bluuebunny/crossref_metadata_2025 huggingface dataset:
Lowering of Proteinuria in Response to Antihypertensive Therapy Predicts Improved Renal Function in Late but Not in Early Diabetic Nephropathy: A Pooled Analysis
Authors: Jerums George , Panagiotopoulos Sianna , Premaratne Erosha , Power David A. , MacIsaac Richard J.
Published: February 2008

In late diabetic nephropathy (DN) the initial lowering of albumin excretion rate (AER) with antihypertensive therapy is proportional to the degree of subsequent preservation of glomerular filtration rate (GFR). Whether a similar relationship exists between AER and GFR in early diabetes is not known. The present analysis has compared AER and GFR responses to antihypertensive therapy in 33 published studies (77 treatment groups) of early and late DN in type 1 (T1) and type 2 (T2) diabetes, analyzed on an intention-to-treat basis. Prospective trials were included if the initial change in AER during the first year of therapy and the change in GFR during at least 2 years of follow-up could be estimated from group mean data. The initial % decreases in AER were 5.9 ± 4.3 (T1), 10.5 ± 5.4 (T2, normotensive) and 18.4 ± 6.2 (T2, hypertensive) in early DN and 7.6 ± 11.1 (T1) and 20.8 ± 5.5 (T2) in late DN. The corresponding annual % rates of decline of GFR were 2.0 ± 0.5 (T1), 1.6 ± 0.5 (T2, normotensive) and 2.1 ± 0.3 (T2, hypertensive) in early DN and 9.8 ± 1.5 (T1) and 9.2 ± 1.1 (T2) in late DN. AER and GFR responses in each treatment group were closely correlated in late nephropathy (T1, r = –0.67, p = 0.03; T2, r = 0.57, p = 0.02) but not in early nephropathy. In contrast to late DN, the initial decrease in AER with antihypertensive therapy was not shown to predict the subsequent rate of decline of GFR in early DN. It follows that assessment of renoprotection during antihypertensive therapy in early nephropathy should be based not only on albuminuria but also on the GFR response.
Protective Role of CYP1A1*2A in the Development of Multiple Myeloma
Authors: Kang Seong-Ho , Kim Tae Young , Kim Ho Young , Yoon Jong-Hyun , Cho Han-Ik , Yoon Sung Soo , Kang Dae Hee , Suh Cheol Won , Lee Jae Hoon , Lee Dong Soon
Published: February 2008

We had previously reported the association of the NQO1*2/*2 polymorphism with a decreased risk for multiple myeloma (MM) in Koreans (odds ratio, OR, 0.24; 95% confidence interval, CI, 0.01–0.68). The associations of polymorphisms of other metabolizing enzymes (CYP1A1, GSTM1 and GSTT1) with the MM risk were investigated in 116 Korean MM patients and 176 Korean controls using TaqMan allelic discrimination and multiplex polymerase chain reaction. The ORs for CYP1A1*1/*2A and CYP1A1*1/*2B genotypes were 0.43 (95% CI, 0.19–0.98) and 0.51 (95% CI, 0.26–0.98), respectively, which was significantly associated with a decreased MM risk. With regard to CYP1A1 alleles, the OR for the CYP1A1*2A allele was 0.57 (95% CI, 0.326–0.995), which was also significantly associated with a decreased MM risk. However, null types of GSTM1 and GSTT1 polymorphisms were not associated with the MM risk. These results were different from those of a previous report on Caucasians which suggested the association of the GSTT1 polymorphism with an increased MM risk and no association of CYP1A1 with the MM risk. The associations of polymorphisms of metabolizing enzymes with the risk for MM differed between Koreans and Caucasians, suggesting an ethnic variation in the susceptibility to MM.
Creation of Ventricular Septal Defects on the Beating Heart in a New Pig Model
Authors: Kozlik-Feldmann R. , Lang N. , Sodian R. , Aumann R. , Rassoulian D. , Hinterseer M. , Schmitz C. , Netz H.
Published: February 2008

Background/Aims: So far, surgical and interventional therapies for muscular ventricular septal defects (mVSDs) beyond the moderator band have had their limitations. Thus, alternative therapeutic strategies should be developed. We present a new animal model for the evaluation of such strategies. Methods: In a pig model (n = 9), anterolateral thoracotomy was performed for exposure of the left ventricle. mVSDs were created under two- and three-dimensional echocardiography with a 7.5-mm sharp punch instrument, which was forwarded via a left ventricular puncture without extracorporeal circulation. Results: Creation of mVSDs was successful in all animals (n = 9) confirmed by echocardiography, hemodynamic measurements and autopsy. The defects were located in the midmuscular (n = 4), apical (n = 1), inlet (n = 2) and anterior part (n = 2) of the muscular septum. All animals were hemodynamically stable for further procedures. The diameter and shunt volume of the mVSDs were 4.8–7.3 mm (mean: 5.9 mm) and 12.9–41.3% (mean: 22.1%), respectively. Autopsy confirmed in all animals the creation of a substantial defect. Conclusion: The described new technique for creation of an mVSD on the beating heart in a pig model is suitable for the evaluation of new therapeutic strategies for mVSD closure.
Vitiligo after Hematopoietic Cell Transplantation: Six Cases and Review of the Literature
Authors: Sanlı Hatice , Akay Bengü Nisa , Arat Mutlu , Koçyigit Pelin , Akan Hamdi , Beksac Meral , Ilhan Osman
Published: February 2008

