bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of vaginal surgery on sexuality and quality of life in women with urinary incontinence or genital descensus
Authors: Helström Lotti , Nilsson Bo 
Published: December 2004

Aim.  To study the effect of vaginal surgery for urinary incontinence and genital descensus on sexual function and quality of life.Methods.  The day before surgery, 118 women, of whom 41 were admitted for urinary incontinence and 77 for genital descensus, accepted to complete a questionnaire containing questions of uterovaginal symptoms, quality of life, and sexuality. One year later, 101 women, of them 88 were sexually active, accepted to complete the same questionnaire by mail.Results.  The women reported improvement in two different scales for quality of life, and there was no difference between surgery for genital descensus and that for urinary stress incontinence. The total score for sexual variables was deteriorated, and the mean frequency of sexual intercourse was reduced. Among women with genital descensus, 14% experienced more urinary incontinence and 13% more dyspareunia after the operation.Conclusion.  Although pelvic floor disorders are known to impair sexual function, there was no improvement in sexuality after surgery for urinary incontinence or genital descensus. On the contrary, it seems that sexual function might deteriorate and dyspareunia get worse after vaginal surgery. The explanation for this might be vulnerability to disturbance of vaginal nerve and blood supply of the vaginal wall resulting in impaired sexual arousal and lubrication.
Views of midwives and gynecologists on legal abortion – a population‐based study
Authors: Hammarstedt Meta , Jacobsson Lars , Wulff Marianne , Lalos Ann 
Published: December 2004

Background.  Little is known about staffs' attitudes and experiences of legal abortion. The aim of this study was to gain knowledge about the views of Swedish midwives and gynecologists on legal abortion. Another aim was to investigate differences between professions and possible impacting factors on these views.Methods.  A questionnaire was sent to a random sample of 258 midwives and 269 gynecologists. The response rate was 84%.Results.  The vast majority of all respondents supported the legislation on induced abortion. A great majority also believed that the woman alone should make the decision, and that abortion was not used as a form of contraception. Generally, there were smaller differences among views of female and male gynecologists than among views of female gynecologists and female midwives. For example, female midwives disagreed more than female gynecologists with the statement: ‘Legal abortion should be permitted even if the woman has felt fetal movements’. The most impacting factors on views were the extent to which the staffs had been working with legal abortion, especially during the last year, and type of profession. Views were, however, not influenced by private experiences of legal abortion.Conclusions.  The present study highlights that midwives and gynecologists overwhelmingly agree that legal abortion should be allowed. The more experience of working with legal abortion, especially current experience, the less restrictive gynecologists and midwives are in their views. Compared with previous studies, staffs have become more liberal in their attitudes toward abortion and the relevant legislation.
Low‐impact exercise during pregnancy – a study of safety
Authors: Larsson Linnea , Lindqvist Pelle G. 
Published: December 2004

Background.  Exercise is an important part of many women's lives. Women are often advised to refrain from physical exercise during pregnancy. The reason given is mainly safety, i.e. fear of maternal hyperthermia, which is known to be related to neural tube defects. However, exercise during pregnancy has not been shown to be related to hyperthermia.Objective.  To study temperature and oxygen saturation responses to low‐impact exercise in healthy pregnant women.Methods.  Forty pregnant women and 11 controls participating in low‐impact aerobic exercise were monitored before exercise, at maximum‐exercise level, and after exercise with regard to core temperature, heart rate, and oxygen saturation level.Results.  The core temperature among the pregnant women did not increase significantly at maximum exercise or after exercise (36.5 versus 36.7 or 36.5 °C, P = 0.1, P = 0.5). None of the pregnant women were even close to approaching a dangerous body temperature at an intensity level of 69% of their maximum heart rate. As compared with pre‐exercise values, oxygen saturation among pregnant women was significantly reduced at both maximum‐exercise and postexercise measurements, but no measurement was below 95% in oxygen saturation.Conclusion.  Low‐impact aerobics at about 70% of one's maximum heart rate appears to be safe in terms of risk of maternal hyperthermia.
The Emperor’s New Computers: Y2K (Re)Visited
Authors: Quigley Kevin 
Published: December 2004

