Burger M.,University of Würzburg |
Grossman H.B.,University of Texas M. D. Anderson Cancer Center |
Droller M.,Mount Sinai Medical Center |
Schmidbauer J.,Medical University of Vienna |
And 10 more authors.
European Urology | Year: 2013
Background Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence. Objective To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence. Design, setting, and participants This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non-muscle-invasive bladder cancer (NMIBC). Intervention A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy. Outcome measurements and statistical analysis We studied the detection of NMIBC (intention to treat [ITT]: n = 831; six studies) and recurrence (per protocol: n = 634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection. Results and limitations BL cystoscopy detected significantly more Ta tumours (14.7%; p < 0.001; odds ratio [OR]: 4.898; 95% CI, 1.937-12.390) and CIS lesions (40.8%; p < 0.001; OR: 12.372; 95% CI, 6.343-24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p < 0.001), significant also in patients with primary (20.7%; p < 0.001) and recurrent cancer (27.7%; p < 0.001), and in patients at high risk (27.0%; p < 0.001) and intermediate risk (35.7%; p = 0.004). In 26.7% of patients, CIS was detected only by BL (p < 0.001) and was also significant in patients with primary (28.0%; p < 0.001) and recurrent cancer (25.0%; p < 0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p = 0.006; RR: 0.761 [0.627-0.924]), and lower in patients with T1 or CIS (p = 0.052; RR: 0.696 [0.482-1.003]), Ta (p = 0.040; RR: 0.804 [0.653-0.991]), and in high-risk (p = 0.050) and low-risk (p = 0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used. Conclusions This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9-12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer. © 2013 European Association of Urology.
Smits J.M.,Eurotransplant International Foundation |
Nossent G.D.,University of Groningen |
Vries E.D.,Eurotransplant International Foundation |
Rahmel A.,Eurotransplant International Foundation |
And 3 more authors.
Journal of Heart and Lung Transplantation | Year: 2011
Background The purpose of the study was to investigate the impact of the lung allocation score (LAS) on mortality among highly urgent (HU) and urgent (U) lung transplant (LTx) candidates in Eurotransplant (ET) and to identify useful additional parameters (LASplus). Methods All adult LTx candidates for whom a first request for HU or U status was made in 2008 in ET were included (N = 317). Patients were followed until LTx, death on the waiting list (WL), delisting, or closure date (i.e., January 10, 2010). The relationship between the LAS/LASplus and waiting list, post-transplant, and overall mortality was assessed with a multivariate regression model. The LAS and LASplus were decomposed into their basic waitlist and post-transplant components. Results Waiting list mortality rate was 22% and 1-year post-transplant mortality rate was 34%. The waitlist component of the LASplus was significantly associated with waiting list mortality (hazard ratio [HR] 1.91, p = 0.021), whereas the LAS was not (p = 0.063). The post-transplant components of both scores were significantly associated with 1-year post-transplant mortality (LAS: HR 2.69, p = 0.005; LASplus: HR 2.55, p = 0.004). Both scores strongly predicted overall mortality (LAS: HR 1.65, p = 0.008; LASplus: HR 1.72, p = 0.005). Conclusion LAS accurately predicts overall mortality in critically ill transplant candidates and should therefore be considered as the basis for a new lung allocation policy in ET. An adjustment of the original LAS may be indicated to accurately predict waiting list mortality. © 2011 International Society for Heart and Lung Transplantation.
Guerrasio L.,Klinikum Grosshadern |
Quinet J.,University Claude Bernard Lyon 1 |
Buttner U.,Klinikum Grosshadern |
Goffart L.,French National Center for Scientific Research
Journal of Neurophysiology | Year: 2010
When primates maintain their gaze directed toward a visual target (visual fixation), their eyes display a combination of miniature fast and slow movements. An involvement of the cerebellum in visual fixation is indicated by the severe gaze instabilities observed in patients suffering from cerebellar lesions. Recent studies in non-human primates have identified a cerebellar structure, the fastigial oculomotor region (FOR), as a major cerebellar output nucleus with projections toward oculomotor regions in the brain stem. Unilateral inactivation of the FOR leads to dysmetric visually guided saccades and to an offset in gaze direction when the animal fixates a visual target. However, the nature of this fixation offset is not fully understood. In the present work, we analyze the inactivation-induced effects on fixation. A novel technique is adopted to describe the generation of saccades when a target is being fixated (fixational saccades). We show that the offset is the result of a combination of impaired saccade accuracy and an altered encoding of the foveal target position. Because they are independent, we propose that these two impairments are mediated by the different projections of the FOR to the brain stem, in particular to the deep superior colliculus and the pontomedullary reticular formation. Our study demonstrates that the oculomotor cerebellum, through the activity in the FOR, regulates both the amplitude of fixational saccades and the position toward which the eyes must be directed, suggesting an involvement in the acquisition of visual information from the fovea. Copyright © 2010 The American Physiological Society.