Aim: To investigate the prevalence and clinical characteristics of vitiligo after allogeneic hematopoietic cell transplantation (AHCT). Methods: The development of vitiligo was analyzed among 421 patients who underwent AHCT in Ibni Sina Hospital (University of Ankara) between 1988 and 2004. Results: Among 421 patients, we describe 6 with generalized vitiligo occurring after AHCT for chronic myelogenous leukemia. Five of them had severe chronic graft-versus-host disease (GVHD). Vitiligo was accompanied by alopecia areata and acquired ichthyosis in 2 patients with GVHD. Conclusion: Melanocyte destruction caused by the autoimmune reactions triggered by chronic GVHD as well as a genetic predisposition might have played a role in the development of vitiligo in our patients. These data support the hypothesis that vitiligo is an autoimmune entity.
Etanercept at Different Dosages in the Treatment of Generalized Pustular Psoriasis: A Case Series
Authors: Esposito M. , Mazzotta A. , Casciello C. , Chimenti S.
Published: February 2008

Background: Generalized pustular psoriasis (GPP) is a severe and disabling variant of psoriasis. The treatment of GPP is challenging, often characterized by side effects or unsatisfactory response. Etanercept is a tumor necrosis factor α blocking agent that demonstrated a consistent efficacy in the control of psoriasis. Objectives: We aimed to evaluate the efficacy and safety profile of etanercept at different dosages in GPP. Methods: Six patients affected by GPP, unresponsive to conventional treatment, received etanercept subcutaneously at the dosages of 25 and 50 mg biweekly for 48 weeks. Results: Our experience led to the observation that the administration of etanercept 50 mg biweekly is an effective dosage, characterized by good efficacy and rapidity of effect. Patients who were continuously treated at this dosage for 24 weeks presented stable conditions and long-term maintenance until week 48 even after a dose reduction to 25 mg. Conclusion: We demonstrated a good and durable efficacy of etanercept in patients affected by GPP.
A Comprehensive Review of Acute Promyelocytic Leukemia in Children
Authors: Mantadakis Elpis , Samonis George , Kalmanti Maria
Published: February 2008

The outcome of patients with acute promyelocytic leukemia (APL) has substantially improved since the successful introduction of tretinoin, and nowadays combining tretinoin with chemotherapy is potentially curative for at least 70–75% of patients with newly diagnosed APL. In most pediatric series, APL represents ≤10% of childhood acute myelogenous leukemia. APL in children is more common in girls and in obese children. It is characterized by a higher incidence of hyperleukocytosis, an increased incidence of microgranular morphology and by more frequent occurrence of the PML/RARα isoforms bcr 2 and bcr 3 compared to adults. Tretinoin-based therapy is curative for the majority of children with APL. Recent data indicate that ≧2 negative RT-PCR assays for PML/RARα on bone marrow performed at least 1 month apart after completing therapy are strongly associated with long-term remissions, while conversion to PCR positivity for PML/RARα during remission is highly predictive of impending relapse. Data from recent studies in adults and limited data from children show that arsenic trioxide is the single most effective agent in APL and deserves immediate study in newly diagnosed children in an effort to further improve prognosis and to limit exposure to conventional cytotoxic chemotherapy.
Endothelial Cilia Are Fluid Shear Sensors That Regulate Calcium Signaling and Nitric Oxide Production Through Polycystin-1
Authors: Nauli Surya M. , Kawanabe Yoshifumi , Kaminski John J. , Pearce William J. , Ingber Donald E. , Zhou Jing
Published: February 2008

Background—

When challenged with extracellular fluid shear stress, vascular endothelial cells are known to release nitric oxide, an important vasodilator. Here, we show that the ability of cultured endothelial cells to sense a low range of fluid shear depends on apical membrane organelles, called cilia, and that cilia are compartments required for proper localization and function of the mechanosensitive polycystin-1 molecule.

Methods and Results—

Cells with the
Pkd1

null/null

or
Tg737

orpk/orpk

mutation encoded for polycystin-1 or polaris, respectively, are unable to transmit extracellular shear stress into intracellular calcium signaling and biochemical nitric oxide synthesis. Cytosolic calcium and nitric oxide recordings further show that fluid shear sensing is a cilia-specific mechanism because other mechanical or pharmacological stimulation does not abolish calcium and nitric oxide signaling in polycystin-1 and polaris mutant endothelial cells. Polycystin-1 localized in the basal body of
Tg737

orpk/orpk

endothelial cells is insufficient for a fluid shear stress response. Furthermore, the optimal shear stress to which the cells respond best does not alter the apical cilia structure but modifies the responsiveness of cells to higher shear stresses through proteolytic modification of polycystin-1.

Conclusions—

We demonstrate for the first time that polycystin-1 (required for cilia function) and polaris (required for cilia structure) are crucial mechanosensitive molecules in endothelial cells. We propose that a distinctive communication with the extracellular microenvironment depends on the proper localization and function of polycystin-1 in cilia.
Microsomal Prostaglandin E Synthase-1 Deletion Suppresses Oxidative Stress and Angiotensin II–Induced Abdominal Aortic Aneurysm Formation
Authors: Wang Miao , Lee Eric , Song Wenliang , Ricciotti Emanuela , Rader Daniel J. , Lawson John A. , Puré Ellen , FitzGerald Garret A.
Published: February 2008

Background—

Microsomal prostaglandin (PG) E
2
synthase-1 (mPGES-1) catalyzes isomerization of the cyclooxygenase product PGH
2
into PGE
2
. Deletion of mPGES-1 modulates experimentally evoked pain and inflammation and retards atherogenesis. The role of mPGES-1 in abdominal aortic aneurysm is unknown.

