bluuebunny/crossref_metadata_2025 huggingface dataset:
Venous thromboembolism during pregnancy is not associated with persistent elevated activated protein C (APC) sensitivity ratio based on the endogenous thrombin potential
Authors: Gerhardt Andrea , Kluft Cornelis , Scharf Rüdiger E. , Zotz Rainer B.
Published: January 2005

Women who are using oral contraceptives can acquire APC resistance, measured by the effect of APC on the endogenous thrombin potential (ETP). The objective of our study was to examine whether persistentAPC resistance determined with an ETP-based normalized APC sensitivity ratio (nAPCsr) is a risk marker for venous thromboembolism in women with pregnancy-associated thromboembolism. We determined the activities of antithrombin, protein C, protein S, and performed a genetic analysis of factor V Leiden G1691A, prothrombin mutation G20210A, and methylenetetrahydrofolate reductase mutation (MTHFR C677T) in 65 women with venous thromboembolism during pregnancy or the puerperium and in 114 normal women. A significantly (p<0.05) higher nAPCsr was present in normal women using hormones, in younger women (≤ 45 yrs), and in women with carrier status of factorV Leiden. In normal women without factor V Leiden a significant (p< 0.05) negative correlation of nAPCsr with age (r= –0.39),antithrombin activity (r= –0.38),protein S activity (r= –0,26),and a significant positive correlation with hormone intake (r= 0.36) was present. nAPCsr is influenced by several coagulation parameters, which are modified by the use of oral contraceptives. Consequently, a multivariate analysis of our data did not show a significant association of nAPCsr to venous thromboembolism, neither as a continuous variable (odds ratio 0.8, 95% CI 0.6–1.1, p=0.10) nor using a cutoff value (nAPCsr cut-off 3.1: odds ratio 1.2, 95% CI 0.3–5.3, p=0.77). Our study demonstrates that nAPCsr is not a risk marker for pregnancy-associated venous thromboembolism.
Antibodies to N-homocysteinylated albumin as a marker for earlyonset coronary artery disease in men
Authors: Undas Anetta , Jankowski Milosz , Twardowska Magdalena , Padjas Agnieszka , Jakubowski Hieronim , Szczeklik Andrzej
Published: January 2005

N-homocysteinylated (Nε-Hcy) proteins and corresponding antibodies have recently been discovered in humans and animals. Increased autoimmune response to Nε -Hcy-proteins has been reported in stroke patients. The aim of the present study was to investigate whether antibodies against N-homocysteinylated albumin are associated with coronary artery disease (CAD).We studied 88 male patients aged 50 years or under with angiographically documented CAD and 100 age-matched apparently healthy men as controls. Serum levels of IgG antibodies against Nε-Hcy-albumin were determined using an enzymelinked immunosorbent assay. Seropositivity to anti-Nε -Hcy-albumin antibodies was 5-fold more frequent in CAD patients than in controls (52.3 % vs 10.0 %; p<0.0001). Plasma Hcy levels in CAD patients were also significantly higher in the former than in the latter group (medians, 13.0 μ M vs 12.1 μ M; p=0.026). Importantly, 41.2% of subjects with plasma total Hcy >14.5 mM were seropositive compared with 25.5 % of normohomocysteinemic individuals (p=0.048).There was a weak correlation between anti-Nε-Hcy-albumin antibodies and Hcy levels (r=0.16; p=0.03). By multivariate logistic regression analysis, seropositivity to anti-Nε-Hcy-albumin antibodies was an independent predictor of early CAD (OR, 14.82; 95% CI, 4.47 to 49.19; p=0.00002). Interestingly, anti-Nε-Hcy-albumin antibodies were associated with C-reactive protein levels (r=0.24; p=0.002). Seropositivity to anti-Nε-Hcy-albumin antibodies showed no association with the MTHFR C677T polymorphism. Our results suggest that seropositivity to antibodies against Nε-homocysteinylated albumin is associated with early-onset CAD. An autoimmune response to Nε-Hcy-albumin may represent a novel mechanism involved in the early development of CAD.
Effect of ethnicity and gender on the incidence of venous thromboembolism in a diverse population in California in 1996
Authors: Zhou Hong , Murin Susan , Harvey Danielle , White Richard H.
Published: January 2005

There have been very few studies that have describe the epidemiology of first-time venous thromboembolism (VTE) in a large, ethnically diverse population. The California Discharge Data Set was used to identify a cohort of cases with incidentVTE in 1996. Cases associated with traditional provoking risk factors were identified and the remaining cases were labeled as idiopathicVTE. Direct standardization using census information was performed to compare incidence rates across races, gender, and gender within race. There were 21,002 cases with incident VTE in 1996, a crude incidence of 90 events per 100,000 adults. Thirty percent of all VTE events were pulmonary embolism. The directly standardized incidence per 100,000 California adults was 93 ± 1.7 ( ± 95% CI) in women, 85 ± 1.7 in men, 103 ± 2.1 in Caucasians, 138 ± 6.5 in African- Americans, 61 ± 2.8 in Hispanics and 29 ± 2.4 in Asian-Pacific Islanders (p<0.001 for all inter-group comparisons). After adjusting for misclassification of race, the incidence of VTE per 100,000 was 104 in Caucasians, 141 in African- Americans, 55 in Hispanics, and 21 in Asian/Pacific-Islanders. The incidence of idiopathic VTE was significantly lower among both Hispanics and Asian/Pacific-Islanders (p<0.001) than Caucasians or African-Americans. African-Americans were more likely, and Hispanics less likely, to be diagnosed with idiopathic pulmonary embolism compared to Caucasians. The 28 day case-fatality rate among cases with idiopathic VTE was 2%, and it was significantly higher among African-Americans (4.1%) compared to Caucasians (1.8%, p<0.001).There are important differences in the incidence of total and idiopathicVTE and in the proportion of events diagnosed as pulmonary embolism among each of the major racial/ethnic groups in California. Further research is needed to explain these observed differences among the different racial/ethnic group.
Gender differences in the administration of prophylaxis to prevent deep venous thrombosis
Authors: Kucher Nils , Tapson Victor F. , Quiroz Rene , Mir Samy S. , Morrison Ruth B. , McKenzie David , Goldhaber Samuel Z. ,   for the DVT FREE Steering Committee
Published: January 2005

