bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenicity of Phytophthora austrocedrae on Austrocedrus chilensis and its relation with mal del ciprés in Patagonia
Authors: Greslebin A. G. , Hansen E. M.
Published: February 2010

Field observations, isolations and pathogenicity tests were performed on Austrocedrus chilensis (Cupressaceae) trees to determine the pathogenicity of Phytophthora austrocedrae and its role in the aetiology of the cypress disease mal del ciprés (MDC) in Argentina. It was found that P. austrocedrae is a primary pathogen of A. chilensis. It was isolated from large necrotic lesions in the inner bark, and superficially in the sapwood, at the root collar and stem, in most of the MDC‐affected stands surveyed along the range of A. chilensis in Argentina. The main symptom in naturally infected trees was a necrotic lesion extending from killed roots up to 1 m up the tree bole. Seedlings, saplings and adult trees were all susceptible to inoculation with P. austrocedrae. Under favourable experimental conditions (flooding), inoculated seedlings suffered massive mortality in less than a month. The importance of diseases caused by Phytophthora spp. in South American forests is discussed.
CC Chemokine Receptor 4 (CCR4) in human allergen‐induced late nasal responses
Authors: Banfield G. , Watanabe H. , Scadding G. , Jacobson M. R. , Till S. J. , Hall D. A. , Robinson D. S. , Lloyd C. M. , Nouri‐Aria K. T. , Durham S. R.
Published: February 2010

To cite this article: Banfield G, Watanabe H, Scadding G, Jacobson MR, Till SJ, Hall DA, Robinson DS, Lloyd CM, Nouri‐Aria KT, Durham SR. CC Chemokine Receptor 4 (CCR4) in human allergen‐induced late nasal responses. Allergy 2010; 65: 1126–1133.

Background:  CC Chemokine receptor 4 (CCR4) is preferentially expressed on Th2 lymphocytes. CCR4‐mediated inflammation may be important in the pathology of allergic rhinitis. Disruption of CCR4 – ligand interaction may abrogate allergen‐induced inflammation.

Methods:  Sixteen allergic rhinitics and six nonatopic individuals underwent both allergen and control (diluent) nasal challenges. Symptom scores and peak nasal inspiratory flow were recorded. Nasal biopsies were taken at 8 h post challenge. Sections were immunostained and examined by light or dual immunofluorescence microscopy for eosinophils, T‐lymphocytes, CCR4+CD3+ and CXCR3+CD3+ cells and examined by in situ hybridization for CCR4, IL‐4 and IFN‐γ mRNA+ cells. Peripheral blood mononuclear cells were obtained from peripheral blood of nine normal donors and the CCR4+CD4+ cells assessed for actin polymerization in response to the CCR4 ligand macrophage‐derived chemokine (MDC/CCL22) and the influence of a CCR4 antagonist tested.

Results:  Allergic rhinitics had increased early and late phase symptoms after allergen challenge compared to diluent; nonatopics did not respond to either challenge. Eosinophils, but not total numbers of CD3+ T cells, were increased in rhinitics following allergen challenge. In rhinitics, there was an increase in CCR4+CD3+ protein‐positive cells relative to CXCR3+CD3+ cells; CCR4 mRNA+ cells were increased and IL‐4 increased to a greater extent than IFN‐γ. CCR4+CD4+ T cells responded to MDC in vitro, and this response was inhibited by the selective CCR4 antagonist.

Conclusion:  Lymphocyte CCR4 expression is closely associated with induction of human allergen‐induced late nasal responses. Blocking CCR4‐ligand interaction may provide a novel therapeutic approach in allergic disease.
Towards a European registry of severe allergic reactions: current status of national registries and future needs
Authors: Worm M. , Timmermans F. , Moneret‐Vautrin A. , Muraro A. , Malmheden Yman I. I. , Lövik M. , Hattersley S. , Crevel R.
Published: February 2010

To cite this article: Worm M, Timmermans F, Moneret‐Vautrin A, Muraro A, Malmheden Yman II, Lövik M, Hattersley S, Crevel R. Towards a European registry of severe allergic reactions: current status of national registries and future needs. Allergy 2010; 65: 671–680.

The incidence of severe allergic reactions is largely unknown and information about triggering allergens, aggravating factors, demography of patients and medical care is lacking. A European wide registry could provide a powerful tool to improve the management of severe allergic reactions from both a medical and a public health perspective. Analysis of existing registries regarding the type and quality of data being collected was used to develop a plan for a pan‐European registry, including the type of system to be used and the range of data to be entered. Surveillance will provide evidence for the efficacy of risk management measures and may identify the emergence of new allergenic foods, and aid monitoring of novel foods, ingredients and technologies. Patients need a clear indication of factors that may increase their risk of having an adverse reaction, which such a registry can help compile. Based on the collected data, food businesses will be able to develop educational programmes for allergen risk assessment and allergen risk communication. Finally, and most importantly preventive measures can be developed and government agencies receive population based data which may be relevant for legislative purposes.
The costs and consequences of omalizumab in uncontrolled asthma from a USA payer perspective
Authors: Campbell J. D. , Spackman D. E. , Sullivan S. D.
Published: February 2010

To cite this article:Campbell JD, Spackman DE, Sullivan SD. The costs and consequences of omalizumab in uncontrolled asthma from a USA payer perspective.Allergy2010;65: 1141–1148.

Background: Omalizumab, an anti‐immunoglobulin E antibody, reduces exacerbations and symptoms in uncontrolled allergic asthma. The study objective was to estimate the costs and consequences of omalizumab compared to usual care from a US payer perspective.

