bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayesian and Belief‐Functions Formulas for Auditor Independence Risk Assessment
Authors: Srivastava Rajendra P. , Mock Theodore J. , Turner Jerry L.
Published: April 2009

This paper illustrates two formulas for assessing independence risk based on the Bayesian and belief‐functions frameworks. These formulas can be used to assess the role of threats to auditor independence as well as the role of threat‐mitigating safeguards. Also, these formulas provide a basis for evaluation of an audit firm's independence risk and a framework to educate stakeholders about the threats faced by the audit firm and the role of effective safeguards in mitigating these risks. The formulas also provide a means for regulators and lawmakers to evaluate whether they have effective safeguards in place given the existence of threats and for auditors to signal to various stakeholders that they have identified significant threats and have effective safeguards in place. To show the potential usefulness of these analytical models, several illustrations addressing increased transparency and the potential impact of regulations are presented.
The Impact of Competing Goals, Experience, and Litigation Consciousness on Auditors' Judgments
Authors: Asare Stephen K. , Cianci Anna M. , Tsakumis George T.
Published: April 2009

This study uses an experiment to examine the interactive effect of goals and experience on auditors' inventory write‐off assessments and the role of litigation consciousness in mediating this effect. We find that when presented with a competing compliance and client relations goal, more experienced auditors were more likely to recommend an inventory write‐off than less experienced auditors. However, when presented with only a compliance goal, auditors were equally likely to recommend an inventory write‐off. The finding that less experienced auditors are more influenced by client relations goals suggests that the early socialization into the profession may be dominated by client relations concerns rather than litigation concerns. Mediation results suggest that auditors' litigation consciousness is a significant mechanism which helps drive the interactive effect of goals and experience on auditors' inventory write‐off assessments. Implications for research, practice, and regulation are discussed.
Protein kinase Cα‐responsive polymeric carrier: its application for gene delivery into human cancers
Authors: Tomiyama Tetsuro , Kang Jeong‐Hun , Toita Riki , Niidome Takuro , Katayama Yoshiki
Published: April 2009

For cancer‐targeting gene delivery, we applied a protein kinase C (PKC)α‐responsive polymeric carrier to human cancers (U‐87 MG [human glioblastoma‐astrocytoma, epithelial‐like cell line] and A549 [human lung adenocarcinoma epithelial cell line]). Two polymers, one a PKCα‐responsive polymer (PPC[S]) containing the phosphorylation site serine, and the other a negative control polymer (PPC[A]), in which the serine was substituted with alanine, were synthesized. No cytotoxicity of the polymer was identified. When the complexes were transfected into cancer cells or tissues in which PKCα was hyper‐activated, the luciferase expression from the PPC(S)/plasmid (pDNA) complex was higher than that from the PPC(A)/pDNA complex. These results show that the phosphorylation of complex by PKCα in cancer cells leads to high gene expression and that our system can be used as a human cancer cell–targeting gene delivery system. (Cancer Sci 2009)
External magnet improves antitumor effect of vinblastine and the suppression of metastasis
Authors: Dandamudi Suman , Patil Vishwesh , Fowle William , Khaw Ban‐An , Campbell Robert B.
Published: April 2009

The use of magnetic drug targeting (MDT) to selectively deliver chemotherapeutic drugs to tumor cells is a widely investigated approach; however, the notion of targeting tumor endothelial cells by this method is a fairly new concept. Positively‐charged (cationic) liposomes have an extraordinarily high affinity for tumor vessels, but heterogeneous targeting is frequently observed. In order to improve on the overall efficiency of targeting tumor vessels, we investigated the use of an externally applied magnetic field together with magnetic cationic liposomes (MCLs) for cancer treatment. We examined the antitumor effect of the chemotherapeutic agent vinblastine loaded in MCLs, using a murine model of melanoma. Two hours following i.v. administration of MCLs, we observed significant tumor vascular uptake with use of an external magnet (15.9 ± 6.3%) compared to no magnet (5 ± 1.3%). The administration of vinblastine‐loaded MCLs with the magnet produced a significant antitumor effect, reducing the presence of tumor nodules in preferential sites of metastasis compared to untreated and free drug control groups. CD31 immunostaining revealed a decrease in the general length of tumor blood vessels, altered vascular morphology and interruptions in the tumor vascular lining for the vinblastine‐loaded MCL groups. Drug‐loaded MCLs with magnetic fields may represent a promising combination approach for cancer treatment. (Cancer Sci 2009)
Molecular diversity and gene expression of cotton ERF transcription factors reveal that group IXa members are responsive to jasmonate, ethylene and Xanthomonas
Authors: CHAMPION ANTONY , HEBRARD EUGENIE , PARRA BENOIT , BOURNAUD CAROLINE , MARMEY PHILIPPE , TRANCHANT CHRISTINE , NICOLE MICHEL
Published: April 2009

