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Biomedical subjects

M Wagner

Publications and source records attributed to M Wagner.

At least 19 recordsLinked to original sources
PubMed2007

WNT5A--target of CUTL1 and potent modulator of tumor cell migration and invasion in pancreatic cancer.

Previously, we have identified the transcription factor CUTL1 as an important mediator of tumor invasion and target of tumor growth factor-beta. Using high-throughput approaches, we identified several putative downstream effectors of CUTL1, among them WNT5A, a secreted member of the Wnt multigene family. The aim of this study was to investigate the role of WNT5A as a novel target of CUTL1 in pancreatic cancer. CUTL1 and WNT5A were stably over-expressed as well as transiently and stably knocked down by RNA interference. Effects on proliferation, migration and invasiveness were investigated by thymidine incorporation, Boyden chamber experiments and time-lapse microscopy. Expression of WNT5A in pancreatic cancer tissues was analyzed by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. We found that CUTL1 transcriptionally up-regulated WNT5A on RNA, protein and promoter level. WNT5A significantly enhanced migration, proliferation and invasiveness, mediating the pro-invasive effects of CUTL1 to a major extent. WNT5A effects were accompanied by a marked modulation of marker genes associated with epithelial-mesenchymal transition. Using RT-PCR and immunohistochemistry, we found that WNT5A is up-regulated early during pancreatic cancerogenesis in pancreatic intraepithelial neoplasias lesions and in invasive pancreatic adenocarcinomas, as compared with normal pancreas tissues. These data identify WNT5A as important target of CUTL1 and as novel mediator of invasiveness and tumor progression in pancreatic cancer.

Cell Line, Tumor↗
PubMed2007

Impulsiveness in obsessive-compulsive disorder: results from a family study.

OBJECTIVE: Although obsessive-compulsive disorder (OCD) is usually conceptualized as an anxiety disorder some studies suggested it to be a deficit of impulse control. The purpose of this study was to assess impulsiveness in OCD families and compare it to control families. METHOD: Seventy cases and their 139 relatives were compared with 70 controls and their 134 relatives from a German family study on OCD (German Epidemiologic Network for OCD Studies). All subjects were interviewed and diagnosed according DSM-IV criteria and were administered the Barratt Impulsiveness Scale (BIS) and PADUA-Inventory to assess obsessive-compulsive symptoms. RESULTS: OCD subjects had significantly higher scores of cognitive impulsiveness. However, first-degree relatives of OCD cases and of controls had comparable BIS-11 scores. Significant associations of aggressive obsessions and checking with cognitive impulsiveness were found. CONCLUSION: OCD is a severe mental disorder that is characterized by a lack of cognitive inhibition. However, impulsiveness does not represent a familial trait in families of OCD subjects.

Adult↗
PubMed2006

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin.

Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

Adult↗
PubMed2006

Bilateral, simultaneous rupture of the quadriceps tendon: a diagnostic pitfall? Report of three cases and meta-analysis of the literature.

Bilateral, simultaneous quadriceps tendon rupture (QTR) represents a rare entity and delay in establishing the correct diagnosis is not uncommon. Another three cases are reported here and in all the correct diagnosis was missed initially. A review of the English and German literature retrieved 105 cases of bilateral, simultaneous QTR and in 32 patients (30.5%) the correct diagnosis was established with delay. In 28 cases--representing 25 men (89.3%) and 3 women (10.7%)--sufficient data was available for further analysis. In the majority of patients (n = 19/28; 67.9%) rupture was associated with trauma, while no trauma was reported in 9/28 cases (32.1%). No direct correlation between age and the kind of rupture form (traumatic/spontaneous) could be detected (P = 0.35). Most partients (n = 18/28; 64.3%) presented risk factors associated with QTR and obesity (n = 6/28; 21.4%) was most frequently encountered. A direct association between the rate of risk factors and the rupture form was not seen (P = 0.5). Overall diagnostic delay lasted 64.7 days on an average (traumatic ruptures 67.7 days/spontaneous ruptures 58.7 days) with this period being longer than 2 weeks in 51.9% and longer than 3 months in 33.3% of patients. Delay varied distinctly in different medical institutions as this period lasted in hospital departments 93.9 days, in ambulances 24 days and in General Practitioners 7.6 days on an average. Initially 25 incorrect diagnoses were established in 21/28 (75%) patients, while 7/28 cases (25%) were discharged initially without any diagnosis. Clinical examination revealed most often palpable suprapatellar gaps (n = 17/24) and effusions (n = 13/24), while the classic trias of painful swelling, suprapatellar gap and loss of knee extension was found in only 58.3% of reported patients (n = 14/24). The correct diagnosis of bilateral QTR was established in 60.7% (n = 17/28) by history and clinical examination alone. In 10.7% (n = 3/28) clinical suspect was supported by sonography and in 14.3% (n = 4/28) by MRT; in 14.3% (n = 4/28) the correct diagnosis represented a by chance finding during diagnostic or operative procedures of other indication. In 52 tendons detailed information about repair was provided and most often transosseous fixation (n = 30/52; 57.7%) and direct repair (n = 14/52; 26.9%) were used, while a tenoplasty was performed in only 15.4% (n = 8/52). Only 34.6% of patients (n = 9/26) with follow-up data (n = 26/28) reported a full recovery with a trend that early surgical repair (limit 2 weeks) improves the final outcome.

