bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vivo and In Vitro Inhibition of Monocyte Adhesion to Endothelial Cells and Endothelial Adhesion Molecules by Eicosapentaenoic Acid
Authors: Yamada Hideto , Yoshida Masayuki , Nakano Yasutaka , Suganami Takayoshi , Satoh Noriko , Mita Tomoya , Azuma Kosuke , Itoh Michiko , Yamamoto Yukio , Kamei Yasutomi , Horie Minoru , Watada Hirotaka , Ogawa Yoshihiro
Published: October 2008

Objective—

A large-scale, prospective, randomized clinical trial has recently revealed that the addition of highly purified eicosapentaenoic acid (EPA) to low-dose statin therapy significantly reduces the incidence of major coronary events. Here we investigated in vivo and in vitro effect of EPA on monocyte adhesion to endothelial cells and adhesion molecules.

Methods and Results—

A new en face immunohistochemistry of endothelial surface in combination with confocal microscopy revealed marked reduction of lipopolysaccharide (LPS)-induced monocyte adhesion to the aortic endothelium in parallel with the suppression of vascular cell adhesion molecule 1 (VCAM-1) and nuclear translocation of nuclear factor-κB p65 in EPA-treated mice relative to vehicle-treated groups. In an in vitro adhesion assay system under physiological flow conditions, EPA inhibited LPS-induced monocyte adhesion and endothelial adhesion molecules. We found significant decrease in plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) and sVCAM-1 in patients with the metabolic syndrome after a 3-month administration of highly purified EPA (1.8 g daily). Multivariate regression analysis revealed that EPA administration is the only independent determinant of sICAM-1 and sVCAM-1.

Conclusions—

This study provides evidence that EPA inhibits monocyte adhesion to endothelial cells in parallel with the suppression of endothelial adhesion molecules in vivo and in vitro.
Loss of SR-A and CD36 Activity Reduces Atherosclerotic Lesion Complexity Without Abrogating Foam Cell Formation in Hyperlipidemic Mice
Authors: Manning-Tobin Jennifer J. , Moore Kathryn J. , Seimon Tracie A. , Bell Susan A. , Sharuk Maia , Alvarez-Leite Jacqueline I. , de Winther Menno P.J. , Tabas Ira , Freeman Mason W.
Published: October 2008

Objective—

The scavenger receptors SR-A and CD36 have been implicated in macrophage foam cell formation during atherogenesis and in the regulation of inflammatory signaling pathways, including those leading to lesional macrophage apoptosis and plaque necrosis. To test the impact of deleting these receptors, we generated
Apoe
−/−
mice lacking both SR-A and CD36 and fed them a Western diet for 12 weeks.

Methods and Results—

We analyzed atheroma in mice, assessing lesion size, foam cell formation, inflammatory gene expression, apoptosis, and necrotic core formation. Aortic root atherosclerosis in
Apoe
−/−
Cd36
−/−
Msr1
−/−
mice, as assessed by morphometry, electron microscopy, and immunohistochemistry, showed no decrease in lesion area or in vivo foam cell formation when compared to
Apoe
−/−
mice. However,
Apoe
−/−
Cd36
−/−
Msr1
−/−
lesions showed reduced expression of inflammatory genes and morphological analysis revealed a ≈30% decrease in macrophage apoptosis and a striking ≈50% decrease in plaque necrosis in aortic root lesions of these mice.

Conclusions—

Although targeted deletion of SR-A and CD36 does not abrogate macrophage foam cell formation or substantially reduce atherosclerotic lesion area in
Apoe
−/−
mice, loss of these pathways does reduce progression to more advanced necrotic lesions. These data suggest that targeted inhibition of these pathways in vivo may reduce lesional inflammation and promote plaque stability.
Platelet-Derived Growth Factor Receptor β Signaling Is Required for Efficient Epicardial Cell Migration and Development of Two Distinct Coronary Vascular Smooth Muscle Cell Populations
Authors: Mellgren Amy M. , Smith Christopher L. , Olsen Gregory S. , Eskiocak Banu , Zhou Bin , Kazi Michelle N. , Ruiz Fernanda R. , Pu William T. , Tallquist Michelle D.
Published: October 2008

The epicardium plays an essential role in coronary artery formation and myocardial development, but signals controlling the development and differentiation of this tissue are not well understood. To investigate the role of platelet-derived growth factor receptor (PDGFR)β in development of epicardial-derived vascular smooth muscle cells (VSMCs), we examined
PDGFR
β
−/−
and
PDGFR
β epicardial mutant hearts. We found that
PDGFR
β
−/−
hearts failed to form dominant coronary vessels on the ventral heart surface, had a thinned myocardium, and completely lacked coronary VSMCs (cVSMCs). This constellation of defects was consistent with a primary defect in the epicardium. To verify that these defects were specific to epicardial derivatives, we generated mice with an epicardial deletion of PDGFRβ that resulted in reduced cVSMCs distal to the aorta. The regional absence of cVSMCs suggested that cVSMCs could arise from 2 sources, epicardial and nonepicardial, and that both were dependent on PDGFRβ. In the absence of PDGFRβ signaling, epicardial cells adopted an irregular actin cytoskeleton, leading to aberrant migration of epicardial cells into the myocardium in vivo. In addition, PDGF receptor stimulation promoted epicardial cell migration, and PDGFRβ-driven phosphoinositide 3′-kinase signaling was critical for this process. Our data demonstrate that PDGFRβ is required for the formation of 2 distinct cVSMC populations and that loss of PDGFRβ-PI3K signaling disrupts epicardial cell migration.
Presynaptic Prostaglandin E2EP1-Receptor Facilitation of Cerebral Nitrergic Neurogenic Vasodilation
Authors: Jadhav Vikram , Jabre Anthony , Chen Mei-Fang , Lee Tony Jer-Fu
Published: October 2008

Background and Purpose—Prostaglandin E2(PGE2) modulates autonomic transmission in the peripheral circulation. We investigated the role of endogenous PGE2and its presynaptic EP1receptor subtype in modulating the autonomic neurotransmission in cerebral vasculature.

