bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of re‐excision on survival after unplanned resection in extremity soft tissue sarcomas
Authors: ATALAY Can , ÇETIN Bahadir , ZARALI Ozan , ALTINOK Mehmet 
Published: August 2005

AbstractBackground:  Patients with extremity soft tissue sarcomas are frequently treated with unplanned resections outside the specialized centers. Those patients treated with unplanned resections are evaluated for possible prognostic factors affecting disease‐free and overall survival.Methods:  Patients were grouped after an unplanned resection as having: positive surgical margins; negative surgical  margins  treated  with  re‐excision;  or  no  further  surgery.  Patients’  age,  gender,  tumor  location, size, grade, group according to the surgical margin status and surgical treatment, adjuvant radio‐ and chemotherapy were evaluated as possible prognostic factors.Results:  Seventy‐three patients were eligible for the study. Twenty‐seven patients (37%) had re‐excision due to positive surgical margins, 28 patients (38.3%) had surgery although the initial margins were negative and 18 patients (24.7%) with negative margins received no more surgery. The median disease‐free and overall survival were 35 and 52 months while 5‐year disease‐free and overall survival were 39% and 65%, respectively. In multivariate analysis, low tumor grade (P = 0.005) and adjuvant radiotherapy (P = 0.002) were the independent prognostic factors prolonging disease‐free survival and only the groups formed according to surgical margins and re‐excision had an independent effect on overall survival (OS) (P = 0.029).Conclusion:  This study has indicated that a re‐excision in case of negative margins may decrease OS. In clinical practice, a re‐excision after unplanned resections should be performed in patients with positive margins.
Papanicolaou smear abnormalities in HIV‐infected women in north India
Authors: BAGGA Rashmi , WANCHU Ajay , RAJWANSHI Arvind , GUPTA KR , PRASAD GRV , GOPALAN Sarala , SACHDEVA RK 
Published: August 2005

AbstractBackground:  Dysplasia on Papanicolaou (Pap) smears have been reported in 15–40% of HIV‐positive women. These rates are 10–11 times higher than those observed among HIV‐negative women. Both the Center for Disease Control and Prevention and the Agency for Healthcare Policy and Research recommend that HIV‐infected women have a gynecologic evaluation including a Pap smear and pelvic examination as part of their initial evaluation.Methods:  We performed pelvic examinations and took Pap smears in HIV‐positive women who attended the immunodeficiency clinic of the Postgraduate Institute of Medical Education and Research, Chandigarh, India, from August 2002 to September 2004. The cytology results were followed by colposcopy and/or biopsy if needed.Results:  There were 136 women included in the study, and the age range was 21–58·years. Fourteen patients were menopausal, two had lactational amenorrhea, and five were pregnant. All were married and the majority (121 women) were parous. None of these women had any gynecologic symptoms. Speculum examination was clinically normal in 44 women, 24 had vaginal discharge suggestive of monilial vaginitis, 24 had vaginal discharge suggestive of a mixed infection and 44 had cervical erosion (with or without vaginitis). Bimanual pelvic examination was normal in nearly all, and only two had adnexal tenderness due to pelvic inflammatory disease. Pap smears were reported as normal in 65% of women and as inflammatory in 20%. Dysplasia was seen in 14 smears with invasive carcinoma in one. Seven women underwent colposcopic examination with directed biopsies where indicated. Despite initial counseling for a need for follow‐up, about one‐quarter of the women did not return to collect Pap smear reports and among this group were seven women with dysplasia.Conclusion:  The high incidence of dysplasia in HIV‐positive women supports the recommendation of regular gynecologic examination including Pap smears in all these women even if they do not have any gynecologic symptoms. However, there is a need to have a better follow‐up so that appropriate therapeutic measures can be taken.
Usual diet before diagnosis and survival from colorectal cancer
Authors: HAYDON Andrew MM , MACINNIS Robert J , ENGLISH Dallas R , GILES Graham G 
Published: August 2005

