bluuebunny/crossref_metadata_2025 huggingface dataset:
Schedule-Dependent Cytotoxic Synergism of Pemetrexed and Erlotinib in Human Non–Small Cell Lung Cancer Cells
Authors: Li Tianhong , Ling Yi-He , Goldman I. David , Perez-Soler Roman
Published: June 2007

Purpose: This study was undertaken to select the optimal combination schedule of erlotinib and pemetrexed for the treatment of relapsed non–small cell lung cancer (NSCLC) using a panel of human NSCLC lines.

Experimental Design: Human NSCLC cell lines, with variable expression of the known molecular determinants of erlotinib sensitivity, were exposed to pemetrexed and erlotinib using different schedules. Antitumor effect was measured by growth inhibition by cell count and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle distribution and apoptosis by flow cytometry, and expression of cell cycle mediators by immunoblots. The cytotoxic interaction between pemetrexed and erlotinib (i.e., synergistic, additive, or antagonistic) was determined by median effect analysis.

Results: When cells were exposed to concurrent pemetrexed and erlotinib or sequential pemetrexed followed by erlotinib, cytotoxic synergism was observed in both erlotinib-sensitive and erlotinib-resistant human NSCLC cell lines. This was independent of the mutation status of epidermal growth factor receptor or K-Ras genes. Synergism was associated with a combination of cell cycle effects from both agents. In contrast, exposure of cells to erlotinib followed by pemetrexed was mostly antagonistic in erlotinib-sensitive cells and additive at best in erlotinib-resistant cells. Antagonism was associated with erlotinib-induced G1-phase blockade of erlotinib-sensitive cells, which protects cells from pemetrexed cytotoxicity. Pemetrexed induced an epidermal growth factor receptor–mediated activation of the phosphatidylinositol 3-kinase/AKT pathway, which was inhibited by erlotinib and a specific phosphatidylinositol 3-kinase inhibitor, LY294002.

Conclusions: The combination of pemetrexed and erlotinib is synergistic in NSCLC in vitro if exposure to erlotinib before pemetrexed is avoided, particularly in tumors that are sensitive to erlotinib. Based on these findings, a randomized phase II study comparing the progression-free survival between an intermittent combination of erlotinib and pemetrexed (experimental arm) and pemetrexed alone (control arm) in patients with relapsing NSCLC has been initiated.
Suppression of pancreatic tumor growth by combination chemotherapy with sulindac and LC-1 is associated with cyclin D1 inhibitionin vivo
Authors: Yip-Schneider Michele T. , Wu Huangbing , Ralstin Matthew , Yiannoutsos Constantin , Crooks Peter A. , Neelakantan Sundar , Noble Stephen , Nakshatri Harikrishna , Sweeney Christopher J. , Schmidt C. Max
Published: June 2007

The design of novel targeted or combination therapies may improve treatment options for pancreatic cancer. Two targets of recent interest are nuclear factor-κB (NF-κB) and cyclooxygenase (COX), known to be activated or overexpressed, respectively, in pancreatic cancer. We have previously shown that parthenolide, a proapoptotic drug associated with NF-κB inhibition, enhanced the growth suppression of pancreatic cancer cells by the COX inhibitor sulindac in vitro. In the present study, a bioavailable analogue of parthenolide, LC-1, and sulindac were evaluated in vivo using a xenograft model of human pancreatic cancer. Treatment groups included placebo, low-dose/high-dose LC-1 (20 and 40 mg/kg), low-dose/high-dose sulindac (20 and 60 mg/kg), and low-dose combination LC-1/sulindac (20 mg/kg each). In MiaPaCa-2 xenografts, tumor growth was inhibited by either high-dose sulindac or LC-1. In BxPC-3 xenografts, tumor size was significantly reduced by treatment with the low-dose LC-1/sulindac combination or high-dose sulindac alone (P < 0.05). Immunohistochemistry of BxPC-3 tumors revealed a significant decrease in Ki-67 and CD31 staining by high-dose sulindac, with no significant changes in COX-1/COX-2 levels or activity in any of the treatment groups. NF-κB DNA-binding activity was significantly decreased by high-dose LC-1. Cyclin D1 protein levels were reduced by the low-dose LC-1/sulindac combination or high-dose sulindac alone, correlating with BxPC-3 tumor suppression. These results suggest that LC-1 and sulindac may mediate their antitumor effects, in part, by altering cyclin D1 levels. Furthermore, this study provides preclinical evidence for the therapeutic efficacy of these agents. [Mol Cancer Ther 2007;6(6):1736–44]
Biomarkers of Cardiovascular Damage
Authors: Collinson Paul O. , Gaze David C.
Published: June 2007

