tbuckley/cabot-search huggingface dataset:
Bleeding time prolongation with streptokinase and its reduction with 1-desamino-8-D-arginine vasopressin.
Authors: M T Johnstone, T Andrews, J A Ware, M A Rudd, D George, M Weinstein, J Loscalzo
Journal: Circulation (1990)

The mechanism by which treatment with thrombolytic agents causes bleeding is not known. Recently, frequency of bleeding events has been shown to correlate with bleeding time, particularly in individuals treated with aspirin. We examined the effects of streptokinase (20,000-60,000 IU/kg) on bleeding time in 40 rabbits pretreated with aspirin, a model for fibrinolytic therapy. We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 microgram/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo. Aspirin increased the bleeding time from a baseline mean +/- SEM value of 119 +/- 15 to 191 +/- 34 seconds in the control group and from 114 +/- 6 to 188 +/- 18 seconds in the experimental group. The addition of streptokinase increased the bleeding time to 592 +/- 119 seconds in the control group and 810 +/- 114 seconds in the experimental group (p = NS). Subsequent infusion of DDAVP decreased the bleeding time in the experimental group to 302 +/- 29 seconds (p less than 0.01 versus streptokinase) compared with 572 +/- 79 seconds (p = NS versus streptokinase) in the control animals given saline placebo. In a subset of rabbits receiving aspirin and streptokinase (40,000-60,000 IU/kg), samples were obtained for platelet aggregation (n = 16), von Willebrand factor antigen concentration (n = 17), and von Willebrand factor multimer distribution (n = 14). Maximal rates of ADP-induced platelet aggregation were not affected by DDAVP infusion, nor was the plasma concentration of von Willebrand factor antigen, quantified by an immunoradiometric assay, significantly affected by DDAVP infusion. Furthermore, the von Willebrand factor multimer ratio decreased with DDAVP administration. These findings indicate that aspirin and streptokinase combined result in a marked increase in bleeding time that can be reduced by DDAVP. This effect of DDAVP is not accompanied by an increase in platelet aggregation response, plasma von Willebrand factor antigen concentration, or von Willebrand factor multimer ratio.
Two-dose-level confirmatory study of the pharmacokinetics and tolerability of everolimus in Chinese patients with advanced solid tumors
Authors: BingHe Xu, YiLong Wu, Lin Shen, DingWei Ye, Annette Jappe, Azzeddine Cherfi, Hui Wang, RuiRong Yuan
Journal: Journal of Hematology & Oncology (2011)

Abstract Background This phase I, randomized, multicenter, open-label study investigated the pharmacokinetics, safety, and efficacy of the oral mammalian target of rapamycin inhibitor everolimus in Chinese patients with advanced solid tumors. Methods A total of 24 patients with advanced breast cancer (n = 6), gastric cancer (n = 6), non-small cell lung cancer (n = 6), or renal cell carcinoma (n = 6) who were refractory to/unsuitable for standard therapy were randomized 1:1 to oral everolimus 5 or 10 mg/day. Primary end points were pharmacokinetic parameters and safety and tolerability. Pharmacokinetic 24-h profiles were measured on day 15; trough level was measured on days 2, 8, 15, 16, and 22. Tolerability was assessed continuously. This final analysis was performed after all patients had received 6 months of study drug or had discontinued. Results Everolimus was absorbed rapidly; median T max was 3 h (range, 1-4) and 2 h (range, 0.9-6) in the 5 and 10 mg/day groups, respectively. Pharmacokinetic parameters increased dose proportionally from the 5 and 10 mg/day doses. Steady-state levels were achieved by day 8 or earlier. The most common adverse events suspected to be related to everolimus therapy were increased blood glucose (16.7% and 41.7%) and fatigue (16.7% and 33.3%) in the everolimus 5 and 10 mg/day dose cohorts, respectively. Best tumor response was stable disease in 10 (83%) and 6 (50%) patients in the 5 and 10 mg/day groups, respectively. Conclusions Everolimus 5 or 10 mg/day was well tolerated in Chinese patients with advanced solid tumors. The observed safety and pharmacokinetic profile of everolimus from this study were consistent with previous studies. Trial registration Chinese Health Authorities 2008L09346
Technology-Driven Triage of Abdominal Trauma: The Emerging Era of Nonoperative Management
Authors: D. Demetriades, G. Velmahos
Journal: Annual Review of Medicine (2003)

