bluuebunny/crossref_metadata_2025 huggingface dataset:
Periictal heart rate variability analysis suggests long‐term postictal autonomic disturbance in epilepsy
Authors: Toth V. , Hejjel L. , Fogarasi A. , Gyimesi C. , Orsi G. , Szucs A. , Kovacs N. , Komoly S. , Ebner A. , Janszky J.
Published: January 2010

Background:  One of the possible pathomechanisms of sudden death in epilepsy (SUDEP) is a postictal dysregulation of autonomic nervous system. We performed a heart rate variability (HRV) analysis of the periictal state to analyze whether a cardiac autonomic disturbance exists after an epileptic seizure.

Methods:  We included 31 periictal video–EEG–ECG recordings of 31 patients with epilepsy who had consecutively undergone pre‐surgical evaluation. Nine generalized tonic‐clonic (GTCS), 15 complex partial, and seven simple motor seizures were included. HRV was evaluated by analyzing 5‐min‐long ECG epochs, sampling from baseline, direct preictal, early‐postictal (<15 min after the seizure), and late‐postictal (5–6 h after the seizure) periods.

Results:  The heart rate was elevated immediately after the seizures, but 5–6 h postictally returned to the baseline level. Time‐domain components of HRV decreased after the seizure and this decrease lasted for 5–6 h. Low‐frequency power decreased in the early‐postictal phase and high‐frequency power of HRV dropped in the late‐postictal phase. GTCS had an impact on short‐term but not on long‐term postictal HRV decrease.

Conclusions:  We found decreased HRV immediately after the seizures, which lasted at least 5–6 h postictally, indicating a long‐term postictal disturbance of the autonomous nervous system. GTCS were accompanied by a more decreased HRV than other seizures. Our results may have relevance in explaining pathomechanism of SUDEP.
Sp proteins play a critical role in histone deacetylase inhibitor‐mediated derepression of CYP46A1 gene transcription
Authors: Nunes Maria João , Milagre Inês , Schnekenburger Michael , Gama Maria João , Diederich Marc , Rodrigues Elsa
Published: January 2010

J. Neurochem. (2010) 113, 418–431.

We investigated whether the CYP46A1 gene, a neuronal‐specific cytochrome P450, responsible for the majority of brain cholesterol turnover, is subject to transcriptional modulation through modifications in histone acetylation. We demonstrated that inhibition of histone deacetylase activity by trichostatin A (TSA), valproic acid and sodium butyrate caused a potent induction of both CYP46A1 promoter activity and endogenous expression. Silencing of Sp transcription factors through specific small interfering RNAs, or impairing Sp binding to the proximal promoter, by site‐directed mutagenesis, led to a significant decrease in TSA‐mediated induction of CYP46A1 expression/promoter activity. Electrophoretic mobility shift assay, DNA affinity precipitation assays and chromatin immunoprecipitation assays were used to determine the multiprotein complex recruited to the CYP46A1 promoter, upon TSA treatment. Our data showed that a decrease in Sp3 binding at particular responsive elements, can shift the Sp1/Sp3/Sp4 ratio, and favor the detachment of histone deacetylase (HDAC) 1 and HDAC2 and the recruitment of p300/CBP. Moreover, we observed a dynamic change in the chromatin structure upon TSA treatment, characterized by an increase in the local recruitment of euchromatic markers and RNA polymerase II. Our results show the critical participation of an epigenetic program in the control of CYP46A1 gene transcription, and suggest that brain cholesterol catabolism may be affected upon treatment with HDAC inhibitors.
Altered brain phospholipid and acylcarnitine profiles in propionic acid infused rodents: further development of a potential model of autism spectrum disorders
Authors: Thomas Raymond H. , Foley Kelly A. , Mepham Jennifer R. , Tichenoff Lisa J. , Possmayer Fred , MacFabe Derrick F.
Published: January 2010

J. Neurochem. (2010) 113, 515–529.

Recent studies have demonstrated intraventricular infusions of propionic acid (PPA) a dietary and enteric short‐chain fatty acid can produce brain and behavioral changes similar to those observed in autism spectrum disorder (ASD). The effects of PPA were further evaluated to determine if there are any alterations in brain lipids associated with the ASD‐like behavioral changes observed following intermittent intraventricular infusions of PPA, the related enteric metabolite butyric acid (BUT) or phosphate‐buffered saline vehicle. Both PPA and BUT produced significant increases (p < 0.001) in locomotor activity (total distance travelled and stereotypy). PPA and to a lesser extent BUT infusions decreased the levels of total monounsaturates, total ω6 fatty acids, total phosphatidylethanolamine plasmalogens, the ratio of ω6 : ω3 and elevated the levels of total saturates in separated phospholipid species. In addition, total acylcarnitines, total long‐chain (C12–C24) acylcarnitines, total short‐chain (C2 to C9) acylcarnitines, and the ratio of bound to free carnitine were increased following infusions with PPA and BUT. These results provide evidence of a relationship between changes in brain lipid profiles and the occurrence of ASD‐like behaviors using the autism rodent model. We propose that altered brain fatty acid metabolism may contribute to ASD.
The amyloid precursor protein intracellular domain (AICD) disrupts actin dynamics and mitochondrial bioenergetics
Authors: Ward Manus W. , Concannon Caoimhín G. , Whyte Jacqueline , Walsh Ciara M. , Corley Brian , Prehn Jochen H. M.
Published: January 2010

