Tübingen, Germany
Tübingen, Germany

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Nielsen A.,Danish Cancer Society | Kjaer S.K.,Danish Cancer Society | Kjaer S.K.,Copenhagen University | Munk C.,Danish Cancer Society | And 2 more authors.
Journal of Medical Virology | Year: 2010

Persisting human papillomavirus (HPV) infection is a critical step in cervical carcinogenesis. This study was conducted to determine the type-specific HPV persistence and risk factors for persistence of high-risk HPV infections in a large cohort of Danish women. The study was based on a population-based prospective cohort study of women aged 20-29 years. Participants were interviewed and underwent two gynecological examinations 2 years apart. Women with Hybrid Capture 2 results at enrolment and a follow-up visit were included in the analysis (n=7,418). Persistence was defined as positivity for the same high-risk HPV type at both examinations. Overall, 4.2% of the women had persistent HPV infection, accounting for 26.9% of the initially HPV-positivewomen.HPV 16,HPV 58, and HPV31, all from species group alpha 9, were the most persistent types; however, other high-risk HPV types that are detected rarely in cancer cases were also likely to persist. The number of high-risk HPV types and detection of HPV 16 infection at baseline and ever use of oral contraceptives increased the risk for persistence. The risk factor analyses also showed that use of an intrauterine device decreased the risk for persistent high-risk HPV infection among women with one high-risk HPV type at baseline. No association was found with viral load or smoking. In conclusion, persistent high-risk HPV infection, especially HPV 16 persistence, was common among women positive for high-risk HPV. © 2010 Wiley-Liss, Inc.


Gosvig C.F.,Danish Cancer Society | Huusom L.D.,Danish Cancer Society | Andersen K.K.,Danish Cancer Society | Iftner A.,Universitaetsklinikum Tuebingen | And 5 more authors.
Gynecologic Oncology | Year: 2013

Objective Women with early cervical cancer or intraepithelial neoplasia grades 2 and 3 (CIN2 +) are treated by conization; however, they still have a higher risk for subsequent CIN2 + than the general female population. Persistence of high-risk (HR) human papillomavirus (HPV) is a key factor in the development of CIN2 +. We investigated persistence and reappearance of type-specific HR HPV infection after conization and evaluated possible co-factors. Methods During 2002-2006, cervical swabs from 604 women were collected before conization, at 4-6 months and at 8-12 months after conization. HPV was detected by HC2 and genotyped by LiPAv2. Information on co-factors was collected through a questionnaire. Associations were assessed by multivariate logistic regression analysis. Results HR HPV persistence rate was 9.5%. The α5/6 species were more likely to persist than α9 species (OR, 2.28; 95% CI, 1.11-4.70). For single infections, a doubling in viral load at enrolment increased the risk for persistence by 36% (95% CI, 1.13-1.63). In addition, margin status was associated with risk of persistence. Smoking, oral contraceptive use and severity of the cervical lesion did not significantly affect persistence. Among the HPV infections that had cleared, 2.2% reappeared. Conclusion Our study indicates that viral load is important in predicting HPV persistence. The α5/6 species were most likely to persist. However, most of these HPV types have a lower carcinogenic potential than the α7/α9 species and may be by-standers. Further studies are needed to assess whether pre-conization viral load can also predict subsequent CIN2 +. © 2013 Elsevier Inc.


Brogaard K.A.,Danish Cancer Society | Munk C.,Danish Cancer Society | Iftner T.,Universitaetsklinikum Tuebingen | Frederiksen K.,Danish Cancer Society | And 2 more authors.
Journal of Medical Virology | Year: 2014