Acute coronary syndromes (ACS) are due to the rupture or erosion of atheromatous plaques. This produces, depending on plaque size, vascular anatomy and degree of collateral circulation, progressive tissue ischaemia which may progress to cardiomyocyte necrosis. This may then result in cardiac remodelling. Serum biomarkers are available which can be used for diagnosis of all of these stages. Markers to detect myocardial ischaemia at the pre-infarction stage are potentially the most interesting but also the most challenging. An ischaemia marker offers the opportunity to intervene to prevent progression to infarction. The problems with potential ischaemia markers are specificity and the reference diagnostic standard against which they can be judged. To date, only one, ischaemia-modified albumin®, has reached the point where clinical studies can be performed. The measurement of the cardiac troponins, cardiac troponin T and cardiac troponin I, have become recognised as the diagnostic reference standard for myocardial necrosis. The sensitive nature of these tests has also revealed that myocardial necrosis is also found in a range of other clinical situations, highlighting the need to use all clinical information for diagnosis of acute myocardial infarction. The measurement of B-type natriuretic peptides can be shown to be diagnostic and prognostic in both ACS and detecting the sequelae of post-infarction myocardial insufficiency. The role of the B-type natriuretic peptides in detection of cardiac failure, both acute and chronic, is well defined but remains the subject of further studies, in ACS.
Consanguineous Marriages and Their Effects on Common Adult Diseases: Studies from an Endogamous Population
Authors: Bener Abdulbari , Hussain Rafat , Teebi Ahmad S.
Published: June 2007

Objectives: The aim of the study was to determine the extent and nature of consanguinity in the Qatari population and its effects on common adult diseases. Subjects and Methods: The study was conducted in urban and semi-urban areas of Qatar between October 2004 and May 2005. The total sample of 1,050 married Qatari females 15 years of age and over were approached for study. The degree of consanguinity between each female and her spouse and the degree of consanguinity between their parents were recorded. Results: Of 1,050 married Qatari females who were approached, 876 agreed to participate in the study, giving an 83.4% response. The rate of consanguinity in the present generation was 51% (95% confidence interval = 47.7–54.4) with a coefficient of inbreeding of 0.023724. The consanguinity rate and coefficient of inbreeding in the current generation were significantly higher than the maternal rate (51.0 vs. 40.3%; p < 0.001; 0.023724 vs. 0.016410 maternal). All types of consanguineous marriages were higher in this generation, particularly first cousins (26.7 vs. 21.4% paternal and 23.1% maternal) and double first cousins (4.3 vs. 2.9% paternal and 0.8% maternal). The current generation of consanguineous parents had a slightly higher risk for most diseases: cancer, mental disorders, heart diseases, gastro-intestinal disorders, hypertension, hearing deficit and diabetes mellitus. All reported diseases were more frequent in consanguineous marriages. Conclusion: The study showed that in a population with a high rate of consanguinity, there is a significant increase in the prevalence of common adult diseases like cancer, mental disorders, heart diseases, gastro-intestinal disorders, hypertension and hearing deficit.
Thrombotic Thrombocytopenic Purpura in a Patient with Brucella Infection Is Highly Responsive to Combined Plasma Infusion and Antimicrobial Therapy
Authors: Erdem Fuat , Kiki İlhami , Gündoğdu Mehmet , Kaya Hasan
Published: June 2007

Objective: To report a case of brucella infection presenting with thrombotic thrombocytopenic purpura (TTP) that responded well to plasma and antimicrobial treatment infusion. Case Presentation and Intervention: A 51-year-old man with moderate confusion, depressed mood and dysarthria was admitted. He was chronically ill, with fever (38.5°C), anemia, jaundice and petechial-purpuric skin lesions. Neurological examination revealed diminished consciousness with a Glasgow coma scale score of 7 and +1 neck rigidity. The hemoglobin and platelet counts were decreased and reticulocyte index, erythrocyte sedimentation rate, as well as serum lactate dehydrogenase and renal dysfunction were elevated. TTP was a possible diagnosis and the patient responded well to plasma infusion and antimicrobial treatment. Conclusion: This report shows that therapy of underlying infection together with plasma infusion may be a successful treatment option for brucellosis-induced TTP.
Differences in Renal Tubule Primary Cilia Length in a Mouse Model of Bardet-Biedl Syndrome
Authors: Mokrzan Elaine M. , Lewis Jacqueline S. , Mykytyn Kirk
Published: May 2007

Background: Bardet-Biedl syndrome (BBS) is a heterogeneous genetic disorder that comprises numerous features, including renal cystic disease. Twelve BBS genes have been identified (BBS1–12). Although the exact functions of the BBS proteins are unknown, evidence suggests that they are involved in cilia assembly, maintenance and/or function. Renal primary cilia dysfunction can lead to cystic kidney disease. To test whether lacking Bbs4 affects cilia assembly and structure, we analyzed primary cilia in Bbs4-null (Bbs4–/–) mice. Methods: Renal tubule cultures from wild-type (Bbs4+/+) and Bbs4–/– mice were examined by immunocytochemistry and scanning and transmission electron microscopy. Results: Our culture conditions generated ciliated epithelial cells that were mostly of collecting duct origin. The microtubule ultrastructure of cilia and basal bodies did not appear disrupted in Bbs4–/– cells. In control cells, cilia length was maximal at 7 days in culture. In cells cultured from Bbs4–/– mice, cilia were shorter initially, but surpassed the length of control cilia by 10 days. Renal primary cilia were also longer in Bbs4–/– kidneys. Conclusions: Lacking Bbs4 does not lead to aberrant cilia or basal body structure. However, the dynamics of cilia assembly is altered in Bbs4–/– cells, suggesting a role for Bbs4 in the regulation of ciliary assembly.
In vivo Assessment of Ectoin: A Randomized, Vehicle-Controlled Clinical Trial
Authors: Heinrich U. , Garbe B. , Tronnier H.
Published: May 2007