Methods: We estimated payer costs, quality‐adjusted survival (QALYs), and the incremental cost‐effectiveness ratio (ICER) of omalizumab compared to usual care using a state‐transition simulation model that included sensitivity analyses. Every 2 weeks, patients could transition between chronic asthma and exacerbation health states. The best available evidence informed the clinical and cost input estimates. Five years of omalizumab treatment followed by usual care was assumed to estimate a lifetime horizon. Omalizumab responders (60.5% of treated) were modeled as a separate scenario where nonresponders reverted back to usual care after 16 weeks of active treatment.

Results: The mean lifetime discounted costs and QALYs were $83 400 and 13.87 for usual care and $174 500 and 14.19 for omalizumab plus usual care resulting in $287 200/QALY (95% interval: $219 300, $557 900). The ICER was $172 300/QALY when comparing omalizumab to usual care in the responder scenario. One‐way sensitivity analyses indicated that the results were sensitive to the difference in treatment‐specific utilities for the chronic state, exacerbation‐associated mortality, omalizumab price, exacerbation rates, and response definition.

Conclusions: The results suggest that adding omalizumab to usual care improves QALYs at an increase in direct medical costs. The cost‐effectiveness of omalizumab is similar to other chronic disease biologics. The value increases when omalizumab response is used to guide long‐term treatment.
Spectral entropy monitoring allowed lower sevoflurane concentration and faster recovery in children
Authors: CHOI S. R. , LIM Y. H. , LEE S. C. , LEE J. H. , CHUNG C. J.
Published: February 2010

Background: Anesthetic titration using spectral entropy monitoring reduces anesthetic requirements and shortens recovery in adult surgical patients. This study was performed to evaluate the effect of entropy monitoring on end‐tidal sevoflurane concentration and recovery characteristics in pediatric patients undergoing sevoflurane anesthesia.

Methods: Seventy‐eight children (aged 3–12 years) scheduled for a tonsillectomy and/or an adenoidectomy were randomly divided into one of two groups: standard practice (Standard) or entropy‐guided (Entropy). In the Standard group, sevoflurane was adjusted to maintain the heart rate and systolic blood pressure (BP) within 20% of the baseline values. In the Entropy group, sevoflurane was adjusted to achieve a state entropy of 40–50. We compared the entropy values, end‐tidal sevoflurane concentration and recovery times between groups.

Results: During maintenance of anesthesia, the entropy and BP values were higher in the Entropy group (P<0.05). The end‐tidal sevoflurane concentration during maintenance was lower in the Entropy group (2.2 (0.3) vol%) compared with the Standard group (2.6 (0.4) vol%) (P<0.05). Recovery times were faster in the Entropy group (P<0.05).

Conclusions: Compared with standard practice, we found that entropy‐guided anesthetic administration was associated with a reduced sevoflurane concentration and a slightly faster emergence and recovery in 3–12‐year‐old children.
Reduced interleukin‐12 release from stimulated monocytes in patients with sepsis after major cancer surgery
Authors: MOKART D. , LEONE M. , SANNINI A. , BRUN J. P. , TURRINI O. , LELONG B. , HOUVENAEGHEL G. , BLACHE J. L. , MEGE J. L. , MARTIN C.
Published: February 2010

Background: Major cancer surgery is a high‐risk situation for sepsis in the post‐operative period. The aim of this study was to assess the relation between the monocyte production of IL‐12 and the development of post‐operative sepsis in patients undergoing major cancer surgery.

Methods: In 19 patients undergoing major cancer surgery, the production of cytokines by basal and lipolysaccharide (LPS)‐stimulated monocytes was measured before and after (from day 1 to day 3 and day 7) surgery. Seven of them developed a post‐operative sepsis. Ten healthy volunteers were used as controls for the assessment of pre‐operative values.

Results: Before surgery, the production of interleukin (IL)‐12 p40 by LPS‐stimulated monocytes was similar in the patients and the healthy volunteers. The production of IL‐12 p40 by unstimulated monocytes was higher in the patients than in the healthy volunteers. IL‐12 production did not differ between the septic and the non‐septic patients. After surgery, the production of IL‐12 p40 was dramatically reduced in the LPS‐stimulated monocytes of the septic patients from day 1 to day 3, as compared with that of the non‐septic patients. Before surgery, the production of IL‐6, IL‐10, and IL‐1 receptor antagonist (IL‐1ra) in the patients was significantly higher than that of the healthy volunteers for both stimulated and unstimulated monocytes. After surgery, the production of these cytokines by both stimulated and unstimulated monocytes of the septic patients was similar to that of the non‐septic patients. Intragroup analysis showed significant changes for IL‐6, IL‐10, and IL‐1ra under all conditions, with the exception of changes in unstimulated monocytes of septic patients that were not significant for IL‐10 release.

Conclusion: After surgery, the septic patients showed drastic failure to up‐regulate monocyte LPS‐stimulated production of IL‐12 p40.
Reciprocal style polymorphisms are not easily categorised: the case of heterostyly inLithodoraandGlandora(Boraginaceae)
Authors: Ferrero V. , Chapela I. , Arroyo J. , Navarro L.
Published: February 2010

