bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental regulation of claudin localization by fetal alveolar epithelial cells
Authors: Daugherty Brandy L. , Mateescu Madalina , Patel Anand S. , Wade Kelly , Kimura Shioko , Gonzales Linda W. , Guttentag Susan , Ballard Philip L. , Koval Michael
Published: September 2004

Tight junction proteins in the claudin family regulate epithelial barrier function. We examined claudin expression by human fetal lung (HFL) alveolar epithelial cells cultured in medium containing dexamethasone, 8-bromo-cAMP, and isobutylmethylxanthanine (DCI), which promotes alveolar epithelial cell differentiation to a type II phenotype. At the protein level, HFL cells expressed claudin-1, claudin-3, claudin-4, claudin-5, claudin-7, and claudin-18, where levels of expression varied with culture conditions. DCI-treated differentiated HFL cells cultured on permeable supports formed tight transepithelial barriers, with transepithelial resistance (TER) >1,700 ohm/cm2. In contrast, HFL cells cultured in control medium without DCI did not form tight barriers (TER <250 ohm/cm2). Consistent with this difference in barrier function, claudins expressed by HFL cells cultured in DCI medium were tightly localized to the plasma membrane; however, claudins expressed by HFL cells cultured in control medium accumulated in an intracellular compartment and showed discontinuities in claudin plasma membrane localization. In contrast to claudins, localization of other tight junction proteins, zonula occludens (ZO)-1, ZO-2, and occludin, was not sensitive to HFL cell phenotype. Intracellular claudins expressed by undifferentiated HFL cells were localized to a compartment containing early endosome antigen-1, and treatment of HFL cells with the endocytosis inhibitor monodansylcadaverine increased barrier function. This suggests that during differentiation to a type II cell phenotype, fetal alveolar epithelial cells use differential claudin expression and localization to the plasma membrane to help regulate tight junction permeability.
Stress response inhibits the nephrotoxicity of cisplatin
Authors: Hanigan Marie H. , Deng Mei , Zhang Lei , Taylor Peyton T. , Lapus Maia G.
Published: September 2004

Salt loading and saline hydration are used to protect patients from cisplatin-induced nephrotoxicity. The mechanism by which salt exerts its protective effect is unknown. As part of an ongoing study of cisplatin nephrotoxicity, an in vitro assay system was developed that models the in vivo exposure and response of proximal tubule cells to cisplatin. In this study, it was discovered that the toxicity of cisplatin toward LLC-PK1 cells varied dramatically according to the tissue culture media used for 3-h cisplatin exposure. Further experiments revealed that minor variations in the sodium concentration among standard tissue culture media modulated cisplatin nephrotoxicity. NaCl has been shown to protect against cisplatin-induced nephrotoxicity in vivo but has never before been demonstrated in vitro. NaCl did not alter the cellular accumulation of cisplatin. NaCl altered the osmolarity of the external media, and its effect was replicated by substituting equiosmolar concentrations of impermeant anions or cations. The change in osmolarity triggered a stress response within the cell that modulated sensitivity to cisplatin. These data resolve several long-standing controversies regarding the mechanism by which salt loading protects the kidney from cisplatin-induced nephrotoxicity.
Age differences in knee extension power, contractile velocity, and fatigability
Authors: Petrella John K. , Kim Jeong-su , Tuggle S. Craig , Hall Samuel R. , Bamman Marcas M.
Published: September 2004

The purposes of this study were to examine age and gender differences in knee extensor strength, power, and fatigue using open- and closed-chain testing procedures. We tested the hypothesis that specific strength (strength/unit muscle mass) would not differ by age, whereas age differences in specific power and fatigue would remain consequent to blunted maximal contractile velocity. Skeletal muscle performance was examined in 28 young (26.9 ± 0.7 yr) and 24 older (63.6 ± 0.8 yr) men and women. Assessments included one-repetition maximum strength for knee extension, leg press, and squat; concentric knee extensor peak power, velocity, and fatigability; and sit-to-stand power, fatigability, and relative neural activation (electromyograph activity during sit-to-stand movement normalized to electromyograph activity during isometric maximum voluntary contraction). Thigh lean mass (TLM; kg) was assessed by dual-energy X-ray absorptiometry. Specific strength (N/kg TLM) and specific power (W/kg TLM) were estimated by dividing absolute values by TLM. Age differences in specific strength were observed for knee extension only (young, 41.2 ± 1.0 N/kg TLM; older, 32.4 ± 1.0 N/kg TLM; P < 0.05). Adjustment for TLM did not negate age differences in knee extension specific power (25–41% lower in older; P < 0.05) across loads tested. Older adults experienced fatigue across 10 repetitions of knee extension as peak velocity fell by 24% ( P < 0.05). Deficits in concentric power persist after adjustment for TLM as maximum contractile velocity falls markedly with aging. Older adults are less capable of sustaining maximum concentric velocity during repetitive contractions. These findings suggest that velocity impairments are a possible contributor to mobility loss and falls risk among older adults. Interventions for improving contractile velocity should be pursued.
Smooth muscle development during postnatal growth of distal bronchioles in infant rhesus monkeys
Authors: Tran Mai-Uyen T. , Weir Alison J. , Fanucchi Michelle V. , Murphy April E. , Van Winkle Laura S. , Evans Michael J. , Smiley-Jewell Suzette M. , Miller Lisa , Schelegle Edward S. , Gershwin Laurel J. , Hyde Dallas M. , Plopper Charles G.
Published: September 2004

