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101.
G M Spencer S M Thorpe I R Sargeant G M Blackman J Solano J S Tobias S G Bown 《Gut》1996,39(5):726-731
BACKGROUND: Palliation of malignant dysphagia is possible by a variety of methods although all have significant drawbacks. Laser therapy is an effective and safe treatment but has to be repeated at four to five weekly intervals to maintain palliation. A means of augmenting the benefits while reducing the need for repeat treatments would be highly beneficial to these patients. AIMS: To prospectively explore the safety and efficacy of intraluminal radiotherapy (brachytherapy) when used to augment laser recanalisation for malignant dysphagia. PATIENTS: Nineteen patients with dysphagia due to advanced adenocarcinoma of the oesophagus or cardia were recruited. METHODS: All patients received laser recanalisation until able to swallow a soft diet or better, before the application of a single dose of brachytherapy (10 Gy at 1 cm from the source). Patients were followed up and treated promptly by further endoscopic means in the event of their dysphagia worsening. RESULTS: Six patients (32%) required no further treatment until death at a median of 10 weeks (range 1-20 weeks). Further therapy was required at a median of 11 weeks (range 4-37 weeks) after brachytherapy for those 13 patients with recurrent dysphagia. Subsequent symptom control required endoscopic intervention at an average of once every nine weeks. There was no mortality associated with laser or brachytherapy. Median survival from initial treatment and including the one survivor was 36 weeks (range 5-132 weeks). CONCLUSIONS: Laser plus brachytherapy offers a safe and effective means of palliating malignant dysphagia due to adenocarcinoma, with a longer dysphagia free interval than historical controls treated with laser alone. 相似文献
102.
Diane Purper-Ouakil Hilario Blasco-Fontecilla Tomas Ros Eric Acquaviva Tobias Banaschewski Sarah Baumeister Elisa Bousquet Aurore Bussalb Marie Delhaye Richard Delorme Renate Drechsler Allison Goujon Alexander Häge Anna Kaiser Louis Mayaud Konstantin Mechler Caroline Menache Olivier Revol Friederike Tagwerker Susanne Walitza Anna Maria Werling Stephanie Bioulac Daniel Brandeis 《Journal of child psychology and psychiatry, and allied disciplines》2022,63(2):187-198
103.
Wienbergen H Schiele R Gitt AK Juenger C Heer T Meisenzahl C Landgraf H Bossaller C Senges J;MITRA PLUS Study Group 《The American journal of cardiology》2002,90(10):1045-1049
We examined the impact of treatment with ramipril versus other angiotensin-converting enzyme (ACE) inhibitors on clinical outcome in unselected patients of the prospective multicenter registry Maximal Individual Therapy of Acute Myocardial Infarction PLUS registry (MITRA PLUS). Of 14,608 consecutive patients with ST-elevation acute myocardial infarction, 4.7% received acute therapy with ramipril, 39.0% received other ACE inhibitor therapy, and 56.3% received no ACE inhibitor therapy. In a multivariate analysis, the treatment with ramipril compared with the treatment without ACE inhibitors was associated with a significantly lower hospital mortality and a lower rate of nonfatal major adverse coronary and cerebrovascular events. Compared with other generic ACE inhibitors, ramipril therapy was independently associated with a significantly lower hospital mortality (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.32 to 0.90) and a lower rate of nonfatal major adverse coronary and cerebrovascular events (OR 0.65, 95% CI 0.46 to 0.93), but not with a lower rate of heart failure at discharge (OR 0.79, 95% CI 0.50 to 1.27). 相似文献
104.