Methods and Results—

The impact of mPGES-1 deletion on formation of angiotensin II–induced abdominal aortic aneurysm was studied in mice lacking low-density lipoprotein receptor (LDLR
−/−
). Male mice deficient in both mPGES-1 and LDLR (mPGES-1
−/−
LDLR
−/−
) and littermate LDLR
−/−
mice were initiated on a high-fat diet at 6 months of age, followed 1 week later by continuous infusion of angiotensin II (1 μg/kg per minute) for an additional 4 weeks. Angiotensin II infusion upregulated aortic expression of cyclooxygenase-2 and mPGES-1, increased aortic macrophage recruitment and vascular nitrotyrosine staining (which reflects local oxidative stress), and augmented urinary excretion of the isoprostane 8,12-
iso
-iPF
2α
-VI (which reflects lipid peroxidation in vivo) and the major metabolite of PGE
2
(PGE-M). Deletion of mPGES-1 decreased both the incidence (87.5% versus 27.3%;
P
=0.02) and the severity of abdominal aortic aneurysm and depressed the aortic and systemic indices of oxidative stress. Deletion of mPGES-1 also depressed urinary PGE-M, whereas it augmented excretion of PGD
2
and PGI
2
metabolites, reflecting rediversion of the accumulated PGH
2
substrate in the double knockouts.

Conclusions—

Deletion of mPGES-1 protects against abdominal aortic aneurysm formation induced by angiotensin II in hyperlipidemic mice, coincident with a reduction in oxidative stress. The potential efficacy of selective inhibition of mPGES-1 in preventing or retarding aneurysm formation warrants further investigation.
The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial
Authors: Menasché Philippe , Alfieri Ottavio , Janssens Stefan , McKenna William , Reichenspurner Hermann , Trinquart Ludovic , Vilquin Jean-Thomas , Marolleau Jean-Pierre , Seymour Barbara , Larghero Jérôme , Lake Stephen , Chatellier Gilles , Solomon Scott , Desnos Michel , Hagège Albert A.
Published: February 2008

Background—

Phase I clinical studies have demonstrated the feasibility of implanting autologous skeletal myoblasts in postinfarction scars. However, they have failed to determine whether this procedure was functionally effective and arrhythmogenic.

Methods and Results—

This multicenter, randomized, placebo-controlled, double-blind study included patients with left ventricular (LV) dysfunction (ejection fraction ≤35%), myocardial infarction, and indication for coronary surgery. Each patient received either cells grown from a skeletal muscle biopsy or a placebo solution injected in and around the scar. All patients received an implantable cardioverter-defibrillator. The primary efficacy end points were the 6-month changes in global and regional LV function assessed by echocardiography. The safety end points comprised a composite index of major cardiac adverse events and ventricular arrhythmias. Ninety-seven patients received myoblasts (400 or 800 million; n=33 and n=34, respectively) or the placebo (n=30). Myoblast transfer did not improve regional or global LV function beyond that seen in control patients. The absolute change in ejection fraction (median [interquartile range]) between 6 months and baseline was 4.4% (0.2; 7.3), 3.4% (−0.3; 12.4), and 5.2% (−4.4; 11.0) in the placebo, low-dose, and high-dose groups, respectively (
P
=0.95). However, the high-dose cell group demonstrated a significant decrease in LV volumes compared with the placebo group. Despite a higher number of arrhythmic events in the myoblast-treated patients, the 6-month rates of major cardiac adverse events and of ventricular arrhythmias did not differ significantly between the pooled treatment and placebo groups.

Conclusions—

Myoblast injections combined with coronary surgery in patients with depressed LV function failed to improve echocardiographic heart function. The increased number of early postoperative arrhythmic events after myoblast transplantation, as well as the capability of high-dose injections to revert LV remodeling, warrants further investigation.
A Quantitative Trait Locus (LSq-1) on Mouse Chromosome 7 Is Linked to the Absence of Tissue Loss After Surgical Hindlimb Ischemia
Authors: Dokun Ayotunde O. , Keum Sehoon , Hazarika Surovi , Li Yongjun , Lamonte Gregory M. , Wheeler Ferrin , Marchuk Douglas A. , Annex Brian H.
Published: February 2008

Background—

Peripheral arterial disease (PAD) caused by occlusive atherosclerosis of the lower extremity has 2 major clinical manifestations. Critical limb ischemia is characterized by rest pain and/or tissue loss and has a ≥40% risk of death and major amputation. Intermittent claudication causes pain on walking, has no tissue loss, and has amputation plus mortality rates of 2% to 4% per year. Progression from claudication to limb ischemia is infrequent. Risk factors in most PAD patients overlap. Thus, we hypothesized that genetic variations may be linked to presence or absence of tissue loss in PAD.