Selective nonoperative management of blunt or penetrating abdominal trauma is safe, has eliminated the complications associated with nontherapeutic laparotomies, and is cost-effective. Appropriately selected investigations, such as focused abdominal sonography for trauma, diagnostic peritoneal lavage, spiral computed tomography (CT) scan, diagnostic laparoscopy, or thoracoscopy and angiography, play a critical role in the triage of patients. Future technological advances, such as improvement of the ultrasonic hardware and software that provide automated interpretation and the availability of portable CT scan machines in the emergency room, may improve the speed and accuracy of the initial evaluation. Improvement of the optical system of minilaparoscopes may allow reliable bedside laparoscopy for suspected diaphragmatic injuries.
CRIF1 Is Essential for the Synthesis and Insertion of Oxidative Phosphorylation Polypeptides in the Mammalian Mitochondrial Membrane
Authors: Soung Jung Kim, Min-chul Kwon, Min Jeong Ryu, Hyo Kyun Chung, Surendar Tadi, Yong Kyung Kim, Jin Man Kim, Sang Hee Lee, Ji Hoon Park, Gi Ryang Kweon, Seung-Wook Ryu, Young Suk Jo, Chul-Ho Lee, Hideyuki Hatakeyama, Yu-ichi Goto, Yong-Hyeon Yim, Jongkyeong Chung, Young-Yun Kong, Minho Shong
Journal: Cell Metabolism (2012)
709 A multicentric prospective assessement of non-alcoholic fatty liver disease in french patients with chronic unexplained hypertransaminasemia
Authors: V. Ratziu, J.F. Cadranel, B. Le Bail, X. Causse, D. Capron, C. Renoue, C. Pilette, V. Oules, E. Gelsi, E. Oberti, N. Le Provost, V. de Ledinghen
Journal: Journal of Hepatology (2006)
Favourable social functioning and health related quality of life of patients with JIA in early adulthood
Authors: M Arkela-Kautiainen
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To evaluate the social functioning and health related quality of life (HRQoL) in patients with juvenile idiopathic arthritis (JIA) in early adulthood. <b>Methods:</b> The patient files of the Rheumatism Foundation Hospital were screened to identify patients born in 1976–1980 diagnosed as having JIA. HRQoL was measured by the RAND 36-item health survey 1.0; spousal relationships and educational and employment status were assessed by questionnaire. The patients were invited to a follow up study. Age and sex matched controls from the community were identified in the Finnish population registry. <b>Results:</b> Of 187 patients identified, 123 participated. Spousal relationships, educational level, and employment status were similar to controls. HRQoL in JIA patients was similar to controls except on the physical functioning scale. At follow up 35% of patients were in remission. Patients with active disease had poorer HRQoL in the physical component than those in remission or controls. The extended oligoarthritis group had the lowest physical and mental score in HRQoL compared with the other JIA subgroups. The patient's own evaluation was the explanatory factor in both the physical and mental component of HRQoL. <b>Conclusion:</b> Social functioning and HRQoL were similar in JIA patients and age, sex, and municipality matched controls. However, patients with extended oligoarthritis attained significantly lower scores in the physical and mental component of HRQoL than oligo- or polyarthritis patients. Special attention in everyday care should be paid to those patients who have active disease or the extended oligoarthritis type of disease.
Predictors of Referral for Psychosocial Services: Recommendations From the Institute of Medicine Report—Cancer Care for the Whole Patient
Authors: Carol L. Alter
Journal: Journal of Clinical Oncology (2008)

al 1 compares referral patterns of patients with late-stage colorectal and lung cancer who were enrolled onto a study that assessed psychosocial functioning in patients with late-stage disease. The authors conducted a retrospective analysis to determine what patient-based characteristics predict referral for psychosocial evaluation and services. The study results indicated that younger age, being unmarried, and presence of depressive symptoms significantly predicted referral for additional services. Interestingly though, they found that fewer than 50% of patients who screened positive for depression were actually referred for psychosocial services. The study thus highlights the importance of psychosocial services for patients with cancer, which was recently addressed in the Institute of Medicine (IOM) report, Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs. 2
RISK FACTORS FOR OVERUSE SHOULDER INJURIES AMONG MALE PROFESSIONAL HANDBALL PLAYERS
Authors: B Clarsen, R Bahr, S Andersson, RM Kristensen, G Myklebust
Journal: British Journal of Sports Medicine (2014)