Warnholtz A Mollnau H Heitzer T Kontush A Möller-Bertram T Lavall D Giaid A Beisiegel U Marklund SL Walter U Meinertz T Munzel T 《Journal of the American College of Cardiology》2002,40(7):1356-1363
OBJECTIVE: With the present studies we sought to determine how treatment with nitroglycerin (NTG) affects endothelial function, oxidative stress and nitric oxide (NO)-downstream signaling in Watanabe heritable hyperlipidemic rabbits (WHHL). BACKGROUND: In vitro experiments have demonstrated potent antiatherosclerotic effects of NO suggesting that treatment with NO-donors such as NTG could compensate for the diminished availability of endothelial NO. Nitric oxide may, however, not only be scavenged by reaction with endothelium-derived superoxide but also form the potent oxidant and inhibitor of vascular function, peroxynitrite (ONOO(-)). METHODS: Watanabe heritable hyperlipidemic rabbits were treated for three days with NTG patches. Normolipidemic New Zealand White rabbits (NZWR) served as controls. Endothelial function was assessed ex vivo with organ chamber experiments and vascular superoxide was quantified using lucigenin (5 and 250 microM) and CLA-enhanced chemiluminescence. Vascular ONOO(-) formation was determined using nitrotyrosine antibodies. The activity of the cGMP-dependent kinase (cGK-I) was assessed by determining the phosphorylation of vasodilator-stimulated phosphoprotein VASP (P-VASP). RESULTS: Nitroglycerin treatment caused endothelial dysfunction in NZWR and WHHL, associated with an increase in superoxide and ONOO(-) production and a substantial drop in cGK-I activity. In vivo NTG-treatment decreased lipophilic antioxidants (alpha- and beta-carotene) in NZWR and WHHL. Treatment of NZWR with NTG also decreased plasma extracellular superoxide dismutase (EC-SOD)-activity. CONCLUSIONS: Nitroglycerin treatment of WHHL with exogenous NO worsens rather than improves endothelial dysfunction secondary to increased formation of superoxide and/or peroxynitrite leading to decreased cGK-I activity. The decrease in plasma levels of alpha- and beta-carotene may be at least in part due to a decrease in EC-SOD activity. 相似文献
105.
Consolato Sergi Katharina Jundt Stefanie Seipp Tobias Goeser Lorenz Theilmann Gerd Otto Herwart F. Otto Walter J. Hofmann 《Journal of hepatology》1998,29(6):861-871
Background/Aims: The aim of the study was to assess the impact factor of HCV and HGV in fulminant hepatic failure.Methods: The 5′-untranslated regions of HCV RNA and HGV RNA and a segment of the core antigen sequence of HBV were amplified after extracting the nucleic acids from snap-frozen tissue aliquots from explanted livers of 26 consecutive patients undergoing orthotopic liver transplantation for fulminant hepatic failure preoperatively diagnosed as either autoimmune (n=2), HAV/HBV (n=8), toxic (n=4) or aetiologically unknown (n=12).Results: HCV RNA was detected in five of 26 (19.2%) livers with fulminant hepatic failure. All five HCV RNA-positive livers belonged to the group of non-toxic, non-autoimmune liver failure (n=20), three of them were found in the group of liver failure with unknown aetiology (n=12) and two in the group of HBV-associated liver failure (n=7), making an HCV incidence of 25%, 25%, and 28.6%, in the different groups, respectively. HGV RNA was detected in 10 of 17 (58.8%) explants and in all four groups of fulminant hepatic failure as defined preoperatively. HBV DNA was identified in six livers of 26 patients (23.1%) with fulminant hepatic failure. Neither HCV RNA nor HBV DNA was detected in the livers of patients with toxic or autoimmune fulminant hepatic failure.Conclusions: These results indicate that HBV and HCV, but not HGV, play an aetiologic role in fulminant hepatic failure. HCV-positive cases were concentrated either in the group of otherwise unexplained fulminant hepatic failure or in the group of HBV fulminant hepatic failure. HGV-positive cases, on the other hand, were found within all four preoperatively defined groups, indicating a role as cofactor rather than as single aetiologic agent. 相似文献
106.