We investigated gender differences in the prescription of prophylaxis against deep vein thrombosis (DVT) in 2,619 patients who developed acute DVT while being hospitalized for reasons other than DVT or were diagnosed with acute DVT as outpatients but who had been hospitalized within 30 days prior to DVT diagnosis. Men were 21% more likely than women to receive prophylaxis (OR 1.21, 95% CI 1.03–1.43; p = 0.021) after adjusting for DVT risk factors, including surgery, trauma, prior DVT, age, and cancer.
Circulating endothelial cells
Authors: Woywodt Alexander , Bertolini Francesco , Bull Todd M. , Buyon Jill P. , Clancy Robert M. , Haubitz Marion , Hebbel Robert P. , Lip Gregory Y. H. , Mancuso Patrizia , Sampol Jose , Solovey Anna , Dignat-George Françoise , Blann Andrew D.
Published: January 2005

Recent research has recognised new populations of non-hematopoïetic cells in the blood. One of these, circulating endothelial cells (CECs), often defined by the expression of membrane glycoprotein CD146, are rarely found in the blood in health, but raised numbers are present in a wide variety of human conditions, including inflammatory, immune, infectious, neoplastic and cardiovascular disease, and seem likely to be evidence of profound vascular insult. An additional population are endothelial progenitor cells, defined by the co-expression of endothelial and immaturity cell surface molecules and also by the ability to form colonies in vitro. Although increased numbers of CECs correlate with other markers of vascular disease, questions remain regarding the precise definition, cell biology and origin of CECs. For example, they may be damaged, necrotic or apopototic, or alive, and could possess procoagulant and/or proinflammatory properties. However, since these cells seem to be representative of in situ endothelium, their phenotype may provide useful information. Indeed, whatever their phenotype, there is growing evidence that CECs may well be a novel biomarker, the measurement of which will have utility in various clinical settings related to vascular injury. Despite this promise, progress is impeded by the diversity of methodologies used to detect these cells. Accordingly, results are sometimes inconclusive and even conflicting. Nevertheless, increased CECs predict adverse cardiovascular events in acute coronary syndromes, suggesting they may move from being simply a research index to having a role in the clinic. The objective of the present communication is to condense existing data on CECs, briefly compare them with progenitor cells, and summarise possible mechanism(s) by which they may contribute to vascular pathology.
The NO/cGMP pathway inhibits Rap1 activation in human platelets via cGMP-dependent protein kinase I
Authors: Danielewski Oliver , Schultess Jan , Smolenski Albert
Published: January 2005

The NO/cGMP signalling pathway strongly inhibits agonist-induced platelet aggregation. However, the molecular mechanisms involved are not completely defined. We have studied NO/cGMP effects on the activity of Rap1, an abundant guanine-nucleotidebinding protein in platelets. Rap1-GTP levels were reduced by NO-donors and activators of NO-sensitive soluble guanylyl cyclase. Four lines of evidence suggest that NO/cGMP effects are mediated by cGMP-dependent protein kinase (cGKI): (i) Rap1 inhibition correlated with cGKI activity as measured by the phosphorylation state ofVASP, an established substrate of cGKI, (ii) 8-pCPT-cGMP, a membrane permeable cGMP-analog and activator of cGKI, completely blocked Rap1 activation, (iii) Rp- 8pCPT-cGMPS, a cGKI inhibitor, reversed NO effects and (iv) expression of cGKI in cGKI-deficient megakaryocytes inhibited Rap1 activation. NO/cGMP/cGKI effects were independent of the type of stimulus used for Rap1 activation. Thrombin-,ADPand collagen-induced formation of Rap1-GTP in platelets as well as turbulence-induced Rap1 activation in megakaryocytes were inhibited. Furthermore, cGKI inhibited ADP-induced Rap1 activation induced by the G α i -coupled P2Y12 receptor alone, i.e. independently of effects on Ca2+-signalling. From these studies we conclude that NO/cGMP inhibit Rap1 activation in human platelets and that this effect is mediated by cGKI. Since Rap1 controls the function of integrin α IIbβ 3 , we propose that Rap1 inhibition might play a central role in the anti-aggregatory actions of NO/cGMP.
A reunification of the US (“NIH”) and International Unit into a single standard for Thrombin
Authors: Whitton Colin , Sands Dawn , Lee Timothy , Chang Andrew , Longstaff Colin
Published: January 2005

