bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular viewpoint
Authors: Anand Sonia S 
Published: January 2007

Question: Are oral anticoagulants (target INR 3.0-4.5) more effective than aspirin (80 mg) in the prevention of infrainguinal bypass-graft occlusion? Population: Patients who required infrainguinal bypass graft surgery (venous or synthetic grafts) for obstructive arterial disease. Design and methods: Randomized, open, clinical trial. A total of 1339 patients randomized to oral anticoagulants (target INR = 3.0-4.5) and 1351 to aspirin (80 mg/day). Treatment was started within 5 days of surgery. Primary outcome was graft occlusion defined as clinical examination and Doppler or duplex ultrasound evaluation and angiography when indicated. Mean length of follow-up was 21 months. Blinded adjudication of primary and secondary outcomes. Intention to treat analysis. Pre-specified subgroup analysis of primary outcome by graft type. Results: In all, 182/1326 (13.7%) discontinued oral anticoagulants and 190/1324 (14.3%) discontinued aspirin. A total of 308/1326 (23.2%) on oral anticoagulants vs 322/1324 (24.3%) on aspirin had graft occlusion; relative risk = 0.95 (95% CI: 0.82-1.11). Secondary outcome composite of cardiovascular death, myocardial infarction, stroke, and amputation was 248/1326 (18.7%) on oral anticoagulants vs 275/1324 (20.8%) on aspirin; relative risk = 0.89 (95% CI: 0.75-1.06). Major hemorrhage was 108/1326 (8.1%) on oral anticoagulants vs 56/1324 (4.2%) on aspirin; relative risk = 1.96 (95% CI: 1.42-2.71). For vein grafts (n = 1546) the relative risk of occlusion was 0.69 (95% CI: 0.54-0.88) on oral anticoagulants vs aspirin. For non-vein grafts (n = 1104) the relative risk of occlusion was 1.26 (95% CI: 1.03-1.55) on oral anticoagulants vs aspirin. The statistical test for interaction between these subgroups was significant (p = 0.002). Conclusion: High intensity warfarin (INR: 3-4.5) does not significantly reduce graft occlusion after infrainguinal bypass compared with aspirin. Oral anticoagulants are associated with a significant increase in major bleeding episodes. Oral anticoagulants and aspirin may alter the pathogenesis of graft re-occlusion differently depending on graft type.
Forearm blood flow measured by venous occlusion plethysmography in healthy subjects and in women with postmastectomy oedema
Authors: Stanton Anthony WB , Holroyd Ben , Northfield John W , Levick J Rodney , Mortimer Peter S 
Published: January 2007

A chronic swelling of the arm may develop following damage to axillary lymph vessels during breast cancer treatment. Certain unusual pathophysiological features of postmastectomy oedema indicate that factors additional to lymphatic damage are important. One factor postulated previously is a haemodynamic abnormality. Forearm blood flow was therefore measured by venous occlusion plethysmography using both a conventional mercury strain gauge and a newer optical volumeter (Perometer®). The latter was initially assessed in healthy subjects. When forearm blood flow was measured using the two methods simultaneously, the strain gauge and Perometer®did not differ significantly for healthy or oedematous arms. Dominant and non-dominant arm blood flow in healthy subjects was similar but with greater variation between sides with the Perometer®. Using the strain gauge, blood flow in the oedematous arm (2.51 6 1.33 ml/100 ml per min) was significantly lower than in the opposite unaffected arm (3.77 6 2.29 ml/100 ml per min; p = 0.026). The Perometer®results showed a similar but nonsignificant trend (p = 0.105). Taking into account the greater limb volume on the affected side, total forearm blood flow was essentially the same in each arm (unaffected: 40.72 6 28.70 ml/min; oedematous: 41.78 6 22.11 ml/min). The reduced blood flow per unit volume of arm was therefore likely to be due to a simple `dilution' effect of the increase in volume. The results indicate that it is unlikely that raised blood flow contributes to oedema formation, contrary to the haemodynamic concept.
A systematic review of compression therapy for venous leg ulcers
Authors: Palfreyman Simon J , Lochiel Rona , Michaels Jonathan A 
Published: January 2007