Methods—The standard in vitro tissue-bath technique was used for measuring changes in isolated porcine basilar arterial tone. Calcium imaging and nitric oxide estimation along with immunohistochemical analysis for cyclo-oxygenase-1, cyclo-oxygenase-2, EP1receptor, PGE synthase, and neuronal nitric oxide synthase were done in cultured sphenopalatine ganglia and basilar artery.

Results—Selective EP1receptor antagonists (SC-19220 and SC-51322) inhibited relaxation of endothelium-denuded basilar arterial rings elicited by transmural nerve stimulation (2 and 8 Hz) without affecting that induced by nicotine or sodium nitroprusside (a nitric oxide donor). The SC-19220 inhibition of transmural nerve stimulation-elicited relaxation was blocked by cyclo-oxygenase inhibitors (salicylic acid and naproxen) but was not affected by guanethidine (a sympathetic neuronal blocker) or atropine. Perivascular cyclo-oxygenase-1- and cyclo-oxygenase-2-immunoreactive fibers were observed in basilar arteries. PGE synthase and EP1receptor immunoreactivities were coincident with neuronal nitric oxide synthase immunoreactivities in perivascular nerves of the basilar arteries and the sphenopalatine ganglia. ω-conotoxin (an N-type calcium channel blocker) significantly blocked transmural nerve stimulation-induced relaxation, which was further attenuated by SC-19220. In cultured sphenopalatine ganglia neurons, exogenous PGE2significantly increased calcium influx and diaminofluorescein fluorescence indicative of nitric oxide synthesis. Both responses were blocked by SC-19220.

Conclusions—These results suggest that neuronal PGE2facilitates nitric oxide release from the cerebral perivascular parasympathetic nitrergic nerve terminals by increasing neuronal calcium influx through activation of presynaptic EP1receptors. PGE2may play an important role in regulating the nitrergic neurovascular transmission in the cerebral circulation.
Positron Emission Tomography Imaging of Poststroke Angiogenesis
Authors: Cai Weibo , Guzman Raphael , Hsu Andrew R. , Wang Hui , Chen Kai , Sun Guohua , Gera Atul , Choi Raymond , Bliss Tonya , He Lina , Li Zi-Bo , Maag Anne-Lise D. , Hori Nobutaka , Zhao Heng , Moseley Michael , Steinberg Gary K. , Chen Xiaoyuan
Published: October 2008

Background and Purpose—

Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) play important roles during neurovascular repair after stroke. In this study, we imaged VEGFR expression with positron emission tomography (PET) to noninvasively analyze poststroke angiogenesis.

Methods—

Female Sprague-Dawley rats after distal middle cerebral artery occlusion surgery were subjected to weekly MRI,
18
F-FDG PET, and
64
Cu-DOTA-VEGF
121
PET scans. Several control experiments were performed to confirm the VEGFR specificity of
64
Cu-DOTA-VEGF
121
uptake in the stroke border zone. VEGFR, BrdU, lectin staining, and
125
I-VEGF
165
autoradiography on stroke brain tissue slices were performed to validate the in vivo findings.

Results—

T2-weighed MRI correlated with the “cold spot” on
18
F-FDG PET for rats undergoing distal middle cerebral artery occlusion surgery. The
64
Cu-DOTA-VEGF
121
uptake in the stroke border zone peaked at ≈10 days after surgery, indicating neovascularization as confirmed by histology (VEGFR-2, BrdU, and lectin staining). VEGFR specificity of
64
Cu-DOTA-VEGF
121
uptake was confirmed by significantly lower uptake of
64
Cu-DOTA-VEGF
mutant
in vivo and intense
125
I-VEGF
165
uptake ex vivo in the stroke border zone. No appreciable uptake of
64
Cu-DOTA-VEGF
121
was observed in the brain of sham-operated rats.

Conclusions—

For the first time to our knowledge, we successfully evaluated the VEGFR expression kinetics noninvasively in a rat stroke model. In vivo imaging of VEGFR expression could become a significant clinical tool to plan and monitor therapies aimed at improving poststroke angiogenesis.
Three-Dimensional MRI Analysis of Individual Volume of Lacunes in CADASIL
Authors: Hervé Dominique , Godin Ophélia , Dufouil Carole , Viswanathan Anand , Jouvent Eric , Pachaï Chahin , Guichard Jean-Pierre , Bousser Marie-Germaine , Dichgans Martin , Chabriat Hugues
Published: October 2008

Background and Purpose—

Three-dimensional MRI segmentation may be useful to better understand the physiopathology of lacunar infarctions. Using this technique, the distribution of lacunar infarctions volumes has been recently reported in patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Whether the volume of each lacune (individual lacunar volume [ILV]) is associated with the patients’ other MRI lesions or vascular risk factors has never been investigated. The purpose of this study was to study the impact of age, vascular risk factors, and MRI markers on the ILV in a large cohort of patients with CADASIL.