The existence of two different units forThrombin in widespread international use has caused confusion for many years. The holders of the WHO International Standard (IS) for Alpha Thrombin and the US Standard (also known as the “NIH Standard”) now report on a collaboration to reunite the International Unit (IU) and the US unit (“NIH unit”).A study was organised involving 25 laboratories in 15 countries to investigate the possibility of preparing a common Standard with a common unit and to investigate aspects of methodology that cause divergence of results using the IS and US Standard. Laboratories were asked to measure the potency of two candidate replacement standards (C, 01/578 and D, 01/580), and potencies were calculated relative to both the existing US Standard (lot J) and the IS (89/588). Data analysis of a total of 128 assays indicated that sample D would make an ideal replacement joint Standard with a potency of 110 IU/ampoule (equivalent to 110 US units per ampoule) based on data from clotting assays. No significant differences in results were observed using fibrinogen of human or bovine origin, or using human plasma. Comparisons of chromogenic and clotting assays indicated that sample D had a similar high proportion of alpha thrombin to the current IS for Alpha Thrombin (89/588). Sample D was adopted as the IS for Thrombin (01/580) and the US Standard (lot K) with a potency of 110 IU/ampoule.
Proatherosclerotic Mechanisms Involving Protein Kinase C in Diabetes and Insulin Resistance
Authors: Rask-Madsen Christian , King George L.
Published: January 2005

In diabetes and insulin resistance, activation of protein kinase C (PKC) in vascular cells may be a key link between elevated plasma and tissue concentrations of glucose and nonesterified fatty acids and abnormal vascular cell signaling. Initial studies of PKC activation in diabetes focused on microvascular complications, but increasing evidence supports that PKC plays a role in several mechanisms promoting atherosclerosis. This review explains how PKC is thought to be activated in diabetes and insulin resistance through de novo synthesis of diacylglycerol. Furthermore, the review summarizes studies that implicate PKC in promoting proatherogenic mechanisms or inhibiting antiatherogenic mechanisms, including studies of endothelial dysfunction; gene induction and activation of vascular NAD(P)H oxidase; endothelial nitric oxide synthase expression and function; endothelin-1 expression; growth, migration, and apoptosis of vascular smooth muscle cells; induction of adhesion molecules; and oxidized low-density lipoprotein uptake by monocyte-derived macrophages.
Vangl2
Acts via RhoA Signaling to Regulate Polarized Cell Movements During Development of the Proximal Outflow Tract
Authors: Phillips Helen M. , Murdoch Jennifer N. , Chaudhry Bill , Copp Andrew J. , Henderson Deborah J.
Published: January 2005

Loop-tail
(
Lp
) mice develop double outlet right ventricle and aortic arch defects, and the defects are caused by mutations in the
Vangl2
gene.
Vangl2
mRNA is found in the outflow tract myocardium, including the myocardializing cells that migrate into the outflow tract cushions. Analysis of muscularization of the outflow tract septum showed that this process is compromised in
Lp/Lp
fetuses. Vangl2 is a component of the noncanonical Wnt, planar cell polarity (PCP) pathway that signals via RhoA. We therefore looked for evidence of polarization in myocardializing cells. In wild-type fetuses, myocardializing cells extend lamellipodia and filopodia into the cushion tissue and reorganize their actin cytoskeleton from a cortical form to stress fibers; behaviors that are characteristic of polarized cells. In contrast,
Lp/Lp
littermates do not extend lamellipodia or filopodia into the cushion tissue, and their actin remains in a cortical form, suggesting that polarized cell migration of myocardializing cells is inhibited in
Lp/Lp
. Several other components of the PCP pathway are also localized in the outflow tract myocardium. In wild-type fetuses, the myocardializing cells coexpress RhoA and one of its downstream mediators, ROCK1. RhoA expression is disrupted in
Lp/Lp
, and is lost from the myocardial-cushion tissue interface, including the presumptive myocardializing cells. These data suggest that Vangl2 is required for the polarization and movement of myocardializing cells into the outflow tract cushions, and that RhoA and ROCK1 are downstream mediators of the PCP signaling pathway in the developing outflow tract.
A Defect of Neuronal Nitric Oxide Synthase Increases Xanthine Oxidase-Derived Superoxide Anion and Attenuates the Control of Myocardial Oxygen Consumption by Nitric Oxide Derived From Endothelial Nitric Oxide Synthase
Authors: Kinugawa Shintaro , Huang Harer , Wang Ziping , Kaminski Pawel M. , Wolin Michael S. , Hintze Thomas H.
Published: January 2005

Endothelial nitric oxide synthase (eNOS) plays an important role in the control of myocardial oxygen consumption (MVO
2
) by nitric oxide (NO). A NOS isoform is present in cardiac mitochondria and it is derived from neuronal NOS (nNOS). However, the role of nNOS in the control of MVO
2
remains unknown. MVO
2
in left ventricular tissues from nNOS
−/−
mice was measured in vitro. Stimulation of NO production by bradykinin or carbachol induced a significant reduction in MVO
2
in wild-type (WT) mice. In contrast to WT, bradykinin- or carbachol-induced reduction in MVO
2
was attenuated in nNOS
−/−
.
S
-methyl-
l
-thiocitrulline, a potent isoform selective inhibitor of nNOS, had no effect on bradykinin-induced reduction in MVO
2
in WT. Bradykinin-induced reduction in MVO
2
in eNOS
−/−
mice, in which nNOS still exists, was also attenuated. The attenuated bradykinin-induced reduction in MVO
2
in nNOS
−/−
was restored by preincubation with Tiron, ascorbic acid, Tempol, oxypurinol, or SB203850, an inhibitor of p38 kinase, but not apocynin. There was an increase in lucigenin-detectable superoxide anion (O
2
−
) in cardiac tissues from nNOS
−/−
compared with WT. Tempol, oxypurinol, or SB203850 decreased O
2
−
in all groups to levels that were not different from each other. There was an increase in phosphorylated p38 kinase normalized by total p38 kinase protein level in nNOS
−/−
compared with WT mice. These results indicate that a defect of nNOS increases O
2
−
through the activation of xanthine oxidase, which is mediated by the activation of p38 kinase, and attenuates the control of MVO
2
by NO derived from eNOS.
Albumin Treatment Reduces Neurological Deficit and Protects Blood–Brain Barrier Integrity After Acute Intracortical Hematoma in the Rat
Authors: Belayev Ludmila , Saul Isabel , Busto Raul , Danielyan Kristine , Vigdorchik Alexey , Khoutorova Larissa , Ginsberg Myron D.
Published: January 2005