Adult↗
PubMed2006

[Requirements for patient-oriented results of research on stroke outcome].

Because assessing the requirements for patient-oriented outcome research on stroke rests on numerous prerequisites, these have to be defined beforehand, at least in a general sense. They consist of the epidemiological dimensions of stroke and related societal challenges; the special features of this disease entity with resulting numerous outcome dimensions; the structure, processes and results of the management of stroke; current outcome measurements with their patient-relevant results including quality of life; and the great importance of individually adapted prevention of recurrences and secondary events, as well as adequate treatment of associated diseases or sequelae. It is only on this basis that in the end those features can be formulated that are needed for patient-relevant outcome research.

Germany↗
PubMed2006

[Changes in the perception of risk factors for stroke in the German population between 1995-1996 and 2000-2001. Results of two representative EMNID surveys].

BACKGROUND AND OBJECTIVE: Stroke is one of the leading causes for death and disability worldwide. A better understanding of the perception of modifiable stroke risk factors in the population is the first step to initiate effective prevention strategies on population level. Changes over 5 years in the risk perception in the general population were investigated by two representative surveys in Germany. METHODS: Nationwide programs to screen voluntary participants for stroke risk were undertaken in 1995-1996 and 2000-2001 by the German Stroke Foundation, in cooperation with the health insurance company BARMER and the Sanofi-Synthelabo Company. As part of these programmes two surveys were performed by TNS-EMNID to collect data on population knowledge. A representative sample of the German population was selected and asked to categorize their perception of stroke risk for common vascular risk factors. RESULTS: A total of 8193 participants were interviewed (4081 in 1995-1996 and 4112 in 2000-2001); 43.5% were (3) 50 years of age and 52.5% were female. Hypertension was rated by 68.3% to be in the highest risk category for stroke, followed by smoking (52.3%), hypercholesterolemia (48.0%), overweight (48.0%), excessive alcohol consumption (32.9%) and diabetes (26.6%). The proportion of participants who graded these factors to be important for stroke occurrence was persistently higher in 2000-2001 than in 1995-1996. CONCLUSION: Perception of modifiable risk factors for stroke increased over a 5-year time period in two representative surveys in Germany. The importance of diabetes mellitus as a risk factor for stroke is especially underestimated in the general population.

Adolescent↗
PubMed2006

[A telephone hotline as an easily accessible service for questions on schizophrenia].

Public relations activities of the German Research Network on Schizophrenia (GRNS) have shown that there is a demand for more information about schizophrenia disorder. This confirms international research findings that relatives of schizophrenia patients are particularly in need of information and support. In response, the GRNS has maintained a telephone hotline since 2001. The hotline is manned by clinical experts, psychiatrists, or psychologists once a week. The telephone calls are documented in a systematic manner. From 2001 to 2003, 3,909 calls were registered. This volume exceeds the limit of the hotline's resources. The telephone hotline is mainly used by relatives of psychotic patients. Most questions relate to the symptoms of schizophrenia and pharmaceutical treatment. The need for emotional support is also a high motivational factor for dialing the hotline number. The telephone hotline seems to be a worthwhile addition to the already existing crisis telephones and should be maintained even after public funding of the network expires.

