bluuebunny/crossref_metadata_2025 huggingface dataset:
The IS6110 Repetitive DNA Element of Mycobacterium tuberculosis Is Not Detected in Exhaled Breath Condensate of Patients with Active Pulmonary Tuberculosis
Authors: Jain Rupali , Schriever Christopher A. , Danziger Larry H. , Cho Sang Hyun , Rubinstein Israel
Published: May 2007

Background: A large tertiary referral hospital in inner-city Chicago. Objectives: To determine whether the IS6110 repetitive DNA element of Mycobacterium tuberculosis is detected in exhaled breath condensate of patients with newly diagnosed active pulmonary tuberculosis. Methods: Ten hospitalized patients with positive Ziehl-Neelson-stained sputum smears were studied. Concurrent sputum cultures for mycobacteria were performed as well. Exhaled breath condensate was collected from each patient within 6 days of initiating antituberculosis chemotherapy (median 1.5 days). These samples were analyzed by polymerase chain reaction (PCR) using primers designed to amplify the IS6110 DNA fragment of M. tuberculosis. Exogenous M. tuberculosis DNA was added to exhaled breath condensate samples to detect PCR inhibitors. Concurrent cultures of exhaled breath condensate for mycobacteria were performed. Results:M. tuberculosis was identified in 9 of 10 sputum cultures. One isolate was identified as Mycobacterium kansasii. The IS6110 repetitive DNA element of M. tuberculosis was not detected in any of the 10 exhaled breath condensate samples. Exogenous M. tuberculosis DNA added to these samples elicited the characteristic band pattern of M. tuberculosis on agarose gel electrophoresis. No PCR inhibitors were detected. Cultures of exhaled breath condensate showed no growth of mycobacteria. Conclusions: The IS6110 repetitive DNA element of M. tuberculosis is not detected in exhaled breath condensate of patients with newly diagnosed active pulmonary tuberculosis.
Pre- and Post-Columbian Gene and Cultural Continuity: The Case of the Gaucho from Southern Brazil
Authors: Marrero Andrea Rita , Bravi Claudio , Stuart Steven , Long Jeffrey C. , Pereira das Neves Leite Fábio , Kommers Trícia , Carvalho Claudia M.B. , Pena Sergio Danilo Junho , Ruiz-Linares Andres , Salzano Francisco Mauro , Cátira Bortolini Maria
Published: May 2007

Objective: To investigate the evolutionary and demographic history of the Gaucho, a distinct population of southern Brazil, relating it to their culture, to assess possible parallel continuity. Methods: Six binary polymorphisms, an Alu insertion polymorphism (YAP) and 12 short tandem repeat loci in the non-recombining region of the Y-chromosome, as well as the sequence of the first hypervariable segment (HVS-I) of the mitochondrial DNA (mtDNA) control region were studied in 150 unrelated males born in the Pampa region of Rio Grande do Sul. Results: Comparison of the results with the other Brazilian and Uruguayan populations, as well as with their putative ancestors, indicated a stronger male Spanish influence than that observed elsewhere in Brazil, a former Portuguese colony. Extensive mtDNA analyses of their Amerindian component gave clear indications of the presence there of material from extinct (Charrua), as well as extant (Guarani) tribes. Conclusions: The genetic analyses contributed in a significant way to reveal that the known cultural continuity between pre- and post-Columbian Pampa populations was also accompanied by an extraordinary genetic continuity.
A Ridge Penalized Principal-Components Approach Based on Heritability for High-Dimensional Data
Authors: Wang Yuanjia , Fang Yixin , Jin Man
Published: May 2007

Objective: To develop a ridge penalized principal-components approach based on heritability that can be applied to high-dimensional family data. Methods: The first principal component of heritability for a trait constellation is defined as a linear combination of traits that maximizes the heritability, which is equivalent to maximize the family-specific variation relative to the subject-specific variation. To analyze high-dimensional data and prevent overfitting, we propose a penalized principal-components approach based on heritability by adding a ridge penalty to the subject-specific variation. We choose the optimal regularization parameter by cross-validation. Results: The principal-components approach based on heritability with and without ridge penalty was compared to the usual principal-components analysis in four settings. The penalized principal-components of heritability analysis had substantially larger coefficients for the traits with genetic effect than for the traits with no genetic effect, while the non-regularized analysis failed to identify the genetic traits. In addition, linkage analysis on the combined traits showed that the power of the proposed methods was higher than the usual principal-components analysis and the non-regularized principal-components of heritability analysis. Conclusions: The penalized principal-components approach based on heritability can effectively handle large number of traits with family structure and provide power gain for linkage analysis. The cross-validation procedure performs well in choosing optimal magnitude of penalty.
MOD-Score Analysis with Simple Pedigrees: An Overview of Likelihood-Based Linkage Methods
Authors: Strauch Konstantin
Published: May 2007

A MOD-score analysis, in which the parametric LOD score is maximized with respect to the trait-model parameters, can be a powerful method for the mapping of complex traits. With affected sib pairs, it has been shown before that MOD scores asymptotically follow a mixture of χ2 distributions with 2, 1 and 0 degrees of freedom under the null hypothesis of no linkage. In that context, a MOD-score analysis yields some (albeit limited) information regarding the trait-model parameters, and there is a chance for an increased power compared to a simple LOD-score analysis. Here, it is shown that with unilineal affected relative pairs, MOD scores asymptotically follow a mixture of χ2 distributions with 1 and 0 degrees of freedom under the null hypothesis, that is, the same distribution as followed by simple LOD scores. No information regarding the trait model can be obtained in this setting, and no power is gained when compared to a LOD-score analysis. An outlook to larger pedigrees is given. The number of degrees of freedom underlying the null distribution of MOD scores, that depends on the type of pedigrees studied, corresponds to the number of explored dimensions related to power and to the number of parameters that can jointly be estimated.
Changes in Plasma TARC Levels during Japanese Cedar Pollen Season and Relationships with Symptom Development
Authors: Xiao Jin-zhong , Kondo Shizuki , Takahashi Noritoshi , Odamaki Toshitaka , Iwabuchi Noriyuki , Miyaji Kazuhiro , Iwatsuki Keiji , Enomoto Tadao
Published: May 2007