Development of smooth muscle in conducting airways begins early in fetal life. Whereas the pattern and regulation of smooth muscle differentiation are well-defined, the impact of airway growth on the process is not. To evaluate the transformations in organization during postnatal growth, smooth muscle bundle organization (size, abundance, and orientation) was mapped in five generations of distal airways of infant rhesus monkeys (5 days and 1, 2, 3, and 6 mo old). On the basis of direct measurement of the bronchiole proximal to the terminal bronchiole, length increased by 2-fold, diameter by 1.35-fold, and surface area by 2.8-fold between 5 days and 6 mo of age. Smooth muscle bundle size was greater in proximal bronchioles than in respiratory bronchioles and did not change with age. However, relative bundle size decreased in proportion to airway size as the airways grew. Relative bundle abundance was constant regardless of airway generation or age. The distribution of smooth muscle bundle orientation changed with age in each airway generation, and there were significant changes in the terminal and respiratory bronchioles. We conclude that smooth muscle undergoes marked organizational changes as airways grow during postnatal development.
Relationship between muscle blood flow and oxygen uptake during exercise in endurance-trained and untrained men
Authors: Kalliokoski Kari K. , Knuuti Juhani , Nuutila Pirjo
Published: September 2004

A recent study showed good correlation between regional blood flow (BF) and oxygen uptake (V̇o2) 30 min after exhaustive exercise. The question that remains open is whether there is similar good correlation between BF and V̇o2also during exercise. We reanalyzed our previous data from a study in which BF and V̇o2was measured in different quadriceps femoris muscles in seven healthy endurance-trained and seven healthy untrained men at rest and during low-intensity intermittent static knee-extension exercise (Kalliokoski KK, Oikonen V, Takala TO, Sipila H, Knuuti J, and Nuutila P. Am J Physiol Endocrinol Metab 280: E1015–E1021, 2001). When the mean values of each muscle were considered, there was good correlation between BF and V̇o2during exercise in both groups ( r2= 0.82 in untrained and 0.97 in trained). However, when calculated individually, the correlations were poorer, and the mean correlation coefficient ( r2) was significantly higher in the trained men (0.71 ± 0.07 vs. 0.40 ± 0.11, P = 0.03). These results suggest that there is large individual variation in matching BF to V̇o2in human skeletal muscles during exercise, ranging from very poor to excellent. Furthermore, this matching seems to be better in the endurance-trained than in untrained men.
Low molecular weight heparin (tinzaparin) therapy for moderate risk thromboprophylaxis during pregnancy
Authors: Bonnar John , Smith Mark , Steer Philip , Savidge Geoff , Norris Lucy
Published: September 2004

Low molecular weight heparin (LMWH) is used increasingly for prophylaxis and treatment of venous thromboembolism during pregnancy. However, the prophylactic dose for patients at moderate risk varies between centers, and the recommended LMWH dose for the non pregnant patient is frequently used in pregnant women. The aim of this study was to investigate the effects of pregnancy on the pharmacokinetics of anti-Xa levels during moderate risk thromboprophylaxis with the LMWH, tinzaparin. In 24 pregnant women, one of three doses of tinzaparin (50, 75 or 100 IU/kg) were given according to the treating physician’s assessment of their risk profile. Four-hour peak anti-Xa levels were measured throughout pregnancy and 24-hour profiles were measured at 28 and 36 weeks gestation. Doses were adjusted when peak anti-Xa levels fell below 0.1 IU/ml and, in some cases, when levels at 10 and 18 hours post injection were undetectable (<0.05 IU/ml). Our results showed that women receiving tinzaparin (50 IU/kg) frequently had peak (4 hour) anti-Xa levels below 0.1IU/ml and that 46% of these patients required dose adjustment. Similarly anti-Xa levels were also found to be low over the 24-hour period. A starting dose of 75 IU/kg, once daily, gave greater anti-Xa cover over the 24-hour period and may avoid the need for dose adjustment. The results suggest that the pharmacokinetics of tinzaparin are affected by pregnancy. Larger studies are required to determine whether an increased tinzaparin dose (75 IU/kg) would be more effective in the prevention of thrombosis during pregnancy than 50 IU/kg
Development of selected coagulation factors and anticoagulants in preterm infants by the age of six months
Authors: Riikonen Pekka , Vahtera Elina , Mahlamäki Eija , Heinonen Kirsti , Kekomäki Riitta , Salonvaara Marjut
Published: September 2004

The development of the coagulation and anticoagulation system in preterm infants was assessed, with special emphasis on extremely low birth weight (ELBW) infants and haemorrhagic or other complications after birth. Coagulation factors II (prothrombin),V (FV),VII (FVII) and X (FX) were analysed at birth and at a corrected age of six months. In addition, antithrombin (AT), protein C (PC) and protein S (PS) were measured at six months, and DNA samples were tested for Factor V Leiden (R506Q). Eighty-two infants, with a median gestational age (GA) of 32 weeks (range 24–36) and a median birth weight of 1562 g (range 695–3520), were studied. Fifteen of these were ELBW infants (range 695-1000g). Prothrombin, FV, FVII and FX reached healthy term six-month-old infant activity levels. Prothrombin and FX did not reach adult values; median activity levels remained at 82% and 78%, respectively. During the follow up, the FV and FVII levels of the ELBW infants (GA 24-27 weeks) increased more than those of the preterm infants born with higher GA (p < 0.001). At birth, prothrombin correlated significantly with FV, FVII and FX (p < 0.001). FVII at birth and at six months correlated significantly with PC (p= 0.021 and p= 0.009, respectively). These findings indicate that the gain in the coagulation factor concentrations in infancy is greatest in infants with the lowest GA at birth. Interesting new inter-relations of coagulation factor and physiological anticoagulant levels may indicate that there are still unrecognised pathways in the function of newborn haemostasis.
Expression of transcription factor Oct-4 and other embryonic genes in CD133 positive cells from human umbilical cord blood
Authors: Baal Nelli , Reisinger Kerstin , Jahr Henning , Bohle Rainer , Liang Olin , Münstedt Karsten , Rao C.V. , Preissner Klaus , Zygmunt Marek
Published: September 2004