J. Neurochem. (2010) 10.1111/j.1471‐4159.2010.06615.x

The amyloid precursor protein (APP) is critically involved in the pathogenesis of Alzheimer’s disease, and is strongly up‐regulated in response to traumatic, metabolic, or toxic insults to the nervous system. The processing of APP by γ/ε‐secretase activity results in the generation of the APP intracellular domain (AICD). Previously, we have shown that AICD induces the expression of genes (transgelin, α2‐actin) with functional roles in actin organization and dynamics and demonstrated that the induction of AICD and its co‐activator Fe65 (AICD/Fe65) resulted in a loss of organized filamentous actin structures within the cell. As mitochondrial function is thought to be reliant on ordered actin dynamics, we examined mitochondrial function in human SHEP neuroblastoma cells inducibly expressing AICD/Fe65. Confocal analysis of the mitochondrial membrane potential (Δψm) identified a significant decrease in the Δψm in the AICD50/Fe65 over‐expressing cells. This was paralleled by significantly reduced ATP levels and decreased basal superoxide production. Over‐expression of the proposed AICD target gene transgelin in SHEP‐SF parental cells and primary neurons was sufficient to destabilize actin filaments, depolarize Δψm, and significantly alter mitochondrial disrtibution and morphology. Our data demonstrate that the induction of AICD/Fe65 or transgelin significantly alters actin dynamics and mitochondrial function in neuronal cells.
High rates of infidelity in the Grey Fantail Rhipidura albiscapa suggest that testis size may be a better correlate of extra‐pair paternity than sexual dimorphism
Authors: HOFFMAN JOSEPH I. , MUNRO KAT , KILNER REBECCA M. , AMOS WILLIAM
Published: January 2010

The Grey Fantail Rhipidura albiscapa is a socially monogamous passerine endemic to Australia. Behavioural and morphological clues point to opposing conclusions as to its breeding system; sexual monomorphism and monochrome colorations suggest monogamy, whereas relatively large testes and a prominent cloacal protruberance are more indicative of multiple mating and sperm competition. We used five highly variable microsatellite loci to investigate the genetic breeding system of this species. Paternity was assigned to 49 of 69 (71%) offspring tested and the overall rate of partner infidelity was high, with 55% of offspring being sired by an extra‐pair male and 64% of all clutches containing extra‐pair young. This puts the Grey Fantail amongst the most promiscuous socially monogamous species yet studied. Where extra‐pair fathers were identified, these were invariably in neighbouring territories, and although larger males did not gain more paternities overall, extra‐pair offspring tended to be fathered by larger males than expected by chance. We interpret our findings in light of some of the potential costs and benefits associated with extra‐pair paternity.
Protein modification and replicative senescence of WI‐38 human embryonic fibroblasts
Authors: Ahmed Emad K. , Rogowska‐Wrzesinska Adelina , Roepstorff Peter , Bulteau Anne‐Laure , Friguet Bertrand
Published: January 2010

Oxidized proteins as well as proteins modified by the lipid peroxidation product 4‐hydroxy‐2‐nonenal (HNE) and by glycation (AGE) have been shown to accumulate with aging in vivo and during replicative senescence in vitro. To better understand the mechanisms by which these damaged proteins build up and potentially affect cellular function during replicative senescence of WI‐38 fibroblasts, proteins targeted by these modifications have been identified using a bidimensional gel electrophoresis‐based proteomic approach coupled with immunodetection of HNE‐, AGE‐modified and carbonylated proteins. Thirty‐seven proteins targeted for either one of these modifications were identified by mass spectrometry and are involved in different cellular functions such as protein quality control, energy metabolism and cytoskeleton. Almost half of the identified proteins were found to be mitochondrial, which reflects a preferential accumulation of damaged proteins within the mitochondria during cellular senescence. Accumulation of AGE‐modified proteins could be explained by the senescence‐associated decreased activity of glyoxalase‐I, the major enzyme involved in the detoxification of the glycating agents methylglyoxal and glyoxal, in both cytosol and mitochondria. This finding suggests a role of detoxification systems in the age‐related build‐up of damaged proteins. Moreover, the oxidized protein repair system methionine sulfoxide reductase was more affected in the mitochondria than in the cytosol during cellular senescence. Finally, in contrast to the proteasome, the activity of which is decreased in senescent fibroblasts, the mitochondrial matrix ATP‐stimulated Lon‐like proteolytic activity is increased in senescent cells but does not seem to be sufficient to cope with the increased load of modified mitochondrial proteins.
JWH018, a common constituent of ‘Spice’ herbal blends, is a potent and efficacious cannabinoid CB1receptor agonist
Authors: Atwood Brady K , Huffman John , Straiker Alex , Mackie Ken
Published: January 2010

Background and purpose: ‘Spice’ is an herbal blend primarily marketed in Europe as a mild hallucinogen with prominent cannabis‐like effects and as a legal alternative to cannabis. However, a recent report identified a number of synthetic additives in samples of ‘Spice’. One of these, the indole derivative JWH018, is a ligand for the cannabinoid receptor 1 (CB1) cannabinoid receptor and inhibits cAMP production in CB1receptor‐expressing CHO cells. Other effects of JWH018 on CB1receptor‐mediated signalling are not known, particularly in neurons. Here we have evaluated the signalling pathways activated by JWH018 at CB1receptors.

Experimental approach: We investigated the effects of JWH018 on neurotransmission in cultured autaptic hippocampal neurons. We further analysed its activation of ERK1/2 mitogen activated protein kinase (MAPK) and internalization of CB1receptors in HEK293 cells stably expressing this receptor.

Key results: In cultured autaptic hippocampal neurons, JWH018 potently inhibited excitatory postsynaptic currents (IC50= 14.9 nM) in a concentration‐ and CB1receptor‐dependent manner. Furthermore, it increased ERK1/2 MAPK phosphorylation (EC50= 4.4 nM). We also found that JWH018 potently induced rapid and robust CB1receptor internalization (EC50= 2.8 nM;t1/2= 17.3 min).

