bluuebunny/crossref_metadata_2025 huggingface dataset:
Verträglichkeit und Wirksamkeit einer 5%igen versus einer 10%igen i.v.-lmmunglobulinpräparation bei erwachsenen Patienten mit Immunthrombozytopenie – eine Pilotstudie
Authors: Wehmeier A. , Zahner J. , Schneider W.
Published: May 2009

Stark erniedrigte Thrombozytenzahlen führen bei autoimmunthrombozy-topenischer Purpura zu einer latenten Blutungsbereitschaft, die bei etwa 2-10% aller erwachsenen Patienten zu schweren intrazerebralen Blutungen führen kann. Durch Gabe von polyvalenten Immunglobulinpräparaten in einer Dosis von 1 g/kg Körpergewicht an 2 aufeinanderfolgenden Tagen kommt es zu einem raschen, jedoch leider nur vorübergehenden Anstieg der Thrombozytenzahlen. Verminderte Volumenbelastung und kürzere Infusionszeiten könnten gerade für ältere Patienten eine Verbesserung dieser Therapieform darstellen. In einer Pilotstudie an 12 Patienten mit Autoimmunthrombozytopenie verglichen wir Effektivität und Verträglichkeit einer neuen 10%igen Immunglobulinpräparation mit dem konventionellen 5 %igen Präparat (Bayer AG, Biologische Präparate, Leverkusen, Deutschland). Patienten mit neu diagnostizierter oder rezidivierter Immunthrombozytopenie wurden zwischen den beiden Präparaten randomisiert, wenn die Thrombozytenzahl unter 20 × 109/1 lag oder eine klinisch manifeste Blutungsneigung bestand. Zwölf Patienten (2 männliche, 10 weibliche) zwischen 25 und 86 Jahren wurden entweder mit dem 5 %igen oder dem 10 %igen IgG-Präparat behandelt. Acht Patienten wiesen Rezidive der Immunthrombozytopenie auf, und 6 Patienten waren mit Kortikosteroiden vorbehandelt. Evaluation von Blutungszeichen und Blutbildkontrollen wurden am 1.-7. sowie am 14. Tag durchgeführt. Während der Infusion erfolgten alle 10 min Messungen der Körpertemperatur und Erfassung potentieller Nebenwirkungen. Bei alien Patienten lag die Thrombozytenzahl 48 h nach Infusionsbeginn über 50 × 109/l, und die Blutungsneigung sistierte. Die beiden Präparate unterschieden sich weder in der Wirkung noch in den potentiellen Nebenwirkungen voneinander. In jeder Behandlungsgruppe trat jeweils am zweiten Behandlungstag eine minderschwere Nebenwirkung auf (Kopfschmerz bzw. Übelkeit). Die Infusionszeit ließ sich durch Verwendung der 10%igen Präparation um durchschnittlich 17% verkürzen, und das Infusionsvolumen wurde halbiert. Aufgrund der Ergebnisse dieser Pilotstudie schließen wir, daß sowohl die 5 %ige als auch die 10%ige Immunglobulinpräparation in der Behandlung der Immunthrombozytopenie im Erwachsenenalter wirksam ist und daß beide Präparate gleich gut vertragen werden.
Stellenwert von Zytokinen in der Sepsis-Diagnostik
Authors: Fraunberger P. , Walli A.K. , Seidel D.
Published: May 2009

Eine Vielzahl von experimentellen und klinischen Studien zeigt, daβ Zytokine eine zentrale Rolle bei der Entstehung der Sepsis spielen. Im Rahmen von Entzündungsreaktionen werden Zytokine freigesetzt, die als Signaltransmitter die verschie-denen Komponenten des Immunsystems zu einer zielgerichte-ten Immunantwort koordinieren. Obwohl an der komplexen Entstehung der Sepsis viele Zytokine beteiligt sind, können im Serum septischer Patienten nur wenige Zytokine wie Interleukin-1 (IL-1), Interleukin-6 (IL-6) und Tumor-Nekrose-Faktor-alpha (TNF) sowie neuerdings auch Interleukin-8 (ΓL-8) und Interleukin-10 (IL-10) verläβlich bestimmt werden. Dariiber hinaus wurden für einige Zytokinantagonisten – wie lösliche TNF-Rezeptoren und der IL-1-Rezeptor-Antagonist (IL-1RA) – ebenfalls meβbare Serumspiegel gefunden. Die höchste prognostische Aussagekraft in der Beurteilung der Sepsis ergibt sich für IL-6-Serumspiegel, die dariiber hinaus mit dem Schweregrad der Organdysfunktion korrelieren. Die klinische Wertigkeit von TNF-Messungen im Serum septischer Patienten ist eingeschränkt, da die TNF-Serumspiegel relativ groβe Variationen aufweisen. Neuere Befunde zeigen aber, daβ lösliche TNF-Rezeptoren auf Grund ihrer längeren biologischen Halbwertzeit besser zur Prognose-Beurteilung (Letalitäts-Risi-ko) geeignet sind. Sowohl für die TNF-Rezeptoren als auch für einige andere Zytokine stehen heute automatisierte Testsyste-me zur Verfügung, die eine Messung innerhalb weniger Stun-den ermöglichen und somit klinisch anwendbar sind.
Ergebnisforschung – Bedeutung für die Sepsis und den septischen Schock
Authors: Witthaut R. , Werdan K.
Published: May 2009

