, and one of the other novel PKC isoforms, PKC epsilon, were not activated by Wnt5a. The PKC delta inhibitor rottlerin significantly blocked co-culture-induced cardiac differentiation in vitro, whereas inhibitors directed against the classical Ca2+-dependent PKC isoforms or a PKC epsilon-inhibitory peptide did not block cardiac differentiation. In accordance, EPC derived from PKC delta heterozygous mice exhibited a significant reduction of Wnt5a-induced cardiac gene expression compared to wild type mice derived EPC. Conclusions/Significance: These data indicate that Wnt5a enhances cardiac gene expressions of EPC via an activation of PKC delta.
Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ,1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy.
Zielsetzung: Ziel des Projekts ist es, ein longitudinales Modell-Curriculum "Kommunikative und soziale Kompetenzen" für die medizinische Ausbildung zur Diskussion zu stellen. Vorgehen und Ergebnisse: Auf einem 2-tägigen Workshop wurde interfakultär und interdisziplinär auf der Grundlage des "Basler Consensus Statements: Kommunikative und soziale Kompetenzen im Medizinstudium" ein Curriculum entwickelt, das deutschsprachigen Fakultäten bei der Planung und Implementierung als Vorlage dienen kann. Das Modell lässt sich als Gesamt-Curriculum oder in Teilmodulen implementieren. Es kann auch bei der Umstellung auf Bachelor- und Masterstudiengänge genutzt werden. Das longitudinale Modell-Curriculum weist neben 131 definierten Ausbildungszielen geeignete didaktische Konzepte und Prüfungsformate auf und gibt Vorschläge, zu welchem Zeitpunkt die verschiedenen Fächer die entsprechenden Lernziele vermitteln können. Fazit: Mit diesem longitudinalen "Modell-Curriculum Kommunikative und Soziale Kompetenzen" liegt für den deutschen Sprachraum erstmalig ein curriculares Instrument vor, das breite Anwendung an einer Vielzahl deutscher, österreichischer und schweizerischer Fakultäten finden und eine Umsetzung des Bologna-Prozesses auch fakultätsübergreifend vereinfachen kann. Schlüsselwörter: Modell-Curriculum, kommunikative/soziale Kompetenzen, Basler Consensus Statement, medizinische Ausbildung, Didaktik, Prüfung, Bologna-Prozess
Background: The standard electrode array for the MED-EL MAESTRO cochlear implant system is 31 mm in length which allows an insertion angle of approximately 720°. When fully inserted, this long electrode array is capable of stimulating the most apical region of the cochlea. No investigation has explored Electrically Evoked Compound Action Potential (ECAP) recordings in this region with a large number of subjects using a commercially available cochlear implant system. The aim of this study is to determine if certain properties of ECAP recordings vary, depending on the stimulation site in the cochlea. Methods: Recordings of auditory nerve responses were conducted in 67 subjects to demonstrate the feasibility of ECAP recordings using the Auditory Nerve Response Telemetry (ART™) feature of the MED-EL MAESTRO system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation. Results: Findings show significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function have been observed. The refractory time shows an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions. Conclusions :Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences could be explained by the location of the stimulating electrode with respect to the neural tissue in the cochlea, a higher density, or an increased neural survival rate of neural tissue in the apex. Trial registration: The Clinical Investigation has the Competent Authority registration number DE/CA126/AP4/3332/18/05.
Jährlich erkranken etwa 425 000 Menschen in Deutschland an Krebs. Die Tendenz ist steigend: Experten gehen davon aus, dass die Zahl der Neuerkrankungen bis zum Jahr 2030 um 50 Prozent zunehmen wird. Doch zu dieser schlechten Nachricht gibt es auch eine gute: Körperliche Aktivität und Sport können das allgemeine Risiko, an bestimmten Krebsformen zu erkranken, vermindern. Dazu zählen vor allem Darmkrebs sowie der nach den Wechseljahren auftretende Brust- und Gebärmutterschleimhautkrebs. Aber auch wer schon erkrankt ist, kann sein Wohlbefinden und Selbstvertrauen durch spezielle Bewegungsprogramme, wie sie an der Goethe-Universität entwickelt werden, steigern. Selbst die Leiden von Patienten mit fortgeschrittenen Krebserkrankungen lassen sich auf diese Weise lindern. Denn Bewegung beeinflusst nicht nur die unmittelbar tumorbedingten Symptome, sondern auch therapiebedingte Nebenwirkungen, insbesondere die der Chemotherapie.
