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971.
972.
Peter Gonschior MD Clemens Pahl Tanya Y. Huehns MRCP Florian Gerheuser MD Aysel Erdemci MD Katharina Larisch MD Marc Dellian MD Stefan Deil MD Alwin-E. Goetz MD Hans A. Lehr MD PhD Berthold Höfling MD 《American heart journal》1995,130(6):1174-1181
Systemic and local delivery on the photosensitive drug Photofrin polyporphyrin was investigated in normal porcine arteries (n = 192). A macroporous balloon and a novel needle injection catheter were used for local drug delivery and compared with systemic delivery. Fluorescence microscopy combined with digital image analysis was used to quantify the drug-related fluorescence. Systemic delivery showed a maximum in the intima at 4 hours. Application with the porous balloon revealed maximum indicator-related fluorescence intensity in the intima after 5 minutes; delivery with the needle injection catheter resulted in a several-fold enhanced maximum in adventitia after 30 minutes compared with the maximum achieved with either systemic injection or porous balloon application. After 21 days fluorescence was detectable in arteries treated with the new needle injection catheter. Local drug delivery is feasible with either system, but prolonged delivery was achieved only with the needle injection catheter. 相似文献
973.
Limperger Verena Kenet Gili Kiesau Bettina Köther Max Schmeiser Malin Langer Florian Juhl David Shneyder Maria Franke Andre Klostermeier Ulrich K. Mesters Rolf Rühle Frank Stoll Monika Steppat Dagmar Kowalski Dorothee Rocke Angela Kuta Piotr Bajorat Tido Torge Antje Neuner Bruno Junker Ralf Nowak-Göttl Ulrike 《Journal of thrombosis and thrombolysis》2021,51(2):494-501
Journal of Thrombosis and Thrombolysis - The role of the A>G polymorphism at position 19911 in the prothrombin gene (factor [F] 2 at rs3136516) as a risk factor for venous thromboembolism... 相似文献
974.
Zender L Hutker S Liedtke C Tillmann HL Zender S Mundt B Waltemathe M Gosling T Flemming P Malek NP Trautwein C Manns MP Kuhnel F Kubicka S 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(13):7797-7802
A major concern in therapy of acute liver failure is protection of hepatocytes to prevent apoptosis and maintain liver function. Small interfering RNA (siRNA) is a powerful tool to silence gene expression in mammalian cells. To evaluate the therapeutic efficacy of siRNA in vivo we used different mouse models of acute liver failure. We directed 21-nt siRNAs against caspase 8, which is a key enzyme in death receptor-mediated apoptosis. Systemic application of caspase 8 siRNA results in inhibition of caspase 8 gene expression in the liver, thereby preventing Fas (CD95)-mediated apoptosis. Protection of hepatocytes by caspase 8 siRNA significantly attenuated acute liver damage induced by agonistic Fas (CD95) antibody (Jo2) or by adenovirus expressing Fas ligand (AdFasL). However, in a clinical situation the siRNAs most likely would be applied after the onset of acute liver failure. Therefore we injected caspase 8 siRNA at a time point during AdFasL- and adenovirus wild type (Adwt)-mediated liver failure with already elevated liver transaminases. Improvement of survival due to RNA interference was significant even when caspase 8 siRNA was applied during ongoing acute liver failure. In addition, it is of particular interest that caspase 8 siRNA treatment was successful not only in acute liver failure mediated by specific Fas agonistic agents (Jo2 and AdFasL) but also in acute liver failure mediated by Adwt, which is an animal model reflecting multiple molecular mechanisms involved in human acute viral hepatitis. Consequently, our data raise hope for future successful application of siRNA in patients with acute liver failure. 相似文献
975.
