bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Potato mop-top virus in Potato Tubers and Sprouts: Combinations of RNA2 and RNA3 Variants and Incidence of Symptomless Infections
Authors: Latvala-Kilby Satu , Aura Johanna M. , Pupola Neda , Hannukkala Asko , Valkonen Jari P. T.
Published: April 2009

Potato mop-top virus (PMTV, genus Pomovirus) causes severe quality problems by inducing necrotic arcs (spraing symptoms) in potato tubers. In this study, coat protein (CP) gene and read-through domain of RNA2 and 8K gene and 3′ untranslated region of RNA3 were characterized from 37 PMTV isolates detected in tubers from fields in Finland and a screenhouse in Latvia. Two distinguishable types of RNA2 and RNA3 were found, each showing only little genetic variability. Sequencing and restriction fragment length polymorphism analysis of polymerase chain reaction amplicons indicated that the majority of PMTV isolates infecting tubers comprise restrictotypes RNA2-II and RNA3-B. The incidence of PMTV-infected tubers in 2006 (2007) was 55 (60), 33 (39), and 62 (68)% in cvs. Kardal, Saturna, and Nicola, respectively, grown in the same field in 2006 (2007). Incidence of PMTV-infected tubers that were symptomless was 100 (90)% in Kardal and 88 (44)% in Saturna, and also high in cvs. Bintje (95%) and Van Gogh (63%), tested only in 2006, whereas it was only 12 (2)% in Nicola. Hence, reliance on visual inspection of spraing will miss a large proportion of infected tubers and risk spreading PMTV to new fields in seed tubers. No specific combination of the types of RNA2 and RNA3 was associated with spraing-expressing or symptomless tubers. Using recombinant PMTV CP for comparison, the concentrations of PMTV CP in tuber and sprout tissue were estimated to reach 57 μg/g. Sprout sap interfered less with enzyme-linked immunosorbent assay than did tuber sap.
Validation of Consensus Quantitative Trait Loci Associated with Resistance to Multiple Foliar Pathogens of Maize
Authors: Asea Godfrey , Vivek Bindiganavile S. , Bigirwa George , Lipps Patrick E. , Pratt Richard C.
Published: April 2009

Maize production in sub-Saharan Africa incurs serious losses to epiphytotics of foliar diseases. Quantitative trait loci conditioning partial resistance (rQTL) to infection by causal agents of gray leaf spot (GLS), northern corn leaf blight (NCLB), and maize streak have been reported. Our objectives were to identify simple-sequence repeat (SSR) molecular markers linked to consensus rQTL and one recently identified rQTL associated with GLS, and to determine their suitability as tools for selection of improved host resistance. We conducted evaluations of disease severity phenotypes in separate field nurseries, each containing 410 F2:3 families derived from a cross between maize inbred CML202 (NCLB and maize streak resistant) and VP31 (a GLS-resistant breeding line) that possess complimentary rQTL. F2:3 families were selected for resistance based on genotypic (SSR marker), phenotypic, or combined data and the selected F3:4 families were reevaluated. Phenotypic values associated with SSR markers for consensus rQTL in bins 4.08 for GLS, 5.04 for NCLB, and 1.04 for maize streak significantly reduced disease severity in both generations based on single-factor analysis of variance and marker-interval analysis. These results were consistent with the presence of homozygous resistant parent alleles, except in bin 8.06, where markers were contributed by the NCLB-susceptible parent. Only one marker associated with resistance could be confirmed in bins 2.09 (GLS) and 3.06 (NCLB), illustrating the need for more robust rQTL discovery, fine-mapping, and validation prior to undertaking marker-based selection.
Elucidation of the Disease Cycle of Olive Anthracnose Caused byColletotrichum acutatum
Authors: Moral Juan , de Oliveira Rodrígues , Trapero Antonio
Published: April 2009

Anthracnose, caused by Colletotrichum acutatum and C. gloeosporioides, is a major fungal disease of olive in many countries. In Spain, the disease has been associated only with a characteristic rot and mummification of mature fruit. The purpose of this study was to determine whether C. acutatum could infect other plant tissues that may serve as sources of inoculum for anthracnose epidemics. Inoculations of young plants or detached leaves and field observations demonstrated that flowers and immature olive fruit are susceptible to the pathogen. Flower infection caused blight of inflorescences and infection of developing fruit. Immature fruit were infected in all phenological stages, although infection remained latent for 7 to 8 months, until the onset of fruit ripening. Fruit susceptibility increased and latent period decreased with maturity. Fruit were required for symptom development on inoculated plants. Plants without fruit were infected but they did not show any disease symptoms. Only plants with rotten fruit developed leaf wilting and branch dieback symptoms several weeks later. These results, together with the low level of pathogen isolation from affected leaves and branches and the toxicity of sterile fungal extracts to olive cuttings, suggest that a toxic substance produced by C. acutatum in rotten fruit may account for this syndrome. Both disease syndromes, fruit rot and branch dieback, developed in several olive cultivars, which were equally susceptible to the pathogen. However, olive cultivars differed in their response to flower and fruit infection. Latent infection of developing fruit during the spring may permit survival of the pathogen during the hot and dry summer and serve as an inoculum source for anthracnose epidemics that develop on ripening fruit in autumn.
Sensitive Detection of Fusarium circinatum in Pine Seed by Combining an Enrichment Procedure with a Real-Time Polymerase Chain Reaction Using Dual-Labeled Probe Chemistry
Authors: Ioos Renaud , Fourrier Céline , Iancu Gabriela , Gordon Thomas R.
Published: April 2009