Several ethylene‐response factor (ERF) transcription factors are believed to play a crucial role in the activation of plant defence responses, but little is known about the relationships between the diversity of this family and the functions of groups or individual ERFs in this process. In this study, 200 ERF genes from the unigene cotton database were identified. Conserved amino acid residues and phylogeny reconstruction using the AP2 conserved domain suggest that the classification into 10 major groups used for Arabidopsis and rice is applicable to the cotton ERF family. Based on in silico studies, we predict that group IX ERF genes in cotton are involved in jasmonate (JA), ethylene (ET) and pathogen responses. To test this hypothesis, we analysed the transcript profiles of the group IXa subfamily in the regulation of specific resistance to Xanthomonas campestris pathovar malvacearum. The expression of four members of group IXa was induced on challenge with X. campestris pv. malvacearum. Furthermore, the expression of several ERF genes of group IXa was induced synergistically by JA in combination with ET, suggesting that the encoded ERF proteins may play key roles in the integration of both signals to activate JA‐ and ET‐dependent responses.
An artificial chimeric derivative of Citrus viroid V involves the terminal left domain in pathogenicity
Authors: SERRA PEDRO , BANI HASHEMIAN SEYED MEHDI , PENSABENE‐BELLAVIA GIOVANNI , GAGO SELMA , DURAN‐VILA NÚRIA
Published: April 2009

The recently described Citrus viroid V (CVd‐V) induces, in Etrog citron, mild stunting and very small necrotic lesions and cracks, sometimes filled with gum. As Etrog citron plants co‐infected with Citrus dwarfing viroid (CDVd) and CVd‐V show synergistic interactions, these host–viroid combinations provide a convenient model to identify the pathogenicity determinant(s). The biological effects of replacing limited portions of the rod‐like structure of CVd‐V with the corresponding portions of CDVd are reported. Chimeric constructs were synthesized using a novel polymerase chain reaction‐based approach, much more flexible than those based on restriction enzymes used in previous studies. Of the seven chimeras (Ch) tested, only one (Ch5) proved to be infectious. Plants infected with Ch5 showed no symptoms and, although this novel chimera was able to replicate to relatively high titres in singly infected plants, it was rapidly displaced by either CVd‐V or CDVd in doubly infected plants. The results demonstrate that direct interaction(s) between structural elements in the viroid RNA (in this case, the terminal left domain) and as yet unidentified host factors play an important role in modulating viroid pathogenicity. This is the first pathogenic determinant mapped in species of the genus Apscaviroid.
Common promoter deletion is associated with 3.9‐fold differential transcription of ovineCCR5and reduced proviral level of ovine progressive pneumonia virus
Authors: White S. N. , Mousel M. R. , Reynolds J. O. , Lewis G. S. , Herrmann‐Hoesing L. M.
Published: April 2009

Chemokine (C‐C motif) Receptor 5 (CCR5)is a chemokine receptor that regulates immune cell recruitment in inflammation and serves as a coreceptor for human immunodeficiency virus (HIV). A humanCCR5coding deletion (termed delta‐32) results in strong resistance to HIV infection, and sequence variants inCCR5regulatory regions have been implicated in delayed progression to acquired immune deficiency syndrome. Both ovine progressive pneumonia virus (OPPV), also known as maedi‐visna, and HIV are macrophage‐tropic lentiviruses, have similar genomic structures, and cause lifelong persistent host infection, suggestingCCR5may have a role in regulating OPPV provirus levels. Therefore, the ovineCCR5genomic sequence was determined, and sequence variants were obtained from the open reading frame and surrounding regulatory sites. OneCCR5variant contained a 4‐base deletion within a binding site for octamer transcription factors in the promoter region. A test for differential transcription from each allele in heterozygous animals showed a 3.9‐fold transcription difference (P < 0.0001). OPPV proviral levels were also measured in 351 naturally exposed Rambouillet, Polypay and Columbia sheep. Deletion homozygotes showed reduced OPPV proviral levels among these animals (P < 0.01). The association of thisCCR5promoter deletion with OPPV levels will need to be validated in additional populations before the deletion can be recommended for widespread use in marker‐assisted selection. However, because of the large impact on transcription and becauseCCR5has roles in inflammation, recruitment of effector cells, and cell‐mediated immunity, this deletion may play a role in the control of infections of many diverse pathogens of sheep.
Stearoyl‐CoA desaturase 1 genotype and stage of lactation influences milk fatty acid composition of Canadian Holstein cows
Authors: Kgwatalala P. M. , Ibeagha‐Awemu E. M. , Mustafa A. F. , Zhao X.
Published: April 2009

Single nucleotide polymorphisms in the coding region of the bovine stearoyl‐CoA desaturase 1 gene have been predicted to result in p.293A (alanine at amino acid 293) and p.293V (valine at amino acid 293) alleles at the stearoyl‐CoA desaturase1 locus. The objectives of this study were to evaluate the extent to which genotypes at the stearoyl‐CoA desaturase 1 locus and stage of lactation influence milk fatty acid composition in Canadian Holstein cows. Cows with the p.293AA genotype had higher C10 index, C12 index and C14 index and higher concentrations of C10:1 (10 carbon fatty acid with one double bond), C12:1 (12 carbon fatty acid with one double bond) and myristoleic acid (C14:1) compared with the p.293AV or p.293VV cows. Cows had higher C18 index and total index, and lower C10 index, C12 index, C14 index and CLA index during early lactation compared with the subsequent lactation stages. Early lactation was also characterized by higher concentrations of oleic acid (C18:1 cis‐9), vaccenic acid (C18:1 trans‐11), linoleic acid (C18:2), monounsaturated fatty acids and total polyunsaturated fatty acids, and lower concentrations of capric acid (C10:0), C10:1, lauric acid (C12:0), C12:1, myristic acid (C14:0), myristoleic acid (C14:1), palmitic acid (C16:0) and total saturated fatty acids compared with the subsequent lactation stages. Neither the stearoyl‐CoA desaturase 1 genotype nor the stage of lactation had an influence on conjugated linoleic acid concentrations in milk.
Prevalence of immunoglobulin E‐mediated food allergy in 6–9‐year‐old urban schoolchildren in the eastern Black Sea region of Turkey
Authors: Orhan F. , Karakas T. , Cakir M. , Aksoy A. , Baki A. , Gedik Y.
Published: April 2009

Background
The prevalence of adverse reactions to food in childhood in Turkey is not known.

