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71.
Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status 总被引:5,自引:0,他引:5 下载免费PDF全文
Thorsélius M Kröber A Murray F Thunberg U Tobin G Bühler A Kienle D Albesiano E Maffei R Dao-Ung LP Wiley J Vilpo J Laurell A Merup M Roos G Karlsson K Chiorazzi N Marasca R Döhner H Stilgenbauer S Rosenquist R 《Blood》2006,107(7):2889-2894
We recently reported that Swedish VH3-21-using chronic lymphocytic leukemia (CLL) patients showed restricted immunoglobulin gene features and poor prognosis despite VH mutation status. To investigate this further, we analyzed the VH and VL gene rearrangements in 90 VH3-21+ patients from Sweden, Germany, Italy, United States, Finland, and Australia and correlated these data with survival and other prognostic markers. Sixty-three percent exhibited mutated VH genes and 37% unmutated VH genes. Fifty (56%) patients displayed a short and homologous heavy-chain CDR3, many of these with the amino acid motif DANGMDV. Also, a highly biased V2-14 use was evident in 72% of patients with a restricted light-chain CDR3, QVWDS(S/G)SDHPWV. Combined restricted heavy- and light-chain CDR3s were found in patients from all included countries. Although VH3-21+ CLLs have a remarkably predominant expression, analyses of kappa deleting element indicated a conserved light-chain rearrangement order. The overall survival was poor in the VH3-21+ cohort (median survival, 88 months), with no significant difference in relation to mutation status or CDR3 homology. High ZAP-70 and CD38 expression was found in both mutated and unmutated VH3-21+ cases as well as a slight increase of 11q-aberrations. In summary, highly restricted B-cell receptors and worse outcome characterize VH3-21+ CLLs independent of geographic origin and mutation status. 相似文献
72.
Background
Rotational thromboelastography (ROTEG) has been proposed as a monitoring tool that can be used to monitor treatment of hemophilia with recombinant factor VIIa (rFVIIa). In these studies special non-standard reagents were used as activators of the coagulation. The aim of this study was to evaluate if standard ROTEG analysis could be used for monitoring of effects of recombinant factor VIIa (rFVIIa) on Hydroxy Ethyl Starch-induced dilutional coagulopathy. 相似文献73.
In vivo fragmentation of heparan sulfate by heparanase overexpression renders mice resistant to amyloid protein A amyloidosis 下载免费PDF全文
Li JP Galvis ML Gong F Zhang X Zcharia E Metzger S Vlodavsky I Kisilevsky R Lindahl U 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(18):6473-6477
Amyloid diseases encompass >20 medical disorders that include amyloid protein A (AA) amyloidosis, Alzheimer's disease, and type 2 diabetes. A common feature of these conditions is the selective organ deposition of disease-specific fibrillar proteins, along with the sulfated glycosaminoglycan, heparan sulfate. We have generated transgenic mice that overexpress human heparanase and have tested their susceptibility to amyloid induction. Drastic shortening of heparan sulfate chains was observed in heparanase-overproducing organs, such as liver and kidney. These sites selectively escaped amyloid deposition on experimental induction of inflammation-associated AA amyloidosis, as verified by lack of material staining with Congo Red, as well as lack of associated polysaccharide, whereas the same tissues from control animals were heavily infiltrated with amyloid. By contrast, the spleens of transgenic mice that failed to significantly overexpress heparanase contained heparan sulfate chains similar in size to those of control spleen and remained susceptible to amyloid deposition. Our findings provide direct in vivo evidence that heparan sulfate is essential for the development of amyloid disease. 相似文献
74.
Udo A. Heuschen M.D. Erik H. Allemeyer M.D. Ulf Hinz M.Sc. Frank Autschbach M.D. Tanja Uehlein Christian Herfarth M.D. Gundi Heuschen M.D. 《Diseases of the colon and rectum》2002,45(6):776-786
PURPOSE: Pouchitis represents a serious threat to patients with ulcerative colitis after restorative proctocolectomy with ileal pouch-anal anastomosis. The frequency of pouchitis is high, and it implies the risk of pouch failure and the risk of malignant mucosal transformation in the pouch. Early detection and precise classification of the inflammatory process are required for adequate therapy, which might be facilitated using a scoring system. The aim of the present study was to validate two existing scoring systems in routine outpatient practice.