Methods—

Of 113 patients with CADASIL, 1568 lacunes were detected and ILV was estimated after automatic segmentation on 3-dimensional T1-weighted imaging. Relationships between ILV and age, blood pressure, cholesterol, diabetes, white matter hyperintensities load, number of cerebral microbleeds, apparent diffusion coefficient, brain parenchymal fraction, and mean and median of distribution of lacunes volumes at the patient level were investigated. We used random effect models to take into account intraindividual correlations.

Results—

The ILV varied from 4.28 to 1619 mm
3
. ILV was not significantly correlated with age, vascular risk factors, or different MRI markers (white matter hyperintensity volume, cerebral microbleed number, mean apparent diffusion coefficient or brain parenchymal fraction). In contrast, ILV was positively correlated with the patients’ mean and median of lacunar volume distribution (
P
=0.0001).

Conclusions—

These results suggest that the ILV is not related to the associated cerebral lesions or to vascular risk factors in CADASIL, but that an individual predisposition may explain predominating small or predominating large lacunes among patients. Local anatomic factors or genetic factors may be involved in these variations.
Genome Screen to Detect Linkage to Common Susceptibility Genes for Intracranial and Aortic Aneurysms
Authors: Worrall Bradford B. , Foroud Tatiana , Brown Robert D. , Connolly E. Sander. , Hornung Richard W. , Huston John , Kleindorfer Dawn , Koller Daniel L. , Lai Dongbing , Moomaw Charles J. , Sauerbeck Laura , Woo Daniel , Broderick Joseph P.
Published: October 2008

Background and Purpose—

Risk for both intracranial aneurysms (IAs) and aortic aneurysms (AAs) is thought to be heritable with mounting evidence for genetic predisposition. The concept of shared risk for these conditions is challenged by differences in age of diagnosis and demographic characteristics. We performed a genomewide linkage analysis in multiplex families with both IA and AA from the Familial Intracranial Aneurysm study.

Methods—

Available medical records of subjects who reported IA or abdominal/thoracic AA were reviewed with adjudication as definite/probable, possible, or not a case. To identify genes contributing to the susceptibility for IA and AA, genomewide linkage analysis was performed in the 26 multiplex IA families who had members who also had thoracic or abdominal AA. Individuals (n=91) were defined as affected if they had an IA (definite/probable) or an aortic or thoracic AA (definite/probable).

Results—

Maximum logarithm of odds (LOD) scores were found on chromosomes 11 (144 cM; LOD=3.0) and 6 (33 cM; LOD=2.3). In both chromosomal regions, analyses of these same 26 families considering only IA as the disease phenotype produced LOD scores of 1.8 and 1.6, respectively.

Conclusions—

Our linkage analysis in these 26 families using the broadest disease phenotype, including IA, abdominal AA, and thoracic AA, supports the concept of shared genetic risk. The chromosome 11 locus appears to confirm earlier independent associations in IA and AA. The chromosome 6 finding is novel. Both warrant further investigation.
How Active Are People With Stroke?
Authors: Rand Debbie , Eng Janice J. , Tang Pei-Fang , Jeng Jiann-Shing , Hung Chihya
Published: October 2008

Background and Purpose—

Accelerometers are a unique tool used to objectively measure free-living physical activity, but their reliability for people with stroke has not been established. The primary aim was to assess the day-to-day reliability of these instruments for the paretic and nonparetic hips. The secondary aims were to measure the amount of physical activity with accelerometers that people with stroke undertake in the community and its relationship with walking capacity (6-minute walk test distance).

Methods—

Forty people with stroke wore one Actical accelerometer on each hip for 3 consecutive days at home and during the 6-minute walk test in the laboratory. The accelerometer measured physical activity using total activity counts per day and energy expenditure (kcal/d).

Results—

Excellent intraclass correlation coefficients (ICCs) for the activity counts (paretic hip ICC
[1,3]
=0.95, nonparetic hip ICC
[1,3]
=0.94) and for the energy expenditure (paretic hip ICC
[1,3]
=0.95, nonparetic hip ICC
[1,3]
=0.95) were found across the 3 consecutive days at home. Excellent ICCs were also found between the paretic versus the nonparetic hips for the activity counts (ICC
[1,3]
=0.98) and for the energy expenditure (ICC
[1,3]
=0.96). Free-living physical activity was very low and 58% of the participants did not meet recommended physical activity levels. Only moderate correlations (
r
=0.6 to 0.73,
P
<0.001) were found between the 6-minute walk test distance in the laboratory and 3-day physical activity recording at home.

Conclusions—

The accelerometer was found to be a reliable objective instrument. The use of accelerometers quantified the low level of free-living physical activity of people with stroke.
Impact of the Approval of Intravenous Recombinant Tissue Plasminogen Activator Therapy on the Processes of Acute Stroke Management in Japan
Authors: Sato Shoichiro , Uehara Toshiyuki , Toyoda Kazunori , Yasui Nobuyuki , Hata Takashi , Ueda Toshihiro , Okada Yasushi , Toyota Akihiro , Hasegawa Yasuhiro , Naritomi Hiroaki , Minematsu Kazuo ,   the Stroke Unit Multicenter Observational (SUMO) Study Group
Published: October 2008

Background and Purpose—

The Ministry of Health, Labor, and Welfare of Japan approved the use of recombinant tissue-type plasminogen activator (rt-PA) for the treatment of acute ischemic stroke in October 2005. The impact of the regulatory approval of rt-PA on the processes of acute stroke management was examined.