Fusarium circinatum is the causal agent of pitch canker disease on numerous Pinus spp. This aggressive fungus may infect pine seed cryptically and, therefore, can easily be spread long distances by the seed trade. F. circinatum has recently been listed as a quarantine organism in numerous countries throughout the world, which prompted the development of a specific and sensitive tool for the detection of this pathogen in conifer seed. A new detection protocol for F. circinatum based on a biological enrichment step followed by a real-time polymerase chain reaction (PCR) assay was developed. Several enrichment protocols were compared and a 72-h incubation of the seed with potato dextrose broth was the most efficient technique to increase F. circinatum biomass before DNA extraction. The relative accuracy, specificity, and sensitivity of the real-time PCR assay was evaluated in comparison with a previously published conventional PCR test on 420 seed DNA extracts. The real-time PCR described here proved to be highly specific and significantly more sensitive than the conventional PCR, and enabled the detection of F. circinatum in samples artificially contaminated with less than 1/1,000 infected seed, as well as in naturally infected samples. Last, in order to routinely check the quality of the seed DNA extracts, a primer–probe combination that targets a highly conserved region within the 18S ribosomal DNA in plants or fungi was successfully developed. This assay allows for quick and reliable detection of F. circinatum in seed, which can help to prevent long-distance spread of the pathogen via contaminated seed lots.
Use of Cross-Flow Membrane Filtration in a Recirculating Hydroponic System to Suppress Root Disease in Pepper Caused by Pythium myriotylum
Authors: Schuerger Andrew C. , Hammer William
Published: April 2009

Zoosporic pathogens in the genera Pythium and Phytophthora cause extensive root disease epiphytotics in recirculating hydroponic vegetable-production greenhouses. Zoospore cysts of Pythium myriotylum Drechsler were used to evaluate the effectiveness of cross-flow membrane filters to control pythiaceous pathogens in recirculating hydroponic systems. Four membrane filter brands (Honeycomb, Polypure, Polymate, and Absolife) were tested alone or in combination to determine which filters would effectively remove infective propagules of P. myriotylum from solutions and reduce disease incidence and severity. Zoospore cysts of P. myriotylum generally measured 8 to 10 μm, and it was hypothesized that filters with pore-sizes <5 μm would be effective at removing 100% of the infective propagules and protect pepper plants from root infection. Single-filter assays with Honeycomb and Polypure brands removed 85 to 95% of zoospore cysts when pore sizes were rated at 1, 5, 10, 20, or 30 μm. Single-filter assays of Polymate and Absolife brands were more effective, exhibiting apparently 100% removal of zoospore cysts from nutrient solutions on filters rated at 1 to 10 μm. However, plant bioassays with Honeycomb and Polymate single filters failed to give long-term protection of pepper plants. Double-filter assays with 1- and 0.5-μm Polymate filters significantly increased the protection of pepper plants grown in nutrient film technique systems but, eventually, root disease and plant wilt could be observed. Insect transmissions by shore flies were not factors in disease development. Scanning electron microscopy images of zoospore cysts entrapped on Polymate filters revealed zoospore cysts that were either fully encysted, partially encysted, or of unusually small size (3 μm in diameter). It was concluded that either the atypically small or pliable pleomorphic zoospore cysts were able to penetrate filter membranes that theoretically should have captured them.
Arabidopsis Actin-Depolymerizing Factor AtADF4 Mediates Defense Signal Transduction Triggered by thePseudomonas syringaeEffector AvrPphB
Authors: Tian Miaoying , Chaudhry Faisal , Ruzicka Daniel R. , Meagher Richard B. , Staiger Christopher J. , Day Brad
Published: April 2009

The actin cytoskeleton has been implicated in plant defenses against pathogenic fungi and oomycetes with limited, indirect evidence. To date, there are no reports linking actin with resistance against phytopathogenic bacteria. The dynamic behavior of actin filaments is regulated by a diverse array of actin-binding proteins, among which is the Actin-Depolymerizing Factor (ADF) family of proteins. Here, we demonstrate that actin dynamics play a role in the activation of gene-for-gene resistance in Arabidopsis (Arabidopsis thaliana) following inoculation with the phytopathogenic bacterium Pseudomonas syringae pv tomato. Using a reverse genetics approach, we explored the roles of Arabidopsis ADFs in plant defenses. AtADF4 was identified as being specifically required for resistance triggered by the effector AvrPphB but not AvrRpt2 or AvrB. Recombinant AtADF4 bound to monomeric actin (G-actin) with a marked preference for the ADP-loaded form and inhibited the rate of nucleotide exchange on G-actin, indicating that AtADF4 is a bona fide actin-depolymerizing factor. Exogenous application of the actin-disrupting agent cytochalasin D partially rescued the Atadf4 mutant in the AvrPphB-mediated hypersensitive response, demonstrating that AtADF4 mediates defense signaling through modification of the actin cytoskeleton. Unlike the mechanism by which the actin cytoskeleton confers resistance against fungi and oomycetes, AtADF4 is not involved in resistance against pathogen entry. Collectively, this study identifies AtADF4 as a novel component of the plant defense signaling pathway and provides strong evidence for actin dynamics as a primary component that orchestrates plant defenses against P. syringae.
Postgraduate Teacher Education (Art and Design) 'Wising‐up' or 'Dumbing‐down'
Authors: Davies Tom
Published: April 2009