AbstractBackground:  Much research has investigated possible links between diet and the risk of colorectal cancer, but little is known about whether dietary habits influence prognosis following diagnosis.Methods:  Incident cases of colorectal cancer were ascertained among participants of the Melbourne Collaborative Cohort Study, a prospective cohort study of 41 528 Australians recruited between 1990 and 1994. Eligible participants had to be diagnosed with a first colorectal cancer between recruitment and 1 August 2002. At recruitment, participants answered a detailed food frequency questionnaire regarding their usual diet. Information on tumor site and stage, treatments given, recurrences and deaths was obtained from a systematic review of medical records.Results:  Altogether, 526 cases of colorectal cancer were ascertained in the follow‐up period. Median follow up time among survivors was 5.5 years and 208 deaths had occurred, including 181 from colorectal cancer. The usual diet measured before diagnosis was not associated with either all‐cause, or colorectal cancer‐specific, mortality. No association was observed for diets high in meat, fruit, vegetables or fiber.Conclusions:  Our study shows no association between usual diet measured sometime before diagnosis and survival from colorectal cancer.
Carboxypeptidase U (TAFIa): a metallocarboxypeptidase with a distinct role in haemostasis and a possible risk factor for thrombotic disease
Authors: Leurs Judith , Hendriks Dirk 
Published: August 2005

SummarySince the discovery of Carboxypeptidase U (CPU) in 1988, considerable information has been gathered about its biochemistry and function in physiological and pathophysiological circumstances. A variety of tools such as assays to measure proCPU and CPU, antibodies raised against (pro)CPU, selective CPU inhibitors and knock-out mice have been developed and are currently being used to explore the role of this metallocarboxypeptidase in different in vivo and in vitro settings. The knowledge that proCPU can be activated by thrombin and plasmin, enzymes with a key function in coagulation and fibrinolysis, and the ability of CPU to remove C-terminal lysine residues has led to the hypothesis that the proCPU/CPU pathway plays a role in the balance between coagulation and fibrinolysis. The maintenance of the equilibrium between coagulation and fibrinolysis is crucial for normal haemostasis and disturbance of this delicate balance can lead either to bleeding tendency or thrombosis. This review provides an update on several aspects of CPU known at the moment, including an extensive overview on the clinical studies performed up till now.J. Leurs is a research assistant of the Fund for Scientific Research Flanders (FWO-Vlaanderen).
Do patients followed in anticoagulation clinics for antiphospholipid syndrome meet criteria for the disorder?
Authors: Kaboli Peter , Halfdanarson Thorvardur , Chan Happy , Hubert Rod , Rosen Seth , White Richard H. , Dunn Andrew S. 
Published: August 2005

SummaryAlthough specific criteria for diagnosing the antiphospholipid syndrome (APS) exist (the Sapporo Criteria), most physicians are not aware these include repeat testing and documentation of either a lupus anticoagulant or medium to high levels of anticardiolipin antibody. Incorrect diagnosis of APS may result in unnecessary long-term anticoagulation. The purpose of this study was to determine the clinical and serological characteristics of patients being treated for APS and concordance with published criteria. This cross-sectional study identified APS patients who were being treated with warfarin at one of three universitybased anticoagulation clinics. Levels of anticardiolipin antibody were classified as low-positive if abnormal but <40 GPL/MPL units and medium/high-positive if ≥40 units. Strength of meeting Sapporo criteria was graded as definite, possible, and not meeting criteria. Of 103 cases, 97 had clinical and laboratory data available. Only 10 cases (10%, 95% Confidence Interval 5 - 19) met criteria for definite APS, 16 (16%, 10 - 26) had a possible diagnosis, and 71 (73%, 63 - 81) did not meet criteria. Of 70 cases that had abnormal anticardiolipin antibody results, only 32 (46%, 34 - 58) had medium/high-positive levels. Repeat laboratory testing was performed in only 49 cases (51%, 40 - 61). We conclude that few patients treated forAPS met Sapporo criteria. Abnormal levels of anticardiolipin antibody were frequently in the low-positive range, and repeat testing was often absent. A quality improvement program that includes review of cases referred for chronic anticoagulation care is recommended to ensure appropriate testing and treatment of patients with suspected APS.
ADAM15 is an adhesion receptor for platelet GPIIb-IIIa and induces platelet activation
Authors: Langer Harald , May Andreas E. , Bültmann Andreas , Gawaz Meinrad 
Published: August 2005

