bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular basis of protein S deficiency
Authors: Fuentes-Prior Pablo , Hurtado Begoña , Frutos Pablo García de , Sala Núria 
Published: October 2007

SummaryProtein S deficiency (PSD) has been the most difficult to study among the classical inherited thrombophilic factors. This is in part due to the peculiar biology of protein S (PS), which has an anticoagulant role but no enzymatic activity,and because it interacts with plasma components that function in both haemostasis and inflammation.Clinically,it also has been difficult to define and standardise valuable assays to determine PS status and implication in thrombosis. Despite these drawbacks, at present heterozygous PS deficiency is well established as an autosomal dominant trait associated with an increased risk of thrombosis from data on familial and population studies. Almost twohundred mutations have been characterised in PROS1, and approximately 30% of them have been characterised in vitro,clarifying the mechanisms leading to PSD. Furthermore, recent studies on the presence of large deletions in PROS1 have increased the number of PSD associated to PROS1 mutations. Finally, the discovery of new functions for PS, both in the anticoagulant system as well as in the interaction with cellular components through receptor tyrosine kinases, is broadening the importance of this molecule in the context of biomedicine.
Thrombomodulin-mediated catabolism of protein C by pleural mesothelial and vascular endothelial cells
Authors: Rezaie Alireza , Idell Steven , Iakhiaev Alexei 
Published: October 2007

SummaryPleural mesothelial and vascular endothelial cells express protein C (PC) pathway components including thrombomodulin (TM) and endothelial protein C receptor (EPCR) and activate PC by the thrombin-TM dependent mechanism.We used these cells as model systems to identify molecules involved in endocytosis and degradation of PC. We find that mesothelial and endothelial cells can bind, internalize and degrade PC.Addition of thrombin markedly induced degradation of PC by these cells in a TM-dependent fashion, implicating the involvement of the thrombin-TM complex in internalization and degradation of PC. This observation defines a novel function for the thrombin-TM complex as a degradation receptor for PC and suggests that PC is degraded concurrent with its activation.A PC Gla-domain mutant, which is unable to bind to the EPCR, was degraded by the cells to a lesser extent than wild-type PC, implicating the PC degradation concurrent with its activation. Consistent with the role of thrombin-TM complex as a degradation receptor, the catalytically inactive thrombin-S195A also induced PC degradation though to a lesser extent than wild-type thrombin.This suggests that generation of activated PC (APC) can contribute to accumulation of degradation products, but is not essential for the thrombin-induced degradation of PC. The thrombin-TMmediated degradation of PC by both cell types suggest a previously unrecognized mechanism, which can contribute to PC consumption.This mechanism may be pathophysiologically relevant and can contribute to an acquired PC deficiency in conditions characterized by sustained thrombin generation.
Fibrinogen-binding proteins of Gram-positive bacteria
Authors: Vannakambadi Ganesh , Höök Magnus , Speziale Pietro , Rivera Jose 
Published: October 2007

SummaryFibrinogen (Fg), the major clotting protein in blood plasma, plays key roles in blood coagulation and thrombosis. In addition, this 340 kD glycoprotein is a stress inducible protein; its synthesis is dramatically upregulated during inflammation or under exposure to stress such systemic infections.This regulation of Fg expression indicates that Fg also participates in the host defense system against infections. In fact, a number of reported studies have demonstrated the involvement of both the intrinsic and extrinsic pathways of coagulation; the thrombotic and the fibrinolytic systems in the pathophysiology of infectious diseases. It is, therefore, perhaps not surprising that many pathogenic bacteria can interact with Fg and manipulate its biology.This review focuses on the major Fg-binding proteins (Fgbps) from Gram-positive bacteria with an emphasis on those that are known to have an effect on coagulation and thrombosis
Venous thromboembolism in patients with active cancer
Authors: Seddighzadeh Ali , Shetty Ranjith , Goldhaber Samuel 
Published: October 2007