Background: Japanese cedar pollinosis (JCPsis) is an immunoglobulin E-mediated type I allergy caused by exposure to Japanese cedar pollen (JCP). Blood thymus and activation-regulated chemokine (TARC) levels are well known as an objective parameter for disease severity for several allergic disorders. The present study aims to evaluate the relationship between TARC levels and disease symptoms during the pollen season. Methods: Analysis was performed of results of symptom scores and blood parameters obtained from 42 JCPsis patients who participated in a probiotic (Bifidobacterium longum BB536) intake trial in the JCP season of 2005 (January to April), using a randomized, double-blind, placebo-controlled design. Results: Significant increases in plasma TARC levels were observed in subjects receiving placebo (p < 0.05 in February and p < 0.01 in March), but not in subjects receiving BB536. Increased plasma TARC levels were markedly greater in subjects who experienced severe symptoms and were thus excluded early from the intervention (placebo group: n = 8; BB536 group: n = 2). Significant differences were found in changes from baseline TARC levels in February and March between the subjects where treatment was terminated early and the remaining ones. Among the remaining subjects, significant positive correlations were found as regards changed values of TARC compared to baseline in March and April with symptom scores recorded in the pollen season. Conclusion: Changed values of blood TARC in the pollen season may offer promising parameters for assessing disease severity and monitoring treatment.
Hospitalizations for Anaphylaxis in Florida: Epidemiologic Analysis of a Population-Based Dataset
Authors: Mulla Zuber D. , Simon Michael R.
Published: May 2007

Background: Previous epidemiologic studies of anaphylaxis have been single-institution investigations. The objective of this study was to determine the annual hospital discharge rate and risk factors for anaphylaxis outcomes throughout Florida. Methods: 464 patients who were hospitalized in Florida for anaphylaxis and discharged in 2001 were identified using a statewide database and ICD-9-CM (International Classification of Diseases, 9th revision, Clinical Modification) codes. Linear regression was used to determine the predictors of length of stay (LOS) and total charges. Relative risks (RR) for ventilator-assisted respiration and anaphylaxis due to food were calculated using binomial regression. Results: Annual hospital discharge rate for anaphylaxis was 2.8/100,000 population. Hospital mortality rate was 0.86%. Median LOS was 1 day. Median total charges was USD 4,982. Asthmatics had increased risk of receiving ventilator-assisted respiration (adjusted RR = 2.72, p = 0.04). Likelihood of hospitalization for anaphylaxis increased with age for both sexes (p < 0.0001). Patients who were <18 years old were three times as likely to be hospitalized for food anaphylaxis (versus other causes) compared to patients who were 71+ years old (adjusted RR = 3.25, p = 0.004). Conclusion: Young age was associated with increased risk of hospitalization for anaphylaxis to foods. Asthmatics had increased risk of receiving ventilator-assisted respiration. Likelihood of hospitalization increased with age.
Premedication with Montelukast Reduces Local Reactions of Allergen Immunotherapy
Authors: Wöhrl Stefan , Gamper Simon , Hemmer Wolfgang , Heinze Georg , Stingl Georg , Kinaciyan Tamar
Published: May 2007

Background: Local reactions (LRs) are a very frequent side effect of specific immunotherapy with allergens and can impair patients’ adherence. Antihistamine pretreatment – originally introduced as a safety measure to reduce anaphylactic side effects – has been the only treatment option for LRs so far, although these swellings usually do not appear immediately but after hours. We were interested whether pretreatment with the leukotriene antagonist montelukast would be better suited for preventing those reactions than pretreatment with the antihistamine desloratadine. Methods: Fifteen patients with a history of severe anaphylactic reactions to hymenoptera stings were enrolled into a prospective, double-blind, randomized, placebo-controlled pilot study. We selected a rush immunotherapy protocol consisting of 19 injections of hymenoptera venom administered over 5 consecutive days, where the majority is developing LRs, and counted the number of injections until an LR of >3 cm occurred. The patients were randomized to 3 treatment groups: premedication with placebo, 10 mg montelukast and 5 mg of the antihistamine desloratadine. Results: Compared with placebo, the occurrence of LRs (>3 cm) was significantly delayed by montelukast (p < 0.01, analysis of variance) but not by desloratadine (p = 0.19). The difference between montelukast and desloratadine was close to significant (p = 0.054). Itching, recorded on a scale from 0 to 5, did not differ between the 3 groups. Conclusion: Montelukast can be useful in the prevention of LRs after specific immunotherapy.
Risk Factors for Allergy due to the Two-Spotted Spider Mite (Tetranychus urticae) among Table Grape Farm Workers
Authors: Jeebhay M.F. , Baatjies R. , Chang Y.-S. , Kim Y.-K. , Kim Y.-Y. , Major V. , Lopata A.L.
Published: May 2007