Methods—

A prospective, multicenter, observational study was conducted between December 2004 and December 2005 in 84 Japanese institutes, including 24 institutes with a stroke unit. We enrolled 4620 consecutive patients who were hospitalized within 72 hours after the onset of completed ischemic stroke; 1089 of them were hospitalized after rt-PA was approved. The patients’ characteristics and the processes of stroke management were compared before and after rt-PA approval.

Results—

Age, gender, stroke subtype, time from onset to hospital visit, and National Institutes of Health Stroke Scale score on admission were similar between the 2 periods. With approval, the percentage of patients treated with intravenous rt-PA therapy increased from 0.7% to 2.6% (
P
<0.001). The rate increased from 0.9% to 5.2% in institutes with a stroke unit (
P
<0.001) but did not increase in other institutes (
P
=0.587). Within 24 hours of stroke onset, conventional MRI (
P
=0.003), diffusion-weighted MRI (
P
<0.001), magnetic resonance angiography (
P
=0.001), carotid ultrasound (
P
=0.004), measurement of prothrombin time or activated partial thromboplastin time (
P
=0.034), and measurement of blood sugar (
P
=0.015) were performed more frequently after rt-PA approval.

Conclusions—

The present results indicate that the approval of intravenous rt-PA therapy resulted in dramatic changes in the processes of management for acute stroke patients.
Embolic Potential of Cardiac Tumors and Outcome After Resection
Authors: ElBardissi Andrew W. , Dearani Joseph A. , Daly Richard C. , Mullany Charles J. , Orszulak Thomas A. , Puga Francisco J. , Schaff Hartzell V.
Published: October 2008

Background and Purpose—

Embolic events have long been thought to occur in patients with cardiac tumors secondary to embolization of tumor fragments; however, there are no large studies examining the epidemiology and occurrence of embolism in this group of patients.

Methods—

From 1957 to 2006, 323 consecutive patients with primary cardiac tumors were treated surgically at our institution. Of these, patients who experienced an embolic event included 80 (cerebrovascular accident 31 [9.7%], transient ischemic attack 30 [9.3%], and other 19 [6%]). Those with no history of an embolic event (n=243 [75%]) were defined as control subjects.

Results—

Age was similar between the case and control groups (mean 54.5 versus 53.9 years,
P
=0.8). A multivariate logistic regression model including tumor location, tumor burden, tumor histology, and cerebrovascular risk factors, indicated that left atrial tumors (OR, 1.95;
P
=0.04), aortic valve tumors (OR, 4.17;
P
=0.002), and smaller tumor burden (OR, 2.20;
P
=0.01) were the most significant factors in the occurrence of embolism (
P
<0.001). The presence of mitral regurgitation (OR, 0.12;
P
=0.006) and decreased functional status (New York Heart Association III/IV; OR, 0.31;
P
<0.001) were protective against the occurrence of embolism. Follow-up was obtained in 82% at a mean follow-up time of 6.17±6.9 years. There were no recurrent embolic events at follow-up. A Kaplan-Meier survival curve demonstrated no difference in survival between both groups (
P
=0.78).

Conclusion—

Aortic valve and left atrial tumors have the greatest anatomic risk for embolism. Furthermore, patients with smaller tumors, minimal symptomatology, and no evidence of mitral regurgitation have a high risk of embolism. Cardiac tumors can be resected with low early mortality, and late survival after operation in the context of an embolic event is similar to patients with cardiac tumors who undergo resection for other indications.
Use of an Exposure‐Response Model to Aid Early Drug Development of an Oral Sphingosine 1‐Phosphate Receptor Modulator
Authors: Rohatagi Shashank , Zahir Hamim , Moberly James B. , Truitt Kenneth E. , Inaba Shin‐ichi , Shimozato Takaichi , Carrothers T. J.
Published: October 2008

Pharmacokinetic (PK) and exposure‐response modeling of a selective sphingosine 1‐phosphate receptor‐1 modulator (CS‐0777) was conducted in an iterative process to guide early clinical development decisions. A model based on preclinical data from monkeys was extrapolated to humans to support a single ascending dose (SAD) study. The model was updated after each cohort, providing guidance on both maximal inhibition and time to recovery for lymphocyte counts. A 2‐compartment PK model with first‐order absorption and elimination was found to describe the monkey and human datasets. The relationship between lymphocyte counts and active metabolite (M‐1) concentrations was modeled via an indirect response model, whereby M‐1 inhibited the reentry of lymphocytes to the circulation. The indirect‐response model based on SAD data had an Imax of approximately 85% and an IC50 of 0.24 ng/mL. Additionally, based on SAD data, similar models were developed for lymphocyte subsets, including CD4 cells. Subsequently, simulations were utilized to design a multiple ascending dose study with adaptive dosing regimens that would meet targeted pharmacodynamic (PD) response thresholds (eg, minimum 40% reduction in lymphocytes) while maintaining CD4 counts above a reasonable safety threshold. In conclusion, model‐based development and use of adaptive designs for dose optimization can reduce the time and number of subjects needed in early clinical development.
Patient education on mobile devices: an e-health intervention for low health literate audiences
Authors: Mackert Michael , Love Brad , Whitten Pamela
Published: October 2008