In order to deal with the threat of Y2K (the Millennium Bug) the UK Government directed an uncreative, resource‐heavy, centralized operation with standardized reporting requirements. The project impacted almost all government systems, from the critical to the mundane. The government’s position was made worse by administrative changes that it had initiated in the 1980s and 1990s that had created a much larger network of delivery partners while at the same time hollowing out IT expertise within the civil service. With little regulation in place, the government was vulnerable to IT opportunists who recognized the financial gains that Y2K offered. An alarmist media also exacerbated the problem. The paper ends by offering some observations regarding the government’s management of IT and how this might be improved to allow the government to pursue its Modernization Agenda.Things did not go right by accident.Cabinet Office Press Release on Y2K, inBeckett 2000a
The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)‐ibuprofen enantiomer in healthy subjects
Authors: Martínez Carmen , García‐Martín Elena , Blanco Gerardo , Gamito Francisco J. G. , Ladero José M. , Agúndez José A. G. 
Published: December 2004

AimsTo study the effect of CYP2C8*3, the most common CYP2C8 variant allele on the dis‐position of (R)‐ibuprofen and the association of CYP2C8*3 with variant CYP2C9 alleles.MethodsThree hundred and fifty‐five randomly selected Spanish Caucasians were screened for the common CYP2C8 and CYP2C9 mutations. The pharmacokinetics of (R)‐ibuprofen were studied in 25 individuals grouped into different CYP2C8 genotypes.ResultsThe allele frequency of CYP2C8*3 (0.17) was found to be higher than that reported for other Caucasian populations (P = 0.0001). The frequencies of CYP2C9*2 and CYP2C9*3 were 0.19 (0.16–0.21) and 0.10 (0.08–0.12), respectively. An association between CYP2C8*3 and CYP2C9*2 alleles was observed, occurring together at a frequency 2.4‐fold higher than expected for a random association of alleles (P = 0.0001). The presence of the CYP2C8*3 allele was found to influence the pharmacokinetics of (R)‐ibuprofen in a gene–dose effect manner. Thus, after administration of 400 mg ibuprofen, the plasma half‐life (95% confidence intervals) for individuals with genotypes CYP2C8*1/*1, CYP2C8*1/*3 and CYP2C8*3/*3, was 2.0 h (1.8–2.2), 4.2 h (1.9–6.5; P < 0.05) and 9.0 h (7.8–10.2; P < 0.002), respectively. A statistically significant trend with respect to the number of variant CYP2C8*3 alleles was also observed for the area under the concentration‐time curve (P < 0.025), and drug clearance (P < 0.03).ConclusionPolymorphism of the CYP2C8 gene was found to be common, with nearly 30% of the population studied carrying the variant CYP2C8*3 allele. The presence of the latter caused a significant effect on the disposition of (R)‐ibuprofen. This suggests that a substantial proportion of Caucasian subjects may show alterations in the disposition of drugs that are CYP2C8 substrates.
Dose‐response to salbutamol via a novel palm sized nebuliser (Aerodose® Inhaler), conventional nebuliser (Pari LC Plus) and metered dose inhaler (Ventolin™ Evohaler™) in moderate to severe asthmatics
Authors: Lipworth Brian J. , Sims Erika J. , Taylor Karla , Cockburn Wendy , Fishman Robert 
Published: December 2004

AimsThe Aerodose® inhaler is a novel, palm‐sized, breath actuated device which requires little patient coordination. This study compared the dose–response of salbutamol delivered by the Aerodose® Inhaler (Aerogen Inc., Mountain View, USA) vs Pari LC Plus jet nebulizer (Pari LC Plus; Pari GmbH, Starnberg, Germany) and Ventolin™ Evohaler™ HFA pMDI (Evohaler; Allen & Hanburys [GlaxoSmithkline], Uxbridge, UK).MethodsTwenty‐two moderate to severe asthmatic patients, mean (s.d.) age: 44.7 (9.4), FEV1: 58.1 (12.0), received 4 cumulative doubling doses of salbutamol in a randomised, investigator blind, balanced crossover design. Spirometry and systemic safety variables (heart rate, blood pressure, T wave amplitude, QTc interval and potassium) were measured at baseline and after each dose.ResultsParallel regression analysis revealed that microgram relative potency ratios for the Aerodose® Inhaler to be five times more efficient for FEV1 than either the Pari LC Plus (0.202, 90% CI: 0.189–0.216) or the Evohaler (0.202, 90% CI: 0.189–0.216), while there was no difference between Pari LC Plus vs Evohaler. Similarly, Aerodose® Inhaler vs. Pari LC Plus showed approximately five‐fold greater potency for all systemic parameters, except blood pressure. As compared to the Evohaler, Aerodose® Inhaler had equivalent potency for plasma potassium and T wave amplitude, but demonstrated greater potency for heart rate and QTc interval.ConclusionsThis study has indicated therefore, that Aerodose® Inhaler is approximately five times as efficient as the Pari LC Plus and Evohaler in relative lung delivery of salbutamol in moderate to severe asthmatics.
Lornoxicam pharmacokinetics in relation to cytochrome P450 2C9 genotype
Authors: Zhang Yifan , Zhong Dafang , Si Dayong , Guo Yingjie , Chen Xiaoyan , Zhou Hui 
Published: December 2004