Background: Three genes have been confirmed as major joint susceptibility genes for endocrine autoimmune disease:human leukocyte antigen class II, cytotoxic T-lymphocyte antigen 4 and protein tyrosine phosphatase non-receptor type 22. Recent studies showed that a genetic variation within the interferon induced helicase domain 1 (IFIH1) locus (rs1990760 polymorphism) is an additional risk factor in type 1 diabetes and Graves' disease (GD). Methods: The aim of the present study was to investigate the role of the rs1990760 polymorphism within the IFIH1 gene in German patients with GD (n=258), Hashimoto's thyroiditis (HT,n=106), Addison's disease (AD,n=195) and healthy controls (HC,n=227) as well as in 55 GD families (165 individuals, German) and 100 HT families (300 individuals, Italian). Furthermore, the interaction between rs1990760 polymorphism with human leukocyte antigen (HLA) risk haplotype DQ2(DQA*0501-DQB*0201), the risk haplotypes DQ2/DQ8 (DQA*0301-DQB*0302) and the status of thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) and TSH receptor antibody (TRAb) in patients and families were analysed. Results:No significant differences were found between the allele and genotype frequencies for rs1990760 IFIH1 polymorphism in patients with GD, HT, AD and HC. Also no differences were observed when stratifying the IFIH1 rs1990760 polymorphism for gender, presence or absence of thyroid antibodies (GD:TRAb and HT:TPOAb/TgAb) and HLA risk haplotypes (DQ2:for GD and HT, DQ2/DQ8:for AD). Furthermore the transmission analysis in GD and HT families revealed no differences in alleles transmission for rs1990760 IFIH1 from parents with or without HLA risk haplotype DQ2 to the affected offspring. In contrast, by dividing the HT parents according to the presence or absence of thyroid Ab titers, mothers and fathers both positive for TPOAb/TgAb overtransmitted the allele A of IFIH1 rs1990760 to their HT affected offspring (61.8% vs 38.2%;p=0.05;corrected p [pc]=0.1). However, these associations did not remain statistically significant after correction of the p-values. Conclusion: In conclusion, our data suggest, no contribution from IFIH1 rs1990760 polymorphism to the pathogenesis of either Graves' disease, Hashimoto's thyroiditis or Addison's disease in our study populations. However, in order to exclude a possible influence of the studied polymorphism in specified subgroups within patients with autoimmune thyroid disease, further investigations in larger populations are needed.
Background Enhanced activity of histone deacetylases (HDAC) is associated with more aggressive tumour behaviour and tumour progression in various solid tumours. The over-expression of these proteins and their known functions in malignant neoplasms has led to the development of HDAC inhibitors (HDI) as new anti-neoplastic drugs. However, little is known about HDAC expression in renal cell cancer. Methods We investigated the expression of HDAC 1, 2 and 3 in 106 renal cell carcinomas and corresponding normal renal tissue by immunohistochemistry on tissue micro arrays and correlated expression data with clinico-pathological parameters including patient survival. Results Almost 60% of renal cell carcinomas expressed the HDAC isoforms 1 and 2. In contrast, HDAC 3 was only detected in 13% of all renal tumours, with particular low expression rates in the clear cell subtype. HDAC 3 was significantly higher expressed in pT1/2 tumours in comparison to pT3/4 tumours. Expression of class I HDAC isoforms correlated with each other and with the proliferative activity of the tumours. We found no prognostic value of the expression of any of the HDAC isoforms in this tumour entity. Conclusion Class I HDAC isoforms 1 and 2 are highly expressed in renal cell cancer, while HDAC 3 shows low, histology dependent expression rates. These unexpected differences in the expression patterns suggests alternative regulatory mechanisms of class I HDACs in renal cell cancer and should be taken into account when trials with isoform selective HDI are being planned. Whether HDAC expression in renal cancers is predictive of responsiveness for HDI will have to be tested in further studies.
