bluuebunny/crossref_metadata_2025 huggingface dataset:
Round Excisions Lead to Shorter Scars and Better Scar Positioning than Traditional Elliptical Excisions
Authors: Seo Soo-Hong , Son Sang-Wook , Kim Il-Hwan
Published: August 2008

Background: As traditional elliptical excisions for skin tumors are designed before surgery, they may waste normal tissue and result in poor outcome, both in terms of the wound length and direction. Objective: To compare the predicted results of elliptical excisions with scars resulting from round excisions with dog ear repairs. Methods: Forty-one patients with skin tumors were prospectively studied. Each lesion was examined and an optimal ellipse was designed and marked on the skin. Only the lesion and the required margin of adjacent skin were excised and closed with dog ear repairs. Precise measurements were conducted at each step. Results: Although many of the lesions required 2 dog ear repairs (59%), the overall sutured wound length was 14% shorter, and the wound direction differed from that of the predicted ellipse in 22% of cases. The shortening effect was distinctive in areas of thick skin, such as the trunk and scalp. Only 3 lesions resulted in a longer final wound length. In total, 29% of the patients required 1 dog ear repair and 12% needed no dog ear repairs. Conclusion: Round excisions with dog ear repairs should be considered prior to traditional elliptical excision as a more beneficial method of skin tumor removal.
Polymorphisms in the LOC387715/ARMS2 Putative Gene and the Risk for Alzheimer’s Disease
Authors: Benerini Gatta Luisa , Vitali Massimiliano , Zanola Alessandra , Venturelli Eliana , Fenoglio Chiara , Galimberti Daniela , Scarpini Elio , Finazzi Dario
Published: August 2008

Background: Age-related macular degeneration (ARMD) and Alzheimer’s disease (AD) are neurodegenerative disorders that share a high prevalence among elderly people, the extracellular deposition of β-amyloid and the involvement of genetic factors in their aetiology. Genetic linkage with the chromosome regions 10q26 and 10q24–25 have been shown for ARMD and AD, respectively. The rs10490924 polymorphism, the major determinant of the 10q26 association with ARMD, determines the A69S substitution in the LOC387715/ARMS2 gene. Little information is available about the expression of the gene in humans. Methods: We analysed the expression of the gene by RT-PCR in the brain and we looked for nucleotide variations in the gene sequence by DHPLC. Results: We found specific gene transcripts in the hippocampus, cortex and cerebellum. The genetic analysis identified two other common variations, which determine the R3H change (rs10490923) and a premature stop codon (rs2736911), respectively. The analysis of their distribution in 213 AD patients and 149 controls revealed a trend for a reduced frequency of the variant allele of rs2736911 in AD patients (p = 0.038), with an odds ratio of 0.631. Conclusion: The LOC387715/ARMS2 gene is expressed in the human brain, and it may concur to the individual risk for AD.
Efficacy of Gemcitabine for Locally Advanced Pancreatic Cancer: Comparison with 5-Fluorouracil-Based Chemoradiotherapy
Authors: Tada Minoru , Arizumi Masatoshi , Nakai Yousuke , Sasaki Takashi , Kogure Hirofumi , Togawa Osamu , Matsubara Saburo , Tsujino Takeshi , Hirano Kenji , Sasahira Naoki , Isayama Hiroyuki , Kawabe Takao , Omata Masao
Published: August 2008

Background: The efficacy of gemcitabine alone has not been established in comparison with conventional chemoradiotherapy for locally advanced pancreatic cancer. Methods: Of 180 consecutive patients with unresectable advanced pancreatic cancer, 93 were locally advanced. Among these 93 patients, 45 were treated with gemcitabine, 18 with concurrent radiotherapy and 5-fluorouracil-based chemotherapy, and 30 received best supportive care (BSC). In cases of metastatic disease, 42 were treated with gemcitabine and 32 received BSC. Overall survival and adverse events were analyzed retrospectively. Results: Median survival time and 1-year survival rate were 11.6, 9.3, 6.7, 7.8 and 2.4 months and 47, 39, 27, 21 and 7% in the groups of gemcitabine, chemoradiotherapy, BSC of locally advanced cancer, and in those of gemcitabine, BSC of metastatic disease, respectively. Gemcitabine and chemoradiotherapy prolonged overall survival time compared with BSC (p = 0.0071). No significant difference in survival was observed between gemcitabine and chemoradiotherapy for locally advanced cases. Adverse events >grade 3 were observed in 25 of 87 (29%) of gemcitabine-treated and in 3 of 18 (17%) of chemoradiotherapy-treated patients. Conclusion: Gemcitabine monotherapy for locally advanced pancreatic cancer could be as effective as previous chemoradiotherapy.
Nephrogenic Systemic Fibrosis: More Questions and Some Answers
Authors: Morcos S.K. , Thomsen H.S.
Published: August 2008

Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder that may develop in patients who have advanced reduction in renal function. A causal relation between gadolinium (Gd3+)-based contrast agents (Gd-CA) and NSF is probable and is supported by the accumulating data in the literature. From those data, the prevalence of NSF is seen to be significantly higher after exposure to gadodiamide than any other gadolinium-based agent. Gd-CA are either linear or macrocyclic chelates and are available as ionic or non-ionic preparations. The molecular structure, whether cyclic or linear, and the ionicity determine the stability of Gd-CA. Linear chelates are flexible open chains which do not offer a strong binding to Gd3+. In contrast, the macrocyclic chelates offer a strong binding to Gd3+ by the virtue of being pre-organised rigid rings of almost optimal size to cage the Gd3+ atom. Non-ionic preparations are also less stable in comparison to the ionic ones, as the binding between Gd3+ and the negatively charged carboxyl groups is stronger than that with amides or alcohol in the non-ionic preparations. According to stability constants and kinetic measurements, the most stable Gd-CA is the ionic-macrocyclic chelate Gd-DOTA and the least stable agents are the non-ionic linear chelates gadodiamide and gadoversetamide. The stability of Gd-CA seems to be an important factor in the pathogenesis of NSF. Gd-CA of low stability are likely to undergo transmetallation and release free Gd ions that may deposit in tissues and attract circulating fibrocytes to initiate the process of fibrosis. There have been no cases of NSF reported in the peer-reviewed literature after the exclusive use of the stable macrocyclic Gd-CA. This minireview covers the clinical and pathological features of NSF and updates the current understanding of the pathophysiology of this condition.
Epigenetic Manifestations in Diet-Related Disorders
Authors: Mariman E.C.M.
Published: August 2008

Epigenetic phenomena are changes in phenotype that are due to resetting of gene expression under the influence of the environment or genetic factors without changing the DNA sequence. Usually this resetting occurs at a certain stage in life and remains fixed thereafter. In humans, evidence for epigenetic involvement in diet-related complex traits and disorders is accumulating. The fetal origins theory indicates that nutrition can influence the later life risk for certain common disorders like the metabolic syndrome. In parent-of-origin effects, the risk for a common disorder like type I diabetes depends on the sex of the parent who transmits genetic risk factors. Interestingly, both dietary and genetic factors can exert their epigenetic influence over several generations. Imprinting, i.e. silencing of one copy of an autosomal pair of genes, can be part of the mechanism pointing to the importance of DNA methylation. In addition, chromatin modifications have been shown to be involved in epigenetic manifestations. The intriguing possibility that diet may influence the direction and extent of epigenetic changes opens new ways for prevention or treatment of common disorders. At the same time, maternal nutrition might be used to actively direct fetal development with consequences for later life performance such as cognitive abilities. More knowledge on those novel applications is needed. This will in part come from novel strategies to map the epigenomic regions, allowing the identification of more genes involved in epigenetics and allowing the study of their response to nutrition.
Real-World Doxercalciferol Treatment in SHPT CKD Stage 3 and 4: An Analysis of Change in iPTH and Accordance to KDOQI Recommendations
Authors: Kumar Neil , Lindberg Jill , David Kristin , Morris Jonathan , Menoyo José
Published: August 2008

Background: National Kidney Foundation’s Kidney Disease Outcome Quality Initiative (KDOQI) guidelines offer an outline for providing standardized care for best outcomes in chronic kidney disease (CKD). It is unknown whether real-world treatment practices follow these guidelines. Methods: The Hectorol® Registry Outcome in Chronic Kidney Disease (HeROICkd™), an observational patient registry, captured information on adult patients with CKD Stage 3 or 4 throughout US clinics during a 9-month observation period. Data were collected quarterly from patients’ medical records, throughout each patient’s normal treatment course. The proportion of patients with intact parathyroid hormone (iPTH) levels within KDOQI guidelines, change in iPTH, Ca, P, and Ca × P product over the 9-month observation period, incidence of hypercalcemia and hyperphosphatemia, and predictors of change in iPTH were examined. Results: 1,339 CKD Stage 3 and 4 patients from 78 nephrology and internal medicine clinics were included. 40% of CKD Stage 3 participants and 45% of Stage 4 had a 30% or greater reduction in iPTH levels from baseline to 9 months follow-up. While the proportion of CKD Stage 3 and 4 participants with iPTH levels within the KDOQI recommendations improved significantly over the 9 months, it was still modest, at 28% and 23%, respectively. Mean doxercalciferol dose was below that recommended in the package insert and a minority of patients had all mineral metabolism parameters (iPTH, Ca, P) regularly recorded in their medical records. Conclusions: The results of this registry, which examined iPTH treatment with doxercalciferol in CKD Stage 3 and 4, suggest that in the real-world treatment setting, the adherence to KDOQI guidelines is not optimal.
Observational Study of the Additive Effects of Pranlukast on Inflammatory Markers of Clinically Stable Asthma with Inhaled Corticosteroids and Long-Acting Beta 2 Agonists
Authors: Tomari Shinya , Matsuse Hiroto , Hirose Hiroko , Tsuchida Tomoko , Fukahori Susumu , Fukushima Chizu , Kawano Tetsuya , Matsuo Nobuko , Kohno Shigeru
Published: August 2008

Background: Little is understood about the additive effects of leukotriene receptor antagonists (LTRA) on asthmatics currently medicated with inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA). Objectives: The present study examines the anti-inflammatory effects of the LTRA pranlukast in addition to ICS and LABA, among asthmatic patients with normal pulmonary function and unremarkable clinical symptoms. Methods: Fifteen adult asthmatics participated in a 2-month, open-label, uncontrolled, prospective, multicenter, observational trial. Patients stabilized (predicted forced expiratory volume in 1 s >80%) by medication with ICS and LABA were also given pranlukast (450 mg daily). Asthma-related symptoms, pulmonary function, blood eosinophil counts and several inflammatory markers in sputum were monitored at week 0, as well as at 4 and 8 weeks after starting therapy with pranlukast. Results: Adding pranlukast did not further improve blood eosinophil counts, pulmonary function and symptoms, but significantly attenuated sputum cysteinyl leukotrienes, tumor necrosis factor-α and interleukin-5 concentrations. Conclusions: Although the clinical relevance remains obscure, adding an LTRA attenuates allergic airway inflammation in some asthmatics undergoing treatment with ICS and LABA.
The Effects of Body Mass Index on Graft Survival in Adult Recipients Transplanted with Single Pediatric Kidneys
Authors: Balamuthusamy Saravanan , Paramesh Anil , Zhang Rubin , Florman Sander , Shenava Rajesh , Islam Tareq , Wagner Janis , Killackey Mary , Alper Brent , Simon Eric E. , Slakey Douglas
Published: August 2008