A significant number of hematopoietic stem/progenitor cells (HSPC) in human umbilical cord blood could serve as a reservoir for the placental vasculature, yet, their morphological and functional features are not completely understood. Here, we describe the characterization of purified CD133+ progenitor cells from umbilical cord blood, a subset of CD34+ hematopoietic progenitors that were grown in proliferation medium containing Flt3-ligand, thrombopoietin and stem cell factor. Following isolation and enrichment of the CD133+ cells by immunomagnetic cell sorting, they remained non-adherent for up to 40 days in culture and expressed different pluripotency markers including Sox-1, Sox-2, FGF-4, Rex-1 and Oct-4. Oct-4 expression was confirmed by laser-assisted single cell picking with subsequent quantitative real-time RT-PCR.The expression of Oct-4 indicates a pluripotent phenotype of CD133+ cells and appears to be of functional relevance: After three weeks in endothelial differentiation medium, suspended cells became adherent, developed an endothelial cell-like morphology, bound fluoresceine isothiocyanate-labeled Ulex europaeus agglutinin-1, took up acetylated Di-LDL, and expressed other endothelial markers such as PECAM-1 or VEGFR-2. Concomitantly, Oct-4 expression was significantly reduced. Moreover, following treatment with retinoic acid, CD133+ cells exhibited neural morphology associated with the expression of β-III-tubulin. CD133+ cells were found to express the luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor, detected by RT-PCR and immunocytochemistry. The recombinant human chorionic gonadotropin induced proliferation of the CD133+ cells in a dose-specific manner. Our results indicate that CD133+ HSPC from umbilical cord blood may have a greater differentiation potential than previously recognized and give rise to proliferative endothelial cells participating in placental vasculogenesis.
Ultrasound affects distribution of plasminogen and tissuetype plasminogen activator in whole blood clots in vitro
Authors: Gherardini Lisa , Mayer Christoph , Gröschl Martin , Kaun Christoph , Benes Ewald , Tschachler Erwin , Huber Kurt , Maurer Gerald , Devcic-Kuhar Branka , Pfaffenberger Stefan , Wojta Johann , Gottsauner-Wolf Michael
Published: September 2004

Ultrasound of 2 MHz frequency and 1.2 W/cm2 acoustic intensity was applied to examine the effect of sonication on recombinant tissue-type plasminogen activator (rt-PA)-induced thrombolysis as well as on the distribution of plasminogen and t-PA within whole blood clots in vitro. Thrombolysis was evaluated quantitatively by measuring clot weight reduction and the level of fibrin degradation product D-dimer (FDP-DD) in the supernatant. Weight reduction in the group of clots treated both with ultrasound and rt-PA was 35.2% ± 6.9% which is significantly higher (p<0.0001) than in the group of clots treated with rt-PA only (19.9% ± 4.3%). FDP-DD level in the supernatants of the group treated with ultrasound and rt-PA increased sevenfold compared to the group treated with rt-PA alone, (14895 ± 2513 ng/ml vs. 2364 ± 725 ng/ml). Localization of fibrinolytic components within the clots was accomplished by using gel-entrapping technique and immunohistochemistry. Spatial distributions of t-PA and plasminogen showed clearly that ultrasound promoted the penetration of rt-PA into thrombi significantly (p<0.0001), and broadened the zone of lysis from 8.9 ± 2.6 µm to 21.2 ± 7.2 µm. We speculate that ultrasound enhances thrombolysis by affecting the distribution of rt-PA within the clot.
Fibrinogen adsorption and platelet adhesion to metal and carbon coatings
Authors: Santin Matteo , Denyer Stephen , Lloyd Andrew , G.Teer Dennis , Field Sue , Mikhalovsky Sergey , Mikhalovska Lyuba
Published: September 2004

In order to study the haemocompatibility of metal and carbon coatings, fibrinogen adsorption and platelet adhesion to various coatings have been investigated.Two metallic coatings titanium and zirconium, and two carbon coatings isotropic diamondlike and isotropic graphite-like coatings, were prepared by plasma vapour deposition onto stainless steel substrate. It has been shown that the adsorption of fibrinogen to metal and carbon coatings and its post-adsorptive transition are dependent on both the material properties and the fibrinogen environment. The adsorption of fibrinogen from human plasma on titanium and zirconium coatings is similar to that on uncoated stainless steel surface. Both carbon coatings adsorb much greater amount of fibrinogen from plasma, and fibrinogen retention by carbon surfaces is also greater than by metal surfaces. Increased numbers of adhered platelets have been found on both carbon coatings in comparison to the metal materials, although this does not correlate with the amount of adsorbed fibrinogen.
P-selectin-targeting of the fibrin selective thrombolytic Desmodus rotundus salivary plasminogen activator α1
Authors: Dong Ningzheng , Da Cunha Valdeci , Citkowicz Andrej , Wu Faye , Vincelette Jon , Larsen Brent , Wang Yi-Xin , Ruan Changgeng , Dole William , Morser John , Wu Qingyu , Pan Junliang
Published: September 2004