Interest in reciprocal floral polymorphisms, such as heterostyly, has increased in recent decades because they can be used as suitable model systems to study mechanisms of outbreeding and disassortative mating in plants. Heterostylous plants are characterised by the presence of discrete morphs that differ in sex organ position and in some other ancillary traits. As regards sex organ deployment, different types of polymorphisms have been described, depending on number and type of discrete classes present in populations and degree of reciprocity between them. However, a clear‐cut characterisation of stylar polymorphisms does not appear to be the best approach when there is great variability among populations because of continuous variation of some of traits examined. A recent study inLithodora sensu lato(recently split into two separate genera,LithodoraandGlandora) showed a wide variation in sex organ position across species in the genus, which warrants precise population analysis of stylar polymorphism and its reciprocity. We provide a detailed morphometric analysis of flower sexual traits and include those considered to be ancillary characters. We report a wide variation in these traits in populations ofLithodora s.l. and highlight the subjectivity of the former characterisation of style polymorphism based on visual inspection. Ancillary traits appear repeatedly inLithodoraandGlandora, particularly in the latter. The appearance of these traits seems to be related to greater reciprocity between sexual whorls inGlandora, with the exception ofG. prostrata.These results agree with evolutionary steps proposed in the build‐up of heterostyly according to some evolutionary models. We also examined variation in polymorphisms in light of current models for evolution of heterostyly, and, more specifically, we sought to verify the prediction that flower traits as a whole (i.e., flower integration) respond to selective pressure to assure the exact location of pollen on the pollinator body. Most reciprocal populations and species, where between‐morph pollen transfer is expected to be higher, would show greater integration. Our results confirm this hypothesis.
Mechanisms of angiogenesis: Role of hydrogen sulphide
Authors: Wang Ming‐Jie , Cai Wen‐Jie , Zhu Yi‐Chun
Published: February 2010

1. Hydrogen sulphide (H2S) has recently been recognized as a gasotransmitter that regulates angiogenesis in vitro and in vivo under physiological and ischaemic conditions.

2. In the present review, the mechanisms underlying angiogenesis are summarized briefly and the most recent progress in H2S‐induced angiogenesis in vivo and in vitro is described. The anti‐angiogenic effects of garlic extracts, which may serve as substrates for H2S‐generating enzymes in vivo, are also discussed.

3. Hydrogen sulphide increases cell growth, migration and the formation of tube‐like structures in cultured endothelial cells. These effects are dependent on activation of the phosphatidylinositol 3‐kinase–Akt–survivin signalling pathway. Neovascularization in vivo has also been demonstrated to be promoted in the mouse Matrigel plug assay, as well as in chicken chorioallantoic membranes. In a rat unilateral hindlimb ischaemic model, treatment with sodium hydrosulphide (NaHS), an H2S donor, promotes significant angiogenesis and improves regional blood flow. These effects may be mediated by interactions between upregulated vascular endothelial growth factor (VEGF) in skeletal muscle cells and VEGF receptor 2 and the downstream signalling element Akt in vascular endothelial cells. However, H2S does not exhibit a pro‐angiogenic effect at a high concentrations/doses.

4. Based on the studies reviewed in the present article, we assume that, at physiologically relevant doses/concentrations, H2S/HS− promote angiogenesis at least partly via the VEGF signalling pathway. At high doses, H2S/HS− may act on additional cellular targets to evoke mechanisms that counteract the pro‐angiogenic pathways. More studies need to be performed analysing the general interactions between H2S/HS− and other molecules, including other gasotranmitters, such as nitric oxide and carbon monoxide (CO).
Bifid epiglottis: Syndromic constituent rather than isolated anomaly
Authors: Tsurumi Haruko , Ito Masaki , Ishikura Kenji , Hataya Hiroshi , Ikeda Masahiro , Honda Masataka , Nishimura Gen
Published: February 2010

Background:  Bifid epiglottis is a congenital malformation defined as a midline‐cleft of the epiglottis, which can be presented as an isolated anomaly as well as a part of malformation complexes. Its common occurrence in Pallister–Hall syndrome (PHS) has recently been attracting special attention. In the embryo, epiglottis, hypothalamus, and digital buds develop synchronously. Some disturbances during this stage may account for the concurrence of bifid epiglottis, hypothalamic hamartoma, and polysyndactyly in PHS. The incidence of bifid epiglottis remains unknown.

Methods:  We report here four children with bifid epiglottis out of 472 children who underwent laryngoscopy during the period from January 1995 to December 2004 in our hospital.

Results:  All four children presented stridor of variable degrees. One had a partial cleft of the epiglottis associated with only tracheomalacia. The other three had a complete cleft of the epiglottis associated with complex malformations: one had accessory auricles with preauricular sinus, polycystic kidney disease with intrahepatic biliary dilatation, endocardial cushion defect, and postaxial polydactyly; another had hypothalamic hamartoma, Hirschsprung disease, and polydactyly, which warranted a diagnosis of PHS; the other had no other dysmorphic features.

Conclusion:  Bifid epiglottis can be presented as a syndromic constituent of congenital malformation syndromes rather than as an isolated anomaly. A high index of suspicion of bifid epiglottis should be raised in children with brachy‐poly‐syndactyly and clinical symptoms of upper airway obstruction.
Efficacy and safety of linezolid in immunocompromised children with cancer
Authors: Moschovi Maria , Trimis Georgios , Tsotra Maria , Chatzi Fotini , Karamolegou Kalliopi , Santou Antina , Tourkantoni Natalia , Chrousos George
Published: February 2010

Background:  The aim of this study was to determine the safety, tolerance and efficacy of linezolid for the treatment of infections from Gram‐positive bacteria in immunocompromised children with cancer.

Methods:  This was a prospective non‐comparative unblinded study in the Hematology/Oncology Unit over a two‐year period, administering linezolid as monotherapy in children with cancer.