Background: There is insufficient data on the impact of recipient body mass index (BMI) on the long-term graft survival of adult patients transplanted with single pediatric kidneys. Methods: We performed a retrospective analysis of adult patients transplanted with single pediatric kidneys at our center. The recipients were classified into 2 groups: group 1 (BMI ≥30) and group 2 (BMI <30). Donor/recipient demographics, postoperative outcomes and survival rates were compared between the 2 groups. Results: There was no significant difference in donor/recipient demographics between the 2 groups. In group 1, the death-censored graft survival (DCGS) at 1, 3 and 5 years was 90% at all 3 time points, and in group 2 it was 86, 68 and 60%, respectively (p = 0.05). The mean glomerular filtration rate (with standard deviation in parentheses) at 1, 3 and 5 years was, respectively, 55 (15), 59 (19) and 55 (28) ml/min for group 1, compared to 65 (28), 69 (23) and 67 (20) ml/min in group 2 (p = NS). Multivariate analysis revealed a hazard ratio of 5.12 (95% confidence interval 1.06–24.7; p = 0.04) for graft loss in nonobese patients when compared to obese patients. Obese patients had an increased risk for acute rejections within the first month of transplant (p = 0.02). Conclusion: Patients with a BMI ≥30 transplanted with single pediatric kidneys have better DCGS rates when compared to nonobese patients.
Gastric Precancerous Lesions and Helicobacter pylori Infection in Relatives of Gastric Cancer Patients from Northeastern Brazil
Authors: Motta Cícero Roberio A. , Cunha Maria P.S.S. , Queiroz Dulciene Maria M. , Cruz Francisco Will S. , Guerra Eder Janes C. , Mota Rosa Maria S. , Braga Lucia L.B.C.
Published: August 2008

Background: Helicobacter pylori infection predisposes to gastric cancer. First-degree relatives of patients with gastric cancer have an increased risk of developing the disease. Aim: To evaluate the prevalence of gastric precancerous gastric lesions and H. pylori infection in first-degree relatives of non-cardia gastric cancer patients. Methods: Gastric cancer relatives (n = 104) from a region with high prevalence of H. pylori infection and gastric cancer were invited for screening endoscopy; 80% of them had dyspeptic symptoms. The control group was composed of patients (n = 118) who concurrently underwent upper gastrointestinal endoscopy for investigation of dyspepsia with no family history of gastric cancer. The groups were matched for gender, age and social class. H. pylori status was evaluated by urease test, and histology and histological parameters were assessed according to the Houston Updated Sydney System. Results: The prevalence of H. pylori infection was high in both the relative (84.7%) and the control (75.9%) groups. Corpus-predominant gastritis was more frequently observed in the relative group, whereas antral gastritis predominated in the controls. The density of lymphoid follicles was higher among the relatives. Also, intestinal metaplasia in the corpus and dysplasia were more prevalent in the cancer relative group than in the control group. Early gastric cancer was detected in 1 relative of gastric cancer patient with high-grade dysplasia. Conclusion: Individuals with a family history of non-cardia gastric cancer need to be routinely screened for H. pylori infection and precancerous gastric lesions.
Site-Specific Targeting of Nanoparticle Prednisolone Reduces In-Stent Restenosis in a Rabbit Model of Established Atheroma
Authors: Joner Michael , Morimoto Katsumi , Kasukawa Hiroaki , Steigerwald Kristin , Merl Sabine , Nakazawa Gaku , John Michael C. , Finn Aloke V. , Acampado Eduardo , Kolodgie Frank D. , Gold Herman K. , Virmani Renu
Published: August 2008

Objective—

TRM-484 is a novel drug consisting of nanoparticles of prednisolone with high affinity to chondroitin sulfate proteoglycans (CSPGs). This may allow for neointimal suppression via directed targeting to areas of injury at systemic concentrations low enough to avoid adverse side effects known to occur with oral delivery of steroids.

Methods and Results—

Atherosclerotic New Zealand white Rabbits were implanted with bare metal stents and randomized to receive intravenous TRM-484 at doses of 1 mg/kg or 0.32 mg/kg starting at the day of stenting and continuing 3 times a week for the duration of the study. Control animals received empty liposomes (placebo) or saline infusion. Stented arterial segments were harvested at 42 days and processed for histomorphometry and immunohistochemistry. Tissue and plasma levels were determined along with confocal microscopic analysis to determine distribution of rhodamine-labeled TRM-484 at various time points. TRM-484 was exclusively observed at sites of stent-induced injury, with absence of drug in contralateral nonstented arteries. Tissue concentration of stented arteries exceeded that of contralateral nonstented arteries by 100-fold 24 hours after administration of 1 mg/kg TRM-484 and resulted in significant reduction of percent stenosis compared to saline and placebo treated rabbits (22.5±4.4 versus 31.0±8.4 and 29.5±8.1%,
P
<0.03).

