bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Gastritis in Dermatitis Herpetiformis: A Controlled Study
Authors: Alakoski Anna , Salmi Teea T. , Hervonen Kaisa , Kautiainen Hannu , Salo Maarit , Kaukinen Katri , Reunala Timo , Collin Pekka
Published: April 2012

Background and Objective. Previous small studies suggest that chronic atrophic gastritis is common in dermatitis herpetiformis (DH). We here examined the frequency and topography of chronic gastritis in 93 untreated DH subjects and in 186 controls with dyspepsia.Methods. Specimens were drawn from the gastric corpus and antrum and examined for atrophy, intestinal metaplasia, andHelicobacter pylori. Duodenal biopsies were taken.Results. Atrophic corpus gastritis was more frequent in DH than in controls (16.0% and 2.7%, resp.,P<0.001); atrophy in the antrum was rare in both groups (3.2% and 1.1%,P=0.34). Intestinal metaplasia was present in 13 (14.0%) DH and 12 (6.5%) control patients (P=0.038) andH. pyloriin 17 (18.3%) and 17 (9.3%) (P=0.028), respectively. Small-bowel villous atrophy was seen in 76% of the DH patients, equally in patients with and without chronic gastritis. One DH patient with atrophic gastritis developed gastric cancer.Conclusion. In DH, chronic atrophic gastritis was common in the corpus, but not in the antrum.H. pyloriwill partly explain this, but corpus atrophy is suggestive of an autoimmune etiology. Atrophic gastritis may increase the risk of gastric cancer. We advocate performing upper endoscopy with sufficient histologic samples in DH.
Proteomic Characterization of a Mouse Model of Familial Danish Dementia
Authors: Vitale Monica , Renzone Giovanni , Matsuda Shuji , Scaloni Andrea , D'Adamio Luciano , Zambrano Nicola
Published: April 2012

A dominant mutation in theITM2B/BRI2gene causes familial Danish dementia (FDD) in humans. To model FDD in animal systems, a knock-in approach was recently implemented in mice expressing a wild-type and mutant allele, which bears the FDD-associated mutation. Since theseFDDKImice show behavioural alterations and impaired synaptic function, we characterized their synaptosomal proteome via two-dimensional differential in-gel electrophoresis. After identification by nanoliquid chromatography coupled to electrospray-linear ion trap tandem mass spectrometry, the differentially expressed proteins were classified according to their gene ontology descriptions and their predicted functional interactions. The Dlg4/Psd95 scaffold protein and additional signalling proteins, including protein phosphatases, were revealed by STRING analysis as potential players in the altered synaptic function ofFDDKImice. Immunoblotting analysis finally demonstrated the actual downregulation of the synaptosomal scaffold protein Dlg4/Psd95 and of the dual-specificity phosphatase Dusp3 in the synaptosomes ofFDDKImice.
Quinhydrone Chemical Passivation of a Silicon Surface for Minority Carrier Bulk-Lifetime Measurements
Authors: Solcansky M. , Vanek J. , Poruba A.
Published: April 2012

For the measurement of the minority carrier bulk-lifetime the characterization method MW-PCD is used, where the result of measurement is the effective carrier lifetime, which is very dependent on the surface recombination velocity and therefore on the quality of a silicon surface passivation. This work deals with an examination of a different solution types for the chemical passivation of a silicon surface. Various solutions are tested on silicon wafers for their consequent comparison. The main purpose is to find optimal solution, which suits the requirements of a time stability and start-up velocity of passivation, reproducibility of the measurements and a possibility of a perfect cleaning of a passivating solution remains from a silicon surface, so that the parameters of a measured silicon wafer will not worsen and there will not be any contamination of the other wafers series in the production after a repetitive return of the measured wafer into the production process. The cleaning process itself is also a subject of a development.
Risk Factors for Endophthalmitis and Retinal Detachment with Retained Intraocular Foreign Bodies
Authors: Parke D. Wilkin , Pathengay Avinash , Flynn Harry W. , Albini Thomas , Schwartz Stephen G.
Published: April 2012

Purpose. To analyze risk factors for endophthalmitis and retinal detachment (RD) in patients with retained intraocular foreign bodies (IOFBs).Design. A retrospective, interventional, consecutive case series.Participants. All patients treated at Bascom Palmer Eye Institute for traumatic IOFBs between 1999 and 2008.Methods. Analysis of visual outcome, mechanism of injury, management, and postoperative course.Results. 108 eyes with IOFBs were identified. Endophthalmitis occurred in 7 eyes (6.4%) at presentation, and risk was higher with vegetable matter exposure (P=0.003). All eyes with posterior segment IOFBs received intravitreal antibiotics and there were no cases of endophthalmitis after initial management. RD was identified in 6 of 108 eyes (5.5%) at presentation. Risk factors were entry more than 5 mm behind the limbus (P<0.001) and posterior segment IOFB (P=0.028). Postoperative RD occurred in 11 of 102 eyes (10.7%). Risk factors for postoperative RD were preoperative endophthalmitis (P=0.001), posterior segment IOFB (P=0.008), and retinal impact sites (P=0.028).Conclusions. Risk factors for endophthalmitis included vegetable matter exposure and delay to initial management. Risk factors for RD were posterior entry site, posterior segment IOFB, endophthalmitis, and retinal impact sites. No eyes developed endophthalmitis after presentation.
Influence of Fructooligosaccharide on Pharmacokinetics of Isoflavones in Postmenopausal Women
Authors: Teekachunhatean Supanimit , Techatoei Sujitra , Rojanasthein Noppamas , Manorot Maleeya , Sangdee Chaichan
Published: April 2012