Conclusions and implications: JWH018, a prominent component of several herbal preparations marketed for their psychoactivity, is a potent and effective CB1receptor agonist that activates multiple CB1receptor signalling pathways. Thus, it is likely that the subjective effects of ‘Spice’ are due to activation of cannabinoid CB1receptors by JWH018, added to this herbal preparation.
Use of Habitats as Surrogates of Biodiversity for Efficient Coral Reef Conservation Planning in Pacific Ocean Islands
Authors: DALLEAU MAYEUL , ANDRÉFOUËT SERGE , WABNITZ COLETTE C.C. , PAYRI CLAUDE , WANTIEZ LAURENT , PICHON MICHEL , FRIEDMAN KIM , VIGLIOLA LAURENT , BENZONI FRANCESCA
Published: January 2010

Abstract:  Marine protected areas (MPAs) have been highlighted as a means toward effective conservation of coral reefs. New strategies are required to more effectively select MPA locations and increase the pace of their implementation. Many criteria exist to design MPA networks, but generally, it is recommended that networks conserve a diversity of species selected for, among other attributes, their representativeness, rarity, or endemicity. Because knowledge of species’ spatial distribution remains scarce, efficient surrogates are urgently needed. We used five different levels of habitat maps and six spatial scales of analysis to identify under which circumstances habitat data used to design MPA networks for Wallis Island provided better representation of species than random choice alone. Protected‐area site selections were derived from a rarity–complementarity algorithm. Habitat surrogacy was tested for commercial fish species, all fish species, commercially harvested invertebrates, corals, and algae species. Efficiency of habitat surrogacy varied by species group, type of habitat map, and spatial scale of analysis. Maps with the highest habitat thematic complexity provided better surrogates than simpler maps and were more robust to changes in spatial scales. Surrogates were most efficient for commercial fishes, corals, and algae but not for commercial invertebrates. Conversely, other measurements of species‐habitat associations, such as richness congruence and composition similarities provided weak results. We provide, in part, a habitat‐mapping methodology for designation of MPAs for Pacific Ocean islands that are characterized by habitat zonations similar to Wallis. Given the increasing availability and affordability of space‐borne imagery to map habitats, our approach could appreciably facilitate and improve current approaches to coral reef conservation and enhance MPA implementation.
Importance of Accounting for Detection Heterogeneity When Estimating Abundance: the Case of French Wolves
Authors: CUBAYNES SARAH , PRADEL ROGER , CHOQUET RÉMI , DUCHAMP CHRISTOPHE , GAILLARD JEAN‐MICHEL , LEBRETON JEAN‐DOMINIQUE , MARBOUTIN ERIC , MIQUEL CHRISTIAN , REBOULET ANNE‐MARIE , POILLOT CAROLE , TABERLET PIERRE , GIMENEZ OLIVIER
Published: January 2010

Abstract:  Assessing conservation strategies requires reliable estimates of abundance. Because detecting all individuals is most often impossible in free‐ranging populations, estimation procedures have to account for a <1 detection probability. Capture–recapture methods allow biologists to cope with this issue of detectability. Nevertheless, capture–recapture models for open populations are built on the assumption that all individuals share the same detection probability, although detection heterogeneity among individuals has led to underestimating abundance of closed populations. We developed multievent capture–recapture models for an open population and proposed an associated estimator of population size that both account for individual detection heterogeneity (IDH). We considered a two‐class mixture model with weakly and highly detectable individuals to account for IDH. In a noninvasive capture–recapture study of wolves we based on genotypes identified in feces and hairs, we found a large underestimation of population size (27% on average) occurred when IDH was ignored.
Reducing the Incidence of Denture Stomatitis: Are Denture Cleansers Sufficient?
Authors: Jose Anto , Coco Brent J. , Milligan Steven , Young Beth , Lappin David F. , Bagg Jeremy , Murray Colin , Ramage Gordon
Published: January 2010

Purpose: Candida albicans is the predominant oral yeast associated with denture stomatitis. With an increasing population of denture wearers, the incidence of denture stomatitis is increasing. Effective management of these patients will alleviate the morbidity associated with this disease. The aim of this study was to examine the capacity of four denture cleansers to efficiently decontaminate and sterilize surfaces covered by C. albicans biofilms.

Materials and Methods: Sixteen C. albicans strains isolated from denture stomatitis patients and strain ATCC 90028 were grown as mature confluent biofilms on a 96‐well format and immersed in Dentural, Medical™ Interporous®, Steradent Active Plus, and Boots Smile denture cleansers according to the manufacturers’ instructions or overnight. The metabolic activity and biomass of the biofilms were then quantified, and scanning electron microscopy (SEM) used to examine treated biofilms.

Results: Dentural was the most effective denture cleanser, reducing the biomass by greater than 90% after 20 minutes. Steradent Active plus was significantly more effective following 10‐minute immersion than overnight (p < 0.001). All cleansers reduced the metabolic activity by greater than 80% following overnight immersion; however, Boots Smile exhibited significantly reduced metabolic activity following only a 15‐minute immersion (p < 0.001). SEM revealed residual C. albicans material following Dentural treatment.

Conclusions: This study showed that denture cleansers exhibit effective anti‐C. albicans biofilm activity, both in terms of removal and disinfection; however, residual biofilm retention that could lead to regrowth and denture colonization was observed. Therefore, alternative mechanical disruptive methods are required to enhance biofilm removal.
Gender Differences in the Amount of Gingival Display During Smiling Using Two Intraoral Dental Biometric Measurements
Authors: Al‐Jabrah Osama , Al‐Shammout Raghda , El‐Naji Waddah , Al‐Ajarmeh Mahasen , Al‐Quran Abdel‐Hakeem
Published: January 2010

Purpose: The aims of this study were to compare gender differences in the width and length of the maxillary right central incisor and the horizontal and vertical overlap of the anterior teeth and to determine the relationships of these two intraoral dental biometric measurements with the amount of gingival display during smiling.