Conclusion—

TRM-484 at doses of 1 mg/kg resulted in significant suppression of in-stent neointimal growth in atherosclerotic rabbits. Site-specific targeting by this nanoparticle steroid in injured atherosclerotic areas might be a valuable and cost-effective approach for the prevention of in-stent restenosis.
Phosphatidylinositol 3-Kinase γ Is a Critical Mediator of Myocardial Ischemic and Adenosine-Mediated Preconditioning
Authors: Ban Kiwon , Cooper Andrew J. , Samuel Sara , Bhatti Adil , Patel Mikin , Izumo Seigo , Penninger Josef M. , Backx Peter H. , Oudit Gavin Y. , Tsushima Robert G.
Published: August 2008

Ischemic preconditioning (IPC) is a potent cellular protective mechanism whereby brief periods of sublethal ischemia protect the myocardium from prolonged ischemia-induced injury. We demonstrate the selective role of phosphatidylinositol 3-kinase (PI3K) isoforms in IPC. Hearts from PI3Kγ knockout mice (PI3Kγ
−/−
) displayed poorer functional recovery and greater tissue injury following IPC compared to wild-type and PI3Kγ
+/−
hearts. Examination of the cell-signaling pathways revealed restored phosphorylation levels of Akt and glycogen synthase kinase (GSK)3β in wild-type hearts, which were abolished in PI3Kγ
−/−
hearts subjected to IPC. Inhibition of GSK3β by LiCl reversed the loss in protection in PI3Kγ
−/−
hearts. In contrast, mice expressing a cardiac-specific kinase-deleted PI3Kα (PI3KαDN) were resistant to injury induced by 30 minutes of ischemia followed by 40 minutes of reperfusion. Furthermore, the resistance of PI3KαDN hearts to ischemia/reperfusion correlated with the persistent expression of p110γ and was blocked by the PI3K inhibitor wortmannin, suggesting the possible enhanced cell signaling through the PI3Kγ pathway. These results demonstrate the importance of the PI3Kγ-Akt-GSK3β signaling pathway in IPC. Selective activation of myocardial PI3Kγ may be an attractive target for the treatment of ischemic heart disease.
Role of the Lysine-Specific Demethylase 1 in the Proinflammatory Phenotype of Vascular Smooth Muscle Cells of Diabetic Mice
Authors: Reddy Marpadga A. , Villeneuve Louisa M. , Wang Mei , Lanting Linda , Natarajan Rama
Published: August 2008

Insulin resistance and type 2 diabetes are major risk factors for vascular complications. Vascular smooth muscle cells (VSMCs) derived from
db
/
db
mice, an established mouse model of type 2 diabetes, displayed enhanced inflammatory gene expression and proatherogenic responses. We examined the hypothesis that aberrant epigenetic chromatin events may the underlying mechanism for this persistent dysfunctional behavior and “memory” of the diabetic cells. Chromatin immunoprecipitation assays showed that levels of histone H3 lysine 4 dimethylation (H3K4me2), a key chromatin mark associated with active gene expression, were significantly elevated at the promoters of the inflammatory genes monocyte chemoattractant protein-1 and interleukin-6 in
db
/
db
VSMCs relative to
db
/+ cells. Tumor necrosis factor-α–induced inflammatory gene expression, H3K4me2 levels, and recruitment of RNA polymerase II at the gene promoters were also enhanced in
db
/
db
VSMCs, demonstrating the formation of open chromatin poised for transcriptional activation in diabetes. On the other hand, protein levels of lysine-specific demethylase1 (LSD1), which negatively regulates H3K4 methylation and its occupancy at these gene promoters, were significantly reduced in
db
/
db
VSMCs. High glucose (25 mmol/L) treatment of human VSMCs also increased inflammatory genes with parallel increases in promoter H3K4me2 levels and reduced LSD1 recruitment. LSD1 gene silencing with small interfering RNAs significantly increased inflammatory gene expression and enhanced VSMC–monocyte binding in nondiabetic VSMCs. In contrast, overexpression of LSD1 in diabetic
db
/
db
VSMCs inhibited their enhanced inflammatory gene expression. These results demonstrate novel functional roles for LSD1 and H3K4 methylation in VSMCs and inflammation. Dysregulation of their actions may be a major mechanism for vascular inflammation and metabolic memory associated with diabetic complications.
A Rho Kinase/Myocardin-Related Transcription Factor-A–Dependent Mechanism Underlies the Sphingosylphosphorylcholine-Induced Differentiation of Mesenchymal Stem Cells Into Contractile Smooth Muscle Cells
Authors: Jeon Eun Su , Park Won Sun , Lee Mi Jeong , Kim Young Mi , Han Jin , Kim Jae Ho
Published: August 2008

