Heneka M.T.,University of Bonn |
Heneka M.T.,German Center for Neurodegenerative Diseases |
Carson M.J.,University of California at Riverside |
Khoury J.E.,Harvard University |
And 41 more authors.
The Lancet Neurology | Year: 2015
Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease. © 2015 Elsevier Ltd.
PubMed | Bethanien Hospital Moers, University of Cologne, Bethanien Hospital, Johanniter Hospital and 12 more.
Type: Journal Article | Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer | Year: 2016
Rearrangements of RET are rare oncogenic events in patients with non-small cell lung cancer (NSCLC). While the characterization of Asian patients suggests a predominance of nonsmokers of young age in this genetically defined lung cancer subgroup, little is known about the characteristics of non-Asian patients. We present the results of an analysis of a European cohort of patients with RET rearranged NSCLC.Nine hundred ninety-seven patients with KRAS/EGFR/ALK wildtype lung adenocarcinomas were analyzed using fluorescence in situ hybridization for RET fusions. Tumor specimens were molecularly profiled and clinicopathological characteristics of the patients were collected.Rearrangements of RET were identified in 22 patients, with a prevalence of 2.2% in the KRAS/EGFR/ALK wildtype subgroup. Co-occurring genetic aberrations were detected in 10 patients, and the majority had mutations in TP53. The median age at diagnosis was 62 years (range, 39-80 years; mean SD, 61 11.7 years) with a higher proportion of men (59% versus 41%). There was only a slight predominance of nonsmokers (54.5%) compared to current or former smokers (45.5%).Patients with RET rearranged adenocarcinomas represent a rare and heterogeneous NSCLC subgroup. In some contrast to published data, we see a high prevalence of current and former smokers in our white RET cohort. The significance of co-occurring aberrations, so far, is unclear.
Palmedo H.,Johanniter Hospital |
Marx C.,University of Bonn |
Ebert A.,Johanniter Hospital |
Kreft B.,Johanniter Hospital |
And 10 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2014
Purpose: This study was designed to assess the additional value of SPECT/CT of the trunk used in conjunction with conventional nuclear imaging and its effects on patient management in a large patient series. Methods: In 353 patients, whole-body scintigraphy (WBS), SPECT, and SPECT/CT were prospectively performed for staging and restaging. SPECT/CT of the trunk was performed in all patients. In the 308 evaluable patients (211 with breast cancer, 97 with prostate cancer), clinical follow-up was used as the gold standard. Bone metastases were confirmed in 72 patients and excluded in 236. Multistep analyses per lesion and per patient were performed. Clinical relevance was expressed in terms of downstaging and upstaging rates on a per-patient basis. Results: In the total patient group, sensitivities, specificities, and negative and positive predictive values on a per-patient basis were 93 %, 78 %, 95 % and 59 % for WBS, 94 %, 71 %, 97 % and 53 % for SPECT, and 97 %, 94 %, 97 % and 88 % for SPECT/CT, respectively. In all subgroups, specificity and positive predictive value were significantly (p < 0.01) better with SPECT/CT. Downstaging of metastatic disease in the total, breast cancer and prostate cancer groups using SPECT/CT was possible in 32.1 %, 33.8 % and 29.5 % of patients, respectively. Upstaging in previously negative patients by additional SPECT/CT was observed in three breast cancer patients (2.1 %). Further diagnostic imaging procedures for unclear scintigraphic findings were necessary in only 2.5 % of patients. SPECT/CT improved diagnostic accuracy for defining the extent of multifocal metastatic disease in 34.6 % of these patients. Conclusions: SPECT/CT significantly improved the specificity and positive predictive value of bone scintigraphy in cancer patients. In breast cancer patients, we found a slight increase in sensitivity. SPECT/CT had a significant effect on clinical management because of correct downstaging and upstaging, better definition of the extent of metastases, and a reduction in further diagnostic procedures. © 2013 Springer-Verlag Berlin Heidelberg.
Neuhaus T.,St Vincenz Hospital |
Ko Y.-D.,Johanniter Hospital |
Stier S.,Hematology and Oncology
Supportive Care in Cancer | Year: 2012
Background Persistent and intractable hiccups are a rather rare, but distressing gastrointestinal symptom found in palliative care patients. Although several recommendations for treatment are given, hiccups often persist. Case reports We describe a new pharmacological approach for successfully treating hiccups in four cancer patients. In the first patient, chronic and intractable hiccups lasted for more than 18 months, but disappeared immediately after swallowing a viscous 2 % lidocaine solution for treatment of mucositis. Based on this experience, we successfully treated three further patients suffering from singultus using a lidocaine-containing gel. To our knowledge, this is the first report about managing hiccups by oral application of a lidocaine solution. © Springer-Verlag 2012.