The objective of the present paper was to determine the influence of fructooligosaccharide (FOS) on the pharmacokinetics of isoflavones in healthy postmenopausal women. The study was a fixed-sequence, two-phase, crossover study. Twelve subjects received a single oral dose of 300 mL of a soy beverage. Blood samples were collected before the dose and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, and 32 h after the administration of the soy beverage. After a washout period of at least 1 week, subjects were assigned to receive oral doses of FOS, 5 g each time, twice a day (after breakfast and dinner) for 14 days, followed by a single oral dose of the same soy beverage on the next day. Blood samples were then collected at the same time points mentioned previously. Plasma isoflavone concentrations were determined by HPLC. Continuous oral administrations of FOS followed by a single oral administration of soy beverage caused significant increases inCmax, AUC0–32, and AUC0–∞of genistein and AUC0–32of daidzein, comparing to those obtained following a single oral dose of soy beverage alone. Other pharmacokinetic parameters (Tmaxandt1/2of both aglycones and AUC0–∞of daidzein) between both regimens were not significantly different.
Ethnic Disparities in the Graduate Labour Market
Authors: Zorlu Aslan
Published: April 2012

This paper examines ethnic wage differentials for the entire population of workers who enrolled for the first time as students at Dutch universities (WO) and colleges (HBO) in 1996 using unique administrative panel data for the period 1996 to 2005 from the Dutch tertiary education system. The study breaks down wage differentials into two components: a component which can be explained by the observed characteristics and an unexplained component. The analysis provides new evidence for the magnitude and the origin of ethnic wage differentials by gender. In general, ethnic wage gap is larger for migrant women than migrant men and larger for Western and Caribbean migrants than for Mediterranean migrants. Ethnic minority workers appear to have larger wage surpluses which is almost entirely explained by their observed favourable characteristics. Most notably, Mediterranean female graduates have significantly positive wage discrimination, while Western female graduates seem to face a small wage penalty.
Pregnancy Followed by Delivery May Affect Circulating Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Levels in Women of Reproductive Age
Authors: Balin Mehmet , Çelik Ahmet , Kobat M. Ali , Baydas Adil
Published: April 2012

Background/Objective. It is known that menopause or lack of endogenous estrogen is a risk factor for endothelial dysfunction and CAD. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved inmultiple phases of vascular dysfunction.The purpose of the current study was to determine the association between soluble LOX-1 (sLOX-1) and pregnancy followed by delivery in women of reproductive age.Materials/Methods. Sixty-eight subjects with pregnancy followed by delivery (group 1) and 57 subjects with nongravidity (group 2) were included in this study. Levels of sLOX-1 were measured in serum by EL SA.Results. Plasma levels of sLOX-1 were significantly lower in Group 1 than Group 2 in women of reproductive age ( ng/mL and , resp., ). There were strong correlations between sLOX-1 levels and the number of gravida (, ). The levels of sLOX-1 highly correlated with the number of parous (, ).Conclusion. Our study demonstrated that serum sLOX-1 levels were associated with pregnancy followed by delivery that might predict endothelial dysfunction. We conclude that pregnancy followed by delivery may delay the beginning and progress of arteriosclerosis and its clinical manifestations in women of reproductive age.
Antinociceptive Activity of Methanol Extract ofMuntingia calaburaLeaves and the Mechanisms of Action Involved
Authors: Sani M. H. Mohd. , Zakaria Z. A. , Balan T. , Teh L. K. , Salleh M. Z.
Published: April 2012

Muntingia calaburaL. (family Elaeocarpaceae) has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract ofM. calaburaleaves (MEMC) and to elucidate the possible mechanism of antinociception involved. Thein vivochemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test) and thermal (hot plate test) models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg) was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P<0.05) antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO) donor), NG-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS)), methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP) pathway), or their combination also caused significant (P<0.05) change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.
Retinoblastoma in the Democratic Republic of Congo: 20-Year Review from a Tertiary Hospital in Kinshasa
Authors: Kazadi Lukusa Aimé , Aloni Michel Ntetani , Kadima-Tshimanga Bertin , Mvitu-Muaka Moïse , Gini Ehungu Jean Lambert , Ngiyulu René , Ekulu Mfutu Pépé , Budiongo Nzazi Aléine
Published: April 2012

Background.To determine clinical profile and management of retinoblastoma among children at Kinshasa in Democratic Republic of Congo.Patients and methods. The medical records of patients with a diagnosis of retinoblastoma seen at the University Hospital of Kinshasa from January 1985 till December 2005 were retrospectively reviewed. Demographic profile, clinical data, modes of treatment and outcome were analysed.Results. A total of 49 children, of whom 40 had adequate data on record were identified as retinoblastoma (28 males and 12 females). Nine cases had bilateral disease. The median age at the first symptoms was 9 months (range, 1 month to 6 years) for unilateral retinoblastoma and 18 months (range, 1 month to 3.5 years) for bilateral retinoblastoma. The median age at the first oncology consultation was 2.4 years (range, 6 months to 6 years) for unilateral retinoblastoma and 2.4years (range, 9 months to 4 years) for bilateral disease. Leukokoria was present in 67.5% of subjects. Seventy-five percent abandoned the treatment. The mortality was 92.5%.Conclusion. In Democratic Republic of Congo, retinoblastoma remains a life threatening disease characterized by late referral to a specialized unit and affordability of chemotherapy; all leading to an extension of the disease and high mortality.
Darinaparsin: Solid Tumor Hypoxic Cytotoxin and Radiosensitizer
Authors: Tian Junqiang , Zhao Hongjuan , Nolley Rosalie , Reese Stephen W. , Young Sarah R. , Li Xuejun , Peehl Donna M. , Knox Susan J.
Published: April 2012

Purpose: Hypoxia is an important characteristic of the solid tumor microenvironment and constitutes a barrier for effective radiotherapy. Here, we studied the effects of darinaparsin (an arsenic cytotoxin) on survival and radiosensitivity of tumor cells in vitro under normoxia and hypoxia and in vivo using xenograft models, compared to effects on normal tissues.