Results:  Seventeen children received linezolid (30 mg/kgr: 3 i.v. per day). Mean duration of linezolid administration was 12.2 days (range, 6–38 days), while the median age of the evaluable patients was 2.2 years (range, 6 months–11.2 years). Primary diagnosis was acute lymphoblastic leukemia (nine patients), brain tumor (three patients), multi‐organ Langerhans cell histiocytosis (two patients), rhabdomyosarcoma, Burkitt's lymphoma and ovarian tumor (one patient each). All patients were in the midst of chemotherapy cycles. Ten out of 17 children had positive blood cultures (methicillin‐resistant Staphylococcus aureus, four patients; vancomycin‐resistant Enterococcus, three patients; penicillin‐resistant Streptococcus pneumoniae, three patients), while seven of the 17 had fever and vancomycin‐resistant Enterococcus in stool cultures. All patients were considered clinically cured after the end of the linezolid regimen (100% efficacy). The main adverse events were thrombocytopenia grade 1–3 and anemia grade 2–3 (four and two patients, respectively). Chemotherapy‐induced myelotoxicity (six patients) was not worsened during linezolid therapy. No bleeding episodes were presented. Self‐limited diarrhea grade 1–2 was presented in four patients (mean duration 2 days). The total adverse event rate was 23.5%; however, there was no premature cessation of linezolid in any patient.

Conclusions:  Linezolid may be another effective and safe therapy to treat infections from resistant Gram‐positive bacteria in immunocompromised children, even in young ages.
Development and validation of a qPCR‐based method for quantifying Shiga toxin‐encoding and other lambdoid bacteriophages
Authors: Rooks David J. , Yan Yaxian , McDonald James E. , Woodward Martin J. , McCarthy Alan J. , Allison Heather E.
Published: February 2010

To address whether seasonal variability exists among Shiga toxin‐encoding bacteriophage (Stx phage) numbers on a cattle farm, conventional plaque assay was performed on water samples collected over a 17 month period. Distinct seasonal variation in bacteriophage numbers was evident, peaking between June and August. Removal of cattle from the pasture precipitated a reduction in bacteriophage numbers, and during the winter months, no bacteriophage infecting Escherichia coli were detected, a surprising occurrence considering that 1031 tailed‐bacteriophages are estimated to populate the globe. To address this discrepancy a culture‐independent method based on quantitative PCR was developed. Primers targeting the Q gene and stx genes were designed that accurately and discriminately quantified artificial mixed lambdoid bacteriophage populations. Application of these primer sets to water samples possessing no detectable phages by plaque assay, demonstrated that the number of lambdoid bacteriophage ranged from 4.7 × 104 to 6.5 × 106 ml−1, with one in 103 free lambdoid bacteriophages carrying a Shiga toxin operon (stx). Specific molecular biological tools and discriminatory gene targets have enabled virus populations in the natural environment to be enumerated and similar strategies could replace existing propagation‐dependent techniques, which grossly underestimate the abundance of viral entities.
Gene diversity of CYP153A and AlkB alkane hydroxylases in oil‐degrading bacteria isolated from the Atlantic Ocean
Authors: Wang Liping , Wang Wanpeng , Lai Qiliang , Shao Zongze
Published: February 2010

Alkane hydroxylases, including the integral‐membrane non‐haem iron monooxygenase (AlkB) and cytochrome P450 CYP153 family, are key enzymes in bacterial alkane oxidation. Although both genes have been detected in a number of bacteria and environments, knowledge about the diversity of these genes in marine alkane‐degrading bacteria is still limited, especially in pelagic areas. In this report, 177 bacterial isolates, comprising 43 genera, were obtained from 18 oil‐degrading consortia enriched from surface seawater samples collected from the Atlantic Ocean. Many isolates were confirmed to be the first oil‐degraders in their affiliated genera including Brachybacterium, Idiomarina, Leifsonia, Martelella, Kordiimonas, Parvibaculum and Tistrella. Using degenerate PCR primers, alkB and CYP153A P450 genes were surveyed in these bacteria. In total, 82 P450 and 52 alkB gene fragments were obtained from 80 of the isolates. These isolates mainly belonged to Alcanivorax, Bacillus, Erythrobacter, Martelella, Parvibaculum and Salinisphaera, some of which were reported, for the first time, to encode alkane hydroxylases. Phylogenetic analysis showed that both genes were quite diverse and formed several clusters, most of which were generated from various Alcanivorax bacteria. Noticeably, some sequences, such as those from the Salinisphaera genus, were grouped into a distantly related novel cluster. Inspection of the linkage between gene and host revealed that alkB and P450 tend to coexist in Alcanivorax and Salinisphaera, while in all isolates of Parvibaculum, only P450 genes were found, but of multiple homologues. Multiple homologues of alkB mostly cooccurred in Alcanivorax isolates. Conversely, distantly related isolates contained similar or even identical sequences. In summary, various oil‐degrading bacteria, which harboured diverse P450 and alkB genes, were found in the surface water of Atlantic Ocean. Our results help to show the diversity of P450 and alkB genes in prokaryotes, and to portray the geographic distribution of oil‐degrading bacteria in marine environments.
Type 2 diabetes in Canada: concentration of risk among most disadvantaged men but inverse social gradient across groups in women
Authors: Dasgupta K. , Khan S. , Ross N. A.
Published: February 2010

Diabet. Med. 27, 522–531 (2010)

Aims  To assess sex‐specific associations of educational and income levels with Type 2 diabetes mellitus.

Methods  Logistic regression analyses (Canadian Community Health Survey, cross‐sectional) adjusted for ethnicity, immigration, urban/rural, overweight/obesity, physical inactivity, smoking, chronic conditions and regular physician.