Methods and Results—

Hindlimb ischemia (murine model of PAD) was induced in C57BL/6, BALB/c, C57BL/6×BALB/c (F1), F1×BALB/c (N2), A/J, and C57BL/6J-Chr7
A/J
/NaJ chromosome substitution strains. Mice were monitored for perfusion recovery and tissue necrosis. Genome-wide scanning with polymorphic markers across the 19 murine autosomes was performed on the N2 mice. Greater tissue loss and poorer perfusion recovery occurred in BALB/c than in the C57BL/6 strain. Analysis of 105 N2 progeny identified a single quantitative trait locus on chromosome 7 that exhibited significant linkage to both tissue necrosis and extent of perfusion recovery. Using the appropriate chromosome substitution strain, we demonstrate that C57BL/6-derived chromosome 7 is required for tissue preservation.

Conclusions—

We have identified a quantitative trait locus on murine chromosome 7 (LSq-1) that is associated with the absence of tissue loss in a preclinical model of PAD and may be useful in identifying gene(s) that influence PAD in humans.
Metabolic Syndrome and Risk of Development of Atrial Fibrillation
Authors: Watanabe Hiroshi , Tanabe Naohito , Watanabe Toru , Darbar Dawood , Roden Dan M. , Sasaki Shigeru , Aizawa Yoshifusa
Published: February 2008

Background—

The metabolic syndrome consists of a cluster of atherosclerotic risk factors, many of which also have been implicated in the genesis of atrial fibrillation (AF). However, the precise role of the metabolic syndrome in the development of AF is unknown.

Methods and Results—

This prospective, community-based, observational cohort study was based on an annual health check-up program in Japan. We studied 28 449 participants without baseline AF. We used 2 different criteria for the metabolic syndrome—the guidelines of the National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATP III) and those of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI)—to study the risk of development of new-onset AF. The metabolic syndrome was present in 3716 subjects (13%) and 4544 subjects (16%) using the NCEP-ATP III and AHA/NHLBI definitions, respectively. During a mean follow-up of 4.5 years, AF developed in 265 subjects (105 women). Among the metabolic syndrome components, obesity (age- and sex-adjusted hazard ratio [HR], 1.64), elevated blood pressure (HR, 1.69), low high-density lipoprotein cholesterol (HR, 1.52), and impaired insulin tolerance (HR, 1.44 [NCEP-ATP III] and 1.35 [AHA/NHLBI]) showed an increased risk for AF. The association between the metabolic syndrome and AF remained significant in subjects without treated hypertension or diabetes by the NCEP-ATP III definition (HR, 1.78) but not by the AHA/NHLBI definition (HR, 1.28).

Conclusions—

The metabolic syndrome was associated with increased risk of AF. The metabolic derangements of the syndrome may be important in the pathogenesis of AF.
Interference With PPARγ Signaling Causes Cerebral Vascular Dysfunction, Hypertrophy, and Remodeling
Authors: Beyer Andreas M. , Baumbach Gary L. , Halabi Carmen M. , Modrick Mary L. , Lynch Cynthia M. , Gerhold Thomas D. , Ghoneim Shams M. , de Lange Willem J. , Keen Henry L. , Tsai Yau-Sheng , Maeda Nobuyo , Sigmund Curt D. , Faraci Frank M.
Published: February 2008

The transcription factor PPARγ is expressed in endothelium and vascular muscle where it may exert antiinflammatory and antioxidant effects. We tested the hypothesis that PPARγ plays a protective role in the vasculature by examining vascular structure and function in heterozygous knockin mice expressing the P465L dominant negative mutation in PPARγ (L/+). In L/+ aorta, responses to the endothelium-dependent agonist acetylcholine (ACh) were not affected, but there was an increase in contraction to serotonin, PGF
2α
, and endothelin-1. In cerebral blood vessels both in vitro and in vivo, ACh produced dilation that was markedly impaired in L/+ mice. Superoxide levels were elevated in cerebral arterioles from L/+ mice and responses to ACh were restored to normal with a scavenger of superoxide. Diameter of maximally dilated cerebral arterioles was less, whereas wall thickness and cross-sectional area was greater in L/+ mice, indicating cerebral arterioles underwent hypertrophy and remodeling. Thus, interference with PPARγ signaling produces endothelial dysfunction via a mechanism involving oxidative stress and causes vascular hypertrophy and inward remodeling. These findings indicate that PPARγ has vascular effects which are particularly profound in the cerebral circulation and provide genetic evidence that PPARγ plays a critical role in protecting blood vessels.
5-Year Control and Treatment of Edema and Increased Capillary Filtration in Venous Hypertension and Diabetic Microangiopathy Using O-(β-Hydroxyethyl)-Rutosides: A Prospective Comparative Clinical Registry
Authors: Belcaro Gianni , Cesarone Maria Rosaria , Ledda Andrea , Cacchio Marisa , Ruffini Irma , Ricci Andrea , Ippolito Edmondo , Di Renzo Andrea , Dugall Mark , Corsi Marcello , Marino Santarelli Anna Rita , Grossi Maria Giovanna
Published: February 2008