Materials and Methods: A total of 61 men and 66 women were included in this study. For each participant, the gingival tissue display during smiling was judged to be either visible or not, and the maximum mesiodistal and incisogingival dimensions of the maxillary right central incisor were measured, along with the amount of horizontal and vertical overlap of anterior teeth using a digital caliper. Gender differences in these parameters and the relationship between subjects showing gingival display when smiling and the two intraoral dental biometric measurements were determined. Statistical analyses of data were performed using SPSS (V11) software. The mean scores for gender were calculated, and a Student's t‐test was used to identify significant differences between both groups. Significance level was set to 0.05.

Results: The age of the participants ranged between 23 and 52, with a mean of 33.47 ± 9.07 years. A relatively small percentage of the subjects (22.05%) displayed gingiva when smiling. More women displayed gingiva when smiling than men, with a 2:1 female:male ratio. Men exhibited significantly (p < 0.05) wider (8.76 ± 0.66 mm) and longer (10.28 ± 0.88 mm) central incisors compared to women (7.92 ± 0.72 mm; 9.27 ± 0.93 mm width and length, respectively). No gender differences were found in the width‐to‐length ratio. Subjects with gingival display had significantly more horizontal (4.28 ± 1.21 mm; p < 0.001), and vertical (3.52 ± 0.66 mm; p < 0.05) overlap of anterior teeth compared to those who did not display gingiva when smiling (2.40 ± 1.03 and 2.30 ± 0.93 mm, respectively).

Conclusions: Significantly more women displayed gingiva in smiling. Men had significantly wider and longer central incisors. No differences were recorded between men and women relative to both the horizontal and vertical anterior tooth overlap. Subjects who displayed gingiva when smiling had more horizontal and vertical overlap of anterior teeth.
Sectional Impressions and Simplified Folding Complete Denture for Severe Microstomia
Authors: Givan Daniel A. , AuClair Wendy A. , Seidenfaden, CDT Julius C. , Paiva Jose
Published: January 2010

A patient presenting with severe microstomia (PDI Class IV) was unable to insert a maxillary complete denture. Sectional final impressions were made using two impression materials and an interlocking custom tray. A folding record base was used for maxillomandibular relationship records. A novel folding maxillary denture with a custom hinge and plunger attachment to lock the denture in the open position was fabricated. The patient was able to insert the collapsed denture, open it intraorally, and enjoy successful masticatory function.
Should plasma from female donors be avoided? A population‐based cohort study of plasma recipients in Sweden from 1990 through 2002
Authors: Tynell Elsa , Andersson Therese M.L. , Norda Rut , Edgren Gustaf , Nyren Olof , Shanwell Agneta , Reilly Marie
Published: January 2010

BACKGROUND: Plasma from female donors has been implicated in the sometimes fatal complication known as transfusion‐related acute lung injury. In studies of patients in intensive care units, worsened gas exchange of the lungs has also been attributed to female plasma. Despite a lack of population‐based evidence, policies have already been introduced to exclude female donor plasma.

STUDY DESIGN AND METHODS: Short‐term mortality after plasma transfusion was investigated using data from the Scandinavian Donations and Transfusions (SCANDAT) database. A cohort of 92,565 patients in 30 Swedish hospitals were followed for 14 days after their first plasma transfusion. The relative risk (RR) of death in recipients of female plasma compared to recipients of only male plasma was estimated from Poisson regression.

RESULTS: Recipients had median age 70 years, received a mean of 4.4 plasma units, and had an overall 14‐day mortality of 8.43%. Sixty‐eight percent were exposed to female plasma, with a 14‐day mortality of 8.85% compared to 7.53% in the nonexposed group. After adjustment for potential confounding factors, the RRs were 1.16 (confidence interval [CI], 1.06‐1.27) and 1.32 (CI, 1.17‐1.49) for those receiving 3 to 4 and 5 or more units of female plasma, respectively. Risk estimates were increased in an analysis of deaths with a concomitant discharge diagnosis involving the respiratory or circulatory system or an adverse reaction.

CONCLUSIONS: This large population‐based cohort study of unselected patients suggests that transfusion of plasma from female donors confers a short‐term survival disadvantage on recipients.
Analysis of sample‐to‐cutoff ratios on chemiluminescent immunoassays used for blood donor screening highlights the need for serologic confirmatory testing
Authors: Kiely Philip , Walker Kyall , Parker Susan , Cheng Anthea
Published: January 2010

BACKGROUND: High sample‐to‐cutoff (s/co) ratios on hepatitis C virus antibody (anti‐HCV) screening immunoassays (IAs) are indicative of confirmed‐positive results and, according to some reports, can be used to determine anti‐HCV status without the need for confirmatory testing. The purpose of this study was to determine whether s/co ratios on hepatitis B surface antigen (HBsAg), antibody to human immunodeficiency virus Types 1 and 2 (anti‐HIV‐1/2), anti‐HCV, and antibody to human T‐lymphotropic virus Types I and II (anti‐HTLV‐I/II) chemiluminescent immunoassays (ChLIAs) can be used to discriminate between biologic false‐reactive (BFR) and confirmed‐positive results.

STUDY DESIGN AND METHODS: In a blood donor population the s/co ratio distributions for BFR and confirmed‐positive results were compared for the Abbott PRISM HBsAg, HIV O Plus, HCV, and HTLV‐I/II ChLIAs to determine the extent of overlap between the two distributions for each assay.

RESULTS: The s/co ratio distributions for BFR and confirmed results overlapped in the range of 10.00 to 60.00, 1.00 to 6.00, 3.00 to 15.00, and 1.00 to 100.00 for the PRISM HIV O Plus, HCV, HTLV‐I/II, and HBsAg assays, respectively.

