bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Delirium with Dexmedetomidine Compared with Morphine Based Therapy after Cardiac Surgery
Authors: Shehabi Yahya , Grant Peter , Wolfenden Hugh , Hammond Naomi , Bass Frances , Campbell Michelle , Chen Jack 
Published: October 2009

Background
Commonly used sedatives/analgesics can increase the risk of postoperative complications, including delirium. This double-blinded study assessed the neurobehavioral, hemodynamic, and sedative characteristics of dexmedetomidine compared with morphine-based regimen after cardiac surgery at equivalent levels of sedation and analgesia.

Methods
A total of 306 patients at least 60 yr old were randomized to receive dexmedetomidine (0.1-0.7 microg x kg(-1) x h(-1)) or morphine (10-70 microg x kg(-1) x h(-1)) with open-label propofol titrated to a target Motor Activity Assessment Scale of 2-4. Primary outcome was the prevalence of delirium measured daily via Confusion Assessment Method for intensive care. Secondary outcomes included ventilation time, additional sedation/analgesia, and hemodynamic and adverse effects.

Results
Of all sedation assessments, 75.2% of dexmedetomidine and 79.6% (P = 0.516) of morphine treatment were in the target range. Delirium incidence was comparable between dexmedetomidine 13 (8.6%) and morphine 22 (15.0%) (relative risk 0.571, 95% confidence interval [CI] 0.256-1.099, P = 0.088), however, dexmedetomidine-managed patients spent 3 fewer days (2 [1-7] versus 5 [2-12]) in delirium (95% CI 1.09-6.67, P = 0.0317). The incidence of delirium was significantly less in a small subgroup requiring intraaortic balloon pump and treated with dexmedetomidine (3 of 20 [15%] versus 9 of 25 [36%]) (relative risk 0.416, 95% CI 0.152-0.637, P = 0.001). Dexmedetomidine-treated patients were more likely to be extubated earlier (relative risk 1.27, 95% CI 1.01-1.60, P = 0.040, log-rank P = 0.036), experienced less systolic hypotension (23% versus 38.1%, P = 0.006), required less norepinephrine (P < 0.001), but had more bradycardia (16.45% versus 6.12%, P = 0.006) than morphine treatment.

Conclusion
Dexmedetomidine reduced the duration but not the incidence of delirium after cardiac surgery with effective analgesia/sedation, less hypotension, less vasopressor requirement, and more bradycardia versus morphine regimen.
Long-term Cognitive Decline in Older Subjects Was Not Attributable to Noncardiac Surgery or Major Illness
Authors: Avidan Michael S. , Searleman Adam C. , Storandt Martha , Barnett Kara , Vannucci Andrea , Saager Leif , Xiong Chengjie , Grant Elizabeth A. , Kaiser Dagmar , Morris John C. , Evers Alex S. 
Published: October 2009

Background
Persistent postoperative cognitive decline is thought to be a public health problem, but its severity may have been overestimated because of limitations in statistical methodology. This study assessed whether long-term cognitive decline occurred after surgery or illness by using an innovative approach and including participants with early Alzheimer disease to overcome some limitations.

Methods
In this retrospective cohort study, three groups were identified from participants tested annually at the Washington University Alzheimer's Disease Research Center in St. Louis, Missouri: those with noncardiac surgery, illness, or neither. This enabled long-term tracking of cognitive function before and after surgery and illness. The effect of surgery and illness on longitudinal cognitive course was analyzed using a general linear mixed effects model. For participants without initial dementia, time to dementia onset was analyzed using sequential Cox proportional hazards regression.

Results
Of the 575 participants, 214 were nondemented and 361 had very mild or mild dementia at enrollment. Cognitive trajectories did not differ among the three groups (surgery, illness, control), although demented participants declined more markedly than nondemented participants. Of the initially nondemented participants, 23% progressed to a clinical dementia rating greater than zero, but this was not more common after surgery or illness.

