bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accumulation of risk markers predicts the incidence of sudden death in patients with chronic heart failure
Authors: Watanabe Jun , Shinozaki Tsuyoshi , Shiba Nobuyuki , Fukahori Kohei , Koseki Yoshito , Karibe Akihiko , Sakuma Masahito , Miura Masahito , Kagaya Yutaka , Shirato Kunio 
Published: September 2005

AbstractBackground:Sudden death is common in chronic heart failure (CHF). Risk stratification is the first step for primary prevention.Aim:To evaluate the use of risk markers for estimating sudden death risk.Methods and results:We prospectively examined 680 stable patients with CHF. Risk markers were evaluated using the Cox's proportional hazard model in a stepwise manner. Ejection fraction <30%, left ventricular end‐diastolic diameter >60 mm, brain natriuretic peptide >200 pg/ml, non‐sustained ventricular tachycardia, and diabetes were significantly associated with increased risk of sudden death. When the number of risk markers were included as co‐variables, only “number of risk markers ≥3” entered the model (hazard ratio 8.95, 95% confidence interval 4.57–17.52), while the effects of individual markers did not enter the model. The annual mortality from sudden death was 11% in patients with 3 or more risk markers and 1.4% in patients with 2 or less.Conclusions:Rather than particular risk markers, the number of accumulated risk markers was a more powerful predictor for sudden death in patients with CHF. The number of risk markers could be useful for risk stratification of sudden death.
Heterotopic ischemic pain attenuates somatosensory evoked potentials induced by electrical tooth stimulation: Diffuse noxious inhibitory controls in the trigeminal nerve territory
Authors: Fujii Keiko , Motohashi Katsunori , Umino Masahiro 
Published: September 2005

AbstractThe purpose of this study was to determine whether the late component of somatosensory evoked potentials (SEP) induced by electrical tooth stimulation and pain intensity are inhibited by heterotopic ischemic stimulation. The tourniquet pressure with 50 mmHg greater than the individual's systolic pressure was applied to the left upper arm for 10 min as ischemic conditioning stimulation. The late component of SEP and visual analogue scale (VAS) were recorded at 4 times and both were significantly decreased when ischemic conditioning stimulation was applied. The maximum reductions in SEP amplitude and the VAS value were 26.1% and 21.2%, respectively, during ischemic conditioning stimulation. After‐effect was observed 5 min after removal of the conditioning stimulation. The present study revealed that heterotopic ischemic stimulation attenuated the late component of SEP induced by electrical tooth stimulation, triggering diffuse noxious inhibitory controls (DNIC) and after‐effects in the trigeminal nerve territory. It was also suggested that the DNIC effect differs, depending on the intensity, kind, and quality of the test and conditioning stimuli.
Ex situ conservation status of an endangered Yangtze finless porpoise population (Neophocaena phocaenoides asiaeorientalis) as measured from microsatellites and mtDNA diversity
Authors: Xia Junhong , Zheng Jinsong , Wang Ding 
Published: September 2005

AbstractThe Yangtze finless porpoise, Neophocaena phocaenoides asiaeorientalis, is an endangered small cetacean that occurs only in the middle and lower reaches of the Yangtze River of China. The establishment of a breeding population of the porpoise in Tian-e-Zhou Baiji National Natural Reserve represents the first attempt at ex situ conservation efforts for a cetacean species. With the goal of effective protection, management, and monitoring of this preserved population, we examined its genetic diversity using 930 bp of mtDNA control region sequences and 13 polymorphic microsatellite loci. A very low level of genetic variation (h = 0.6010 ± 0.0029 s.d.; π = 0.0007 ± 0.0000002 s.d.) in the mtDNA control region sequences and a moderate genetic diversity (Ho = 0.5740 ± 0.2575 s.d.) in the microsatellites were detected in the population. It is necessary to introduce more individuals with representative genetic variations into the reserve in order to form a larger and healthier group structure for long-term survival of the population. Successful establishment of the Yangtze finless porpoise population in the Reserve also provides a useful model for an ex situ conservation programme for other rare and endangered species.
The application of qualitative risk assessment methodology to prioritize issues for fisheries management
Authors: Fletcher W.J. 
Published: September 2005