Angele M.K.,Klinikum Grosshadern |
Pratschke S.,Klinikum Grosshadern |
Hubbard W.J.,University of Alabama at Birmingham |
Chaudry I.H.,University of Alabama at Birmingham
Virulence | Year: 2014
During sepsis, a complex network of cytokine, immune, and endothelial cell interactions occur and disturbances in the microcirculation cause organ dysfunction or even failure leading to high mortality in those patients. In this respect, numerous experimental and clinical studies indicate sex-specific differences in infectious diseases and sepsis. Female gender has been demonstrated to be protective under such conditions, whereas male gender may be deleterious due to a diminished cell-mediated immune response and cardiovascular functions. Male sex hormones, i.e., androgens, have been shown to be suppressive on cell-mediated immune responses. In contrast, female sex hormones exhibit protective effects which may contribute to the natural advantages of females under septic conditions. Thus, the hormonal status has to be considered when treating septic patients. Therefore, potential therapies could be derived from this knowledge. In this respect, administration of female sex hormones (estrogens and their precursors) may exert beneficial effects. Alternatively, blockade of male sex hormone receptors could result in maintained immune responses under adverse circulatory conditions. Finally, administration of agents that influence enzymes synthesizing female sex hormones which attenuate the levels of proinflammatory agents might exert salutary effects in septic patients. Prospective patient studies required for transferring those important experimental findings into the clinical arena. © 2014 Landes Bioscience.
Achenbach S.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Delgado V.,Leiden University |
Hausleiter J.,Klinikum Grosshadern |
Schoenhagen P.,Cleveland Clinic |
And 2 more authors.
Journal of Cardiovascular Computed Tomography | Year: 2012
Computed tomography (CT) plays an important role in the workup of patients who are candidates for implantation of a catheter-based aortic valve, a procedure referred to as transcatheter aortic valve implantation (TAVI) or transcatheter aortic valve replacement (TAVR). Contrast-enhanced CT imaging provides information on the suitability of the peripheral access vessels to accommodate the relatively large sheaths necessary to introduce the prosthesis. CT imaging also provides accurate dimensions of the ascending aorta, aortic root, and aortic annulus which are of importance for prosthesis sizing, and initial data indicate that compared with echocardiographic sizing, CT-based sizing of the prosthesis may lead to better results for postprocedural aortic valve regurgitation. Finally, CT permits one to predict appropriate fluoroscopic projections which are oriented orthogonal to the aortic valve plane. This consensus document provides recommendations about the use of CT imaging in patients scheduled for TAVR/TAVI, including data acquisition, interpretation, and reporting. © 2012 Society of Cardiovascular Computed Tomography.
Huppmann P.,Klinikum Grosshadern |
Huppmann P.,Ludwig Maximilians University of Munich |
Sczepanski B.,University Hospital of Tuebingen |
Boensch M.,University Hospital of Tuebingen |
And 5 more authors.
European Respiratory Journal | Year: 2013
Pulmonary rehabilitation is recommended for patients with chronic lung diseases including idiopathic pulmonary fibrosis according to international guidelines. However, data for patients with interstitial lung disease (ILD) are limited. We examined the effect of an inpatient pulmonary rehabilitation on functional status and quality of life in ILD patients. We evaluated 402 consecutive ILD patients who were admitted to a specialised pulmonary rehabilitation centre (1999́2010). All patients performed a standardised pulmonary rehabilitation programme including pulmonary function tests, blood-gas analysis, 6-min walk test (6MWT), dyspnoea rating and health-related quality of life questionnaire (the 36-item short-form health survey; SF-36) on admission and discharge. Mean duration of pulmonary rehabilitation was 30±1 days. 6MWT distance improved by 46±3 m (308±6 m versus 354±6 m; p=0.001). Dyspnoea rating did not change. Lung function testing showed marginal improvement of vital capacity (+1±0%; p=0.002). The SF-36 questionnaire demonstrated an increase in all eight sub-scores as well as in the physical and mental health summary scores (physical 6́1 points, p=0.001; mental health 10́1 points, p=0.001). Moreover, patients with signs of pulmonary hypertension also benefited from pulmonary rehabilitation. In a large cohort of patients with ILD, pulmonary rehabilitation had a positive impact on functional status and quality of life. Considering the limited treatment options in this patient population pulmonary rehabilitation appears to be a valuable adjunct therapy. Copyright © ERS 2013.
Levin J.,Klinikum Grosshadern |
Botzel K.,Klinikum Grosshadern |
Giese A.,Ludwig Maximilians University of Munich |
Vogeser M.,Klinikum Grosshadern |
Lorenzl S.,Klinikum Grosshadern
Dementia and Geriatric Cognitive Disorders | Year: 2010
Background/Aims: Increasing evidence suggests that elevated levels of homocysteine (Hcy) and methylmalonate (MMA) may be involved in the pathogenesis of neurodegenerative diseases. Methods: The urine levels of MMA and serum levels of Hcy as well as folic acid and vitamin B 12 were measured in patients suffering from the distinct neurodegenerative diseases progressive supranuclear palsy (PSP), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), and compared to age- and gender-matched control subjects. Results: We found significantly elevated concentrations of Hcy (PD 15.1, PSP 15.8, ALS 13.9, control 11.2 μmol/l) and MMA (PD 3.7, PSP 3.1, ALS 3.7, control 1.8 mg/g) in all patient groups in comparison with controls. Levels of Hcy and MMA did not differ significantly between the neurodegenerative diseases. Conclusion: Our findings might imply that Hcy and MMA are released as a consequence of neurodegeneration regardless of the underlying cause and serve as surrogate markers of neurodegeneration. Alternatively they might be directly implicated in the pathogenesis of these diseases. Since elevated levels of both Hcy and MMA are neurotoxic, further studies might investigate the effect of vitamin therapy on disease progression. Copyright © 2010 S. Karger AG, Basel.