AimsTo investigate the pharmacokinetics of lornoxicam and the relationship with CYP2C9 polymorphism in healthy Chinese subjects.MethodsA single oral dose of 8 mg lornoxicam was administered to 18 healthy Chinese male subjects. Plasma was sampled for 24 h post dose, and plasma concentrations of lornoxicam were measured using a validated LC/MS/MS method. CYP2C9 genotype was determined by polymerase chain reaction‐based restriction fragment length polymorphism or by direct sequencing of the coding region of the CYP2C9 gene.ResultsOf the18 subjects, one subject was found to be a very poor metabolizer of lornoxicam with a long t1/2 of 106 h, a low CL/F of 0.71 ml min−1, and a high AUC0–∞ of 187.6 µg ml−1 h. Genotyping studies revealed that this subject was heterozygous for CYP2C9*3 and a new variant CYP2C9 allele. Of the other 17 subjects, 13 were *1/*1 carriers, three were *1/*3 carriers, and one was a *1/*2 carrier. Mean AUC0–∞ values (95% confidence intervals) of lornoxicam were 9.25 (6.55, 11.95) vs. 4.75 (3.55, 5.95) µg ml−1 h in *1 heterozygotes vs.*1 homozygotes, and mean CL/F values were 14.8 (10.2, 19.4) vs. 32.9 (24.5, 41.3) ml min−1, respectively (P < 0.05 for both AUC and CL/F).ConclusionsThe results show that the pharmacokinetics of lornoxicam are dependent on CYP2C9 polymorphism. In particular, the presence of the CYP2C9*3 allele impairs the oral clearance of lornoxicam.
A population‐based assessment of the potential interaction between serotonin‐specific reuptake inhibitors and digoxin
Authors: Juurlink David N. , Mamdani Muhammad M. , Kopp Alexander , Herrmann Nathan , Laupacis Andreas 
Published: December 2004

Aim In vitro evidence suggests that some serotonin‐specific reuptake inhibitors (SSRIs) inhibit P‐glycoprotein, a multidrug efflux pump responsible for the elimination of several drugs including digoxin. We sought to determine if some SSRIs cause digoxin toxicity in the clinical setting.MethodsPopulation‐based nested case–control study set in Ontario, Canada from 1994 to 2001. We studied all patients 66 years or older treated with digoxin. Prescription and hospital admission records were analysed to determine the relationship between the initiation of SSRI therapy and hospital admission for digoxin toxicity in the subsequent 30 days.ResultsAmong 245 305 older patients treated with digoxin, we identified 3144 cases of digoxin toxicity. After adjusting for potential confounders, we observed an increased risk of digoxin toxicity following initiation of paroxetine [odds ratio (OR) 2.8; 95% confidence interval (CI) 1.6, 4.7], fluoxetine (OR 2.9; 95% CI 1.5, 5.4), sertraline (OR 3.0; 95% CI 1.9, 4.7), and fluvoxamine (OR 3.0; 95% CI 1.5, 5.7). However, an elevated risk was also seen with tricyclic antidepressants (OR 1.5; 95% CI 1.0, 2.4) and benzodiazepines (OR 2.1; 95% CI 1.7, 2.5), drugs classes having no known pharmacokinetic interaction with digoxin. There was no statistical difference in the risk of digoxin toxicity among any of the agents tested.ConclusionsWe found no major discrepancy in the risk of digoxin toxicity after initiation of various SSRI antidepressants, suggesting that the inhibition of P‐glycoprotein by sertraline and paroxetine observed in vitro is unlikely to be of major clinical significance.
National differences in publishing papers on adverse drug reactions
Authors: Ferner R. E. , Aronson J. K. 
Published: December 2004