Loss of vascular barrier function causes leak of fluid and proteins into tissues, extensive leak leads to shock and death. Barriers are largely formed by endothelial cell-cell contacts built up by VE-cadherin and are under the control of RhoGTPases. Here we show that a natural plasmin digest product of fibrin, peptide Bß15-42 (also called FX06), significantly reduces vascular leak and mortality in animal models for Dengue shock syndrome. The ability of Bß15-42 to preserve endothelial barriers is confirmed in rats i.v.-injected with LPS. In endothelial cells, Bß15-42 prevents thrombin-induced stress fiber formation, myosin light chain phosphorylation and RhoA activation. The molecular key for the protective effect of Bß15-42 is the src kinase Fyn, which associates with VE-cadherin-containing junctions. Following exposure to Bß15-42 Fyn dissociates from VE-cadherin and associates with p190RhoGAP, a known antagonists of RhoA activation. The role of Fyn in transducing effects of Bß15-42 is confirmed in Fyn -/- mice, where the peptide is unable to reduce LPS-induced lung edema, whereas in wild type littermates the peptide significantly reduces leak. Our results demonstrate a novel function for Bß15-42. Formerly mainly considered as a degradation product occurring after fibrin inactivation, it has now to be considered as a signaling molecule. It stabilizes endothelial barriers and thus could be an attractive adjuvant in the treatment of shock.
Background Bacterial DNA containing motifs of unmethylated CpG dinucleotides (CpG-ODN) initiate an innate immune response mediated by the pattern recognition receptor Toll-like receptor 9 (TLR9). This leads in particular to the expression of proinflammatory mediators such as tumor necrosis factor (TNF-alpha) and interleukin-1beta (IL-1beta). TLR9 is expressed in human and murine pulmonary tissue and induction of proinflammatory mediators has been linked to the development of acute lung injury. Therefore, the hypothesis was tested whether CpG-ODN administration induces an inflammatory response in the lung via TLR9 in vivo. Methods Wild-type (WT) and TLR9-deficient (TLR9-D) mice received CpG-ODN intraperitoneally (1668-Thioat, 1 nmol/g BW) and were observed for up to 6 hrs. Lung tissue and plasma samples were taken and various inflammatory markers were measured. Results In WT mice, CpG-ODN induced a strong activation of pulmonary NFKB as well as a significant increase in pulmonary TNF-alpha and IL-1beta mRNA/protein. In addition, cytokine serum levels were significantly elevated in WT mice. Increased pulmonary content of lung myeloperoxidase (MPO) was documented in WT mice following application of CpG-ODN. Bronchoalveolar lavage (BAL) revealed that CpG-ODN stimulation significantly increased total cell number as well as neutrophil count in WT animals. In contrast, the CpG-ODN-induced inflammatory response was abolished in TLR9-D mice. Conclusion This study suggests that bacterial CpG-ODN causes lung inflammation via TLR9.
Background During gram-negative sepsis, lipopolysaccharide (LPS) induces tissue factor expression on monocytes. The resulting disseminated intravascular coagulation leads to tissue ischemia and worsens the prognosis of septic patients. There are indications, that fever reduces the mortality of sepsis, the effect on tissue factor activity on monocytes is unknown. Therefore, we investigated whether heat shock modulates LPS-induced tissue factor activity in human blood. Methods Whole blood samples and leukocyte suspensions, respectively, from healthy probands (n = 12) were incubated with LPS for 2 hours under heat shock conditions (43°C) or control conditions (37°C), respectively. Subsequent to further 3 hours of incubation at 37°C the clotting time, a measure of tissue factor expression, was determined. Cell integrity was verified by trypan blue exclusion test and FACS analysis. Results Incubation of whole blood samples with LPS for 5 hours at normothermia resulted in a significant shortening of clotting time from 357 ± 108 sec to 82 ± 8 sec compared to samples incubated without LPS (n = 12; p < 0.05). This LPS effect was mediated by tissue factor, as inhibition with active site-inhibited factor VIIa (ASIS) abolished the effect of LPS on clotting time. Blockade of protein synthesis using cycloheximide demonstrated that LPS exerted its procoagulatory effect via an induction of tissue factor expression. Upon heat shock treatment, the LPS effect was blunted: clotting times were 312 ± 66 s in absence of LPS and 277 ± 65 s in presence of LPS (n = 8; p > 0.05). Similarly, heat shock treatment of leukocyte suspensions abolished the LPS-induced tissue factor activity. Clotting time was 73 ± 31 s, when cells were treated with LPS (100 ng/mL) under normothermic conditions, and 301 ± 118 s, when treated with LPS (100 ng/mL) and heat shock (n = 8, p < 0.05). Control experiments excluded cell damage as a potential cause of the observed heat shock effect. Conclusion Heat shock treatment inhibits LPS-induced tissue factor activity in human whole blood samples and isolated leukocytes.