During thrombosis, P-selectin is expressed on the surface of activated endothelial cells and platelets. We hypothesized that targeting a plasminogen activator (PA) to P-selectin would enhance local thrombolysis and reduce bleeding risk. Previously, a urokinase (uPA)/anti-P-selectin antibody (HuSZ51) fusion protein was shown to increase fibrinolysis in a hamster pulmonary embolism model. To explore the therapeutic potential of this targeting strategy, we fused the fibrin-selective Desmodus rotundus salivary PA α1 (dsPAα1) to HuSZ51 and compared the fibrinolytic activity of P-selectin-targeted dsPAα1 (HuSZ51-dsPAα1) to unmodified dsPAα1 in vitro and in vivo. HuSZ51-dsPAα1 and dsPAα1 were expressed in CHO cells and purified to homogeneity by affinity chromatography. HuSZ51dsPAα1 bound to thrombin-activated human and dog platelets with comparable affinities to that of parental antibody SZ51. The fusion protein retained the catalytic activities of dsPAα1 in chromogenic and clot lysis assays, indicating that dsPAα1 is fully functional when fused to HuSZ51. Compared to dsPAα1, HuSZ51-dsPAα1 had similar thrombolytic efficacy in a rat pulmonary embolism model and anti-thrombotic potency in a dog model of femoral artery thrombosis. However, HuSZ51dsPAα1 was less effective in lysis of preexisting arterial thrombi in the dog model. The reduced arterial thrombolysis was not due to the pharmacokinetic properties of HuSZ51-dsPAα1 because antigen level and amidolytic activity were higher in plasma from HuSZ51-dsPAα1-treated groups than corresponding dsPAα1-treated groups. These data indicate that the thrombolytic efficacy of HuSZ51-dsPAα1 varied dependent on the physical composition of thrombi. The lack of stimulation by fibrin in arterial thrombi may contribute to the attenuated thrombolytic efficacy of HuSZ51-dsPAα1 in the dog model.
On the mode of action of thrombin-induced angiogenesis: thrombin peptide, TP508, mediates effects in endothelial cells via αvβ3 integrin
Authors: Tsopanoglou Nikos , Papaconstantinou Matthew , Flordellis Christodoulos , Maragoudakis Michael
Published: September 2004

In a previous report we have presented evidence that thrombin interacts with αvβ3
integrin in endothelial cells at the molecular and cellular level. This interaction was shown to be of functional significance in vitro and in vivo and contributed to activation of angiogenesis by thrombin. In the present study, we have used a synthetic thrombin peptide, TP508, which represents residues 183 to 200 of human thrombin. This peptide lacks the catalytic site of thrombin but contains the thrombin RGD sequence. Immobilized (surface-coated) TP508 peptide, like thrombin, supported αvβ3
integrin-dependent endothelial cell attachment and haptotactic migration. These effects were specific (a scrambled TP508 peptide was without effect), and dosedependent. The RGD sequence was essential since a modified TP508 peptide, which contained RAD sequence instead of RGD, was inactive. Immobilized TP508 peptide stimulated phosphorylation of mitogen-activated protein kinases and focal adhesion kinase, the signal transduction pathways characteristic for integrin activation. On the other hand, TP508 peptide, when in solution, did not mimic other thrombin-promoted angiogenic effects, such as that of activation gelatinase A, upregulation of expression of vascular endothelial growth factor receptor mRNA or prostacyclin PGI2 release in endothelial cells. On the contrary, soluble TP508 acted as an antagonist for the aforementioned effects of thrombin. TP508 peptide inhibited these thrombin-induced effects through a RGD and α.
vβ3-related mechanism. The antagonism with thrombin or thrombin receptor activating peptide was specific and involved at least in part mitogen-activated protein kinases activation. These results point to the importance of RGD sequence of thrombin in mediating effects on endothelial cells and angiogenesis.
An in vitro study on the mechanisms of coagulation activation in acute myelogenous leukemia (AML): role of tissue factor regulation by cytotoxic drugs and GM-CSF
Authors: Amirkhosravi Ali , Loges Sonja , Meyer Todd , Eifrig Barbara , Hossfeld Dieter , Fiedler Walter , Francis John , Langer Florian
Published: September 2004

AML patients may suffer from a disseminated coagulopathy, which can aggravate a pre-existing bleeding tendency due to thrombocytopenia and platelet dysfunction. The cellular and molecular mechanisms underlying this coagulopathy, however, are not completely understood. Indeed, the broad and increasing therapeutic use of cytotoxic drugs and growth factors is likely to contribute to the complexity of hemostatic abnormalities encountered in this hematologic malignancy. The nature of coagulation activation in AML was therefore investigated in vitro using the human leukemic cell line, HL60. Tissue factor (TF) was almost entirely located on the cell surface and bound factor VIIa, but only 15-25% of this TF was primarily functionally active. Treatment with increasing concentrations of daunorubicin or cytosine-β-D-arabinofuranoside, two cytotoxic drugs commonly used in AML therapy, induced apoptosis and secondary necrosis of HL60 cells and resulted in marked decryption of TF PCA independent of de novo protein synthesis. This PCAmodulating effect was concomitant with and functionally dependent on the exposure of phosphatidylserine on the outer membrane leaflet. Similar observations were made in analogous ex vivo studies on patient-derived myeloblasts. Incubation of HL60 cells with GM-CSF, a cytokine expressed in the bone marrow microenvironment and used as an adjunct to AML treatment, evoked a cellular response, which included both enhanced TF production and release of VEGF-A and uPA into the culture medium. We conclude that both decryption of preformed TF PCA by chemotherapeutic drugs and de novo induction of TF by cytokines such as GM-CSF can regulate the procoagulant phenotype of HL60 cells in vitro.
Delayed immunologic thrombocytopenia induced by abciximab
Authors: Clofent-Sanchez Gisèle , Jais Catherine , Bermejo Emilse , Leroux Lionel , Coste Pierre , Nurden Alan , Nurden Paquita
Published: September 2004