The knowledge on risk factors of being human papillomavirus (HPV)-positive among older women is sparse. The aim was to determine the frequency of oncogenic HPV appearance after 7 years among initially HPV-negative women and to examine potential risk factors that influence the occurrence of HPV in older women using multiple logistic regression. For comparison, a younger cohort of women examined under identical study settings was included. This prospective cohort study comprised 1,577 older women (age 40-50 at enrolment) and 2,920 women aged 22-32. Participants were interviewed and underwent a gynecological examination at two time points (7 years apart). Cervical samples were tested for HPV using Hybrid Capture 2 (HC2) and only women who tested HC2-negative at baseline were included. The HPV prevalence among older and younger women was 6.4% and 10.7%, respectively, and there was no "second peak" observed among older women. Recent sexual partners were a strong determinant of HPV appearance irrespective of age. Lifetime number of sexual partners was a significant risk factor for HPV appearance among older women, even after adjustment for recent sexual behavior. In addition, menopause was associated with a non-significantly increased risk of HPV appearance at follow-up. In conclusion, appearance of HPV in previously HPV-negative older women may be due to both recent sexual behavior and previous exposure that is, reactivation of a latent HPV infection. © 2014 Wiley Periodicals, Inc.


Petry K.U.,Zentrum fur Frauenheilkunde | Rinnau F.,Zentrum fur Frauenheilkunde | Bohmer G.,Zentrum fur Frauenheilkunde | Hollwitz B.,Zentrum fur Frauenheilkunde | And 4 more authors.
BMC Cancer | Year: 2013

Background: Primary human papilloma virus (HPV) screening is more effective than cytology in reducing the risk of cervical cancer, but screening intervals should be extended in HPV-negative women. However, some Markov models predicted that long intervals are associated with an excess risk of cervical cancer. The aim of this analysis was to estimate the real-life risks and benefits of annual Papanicolaou (Pap) screening in HPV-negative women with normal cytology.Methods: Women with negative Hybrid Capture 2 (HC2) results and normal cytology at the time of inclusion in the Hannover HPV screening trial underwent annual Pap smears for 5 years. A subgroup was randomly selected for retesting with cytology, HC2, and colposcopy 60-68 months after recruitment.Results: Of 4236 women included, 3406 had at least one Pap smear, but only 1185 attended all five annual screening visits. The proportion of women with at least one abnormal smear was 14.4% in 60 months. The probability of abnormal smears increased continuously over time. No case of ≥ CIN2+ was observed during 5 years. Of 605 women selected for subgroup analysis, 292 agreed to be retested (48.3%). The rate of high-risk HPV at 60-68 months was 3.0% (9/296).Conclusions: The long-term risk of high-grade neoplasia after an initial negative HC2 test and normal cytology result was low, while the rate of false-positive abnormal Pap smears was significant and increased constantly over time. Pap smear screening of HPV-negative women more frequently than every 5 years could be potentially harmful and seems to be of little clinical value. © 2013 Petry et al.; licensee BioMed Central Ltd.


Kraemer B.F.,University of Utah | Kraemer B.F.,Universitaetsklinikum Tuebingen | Campbell R.A.,University of Utah | Schwertz H.,University of Utah | And 9 more authors.
PLoS Pathogens | Year: 2011

Human β-defensins (hBD) are antimicrobial peptides that curb microbial activity. Although hBD's are primarily expressed by epithelial cells, we show that human platelets express hBD-1 that has both predicted and novel antibacterial activities. We observed that activated platelets surround Staphylococcus aureus (S. aureus), forcing the pathogens into clusters that have a reduced growth rate compared to S. aureus alone. Given the microbicidal activity of β-defensins, we determined whether hBD family members were present in platelets and found mRNA and protein for hBD-1. We also established that hBD-1 protein resided in extragranular cytoplasmic compartments of platelets. Consistent with this localization pattern, agonists that elicit granular secretion by platelets did not readily induce hBD-1 release. Nevertheless, platelets released hBD-1 when they were stimulated by α-toxin, a S. aureus product that permeabilizes target cells. Platelet-derived hBD-1 significantly impaired the growth of clinical strains of S. aureus. hBD-1 also induced robust neutrophil extracellular trap (NET) formation by target polymorphonuclear leukocytes (PMNs), which is a novel antimicrobial function of β-defensins that was not previously identified. Taken together, these data demonstrate that hBD-1 is a previously-unrecognized component of platelets that displays classic antimicrobial activity and, in addition, signals PMNs to extrude DNA lattices that capture and kill bacteria. © 2011 Kraemer et al.