Introduction: Immune paralysis with massive T-cell apoptosis is a central pathogenic event during sepsis and correlates with septic patient mortality. Previous observations implied a crucial role of peroxisome proliferator-activated receptor gamma (PPARγ) during T-cell apoptosis.
Methods: To elucidate mechanisms of PPARγ-induced T-cell depletion, we used an endotoxin model as well as the caecal ligation and puncture sepsis model to imitate septic conditions in wild-type versus conditional PPARγ knockout (KO) mice.
Results: PPARγ KO mice showed a marked survival advantage compared with control mice. Their T cells were substantially protected against sepsis-induced death and showed a significantly higher expression of the pro-survival factor IL-2. Since PPARγ is described to repress nuclear factor of activated T cells (NFAT) transactivation and concomitant IL-2 expression, we propose inhibition of NFAT as the underlying mechanism allowing T-cell apoptosis. Corroborating our hypothesis, we observed up-regulation of the pro-apoptotic protein BIM and downregulation of the anti-apoptotic protein Bcl-2 in control mice, which are downstream effector proteins of IL-2 receptor signaling. Application of a neutralizing anti-IL-2 antibody reversed the pro-survival effect of PPARγ-deficient T cells and confirmed IL-2-dependent apoptosis during sepsis.
Conclusion: Apparently antagonizing PPARγ in T cells might improve their survival during sepsis, which concomitantly enhances defence mechanisms and possibly provokes an increased survival of septic patients.
Background: The c-Cbl-associated protein (CAP), also known as ponsin, localizes to focal adhesions and stress fibers and is involved in signaling events. Phosphorylation has been described for the other two members of the sorbin homology family, vinexin and ArgBP2, but no data exist about the putative phosphorylation of CAP. According to previous findings, CAP binds to tyrosine kinase c-Abl. However, it is not known if CAP is a substrate of c-Abl or other tyrosine kinases or if phosphorylation regulates its localization.
Results: We here show that CAP is Tyr phosphorylated by and interacts with both c-Abl and c-Src. One major phosphorylation site, Tyr360, and two minor contributors Tyr326 and Tyr632 were identified as Abl phosphorylation sites, whereas Src preferentially phosphorylates Tyr326 and Tyr360. Phosphorylation of CAP was not necessary for its localization to focal adhesions and stress fibers, but Tyr326Phe substitution alters the function of CAP during cell spreading.
Conclusion: This is the first demonstration of phosphorylation of CAP by any kinase. Our findings suggest that coordinated action of Src and Abl might regulate the function of CAP and reveal a functional role especially for the Src-mediated Tyr phosphorylation of CAP in cell spreading.
Objectives: We sought to investigate whether statin therapy affects the association between preprocedural C-reactive protein (CRP) levels and the risk for recurrent coronary events in patients undergoing coronary stent implantation.
Background: Low-grade inflammation as detected by elevated CRP levels predicts the risk of recurrent coronary events. The effect of inflammation on coronary risk may be attenuated by statin therapy.
Methods: We investigated a potential interrelation among statin therapy, serum evidence of inflammation, and the risk for recurrent coronary events in 388 consecutive patients undergoing coronary stent implantation. Patients were grouped according to the median CRP level (0.6 mg/dl) and to the presence of statin therapy.