Schulte-Frohlinde E Wagenpfeil S Willis J Lersch C Eckel F Schmid R Schusdziarra V 《Journal of gastroenterology and hepatology》2007,22(8):1241-1248
BACKGROUND AND AIM: Imbalance of circulating branched chain amino acids (BCAA) versus aromatic amino acids (AAA) and hyperinsulinemia are common metabolic alterations in patients with liver cirrhosis. The aim of this study was to characterize the effect of the carbohydrate component of a protein-rich mixed meal on postprandial plasma concentrations of 21 amino acids, insulin and C-peptide in patients with compensated liver cirrhosis. Furthermore, the effect of a dietary intervention on the metabolic alterations in cirrhotic patients was examined. METHODS: Eighteen patients with cirrhosis and 12 healthy volunteers received a protein-rich meal (pork filet 200 g) with or without carbohydrates (bread 50 g, glucose 20 g). A subgroup of four cirrhotic patients received an isoenergetic (117 kJ/kg bw) carbohydrate-enriched (60%) and -restricted (20%) diet for 7 days each. RESULTS: In the cirrhotic patients, basal plasma insulin and C-peptide concentrations were significantly elevated. The ingestion of a protein-rich meal without additional carbohydrates led to a significantly greater increase of insulin and C-peptide in the cirrhotic patients compared to controls. Postprandial increases of leucine and isoleucine were reduced, whereas those of phenylalanine were higher in cirrhotic patients. The addition of carbohydrates led to higher insulin and C-peptide plasma concentrations in cirrhotic patients. Postprandial BCAA increases were more impaired in the cirrhotic group after additional carbohydrate ingestion (46%vs 82%). After the carbohydrate-restricted diet for 7 days BCAA plasma levels increased but the BCAA/AAA ratio remained unaltered. CONCLUSIONS: The carbohydrate content of a meal enhances reduction of BCAA plasma concentrations in clinically stable cirrhotic patients. An imbalanced BCAA/AAA ratio cannot be avoided by a carbohydrate-reduced diet alone, supporting mandatory BCAA supplementation. 相似文献
976.
Grasemann H Stehling F Brunar H Widmann R Laliberte TW Molina L Döring G Ratjen F 《Chest》2007,131(5):1461-1466
BACKGROUND: In cystic fibrosis (CF) patients, the absence or dysfunction of the chloride channel CF transmembrane conductance regulator (CFTR) results in reduced chloride ion transport in respiratory epithelial cells. Moli1901 stimulates an alternative chloride channel and may thus compensate for the CFTR deficiency in the airway epithelium of CF patients. METHODS: A phase II, placebo-controlled, double-blinded, single-center, multiple (5 consecutive days), rising-dose (daily dose, 0.5, 1.5, or 2.5 mg of Moli1901) study was conducted to investigate the safety and tolerability of multiple doses of aerosolized inhaled Moli1901 in 24 patients with CF and stable lung disease. RESULTS: Moli1901 was well tolerated in all but one CF patient, in whom a transient significant decrease in FEV(1) developed following inhalation, which resolved spontaneously, and in a second patient in whom transient throat numbness developed during drug inhalation. A significant improvement of FEV(1) was observed in the group receiving treatment with 2.5 mg/d Moli1901 compared to the group receiving placebo (p = 0.01 [Wilcoxon test]). Moli1901 was not detected in the plasma of the highest dose group. CONCLUSIONS: The inhalation of Moli1901 up to a total cumulative dose of 12.5 mg appears to be safe in adult patients with CF. In addition, Moli1901 had a sustained beneficial effect on pulmonary function, which supports further studies of its efficacy in CF patients. 相似文献
977.
Florian Hitzenbichler Michaela Simon Thomas Holzmann Michael Iberer Markus Zimmermann Bernd Salzberger Frank Hanses 《Infection》2018,46(3):325-331
Purpose
Escherichia coli urine isolates from patients presenting to the emergency department at a German tertiary care hospital were retrospectively analyzed from January 2015–March 2017 to determine antibiotic resistance patterns and patient risk factors for resistance.Methods
Uncomplicated urinary tract infection (UTI) was defined as UTI in the otherwise healthy patient without relevant co-morbidities and complications. Patients were assumed to have UTI if diagnosis was made by the attending physician with conclusive dipstick results. For subgroup analysis, only patients with symptoms suggestive for UTI documented in their records were included.Results
228 patients with a UTI diagnosed by the attending physician with E. coli isolated in urine culture were included. 154/228 patients had documented symptomatic UTI, 57/154 had uncomplicated infection, 76/154 patients had cystitis, and 124/154 were female. Resistance rates of uncomplicated UTI in symptomatic patients were: ciprofloxacin 10.5%, cotrimoxazole 15.8%, amoxicillin/clavulanic acid 5.3%, nitrofurantoin 0% (CLSI MICs). Previous hospitalization in the last 3 months (including patients living in a long-term care facility) was significantly correlated with resistance to ciprofloxacin, cotrimoxazole and amoxicillin/clav. Previous hospitalization was a strong predictor of resistance to ciprofloxacin and cotrimoxazole in multivariate analysis also. Other risk factors correlated with resistance were hematological malignancy (for cotrimoxazole) and renal transplantation (for ciprofloxacin).Conclusions
Cotrimoxazole is still an alternative for treating uncomplicated cystitis. Previous hospitalization in the last 3 months was a strong predictor of resistance to cotrimoxazole and ciprofloxacin. Other risk factors which might help guide empirical therapy are hematological malignancy and renal transplantation.978.