Objective
We aimed to investigate the prevalence and characteristics of IgE‐mediated food allergies (FAs) in 6–9‐year‐old urban schoolchildren.

Methods
This cross‐sectional study recruited 3500 of the randomly selected 6–9‐year‐old urban schoolchildren from the eastern Black Sea region of Turkey during 2006. Following a self‐administered questionnaire completed by the parents and the child, consenting children were invited for skin prick tests (SPTs) and oral food challenges. Children with suspected IgE‐mediated FA were skin prick tested with a predefined panel of food allergens (milk, hen's egg, soy, wheat, peanut, fish, and hazelnut), aeroallergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat, dog, Alternaria, grass pollen mix, weed pollen mix, and tree pollen mix), and food allergens reported in the questionnaire. All children with a positive SPT to any food were invited for a double‐blind, placebo‐controlled food challenge (DBPCFC). The prevalence of IgE‐mediated FA was established using DBPCFCs.

Results
The response rate to the questionnaire was 78.2% (2739/3500). The estimated prevalence of parental‐reported IgE‐mediated FA was 5.7% (156/2739) [95% confidence interval (CI), 4.83–6.57%]. The rate of sensitization to the food allergens was 33.1% (48/145) in the parental‐reported group. The confirmed prevalence of IgE‐mediated FA by means of DBPCFC in 6–9‐year‐old urban schoolchildren living in the eastern Black Sea region of Turkey was 0.80% (22/2739) (95% CI, 0.47–1.13%). The most common allergenic foods were beef (31.8%), cow's milk (18.1%), cocoa (18.1%), hen's egg (13.6%), and kiwi (13.6%).

Conclusions
The rate of reported IgE‐mediated FA was significantly higher than clinically confirmed FA by means of DBPCFC (odds ratio, 7.46; 95% CI, 4.67–12.01; P<0.0001). The order of allergenic foods was different and somewhat unique to the eastern Black Sea region of Turkey when compared with western countries.
Clinical associations of the genetic variants of CTLA‐4, Tg, TSHR, PTPN22, PTPN12 and FCRL3 in patients with Graves’ disease
Authors: Li‐qun Gu , Wei Zhu , Shuang‐xia Zhao , Lin Zhao , Min‐jia Zhang , Bin Cui , Huai‐dong Song , Guang Ning , Yong‐ju Zhao
Published: April 2009

Objective  Graves’ disease (GD) is an organ‐specific autoimmune disorder. Both immune‐modulating genes and thyroid‐specific genes are involved in its genetic pathogenesis. It remains unclear, however, how the interactions of various susceptibility genes contribute to the pathogenesis and clinical severity of the disease. The purpose of this study was to investigate the relationships between GD and single nucleotide polymorphisms (SNPs) from CTLA‐4, PTPN22, PTPN12, FCRL3 (general autoimmunity genes regulating T and B cells) and the TSHR and Tg genes (disease‐specific genes). Furthermore, we evaluated the influences these SNPs have on the risk and severity of GD.

Design and methods  This cross‐sectional clinical study was performed in 436 GD patients and 316 healthy, gender‐matched individuals. Twenty‐eight SNPs from CTLA‐4, PTPN22, PTPN12, FCRL3, TSHR and Tg genes were genotyped and their associations with the risk and severity of GD were analysed.

Results  The CTLA‐4 rs231779, Tg rs2069550 and PTPN22 rs3789604 SNPs were associated with GD, with additive risk effects present in rs231779 and rs2069550. The ACACC and ACGCT haplotypes, composed of five SNPs in the CTLA‐4 gene (rs4553808, rs5472909, rs231775, rs231777 and rs231779), were protective and risk haplotypes respectively. The AA genotype of PTPN22 rs3789604 and AA genotype of FCRL3 rs7528684 were correlated with a reduced risk of GD, while the CC genotype of TSHR rs2239610 was associated with higher serum concentrations of FT4 and TRAb. Logistic analysis confirmed the contribution of CTLA‐4 rs231779 to the development of GD.

Conclusions  These preliminary results demonstrate that the immune‐regulatory gene CTLA‐4 and the thyroid‐specific gene Tg contribute to the risk of Graves’ disease with additive effects, while PTPN22 rs3789604 and FCRL3 rs7528684 polymorphisms are protective against the disease. In addition, the TSHR rs2239610 SNP is related to the severity of Graves’ disease.
Cost minimization analysis to compare activated prothrombin complex concentrate (APCC) and recombinant factor VIIa for haemophilia patients with inhibitors undergoing major orthopaedic surgeries
Authors: BONNET P. O. , YOON B. S. , WONG W.‐Y. , BOSWELL K. , EWENSTEIN B. M.
Published: April 2009