Keller M Gerbes AL Kulhanek-Heinze S Gerwig T Grutzner U van Rooijen N Vollmar AM Kiemer AK 《World journal of gastroenterology : WJG》2005,11(47):7418-7429
AIM: To determine functional consequences of this activation, whereby we focused on a potential regulation of the hepatocyte cytoskeleton during ischemia and reperfusion. METHODS: For in vivo experiments, animals received ANP (5 μg/kg) intravenously. In a different experimental setting, isolated rat livers were perfused with KH-buffer ±ANP (200 nmol/L)±SB203580 (2 μmol/L). Livers were then kept under ischemic conditions for 24 h, and either transplanted or reperfused. Actin, Hsp27, and phosphorylated Hap27 were determined by Western blotting, p38 MAPK activity by in vitro phosphorylation assay. F-actin distribution was determined by confocal microscopy. RESULTS: We first confirmed that ANP preconditioning leads to an activation of p38 MAPK and observed alterations of the cytoskeleton in hepatocytes of ANP-preconditioned organs. ANP induced an increase of hepatic F-actin after ischemia, which could be prevented by the p38 MAPK inhibitor SB203580 but had no effect on bile flow. After ischemia untreated livers showed a translocation of Hsp27 towards the cytoskeleton and an increase in total Hsp27, whereas ANP preconditioning prohibited translocation but caused an augmentation of Hsp27 phosphorylation. This effect is also mediated via p38 MAPK, since it was abrogated by the p38 MAPK inhibitor SB203580. CONCLUSION: This study reveals that ANP-mediated p38 MAPK activation leads to changes in hepatocyte cytoskeleton involving an elevation of phosphorylated Hsp27 and thereby for the first time shows functional consequences of ANP-induced hepatic p38 MAPK activation. 相似文献
107.
Kiemer AK Gerwig T Gerbes AL Meissner H Bilzer M Vollmar AM 《Journal of hepatology》2003,38(4):490-498
BACKGROUND/AIMS: Pretreatment with atrial natriuretic peptide (ANP) attenuates ischemia-reperfusion injury of livers via cGMP. Heme oxygenase-1 (HO-1) is known as a protective mediator in ischemia-reperfusion injury. The aim of this study was to investigate whether ANP affects the expression of HO-1. METHODS: Rat livers were perfused with KH-buffer with/without ANP or 8-Br-cGMP, kept in UW solution (4 degrees C, 24 h), and reperfused. HO-1 mRNA and protein was determined by Northern and Western blot, in situ hybridization, and immunohistochemistry in livers or isolated liver cells. RESULTS: ANP significantly elevated HO-1 mRNA expression at the end of the preconditioning period and was without effects at the end of ischemia and during reperfusion. 8-Br-cGMP did not affect HO-1 mRNA expression. In situ hybridization as well as immunohistological double-staining revealed that Kupffer cells but not hepatocytes showed HO-1 mRNA and protein expression. Hepatocytes revealed no changes in HO-1 protein whereas Kupffer cells showed a marked increase in HO-1 protein after ANP treatment. Inhibition of HO-1 did not abrogate hepatoprotection conveyed by ANP. CONCLUSION: Our data show the potency of ANP to specifically induce HO-1 in Kupffer cells independently of cGMP. This increased expression of HO-1 is not involved in hepatoprotection conferred by ANP being in line with the knowledge that ANP mediates hepatoprotection via cGMP. 相似文献
108.
Peikert T Finkielman JD Hummel AM McKenney ME Gregorini G Trimarchi M Specks U 《Arthritis and rheumatism》2008,58(5):1546-1551
OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) binding to neutrophil elastase (NE) and proteinase 3 (PR3) are detectable in most patients with cocaine-induced midline destructive lesions (CIMDL), but the pathogenic role and antigen specificity of these antibodies are unknown. This study was undertaken to assess the effects of NE ANCA on the enzymatic activity of NE, to determine whether these antibodies interfere with the physiologic effect of secretory leukoprotease inhibitor (SLPI), and to investigate the antigen specificity of both NE and PR3 ANCA in patients with CIMDL. We also compared the binding of PR3 ANCA in patients with CIMDL with that in patients with Wegener's granulomatosis (WG). METHODS: PR3 ANCA and NE ANCA were detected by capture enzyme-linked immunosorbent assays (ELISAs) and by indirect immunofluorescence. IgG was purified from the patients' sera, and the influence of NE ANCA on the enzymatic activity of NE and on the inhibitory activity of SLPI was investigated by determining the hydrolysis of N-methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide by NE. RESULTS: IgG from NE ANCA-positive sera of patients with CIMDL inhibited the enzymatic activity of NE and did not interfere with the activity of SLPI. In contrast to the findings in WG sera, measurement of PR3 ANCA in CIMDL sera showed only fair to moderate concordance between the 2 different capture ELISAs. Cross-inhibition experiments demonstrated that NE ANCA and PR3 ANCA represent distinct autoantibodies in patients with CIMDL. CONCLUSION: The functional effects of NE ANCA on the enzymatic activity of NE or on the activity of SLPI cannot be implicated in the pathogenesis of CIMDL. The autoimmune reaction that targets neutrophil serine proteases in patients with CIMDL is frequently directed against more than one antigen. The ANCA response, including the reactivity of PR3 ANCA, in patients with CIMDL differs from what has been described in patients with WG. 相似文献
109.