Neben Antibiotika und der supportiven Behandlung der Sepsis stehen für die Therapie der Sepsis und des septischen Schocks additive Therapiemaβnahmen zur Verfügung, die auf eine Unterbrechung der aktivierten Toxin-/Mediatornetzwerke ab-zielen. Trotz dieser umfangreichen Therapiestrategie zur Ver-besserung der Behandlung ist die Sterblichkeit an Sepsis und septischem Schock vergleichbar hoch wie 1909. Die enttäu-schenden Ergebnisse klinischer Sepsisstudien des vergangenen Jahrzehnts werfen die Frage auf, ob unsere Grundannahmen und Konzepte der Sepsistherapie wirksam sind und dem Krankheitsbild gerecht werden. Ergebnisforschung bezeichnet ein sich rasch entwickelndes Gebiet, das unter Verwendung von klinischen, epidemiologischen, ökonomischen und psychometrischen Parametern ver-sucht, die Prognose («Outcome») der Patienten multidisziplinär zu erfassen und gesicherte und wirksame Behandlungsstra-tegien zu entwickeln. Wenden wir die Hilfsmittel der Ergebnisforschung auf die Sepsis an, so müssen wir feststellen, daβ unsere gegenwärtigen Sepsis-Therapiestrategien weniger gesi-chert sind, als wir vielleicht annehmen. Die widersprüchlichen Ergebnisse additiver Sepsis-Therapiestudien unterstreichen die Bedeutung klinischer Studien (Phase III) als Goldstandard für die Beurteilung einzelner Sepsis-Therapiemaβnahmen.
9p21 is a Shared Susceptibility Locus Strongly for Coronary Artery Disease and Weakly for Ischemic Stroke in Chinese Han Population
Authors: Ding Hu , Xu Yujun , Wang Xiaojing , Wang Qi , Zhang Lan , Tu Yuanchao , Yan Jiangtao , Wang Wei , Hui Rutai , Wang Cong-Yi , Wang Dao Wen
Published: May 2009

Background—

Recent studies on genome-wide association have identified common variants on chromosome 9p21 associated with coronary artery disease (CAD). Given that ischemic stroke and CAD share several aspects of etiology and pathogenesis, we investigated the association of variants on chromosome 9p21 with ischemic stroke and CAD in the Chinese Han population by capturing the majority of diversity in this locus using haplotype-tagging single-nucleotide polymorphisms.

Methods and Results—

We performed a shared control-cases study using 15 tagging single-nucleotide polymorphisms and 2 previously reported susceptibility single-nucleotide polymorphisms spanning 58 kb of the chromosome of 9p21 in a set of 558 patients with ischemic stroke, 510 patients with CAD, and 557 unaffected participants (controls) in the Chinese Han population. The association analyses were performed at both SNP and haplotype levels. We further verified our findings in an independent cohort of 442 ischemic stroke cases and 502 control subjects. In the first study, rs2383206, rs1004638, and rs10757278 in block 3 were significantly associated with CAD but not with ischemic stroke independent of traditional cardiovascular risk factors in additive model (
P
=0.002 to 0.0001, q=0.026 to 0.004). Analysis from all blocks revealed that haplotype profiles of block 3 on 9p21 were significantly different between shared control and cases of CAD (
P
=1.3�10
−10
, q=1.2�10
−9
) and ischemic stroke (
P
=1.7�10
−6
, q=7.7�10
−6
). In the expanded second case-control study, block 3 on 9p21 remained associated with ischemic stroke (
P
=2.6�10
−4
, q=6.3�10
−4
).

Conclusions—

Our results suggest for the first time that 9p21 is a shared susceptibility locus, strongly for CAD and weakly for ischemic stroke, in a Chinese Han population.
Angiotensin II–Mediated Adaptive and Maladaptive Remodeling of Cardiomyocyte Excitation–Contraction Coupling
Authors: Gusev Konstantin , Domenighetti Andrea A. , Delbridge Lea M.D. , Pedrazzini Thierry , Niggli Ernst , Egger Marcel
Published: May 2009

Cardiac hypertrophy is associated with alterations in cardiomyocyte excitation–contraction coupling (ECC) and Ca
2+
handling. Chronic elevation of plasma angiotensin II (Ang II) is a major determinant in the pathogenesis of cardiac hypertrophy and congestive heart failure. However, the molecular mechanisms by which the direct actions of Ang II on cardiomyocytes contribute to ECC remodeling are not precisely known. This question was addressed using cardiac myocytes isolated from transgenic (TG1306/1R [TG]) mice exhibiting cardiac specific overexpression of angiotensinogen, which develop Ang II–mediated cardiac hypertrophy in the absence of hemodynamic overload. Electrophysiological techniques, photolysis of caged Ca
2+
and confocal Ca
2+
imaging were used to examine ECC remodeling at early (≈20 weeks of age) and late (≈60 weeks of age) time points during the development of cardiac dysfunction. In young TG mice, increased cardiac Ang II levels induced a hypertrophic response in cardiomyocyte, which was accompanied by an adaptive change of Ca
2+
signaling, specifically an upregulation of the Na
+
/Ca
2+
exchanger–mediated Ca
2+
transport. In contrast, maladaptation was evident in older TG mice, as suggested by reduced sarcoplasmic reticulum Ca
2+
content resulting from a shift in the ratio of plasmalemmal Ca
2+
removal and sarcoplasmic reticulum Ca
2+
uptake. This was associated with a conserved ECC gain, consistent with a state of hypersensitivity in Ca
2+
-induced Ca
2+
release. Together, our data suggest that chronic elevation of cardiac Ang II levels significantly alters cardiomyocyte ECC in the long term, and thereby contractility, independently of hemodynamic overload and arterial hypertension.
Chloride Intracellular Channel-4 Is a Determinant of Native Collateral Formation in Skeletal Muscle and Brain
Authors: Chalothorn Dan , Zhang Hua , Smith Jennifer E. , Edwards John C. , Faber James E.
Published: May 2009