Background and Purpose—

Acute intracerebral hemorrhage (ICH) is a common and severe form of stroke. To date, medical management of ICH has had scant impact on morbidity and mortality. Because albumin therapy is markedly neuroprotective in preclinical models of ischemic stroke, and because ischemic and hemorrhagic stroke share several common injury mechanisms, we hypothesized that albumin therapy might also benefit ICH.

Methods—

Acute intracortical hematoma was produced in anesthetized, normothermic rats by the single stereotaxic injection of 50 μL of autologous, nonheparinized whole blood over 5 minutes. Separate animal groups were treated either with 25% human albumin, 1.25 g/kg, or with intravenous saline vehicle at 60 minutes after ICH. Neurobehavior was quantified sequentially over the next 2 to 7 days. Damage to the blood–brain barrier was assessed at 2 days after ICH by fluorometric measurement of Evans blue extravasation in dissected brain regions.

Results—

High-grade neurological deficits were present in all rats at 50 minutes after ICH (score 10.3±0.2, mean±SEM [maximal score 12]). Albumin-treated rats showed improved neuroscores relative to saline-treated animals beginning within hours of treatment and persisting throughout the 7-day survival period. At 3 and 7 days, mean total neuroscores of the albumin group were 38% to 43% lower than in saline-treated animals. Perihematomal Evans blue discoloration was readily evident in saline-treated ICH rats but was reduced by albumin treatment. Hemispheric Evans blue content ipsilateral to the hematoma was reduced by 49% by albumin treatment (albumin 93.9±13.3 versus saline 184.7±33.7 mg/g,
P
<0.05). Hematoma volume and brain swelling were not affected by albumin treatment.

Conclusions—

Prompt albumin therapy improves neurological function and blood–brain barrier integrity after acute intracortical hematoma. These observations have important potential clinical implications.
Blood Pressure and Vessel Recanalization in the First Hours After Ischemic Stroke
Authors: Mattle Heinrich P. , Kappeler Liliane , Arnold Marcel , Fischer Urs , Nedeltchev Krassen , Remonda Luca , Jakob Stephan M. , Schroth Gerhard
Published: January 2005

Background and Purpose—

Transient elevation of arterial blood pressure (BP) is frequent in acute ischemic stroke and may help to increase perfusion of tissue jeopardized by ischemia. If this is true, recanalization may eliminate the need for this BP elevation.

Methods—

We analyzed BP in 149 patients with acute ischemic stroke on admission to the hospital and 1 and 12 hours after intraarterial thrombolysis. BP values of patients with adequate recanalization were compared with BP values of patients with inadequate recanalization. Recanalization was determined on cerebral arteriography after thrombolysis using thrombolysis in myocardial infarction grades.

Results—

Systolic, mean, and diastolic arterial BP decreased significantly from admission to 12 hours after thrombolysis in all patients (
P
<0.001). Before thrombolysis, patients with adequate and inadequate recanalization showed equal systolic (147.4 and 148.0 mm Hg), mean (102.1 and 104.1 mm Hg), and diastolic (79.5 and 82.1 mm Hg) BP values. Twelve hours after thrombolysis, patients with adequate recanalization had lower values than those with inadequate recanalization (systolic BP, 130 versus 139.9 mm Hg; mean BP, 86.8 versus 92.2 mm Hg; and diastolic, BP 65.2 versus 68.3 mm Hg). Two-way repeated ANOVA analysis showed a significant group × time interaction for systolic BP, indicating a larger systolic BP decrease when recanalization succeeded (
P
=0.019).

Conclusion—

The course of elevated systolic but not diastolic BP after acute ischemic stroke was found to be inversely associated with the degree of vessel recanalization. When recanalization failed, systolic BP remained elevated longer than when it succeeded.
Ethnic Disparities in Stroke
Authors: Stansbury James P. , Jia Huanguang , Williams Linda S. , Vogel W. Bruce , Duncan Pamela W.
Published: January 2005

Background and Purpose—

Evidence for ethnic disparities in stroke incidence, severity, and mortality has continued to mount in recent years. However, the picture for disparities in acute management and rehabilitation remains more ambiguous. The objective of this report is to summarize current evidence from stroke epidemiology and studies focusing on disparities in stroke care and disability, suggesting courses for action.

Methods—

A comprehensive search of current literature on ethnic/racial variation in stroke incidence, mortality, and severity, as well as acute and postacute patient care was performed.

Results—

Recent evidence unambiguously reaffirms a greater burden of disease in stroke, greater mortality, and greater severity of strokes for blacks. Evidence for disparities in acute and postacute care is less conclusive, as is the evidence for disparities among other ethnic groups. Evidence for health disparities in stroke care across settings, regions, and the continuum of care varies considerably.