The aim of the study was to assess an Ectoin formulation with regard to the antiageing properties. The study was designed as a monocentric, randomized, double-blind application test, in order to ensure the compatibility and the efficacy of Ectoin in comparison to a vehicle emulsion. A total of 104 voluntary healthy female test subjects were included in the study. Moisturizing properties as well as other parameters of skin ageing, like skin surface structure and skin elasticity, were determined for treatment A (vehicle) and treatment B (with 2% Ectoin) versus an untreated control. Statistical evaluations according to the Wilcoxon rank-sum test indicate a general preference for the Ectoin treatment by the test subjects in both the application and the efficacy tests. None of the participating test subjects had any side effects throughout the study. In terms of antiageing properties, previous in vitro studies could be confirmed by this clinical trial, clarifying that the natural cell protection concept of Ectoin is transferable to skin care with manifold benefits.
T Cells Survey the Stability of the Self: A Testable Hypothesis on the Homeostatic Role of TCR-MHC Interactions
Authors: Bakács Tibor , Mehrishi Jitendra N. , Szabados Tamás , Varga László , Szabó Miklós , Tusnády Gábor
Published: June 2007

In the lifetime of an individual, every single gene will have undergone mutation on about 1010 separate occasions. Nevertheless, cancer occurs mainly with advancing age. Here, we hypothesize that the evolutionary pressure driving the creation of the T cell receptor (TCR) repertoire was primarily the homeostatic surveillance of the genome. The subtly variable T cells may in fact constitute an evolutionary link between the invariable innate and hypervariable B cell systems. The new model is based on the homeostatic role of T cells, suggesting that molecular complementarity between the positively selected TCR and the self peptide-presenting major histocompatibility complex molecules establishes and regulates homeostasis, strictly limiting variations of its components. Notwithstanding, the ‘homeostatic role of T cells’ model offers a more realistic explanation as to how a naïve clonal immune system can cope with the much faster replicating pathogens, despite a limited repertoire that is capable of facing only a small fraction of the vast antigenic universe at a time.
Inflammatory Fibroid Polyp or Vanek’s Tumour
Authors: Paikos D. , Moschos J. , Tzilves D. , Koulaouzidis A. , Kouklakis G. , Patakiouta F. , Kontodimou K. , Tarpagos A. , Katsos I.
Published: June 2007

We report a case of a 65-year-old woman who presented with recurrent episodes of severe, postprandial abdominal pain followed by projectile vomiting. Gastroscopy revealed a large polyp in the prepyloric region. During peristalsis, the polyp was repeatedly ‘passing’ through the pylorus into the duodenal bulb, hence obstructing the lumen. The polyp was eventually removed in a piecemeal fashion. Histopathologic examination revealed an inflammatory fibroid polyp (known also as Vanek’s tumour). A brief review on inflammatory fibroid polyps follows.
The Prevalence of Resistant Bacterial Colonization in Chronic Hemodialysis Patients
Authors: Hadley Alexander C. , Karchmer Tobi B. , Russell Gregory B. , McBride Debra G. , Freedman Barry I.
Published: June 2007

Backgound: Hospitalized dialysis patients are at increased risk for colonization and infection with resistant bacterial strains. Methods: We performed a cross-sectional analysis of the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) colonization in 198 hemodialysis outpatients, 75 of whom had longitudinal screening data from prior hospitalization. Nasal specimens for MRSA, perirectal specimens for VRE, and permanent catheter exit site specimens were collected. Results: MRSA colonization was present in 5.6% and VRE colonization in 3.14%. Univariate analyses revealed that prior exposure (defined as infection/colonization) with MRSA, hospitalization, and low serum albumin were associated with MRSA colonization. VRE colonization was associated with hospitalization, prior VRE or MRSA exposure, low serum albumin, and low ferritin. Multivariate analyses revealed MRSA colonization was predicted by prior MRSA exposure and VRE colonization was predicted by prior VRE exposure and number of hospitalizations. Among the 75 participants with longitudinal screening data, MRSA colonization was associated with prior MRSA history, and VRE colonization was associated with prior MRSA or VRE. Conclusions: Generally low rates of MRSA and VRE colonization were observed in hemodialysis outpatients. Prior hospital screening was predictive of future outpatient colonization and may be useful in risk assessment.
Effect of an Increase in Brain Serotonin on the Osmoregulatory Response to a Hypo- or Hyperosmotic Load in Wistar and Vasopressin-Deficient Brattleboro Rats
Authors: Ivanova L. , Kochkaeva L. , Melidi N.
Published: June 2007