SummaryPatients with cancer have an increased risk of venous thromboembolism (VTE).To further define the demographics, comorbidities, and risk factors of VTE in these patients, we analyzed a prospective registry of 5,451 patients with ultrasound confirmed deep vein thrombosis (DVT) from 183 hospitals in the United States. Cancer was reported in 1,768 (39%), of whom 1,096 (62.0%) had active cancer. Of these, 599 (54.7%) were receiving chemotherapy, and 226 (20.6%) had metastases. Lung (18.5%), colorectal (11.8%), and breast cancer (9.0%) were among the most common cancer types. Cancer patients were younger (median age 66 years vs. 70 years; p<0.0001), were more likely to be male (50.4% vs. 44.5%; p=0.0005), and had a lower average body mass index (26.6 kg/m2 vs. 28.9 kg/m2; p<0.0001). Cancer patients less often received VTE prophylaxis prior to development of DVT compared to those with no cancer (308 of 1,096, 28.2% vs. 1,196 of 3,444, 34.6%; p<0.0001). For DVT therapy, low-molecular-weight heparin (LMWH) as monotherapy without warfarin (142 of 1,086, 13.1% vs. 300 of 3,429, 8.7%; p<0.0001) and inferior vena caval filters (234 of 1,086, 21.5% vs. 473 of 3,429, 13.8%; p<0.0001) were utilized more often in cancer patients than in DVT patients without cancer. Cancer patients with DVT and neurological disease were twice as likely to receive inferior vena caval filters than those with no cancer (odds ratio 2.17, p=0.005). In conclusion, cancer patients who develop DVT receive prophylaxis less often and more often receive filters than patients with no cancer who develop DVT. Future studies should focus on ways to improve implementation of prophylaxis in cancer patients and to further define the indications, efficacy, and safety of inferior vena caval filters in this population.
Current pharmacogenetic developments in oral anticoagulation therapy: The influence of variant VKORC1 and CYP2C9 alleles
Authors: Bevans Carville , Fregin Andreas , Geisen Christof , Müller-Reible Clemens , Watzka Matthias , Oldenburg Johannes 
Published: October 2007

SummaryFor decades coumarins have been the most commonly prescribed drugs for therapy and prophylaxis of thromboembolic conditions. Despite the limitation of their narrow therapeutic dosage window, the broad variation of intra- and inter-individual drug requirement, and the relatively high incidence of bleeding complications,prescriptions for coumarins are increasing due to the aging populations in industrialised countries.The identification of the molecular target of coumarins,VKORC1, has greatly improved the understanding of coumarin treatment and illuminated new perspectives for a safer and more individualized oral anticoagulation therapy. Mutations and SNPs within the translated and non-translated regions of the VKORC1 gene have been shown to cause coumarin resistance and sensitivity,respectively. Besides the known CYP2C9 variants that affect coumarin metabolism, the haplotype VKORC1*2 representing a frequent SNP within the VKORC1 promoter has been identified as a major determinant of coumarin sensitivity,reducingVKORC1 enzyme activity to 50% of wild type. Homozygous carriers of the VKORC1*2 allele are strongly predisposed to coumarin sensitivity. Using individualized dose adaptation, a significant reduction of bleeding complications can be expected, especially in the initial drug saturation phase. Furthermore, concomitant application of low dose vitamin K may significantly reduce intra-individual coumarin dose variation and, thus, may stabilize oral anticoagulation therapy. The use of new pharmacogenetics-based dosing schemes and the concomitant application of low-dose vitamin K with coumarins will decidedly influence the current practice of oral anticoagulation and greatly improve coumarin drug safety.
Injustifiable use of gastroprotection in advanced cancer patients
Authors: Mercadante Sebastiano , David Fabrizio , Riina Salvatore , Girelli Davide 
Published: October 2007

The aim of this survey was to prospectively collect data about gastroprotector prescription at admission of an acute pain relief and palliative care unit. An observational survey was performed on three-hundred consecutive patients. Reasons for admission, concomitant treatment and use of drugs were recorded at admission. About 60.6% patients had been prescribed proton pump inhibitors or anti-H2 receptors agents. Of these patients, possible risk factors were nonsteroidal anti-inflammatory drugs (41, 22.5%), corticosteroids (43, 23.6%), age > 75 years (27, 14.8%). In only 25 admissions (13.7%) prescription corresponded to Italian drug agency recommendations with an odds ratio of an off-label prescription of 7.28. In a relatively high percentage of admissions (55%), patients receiving gastroprotectors were on chemotherapy, with an odds ratio of 1.42. This survey showed that gastroprotectors are often prescribed regardless of Health Care System regulations, as only a minority of patients satisfied the requirements of an appropriate and refundable prescription. The attitudes of oncologists who prescribe gastroprotectors for a putative protective effects are not supported by evidence. Health Care Service in Italy should be aware of these problems to improve the strategies of budgeting the drug expense in a better way or providing further guidelines based on studies able to demonstrate the real cost-benefit ratio of this class of drugs. Palliative Medicine 2007; 21 : 631—633
No Effect of a Graded Training Program on the Number of Running-Related Injuries in Novice Runners
Authors: Buist Ida , Bredeweg Steef W. , van Mechelen Willem , Lemmink Koen A. P. M. , Pepping Gert-Jan , Diercks Ron L. 
Published: October 2007