AimsTo examine how countries differ in attitudes to adverse drug reactions by examining published scientific papers.MethodsWe searched Ovid EMBASE for publications indexed by the category ′therapeutic agents′, and the subcategory ′adverse effects′, by country for 43 countries.ResultsWe counted 1 810 202 papers world‐wide regarding therapeutic agents during 14 years, of which 195 154 (10.8%) were included in the adverse effects subcategory. There were substantial differences between countries, not explained by population, economic variation, overall publication rate on therapeutic agents, or the presence of large indigenous pharmaceutical companies.ConclusionsMany local cultural factors influence the ratio of papers on adverse reactions to all drug effects, so it may be difficult to improve their recognition and reporting by international efforts.
How do follicular dendritic cells interact intimately with B cells in the germinal centre?
Authors: Park Chan‐Sik , Choi Yong Sung 
Published: December 2004

SummaryThe germinal centre is a dynamic microenvironment where antigen‐activated B cells rapidly expand and differentiate, generating plasma cells and memory B cells. These cellular events are accompanied by dramatic changes in the antibody molecules that undergo somatic hypermutation and isotype switching. Follicular dendritic cells (FDCs) are the stromal cells located in the germinal centre. Although the capacity of FDCs to present antigen to B cells through antigen–antibody complexes has been recognized for many years, additional critical functions of FDCs have only recently been recognized. FDCs prevent apoptosis of germinal centre B cells and stimulate cellular interaction and proliferation. Here, we review the FDC signalling molecules that have recently been identified, some of which offer potential therapeutic targets for autoimmune diseases and B‐cell lymphomas.
Identification of novel heat shock factor‐dependent genes and biochemical pathways in Arabidopsis thaliana
Authors: Busch Wolfgang , Wunderlich Markus , Schöffl Fritz 
Published: December 2004

SummaryIn order to assess specific functional roles of plant heat shock transcription factors (HSF) we conducted a transcriptome analysis of Arabidopsis thaliana hsfA1a/hsfA1b double knock out mutants and wild‐type plants. We used Affymetrix ATH1 microarrays (representing more than 24 000 genes) and conducted hybridizations for heat‐treated or non‐heat‐treated leaf material of the respective lines. Heat stress had a severe impact on the transcriptome of mutant and wild‐type plants. Approximately 11% of all monitored genes of the wild type showed a significant effect upon heat stress treatment. The difference in heat stress‐induced gene expression between mutant and wild type revealed a number of HsfA1a/1b‐regulated genes. Besides several heat shock protein and other stress‐related genes, we found HSFA‐1a/1b‐regulated genes for other functions including protein biosynthesis and processing, signalling, metabolism and transport. By screening the profiling data for genes in biochemical pathways in which known HSF targets were involved, we discovered that at each step in the pathway leading to osmolytes, the expression of genes is regulated by heat stress and in several cases by HSF. Our results document that in the immediate early phase of the heat shock response HSF‐dependent gene expression is not limited to known stress genes, which are involved in protection from proteotoxic effects. HsfA1a and HsfA1b‐regulated gene expression also affects other pathways and mechanisms dealing with a broader range of physiological adaptations to stress.
High‐throughput protein localization in Arabidopsis using Agrobacterium‐mediated transient expression of GFP‐ORF fusions
Authors: Koroleva Olga A. , Tomlinson Matthew L. , Leader David , Shaw Peter , Doonan John H. 
Published: December 2004

SummaryWe describe a streamlined and systematic method for cloning green fluorescent protein (GFP)‐open reading frame (ORF) fusions and assessing their subcellular localization in Arabidopsis thaliana cells. The sequencing of the Arabidopsis genome has made it feasible to undertake genome‐based approaches to determine the function of each protein and define its subcellular localization. This is an essential step towards full functional analysis. The approach described here allows the economical handling of hundreds of expressed plant proteins in a timely fashion. We have integrated recombinational cloning of full‐length trimmed ORF clones (available from the SSP consortium) with high‐efficiency transient transformation of Arabidopsis cell cultures by a hypervirulent strain of Agrobacterium. To demonstrate its utility, we have used a selection of trimmed ORFs, representing a variety of key cellular processes and have defined the localization patterns of 155 fusion proteins. These patterns have been classified into five main categories, including cytoplasmic, nuclear, nucleolar, organellar and endomembrane compartments. Several genes annotated in GenBank as unknown have been ascribed a protein localization pattern. We also demonstrate the application of flow cytometry to estimate the transformation efficiency and cell cycle phase of the GFP‐positive cells. This approach can be extended to functional studies, including the precise cellular localization and the prediction of the role of unknown proteins, the confirmation of bioinformatic predictions and proteomic experiments, such as the determination of protein interactions in vivo, and therefore has numerous applications in the post‐genomic analysis of protein function.
Immunoglobulin A‐deficient mice exhibit altered T helper 1‐type immune responses but retain mucosal immunity to influenza virus
Authors: Zhang Yongxin , Pacheco Susan , Acuna Catherine L. , Switzer Kirsten C. , Wang Ying , Gilmore Xyanthine , Harriman Gregory R. , Mbawuike Innocent N. 
Published: December 2004