METHOD: The Heidelberg Pouchitis Activity Score and the Pouchitis Disease Activity Index developed at the Mayo Clinic were simultaneously prospectively applied in a consecutive series of 103 outpatient consultations of 41 patients at our hospital and comparatively validated against the diagnosis of pouchitis or no pouchitis concurrently made by a physician and a surgeon.
RESULTS: The median score of examinations in which the clinicians diagnosis was consistent with pouchitis were significantly higher than those of examinations inconsistent with pouchitis in both scoring systems (Heidelberg Pouchitis Activity Score, 17 (interquartile range, 14–21) and 8 (interquartile range, 5–10), respectively, P < 0.001; Pouchitis Disease Activity Index, 7 (interquartile range, 5–8) and 2.5 (interquartile range, 1–4), respectively, P < 0.001). The sensitivity and specificity in the two total scores were 84 and 79.5 percent, respectively (Heidelberg Pouchitis Activity Score), and 60 and 96.2 percent, respectively (Pouchitis Disease Activity Index); in the field clinical manifestations 44 and 73.1 percent, respectively (Heidelberg Pouchitis Activity Score), and 20 and 87.2 percent, respectively (Pouchitis Disease Activity Index); in the field endoscopic manifestations 88 and 83.3 percent, respectively (Heidelberg Pouchitis Activity Score), and 60 and 89.7 percent, respectively (Pouchitis Disease Activity Index); and in the field histologic manifestations 72 and 76.9 percent, respectively (Heidelberg Pouchitis Activity Score), and 44 and 96.2 percent, respectively (Pouchitis Disease Activity Index). Lowering the cutoff point for diagnosis of pouchitis in the Pouchitis Disease Activity Index by 2 points (pouchitis: score 5) would result in an 88 percent sensitivity and a 67 percent specificity.
CONCLUSIONS: Specificity and sensitivity of the Heidelberg Pouchitis Activity Score were satisfactory. The cutoff point for diagnosing pouchitis in the Pouchitis Disease Activity Index would have to be lowered to reach an acceptable sensitivity and specificity. The very poor validity of the field clinical manifestations in diagnosing pouchitis emphasizes the need for endoscopic and histologic examination for detection of pouchitis. The issue of whether the diagnosis of pouchitis should be based on endoscopic and histologic features alone, instead of additionally taking clinical features into account, should be addressed in future studies. 相似文献
75.
Marcus Bahra Dietmar Jacob Jan M. Langrehr Ulf P. Neumann Peter Neuhaus 《Journal of hepato-biliary-pancreatic sciences》2008,15(5):501-507
Background/Purpose
Carcinoma of the distal bile duct is associated with poor prognosis. Surgical resection remains the only potentially curative treatment. We conducted a retrospective study to identify prognostic factors determining longterm survival.Methods
From 1990 to 2006, 95 patients with distal and/or middle bile duct carcinoma had resections. Fifty-four patients underwent pylorus-preserving pancreaticoduodenectomy (57%) and 41 patients underwent standard Kausch-Whipple pancreaticoduodenectomy (43%). Nine patients underwent pancreaticoduodenectomy including portal vein resection (9%).Results
Overall 1-, 3-, and 5-year survival rates were 60%, 36%, and 29%, respectively. Five-year survival after R0 resection was 34%, and after R1 resection it was 0%. Four patients died during their hospital stay (4%). Multivariate analysis showed negative resection margins (P = 0.040), lymphatic vessel invasion (P = 0.036), and portal vein infiltration (P = 0.027) as strong predictors for survival, whereas the location of the tumor (distal bile duct vs middle bile duct) and lymph node status were not identified as independent prognostic factors.Conclusions
Five-year survival depends strongly on negative resection margins, independent of nodal status. Portal vein resections in patients with portal vein involvement fail to ameliorate long-term survival. Primary tumor site — middle bile duct or distal bile duct — did not determine prognosis.76.
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.77.