Feuerecker B.,TU Munich | Pirsig S.,TU Munich | Seidl C.,TU Munich | Aichler M.,Helmholtz Center Munich | And 3 more authors.
Cancer Biology and Therapy | Year: 2012

Cancer cells convert glucose preferentially to lactate even in the presence of oxygen (aerobic glycolysis-Warburg effect). New concepts in cancer treatment aim at inhibition of aerobic glycolysis. Pyruvate dehydrogenase converts pyruvate to acetylCoA thus preventing lactate formation. Therefore, the aim of this study was to evaluate compounds that could activate pyruvate dehydrogenase in cancer cells. We investigated the effects of (R)-(+)-α-lipoic acid (LPA ) and dichloroacetate (DCA), possible activators of pyruvate dehydrogenase, on suppression of aerobic glycolysis and induction of cell death. The neuroblastoma cell lines Kelly, SK-N-SH , Neuro-2a and the breast cancer cell line SkBr3 were incubated with different concentrations (0.1-30 mM) of LPA and DCA. The effects of both compounds on cell viability/proliferation (WST-1 assay), [18F]-FDG uptake, lactate production and induction of apoptosis (flow cytometric detection of caspase-3) were evaluated. Furthermore, NMRI nu/nu mice that had been inoculated s.c. with SkBr3 cells were treated daily for four weeks with LPA (i.p, 18.5 mg/kg) starting at day 7 p.i. Tumor development was measured with a sliding calliper and monitored via [18F]-FDG-PE T. Residual tumors after therapy were examined histopathologically. These data suggests that LPA can reduce (1) cell viability/proliferation, (2) uptake of [18F]-FDG and (3) lactate production and increase apoptosis in all investigated cell lines. In contrast, DCA was almost ineffective. In the mouse xenograft model with s.c. SkBr3 cells, daily treatment with LPA retarded tumor progression. Therefore, LPA seems to be a promising compound for cancer treatment. © 2012 Landes Bioscience.


Rothermund E.,University of Ulm | Kilian R.,University of Ulm | Hoelzer M.,Sonnenbergklinik | Mayer D.,Daimler AG | And 4 more authors.
BMC Public Health | Year: 2012

Background: Mental health issues are gaining in importance in society and the economic system. At the same time, the accessibility and stigmatisation of the mental health care system in Germany can obstruct help-seeking behavior and delay early psychotherapeutic interventions. Therefore, new models of care are being established at the interface of company-supported health promotion and conventional health insurance sponsored outpatient care for people developing mental illnesses. Two large industrial companies, in cooperation with two psychosomatic clinics, have recently established a model of psychosomatic consultation in the workplace. This new model of care offers the opportunity for a first psychotherapeutic door to door consultation with occupational medicine within the industrial workplace. The main empirical goals of this study are:.1) Describing the differences between patients who use this new diagnostic and therapeutic offer within the industrial workplace vs. patients who visit a conventional regional outpatient clinic, especially in regard to symptom duration and severity, work ability, and demographic characteristics, and.2) A first evaluation of how patients may benefit more from this new model of care compared to those first seen by standard outpatient care.In the qualitative part of the study, occupational physicians, psychosomatic therapists, involved personnel and select employees of the involved companies will be asked to comment on their experiences with this new approach. Methods/Design. The implementation study will take place in Ulm and in Stuttgart, with each site looking at one regional conventional psychosomatic outpatient clinic and one psychosomatic consultation offer within the workplace. 70 consecutive patients in each setting will be recruited (overall n=280). For the cross-sectional study and pre-post comparison we will use established and validated survey instruments (PHQ, SF-12, WAI, MBI, IS) as well as standardized questions about health care use. For data analysis, we will use uni- and multivariate analytical methods. Qualitative data analysis (expert interviews) will be carried out using Mayrings content analysis method. Discussion. The results of this study have the potential to provide evidence-based knowledge about an innovative model of psychotherapeutic outpatient care and to further promote tailored solutions for early psychotherapeutic interventions within the worksite. Trial Registration. DRKS00003184. © 2012 Rothermund et al.; licensee BioMed Central Ltd.