Antoine?Thico?pé David?Laharie Denis?Smith Edouard?Chabrun Anne?Rullier Florian?Poullenot Eric?Rullier Quentin?DenostEmail author 《International journal of colorectal disease》2018,33(7):963-966
Aim
Inflammatory bowel diseases (IBD) are associated with an increased risk for colorectal cancer (CRC). However and despite significant advances in the management of IBD and CRC, the prognosis of IBD-related CRC (IBD-CRC) remains controversial. The aim of the present case-control study was to compare the prognosis of IBD-CRC to sporadic CRC.Methods
Consecutive patients operated for IBD-CRC from 2004 to 2014 were recruited and matched with sporadic CRC (ratio 3:1) from the same center. Matching was performed on gender, tumor stage, and location and period of surgery. Endpoints were postoperative morbidity (Dindo-Clavien III-V), quality of surgery, and long-term oncological outcomes.Results
Among 1498 CRC patients operated during the study period, 21 patients were identified with IBD-CRC and matched to 63 patients with sporadic CRC (S-CRC). Patients with IBD-CRC were significantly younger (p?<?0.001), had multifocal lesions more frequently (p?=?0.04), and undergone abdominoperineal excision and coloproctectomy more often (p?=?0.001). Postoperative morbidity was not significantly different between the two groups (25 vs. 14%; p?=?0.309), as well as the rate of R0 resection (86 vs. 95%; p?=?0.162). Five-year disease-free and overall survival were 71 and 81% in patients with IBD-CRC and 69% (p?=?0.801) and 78% (p?=?0.845) in those with S-CRC, respectively.Conclusion
In a case-control study of patients operated for CRC within the last decade, the prognosis of cancer associated with IBD is similar to sporadic cancer.979.
Susanna?Nikolaus Georg?H.?Waetzig Sven?Butzin Monika?Ziolkiewicz Natalie?Al-Massad Florian?Thieme Ulf?L?vgren Birgitte?B.?Rasmussen Torsten?M.?Reinheimer Dirk?Seegert Philip?Rosenstiel Silke?Szymczak Stefan?SchreiberEmail authorView authors OrcID profile 《International journal of colorectal disease》2018,33(7):927-936
Purpose
Interleukin-6 (IL-6) production and signalling are increased in the inflamed mucosa in inflammatory bowel diseases (IBD). As published serum levels of IL-6 and its soluble receptors sIL-6R and sgp130 in IBD are from small cohorts and partly contradictory, we systematically evaluated IL-6, sIL-6R and sgp130 levels as markers of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC).Methods
Consecutive adult outpatients with confirmed CD or UC were included, and their disease activity and medication were monitored. Serum from 212 CD patients (815 measurements) and 166 UC patients (514 measurements) was analysed, and 100 age-matched healthy blood donors were used as controls.Results
IL-6 serum levels were significantly elevated in active versus inactive CD and UC, also compared with healthy controls. However, only a fraction of IBD patients showed increased serum IL-6. IL-6 levels ranged up to 32.7 ng/mL in active CD (>?5000-fold higher than in controls), but also up to 6.9 ng/mL in inactive CD. Increases in active UC (up to 195 pg/mL) and inactive UC (up to 27 pg/mL) were less pronounced. Associations between IL-6 serum levels and C-reactive protein concentrations as well as leukocyte and thrombocyte counts were observed. Median sIL-6R and sgp130 levels were only increased by up to 15%, which was considered of no diagnostic significance.Conclusions
Only a minority of IBD patients shows elevated IL-6 serum levels. However, in these patients, IL-6 is strongly associated with disease activity. Its soluble receptors sIL-6R and sgp130 do not appear useful as biomarkers in IBD.980.
9‐month results of polymer‐free sirolimus eluting stents in young patients compared to a septuagenarian and octogenarian all‐comer population 下载免费PDF全文
Behrouz Kherad MD Matthias Waliszewski PhD Matthias Leschke MD Muhammad Ali Kader MD Liew Houng Bang MD Fernando Lozano Ruiz‐Poveda MD Burkert Pieske MD Florian Krackhardt MD 《Journal of interventional cardiology》2018,31(3):338-344