bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interstitial Fluid Pressure as a Prognostic Factor in Cervical Cancer Following Radiation Therapy
Authors: Yeo Seung-Gu , Kim Jun-Sang , Cho Moon-June , Kim Ki-Hwan , Kim Jae-Sung 
Published: September 2009

AbstractPurpose: To investigate tumor interstitial fluid pressure as a prognostic factor for recurrence-free survival in patients with cervical cancer following radiation therapy.Experimental Design: Tumor interstitial fluid pressure was measured in 55 cervical cancer patients who received radiation therapy between August 1998 and September 2002. Interstitial fluid pressure measurements were made before radiation therapy (pre–radiation therapy interstitial fluid pressure) and after a median of 28.8 Gy in 16 fractions (range, 25.2-30.6 Gy in 14-17 fractions) of radiation therapy (mid–radiation therapy interstitial fluid pressure), using a modified wick-in-needle technique. Median follow-up was 74 months (range, 2-118 months). The Kaplan-Meier method with the log-rank test and Cox's proportional hazard model were used in univariate and multivariate analyses, respectively, of prognostic factors for recurrence-free survival.Results: Median pre–radiation therapy and mid–radiation therapy interstitial fluid pressure were 29.0 mm Hg (range, 4.0-93.9 mm Hg) and 20.0 mm Hg (range, −1.2 to 29.6 mm Hg), respectively (P = 0.001). Pre–radiation therapy interstitial fluid pressure was significantly higher in adenocarcinomas than squamous cell carcinomas (P = 0.028). Significant reduction of interstitial fluid pressure was noted only in patients with complete responses (P = 0.002), and mid–radiation therapy interstitial fluid pressure was significantly lower in patients with complete responses (P = 0.036). In the multivariate analysis including interstitial fluid pressures and clinical variables, pre–radiation therapy interstitial fluid pressure was an independent prognostic factor for local and distant recurrence-free survival (P = 0.001 and 0.027, respectively).Conclusions: Mid–radiation therapy interstitial fluid pressure measurement may be useful in predicting radiation therapy responses, and pre–radiation therapy interstitial fluid pressure was a significant prognostic factor for local and distant relapse-free survival in patients with cervical cancer after radiation therapy. (Clin Cancer Res 2009;15(19):6201–7)
A Phase I Study of Sunitinib plus Bevacizumab in Advanced Solid Tumors
Authors: Rini Brian I. , Garcia Jorge A. , Cooney Matthew M. , Elson Paul , Tyler Allison , Beatty Kristi , Bokar Joseph , Mekhail Tarek , Bukowski R.M. , Budd G. Thomas , Triozzi Pierre , Borden Ernest , Ivy Percy , Chen Helen X. , Dowlati Afshin , Dreicer Robert 
Published: September 2009

Abstract
Purpose: Bevacizumab is an antibody against vascular endothelial growth factor; sunitinib is an inhibitor of vascular endothelial growth factor and related receptors. The safety and maximum tolerated dose of sunitinib plus bevacizumab was assessed in this phase I trial.
Experimental Design: Patients with advanced solid tumors were treated on a 3+3 trial design. Patients received sunitinib daily (starting dose level, 25 mg) for 4 weeks on followed by 2 weeks off and bevacizumab (starting dose level, 5 mg/kg) on days 1, 15, and 29 of a 42-day cycle. Dose-limiting toxicities during the first 6-week cycle were used to determine the maximum tolerated dose.
Results: Thirty-eight patients were enrolled. Patients received a median of 3 cycles of treatment (range, 1-17+). There was one dose-limiting toxicity (grade 4 hypertension) at 37.5 mg sunitinib and 5 mg/kg bevacizumab. Grade 3 or greater toxicity was observed in 87% of patients including hypertension (47%), fatigue (24%), thrombocytopenia (18%), proteinuria (13%), and hand-foot syndrome (13%). Dose modifications and delays were common at higher dose levels. No clinical or laboratory evidence of microangiopathic hemolytic anemia was observed. Seven patients had a confirmed Response Evaluation Criteria in Solid Tumors–defined partial response (18%; 95% confidence interval, 8-34%). Nineteen of the 32 patients with a postbaseline scan (59%) had at least some reduction in overall tumor burden (median, 32%; range, 3-73%).
Conclusions: The combination of sunitinib and bevacizumab in patients with advanced solid tumors is feasible, albeit with toxicity at higher dose levels and requiring dose modification with continued therapy. Antitumor activity was observed across multiple solid tumors. (Clin Cancer Res 2009;15(19):6277–83)
Heptest-STAT, a new assay for monitoring of low-molecular-weight heparins, is not influenced by pregnancy-related changes of blood plasma
Authors: Zharkowa Ulyana , Elmas Elif , Ahmad-Nejad Parviz , Neumaier Michael , Borggrefe Martin , Dempfle Carl-Erik 
Published: September 2009