The aim of the study was to determine the relative effectiveness of compression therapies used in the treatment of venous leg ulcers. Randomized controlled trials (RCT) were sought using a search strategy that aimed to identify relevant RCT by searching eight electronic databases (including Medline, Embase and CINHAL), conference proceedings and hand searching key journals. In addition, citations within papers were scrutinized to identify any relevant studies. Suitability for inclusion in this review was determined by a critical appraisal of key determinants of the quality of the trials. Trials that included patients of mixed ulcer aetiology were excluded unless the results of patients with venous disease were reported separately. Data was extracted independently by two reviewers and synthesized quantitatively and qualitatively. Losses to follow-up/withdrawals were assumed to be failures of treatment. A total of 132 articles were identified, and of these eight fulfilled the inclusion criteria. The remaining 126 trials were excluded due to trial design flaws, the inclusion of mixed/arterial aetiology ulcers or because they were non-RCT. Meta-analysis using a random-effects model showed the benefits of multi-layer and elastic compression bandages. It was concluded that more high-quality trials are required and that more emphasis should be placed on economic and quality of life data to try to ascertain the cost-effectiveness and utility of the treatment options available.
Circadian variation and triggering of cardiovascular events
Authors: Willich Stefan N 
Published: January 2007

Myocardial infarction and sudden cardiac death demonstrate a marked circadian variation with an increased risk during the morning after awakening and arising. The recognition of the morning increase of acute cardiovascular events has convinced many that they may be triggered by morning activities. It is of note, however, that cardiovascular events occur throughout the day - even if at lower frequency compared with the morning. There is a strong association between external triggers and the onset of myocardial infarction and sudden cardiac death beyond what is to be expected by chance alone. The magnitude of this association (relative risk two-to threefold) is comparable with the known long-term risk factors of cardiac disease. Trigger factors occur relatively frequently and may play a causative role in up to 20% of cases of acute coronary syndromes. Physical exertion, bursts of anger and sexual activity have been proved to have triggering potential. Other possible triggers include external and environmental events such as earthquakes, war threat and climatic factors. The pathophysiological links between external triggers and the onset of cardiovascular events are important in addressing the question of a causal relationship between triggers and disease onset and in perhaps improving preventive strategies.
Incidence and determinants of mortality and cardiovascular events in diabetes mellitus: a meta-analysis
Authors: Kanters Suzan DJM , Banga Jan-Dirk , Stolk Ronald P , Algra Ale 
Published: January 2007

Patients with diabetes mellitus are at increased risk of developing atherosclerotic disease. The extent of this additional risk and its determinants are not well known, but this information is needed for sample-size estimations in intervention studies. Therefore, a meta-analysis of epidemiologic studies on this subject was performed. Medline was searched from 1966 onwards, including the reference lists of all relevant publications. A total of 27 prospective follow-up studies in the English language that allowed calculation of the unadjusted incidence of one of the predefined outcome events were included. The influence of age, sex, type of diabetes, duration of diabetes, year of study, HbA1c, cholesterol level, blood pressure and smoking on these incidences was studied by means of univariate Poisson regression analysis. Overall total mortality was 2.9% per year (95% CI 2.8-3.0; 27 studies), and for death from all vascular causes was 1.4% per year (95% CI 1.3-1.4; 16 studies). Only two studies were found that reported on the incidence of the composite outcome `event death from all vascular causes, non-fatal myocardial infarction, or non-fatal stroke'. In univariate analysis, age, year of study, total cholesterol and systolic blood pressure were positively related to total mortality and death from all vascular causes. After adjustment for age, or limiting the analyses to studies in patients with type 2 diabetes only (n = 11), these relationships remained statistically significant. In conclusion, the overall yearly total mortality in diabetes mellitus is 2.9% and for death from all vascular causes is 1.4%. There are few data on the incidence of composite cardiovascular outcome events.
Female genital mutilation
Authors: Khaled MA , Cox Charles 
Published: January 2007