This independent prospective controlled trial evaluates the efficacy of O-(β-hydroxyethyl)-rutosides (HR) during 5 years of administration against signs and symptoms and further degeneration of microcirculatory disturbances. The protective effect of HR in preventing end-point complications such as venous ulceration is evaluated. This study is based on evaluation of edema and the capillary filtration rate (CFR) in association with a clinical score scale. Patients having a severe degree of chronic venous insufficiency (CVI) and venous microangiopathy and completing at least 5 years of treatment are included. The following 4 groups are considered: group A (patients with CVI but without diabetes mellitus, receiving 1500 mg/d of HR), group B (patients with CVI and diabetes mellitus, receiving 2 g/d of HR), group C (control subjects receiving no pharmacologic or compression treatment), and group D (patients using elastic compression stockings only). All patients received the “best” available treatment. No adverse effects or intolerance is noted, with good compliance (>85%). In group A, there is a statistically significant decrease in the CFR during 5 years of follow-up. In group B, the decrease in the CFR is greater than that in group A. Reductions in edema, swelling, and the CFR during 5 years are notable, and values approach normal levels. During 5 years, HR is effective in treating venous edema and hypertension and in preventing deterioration of the distal venous system. The prevention of ulcerations with HR is another important observation. The effects of HR seem to be partially dose related, and tolerability and compliance are good.
Sociological Textbooks in Argentina and Mexico, 1940—60
Authors: Pereyra Diego Ezequiel
Published: February 2008

It is commonly believed that the teaching of sociology spread in Latin America only after 1960. However, sociological textbooks were published before then in response to increasing demand. A comparative analysis is made of eight books, four each from Argentina and Mexico; these are a broad cross-section of those then available to local students and cited in reading lists. Common and divergent topics, traditions, concepts, research methods, theories and cross-references are sought, and reasons for the similarities and differences are explored, with special attention to possible US influence. This teaching material is placed in the context of the local institutionalization of sociology at this period, and the history of sociological ideas in the region.
The Paradox of Majority Underrepresentation in Special Education in India
Authors: Kalyanpur Maya
Published: February 2008

In contrast to the phenomenon of minority overrepresentation in special education in developed countries such as the United States, a paradoxical situation occurs in many developing countries, whereby majority populations are underrepresented in the educational system. The author examines some of the prevailing and traditional societal and political-economic factors specific to India that contribute to this underrepresentation, such as a paucity of resources that affects children from low socioeconomic backgrounds, gender differences in child rearing and educational expectations that affect girls, and negative attitudes toward disability.
Computerized Maze Navigation and On-Road Performance by Drivers With Dementia
Authors: Ott Brian R. , Festa Elena K. , Amick Melissa M. , Grace Janet , Davis Jennifer D. , Heindel William C.
Published: February 2008

This study examined the ability of computerized maze test performance to predict the road test performance of cognitively impaired and normal older drivers. The authors examined 133 older drivers, including 65 with probable Alzheimer disease, 23 with possible Alzheimer disease, and 45 control subjects without cognitive impairment. Subjects completed 5 computerized maze tasks employing a touch screen and pointer as well as a battery of standard neuropsychological tests. Parameters measured for mazes included errors, planning time, drawing time, and total time. Within 2 weeks, subjects were examined by a professional driving instructor on a standardized road test modeled after the Washington University Road Test. Road test total score was significantly correlated with total time across the 5 mazes. This maze score was significant for both Alzheimer disease subjects and control subjects. One maze in particular, requiring less than 2 minutes to complete, was highly correlated with driving performance. For the standard neuropsychological tests, highest correlations were seen with Trail Making A (TrailsA) and the Hopkins Verbal Learning Tests Trial 1 (HVLT1). Multiple regression models for road test score using stepwise subtraction of maze and neuropsychological test variables revealed significant independent contributions for total maze time, HVLT1, and TrailsA for the entire group; total maze time and HVLT1 for Alzheimer disease subjects; and TrailsA for normal subjects. As a visual analog of driving, a brief computerized test of maze navigation time compares well to standard neuropsychological tests of psychomotor speed, scanning, attention, and working memory as a predictor of driving performance by persons with early Alzheimer disease and normal elders. Measurement of maze task performance appears to be useful in the assessment of older drivers at risk for hazardous driving.
Neuropsychological Correlates of Self-Reported Depression and Self-Reported Cognition Among Patients With Mild Cognitive Impairment
Authors: Bruce Jared M. , Bhalla Rishi , Westervelt Holly James , Davis Jennifer , Williams Vanessa , Tremont Geoffrey
Published: February 2008

Patients with mild cognitive impairment (MCI) frequently experience significant depressive symptomatology and report cognitive disturbances. To date, no studies have examined the relationship between MCI patients' neuropsychologic functioning, self-reported depressive symptoms, and self-reported cognitive difficulties. In this study, 82 MCI patients completed a comprehensive neuropsychological evaluation that included the Beck Depression Inventory (BDI). A subset of 41 patients and informants also completed a measure of cognitive difficulties. Poorer memory functioning was associated with fewer self-reported depressive symptoms and fewer cognitive complaints.
Self-Care and Professionally Guided Care in Osteoarthritis
Authors: Albert Steven M. , Musa Donald , Kwoh C. Kent , Hanlon Joseph T. , Silverman Myrna
Published: February 2008

Objective: The aim of this study was to examine the prevalence of self-management practices among older White and African American persons with osteoarthritis. Self-management was defined broadly to include all behaviors adopted to reduce morbidity, whether recommended by physicians or not. Methods: A population-based sample of Medicare beneficiaries ( N = 551) was recruited. An expanded set of self-management behaviors using structured and open-ended inquiry, along with use of arthritis-specific medications was elicited. Results: Few differences in self-care behaviors between race groups were found. However, older African American persons were significantly less likely to have prescriptions for nonsteroidal anti-inflammatory agents (NSAIDs) and more likely to use over-the-counter nonprescription analgesics. Discussion: Older White and African American persons made similar use of self-care strategies to reduce disease morbidity. African Americans without access to prescription pain relievers substituted nonprescription analgesics. A broader view of self-management is valuable for assessing the ways people may move between professionally guided care and self-care.
Understanding the views of parents of children with special needs about the nursing care their child receives when in hospital: a qualitative study
Authors: Avis Mark , Reardon Rachel
Published: February 2008