SummaryCell adhesion and proteolytic matrix degradation are central processes in atherosclerosis. Being a member of the family of ADAMs (“a disintegrin and metalloproteinase”), metargidin (ADAM15) combines a metalloproteinase domain and an RGD aminoacid sequence. We studied the potential role of ADAM15 as an adhesion receptor on endothelial cells and interactions between platelets and ADAM15 with respect to platelet adhesion, activation and thrombus formation. ADAM15 was found to be expressed on cultured endothelial cells (HUVEC). Platelet adhesion to immobilized recombinantADAM15 was effectively enhanced under both static and high shear rate conditions reaching the maximum level of adhesion to fibrinogen. Consistently, platelet adhesion onto ADAM15 overexpressing endothelial cells was significantly increased. Adhesion to ADAM15 was reduced by blockade of GPIIb-IIIa using neutralizing anti-αIIbβ3 mAbs (7E3, 2G12), but not by anti-α
v
β3 (LM609). Soluble ADAM15 binds to activated but not to resting GPIIb-IIIa. Moreover, platelets adherent to ADAM15 additionally attracted platelets under high shear rates indicating an initial role of platelet- ADAM15 interactions for thrombus formation. Furthermore, incubation of platelets with solubleADAM15 showed a dose-dependent increase in secretion of CD62P and CD40L. ADAM15 is expressed on endothelial cells and can serve as an adhesion receptor for platelets via GPIIb-IIIa binding. Platelet adhesion to ADAM15 leads to platelet activation, secretion and promotes thrombus formation. Thus, ADAM15 may represent a novel target for antithrombotic strategies in cardiovascular pathologies.
Postprandial elevation of tissue factor antigen in the blood of healthy adults
Authors: Mackman Nigel , Tilley Rachel E. , Rutledge John C. , Motton Deborah D. 
Published: August 2005

SummaryAtherosclerosis is a dynamic disease involving lipid metabolism, inflammation and thrombosis. A key factor in thrombosis is tissue factor, a small transmembrane glycoprotein. Tissue factor binds FactorVIIa, and this complex converts Factor X to Factor Xa, leading to thrombin generation and fibrin formation. Inhibition of this pathway is by tissue factor pathway inhibitor (TFPI). Tissue factor is found sequestered within atherosclerotic plaques, and plaque rupture allows tissue factor exposure to the circulation, leading to formation of a thrombus. Tissue factor is also associated with membrane microparticles in the circulation, most likely released from monocytes activated by an inflammatory event. We hypothesize that consumption of a typical western diet that is moderate in fat content leads to elevated levels of circulating tissue factor that may act as a marker of a pro-thrombotic state. Healthy volunteers, aged 18-55, consumed a moderate (40%) fat meal, with blood taken before and 3.5 and 6 h after the meal. Plasma was isolated and assayed for plasma triglycerides, tissue factor, thrombin antithrombin (TAT) complexes, TFPI and TNFα. The levels of circulating tissue factor increased 56% (from 78 pg/ml to120 pg/ml) 3.5 h after the meal. Levels decreased, but had not returned to baseline 6 h postprandially. No significant differences in TAT, TFPI and TNFá levels were observed postprandially. These results demonstrate increased tissue factor levels in individuals who consumed a moderate fat diet. This suggests that the typical western diet may play a larger role in cardiovascular disease than merely altering lipid profiles.
The decellularized porcine heart valve matrix in tissue engineering
Authors: Kasimir Marie-Theres , Weigel Guenter , Sharma Jyotindra , Rieder Erwin , Seebacher Gernot , Wolner Ernst , Simon Paul 
Published: August 2005

SummaryAn approach in tissue engineering of heart valves is the use of decellularized xenogeneic matrices to avoid immune response after implantation. The decellularization process must preserve the structural components of the extracellular matrix to provide a biomechanically stable scaffold. However, it is known that in vascular lesions platelet adhesion to extracellular matrix components occurs and platelet activation is induced. In the present study we examined the effects of a decellularized porcine heart valve matrix on thrombocyte activation and the influence of re-endothelialisation in vitro. Porcine pulmonary conduits were decellularized using Triton X-100, Na-deoxycholate and Igepal CA-630® followed by a ribonuclease digestion. Cryostat sections of decellularized heart valves with and without seeding with human umbilical vein endothelial cells (HUVEC) were incubated with platelet rich plasma. Samples were either stained with fluorescent antibodies for CD41 and PAC-1 (recognizing the activated fibrinogen receptor) or fixed with glutaraldehyde. Thereafter, the samples were processed for laser scanning microscopy (LSM) or scanning electron microscopy (SEM). Examination by LSM showed numerous platelets with co-localized staining for CD41 and PAC-1 on the nonseeded decellularized heart valve matrix whereas after seeding with endothelial cells no platelet activation was detected. SEM revealed platelet adhesion and aggregate formation only on the surface of the non-seeded or partially denuded matrix specimens. We show in this study that the decellularized porcine matrix acts as a platelet-activating surface. Seeding with endothelial cells effectively abolishes the platelet adhesion and activation and therefore is necessary to eliminate thrombogenicity in tissue engineered heart valves.
Effect of nitroxyl on human platelets function
Authors: Bermejo Emilse , Alberto Fabiana , Rosenstein Ruth E. , Bari Sara E. , Lazzari María A. , Sáenz Daniel A. 
Published: August 2005