The capacity of the collateral circulation to lessen injury in occlusive vascular disease depends on the density and caliber of native (preexisting) collaterals, as well as their ability to outwardly remodel in ischemia. Native collateral conductance varies widely among healthy individuals, yet little is known about what specifies collateral formation. Chloride intracellular channel (CLIC)4 protein is required for endothelial cell hollowing, a process necessary for vessel formation during embryogenesis and ischemia. Whether CLIC4 has other physiological roles in vascular biology is uncertain. We studied collateral formation and remodeling in mice deficient in CLIC1 and CLIC4. Vascular responses to femoral artery ligation were similar in
Clic1
−/−
and wild-type mice. In contrast, immediately after ligation perfusion dropped more in
Clic4
−/−
than wild-type mice, suggesting fewer preexisting collaterals, a finding confirmed by angiography, greater ischemia, and worse recovery of perfusion; however, collateral remodeling was unaffected. Likewise, native cerebral collateral density in
Clic4
−/−
(but not
Clic1
−/−
) mice was reduced, resulting in severe infarctions. This was associated with impaired perinatal formation and stabilization of nascent collaterals.
Clic4
hemizygous mice had intermediate deficits in the above parameters, suggesting a gene-dose effect. Ischemia augmented CLIC1 and CLIC4 expression similarly in wild-type mice. However, CLIC1 increased 3-fold more in
Clic4
−/−
mice, suggesting compensation. Despite greater ischemia in
Clic4
−/−
mice, hypoxia-inducible factor-1α, vascular endothelial growth factor (VEGF) and angiopoietin-2 increased less compared to wild-type, suggesting CLIC4 exerts influences upstream of hypoxia-inducible factor-1α-VEGF signaling. Hence, CLIC4 represents the second gene that, along with VEGF shown by us previously, specifies native collateral formation.
Physical and Functional Interaction Between Calcineurin and the Cardiac L-Type Ca
2+
Channel
Authors: Tandan Samvit , Wang Yanggan , Wang Thomas T. , Jiang Nan , Hall Duane D. , Hell Johannes W. , Luo Xiang , Rothermel Beverly A. , Hill Joseph A.
Published: May 2009

The L-type Ca
2+
channel (LTCC) is the major mediator of Ca
2+
influx in cardiomyocytes, leading to both mechanical contraction and activation of signaling cascades. Among these Ca
2+
-activated cascades is calcineurin, a protein phosphatase that promotes hypertrophic growth of the heart. Coimmunoprecipitations from heart extracts and pulldowns using heterologously expressed proteins provided evidence for direct binding of calcineurin at both the N and C termini of α
1
1.2. At the C terminus, calcineurin bound specifically at amino acids 1943 to 1971, adjacent to a well-characterized protein kinase (PK)A/PKC/PKG phospho-acceptor site Ser1928. In vitro assays demonstrated that calcineurin can dephosphorylate α
1
1.2. Channel function was increased in voltage-clamp recordings of
I
Ca,L
from cultured cardiomyocytes expressing constitutively active calcineurin, consistent with previous observations in cardiac hypertrophy in vivo. Conversely, acute suppression of calcineurin pharmacologically or with specific peptides decreased
I
Ca,L
. These data reveal direct physical interaction between the LTCC and calcineurin in heart. Furthermore, they demonstrate that calcineurin induces robust increases in
I
Ca,L
and highlight calcineurin as a key modulator of pathological electrical remodeling in cardiac hypertrophy.
Adjuvant Embolization With
N
-Butyl Cyanoacrylate in the Treatment of Cerebral Arteriovenous Malformations
Authors: Starke Robert M. , Komotar Ricardo J. , Otten Marc L. , Hahn David K. , Fischer Laura E. , Hwang Brian Y. , Garrett Matthew C. , Sciacca Robert R. , Sisti Michael B. , Solomon Robert A. , Lavine Sean D. , Connolly E. Sander , Meyers Philip M.
Published: May 2009

Background and Purpose—

The purpose of this study was to assess the frequency, severity, and predictors of neurological deficits after adjuvant embolization for cerebral arteriovenous malformations.

Methods—

From 1997 to 2006, 202 of 275 patients with arteriovenous malformation received embolization before microsurgery (n=176) or radiosurgery (n=26). Patients were examined before and after endovascular embolization and at clinical follow-up (mean, 43.4±34.6 months). Outcome was classified according to the modified Rankin Scale. New neurological deficits after embolization were defined as minimal (no change in overall modified Rankin Scale), moderate (modified Rankin Scale ≤2), or significant (modified Rankin Scale >2).

Results—

Two hundred two patients were treated in 377 embolization procedures. There were a total of 29 new clinical deficits after embolization (8% of procedures; 14% of patients), of which 19 were moderate or significant. Postembolization deficits resolved in a significant number of patients over time (
P
<0.0001). Five patients had persistent neurological deficits due to embolization (1.3% of procedures; 2.5% of patients). In multivariate analysis, the following variables significantly predicted new neurological deficit after embolization: complex arteriovenous malformation with treatment plan specifying more than one embolization procedure (OR, 2.7; 95% CI, 1.4 to 8.6), diameter <3 cm (OR, 3.2; 95% CI, 1.2 to 9.1), diameter >6 cm (OR, 6.2; 95% CI, 1.0 to 57.0), deep venous drainage (OR, 2.7; 95% CI, 1.1 to 6.9), or eloquent location (OR, 2.4; 95% CI, 1.0 to 5.7). These variables were weighted and used to compute an arteriovenous malformation Embolization Prognostic Risk Score for each patient. A score of 0 predicted no new deficits, a score of 1 predicted a new deficit rate of 6%, a score of 2 predicted a new deficit rate of 15%, a score of 3 predicted a new deficit rate of 21%, and a score of 4 predicted a new deficit rate of 50% (
P
<0.0001).