Serotonin and its receptor agonists stimulate the release of arginine vasopressin (AVP) into peripheral blood under intraventricular injection. To test the hypothesis that brain serotonin can modulate the development of natural osmoregulatory responses, the effect of an increase in endogenous brain serotonin on the response to an intragastric hypo- or hyperosmotic loading was studied in Wistar and AVP-deficient Brattleboro rats. 5-Hydroxytryptophan (5-HTP), the rate-limiting serotonin biosynthesis precursor known to increase the brain level of serotonin, was injected intraperitoneally (5 mg/100 g body weight). The renal functional parameters (glomerular filtration rate [GFR], free water reabsorption, and urine flow rate) were monitored during the 4 h after intragastric infusion of water or a 2% NaCl solution (5% of body weight). Plasma AVP was measured by radioimmunoassay. In Wistar rats, intraperitoneal injection of 5-HTP at the same time as water loading prevented the development of the renal diuretic response: there was no increase in urine flow rate and GFR, and free water reabsorption remained at the high level. In AVP-deficient Brattleboro rats, unlike Wistar rats, 5-HTP treatment was without effect on the renal function parameters. In Wistar rats, injection of 5-HTP at the peak of water diuresis produced an abrogation of the diuretic response to water loading due to the increase in free water reabsorption. Plasma AVP increased from 1.2 ± 0.4 to 4.2 ± 1.6 pg/ml (n = 8 in each group, p < 0.01). Hyperosmotic treatment of Wistar rats with a 2% NaCl solution stimulated AVP secretion compared to baseline (from 3.2 ± 0.1, n = 7 to 5.6 ± 0.9, n = 7, p < 0.01), and the saluretic response developed on the background of high free water reabsorption. When injected concomitantly with NaCl solution, 5-HTP revealed no additive effect on plasma AVP and on free water reabsorption. We conclude that the 5-HTP-caused increase in brain serotonin contributed significantly to the dynamics of changes in the osmoregulatory response to the hypo-osmotic challenge due to stimulation of AVP secretion. 5-HTP had no additive effect on the osmoregulatory response to hyperosmotic loading. Peripherally injected 5-HTP had no effect on the renal function, being absent in AVP-deficient Brattleboro rats.
Titration Efficacy of Two Auto-Adjustable Continuous Positive Airway Pressure Devices Using Different Flow Limitation-Based Algorithms
Authors: Hertegonne Katrien B. , Rombaut Bart , Houtmeyers Philippe , Van Maele Georges , Pevernagie Dirk A.
Published: June 2007

Background: Auto-adjustable continuous positive airway pressure devices are widely used in titration procedures to determine therapeutic pressure levels in obstructive sleep apnea patients. However, differences in operational characteristics may influence the effect on the apnea-hypopnea index (AHI). Objectives: We compared the titration performance of two devices based on detection of inspiratory flow limitation, i.e. the Respironics REMstar Auto™ (RR) and the ResMed Spirit™ (RS). Methods: Fifty obstructive sleep apnea patients were recruited for a double-blind randomized crossover trial. Both devices were employed overnight by means of split-night polysomnography. The primary outcome was the AHI. Secondary outcome measures were the snoring index, pressure profiles and subjective appraisal of sleep quality assessed the morning after the sleep study. The Wilcoxon signed rank test for matched pairs was applied to assess differences between treatment conditions. Results: No significant differences were found in sleep parameters, subjective sleep quality and snoring index. The use of the RR was associated with a significantly lower AHI in comparison with the RS [mean (SD) 6.9 (11.6)/h vs. 9.4 (9.2)/h, p = 0.004]. This result was obtained at significantly lower pressure levels [P95 9.2 (2.3) cm H2O vs. 10.2 (1.5) cm H2O, p = 0.001]. Conclusion: While the RR provided a lower AHI than the RS at lower pressure levels, it could not be assessed whether this difference was relevant for clinical outcomes. However, this face-to-face comparison of Auto-adjustable continuous positive airway pressure devices seems useful for the assessment of titration efficacy.
Mouse Models for Atherosclerosis and Pharmaceutical Modifiers
Authors: Zadelaar Susanne , Kleemann Robert , Verschuren Lars , de Vries-Van der Weij Jitske , van der Hoorn José , Princen Hans M. , Kooistra Teake
Published: June 2007

Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically and will develop lesions comparable to those in humans. The mouse is the most useful, economic, and valid model for studying atherosclerosis and exploring effective therapeutic approaches. Among the most widely used mouse models for atherosclerosis are apolipoprotein E–deficient (ApoE
−/−
) and LDL receptor–deficient (LDLr
−/−
) mice. An up-and-coming model is the ApoE*3Leiden (E3L) transgenic mouse. Here, we review studies that have explored how and to what extent these mice respond to compounds directed at treatment of the risk factors hypercholesterolemia, hypertriglyceridemia, hypertension, and inflammation. An important outcome of this survey is that the different models used may differ markedly from one another in their response to a specific experimental manipulation. The choice of a model is therefore of critical importance and should take into account the risk factor to be studied and the working spectrum of the compounds tested.
Oxidized Phospholipids, Lipoprotein(a), Lipoprotein-Associated Phospholipase A2 Activity, and 10-Year Cardiovascular Outcomes
Authors: Kiechl Stefan , Willeit Johann , Mayr Manuel , Viehweider Brigitte , Oberhollenzer Martin , Kronenberg Florian , Wiedermann Christian J. , Oberthaler Sabine , Xu Qingbo , Witztum Joseph L. , Tsimikas Sotirios
Published: June 2007

Background—

Oxidized phospholipids (OxPL) circulate on apolipoprotein B-100 particles (OxPL/apoB), and primarily on Lp(a) lipoprotein (a) [Lp(a)]. The relationship of OxPL/apoB levels to future cardiovascular events is not known.