This article reports a qualitative study designed to explore parents' views on how their child with additional needs had been cared for by hospital nursing staff, focusing on how well their own and their child's needs had been identified and met. Twelve interviews with parents of children with additional needs and a thematic analysis of the interview data was conducted. Four themes were developed to provide an insight into parents' views about their experiences: their prior experiences of hospital care, including the process of being told the original diagnosis; communication with staff; nurse—parent relationships; and perceptions of nurses and nursing care. It concludes that parents experience some difficulties in developing a trusting relationship with the nurses caring for their child with additional needs. Parents perceive that nurses are not always able to recognize and respond to their needs when caring for their child. Failure to address these needs can interfere with the development of effective nurse—parent relationships.
Time Being: difficulties in integrating arts in health
Authors: Eades Guy , Ager Jacqui
Published: February 2008

A programme of `arts as healthcare', Time Being (TB), was established and delivered as arts on prescription (AoP) by Healing Arts on the Isle of Wight over the period October 2002—March 2005. Its aim was to demonstrate and identify the benefits arising to an individual's health as a result of participation in structured creative programmes and activity, with the objective of the programme becoming part of the locally commissioned NHS services of the primary care trust. Evaluation and testimony from participants demonstrate the impact creativity has in contributing to the improvement in health of an individual and the individual's appreciation and understanding of their own health. The response to the evaluation by the commissioning sector of the NHS, primary care trust, indicates the difficulties and reluctance of this sector to embrace and commission arts in health programmes. The conclusion is that providers such as Healing Arts are required to undertake further detailed cost—benefit, cash—efficiency, and quantified health—gain analysis on the role of arts and creativity as part of healthcare for it to become integrated into NHS healthcare delivery.
Assessment for Instructional Planning
Authors: Hosp John L. , Ardoin Scott P.
Published: February 2008

Assessment is a common task in education that has many varied purposes. One of these is the use of assessment data to make decisions about instructional planning. This article presents a framework for how to use assessment data to plan instruction. It also provides some background on terminology of assessment for instructional planning, considerations for the development or use of assessment measures, and guidance for designing instruction.
Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells
Authors: Anderson Britt E. , Taylor Patricia A. , McNiff Jennifer M. , Jain Dhanpat , Demetris Anthony J. , Panoskaltsis-Mortari Angela , Ager Ann , Blazar Bruce R. , Shlomchik Warren D. , Shlomchik Mark J.
Published: February 2008

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation. Effector memory T cells (TEM) do not cause GVHD but engraft and mount immune responses, including graft-versus-tumor effects. One potential explanation for the inability of TEM to cause GVHD is that TEM lack CD62L and CCR7, which are instrumental in directing naive T cells (TN) to lymph nodes (LN) and Peyer patches (PP), putative sites of GVHD initiation. Thus TEM should be relatively excluded from LN and PP, possibly explaining their inability to cause GVHD. We tested this hypothesis using T cells deficient in CD62L or CCR7, transplant recipients lacking PNAd ligands for CD62L, and recipients without LN and PP or LN, PP, and spleen. Surprisingly, CD62L and CCR7 were not required for TN-mediated GVHD. Moreover, in multiple strain pairings, GVHD developed in recipients that lacked LN and PP. Mild GVHD could even be induced in mice lacking all major secondary lymphoid tissues (SLT). Conversely, enforced constitutive expression of CD62L on TEM did not endow them with the ability to cause GVHD. Taken together, these data argue against the hypothesis that TEM fail to induce GVHD because of inefficient trafficking to LN and PP.
Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study
Authors: Winston Drew J. , Young Jo-Anne H. , Pullarkat Vinod , Papanicolaou Genovefa A. , Vij Ravi , Vance Estil , Alangaden George J. , Chemaly Roy F. , Petersen Finn , Chao Nelson , Klein Jared , Sprague Kellie , Villano Stephen A. , Boeckh Michael
Published: February 2008

The anti-cytomegalovirus (CMV) activity and safety of oral maribavir in CMV-seropositive allogeneic stem-cell transplant recipients were evaluated in a randomized, double-blind, placebo-controlled, dose-ranging study. After engraftment, 111 patients were randomized to receive CMV prophylaxis with maribavir (100 mg twice daily, 400 mg once daily, or 400 mg twice daily) or placebo. Within the first 100 days after transplantation, the incidence of CMV infection based on CMV pp65 antigenemia was lower in each of the respective maribavir groups (15%, P = .046; 19%, P = .116; 15%, P = .053) compared with placebo (39%). Similarly, the incidence of CMV infection based on plasma CMV DNA was lower in each of the respective maribavir groups (7%, P = .001; 11%, P = .007; 19%, P = .038) compared with placebo (46%). Anti-CMV therapy was also used less often in patients receiving each respective dose of maribavir (15%, P = .001; 30%, P = .051; 15%, P = .002) compared with placebo (57%). There were 3 cases of CMV disease in placebo patients but none in the maribavir patients. Adverse events, mostly taste disturbance, nausea, and vomiting, were more frequent with maribavir. Maribavir had no adverse effect on neutrophil or platelet counts. These results show that maribavir can reduce the incidence of CMV infection and, unlike ganciclovir, does not cause myelosuppression. This trial is registered at www.ClinicalTrials.gov as #NCT00223925.
Local radiotherapy of exposed murine small bowel: Apoptosis and inflammation
Authors: Polistena Andrea , Johnson Louis Banka , Ohiami-Masseron Salomé , Wittgren Lena , Bäck Sven , Thornberg Charlotte , Gadaleanu Virgil , Adawi Diya , Jeppsson Bengt
Published: February 2008

Background

Preoperative radiotherapy of the pelvic abdomen presents with complications mostly affecting the small bowel. The aim of this study was to define the features of early radiation-induced injury on small bowel.