SummaryWe have previously demonstrated that immunoglobulin A (IgA)−/− knockout (KO) mice exhibit levels of susceptibility to influenza virus infection that are similar to those of their normal IgA+/+ littermates. To understand the mechanism of this apparent mucosal immunity without IgA, immunoglobulin isotype and T helper 1 (Th1)‐type [interferon‐γ (IFN‐γ)] and Th2‐type [interleukin (IL)‐4, IL‐5)] cytokine responses to influenza vaccine were evaluated. Intranasal immunization with influenza virus subunit vaccine plus cholera toxin/cholera toxin B subunit (CT/CTB) induced significant influenza virus‐specific immunoglobulin G (IgG) antibody in the serum and nasal passages of both IgA−/− and IgA+/+ mice, while IgA antibodies were induced only in IgA+/+ mice. IgA KO mice exhibited an IgG1 subclass haemagglutinin (HA)‐specific response but no detectable IgG2a and IgG2b responses. In contrast, IgA+/+ mice exhibited significant IgG1 as well as IgG2a responses. This indicates a predominant Th2‐type response in IgA KO mice compared to normal mice. Following stimulation with influenza virus in vitro, splenic lymphocytes from immunized IgA−/− mice produced significantly lower levels of IFN‐γ than IgA+/+ mice (P < 0·001), but elaborated similar levels of IL‐4 and IL‐5. This was true at both protein and mRNA levels. Immunized mice were challenged intranasally with a small inoculum of influenza virus to allow deposition of virus in the nasal mucosal passages. Compared to non‐immunized mice, immunized IgA−/− and IgA+/+ mice exhibited significant, but similar levels of reduction in virus titres in the nose and lung. These results demonstrate that in addition to IgA deficiency, IgA gene deletion also resulted in down‐regulated Th1‐type immune responses and confirm our previous data that IgA antibody is not indispensable for the prevention of influenza virus infection.
Beta diversity of angiosperms in temperate floras of eastern Asia and eastern North America
Authors: Qian Hong , Ricklefs Robert E. , White Peter S. 
Published: December 2004

AbstractThe diversity of a region reflects both local diversity and the turnover of species (beta diversity) between areas. The angiosperm flora of eastern Asia (EAS) is roughly twice as rich as that of eastern North America (ENA), in spite of similar area and climate. Using province/state‐level angiosperm species floras, we calculated beta diversity as the slope of the relationship between the log of species similarity (S ) and either geographic distance or difference in climate. Distance‐based beta diversity was 2.6 times greater in the north–south direction in EAS than in ENA and 3.3 times greater in the east–west direction. When ln S was related to distance and climate difference in multiple regressions, both distance and climate PC1 were significant effects in the north–south direction, but only geographic distance had a significant, unique influence in the east–west direction. The general predominance of distance over environment in beta diversity suggests that history and geography have had a strong influence on the regional diversity of these temperate floras.
Interactions between spatially separated herbivores indirectly alter plant diversity
Authors: van Ruijven Jasper , De Deyn Gerlinde B. , Raaijmakers Ciska E. , Berendse Frank , van Der Putten Wim H. 
Published: December 2004

AbstractAbove‐ and belowground herbivores promote plant diversity when selectively feeding on dominant plant species, but little is known about their combined effects. Using a model system, we show that neutral effects of an aboveground herbivore and positive effects of a belowground herbivore on plant diversity became profoundly negative when adding these herbivores in combination. The non‐additive effects were explained by differences in plant preference between the aboveground‐ and the belowground herbivores and their consequences for indirect interactions among plant species. Simultaneous exposure to aboveground‐ and belowground herbivores led to plant communities being dominated by a few highly abundant species. As above‐ and belowground invertebrate herbivores generally differ in their mobility and local distribution patterns, our results strongly suggest that aboveground–belowground interactions contribute to local spatial heterogeneity of diversity patterns within plant communities.