This research is part of an on‐going investigation into student teachers' perceptions of theory and practice within Initial Teacher Training [ITT] and beyond. Respondents were drawn from a number of specialist ITT providers, and supple‐mented from other sources. [1] The enquiry grew out of earlier research into examination courses in Key Stage 4 and teachers' dependency on 'orthodox' approaches and content. [2] The likelihood of challenging or breaking down this dependency seemed to rely on student teachers' ability to critique current practices and speculate as to alternatives, which is made more problem‐ atic because of the drastic reduction of time allocation in ITT. [3] This report in part is predicated on the belief that the enforced, crude division of time spent in, and out, of schools polarises theory and practice in the minds of students. This, in turn, tends to undermine the opportunities to explore and experiment with teaching and learning styles, and the degree to which students value and employ theory and make use of, and extend, their subject knowledge. [4]
Classification of OprD sequence and correlation with antimicrobial activity of carbapenem agents in Pseudomonas aeruginosa clinical isolates collected in Japan
Authors: Sanbongi Yumiko , Shimizu Atsuyuki , Suzuki Takahisa , Nagaso Hiroshi , Ida Takashi , Maebashi Kazunori , Gotoh Naomasa
Published: April 2009

A total of 99 clinical isolates of metallo‐ß‐lactamase‐negative Pseudomonas aeruginosa collected in Japan between 1998 and 2001 were studied for their susceptibilities to carbapenem agents and corresponding oprD gene mutations. The OprD sequence of each strain was grouped into two major classes, based on the pattern of alterations. Eighty strains (80.8%) were so‐called ‘full length type’, whose OprD proteins were fully encoded. The remaining 19 strains (19.2%) were so‐called ‘defective type’, which possessed deletions or major alterations that might cause conformational changes in the OprD porin protein. The changes in ‘defective type’ strains led to 15‐, 17‐ and 23‐fold increases in the geometric mean MIC for imipenem, meropenem and biapenem compared with ‘full length type’ strains, respectively. ‘Full length type’ strains were further classified into six carbapenem susceptible types with the exception of four carbapenem‐resistant subtypes with additional amino acid substitutions at D43, G183, R154, G314, G316. However, ‘defective type’ strains were classified into four types as follows: 10 strains which contained a stop codon within the coding region; six strains which contained IS; one strain with a short deletion near the C‐terminal domain; and two strains without a stop codon in the sequenced region. Western blot analysis using OprD antibody showed that binding abilities of OprD proteins against ‘full length type’ strains were normal, whereas those against ‘defective type’ strains were lost without exception. These results indicate that OprD structure and antimicrobial activities for carbapenem agents proved to be highly correlated in P. aeruginosa
Effect of GM‐CSF on cytokine induction by soluble β‐glucan SCG in vitro in β‐glucan‐treated mice
Authors: Hida Toshie H. , Kawaminami Hiromi , Ishibashi Ken‐ichi , Miura Noriko N. , Adachi Yoshiyuki , Yadomae Toshiro , Ohno Naohito
Published: April 2009

SCG is a 6‐branched 1,3‐β‐d‐glucan, which are major cell wall structural components in fungi. Leukocytes from DBA/1 and DBA/2 mice are highly sensitive to SCG, producing cytokines such as GM‐CSF, IFN‐γ, TNF‐α and IL‐12p70, but not IL‐6. GM‐CSF plays a key biological role in this activity. In the present study, we examined the effect of giving i.p. SCG to DBA/2 mice on cytokine production in vitro. SCG was given i.p. to DBA/2 mice on day 0. Splenocytes were prepared on day 7 and cultured in the presence of SCG in vitro. The levels of cytokine production induced by SCG in vitro were lower in the cells from SCG‐treated mice than in control mice. Expression of the β‐glucan receptor, dectin‐1, in SCG‐treated mice was comparable with that shown in control mice. However, the consumption of exogenously added rmGM‐CSF in vitro was observed in SCG‐treated mice. The addition of a large amount of rmGM‐CSF to the culture medium resulted in larger amounts of TNF‐α and IL‐6 in SCG‐treated mice than in normal mice. These results suggested that GM‐CSF was closely related with the reactivity of β‐glucan. Giving SCG increased the number of macrophages and granulocytes in the spleen. These results suggested that in SCG‐treated mice, a change of cell population would be related to modulation of the profile of cytokine production induced by SCG in vitro.
Mechanisms of change in motivational interviewing: a review and preliminary evaluation of the evidence
Authors: Apodaca Timothy R. , Longabaugh Richard
Published: April 2009

Aims  Motivational interviewing (MI) is an efficacious treatment for substance use disorders. However, little is known about how MI exerts its therapeutic effects. This review is a first attempt to summarize and evaluate the evidence for purported within‐session mechanisms of change. The primary question of interest was: which MI constructs and variables appear to be the most promising candidates for mechanisms of change?

Methods  Literature searches were conducted to identify studies delivering MI in an individual format for the treatment of substance use disorders. Our search identified a total of 152 studies for review; 19 studies met inclusion criteria by providing data on at least one link in the causal chain model under examination. Effect size estimates were calculated for every possible step in the causal model where sufficient data were provided by study authors.

Results  Four constructs of therapist behavior were evaluated: MI‐Spirit, MI‐Consistent behaviors, MI‐Inconsistent behaviors and therapist use of specific techniques. Five constructs of client behavior were evaluated: change talk/intention, readiness to change, involvement/engagement, resistance and the client's experience of discrepancy. The absence of experimental and full mediation studies of mechanisms of change was notable. Effect sizes were generally mixed.