Summary.  Benefits of bypassing agents for maintaining haemostasis in major surgeries have been described in the literature; however, their use has a substantial economic impact. This study assessed the cost of FEIBA, an activated prothrombin complex concentrate and recombinant factor VIIa (rFVIIa) when used in inhibitor patients undergoing major surgeries. After reviewing published literature, a cost minimization model was developed describing dosing regimens recommended and used during major surgeries for FEIBA (pre‐operative: 75–100 U kg−1; postoperative: 75–100 U kg−1 q 8–12 h days 1–5 and 75–100 U kg−1 q 12 h days 6–14) and rFVIIa (pre‐operative: 90 μg kg−1; intra‐operative: 90 μg kg−1 q 2 h; postoperative: 90 μg kg−1 q 2–4 h days 1–5 and 90 μg kg−1 q 6 h days 6–14). Using a 75 kg patient and US prices, total drug cost was calculated for three scenarios: use of FEIBA or rFVIIa alone and a third case combining rFVIIa pre‐ and intra‐operative and FEIBA throughout a 14‐day postoperative period. Dosage amounts of modelled bypassing agents were similar to cases in the literature. Using FEIBA instead of rFVIIa would decrease total drug cost by >50% and save over $400 000 per surgery. Sequential use of both bypassing agents would increase total drug cost by 9% when compared with FEIBA alone, but would remain >40% lower than rFVIIa alone. Univariate sensitivity analyses confirmed robustness of results. As large amounts of bypassing agents are necessary for patients with inhibitors to undergo major surgeries, cost is a major consideration. Use of FEIBA alone or in combination with rFVIIa has emerged as a cost‐saving approach.
Griefing in virtual worlds: causes, casualties and coping strategies
Authors: Chesney Thomas , Coyne Iain , Logan Brian , Madden Neil
Published: April 2009

A virtual world is a computer‐simulated three‐dimensional environment. They are increasingly being used for social and commercial interaction, in addition to their original use for game playing. This paper studies negative behaviour, or ‘griefing’, inside one virtual world through a series of observations and focus groups with users. Data were collected to identify griefing behaviours and their impact, examine why griefing happens and who the likely targets and perpetrators are, and suggest strategies for coping with it. Findings show that griefing behaviour is common. It is defined as unacceptable, persistent behaviour and is typically targeted at inexperienced residents by those with more knowledge of the virtual world. Community and individual coping strategies are identified and discussed.
Range‐wide phylogeography of the European temperate‐montane herbaceous plant Meum athamanticum Jacq.: evidence for periglacial persistence
Authors: Huck Stefan , Büdel Burkhard , Kadereit Joachim W. , Printzen Christian
Published: April 2009

Aim  The aim of this study is to analyse the genetic population structure of Meum athamanticum Jacq. in order to explore the alternative hypotheses (1) that the central and northern highland populations are the result of post‐glacial recolonization from southern refugia, and the disjunct distribution of M. athamanticum can be explained by modern ecological conditions, or (2) that extant populations north of the Alps and Pyrenees persisted in situ during glacial periods.

Location  Europe.

Methods  Variation of amplified fragment length polymorphisms (AFLPs) was analysed for 23 populations from the entire range of the species. We used band‐based approaches and methods based on allele frequencies to measure genetic diversity and to identify population structure.

Results  Our analyses reveal a north–south differentiation within M. athamanticum. High levels of genetic diversity, as well as private fragments, are found in populations both north and south of the Alps. Differentiation among populations is lower in the northern than in the southern population group, and significant isolation‐by‐distance is found only in the latter group.

Main conclusions  Our results indicate that M. athamanticum survived the last ice age in multiple refugia throughout its contemporary range and did not expand into areas north of the Alps from southern refugia. We found evidence that regional‐scale migration in northern, formerly periglacial, parts of the species range has resulted in the intermingling of populations. In contrast, southern populations are characterized by long‐term isolation. The south‐west Alps represent an area where immigration and mixing of populations from northern and southern refugia appears to have taken place.
Environmental effects on Neotropical liana species richness
Authors: Van Der Heijden Geertje M. F. , Phillips Oliver L.
Published: April 2009

Aim  Lianas differ physiologically from trees, and therefore their species‐richness patterns and potential climate‐change responses might also differ. However, multivariate assessments of spatial patterns in liana species richness and their controls are lacking. Our aim in this paper is to identify the environmental factors that best explain the variation in liana species richness within tropical forests.

Location  Lowland and montane Neotropical forests.

Methods  We quantified the contributions of environmental variables and liana and tree‐and‐shrub abundance to the species richness of lianas, trees and shrubs ≥ 2.5 cm in diameter using a subset of 65 standardized (0.1 ha) plots from 57 Neotropical sites from a global dataset collected by the late Alwyn Gentry. We used both regression and structural equation modelling to account for the effects of environmental variables (climate, soil and disturbance) and liana density on liana species richness, and we compared the species‐richness patterns of lianas with those of trees and shrubs.

Results  We found that, after accounting for liana density, dry‐season length was the dominant predictor of liana species richness. In addition, liana species richness was also related to stand‐level wood density (a proxy for disturbance) in lowland forests, a pattern that has not hitherto been shown across such a large study region. Liana species richness had a weak association with soil properties, but the effect of soil may be obscured by the strong correlation between soil properties and climate. The diversity patterns of lianas and of trees and shrubs were congruent: wetter forests had a greater species richness of all woody plants.