Providing health information to low health literate audiences remains a challenge. Beyond message design, realistic delivery models are needed for delivering information to a traditionally hard-to-reach audience. This study investigated two e-health interventions to provide health information on mobile devices — one providing diabetes information and one offering childcare information. Both were well-received, and most of the subjects' usability issues related to the translation of these interventions to the mobile device's smaller screen. The diabetes website was effective in providing information to study participants (as measured by pre- and post-tests of knowledge), while the childcare website was not. Continued work in this area could explore improved design strategies for mobile devices — a delivery model that could be used in doctors' offices, for example. Effective delivery of health information to low health literate audiences is an important issue, and this research highlights a critical element by targeting another potential delivery model.
Childhood Brain Tumors: Accomplishments and Ongoing Challenges
Authors: Packer Roger J.
Published: October 2008

The management of childhood brain tumors, which consist of many different histological subtypes, continues to be a challenge. Outcome, measured not only by survival rates but also by the effects of disease and therapy on quality of life, has improved over the past two decades for some tumor types, most notably medulloblastomas. For others, however, there has been little progress, and quality of life for long-term survivors remains suboptimal. Because of advances in our understanding of the biology underlying childhood brain tumors, treatments may change dramatically in the years ahead. Accordingly, survival rates may improve and long-term sequelae lessen.
Using Neurofibromatosis-1 to Better Understand and Treat Pediatric Low-Grade Glioma
Authors: Gutmann David H.
Published: October 2008

Relatively little is known about the seminal genetic events that trigger the development of low-grade gliomas in children. Genetically engineered mouse models of the neurofibromatosis-1—inherited tumor predisposition syndrome have identified key intracellular growth control pathways, defined the contribution of the tumor microenvironment to glioma growth, and helped researchers understand the genetic basis for glioma susceptibility. In addition, genetically engineered mouse low-grade glioma models have recently been used in preclinical therapeutic studies to evaluate the efficacy of particular biologically based therapies and to define outcome measures.
Stem Cells and the Origin and Propagation of Brain Tumors
Authors: Emmenegger Brian A. , Wechsler-Reya Robert J.
Published: October 2008

In recent years there has been a flood of interest in the relationship between brain tumors and stem cells. Some investigators have focused on the sensitivity of normal stem cells to transformation, others have described phenotypic or functional similarities between tumor cells and stem cells, and still others have suggested that tumors contain a subpopulation of ``cancer stem cells'' that is crucial for tumor maintenance or propagation. Although all these concepts are interesting and provide insight into the origins and properties of brain tumors, the use of similar terms to describe them has led to confusion. The goal of this review is to sort out some of that confusion and highlight what we know and what we have yet to learn.
Convection-Enhanced Delivery for the Treatment of Pediatric Neurologic Disorders
Authors: Song Debbie K. , Lonser Russell R.
Published: October 2008

Direct perfusion of specific regions of the central nervous system by convection-enhanced delivery is becoming more widely used for the delivery of compounds in the research and treatment of various neural disorders. In contrast to other currently available central nervous system delivery techniques, convection-enhanced delivery relies on bulk flow for distribution of solute. This allows for safe, targeted, reliable, and homogeneous delivery of small—molecular-weight and large—molecular-weight substances over clinically relevant volumes in a manner that bypasses the blood-central nervous system barrier. Recent studies have also shown that coinfused imaging surrogate tracers can be used to monitor and control the convective distribution of therapeutic agents in vivo. The unique features of convection-enhanced delivery, including the ability to monitor distribution in realtime, provide an opportunity to develop new research and treatment paradigms for pediatric patients with a variety of intrinsic central nervous system disorders.
Preventing Neurocognitive Late Effects in Childhood Cancer Survivors
Authors: Askins Martha A. , Moore Bartlett D.
Published: October 2008

Neurocognitive late effects are common sequelae of cancer in children, especially in those who have undergone treatment for brain tumors or in those receiving prophylactic cranial radiation therapy to treat leukemia. Neurocognitive morbidity in attention, executive functioning, processing speed, working memory, and memory frequently occurs and contributes to declines in intellectual and academic abilities. Oncologists are faced with the challenge of using the most effective, often the most intense, therapy to achieve the primary goal of medical success, balanced with the desire to prevent adverse late effects. Not all children with similar diagnoses and treatment have identical neurocognitive outcomes; some do very poorly and some do well. Attention now turns to the reliable prediction of risk for poor outcomes and then, using risk-adapted therapy, to preserve neurocognitive function. Prevention of late effects through rehabilitative strategies, continuation of school, and pharmacotherapy will be explored.
Hyaluronan Regulates Ceruloplasmin Production By Gliomas and Their Treatment-Resistant Multipotent Progenitors
Authors: Tye Sandra L. , Gilg Anne G. , Tolliver Lauren B. , Wheeler William G. , Toole Bryan P. , Maria Bernard L.
Published: October 2008