Background: Recent studies have reported an increased prevalence of respiratory symptoms among farm workers. The aim of this study was to identify risk factors associated with spider mite allergy among table grape farm workers. Methods: A cross-sectional study of 207 workers in table grape farms was conducted. Skin prick tests used extracts of 8 common aeroallergens, grape mould (Botrytis cinerea) and Tetranychus urticae. Specific IgE to T. urticae was quantified using ImmunoCAP (Phadia). Erythrocyte cholinesterase levels were determined using the Test-mate ChE Cholinesterase Test System (model 460). Results: The average duration of employment of workers was 10 years and 12% were pesticide crop sprayers. Work-related wheeze (26%), ocular-nasal (24%) and urticaria/skin symptoms (14%) were more prevalent in the orchards. The prevalence of sensitization (skin prick test) was highest to T. urticae (22%) followed by house dust mite (16%), with 25% being atopic. The prevalence of allergy to T. urticae (skin reactivity and work-related symptoms) was 9.5%, with respiratory allergy (6%) more common than skin allergy (3%). Work-related ocular-nasal (OR = 4.9) and skin (OR = 3.7) symptoms were more commonly reported by pesticide crop sprayers. Workers with T. urticae-allergic rhino-conjunctivitis and probable asthma were more likely to be atopic, spray pesticides and have low (<30 U/g hemoglobin) erythrocyte cholinesterase levels. Conclusions: This study demonstrated that spider mite, T. urticae, is an important outdoor allergen among table grape farm workers. The increased risk of spider mite allergy appears to be related to high pesticide exposure among crop sprayers.
Anaphylaxis to Gadobenate Dimeglumine (Multihance®): A Case Report
Authors: Kalogeromitros Dimitrios C. , Makris Michael P. , Aggelides Xenophon S. , Spanoudaki Nektaria , Gregoriou Stamatios G. , Avgerinou Georgia , Rigopoulos Dimitrios G.
Published: May 2007

Background: Gadolinium chelates are relatively safe contrast media used in MRI. Immediate severe adverse effects are exceptionally rare and mostly concern mild anaphylactoid reactions. We report a case of anaphylaxis to gadobenate dimeglumine (Gd-BOPTA, Multihance®), a gadolinium-based contrast agent. Methods: A 32-year-old female patient with a personal history of multiple sclerosis, while undergoing an MRI scan, developed bronchospasm and acute urticaria with diffuse giant pruritic plaques in the first minute of Gd-BOPTA infusion. The procedure was cancelled and acute treatment of the reaction took place. The patient reported 2 additional MRI scans with definite use of unknown contrast media in the past 2 years without any adverse effect. Blood samples were obtained 2 and 48 h after the reaction for measurement of serum tryptase concentration (Pharmacia Diagnostics, Uppsala, Sweden). Skin prick tests and intradermal tests were performed using 1:1,000, 1:100 and 1:10 dilution of the offending agent and alternative gadolinium-based agents [gadodiamide (Omniscan®) and gadoteric acid (Dotarem®)]. A group of 10 nonatopic individuals who underwent the same skin testing comprised the control group. Results: Tryptase concentration was highly elevated 2 h after the reaction (21 µg/l) compared with that at 48 h (3 µg/l). Skin prick tests in our patient were all negative, while intradermal testing with 0.03 ml of 1:100 and 1:10 preparations of Multihance showed a definite positive wheal-and-flare reaction. Skin tests to the alternative agents showed no response. In the control group, all performed tests were negative. Conclusion: We report the first case of an allergic reaction to gadobenate dimeglumine. Besides, skin testing seems to be a precious diagnostic tool which, if positive, strongly suggests a mast cell-mediated underlying mechanism.
Capecitabine-Induced Headache Responding to Diltiazem
Authors: Raman Arun K. , Fakih Marwan G.
Published: May 2007

Background: Headaches have been reported as a potential side effect of capecitabine therapy. However, severe limiting headaches are rarely experienced in this setting and no known therapy has been described for such a serious side effect. Results: We report the case of a patient treated with capecitabine and radiation for rectal adenocarcinoma. The patient developed grade 3 capecitabine-induced headache. A cause-effect relationship to capecitabine was suggested due to resolution of headache with capecitabine withdrawal and reappearance with capecitabine rechallenge. The patient’s headache resolved with diltiazem therapy and she was able to complete capecitabine and radiation therapy without further adverse events. Conclusions: Capecitabine and 5-fluorouracil (5-FU) are known vasospasm inducers. We hypothesize that capecitabine-induced headache is vascular in nature. This likely explains the noted response to a calcium channel blocker (CCB), namely diltiazem. CCBs should be considered in the treatment of 5-FU or capecitabine-induced headaches.
Involvement of NMDA Receptors in Thiopental-Induced Loss of Righting Reflex, Antinociception and Anticonvulsion Effects in Mice
Authors: Ge Zhi Jun , Zhang Li Cai , Zeng Yin Ming , Da Ti Jun , Wang Jun Ke , Cui Guo Xin , Tan Yong Fei , Zhao Yan Ping , Liu Guo Jun
Published: May 2007

