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Hanefeld M.,TU Dresden | Pistrosch F.,TU Dresden | Pistrosch F.,Universitatsklinik Carl Gustav Carus | Koehler C.,TU Dresden | Chiasson J.L.,Center Hospitalier Of Luniversite Of Montreal
Journal of Hypertension | Year: 2012

Background: Type 2 diabetes mellitus and hypertension are closely associated and contribute together to microvascular and macrovascular end-organ damage. Prevalence of hypertension is increased even in the prediabetic state. However, there is little information available about the relationship between incidence of hypertension and a deterioration of glucose tolerance from impaired glucose tolerance (IGT) to diabetes. Methods: To clarify these issues we analysed data from the Stop non insulin dependent diabetes mellitus (STOP-NIDDM) trial-a prospective interventional study for the prevention of type 2 diabetes in people with prediabetes using the alpha-glucosidase inhibitor acarbose. Hypertension was already present at study entry in 702 (51.3%) of 1368 patients who were eligible for intention-to-treat analysis. Results: A total of 96 out of the 666 normotensive individuals at baseline developed hypertension during the 3.3-year follow-up. The strongest risk factors for time to development of hypertension were abdominal obesity at baseline [hazard ratio 1.91, 95% confidence interval (CI) 1.19-3.05, P < 0.01] and worsening of glucose tolerance (hazard ratio 1.54, 95% CI 1.02-2.32, P < 0.05), whereas acarbose treatment reduced the risk of hypertension (hazard ratio 0.59, 95% CI 0.39-0.90, P < 0.05). Conclusion: A significant relationship was found between the development of type 2 diabetes and hypertension in patients with IGT, and treatment with acarbose, which primarily improved postprandial hyperglycaemia, reduced the incidence of hypertension as well as diabetes. This suggests that the two entities shared 'common soil'. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Lordick F.,TU Munich | Luber B.,TU Munich | Lorenzen S.,TU Munich | Hegewisch-Becker S.,Onkologische Schwerpunktpraxis Eppendorf | And 10 more authors.
British Journal of Cancer | Year: 2010

Background:Cetuximab enhances the efficacy of chemotherapy in several cancer types. This trial assessed the activity of cetuximab and chemotherapy in advanced gastric cancer.Methods:Patients with previously untreated, metastatic, gastric cancer received cetuximab 400 mg m 2 at first infusion followed by weekly infusions of 250 mg m 2 combined with FUFOX (oxaliplatin 50 mg m 2, 5-FU 2000 mg m 2, and DL-folinic acid 200 mg m 2 d1, 8, 15 and 22 qd36). The primary endpoint was tumour response.Results:Overall, 52 patients were enrolled. The most common grade 3/4 toxicities were diarrhoea (33%), and skin toxicity (24%). Efficacy was evaluable in 46 patients who showed a response rate of 65% (CI 95%: 50-79%) including four complete responses. Time to progression (TTP) was 7.6 months (CI 95%: 5.0-10.1 months) and overall survival (OS) was 9.5 months (CI 95%: 7.9-11.1 months). Epidermal growth factor receptor (EGFR) was detectable in 60% of tumours but showed no correlation with treatment outcome. A KRAS mutation was found in only 1 of 32 (3%) tumour samples analysed.Conclusion: Cetuximab plus FUFOX showed an interesting high response rate in metastatic gastric cancer. Cetuximab plus platinum-fluoropyrimidine chemotherapy is at present being investigated in a phase III randomised controlled trial. © 2010 Cancer Research UK. Source

Braun S.,Universitatsklinik Carl Gustav Carus | Kolditz M.,Universitatsklinik Carl Gustav Carus | Halank M.,Universitatsklinik Carl Gustav Carus | Weise M.,Universitatsklinik Carl Gustav Carus Dresden | And 2 more authors.
Deutsche Medizinische Wochenschrift | Year: 2011

History and admission findings: A 49-year-old woman was admitted because of hemoptysis for four months. Several bronchoscopies and thoracic computed tomographies at other hospitals had not revealed the cause of the sustained hemoptysis. Eight months before admission she had undergone pulmonary vein ablation (PVA) for paroxysmal atrial fibrillation. After the PVA she had initially received oral anticoagulation, but this had been stopped because of the hemoptysis. Physical examination at admission to our hospital was unremarkable except for moderate obesity and arterial hypertension Investigations: Ventilation/perfusion scintigraphy demonstrated combined ventilation and perfusion deficits in the left lower lobe. Transesophageal echocardiography strongly suggested stenoses of the left pulmonary veins. 3-D reconstruction of previously recorded computed tomographic images showed absence of the left inferior pulmonary vein (LIPV) and marked stenosis of the left superior pulmonary vein (LSPV). Diagnosis: It was confirmed that the hemoptysis was caused by stenosis of the left pulmonary veins, resulting from the previous PVA. Treatment and course: Percutaneous transseptal balloon dilatation of the upper and lower pulmonary veins was successfully performed. The patient was put on oral anticoagulation and discharged home free of symptoms. Conclusion: Pulmonary vein stenosis must be considered as the most likely cause of hemoptysis and respiratory symptoms after pulmonary vein ablation for atrial fibrillation. Because of ever more frequent interventions to treat atrial fibrillation and other atrial arrhythmias, great clinical vigilance and an interdisciplinary approach is mandatory to assure optimal assessment of patients with acquired pulmonary vein stenosis. © 2011 Georg Thieme Verlag KG Stuttgart · New York. Source