Background Although running has positive effects on health and fitness, the incidence of a running-related injury (RRI) is high. Research on prevention of RRI is scarce; to date, no studies have involved novice runners. Hypothesis A graded training program for novice runners will lead to a decrease in the absolute number of RRIs compared with a standard training program. Study Design Randomized controlled trial; Level of evidence, 1. Methods GRONORUN (Groningen Novice Running) is a 2-armed randomized controlled trial comparing a standard 8-week training program (control group) and an adapted, graded, 13-week training program (intervention group), on the risk of sustaining an RRI. Participants were novice runners (N = 532) preparing for a recreational 4-mile (6.7-km) running event. The graded 13-week training program was based on the 10% training rule. Both groups registered information on running characteristics and RRI using an Internet-based running log. The primary outcome measure was RRIs per 100 participants. An RRI was defined as any musculoskeletal complaint of the lower extremity or back causing a restriction of running for at least 1 week. Results The graded training program was not preventive for sustaining an RRI (χ 2 = 0.016, df = 1, P = .90). The incidence of RRI was 20.8% in the graded training program group and 20.3% in the standard training program group. Conclusions This randomized controlled trial showed no effect of a graded training program (13 weeks) in novice runners, applying the 10% rule, on the incidence of RRI compared with a standard 8-week training program.
A Comprehensive Rehabilitation Program with Quadriceps Strengthening in Closed versus Open Kinetic Chain Exercise in Patients with Anterior Cruciate Ligament Deficiency
Authors: Tagesson Sofi , Öberg Birgitta , Good Lars , Kvist Joanna 
Published: October 2007

Background There is no consensus regarding the optimal rehabilitation regimen for increasing quadriceps strength after anterior cruciate ligament (ACL) injury. Hypothesis A comprehensive rehabilitation program supplemented with quadriceps strengthening in open kinetic chain (OKC) exercise will increase quadriceps strength and improve knee function without increasing static or dynamic sagittal tibial translation, compared with the same comprehensive rehabilitation program supplemented with quadriceps strengthening in closed kinetic chain (CKC) exercise, in patients with acute ACL deficiency. Study Design Randomized controlled trial; Level of evidence, 1. Methods Forty-two patients were tested a mean of 43 days (range, 20–96 days) after an ACL injury. Patients were randomized to rehabilitation with CKC quadriceps strengthening (11 men and 9 women) or OKC quadriceps strengthening (13 men and 9 women). Aside from these quadriceps exercises, the 2 rehabilitation programs were identical. Patients were assessed after 4 months of rehabilitation. Sagittal static translation and dynamic tibial translation were evaluated with a CA-4000 electrogoniometer. Muscle strength, jump performance, and muscle activation were also assessed. Functional outcome was evaluated by determining the Lysholm score and the Knee Injury and Osteoarthritis Outcome Score. Results There were no group differences in static or dynamic translation after rehabilitation. The OKC group had significantly greater isokinetic quadriceps strength after rehabilitation ( P = .009). The hamstring strength, performance on the 1-repetition-maximum squat test, muscle activation, jump performance, and functional outcome did not differ between groups. Conclusions Rehabilitation with OKC quadriceps exercise led to significantly greater quadriceps strength compared with rehabilitation with CKC quadriceps exercise. Hamstring strength, static and dynamic translation, and functional outcome were similar between groups. Patients with ACL deficiency may need OKC quadriceps strengthening to regain good muscle torque.
A 10-Year Prospective Trial of a Patient Management Algorithm and Screening Examination for Highly Active Individuals with Anterior Cruciate Ligament Injury
Authors: Hurd Wendy J. , Axe Michael J. , Snyder-Mackler Lynn 
Published: October 2007