Sphingosylphosphorylcholine (SPC) induces differentiation of human adipose tissue–derived mesenchymal stem cells (hADSCs) to smooth muscle cells (SMCs). In the present study, we characterized contractile and ion channel properties of SMCs differentiated from hADSCs (hADSC-SMCs) as a result of SPC treatment, and we investigated the molecular mechanisms involved in the SPC-induced differentiation. Using in vitro collagen gel lattice contraction and whole cell patch clamp, we showed that the hADSC-SMCs expressed functional L-type voltage-gated Ca
2+
channels and contractile activities in response to KCl, carbachol, and the L-type Ca
2+
channel opener Bay K8644, whereas the L-type Ca
2+
channel blocker nifedipine abrogated the contractility of hADSC-SMCs. Furthermore, hADSC-SMCs expressed functional big conductance Ca
2+
-activated K
+
(BK
Ca
) channels, and the BK
Ca
channel blocker iberiotoxin potentiated the Bay K8644-stimulated contractility of the hADSC-SMCs, indicating that these cells exhibited SMC-like contractile characteristics. SPC activated RhoA in hADSCs and pretreatment with the Rho kinase inhibitor Y27632 or by overexpression of dominant-negative mutants of RhoA or Rho kinase completely abrogated the SPC-induced differentiation of hADSCs into SMCs. SPC also increased the expression levels of myocardin-related transcription factor (MRTF)-A, a transcription factor involved in smooth muscle differentiation, in hADSCs. Small interference RNA–mediated depletion of endogenous MRTF-A abolished the SPC-induced differentiation of hADSCs into SMCs. Furthermore, SPC promoted nuclear translocation of MRTF-A, and pharmacological inhibition of Rho kinase blocked this effect. These results suggest that SPC induced differentiation of hADSCs into contractile SMCs through a mechanism involving RhoA/Rho kinase–dependent nuclear translocation of MRTF-A.
Secondary Prevention in a Large Stroke Population
Authors: Wettermark Björn , Persson Anna , von Euler Mia
Published: August 2008

Background and Purpose—

In this study, linked, anonymous data from The National Hospital Discharge Register and the Swedish Prescribed Drug Register were used for studying to what extent recommended drugs for secondary prevention after stroke and TIA were purchased by patients in the region of Stockholm, Sweden (2 million inhabitants).

Methods—

Data on purchased drugs for secondary stroke prevention during July 2005 to June 2006 by 17 902 patients >18 years discharged after stroke or TIA during the period 1997 to June 2005 were analyzed by age, gender, and year of discharge.

Results—

Antiplatelets and warfarin were purchased by 87% of all stroke and 83% of all TIA patients, antihypertensives by 74% and 70%, and lipid lowering drugs by 41% and 39%, respectively.

Conclusion—

Time after discharge had only a minor influence on the proportion of patients purchasing the medicines.
Variability in Modified Rankin Scoring Across a Large Cohort of International Observers
Authors: Quinn Terence J. , Dawson Jesse , Walters Matthew R. , Lees Kennedy R.
Published: August 2008

Background and Purpose—

The modified Rankin scale (mRS) is the most commonly used outcome measure in stroke trials. However, substantial interobserver variability in mRS scoring has been reported. These studies likely underestimate the variability present in multicenter clinical trials, because exploratory work has only been undertaken in single centers by a few observers, all of similar training. We examined mRS variability across a large cohort of international observers using data from a video training resource.

Methods—

The mRS training package includes a series of “real-life” patient interviews for grading. Training data were collected centrally and analyzed for variability using kappa statistics. We examined variability against a standard of “correct” mRS grades; examined variability by country; and for UK assessors, examined variability by center and by professional background of the observer.

Results—

To date, 2942 assessments from 30 countries have been submitted. Overall reliability for mRS grading has been moderate to good with substantial heterogeneity across countries. Native English language has had little effect on reliability. Within the United Kingdom, there was no significant variation by profession.

Conclusion—

Our results confirm interobserver variability in mRS assessment. The heterogeneity across countries is intriguing because it appears not to be related solely to language. These data highlight the need for novel strategies to improve reliability.
Higher Risk Factor Burden and Worse Outcomes in Urban Carotid Endarterectomy Patients
Authors: Chaturvedi Seemant , Madhavan Ramesh , Santhakumar Sunitha , Mehri-Basha Maysaa , Raje Nikita
Published: August 2008

Background and Purpose—

Previous multicenter carotid endarterectomy (CEA) studies had screening criteria for patient comorbidities and very few blacks. We assessed the hypothesis that CEA results from two urban hospitals would approximate those of the previous multicenter trials.

Methods—

A retrospective chart review was completed at two urban hospitals for CEA procedures done in 2003 and 2004. Demographic information and past medical history was recorded. In hospital perioperative complications (stroke or myocardial infarction [MI]) were noted. We calculated an expected perioperative stroke rate based on trial figures and our proportion of symptomatic and asymptomatic patients.

Results—

Patients in our cohort had significantly higher rates of hypertension, diabetes, smoking, black race, and elderly status compared to previous trials. The expected perioperative stroke was 3.1%, and the observed stroke rate was 4.7% (
P
=0.36). Observed rates of MI (6.7%,
P
<0.001)) and stroke or MI (11.3%,
P
<0.0001) were higher than expected based on the previous trials. The stroke or MI rate in black subjects was higher (15.4% versus 5.6%,
P
=0.065) and this was significant at the hospital with lower CEA volume.