Main conclusions  The primary association of both liana and tree‐and‐shrub species richness with water availability suggests that, if parts of the Neotropics become drier as a result of climate change, substantial declines in the species richness of woody plants at the stand level may be anticipated.
Variability in thermal and UV‐B energy fluxes through time and their influence on plant diversity and speciation
Authors: Willis K. J. , Bennett K. D. , Birks H. J. B.
Published: April 2009

Throughout Earth’s history there have been temporal and spatial variations in the amount of visible and ultraviolet radiation received by ecosystems. This paper examines if temporal changes in these forms of energy receipt could have influenced the tempo and mode of plant diversity and speciation, focusing in particular upon Cenozoic time‐scales. Evidence for changing patterns of plant diversity and speciation apparent in various fossil records and molecular phylogenies are considered alongside calculated changes in thermal and solar ultraviolet energy (specifically UV‐B) over the past 50 Myr. We suggest that changes in thermal energy influx (amount and variability) affected the tempo of evolution through its influence upon community dynamics (e.g. population size, diversity, turnover, extinctions). It was not only the amount of thermal energy but also variability in its flux that may have influenced these processes, and ultimately the rate of diversification. We suggest that variations in UV‐B would have influenced the mode and tempo of speciation through changes to genome stability during intervals of elevated UV‐B. We argue, therefore, that although variability in thermal energy and UV‐B fluxes through time may lead to the same end‐point (changing the rate of diversification), the processes responsible are very different and both need to be considered when linking evolutionary processes to energy flux.
Kerguelen Plateau and the Late Cretaceous southern‐continent bioconnection hypothesis: tales from a topographical ocean
Authors: Ali Jason R. , Aitchison Jonathan C.
Published: April 2009

Aim  To evaluate rigorously an influential palaeobiogeographical hypothesis which states that in the Late Cretaceous (until c. 80 Ma) the Kerguelen Plateau provided a terrestrial causeway between East Antarctica and India that, in turn, formed part of a longer overland route between South America and Madagascar.

Location  Southern Ocean, Indian Ocean, East Antarctica, India and Madagascar.

Methods  Palaeogeographical modelling drawing on geological and geophysical data, bathymetric charts and plate tectonic reconstructions.

Results  During the Late Cretaceous, only small portions of the present‐day Kerguelen Plateau were sub‐aerial. Additionally, the plateau’s north‐north‐west and south‐south‐east ends did not directly abut India and Antarctica, but instead were separated by large gaps. Thus, the notion that the two continents were then linked by a land route running the entire length of the edifice is almost certainly incorrect.

Main conclusions  The currently available physical evidence indicates that the Late Cretaceous southern‐continent connection hypothesis, which is based exclusively on biological data, is untenable. Assuming the fossil and/or extant biological records of Madagascar–India are closely related to those of South America, alternative palaeogeographical scenarios need to be explored to explain this conundrum. Overwater dispersal and/or an alternative passage involving a more direct route via Africa (with crossings of the Mozambique Channel and a then appreciably narrower Central Atlantic) should be considered.
Rituximab in auto‐immune haemolytic anaemia and immune thrombocytopenic purpura: a Belgian retrospective multicentric study
Authors: Dierickx D. , Verhoef G. , Van Hoof A. , Mineur P. , Roest A. , Triffet A. , Kentos A. , Pierre P. , Boulet D. , Bries G. , Lê P‐Q , Janssens A. , Delannoy A.
Published: April 2009

Objectives.  For better characterizing the effect of anti‐CD20 therapy, we analysed the use of rituximab in Belgian patients experiencing auto‐immune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP).

Design.  We performed a retrospective multicentric analysis of patients with AIHA and ITP treated with rituximab in Belgium.

Setting.  Haematological departments were invited to fill in a questionnaire about patient and disease characteristics.

Subjects.  All patients with AIHA and ITP, both primary and secondary to other diseases, who received one or more courses of rituximab during their disease course were included. Sixty‐eight courses of rituximab in 53 patients with AIHA and 43 courses in 40 patients with ITP were analyzed.

Intervention.  Response rates, duration of response and factors predictive for response were assessed.

Results.  All patients were given rituximab after failing at least one previous line of treatment, including splenectomy in 19% and 72.5% of AIHA‐patients and ITP‐patients respectively. Overall response rates were 79.2% in AIHA and 70% in ITP, with a median follow‐up since first rituximab administration of 15 months (range 0.5–62) in AIHA and 11 months (range 0–74) in ITP. Progression free survival at 1 and 2 years were 72% and 56% in AIHA and 70% and 44% in ITP. In this retrospective analysis we were not able to identify pretreatment characteristics predictive for response to rituximab. Nine patients with AIHA and three patients with ITP were given one or more additional courses of rituximab. Most of these patients, who had responded to a previous course, experienced a new response comparable to the previous one, both in terms of quality and of duration of response. Finally, the outcome of patients who failed to respond to rituximab therapy was poor both in terms of response to subsequent therapy and in terms of survival.

Conclusions.  This study confirms that rituximab induces responses in a majority of previously treated patients with AIHA and ITP. Response duration generally exceeds 1 year. Retreatment with rituximab in responding patients is most often successful. The outcome of patients who fail on rituximab is poor. We were not able to identify pretreatment patient characteristics predicting for response.
Influence of the injection site on the pharmacokinetics of amoxicillin after intramuscular administration of a conventional and a long‐acting formulation in sheep
Authors: DELIS G. , BATZIAS G. , THEODOSIADOU E. , KOUNENIS G. , KOUTSOVITI‐PAPADOPOULOU M.
Published: April 2009