Methods and Results—

The Bruneck study is a prospective population-based survey of 40- to 79-year-old men and women recruited in 1990. Plasma levels of OxPL/apoB and lipoprotein (a) [Lp(a)] were measured in 765 subjects in 1995 and incident cardiovascular disease (CVD), defined as cardiovascular death, myocardial infarction, stroke, and transient ischemic attack, was assessed from 1995 to 2005. During the follow-up period, 82 subjects developed CVD. In multivariable analysis, which included traditional risk factors, high sensitivity C-reactive protein (hsCRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, subjects in the highest tertile of OxPL/apoB had a significantly higher risk of cardiovascular events than those in the lowest tertile (hazard ratio[95% CI] 2.4[1.3 to 4.3],
P
=0.004). The strength of the association between OxPL/apoB and CVD risk was amplified with increasing Lp-PLA2 activity (
P
=0.018 for interaction). Moreover, OxPL/apoB levels predicted future cardiovascular events beyond the information provided by the Framingham Risk Score (FRS). The effects of OxPL/apoB and Lp(a) were not independent of each other but they were independent of all other measured risk factors.

Conclusions—

This study demonstrates that OxPL/apoB levels predict 10-year CVD event rates independently of traditional risk factors, hsCRP, and FRS. Increasing Lp-PLA2 activity further amplifies the risk of CVD mediated by OxPL/apoB.
Stage-Specific Role of Endogenous Smad2 Activation in Cardiomyogenesis of Embryonic Stem Cells
Authors: Kitamura Ryoji , Takahashi Tomosaburo , Nakajima Norio , Isodono Koji , Asada Satoshi , Ueno Hikaru , Ueyama Tomomi , Yoshikawa Toshikazu , Matsubara Hiroaki , Oh Hidemasa
Published: June 2007

The role of Smads and their specific ligands during cardiomyogenesis in ES cells was examined. Smad2 was activated bimodally in the early and late phases of cardiac differentiation, whereas Smad1 was activated after the middle phase. Nodal and Cripto were expressed in the early stage and then downregulated, whereas transforming growth factor-β and activin were expressed only in the late phase. Suppression of early Smad2 activation by SB-431542 produced complete inhibition of endodermal and mesodermal induction but augmented neuroectodermal differentiation, followed by poor cardiomyogenesis, whereas inhibition during the late phase alone promoted cardiomyogenesis. Inhibitory effect of Smad2 on cardiomyogenesis in the late phase was mainly mediated by transforming growth factor-β, and inhibition of transforming growth factor-β–mediated Smad2 activation resulted in a greater replicative potential in differentiated cardiac myocytes and enhanced differentiation of nonmyocytes into cardiac myocytes. Thus, endogenous Smad2 activation is indispensable for endodermal and mesodermal induction in the early phase. In the late phase, endogenous transforming growth factor-β negatively regulates cardiomyogenesis through Smad2 activation by modulating proliferation and differentiation of cardiac myocytes.
Meta-Analysis Comparing the Effectiveness and Adverse Outcomes of Antifibrinolytic Agents in Cardiac Surgery
Authors: Brown Jeremiah R. , Birkmeyer Nancy J.O. , O’Connor Gerald T.
Published: May 2007

Background—

Since the 1980s, antifibrinolytic therapies have assisted surgical teams in reducing the amount of blood loss. To date, however, serious questions remain regarding the safety and effectiveness of these agents.

Methods and Results—

We conducted a meta-analysis to compare aprotinin, ε-aminocaproic acid, and tranexamic acid with placebo and head to head on 8 clinical outcomes from 138 trials. Published randomized controlled trial data were collected from OVID/PubMed. Outcomes included total blood loss, transfusion of packed red blood cells, reexploration, mortality, stroke, myocardial infarction, dialysis-dependent renal failure, and renal dysfunction (0.5-mg/dL increase in creatinine from baseline). All agents were effective in significantly reducing blood loss by 226 to 348 mL and the proportion of patients transfused with packed red blood cells over placebo. Only high-dose aprotinin reduced the rate of reexploration (relative risk, 0.49; 95% CI, 0.33 to 0.73). There were no significant risks or benefits for any agent for mortality, stroke, myocardial infarction, or renal failure. However, high-dose aprotinin significantly increased the risk of renal dysfunction (relative risk, 1.47; 95% CI, 1.12 to 1.94), 12.9% versus 8.4%. Compared head to head, high-dose aprotinin demonstrated significant reduction in total blood loss over ε-aminocaproic acid (−184 mL; 95% CI, −256 to −112) and tranexamic acid (−195 mL; 95% CI, −286 to −105). There were no significant differences among any agent when compared head to head on other outcomes.

Conclusions—

All antifibrinolytic agents were effective in reducing blood loss and transfusion. There were no significant risks or benefits for mortality, stroke, myocardial infarction, or renal failure. However, high-dose aprotinin was associated with a statistically significant increased risk of renal dysfunction.
Debunking 7 Myths That Hamper the Realization of Randomized Controlled Trials on Intra-Arterial Thrombolysis for Acute Ischemic Stroke
Authors: Ciccone Alfonso , Valvassori Luca , Gasparotti Roberto , Scomazzoni Francesco , Ballabio Elena , Sterzi Roberto
Published: June 2007

Background and Purpose—

Although intravenous (IV) thrombolysis is the standard treatment for patients with ischemic stroke occurring within 3 hours from symptom onset, a few interventional neuroradiologists have been treating this category of patients by an intra-arterial (IA) route for >25 years. However, evidence is still required to support the clinical feeling that IA treatment, which needs longer time and greater complexity, leads to a better outcome. Therefore, the objective of the present review was to analyze beliefs and myths underlying the selection of patients for IA thrombolysis.