Female genital mutilation (FGM) is practiced worldwide, including in the UK. The term ‘female circumcision’ suggests a relatively benign procedure, inviting comparison with male circumcision, which, although usually medically unnecessary and uncomfortable, rarely causes long-term problems. In fact, the female procedure is responsible for long-term gynaecological morbidity and greatly increased mortality and morbidity in childbirth for both mother and baby. For many reasons - cultural, religious and sexual - worldwide efforts to reduce the practice are meeting resistance. This paper sets out the methods and classification of FGM, the position of the World Health Organization and other international agencies, and considers the problems from a British perspective.
Prevention of post-traumatic clinical capillary leak syndrome
Authors: Gosling Peter 
Published: January 2007

Systemic capillary leak is an early feature of the inflammatory response to localized injury, and is proportional to the severity of the inflammatory insult. Loss of local control of inflammation leads to an exaggerated systemic inflammatory response known as systemic inflammatory response syndrome (SIRS). SIRS is associated with multiple organ failure and death when there is failure to maintain homeostasis. Whilst the application of molecular biology and recombinant techniques have produced major advances in our understanding of the mediation of the inflammatory response, there is no agent currently available which will prevent SIRS and reduce the incidence of post-traumatic multiple organ failure. In the meantime, a more practical approach to the avoidance of SIRS and its attendant capillary leak syndrome is to attempt to reduce the deleterious effects of interstitial oedema by tailoring treatment to the rapid changes in capillary permeability.
Maxillofacial trauma: principles of management, priorities and basic techniques
Authors: David DJ 
Published: January 2007

The management of maxillofacial trauma involves organs and regions managed by various well-established health care disciplines and is therefore multidisciplinary. The organization of this multidisciplinary care includes: •Facility and personnel - the facility requires all the relevant diagnostic material and the personnel must have a special interest in maxillofacial trauma and form a dedicated team. •Principles of management of facial fractures - these involve setting priorities, understanding the indications for operative intervention and developing techniques, of which one of the most significant is the wider exposure of the maxillofacial skeleton. This, together with interosseous fixation with mini- and microplates and the use of primary bone grafting, has brought about the most significant advances in this area of patient management. Three case studies are presented, the first of which illustrates the management of a fractured zygoma requiring open reduction and internal fixation, using modern radiology to make the diagnosis and to check the correction. Case study two is an orbito-cranial fracture with major cranio-cerebral injury, highlighting the problems associated with a breech of the anterior cranial base and a cerebrospinal fluid rhinorrhoea. The third case illustrates a complex fracture involving the orbit and nasoethmoid complex, maxilla and mandible and illustrates the practical implication of the principles outlined in the paper.
Molecular analysis of the methylprednisolone-mediated inhibition of NK-cell function: evidence for different susceptibility of IL-2– versus IL-15–activated NK cells
Authors: Chiossone Laura , Vitale Chiara , Cottalasso Francesca , Moretti Sara , Azzarone Bruno , Moretta Lorenzo , Mingari Maria Cristina 
Published: January 2007

AbstractSteroids have been shown to inhibit the function of fresh or IL-2–activated natural killer (NK) cells. Since IL-15 plays a key role in NK-cell development and function, we comparatively analyzed the effects of methylprednisolone on IL-2– or IL-15–cultured NK cells. Methylprednisolone inhibited the surface expression of the major activating receptors NKp30 and NKp44 in both conditions, whereas NK-cell proliferation and survival were sharply impaired only in IL-2–cultured NK cells. Accordingly, methylprednisolone inhibited Tyr phosphorylation of STAT1, STAT3, and STAT5 in IL-2–cultured NK cells but only marginally in IL-15–cultured NK cells, whereas JAK3 was inhibited under both conditions. Also, the NK cytotoxicity was similarly impaired in IL-2– or IL-15–cultured NK cells. This effect strictly correlated with the inhibition of ERK1/2 Tyr phosphorylation, perforin release, and cytotoxicity in a redirected killing assay against the FcRγ+ P815 target cells upon cross-linking of NKp46, NKG2D, or 2B4 receptors. In contrast, in the case of CD16, inhibition of ERK1/2 Tyr phosphorylation, perforin release, and cytotoxicity were not impaired. Our study suggests a different ability of IL-15–cultured NK cells to survive to steroid treatment, thus offering interesting clues for a correct NK-cell cytokine conditioning in adoptive immunotherapy.
The C/EBPδ tumor suppressor is silenced by hypermethylation in acute myeloid leukemia
Authors: Agrawal Shuchi , Hofmann Wolf-Karsten , Tidow Nicola , Ehrich Mathias , Boom Dirk van den , Koschmieder Steffen , Berdel Wolfgang E. , Serve Hubert , Müller-Tidow Carsten 
Published: January 2007