Potentiation of GABAA receptor-mediated inhibitory neurotransmission contributes to the anesthetic action of thiopental. However, the inhibiting action of general anesthetic on excitatory neurotransmission also purportedly underlies its effects. The aim of the study was to elucidate the role of glutamate receptors (NMDA and AMPA receptors) in thiopental-induced anesthesia. Intracerebroventricular (i.c.v.) NMDA (50 ng) significantly increased the induction time of loss of righting reflex and decreased sleep time induced by intraperitoneal injection (i.p.) of thiopental (50 mg/kg). Furthermore, NMDA at 50 ng i.c.v. increased the 50% effective dose values for thiopental to produce loss of righting reflex and immobility in response to noxious tail clamp by 25% and 21% (p < 0.05), respectively. However, intrathecal (IT) administration of NMDA or both of i.c.v. or IT administration of AMPA did not show such antagonizing effects on thiopental action at subconvulsive dose. Finally, thiopental (25 mg/kg i.p.) inhibited convulsions induced by NMDA (0.4 µg i.c.v.) or bicuculline (0.6 µg i.c.v.). However, i.p. muscimol (1 mg/kg) blocked the convulsions induced by bicuculline, but not those induced by NMDA at 3 mg/kg. Similarly, i.p. MK-801 (0.1 mg/kg) antagonized NMDA-induced convulsions, but not bicuculline-induced convulsions at 0.3 mg/kg. Therefore, we suggest that the effects of the selective GABAA and NMDA receptors on convulsive behavior are special to their sites of action, and that the inhibitory action of thiopental on NMDA receptors is possibly not mediated by secondary effects of its GABAA receptors agonism. These results above indicate the involvement of NMDA receptors in thiopental-induced anesthesia in mice.
Comparison of Accuracy and Precision between Frame-Based and Frameless Stereotactic Navigation for Deep Brain Stimulation Electrode Implantation
Authors: Bjartmarz Hjálmar , Rehncrona Stig
Published: May 2007

The accuracy and precision of frameless neuronavigation as compared to conventional frame-based stereotaxy for implantation of deep brain stimulation (DBS) electrodes were studied in 14 patients with essential tremor. DBS electrodes were implanted bilaterally in the ventrolateral thalamus [ventrointermediate nucleus (VIM)] in one procedure. Frameless neuronavigation was used on one side and the conventional frame-based technique on the other. Targeting was guided by MRI and CT imaging. Intraoperative stereotactic plain X-ray verified final electrode positions and electrode deviations from the planned target were measured. Clinical outcome was evaluated with the Essential Tremor Rating Scale. Thirteen of the patients were eligible for measuring electrode deviations and 10 of them were available for a clinical follow-up. Electrode deviations from target were larger using the frameless technique in the medial-lateral (x: 1.9 ± 1.3 mm) and anterior-posterior (y:0.9 ± 0.8 mm) directions as compared to the frame-based technique (x: 0.5 ± 0.5 and y: 0.4 ± 0.4 mm) but similar in the superior-inferior direction (z). The vector of deviation was 2.5 ± 1.4 mm with the frameless technique and 1.2 ± 0.6 with the frame-based technique. The differences were statistically significant (p < 0.05–0.001). The dispersion was larger with the frameless technique as represented by the larger standard deviations in all three planes. At clinical follow-ups, tremor reduction was similar irrespective of the implantation technique. It is concluded that conventional frame-based stereotaxy has higher accuracy/precision for hitting a small brain target than the frameless technique. However, the difference is relatively small and does not influence the clinical result of DBS electrode implantations in the VIM when treating tremor.
Effects of Unfractionated Heparin and Glycoprotein IIb/IIIa Antagonists Versus Bivalirdin on Myeloperoxidase Release From Neutrophils
Authors: Li Guohong , Keenan Alison C. , Young Justin C. , Hall Margaret J. , Pamuklar Zehra , Ohman E. Magnus , Steinhubl Steven R. , Smyth Susan S.
Published: May 2007

Objectives—

The objective of this study was to determine whether adjunctive therapy during percutaneous coronary intervention (PCI) affects markers of systemic inflammation or platelet activation. Despite different mechanisms of action, direct-thrombin inhibition with bivalirudin during PCI provided similar protection from periprocedural and chronic ischemic complications as compared with unfractionated heparin (UFH) plus planned use of GPIIb/IIIa antagonists in the REPLACE-2 and ACUITY trials.

Methods and Results—

Patients undergoing nonurgent PCI of a native coronary artery were randomized to receive adjunctive therapy with bivalirudin or UFH+eptifibatide. Interleukin (IL)-6 and C-reactive protein (CRP) transiently increased in both groups after PCI. In the UFH+eptifibatide, but not the bivalirudin group, myeloperoxidase (MPO) levels were elevated 2.3-fold above baseline (
P
=0.004) immediately after PCI. In an in vitro assay, heparin and to a lesser extent enoxaparin, but not bivalirudin or eptifibatide, stimulated MPO release from and binding to neutrophils and neutrophil activation. A mouse model of endoluminal femoral artery denudation was used to investigate further the importance of MPO in the context of arterial injury.

Conclusions—

Adjuvant therapy during PCI may have undesired effects on neutrophil activation, MPO release, and systemic inflammation.
RhoGDI-1 Modulation of the Activity of Monomeric RhoGTPase RhoA Regulates Endothelial Barrier Function in Mouse Lungs
Authors: Gorovoy Matvey , Neamu Radu , Niu Jiaxin , Vogel Stephen , Predescu Dan , Miyoshi Jun , Takai Yoshimi , Kini Vidisha , Mehta Dolly , Malik Asrar B. , Voyno-Yasenetskaya Tatyana
Published: May 2007