SummaryMonitoring of anti-factor Xa activity is often performed during treatment with low-molecular-weight heparins (LMWHs) in pregnancy because the anticoagulant effect may decrease as pregnancy progresses, but assays for anti-factor Xa activity are unavailable in many clinical institutions caring for pregnant women. Heptest-STAT is a new clotting assay for monitoring of LMWHs, which has been optimised for use in near-patient laboratory instrumentation. It has been suggested that monitoring of LMWHs requires the use of individual calibration curves for each LMWH.We compared the dose response of four conventional LMWHs and fondaparinux in normal plasma, and plasma from women in first, second and third trimester of pregnancy. Three concentrations of LMWHs, fondaparinux, or unfractionated heparin were added to pooled plasma samples from nonpregnant women (n=10), and pregnant women in first (n=10), second (n=10) and third (n=10) trimester of pregnancy. Heptest results are not influenced by the stage of pregnancy. In contrast, dose-related aPTT prolongation declines during pregnancy. All LMWHs tested, as well as fondaparinux, display a similar doseresponse in Heptest compared to the chromogenic anti-factor Xa assay. Heptest-STAT can be used with the same standard calibration for non-pregnant and pregnant patients and for all LMWHs under investigation, including fondparinux. No individual calibrations are necessary.
From heparin to EP217609: The long way to a new pentasaccharide-based neutralisable anticoagulant with an unprecedented pharmacological profile
Authors: Nancy-Portebois Vanessa , Dubreucq Guy , Motte Vincent , de Kort Martin , van Boeckel Constant , Vogel Gerard , Wisse Jeffry , Petitou Maurice , Meuleman Dick 
Published: September 2009

SummaryThe elucidation of the structure of the antithrombin binding sequence in heparin has given a large impulse to the rational design of heparin related drugs. De novo chemical synthesis of the corresponding pentasaccharide as well as simplified analogues has provided very specific, antithrombin-mediated inhibitors of factor Xa with various pharmacokinetic profiles. Fondaparinux and idraparinux are examples of such compounds that have found clinical application as antithrombotics. Because of the very specific binding to antithrombin the pharmacokinetics of pentasaccharides can be predicted and transferred to other molecules covalently bound to them. The new chemical entities thus obtained display a wide array of antithrombotic activities, giving improved heparin molecules as well as new anticoagulants, devoid of the undesired side effects of heparin and with unprecedented pharmacological profiles. In this context, a direct thrombin inhibitor was covalently coupled to a pentasaccharide by an inert spacer.This compound, EP42675 exerts antithrombin mediated anti-factor Xa activity together with direct thrombin inhibiting capacity. It displays favourable pharmacokinetics as imposed by the pentasaccharide. EP42675 was further modified by the introduction of a biotin moiety in its structure.The new entity obtained, EP217609 exerts the same pharmacological profile as EP42675 and it can be instantaneously neutralised by injection of avidin. Due to this unprecedented mechanism of anticoagulant activity and its ability to be neutralised,EP217609 deserves to be investigated in clinical settings where direct thrombin inhibition is required.
Impact of long-term testosterone treatment on plasma levels of free TFPI and TF-induced thrombin generation ex vivo in elderly men with low testosterone levels
Authors: Agledahl Ingvild , Svartberg Johan , Hansen John-Bjarne , Brodin Ellen 
Published: September 2009