Abstract
Aberrant DNA methylation is the most frequent molecular alteration in acute myeloid leukemia (AML). To identify methylation-silenced genes in AML, we performed microarray analyses in U937 cells exposed to the demethylating agent 5-aza-deoxy-cytidine. Overall, 274 transcripts were significantly induced. Interestingly, C/EBPδ expression was significantly induced (more than 10-fold) by demethylation whereas expression of all other C/EBP family members remained unchanged. The C/EBPδ promoter was strongly methylated in different leukemic cell lines and showed signs of a repressed chromatin state. Analyses of the promoter regions of the entire C/EBP family (α, β, γ, δ, ϵ, ζ) in bone marrow samples from AML patients (n = 80) and controls (n = 15) by mass spectrometry revealed that C/EBPδ is the most commonly hypermethylated C/EBP gene in AML. Hypermethylation occurred in more than 35% of AML patients at primary diagnosis. A significant correlation (P = .016) was observed between hypermethylation of the C/EBPδ promoter and low expression of C/EBPδ in AML patients. C/EBPδ promoter activity was strongly repressed by methylation in vitro, and transcriptional repression partially depended on MeCP2 activity. C/EBPδ exhibited growth-inhibitory properties in primary progenitor cells as well as in Flt3-ITD–transformed cells. Taken together, C/EBPδ is a novel tumor suppressor gene in AML that is silenced by promoter methylation.
Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent intestinal IgA production
Authors: Kunisawa Jun , Kurashima Yosuke , Gohda Masashi , Higuchi Morio , Ishikawa Izumi , Miura Fumi , Ogahara Ikuko , Kiyono Hiroshi 
Published: January 2007

AbstractSphingosine 1-phosphate (S1P) is known to play a pivotal role in the regulation of lymphocyte emigration from organized lymphoid tissues such as the peripheral lymph nodes and thymus, but its immunologic role in unorganized and diffused tissues remains to be elucidated. Here we show that the trafficking of peritoneal B cells is principally regulated by S1P. All peritoneal B cells including B1a, B1b, and B2 B cells express comparable levels of the type 1 S1P receptor. Thus, treatment with FTY720, an S1P receptor modulator, caused the rapid disappearance of peritoneal B cells by inhibiting both their emigration from parathymic lymph nodes and their recirculation from the blood into the peritoneal cavity without affecting their progenitor populations. These changes did not affect natural plasma antibody production or phosphorylcholine (PC)–specific antibody production in serum after peritoneal immunization with heat-killed Streptococcal pneumoniae (R36A). However, FTY720 dramatically reduced peritoneal B cell-derived natural intestinal secretory IgA production without affecting the expression of J-chain and polyimmunoglobulin receptors. Additionally, FTY720 impaired the generation of PC-specific fecal IgA responses after oral immunization with R36A. These findings point to a pivotal role for S1P in connecting peritoneal B cells with intestinal B-cell immunity.
HOXA10 is a critical regulator for hematopoietic stem cells and erythroid/megakaryocyte development
Authors: Magnusson Mattias , Brun Ann C. M. , Miyake Noriko , Larsson Jonas , Ehinger Mats , Bjornsson Jon Mar , Wutz Anton , Sigvardsson Mikael , Karlsson Stefan 
Published: January 2007