Abciximab is an anti-GPIIb-IIIa drug widely used to prevent thrombotic complications during percutaneous coronary intervention. We now report on the immunologic origin of thrombocytopenia developing between 7 and 12 days after the onset of abciximab infusion. Antibodies directed against abciximabcoated platelets were located in 5 patients with delayed thrombocytopenia, just as they were present in a patient whose platelet count fell within a few hours after receiving the drug. Abciximab-dependent IgG antibody was revealed in serum using control platelets in the monoclonal antibody immobilization of platelet antigens assay (MAIPA) performed with SZ22, a MoAb to GPIIb. The presence of IgG antibodies specific for platelets sensitized with abciximab was confirmed by flow cytometry. They were not located in 13 patients receiving abciximab but whose platelet counts remained stable. For three patients, antibodies were transient and their presence related to the extent of the thrombocytopenia. Surprisingly, antibodycontaining plasma from three patients induced abciximabdependent activation and aggregation of normal platelets, a finding confirmed by electron microscopy. Immunogold labeling revealed that abciximab was associated with platelets in the aggregate, suggesting that its inhibitory effect was overcome by the platelet stimulation. In summary, these results show that abciximab-dependent thrombocytopenia can be delayed and potentially prothrombotic.
The effect of homocysteine reduction by B-vitamin supplementation on markers of endothelial dysfunction
Authors: Peeters Anita , van der Molen Els , Blom Henk , den Heijer Martin
Published: September 2004

Hyperhomocysteinemia is a risk factor for arterial vascular disease and venous thrombosis. The pathophysiology of this relation is unclear, but several studies suggest that hyperhomocysteinemia impairs endothelial function. We examined the effect of homocysteine lowering by B-vitamin supplementation on tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI) and von Willebrand factor (vWf) markers of endothelial dysfunction in hyperhomocysteinemic and normohomocysteinemic volunteers. A total of 123 healthy volunteers were randomized to placebo or B-vitamins (5 mg folic acid, 0.4 mg hydroxycobalamin and 50 mg pyridoxine) daily for 8 weeks. Before and after the intervention period, blood samples were taken for measurements of homocysteine, tPA, PAI and vWf.There was no evident association between homocysteine concentration and concentrations of markers of endothelial dysfunction at baseline.The mean reduction of homocysteine concentration was 31% (95%CI 22.7 to 39.1) in the B-vitamin group compared to 3% reduction in the placebo group. Concentrations of tPA, PAI and vWf did not change after supplementation of B-vitamins. In conclusion, the results of our study show that homocysteine reduction by B-vitamin supplementation has no effect on markers of endothelial dysfunction in healthy volunteers.
Total tissue factor pathway inhibitor is an independent risk factor for symptomatic paediatric venous thromboembolism and stroke
Authors: Duering Christine , Kosch Andrea , Langer Claus , Thedieck Sabine , Nowak-Göttl Ulrike
Published: September 2004

Tissue factor pathway inhibitor (TFPI) plays an important role in inhibiting tissue factor-induced coagulation by a factor Xadependent pathway of the activated tissue-factor VIIa complex. Decreased values of the latter inhibitor have been recently reported in adult patients with venous thrombosis (VT) or ischaemic stroke (IS). The present case-control study was therefore performed to evaluate whether a decreased TFPI concentration is also involved in paediatric symptomatic thromboembolism (ST). Total TFPI concentrations were measured along with established prothrombotic risk factors six to twelve months after the acute thrombotic onset in 144 Caucasian children aged 0.6 to 18 years (VT: n=80; IS: n=64). The cut-off values defined as age-dependent 10th percentiles were obtained from 244 healthy controls. Median (range) values of TFPI were significantly lower in patients compared with control subjects [50.0(20.0-132.3) ng/ml vs. 59.5(25.4-117.4) ng/ml; p-value < 0.0001]. In addition, 42 of the 144 patients (29.2%) compared with 25 of the 244 controls (10.2%) showed TFPI concentrations below the 10th age-dependent percentiles. Compared to baseline values 78.6% of children with total TFPI Ag < 10th percentiles showed a low response to enoxaparin administration, whereas in children with normal baseline TFPI values 30% show a low TFPI release (p= 0.007). Multivariate analysis adjusted for the presence of established prothrombotic risk factors showed a significantly increased odds ratio (OR) and 95% confidence interval (CI) for patients with ST [OR/CI: 3.8/2.2-6.6; p< 0.0001]. Data shown here give evidence that total TFPI concentrations below the 10th age-dependent percentiles independently increase the risk of ST in Caucasian children 3.8-fold.
High plasma heparin cofactor II activity protects from restenosis after femoropopliteal stenting
Authors: Exner Markus , Sabet Schila , Mlekusch Wolfgang , Amighi Jasmin , Handler Sylvia , Quehenberger Peter , Kalifeh Neda , Wagner Oswald , Minar Erich , Schillinger Martin
Published: September 2004