The pharmacokinetics of amoxicillin (AMX) were investigated in sheep following intravenous (i.v.) and intramuscular (i.m) injection, comparing two different drug formulations, a conventional and a long‐acting AMX‐trihydrate suspension. For the i.m. application two different injections sites, the neck area and the hind limb were used to identify possible differences in the kinetic parameters related to the site of injection. A three‐compartment open model could best describe AMX disposition after i.v. administration. Data analysis after i.m. administration of the conventional suspension at both injection sites revealed the occurrence of a flip‐flop phenomenon, clearly indicating that absorption of AMX is the rate‐limiting step of its overall disposition. A moderate effect of the injection site was observed with a tendency for the neck area to be advantageous, mainly in terms of rate rather than extent of absorption. Injection of the long‐acting formulation led to a focal depot formation, thus yielding lower but remarkably prolonged serum AMX levels reflected in the respective terminal half‐lives. The concentration–time profile of AMX after administration of the long‐acting formulation was less affected by the injection site, but the low serum levels justify its use only in cases in which a high susceptibility of the involved bacterial population is confirmed.
Avian influenza and South Jakarta primary healthcare workers: a controlled mixed‐method study
Authors: Koh Gerald Choon‐Huat , Abikusno Nugroho , Kwing Cheong Seng , Yee Wong Teck , Kusumaratna Rina , Sundram Meena , Koh Kelvin , Eng Chia Sin , Koh David
Published: April 2009

Objective  To study the attitudes, concerns, perceived impact, coping strategies, knowledge on avian influenza (AI) and personal protection measures, and institutional and personal preparedness for AI among all Indonesian primary healthcare workers (PHW).

Methods  Questionnaire survey of PHW from four public primary healthcare clinics in South Jakarta (n = 333), with Singaporean PHW from 18 such clinics as controls (n = 1321). Twelve focus group discussions with 51 South Jakarta PHW were also conducted. Quantitative and qualitative data were analysed separately with statistical and thematic analysis, respectively, then combined.

Results  South Jakarta PHW had positive attitudes but major concerns about contracting AI, difficulties in diagnosing human AI and inadequacy of personal protection provided. South Jakarta PHW are less knowledgeable about AI and use of personal protection equipment, and reported poorer awareness, availability and participation in AI preparation activities. Only 3% of South Jakarta PHW received influenza vaccination in the preceding 6 months and few felt prepared for AI.

Conclusions  South Jakarta primary healthcare workers are not well prepared for avian influenza. There is an urgent need to build their primary healthcare capacity to protect them and contain this global health threat.
CD36 deficiency protects against malarial anaemia in children by reducing Plasmodium falciparum‐infected red blood cell adherence to vascular endothelium
Authors: Chilongola Jaffu , Balthazary Sakurani , Mpina Maximillian , Mhando Martin , Mbugi Erasto
Published: April 2009

Objective  CD36 is a receptor that occurs on the surface of activated immune cells, vascular endothelial cells and participates in phagocytosis and lipid metabolism. CD36 is known to be the major endothelial receptor molecule for field isolates of Plasmodium falciparum. A T1264G mutation in exon X of the gene leads to deficiency of CD36. This study aimed at determining associations between CD36 deficiency, P. falciparum in vitro adherence on purified CD36 and anaemia among children in an endemic area.

Methods  Genotypes were determined by nested polymerase chain reaction of isolated DNA from filter blood spots followed by Restriction Fragment Length Polymorphism (RFLP). Plasmodium falciparum adherence assays were performed on immobilized purified CD36.

Results  The data indicate that CD36 is an important cytoadherence receptor that mediates adherence to most P. falciparum field isolates. Our findings also suggest that mutations causing CD36 deficiency may confer significant protection against malarial anaemia (MA) in children (χ2 = 8.58, P < 0.01).

Conclusion  That the protective role that CD36 deficiency may confer against MA in children seems to be mediated through reduced cytoadherence of infected red blood cells to vascular endothelium.
Severe vitamin D deficiency among heart and liver transplant recipients
Authors: Stein Emily M. , Cohen Adi , Freeby Matthew , Rogers Halley , Kokolus Shannon , Scott Vanessa , Mancini Donna , Restaino Susan , Brown Robert , McMahon Donald J. , Shane Elizabeth
Published: April 2009

Abstract:  Introduction:  Although patients with end‐stage organ failure are at high risk for vitamin D deficiency because of limited sunlight exposure and hepatic dysfunction, few studies have measured 25‐hydroxy vitamin D (25OHD) at the time of transplantation.

Methods:  We measured serum 25OHD immediately after transplantation in 69 heart and liver transplant recipients.

Results:  Forty‐six heart and 23 liver transplant recipients were evaluated (mean age 53 yr). Mean 25OHD was well below the lower limit of the normal range (43.2 ± 21.2 nmol/L). Ninety‐one percent had levels below 75 nmol/L, the threshold commonly used to denote sufficiency, and 71% had levels below 50 nmol/L. Severe deficiency (25OHD <25 nmol/L) was found in 16%. Vitamin D levels did not differ by race, age, gender, or season. Mean 25OHD was lower among liver than heart transplant recipients (34.4 ± 17.5 vs. 47.7 ± 20.7 nmol/L; p < 0.03). Among liver transplant recipients, 22% had undetectable levels (<17 nmol/L).

Conclusions:  Vitamin D deficiency is highly prevalent among heart and liver transplant recipients; those with liver failure are at greatest risk. As vitamin D deficiency has many serious skeletal and extra‐skeletal sequelae, physicians who treat transplant patients should maintain a high degree of vigilance for this problem.
Anaesthesiological considerations on tocolytic and uterotonic therapy in obstetrics
Authors: VERCAUTEREN M. , PALIT Ş. , SOETENS F. , JACQUEMYN Y. , ALAHUHTA S.
Published: April 2009

Aim: Significant side effects of tocolytic and uterotonic substances may be of concern to the anaesthesiologist. Recently, new drugs have been introduced having less side effects for both the mother and the neonate.