Frilling B Schiele R Gitt AK Zahn R Schneider S Glunz HG Gieseler U Jagodzinski E Senges J;Maximal Individual Therapy in Acute Myocardial Infarction Study Group 《American heart journal》2004,148(2):306-311
Background
A meta-analysis of randomized trials has shown a significant reduction of mortality rate in patients receiving aspirin for secondary prevention after acute myocardial infarction (AMI). However, a significant number of patients do not receive aspirin after AMI. Little is known about why aspirin is withheld or the long-term outcome of these patients today.Methods
The Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) registry is a multicenter registry of patients with AMI in Germany.Results
Of 4902 patients, 509 (10%) did not receive aspirin at the time of discharge from the hospital. The mean follow-up period for these patients was 17 months. Relative contraindications to aspirin were significantly associated with the withholding of aspirin (in-hospital bleeding: odds ratio [OR], 3.56; 95% CI, 1.86-6.80; history of peptic ulcer: OR, 2.49; 95% CI, 1.62-3.83). Absolute contraindications to aspirin were rare (2.2%). Other medications of proven benefit were also given less often in these patients (β-blockers: 49.0% vs 61.9%, P <.001; angiotensin-converting enzyme inhibitors: 65.6% vs 70.2%, P = .06; statins: 12.2% vs 15.1%, P = .10). Patients who were not given aspirin were at high risk for vascular events. They were more likely to have a history of prior AMI (OR, 1.34; 95% CI, 1.02-1.79), were in critical clinical condition at admission more often (cardiogenic shock: OR, 1.98; 95% CI, 1.09-3.56; overt heart failure: OR, 1.6; 95% CI, 1.05-2.3), and received acute revascularization less often (OR, 1.32; 95% CI, 1.05-1.67). The 1-year mortality was 2-times higher in patients who did not receive aspirin than in patients who did receive aspirin (16.5% vs 8.3%, P <.001). A significant association of withheld aspirin at discharge with a higher long-term mortality rate was confirmed with multivariate analysis (OR, 1.62; 95% CI, 1.15-2.29).Conclusions
Ten percent of patients who sustained an AMI did not receive aspirin at the time of hospital discharge. Most of these patients were at high risk for cardiovascular events. Withheld aspirin was significantly associated with higher mortality rate during follow up. 相似文献78.
Harald?S?derb?ckEmail authorView authors OrcID profile Ulf?Gunnarsson Per?Hellman Gabriel?Sandblom 《International journal of colorectal disease》2018,33(10):1411-1417
Background
Our knowledge on the incidence of incisional hernia and risk factors for developing incisional hernia following surgery for colorectal cancer is far from complete.Methods
All procedures registered in the Swedish Colorectal Cancer Register (SCRCR) 2007–2013 were identified. Patients with comorbid disease diagnoses, registered at admissions and visits prior to the procedure and relevant to this study, were obtained from the National Patient Register (NPR). These diagnoses included cardiovascular disease, connective tissue disorders, liver cirrhosis, renal failure, diabetes, chronic obstructive lung disease and chronic inflammatory conditions. Data on occurrence of incisional hernias were obtained by combining data from the SCRCR and the NPR (International Classification of Diseases code).Results
During 2007–2013, 39,984 procedures were registered in the SCRCR. After excluding laparoscopic procedures, procedures repeated on the same patient, procedures with concomitant liver resection and procedures without laparotomy, 28,913 cases remained for analysis. Five years after surgery, the cumulative incidence of incisional hernia was 5.3%. In multivariate proportional hazard analysis, significantly increased risk for incisional hernia was found for the male gender (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.21–1.62), operation time exceeding 180 min (HR 1.25, CI 1.08–1.45), body mass index (BMI) >?30 (HR 1.78, CI 1.51–2.09), age <?70 years (HR 1.34, CI 1.16–1.56) and postoperative wound complication (HR 2.09, CI 1.70–2.58).Discussion
Men, patients younger than 70 years and patients with BMI?>?30 face a higher risk for incisional hernia. The risk is also increased in cases where the procedure takes longer than 3 h or where postoperative wound complications occur. These patients will benefit from measures aimed at preventing the development of incisional hernia.79.
Li X Tjwa M Van Hove I Enholm B Neven E Paavonen K Jeltsch M Juan TD Sievers RE Chorianopoulos E Wada H Vanwildemeersch M Noel A Foidart JM Springer ML von Degenfeld G Dewerchin M Blau HM Alitalo K Eriksson U Carmeliet P Moons L 《Arteriosclerosis, thrombosis, and vascular biology》2008,28(9):1614-1620
80.
Mia Forslin Katharina Fink Ulf Hammar Lena von Koch Sverker Johansson 《Archives of physical medicine and rehabilitation》2018,99(8):1483-1490