Methods and Results—

We identified and debunked the following myths on IA thrombolysis: (1) IA thrombolysis works better than IV because it achieves higher recanalization rates; (2) IA thrombolysis works better than IV after the 3-hour window; (3) IA thrombolysis works better than IV in vertebrobasilar stroke; (4) carotid duplex, transcranial doppler, CT angiography, or MRA should be used to screen for major vessel occlusion treatable with IA thrombolysis; (5) to be treated with IA thrombolysis, patients should be selected with diffusion/perfusion MRI; (6) IA thrombolysis should be used as a “rescue” therapy for IV thrombolysis; and (7) the efficacy of IA thrombolysis depends on the thrombolytic agent or the device used.

Conclusion—

Evidence on acute stroke management with IA thrombolysis is scant. Therefore, neither clinicians nor patients have enough information to make truly informed decisions about the most appropriate treatment. Only randomized controlled trials can clear uncertainties about the possible superiority of IA over IV thrombolysis. Regretfully, case series on IA treatment have limited the organization of such trials and have only favored the spread of myths.
Beyond Conventional Stroke Guidelines
Authors: Norrving Bo , Wester Per , Sunnerhagen Katharina Stibrant , Terént Andreas , Sohlberg Anna , Berggren Fredrik , Wester Per-Olov , Asplund Kjell ,   National Board of Health and Welfare, Stockholm, Sweden
Published: June 2007

Background and Purpose—

Priorities in the care of stroke patients are often intuitive. An open and translucent priority-setting procedure would benefit patients, professionals, and decision-makers. Prioritization is an innovative part of the new Swedish national stroke guidelines.

Methods—

Working groups identified diagnostic procedures, interventions and therapies in stroke care, assessed each one according to severity (needs), effect of action, level of scientific evidence and cost-effectiveness. The items were then ranked into priority groups from 1 (highest) to 10 (lowest). Procedures lacking evidence for routine clinical use were also identified (and entered a do-not-do list), as well as procedures in research and development. Resource allocations resulting from the priority-setting process were identified.

Results—

Of 102 core procedures identified, 50 were assigned to high-priority groups (1–3), 29 to moderate priority groups (4–7) and 23 to low priority groups (8–10). Almost a quarter were graded 8 to 10, indicating that they may not necessarily be applied if resources are scarce. Twenty-eight procedures were assigned to the do-not-do list and 16 to the research and development list.

Conclusions—

In stroke services, it is possible to identify not only diagnostic procedures and interventions with high priority, but also a considerable number of items used today that have low priority or should not be used at all. Strict adherence to the guidelines would result in a substantial reallocation of resources from low-priority to high-priority areas.
Can Mass Media Influence Emergency Department Visits for Stroke?
Authors: Hodgson Corinne , Lindsay Patrice , Rubini Frank
Published: June 2007

Background and Purpose—

Television advertising has been associated with significant increases in the knowledge of the warning signs of stroke among Ontarians aged 45 and older. However, to date there has been little data on the relationship between knowledge of the warning signs of stroke and behavior.

Methods—

Data on presentation to regional and enhanced district stroke center emergency departments were obtained from the Registry of the Canadian Stroke Network for a 31-month period between mid 2003 and the beginning of 2006. Public opinion polling was used to track knowledge of the warning signs of stroke among Ontarians aged 45 and older.

Results—

The public’s awareness of the warning signs of stroke increased during 2003 to 2005, decreasing in 2006 after a 5-month advertising blackout. There was a significant increase in the mean number of emergency department visits for stroke over the study period. A campaign effect independent of year was observed for total presentations, presentation within 5 hours of last seen normal, and presentation within 2.5 hours. For TIAs there was a strong campaign effect but no change in the number of presentations by year.

Conclusions—

Continuous advertising may be required to build and sustain public awareness of the warning signs of stroke. There are many factors that may influence presentation for stroke and awareness of the warning signs may be only one. However, results of this study suggest there may be an important correlation between the advertising and emergency department presentations with stroke, particularly for TIAs.
Export Orientation and Technological Intensities in Auto Parts Firms in East and Southeast Asia: Does Ownership Matter?
Authors: Rasiah Rajah
Published: June 2007

This paper examines the statistical relationships involving export intensity, embedding environment, and three types of technological intensity (human resource intensity, process technology intensity, and research and development intensity). The embedding environment measures the degree of infrastructure support for innovation. The sample consists of auto parts firms in China, Indonesia, Korea, Malaysia, The Philippines, Taiwan, and Thailand. For the local sample, export intensity and the embedding environment are positively significant for the three technological intensities. For the foreign sample, export intensity and embedding environment are positively significant only for the research and development intensity. The strong positive relationship between foreign ownership and export intensity shows that foreign firms enjoy greater access in export markets.
Reducing the Number of Fitness Evaluations in Graph Genetic Programming Using a Canonical Graph Indexed Database
Authors: Niehaus Jens , Igel Christian , Banzhaf Wolfgang
Published: May 2007

In this paper we describe the genetic programming system GGP operating on graphs and introduce the notion of graph isomorphisms to explain how they influence the dynamics of GP. It is shown empirically how fitness databases can improve the performance of GP and how mapping graphs to a canonical form can increase these improvements by saving considerable evaluation time.
The Shape and Dimensions of Plain Knitted Fabric: A Fabric Mechanical Model
Authors: Ka Fai Choi  , Tin Yee Lo
Published: May 2007