Experimental Design: The cytotoxicity and radiosensitization of darinaparsin were first tested in vitro in a variety of solid tumor cell lines under both normoxia and hypoxia and compared with arsenic trioxide (ATO, an arsenical with reported cytotoxic and radiosensitizing activities on tumor cells). The effects were then tested in mouse models of xenograft tumors derived from tumor cell lines and clinical tumor specimens. The potential mechanisms of darinaparsin effects, including reactive oxygen species (ROS) generation, cellular damage, and changes in global gene expression, were also investigated.

Results: In comparison with ATO, darinaparsin had significantly higher in vitro cytotoxic and radiosensitizing activities against solid tumor cells under both normoxia and hypoxia. In vivo experiments confirmed these activities at doses that had no systemic toxicities. Importantly, darinaparsin did not radiosensitize normal bone marrow and actually radioprotected normal intestinal crypts. The darinaparsin-mediated antitumor effects under hypoxia were not dependent on ROS generation and oxidative damage, but were associated with inhibition of oncogene (RAS and MYC)-dependent gene expression.

Conclusion: Darinaparsin has significant and preferential cytotoxic and radiosensitizing effects on solid tumors as compared with normal cells. Darinaparsin may therefore increase the therapeutic index of radiation therapy and has near term translational potential. Clin Cancer Res; 18(12); 3366–76. ©2012 AACR.
Coadministration of Epithelial Junction Opener JO-1 Improves the Efficacy and Safety of Chemotherapeutic Drugs
Authors: Beyer Ines , Cao Hua , Persson Jonas , Song Hui , Richter Maximilian , Feng Qinghua , Yumul Roma , van Rensburg Ruan , Li Zongyi , Berenson Ronald , Carter Darrick , Roffler Steve , Drescher Charles , Lieber André
Published: April 2012

Purpose: Epithelial junctions between tumor cells inhibit the penetration of anticancer drugs into tumors. We previously reported on recombinant adenovirus serotype 3–derived protein (JO-1), which triggers transient opening of intercellular junctions in epithelial tumors through binding to desmoglein 2 (DSG2), and enhances the antitumor effects of several therapeutic monoclonal antibodies. The goal of this study was to evaluate whether JO-1 cotherapy can also improve the efficacy of chemotherapeutic drugs.

Experimental Design: The effect of intravenous application of JO-1 in combination with several chemotherapy drugs, including paclitaxel/Taxol, nanoparticle albumin–bound paclitaxel/Abraxane, liposomal doxorubicin/Doxil, and irinotecan/Camptosar, was tested in xenograft models for breast, colon, ovarian, gastric and lung cancer. Because JO-1 does not bind to mouse cells, for safety studies with JO-1, we also used human DSG2 (hDSG2) transgenic mice with tumors that overexpressed hDSG2.

Results: JO-1 increased the efficacy of chemotherapeutic drugs, and in several models overcame drug resistance. JO-1 treatment also allowed for the reduction of drug doses required to achieve antitumor effects. Importantly, JO-1 coadmininstration protected normal tissues, including bone marrow and intestinal epithelium, against toxic effects that are normally associated with chemotherapeutic agents. Using the hDSG2-transgenic mouse model, we showed that JO-1 predominantly accumulates in tumors. Except for a mild, transient diarrhea, intravenous injection of JO-1 (2 mg/kg) had no critical side effects on other tissues or hematologic parameters in hDSG2-transgenic mice.

Conclusions: Our preliminary data suggest that JO-1 cotherapy has the potential to improve the therapeutic outcome of cancer chemotherapy. Clin Cancer Res; 18(12); 3340–51. ©2012 AACR.
Fetal MRI-Calculated Total Lung Volumes in the Prediction of Short-Term Outcome in Giant Omphalocele: Preliminary Findings
Authors: Danzer Enrico , Victoria Teresa , Bebbington Michael W. , Siegle Jennifer , Rintoul Natalie E. , Johnson Mark P. , Flake Alan W. , Adzick N. Scott , Hedrick Holly L.
Published: April 2012

Objective: To determine the value of fetal MRI-calculated total lung volumes (TLV) in the prediction of short-term outcome in patients with giant omphalocele (GO). Material and Methods: We reviewed all cases of GO undergoing fetal MRI after 21 weeks’ gestation and receiving postnatal care at our institution between 2003 and 2010. Observed/expected (O/E) TLV was calculated using age-matched TLV normograms [Radiology 2001;219:236–241]. Postnatal outcomes were stratified based on O/E TLV above or below 50% of expected. Results: Seventeen GO cases fulfilled the entry criteria. The mean age at fetal MRI evaluation was 25.8 ± 4.8 weeks’ gestation. The mean GO TLV (21.0 ± 13.2) was lower than age-matched population norms (p < 0.001), resulting in a mean O/E TLV of 52.3 ± 16.8%. The mean gestational age at delivery was 36.8 ± 1.6 weeks. Overall survival was 94%. Fourteen (88%) infants underwent staged reduction, and 2 underwent silver sulfadiazine treatment and delayed repair. Infants with ≤50% of predicted O/E TLV (n = 11, 65%) had lower Apgar scores at birth (p = 0.03), prolonged ventilatory support (p = 0.004), delayed oral intake (p = 0.03), and longer hospitalization (p = 0.03) compared to patients with ≥50% of expected O/E TLV. Two infants (both O/E TLV <50%) required tracheostomy placement. Conclusion: In the assessment of GO fetuses, MRI-based O/E TLV of <50% was predictive of increased postnatal morbidity.
Mitochondria Distinguish Granule-Stored from de novo Synthesized Tumor Necrosis Factor Secretion in Human Mast Cells
Authors: Zhang Bodi , Weng Zuyi , Sismanopoulos Nikolaos , Asadi Sharhzad , Therianou Anastasia , Alysandratos Konstantinos-Dionysios , Angelidou Asimenia , Shirihai Orian , Theoharides Theoharis C.
Published: April 2012