Conclusions—

Small and large size, eloquent location, deep venous drainage, and complex vascular anatomy requiring multiple embolization procedures are risk factors for the development of immediate postembolization neurological deficits. Nevertheless, a significant number of patients with treatment-related neurological deficits improve over time. The low incidence of permanent neurological deficits underscores the usefulness of this technique in carefully selected patients.
Assessing Reperfusion and Recanalization as Markers of Clinical Outcomes After Intravenous Thrombolysis in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET)
Authors: De Silva Deidre A. , Fink John N. , Christensen Soren , Ebinger Martin , Bladin Christopher , Levi Christopher R. , Parsons Mark , Butcher Ken , Barber P. Alan , Donnan Geoffrey A. , Davis Stephen M.
Published: May 2009

Background and Purpose—

Reperfusion and recanalization have both been used as surrogate markers of clinical outcome in trials of stroke thrombolysis. We aimed to prove that the beneficial impact of recanalization with intravenous tissue plasminogen activator on clinical outcomes is attributable to reperfusion in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET).

Methods—

EPITHET was a prospective, randomized, placebo-controlled trial of intravenous tissue plasminogen activator in the 3- to 6-hour window. Reperfusion was defined as >90% reduction in magnetic resonance perfusion-weighted imaging lesion volume and recanalization as improvement of MR angiographic Thrombolysis In Myocardial Infarction grading by ≥2 points from baseline to Day 3 to 5.

Results—

At Day 3 to 5, reperfusion and recanalization with intravenous tissue plasminogen activator were strongly correlated. Reperfusion was associated with improved clinical outcome independent of whether recanalization occurred. In contrast, recanalization was not associated with clinical outcome when reperfusion was included as a covariate in regression analyses.

Conclusion—

Reperfusion is a surrogate marker of clinical outcomes independent of recanalization based on the criteria applied in EPITHET. The impact of recanalization on clinical outcomes was attributable to reperfusion.
Mitochondrial Targets for Stroke
Authors: Vosler Peter S. , Graham Steven H. , Wechsler Lawrence R. , Chen Jun
Published: May 2009

Background and Purpose—

Stroke is a major cause of death and disability, and it is imperative to develop therapeutics to mitigate stroke-related injury. Despite many promising prospects, attempts at translating neuroprotective agents that show success in animal models of stroke have resulted in very limited clinical success.

Summary of Review—

This review discusses reasons for the lack of translational success based on the therapeutic targets tested and the pathophysiology of stroke. New recanalization therapies and alternative therapeutic strategies are discussed concerning mitochondria-mediated cell death. Mitochondrial death-regulation pathways are divided into 3 categories: Upstream signaling pathways, agents that target mitochondria directly, and downstream death-execution effectors. The apoptosis signal-related kinase/c-Jun-terminal kinase pathway is used as an example to provide rationale as to why inhibiting signaling pathway upstream of mitochondrial dysfunction is a promising therapeutic approach. Finally, the mechanisms of autophagy and mitochondrial biogenesis are discussed in relation to stroke.

Conclusions—

Increasing evidence suggests that reperfusion is necessary for improved neurological outcomes after stroke. Development of improved recanalization methods with increased therapeutic windows will aid in improving clinical outcome. Adjunct neuroprotective interventions must also be developed to ensure maximal brain tissue salvage. Targeting prodeath signaling pathways upstream of mitochondrial damage is promising for potential clinically effective treatment. Further understanding of the roles of equilibrium of autophagy and mitochondrial biogenesis in the pathogenesis of stroke could also lead to novel therapeutics.
Stroke Risk of Blood Pressure Indices Determined by Home Blood Pressure Measurement
Authors: Inoue Ryusuke , Ohkubo Takayoshi , Kikuya Masahiro , Metoki Hirohito , Asayama Kei , Kanno Atsuhiro , Obara Taku , Hirose Takuo , Hara Azusa , Hoshi Haruhisa , Totsune Kazuhito , Satoh Hiroshi , Kondo Yoshiaki , Imai Yutaka
Published: May 2009

Background and Purpose—

The purpose of this prospective cohort study was to investigate associations between stroke and blood pressure (BP) indices (systolic BP [SBP], diastolic BP [DBP], mean BP, and pulse pressure [PP]) determined by home BP measurement.

Methods—

Associations between stroke and BP indices were examined in a rural Japanese population. Home BP data of 2369 subjects (40% men) ≥35 years of age (mean, 59 years) without a history of stroke were obtained. Associations between stroke and each index were determined using Cox proportional hazards regression and the likelihood ratio (LR) test.