Caregivers↗
PubMed2006

Enhanced expression and clinical significance of CC-chemokine MIP-3 alpha in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most frequent visceral neoplasms worldwide. Using RT-PCR, ELISA, microdissection and immunohistochemistry, we investigated the expression profiles of CCL19, CCL20, CCL21 and CXCL12 and their receptors in tumourous and tumour neighbouring tissues from patients with HCC and in nonmalignant liver lesions, respectively. All chemokines were found to be expressed in normal liver and HCC tissues, yet CCL20 was the only chemokine showing significant upregulation in HCC tissues. Clinicopathological analysis revealed a distinct increase in CCL20 expression rates in HCC tissues of grade III tumours in comparison to HCC tissues from grade II tumours. On mRNA level, only chemokine receptor CCR6 revealed significant upregulation in HCC tissues. However, immunohistochemical studies indicated a marked CCR6 expression accumulated in a streak of normal cells along the tumour invasion front in all our HCC specimens which could provide a stimulative signal for the tumour to further expand. The present findings show significant overexpression of CCL20 in the tumour tissues and marked overexpression of the corresponding receptor CCR6 in the tumour invasion front of HCC patients in comparison to normal liver. Moreover, CCL20 expression was found to correlate with tumour grade and therefore, we suggest that the CCL20/CCR6 system may be involved in hepatocarcinogenesis.

Adult↗
PubMed2006

Parvovirus B19 detected in Rosai-Dorfman disease in nodal and extranodal manifestations.

Sinus histiocytosis with massive lymphadenopathy (SHML), also designated as Rosai-Dorfman disease (RDD), is a rare benign reactive lymphoproliferative disorder. It is defined by a characteristic histopathology with sinus histiocytosis and haemophagocytosis known as emperipolesis. In histiocytes S100 is strongly expressed, whereas CD1a staining typically is negative. The disease mainly manifests at a single lymph node; however, multilocular and extranodal affection can occur. Causative infectious agents, and virus infections in particular, have repeatedly been suspected, although until now the origin of the disease has been unclear. Four cases of RDD (two nodal sites and two extranodal upper respiratory tract sites) were analysed for parvovirus B19 (B19) infection by immunohistochemistry to detect B19 capsid proteins VP1/VP2. In all the four cases, huge numbers of B19-positive cells were partly detected. The positive cells were identified either as lymphocytes or, in one extranodal case, also as respiratory epithelial cells. This is the first report of B19 infection in RDD tissue, indicating that B19 may be associated with the pathogenesis of SHML.

Adult↗
PubMed2006

Ecophysiology and niche differentiation of Nitrospira-like bacteria, the key nitrite oxidizers in wastewater treatment plants.

Nitrite-oxidizing bacteria of the genus Nitrospira are key nitrifiers in wastewater treatment plants. Pure cultures of these organisms are unavailable, but cultivation-independent molecular methods make it possible to detect Nitrospira-like bacteria in environmental samples and to investigate their ecophysiology. Comprehensive screening of natural and engineered habitats and of public databases for 16S rRNA sequences of Nitrospira-like bacteria revealed a surprisingly high biodiversity in the genus Nitrospira, which comprises at least four phylogenetic sublineages. All Nitrospira-like bacteria detected in wastewater treatment plants belonged to the sublineages I and II. Subsequently, the population dynamics of different Nitrospira-like bacteria were monitored, by quantitative fluorescence in situ hybridization with rRNA-targeted probes, confocal laser scanning microscopy and digital image analysis, during incubation of nitrifying activated sludge in media containing different nitrite concentrations. These experiments showed that Nitrospira-like bacteria, which were affiliated with the phylogenetic sublineages I or II of the genus Nitrospira, responded differently to nitrite concentration shifts. Previously unknown properties of Nitrospira-like bacteria were discovered in the course of an environmental genomics project. Implications of the obtained results for fundamental understanding of the microbial ecology of nitrite oxidizers as well as for future improvement of nutrient removal in wastewater treatment plants are discussed.

Bacteria↗
PubMed2006

Characterization of Listeria monocytogenes isolates from 50 small-scale Austrian cheese factories.