Conclusions  The most consistent evidence was found for three constructs: client change talk/intention (related to better outcomes); client experience of discrepancy (related to better outcomes); and therapist MI‐Inconsistent behavior (related to worse outcomes). Regarding therapist use of specific techniques, use of a decisional balance exercise showed the strongest association to better outcomes.
An analysis of cocaine powder in the Netherlands: content and health hazards due to adulterants
Authors: Brunt Tibor M. , Rigter Sander , Hoek Jani , Vogels Neeltje , Van Dijk Peter , Niesink Raymond J. M.
Published: April 2009

Aims To report on trends in the content and adulterants present in street cocaine (powder) in the Netherlands and to describe the associated health hazards.

Design and participants Drug consumers handed in samples of cocaine powder from 1999 to 2007 for analysis. Reports were compiled of users' experiences with the samples received.

Measurements and analysis Linear regression analysis was used to assess the trend in adulterated cocaine powder across the study period, and comparison of reported adverse effects of adulterated with those of unadulterated cocaine by Fisher's exact test.

Findings There has been a statistically significant upward trend in the occurrence of adulterated cocaine powder over the years. Adulterated cocaine was associated more frequently with reported adverse effects than unadulterated cocaine. Phenacetin, hydroxyzine and diltiazem appeared to be three adulterants contributing to these adverse effects.

Conclusions An increase in adulterants was detected in the analysed cocaine powder between 1999 and 2007. This increase is associated with relatively more adverse effects with cocaine use. The cardiac and hallucinatory effects that were reported more frequently are not understood clearly. Adverse effects are likely to be due to several factors, including interactions of adulterants with cocaine and the route of administration.
Reduced affective symptoms during tobacco dependence treatment with varenicline
Authors: Grosshans Martin , Mutschler Jochen , Hermann Derik , Mann Karl , Diehl Alexander
Published: April 2009

Background  The nicotinic acetylcholine receptor partial agonist varenicline has been shown to be effective in the treatment of tobacco dependence, but has been reported to induce exacerbations of psychiatric symptoms in subjects with pre‐existing psychiatric disorders.

Case description  We report a tobacco‐dependent patient who developed depression and suicidal tendencies during several cessation attempts, but was finally able to stay nicotine‐abstinent by taking varenicline.

Conclusion  In this case varenicline did not lead to exacerbation but appeared to improve the affective symptoms.
Comparing the effects of entertainment media and tobacco marketing on youth smoking in Germany
Authors: Sargent James D. , Hanewinkel Reiner
Published: April 2009

Aims  To examine differential effects of smoking in films and tobacco advertising on adolescent smoking. We hypothesize that movie smoking will have greater effects on smoking initiation, whereas tobacco advertising receptivity will primarily affect experimentation.

Design  Longitudinal observational study of adolescents.

Setting  School‐based surveys conducted in Schleswig‐Holstein, Germany.

Participants  A total of 4384 adolescents age 11–15 years at baseline and re‐surveyed 1 year later; ever smoking prevalence was 38% at time 1.

Measurements  The main outcome variable combined two items assessing life‐time and current smoking (alpha = 0.87). Baseline never smokers were analyzed separately from those who had tried smoking (ever smokers). Exposure to smoking in 398 internationally distributed US movies was modeled as a continuous variable, with 0 corresponding to the 5th percentile and 1 to the 95th percentile of exposure. Tobacco marketing receptivity consisted of naming a brand for a favorite tobacco advertisement. Ordinal logistic regressions controlled for socio‐demographics, other social influences, personality characteristics of the adolescent and parenting style.

Findings  Whereas 34% of ever smokers were receptive to tobacco marketing at time 1, only 6% of never smokers were. Among time 1 never smokers, exposure to movie smoking was a significantly stronger predictor of higher time 2 smoking level [adjusted proportional odds ratio = 2.76, 95% confidence interval (1.84, 4.15)] than was tobacco marketing receptivity (1.53 [1.07, 2.20]). Among time 1 ever smokers, both tobacco marketing receptivity and exposure to movie smoking predicted higher levels of time 2 smoking [2.17 (1.78, 2.63) and 1.62 (1.18, 2.23), respectively], and the two estimates were not significantly different.

Conclusions  In this longitudinal study, exposure to movie smoking was a stronger predictor of smoking initiation than tobacco marketing receptivity, which was more common among ever smokers. The results suggest that entertainment media smoking should be emphasized in programs aimed at preventing onset, and both exposures should be emphasized in programs aimed at experimental smokers.
Assessing motivation to quit smoking in people with mental illness: a review
Authors: Siru Ranita , Hulse Gary K. , Tait Robert J.
Published: April 2009

Background  People with mental health (MH) disorders smoke at higher rates, are more nicotine‐dependent and suffer greater morbidity and mortality from smoking‐related illnesses than the general population. Helping these people to quit smoking is a public health priority; however, many MH professionals assume that those with mental illness are not motivated to quit.

Objectives  To use predetermined criteria to identify, review critically and evaluate empirically all English language, peer‐reviewed data on motivation to quit smoking in MH populations.

Methods  A systematic search was conducted and key data on subject characteristics, measures of motivation and other variables abstracted. χ2 analyses were used to compare motivation between MH and general populations, between in‐patients and out‐patients and between people with depression and people with psychotic disorders.

Results  Evidence suggests that people with MH disorders are as motivated to quit smoking as the general population, although those with psychotic disorders may be less motivated than individuals with depression. Although readiness to cease smoking was assessed in 14 studies, only two evaluated motivation to quit smoking in in‐patient populations.