SummaryMen have a higher incidence of cardiovascular disease (CVD) than women of similar age, and it has been suggested that testosterone may influence the development of CVD. Recently, we demonstrated that elderly men with low testosterone levels had lower plasma levels of free tissue factor pathway inhibitor (TFPI) Ag associated with shortened tissue factor (TF)-induced coagulation initiation in a population based case-control study. Our hypothesis was that one year of testosterone treatment to physiological levels in elderly men would increase the levels of free TFPI Ag in plasma and have a favorable effect on TF-induced coagulation. Twenty-six men with low testosterone levels (≤11.0 nM) were randomly assigned to treatment with intramuscular testosterone depot injections (testosterone undecanoate 1,000 mg) or placebo in a double-blinded study. Each participant received a total of five injections, at baseline, 6, 16, 28 and 40 weeks, and TF-induced thrombin generation ex vivo and plasma free TFPI Ag were measured after one year. At the end of the study total and free testosterone levels were significantly higher in the testosterone treated group (14.9 ± 4.5 nM vs. 8.1 ± 2.4 nM; p<0.001, and 363.3 ± 106.6 pM vs. 187.3 ± 63.2 pM; p<0.001, respectively). Testosterone treatment for one year did neither cause significant changes in TF-induced thrombin generation ex vivo nor changes in plasma levels of free TFPI Ag. In conclusion, normalising testosterone levels by testosterone treatment for 12 months in elderly men did not affect TF-induced coagulation or plasma TFPI levels. The potential antithrombotic role of testosterone therapy remains to be elucidated.
Constriction of carotid arteries by urokinase-type plasminogen activator requires catalytic activity and is independent of NH2-terminal domains
Authors: Massey Philip , Tanaka Shinji , Buckler Joshua , Jiang Bo , McCourtie Anton , Qian Kun , Tom Clifford , Stempien-Otero April , Wen Shan , Luttrell Ian , Chitaley Kanchan , Dichek David 
Published: September 2009

SummaryUrokinase-type plasminogen activator (uPA) is expressed at increased levels in stenotic, atherosclerotic human arteries. However, the biological roles of uPA in the artery wall are poorly understood. Previous studies associate uPA with both acute vasoconstriction and chronic vascular remodeling and attribute uPA-mediated vasoconstriction to the kringle – not the catalytic domain of uPA. We used an in-vivo uPA overexpression model to test the hypothesis that uPA-induced vasoconstriction is a reversible vasomotor process that can be prevented – and uPA fibrinolytic activity preserved – by: 1) removing the growth factor and kringle domains; or 2) anchoring uPA to the endothelial surface. To test this hypothesis we constructed adenoviral vectors that express: wild-type rabbit uPA (AduPA); a uPA mutant lacking the NH2-terminal growth-factor and kringle domains (Adu-PAdel); a mutant lacking catalytic activity (AduPAS→A), and a cell-surface anchored mutant (AdTMuPA). uPA mutants were expressed and characterised in vitro and in carotid arteries in vivo. uPAS→A had no plasminogen activator activity. Activity was similar for uPA and uPAdel, whereas AdTMuPA had only cell-associated activity. AduPAS→A arteries were not constricted. AduPA, AduPAdel, and AdTM-uPA arteries were constricted (approximately 30% smaller lumens; p≤0.008 vs. AdNull arteries). Papaverine reversed constriction of AduPA arteries. uPA-mediated arterial constriction is a vasomotor process that is mediated by uPA catalytic activity, not by the NH2-terminal domains. Anchoring uPA to the endothelial surface does not prevent vasoconstriction. uPA catalytic activity, generated by artery wall cells, may contribute to lumen loss in human arteries. Elimination of uPA vasoconstrictor activity requires concomitant loss of fibrinolytic activity.
Glanzmann’s thrombasthenia (defective platelet integrin αIIb-β3): proposals for management between evidence and open issues
Authors: Di Minno Giovanni , Di Minno Matteo , Poon Man-Chiu , Coppola Antonio 
Published: September 2009