Methods: A literature search was undertaken mainly focusing on meta‐analyses, to review the possible side effects that might affect the course of anaesthesia and to suggest which precautions should be considered to prevent the occurrence of significant interactions with anaesthetic manipulations and drugs.

Results: Magnesium sulphate has a proven benefit in lowering systolic blood pressure and preventing the occurrence of eclampsia, but not as a tocolytic. β‐adrenergic agonists are being abandoned due to the availability of tocolytic agents causing less side effects. Calcium channel blockers (CCB) are frequently used but can cause major maternal cardiovascular complications. Nitroglycerin seems to be appreciated as an acute tocolytic rather than a routine substance during pre‐term labour. Cyclo‐oxygenase‐2 inhibitors are still under investigation but their tocolytic benefit is questionable mainly due to foetal side effects. Atosiban is considered the first‐choice tocolytic. With respect to oxytocic drugs, oxytocine, prostaglandines and methylergometrine may all cause serious side effects especially when combined. The cardiovascular side effects of prostaglandins and methylergometrine can be life‐threatening. Both oxytocin and carbetocin have a rather low risk for maternal complications.

Conclusion: Atosiban and CCB are at least as effective tocolytic agents as β‐mimetics but have significantly less side effects. Magnesium sulphate can cause neuromuscular blockade, especially when combined with CCB. Concerning oxytocic agents, short‐acting oxyctocin and long‐acting carbetocin have the least side effects as compared with prostaglandins and methylergometrine.
Sensory function and pain in a population of patients treated for breast cancer
Authors: VILHOLM O. J. , COLD S. , RASMUSSEN L. , SINDRUP S. H.
Published: April 2009

Background: Chronic pain is often reported after surgery for breast cancer. This study examined pain and sensory abnormalities in women following breast cancer surgery.

Methods: Sensory tests were carried out on the operated and contra‐lateral side in 55 women with chronic pain after breast cancer treatment and in a reference group of 27 pain‐free women, who had also undergone treatment for breast cancer. Testing included a numeric rating score of spontaneous pain, detection and pain threshold to thermal and dynamic mechanical stimuli and temporal summation to repetitive pinprick stimulation. The neuropathic pain symptom inventory was applied for participants with chronic pain.

Results: The mean age was 58.6 years for the pain patients and 60.6 years for the pain‐free patients. Thermal thresholds were significantly higher on the operated side than on the contra‐lateral side in both groups and side difference in warmth detection threshold was significantly higher in the pain group than in the pain‐free group (mean 3.8 °C vs. 1.1 °C, P=0.01). The frequency of cold allodynia was higher in participants with pain than in pain‐free participants (15/53 vs. 1/25, P=0.01), and the frequency of temporal summation evoked by repetitive pinprick was higher in participants with pain than in pain‐free participants (23/53 vs. 2/25, P=0.0009). The frequency of dynamic mechanical allodynia did not differ significantly between the two groups.

Conclusion: These findings suggest that chronic pain after surgery for breast cancer is associated with sensory hyperexcitability and is a neuropathic pain condition.
Oxytocin infusion: acute hyponatraemia, seizures and coma
Authors: BERGUM D. , LONNÉE H. , HAKLI T. F.
Published: April 2009

Hyponatremia is not uncommon, serious cases can cause dangerous complications as seizures, brain damage and even death. We present a case of a young mother with post partum hemorrhage and some of the serious complications.
Pulse oximeter perfusion index as an early indicator of sympathectomy after epidural anesthesia
Authors: GINOSAR Y. , WEINIGER C. F. , MEROZ Y. , KURZ V. , BDOLAH‐ABRAM T. , BABCHENKO A. , NITZAN M. , DAVIDSON E. M.
Published: April 2009

Background: The pulse oximeter perfusion index (PI) has been used to indicate sympathectomy‐induced vasodilatation. We hypothesized that pulse oximeter PI provides an earlier and clearer indication of sympathectomy following epidural anesthesia than skin temperature and arterial pressure.

Methods: Forty patients received lumbar epidural catheters. Patients were randomized to receive either 10 ml 0.5% bupivacaine or 10 ml 0.25% bupivacaine. PI in the toe, mean arterial pressure (MAP) and toe temperature were all assessed at baseline and at 5, 10 and 20 min following epidural anesthesia. The effect of epidural anesthesia over time was assessed by repeated measures analysis of variance. Additionally, we defined clinically evident sympathectomy criteria (a 100% increase in the PI, a 15% decrease in MAP and a 1 °C increase in toe temperature). The numbers of patients demonstrating these changes for each test were compared using the McNemar test for each time point.

Results: Twenty‐nine subjects had photoplethysmography signals that met a priori signal quality criteria for analysis. By 20 min, PI increased by 326%, compared with a 10% decrease and a 3% increase in MAP and toe temperature, respectively. For PI 15/29, 26/29 and 29/29 of the subjects met the sympathectomy criteria at 5, 10 and 20 min, respectively, compared with 4/29, 6/29 and 18/29 for MAP changes and 3/29, 8/29 and 14/29 for toe temperature changes.