Ceruloplasmin (glycosylphosphatidylinositol-linked ferroxidase associated with normal astrocytes) can also be secreted by glioma cells, where its function is unknown. Ceruloplasmin is not only present in glioma cells and in human glioma specimens but also is enriched in highly malignant glioma stem-like cells. Hyaluronan is a large extracellular glycosaminoglycan that enhances malignant glioma behaviors by interacting with CD44 receptors and by downstream activation of signaling proteins and transporters associated with malignancy. We examined the relationship between hyaluronan and ceruloplasmin expression in glioma stem-like cells. Antagonism of hyaluronan interactions with short-fragment hyaluronan oligomers decreased ceruloplasmin expression in parental and stem-like glioma cells in vivo and in cell culture, implying that hyaluronan regulates ceruloplasmin expression. Further gain and loss-of-function studies are needed to fully define the relationship between hyaluronan and ceruloplasmin, and ceruloplasmin's effect on malignant behaviors.
Regression of Subependymal Giant Cell Astrocytoma With Rapamycin in Tuberous Sclerosis Complex
Authors: Koenig Mary Kay , Butler Ian J. , Northrup Hope
Published: October 2008

The authors present a 21-year-old woman who has been receiving rapamycin for 5 months for bilateral subependymal giant cell astrocytomas. The patient was started at a dose of 0.2 mg/kg/day. Levels were maintained between 11 and 13 ng/mL. Magnetic resonance imaging of the brain 2½ months after initiating rapamycin demonstrated a decrease in size of both astrocytomas (11 to 7.5 mm on the right and 8 to 5 mm on the left). Further studies are needed with prolonged observation to confirm these findings, determine the length of necessary treatment, and evaluate recurrence risk after discontinuation of rapamycin.
Chemotherapy for Malignant Brain Tumors of Childhood
Authors: Gottardo Nicholas G. , Gajjar Amar
Published: October 2008

During the past 3 decades, chemotherapeutic agents for the treatment of pediatric brain tumors have been extensively evaluated in a myriad of schedules, doses, and combinations. Remarkable advances in outcome have been achieved for certain children, notably those with medulloblastoma, but with a high cost to quality of life. In addition, the success achieved for medulloblastoma is offset by lack of progress for high-grade glioma. Despite intensive investigation, no single chemotherapeutic regimen stands out for children with high-grade glioma, with most succumbing to their disease. Further treatment intensification using conventional nonspecific chemotherapy is more likely to result in additional toxicity without major advances in survival. Genome-wide analysis using microarray technology has contributed significantly to our understanding of tumor biology, shifting the focus onto novel agents that target molecular changes crucial for tumor proliferation or survival. These selective agents are likely to be less toxic to normal cells and more effective.
Searching for a Chinese Civil Society Model
Authors: Salmenkari Taru
Published: October 2008

This study hypothesizes that the Chinese state uses NGOs as objects of consultation for improving its policymaking in the same way it consults mass organizations, democratic parties, and official professional associations to obtain specialist information. This model of consultation is based on the mass-line model and on its application within democratic centralist administrative hierarchies. The investigation shows that, apart from their main social or environmental tasks, Chinese NGOs indeed inform the state, many of them with policy formulation in mind. It also shows that the Chinese state uses democratic centralist vocabulary to describe the tasks that it assumes NGOs should undertake. However, apart from the mass-line type of consultation, both NGOs and the state have other conceptions about the proper roles for NGOs. The state now promotes the idea of civil society as an independent service provider, while NGOs seek an even larger sphere of social autonomy and self-organization.
Negotiating Three Worlds
Authors: Holkup Patricia A. , Rodehorst T. Kim , Wilhelm Susan L. , Kuntz Sandra W. , Weinert Clarann , Stepans Mary Beth Flanders , Salois Emily Matt , Hand Bull Jacqueline Left , Hill Wade G.
Published: October 2008

Purpose: The purpose of this article is to use a cross-cultural model to guide the exploration of common issues and the dynamic interrelationships surrounding entrée to tribal communities as experienced by four nursing research teams. Method: Members of four research teams discuss the primary lessons learned about successful strategies and challenges encountered during their projects' early stages. Results: Understanding the cultural values of relationship and reciprocity is critical to the success of research projects conducted in Native American communities. Discussion: Conducting cross-cultural research involves complex negotiations among members of three entities: academia, nursing science, and tribal communities. The lessons learned in these four research projects may be instructive to investigators who have the opportunity to conduct research with tribal communities .
Determinants of Latina Obesity in the United States
Authors: Yeh Ming-Chin , Viladrich Anahi , Bruning Nancy , Roye Carol
Published: October 2008

Obesity has reached epidemic proportions in the United States. Hispanic American women in particular have higher rates of obesity than their non-Hispanic White counterparts. In this article, the authors review the existing literature on acculturation as it relates to obesity and health behaviors among U.S. Hispanic women. In addition, a conceptual framework is proposed to examine factors contributing to obesity through “selective acculturation.” This concept challenges traditionally held unilateral assumptions that underscore Hispanic women's unhealthful behavioral patterns by explaining a process whereby Hispanic women both maintain some older health-related behaviors and acquire new ones once they settle in a new culture.
3D MPRAGE improves classification of cortical lesions in multiple sclerosis
Authors: Nelson F , Poonawalla A , Hou P , Wolinsky JS , Narayana PA
Published: October 2008

Background

Gray matter lesions are known to be common in multiple sclerosis (MS) and are suspected to play an important role in disease progression and clinical disability. A combination of magnetic resonance imaging (MRI) techniques, double-inversion recovery (DIR), and phase-sensitive inversion recovery (PSIR), has been used for detection and classification of cortical lesions. This study shows that high-resolution three-dimensional (3D) magnetization-prepared rapid acquisition with gradient echo (MPRAGE) improves the classification of cortical lesions by allowing more accurate anatomic localization of lesion morphology.