Conclusions  People with MH disorders are motivated to quit smoking, although more research is needed looking at in‐patient populations. The commonly held false belief that people with MH disorders are not motivated to cease smoking means that opportunities to encourage smoking cessation among this disenfranchised group are being missed.
Addiction research centres and the nurturing of creativity: The Swiss Institute for the Prevention of Alcohol and Drug Problems. Past, present and future
Authors: Kuntsche Emmanuel , Maffli Etienne , Kuntsche Sandra , Delgrande Jordan Marina
Published: April 2009

The aim of this paper is to offer an account of the history, the current status and the future of substance use research at the Swiss Institute for the Prevention of Alcohol and Drug Problems (SIPA). Although founded originally by the temperance movement in 1901, its policy has shifted over time towards one which accepts an alcohol‐consuming culture made up of self‐determined but well‐informed consumers, while still supporting those who choose to live an abstinent life. In the beginning, SIPA was involved primarily in collecting alcohol‐related information and making it available to professionals and the general public. From the late 1960s SIPA began conducting its own research projects; by the mid‐1970s it had set up its own in‐house research department. In 2001, SIPA was appointed a World Health Organization (WHO) Collaborating Centre for Substance Abuse, Research, Prevention and Documentation. As a private non‐governmental organization, most of its funding comes from external research commissions. SIPA participates in a variety of international projects [e.g. Gender Alcohol and Culture: An International Study (GenACIS), European School Survey Project on Alcohol and Drugs (ESPAD) and Health Behaviour in School‐aged Children (HBSC)] and contributes to numerous national research projects dealing with substance use. It has also forged close links with more than 50 other research institutions in Switzerland and world‐wide. Thanks to its work over the last 30 years, SIPA has become a chief port of call for alcohol use research in Switzerland. In the future, SIPA will continue to monitor substance use, while stepping up its prevention research activities and ensuring that it is able to react more promptly to emerging phenomena.
Improving substance abuse treatment enrollment in community syringe exchangers
Authors: Kidorf Michael , King Van L. , Neufeld Karin , Peirce Jessica , Kolodner Ken , Brooner Robert K.
Published: April 2009

Aims  The present study evaluated the effectiveness of an intervention combining motivational enhancement and treatment readiness groups, with and without monetary incentives for attendance and treatment enrollment, on enhancing rates of substance abuse treatment entry among new registrants at the Baltimore Needle Exchange Program (BNEP).

Design  Opioid‐dependent study participants (n = 281) referred by the BNEP were assigned randomly to one of three referral interventions: (i) eight individual motivational enhancement sessions and 16 treatment readiness group sessions (motivated referral condition—MRC); (ii) the MRC intervention with monetary incentives for attending sessions and enrolling in treatment—MRC+I); or (iii) a standard referral condition which directed participants back to the BNEP for referral (standard referral—SRC). Participants were followed for 4 months.

Findings  MRC+I participants were more likely to enroll in any type of treatment than MRC or SRC participants (52.1% versus 31.9% versus 35.5%; χ2 = 9.12, P = 0.01), and more likely to enroll in treatment including methadone than MRC or SRC participants (40.4% versus 20.2% versus 16.1%; χ2 = 16.65, P < 0.001). MRC+I participants also reported less heroin and injection use than MRC and SRC participants.

Conclusions  Syringe exchange sites can be effective platforms to motivate opioid users to enroll in substance abuse treatment and ultimately reduce drug use and number of drug injections.
Pressure volume curves of paediatric laryngeal mask airways
Authors: Wallace C. J. , Chambers N. A. , Erb T. O. , Von Ungern‐Sternberg B. S.
Published: April 2009

Hyperinflation of the laryngeal mask airway cuff may exert high pressure on pharyngeal and laryngeal structures. In vitro data show that high intra cuff pressures may occur when inflated to only 30% of the manufacturer’s recommended maximum inflation volume. We prospectively assessed the pressure volume curves of paediatric sized laryngeal mask airways (size 1–3) in 240 consecutive children (0–15 years). Following laryngeal mask airway insertion the cuff was inflated with 1‐ml increments of air up to the maximum recommended by the manufacturer. After each ml cuff pressure was measured. At the end all cuff pressures were adjusted to 55 cmH2O. The maximum recommended volume resulted in high intracuff pressures in all laryngeal mask airway brands and sizes studied. Approximately half the maximum volume produced a cuff pressure ≥ 60 cmH2O. This occurred in all brands and all sizes studied. We recommend that cuff manometers should be used to guide inflation in paediatric laryngeal mask airways.
Subacute pain and function after fast‐track hip and knee arthroplasty
Authors: Andersen L. Ø. , Gaarn‐Larsen L. , Kristensen B. B. , Husted H. , Otte K. S. , Kehlet H.
Published: April 2009

In a well‐defined fast‐track setup for total hip and knee arthroplasty, with a multimodal analgesic regimen consisting of intra‐operative local anaesthetic infiltration and oral celecoxib, gabapentin and paracetamol for 6 days postoperatively, we conducted a prospective, consecutive, observational study. The purpose was to describe the prevalence and intensity of subacute postoperative pain and opioid related side effects, use of analgesics and functional ability 1–10 and 30 days postoperatively. Fast‐track total hip and knee arthroplasty with early discharge (< 3 days) resulted in acceptable levels of pain and postoperative nausea and vomiting with concomitant low use of opioids in > 95% of patients after discharge before day 10 after total hip arthroplasty. However, after total knee arthroplasty 52% patients reported moderate pain (VAS 30–59 mm), and 16% severe pain (VAS ≥ 60 mm) when walking 1 month after surgery with a concomitant increase in the use of strong opioids. These results emphasise the need for improvement in analgesia after discharge following total knee arthroplasty, to facilitate rehabilitation.
Abdominal compartment syndrome during hip arthroscopy
Authors: Sharma A. , Sachdev H. , Gomillion M.
Published: April 2009