Eichler C.,University of Cologne |
Hubbel A.,Johanniter Hospital |
Zarghooni V.,University of Cologne |
Thomas A.,Charité - Medical University of Berlin |
And 3 more authors.
Anticancer Research | Year: 2012
Aim: The objective of this study was the investigation of a possible improvement of tumor resection rate, i.e. R0 vs. R1 resection when intraoperative ultrasound evaluation of tissue margins is used during breast-conserving surgery (BCS). Patients and Methods: A total of 250 cases were evaluated retrospectively. The impact of ultrasound analysis onto clean margin rates was evaluated. A subgroup analysis assessed histology, stage, and neoadjuvant therapy with respect to R0 resection rate and ultrasound evaluation. Results: Of 250 BCS cases 84, (33.6%) underwent intraoperative ultrasound and 166 (66.4%) did not. Clean primary surgical margins (R0) were demonstrated for 218 (87.2%) patients after histological analysis. R0 resection was achieved in 81 (96.4%) patients in the ultrasound group compared to 137 (82.5%) in the control group. The difference between the two groups is significant. Conclusion: This study revealed a significant increase in R0 resection rates when intraoperative ultrasound was used to evaluate surgical margins.
PubMed | Bergmannsheil und Kinderklinik Buer and Johanniter Hospital
Type: Journal Article | Journal: Burns : journal of the International Society for Burn Injuries | Year: 2016
Burn scars remain a serious physical and psychological problem for the affected people. Clinical studies as well as basic scientific research have shown that medical needling can significantly increase the quality of burn scars with comparatively low risk and stress for the patient with regards to skin elasticity, moisture, erythema and transepidermal water loss. However, medical needling has no influence on repigmentation of large hypopigmented scars. The goal of this study is to evaluate whether two established methods - needling (for improvement of scar quality) and non-cultured autologous skin cell suspension (for repigmentation) - can be successfully combined. Twenty subjects with mean age of 33 years (6-60 years) with scars from deep second and third degree burns have been treated. The average treated surface area was 94cm
Pieper C.C.,University of Bonn |
Meyer C.,University of Bonn |
Vollmar B.,University of Rostock |
Hauenstein K.,University of Rostock |
And 2 more authors.
CardioVascular and Interventional Radiology | Year: 2015
Background: This study aimed to evaluate the embolic properties, time to reperfusion, and histologic changes in temporary embolization of liver tissue with degradable starch microspheres (DSM) in a swine model.Methods: In four adult minipigs, DSMs were injected into the right or left hepatic artery on the lobar level until complete stasis of the blood flow was detectable angiographically. The time required to complete angiographically determined reperfusion was noted. The animals were killed 3 h after complete reperfusion, and samples were taken from the liver. Histologic examinations of the embolized liver parenchyma and untreated tissue were performed.Results: Hepatic arterial embolization using DSMs was technically successful in all cases, with complete blood flow stasis shown by control angiography. A single vial of DSMs (450 mg/7.5 ml) was sufficient to embolize a whole liver lobe in all cases. Angiography showed complete reconstitution of hepatic arterial perfusion after a mean time to reperfusion of 32 ± 6.1 min (range, 26–39 min). Hematoxylin and eosin staining showed no histologically detectable differences between untreated tissue and parenchyma embolized with DSMs except for mild sinusoidal congestion in one case. Indirect in situ DNA nick end labeling staining (TUNEL) showed only single positive hepatocytes, indicating apoptosis.Conclusion: Temporary embolization of the hepatic artery using DSMs is feasible with complete reperfusion after 30 min in pigs. Even after complete arterial blood flow stasis, no extensive tissue damage to the embolized liver parenchyma was observed at histologic examinations in this short-term study. © 2014, Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).