Results  Compared to women with some post‐secondary education, Type 2 diabetes was more likely in both high school graduates without post‐secondary education [odds ratio (OR) 1.27, 95% confidence interval (CI) 1.07–1.51] and high school non‐completers (OR 1.73, 95% CI 1.47–2.04); among men, definitive conclusions in high school graduates without post‐secondary education could not be drawn (OR 0.93, 95% CI 0.78–1.12), but Type 2 diabetes was more likely in high school non‐completers (OR 1.26, 95% CI 1.08–1.48). Compared to women with the highest income, Type 2 diabetes was three times more likely in the lowest income group (OR 2.90, 95% CI 2.25–3.73), 2.53 times more likely in the low middle income group (OR 2.53, 95% CI 1.98–3.24) and 55% more likely in the high middle income group (OR 1.55, 95% CI 1.20–2.01). Among men, Type 2 diabetes was approximately 40% more likely in both the lowest (OR 1.41, 95% CI 1.10–1.80) and low middle income groups (OR 1.39, 95% CI 1.12–1.71); definitive conclusions in the high middle income group could not be drawn (OR 1.05, 95% CI 0.87–1.28).

Conclusions  In women, Type 2 diabetes increased monotonically with lower educational and income levels; in men, Type 2 diabetes was concentrated in the least educated and least affluent. Our findings support the need for policies and practices that lower diabetes risk among the most disadvantaged women and men and moderately disadvantaged women.
Occurrence of microalbuminuria in young people with Type 1 diabetes: importance of age and diabetes duration
Authors: Alleyn C. R. , Volkening L. K. , Wolfson J. , Rodriguez‐Ventura A. , Wood J. R. , Laffel L. M. B.
Published: February 2010

Diabet. Med. 27, 532–537 (2010)

Aims  To determine the occurrence of microalbuminuria in young people with Type 1 diabetes mellitus followed prospectively for 2 years and to relate the presence of persistent elevations in urinary albumin excretion (UAE) to age, diabetes duration, puberty and other factors.

Methods  During a 2 year period, random urine samples were obtained from 471 patients, aged 8–18 years (mean ±sd 12.9 ± 2.3 years) with Type 1 diabetes duration 5.6 ± 3.0 years, as part of routine clinical care. Urine albumin and creatinine concentrations were measured in 1310 samples (median, 3 samples per patient) and the albumin:creatinine ratio was calculated (in micrograms albumin per milligram creatinine). Height, weight, blood pressure (BP), glycated haemoglobin (HbA1c), blood glucose monitoring frequency and Tanner staging were collected from patients’ medical records.

Results  Twenty‐three per cent of patients had one or more sample with elevated UAE (≥20 μg/mg) and 9.3% had persistent elevations (≥2 samples ≥20 μg/mg). Those with and without persistent microalbuminuria did not differ significantly in age, diabetes duration, z–score for body mass index, pubertal status or BP percentile. Ten per cent of children <13 years old and 9% of children ≥13 years old had persistent microalbuminuria. Persistent microalbuminuria was significantly associated with diabetes duration only in older children (duration 0.5–3 years, 4%; 4–6 years, 8%; ≥7 years, 14%; P = 0.02, trend test). Mean HbA1c over the 2 years was 8.7 ± 1.2%. In a logistic regression model, mean HbA1c was the only significant predictor of persistent microalbuminuria (odds ratio 1.3, 95% confidence interval 1.0–1.6, P = 0.05).

Conclusions  Microalbuminuria in older children with Type 1 diabetes is likely to be clinically significant. In younger children, it may reflect functional, reversible renal changes. Longitudinal analysis is needed to confirm the probable transient nature of microalbuminuria in young patients with Type 1 diabetes.
Severe statin‐induced rhabdomyolysis mimicking Guillain–Barré syndrome in four patients with diabetes mellitus treated with fusidic acid
Authors: Collidge T. A. , Razvi S. , Nolan C. , Whittle M. , Stirling C. , Russell A. J. C. , Mann A. C. , Deighan C. J.
Published: February 2010

Diabet. Med. 27, 696–700 (2010)

Background  An interaction between fusidic acid and HMG coenzyme A reductase inhibitors (statins), resulting in rhabdomyolysis, has been described. Pain and mild weakness are common presenting symptoms.

Case report  We report four patients with Type 2 diabetes prescribed long‐term statin treatment who, following treatment with fusidic acid, presented atypically with painless, severe flaccid paralysis suggestive of Guillain–Barré syndrome. This, together with nerve conduction studies consistent with Guillain–Barré syndrome, resulted in the delayed recognition of rhabdomyolysis in these cases.

Conclusions  The addition of fusidic acid can precipitate rhabdomyolysis in patients with diabetes already taking a statin. This can present with rapidly progressive weakness resembling Guillain–Barré syndrome. We recommend that creatine kinase is checked in patients with diabetes on statin therapy who present with profound weakness and routinely in those commenced on prolonged courses of fusidic acid.
Prevalence and nature of anaemia in a prospective, population‐based sample of people with diabetes: Teesside anaemia in diabetes (TAD) study
Authors: Jones S. C. , Smith D. , Nag S. , Bilous M. T. , Winship S. , Wood A. , Bilous R. W.
Published: February 2010

Diabet. Med. 27, 655–659 (2010)

Aims  Anaemia occurs in 25% of people attending hospital diabetes clinics, but this may not be representative of all people with diabetes. We aimed to determine the prevalence of anaemia in a prospective population‐based sample stratified by estimated glomerular filtration rate (eGFR) using the 4‐point Modification of Diet in Renal Disease (MDRD) formula.