Conclusions—

Minority ethnic groups have higher rates or more severe stroke, but variations in prognosis for clinical outcomes other than mortality remain less certain. There is considerable need for more studies that take into account regional ethnic variations in treatment and outcomes, and for better documentation of stroke outcomes among groups in addition to blacks. Dealing with ethnic disparities in stroke will be served by sustained attention to quality improvement in high-impact areas in stroke care, complemented by initiatives that promote cultural competence.
Estradiol Regulates Angiopoietin-1 mRNA Expression Through Estrogen Receptor-α in a Rodent Experimental Stroke Model
Authors: Ardelt Agnieszka A. , McCullough Louise D. , Korach Kenneth S. , Wang Michael M. , Munzenmaier Diane H. , Hurn Patricia D.
Published: January 2005

Background and Purpose—

Female, compared with male, animals are protected from cerebral ischemic injury. Physiological concentrations of 17β-estradiol (E2) reduce damage in experimental stroke. E2 augments angiogenesis in reproductive organs and noncerebral vascular beds. We hypothesized that E2 protects brain in stroke through modulation of angiogenesis. We quantified molecular markers of angiogenesis and capillary density before and after unilateral middle cerebral artery occlusion (MCAO).

Methods—

Female animals were ovariectomized, treated with 25 μg E2 or placebo implants, and subjected to 2-hour MCAO and 22 hours of reperfusion. Brain angiopoietin-1 (Ang-1), Ang-2, Tie-1, Tie-2, vascular endothelial growth factor (VEGF), VEGF R1, and VEGF R2 mRNA levels were determined by RNAse protection assays, and CD31-positive vessels were counted.

Results—

E2, but not ischemia, upregulated cerebral Ang-1 mRNA by 49%. Capillary density was higher in the brains of E2-treated animals. In estrogen receptor-α knockout (ERKO) mice, E2-mediated induction of Ang-1 mRNA was absent relative to wild-type littermates.

Conclusions—

These results suggest that E2 increases Ang-1 and enhances capillary density in brain under basal conditions, priming the MCA territory for survival after experimental focal ischemia.
Visual signaling and reproductive biology in a nocturnal treefrog, genus Hyla (Anura: Hylidae)
Authors: Hartmann Paulo , Hartmann Marília , Haddad Célio
Published: January 2005

We investigated reproductive activity, courtship behavior, call structure, body size, clutch size, oviposition site, and reproductive mode of Hyla sp. (aff. ehrhardti). Males called in all months, but showed a peak of activity during the rainy season. Three pair formations were observed and courtship involved stereotyped behavioral sequences, including visual signaling. Males emitted three different vocalization types: advertisement calls, courtship calls, and a vocalization of unknown function. Females attained larger body sizes than males and deposited an average of 74.5 unpigmented eggs per clutch. Early larval stages are aquatic but restricted to water in constructed subterranean nests; subsequent to flooding of nests, exotrophic tadpoles live in ponds or streams. Courtship behavior in Hyla sp. (aff. ehrhardti) is complex and the diverse repertoire of limb movements, exhibited by males, probably provide visual stimuli to females in this nocturnal treefrog. Hyla sp. (aff. ehrhardti) belongs to the H. albomarginata group. Considering the reproductive modes in this group, the complexes of H. albosignata and of H. albofrenata can be considered more close related to each other than to the H. albomarginata complex.
A Consumer-Behavior Perspective on Intimate Partner Violence
Authors: Stephens Debra Lynn , Hill Ronald Paul , Gentry James W.
Published: January 2005

This research examines women’s experiences of and responses to intimate partner violence using the perspective of the extended self. From in-depth interviews with a demographically diverse group of women in the United States, the primary theme to emerge was that chronic abuse is experienced as the male partner’s ongoing campaign to incorporate the abused woman into his extended self, by appropriating or destroying the aspects of her that give her autonomy. The most important implication for agencies serving abused women is that many of their clients are faced with the daunting task of repairing or reconstructing their core and extended selves, a process that may necessitate the long-term commitment of agency resources without the imposition of restricted, institutionally imposed identities that would serve only to impede clients’ reclamation of their autonomy.
The Impact of Genetic Information on Policy and Clinical Practice
Authors: Abel Elizabeth , Horner Sharon D. , Tyler Diane , Innerarity Sheryl A.
Published: January 2005

This article discusses genetics-related policy issues that have an impact on health care systems, health care providers, and their patients: privacy, mass screening, family screening, and knowledge dissemination. Access, cost, and ethical implications are important discussant points for each of these genetic-related policy issues. Embedded in the issue of privacy are concerns of insurability, confidentiality, and discrimination. The public health policy implications related to mass screening programs include efficacy of the screening tests, availability of primary and secondary interventions, access, costs, and program evaluation. Policy issues for family screening are similar to mass screening, with added concerns about privacy and availability of adequate resources, including health care providers and counselors trained in genetics. Knowledge dissemination is critical to maintaining currency of clinical information and applications of genetic technologies and treatments. As genetic information expands, the need for knowledge dissemination will increase. The importance of advanced practice nurses’ involvement in these policy issues is discussed.
Striving for Congruence: The Interconnection Between Values, Practice, and Political Action
Authors: Murphy Nancy , Canales Mary K. , Norton Sally A. , DeFilippis Jeannette
Published: January 2005

In the current U.S. health care system, both good health and a higher quality of health care are more likely to be experienced by those who have access to money, power, and privilege. Consequently, serious health disparities exist between the rich and poor, White people and people of color, and men and women. The American Association of Colleges of Nursing (AACN) has made explicit the values that form the cornerstone of professional nursing: altruism, autonomy, human dignity, integrity, and social justice. In this article, the authors explore the interconnections between values explicated by the AACN and nursing practices and policies. The authors draw on work in the field of pain management, cultural competency, and harm reduction as exemplars of this interconnection. The authors propose that through political action, nurses can strive for congruence between their professional values, practice, and policies and subsequently effect change and improve health outcomes.
The Culture of Safety
Authors: Milstead Jeri A.
Published: January 2005