CONCLUSION: Although high s/co ratios were predictive of confirmed‐positive results in all four assays, a number of confirmed‐positive samples gave low values while some biologic false‐positive samples showed high values. As the s/co ratio distributions for BFR and confirmed‐positive results overlapped for all four PRISM assays, this study highlights the importance of serologic confirmatory testing and the need for caution when using screening IA results to assign a final donor status.
Blood transfusions increase cerebral, splanchnic, and renal oxygenation in anemic preterm infants
Authors: Dani Carlo , Pratesi Simone , Fontanelli Giulia , Barp Jacopo , Bertini Giovanna
Published: January 2010

BACKGROUND: Multiprobe near infrared spectroscopy (NIRS) has been used to study regional cerebral (rSO2C), splanchnic (rSO2S), and renal (rSO2R) tissue oxygenation in newborns. We used this method to study the effects of red blood cell (RBC) transfusions in anemic preterm infants to assess if thresholds for transfusions were appropriate for recognizing a clinical condition permitting tissue oxygenation improvement.

STUDY DESIGN AND METHODS: Multiprobe NIRS (INVOS 5100, Somanetics) was applied during transfusion to 15 preterm infants with symptomatic anemia of prematurity (hematocrit level of <25%). rSO2C, rSO2S, and rSO2R were recorded at selected times, and then fractional oxygen cerebral extraction ratio [FOEC: (SaO2‐rSO2C)/SaO2], fractional oxygen splanchnic extraction ratio [FOES: (SaO2‐rSO2S)/SaO2], fractional oxygen renal extraction ratio [FOER: (SaO2‐rSO2R)/SaO2], cerebrosplanchnic oxygenation ratio [CSOR: (rSO2S/rSO2C)], and cerebrorenal oxygenation ratio [CROR: (rSO2R/rSO2C)] were calculated. In addition, we used Doppler ultrasonography for evaluating cerebral blood flow (CBF), splanchnic blood flow (SBF), and renal blood flow (RBF) velocity.

RESULTS: rSO2C, rSO2S, and rSO2R significantly increased during transfusions, while FOEC, FOES, and FOER decreased. CSOR and CROR increased during transfusions. CBF velocity decreased during the study period, while SBF and RBF velocities did not vary.

CONCLUSION: RBC transfusions performed at used thresholds permitted an increase in cerebral, splanchnic, and renal oxygenation. The associated decreases in oxygen tissue extraction might suggest that transfusions were well timed for preventing tissue hypoxia or too early and theoretically prooxidant. Further studies could help to clarify this issue.
Gravity sedimentation of granulocytapheresis concentrates with hydroxyethyl starch efficiently removes red blood cells and retains neutrophils
Authors: Bryant Barbara J. , Yau Yu Ying , Byrne Phyllis J. , Stroncek David F. , Leitman Susan F.
Published: January 2010

BACKGROUND: Transfusion of granulocytapheresis concentrates can be limited by the volume of incompatible donor red blood cells (RBCs) in the component. Efficient reduction of RBCs in granulocyte units would result in safe transfusion of RBC‐incompatible units.

STUDY DESIGN AND METHODS: Granulocyte concentrates were collected by continuous‐flow apheresis from granulocyte–colony‐stimulating factor (G‐CSF) and dexamethasone‐stimulated volunteer donors, with 6% hydroxyethyl starch (HES) added continuously during apheresis as a RBC sedimenting agent to enhance granulocyte collection efficiency. After collection, the component was placed in a plasma extractor for 4 hours. A sharp line of demarcation between the starch‐sedimented RBCs and the granulocyte‐rich supernatant developed, and the supernatant was transferred to a sterilely docked transfer pack. RBC reduction and white blood cell recovery were determined.

RESULTS: Gravity sedimentation was performed on 165 granulocyte concentrates. Mean sedimentation time was 267 minutes (range, 150‐440 min). RBC depletion was 92% (range, 71%‐99%) with mean residual RBC content of 3.2 ± 1.4 mL. Twelve percent of components contained less than 2 mL of RBCs. Mean granulocyte and platelet (PLT) recoveries were 80 and 81%, respectively. There were no transfusion reactions or signs of hemolysis after transfusion of 66 RBC‐incompatible granulocyte concentrates (RBC volume, 1.6‐8.2 mL). The remaining concentrates were used for topical or intrapleural applications.

CONCLUSIONS: RBCs were significantly reduced and granulocytes and PLTs effectively retained in G‐CSF/steroid–mobilized granulocyte components collected with HES and processed by gravity sedimentation. This procedure allows safe transfusion of RBC‐incompatible sedimented granulocyte units and may be used to expand the pool of available granulocyte donors for specific recipients.
Extracorporeal photochemotherapy in graft‐versus‐host disease: a longitudinal study on factors influencing the response and survival in pediatric patients
Authors: Perotti Cesare , Del Fante Claudia , Tinelli Carmine , Viarengo Gianluca , Scudeller Luigia , Zecca Marco , Locatelli Franco , Salvaneschi Laura
Published: January 2010

BACKGROUND: Extracorporeal photochemotherapy (ECP) is a valid therapeutic option in the treatment of acute and chronic graft‐versus‐host disease (aGVHD and cGVHD, respectively). No standard clinical and laboratory criteria of response to ECP treatment are available at the moment.

STUDY DESIGN AND METHODS: Clinical and laboratory variables on 73 pediatric patients with aGVHD (n = 50) and cGVHD (n = 23) were correlated with response to ECP and survival.

RESULTS: An overall response (OR) was obtained in 34 of 50 (68%) aGVHD and in 16 of 23 (69.5%) cGVHD patients. Steroid tapering within 30 days of 1.3 mg/kg in OR (p = 0.004) was the sole highly significant correlation with response found in aGVHD while no correlation emerged for cGVHD (p = 0.28). Among aGVHD patients, response to ECP was inversely associated with death: among OR, deaths were 13 of 34 (38.2%), while among nonresponders, deaths were 15 of 16 (93.8%; p < 0.001). On the other hand, decrease of steroid dose at 30 days was associated with survival: for each 1 mg/kg reduction, the hazard ratio was 2.2, and the 95% confidence interval was 1.5 to 3.2 (p < 0.001). No other clinical or laboratory variables statistically associated with survival were found.