Hashemiyoon R.,University of Cologne |
Kuhn J.,University of Cologne |
Kuhn J.,Johanniter Hospital |
Visser-Vandewalle V.,University of Cologne
Brain Topography | Year: 2016
Gilles de la Tourette syndrome is a complex, idiopathic neuropsychiatric disorder whose pathophysiological mechanisms have yet to be elucidated. It is phenotypically heterogeneous and manifests more often than not with both motor and behavioral impairment, although tics are its clinical hallmark. Tics themselves present with a complex profile as they characteristically wax and wane and are often preceded by premonitory somatosensory sensations to which it is said a tic is the response. Highly comorbid with obsessive–compulsive disorder and attention deficit-hyperactivity disorder, it is purported to be an epigenetic, neurodevelopmental spectrum disorder with a complex genetic profile. It has a childhood onset, occurs disproportionately in males, and shows spontaneous symptomatic attenuation by adulthood in the majority of those afflicted. Although not fully understood, its neurobiological basis is linked to dysfunction in the cortico-basal ganglia–thalamo–cortical network. Treatment modalities for Tourette syndrome include behavioral, pharmacological and surgical interventions, but there is presently no cure for the disorder. For those severely affected, deep brain stimulation (DBS) has recently become a viable therapeutic option. A key factor to attaining optimal results from this surgery is target selection, a topic still under debate due to the complex clinical profile presented by GTS patients. Depending on its phenotypic expression and the most problematic aspect of the disorder for the individual, one of three brain regions is most commonly chosen for stimulation: the thalamus, globus pallidus, or nucleus accumbens. Neurophysiological analyses of intra- and post-operative human electrophysiological recordings from clinical DBS studies suggest a link between tic behavior and activity in both the thalamus and globus pallidus. In particular, chronic recordings from the thalamus have shown a correlation between symptomatology and (1) spectral activity in gamma band power and (2) theta/gamma cross frequency coherence. These results suggest gamma oscillations and theta/gamma cross correlation dynamics may serve as biomarkers for dysfunction. While acute and chronic recordings from human subjects undergoing DBS have provided better insight into tic genesis and the neuropathophysiological mechanisms underlying Tourette syndrome, these studies are still sparse and the field would greatly benefit from further investigations. This review reports data and discoveries of scientific and clinical relevance from a wide variety of methods and provides up-to-date information about our current understanding of the pathomechanisms underlying Tourette syndrome. It gives a comprehensive overview of the current state of knowledge and addresses open questions in the field. © 2016 The Author(s)
Krolop L.,University of Bonn |
Ko Y.-D.,Johanniter Hospital |
Schwindt P.F.,Oncology Practice |
Schumacher C.,St Elisabeth Hospital Cologne Hohenlind |
And 2 more authors.
BMJ Open | Year: 2013
Objective: To develop and evaluate a multiprofessional modular medication management to assure adherence to capecitabine. Methods: The study was conducted as a prospective, multicentred observational cohort study. All participants received pharmaceutical care consisting of oral and written information. Daily adherence was defined as percentage of days with correctly administered capecitabine doses and assessed using medication event monitoring. According to their daily adherence during the first cycle, patients were identified as initially non-adherent (<90% adherence) or adherent (≥90% adherence). Initially non-adherent patients received additional adherence support. Results: Seventy-three patients with various tumour entities were enrolled, 58 were initially adherent and 15 non-adherent. Median daily adherence of initially non-adherent patients increased from 85.7% to 97.6% during the observation period of six cycles. Throughout all cycles, median daily adherence of initially adherent patients was 100.0%. Daily adherence was not associated with sociodemographic and disease-related factors. No patient was non-persistent. Conclusions: An early adherence screening effectively distinguishes between patients adhering and nonadhering to capecitabine. The provision of specific adherence support is associated with enhanced adherence of initially non-adherent patients, whereas initially adherent patients remain adherent for at least six cycles without specific support. Our needs-based approach helps to use available resources for adherence management efficiently.
Simons S.,Institute of Pharmacy |
Ringsdorf S.,Institute of Pharmacy |
Braun M.,University of Bonn |
Mey U.J.,University of Bonn |
And 5 more authors.
Supportive Care in Cancer | Year: 2011
Purpose In this prospective multi-centre observational cohort study, we investigated the effect of an intensified multidisciplinary pharmaceutical care programme on the adherence of cancer patients treated with capecitabine, a prodrug of fluorouracil. Patients and methods Twenty-four colorectal and 24 breast cancer patients participated in this study. Patients of the control group (n=24) received standard care, patients of the intervention group (n=24) received intensified pharmaceutical care consisting of written and spoken information. Adherence to capecitabine chemotherapy was measured using an electronic medication event monitoring system (MEMS™). Results Patients in the intervention group exhibited an enhanced but not significantly different mean overall adherence compared to the control group (97.9% vs 90.5%, p=0.069). Mean daily adherence was significantly higher in the intervention group (96.8% vs 87.2%, p=0.029). Variability of both adherence parameters was considerably reduced when pharmaceutical care was provided. At the end of the observation period of 126 days, the probability of still being treated with capecitabine was found to be 48% in the control group and 83% in the intervention group (p=0.019, log-rank test). The relative risk for a deviating drug intake interval, i.e. <10 or >14 instead of 12 h, in the intervention group was found to be 0.51 (95% CI, 0.46-0.56) compared with the control group (p<0.05, Chi-square test). Conclusions The provision of intensified pharmaceutical care can enhance adherence to and prolong treatment with capecitabine. The results underline the importance of multidisciplinary care to assure the effectiveness of oral chemotherapy. © 2011 Springer-Verlag.