Hip arthroscopy is recognised as a highly effective means of treating joint disorders. The majority of complications associated with hip arthroscopy involve neurovascular traction injury. We report a relatively unusual complication of hip arthroscopy, extravasation of irrigation fluid into the retroperitoneal and intraperitoneal cavities, resulting in abdominal compartment syndrome.
Monosodium glutamate ‘allergy’: menace or myth?
Authors: Williams A. N. , Woessner K. M.
Published: April 2009

Monosodium glutamate (MSG) is a salt form of a non‐essential amino acid commonly used as a food additive for its unique flavour enhancing qualities. Since the first description of the ‘Monosodium glutamate symptom complex’, originally described in 1968 as the ‘Chinese restaurant syndrome’, a number of anecdotal reports and small clinical studies of variable quality have attributed a variety of symptoms to the dietary ingestion of MSG. Descriptions of MSG‐induced asthma, urticaria, angio‐oedema, and rhinitis have prompted some to suggest that MSG should be an aetiologic consideration in patients presenting with these conditions. This review prevents a critical review of the available literature related to the possible role of MSG in the so‐called ‘Chinese restaurant syndrome’ and in eliciting asthmatic bronchospasm, urticaria, angio‐oedema, and rhinitis. Despite concerns raised by early reports, decades of research have failed to demonstrate a clear and consistent relationship between MSG ingestion and the development of these conditions.
Allergen extract‐induced interleukin‐10 in human memory B cells inhibits immunoglobulin E production
Authors: Milovanovic M. , Heine G. , Zuberbier T. , Worm M.
Published: April 2009

Background
Elevated specific IgE antibody levels are common in atopic individuals, caused by T‐helper type 2‐dominated B cell activation. The induction of antigen‐specific IL‐10 secreting T cells is discussed as an important mechanism during specific immunotherapy. By contrast the presence and function of B cell‐derived IL‐10 is not well defined yet.

Objective
We investigated whether type‐I allergen extracts induce IL‐10 expression in human B cells and analysed its functional role on IgE production.

Methods
Human peripheral B cells were stimulated with grass pollen, house dust mite (HDM) (Dermatophagoides pteronyssimus; Der p) and dog allergen extract. Expression of IL‐10 by activated human B cells was determined by flow cytometric analysis and ELISA. Functional analysis considering immunoglobulin production was assayed by ELISA.

Results
The allergen extracts studied induced IL‐10 expression in B cells. However, the ability to induce IL‐10 differed between the allergen extracts. The most potent allergen extract was dog (169±28 pg/mL), followed by grass pollen (141±10 pg/mL) and HDM allergen (125±11 pg/mL). Upon allergen extract stimulation only CD27 expressing memory B cells produced IL‐10 and co‐expressed the very early activation antigen CD69. The addition of allergen extracts to B cells activated by anti‐CD40 and IL‐4 selectively inhibited IgE which was dependent on allergen extract‐induced IL‐10. By contrast the other immunoglobulin subclasses like IgA, IgG or IgM were not altered upon allergen extract challenge.

Conclusion
Our data indicate that allergen‐activated memory B cells can modulate IgE production through secretion of IL‐10.
Adiponectin levels in adolescent girls with polycystic ovary syndrome (PCOS)
Authors: Pinhas‐Hamiel Orit , Singer Sigal , Pilpel Nurit , Koren Ilana , Boyko Valentina , Hemi Rina , Pariente Clara , Kanety Hannah
Published: April 2009

Objective  To determine serum adiponectin concentrations in adolescent girls with and without polycystic ovary syndrome (PCOS) and to assess possible correlations of adiponectin levels with insulin and androgen levels.

Design  Prospective case–control study.

Setting  Endocrine clinics in the community.

Patients  Forty‐four adolescent girls were grouped as follows: 14 were overweight [body mass index (BMI) standard deviation score >1·645] with PCOS; 16 were lean (BMI SDS <1·036) with PCOS; and 14 were lean (BMI SDS <1·036) without PCOS.

Intervention  Blood samples were collected from all girls between 8 and 11 am, after an overnight fast.

Main outcome measures  Serum levels of adiponectin, leptin, insulin, Müllerian‐inhibiting substance, luteinizing hormone, follicle‐stimulating hormone, testosterone, 17‐alpha‐hydroxyprogesterone, androstendione, dehydroepiandrosterone sulphate (DHEAS) and 17β‐oestradiol.

Results  Adiponectin concentrations were significantly decreased in obese adolescents with PCOS (10·5 ± 5·5 μg/ml) compared with that in lean girls with or without PCOS (16·9 ± 8·64 and 18·0 ± 7·4 μg/ml respectively). Leptin levels were significantly elevated in obese adolescents with PCOS compared with the levels in normal weight adolescents with PCOS, and compared with that in normal weight controls. Insulin levels were markedly higher in obese adolescents with PCOS compared with that in normal weight adolescents (12·3 ± 12·2 vs. 4·5 ± 2·9, P < 0·05), and compared with that in normal weight PCOS adolescents (7·4 ± 4·9); however, this difference was not statistically significant. Insulin levels did not differ between normal weight adolescents with PCOS and normal controls. Adiponectin concentrations correlated inversely with BMI, leptin and insulin.