Methods  All 7331 patients on our district register were stratified by eGFR. Seven hundred and thirty were approached by letter on two occasions. Two hundred and thirty‐four (32%) returned questionnaires and blood samples. Responders (R), non‐responders (NR) and the whole cohort (C) were similar: mean ± sd age R 61.7 ± 12.7 years; NR 61.3 ± 15.1 years; C 61.8 ± 14.2 years; diabetes duration R 8.8 ± 8.6 years; NR 8.2 ± 7.9 years; C 7.5 ± 7.8 years, Type 1 diabetes R 10.1%, NR 10.8%, C 9.4%. Anaemia was defined using World Health Organization criteria: haemoglobin < 13 g/dl for men, < 12 g/dl for women.

Results  Previously undiagnosed anaemia was present in 15% of the whole group, 36% with eGFR < 60 ml/min per 1.73 m2 and 9% of those with eGFR > 60 ml/min per 1.73 m2. Anaemia was as a result of erythropoietin deficiency in 34%, abnormal haematinics in 40% and was unexplained in 26% of patients. Five per cent of the patients had anaemia below the treatment threshold of 11 g/dl.

Conclusions  The prevalence of unrecognized anaemia in population‐based cohorts is lower than that in hospital‐based studies. Current clinical surveillance in the UK is failing to detect anaemia in stage 3–5 chronic kidney disease (eGFR < 60 ml/min per 1.73 m2) and current guidelines will not detect 9% of diabetic patients with anaemia and an eGFR > 60 ml/min per 1.73 m2.
A systematic review of scoring systems for diabetic foot ulcers
Authors: Karthikesalingam A. , Holt P. J. E. , Moxey P. , Jones K. G. , Thompson M. M. , Hinchliffe R. J.
Published: February 2010

Diabet. Med. 27, 544–549 (2010)

Aims  Foot ulcers are a common and important complication of diabetes. Variation in the clinical presentation of this disease has resulted in a paucity of evidence from comparable studies to guide optimal clinical management. A validated scoring system might help clinicians and researchers in everyday assessment and management of patients or the development and assessment of new therapies. The aim of the present review was to critically appraise the published literature of wound scoring systems for diabetic foot ulcers.

Methods  An electronic search was performed using the EMBASE and MEDLINE databases from 1966 until 2009 for scoring systems for diabetic foot ulcers. The literature review conformed to PRISMA statement standards.

Results  The literature search identified 197 articles, of which 180 were excluded. Eleven scoring systems and six validation or comparative studies are described.

Conclusions  Many scoring systems exist for classification of the diabetic foot, few of which have been validated. Detailed scoring systems offer a valuable method for the comparison of data from different diabetic foot centres. Simplistic scoring systems may be used in clinical practice and the choice of scoring system should be determined by the population under study.
Safety and tolerability of high doses of taspoglutide, a once‐weekly human GLP‐1 analogue, in diabetic patients treated with metformin: a randomized double‐blind placebo‐controlled study1,2
Authors: Ratner R. , Nauck M. , Kapitza C. , Asnaghi V. , Boldrin M. , Balena R.
Published: February 2010

Diabet. Med. 27, 556–562 (2010)

Aims  The study objective was to investigate the safety and tolerability of up‐titration to high doses of taspoglutide, a once‐weekly human glucagon‐like peptide‐1 analogue, in subjects with Type 2 diabetes inadequately controlled on metformin alone.

Methods  In this double‐blind phase II trial, subjects were randomized to placebo or taspoglutide (20 mg; three separate groups) administered once weekly by subcutaneous injection for 4 weeks. This was followed by dose maintenance at 20 mg, or titration to 30 mg (20/30) or 40 mg (20/40) once weekly with matched placebo for an additional 4 weeks. Subjects were monitored for adverse events (AEs) throughout the study and 4‐week follow‐up.

Results  One hundred and twenty‐nine subjects were randomized and treated [mean age 57 years, mean baseline glycated haemoglobin (HbA1c), 7.9%]. The most frequently reported AEs were nausea and vomiting. The number of patients reporting gastrointestinal AEs did not increase following titration to higher doses of taspoglutide or when continuing the initial 20 mg regimen. Three subjects were withdrawn from the study as a result of gastrointestinal AEs (one before and two after titration to higher doses). Although not designed to investigate efficacy, improvement in glycaemic control was observed in all active arms of the study. The proportion of subjects achieving HbA1c < 7.0% after 8 weeks of treatment was 72, 53 and 70% in the 20/20‐, 20/30‐ and 20/40‐mg arms, respectively, vs. 19% for placebo.

Conclusions  Taspoglutide was safe, well tolerated at high doses and efficacious for lowering HbA1c. Up‐titration of dose was not associated with a worsening AE profile.
National Support for Film Production in the EU: An Analysis of the Commission Decision‐Making Practice
Authors: Bellucci Lucia
Published: February 2010

This article deals with the cultural welfare concerning cinema, a medium capable of both painting and shaping society. It aims to investigate the impact of the European integration on national film promotional law, by studying the European Commission decision‐making practice in the field of State aid to cinematographic works. The analysis shows that this practice can be understood in two main phases that are delineated by the adoption of specific criteria. These criteria are explored by highlighting the most elucidating cases. Furthermore, this analysis discloses two relevant conflicts: within the Commission itself and between the Commission and the Member States. Particular emphasis is placed on the latter, which is explored with regard to: the European national film agencies' polarisation of the conflict, the main form of dispute settlement adopted by the Commission, and the legal obligations imposed by Member States upon TV broadcasters to invest in audiovisual1 production. The analysis ends with an evaluation of the above‐mentioned impact and a few remarks on some unresolved issues related to the conflict between the Commission and the Member States.
Contingency Planning for Large‐Scale Floods in the Netherlands
Authors: Ten Brinke W. B. M. , Kolen B. , Dollee A. , Van Waveren H. , Wouters K.
Published: February 2010