Results—

During follow-up (mean, 11.7 years), 238 strokes occurred. The LR test showed that SBP and mean BP were significantly more strongly associated with total and ischemic stroke than DBP and PP (LR χ
2
≥9.3,
P
<0.01 for SBP/mean BP, LR χ
2
≤3.8,
P
≥0.05 for DBP/PP). SBP tended to be more strongly associated with total/ischemic stroke than mean BP (LR χ
2
=3.8,
P
=0.05 for SBP, LR χ
2
≤0.2,
P
>0.6 for mean BP). PP tended to be slightly more strongly associated with ischemic stroke than DBP (LR χ
2
=7.5,
P
<0.01 for DBP, LR χ
2
=9.3,
P
<0.01 for PP), whereas DBP was significantly more strongly associated with hemorrhagic stroke than PP (LR χ
2
=9.2,
P
<0.01 for DBP, LR χ
2
=2.5,
P
=0.01 for PP).

Conclusion—

PP obtained from home BP measurements was weakly associated with stroke, whereas SBP showed the strongest association. Additionally, DBP and PP may be associated with different stroke types.
Remodeling of the Corticospinal Innervation and Spontaneous Behavioral Recovery After Ischemic Stroke in Adult Mice
Authors: Liu Zhongwu , Zhang Rui Lan , Li Yi , Cui Yisheng , Chopp Michael
Published: May 2009

Background and Purpose—

To elucidate how the motor pathways rewire the denervated tissue after stroke, we investigated remodeling of the corticospinal tract (CST) in transgenic mice with yellow fluorescent protein CST labeling in conjunction with transsynaptic pseudorabies virus retrograde tracing.

Methods—

Adult male CST-yellow fluorescent protein mice were subjected to permanent right middle cerebral artery occlusion (n=8/group). Foot-fault test was performed to monitor functional deficit and recovery. Pseudorabies virus tracer was injected into the left forelimb muscles at 1 or 4 weeks after middle cerebral artery occlusion (4 days before euthanasia), respectively. A third group of CST-yellow fluorescent protein mice without middle cerebral artery occlusion was used for normal control (n=6). The yellow fluorescent protein labeling of CST in the cervical cord and pseudorabies virus labeling of pyramidal neurons in the bilateral cortices were measured on vibratome sections using a confocal imaging system.

Results—

Compared with normal animals, axonal density in the stroke-affected side of the cervical cord was significantly decreased at 11 days (
P
<0.001) and significantly increased at 32 days after stroke compared with the Day 11 values (
P
<0.05). Pseudorabies virus labeling was significantly decreased in the ischemic hemisphere 11 days after middle cerebral artery occlusion (
P
<0.001). In contrast, a significant increase was observed in pseudorabies virus labeling of bilateral cortices 32 days after stroke compared with 11 days (
P
<0.05). The CST axonal density in the denervated spinal cord and pyramidal neuron labeling in the bilateral cortices were significantly correlated with behavioral recovery (
P
<0.05).

Conclusions—

Spontaneous functional recovery after stroke may, at least in part, be attributed to neuronal remodeling in the corticospinal system.
Clinical response to risperidone in relation to plasma drug concentrations in acutely exacerbated schizophrenic patients
Authors: Yasui-Furukori N. , Saito M. , Nakagami T. , Furukori H. , Suzuki A. , Kondo T. , Kaneko S.
Published: May 2009

There are no data indicating a clear relationship between the clinical effect of risperidone and plasma drug concentration. In this study, 51 patients with acutely exacerbated schizophrenia received 6 mg risperidone/day for 4 weeks. A clinical evaluation using the Brief Psychiatric Rating Scale (BPRS) and Udvalg for Klinicke Undersøgelser (UKU) side effect rating scale were performed at baseline and each week. Significant ( P < 0.05) correlations were found between plasma concentrations of risperidone and improved total BPRS scores, positive and cognitive symptoms. Plasma concentrations of the active moiety were significantly ( P < 0.05) correlated with improved total BPRS scores. Improved score and percent improvement in anxiety-depression subscale were significantly ( P < 0.01) correlated with plasma concentrations of the active moiety. The sum of total UKU side effect scores from 1 to 4 weeks was significantly correlated with plasma concentration of both risperidone (rs = 0.319, P < 0.05) and active moiety (rs = 0.373, P < 0.01). The sum of the psychic subgroup scores was significantly correlated with plasma concentrations of active moiety (rs = 0.318, P < 0.05). Results suggest that plasma drug concentrations are, to some extent, associated with improved scores in some psychopathological schizophrenic symptoms and sedative side effects. These findings should be replicated with a larger patient sample.
A Grounded Investigation of Genred Guidelines in Cancer Care Deliberations
Authors: Teston Christa B.
Published: May 2009

Genred documents facilitate collaboration and workplace practices in many ways—particularly in the medical workplace. This article represents a portion of a larger grounded investigation of how medical professionals invoke a wide range of rhetorical strategies when deliberating about complex patient cases during weekly, multidisciplinary deliberations called Tumor Board meetings. Specifically, the author explores the role of one key document in oncological practice, the Standard of Care document. Each Standard of Care document (one for every known cancer) presents a set of national guidelines intended to standardize the treatment of cancer. Tumor Board participants invoke these guidelines as evidence for or against particular future action. In order to better understand how genred, generalizable guidelines like Standard of Care documents afford decision making amid uncertainty, the author conducts a temporal and contextual analysis of the document's use during deliberations as well as a modified Toulminian analysis of a representative sample. Results suggest that, while on its own the document achieves an authoritative, charter-like purpose, it fails to make explicit a link between individual patients' experiences and the profession's expectations for how to act. Implications for how genred, generalizable guidelines—given the way they encourage certain ways of seeing over others—organize and authorize work are discussed, and a modified Toulminian approach to understanding the relationship between claim and evidence in multimodal texts is modeled.
Evaluation of hormonal change, biochemical parameters, and histopathological status of uterus in rats exposed to 50-Hz electromagnetic field
Authors: Aydin M , Cevik A , Kandemir FM , Yuksel M , Apaydin AM
Published: May 2009