Conclusions  Hypoadiponectinaemia is evident only in obese adolescents with PCOS and therefore does not seem to be involved in the pathogenesis of PCOS in this age group.
Measuring patient‐reported outcomes in haemophilia clinical research
Authors: GLOBE D. , YOUNG N. L. , VON MACKENSEN S. , BULLINGER M. , WASSERMAN J. ,   AND ON BEHALF OF THE HEALTHRELATED QUALITY OF LIFE EXPERT WORKING GROUP OF THE INTERNATIONAL PROPHYLAXIS STUDY GROUP
Published: April 2009

Summary. Patient‐reported outcome (PRO) measures have been used to assess quality of life and health state preferences from the patient’s perspective. However, they have not been fully utilized in haemophilia clinical practice and research. A series of meetings were convened to review and document the state of the art in PROs relevant to haemophilia. Experts developed a process for selection of measures and identified published measures of health‐related quality of life (HRQoL) relevant to patients with haemophilia. These were synthesized and reviewed. Patient preference measures were also identified and reviewed. Although the majority of measures were developed for and validated in adults, several measures were identified for use in paediatric populations. This paper recommends an approach to the selection of PROs for application in haemophilia clinical research and practice and identifies several potential measures relevant for application in haemophilia clinical research and practice.
Combined homology modelling and evolutionary significance evaluation of missense mutations in blood clotting factor VIII to highlight aspects of structure and function
Authors: MARKOFF A. , GERKE V. , BOGDANOVA N.
Published: April 2009

Summary.  Most small lesions in the factor VIII (FVIII) gene that cause haemophilia A (HA) are single nucleotide substitutions resulting in amino acid replacing (missense) mutations and leading to various phenotypes, ranging from mild to severe. We took a combined approach of homology modelling and quantitative evaluation of evolutionary significance of amino acid replacing alterations using the Grantham Matrix Score (GMS) to assess their structural effects and significance of pathological expression. Comparative homology models of all amino acid substitutions summarized in the FVIII mutations database plus these identified and reported lately by us or by our collaborators were evaluated. Altogether 640 amino acid replacing mutations were scored for potential distant or local conformation changes, influence on the molecular stability and predicted contact residues, using available FVIII domain models. The average propensity to substitute amino acid residues by mutation was found comparable to the overall probability of de novo mutations. Missense changes reported with various HA phenotypes were all confirmed significant using GMS. The fraction of these, comprising residues apparently involved in intermolecular interactions, exceeds the average proportion of such residues for FVIII. Predicted contact residues changed through mutation were visualized on the surface of FVIII domains and their possible functional implications were verified from the literature and are discussed considering available structural information. Our predictive modelling adds on the current view of domain interface molecular contacts. This structural insight could aid in part to the design of engineered FVIII constructs for therapy, to possibly enhance their stability and prolong circulating lifetime.
Concomitant infusion of low doses of rFVIIa and FEIBA in haemophilia patients with inhibitors
Authors: MARTINOWITZ U. , LIVNAT T. , ZIVELIN A. , KENET G.
Published: April 2009

Summary.  Patients with severe haemophilia A and an inhibitor may become refractory to FEIBA and/or recombinant factor VIIa (rFVIIa). Sequential therapy with both products has been reported in such patients. In this pilot study, we examined the safety and efficacy of combined rFVIIa and FEIBA therapy in patients with haemophilia A and inhibitors during bleeding episodes. We also tried to evaluate whether thrombin generation (TG), by various mixtures of these agents, can serve as a guide for tailoring therapy. TG was measured in plasma taken from eight haemophilia A patients. Increasing concentrations of rFVIIa, FEIBA or both were added ex vivo to the plasmas, and TG was induced by recalcification. Since low concentrations of rFVIIa and FEIBA had either an additive or a synergistic effect in all patients, the lowest combination, yielding TG comparable or lower than TG achieved with either FEIBA 100 U kg−1 or rFVIIa 160 μg kg−1 alone, was selected for the treatment of bleeding episodes. Five patients with a high titre of an inhibitor (8–1300 BU), including one previously refractory to infusions of rFVIIa at doses up to 400 μg kg−1 X4 daily, were treated with combinations of 30–70 μg kg−1 rFVIIa and 20–30 U kg−1 FEIBA during a total number of 400 bleeding episodes with excellent haemostatic effect. No adverse events and no DIC were observed following these infusions. Concomitant infusion of low‐dose rFVIIa and low‐dose FEIBA, seems to be safe, efficacious and economical in patients refractory to rFVIIa and probably other haemophilia A patients with an inhibitor.
Comorbidities and bleeding pattern in elderly haemophilia A patients
Authors: MIESBACH W. , ALESCI S. , KREKELER S. , SEIFRIED E.
Published: April 2009