Background: Mast cells are immune cells derived from hematopoietic precursors that mature in the tissue microenvironment. Mast cells are critical for allergic, immune and inflammatory processes, many of which involve tumor necrosis factor (TNF). These cells uniquely store TNF in their secretory granules. Upon stimulation, mast cells rapidly (30 min) secrete β-hexosaminidase and granule-stored TNF through degranulation, but also increase TNF mRNA and release de novo synthesized TNF 24 h later. The regulation of these two distinct pathways is poorly understood. Methods: Human LAD2 leukemic mast cells are stimulated by substance P. TNF secretion and gene expression were measured by ELISA and real-time PCR, and mitochondrial dynamics was observed in live cells under confocal microscopy. Cell energy consumption was measured in terms of oxygen consumption rate. Results: Here, we show that granule-stored TNF is preformed, and its secretion from LAD2 mast cells stimulated by substance P (1) exhibits higher energy consumption and is inhibited by the mitochondrial ATP pump blocker oligomycin, (2) shows rapid increase in intracellular calcium levels, and (3) exhibits reversible mitochondrial translocation, from a perinuclear distribution to the cell surface, as compared to de novo synthesized TNF release induced by lipopolysaccharide. This mitochondrial translocation is confirmed using primary human umbilical cord blood-derived mast cells stimulated by an allergic trigger (IgE/streptavidin). Conclusion: Our findings indicate that unique mitochondrial functions distinguish granule-stored from newly synthesized TNF release from human mast cells, thus permitting the versatile involvement of mast cells in different biological processes.
Systemic Up-Regulation of TLR4 Causes Lipopolysaccharide-Induced Augmentation of Nasal Cytokine Release in Allergic Rhinitis
Authors: Ekman A.-K. , Virtala R. , Fransson M. , Adner M. , Benson M. , Jansson L. , Cardell L.O.
Published: April 2012

Background: Allergic rhinitis is a systemic disorder, and it is clinically well recognized that it can be aggravated by infection. Activation of the innate immune system constitutes a critical element in the process. Toll-like receptors (TLRs) comprise a part of the innate immune system, and lipopolysaccharide (LPS)-induced activation of TLR4 represents bacterial-induced interactions in various model systems. The present study examines how TLR2 and TLR4 expression is affected by symptomatic allergic rhinitis, and if LPS added upon allergen affects nasal cytokine release. Methods: In patients with pollen-induced allergic rhinitis and healthy non-allergic volunteers, nasal lavage (NAL), peripheral blood and bone marrow were sampled before and during the pollen season. TLR2 and TLR4 expression was determined flow cytometrically. Changes in the TLR receptor expression pattern were evaluated by a nasal challenge with allergen followed by LPS, or vice versa. Symptoms along with cells and cytokines in NAL were analyzed. Results: TLR4 expression increased in leukocytes in NAL, peripheral blood and bone marrow during symptomatic allergic rhinitis. A similar increase was seen for TLR2 in neutrophils in blood. Nasal challenge with allergen followed by LPS augmented the release of IL-4, IL-5, IL-10, IL-13, IFN-γ and TNF-α. Conclusion: A systemic up-regulation of TLR4 in symptomatic allergic rhinitis may explain why LPS preceded by allergen increases nasal cytokine release.
The Frequency and Significance of Radiologically Detected Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer
Authors: Varol Yelda , Varol Umut , Karaca Burcak , Karabulut Bulent , Sezgin Canfeza , Uslu Ruchan
Published: April 2012

Objective: To investigate the frequency and significance of pulmonary nodules in patients with colorectal cancer (CRC). Subjects and Methods: Medical records of 1,344 patients with CRC who underwent thoracic computerized tomography scans between January 2003 and December 2009 were reviewed. Those with any distant metastatic disease or who were already known to have pulmonary malignancies were excluded. Number, size, shape and location of the nodules were evaluated. A multivariate analysis was performed to determine the predictive factors for evidence of metastases. Results: Of the 1,344 patients, 55 (4.09%) had nodules that met the criteria of an indeterminate pulmonary nodule. The mean follow-up time was 25 ± 17.9 months and the mean time to develop pulmonary metastasis was 15.5 ± 6.4 months. The nodules of 17 (30.9%) patients showed progression at follow-up; 8 had metastasized. Multivariate analysis showed multiple indeterminate pulmonary nodules (p = 0.006) of parenchymal localization (p = 0.016) with an irregular border (p = 0.002), which is predictive of metastatic disease. Conclusion: Our study has shown that multiple indeterminate pulmonary nodules with an irregular border in a parenchymal location were more likely to represent metastatic disease. However, the frequency of the occurrence of indeterminate pulmonary metastases of CRC was low.
Isolated Absence of Septum Pellucidum: Prenatal Diagnosis and Outcome
Authors: García-Arreza Aida , García-Díaz Lutgardo , Fajardo Manuel , Carreto Práxedes , Antiñolo Guillermo
Published: April 2012