Background Overuse shoulder injuries are common among professional male handball players. However, little is known about risk factors for the development of injury. Objective To determine whether rotator cuff strength, glenohumeral joint range of motion and scapular stability are associated with the presence of overuse shoulder problems among elite male handball players. Design Prospective cohort study. Setting The Norwegian professional handball league for men (Postenliga). Participants A total of 206 professional players were tested prior to the 2011–12 season and followed prospectively over the course of the season (30 weeks). During this time, shoulder problems were registered bi-weekly using the Oslo Sports Trauma Research Center Overuse Injury Questionnaire. Sufficient data was collected from 162 players to be able to be included in risk-factor analyses. Risk factor assessment Risk factor measures included: (1) Glenohumeral internal and external rotation range using a digital inclinometer; (2) isometric internal rotation, external rotation and abduction strength using a hand-held dynamometer, and (3) assessment of scapular control, using a validated subjective protocol. Main outcome measurements A cumulative severity score was calculated for each player based on their questionnaire responses. The score reflects the degree to which they experienced shoulder pain throughout the season, as well as reductions in handball participation and performance due to shoulder problems. Results The average prevalence of shoulder problems throughout the season was 28% (95% CI: 25–31%). A significant associations was found between obvious scapular dyskinesis and shoulder problems (OR 11.6, 95% CI 2.0–68.4, P&lt;.05). Players with shoulder problems also had reduced Glenohumeral total rotational motion (mean difference 9°, P&lt;.05). No significant associations were identified between isometric strength and shoulder problems. Conclusions The prevalence of overuse shoulder problems is high among male professional handball players. This study provides important information which may help to guide the development of prevention programs.
The Effects of Neoadjuvant Anastrozole and Tamoxifen on Circulating Vascular Endothelial Growth Factor and Soluble Vascular Endothelial Growth Factor Receptor 1 in Breast Cancer
Authors: Susana Banerjee, Sunil Pancholi, Roger A'Hern, Zara Ghazoui, Ian E. Smith, Mitch Dowsett, Lesley-Ann Martin
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Vascular endothelial growth factor (VEGF) is a key angiogenic factor mediating neovascularization. Soluble VEGF receptor 1 (sVEGFR-1) is an intrinsic negative counterpart of VEGF signaling and the ratio of sVEGFR-1 to VEGF has been shown to be a prognostic factor. Estrogen-bound estrogen receptor enhances VEGF expression, providing a common link between these signaling pathways that may be targeted by endocrine therapy. We investigated the effects of anastrozole and tamoxifen over time on serum VEGF and sVEGFR-1. Experimental Design: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) trial compared the preoperative use of anastrozole with tamoxifen in postmenopausal women with estrogen receptor–positive primary operable breast cancer over 12 weeks. Circulating VEGF and sVEGFR-1 were measured by ELISA in 106 patients treated with anastrozole or tamoxifen alone at baseline and after 2 and 12 weeks of treatment. Results: The increase in serum VEGF from baseline to 12 weeks was significantly different between anastrozole and tamoxifen (anastrozole versus tamoxifen, 6% versus 38%; P = 0.047). There was a significant increase in sVEGFR-1 levels after 12 weeks of anastrozole (P = 0.037). The sVEGFR-1/VEGF ratio significantly decreased in the tamoxifen arm (P = 0.013) and the change in sVEGFR-1/VEGF ratio from baseline to 12 weeks was significantly different between anastrozole and tamoxifen (anastrozole versus tamoxifen, 24% increase versus 34% decrease; P = 0.013). Conclusions: Treatment with anastrozole and tamoxifen resulted in differential effects on serum angiogenic markers. This may be related to the relative effectiveness of the treatments. These data provide further support for cross talk between estrogen receptor and VEGF.
Oxidative Stress and Diabetic Complications
Authors: Ferdinando Giacco, Michael Brownlee
Journal: Circulation Research (2010)