CONCLUSIONS: Our results demonstrate that steroid tapering within the first 30 days of ECP treatment in aGVHD and response to ECP in acute and chronic GVHD are the only variables influencing response and survival, respectively.
An active hemovigilance program characterizing the safety profile of 7483 transfusions with plasma components prepared with amotosalen and UVA photochemical treatment
Authors: Cazenave Jean‐Pierre , Waller Chantal , Kientz Daniel , Mendel Isabelle , Lin Lily , Jacquet Michele , Propst Meisa , Liu Weiqun , Corash Laurence , Sundin David , Defoin Laurence , Messe Nathalie , Osselaer Jean‐Claude
Published: January 2010

BACKGROUND: Photochemical pathogen inactivation treatment (PCT) of plasma components with amotosalen and UVA has been implemented in Europe. To establish a postapproval safety database, an active hemovigilance (HV) program utilizing an electronic data capture system (EDCS) was initiated.

STUDY DESIGN AND METHODS: The response to transfusion was documented after each PCT‐plasma transfusion. The primary outcome was the incidence of acute transfusion reactions (ATRs) within 24 hours of transfusion. An ATR was defined as an adverse event (AE) possibly related, probably related, or related to the PCT‐plasma transfusion. For AEs, the following were collected: time of event after transfusion, clinical description, vital signs, clinical and laboratory test results, severity (Grade 0‐4), seriousness, and causal relationship to transfusion of PCT‐plasma.

RESULTS: To date, 3232 patients (59.1% male) with a primary indication for plasma transfusion due to a hematology disorder (23.1%), surgery (32.4%), or a general medical condition (44.4%) received 7483 PCT‐plasma transfusions (composed of 19,069 apheresis plasma components). The mean age of the patient population was 57.3 years (2884 adults, 160 children, and 188 infants). ATRs were reported for 8/7483 transfusions (0.11%; 95% confidence interval [CI], 0.03‐0.19) and 8/3232 patients (0.25%; 95% CI, 0.08‐0.42%). Five ATRs were of Grade 1 severity. The remaining three ATRs were classified as serious. No deaths or episodes of transfusion‐related acute lung injury attributed to a PCT‐plasma transfusion were reported.

CONCLUSION: PCT‐plasma transfusions were well tolerated in routine clinical use. The EDCS HV program facilitated collection and reporting of safety information on a real‐time basis from multiple sites.
A New Method to Evaluate Linear Block at the Left Atrial Roof: Is It Reliable Without Pacing?
Authors: SANG CAIHUA , JIANG CHENXI , DONG JIANZENG , LIU XINGPENG , YU RONGHUI , LONG DEYONG , TANG RIBO , GAO LINGYUN , NING MAN , CHEN GANG , LI WEIJU , MA CHANGSHENG
Published: January 2010

A New Method to Evaluate Linear Block at the Left Atrial Roof. Objective: The present study aimed to evaluate a new method for validation of complete linear block at the left atrial (LA) roof.

Background:
Linear lesions at the LA roof have been reported to improve the success rate of catheter ablation of atrial fibrillation (AF).

Methods:
Complete linear block at the LA roof was evaluated in 31 patients after complete isolation of pulmonary vein antrum (PVA) using a simple method. We hypothesized that complete linear block of the LA roof could be confirmed during sinus rhythm if (1) a continuous line of double potentials could be recorded at the LA roof, and (2) the activation sequence along the posterior wall changed to caudocranial. The results of this method were compared with standard pacing techniques.

Results:
Thirty‐nine lines were assessed using this method: 8 before and 31 after achievement of complete conduction block. After validation of complete linear block at the LA roof, double potentials with a mean interpotential interval of 60 ± 13 ms were recorded in 25 patients and electroanatomical mapping of the left atrium showed the activation sequence of posterior wall changed to caudocranial in all 31 patients during sinus rhythm. The sensitivity, specificity, positive and negative predictive values of this method for validating complete linear block were 100%, 88.9%, 96.8%, and 100%, respectively.

Conclusion:
A corridor of double potentials along the roof line and a caudocranial activation sequence along the posterior wall during sinus rhythm can indicate conduction block at the LA roof after PVA isolation. (J Cardiovasc Electrophysiol, Vol. pp. 741‐746, July 2010)
Device‐Related Infection Among Patients With Pacemakers and Implantable Defibrillators: Incidence, Risk Factors, and Consequences
Authors: NERY PABLO B. , FERNANDES RUSSELL , NAIR GIRISH M. , SUMNER GLEN L. , RIBAS CARLOS S. , MENON SYAMKUMAR M. DIVAKARA , WANG XIAOYIN , KRAHN ANDREW D. , MORILLO CARLOS A. , CONNOLLY STUART J. , HEALEY JEFF S.
Published: January 2010

Risk Factors and Complications of Pacemaker and ICD Infection. Background: Device‐related infection is a major limitation of device therapy for cardiac arrhythmia.

Methods:
The authors analyzed the incidence and risk factors for cardiac device infection (CDI) among consecutive patients implanted with pacemaker (PM) or implantable cardioverter defibrillator (ICD) (including cardiac resynchronization therapy devices) at a tertiary health center in Hamilton, Ontario, Canada. Most patients with device‐related infections were identified by an internal infection control system that reports any positive wound and blood cultures following surgery, between 2005 and the present. A retrospective review of patient records was also performed for all patients who received an ICD or PM between July 1, 2003 and March 20, 2007.