Summary.  The increasing numbers of comorbidities related to higher age and their treatment constitute a challenge in the treatment of haemophiliacs. Comparing prevalences of morbidities in the elderly haemophilia A population (n = 29) and the general elderly population of Germany reveals some differences. HCV infections are more frequent in the elderly haemophilia population (69% vs. 0.6%). Prevalence of cancer was five times higher than in the age matched general population (28% vs. 5.2%). Cardiac diseases seem to be less frequent although the prevalences of cardiovascular risk factors like hypertension, diabetes, and body mass index (BMI) >25 do not differ in comparison to the general population. A reduction of bleeding symptoms or dosage of FVIII could not be observed. There is a tendency of increasing bleeding symptoms with increasing age of the patients due to more frequent spontaneous joint bleedings, malignancies or treatment with phenprocoumon or ASA. In consequence, FVIII dosage had to be increased in eight patients (28%). Our patient population at the age >60 years is very small and no statistical evidence can be shown, therefore appropriate treatment of elderly haemophiliacs needs further evaluation in multicentre studies with sufficient patient numbers.
Increase in frequency of myeloid‐derived suppressor cells in mice with spontaneous pancreatic carcinoma
Authors: Zhao Fei , Obermann Sonja , Von Wasielewski Reinhard , Haile Lydia , Manns Michael P. , Korangy Firouzeh , Greten Tim F.
Published: April 2009

Pancreatic adenocarcinoma is one of the deadliest cancers with poor survival and limited treatment options. Immunotherapy is an attractive option for this cancer that needs to be further developed. Tumours have evolved a variety of mechanisms to suppress host immune responses. Understanding these responses is central in developing immunotherapy protocols. The aim of this study was to investigate potential immune suppressor mechanisms that might occur during development of pancreatic tumours. Myeloid‐derived suppressor cells (MDSC) from mice with spontaneous pancreatic tumours, mice with premalignant lesions as well as wild‐type mice were analysed. An increase in the frequency of MDSC early in tumour development was detected in lymph nodes, blood and pancreas of mice with premalignant lesions and increased further upon tumour progression. The MDSC from mice with pancreatic tumours have arginase activity and suppress T‐cell responses, which represent the hallmark functions of these cells. Our study suggests that immune suppressor mechanisms generated by tumours exist as early as premalignant lesions and increase with tumour progression. These results highlight the importance of blocking these suppressor mechanisms early in the disease in developing immunotherapy protocols.
Chimeric IgG4 PR3‐ANCA induces selective inflammatory responses from neutrophils through engagement of Fcγ receptors
Authors: Hussain Abdullah , Pankhurst Tanya , Goodall Margaret , Colman Rachel , Jefferis Royston , Savage Caroline O. S. , Williams Julie M.
Published: April 2009

Anti‐proteinase 3 antibodies are implicated in the pathogenesis of small vessel vasculitis. These are primarily immunoglobulin G (IgG), with different subclasses predominating at different stages of disease. However, little is known of their respective roles in pathogenesis. We have previously shown that patient IgG4 was able to induce superoxide release from human neutrophils. To circumvent difficulties in separating the subclasses and additional differences in polyclonal patient antibodies we have generated monoclonal mouse/human IgG1 and IgG4 anti‐proteinase 3 antibodies. Using these antibodies we have compared effects of IgG1 and IgG4 on human neutrophils in terms of superoxide release, cytokine production, degranulation and adhesion. Additionally we have investigated the interaction of the subclasses with Fc receptors expressed by the neutrophil. Chimeric antibodies were generated using human constant regions of each subclass and a variable region taken from a monoclonal antibody directed against proteinase 3. Superoxide release from neutrophils was measured by the reduction of ferricytochrome C, degranulation by the conversion of a synthetic colour substrate, cytokine release by interleukin‐8 enzyme‐linked immunosorbent assay, and adhesion by a flow‐based adhesion assay. Fc receptor binding was assessed using blocking antibodies. The IgG4 anti‐proteinase 3 was able to induce a dose‐dependent release of superoxide, degranulation and adhesion. The antibody was not able to stimulate the secretion of interleukin‐8. Fc receptors were essential for neutrophil stimulation and the constitutive Fc receptors were necessary for different stimulatory pathways. The IgG4 anti‐proteinase 3 antibodies are able to stimulate neutrophils to undergo a pro‐inflammatory response and may play a role in the pathogenesis of small vessel vasculitis.
A tolerogenic peptide down‐regulates mature B cells in bone marrow of lupus‐afflicted mice by inhibition of interleukin‐7, leading to apoptosis
Authors: Ben‐David Hava , Sharabi Amir , Parameswaran Reshmi , Zinger Heidy , Mozes Edna
Published: April 2009

Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by T and B cells. It is characterized by a variety of autoantibodies and systemic clinical manifestations. A tolerogenic peptide, designated hCDR1, ameliorated the serological and clinical manifestations of SLE in both spontaneous and induced models of lupus. In the present study, we evaluated the status of mature B cells in the bone marrow (BM) of SLE‐afflicted mice, and determined the effect of treatment with the tolerogenic peptide hCDR1 on these cells. We demonstrate herein that mature B cells of the BM of SLE‐afflicted (New Zealand Black × New Zealand White)F1 mice were largely expanded, and that treatment with hCDR1 down‐regulated this population. Moreover, treatment with hCDR1 inhibited the expression of the pathogenic cytokines [interferon‐γ and interleukin (IL)‐10], whereas it up‐regulated the expression of transforming growth factor‐β in the BM. Treatment with hCDR1 up‐regulated the rates of apoptosis of mature B cells. The latter was associated with inhibited expression of the survival Bcl‐xL gene and of IL‐7 by BM cells. Furthermore, the addition of recombinant IL‐7 abrogated the suppressive effects of hCDR1 on Bcl‐xL in the BM cells and resulted in elevated levels of apoptosis. Hence, the down‐regulated production of IL‐7 contributes to the hCDR1‐mediated apoptosis of mature B cells in the BM of SLE‐afflicted mice.