Methods

11 patients with MS with previously identified cortical lesions were scanned using DIR, PSIR, and 3D MPRAGE. Lesions were identified on DIR and PSIR and classified as purely intracortical or mixed. MPRAGE images were then examined, and lesions were re-classified based on the new information.

Results

The high signal-to-noise ratio, fine anatomic detail, and clear gray-white matter tissue contrast seen in the MPRAGE images provided superior delineation of lesion borders and surrounding gray-white matter junction, improving classification accuracy. 119 lesions were identified as either intracortical or mixed on DIR/PSIR. In 89 cases, MPRAGE confirmed the classification by DIR/PSIR. In 30 cases, MPRAGE overturned the original classification.

Conclusion

Improved classification of cortical lesions was realized by inclusion of high-spatial resolution 3D MPRAGE. This sequence provides unique detail on lesion morphology that is necessary for accurate classification.
Association of the HLA-DRB1 alleles with characteristic MRI features of Asian multiple sclerosis
Authors: Matsuoka T , Matsushita T , Osoegawa M , Kawano Y , Minohara M , Mihara F , Nishimura Y , Ohyagi Y , Kira J
Published: October 2008

Background

In Asian patients with multiple sclerosis (MS), a paucity of brain lesions and longitudinally extensive spinal cord lesions (LESCLs) extending three or more vertebral segments are characteristic findings on magnetic resonance imaging (MRI). We aimed to disclose possible factors contributing to the development of such MRI features.

Method

Genotyping of HLA-DRB1 and -DPB1 alleles was performed in 121 consecutive Japanese patients with clinically definite MS based on the Poser criteria and 125 healthy controls. Possible factors associated with MRI features were determined by multiple logistic analysis. Patients with MS were classified based on the presence or absence of brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) and LESCLs. Barkhof brain lesion–negative (−) patients had a markedly lower frequency of HLA-DRB1*0901 than controls ( Pcorr < 0.05), whereas the frequency of DRB1*1501 was increased in the Barkhof brain lesion–positive (+) group, although this increase was not significant after correction. No Barkhof(−)LESCL(+) patients carried DRB1*0901 ( Pcorr < 0.05), despite this being the most common allele in Japanese. The Barkhof(−)LESCL(−) group showed a significant increase in the frequency of DRB1*0405 compared with controls ( Pcorr < 0.05). None of the DPB1 alleles were significantly different among the groups. Using multiple logistic analysis, the absence of oligoclonal bands was positively associated with an absence of Barkhof brain lesions, whereas a higher EDSS score was positively associated with the presence of LESCLs; however, the presence of anti-aquaporin-4 antibodies was not associated with either feature.

Conclusion

The characteristic MRI features in Asians are partly related to distinct HLA-DRB1 gene alleles and an absence of oligoclonal bands.
Listening to students
Authors: Rae Agnes M. , Cochrane David K.
Published: October 2008

Written assessment feedback has not been widely researched despite higher education students continually expressing the need for meaningful and constructive feedback. This qualitative study employing focus groups captures and interprets the student perspective of written assessment feedback. Participants were Registered Nurses and non-traditional entrants to higher education. The findings generated a framework of themes and categories representing the feedback process experienced by the students. The themes were `learning from', `the process of receiving' and `making sense of' feedback. When this framework incorporates strategies such as `feed-forward', self-managed learning and personalized guidance it then represents a heuristic model of effective written assessment feedback. The model, created as a result of the research, should enhance the student experience and aid understanding of the complex processes associated with providing written assessment feedback.
The importance of establishing relevance in motivating student learning
Authors: Kember David , Ho Amber , Hong Celina
Published: October 2008

This article reports findings from a study which interviewed 36 undergraduate students about aspects of the teaching and learning environment which motivated or demotivated their study. It was found that students were motivated by a teaching environment characterized by eight main elements. This article reports in detail on the element of establishing relevance, as this seemed very important to the interviewees. The interviewees found that teaching abstract theory alone was demotivating. Relevance could be established through: showing how theory can be applied in practice, establishing relevance to local cases, relating material to everyday applications, or finding applications in current newsworthy issues. The traditional building block curriculum, which devotes substantial parts of initial courses to basic theory, could demotivate students if they could not see how the theory was applicable to the discipline or profession. The problem could be alleviated by a course which revealed a curriculum map showing the application of basic material in more advanced courses, or by early periods of exposure to professional practice in professional programmes. Professional programmes faced a double-edged sword with respect to relevance in that it could be established by demonstrating that material was relevant to a future career. However, students could easily become demotivated if they could not see the relevance of theoretical material, since they had chosen a professional programme in the expectation that it would prepare them well for their future career.
Domestic Violence Against Men in Primary Care in Nigeria
Authors: Dienye Paul O. , Gbeneol Precious K.
Published: October 2008

Domestic violence against men is rare in Nigeria. This study was aimed at assessing the prevalence of domestic violence against men, the sociodemographic characteristics of victims, and the pattern of injury sustained in a primary care setting. This was a retrospective study over a period of 5 years in which all the medical records of patients were retrieved and information on domestic violence extracted from them and transferred to a data sheet. Those whose records were grossly deficient were excluded from the study. A total of 220,000 patients were seen of which 48 (22 per 100,000) were victims of domestic violence. There were only five married male victims with a prevalence of 0.0023%. The injuries observed were scratches, bruises, welts, and scalds. The primary care physician needs a high index of suspicion to be able to detect it.
Studying home health care nurses and aides: research design and challenges
Authors: Markkanen Pia , Chalupka Stephanie M , Galligan Catherine , Sama Susan R , Gore Rebecca J , Kim Hyun , Bello Anila , Kriebel David , Quinn Margaret
Published: October 2008