Fateh-Moghadam S.,Universitaetsklinikum Tuebingen | Voesch S.,Universitaetsklinikum Tuebingen | Htun P.,Universitaetsklinikum Tuebingen | Jorbenadze R.,Universitaetsklinikum Tuebingen | And 3 more authors.
Thrombosis and Haemostasis | Year: 2016

Stroke and thromboembolic events after transfemoral aortic valve replacement (TAVR) continue to be a problem. The aim of our study was to compare platelet aggregation (Agg) and platelet activation (PA) observed with two different catheter valves, the ESV-XT and the newer ESV-3 valve in patients (pts) undergoing TAVR on dual antiplatelet therapy (DAPT). A total of 174 patients with severe aortic stenosis and high surgical risk successfully underwent TAVR (60 ESV-XT; 114 ESV-3). Platelet Agg and PA (CD62P expression) were evaluated before and the following three days after TAVR under DAPT. Platelet Agg was inhibited to the same extent in both valve types and there was no significant difference in platelet drop between both valve types between day 0 and day 3 [ESV-XT vs ESV-3: median (25th-75th percentile): platelet count (x1000): 55 (42-74) vs 61(42-93), p=0.280]. However, there was an enhanced CD62P expression directly after TAVR with the ESV-XT compared to the ESV-3 [CD62P (MIF): 7.4 (6.8-8.6) vs 6.6 (6-7.9), p=0.014]. Surface expression of platelet CD62P was associated with the occurrence of residual aortic regurgitation (AR) and was significantly higher in patients with residual AR [CD62P (mild AR) vs CD 62P (no or trace AR): 7.9 (7.3-9.1) vs 7.1 (6.4-8.0), p < 0.001)]. PA was significantly enhanced in patients with the ESV-XT compared to the ESV-3 valve and was associated with the amount of residual AR which was significantly reduced by ESV-3. This may have implications for thromboembolic events following TAVR procedure. © Schattauer 2016.


CD endocarditis is a potentially lethal complication after implantation of permanent pacemakers or implantable cardioverter-defibrillators. Complete extraction of the hardware along with antibiotic treatment is the standard therapy. However, there is no standard procedure in the treatment of lead-associated infective endocarditis with large thrombotic vegetations. The authors present the case of a 60-year-old patient with a large vegetation located on the right atrial lead. Due to a high surgical and thrombembolic risk, especially of acute massive pulmonary embolism, the patient received recombinant tissue plasminogen activator to dissolve the thrombus under echocardiographic monitoring. The thrombotic masses were substantially reduced after thrombolysis. Therefore, standard transvenous extraction of the leads could be performed and high risk cardiac re-operation could be avoided.


PubMed | Universitaetsklinikum Tuebingen
Type: Comparative Study | Journal: Thrombosis and haemostasis | Year: 2015

Stroke and thromboembolic events after transfemoral aortic valve replacement (TAVR) continue to be a problem. The aim of our study was to compare platelet aggregation (Agg) and platelet activation (PA) observed with two different catheter valves, the ESV-XT and the newer ESV-3 valve in patients (pts) undergoing TAVR on dual antiplatelet therapy (DAPT). A total of 174 patients with severe aortic stenosis and high surgical risk successfully underwent TAVR (60 ESV-XT; 114 ESV-3). Platelet Agg and PA (CD62P expression) were evaluated before and the following three days after TAVR under DAPT. Platelet Agg was inhibited to the same extent in both valve types and there was no significant difference in platelet drop between both valve types between day 0 and day 3 [ESV-XT vs ESV-3: median (25th-75th percentile): platelet count (x1000): 55 (42-74) vs 61(42-93), p=0.280]. However, there was an enhanced CD62P expression directly after TAVR with the ESV-XT compared to the ESV-3 [CD62P (MIF): 7.4 (6.8-8.6) vs 6.6 (6-7.9), p=0.014]. Surface expression of platelet CD62P was associated with the occurrence of residual aortic regurgitation (AR) and was significantly higher in patients with residual AR [CD62P (mild AR) vs CD 62P (no or trace AR): 7.9 (7.3-9.1) vs 7.1 (6.4-8.0), p <0.001)]. PA was significantly enhanced in patients with the ESV-XT compared to the ESV-3 valve and was associated with the amount of residual AR which was significantly reduced by ESV-3. This may have implications for thromboembolic events following TAVR procedure.

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