Conclusions—

In two urban hospitals, CEA results were significantly worse than previous trials. Patient selection is likely to play a role because our cohort had higher numbers of hypertensives, diabetics, smokers, blacks, and elderly patients. Clinicians need to carefully consider the risk/benefit ratio of CEA in urban patients because our study shows that these patients have a large number of medical comorbidities and worse outcomes after CEA.
Brain Microbleeds and Global Cognitive Function in Adults Without Neurological Disorder
Authors: Yakushiji Yusuke , Nishiyama Masanori , Yakushiji Satomi , Hirotsu Tatsumi , Uchino Akira , Nakajima Junko , Eriguchi Makoto , Nanri Yusuke , Hara Megumi , Horikawa Etsuo , Kuroda Yasuo
Published: August 2008

Background and Purpose—

Increasing attention has been paid to associations between cognitive dysfunction and brain microbleeds (MBs). Because all previous studies have investigated patients with neurological disorders, we examined subjects without neurological disorder in order to clarify pathogenic relationships.

Methods—

A total of 518 consecutive adults without neurological disorder who had undergone health-screening tests of the brain were studied prospectively. Gradient-echo T2*-weighted MRI using a 1.5-T system was used to detect MBs. The Mini-Mental State Examination (MMSE) was administered to determine cognitive functions. MMSE scores <27 or >1.5 SDs below the age-related mean were regarded as subnormal.

Results—

MBs were found in 35 subjects (6.8%). MMSE score <27 was found in 25 subjects (4.8%), with MMSE score >1.5 SDs below the age-related mean in 34 subjects (6.6%). Univariate analysis showed presence and number of MBs, short duration of education, and severe white matter hyperintensities as significantly associated with subnormal scores. In logistic regression analysis, presence of MBs (odds ratio [OR], 5.44; 95% CI, 1.83 to 16.19) and number of MBs (OR, 1.32; 95% CI, 1.04 to 1.68) still displayed significant associations with MMSE score <27. Logistic regression analysis revealed a significant relationship between presence (OR, 3.93; 95% CI, 1.44 to 10.74) and number (OR, 1.26; 95% CI, 1.01 to 1.59) of MBs and MMSE score >1.5 SDs below the age-related mean. Among MMSE subscores, “attention and calculation” was significantly lower in MB-positive subjects (
P
=0.017).

Conclusions—

MBs appear to be primarily associated with global cognitive dysfunction.
Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1)
Authors: Macdonald R. Loch , Kassell Neal F. , Mayer Stephan , Ruefenacht Daniel , Schmiedek Peter , Weidauer Stephan , Frey Aline , Roux Sebastien , Pasqualin Alberto
Published: August 2008

Background and Purpose—This randomized, double-blind, placebo-controlled, dose-finding study assessed efficacy and safety of 1, 5, and 15 mg/h intravenous clazosentan, an endothelin receptor antagonist, in preventing vasospasm after aneurysmal subarachnoid hemorrhage.

Methods—Patients (n=413) were randomized to placebo or clazosentan beginning within 56 hours and continued up to 14 days after initiation of treatment. The primary end point was moderate or severe angiographic vasospasm based on centrally read, blinded evaluation of digital subtraction angiography at baseline and 7 to 11 days postsubarachnoid hemorrhage. A morbidity/mortality end point, including all-cause mortality, new cerebral infarct from any cause, delayed ischemic neurological deficit due to vasospasm, or use of rescue therapy, was evaluated by local assessment. Clinical outcome was assessed by the extended Glasgow Outcome Scale at 12 weeks.

Results—Moderate or severe vasospasm was reduced in a dose-dependent fashion from 66% in the placebo group to 23% in the 15 mg/h clazosentan group (risk reduction, 65%; 95% CI, 47% to 78%;P<0.0001). No significant effects were seen on secondary end points. Post hoc analysis using a centrally assessed morbidity/mortality end point that included death and rescue therapy but only cerebral infarcts and delayed ischemic neurological deficit due to vasospasm on central review showed a trend toward improvement with clazosentan (37%, 28%, and 29% in the 1, 5, and 15 mg/h groups versus 39% in the placebo group, nonsignificant). Clazosentan was associated with increased rates of pulmonary complications, hypotension, and anemia.

Conclusions—Clazosentan significantly decreased moderate and severe vasospasm in a dose-dependent manner and showed a trend for reduction in vasospasm-related morbidity/mortality in patients with aneurysmal subarachnoid hemorrhage when centrally assessed. Overall, the adverse effects were manageable and not considered serious.
Differential Roles of NMDA Receptor Subtypes in Ischemic Neuronal Cell Death and Ischemic Tolerance
Authors: Chen Min , Lu Ting-Jia , Chen Xiao-Jing , Zhou Yang , Chen Qian , Feng Xiao-Yan , Xu Li , Duan Wen-Hu , Xiong Zhi-Qi
Published: August 2008

Background and Purpose—

Activation of NMDA subtypes of glutamate receptors is implicated in cell damage induced by ischemia as well as for the establishment of ischemic tolerance after ischemic preconditioning in animal models. We investigated the contributions of NR2A- and NR2B-containing NMDA receptors to ischemic cell death and ischemic tolerance in a rat model of transient global ischemia.

Methods—

Transient global ischemia was produced in rats by 4-vessel occlusion. Neuronal injury was analyzed by Fluoro-Jade B and Nissl staining. Phosphorylation of CREB was detected by Western blotting and immunohistochemistry. In situ hybridization and reverse transcriptase-polymerase chain reaction were used to evaluate the mRNA level of
cpg15
and
bdnf
.

Results—

NR2A subtype-specific antagonist NVP-AAM077 enhanced neuronal death after transient global ischemia and abolished the induction of ischemic tolerance. In contrast, NR2B subtype-specific antagonist ifenprodil attenuated ischemic cell death and enhanced preconditioning-induced neuroprotection. Furthermore, selectively blocking NR2A-, but not NR2B-, containing NMDA receptors inhibited ischemia-induced phosphorylation of CREB and the subsequent upregulation of CREB target genes such as
cpg15
and
bdnf.