Septal agenesis is a rare cerebral developmental anomaly characterized by partial or complete absence of the septum pellucidum (ASP). Septal agenesis may be associated with various congenital brain malformations, namely holoprosencephaly, septooptic dysplasia (SOD), schizencephaly or agenesis of the corpus callosum. Current imaging technologies do not enable differentiation in utero between isolated ASP and SOD. This is due to the fact that optic nerve hypoplasia and endocrine anomalies are never ruled out completely. We report a case of prenatal diagnosis of isolated ASP based on 2D and 3D ultrasound and fetal MRI. Postnatal MRI confirmed prenatal findings and the boy is currently doing well at 18 months of age.
The acceleration of the propagation phase of thrombin generation in patients with steady-state sickle cell disease is associated with circulating erythrocyte-derived microparticles
Authors: Gerotziafas Grigoris , Van Dreden Patrick , Chaari Mourad , Galea Vassiliki , Khaterchi Amir , Lionnet Francois , Stankovic-Stojanovic Katice , Blanc-Brude Olivier , Woodhams Barry , Maier-Redelsperger Micheline , Girot Robert , Hatmi Mohamed , Elalamy Ismail
Published: April 2012

Sickle cell disease (SCD) is linked to hypercoagulability and is characterised by high concentrations of erythrocyte-derived microparticles (Ed-MPs). However, the impact of procoagulant cell-derived microparticles on the thrombin generation process remains unclear. We analysed the alterations of each phase of thrombin generation (TG) in relation to the concentration of erythrocyte- or platelet-derived microparticles (Ed-MPs and Pd-MPs) in a cohort of patients with steady-state SCD. We studied 92 steady-state SCD patients, 19 of which were under treatment with hydroxyurea, and 30 healthy age- and sex-matched individuals. TG was assessed by calibrated automated thrombogram. Ed-MP and Pd-MP expressing or not phosphatidylserine (PS) were determined by means of flow cytometry. Procoagulant phospholipid-dependent activity in the plasma was evaluated by the Procoag-PPL assay. Levels of thrombomodulin and haemoglobin in the plasma as well as red blood cell and reticulocyte counts were measured. SCD patients, independently of the administration of hydroxyurea, were marked by a significant acceleration in the propagation phase of TG which correlated with the Ed-MP/PS+ concentration. TG was significantly attenuated in hydroxyurea-treated patients. In conclusion, the acceleration of the propagation phase of TG, driven by Ed-MP/PS+, is a major functional alteration in blood coagulation in patients with steady-state SCD. Treatment with hydroxyurea, in addition to the regulation of haemolysis, lowers Ed-MPs and attenuates thrombin generation. The thrombogram could be a useful tool for the diagnosis of hypercoagulability and optimisation of the treatment in patients with SCD.
A nation-wide analysis of venous thromboembolism in 497,180 cancer patients with the development and validation of a risk-stratification scoring system
Authors: Liu Chun-Yu , Yang Muh-Hwa , Chiang Shu-Chiung , Hsu Hui-Chi , Hong Ying-Chung , Hsiao Liang-Tsai , Liu Jin-Hwang , Chiou Tzeon-Jye , Chen Po-Min , Lee Tzong-Shyuan , Chou Li-Fang , Tzeng Cheng-Hwai , Yu Yuan-Bin , Gau Jyh-Pyng , Chen Tzeng-Ji
Published: April 2012

The Asian population is thought to have a low risk of venous thromboembolism (VTE), but the epidemiology of VTE in cancer patients remains unclear. The National Health Insurance Research Database of Taiwan was used to find hospitalised patients newly-diagnosed with cancer to determine the incidence of VTE in cancer patients and to identify the risk factors for VTE. Between 1997 and 2005, 497,180 cancer patients were identified. During a median follow-up of 21.3 months (range 0–119.9 months), 5,296 patients developed VTE. The estimated incidence was 185 events per 100,000 person-years. Patients with a prior history of VTE and female patients between the ages of 40 and 80 carried high risk of VTE. The rate of VTE was relatively high in patients with myeloma, prostate cancer, lung cancer, gynaecologic cancers, sarcoma, and metastasis of unknown origin. We developed a risk-stratification scoring system to divide the cancer patients into four discrete risk groups (very low risk, low risk, intermediate, and high risk). The incidence of VTE in each group was 0.5%, 0.9%, 1.5%, and 8.7%, respectively (p < 0.001). This scoring system was validated in a separate patient cohort. In conclusion, VTE is a distinct burden for cancer patients in Taiwan. The risk scoring system could prove helpful in decision-making concerning thromboprophylaxis in cancer patients.

Note: The results of this paper were presented as an Asian-Pacific Scholarship Award at the 23rd Congress of the International Society on Thrombosis and Haemostasis, Kyoto, Japan, 23–28 July 2011.
Increased platelet aggregation and serum thromboxane levels in aspirin-treated patients with prior myocardial infarction
Authors: Larsen Sanne , Grove Erik , Kristensen Steen , Neergaard-Petersen Søs , Hvas Anne-Mette
Published: April 2012