A new paradigm is emerging as a result of the Institute of Medicine reports on medical errors. The Joint Commission on Accreditation of Healthcare Organizations, state licensing boards, academic institutions, and health care businesses are considering their missions and goals vis-à-vis a culture of patient safety. The author presents three examples that converge to indicate that the culture of safety represents a paradigm shift for the education, delivery, funding, and evaluation of health and medical care. The system, not the individual, must be recognized as the problem; reprimanding the person who committed an error is not a solution. Health care delivery systems that reduce this potential for error must be created.
The Influence of a Change in Medicare Reimbursement on the Effectiveness of Stage III or Greater Decubitus Ulcer Home Health Nursing Care
Authors: Eaton Melody K.
Published: January 2005

This study was designed to describe and evaluate the influence of a change in a Medicare reimbursement on the effectiveness of home health nursing care for stage III or greater decubitus ulcer patients. This health policy originated from the Balanced Budget Act (BBA) of 1997 and took its full effect with initiation of the Prospective Payment System (PPS) on October 1, 2000. A quantitative quasi-experimental design used OASIS data from the state of Virginia to evaluate 555 stage III or greater decubitus ulcer patients, age 65 or older. Comparisons were investigated between pre-PPS, 2000, and post-PPS, 2001, outcomes related to reported ulcer healing, lengths of stay, and discharge disposition. Results demonstrated significant differences for the outcomes studied. In addition, sanitation, ulcer healing, and discharge disposition were linked as predictors for length of stay. Results demonstrated that PPS has affected nursing care effectiveness for stage III or greater decubitus ulcer home health patients.
The Health Bus: Healthcare for Marginalized Populations
Authors: Daiski Isolde
Published: January 2005

The Health Bus, an innovative outreach program, serves the marginalized population of a large Canadian city. In this article, a needs assessment/evaluation study of its services is discussed. Barriers to mainstream healthcare and solutions are examined. This study was qualitative, descriptive, and exploratory and surveyed 58 client volunteers of the program through semistructured interviews and focus groups. Thematic analysis of data was carried out. The Health Bus was found to provide basic healthcare and supplies effectively. Clients value respectful treatment, competency of healthcare professionals, and accessibility, whereas disrespectful treatments and lack of transportation are barriers to mainstream healthcare. A conclusion of this study is that Health Bus services should be expanded with clients’ input. Mainstream institutions need flexibility and a change in attitudes toward the marginalized.
Mid-career Opportunity for Nurses: Learning and Growing Through a Health Policy Internship
Authors: Falk Nancy L.
Published: January 2005

This article shares the experience and insight gained from a mid-career policy internship offered through the National Academy of Social Insurance. The author is a nursing doctoral student who interned on veterans’ long-term care projects with the Health Care Team at the Government Accountability Office in Washington, D.C. As the average age of nurses continues to rise and society faces nursing shortages, new opportunities and solutions must be considered to keep aging nurses in the workforce. A mid-career internship is a very real option that will benefit health policy organizations, the nursing community, and aging nurses.
Physiological relevance of antigen presentasome (APS), an acquired MHC/costimulatory complex, in the sustained activation of CD4+ T cells in the absence of APCs
Authors: Zhou Jun , Tagaya Yutaka , Tolouei-Semnani Roshanak , Schlom Jeffrey , Sabzevari Helen
Published: January 2005

T-cell interaction with antigen-presenting cells (APCs) results in activation and clonal expansion of naive T cells. CD80 expression/acquisition in T cells has been implicated in disease processes in patients with rheumatoid arthritis and multiple myeloma and patients infected with HIV. Our previous data indicate that antigen-specific activation of naive T cells results in T-cell acquisition of CD80 molecules from APCs. However, the functional relevance of the acquired CD80 by T cells in signal pathways has remained unresolved. This study aims to define for the first time the role of acquired CD80 in T-cell clonal expansion. We demonstrate the following: (1) T cells, upon CD80 acquisition, sustain their proliferative response in the absence of APCs; (2) T cells that acquire CD80 sustain the activity of transcriptional factors such as nuclear factor-κB (NFκB) and activator protein-1 (AP1) for 24 hours after separation from APCs and up-regulate signal transducer and activator of transcription-5 (Stat5) in the absence of APCs or exogenous signal 1; and (3) maintenance of these signals results in unique cytokine production. Collectively, our data support the unique concept that naive T cells sustain their activation by removing “antigen presentasome” (APS; eg, antigen-presenting complex) from APCs, thereby releasing the constraint of APC requirement for further activation. (Blood. 2005;105: 3238-3246)
Allogeneic hematopoietic cell transplantation for infants with acute lymphoblastic leukemia
Authors: Sanders Jean E. , Im Ho Joon , Hoffmeister Paul A. , Gooley Ted A. , Woolfrey Ann E. , Carpenter Paul A. , Andrews Robert G. , Bryant Eileen M. , Appelbaum Frederick R.
Published: January 2005