Oxidative stress plays a pivotal role in the development of diabetes complications, both microvascular and cardiovascular. The metabolic abnormalities of diabetes cause mitochondrial superoxide overproduction in endothelial cells of both large and small vessels, as well as in the myocardium. This increased superoxide production causes the activation of 5 major pathways involved in the pathogenesis of complications: polyol pathway flux, increased formation of AGEs (advanced glycation end products), increased expression of the receptor for AGEs and its activating ligands, activation of protein kinase C isoforms, and overactivity of the hexosamine pathway. It also directly inactivates 2 critical antiatherosclerotic enzymes, endothelial nitric oxide synthase and prostacyclin synthase. Through these pathways, increased intracellular reactive oxygen species (ROS) cause defective angiogenesis in response to ischemia, activate a number of proinflammatory pathways, and cause long-lasting epigenetic changes that drive persistent expression of proinflammatory genes after glycemia is normalized (“hyperglycemic memory”). Atherosclerosis and cardiomyopathy in type 2 diabetes are caused in part by pathway-selective insulin resistance, which increases mitochondrial ROS production from free fatty acids and by inactivation of antiatherosclerosis enzymes by ROS. Overexpression of superoxide dismutase in transgenic diabetic mice prevents diabetic retinopathy, nephropathy, and cardiomyopathy. The aim of this review is to highlight advances in understanding the role of metabolite-generated ROS in the development of diabetic complications.
Function-informed transcriptome analysis of Drosophila renal tubule.
Authors: Jing Wang, Laura Kean, Jingli Yang, Adrian K Allan, Shireen A Davies, Pawel Herzyk, Julian AT Dow
Journal: Genome biology (2004)

Abstract Background Comprehensive, tissue-specific, microarray analysis is a potent tool for the identification of tightly defined expression patterns that might be missed in whole-organism scans. We applied such an analysis to Drosophila melanogaster Malpighian (renal) tubule, a defined differentiated tissue. Results The transcriptome of the D. melanogaster Malpighian tubule is highly reproducible and significantly different from that obtained from whole-organism arrays. More than 200 genes are more than 10-fold enriched and over 1,000 are significantly enriched. Of the top 200 genes, only 18 have previously been named, and only 45% have even estimates of function. In addition, 30 transcription factors, not previously implicated in tubule development, are shown to be enriched in adult tubule, and their expression patterns respect precisely the domains and cell types previously identified by enhancer trapping. Of Drosophila genes with close human disease homologs, 50 are enriched threefold or more, and eight enriched 10-fold or more, in tubule. Intriguingly, several of these diseases have human renal phenotypes, implying close conservation of renal function across 400 million years of divergent evolution. Conclusions From those genes that are identifiable, a radically new view of the function of the tubule, emphasizing solute transport rather than fluid secretion, can be obtained. The results illustrate the phenotype gap: historically, the effort expended on a model organism has tended to concentrate on a relatively small set of processes, rather than on the spread of genes in the genome.
Metabolic basis of hyperapobetalipoproteinemia. Turnover of apolipoprotein B in low density lipoprotein and its precursors and subfractions compared with normal and familial hypercholesterolemia.
Authors: B Teng, A D Sniderman, A K Soutar, G R Thompson
Journal: Journal of Clinical Investigation (1986)

The turnover of apolipoprotein B (apo B) in very low density, intermediate density, and low density lipoproteins (VLDL, IDL, and LDL) and in the light and heavy fractions of LDL was determined in seven patients with hyperapobetalipoproteinemia (hyperapo B), six normolipidemic subjects, and five patients with heterozygous familial hypercholesterolemia (FH). After receiving an injection of 125I-VLDL, hyperapo B patients were found to have a higher rate of synthesis of VLDL-apo B than controls (40.1 vs. 21.5 mg/kg per d, P less than 0.05) but a reduced fractional catabolic rate (FCR) (0.230 vs. 0.366/h, P less than 0.01). After receiving an injection of 131I-LDL, hyperapo B patients had higher rates of LDL-apo B synthesis than controls (23.1 vs. 13.0 mg/kg per d, P less than 0.001), as did FH patients (22.7 mg/kg per d). The FCR of LDL was similar in hyperapo B patients and controls (0.386 vs. 0.366/d) but was markedly decreased in FH patients (0.192/d). Most subjects exhibited precursor-product relationships between VLDL and IDL, and all did between IDL and light LDL; an analogous relationship between light and heavy LDL was evident in most hyperapo B patients and controls but not in FH patients. Simultaneous injection of differentially labeled LDL fractions and deconvolution analysis showed increased light LDL synthesis with normal conversion into heavy LDL in hyperapo B, whereas in FH conversion of light LDL was reduced and there was independent synthesis of heavy LDL. These data show that the increased concentration of LDL-apo B in hyperapo B is solely due to increased LDL synthesis, which is secondary to increased VLDL synthesis; in contrast, in FH there is both an increase in synthesis of LDL (which is partly VLDL-independent) and reduced catabolism.
Serum zinc, bronchiectasis, and bronchial carcinoma
Authors: J. M. Beeley, C. S. Darke, G. Owen, R. D. Cooper
Journal: Thorax (1974)