SummaryThere is a growing body of evidence on the role of nitric oxide (NO) in human platelet physiology regulation. Recently, interest has developed in the functional role of an alternative redox form of NO, namely nitroxyl (HNO/NO-), because it is formed by a number of diverse biochemical reactions. The aim of the present study was to comparatively analyze the effect of HNO and NO on several functional parameters of human platelets. For this purpose, sodium trioxodinitrate (Angeli’s salt, AS) and sodium nitroprusside (SNP) were used as HNO and NO releasers, respectively. Both AS and SNP significantly inhibited platelet aggregation and ATP release induced by different agonists and adrenaline. AS or SNP did not modify the expression of platelet glycoproteins (Ib, IIb-IIIa, Ia-IIa, IV), whereas they substantially decreased the levels of CD62P, CD63 and of PAC-1 (a platelet activated glycoprotein IIb/IIIa epitope) after the stimulation with ADP. AS and SNP significantly increased cGMP accumulation in a 1H-[1,2,4]oxadiazolo [4,3-a] quinoxalin-1-one (ODQ)-sensitive manner. However, while L-cysteine reduced the effect of AS, it increased the effect of SNP on this parameter. Accordingly, a differential effect of L-cysteine was observed on the antiaggregatory effect of both compounds. In summary, these results indicate that HNO is an effective inhibitor of human platelet aggregation.
Drug interactions and risk of acute bleeding leading to hospitalisation or death in patients with chronic atrial fibrillation treated with warfarin
Authors: Hollowell Jennifer , Meier Christoph R. , Haefeli Walter E. , Gasse Christiane 
Published: August 2005

SummaryAlthough drug interactions with warfarin are an important cause of excessive anticoagulation, their impact on the risk of serious bleeding is unknown. We therefore performed a cohort study and a nested case-control analysis to determine the risk of serious bleeding in 4152 patients (aged 40–84 years) with nonvalvular atrial fibrillation (AF) taking long-term warfarin (>3 months). The study population was drawn from the UK General Practice Research Database. More than half (58%) of eligible patients used potentially interacting drugs during continuous warfarin treatment. Among 45 identified cases of incident idiopathic bleeds (resulting in hospitalisation within 30 days or death within 7 days) and 143 matched controls, more cases than controls took ≥1 potentially interacting drug within the preceding 30 days (62.2% vs. 35.7%) and used >4 drugs (polypharmacy) within the preceding 90 days (80.0% vs. 66.4%). Conditional logistic regression analysis yielded an odds ratio (OR) of 3.4 (95% confidence interval [CI]: 1.4–8.5) for the risk of serious bleeding in patients treated with warfarin and ≥1 drugs potentially increasing the effect of warfarin vs. warfarin alone adjusted for polypharmacy, diabetes, hypertension, heart failure, and thyroid disease; the adjusted OR for the combined use of warfarin and aspirin vs. warfarin alone was 4.5 (95% CI: 1.1–18.1). We conclude that concurrent use of potentially interacting drugs with warfarin is associated with a 3 to 4.5-fold increased risk of serious bleeding in long-term warfarin users.
The potential role of platelet microparticles in atherosclerosis
Authors: Tan Kiat T. , Lip Gregory Y. H. 
Published: August 2005