SummaryGlanzmann’s Thrombasthenia (GT) is a rare autosomal recessive bleeding disorder, characterized by a quantitative or qualitative defect of platelet surface αIIb-β3 integrin. Presently, no specific guideline/algorithm for clinical management for GT is available. Due to the rarity and heterogeneity of inherited platelet abnormalities, recommendations and guidelines are based on reports from opinions and clinical experience of panel of experts, and refer to the general management of platelet disorders. Based on the limited evidence in the area and on the strategies in clinical settings of inherited/acquired platelet defects, proposals for management of minor bleeding; moderate/major bleeding unresponsive to conservative management; major surgery; minor surgery and dental procedures for GT patients without, or with anti-platelet isoantibodies are reported. In addition to life-style advices and continuous patient education programs, when and how to employ/combine local measures, antifibrinolytic agents, hormone treatment, platelet transfusions and recombinant activated Factor VII is described. The prospective collection of treatments in GT patients recently established (Glanzmann’s Thrombasthenia Registry, GTR), based on a careful definition of clinical settings and outcomes, is likely to provide newer insight for optimising clinical management in GT.
HD1, a thrombin- and prothrombin-binding DNA aptamer, inhibits thrombin generation by attenuating prothrombin activation and thrombin feedback reactions
Authors: Kretz Colin , Cuddy Karl , Stafford Alan , Fredenburgh James , Roberts Robin , Weitz Jeffrey 
Published: September 2009

SummaryHD1, a DNA aptamer, binds exosite 1 on thrombin and blocks its clotting activity. Because HD1 also binds prothrombin and inhibits its activation by prothrombinase, we hypothesised that HD1 would be a more potent inhibitor of coagulation than other exosite 1-directed ligands, such as Hir54–65(SO3
-). Supporting this concept, the effect of HD1 on the prothrombin time and activated partial thromboplastin time was twofold greater than that of Hir54–65(SO3
-) even though both agents inhibited thrombin-mediated factor (F) V and FVIII activation to a similar extent. In thrombin generation assays, HD1 (a) delayed the lag time, (b) reduced peak thrombin concentration, and (c) decreased endogenous thrombin potential to a greater extent than Hir54–65(SO3
-). To eliminate thrombin feedback, studies were repeated in FV- and/or FVIII-deficient plasma supplemented with FVa and/or FVIIIa. Only HD1 prolonged the lag time in FV- and FVIII-deficient plasma supplemented with FVa and FVIIIa. In contrast, HD1 and Hir54–65(SO3
-) inhibited the lag time in FVIII-deficient plasma supplemented with FVIIIa and in normal plasma. The more potent anticoagulant properties of HD1, therefore, reflect its capacity to attenuate FV activation by thrombin and inhibit prothrombinase assembly. These findings identify prothrombin as a potential target for new anticoagulants.
Studies on the biology of the frog Rana dalmatina BONAPARTE during the breeding season in Greece (Amphibia: Anura: Ranidae)
Authors: Sofianidou Th. S. , Kyriakopoulou-Sklavounou P. 
Published: September 2009

Abstract
Studies on the biology and ecology of Rana dalmatina during its breeding season have been performed in the region of Gallikos river for some years. Animals hibernated in their home range. They emerged from hibernation shortly before the onset of oviposition. Spawning period ranged from the 25th of January to the 15th of March, depending on the weather conditions. In some years it was continuous with 1-3 peaks of oviposition, in others interrupted for shorter or longer time periods depending on the temperature. The mean numberofeggs per female estimated in 190 egg masses was 985 (445-1761) and the mean diameter of the eggs measured in samples from 20 different egg masses was 1.78 mm (1.49-2.04). The mean diameter of the eggs was positively correlated with the number of eggs in each egg mass.
Genetic differentiation between hybridizing species Bombina bombina and Bombina variegata (Salientia, Discoglossidae) in Poland*
Authors: Szymura Jacek M. 
Published: September 2009

AbstractNEI'S genetic distance estimate (D) between Polish Bombina bombina and B. variegata based on electrophoretic comparisions of 29 proteins encoded at 39 presumptive gene loci, is 0.487±0.127. This estimate suggests Pliocene separation of the species, in agreement with the fossil record. Remnants of B. bombina-like and B. variegata - like animals from Upper Pliocene have been found in Czechoslovakia, and B. bombina- like animals from the same period have also been found in Poland. Separation of European Bombina was probably connected with an ecological shift of ancestors of B. bombina, the most derived species of the genus, to lowland environment. The Pliocene divergence proposed here is considerably earlier than that postulated by MERTENS (1928) who linked Bombina speciation events to Pleistocene glaciations. Comparisons ofgenetic divergence measures and the fossil record for three other species pairs of European amphibians (Triturus cristatus/marmoratus, Bufo calamita/viridis and Rana lessonae/ridibunda) provide additional evidence that pre-Pleistocene speciations in the extant European amphibian fauna were more important than is traditionally believed.
Seasonal and Sexual Differences in the Effects of Parathyroidectomy in the Indian Garden Lizard Calotes versicolor with a Note on Follicle Formation in Reptilian Parathyroids
Authors: Akbarsha M.A. 
Published: September 2009