A new knitted fabric mechanical model was developed using the energy model of knitted loop which was described in a previous paper [ Textile Res. J. 73(8), 739—748 (2003)]. It was assumed that the shape of the yarn after knitting was curved and had non-linear mechanical properties. In developing the model, the effect of residual torque on yarn was considered. The loops were allowed to rotate such that the geometry of each loop was no longer symmetrical. The new fabric model allowed predictions of both fabric dimensions and wale spirality. Experimental results showed that there was excellent agreement between the calculated and measured values for both course spacing and spirality. For the first time, wale spirality was predicted within a theoretical framework.
Filtering and withdrawing: strategies for coping with information overload in everyday contexts
Authors: Savolainen Reijo
Published: June 2007

The study investigates the ways in which people experience information overload in the context of monitoring everyday events through media such as newspapers and the internet. The findings are based on interviews with 20 environmental activists in Finland in 2005. The perceptions of the seriousness of problems caused by information overload varied among the participants. On the one hand, information overload was experienced as a real problem particularly in the networked information environments. On the other hand, information overload was perceived as an imagined problem with some mythical features. Two major strategies for coping with information overload were identified. The filtering strategy is based on the determined weeding out of material deemed useless. This strategy is favoured in networked information environments. The withdrawal strategy is more affectively oriented, emphasizing the need to protect oneself from excessive information supply by keeping the number of information sources to a minimum.
The folksonomy tag cloud: when is it useful?
Authors: Sinclair James , Cardew-Hall Michael
Published: June 2007

The weighted list, known popularly as a `tag cloud', has appeared on many popular folksonomy-based web-sites. Flickr, Delicious, Technorati and many others have all featured a tag cloud at some point in their history. However, it is unclear whether the tag cloud is actually useful as an aid to finding information. We conducted an experiment, giving participants the option of using a tag cloud or a traditional search interface to answer various questions. We found that where the information-seeking task required specific information, participants preferred the search interface. Conversely, where the information-seeking task was more general, participants preferred the tag cloud. While the tag cloud is not without value, it is not sufficient as the sole means of navigation for a folksonomy-based dataset.
Moving beyond tacit and explicit distinctions: a realist theory of organizational knowledge
Authors: Jashapara Ashok
Published: June 2007

This paper challenges the popular notions of tacit and explicit organizational knowledge and argues that its philosophical underpinnings derived from Gilbert Ryle are problematic due to their logical behaviourist perspective. The paper articulates the philosophical problem as the neglect of any role for the mind in organizational activity and the representation of mental activity as purely a set of behaviours. An alternative realist philosophy is advanced taking into account the potential of adopting a number of competing philosophical perspectives. The paper forwards a realist theory of organizational knowledge that moves beyond the surface behaviours of tacit and explicit knowledge and argues that collective consciousness and organizational memory play primary and deeper roles as knowledge processes and structures. Consciousness is not a Hegelian world spirit but rather a real process embedded in people's brains and mental activity. Further, the paper argues that organizational routines provide the contingent condition or `spark' to activate organizational knowledge processes. The implications of this model are explored in relation to the measurement of intellectual capital. The theory developed in this paper represents the first attempt to provide a coherent philosophically grounded framework of organizational knowledge that moves organizational theory beyond neat conversion processes of tacit and explicit knowledge.
Gender Patterns in Provider Role Attitudes and Behavior
Authors: Loscocco Karyn , Spitze Glenna
Published: June 2007

Although much has been written on rapidly changing work and family roles, relatively little is known about the provider side of the work—family nexus. Using data from a study of gender, work, and family among the self-employed, we examine abstract and specific attitudes as well as behavior relating to the provider role. Results show gender differences and similarities in the meaning and influence of the provider role. Women exhibit more egalitarian attitudes even in this realm associated with men, yet similar proportions of women and men are unable to realize their preferences for how much providing to do. Incongruence in providing attitudes and behavior has more consequence for men's than for women's psychological well-being. Although there appears to be less of a stall in the provider side of the work—family system than in unpaid family work, the results suggest the continued importance of the man as good provider.
Perceptions of college-level music performance majors teaching applied music lessons to young students
Authors: Fredrickson William E.
Published: June 2007

The present study was designed to examine the reflections of college music performance majors ( N = 12) who were teaching private music lessons. Students were instructed to keep a journal during one private lesson of their choice per week. Results indicated initial expectations of lessons that were consistently lower than lesson evaluations after the fact, teacher concerns about student motivation and practice, and a relatively low connection between teacher perceptions of the best and worst aspects of their teaching with the best and worst aspects of student learning. Directions for future research include continued objective evaluation of cause-and-effect relationships between teaching and learning in one-on-one situations, evaluation of career goals and opportunities for college-level music performance majors, and pedagogical content and focus for musicians studying music teaching in higher education.
The use of gesture techniques in children's singing
Authors: Liao Mei-Ying , Davidson Jane W.
Published: June 2007