Conclusions
The study did not detect long-term cognitive decline independently attributable to surgery or illness, nor were these events associated with accelerated progression to dementia. The decision to proceed with surgery in elderly people, including those with early Alzheimer disease, may be made without factoring in the specter of persistent cognitive deterioration.
Moist lower montane rainforest classification: a case study from Bwindi Impenetrable National Park, Uganda
Authors: Chaigneau Tomas , Ahrends Antje , Argent Jennifer , Riddhiraska Naboon , Marchant Rob 
Published: October 2009

AbstractMoist lower montane vegetation has rarely been classified beyond broad zonational belts over large altitudinal ranges due to highly diverse species composition and structure. This study shows it is possible to further classify such forest types within Bwindi‐Impenetrable National Park (BINP), and that these assemblages can be explained by a combination of environmental conditions and past management. Botanical and environmental data were collected along some 4000 m of linear transects from the area surrounding Mubwindi Swamp, BINP. Ordination using Nonmetric Multidimensional Scaling (NMDS) and classification using Two‐way Indicator Species Analysis (TWINSPAN) successfully identified four different species assemblages. These forest types were then named on the basis of the ecological characteristics of the species within the group, and the environmental conditions influencing the distribution and past disturbance of the forest. The techniques used were in agreement for three out of the four forest types identified. Analysis using an environmental overlay showed a significant association between forest type and altitude. The results of this study indicate that a regional classification of forest types within moist lower montane forest belt using only tree species is possible, and that the forest types identified can be explained by environmental conditions and past management.
Review article: the current management of acute liver failure
Authors: CRAIG D. G. N. , LEE A. , HAYES P. C. , SIMPSON K. J. 
Published: October 2009

Aliment Pharmacol Ther 31, 345–358SummaryBackground  Acute liver failure is a devastating clinical syndrome with a persistently high mortality rate despite critical care advances. Orthotopic liver transplantation (OLT) is a life‐saving treatment in selected cases, but effective use of this limited resource requires accurate prognostication because of surgical risks and the requirement for subsequent life‐long immunosuppression.Aim  To review the aetiology of acute liver failure, discuss the evidence behind critical care management strategies and examine potential treatment alternatives to OLT.Methods  Literature review using Ovid, PubMed and recent conference abstracts.Results  Paracetamol remains the most common aetiology of acute liver failure in developed countries, whereas acute viral aetiologies predominate elsewhere. Cerebral oedema is a major cause of death, and its prevention and prompt recognition are vital components of critical care support, which strives to provide multiorgan support and ‘buy time’ to permit either organ regeneration or psychological and physical assessment prior to acquisition of a donor organ. Artificial liver support systems do not improve mortality in acute liver failure, whilst most other interventions have limited evidence bases to support their use.Conclusion  Acute liver failure remains a truly challenging condition to manage, and requires early recognition and transfer of patients to specialist centres providing intensive, multidisciplinary input and, in some cases, OLT.
Increased vascular permeability precedes cellular inflammation as asthma control deteriorates
Authors: Khor Y. H. , Teoh A. K. Y. , Lam S. M. , Mo D. C. Q. , Weston S. , Reid D. W. , Walters E. H. 
Published: October 2009

SummaryBackground
Airway microcirculation is abnormal in asthma but the role of vascular changes in asthma deteriorations remains poorly defined. We prospectively assessed the vascular changes accompanying worsening of asthma control by using an inhaled corticosteroid (ICS) dose‐reduction model.Objectives
To evaluate airway vascularity, vascular permeability and expression of vascular endothelial growth factor (VEGF) in early asthma deterioration induced by ICS back‐titration.Methods
Twenty mild‐to‐moderate persistent symptomatic asthmatics on low‐to‐moderate ICS were recruited and treated with 4 weeks of high‐dose fluticasone propionate (1000 μg/day) to achieve symptom control. This was followed by dose reduction to half of the pre‐study doses for 4–8 weeks until the symptoms began to return. Endobronchial biopsy and bronchoalveolar lavage (BAL) samples were obtained after both treatment periods.Results
Vascularity as measured by the number and size of blood vessels, as well as VEGF expression did not change following ICS reduction. Even on high‐dose ICS, perivascular albumin staining and BAL microalbumin levels in asthmatic subjects, as markers of permeability, were elevated when compared with normal subjects and both further increased significantly after ICS reduction. There was a significant association between changes in vascular leakiness and clinical deterioration. Increases in airway albumin correlated with previously reported increases in airway wall infiltration with T lymphocytes.Conclusions
Our results suggest that airway vascular leakage is a major pathophysiologic feature of early asthma deterioration, occurring before recrudescence of cellular inflammation.
Midostaurin (PKC412) inhibits immunoglobulin E‐dependent activation and mediator release in human blood basophils and mast cells
Authors: Krauth M.‐T. , Mirkina I. , Herrmann H. , Baumgartner C. , Kneidinger M. , Valent P. 
Published: October 2009