Conclusions—

We found that NR2A- and NR2B-containing NMDA receptor subtypes play differential roles in ischemic neuronal death and ischemic tolerance, suggesting attractive new strategies for the development of drugs for patients with stroke.
Sampling Errors in Ensemble Kalman Filtering. Part I: Theory
Authors: Sacher William , Bartello Peter
Published: August 2008

This paper discusses the quality of the analysis given by the ensemble Kalman filter in a perfect model context when ensemble sizes are limited. The overall goal is to improve the theoretical understanding of the problem of systematic errors in the analysis variance due to the limited size of the ensemble, as well as the potential of the so-called double-ensemble Kalman filter, covariance inflation, and randomly perturbed analysis techniques to produce a stable analysis—that is to say, one not subject to filter divergence. This is achieved by expressing the error of the ensemble mean and the analysis error covariance matrix in terms of the sampling noise in the background error covariance matrix (owing to the finite ensemble estimation) and by comparing these errors for all methods. Theoretical predictions are confirmed with a simple scalar test case. In light of the analytical results obtained, the expression of the optimal covariance inflation factor is proposed in terms of the limited ensemble size and the Kalman gain.
The Nomenclature of Enslaved Africans as Real Property or Chattels Personal
Authors: Copeland Roy W.
Published: August 2008

The enslaved Africans’ attachment to the land on which they toiled was multifaceted. Beyond their classification as slaves, the question of whether or not they should be deemed chattel property or real property did little to detract from the moral repugnance of enslavement. The classification of slaves by courts and legislatures reflected how those institutions sought to maximize the value of slaves to their owners. As slavery became the foundation of the South’s economy and the value of slave labor increased, courts and legislatures became less inclined to annex slaves to the land. Slaves were deemed transitory, thereby allowing slaveholders to lease the enslaved’s labor. The emphasis was thus focused on the slaves’ value as “things,” and as such the humanity of the enslavement of Black people was never a factor in the opinions of the courts or in the statutory enactments of legislatures.
Interlaminar Fracture Behavior of Nanoclay Reinforced Glass Fiber Composites
Authors: Subramaniyan Arun K. , Sun C.T.
Published: August 2008

The effect of nanoclay on the interlaminar fracture toughness of glass fiber composites was studied. Mode I and mode II tests were conducted to measure the interlaminar fracture toughness of nanoclay reinforced composites. A reduction in interlaminar fracture toughness (both mode I and mode II) was observed in the nanoclay reinforced fiber composites. Alignment of nanoclay along the fiber axis was found to be a possible reason for this reduction.
The Blast Behavior of Fiber Reinforced Thermoplastic Laminates
Authors: Yahya M. Yazid , Cantwell W.J. , Langdon G.S. , Nurick G.N.
Published: August 2008

This article presents the results of a series of blast tests on a carbon fiber-reinforced poly-ether-imide (PEI) and a glass fiber-reinforced PEI composite. Initially, the fracture properties of the two composite systems were characterized through a series of flexural and interlaminar fracture tests. Blast testing was then undertaken on a ballistic pendulum facility, capable of measuring the impulse imparted by the plastic explosive. Delamination, localized fiber buckling, fiber fracture, and shear failure at the boundary of the clamped plates were identified as the primary failure mechanisms in the laminates, with their severity depending on the panel thickness and the applied impulse. Delamination was very localized along the center plane of the laminate, a reflection of the very high interlaminar fracture toughness of these composites. The critical impulse for rear surface fiber fracture has been found to increase rapidly with laminate thickness for the range of panels considered here. The impulses associated with the onset of rear-surface fiber fracture and complete failure of the target were similar, suggesting that rear surface fiber fracture is a pre-cursor to complete failure in these laminates. Limited tests on the glass fiber-reinforced PEI system showed that it offers a superior blast resistance to its carbon fiber counterpart.
Characterizing Mechanical Properties of Particulate Nanocomposites Using Micromechanical Approach
Authors: Tsai Jia-Lin , Tzeng Shi-Hua
Published: August 2008

This research aims to propose a continuous micromechanical model for characterizing the mechanical properties of the nanocomposites containing silica nanoparticles embedded in polyimide matrix. The molecular structures of the nanocomposites were established through molecular dynamic (MD) simulation, from which the non-bonded gap as well as the non-bonded energy between the nano-sized inclusion and the surrounding matrix were evaluated. It was postulated that the normalized non-bonded energy (non-bonded energy divided by surface area of the inclusion) is correlated with the degree of interfacial interaction. Subsequently, an effective interphase micromechanical model including inclusion, matrix and effective interphase was developed, in which the dimension of the effective interphase was assumed equal to the non-bonded gap and the corresponding elastic stiffness was calculated from the normalized non-bonded energy. Comparison of the results calculated from the micromechanical model and the MD simulation indicates that the effective interphase model is capable of describing Young's modulus of particulate nanocomposites with accuracy. In addition, it was revealed that when the particulate size decreases, the corresponding modulus of the nanocomposites increases.
Anisotropic Mechanical Properties of Lattice Grid Composites
Authors: Fan H.L. , Fang D.N.
Published: August 2008