The purpose of this study was to begin to explore the link of gesture and voice when teaching children and to examine how the children used these gestures in singing. Semi-structured interviewing techniques and observation were used extensively to collect information from the respondents. Five children were asked to participate in this preliminary work individually. The results demonstrated that there was a link between children's singing voice and their use of gesture by observing the Dalcrozian mirror and follow games. The functions of gestures could be defined as being for focus, guidance, support, good intonation and sensation. In addition, some specific teaching techniques were required for achieving a more effective gesture and a more successful sound. Gesture techniques helped the children to improve their vocal techniques and correct their vocal faults. This study opened the field for the full study of gesture in aiding children's singing.
Entrepreneurial Social Capital Unplugged
Authors: Bowey James L. , Easton Geoff
Published: June 2007

First, we develop a macro level explanation for how changes in social capital occur. Second, we apply a dynamic approach to social capital by examining on a more micro level the activities which are involved with and contribute to the increase or decrease in social capital in, largely dyadic, relationships within entrepreneurial networks.Third, we propose a more robust notion of social capital.We found that five key relationship-driving forces were involved in developing social capital.The research findings suggested that entrepreneurs seem to have a strikingly similar modus operandi when it comes to creating and destroying their network social capital. Activities such as the reciprocal trading of favours, socializing, joint problem-solving, delivering to expectation and using transparent communications were crucial to both. Finally, we discovered that entrepreneurs managed their network relationships heuristically relying on social capital, particularly by leveraging the productive ambiguity of this crucial [net]work asset.
Ethnic Minority Businesses in Scotland and the Role of Social Capital
Authors: Deakins David , Ishaq Mohammed , Smallbone David , Whittam Geoff , Wyper Janette
Published: June 2007

This article reports findings from a scoping study, commissioned by the Scottish Executive, on ethnic minority businesses (EMBs) and their distinctive importance in Scotland. The study combines quantitative and qualitative analysis and builds upon previous research undertaken in the UK and Scotland to investigate the changing importance of known issues with EMBs for Scotland. The role and importance of social capital for EMBs in Scotland has not been explored in previous research, although because of strong informal networks, it has been feasible to assume that its role is beneficial. In this article, we examine the role of social capital and demonstrate that its role is more complex and diverse.
A Comparison of EQ-5D Index Scores Derived from the US and UK Population-Based Scoring Functions
Authors: Nan Luo  , Johnson Jeffrey A. , Shaw James W. , Coons Stephen Joel
Published: June 2007

The authors recently introduced a new preference-based scoring function for the EQ-5D (D1 model) based on time tradeoff valuations from the general adult US population. In this study, they compared the EQ-5D index scores derived from the US (D1) algorithm to the more familiar UK (N3) algorithm. They compared preference-based EQ-5D index scores for all possible EQ-5D health states and differences in EQ-5D index scores between pairs of EQ-5D health states predicted by the D1 and N3 models. The responsiveness of D1- and N3-predicted EQ-5D index scores was assessed using simulated transitions between EQ-5D health states. The mean (SD) EQ-5D index scores for all 243 health states predicted by the D1 and N3 models were 0.37 (0.23) and 0.14 (0.31), respectively. The mean (SD) absolute difference in EQ-5D index scores for all 29,403 pairs of health states was 0.25 (0.19) and 0.35 (0.27), according to the D1 and N3 models, respectively. The D1 and N3 models were consistent in predicting gains/losses for 27,592 (94%) transitions between EQ-5D health state pairs; Cohen effect size, calculated using these 27,592 consistent transitions, was 1.58 and 1.59 for the D1 and N3 models, respectively. Based on these simulation results, it appears that the D1 model would lead to smaller gains in quality-adjusted life years than the N3 model; however, their responsiveness appears to be similar. Empirical studies are needed to examine whether these 2 EQ-5D scoring functions would lead to different conclusions in cost-utility analyses.
A Graphical Decision-Theoretic Model for Neonatal Jaundice
Authors: Gómez Manuel , Bielza Concha , Fernández del Pozo Juan A. , Ríos-Insua Sixto
Published: June 2007

Background. Neonatal jaundice is treated daily at all hospitals. However, the routine, urgency, and case load of most doctors stop them from carefully analyzing all the factors that they would like to (and should) take into account. This article develops a complex decision support system for neonatal jaundice management. Methods. The problem is represented by means of an influence diagram, including admission and treatment decisions. The corresponding uncertainty model is built with the aid of both historical data and subjective judgments. Parents and doctors were interviewed to elicit a multiattribute utility function. The decision analysis cycle is completed with sensitivity analyses and explanations of the results. Results. The construction and use of this decision support system for jaundice management have induced a profound change in daily medical practice, avoiding aggressive treatments—there have been no exchange transfusions in the past 3 years—and reducing the lengths of stay at the hospital. More information is now taken into account to decide on treatments. Interestingly, after embarking on this modeling effort, physicians came to view jaundice as a much more difficult problem than they had initially thought. Comparisons between real cases and system proposals revealed that treatments by nonexpert doctors tend to be longer than what expert doctors would administer. Conclusion. The system is especially designed to help neonatologists in situations in which their lack of experience may lead to unnecessary treatments. Different points of view from several expert doctors and, more interestingly, from parents are taken into account. This knowledge gives a broader picture of the medical problem— incorporating new action criteria, new agents to intervene, more uncertainty variables—to get an insight into the suitability of each therapeutic decision for each patient situation. The benefits gained and the usefulness perceived by neonatologists are worth the increased and time-consuming effort of developing this complex system. Although specially designed for a specific hospital and for neonatal jaundice management, it can be easily adapted to other hospitals and problems.