SummaryBackground
KIT tyrosine kinase inhibitors (TKI), such as nilotinib or midostaurin (PKC412), are increasingly used in clinical trials to counteract neoplastic cell growth in patients with aggressive mast cell (MC) disorders. However, these patients suffer not only from MC infiltration and consecutive organ damage but also from MC mediator‐related symptoms.Methods
We examined the effects of three KIT TKI, imatinib, nilotinib, and midostaurin, on IgE‐dependent mediator release in normal human blood basophils and cultured cord blood cell‐derived MC, and on spontaneous histamine secretion in the MC leukaemia cell line HMC‐1 and the basophil cell line KU812.Results
The multi‐kinase inhibitor midostaurin that interacts with KIT and protein kinase C was found to counteract anti‐IgE‐induced mediator release in blood basophils and cultured cord blood cell‐derived MC in all samples examined. By contrast, no effects of imatinib or nilotinib on histamine secretion in basophils or MC were found. The effects of midostaurin on histamine release were dose‐dependent and occurred at pharmacologic concentrations (IC50 10‐100 nm). Midostaurin was also found to inhibit the IgE‐dependent up‐regulation of CD63 on cultured cord blood cell‐derived human MC, but did not inhibit IgE‐dependent up‐regulation of CD63 or CD203c in human blood basophils.Conclusion
Midostaurin may be a beneficial drug in aggressive systemic mastocytosis not only because of its growth‐inhibitory effects but also because of its additional effects on activation and mediator release in MC and basophils.
The interaction of glutathione S‐transferase M1‐null variants with tobacco smoke exposure and the development of childhood asthma
Authors: Rogers A. J. , Brasch‐Andersen C. , Ionita‐Laza I. , Murphy A. , Sharma S. , Klanderman B. J. , Raby B. A. 
Published: October 2009

SummaryBackground
The glutathione S‐transferase M1 (GSTM1)‐null variant is a common copy number variant associated with adverse pulmonary outcomes, including asthma and airflow obstruction, with evidence of important gene‐by‐environment interactions with exposures to oxidative stress.Objective
To explore the joint interactive effects of GSTM1 copy number and tobacco smoke exposure on the development of asthma and asthma‐related phenotypes in a family‐based cohort of childhood asthmatics.Methods
We performed quantitative PCR‐based genotyping for GSTM1 copy number in children of self‐reported white ancestry with mild to moderate asthma in the Childhood Asthma Management Program. Questionnaire data regarding intrauterine (IUS) and post‐natal, longitudinal smoke exposure were available. We performed both family‐based and population‐based tests of association for the interaction between GSTM1 copy number and tobacco smoke exposure with asthma and asthma‐related phenotypes.Results
Associations of GSTM1‐null variants with asthma (P=0.03), younger age of asthma symptom onset (P=0.03), and greater airflow obstruction (reduced forced expiratory volume in 1 s / forced vital capacity, P=0.01) were observed among the 50 children (10% of the cohort) with exposure to IUS. In contrast, no associations were observed between GSTM1‐null variants and asthma‐related phenotypes among children without IUS exposure. Presence of at least one copy of GSTM1 conferred protection.Conclusion
These findings support an important gene‐by‐environment interaction between two common factors: increased risk of asthma and asthma‐related phenotypes conferred by GSTM1‐null homozygosity in children is restricted to those with a history of IUS exposure.
Auxiliary role for d‐alanylated wall teichoic acid in Toll‐like receptor 2‐mediated survival of Staphylococcus aureus in macrophages
Authors: Shiratsuchi Akiko , Shimizu Kaori , Watanabe Ikuko , Hashimoto Yumi , Kurokawa Kenji , Razanajatovo Iony M. , Park Keun H. , Park Hae K. , Lee Bok L. , Sekimizu Kazuhisa , Nakanishi Yoshinobu 
Published: October 2009