Contingency plans for hazards are based on scenarios at different scales. The most extreme scenarios reflect the idea of ‘think the unthinkable’. For large‐scale floods in the Netherlands, this idea has been given an upper limit called ‘worst credible floods’: an upper limit for floods that are still considered realistic or credible by experts. Considering the enormous impact of a worst credible flood in the Netherlands and the uncertainty of how a disaster might unfold, a realistic preparation for flood disasters should leave room for improvisation and should be based on relatively simple plans, and on public awareness. The huge consequences of worst credible floods show that the country's safety will continue to depend on pro‐active and preventive measures.
The Interplay of Organization Type, Organization Size, and Practitioner Role on Perceived Crisis Preparedness: A Cognitive Appraisal Approach
Authors: Jin Yan
Published: February 2010

This study examined the perceived crisis preparedness of a random sample of public relations practitioners in the United States (N=144) as evidenced in their assessment of crisis situation and organizational resources. The main effects of organization size and practitioner role were evident on practitioner's perceived crisis preparedness in different crisis situations. Organization type was found to be effective only when it interplayed with either practitioner role or organization size.
A Tear in the Social Fabric: Communities Dealing with Socially Generated Crises
Authors: Enander Ann , Lajksjö Örjan , Tedfeldt Eva‐Lena
Published: February 2010

The purpose of the study was to develop knowledge about demands and experiences relating to management of socially generated crises in local communities. Interviews were conducted in four municipalities with experiences of such situations, e.g., widely publicized murders, suicides or cases of sexual abuse. A modified grounded theory analysis of the interviews identified six central themes. Two themes pertained to the actual event and its consequences; two concerned the management of the crisis; and two themes focused on reactions and needs among those involved. Basic tensions were identified between confidentiality and openness, between support and accountability and between empathy and distancing. Similarities and differences in relation to management of other kinds of crises are discussed.
Functional specialization and ontogenetic scaling of limb anatomy in Alligator mississippiensis
Authors: Allen Vivian , Elsey Ruth M. , Jones Nicola , Wright Jordon , Hutchinson John R.
Published: February 2010

Crocodylians exhibit a fascinating diversity of terrestrial gaits and limb motions that remain poorly described and are of great importance to understanding their natural history and evolution. Their musculoskeletal anatomy is pivotal to this diversity and yet only qualitative studies of muscle‐tendon unit anatomy exist. The relative masses and internal architecture (fascicle lengths and physiological cross‐sectional areas) of muscles of the pectoral and pelvic limbs of American alligators (Alligator mississippiensis Daudin 1801) were recorded for an ontogenetic series of wild specimens (n = 15, body masses from 0.5 to 60 kg). The data were analysed by reduced major axis regression to determine scaling relationships with body mass. Physiological cross‐sectional areas and therefore muscle force‐generating capacity were found to be greater in the extensor (anti‐gravity) muscles of the pelvic limb than in the pectoral limb, reflecting how crocodylians differ from mammals in having greater loading of the hindlimbs than the forelimbs. Muscle masses and architecture were generally found to scale isometrically with body mass, suggesting an ontogenetic decrease in terrestrial athleticism. This concurs with the findings of previous studies showing ontogenetic decreases in limb bone length and the general scaling principle of a decline of strength : weight ratios with increasing size in animals. Exceptions to isometric scaling found included positive allometry in fascicle length for extensor musculature of both limbs, suggesting an ontogenetic increase in working range interpreted as increasing postural variability – in particular the major hip extensors – the interpretation of which is complicated by previous described ontogenetic increase of moment arms for these muscles.
The elastic network of articular cartilage: an immunohistochemical study of elastin fibres and microfibrils
Authors: Yu Jing , Urban Jill P. G.
Published: February 2010

The elastic network of articular cartilage was investigated by immunohistochemistry using specific antibodies to elastin and fibrillin‐1. Articular cartilage was dissected from defined regions of bovine metacarpophalangeal joints. Elastin fibres and microfibrils were dual‐immunostained by labelling with distinct fluorescent dyes. A conventional fluorescence microscope combined with a polarized light filter was used to study the organization and degree of colocalization of elastin fibres, microfibrils and of the collagen network. We observed an elaborately organized elastic network. In the uppermost superficial zone, where few cells were present, elastin fibres and microfibrils formed a dense three dimensional network showing some degree of colocalization. The thickness and organization of this elastic network varied dramatically from region to region and was most extensive in the metacarpal palmar region. In the middle and deep zones, very few elastin fibres were observed but microfibrils formed a network in the inter‐territorial matrix and dense network around the cells. Our finding of a three dimensional network of dense, well organized elastin fibres and microfibrils in the surface zone of the articular cartilage matrix, and a dense network of microfibrils around the cells deeper into the tissue suggests the elastic network could play both a mechanical and a biological role in articular cartilage.
Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population‐based cohort study
Authors: BEAINO GHADA , KHOSHNOOD BABAK , KAMINSKI MONIQUE , PIERRAT VÉRONIQUE , MARRET STÉPHANE , MATIS JACQUELINE , LEDÉSERT BERNARD , THIRIEZ GÉRARD , FRESSON JEANNE , ROZÉ JEAN‐CHRISTOPHE , ZUPAN‐SIMUNEK VÉRONIQUE , ARNAUD CATHERINE , BURGUET ANTOINE , LARROQUE BÉATRICE , BRÉART GÉRARD , ANCEL PIERRE‐YVES ,   for the EPIPAGE Study Group
Published: February 2010

Aim  The aim of this study was to assess the independent role of cerebral lesions on ultrasound scan, and several other neonatal and obstetric factors, as potential predictors of cerebral palsy (CP) in a large population‐based cohort of very preterm infants.