Rho family GTPases have been implicated in the regulation of endothelial permeability via their actions on actin cytoskeletal organization and integrity of interendothelial junctions. In cell culture studies, activation of RhoA disrupts interendothelial junctions and increases endothelial permeability, whereas activation of Rac1 and Cdc42 enhances endothelial barrier function by promoting the formation of restrictive junctions. The primary regulators of Rho proteins, guanine nucleotide dissociation inhibitors (GDIs), form a complex with the GDP-bound form of the Rho family of monomeric G proteins, and thus may serve as a nodal point regulating the activation state of RhoGTPases. In the present study, we addressed the in vivo role of RhoGDI-1 in regulating pulmonary microvascular permeability using
RhoGDI-1
−/−
mice. We observed that basal endothelial permeability in lungs of
RhoGDI-1
−/−
mice was 2-fold greater than wild-type mice. This was the result of opening of interendothelial junctions in lung microvessels which are normally sealed. The activity of RhoA (but not of Rac1 or Cdc42) was significantly increased in
RhoGDI-1
−/−
lungs as well as in cultured endothelial cells on downregulation of RhoGDI-1 with siRNA, consistent with RhoGDI-1–mediated modulation RhoA activity. Thus, RhoGDI-1 by repressing RhoA activity regulates lung microvessel endothelial barrier function in vivo. In this regard, therapies augmenting endothelial RhoGDI-1 function may be beneficial in reestablishing the endothelial barrier and lung fluid balance in lung inflammatory diseases such as acute respiratory distress syndrome.
Flow Antagonizes TNF-α Signaling in Endothelial Cells by Inhibiting Caspase-Dependent PKCζ Processing
Authors: Garin Gwenaele , Abe Jun-ichi , Mohan Amy , Lu Weimin , Yan Chen , Newby Andrew C. , Rhaman Arshad , Berk Bradford C.
Published: May 2007

Unidirectional laminar flow is atheroprotective, in part by inhibiting cytokine-mediated endothelial cell (EC) inflammation and apoptosis. Previously, we showed that flow inhibited TNF-α signaling by preventing activation of JNK. Recently, PKCζ was identified as the PKC isoform most strongly regulated by flow pattern, with increased PKCζ activity in regions of disturbed flow versus unidirectional flow. Interestingly, PKCζ is cleaved by caspases after TNF-α stimulation to generate a 50-kDa truncated form (CATζ, catalytic domain of PKCζ) with a higher kinase activity than the full-length protein. We hypothesized that flow would inhibit TNF-α–mediated PKCζ cleavage and thereby CATζ formation. We found that PKCζ activity was required for TNF-α–mediated JNK and caspase-3 activation in ECs. PKCζ was rapidly cleaved to generate CATζ in cultured bovine and human aortic ECs and in intact rabbit vessels stimulated with TNF-α. This truncated form of PKCζ enhanced JNK and caspase-3 activation. Interestingly, PKCζ cleavage was prevented by inhibitors of PKCζ, JNK, and caspase activities, suggesting that these enzymes, via regulating CATζ formation, modulate caspase-3 activity in ECs. Finally, we found that flow reduced caspase-dependent processing of PKCζ and caspase-3 activation. These results define a novel role for PKCζ as a shared signaling mediator for flow and TNF-α, and important for flow-mediated inhibition of proinflammatory and apoptotic events in ECs.
Downregulation of the Hemoglobin Scavenger Receptor in Individuals With Diabetes and the Hp 2-2 Genotype
Authors: Levy Andrew P. , Purushothaman K. Raman , Levy Nina S. , Purushothaman Meerarani , Strauss Merav , Asleh Rabea , Marsh Stuart , Cohen Osher , Moestrup Soren K. , Moller Holger J. , Zias Elias A. , Benhayon Daniel , Fuster Valentin , Moreno Pedro R.
Published: May 2007

In individuals with diabetes mellitus (DM), the haptoglobin (Hp) genotype is a major determinant of susceptibility to myocardial infarction. We have proposed that this is because of DM and Hp genotype–dependent differences in the response to intraplaque hemorrhage. The macrophage hemoglobin scavenging receptor CD163 plays an essential role in the clearance of hemoglobin released from lysed red blood cells after intraplaque hemorrhage. We sought to test the hypothesis that expression of CD163 is DM and Hp genotype–dependent. CD163 was quantified in plaques by immunohistochemistry, on peripheral blood monocytes (PBMs) by FACS, and as soluble CD163 (sCD163) in plasma by ELISA. In DM plaques, despite an increase in macrophage infiltration, CD163 immunoreactivity was lower, resulting in a dramatic reduction in the percentage of macrophages expressing CD163 (27±2% versus 70±2%,
P
=0.0001). In individuals with DM as compared with individuals without DM, the percentage of PBMs expressing CD163 was reduced (3.7±0.6% versus 7.1±0.9%,
P
<0.002) whereas soluble plasma CD163 was increased (2.6±1.1 μg/mL versus 1.6±0.8 μg/mL,
P
<0.0005). Among DM individuals, the Hp 2-2 genotype was associated with a decrease in the percentage of PBMs expressing CD163 (2.3±0.5% versus 5.6±1.3%,
P
=0.01) and an increase in plasma soluble CD163 (3.0±0.2 μg/mL versus 2.3±0.2 μg/mL,
P
=0.04). Taken together, these results demonstrate an impaired hemoglobin clearance capacity in Hp 2-2 DM individuals and may provide the key insight explaining the increased incidence of myocardial infarction in this population.
Effect of Gender on NADPH-Oxidase Activity, Expression, and Function in the Cerebral Circulation
Authors: Miller Alyson A. , Drummond Grant R. , Mast Anja E. , Schmidt Harald H.H.W. , Sobey Christopher G.
Published: May 2007

Background and Purpose—

This study tested whether NADPH-oxidase activity, expression, and functional effects on vascular tone are influenced by gender in the rat cerebral circulation and whether such differences are estrogen-dependent.