<b>Beeley, J. M., Darke, C. S., Owen, G., and Cooper, R. D. (1974).</b><i>Thorax</i>, <b>29</b>, 21-25. <b>Serum zinc, bronchiectasis, and bronchial carcinoma.</b> Serum zinc levels were measured by atomic absorption spectrophotometry in 65 patients with proven bronchiectasis; the mean level was 93 μg/100 ml, while the levels in two groups of healthy control subjects were 88·6 and 92·7 μg/100 ml respectively. The range of individual values was similar in all groups and the differences between the mean serum zinc levels of the two groups of control subjects and the mean level of the group of patients with bronchiectasis were small and did not attain significance at the conventional 0·05 level. In contrast, the mean level in bronchial carcinoma patients (75·9 μg/100 ml) was significantly less than in each of the other groups of subjects. Zinc sulphate was administered for six weeks on a double-blind cross-over basis to patients with bronchiectasis and, although serum zinc levels rose, no detectable clinical improvement resulted. No definitive evidence of zinc deficiency in bronchiectasis has been established.
Sensitization of Mesothelioma Cells to Tumor Necrosis Factor–Related Apoptosis–Inducing Ligand–Induced Apoptosis by Heat Stress via the Inhibition of the 3-Phosphoinositide-Dependent Kinase 1/Akt Pathway
Authors: Melissa H. Pespeni, Maki Hodnett, Keith S. Abayasiriwardana, Jérémie Roux, Marybeth Howard, V. Courtney Broaddus, Jean-François Pittet
Journal: Cancer Research (2007)

Abstract Heat stress may enhance the effect of apoptosis-inducing agents in resistant tumor cells. One such agent is the tumor necrosis factor–related apoptosis–inducing ligand (TRAIL), which has attracted intense interest for its ability to induce apoptosis in tumors without affecting nonmalignant cells. We therefore tested whether heat stress potentiates TRAIL-induced apoptosis in mesothelioma cells, its cell type being resistant to TRAIL alone. We found that heat stress enhanced the apoptosis caused by TRAIL but not by chemotherapy. To explain this potentiation, we found that heat stress decreased Akt phosphorylation via the dissociation of heat shock protein 90 (Hsp90) from its client protein 3-phosphoinositide-dependent kinase 1 (PDK-1), a major Akt kinase. The role of Hsp90 and the Akt pathway was confirmed by showing that inhibitors of Hsp90 and the phosphatidyilinositol-3 kinase/Akt pathway reproduced the effect of heat stress on TRAIL-induced apoptosis and that the effect of inhibiting Hsp90 on TRAIL-induced apoptosis could be overcome by activating the Akt pathway with a constitutively active construct of the Akt kinase PDK-1. The effect of heat stress involved multiple steps of the apoptotic machinery. Heat stress potentiated the death receptor pathway, as shown by an increase in TRAIL-induced caspase 8 cleavage. Nonetheless, knockdown of Bid, the main intermediary molecule from the death receptor pathway to the mitochondria, inhibited the effect of heat stress, showing that mitochondrial amplification was required for potentiation by heat stress. In summary, these results support the novel concept that heat stress inhibits the Akt pathway by dissociating PDK-1 from its chaperone Hsp90, leading to potentiation of TRAIL-induced apoptosis in resistant malignant cells. [Cancer Res 2007;67(6):2865–71]
LATE-TERM SAFETY AND EFFICACY OUTCOMES FOLLOWING TREATMENT WITH ZOTAROLIMUS-ELUTING STENTS: 5-YEAR RESULTS OF THE POOLED ENDEAVOR TRIALS PROGRAM
Authors: David E. Kandzari, Martin B. Leon, William Wijns, Ian T. Meredith, Jean Fajadet, Donald E. Cutlip, Laura Mauri
Journal: Journal of the American College of Cardiology (2010)