Ruge M.I.,University of Cologne |
Ilmberger J.,Ludwig Maximilians University of Munich |
Tonn J.-C.,Klinikum Grosshadern |
Kreth F.-W.,Klinikum Grosshadern
Journal of Neuro-Oncology | Year: 2011
The present prospective study intends to evaluate health-related quality of life (HRQL) and cognitive functioning in adult patients with supratentorial World Health Organization (WHO) grade II glioma (LGG) prior to observation/therapy and to determine possible influences of tumor-related factors on these measures. Adult patients with biopsy-proven supratentorial LGG were considered eligible (study period 18 months). Besides detailed documentation of patient clinical status we evaluated HRQL using the Short Form-36 (SF-36) Health Survey and applied the Beck Depression Inventory. Furthermore, attention and verbal memory functions were tested. Data from matched healthy control populations served as reference, and T-values were compared using Mann-Whitney U tests. For correlation of scores the Pearson test was utilized. Thirty-three patients with median Karnofsky Performance Status (KPS) of 80 were evaluated. Selective and divided attention showed significant impairment (P<0.005), while verbal memory functions were unaffected. HRQL evaluated by SF-36 Health Survey was significantly reduced predominantly in the psychological domains (P<0.025 to P<0.0005). Nine patients displayed mild to moderate depression. Duration of symptoms ≥ 20 weeks and presence of seizures negatively affected aspects of HRQL, while cognitive functions were not influenced. KPS < 80 correlated significant only with reduced physical functioning (P< 0.002) and role functioning (P<0.01) on the SF-36 Health Survey. While displaying good clinical status, patients with LGG showed significant impairment in aspects of attention and affections of HRQL already at time of diagnosis. These results suggest that these impairments originate from the tumor and/or potentially from confrontation with the diagnosis itself. © Springer Science+Business Media, LLC. 2010.
Lezius F.,Klinikum Grosshadern |
Adrion C.,Institute For Medizinische Informationsverarbeitung |
Mansmann U.,Institute For Medizinische Informationsverarbeitung |
Jahn K.,Klinikum Grosshadern |
Strupp M.,Klinikum Grosshadern
European Archives of Oto-Rhino-Laryngology | Year: 2011
The objective of this study was to evaluate the clinical benefit and the side effects of high dosages of betahistine dihydrochloride (288-480 mg/day) in patients with severe Menière's disease (MD). In this case series 11 patients with MD who had not responded sufficiently to a dosage of 144 mg/day of betahistine dihydrochloride were treated on an individual basis with daily dosages between 288 and 480 mg of betahistine dihydrochloride. The number of attacks per month and the side effects were monitored. Non-parametric tests were used for statistical analysis. As a result, the frequency and the severity of vertigo were significantly reduced in all patients. The side effects were mild, self-limiting, and did not require any change in the treatment strategy. Despite the considerable limitations of an observational study-in particular in MD-high dosages of betahistine dihydrochloride between 288 and 480 mg/day seem to be effective in patients who do not sufficiently respond to lower dosages. Moreover, such dosages are well tolerated. © 2011 Springer-Verlag.
Paumgartner G.,Klinikum Grosshadern
Journal of Digestive Diseases | Year: 2010
New insights into the molecular mechanisms of bile formation and cholestasis have provided new concepts for pharmacotherapy of cholestatic liver diseases. The major aim in all forms of cholestasis is the reduction of hepatocellular retention of bile acids and other potentially toxic constituents of bile. Reduction of hepatocellular retention may be achieved by drugs that stimulate hepatocellular secretion via the canalicular route into the bile or via the alternative route across the basolateral membrane into the blood, and by drugs that stimulate the hepatocellular metabolism of hydrophobic bile acids to hydrophilic, less toxic metabolites. In cholestatic liver diseases that start with an injury of the biliary epithelium (e.g., primary biliary cirrhosis; PBC), protection of the cholangiocytes against the toxic effects of hydrophobic bile acids is most important. When hepatocellular retention of bile acids has occurred, the inhibition of bile acid-induced apoptosis becomes another target of therapy. Ursodeoxycholic acid protects the biliary epithelium by reducing the toxicity of bile, stimulates hepatobiliary secretion by upregulating transporters and inhibits apoptosis. It is the mainstay of therapy in PBC but of benefit also in a number of other cholestatic liver diseases. New drugs such as 6-ethyl-chenodeoxycholic acid and 24-nor-ursodeoxycholic acid are being evaluated for the treatment of cholestatic liver diseases. © 2010 The Author. Journal compilation © 2010 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology and Blackwell Publishing Asia Pty Ltd.