Background: The activity of the epidermal growth factor receptor (EGFR)-directed monoclonal antibody cetuximab combined with oxaliplatin/leucovorin/5-fluorouracil (FUFOX) was assessed in first-line metastatic gastric and oesophago-gastric junction (OGJ) cancer in a prospective phase II study showing a promising objective tumour response rate of 65% and a low mutation frequency of KRAS (3%). The aim of the correlative tumour tissue studies was to investigate the relationship between EGFR gene copy numbers, activation of the EGFR pathway, expression and mutation of E-cadherin, V600E BRAF mutation and clinical outcome of patients with gastric and OGJ cancer treated with cetuximab combined with FUFOX.Methods: Patients included in this correlative study (n = 39) were a subset of patients from the clinical phase II study. The association between EGFR gene copy number, activation of the EGFR pathway, abundance and mutation of E-cadherin which plays an important role in these disorders, BRAF mutation and clinical outcome of patients was studied. EGFR gene copy number was assessed by FISH. Expression of the phosphorylated forms of EGFR and its downstream effectors Akt and MAPK, in addition to E-cadherin was analysed by immunohistochemistry. The frequency of mutant V600E BRAF was evaluated by allele-specific PCR and the mutation profile of the E-cadherin gene CDH1 was examined by DHPLC followed by direct sequence analysis. Correlations with overall survival (OS), time to progression (TTP) and overall response rate (ORR) were assessed.Results: Our study showed a significant association between increased EGFR gene copy number (≥ 4.0) and OS in gastric and OGJ cancer, indicating the possibility that patients may be selected for treatment on a genetic basis. Furthermore, a significant correlation was shown between activated EGFR and shorter TTP and ORR, but not between activated EGFR and OS. No V600E BRAF mutations were identified. On the other hand, an interesting trend between high E-cadherin expression levels and better OS was observed and two CDH1 exon 9 missense mutations (A408V and D402H) were detected.Conclusion: Our finding that increased EGFR gene copy numbers, activated EGFR and the E-cadherin status are potentially interesting biomarkers needs to be confirmed in larger randomized clinical trials.Trial registration: Multicentre clinical study with the European Clinical Trials Database number 2004-004024-12. © 2011 Luber et al.; licensee BioMed Central Ltd. Source

Hanefeld M.,GWT TUD GmbH | Ganz X.,GWT TUD GmbH | Ganz X.,Universitatsklinik Carl Gustav Carus
Diabetes Aktuell | Year: 2013

Lipoprotein disorders are common companions (> 50 % prevalence) of diabetes. They are in a complex way interrelated with the pathophysiology of dysglycemia and visceral obesity. Increased LDL-Cholesterol in particular small dense LDL are the most important modifyable cardiovascular risk factor in patients with type 2 diabetes. However HDL deficits and increased triglycerides are mainly triggers of cardiovascular risk in patients with metabolic-vascular syndrome. The rational diagnostics therefore implies the lipid-triad: LDL-Cholesterol, triglycerides und HDL-cholesterol. In patients with already existing cardiovascular diseases Apo B and Lp(a) measurement is recommended. Lifestyle intervention according to ESC guidelines is the basis of a rational therapy with no principle difference to recommendations to established diabetes diet and recommendations for fitness training. Type 2 diabetes can be considered as equivalent of cardiovascular disease. Therefore all guidelines recommend a statin therapy as essential part of cardiovascular prevention. Simvastatin and atorvastatin are standard drugs. The hypertriglyceridemia/low HDL syndrome requires a risk adjusted individualized approach as add-on therapy to statins or as monotherapy if statins are not tolerated. In the case of hypertriglyceridemia/low HDL Fibrates (Fenofibrate, Bezafibrate) are recommended. For hypertriglyceridemia Omega 3 Fatty acids may be beneficial. Chylomicrone syndroms request a strict prohibition of alcohol and restriction of fat intake < 10-20 %. While the benefit of statin treatment has a evidence level of 1a because of a bulk of data of controlled outcome studies the add-on therapy with fibrates and Omega 3 Fatty acids must be individualized. It remains however a rational option of multimodal lipid therapy in patients with the metabolic vascular syndrome. Source

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