The role of transplantation in infants with acute lymphoblastic leukemia (ALL) is not defined. We analyzed results of 40 infants diagnosed before age 12 months who received a hematopoietic cell transplant (HCT) between July 1982 and February 2003 in first complete remission (CR1; n = 17), CR2/3 (n = 7), or relapse (n = 16). Patients were conditioned with cyclophosphamide with total body irradiation (n = 39) or busulfan (n = 1). Donors were matched related (n = 8), mismatched related (n = 16), or unrelated (n = 16). Graft-versus-host disease (GVHD) prophylaxis was methotrexate or cyclosporine (n = 7) or methotrexate plus cyclosporine (n = 33). Thirty-nine patients engrafted, 20 developed acute GVHD, and 7 developed chronic GVHD. Sixteen patients relapsed and 7 died of other causes. Patients in CR1 had disease-free survival (DFS) of 76% compared with 45% for CR2/CR3 and 8% for relapse (P < .001). Of 33 patients with cytogenetic data, 26 (79%) had MLL gene rearrangement. Fourteen of these 26 were in CR1 and 11 survive in remission. Outcome was associated with phase of disease, but having the MLL gene was not a factor predictive of outcome. Late effects included growth and other hormone deficiencies. These data demonstrate that infants with ALL and MLL gene have excellent DFS when they received transplants in CR1, and consideration for transplantation in CR1 is warranted.
Impact of TCR status and genotype on outcome in adult T-cell acute lymphoblastic leukemia: a LALA-94 study
Authors: Asnafi Vahid , Buzyn Agnes , Thomas Xavier , Huguet Francoise , Vey Norbert , Boiron Jean-Michel , Reman Oumedaly , Cayuela Jean-Michel , Lheritier Veronique , Vernant Jean-Paul , Fiere Denis , Macintyre Elizabeth , Dombret Hervé
Published: January 2005

Patients with T-cell acute lymphoblastic leukemias (T-ALLs) within the Leucémies Aiguës Lymphoblastiques de l'Adulte-94 (LALA-94) prospective trial were treated with a 4-drug per 4-week induction, with intermediate-dose cytarabine and mitoxantrone salvage treatment for patients not achieving complete remission (CR) in 1 course. Only the latter received allografts, if possible, thus providing an informative setting for assessing early response. Representative patients with T-ALL (91 patients) were classified into surface T-cell receptor (TCR)–expressing T-ALL patients (TCRαβ+ or TCRγδ+), pre-αβ T-ALL patients (cTCRβ+, TCR–), and immature (IM) cTCRβ–, TCR– T-ALL patients; 81 patients underwent genotyping for SIL-TAL1, CALM-AF10, HOX11, and HOX11L2. Overall, CR was obtained in 81 (89%) patients; relapse rate was 62% at 4 years and overall survival (OS) rate was 38%. CR rate was significantly lower in IM T-ALL patients after 1 course (45% vs 87%; P < .001) and after salvage (74% vs 97%; P = .002), with the latter inducing a higher rate of CR (9 [64%] of 14) than initial induction. Once CR was obtained, cumulative relapse rates were similar for IM, pre-αβ, and TCR+ T-ALL patients (P = .51), but were higher in HOX11L2 (83%) and SIL-TAL1 (82%) T-ALL patients compared with other genetic subgroups (48%; P = .05). This was associated with an inferior OS for HOX11L2 T-ALLs (13% vs 47% in HOX11L2-T-ALLs; P = .009). The majority of patients with HOX11 T-ALL underwent allografting, predominantly in second CR, but were not associated with a superior OS. Both TCR and genotypic stratification can therefore contribute to risk-adapted management of adult T-ALLs.
Transglutaminase-mediated oligomerization of the fibrin(ogen) αC domains promotes integrin-dependent cell adhesion and signaling
Authors: Belkin Alexey M. , Tsurupa Galina , Zemskov Evgeny , Veklich Yuri , Weisel John W. , Medved Leonid
Published: January 2005

Interactions of endothelial cells with fibrin(ogen) are implicated in inflammation, angiogenesis, and wound healing. Cross-linking of the fibrinogen αC domains with factor XIIIa generates ordered αC oligomers mimicking polymeric arrangement of the αC domains in fibrin. These oligomers and those prepared with tissue transglutaminase were used to establish a mechanism of the αC domain–mediated interaction of fibrin with endothelial cells. Cell adhesion and chemical cross-linking experiments revealed that oligomerization of the αC domains by both transglutaminases significantly increases their RGD (arginyl–glycyl–aspartate)–dependent interaction with endothelial αVβ3 and to a lesser extent with αVβ5 and α5β1 integrins. The oligomerization promotes integrin clustering, thereby increasing cell adhesion, spreading, formation of prominent peripheral focal contacts, and integrin-mediated activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) signaling pathways. The enhanced integrin clustering is likely caused by ordered juxtaposition of RGD-containing integrin-binding sites upon oligomerization of the αC domains and increased affinity of these domains for integrins. Our findings provide new insights into the mechanism of the αC domain–mediated interaction of endothelial cells with fibrin and imply its potential involvement in cell migration. They also suggest a new role for transglutaminases in regulation of integrin-mediated adhesion and signaling via covalent modification of integrin ligands.
Airway responsiveness to hypertonic saline: dose-response slope or PD15?
Authors: de Meer G. , Marks G. B. , de Jongste J. C. , Brunekreef B.
Published: January 2005

The result of airway challenge test with hypertonic saline (HS) is expressed as the dose causing a 15% fall in forced expiratory volume in one second (FEV1; PD15). A noncensored measure, such as the dose-response slope (DRS), allows the evaluation of the risk of asthma for subjects with a fall in FEV1 <15%. The aim of this study was to assess the relationship between airway responsiveness to HS by PD15 or DRS, asthma symptoms and markers of eosinophilic inflammation.