High heparin cofactor II (HCII) activity has recently been described to protect from coronary instent restenosis, presumably by inactivating thrombin in injured arteries. In this study, we investigated the association of HCII activity and restenosis after femoropopliteal stenting. We studied 63 consecutive patients with peripheral artery disease who underwent femoropopliteal stent implantation after initial failure of plain balloon angioplasty due to a significant residual stenosis (>30% lumen diameter reduction) or a flow limiting dissection. HCII activity was measured before stenting and patients were followed for median 10 months (interquartile range 6 to 17) for the occurrence of a first instent restenosis, defined as a >50% lumen diameter reduction by color coded duplex sonography and confirmed by angiography. Cumulative freedom from restenosis at 6 and 12 months in patients with lower HCII activity (≤100%, lower tertile, n=20) was 84% and 35% as compared to 93% and 72% in patients with high HCII activity (>100%, middle and upper tertile, n=43; p=0.024 by Log Rank test). Adjusting for the material of the implanted stents (nitinol vs.Wallstents), patients with a high HCII activity had a 0.39-fold reduced risk for instent restenosis (95% CI 0.17 to 0.90, p=0.028), additional adjustment for diabetes mellitus, poor run-off, critical limb ischemia and cumulative length of the stented segment did not alter the observed effect. Higher activity of heparin cofactor II may exert a protective effect against instent restenosis also in the femoropopliteal vessel area, confirming a prior observation after coronary stenting.
Low molecular weight heparin for the prophylaxis of thromboembolism in women with prosthetic mechanical heart valves during pregnancy
Authors: Lee-Parritz Aviva , Ansell ack , Oran Betul
Published: September 2004

Increased thromboembolic events occur in women with mechanical prosthetic valves during pregnancy, and selecting an effective and safe anticoagulant is still a challenge. Low molecular weight heparin (LMWH) is a promising alternative, but a recent warning and label change about its use in patients with mechanical prosthetic valves has caused confusion among physicians. The aim of the present study was to review the risks of maternal and fetal complications with mechanical heart valves treated with LMWH during pregnancy. We performed a review of the current medical literature through MEDLINE and EMBASE (1989 to 2004). Additional data sources included abstract proceedings, and reference lists of selected articles. Among 81 pregnancies in 75 women, the proportion of valve thrombosis was 8.64% (7/81; 95% CI, 2.52%–14.76%). The frequency of overall thromboembolic complication (TEC) was 12.35% (10/81; 95% CI, 5.19%–19.51%). Nine of ten patients with TEC received a fixed dose of LMWH and two of these received a fixed low dose of LMWH. Among 51 pregnancies whose anti-factor Xa levels were monitored, only one patient was reported to have a thromboembolic complication. The frequency of live births with LMWH was 87.65% (95%CI, 80.49%94.81%). In pregnant women with mechanical heart valves, LMWH appears to be a suitable option to a vitamin K antagonist. The use of LMWH warrants monitoring and appropriate dose adjustments to maintain a 4–6 hr post-injection anti-factor Xa level at a minimum of 1.0 U/ml to decrease the incidence of TEC.
Moving Democracy
Authors: Coles Romand
Published: September 2004

Practices of listening, receptive corporeal traveling, and moving the democratic table among different constituencies and locations are vital to democratic struggles in a heterogeneous world. Marginalizing these practices weakens ethical-political vision and the strategic capacities of radical democracy. First, this article discusses the importance of moving beyond the accent on voice in a lot of democratic theory, to focus more on practices of listening. Second, it discusses the limits of listening and theorizes the need for practices of receptive corporeal traveling beyond the power-saturated borders and scripted flows of human bodies that characterize most cities. Third, it suggests these insights might alter a fundamental metaphor underpinning many democratic theories, through a critical discussion of the imaginary of the solid democratic “table.” It is better to construe democracy as “tabling”: an activity in which the tables of engagement must be repeatedly altered by being moved and multiplied.
Elite Domination and the Clever Citizen
Authors: Zumbrunnen John
Published: September 2004

Aristophanes has often been read as a conservative who was nostalgic for the days before the advent of radical democracy in Athens. This article offers a more complex reading, centering on the portrayal of ordinary citizens in Archarnians and Knights Focusing on their “cleverness,” Aristophanes recognizes both the potential of ordinary citizens and their limitations as heroes in the struggle against elite domination of democratic politics. This complex portrayal of ordinary citizens, the author suggests, complements recent calls for a more agonistic democratic politics.
Hume and the (False) Luster of Justice
Authors: Krause Sharon R.
Published: September 2004

The close connection between norms and motives that is characteristic of Hume’s moral theory threatens to break down when it comes to the political matter of justice. Here a gap arises between the moral approval of justice, which is based on its utility, and the desires that motivate just action, which utility cannot fully explain. Therefore the obligation to justice may seem to be motivationally unsupported. This difficulty is compounded by the fact that, for Hume, no obligation can arise unless a normally effective motivation exists for it. In addition to disabling just action, then, the motivational deficit threatens to undercut the normative status of justice as a virtue. A solution to this dilemma lies in what Hume calls the “immediately agreeable” condition of “integrity” or “character.” The agreeableness of integrity indirectly confers upon justice a luster that makes it attractive and obligatory even when it does not actually serve the interests of individual or society, and when self-interest and sympathy fall short in sustaining compliance.
John Locke, Carolina, and the Two Treatises of Government
Authors: Armitage David
Published: September 2004