AbstractThe Homeobox (Hox) transcription factors are important regulators of normal and malignant hematopoiesis because they control proliferation, differentiation, and self-renewal of hematopoietic cells at different levels of the hematopoietic hierarchy. In transgenic mice we show that the expression of HOXA10 is tightly regulated by doxycycline. Intermediate concentrations of HOXA10 induced a 15-fold increase in the repopulating capacity of hematopoietic stem cells (HSCs) after 13 days of in vitro culture. Notably, the proliferation induction of HSC by HOXA10 was dependent on the HOXA10 concentration, because high levels of HOXA10 had no effect on HSC proliferation. Furthermore, high levels of HOXA10 blocked erythroid and megakaryocyte development, demonstrating that tight regulation of HOXA10 is critical for normal development of the erythroid and megakaryocytic lineages. The HOXA10-mediated effects on hematopoietic cells were associated with altered expression of genes that govern stem-cell self-renewal and lineage commitment (eg, hepatic leukemia factor [HlF], Dickkopf-1 [Dkk-1], growth factor independent-1 [Gfi-1], and Gata-1). Interestingly, binding sites for HOXA10 were found in HLF, Dkk-1, and Gata-1, and Dkk-1 and Gfi-1 were transcriptionally activated by HOXA10. These findings reveal novel molecular pathways that act downstream of HOXA10 and identify HOXA10 as a master regulator of postnatal hematopoietic development.
How I treat refractory acute GVHD
Authors: Deeg H. Joachim 
Published: January 2007

AbstractGraft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) is associated with considerable morbidity and mortality, particularly in patients who do not respond to primary therapy, which usually consists of glucocorticoids (steroids). Approaches to therapy of acute GVHD refractory to “standard” doses of steroids have ranged from increasing the dose of steroids to the addition of polyclonal or monoclonal antibodies, the use of immunotoxins, additional immunosuppressive/chemotherapeutic interventions, phototherapy, and other means. While many pilot studies have yielded encouraging response rates, in most of these studies long-term survival was not improved in comparison with that seen with the use of steroids alone. A major reason for failure has been the high rate of infections, including invasive fungal, bacterial, and viral infections. It is difficult to conduct controlled prospective trials in the setting of steroid-refractory GVHD, and a custom-tailored therapy dependent upon the time after HCT, specific organ manifestations of GVHD, and severity is appropriate. All patients being treated for GVHD should also receive intensive prophylaxis against infectious complications.
Widespread Alu repeat-driven expansion of consensus DR2 retinoic acid response elements during primate evolution
Authors: Laperriere David , Wang Tian-Tian , White John H , Mader Sylvie 
Published: January 2007

Abstract

Background
Nuclear receptors are hormone-regulated transcription factors whose signaling controls numerous aspects of development and physiology. Many receptors recognize DNA hormone response elements formed by direct repeats of RGKTCA motifs separated by 1 to 5 bp (DR1-DR5). Although many known such response elements are conserved in the mouse and human genomes, it is unclear to which extent transcriptional regulation by nuclear receptors has evolved specifically in primates.

Results
We have mapped the positions of all consensus DR-type hormone response elements in the human genome, and found that DR2 motifs, recognized by retinoic acid receptors (RARs), are heavily overrepresented (108,582 elements). 90% of these are present in Alu repeats, which also contain lesser numbers of other consensus DRs, including 50% of consensus DR4 motifs. Few DR2s are in potentially mobile AluY elements and the vast majority are also present in chimp and macaque. 95.5% of Alu-DR2s are distributed throughout subclasses of AluS repeats, and arose largely through deamination of a methylated CpG dinucleotide in a non-consensus motif present in AluS sequences. We find that Alu-DR2 motifs are located adjacent to numerous known retinoic acid target genes, and show by chromatin immunoprecipitation assays in squamous carcinoma cells that several of these elements recruit RARs in vivo. These findings are supported by ChIP-on-chip data from retinoic acid-treated HL60 cells revealing RAR binding to several Alu-DR2 motifs.

Conclusion
These data provide strong support for the notion that Alu-mediated expansion of DR elements contributed to the evolution of gene regulation by RARs and other nuclear receptors in primates and humans.