Results: A primary combined end point event occurred significantly more frequently in patients with elevated CRP levels without statin therapy (RR [relative risk] 2.37, 95% CI [confidence interval] [1.3 to 4.2]). Importantly, in the presence of statin therapy, the RR for recurrent events was significantly reduced in the patients with elevated CRP levels (RR 1.27 [0.7 to 2.1]) to about the same degree as in patients with CRP levels below 0.6 mg/dl and who did not receive statin therapy (RR 1.1 [0.8 to 1.3]).
Conclusions: Statin therapy significantly attenuates the increased risk for major adverse cardiac events in patients with elevated CRP levels undergoing coronary stent implantation, suggesting that statin the rapy interferes with the detrimental effects of inflammation on accelerated atherosclerotic disease progression following coronary stenting.
Einleitung: Anastomoseninsuffizienzen sind schwerwiegende Komplikationen nach Kolonresektionen. Nur selten sind klinische oder laborchemische Zeichen Vorboten einer Insuffizienz. Material und Methoden: Wir haben unser Patientenkollektiv nach kolorektalen Resektionen retrospektiv untersucht in Hinblick auf einen Anstieg des C-rektiven Proteins (CRP) postoperativ als Zeichen einer Insuffizienz. Hierzu wurde der Unterschied vom präoperativen Messwert zum Messwert am 1. bis 7. postoperativen Tag berechnet. Bei Patienten mit Anastomoseninsuffizienz wurden die Werte nur bis zum Tag der Insuffizienz einbezogen, um einen Anstieg durch eine eventuelle Revision auszuklammern. Ergebnisse: Im Zeitraum von 8/2002 bis 8/2005 wurden bei 342 Patienten eine Kolonresektion durchgeführt. Im einzelnen waren dies 101 (29,5%) Sigmaresektionen, 89 (26,0%) Hemikolektomien rechts, 56 (16,4%) Rektumresektionen, 38 (11,1%) Ileocoecalresektionen, 24 (7,0%) Hemikolektomien links, 22 (6,4%) Segmentresektionen, 12 (3,5%) Kolektomien. Das Alter der Patienten lag bei 61,6 +/- 15,0 Jahren. Es wurden 142 (41,5%) Frauen und 200 (58,5%) Männer operiert, 301 (88%) Patienten elektiv und 41 (12%) als Notfall. Die Inzidenz von symptomatischen und asymptomatischen Anastomosen-insuffizienzen lag im Gesamtkollektiv bei 26/342 (7,6%), sie traten durchschnittlich 8,7 +/- 7,1 (1-27) Tage nach der Operation auf. Eine Analyse der CRP-Werte ergab bei den Patienten die im Verlauf eine Anastomoseninsuffizienz entwickelten signifikant höhere Anstiege von präoperativ bis zum 3. (+10,9 mg/dl versus +16,5 mg/dl, p=0,018), 5. (+4,2 mg/dl versus +13,1 mg/dl, p=0,002), 6. (+3,8 mg/dl versus +14,6 mg/dl, p=0,002), und 7. (+2,8 mg/dl versus +18,3 mg/dl, p<0,001) postoperativen Tag. Die Differenz zum 4. postoperativen Tag zeigte keinen signifikanten Unterschied (+6,5 mg/dl versus +11,2 mg/dl, p=0,3). Die absoluten Messwerte waren nicht signifikant unterschiedlich. Andere Laborparameter wie Leukozyten, Kreatinin, Albumin ergaben keinen Unterschied im Vergleich der beiden Gruppen.Die Untersuchung von Risikofaktoren für eine Anastomoseninsuffizienz konnte keinen signifikanten Unterschied zeigen für: Alter, Geschlecht, ASA, OP-Dauer, Zugang (offen oder laparoskopisch), benigne oder maligne Erkrankung, Kolon- oder Rektumresektion, elektive oder Notfalloperation. Schlussfolgerung: Der Verlauf des CRP ist ein signifikanter Marker für das Auftreten von Anastomoseninsuffizienzen nach kolorektalen Resektionen.