Methods

54 mice were divided into two groups (36 irradiated and 18 sham irradiated). Animals were placed on a special frame and (in the radiated group) the exteriorized segment of ileum was subjected to a single absorbed dose of 19 or 38 Gy radiation using 6 MV high energy photons. Specimens were collected for histology, immunohistochemistry (IHC) and ELISA analysis after 2, 24 and 48 hours. Venous blood was collected for systemic leucocyte count in a Burker chamber.

Results

Histology demonstrated progressive infiltration of inflammatory cells with cryptitis and increased apoptosis. MIP-2 (macrophage inflammatory protein) concentration was significantly increased in irradiated animals up to 48 hours. No significant differences were observed in IL-10 (interleukin) and TNF-α (tumour necrosis factor) levels. IHC with CD45 showed a significant increase at 2 hours of infiltrating leucocytes and lymphocytes after irradiation followed by progressive decrease with time. Caspase-3 expression increased significantly in a dose dependent trend in both irradiated groups up to 48 hours.

Conclusion

Acute small bowel injury caused by local irradiation is characterised by increased apoptosis of crypt epithelial cells and by lymphocyte infiltration of the underlying tissue. The severity of histological changes tends to be dose dependent and may affect the course of tissue damage.
Eggs modulate the inflammatory response to carbohydrate restricted diets in overweight men
Authors: Ratliff Joseph C , Mutungi Gisella , Puglisi Michael J , Volek Jeff S , Fernandez Maria Luz
Published: February 2008

Background

Carbohydrate restricted diets (CRD) consistently lower glucose and insulin levels and improve atherogenic dyslipidemia [decreasing triglycerides and increasing HDL cholesterol (HDL-C)]. We have previously shown that male subjects following a CRD experienced significant increases in HDL-C only if they were consuming a higher intake of cholesterol provided by eggs compared to those individuals who were taking lower concentrations of dietary cholesterol. Here, as a follow up of our previous study, we examined the effects of eggs (a source of both dietary cholesterol and lutein) on adiponectin, a marker of insulin sensitivity, and on inflammatory markers in the context of a CRD.

Methods

Twenty eight overweight men [body mass index (BMI) 26–37 kg/m2] aged 40–70 y consumed an ad libitum CRD (% energy from CHO:fat:protein = 17:57:26) for 12 wk. Subjects were matched by age and BMI and randomly assigned to consume eggs (EGG, n = 15) (640 mg additional cholesterol/day provided by eggs) or placebo (SUB, n = 13) (no additional dietary cholesterol). Fasting blood samples were drawn before and after the intervention to assess plasma lipids, insulin, adiponectin and markers of inflammation including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1(VCAM-1).

Results

Body weight, percent total body fat and trunk fat were reduced for all subjects after 12 wk (P < 0.0001). Increases in adiponectin were also observed (P < 0.01). Subjects in the EGG group had a 21% increase in this adipokine compared to a 7% increase in the SUB group (P < 0.05). Plasma CRP was significantly decreased only in the EGG group (P < 0.05). MCP-1 levels were decreased for the SUB group (P < 0.001), but unchanged in the EGG group. VCAM-1, ICAM-1, TNF-α, and IL-8 were not modified by CRD or eggs.

Conclusion

A CRD with daily intake of eggs decreased plasma CRP and increased plasma adiponectin compared to a CRD without eggs. These findings indicate that eggs make a significant contribution to the anti-inflammatory effects of CRD, possibly due to the presence of cholesterol, which increases HDL-C and to the antioxidant lutein which modulates certain inflammatory responses.
Extracardiac Fontan with T-shape conduit in non-confluent pulmonary arteries
Authors: Kwak Jae Gun , Lee Jeong Ryul , Jang Woo-Sung , Bae Eun Jung
Published: February 2008

A 34 months-old male patient with double inlet right ventricle with nonconfluent pulmonary arteries who underwent successful extracardiac fenestarated Fontan procedure using pre-designed T-shaped PTFE vascular graft after multi-step rehabilitation of the diminutive hilar pulmonary arteries. At first we performed 6 mm confluent pulmonary artery vascular graft implantation with 4 mm BT shunt at patient's 4 weeks old. At 9 months of patient, we upsized the confluent pulmonary arterial graft to 8 mm with bidirectional cavopulmonary connection, and, at 34 months, we performed extracardiac conduit Fontan procedure with pre-designed T-shape conduit including the confluent pulmonary arterial portion at last. Patient shows excellent functional status and development.
Biomarker profiles in serum and saliva of experimental Sjögren's syndrome: associations with specific autoimmune manifestations
Authors: Delaleu Nicolas , Immervoll Heike , Cornelius Janet , Jonsson Roland
Published: February 2008

Introduction

Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly targets the exocrine glands. The aim of this study was to investigate the involvement of 87 proteins measured in serum and 75 proteins analyzed in saliva in spontaneous experimental SS. In addition, we intended to compute a model of the immunological situation representing the overt disease stage of SS.