Background A treatment algorithm and screening examination have been developed to guide patient management and prospectively determine potential for highly active individuals to succeed with nonoperative care after anterior cruciate ligament rupture. Objective To prospectively characterize and classify the entire population of highly active individuals over a 10-year period and provide final outcomes for individuals who elected nonoperative care. Methods Inclusion criteria included presentation within 7 months of the index injury and an International Knee Documentation Committee level I or II activity level before injury. Concomitant injury, unresolved impairments, and a screening examination were used as criteria to guide management and classify individuals as noncopers (poor potential) or potential copers (good potential) for nonoperative care. Results A total of 832 highly active patients with subacute anterior cruciate ligament tears were seen over the 10-year period; 315 had concomitant injuries, 87 had unresolved impairments, and 85 did not participate in the classification algorithm. The remaining 345 patients (216 men, 129 women) participated in the screening examination a mean of 6 weeks after the index injury. There were 199 subjects classified as noncopers and 146 as potential copers. Sixty-three of 88 potential copers successfully returned to preinjury activities without surgery, with 25 of these patients not undergoing anterior cruciate ligament reconstruction at the time of follow-up. Conclusion The classification algorithm is an effective tool for prospectively identifying individuals early after anterior cruciate ligament injury who want to pursue nonoperative care or must delay surgical intervention and have good potential to do so.
No Advantages in Repairing a Type II Superior Labrum Anterior and Posterior (SLAP) Lesion When Associated with Rotator Cuff Repair in Patients over Age 50
Authors: Franceschi Francesco , Longo Umile Giuseppe , Ruzzini Laura , Rizzello Giacomo , Maffulli Nicola , Denaro Vincenzo 
Published: October 2007

Background Arthroscopic management has been recommended for some superior labrum anterior and posterior (SLAP) lesions, but no studies have focused on patients over 50 years of age with rotator cuff tear and a type II SLAP lesion. Hypothesis In patients over 50 years of age with an arthroscopically confirmed lesion of the rotator cuff and a type II SLAP lesion, there is no difference between (1) repair of both lesions and (2) repair of the rotator cuff tear without repair of the SLAP II lesion but with a tenotomy of the long head of the biceps. Study Design Randomized controlled clinical trial; Level of evidence, 1. Methods We recruited 63 patients. In 31 patients, we repaired the rotator cuff and the type II SLAP lesion (group 1). In the other 32 patients, we repaired the rotator cuff and tenotomized the long head of the biceps (group 2). Seven patients (2 in group 1 and 5 in group 2) were lost to final follow-up. Results At a minimum 2.9 years’ follow-up, statistically significant differences were seen with respect to the University of California, Los Angeles (UCLA) score and range of motion values. In group 1 (SLAP repair and rotator cuff repair), the UCLA showed a statistically significant improvement from a preoperative average rating of 10.4 (range, 6–14) to an average of 27.9 (range, 24–35) postoperatively ( P < .001). In group 2 (biceps tenotomy and rotator cuff repair), the UCLA showed a statistically significant improvement from a preoperative average rating of 10.1 (range, 5–14) to an average of 32.1 (range, 30–35) postoperatively ( P < .001) There was a statistically significant difference in total postoperative UCLA scores and range of motion when comparing the 2 groups postoperatively ( P < .05). Conclusions There are no advantages in repairing a type II SLAP lesion when associated with a rotator cuff tear in patients over 50 years of age. The association of rotator cuff repair and biceps tenotomy provides better clinical outcome compared with repair of the type II SLAP lesion and the rotator cuff.
Double-Bundle Anterior Cruciate Ligament Reconstruction Using Hamstring Autografts and Bioabsorbable Interference Screw Fixation
Authors: Järvelä Timo , Moisala Anna-Stina , Sihvonen Raine , Järvelä Sally , Kannus Pekka , Järvinen Markku 
Published: October 2007