The antiplatelet effect of aspirin displays considerable inter-individual variability. We investigated the antiplatelet effect of aspirin in patients with coronary artery disease on aspirin mono-therapy with and without prior myocardial infarction (MI). Further, we investigated whether the effect of aspirin differed between patients with and without aspirin use at the time of MI onset. We performed a study on 231 patients, including 171 with prior MI. Among patients with only one prior MI (116 patients), 59 patients were on aspirin at the time of MI onset. All patients received 75 mg aspirin as mono-therapy. Platelet aggregation was assessed by multiple electrode aggregometry (Multiplate®) and Verify -Now®, and platelet activation was evaluated by soluble P-selectin. Furthermore, we measured serum thromboxane B2. MI patients had higher median platelet aggregation levels than patients without prior MI when evaluated by Multiplate® (parachidonic acid<0.0001, pcollagen=0.20). This was not supported by VerifyNow®. Furthermore, MI patients had higher median serum thromboxane B2 levels than patients without prior MI (p=0.01). Patients on aspirin before MI onset had significantly higher median aggregation levels compared with MI patients not on aspirin when evaluated by Multiplate® (pcollagen=0.02) and VerifyNow® (p<0.0001). In conclusion, patients with prior MI had higher platelet aggregation levels than patients without prior MI when evaluated by Multiplate®, despite same aspirin dose and optimal compliance. Serum thromboxane B2 levels were higher in MI patients than in patients without prior MI. Finally, patients on aspirin before MI onset had higher aggregation levels compared with patients not on aspirin.
Histopathological comparison of biodegradable polymer and permanent polymer based sirolimus eluting stents in a porcine model of coronary stent implantation
Authors: Koppara Tobias , Joner Michael , Bayer Gerd , Steigerwald Kristin , Diener Tobias , Wittchow Eric
Published: April 2012

Biodegradable stent coatings were recently introduced as a potential solution to overcome sustained inflammatory responses observed with permanent polymer-based drug-eluting stents. In a preliminary study, selected biodegradable or permanent polymer-based sirolimus-eluting stent (SES) formulations were screened for effectiveness in comparison to bare metal stents (BMS) at 28 days. Subsequently, the most favourable SES formulation was compared to commercially available SES (CypherTM) at 28,90 and 180 days to investigate the histopathologic response as well as tissue, blood and organ pharmacokinetics. Overlapping SES implantation was conducted to evaluate vascular healing at 28 days in this particular setting. SES with biodegradable poly (L-lactide) polymer (PLLA) or poly(lactide-co-glycolide) showed the most favourable outcome with regards to reductions in neointimal area in comparison to BMS at 28 days. The PLLA SES showed a similar reduction in neointimal area compared to CypherTM at 28 days, with significant greater reductions at 90 and 180 days (1.7 ± 0.7 mm2 vs. 3.1 ± 1.5 mm2, p=0.03 and 1.8 ± 1.2 mm2 vs. 3.0 ± 1.5 mm2, p=0.01, respectively). Sirolimus vascular tissue concentrations were detectable up to 90 days following implantation. Overlapping stented segments showed favourable histopathologic results with respect to fibrin deposition and endothelialisation at 28 days. In conclusion, the use of PLLA as drugeluting matrix resulted in mild inflammatory responses in the presence of effective sirolimus tissue concentrations. The greater efficacy observed at long-term follow-up in PLLA SES compared to CypherTM may be a multifactorial result of stent design, polymer biocompatibility and improved release kinetics.
Peroxisome proliferator-activated receptor-alpha agonists repress expression of thrombin-activatable fibrinolysis inhibitor by decreasing transcript stability
Authors: Masuda Yutaka , Saotome Dan , Takada Kimihiko , Sugimoto Katsuyoshi , Sasaki Tomoyuki , Ishii Hidemi
Published: April 2012

Thrombin-activatable fibrinolysis inhibitor (TAFI) (carboxypeptidase B2) is a plasma zymogen that is biosynthesised in the liver and released into the circulation. Activated TAFI is a prothrombotic factor which inhibits fibrin clot lysis. Cultured human hepatoma HepG2 cells were treated with peroxisome proliferator-activated receptor (PPAR)α, β or γ agonists, and the levels of TAFI antigen and mRNA (here, termed CPB2 mRNA) were measured. HepG2 cells treated with the PPARα agonist WY14643, but not agonists for PPARβ or PPARγ, decreased their release of TAFI antigen into the conditioned medium. In parallel, there were decreased levels of CPB2 mRNA and TAFI antigen in the cells. The WY14643-mediated decrease in CPB2 mRNA levels was accelerated by overexpression of PPARα and abolished by RNA interference of PPARA mRNA. CPB2 gene promoter activity was not influenced by treatment of the cells with WY14643. The half-life of the CPB2 transcript was shortened by treatment with WY14643 as compared with that of the control, and the decreased half-life of mRNA returned to control levels by treatment with a PPARα antagonist MK886 or transfection of PPARΑ-specific siRNA to WY14643-treated HepG2 cells. The present results suggest that PPARα agonists not only play a hypolipidaemic role, but also decrease the expression of TAFI, a prothrombotic factor, by decreasing stability of CPB2 transcripts.
Early Repolarization Is an Independent Predictor of Occurrences of Ventricular Fibrillation in the Very Early Phase of Acute Myocardial Infarction
Authors: Naruse Yoshihisa , Tada Hiroshi , Harimura Yoshie , Hayashi Mayu , Noguchi Yuichi , Sato Akira , Yoshida Kentaro , Sekiguchi Yukio , Aonuma Kazutaka
Published: April 2012

Background—

Recent evidence has linked early repolarization (ER) to idiopathic ventricular fibrillation (VF) in patients without structural heart disease. However, no studies have clarified whether or not there is an association between ER and the VF occurrences after the onset of an acute myocardial infarction (AMI).