Abstract
Implementing more holistic forms of fisheries management (e.g. Ecologically Sustainable Development (ESD), Ecosystem-Based Fisheries Management) usually increases the number and scope of impacts requiring assessment. This study examined the effectiveness of a qualitative risk assessment process, developed as part of a National ESD framework, for prioritizing issues across the seven most valuable Western Australian commercial fisheries. Structured stakeholder workshops were used to identify issues across three ecological areas: retained species (i.e. target and by-product), non-retained (i.e. discarded and protected) species, and the broader ecosystem for each fishery. The risk associated with each issue was assessed using one of five sets of consequence criteria specifically developed to cover fishery-related impacts. The risk scores, for which suitably detailed justifications were written, determined the level of reporting and management required for each issue. Despite an additional 96 “non-target species issues” being identified at the workshops from a total of 115 issues, of the 27 issues requiring explicit management actions, just six new issues were added by this process. In addition, it identified where modifications of some of the existing arrangements were necessary. Finally, the system significantly improved stakeholder involvement and therefore acceptance of the outcomes. Given this success, risk assessment has now been applied to all Western Australia's export fisheries and to the development or review of many other systems, thereby improving the entire management process.
Stability, energetic particles, waves and current drive summary
Authors: Stambaugh R.D. 
Published: September 2005

This is the summary paper for the subjects of plasma stability, energetic particles, waves and current drive at the 20th IAEA Fusion Energy Conference, Vilamoura, Portugal, 1–6 November 2004. Material summarized herein was drawn from 65 contributed papers and 21 overview papers. The subject-wise distribution of contributed papers is shown in the following table:

Subject
Papers

Resistive wall modes
7

Disruptions
6

Neoclassical tearing modes
6

Edge localized modes and the edge pedestal
13

Other stability topics
9

Alfvén modes
9

Wave physics
10

Current drive
5

Total
65

Significant advances have been reported on the principal instabilities in magnetically confined plasmas, even extending to the burning plasma state. Wave-plasma physics is maturing and novel methods of current drive and non-inductive current generation are being developed.
Effect of IL‐2‐Bax, a novel interleukin‐2‐receptor‐targeted chimeric protein, on bleomycin lung injury1
Authors: Segel Michael J. , Aqeilan Rami , Zilka Keren , Lorberboum‐Galski Haya , Wallach‐Dayan Shulamit B. , Conner Michael W. , Christensen Thomas G. , Breuer Raphael 
Published: September 2005

SummaryThe role of lymphocytes in the pathogenesis of lung fibrosis is not clear, but the weight of the evidence supports a pro‐fibrotic effect for lymphocytes. The high‐affinity interleukin‐2 receptor (haIL‐2R) is expressed on activated, but not quiescent, T lymphocytes. This selective expression of haIL‐2R provides the basis for therapeutic strategies that target IL‐2R‐expressing cells. We hypothesized that elimination of activated lymphocytes by IL‐2R‐targeted chimeric proteins might ameliorate lung fibrosis. We investigated the effects of IL‐2‐Bax, a novel apoptosis‐inducing IL‐2R‐targeted chimeric protein, on bleomycin‐induced lung injury in mice. Treatment groups included (i) a single intratracheal instillation of bleomycin and twice‐daily intraperitoneal injections of IL‐2‐Bax; (ii) intratracheal bleomycin and intraperitoneal IL‐2‐PE664Glu, an older‐generation chimeric protein; (iii) intratracheal bleomycin/intraperitoneal PBS; (iv) intratracheal saline/intraperitoneal PBS. Lung injury was evaluated 14 days after intratracheal instillation by cell count in bronchoalveolar lavage (BAL) fluid, semi‐quantitative and quantitative histomorphological measurements and by biochemical analysis of lung hydroxyproline. Bleomycin induced a BAL lymphocytosis that was significantly attenuated by IL‐2‐Bax and IL‐2‐PE664Glu. However, morphometric parameters and lung hydroxyproline were unaffected by the chimeric proteins. These results show that IL‐2‐Bax reduces the lymphocytic infiltration of the lungs in response to bleomycin, but this effect is not accompanied by a decrease in lung fibrosis.
Evaluation of human knee meniscus biopsies with near‐infrared, reflectance confocal microscopy. A pilot study
Authors: Campo‐Ruiz Vanessa , Patel Dinesh , Anderson R. Rox , Delgado‐Baeza Emilio , González Salvador 
Published: September 2005