According to the equivalent continuum method and coordinates transformation, the anisotropic properties of the stiffness and the strength of planer lattice grid composites were researched. Anisotropic properties of various lattice grid composites with three to five stacks of struts were discussed and compared. The criteria of stiffness isotropy and orthotropy were concluded. Ordinarily, the grid stiffness is anisotropic. But with two or four symmetries the lattice is orthotropic and quasi-isotropic with at least six symmetries. The initial yield or brittle failure strength of typical lattice grid compoaites was studied and compared. The strength of the lattice grid composite is always anisotropic, even if their stiffness is quasi-isotropic. The degree of anisotropy of the strength is normally stronger than the stiffness anisotropy. With more symmetries, more bar rows and more uniform equivalent rigidities of struts, the variation of the strength gets smaller.
The Nominative and Infinitive in Late Modern English
Authors: Noël Dirk
Published: August 2008

The English nominative and infinitive pattern (NCI), consisting of a passive utterance, cognition or perception verb followed by a to-infinitive, is the formal realization of at least three form-meaning pairings (or “constructions”). One of these is simply an instantiation of the passive construction. The other two have a “qualificational” function and are used to offer descriptions or serve as evidentiality markers. Although from a synchronic perspective the “evidential NCI construction” can be construed as a grammaticalization of the passive NCI, no such grammaticalization has taken place in English: Like the passive NCI, the evidential NCI is a borrowing from Latin. From a diachronic construction grammatical perspective, an investigation of the English history of the NCI pattern can still be interesting, however, in that it can reveal changes in the distribution of the pattern over different genres and provide evidence for its growing schematicity. This illustrates the complementarity of grammaticalization theory and diachronic construction grammar.
Genetic Correlates of Adult Attachment Style
Authors: Gillath Omri , Shaver Phillip R. , Baek Jong-Min , Chun David S.
Published: August 2008

Attachment theory attempts to explain effects of social experiences, not genes, on personality development. Most studies of the development of attachment insecurities support this emphasis on social experiences rather than genes, although there are exceptions. In the present study, the authors examine associations between attachment insecurities and particular genetic polymorphisms related to emotions and social behavior. They find that (a) anxious attachment is associated with a polymorphism of the DRD2 dopamine receptor gene, (b) avoidant attachment is associated with a polymorphism of the 5HT2A serotonin receptor gene, and (c) the rs53576 A polymorphism of the OXTR oxytocin receptor gene is not associated with attachment insecurities. These findings suggest that attachment insecurities are partially explained by particular genes, although there is still a great deal of individual difference variance that remains to be explained by other genes or social experiences.
Changes in Health Between Ages 54 and 65
Authors: Warren John Robert , Carayon Pascale , Hoonakker Peter
Published: August 2008

The authors model the relationships between socioeconomic status (SES), working conditions, and changes between ages 54 and 65 in three very different health outcomes. To what extent is SES associated with changes in health net of the working conditions? At the same time, to what extent are working conditions associated with health net of SES? To address these questions the authors use unique data from a single cohort of women and men to model changes in health between ages 54 and 65. Although results vary across outcomes, there are some circumstances in which associations between SES and changes in health are attributable to working conditions, and there are other circumstances in which associations between working conditions and changes in health are attributable to SES. The largely disconnected literatures on health disparities (in the social sciences and public health) and job design (in occupational stress and ergonomics) could and should be fruitfully integrated.
The Effect of Variations in Nurse Staffing on Patient Length of Stay in the Acute Care Setting
Authors: Tschannen Dana , Kalisch Beatrice J.
Published: August 2008

This study examines the relationship between nurse staffing and patient length of stay (LOS). Data were collected on nurses employed and patients admitted to one of four study units located in two Midwest hospitals. Three nursing variables (hours per patient day [HPPD], skill mix, and nursing expertise) were collected through survey and administrative forms. The nursing data were then linked with patient-specific characteristics (deviation from expected LOS) to test the relationship at the patient level of analysis. Average HPPD was a positive predictor of deviation from expected LOS, whereas overall expertise was a negative predictor of deviation from expected LOS. Higher staffing levels may result in patients being discharged sooner than expected. Nurse administrators must consider the quantity as well as quality of staff when determining optimal staffing levels. Unit staffing levels must include nurses who have both experiential and theoretical knowledge in order to achieve optimal patient outcomes.
The Bugs Eat the Waste: What Else is There to Know?
Authors: Van de Poel Ibo
Published: August 2008

New technologies may give rise to new professions, but existing professions may also try to acquire a role in the design of already existing artefacts that are designed by another profession. If they do so successfully, this may trigger technological change. A case study on the design of sewage treatment plants is presented, in which since the beginning of the 20th century microbiological and biotechnological researchers have tried to acquire a larger role at the cost of the traditionally involved civil engineers. The case is analysed with the help of Abbott's conceptual framework for professional competition. Two routes for professional competition that are typical for engineering, but that are not yet distinguished by Abbott, are identified and analysed: the development of new design parameters and the development of new design approaches.
Working with Brain Scans
Authors: Alac Morana
Published: August 2008

A significant part of functional magnetic resonance imaging (fMRI) practice in neuroscience is spent in front of computer screens. To investigate the brain neuroscientists work with digital images. This paper recovers practical dealings with brain scans in fMRI laboratories to focus on the achievement of seeing in the digital realm. While looking at brain images, neuroscientists gesture and manipulate digital displays to manage and make sense of their experimental data. Their gestural engagements are seen as dynamical phenomenal objects enacted at the junction between the digital world of technology and the world of embodied action.