This study investigates the effects of the electromagnetic field (EMF) resulting from the 170 kV high-voltage power lines on hormonal status, on progesterone and 17-β estradiol levels, and on morphology of the uterus and ovaries associated with biochemical parameters of adult Wistar female rats. The rats were assigned to experimental (21) and control groups (7). The rats in the experimental group were housed in a wooden barn with 7.5 m vertical distance to the power line. Groups 1, 2, and 3 were exposed continuously (24 h) to electric-electromagnetic fields (ELF-EMFs) (48.21 ± 1.58 mG) for 1, 2, and 3 months, respectively. The rats of group 4 served as the control and were placed in laboratory conditions (The average value of the ELF was 0.75 ± 0.05 V/m. The value of the EMF was calculated to be 0.48 ± 0.05 mG.). Significant ( P < 0.05) decreases were determined among the groups in terms of reproductive organ weights (uterus and ovaries) and progesterone and estrogen levels in relation to the varying periods of the estrous cycle. Although marked reductions ( P < 0.05) were observed among the groups in relation to plasma catalase activity, depending on exposure time, no significant differences were found in terms of glutathione and malondialdehyde levels. It is concluded that exposure to the ELF-EMFs for different time periods produced significant decreases in plasma catalase activities in the 3-month exposure groups but no effects on progesterone level, on 17-β estradiol level, or on the morphology and weight of uterus and ovaries.
Tumorigenesis in B6C3F1 mice exposed to ozone in combination with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and dietary dibutyl phthalate
Authors: Kim Min Young , Cho Myung Haing
Published: May 2009

Although ozone exposure has been suspected as a risk factor for the development of lung cancer, data are still inconclusive. Studies in the literature infrequently recognize that the potential toxicity of ozone could be influenced by the combined exposure with other environmental carcinogens. To evaluate the carcinogenic potential of ozone alone or in combination with other toxicants, male and female B6C3F1 mice were exposed through inhalation and diet, to 0.5 ppm of ozone, 1.0 mg/kg of 4-( N-methyl- N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 5000 ppm of dibutyl phthalate (DBP), individually and in combination for 1 year. No treatment-related death was seen, but significant differences in body and organ weights between control and treated mice were observed during the study. No tumor incidence was found in mice of either gender exposed to ozone alone. Pulmonary neoplasms were found in both, male and female mice exposed to NNK alone and in combination, ozone with NNK only or NNK plus DBP. Oviductal carcinomas were observed in females exposed to DBP alone and together with ozone plus NNK. These results indicate that ozone alone is not a lung carcinogen and in conjunction with NNK and/or DBP have no effect on tumor development in B6C3F1 mice under our experimental conditions.
Enteral Feeding Misconnections: An Update
Authors: Guenter Peggi , Hicks Rodney W. , Simmons Debora
Published: May 2009

Enteral misconnections are defined as inadvertent connections between enteral feeding systems and nonenteral systems such as intravascular lines, peritoneal dialysis catheters, tracheostomy tube cuffs, medical gas tubing, and so on. Sentinel event data and causative factors are outlined along with potential solutions to prevent such medical errors. The solutions can be grouped into 3 areas: (1) education, awareness, and human factors; (2) purchasing strategies; and (3) design changes. Updates on safety innovations and programs are presented.
Overview of Infant and Pediatric Formulas
Authors: Joeckel Rebecca J. , Phillips Sharon K.
Published: May 2009

Because every child has individual needs, there are a variety of infant and pediatric formulas from which to choose. Not only are there several categories of formulas including milk protein‐based, soy protein‐based, hydrolyzed protein, and amino acid‐based, but there are differences between products within each category. Research is being done in the area of formula design for the prevention or treatment of disease. In this article, the authors review types of formulas and their indications for use for infants and children, and review current literature on formula trends.
Enteral Nutrition Formulas: Which Formula Is Right for Your Adult Patient?
Authors: Chen Yimin , Peterson Sarah J.
Published: May 2009

In the last few decades, there has been tremendous advancement in the area of enteral nutrition formulas. Enteral nutrition makes it possible to provide important substrates for those who cannot or will not meet daily requirements via oral intake but who have an intact digestive system. Numerous enteral nutrition formulas are currently available, with a large portion of them targeting specific disease conditions, thus making it a daunting task at times for a clinician to sort through all the possibilities and decide on the most appropriate formula. This review provides a close examination of various enteral formula categories and presents proposed mechanisms of specialized ingredients, followed by a thorough evidence‐based analysis of existing literature before making recommendations for the various enteral formula categories.
College Students' Crime-Related Fears on Campus
Authors: Fisher Bonnie S. , May David
Published: May 2009

Gender plays a central role in the study of crime-related fear as does the description of various fear-provoking cues in the environment. Despite the ever-growing body of crime-related fear research, few researchers have examined which fear-provoking cues, if any, are gendered. Using a large sample of undergraduates from a public university, this article explores the gendered nature of fear-provoking cues and crime-related fears while on campus. Bivariate and multivariate results suggest that fear-provoking cues are not gendered for fear of larceny-theft or fear of assault. These results inform the fear of crime research on a number of dimensions and have implications for future research.
Considering the Gendered Nature of Constrained Behavior Practices Among Male and Female College Students
Authors: Rader Nicole E. , Cossman Jeralynn S. , Allison Marisa
Published: May 2009