Methods—

NADPH-stimulated superoxide production by cerebral (basilar [BA]; middle cerebral) arteries from male and female Sprague-Dawley rats was measured using lucigenin-enhanced chemiluminescence and dihydroethidium. Protein expression of Nox1, Nox2, Nox4, superoxide dismutase 1 (SOD1), SOD2, and SOD3 was measured using Western blotting. Vascular responses of BA to NADPH were assessed in a myograph. Some female rats were ovariectomized and treated with either vehicle (dimethyl sulfoxide) or 17β-estradiol.

Results—

NADPH-stimulated superoxide production by BA and middle cerebral arteries from males was approximately 2-fold greater than vessels from females. Superoxide production was virtually abolished by the NADPH-oxidase inhibitor, diphenyleneiodonium. Protein expression of Nox1 and Nox4 in BA was also higher in males than in females (2.4- and 2.8-fold, respectively), whereas Nox2, SOD1, SOD2, and SOD3 expression did not differ between genders. NADPH induced greater vasorelaxant effects in BA from males versus females (
P
<0.05). The hydrogen peroxide scavenger, catalase, abolished these NADPH-induced relaxations. NADPH-stimulated superoxide production by BA from ovariectomized rats treated with vehicle was 3-fold greater than levels in intact females. Treatment of ovariectomized rats with 17β-estradiol decreased superoxide production (
P
<0.05). NADPH-induced relaxations of BA were smaller in 17β-estradiol-treated than in vehicle-treated ovariectomized rats (
P
<0.05).

Conclusions—

NADPH-oxidase activity and function are lower in cerebral arteries of female rats. These gender differences are estrogen-dependent and are associated with lower Nox1 and Nox4 expression.
Evaluation of Fatigue Scales in Stroke Patients
Authors: Mead Gillian , Lynch Joanna , Greig Carolyn , Young Archie , Lewis Susan , Sharpe Michael
Published: May 2007

Background and Purpose—

There is little information on how to best measure poststroke fatigue. Our aim was to identify which currently available fatigue scale is most valid, feasible, and reliable in stroke patients.

Methods—

Fatigue scales were identified by systematic search, and the 5 with the best face validity were identified by expert consensus. Feasibility (ie, did patients provide answers?) and internal consistency (an aspect of reliability) of these scales were evaluated by interviewing 55 stroke patients. Test-retest reliability was assessed by reinterviewing 51 patients, interrater reliability was assessed by rerating audio recordings, and convergent validity was assessed by measuring the correlation between scale scores.

Results—

Of the 52 scales identified, the SF-36v2 (vitality component), the fatigue subscale of the Profile of Mood States, the Fatigue Assessment Scale, the general subscale of the Multidimensional Fatigue Symptom Inventory, and the Brief Fatigue Inventory had the best face validity. The Brief Fatigue Inventory was unfeasible to administer and was omitted. Of the remaining 4 scales, the Fatigue Assessment Scale had the poorest internal consistency. Test-retest reliability for individual scale questions ranged from fair to good; the Fatigue Assessment Scale had the narrowest limits of agreement for the total score, indicating the best test-retest reliability. Interrater reliability for individual questions ranged from good to very good, and there was no significant mean difference in total scores for any scale. Convergent validity was moderate to high for the total scores of the 4 scales.

Conclusions—

All four scales were valid and feasible to administer to stroke patients. The Fatigue Assessment Scale had the best test-retest reliability but the poorest internal consistency.
Prothrombotic Mutations as Risk Factors for Cryptogenic Ischemic Cerebrovascular Events in Young Subjects With Patent Foramen Ovale
Authors: Botto Nicoletta , Spadoni Isabella , Giusti Sandra , Ait-Ali Lamia , Sicari Rosa , Andreassi Maria Grazia
Published: May 2007

Background and Purpose—

Patent foramen ovale (PFO) has been identified as a potential risk factor for cerebrovascular ischemia. Procoagulant mutations may increase the risk and impact the choice of appropriate therapy for secondary prevention. We evaluated the prevalence of the 2 most common genetic risk factors for thromboembolism, factor V Leiden (G1691A) and prothrombin G20210A, in young PFO patients who were referred for percutaneous transcatheter closure of their PFO.

Methods—

Ninety-seven patients (50 men; mean±SD age, 40.9±10.0 years) with first-ever cerebrovascular events before the age of 55 years and 160 age-matched control subjects (69 men; mean±SD age, 40.4±10.5 years) were recruited into the study. Factor V Leiden and prothrombin G20210A mutations were detected by using a multiplex allele-specific polymerase chain reaction assay.

Results—

The prevalence of subjects carrying at least 1 prothrombotic genotype was significantly higher in the group of PFO patients than in the group of controls (10.3% vs 2.5%; χ
2
=7.2,
P
=0.008). Two patients (2.1%) versus 1 control subject (0.6%) and 8 cases (8.2%) versus 3 controls (1.9%) were carriers for factor V Leiden and prothrombin G20210A mutations, respectively. After adjustment for other vascular risk factors, the combination of either factor V Leiden or prothrombin G20210A and PFO was associated with a 4.7-fold (95% CI=1.4 to 16.1;
P
=0.008) increased risk of cerebral ischemia in young patients.

Conclusions—

Our results indicate that prothrombotic mutations are important risk factors for cerebral ischemia in young patients with PFO. Screening for thrombotic mutations should be considered in young patients with PFO-related ischemic events.
Cerebral Vascular Dysfunction During Hypercholesterolemia
Authors: Kitayama Jiro , Faraci Frank M. , Lentz Steven R. , Heistad Donald D.
Published: May 2007

Background and Purpose—

Studies of peripheral arteries in hypercholesterolemic animals suggest that increased generation of superoxide contributes to endothelial dysfunction, especially in the presence of atherosclerotic lesions. We tested the hypothesis that vasomotor function is impaired in cerebral arterioles during hypercholesterolemia through a mechanism that involves oxidative stress.