Results:
A total of 24 infections were identified among 2,417 patients having device surgery (1%). Fifteen of these infections (60%) were diagnosed within 90 days of the last surgical procedure. Univariate analysis showed that patients presenting with CDI were more likely to have had a device replacement, rather than a new implant, had more complex devices (dual/triple chamber vs single), and were more likely to have had a prior lead dislodgement. Multivariate analysis found device replacement (P = 0.02) and cardiac resynchronization therapy (CRT)/dual‐chamber devices (P = 0.048) to be independent predictors of infection. One patient developed septic pulmonary emboli after having laser‐assisted lead extraction. No patient died and 22 patients received a new device.

Conclusion:
CDI occurs in about 1% of cases in high volume facilities. Pulse generator replacement surgery and dual‐ or triple‐chamber device implantation were associated with a significantly increased risk of infection. (J Cardiovasc Electrophysiol, Vol. pp. 786‐790, July 2010)
Simultaneous Improvement in Aortic Distensibility and Coronary Flow Velocity Reserve after Successful Coronary Interventions
Authors: Nemes Attila , Ungi Imre , Csanády Miklós , Forster Tamás
Published: January 2010

Objective: Deteriorations in coronary flow velocity reserve (CFR) and aortic distensibility have been demonstrated in coronary artery disease. The objective of the present study was a simultaneous echocardiographic evaluation of the CFR and aortic distensibility indices before and after successful percutaneous coronary interventions (PCI) in patients with left anterior descending coronary artery (LAD) disease. Methods: The study population, comprising 12 patients (4 women and 8 men) with significant proximal LAD stenosis, were compared with matched controls. Transesophageal echocardiography (TEE) was carried out to evaluate the CFR and aortic distensibility indices (the aortic elastic modulus E(p) and Young's circumferential static elastic modulus E(s)) before and after PCI to the LAD. The subjects underwent TEE on average 8 ± 11 days before PCI and 25 ± 6 weeks after PCI. Results: An improvement in CFR was demonstrated in patients with LAD stenosis after successful PCI (1.71 ± 0.36 vs. 2.08 ± 0.28, P < 0.05), which paralleled the decreases in E(p) (936 ± 544 mmHg vs. 567 ± 184 mmHg, P < 0.05) and E(s) (10,207 ± 6,295 mmHg vs. 5,831 ± 2,010 mmHg, P < 0.05) during the follow‐up. Conclusion: The aortic distensibility improves in parallel with the increase in CFR in patients with LAD stenosis after successful PCI. (Echocardiography 2010;27:311‐316)
Antiphospholipid Antibody Syndrome: Coexistence of Left Ventricular Apical Thrombus and Deep Vein Thrombosis Causing Pulmonary Thromboembolism in a Patient with Systemic Lupus Erythematosus
Authors: Acikel Sadik , Akdemir Ramazan , Dogan Mehmet , Kilic Harun , Yesilay Asuman Bicer
Published: January 2010

We report a 36‐year‐old woman with a 1‐year history of systemic lupus erythematosus who was admitted with acute onset of dyspnea and chest pain. She presented with a classic medical history of antiphospholipid antibody syndrome, including spontaneous abortion, deep venous thrombosis, and clinical manifestations of lupus activation. The differential diagnosis was made after a detailed history and examinations with transthoracic/transesophageal echocardiography, deep venous ultrasonography, chest computed tomography, and coronary angiography. This case demonstrates a left ventricular apical thrombus in angiographically normal coronary arteries and also deep vein thrombosis causing acute pulmonary thromboembolism. Antiaggregant and anticoagulant therapies were initiated as a result of the presence of a left ventricular apical thrombus and deep venous thrombosis, which is predisposed to recurrent pulmonary or systemic embolization. Control echocardiography demonstrated resolution of apical thrombus and normalized left ventricular systolic function after aspirin, warfarin, and immunosuppressive therapy for 2 months. (ECHOCARDIOGRAPHY 2010;27:198‐201)
Evaluation of Left Ventricular Circumferential Contraction Functions in Obese Patients
Authors: Sürücü Hüseyin , Tatlı Ersan , Boz Hakkı , Meriç Mehmet
Published: January 2010

Background: We aim to evaluate left ventricular (LV) function abnormalities, especially circumferential contraction functions, in obese patients. Method: Cases without coronary artery disease (CAD) were divided into two groups according to their body mass indexes (BMI). Results: Female predominance (P = 0.002), systolic blood pressure (BP) (P = 0.001), diastolic BP (P = 0.001), waist circumference (P < 0.001), left atrium (P < 0.001), LV end‐diastolic diameter (P = 0.046), LV mass index (P = 0.001), and LV stroke volume (P = 0.016) were prominent in obese patients (BMI ≥ 27). In obese patients, transmitral late velocity (P = 0.005) was prominent, and pulmonary vein antegrade diastolic velocity (PV‐D) (P = 0.002) and mitral annular early diastolic pulsed‐wave tissue Doppler imaging (pw‐TDI) velocity (annular Ea) (P = 0.032) were lower. Transmitral late velocity was positively correlate with stroke volume (P = 0.029) and systolic BP (P < 0.001). Negatively correlation between PV‐D and diastolic BP (P = 0.046) was found. And also, annular Ea velocity was negatively correlate with systolic BP (P = 0.017) and diastolic BP (P = 0.031). These findings may reflect LV longitudinal contraction abnormalities (LVLCA) and underlying mechanism that is responsible for LVLCA, may be volume and afterload alterations. However, LV circumferential contraction functions that evaluate by using pw‐TDI, were not different among the groups. Conclusion: In obese patients without CAD, it was clearly said that while LVLCA were evident, LV circumferential contraction abnormalities were not. This differentiation may be explained by subepicardial myocardial fiber that is responsible for LV circumferential contractions is supplied by coronary arteries, subendocardial myocardial fiber that is responsible for LV longitudinal contractions, is supplied by systemic circulation via LV cavity penetration. (ECHOCARDIOGRAPHY 2010;27:378‐383)
Estimation of Coronary Flow Velocity Reserve Using Transthoracic Doppler Echocardiography and Cold Pressor Test Might Be Useful for Detecting of Patients with Variant Angina
Authors: Hwang Hui‐Jeong , Chung Woo‐Baek , Park Jeong‐Hwan , Oh Su‐Sung , Chung Jong‐Won , Choi Yun‐Seok , Youn Ho‐Joong
Published: January 2010