SummaryThe release of microvesicles (‘platelet microparticles’, PMPs) by activated platelets has been shown to be an integral part of the thrombotic process. PMPs are believed to mediate many biological processes as they possess various platelet membrane proteins and bioactive lipids. Of note, there is a growing body of evidence that PMPs are involved in all stages in the pathobiology of atherosclerosis. In addition to their role in thrombosis, PMPs may also have a pro-inflammatory effect, which promotes the development of atherosclerosis. Also, bioactive lipids in PMPs have been shown to have important effects on angiogenesis. This review summarises the various studies on the possible role of PMPs in the progression of atherosclerosis.
Stereoselective inhibition of human platelet aggregation by R-138727, the active metabolite of CS-747 (Prasugrel, LY640315), a novel P2Y12 receptor inhibitor
Authors: Hasegawa Michihiro , Sugidachi Atsuhiro , Ogawa Taketoshi , Isobe Takashi , Jakubowski Joseph A. , Asai Fumitoshi 
Published: August 2005

SummaryCS-747 (Prasugrel, LY640315) is a thienopyridine antiplatelet prodrug that is metabolized to the thiol-containing active metabolite R-138727, which binds to and irreversibly inhibits the platelet P2Y12 ADP receptor. R-138727 is composed of 4 stereoisomers, (R, S)-, (R, R)-, (S, S)-, and (S, R)-isomers (the first letter for the configuration of a chiral center at the sulfur-bearing position and the second for that at the benzylic position). In the present study, we determined the stereoselectivity of P2Y12 antagonist effects by assessing the antagonism of the [3H]-2-MeS-ADP that binds to human P2Y12 receptors expressed in Chinese hamster ovary cells as an affinity assay, and by the inhibition of ADP-induced aggregation of washed human platelets as a functional assay. R-138727 and its 2 components, R-99224, a mixture of (R, S)- and (S, R)-isomers and R-100364, a mixture of (R, R)- and (S, S)-isomers, inhibited [3H]-2-MeS-ADP binding and platelet aggregation. The rank order of potency of these compounds were identical in both assays: R-99224>R-138727>> R-100364. Inhibition of ADP-induced platelet aggregation by R-138727 and R-99224 was concentration- and time-related. In experiments using the 4 single stereo-isomers, all isomers inhibited ADP-induced platelet aggregation, but the (R, S)-isomer was found to be the most potent, followed by the (R, R)-isomer. These in vitro studies indicate that R-138727 is an effective antagonist of P2Y12 and potent inhibitor of ADP-induced platelet aggregation, and that these antiplatelet activities of R-138727 are largely dependent on its (R, S)-isomer. This suggests that the (R)- configuration of the reactive thiol group of the active metabolite of CS-747 is critical for P2Y12 and platelet inhibitory activities.
Association of MTRR A66G polymorphism (but not of MTHFR C677T and A1298C, MTR A2756G, TCN C776G) with homocysteine and coronary artery disease in the French population
Authors: Juilliére Yves , Candito Mirande , Adjalla Charles E. , Gibelin Pierre , Herbeth Bernard , Obberghen Emmanuel Van , Guéant Jean-Louis , Guéant-Rodriguez Rosa-Maria 
Published: August 2005

Summarymethylenetetrahydrofolate reductase polymorphism (MTHFR C677T) is an established determinant of homocysteine plasma level (t-Hcys) while its association with coronary artery disease (CAD) seems to be more limited. In contrast, the association of the substitutions A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR) and C776G of transcobalamin (TCN) to both t-Hcys and CAD needs to be evaluated further. The objective was to evaluate the association of these polymorphisms with t-Hcys and CAD in a French population. We investigated the individual and combined effects of these polymorphisms and of vitamin B12 and folates with t-Hcys in 530 CAD patients and 248 matched healthy controls. t-Hcys was higher in the CAD group than in controls (11.8 vs 10.4 μM, P<0.0001) and in carriers of MTRR AA and MTHFR 677TT than in those carrying the most frequent allele of both polymorphisms (13.8 vs 11.4 μM, P=0.0102 and 12.5 vs 11.0 mM, P=0.0065 respectively). The frequency of MTRR A allele was higher in CAD patients than in controls (0.48 [95% CI: 0.44-0.52] vs 0.38 [95% CI: 0.32-0.44], P=0.0081) while no difference was observed for MTHFR 677T frequency. In multivariate analysis, t-Hcys > median and MTRR AA genotype were two significant independent predictors of CAD with respective odds ratios of 3.1 (95 % CI: 1.8-5.1, P<0.0001) and 4.5 (95% CI: 1.5-13.1, P=0.0051). In conclusion, in contrast to North Europe studies, MTRR AA genotype is a genetic determinant of moderate hyperhomocysteinemia associated with CAD in a French population without vitamin fortification.