SummaryKnee cartilage biopsy is used to confirm the pathology in both clinical and experimental conditions and often guides diagnosis and therapeutic strategies. Current histopathological techniques are time consuming, induce tissue artefacts and often prevent further evaluation, once the tissue has been fixed. Hence, there is a potential need for a fast and nondestructive imaging technique for unfixed tissue. Near‐infrared, reflectance confocal microscopy (CM) allows real‐time, virtual sectioning of unstained, bulk tissue samples. This pilot study evaluates the use of CM in the assessment of meniscus histopathology in a series of 26 freshly‐excised human meniscus samples compared to standard light microscopy of stained sections. CM images of the meniscus show cell and matrix detail, depicting morphologic features of collagen and elastic fibres, vessels and nerve endings. In addition, crystal deposits of gout and pseudogout are also demonstrable. Thus, CM is a novel imaging technique that could enable the pathologist to make a rapid microscopic evaluation of cartilage in a fresh and unfixed fashion.
Analysing the effect of novel therapies on cytokine expression in experimental arthritis
Authors: Williams Richard O. , Inglis Julia J. , Simelyte Egle , Criado Gabriel , Sumariwalla Percy F. 
Published: September 2005

SummaryType II collagen‐induced arthritis (CIA) is an animal model of rheumatoid arthritis that has been used extensively to address questions of disease pathogenesis and to validate novel therapeutic targets. Susceptibility to CIA is strongly associated with major histocompatibility complex class II genes, and the development of arthritis is accompanied by a robust T‐ and B‐cell response to type II collagen. The main pathological features of CIA include proliferative synovitis with infiltration of inflammatory cells, pannus formation, cartilage degradation, erosion of bone and fibrosis. Pro‐inflammatory cytokines, such as tumour necrosis factor α and interleukin‐1β, are expressed in the arthritic joints in both murine CIA and human rheumatoid arthritis, and blockade of these molecules results in amelioration of disease. Hence, there is a great deal of interest in the development of small‐molecular‐weight inhibitors of pro‐inflammatory cytokines. There is also interest in the development and testing of drugs with the capacity to modulate the immune pathways involved in driving the inflammatory response in arthritis. For these reasons, there is a need to monitor the effect of novel treatments on cytokine expression in vivo. In this review, we outline the various techniques used to detect cytokines in experimental arthritis and describe how these techniques have been used to quantify changes in cytokine expression following therapeutic intervention.
Preservation of platelet responsiveness to nitroglycerine despite development of vascular nitrate tolerance
Authors: Holmes Andrew S. , Chirkov Yuliy Y. , Willoughby Scott R. , Poropat Susan , Pereira Jeremy , Horowitz John D. 
Published: September 2005

AimsOrganic nitrates, via nitric oxide (NO) release, induce vasodilatation and inhibit platelet aggregation. Development of nitrate tolerance in some vascular preparations may be associated with diminished responsiveness to NO. To date it is not known to what extent vascular tolerance to organic nitrates is associated with acquired platelet hypo‐responsiveness to NO. In the current study we compared the acute and chronic effects of sustained release (SR) isosorbide 5′ mono‐nitrate (ISMN) and transdermal nitroglycerine (TD‐NTG) on blood vessels (effects on apparent arterial stiffness) and platelets (effects on responsiveness to NO donors) in patients with stable angina pectoris (SAP).MethodsPatients (n = 34) with SAP entered a blinded randomized crossover study of ISMN (120 mg) vs. intermittent TD‐NTG (15 mg 24 h−1). Effects of each nitrate on pulse wave reflection (augmentation index (AIx)), platelet response to adenosine di‐phosphate (ADP 1 µmol l−1), nitroglycerine (NTG 100 µmol l−1) and the non‐nitrate NO donor sodium nitroprusside (SNP 10 µmol l−1), were measured pre‐dose, 4 and 8 h post dose, on three occasions: 1) at the end of a pre‐nitrate phase, 2) after dosing for 7 days and 3) following 14 days of full dose therapy with either nitrate.ResultsAcutely, both ISMN and TD‐NTG markedly reduced AIx. After 14 days, these effects were significantly attenuated (anova, P = 0.018) but not abolished, indicating development of nitrate tolerance. Neither nitrate preparation affected ADP (1 µmol l−1)‐induced platelet aggregation. Platelet responsiveness to NTG (100 µmol l−1) and SNP (10 µmol l−1) was not diminished during chronic nitrate therapy, and there was no evidence of ‘rebound’ hyper‐aggregability during ‘nitrate‐free’ periods.ConclusionsChronic therapy with either ISMN or TD‐NTG is associated with development of vascular tolerance. Despite the induction of vascular tolerance, platelet responsiveness to NTG and SNP remains unaffected. Therefore, development of vascular tolerance is unlikely to compromise the anti‐aggregatory effects of organic nitrates, or those of endogenous NO.
The quality of information on monitoring for haematological adverse drug reactions
Authors: Ferner R. E. , Coleman Jamie , Pirmohamed Munir , Constable Simon A. , Rouse Andrew 
Published: September 2005