One hundred eighty-one small-scale cheese factories (annual production < 100,000 kg) were tested for the presence of Listeria monocytogenes in cheese and smear samples from 1997 to 2000. In total, 2615 samples were drawn. Fifty (27.6%) of 181 enterprises yielded L. monocytogenes. From 14 of the cheese-making facilities, we obtained more than four L. monocytogenes isolates. A total of 182 mostly cheese- and smear-borne L. monocytogenes strains were characterized by serotyping and pulsed-field gel electrophoresis. In 12 of 14 cheese factories, over half of the L. monocytogenes isolates were genetically indistinguishable by pulsetype. On average, genetically indistinguishable isolates were recovered for 11.9 months. Regarding serotypes, 27.3% of the isolates were of serovar 4b. Inadequate personal hygiene could explain the high prevalence of serovar 4b isolates in small-scale cheesemaking facilities. Forty-two percent of the serovar 4b isolates recovered from epidemiologically unlinked facilities (in comparison to 40 and 29% of the 1/2a and 1/2b isolates, respectively) were genetically indistinguishable from at least one other isolate. Indistinguishable serovar 1/2a and 1/2b isolates belonged to five and six different pulsetypes, respectively, whereas serovar 4b isolates belonged to only two pulsetypes. This finding suggested a wide distribution of genetically homologous serovar 4b isolates among the facilities tested in our study.

Austria↗
PubMed2006

Open fractures and infection.

Open fractures still represent a major challenge for the treating surgeon and frequently demand a complex of soft tissue and bone procedures to achieve an undisturbed healing with adequate limb function. However, despite improvement in operative techniques and antibiotic therapy septic complications still occur in severe open fracture forms up to 50%. They are still deleterious for the patient as well as a major economic factor for the treating hospital. Radical (repetitive) debridement of the wound and coverage of soft tissue defects are of utmost importance in the prophylaxis of septic complications along with antibiotic therapy. If the local wound requires flap coverage, early performed procedures yield a clear decrease of infection rates even in most severe fracture forms. Osseous stabilization contributes to infection prophylaxis, especially when the implants can be inserted in a minimal invasive way and provide an adequate handling of soft tissues and the wound. Thus, most often intramedullary nails and external fixators are used today for osteosynthesis. Recently developed plates with angular stability offer a promising alternative even in open fractures, especially when there is an extension of the fracture into the meaphyseal area though indications have to be evaluated. Manifest septic complications demand an early and aggressive approach with radical eradication of the septic topic. While acute infections require most often only minor surgical procedures and offer the chance to leave implants in situ, chronic infections usually demand complex reconstructive measures of bones and soft tissues.

Debridement↗
PubMed2005

Laparoscopic ventral hernia repair is safe and cost effective.

BACKGROUND: Ventral hernia repair is increasingly performed by laparoscopic means since the introduction of dual-layer meshes. This study aimed to compare the early complications and cost effectiveness of open hernia repair with those associated with laparoscopic repair. METHODS: Open ventral hernia repair was performed for 92 consecutive patients using a Vypro mesh, followed by laparoscopic repair for 49 consecutive patients using a Parietene composite mesh. RESULTS: The rate of surgical-site infections was significantly higher with open ventral hernia repair (13 vs 1; p = 0.03). The median length of hospital stay was significantly shorter with laparoscopic surgery (7 vs 6 days; p = 0.02). For laparoscopic repair, the direct operative costs were higher (2,314 vs 2,853 euros; p = 0.03), and the overall hospital costs were lower (9,787 vs 7,654 euros; p = 0.02). CONCLUSIONS: Laparoscopic ventral hernia repair leads to fewer surgical-site infections and a shorter hospital stay than open repair. Despite increased operative costs, overall hospital costs are lowered by laparoscopic ventral hernia repair.

Adult↗
PubMed2005

Use of multiple data streams to conduct Bayesian biologic surveillance.

INTRODUCTION: Emergency department (ED) records and over-the-counter (OTC) sales data are two of the most commonly used sources of data for syndromic surveillance. The majority of detection algorithms monitor these data sources separately and either do not combine them or combine them in an ad hoc fashion. This report outlines a new causal model that combines the two data sources coherently to perform outbreak detection. OBJECTIVES: This report describes the extension of the Population-wide Anomaly Detection and Assessment (PANDA) Bayesian biologic surveillance algorithm to combine information from multiple data streams. It also outlines the assumptions and techniques used to make this approach scalable for real-time surveillance of a large population. METHODS: A causal Bayesian network model used previously was extended to incorporate evidence from daily OTC sales data. At the level of individual persons, the actions that result in the purchase of OTC products and in admission to an ED were modeled. RESULTS: Preliminary results indicate that this model has a tractable running time consisting of 209 seconds for initialization and approximately 4 seconds for every hour's worth of ED data, as measured on a Pentium-4 three-Gigahertz machine with two Gigabytes of RAM. CONCLUSION: Preliminary results for surveillance using a new Bayesian algorithm that models the interaction between ED and OTC data are positive regarding the run time of the algorithm.