Methods

Nondiabetic, nonobese diabetic (NOD) mice aged 21 weeks were evaluated for salivary gland function, salivary gland inflammation and extraglandular disease manifestations. The analytes, comprising chemokines, cytokines, growth factors, autoantibodies and other biomarkers, were quantified using multi-analyte profile technology and fluorescence-activated cell sorting. Age-matched and sex-matched Balb/c mice served as a reference.

Results

We found NOD mice to exhibit impaired salivary flow, glandular inflammation and increased secretory SSB (anti-La) levels. Thirty-eight biomarkers in serum and 34 in saliva obtained from NOD mice were significantly different from those in Balb/c mice. Eighteen biomarkers in serum and three chemokines measured in saliva could predict strain membership with 80% to 100% accuracy. Factor analyses identified principal components mostly correlating with one clinical aspect of SS and having distinct associations with components extracted from other families of proteins.

Conclusion

Autoimmune manifestations of SS are greatly independent and associated with various immunological processes. However, CD40, CD40 ligand, IL-18, granulocyte chemotactic protein-2 and anti-muscarinic M3 receptor IgG3 may connect the different aspects of SS. Processes related to the adaptive immune system appear to promote SS with a strong involvement of T-helper-2 related proteins in hyposalivation. This approach further established saliva as an attractive biofluid for biomarker analyses in SS and provides a basis for the comparison and selection of potential drug targets and diagnostic markers.
Tumor-infiltrating myeloid-derived suppressor cells are pleiotropic-inflamed monocytes/macrophages that bear M1- and M2-type characteristics
Authors: Umemura Naoki , Saio Masanao , Suwa Tatsuhiko , Kitoh Yusuke , Bai Juncheng , Nonaka Kenichi , Ouyang Guan-Feng , Okada Makoto , Balazs Margit , Adany Roza , Shibata Toshiyuki , Takami Tsuyoshi
Published: February 2008

Here, tumor-infiltrating CD11b+ myelomonocytoid cells in murine colon adenocarcinoma-38 and GL261 murine glioma were phenotypically characterized. Over 90% were of the CD11b+F4/80+ monocyte/macrophage lineage. They also had a myeloid-derived suppressor cell (MDSC) phenotype, as they suppressed the proliferation of activated splenic CD8+ T cells and had a CD11b+CD11c+Gr-1lowIL-4Rα+ phenotype. In addition, the cells expressed CX3CR1 and CCR2 simultaneously, which are the markers of an inflammatory monocyte. The MDSCs expressed CD206, CXCL10, IL-1β, and TNF-α mRNAs. They also simultaneously expressed CXCL10 and CD206 proteins, which are typical, classical (M1) and alternative (M2) macrophage activation markers, respectively. Peritoneal exudate cells (PECs) strongly expressed CD36, CD206, and TGF-β mRNA, which is characteristic of deactivated monocytes. The MDSCs also secreted TGF-β, and in vitro culture of MDSCs and PECs with anti-TGF-β antibody recovered their ability to secrete NO. However, as a result of secretion of proinflammatory cytokines, MDSCs could not be categorized into deactivated monocyte/macrophages. Thus, tumor-infiltrating MDSCs bear pleiotropic characteristics of M1 and M2 monocytes/macrophages. Furthermore, CD206 expression by tumor-infiltrating MDSCs appears to be regulated by an autocrine mechanism that involves TGF-β.
A Multicenter Randomized Trial of Breast Intensity-Modulated Radiation Therapy to Reduce Acute Radiation Dermatitis
Authors: Pignol Jean-Philippe , Olivotto Ivo , Rakovitch Eileen , Gardner Sandra , Sixel Katharina , Beckham Wayne , Vu Thi Trinh Thuc , Truong Pauline , Ackerman Ida , Paszat Lawrence
Published: February 2008

Purpose

Dermatitis is a frequent adverse effect of adjuvant breast radiotherapy. It is more likely in full-breasted women and when the radiation is distributed nonhomogeneously in the breast. Breast intensity-modulated radiation therapy (IMRT) is a technique that ensures a more homogeneous dose distribution.

Patients and Methods

A multicenter, double-blind, randomized clinical trial was performed to test if breast IMRT would reduce the rate of acute skin reaction (notably moist desquamation), decrease pain, and improve quality of life compared with standard radiotherapy using wedges. Patients were assessed each week during and up to 6 weeks after radiotherapy.

Results

A total of 358 patients were randomly assigned between July 2003 and March 2005 in two Canadian centers, and 331 were included in the analysis. Breast IMRT significantly improved the dose distribution compared with standard radiation. This translated into a lower proportion of patients experiencing moist desquamation during or up to 6 weeks after their radiation treatment; 31.2% with IMRT compared with 47.8% with standard treatment (P = .002). A multivariate analysis found the use of breast IMRT (P = .003) and smaller breast size (P < .001) were significantly associated with a decreased risk of moist desquamation. The use of IMRT did not correlate with pain and quality of life, but the presence of moist desquamation did significantly correlate with pain (P = .002) and a reduced quality of life (P = .003).

Conclusion

Breast IMRT significantly reduced the occurrence of moist desquamation compared with a standard wedged technique. Moist desquamation was correlated with increased pain and reduction in the quality of life.