Recent scholarship on John Locke’s Two Treatises of Government has drawn particular attention to the colonial antecedents and applications of the theory of appropriation in chapter V of theSecond Treatise. This attention has coincided with a more general interest among political theorists in the historical and theoretical relationship between liberalism and colonialism. This essay reviews the surviving evidence for Locke’s knowledge of the Carolina colony and argues that it was both more extensive and more enduring than previous commentators have suggested. In particular, the essay provides evidence that Locke was engaged in revising the Fundamental Constitutions of Carolina at just the moment in the summer of 1682 when he was most likely to have composed chapter V of theSecond Treatise and hence that there was an immediate and identifiable colonial context that contributed to his distinctive theory of property.
Rank Size Distribution of International Financial Centers
Authors: Poon Jessie P. H. , Eldredge Bradly , Yeung David
Published: September 2004

The observation that global finance is concentrated in only a small number of international centers and cities has raised the question if worldwide financial integration is being achieved at the expense of increased international urban inequality. This article examines the spatial organization of stock markets for some forty-five cities. While New York, London, and Tokyo are undisputed hosts to the largest stock markets in the world, the analysis shows that inequality among international financial centers and cities has diminished between 1980 to 1999 with increased competition from regional financial centers and emerging markets.
Using Supportive Communication to Foster the Pharmacy Director-Clinical Pharmacist Relationship
Authors: Latif David A.
Published: September 2004

The quality of the pharmacy director-clinical pharmacist relationship is critical not only to the professional development success of the clinical pharmacist and the intrinsic satisfaction of the pharmacy director but also to the likelihood of the clinical pharmacist’s staying at the institution. This article advocates the incorporation of supportive communication principles into a regularly scheduled personal management interview program between pharmacy directors and their clinical pharmacists. A detailed discussion of how pharmacy directors might implement a personal management interview program that incorporates 8 principles of supportive communication is provided.
The Clinical Impact of Administering Warfarin to Post-Myocardial Infarction Patients
Authors: Earl Marc A. , Mauro Vincent F.
Published: September 2004

This article reviews recent trials that have compared aspirin to anticoagulation in post-myocardial infarction (MI) patients. Warfarin dosed to international normalized ratios (INRs) between 2.8 and 4.2 was superior to placebo in reducing morbidity and mortality; however, post-MI patients are generally receiving aspirin. When aspirin therapy was compared to warfarin plus aspirin, no clinical benefit occurred when warfarin was dosed to achieve INRs less than 2.0. In contrast, warfarin reduced morbidity and mortality compared to aspirin when it was dosed as monotherapy to achieve INRs between 3.0 and 4.0 or used with aspirin 75 to 80 mg daily and dosed to INRs between 2.0 and 2.5. With respect to mortality alone, warfarin was superior to aspirin only when it was used as monotherapy and compared to aspirin 80 mg daily. No difference in mortality was observed when warfarin monotherapy was compared to aspirin 160 mg daily.
Pharmacy Preparedness for Incidents Involving Nuclear, Biological, or Chemical Weapons
Authors: Burda Anthony M. , Sigg Todd
Published: September 2004

Recent worldwide terrorist attacks and hoaxes have heightened awareness that more incidents involving weapons of mass destruction (WMD) may occur in the United States. With federal funding assistance, local domestic preparedness programs have been initiated to train and equip emergency services and emergency department personnel in the management of large numbers of casualties exposed to nuclear, biological, or chemical (NBC) agents. Hospital pharmacies will be required to provide antidotes, antibiotics, antitoxins, and other pharmaceuticals in large amounts and/or have the capability for prompt procurement. Pharmacists should become knowledgeable in drug therapy of NBC threats with respect to nerve agents, cyanide, pulmonary irritants, radio-nucleotides, anthrax, botulism, and other possible WMD.
Epidemiology, Diagnosis, and Treatment of Chronic Hepatitis C
Authors: Matthews Jason D. , Bini Edmund J.
Published: September 2004

The hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma and is also a common indication for liver transplantation. Interferon alfa monotherapy leads to a sustained virologic response in only 10% to 15% of HCV-infected patients. The sustained virologic response rates can be increased to approximately 40% with interferon alfa-2b and ribavirin combination therapy for up to 48 weeks. However, recent clinical trials demonstrated that pegylated interferon in combination with ribavirin can improve the response rates even further, with more than 50% of patients having a sustained virologic response to treatment. Although new therapies are emerging, significant progress must be made to reduce the morbidity and mortality from HCV infection.
Advances in the Treatment of Erectile Dysfunction: A Focus on Tadalafil
Authors: Norwood Daryl A. , Eraikhuemen Nathaniel E. , Larose-Pierre Margareth , Branch Evans , Norwood Rhonda M.
Published: September 2004