Aims To examine the adequacy of instructions to monitor for haematological adverse drug reactions in the Summary of Product Characteristics.Methods We searched the United Kingdom eMedicines Compendium to identify instructions to monitor for haematological adverse drug reactions, and selected 84 Summaries of Product Characteristics for nonhaematological drugs, which were then scored independently by five clinicians, using a scale we devised, the Systematic Instructions for Monitoring (SIM) score. A subset of comparable summaries from Australian and United States summaries was also examined.Results The SIM scores for the five clinicians agreed well: Kendall's coefficient of concordance = 0.937, P < 0.0001. The median SIM score for the 84 UK summaries was 13 [95% confidence interval (CI) for median 12, 15] out of a possible 31. Over 40% fell below a hypothetical minimally acceptable score of 12/31. SIM scores were on average 2.0 (95% CI 0.4, 3.8) higher for Australian summaries; US summaries had intermediate scores that did not significantly differ from those in Australia or the UK.Conclusions Instructions on monitoring for adverse drug reactions are often inadequate. Pharmaceutical companies and regulatory agencies should produce clear guidance on monitoring, and the data to support it.
Effects of food and formulation on the relative bioavailability of bismuth biskalcitrate, metronidazole, and tetracycline given for Helicobacter pylori eradication
Authors: Spénard Jean , Aumais Christian , Massicotte Julie , Brunet Jean‐Sébastien , Tremblay Claude , Grace Michael , Lefebvre Marc 
Published: September 2005

AimsTo evaluate the effects of food and formulation on the pharmacokinetics of bismuth biskalcitrate, metronidazole and tetracycline when combined in a new 3‐in‐1 single capsule (BMT) for eradication of Helicobacter pylori.MethodsIn a randomized, 3 × 3 cross‐over design, 23 healthy males received one dose of BMT in the fed and fasting states and equivalent doses of the three drugs given together but as separate capsules while fasting. Bioequivalence was evaluated according to 90% confidence intervals (CIs) of ratios of geometric least square means for Cmax, AUCt, and AUC∞.ResultsWith respect to food, none of the three drugs met bioequivalence guidelines. Bismuth had lower limit CIs ranging from 12% for Cmax to 25% for AUC∞. The corresponding values for tetracycline were 59% and 51%. Metronidazole had a lower limit CI of 74% for Cmax. With respect to formulation, bismuth had lower limits of CIs ranging from 39% for Cmax to 50% for AUCt and higher limits of 146% for AUCt, metronidazole met bioequivalence guidelines, and tetracycline had lower limits of CIs between 72% for AUCt and 74% for AUC∞.ConclusionsFood significantly decreased the relative bioavailability of each drug but formulation was without effect. This decrease may be beneficial when a local gastric action is needed, as confirmed by a near 90% eradication rate when this combined capsule is administered with food to treat gastro‐duodenal local infection by H. pylori.
S‐Naproxen and desmethylnaproxen glucuronidation by human liver microsomes and recombinant human UDP‐glucuronosyltransferases (UGT): role of UGT2B7 in the elimination of naproxen
Authors: Bowalgaha Kushari , Elliot David J. , Mackenzie Peter I. , Knights Kathleen M. , Swedmark Stellan , Miners John O. 
Published: September 2005