AbstractMale and female C. versicolor were parathyroidectomized and/or administered with parathyroid extract during summer and winter. Sexual as well as seasonal differences were noticed in the effects. The results correlate with the often reported seasonal histophysiological changes in the parathyroids, suggesting "physiological parathyroidectomy" in winter lizards. Oestrogen induced hypercalcemiaappears to prevail in female lizards during the breeding season. Seasonal histological studies on the parathyroids ofthis lizard suggest that the often reported parathyroid follicles in reptiles originate due to degeneration of secretory parenchyma and that the follicular luminal content is only a condensate of the material released during degeneration. Though such follicle formation has also been reported in mammalian parathyroids, the causative factors seem to differ.
Análisis Osteométrico de las Regiones Sacra y Presacra de la Columna Vertebral en los Lagartos Ibéricos Lacerta viridis LAURENTI, Lacerta lepida DAUDIN y Lacerta schreiberi BEDRIAGA
Authors: Barbadillo L.J. , Sanz J.L. 
Published: September 2009

AbstractAn osteometric analysis of sacral and presacral regions in three species of iberian lizards (Lacerta lepida, L. schreiberi and L. viridis) has been carried out. For this purpose, 11 osteometric vertebral parameters were proposed, and some of the parameters used by other authors were revised. The topographical variation of the most significant parameters were described and several indices based on them were elaborated. Lacerta viridis differs considerably from L. schreiberi and L. lepida, both qualitatively and quantitatively, especially in the positions of the maximum and minimum for each parameter, and in the percentage of general elongation of the presacral vertebrae, more marked in L. viridis than in the other two species. The sexual and ontogenetic variations include qualitative and quantitative differences as well. A greater percentage of elongation of presacral vertebrae exists in the females. There is some sexual correlation of the existence oscillations in certain parameters (for example pre-postzygapophysis distance) along the vertebral axis (L. lepida and L. schreiberi). The relative height of the neurapophysis shows the most important ontogenetic variation. It is progressively enhanced with size. The vertebral widening that occurs in the last presacral zone is more marked in immature individuals. An interspecific vertebral diagnosis (of particular importance in the axis and sacrum) is proposed.
Ecology of a Snake Community in Northeastern Brazil
Authors: Vitt Laurie J. , Vangilder Larry D. 
Published: September 2009

Abstract
Nineteen species of snakes representing four families were simultaneously studied in a caatinga habitat of northeastern Brazil. Of these, 10 are terrestrial, 3 are terrestrial-aquatic, 1 is arboreal-terrestrial, 4 are arboreal, and 1 is terrestrial-fossorial. Four species are nocturnal, 5 species are nocturnal and diurnal, and 10 are strictly diurnal. Diets include mammals, birds, bird eggs, lizards, snakes, frogs, toads, and reptile eggs, with some snake species being food specialists and others being food generalists. Surprisingly, none of the species of snakes at the study site feed on invertebrates. A diversity of reproductive tactics is evident among the species in this snake community. There are oviparous and viviparous species, and clutch/brood size may be large or small depending upon the species. Both clutch/brood size and neonate (or egg) size were correlated with body size of female snakes. A principal components analysis (PCA) of morphological data revealed that two axes, one representing variation in body size and one representing variation in tail length and head size, explained 95% ofthe variation in the data. Portions of the morphological results corresponded well with ecological data. However, in some instances the morphological results were discordant with ecological results. Certain patterns, for example appear to have a phylogenetic basis. It is concluded that morphological analyses of snake communities cannot be adequately interpreted in the absence of ecological data.
Analyse de la parade de Pelomedusa subrufa subrufa (LACEPEDE)
Authors: Bels Vincent 
Published: September 2009

AbstractPelomedusa subrufa subrufa (LACÉPÈDE) use diverse and unusual displays in courtship. Males show behaviors such as head-head (tête-tête), head bobbing (balancement de la tête) and biting to guide the female to stabilisation. Female's stabilisation is realized when the male mounts the female. Behavioral units are considered in their sequences in order to establishe the different possibilities of courtship leading to copulation in this species. Visual, tactile or chemical cues seem to be important in each behavior.