SummaryWe previously reported that Staphylococcus aureus avoids killing within macrophages by exploiting the action of Toll‐like receptor 2 (TLR2), which leads to the c‐Jun N‐terminal kinase (JNK)‐mediated inhibition of superoxide production. To search for bacterial components responsible for this event, a series of S. aureus mutants, in which the synthesis of the cell wall was interrupted, were screened for the level of JNK activation in macrophages. In addition to a mutant lacking the lipoproteins that have been suggested to act as a TLR2 ligand, two mutant strains were found to activate the phosphorylation of JNK to a lesser extent than the parental strain, and this defect was recovered by acquisition of the corresponding wild‐type genes. Macrophages that had phagocytosed the mutant strains produced more superoxide than those engulfing the parental strain, and the mutant bacteria were more efficiently killed in macrophages than the parent. The genes mutated, dltA and tagO, encoded proteins involved in the synthesis of d‐alanylated wall teichoic acid. Unlike a cell wall fraction rich in lipoproteins, d‐alanine‐bound wall teichoic acid purified from the parent strain by itself did not activate JNK phosphorylation in macrophages. These results suggest that the d‐alanylated wall teichoic acid of S. aureus modulates the cell wall milieu for lipoproteins so that they effectively serve as a ligand for TLR2.
Eosinophils infiltrate thyroids, but have no apparent role in induction or resolution of experimental autoimmune thyroiditis in interferon‐γ−/− mice
Authors: Fang Yujiang , Chen Kemin , Jackson Daniel A. , Sharp Gordon C. , Braley‐Mullen Helen 
Published: October 2009

SummaryGranulomatous experimental autoimmune thyroiditis (G‐EAT) is induced by mouse thyroglobulin (MTg)‐sensitized splenocytes activated with MTg and interleukin (IL)‐12. Our previous studies showed that, when used as donors and recipients, interferon (IFN)‐γ−/− and wild‐type (WT) DBA/1 mice both develop severe G‐EAT. Thyroid lesions in IFN‐γ−/− mice have many eosinophils and few neutrophils, while those in WT mice have extensive neutrophil infiltration and few eosinophils. Thyroid lesions in IFN‐γ−/− mice consistently resolve by day 40–50, whereas those in WT mice have ongoing inflammation and fibrosis persisting for more than 60 days. To determine if the extensive infiltration of eosinophils in thyroids of IFN‐γ−/− mice contributes to thyroid damage and/or early resolution of G‐EAT, anti‐IL‐5 was used to inhibit migration of eosinophils to thyroids. G‐EAT severity was compared at day 20 and day 40–50 in IFN‐γ−/− recipients given anti‐IL‐5 or control immunoglobulin G (IgG). Thyroids of anti‐IL‐5‐treated IFN‐γ−/− mice had few eosinophils and more neutrophils at day 20, but G‐EAT severity scores were comparable to those of control IgG‐treated mice at both day 20 and day 40–50. Expression of chemokine (C‐X‐C motif) ligand 1 (CXCL1) mRNA was higher and that of chemokine (C‐C motif) ligand 11 (CCL11) mRNA was lower in thyroids of anti‐IL‐5‐treated IFN‐γ−/− mice. IL‐5 neutralization did not influence mRNA expression of most cytokines in IFN‐γ−/− mice. Thus, inhibiting eosinophil migration to thyroids did not affect G‐EAT severity or resolution in IFN‐γ−/− mice, suggesting that eosinophil infiltration of thyroids occurs as a consequence of IFN‐γ deficiency, but these cells have no apparent pathogenic role in G‐EAT.
Maternal investment and size‐specific reproductive output in carcharhinid sharks
Authors: Hussey Nigel E. , Wintner Sabine P. , Dudley Sheldon F. J. , Cliff Geremy , Cocks David T. , Aaron MacNeil M. 
Published: October 2009

Summary1. Life‐history theory predicts that organisms will provide an optimal level of parental investment for offspring survival balanced against the effects on their own survival and future reproductive potential.2. Optimal resource allocation models also predict an increase in reproductive output with age as expected future reproductive effort decreases. To date, maternal investment in sharks has received limited attention.3. We found that neonatal dusky sharks (Carcharhinus obscurus) are not independent from maternal resource allocation at the point of parturition but instead are provisioned with energy reserves in the form of an enlarged liver that constitutes approximately 20% of total body mass.4. Analysis of long‐term archived data sets showed that a large proportion of this enlarged liver is utilized during the first weeks or months of life suggesting that the reported weight loss of newborn sharks signifies a natural orientation process and is not necessarily related to prey abundance and/or indicative of high mortality rates.5. Interrogation of near‐term pup mass in two carcharhinids, the dusky and spinner shark (Carcharhinus brevipinna), further revealed an increase in reproductive output with maternal size, with evidence for a moderate decline in the largest mothers.6. For the dusky shark, there was a trade‐off between increasing litter size and near‐term pup mass in support of optimal offspring size theory.7. For both the dusky and spinner shark, there was a linear increase in near‐term pup mass with month, which may indicate variable parturition strategies and/or that carcharhinids are able to adjust the length of the gestation period.8. The identification of optimal size‐specific reproductive output has direct implications for improving the reproductive potential of exploited shark populations and for structuring future management strategies.
Interaction of functional FCER2 promoter polymorphism and phenotype‐associated haplotypes
Authors: Potaczek D. P. , Wang Q.‐H. , Sanak M. , Tokura T. , Matsuda H. , Dziedzina S. , Nakano N. , Hara M. , Ogawa H. , Szczeklik A. , Okumura K. , Nishiyama C. 
Published: October 2009