Home health care (HHC) is growing rapidly and yet health and safety conditions of HHC clinicians are poorly understood. Study of this workforce presents unique challenges because it is decentralised, often part-time and mobile. As part of a larger project on sharps injuries and blood exposures in HHC, this paper addresses the challenges of recruiting a large cohort of HHC nurses and aides and describes novel cross-sectional survey methodology. Recruitment was conducted with cooperation from eight HHC agencies and two labour unions. Intensive personal contacts and a financial incentive ($25) were employed. Some groups of HHC clinicians could be contacted only by mail, while others were contacted during a promotional “mini-fair” at their agency. A total of 1772, 18-page health and safety surveys were distributed and 1225 usable surveys were collected. This 69% overall response rate is better than that in many recent health surveys. Survey returns were highest (67—91%) where promotional events were held. The mailing-only strategy generated lower response rates (53—55%), despite the same financial incentive. Despite the challenges of reaching out to the decentralised HHC workforce, adequate response to a detailed health survey is possible, using appropriate techniques and with the close cooperation of employers and labour unions.
Perception of colorectal cancer risk does not enhance participation in screening
Authors: Dear Keith , Scott Leitha , Chambers Sharon , Corbett Mike C. , Taupin Doug
Published: October 2008

High participation is a key requirement for effective cancer screening. Many strategies to improve participation hold that a person's knowledge and beliefs dictate screening behavior. We compared perception of colon cancer risk in participants and nonparticipants in a population-based study of screening colonoscopy, and also assessed past screening behavior. Surprisingly, while past screening behavior was a predictor of participation, we found that participants perceived their risk of colorectal cancer to be significantly and substantially lower than the real figure and that of nonparticipants. Our data suggest that health promotion strategies aimed at improving health knowledge may not be effective in improving population screening rates.
Review: Causes of, and therapeutic approaches for, proton pump inhibitor-resistant gastroesophageal reflux disease in Asia
Authors: Kinoshita Yoshikazu , Ishihara Shunji
Published: October 2008

Proton pump inhibitors (PPIs) are the most widely used drugs for treatment of gastroesophageal reflux disease. However, approximately 20% of patients with reflux esophagitis and 40% of those with nonerosive reflux diseases complain of troublesome symptoms, even during treatment with PPIs. In patients with reflux esophagitis, dose escalation and co-administration with a histamine H2-receptor antagonist are potential approaches, since the major cause of PPI resistance is incomplete suppression of gastric acid secretion. On the other hand, for patients with nonerosive reflux disease, switching from PPIs to pain modulators is often necessary for improvement of symptoms, since 25% of patients with nonerosive reflux disease have symptoms not caused by gastroesophageal acid reflux. Therapeutic approaches for PPI-resistant patients with reflux esophagitis and nonerosive reflux diseases are considered according to pathogenesis.
Sonographic Detection of the Ovarian Hyperreactio Luteinalis in Pregnancy
Authors: Grochal Frantisek , Turner Cheryl Delynne , Chern Andrew L. , Wilters John , Jeanty Philippe
Published: October 2008

Hyperreactio luteinalis is a rare, benign ovarian finding during pregnancy, but its sonographic appearance can imitate a malignant process, and the ovarian enlargement predisposes a woman carrying this anomaly to other complications. The management of hyperreactio luteinalis during pregnancy is preferably conservative, and surgical treatment is reserved for the cases with associated complications. This article reviews maternal ovarian hyperreactio luteinalis in pregnancy and demonstrates an example. Proper assessment of the maternal hyperreactio luteinalis helps to prevent its unnecessary surgical treatment.
Sonography as a Preferred Diagnostic Tool to Assess Shoulder Displacement in Brachial Plexus Palsy
Authors: Zhang Shuzhen , Ezaki Marybeth
Published: October 2008

Sonographic imaging of the shoulder in an infant is a challenge for pediatric physicians, radiologists, and sonographers. At the Texas Scottish Rite Hospital for Children, sonographic techniques have been used to examine the posterior aspect of the glenohumeral joint in patients with brachial plexus palsy. Between 1999 and 2006 146 patients were evaluated by sonography, including 124 patients who were assessed both before and after therapeutic intervention. The sonographic findings were accurate and reliable in providing diagnostic information. The advantages are that ultrasonic energy involves no ionizing radiation and is noninvasive, examination times are shorter than computed tomography (CT) or magnetic resonance imaging (MRI), costs are lower, and no sedation is needed in preparation. Results showed that when properly performed, sonography is a diagnostic tool preferable over plain x-ray, CT, MRI, and arthrography in evaluating the shoulder in infants.
Sonographic Evaluation of Interstitial (Cornual) Ectopic Pregnancy
Authors: Wright Chelsey N.
Published: October 2008

Interstitial ectopic pregnancy, also referred to as a cornual ectopic pregnancy, is a rare form of ectopic pregnancy. The sonographic appearance of interstitial ectopic pregnancy is complex and varied, making an accurate diagnosis difficult and thorough clinical correlation necessary. Interstitial ectopic pregnancies carry an elevated risk of maternal mortality compared with other ectopic pregnancies, making expedient diagnosis and treatment important.