Meeting Abstract : Deutscher Kongress für Orthopädie und Unfallchirurgie ; 73. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie ; 95. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie ; 50. Tagung des Berufsverbandes der Fachärzte für Orthopädie und Unfallchirurgie ; 21. - 24.10.2009, Berlin Fragestellung: Evaluierung der intraoperativen Bildgebung mit einem motorgesteuerten 3D-Bildwandlersystem hinsichtlich des klinischen Zusatznutzens sowie der Praktikabilität bei der Versorgung intraartikulärer Frakturen im Bereich des OSG und USG. Methodik: In einer prospektiven klinischen Studie wurde bei 36 Patienten mit intraartikulärer Fraktur im Bereich von OSG und USG die intraoperative Bildgebung mit einem 3D-Bildwandler der neuesten Generation (Siemens® Arcadis Orbic 3D) im Rahmen der indizierten operativen Versorgung durchgeführt. Die Frakturen wurden unfallchirurgisch durch erfahrene Operateure mit Hilfe konventioneller 2D-Bildgebung reponiert und osteosynthetisch versorgt. Anschließend erfolgte vor Wundverschluss die Generierung des hochauflösenden multiplanaren 3D-Bilddatensatzes aus 100 Einzeldurchleuchtungen, welche im Rahmen einer einminütigen Rotation um das Untersuchungsgebiet akquiriert wurden. Die Bildanalyse hinsichtlich Reposition und Implantatlage erfolgte durch den Operateur. Sofern aufgrund der gewonnenen Informationen die Revisionsindikation bestand, erfolgte diese unmittelbar im Anschluss. Neben der Korrekturrate wurde die subjektive Wertigkeit der 3D-Bildgebung durch den Operateur ferner anhand des benötigten Zeitbedarfs, der Beurteilung des klinischen Nutzens (VAS 1–10) und der Benutzerfreundlichkeit (VAS 1–10) beurteilt. Ergebnisse und Schlussfolgerungen: Insgesamt wurde die 3D-Bildgebung bei der operativen Versorgung von 36 Frakturen eingesetzt (Pilon tibiale: n=10, bi-/trimalleoläre OSG-Luxationsfrakturen: n=8, Talus: n=4, Calcaneus: n=14). In 9 von 36 Fällen (25%) wurde auf Basis der Bildgebungsinformationen durch den Operateur die Indikation zur Revision der Reposition oder Implantatlage gestellt. Weitere osteosynthesebedingte Revisionen waren im postoperativen Verlauf nicht indiziert. Mit einer Ausnahme zeigte sich das Bildwandlersystem stets stabil und ohne technische Probleme. Die zusätzliche OP-Zeit lag im Mittel bei 9 Minuten (6,5–15 Minuten). Die erforderliche Untersuchungszeit sank tendenziell mit zunehmender Anwendung, eine entsprechend steile Lernkurve war ableitbar. Die 3D-Bilgebung wurde bei allen Eingriffen als sehr hilfreich betrachtet, der Mittelwert auf der VAS bezüglich des klinischen Zusatznutzens lag bei 8,3 (6–10), bezüglich der Benutzerfreundlichkeit bei 8,7 (7–10). Die 3D-Bildgebung stellt ein sicheres und zuverlässiges Verfahren zur intraoperativen Evaluierung der osteosynthetischen Versorgung im Bereich des OSG und USG dar und kann ein etwaig indiziertes strahlenintensiveres CT postoperativ ersetzen. Die sichere Identifikation von Fehlstellungen und Implantatfehllagen ermöglicht noch im OP die sofortige Revision. Die Anwendung ist einfach zu erlernen und verlängert die OP-Dauer lediglich in überschaubarem Umfang. Den hohen Investitionskosten steht somit bei regelmäßiger Anwendung ein bedeutsames Kosteneinsparpotenzial gegenüber.