Methods and Results—

This study retrospectively included 220 consecutive patients with an AMI (57 female; mean age, 69 ± 11 years) in whom the 12-lead ECGs before the AMI onset could be evaluated. The patients were classified on the basis of a VF occurrence within 48 hours after the AMI onset. Early repolarization was defined as an elevation of the QRS-ST junction of >0.1 mV from baseline in at least 2 inferior or lateral leads, manifested as QRS slurring or notching. Twenty-one (10%) patients had a VF occurrence within 48 hours of the AMI onset. A multivariate analysis revealed that ER (odds ratio [OR], 7.31; 95% confidence interval [CI], 2.21–24.14;
P
<0.01), a time from the onset to admission of <180 minutes (OR, 3.77; 95% CI, 1.13–12.59;
P
<0.05), and a Killip class greater than I (OR, 13.60; 95% CI, 3.43–53.99;
P
<0.001) were independent predictors of VF occurrences. As features of the ER pattern, a J-point elevation in the inferior leads, greater magnitude of the J-point elevation, notched morphology of the ER, and ER with a horizontal/descending ST segment, all were significantly associated with a VF occurrence.

Conclusions—

The presence of ER increased the risk of VF occurrences within 48 hours after the AMI onset.
Predictors of Increased Intravenous Tissue Plasminogen Activator Use Among Hospitals Participating in the Massachusetts Primary Stroke Service Program
Authors: Rost Natalia S. , Smith Eric E. , Pervez Muhammad A. , Mello Philip , Dreyer Paul , Schwamm Lee H.
Published: April 2012

Background—

We sought to determine if intravenous tissue plasminogen activator (IV tPA) use for acute ischemic stroke increased in Massachusetts in association with the Primary Stroke Service program, a statewide stroke center designation and quality improvement initiative.

Methods and Results—

We analyzed prospectively acquired data from the Massachusetts Department of Public Health between October 2004 and June 2008, including 10 045 consecutive emergency department–based acute ischemic stroke encounters arriving ≤3 hours after stroke onset at 69 participating Massachusetts PSS hospitals. The overall rate of IV tPA use was 854 of 3866 (22.1%) of patients arriving ≤2 hours of symptom onset. IV tPA use increased steadily from 2005 (the first full year of the program) to 2008 (18.4%, 21.9%, 22.6%, 25.5%;
P
=0.001). Patients treated with IV tPA were more likely to be younger (72.3±14.1 versus 74.7±14.0 years,
P
<0.005) and to have presented after emergency medical services rerouting in July 2005 (96% versus 94%,
P
=0.009). Patients who arrived at hospitals with a performance achievement award from the Get With The Guidelines-Stroke program were more likely to receive IV tPA after versus before award recognition (28.1% versus 22.3%,
P
<0.001).

Conclusions—

In this nearly complete capture of statewide data, rates of IV tPA improved significantly in Massachusetts from 2005 to 2008 in association with a state Primary Stroke Service designation program. Further studies are needed to confirm that treatment disparities exist for older acute ischemic stroke patients and that the rates of thrombolysis have increased above and beyond secular trends.
Added Predictive Ability of the CHA
2
DS
2
VASc Risk Score for Stroke and Death in Patients With Atrial Fibrillation
Authors: Larsen Torben Bjerregaard , Lip Gregory Y.H. , Skjøth Flemming , Due Karen Margrete , Overvad Kim , Hvilsted Rasmussen Lars
Published: April 2012

Background—

The objective of this study was to evaluate the added predictive ability of the CHA
2
DS
2
VASc prediction rule for stroke and death in a nonanticoagulated population of patients with atrial fibrillation.

Methods and Results—

We included 1603 nonanticoagulated patients with incident atrial fibrillation from a Danish prospective cohort study of 57 053 middle-aged men and women. The Net Reclassification Improvement was calculated as a measure to estimate any overall improvement in reclassification with the CHA
2
DS
2
VASc sore as an alternative to the CHADS
2
score. After 1-year follow-up, crude incidence rates were 3.4 per 100 person-years for stroke and 13.6 for death. After a mean follow-up of 5.4 years (±3.7 years), the crude incidence rates for stroke and death were 1.9 and 5.6, respectively. During the entire observation period, the c-statistics and negative predictive values were similar for both risk scores. The Net Reclassification Improvement analysis showed that 1 of 10 reclassified atrial fibrillation patients would have been upgraded correctly using the CHA
2
DS
2
VASc score.

Conclusions—

Both the CHADS
2
as well as the CHA
2
DS
2
VASc risk score can exclude a large proportion of patients from having high risk of stroke or death. However, using the CHA
2
DS
2
VASc risk score, fewer patients will fulfill the criterion for low risk (and are truly low risk for thromboembolism). For every 10 extra patients transferred to the treatment group at 5 years, using the CHA
2
DS
2
VASc risk score, 1 patient would have had a stroke that might have been avoided with effective treatment.
Effects of Aging on Angiogenesis
Authors: Lähteenvuo Johanna , Rosenzweig Anthony
Published: April 2012

Aging is a dominant risk factor for most forms of cardiovascular disease. Impaired angiogenesis and endothelial dysfunction likely contribute to the increased prevalence of both cardiovascular diseases and their adverse sequelae in the elderly. Angiogenesis is both an essential adaptive response to physiological stress and an endogenous repair mechanism after ischemic injury. In addition, induction of angiogenesis is a promising therapeutic approach for ischemic diseases. For these reasons, understanding the basis of age-related impairment of angiogenesis and endothelial function has important implications for understanding and managing cardiovascular disease. In this review, we discuss the molecular mechanisms that contribute to impaired angiogenesis in the elderly and potential therapeutic approaches to improving vascular function and angiogenesis in aging patients.
FOXOs and Sirtuins in Vascular Growth, Maintenance, and Aging
Authors: Oellerich Mark F. , Potente Michael
Published: April 2012