Previous research suggests that individuals engage in a variety of constrained behaviors to protect themselves from potential victimization. Although research controls for gender and constrained behaviors in fear of crime models, few studies consider constrained behaviors through a gendered lens. Using university survey data as an exploratory case study, this article hypothesizes that men and women use different types of constrained behaviors and, using factor analysis, constructs a gender-sensitive typology of four distinctive types of constrained behaviors. The results suggest that women are more likely to engage in all four types of constrained behaviors and that a variety of gender differences in behavioral responses to fear in crime are apparent when comparing across the four categories.
Thermomechanical Modelization of a New Active Material
Authors: Drobez Hervé , L'Hostis Gildas , Buet Gautier Karine , Laurent Fabrice , Durand Bernard
Published: May 2009

The controlled behavior of composite material (CBCM) is a thermomechanical active composite using Joule effect and heterogeneous thermal elongation properties as an actuator within composite structures. An ‘active layer’ made of carbon yarns is used as internal source of heat. To help the design of this composite a simple model based on thermomechanical and composite homogenization considerations is presented. A three-point bending test is used to compare the calculated results to experimental results. A good accordance between the relevant data (maximum of deflection and temperature on the plate) at stabilization being observed, the model is used to study the influence of some parameters. The position of the active layer, a design parameter of great importance, is particularly studied and an optimized solution is proposed. Then, the model is used for a sensitivity analysis of some design and working parameters. Finally, the results of a FEM model are compared to the previous.
Work Motivations, Satisfactions, and Health Among Managers
Authors: Burke Ronald J. , Fiksenbaum Lisa
Published: May 2009

Individuals in managerial and professional jobs are now working longer hours for a variety of reasons. Building on previous research on workaholism and on types of passion, the results of an exploratory study of correlates of work-based passion and addiction are presented. Data were collected from 530 Canadian managers and professionals, MBA graduates of a single university, using anonymously completed questionnaires. The following results were noted. First, scores on passion and addiction were significantly and positively correlated. Second, managers scoring higher on passion and on addiction were both more heavily invested in their work. Third, managers scoring higher on passion also indicated less obsessive job behaviors, greater work and extrawork satisfactions, and higher levels of psychological well-being. Fourth, managers scoring higher on addiction indicated more obsessive job behaviors, lower work and extrawork satisfactions, and lower levels of psychological well-being. Fifth, managers scoring higher on addiction saw their world in dog-eat-dog terms and their organizational cultures as less supportive of work—personal life balance; this pattern was in the opposite direction among managers scoring higher on passion.
Centrality of and Investment in Work and Family Among Israeli High-Tech Workers
Authors: Snir Raphael , Harpaz Itzhak , Ben-Baruch Dorit
Published: May 2009

Workers’ attitudes concerning the competition for individual’s resources between work and family are expressed by the relative centrality they attribute to each of these domains. This competition is also manifested in the tradeoff between work and family time. The study deals with 319 Israeli high-tech workers. We examined the effect of parenthood on men and on women regarding the centrality of and investment in work and family in the bicultural context of the Israeli high-tech industry (i.e., the family-centered Israeli society on the one hand, and the masculine work-centered high-tech industry on the other hand). A contrasting parenthood effect on men and women was found. Fathers showed higher relative work centrality than childless men, whereas mothers showed lower relative work centrality than women without children. Fathers invested more weekly hours in paid work than childless men, whereas mothers invested fewer weekly hours in paid work than women without children. In the parents’ sub-sample, mothers evinced higher relative family centrality than fathers. Mothers also invested more weekly hours in childcare and core housework tasks than fathers. The uniqueness of the findings is that the contrasting parenthood effect prevails even in the demanding high-tech sector, in which women are expected to work long hours and play down their care-giving activities. Nevertheless, it should be stressed that mothers struggled to juggle active family caring with a career, rather than give up either of them. We also found that mothers invested more weekly hours in work in general (paid and unpaid work) than fathers.
Effect of parenteral cladribine on relapse rates in patients with relapsing forms of multiple sclerosis: results of a 2-year, double-blind, placebo-controlled, crossover study
Authors: Stelmasiak Z , Solski J , Nowicki J , Jakubowska B , Ryba M , Grieb P
Published: May 2009

Objective

This randomized, 2-year, double-blind, placebo-controlled, crossover study evaluated cladribine for relapsing forms of multiple sclerosis.

Design

Patients ( n = 84) received seven 5-day courses of subcutaneous cladribine at 5 mg/day (group A) or placebo (group B) in year 1; treatment was reversed in year 2.

Results

Cladribine was well tolerated and associated with a favorable safety profile. Mean Expanded Disability Status Scale scores remained stable. In group A, mean relapse rates were 0.15 in year 1 (cladribine) and 0.42 in year 2. In group B, relapse rates were 0.61 in year 1 and 0.50 in year 2 (cladribine). Patients required fewer steroid courses during cladribine periods. The therapeutic efficacy of cladribine was associated with a sustained reduction in lymphocyte count.
Twin studies and the heritability of MS: a conclusion
Authors: Hawkes CH , Macgregor AJ
Published: May 2009

Objective

The classical twin study has the potential to evaluate the relative contribution of genes and environment and guide further research strategies, provided the sampling and methods of analysis are correct. We wish to review all the more informative twin studies on multiple sclerosis (MS).

Methods

We examined six large population-based twin studies in MS and calculated indices of heritability (h2), which is the traditional method of assessing genetic contribution to disease and to allow comparison between studies.

Results

This index was found to vary widely from 0.25 to 0.76 with large confidence intervals that reflect small sample size and prevent robust interpretation.