Tobias Sieckmann Hatem Elmongy Magnus Ericsson Hasanuzzaman Bhuiyan Mikael Lehtihet Lena Ekstrm 《Drug testing and analysis》2020,12(6):711-719
The detection of low doses of recombinant growth hormone is a challenge in antidoping testing. Future testing may lead toward the longitudinal monitoring of IGF‐I and P‐III‐NP in an endocrine module. Additional biomarkers, for example vitamin D binding protein, alpha‐HS‐glycoprotein, fibronectin 1, and decorin have been identified in different omics studies. This was a longitudinal study of the usefulness of these putative biomarkers in relation to 2 weeks administration of low doses of recombinant growth hormone in healthy male volunteers. Moreover, the hematological parameters included in the athlete biological passport were studied as well as the serum concentration of testosterone and dihydrotestosterone. Fibronectin 1 increased by 20% during the treatment period (P ? 0.05), confirming the previous finding. Alpha‐HS‐glycoprotein decreased by 25% up to 3 weeks after treatment (P ? 0.05), contradicting previous results. The addition of fibronectin 1 increased the likelihood of detecting recombinant growth hormone intake based on individual calculated thresholds in some of the participants compared with the GH2000, IGF‐I, and P‐III‐NP. The multiplication of fibronectin 1 concentration by IGF‐I resulted in the most profound (up to 4‐fold) changes. A minor 15% increase (P = 0.003) in the reticulocyte percentage was observed, but the changes did not lead to any atypical profile based on individual passport thresholds. Vitamin D binding protein, decorin, testosterone, and dihydrotestosterone were not affected by growth hormone. Dihydrotestosterone sulfate was negatively correlated with IGF‐I at baseline (R = –0.50, P = 0.003) and post dose (R = –0.59, P = 0.01). In conclusion, fibronectin 1 was verified as a promising future biomarker for detecting low doses of recombinant growth hormone. 相似文献
110.
Franziska Gaunitz Tobias Kieliba Mario Thevis Katja Mercer‐Chalmers‐Bender 《Drug testing and analysis》2020,12(1):27-40
This article comprises the development and validation of a protocol for the qualitative analysis of 61 phase I synthetic cannabinoid metabolites in urine originating from 29 synthetic cannabinoids, combining solid‐phase extraction (SPE) utilizing a reversed phase silica‐based sorbent (phenyl) with liquid chromatography–tandem mass spectrometry (LC?MS/MS). Validation was performed according to the guidelines of the German Society of Toxicological and Forensic Chemistry. Sufficient chromatographic separation was achieved within a total runtime of 12.3 minutes. Validation included specificity and selectivity, limit of detection (LOD), recovery and matrix effects, as well as auto‐sampler stability of processed urine samples. LOD ranged between 0.025 ng/mL and 0.5 ng/mL in urine. Recovery ranged between 43% and 97%, with only two analytes exhibiting recoveries below 50%. However, for those two analytes, the LODs were 0.05 ng/mL in urine. In addition, matrix effects between 81% and 185% were determined, whereby matrix effects over 125% were observed for 10 non‐first‐generation synthetic cannabinoid metabolites. The developed method enables the rapid and sensitive detection of synthetic cannabinoid metabolites in urine, complementing the spectrum of existing analytical tools in forensic case work. Finally, application to 61 urine samples from both routine and autopsy case work yielded one urine sample that tested positive for ADB‐PINACA N‐pentanoic acid. 相似文献