Blood vessels form the first organ in the developing embryo and build extensive networks that supply all cells with nutrients and oxygen throughout life. As blood vessels get older, they often become abnormal in structure and function, thereby contributing to numerous age-associated diseases including ischemic heart and brain disease, neurodegeneration, or cancer. First described as regulators of the aging process in invertebrate model organisms, Forkhead box “O” (FOXO) transcription factors and sirtuin deacetylases are now emerging as key regulators of mammalian vascular development and disease. The integration of individual FOXO and sirtuin family members into various aspects of vessel growth, maintenance, and function provides new perspectives on disease mechanisms of aging, the most important risk factor for medical maladies of the vascular system.
Telomeres and Mitochondria in the Aging Heart
Authors: Moslehi Javid , DePinho Ronald A. , Sahin Ergün
Published: April 2012

Studies in humans and in mice have highlighted the importance of short telomeres and impaired mitochondrial function in driving age-related functional decline in the heart. Although telomere and mitochondrial dysfunction have been viewed mainly in isolation, recent studies in telomerase-deficient mice have provided evidence for an intimate link between these two processes. Telomere dysfunction induces a profound p53-dependent repression of the master regulators of mitochondrial biogenesis and function, peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and PGC-1β in the heart, which leads to bioenergetic compromise due to impaired oxidative phosphorylation and ATP generation. This telomere-p53-PGC mitochondrial/metabolic axis integrates many factors linked to heart aging including increased DNA damage, p53 activation, mitochondrial, and metabolic dysfunction and provides a molecular basis of how dysfunctional telomeres can compromise cardiomyocytes and stem cell compartments in the heart to precipitate cardiac aging.
Risk of Intracerebral Hemorrhage in Patients With Cerebral Microbleeds Undergoing Endovascular Intervention
Authors: Soo Yannie O.Y. , Siu Deyond Y.W. , Abrigo Jill , Yu Simon , Ng Nick , Ahuja Anil T. , Wong Lawrence K.S. , Leung Thomas W.
Published: April 2012

Background and Purpose—

Cerebral microbleeds (CMBs) on MRI gradient echo images are hemosiderin deposits, which may predict intracerebral hemorrhage (ICH). The risk of ICH in patients with CMBs could be exacerbated by the use of antithrombotics. The purpose of our study is to prospectively evaluate the risk of ICH in patients with ischemic stroke who receive dual antiplatelet therapy for endovascular intervention.

Methods—

We analyzed MRI of 133 patients admitted consecutively for intra- and extracranial stenting for symptomatic large artery atherosclerosis who received aspirin and clopidogrel. Quantity and location of CMBs were recorded by neuroradiologists independent from the angioplasty team. The primary end point was symptomatic ICH as evident in CT of the brain within 12 weeks of procedure.

Results—

CMBs were identified in 23 patients. Mean number of CMBs was 2.3±1.6. Four patients had >5 CMBs. Forty-seven patients had intracranial stents, 84 patients had extracranial stents, and 2 patients had both intracranial and extracranial stents. There was no difference in risk of symptomatic ICH between those with (4.3%) and without CMBs (5.5%) patient with CMBs (
P
=1.000).

Conclusions—

The presence of a small number of CMBs does not cause a large increase in the short-term risk of symptomatic ICH in patients with ischemic stroke who undergo endovascular intervention with dual antiplatelet therapy. The risk of ICH in patients with ≥5 CMBs, however, remains unclear. Further studies with a larger sample size of patients with multiple CMBs are needed.
Timing of Intra-Arterial Neural Stem Cell Transplantation After Hypoxia–Ischemia Influences Cell Engraftment, Survival, and Differentiation
Authors: Rosenblum Sahar , Wang Nancy , Smith Tenille N. , Pendharkar Arjun V. , Chua Joshua Y. , Birk Harjus , Guzman Raphael
Published: April 2012

Background and Purpose—

Intra-arterial neural stem cell (NSC) transplantation shows promise as a minimally invasive therapeutic option for stroke. We assessed the effect of timing of transplantation on cell engraftment, survival, and differentiation.

Methods—

Mouse NSCs transduced with a green fluorescent protein and renilla luciferase reporter gene were transplanted into animals 6 and 24 hours and 3, 7, and 14 days after hypoxia–ischemia (HI). Bioluminescent imaging was used to assess cell survival at 6 hours and 4 and 7 days after transplantation. Immunohistochemistry was used to assess NSC survival and phenotypic differentiation 1 month after transplantation. NSC receptor expression and brain gene expression were evaluated using real-time reverse transcription–quantitative polymerase chain reaction to elucidate mechanisms of cell migration. Boyden chamber assays were used to assess cell migratory potential in vitro.

Results—

NSC transplantation 3 days after HI resulted in significantly higher cell engraftment and survival at 7 and 30 days compared with all other groups (
P
<0.05). Early transplantation at 6 and 24 hours after HI resulted in significantly higher expression of glial fibrillary acidic protein (
P
=0.0140), whereas late transplantation at 7 and 14 days after HI resulted in higher expression of β-tubulin (
P
<0.0001). Corroborating the high cell engraftment 3 days after HI was robust expression of vascular cell adhesion molecule-1, CCL2, and CXCL12 in brain homogenates 3 days after HI.

Conclusion—

Intra-arterial transplantation 3 days after HI results in the highest cell engraftment. Early transplantation of NSCs leads to greater differentiation into astrocytes, whereas transplantation at later time points leads to greater differentiation into neurons.