Algorithms↗
PubMed2005

High-fidelity injection detectability experiments: a tool for evaluating syndromic surveillance systems.

INTRODUCTION: When public health surveillance systems are evaluated, CDC recommends that the expected sensitivity, specificity, and timeliness of surveillance systems be characterized for outbreaks of different sizes, etiologies, and geographic or demographic scopes. High-Fidelity Injection Detectability Experiments (HiFIDE) is a tool that health departments can use to compute these metrics for detection algorithms and surveillance data that they are using in their surveillance system. OBJECTIVE: The objective of this study is to develop a tool that allows health departments to estimate the expected sensitivity, specificity, and timeliness of outbreak detection. METHODS: HiFIDE extends existing semisynthetic injection methods by replacing geometrically shaped injects with injects derived from surveillance data collected during real outbreaks. These injects maintain the known relation between outbreak size and effect on surveillance data, which allows inferences to be made regarding the smallest outbreak that can be expected to be detectable. RESULTS: An example illustrates the use of HiFIDE to analyze detectability of a waterborne Cryptosporidium outbreak in Washington, DC. CONCLUSION: HiFIDE enables public health departments to perform system validations recommended by CDC. HiFIDE can be obtained for no charge for noncommercial use (http://www.hifide.org).

Cryptosporidiosis↗
PubMed2005

Eosinophil granulocytes are activated during the remission phase of ulcerative colitis.

AIM: The aim of this study was to establish a method of investigating intestinal eosinophil and neutrophil granulocytes by flow cytometry, and to compare the distribution and activity of these cells in different stages of ulcerative colitis (UC). METHODS: Biopsy samples were taken from six locations of the entire colon and from the terminal ileum in 10 patients with active total UC, 10 patients with inactive total UC, eight patients with active distal UC, and 11 control subjects. Cell suspensions from biopsies and from peripheral blood were incubated with fluorophore conjugated monoclonal antibodies. The use of scatter plot-gating and specific antibodies was established in a flow cytometry assay. RESULTS: Eosinophils were more numerous and more active in patients with active UC than in controls. Interestingly, during inactive UC, the number of activated eosinophils was even larger. Eosinophil activity was high in the rectum of patients with distal colitis but was also slightly elevated in the proximal colon. Neutrophils were increased in number and activity during active but not inactive UC. In patients with distal colitis, activated neutrophils were only found in the sigmoid colon and rectum. CONCLUSION: With this method, we confirm that neutrophils participate in the inflammatory process during active UC, and that they express a resting phenotype during remission. The finding of activated eosinophils in inflamed intestine strengthens the view of these cells as proinflammatory and tissue damaging. Nevertheless, our new finding of high eosinophil activation during inactive UC suggests that eosinophils play a role in repair of injured epithelium.

Adult↗
PubMed2005

Randomized clinical trial of pylorus-preserving duodenopancreatectomy versus classical Whipple resection-long term results.

BACKGROUND: It is not known whether pylorus-preserving duodenopancreatectomy is as effective as the classical Whipple procedure in the resection of pancreatic and periampullary tumours. A prospective randomized trial was undertaken to compare the results of the two procedures. METHODS: Clinical data, histological findings, short-term results, survival and quality of life of all patients having surgery for suspected pancreatic or periampullary cancer between June 1996 and September 2001 were analysed. RESULTS: Two hundred and fourteen patients were randomized to undergo either a standard or a pylorus-preserving Whipple resection. After exclusion of 84 patients on the basis of intraoperative findings, 130 patients (66 standard Whipple operation and 64 pylorus-preserving resection) were entered into the trial. Of these, 110 patients with proven adenocarcinoma (57 standard Whipple and 53 pylorus-preserving resection) were analysed for long-term survival and quality of life. There was no difference in perioperative morbidity. Long-term survival, quality of life and weight gain were identical after a median follow-up of 63.1 (range 4-93) months. At 6 months, capacity to work was better after the pylorus-preserving procedure (77 versus 56 per cent; P = 0.019). CONCLUSION: Both procedures were equally effective for the treatment of pancreatic and periampullary cancer. Pylorus-preserving Whipple resection offers some minor advantages in the early postoperative period, but not in the long term.

Adult↗