AimsTo characterize the kinetics of S‐naproxen (‘naproxen’) acyl glucuronidation and desmethylnaproxen acyl and phenolic glucuronidation by human liver microsomes and identify the human UGT isoform(s) catalysing these reactions.MethodsNaproxen and desmethylnaproxen glucuronidation were investigated using microsomes from six and five livers, respectively. Human recombinant UGTs were screened for activity towards naproxen and desmethylnaproxen. Where significant activity was observed, kinetic parameters were determined. Naproxen and desmethylnaproxen glucuronides were measured by separate high‐performance liquid chromatography methods.ResultsNaproxen acyl glucuronidation by human liver microsomes followed biphasic kinetics. Mean apparent Km values (±SD, with 95% confidence interval in parentheses) for the high‐ and low‐affinity components were 29 ± 13 µm (16, 43) and 473 ± 108 µm (359, 587), respectively. UGT 1A1, 1A3, 1A6, 1A7, 1A8, 1A9, 1A10 and 2B7 glucuronidated naproxen. UGT2B7 exhibited an apparent Km (72 µm) of the same order as the high‐affinity human liver microsomal activity, which was inhibited by the UGT2B7 selective ‘probe’ fluconazole. Although data for desmethylnaproxen phenolic glucuronidation by human liver microsomes were generally adequately fitted to either the single‐ or two‐enzyme Michaelis–Menten equation, model fitting was inconclusive for desmethylnaproxen acyl glucuronidation. UGT 1A1, 1A7, 1A9 and 1A10 catalysed both the phenolic and acyl glucuronidation of desmethylnaproxen, while UGT 1A3, 1A6 and 2B7 formed only the acyl glucuronide. Atypical glucuronidation kinetics were variably observed for naproxen and desmethylnaproxen glucuronidation by the recombinant UGTs.ConclusionUGT2B7 is responsible for human hepatic naproxen acyl glucuronidation, which is the primary elimination pathway for this drug.
No positive association between adrenergic receptor variants of α2cDel322–325, β1Ser49, β1Arg389 and the risk for heart failure in the Japanese population
Authors: Nonen Shinpei , Okamoto Hiroshi , Akino Masatoshi , Matsui Yutaka , Fujio Yasushi , Yoshiyama Minoru , Takemoto Yasuhiko , Yoshikawa Junichi , Azuma Junichi , Kitabatake Akira 
Published: September 2005

AimsWe investigated the correlation of adrenergic receptor polymorphisms, α2cDel322–325, β1Ser49Gly and β1Arg389Gly, with the risk of heart failure in the Japanese population.MethodsThese polymorphisms were analysed by polymerase chain reaction‐restriction fragment length polymorphism in patients with chronic heart failure due to idiopathic dilated cardiomyopathy (DCM) and compared with the control group.ResultsThere were no differences or any trends in the allele and genotype frequencies of the β1Ser49Gly and β1Arg389Gly polymorphisms. The allele frequency of the α2cDel322–325 variant was lower in patients than in controls (0.11 vs. 0.04, P = 0.011 < 0.017, by Bonferroni correction), while the genotype frequency just failed to reach significance (P = 0.022 > 0.017, by Bonferroni correction).ConclusionsIn this population, the variants β1Ser49, β1Arg389, and α2cDel322–325 do not appear to be risk factors for chronic heart failure due to DCM. The α2cDel322–325 variant may in fact confer some protection.
Rhythm vs. rate control of atrial fibrillation meta‐analysed by number needed to treat
Authors: Kumana Cyrus R. , Cheung Bernard M. Y. , Cheung Giselle T. Y. , Ovedal Tori , Pederson Bjorn , Lauder Ian J. 
Published: September 2005

BackgroundWhenever feasible, rhythm control of atrial fibrillation (AF) was generally preferred over rate control, in the belief that it offered better symptomatic relief and quality of life, and eliminated the need for anticoagulation. However, recent trials appear to challenge these assumptions.AimsTo explore the desirability of rhythm vs. rate control of AF by systematic review of pertinent, published, randomized controlled trials (RCTs) and a meta‐analysis by number needed to treat (NNT) year−1, with respect to diverse clinically important outcomes.MethodsRCTs of outcome primarily comparing rate vs. rhythm control in patients with spontaneous AF were identified. For each outcome and assuming rhythm control to be the active treatment, relative risk reduction (RRR) and NNT year−1 were derived for individual trials together with an NNT year−1 for all trials combined; corresponding 95% confidence intervals (CI) were also calculated. Adverse drug reaction (ADR) and quality of life reporting were also assessed.ResultsIn all, data from five suitable RCTs (entailing 5239 patients) were analysed. For hospitalization, available RRRs and NNT year−1 values were all clinically and statistically significant. Overall, one additional patient was hospitalized for every 35 assigned to rhythm control (95% CI 27, 48). For the endpoints of death, ‘ischaemic’ stroke and ‘non‐CNS’ bleeding, there was no significant difference. ADRs were significantly more common in rhythm control patients, whereas quality of life assessments revealed no difference. Thromboembolism was associated with cessation of or subtherapeutic anticoagulation, irrespective of treatment assignment.ConclusionReduced risk of hospitalization and non‐inferiority for other endpoints all favour rate control, the less costly strategy. If symptoms of AF are not a problem, treatment should target optimizing rate control and more widespread and effective prophylactic anticoagulation.