Method  As part of EPIPAGE, a population‐based prospective cohort study, perinatal data and outcome at 5 years of age were recorded for 1812 infants born before 33 weeks of gestation in nine regions of France in 1997.

Results  The study group comprised 942 males (52%) and 870 females with a mean gestational age of 30 weeks (SD 2wks; range 24–32wks) and a mean birthweight of 1367g (SD 393g; range 450–2645g). CP was diagnosed at 5 years of age in 159 infants (prevalence 9%; 95% confidence interval [CI] 7–10%), 97 males and 62 females, with a mean gestational age of 29 weeks (SD 2wks; range 24–32wks) and a mean birthweight of 1305g (SD 386g; range 500–2480g). Among this group, 67% walked without aid, 14% walked with aid, and 19% were unable to walk. Spastic, ataxic, and dyskinetic CP accounted for 89%, 7%, and 4% of cases respectively. The prevalence of CP was 61% among infants with cystic periventricular leukomalacia, 50% in infants with intraparenchymal haemorrhage, 8% in infants with grade I intraventricular haemorrhage, and 4% in infants without a detectable cerebral lesion. After controlling for cerebral lesions and obstetric and neonatal factors, only male sex (odds ratio [OR] 1.52; 95% CI 1.03–2.25) and preterm premature rupture of membranes or preterm labour (OR 1.72; 95% CI 0.95–3.14) were predictors of the development of CP in very preterm infants.

Interpretation  Cerebral lesions were the most important predictor of CP in very preterm infants. In addition, infant sex and preterm premature rupture of membranes or preterm labour were also independent predictors of CP.
Influenza A/H1N1 (2009) infection in pregnancy—an Asian perspective
Authors: Lim ML , Chong CY , Tee WSN , Lim WY , Chee JJ
Published: February 2010

Please cite this paper as: Lim M, Chong C, Tee W, Lim W, Chee J. Influenza A/H1N1 (2009) infection in pregnancy—an Asian perspective. BJOG 2010;117:551–556.

Objective  To describe the characteristics of an obstetric population with influenza A/H1N1 (2009) infection, with a focus on the need for hospitalisation and complications.

Design  Cohort study.

Setting  Tertiary referral centre.

Population  Two hundred and eleven pregnant women with influenza A/H1N1 (2009) infection diagnosed by nasopharyngeal swab polymerase chain reaction (PCR).

Methods  Obstetric patients presenting to our centre were recruited and followed up. Data collected included demographic and clinical information.

Main outcome measures  H1N1 and pregnancy complications, and hospitalisation needs.

Results  The median age of the cohort was 29.0 years (range 16–42 years), the median gestation at referral was 23.0 weeks (range 4–38 weeks), the median time interval between illness onset and presentation was 2.0 days (range 1–7 days), and the median time interval between illness onset and commencement of oseltamivir was 2.0 days (range 1–11 days). Hospital admission was significantly associated with the presence of co‐morbidity (OR 4.14, 95% CI 1.82–9.37, P = 0.0001), breathlessness (OR 5.2, 95% CI 2.19–12.41, P = 0.0003) and sore throat (OR 0.35, 95% CI 0.16–0.73, P = 0.005). There were two cases of pneumonia complicating H1N1 infection, but no mortality. Nine cases developed pregnancy complications. All women recovered.

Conclusions  The need for hospitalisation was significantly associated with breathlessness and co‐morbidity. There was minimal morbidity and no mortality observed. We attribute this to early presentation, diagnosis and treatment.
A structural basis for the inhibition of collagen‐stimulated platelet function by quercetin and structurally related flavonoids
Authors: Wright Bernice , Moraes Leonardo A , Kemp Charles F , Mullen William , Crozier Alan , Lovegrove Julie A , Gibbins Jonathan M
Published: February 2010

Background and purpose: Molecular mechanisms underlying the links between dietary intake of flavonoids and reduced cardiovascular disease risk are only partially understood. Key events in the pathogenesis of cardiovascular disease, particularly thrombosis, are inhibited by these polyphenolic compounds via mechanisms such as inhibition of platelet activation and associated signal transduction, attenuation of generation of reactive oxygen species, enhancement of nitric oxide production and binding to thromboxane A2receptors.In vivo, effects of flavonoids are mediated by their metabolites, but the effects and modes of action of these compounds are not well‐characterized. A good understanding of flavonoid structure–activity relationships with regard to platelet function is also lacking.

Experimental approach: Inhibitory potencies of structurally distinct flavonoids (quercetin, apigenin and catechin) and plasma metabolites (tamarixetin, quercetin‐3′‐sulphate and quercetin‐3‐glucuronide) for collagen‐stimulated platelet aggregation and 5‐hydroxytryptamine secretion were measured in human platelets. Tyrosine phosphorylation of total protein, Syk and PLCγ2 (immunoprecipitation and Western blot analyses), and Fyn kinase activity were also measured in platelets. Internalization of flavonoids and metabolites in a megakaryocytic cell line (MEG‐01 cells) was studied by fluorescence confocal microscopy.

Key results: The inhibitory mechanisms of these compounds included blocking Fyn kinase activity and the tyrosine phosphorylation of Syk and PLCγ2 following internalization. Principal functional groups attributed to potent inhibition were a planar, C‐4 carbonyl substituted and C‐3 hydroxylated C ring in addition to a B ring catechol moiety.

Conclusions and implications: The structure–activity relationship for flavonoids on platelet function presented here may be exploited to design selective inhibitors of cell signalling.