Background Chemoresistance acquisition may influence cancer cell biology. Here, bioinformatics analysis of gene expression data was used to identify chemoresistance-associated changes in neuroblastoma biology. Results Bioinformatics analysis of gene expression data revealed that expression of angiogenesis-associated genes significantly differs between chemosensitive and chemoresistant neuroblastoma cells. A subsequent systematic analysis of a panel of 14 chemosensitive and chemoresistant neuroblastoma cell lines in vitro and in animal experiments indicated a consistent shift to a more pro-angiogenic phenotype in chemoresistant neuroblastoma cells. The molecular mechanims underlying increased pro-angiogenic activity of neuroblastoma cells are individual and differ between the investigated chemoresistant cell lines. Treatment of animals carrying doxorubicin-resistant neuroblastoma xenografts with doxorubicin, a cytotoxic drug known to exert anti-angiogenic activity, resulted in decreased tumour vessel formation and growth indicating chemoresistance-associated enhanced pro-angiogenic activity to be relevant for tumour progression and to represent a potential therapeutic target. Conclusions A bioinformatics approach allowed to identify a relevant chemoresistance-associated shift in neuroblastoma cell biology. The chemoresistance-associated enhanced pro-angiogenic activity observed in neuroblastoma cells is relevant for tumour progression and represents a potential therapeutic target.
TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma
(2009)
Proliferation and survival of Hodgkin and Reed/Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (cHL), are dependent on constitutive activation of nuclear factor {kappa}B (NF-{kappa}B). NF-{kappa}B activation through various stimuli is negatively regulated by the zinc finger protein A20. To determine whether A20 contributes to the pathogenesis of cHL, we sequenced TNFAIP3, encoding A20, in HL cell lines and laser-microdissected HRS cells from cHL biopsies. We detected somatic mutations in 16 out of 36 cHLs (44%), including missense mutations in 2 out of 16 Epstein-Barr virus–positive (EBV+) cHLs and a missense mutation, nonsense mutations, and frameshift-causing insertions or deletions in 14 out of 20 EBV– cHLs. In most mutated cases, both TNFAIP3 alleles were inactivated, including frequent chromosomal deletions of TNFAIP3. Reconstitution of wild-type TNFAIP3 in A20-deficient cHL cell lines revealed a significant decrease in transcripts of selected NF-{kappa}B target genes and caused cytotoxicity. Extending the mutation analysis to primary mediastinal B cell lymphoma (PMBL), another lymphoma with constitutive NF-{kappa}B activity, revealed destructive mutations in 5 out of 14 PMBLs (36%). This report identifies TNFAIP3 (A20), a key regulator of NF-{kappa}B activity, as a novel tumor suppressor gene in cHL and PMBL. The significantly higher frequency of TNFAIP3 mutations in EBV– than EBV+ cHL suggests complementing functions of TNFAIP3 inactivation and EBV infection in cHL pathogenesis.
Background: In this interdisciplinary project, the biological effects of heavy ions are compared to those of X-rays using tissue slice culture preparations from rodents and humans. Advantages of this biological model are the conservation of an organotypic environment and the independency from genetic immortalization strategies used to generate cell lines. Its open access allows easy treatment and observation via live-imaging microscopy. Materials and methods: Rat brains and human brain tumor tissue are cut into 300 micro m thick tissue slices. These slices are cultivated using a membrane-based culture system and kept in an incubator at 37°C until treatment. The slices are treated with X-rays at the radiation facility of the University Hospital in Frankfurt at doses of up to 40 Gy. The heavy ion irradiations were performed at the UNILAC facility at GSI with different ions of 11.4 A MeV and fluences ranging from 0.5–10 x 106 particles/cm². Using 3D-confocal microscopy, cell-death and immune cell activation of the irradiated slices are analyzed. Planning of the irradiation experiments is done with simulation programs developed at GSI and FIAS. Results: After receiving a single application of either X-rays or heavy ions, slices were kept in culture for up to 9d post irradiation. DNA damage was visualized using gamma H2AXstaining. Here, a dose-dependent increase and time-dependent decrease could clearly be observed for the X-ray irradiation. Slices irradiated with heavy ions showed less gamma H2AX-positive cells distributed evenly throughout the slice, even though particles were calculated to penetrate only 90–100 micro m into the slice. Conclusions: Single irradiations of brain tissue, even at high doses of 40 Gy, will result neither in tissue damage visible on a macroscopic level nor necrosis. This is in line with the view that the brain is highly radio-resistant. However, DNA damage can be detected very well in tissue slices using gamma H2AX-immuno staining. Thus, slice cultures are an excellent tool to study radiation-induced damage and repair mechanisms in living tissues.