AbstractLow‐affinity IgE receptor gene (FCER2) rs3760687 polymorphism was found to be associated with differential binding affinity of transcription factors Sp1 and Sp3 leading to altered transcriptional activity. Haplotypic interaction of functional FCER2 polymorphisms (rs28364072, rs2228137 and rs3760687) might potentially provide a background for genotype–phenotype associations previously observed for some rather non‐functional FCER2 variants.
Molecular variation at the HLA‐A, B, C, DRB1, DQA1, and DQB1 loci in full heritage American Indians in Arizona: private haplotypes and their evolution
Authors: Williams R. , Chen Y.‐F. , Endres R. , Middleton D. , Trucco M. , Williams J. Dunn , Knowler W. 
Published: October 2009

AbstractA sample of 492 full heritage, unrelated residents of the Gila River Indian Community (GRIC) of Arizona were characterized for their high‐resolution DNA alleles at the HLA‐A, B, C, DRB1, DQA1, and DQB1 loci. Only five allelic categories are found at HLA‐A, 10 at HLA‐B, 8 at HLA‐C and HLA‐DR, and 4 at DQA1 and DQB1. There is little evidence for population structure at the 6 loci. Two ‘private’ alleles, B*5102 and B*4005, which are found nearly exclusively in American Indian populations in the desert southwest and northern Mexico, are likely new mutations after the first inhabitation of the area, the evolution of which are reflected in the contemporary distribution of their respective haplotypes. DRB1*1402 has the highest reported frequency of any specificity at the DRB1 locus, 0.7461, and serves as a sensitive probe for locating related east Asian populations. The haplotypes in this population also exhibit a highly restricted distribution and strong genetic disequilibria, which has important implications for matching solid organ and bone marrow allografts. It is shown that, when one considers HLA‐A‐B‐DRB1 homozygotes as allograft donors for all full heritage members of the GRIC, 50% of the community would find a non‐mismatched organ within the homozygotes for the six most common haplotypes. This raises questions about transplantation policy and whether, in the presence of high‐frequency private alleles and a restricted number of haplotypes, the full heritage American Indian community of the desert southwest should act as its own pool of donors for its affected members.
Transrectal high‐intensity focused ultrasound for the treatment of localized prostate cancer: Eight‐year experience
Authors: Uchida Toyoaki , Shoji Sunao , Nakano Mayura , Hongo Satoko , Nitta Masahiro , Murota Akiko , Nagata Yoshihiro 
Published: October 2009

Objective:  To report on the long‐term results of high‐intensity focused ultrasound in the treatment of localized prostate cancer.Methods:  A total of 517 men with stage T1c–T3N0M0 prostate cancer treated with Sonablate devices (Focus Surgery, Indianapolis, IN, USA) between January 1999 and December 2007 were included in the study. Biochemical failure was defined according to the Phoenix definition (prostate‐specific antigen nadir + 2 ng/mL).Results:  The median follow‐up period for all patients was 24.0 months (range, 2 to 88). The biochemical disease‐free rate (BDFR) in all patients at 5 years was 72%. The BDFR in patients with stage T1c, T2a, T2b, T2c and T3 groups at 5 years were 74%, 79%, 72%, 24% and 33%, respectively (P < 0.0001). BDFR in patients in the low, intermediate and high‐risk groups at 5 years were 84%, 64% and 45%, respectively (P < 0.0001). The BDFR in patients treated with or without neoadjuvant hormonal therapy at 7 years were 73% and 53% (P < 0.0001), respectively. In multivariate analysis, pretreatment prostate‐specific antigen levels (hazard ratio 1.060; P < 0.0001; 95% confidence interval 1.040–1.080), neoadjuvant hormonal therapy (hazard ratio 2.252; P < 0.0001; 95% confidence interval 1.530–3.315) and stage (P = 0.0189) were demonstrated to be statistically significant variables. Postoperative erectile dysfunction was noted in 33 out of 114 (28.9%) patients who were preoperatively potent.Conclusions:  High‐intensity focused ultrasound therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer, particularly those with low‐ and intermediate‐risk cancer.