Purpose: The cold pressor test (CPT) has been used to detect variant angina, but its sensitivity in predicting vasospasm is low. The aim of this study was to determine whether estimates of the coronary flow velocity reserve (CFVR) in the distal left anterior descending coronary artery (dLAD) using transthoracic echocardiography (TTE) and CPT are useful tool to predict variant angina. Methods: 65 patients (mean age = 52 ± 10 years; male:female = 41:24) who had normal coronary artery on angiography and underwent acetylcholine provocation test were enrolled and divided into the spasm group (n = 31) and the no spasm group (n = 34). During CPT, the peak (PDV) and mean diastolic flow velocity (MDV) of the dLAD were estimated using TTE with a high‐frequency transducer, and electrocardiography, blood pressures, heart rate, and symptoms were monitored every 30 seconds. CPT%PDV and CPT%MDV were defined as the percentage changes in PDV and MDV during CPT, respectively. Results: CPT%PDV was 4.99 ± 23.62% in the spasm group and 52.75 ± 24.78% in the no spasm group (P < 0.001). CPT%MDV was 6.83 ± 23.81% in the spasm group and 50.22 ± 27.83% in the no spasm group (P < 0.001). CPT%PDV<31.1% had a sensitivity of 93.5% and a specificity of 82.4% in predicting variant angina (95% confidence interval [CI]: 0.939–0.979, P < 0.001). CPT%MDV<30.55% had a sensitivity of 90% and a specificity of 76.5% in predicting variant angina (95% CI: 0.884–0.950, P < 0.001). Conclusion: The measurement of changes in the coronary flow velocity of the dLAD using TTE and CPT might be useful for the estimation of endothelial dysfunction in patients with variant angina. (ECHOCARDIOGRAPHY 2010;27:435‐441)
Correction for Covariate Measurement Error in Nonparametric Longitudinal Regression
Authors: Rummel D. , Augustin T. , Küchenhoff H.
Published: January 2010

Summary We introduce a correction for covariate measurement error in nonparametric regression applied to longitudinal binary data arising from a study on human sleep. The data have been surveyed to investigate the association of some hormonal levels and the probability of being asleep. The hormonal effect is modeled flexibly while we account for the error‐prone measurement of its concentration in the blood and the longitudinal character of the data. We present a fully Bayesian treatment utilizing Markov chain Monte Carlo inference techniques, and also introduce block updating to improve sampling and computational performance in the binary case. Our model is partly inspired by the relevance vector machine with radial basis functions, where usually very few basis functions are automatically selected for fitting the data. In the proposed approach, we implement such data‐driven complexity regulation by adopting the idea of Bayesian model averaging. Besides the general theory and the detailed sampling scheme, we also provide a simulation study for the Gaussian and the binary cases by comparing our method to the naive analysis ignoring measurement error. The results demonstrate a clear gain when using the proposed correction method, particularly for the Gaussian case with medium and large measurement error variances, even if the covariate model is misspecified.
Pneumocystis carinii and Pneumocystis wakefieldiae in Wild Rattus norvegicus Trapped in Thailand
Authors: CHABÉ MAGALI , HERBRETEAU VINCENT , HUGOT JEAN‐PIERRE , BOUZARD NOEMI , DERUYTER LUCIE , MORAND SERGE , DEI‐CAS EDUARDO
Published: January 2010

ABSTRACT. This work reports for the first time the presence of two Pneumocystis species in wild Rattus norvegicus specimens from Thailand. Pneumocystis DNA was detected in 57.7% (15/26) wild rats without apparent association with typical pneumocystosis. Pneumocystis carinii was found alone in five rats (19.2%), Pneumocystis wakefieldiae was detected alone in six rats (23.1%), and two rats were infected by both species (7.7%). In addition, a new P. wakefieldiae variant sequence has been identified in three wild R. norvegicus specimens caught in the same geographical area. The high frequency of Pneumocystis in wild rats documented in this study and the apparent scarcity of severe pneumocystosis were consistent with an efficient circulation of rat Pneumocystis species in ecosystems.
Genetic Diversity of Populations of Monilinia fructicola (Fungi, Ascomycota, Helotiales) from China
Authors: FAN JIN‐YAN , GUO LI‐YUN , XU JIAN‐PING , LUO YONG , MICHAILIDES THEMIS J.
Published: January 2010

ABSTRACT. The genetic variation among 128 isolates of Monilinia fructicola (Fungi, Ascomycota, Helotiales) from China was analyzed using Inter‐Simple Sequence Repeat (ISSR) markers and compared with those of samples from California, USA and New Zealand. A total of 72 reproducible DNA fragments were scored, of which 87.5% (63/72) were polymorphic. The Nei's gene diversity and Shannon's diversity indices of three Chinese regional populations were very similar to that from California. However, several differences were observed among geographic populations of M. fructicola from both within China and between China and California. The analysis of molecular variance (AMOVA) of isolates from different geographic locations suggested that most of the observed genetic variation was found within populations. Results of this study are inconsistent with the hypothesis that the Chinese populations of M. fructicola were derived from a single or few recent migrants from other countries. Instead, our results suggest that M. fructicola has been in China long before its first official recording in 2003.