Background Conventional anterior cruciate ligament reconstruction techniques have focused on restoration of the anterome-dial bundle only, which, however, may be insufficient in restoring the rotational stability of the knee. Hypothesis Rotational stability of the knee is better when using a double-bundle technique instead of a single-bundle technique for anterior cruciate ligament reconstruction. Study Design Randomized controlled clinical trial; Level of evidence, 1. Methods Seventy-seven patients were randomized into 3 different groups for anterior cruciate ligament reconstruction with hamstring tendons: double-bundle with bioabsorbable screw fixation (n = 25), single-bundle with bioabsorbable screw fixation (n = 27), and single-bundle with metallic screw fixation (n = 25). The evaluation methods were clinical examination, KT-1000 arthrometric measurement, and the International Knee Documentation Committee and Lysholm knee scores. Results There were no differences between the study groups preoperatively. Seventy-three patients (95%) were available at a minimum 2-year follow-up (range, 24–35 mo). The rotational stability of the knee, as evaluated by the pivot-shift test, was the best in the patients in the double-bundle group. In addition, the patients in the single-bundle groups had more graft failures than those in the double-bundle group. Concerning the anterior stability of the knee as measured with the KT-1000 arthrometer, the group differences were not statistically significant. No significant differences were found between the groups in knee scores. Conclusion Rotational stability of the knee is better when using the double-bundle technique instead of the single-bundle technique in anterior cruciate ligament reconstruction.
Changes in Blood Flow of Anterior and Middle Cerebral Arteries Following Carotid Endarterectomy: A Transcranial Doppler Study
Authors: Maltezos C.K. , Papanas N. , Papas T.T. , Georgiadis G.S. , Dragoumanis C.K. , Marakis J. , Maltezos E. , Lazarides M.K. 
Published: October 2007

Aim: The aim of the present study was to evaluate the changes in blood flow of anterior and middle cerebral arteries following carotid endarterectomy, using transcranial Doppler (TCD) flow studies. Patients and methods: This study included 100 patients (72 men, mean age 65 years) who underwent carotid endarterectomy because of high-grade carotid stenosis or symptoms of ischemic stroke. Endarterectomy was performed by a distal shunt between the common carotid and internal carotid arteries. Blood flow in the anterior and middle cerebral arteries was assessed by TCD preoperatively and also in the postoperative period (1st and 4th day; 1st, 6th, and 12th month). Collateral circulation in the Willis circle was evaluated by common carotid compression. Results: Patients with bilateral carotid stenosis ≥70% exhibited a significantly increased flow velocity in the ipsilateral anterior cerebral artery (ACA), middle cerebral artery (MCA), and in the contralateral ACA. Patients with entirely occluded contralateral internal carotid artery showed the most pronounced changes in cerebral hemodynamics. Blood flow velocities returned to the preoperative values at 1 to 12 months following endarterectomy. Hyperperfusion syndrome was manifested in 14 patients, who exhibited significantly higher flow velocities in the ipsilateral MCA compared with asymptomatic patients. Conclusions: A transient bilateral increase of blood flow velocity in the anterior part of the Willis circle may often occur in the immediate postoperative period following carotid endarterectomy. Although its clinical significance is not entirely understood, this increase may be associated with cerebral hyperperfusion syndrome.
Nonatherosclerotic Pathology of the Neck Vessels: Prevalence and Flow Patterns
Authors: Labropoulos Nicos , Leon Luis R. , Gonzalez-Fajardo Jose A. , Mansour Ashraf M. , Kang Steven S. 
Published: October 2007

Objectives: To determine the prevalence and flow characteristics of nonatherosclerotic pathologies of the cervical vessels. Design: From 1997 to 2003, 11 480 ultrasound tests were performed for neck vessel evaluation on patients with cerebrovascular symptoms and trauma, and on asymptomatic patients with a bruit, cervical mass, or prior to aortocoronary bypass. When necessary, these findings were confirmed by other imaging modalities. Results: A total of 3010 repeated tests were excluded, leaving 8470 patients. The prevalence of nonatherosclerotic pathologies (n = 55) was 0.65%. The most common was thromboembolism (n = 19, 0.22%), followed by dissection (n = 16, 0.19%), carotid body tumors (n = 5, 0.06%), aneurysms (n = 4, 0.05%), fibromuscular dysplasia (n = 4, 0.05%), Takayasu's arteritis (n = 1, 0.01%), pseudoaneurysms (n = 5, 0.06%), and arteriovenous fistulae (n = 1, 0.01%). Cerebrovascular symptoms were present in 27 patients (49%). Conclusion: Nonatherosclerotic pathology accounts for 0.65% of patients referred for neck vessel evaluation. About half of them are symptomatic. Diagnosis of these pathologies and knowledge of their flow characteristics is important for patient management.