Conclusions: PI was an earlier, clearer and more sensitive indicator of the development of epidural‐induced sympathectomy than either skin temperature or MAP.
Circulatory arrest in late pregnancy: caesarean section a vital decision for both mother and child
Authors: ZDOLSEK H. J. , HOLMGREN S. , WEDENBERG K. , LENNMARKEN C.
Published: April 2009

Circulatory arrest during pregnancy is extremely rare and there should be a well‐planned strategy for its management in all hospitals. To consider the priority of the mother's life over the child's and an unwarranted pre‐term delivery may lead to hesitancy and uncertainty and jeopardize both of them. In these situations, speed is a priority. Cardiopulmonary resuscitation should commence immediately. The anaesthesiologist should be well aware of the possible advantage of a caesarean section. Even if the obstetrician is responsible for the decision to perform the operation, the anaesthesiologist should strongly support the action. An ‘emergency caesarean kit’ with the essential surgical instruments should be immediately available in every labour ward and emergency department.
Pulmonary edema in the transurethral resection syndrome induced with mannitol 5%
Authors: WANG J. H. , HE Q. , LIU Y. L. , HAHN R. G.
Published: April 2009

Two patients developed the transurethral resection (TUR) syndrome after having absorbed mannitol 5% during TUR of the prostate. Both developed pulmonary edema and became severely hypoatremic (lowest serum sodium 99 and 97 mmol/l, respectively). Hypertonic saline was infused to raise the serum sodium level and plasma volume expansion used to combat hypotension. One patient also required positive‐pressure ventilation and intravenous administration of norepinephrine. Both patients recovered completely
Cerebral epidural hematoma following cerebrospinal fluid drainage during thoracoabdominal aortic repair
Authors: JEONG Y. B. , CHOI W. J. , HAN S. H. , CHOI I. C.
Published: April 2009

Cerebrospinal fluid (CSF) drainage is a common adjunct to thoracoabdominal aortic aneurysm (TAAA) repair. CSF drainage may improve perioperative spinal cord perfusion and thereby decrease the incidence of paraplegia or paraparesis. Complications of CSF drainage may arise. We present a case of cerebral epidural hematoma (EDH), possibly arising from excessive CSF drainage, during thoracoabdominal aortic repair.
Genetic variability of heat tolerance, and its effect on yield and fibre quality traits in upland cotton (Gossypium hirsutum L.)
Authors: Azhar F. M. , Ali Z. , Akhtar M. M. , Khan A. A. , Trethowan R.
Published: April 2009

Global temperature is rising because of increasing concentrations of CO2 and other greenhouse gases (e.g. methane, nitrous oxide, etc.) in the atmosphere because of the excessive use of fossil fuels. High temperature causes heat stress which reduces crop productivity. The development of heat‐tolerant varieties is feasible and will help mitigate the effects of climate change. Fifty‐one cotton accessions were screened in heat‐stressed and non‐stressed conditions in the glasshouse and field. Relative cell injury percentage (RCI %), a measure of cell membrane thermostability (CMT), was used to assess heat tolerance. Heat‐tolerant accessions had more stable yield and yielded more seed cotton with better quality fibre than the heat‐intolerant accessions across four environments. The responses of the 51 accessions to all four environments for the measured traits were strongly associated. RCI % of the accessions and hybrids was strongly and negatively associated with yield and fibre traits. CMT was concluded to be a useful technique for identification of heat‐tolerant cotton.
Inhibitory effect of 1,8‐cineole on guinea‐pig airway challenged with ovalbumin involves a preferential action on electromechanical coupling
Authors: Bastos Vasco PD , Brito Teresinha S , Lima Francisco JB , Pinho João PM , Lahlou Saad , Abreu Matos Francisco J , Santos Armênio A , Caldas Magalhães Pedro J
Published: April 2009

1,8‐Cineole is a terpenoid constituent of essential oils with anti‐inflammatory properties. It reduces the neural excitability, functions as an antinociceptive agent and has myorelaxant actions in guinea‐pig airways. The aim of the present study was to investigate the mechanism underlying the myorelaxant effects of 1,8‐cineole in guinea‐pig isolated trachea from either naïve guinea‐pigs or ovalbumin (OVA)‐sensitized animals subjected to antigenic challenge.

Isometric recordings were made of the tone of isolated tracheal rings. Rings with an intact epithelium relaxed beyond basal tone in the presence of 1,8‐cineole (6.5 × 10−6to 2 × 10−2 mol/L) in a concentration‐dependent manner (P < 0.001,anova) with a pD2value of 2.23 (95% confidence interval 2.10–2.37). Removal of the epithelium or pretreatment of intact tissue for 15 min with 50 µmol/LNG‐nitro‐l‐arginine methyl ester, 5 mmol/L tetraethylammonium, 0.5 µmol/L tetrodotoxin or 5 µmol/L propranolol did not alter the potency (pD2) or the maximal myorelaxant effect (Emax) of 1,8‐cineole.

1,8‐Cineole also significantly decreased the Schultz‐Dale contraction induced by OVA, mainly in preparations from OVA‐sensitized animals submitted to antigen challenge. 1,8‐Cineole decreased tracheal hyperresponsiveness to KCl and carbachol caused by antigen challenge and almost abolished the concentration–response curves to KCl, whereas it had little effect on the concentration–response curves to carbachol. Under Ca2+‐free conditions and in the presence of 10−4 mol/L acetylcholine, neither 1,8‐cineole (6.5 × 10−3 mol/L) nor verapamil (1 × 10−5 mol/L) affected Ca2+‐induced contractions, but they almost abolished Ba2+‐induced contractions.

In conclusion, the findings of the present study show that 1,8‐cineole is a tracheal myorelaxant that acts preferentially on contractile responses elicited electromechanically.