Data on current wheeze and airway responsiveness were obtained for 1,107 children (aged 8–13 yrs). Blood eosinophils and serum eosinophil cationic protein (ECP) were assessed in subsets (n = 683 and 485). PD15 was assessed if FEV1 fell ≥15%, and the DRS was calculated for all tests. Graphs were constructed to visualise relationships with current wheeze, blood eosinophils and serum ECP. Odds ratios and Spearman's correlation coefficients were calculated to quantify these relationships.

Children with features of asthma had lower PD15 and higher DRS, and separation was most pronounced for DRS. Prevalence of current wheeze increased continuously over the entire range of DRS values. Blood eosinophils were significantly higher only for the highest values of DRS.

In conclusion, the continuous relationship between airway responsiveness and asthma symptoms is in favour of a noncensored measure of airway responsiveness, such as the dose-response slope.
Metalloproteinases and tissue inhibitors of metalloproteinases in exudative pleural effusions
Authors: Iglesias D. , Alegre J. , Alemán C. , Ruíz E. , Soriano T. , Armadans L. I. , Segura R. M. , Anglés A. , Monasterio J. , Fernández de Sevilla T.
Published: January 2005

The aim of this study was to assess the expression of several metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in exudative pleural effusions, and their relationship with inflammatory and fibrinolytic mediators in parapneumonic effusions.

The study included 51 parapneumonic effusions (30 empyema or complicated parapneumonic, 21 noncomplicated parapneumonic), 28 tuberculous, 30 malignant and 30 transudates. Inflammatory markers (tumour necrosis factor-α, interleukin-8, polymorphonuclear elastase), fibrinolytic system variables (tissue plasminogen activator (PA), urokinase PA (u-PA), plasminogen activation inhibitor (PAI)-1, PAI-2), and several MMPs (MMP-1, MMP-2, MMP-8, MMP-9) and TIMPs (TIMP-1, TIMP-2) were determined by ELISA in plasma and pleural fluid.

Elevated MMP-2 and TIMP-1 concentrations were observed in all the pleural fluid samples studied. The group of empyema or complicated parapneumonic effusions showed higher MMP-1, MMP-8 and MMP-9 concentrations than the remaining exudates. There was no correlation between MMP and TIMP levels in plasma and pleural fluid in this group of effusions. In parapneumonic effusions, MMP-1, MMP-8 and MMP-9 showed a positive correlation with the inflammatory markers and with u-PA and PAI-1. Moreover, there was a relationship between MMP-8 concentration in pleural fluid and pleural thickening at the end of treatment.

In conclusion, elevated metalloproteinase-1, -8 and -9 expression was found in parapneumonic pleural effusions. These metalloproteinases could be implicated in the local inflammatory response existing in this group of effusions.
Most obstructive sleep apnoea patients exhibit vigilance and attention deficits on an extended battery of tests
Authors: Mazza S. , Pépin J-L. , Naëgelé B. , Plante J. , Deschaux C. , Lévy P.
Published: January 2005

Excessive daytime sleepiness, fatigue and altered attention are often experienced by obstructive sleep apnoea (OSA) patients. Although attentional problems are presumably responsible for part of the daytime functioning impairment in OSA, thorough investigation is unusual. Clinicians usually attribute these symptoms to somnolence. In clinical practice, only one isolated test is generally used to assess vigilance and attentional defects. It was hypothesised that most OSA patients exhibit a broad range of attentional deficits, beyond impaired maintenance of wakefulness, and a specific battery of tests is needed to correctly assess them.

Three attentional tests were performed at 9:00, 11:00 and 13:30 h, measuring maintenance of wakefulness, sustained attention and divided attention. Twenty OSA patients (aged 51±12 yrs, apnoea/hypopnoea index 45±22 h) and 40 control subjects (aged 48.4±9.9 yrs) were tested.

OSA patients performed significantly less well on the three tests than the controls at the three sessions. This battery of tests demonstrated that 95% of patients had vigilance and/or attentional impairment. Impairment patterns varied between patients.

Vigilance is impaired in obstructive sleep apnoea patients over a wide range of attentional processes. Not only is their ability to remain awake in monotonous situations impaired but their ability to maintain attention in more stimulating conditions is also affected. A single test of vigilance is not sufficient and could underestimate impaired vigilance and attention in some patients.
Efficacy of fluticasone on cough: a randomised controlled trial
Authors: Ponsioen B. P. , Hop W. C. J. , Vermue N. A. , Dekhuijzen P. N. R. , Bohnen A. M.
Published: January 2005

Cough may be the consequence of bronchial hyperresponsiveness (BHR) and inflammation. This study was designed to investigate the short-term effects of an inhaled steroid (fluticasone propionate (FP)) on cough, and to determine the effects of smoking, BHR, allergy and forced expiratory volume in one second (FEV1) on the efficacy of FP.

In a community-based primary healthcare centre, 135 previously healthy adults suffering from cough for ≥2 weeks were enrolled in a randomised, double-blind, placebo-controlled trial of inhaled FP 500 µgb.i.d.for 2 weeks. Participants completed daily diary cards of lower respiratory tract symptoms. The primary outcome measure was the decrease in mean total daily cough score (0–6) during the second week of treatment.

In the FP group, the cough score decreased from 3.8 at baseline to mean±sem1.4±0.2 during the second week. In the placebo group, this decrease was from 3.8 to 1.9±0.1 and was statistically significantly less. A favourable effect of FP was only detectable in nonsmokers, in whom the score was 0.9 points lower compared with placebo. The clinical relevance of this finding has to be established further. Allergy, FEV1 and BHR at baseline did not affect the efficacy of FP.

In conclusion, anti-inflammatory treatment with the inhaled steroid fluticasone propionate reduces cough in otherwise healthy adults who do not smoke.