Methods—

Apolipoprotein E–deficient (apoE
−/−
) mice were fed a normal or a high-fat diet for >6 months. ApoE
+/−
mice fed a normal diet were used as normocholesterolemic controls. Responses of cerebral arterioles were examined in open cranial windows in vivo in anesthetized mice.

Results—

In apoE
−/−
mice, intimal area was increased only in the proximal aorta on the normal diet and also markedly increased in the distal aorta on the high-fat diet. There were no increases in intimal area in the aortas of control mice or in the cerebral arterioles in any group. The dilator response of cerebral arterioles to ACh (10 μmol/L) in control mice (26±4% increase in diameter) was reduced in apoE
−/−
mice on either the normal (13±2%) or the high-fat (13±3%) diet (
P
<0.05 vs control). NADPH (10 μmol/L), a substrate for NADPH oxidase, produced dilator responses in control mice (8±4%) that were significantly increased in apoE
−/−
mice on the high-fat diet (16±2%,
P
<0.05 vs control). Tempol, a superoxide scavenger, and apocynin, an inhibitor of NADPH oxidase, significantly increased vasodilator responses to ACh and decreased vasodilation to NADPH in apoE
−/−
mice on the high-fat diet. Nitroprusside produced a similar dilatation in the cerebral arterioles of all groups.

Conclusions—

Hypercholesterolemia is associated with oxidative stress and endothelial dysfunction in cerebral arterioles, despite the absence of atherosclerotic lesions.
The Interventional Management of Stroke (IMS) II Study
Authors:   The IMS II Trial Investigators
Published: May 2007

Background and Purpose—

The purpose of this study was to further investigate the feasibility and safety of a combined intravenous and intra-arterial approach to recanalization for ischemic stroke.

Methods—

Subjects, ages 18 to 80, with a baseline NIHSS ≥10 had intravenous recombinant tissue plasminogen activator (rt-PA) started (0.6 mg/kg over 30 minutes) within 3 hours of onset. For subjects with an arterial occlusion at angiography, additional rt-PA was administered via the EKOS micro-infusion catheter or a standard microcatheter at the site of the thrombus up to a total dose of 22 mg over 2 hours of infusion or until thrombolysis.

Results—

The 81 subjects had a median baseline NIHSS score of 19. The median time to initiation of intravenous rt-PA was 142 minutes as compared with 108 minutes for placebo and 90 minutes for rt-PA–treated subjects in the NINDS rt-PA Stroke Trial (
P
<0.0001). The 3-month mortality in IMS II subjects was 16% as compared with the mortality of placebo (24%) and rt-PA–treated subjects (21%) in the NINDS rt-PA Stroke Trial. The rate of symptomatic intracerebral hemorrhage in IMS II subjects (9.9%) was not significantly different than that for rt-PA treated subjects in the NINDS t-PA Stroke Trial (6.6%). IMS II subjects had significantly better outcomes at 3 months than NINDS placebo-treated subjects for all end points (OR ≥2.7) and better outcomes than NINDS rt-PA–treated subjects as measured by the Barthel Index and Global Test Statistic.

Conclusions—

A randomized trial of standard intravenous rt-PA as compared with a combined intravenous and intra-arterial approach is warranted and has begun.
Planetary Wave Response to Surface Forcing and Instability in the Presence of Mean Flow and Topography
Authors: Killworth Peter D. , Blundell Jeffrey R.
Published: May 2007

The local response of an ocean with slowly varying mean flow, stratification, and topography to two sources of disturbance is examined, concentrating on whether the resulting surface elevations are observable. The first is the ocean response to surface forcing (Ekman pumping or buoyancy forcing). For typical amplitudes of random forcing, while much of the ocean response is small (surface elevations less than 1 mm), there are sufficient near resonances (or pseudoresonances involving a critical layer) to produce elevations of 1 cm or more in much of the ocean. The second source is baroclinic instability. The fastest linear growth rate, as well as those for specific wavelengths, is computed globally. Almost all of the ocean is baroclinically unstable, and the most unstable waves are found to possess a small wavelength (often less than 10 km) with a disturbance concentrated near the surface: e-folding times O(20 days) are frequently found. However, the phase speed for the disturbances is almost everywhere slower westward than free planetary waves with mean flow and topography. Since the free waves propagate at speeds similar to observations, instability may be a good source of variability but is probably not responsible directly for observed wave propagation.
A Simple Model of Millennial Oscillations of the Thermohaline Circulation
Authors: Colin de Verdière A.
Published: May 2007

Stommel’s two-box model of thermohaline circulation is modified to include the possibility of convection. When reduced to a two-degrees-of-freedom dynamical system, the model exhibits the well-known multiple (thermal and haline) steady states as well as new convective thermal steady states. However, for some values of the control parameters (such as the freshwater flux) oscillations occur. Millennial period oscillatory regimes correspond to switches between the Stommel’s haline fixed point and the convective thermal state, both of which are unstable in a window of precipitation values. The transitions between steady and oscillatory regimes at the boundaries of the window are global bifurcations, which in some cases have an infinite period character. This character is due either to the proximity of the Stommel saddle node bifurcation or to the infinite time it takes for the convection to resume when the system is in the haline regime. The oscillations bear a close relationship to those of Welander’s flip–flop model. The physics of this class of millennial oscillations may be relevant to those observed in more complex OGCMs and may help to rationalize certain features of the millennial band oscillations that punctuate the last glacial period.
Coupled Interannual Rossby Waves in a Quasigeostrophic Ocean–Atmosphere Model
Authors: Farneti Riccardo
Published: May 2007