Conclusion

Overall the studies support a genetic contribution to disease; however, the imprecision of the heritability estimates and potential biases that they contain mean that very little inference can be drawn its exact size. Given that the magnitude of genetic effect cannot be measured because of the relative infrequency of MS; the consequent difficulty in collecting an informative sample; and in many countries, the lack of a comprehensive twin register, we suggest that further twin prevalence surveys should not be undertaken. Twin studies could be used more effectively in other ways, such as the co-twin case–control approach.
Unilateral Versus Bilateral First Ray Surgery
Authors: Fridman Robert , Cain Jarrett D. , Weil Lowell , Weil Lowell Scott , Ray Thomas Brent
Published: May 2009

Many studies have evaluated bilateral versus unilateral surgery in large joints, but limited research is available to compare outcomes of bilateral staged foot surgeries versus synchronous bilateral foot surgery. In total, 186 consecutive cases of first metatarsal-phalangeal (MTP) joint surgery were prospectively included in this study; 252 procedures were performed: 120 were unilateral or staged bilateral operations, and 66 were synchronous bilateral operations. Patients were evaluated at 6 and 12 weeks for specific early complications and surveyed about their return to work, activities of daily living, shoe gear requirements, satisfaction, and reasons for choosing staged or synchronous surgery. In addition, a cost analysis was performed on all surgical scenarios. Student t test showed no statistical significance between groups in all clinical settings to a 95% confidence level. Complication rates were similar and few in all situations. Patients were very satisfied when choosing bilateral synchronous surgery and would elect to repeat it the same way 97% of the time. The economic costs to the health system average 25% greater when patients undergoing first MTP joint surgery have the procedure performed one foot at a time. Combined with the time lost from work, this reveals a significant economic cost to both society and patient.
A common bipotent progenitor generates the erythroid and megakaryocyte lineages in embryonic stem cell–derived primitive hematopoiesis
Authors: Klimchenko Olena , Mori Marcella , DiStefano Antonio , Langlois Thierry , Larbret Frédéric , Lecluse Yann , Feraud Olivier , Vainchenker William , Norol Françoise , Debili Najet
Published: May 2009

The megakaryocytic (MK) and erythroid lineages are tightly associated during differentiation and are generated from a bipotent megakaryocyte-erythroid progenitor (MEP). In the mouse, a primitive MEP has been demonstrated in the yolk sac. In human, it is not known whether the primitive MK and erythroid lineages are generated from a common progenitor or independently. Using hematopoietic differentiation of human embryonic stem cells on the OP9 cell line, we identified a primitive MEP in a subset of cells coexpressing glycophorin A (GPA) and CD41 from day 9 to day 12 of coculturing. This MEP differentiates into primitive erythroid (GPA+CD41−) and MK (GPA−CD41+) lineages. In contrast to erythropoietin (EPO)–dependent definitive hematopoiesis, KIT was not detected during erythroid differentiation. A molecular signature for the commitment and differentiation toward both the erythroid and MK lineages was detected by assessing expression of transcription factors, thrombopoietin receptor (MPL) and erythropoietin receptor (EPOR). We showed an inverse correlation between FLI1 and both KLF1 and EPOR during primitive erythroid and MK differentiation, similar to definitive hematopoiesis. This novel MEP differentiation system may allow an in-depth exploration of the molecular bases of erythroid and MK commitment and differentiation.
A physiological model of patient-reported breathlessness during daily activities in COPD
Authors: Jolley C. J. , Moxham J.
Published: May 2009

Breathlessness during daily activities has a significant impact on quality of life in chronic obstructive pulmonary disease. Herein, we present a physiological model of patient-reported breathlessness based on the relationship between ventilatory load, respiratory muscle capacity, neural respiratory drive and neuromechanical dissociation during daily activities. This model should facilitate an understanding of the mechanisms driving increased intensity of breathlessness during daily activities and the relief of breathlessness following medical or surgical interventions.

The model should also provide a structure on which to base the development of patient-reported outcome instruments to measure the severity of breathlessness during daily activities in chronic obstructive pulmonary disease.
Prevalence of asthma control among adults in France, Germany, Italy, Spain and the UK
Authors: Demoly P. , Paggiaro P. , Plaza V. , Bolge S. C. , Kannan H. , Sohier B. , Adamek L.
Published: May 2009

The objectives of this article were to estimate the prevalence of asthma control and describe the characteristics of at least well-controlled (ALWC)versusnot well-controlled (NWC) asthmatics.

Data were obtained from the European National Health and Wellness Survey, an internet-based, cross-sectional study of 37,476 adults in France, Germany, Italy, Spain and the UK. Analysis was limited to 2,337 respondents who self-reported a physician diagnosis. Based on the Asthma Control Test (ACT), respondents were grouped as ALWC (ACT ≥20) and NWC (ACT ≤19).

The prevalence of diagnosed asthma across five countries was estimated to be 5.8% (14 million extrapolated for the European Union population). Of these, 50.4% (7.1 million) were NWC. Compared with ALWC, NWC were older (15.8versus15.0%; p<0.001), less likely to be college educated (28.7versus36.3%; p<0.001) and more likely to be obese (30.0versus22.7%; p<0.001), experience depression (28.0versus18.7%; p<0.001) and smoke (34.7versus25.0%; p<0.001). The NWC had more occasions of contact with healthcare providers and were more likely to use controller and rescue medications, but with less adherence.

A substantial portion of asthmatics are NWC. However, the proportion of NWC asthmatics found in this study was less than in previously reported. Patients and physicians need to be educated on the importance of asthma control and adherence to treatments.