Erectile dysfunction (ED) affects more than 150 million men and their partners throughout the world. Sildenafil, the first oral phosphodiesterase-type 5 (PDE-5) inhibitor approved for the treatment of ED, has led to the discovery of 2 more products in this class, with tadalafil being the latest. Tadalafil has proven to be well tolerated in various clinical studies and has demonstrated effectiveness in men with mild to severe ED, regardless of severity, etiology, or age. One major characteristic that may distinguish tadalafil from other oral PDE-5 inhibitors is its extensive duration of effect. Tadalafil has a therapeutic duration of up to 36 hours that may allow patients to engage in sexual activity at their own convenience rather than in a limited time period. This, along with other clinical and practical advantages, should make tadalafil an attractive alternative to currently available treatments options. This article summarizes the pharmacology, pharmacokinetics, adverse effects, and clinical efficacy of tadalafil.
Evaluation of Inhaler Technique Using the Aerosol Inhalation Monitor
Authors: Sarvis Carrie A. , Tice Angela L. , Plake Kimberly S.
Published: September 2004

The objective of this study is to determine if the Aerosol Inhalation Monitor (AIM) can assist patients in learning correct inhaler technique and assess retention. A 9-month study was conducted in 5 Midwest pharmacies. Patients were eligible if they had filled a prescription for a metered-dose inhaler within 6 months. Consenting patients demonstrated their inhaler technique using the AIM. If they used improper technique, patients were trained and allowed to retry. Positive test patients (2 consecutive proper technique demonstrations without aid of the gauges) were assessed in 2 to 3 weeks for retention. Of 33 patients, 2 used their inhaler correctly without training. After 2 training periods, 48.5% of these patients failed to demonstrate correct technique. The AIM can assist pharmacists in inhaler technique training and can promote partnerships in the care of asthma patients by determining the need for spacers, alternative delivery methods, or further training.
Temporizing with Time Wars
Authors: Kettler David , Loader Colin
Published: September 2004

Karl Mannheim’s orientations to time can be plotted between subjectivist and objectivist extremes. The latter corresponds to social engineering, while the former offers the context in which Mannheim uses Hobbes’s primaeval war to imagine the chaotic struggle over time that he hopes to escape. Mannheim’s distinctive achievement is ‘dynamic sociology’, an experimental approach marked by the recognition not only of historicity in social phenomena and concepts but also of the opportunities thereby provided for clarifying meaning on terms congruent with the experiences of contemporary humankind. Mannheim’s initial statement of ‘dynamic sociology’ is refined by his better-known studies of generations, ideologies, and utopias, which specify his awareness of co-existent multiple time worlds. Coordination is left to ad hocmediation. This does not answer Mannheim’s deepest fears and wishes, but he has the discipline to settle for less.
Social Policy and Time
Authors: Fitzpatrick Tony
Published: September 2004

Time is crucial to the implementation, operation and effectiveness of social policies, yet the subject has often treated the meaning of time as theoretically unproblematic. It focuses more upon what policies do and less upon the contexts within which the practices and assumptions of social actors are embedded. The article offers a more sophisticated theoretical account of time upon which is based an exploration of the main temporal features of welfare capitalism. It then goes on to examine three recent and prominent research projects in order to show how and why they fail to incorporate a convincing social theory of time.
From Negotiation to Implementation
Authors: PÈlisse JÈrÙme
Published: September 2004

In 1998, and then again in 2000, the French government adopted laws designed to reduce working time to 35 hours a week. This article will deal with two questions concerning this legislative process, which had already been anticipated by a 1996 law on the collective reduction of working time. The first of these questions bears on the originality of the role of the State based on the co-production of legal norms, a process in which the collective bargaining plays a significant part. In this case it is how the law is designed that is under scrutiny. The second question is directed towards the implementation of the law, and involves the exploitation of part of an empirical study of negotiations and applications at a company level. Thought is given to the way in which the rules are applied and the thesis is put forward that the implementation of legal rulings blurs traditional distinctions, between, for example, individual and collective labour law, and gives rise to questions as to the ways in which company self-regulation can develop.
Time Enough to Work
Authors: Farmer Steven , Seers Anson
Published: September 2004

This article frames an individual-level theoretical framework for the application of McGrath and Kelly’s (1986) social entrainment model to employee task work from a motivation theory perspective. We review theoretical constructs and empirical research findings that may elucidate how social entrainment shapes the direction, level, and persistence of efforts of individuals at work. We present propositions to guide research on motivational factors in task entrainment, and present suggestions for future elaborations and extensions of our theoretical framework for the temporal features of task work at the group level of analysis.
Visuality, Dromology and Time Compression
Authors: Bartram Rob
Published: September 2004

This article presents a case for retheorizing visual culture, by establishing conceptual links between visuality, dromology and time compression. More specifically, it establishes the mutually constitutive relationship forged between visuality and the Western cultural imperative to compress the transmission time delay of visualizing technologies. I argue that the Western cultural pursuit of ubiquitous and simultaneous vision not only creates a new form of ocularcentrism, but generates potentially detrimental consequences for ‘human relations’ and diminishes human control over democratic processes. The article is enriched and focused by drawing upon the recent work of Paul Virilio. Virilio’s phenomenologically inspired critique of visualizing technology prompts us to rethink visuality as an active, embodied practice constituting important lived experiences.
From Time to Action
Authors: Weik Elke
Published: September 2004

Although many authors in the field of sociology and social theory have integrated temporal features into their theories, there is still a lack of theories based ontime. This is mostly due to the complexity of the phenomenon of time, which not only produces a number of paradoxes, but also spans the complete realm of the natural and social sciences. Moreover, time is often conceptualized in its common sense, Newtonian shape, thus ignoring major theoretical developments of the last century. One philosopher who has attempted to address these shortcomings is A. N. Whitehead. The present contribution draws on his philosophy in order to develop a theory of action based on a post-relativity concept of time.