Rossby wave propagation is investigated in the framework of an idealized middle-latitude quasigeostrophic coupled ocean–atmosphere model. The Rossby waves are observed to propagate faster than both the classical linear theory (unperturbed solution) and the phase speed estimates when the effect of the zonal mean flow is added (perturbed solution). Moreover, using statistical eigentechniques, a clear coupled Rossby wave mode is identified between a baroclinic oceanic Rossby wave and an equivalent barotropic atmospheric wave. The spatial phase relationship of the coupled wave is similar to the one predicted by Goodman and Marshall, suggesting a positive ocean–atmosphere feedback. It is argued that oceanic Rossby waves can be efficiently coupled to the overlying atmosphere and that the atmospheric coupling is capable of adding an extra speedup to the wave; in fact, when the ocean is simply forced, the Rossby wave propagation speed approaches the perturbed solution.
Determination of the Bending Characteristic Parameters of the Bending Evaluation System of Fabric and Yarn
Authors: Yu Weidong , Du Zhaoqun
Published: May 2007

The bending evaluation system of fabric and yarn (BES-FY) can measure the bending, weight, friction and tensile properties of fabric and yarn through a pull-out test and delineate the relationship between the mechanical geometry and the corresponding deforming process, so as to quantify the comprehensive hand of fabric and yarn. The bending process of the BES-FY system was mainly investigated in the present study. Two bending models were developed under different conditions and the corresponding formulae for bending rigidity were also obtained. The optimum point and range for calculating the bending rigidity was acquired by experimental and analytical investigation, which involved study of the relationships between bending rigidity—curvature. These can be divided into three sections, namely, linear, quadratic and constant function, and through the comparisons between the bending rigidity of the two bending models and that of KES-FB2 and FAST-2, the better bending model was selected to characterize the bending properties of fabric and yarn.
Unrealistic Assumptions in Rational Choice Theory
Authors: Lehtinen Aki , Kuorikoski Jaakko
Published: May 2007

The most common argument against the use of rational choice models outside economics is that they make unrealistic assumptions about individual behavior. We argue that whether the falsity of assumptions matters in a given model depends on which factors are explanatorily relevant. Since the explanatory factors may vary from application to application, effective criticism of economic model building should be based on model-specific arguments showing how the result really depends on the false assumptions. However, some modeling results in imperialistic applications are relatively robust with respect to unrealistic assumptions.
Review Essay: Historiographic Self-consciousness
Authors: Tucker Aviezer
Published: May 2007

Historians tend to present what they do in terms of prevailing epistemic values that have little to do with their actual practices. Practical knowledge of how does not generate necessarily abstract theoretical knowledge of what. Mark Bevir's The Logic of the History of Ideas attempts to integrate his normative philosophy of historiography with contemporary philosophy of language and epistemology, intentionalist theory of meaning, and coherentist epistemology, on a sophisticated and well-informed level. Yet it is written from the perspective of a particular school and set to normatively defend its research program and assumptions. Sewell's Logics of History is innocent of contemporary epistemology and the philosophies of science and the social sciences, and it shows, mostly in conceptual confusions. Katz's God's Last Words is completely innocent of philosophy, but is still excellent precisely because it makes no theoretical assumption and unreflectively carries on with making sense of the evidence.
Review Essay: The Mind as a Scientific Object
Authors: Shani Itay
Published: May 2007

The prevailing message of this volume lies in the claim that psychology ought to come to terms with the irreducible cultural dimensions of mind. Though this is an important message, the author argues that an uncritical shift in favor of a cultural approach runs the risk of imposing uniquely human characteristics on the general study of the mind. Moreover, by treating the nature-nurture dichotomy as an axiom, the bulk of the articles in this collection fail to consider the possibility of transcending this basic dualism. Nevertheless, this is a rewarding read and the book's plea for a greater emphasis on the cultural aspects of mind makes it both timely and unique.
Comparison of Continuous Drip of Midazolam or Lidocaine in the Treatment of Intractable Neonatal Seizures
Authors: Shany Eilon , Benzaqen Oshra , Watemberg Nathan
Published: May 2007

Seizures constitute the most common neurological symptom in the neonatal period. Treatment usually involves the administration of intravenous benzodiazepines followed by either phenobarbital or phenytoin. For nonresponsive cases, continuous intravenous drip of either midazolam or lidocaine has been suggested for seizure control. Some reports suggest that seizures themselves may have a deleterious effect on long-term neurological outcome. Therefore, there is a need to find treatment regimens with better efficacy to provide maximum seizure control. The authors compared the effectiveness of lidocaine and midazolam in the treatment of intractable seizures in newborn infants born at or after 36 weeks of gestation who suffered from hypoxic-ischemic encephalopathy and who had their cerebral activity monitored. Thirty infants were included in the study: 22 received lidocaine, and 8 received midazolam. Seventeen (77%) infants had a good or partial response to lidocaine, and 4 (50%) had a partial response to midazolam. Of 20 infants diagnosed with hypoxic-ischemic encephalopathy grade 2, 18 (90%) responded to second-line treatment (14 [93%] of 15 to lidocaine and 4 [80%] of 5 to midazolam). Among 10 infants with hypoxic-ischemic encephalopathy grade 3, only 3 (30%) responded to second-line treatment (all 3 to lidocaine, none to midazolam). The findings suggest that lidocaine may be more effective than midazolam in reducing or controlling refractory neonatal seizures. The lower response rate to midazolam was more evident in infants with severe hypoxic-ischemic encephalopathy (grade 3).