bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can rock climbing lead to Dupuytren’s disease?
Authors: Logan A J , Mason G , Dias J , Makwana N 
Published: August 2005

Objectives:To determine if rock climbing is a significant factor in the development of Dupuytren’s disease in men, and, if so, what is the most likely related factor.Methods:Questionnaires were distributed to all 1100 members of the Climbers’ Club of Great Britain. These detailed basic information about the climber, the presence of Dupuytren’s disease, and any known risk factors for its development.Results:About half (51%) of the questionnaires were returned. The respondents were almost entirely male. It was revealed that 19.5% of male climbers had developed Dupuytren’s disease. There was a significantly higher life time intensity of climbing activity in those with the disease. An earlier age of onset of the disease was found in climbers compared with the general population.Conclusions:This study further strengthens the hypothesis that repetitive trauma to the palmar fascia predisposes to the development of Dupuytren’s disease in men.
ASCERTAINING THE CORE COLLAPSE SUPERNOVA MECHANISM: The State of the Art and the Road Ahead
Authors: Mezzacappa Anthony 
Published: August 2005

▪ Abstract  More than four decades have elapsed since modeling of the core collapse supernova mechanism began in earnest. To date, the mechanism remains elusive, at least in detail, although significant progress has been made in understanding these multiscale, multiphysics events. One-, two-, and three-dimensional simulations of or relevant to core collapse supernovae have shown that (a) neutrino transport, (b) fluid instabilities, (c) rotation, and (d) magnetic fields, together with proper treatments of (e) the sub- and super- nuclear density stellar core equation of state, (f) the neutrino interactions, and (g) gravity are all important. The importance of these ingredients applies to both the explosion mechanism and to phenomena directly associated with the mechanism, such as neutron star kicks, supernova neutrino and gravitational wave emission, and supernova spectropolarimetry. Not surprisingly, current two- and three-dimensional models have yet to include (a)–(d) with sufficient realism. One-dimensional spherically symmetric models have achieved a significant level of sophistication but, by definition, cannot incorporate (b)–(d), except phenomenologically. Fully general relativistic spherically symmetric simulations with Boltzmann neutrino transport do not yield explosions, demonstrating that some combination of (b), (c), and (d) is required to achieve this. Systematic layering of the dimensionality and the physics will be needed to achieve a complete understanding of the supernova mechanism and phenomenology. The past modeling efforts alluded to above have illuminated that core collapse supernovae may be neutrino driven, magnetohydrodynamically (MHD) driven, or both, but uncertainties in the current models prevent us from being able to answer even this most basic question. And it may be that more than one possibility is realized in nature. Nonetheless, if a supernova is neutrino driven, magnetic fields will likely have an impact on the dynamics of the explosion. Similarly, if a supernova is MHD driven, the neutrino transport will dictate the dynamics of stellar core collapse, bounce, and the postbounce evolution, which in turn will create the environment in which an MHD-driven explosion would occur. Thus, although reduction will allow us to sort out the roles of each of the major physics components listed above, we will not obtain a quantitative, and perhaps even qualitative, understanding of core collapse supernovae until all components and their coupling are included in the models with sufficient realism.
PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial. [ISCRTN 74418480]
Authors: van Breda Eric J , van der Worp H Bart , van Gemert H Maarten A , Algra Ale , Kappelle L Jaap , van Gijn Jan , Koudstaal Peter J , Dippel Diederik WJ ,   the PAIS investigators
Published: August 2005

Abstract

Background
In patients with acute stroke, increased body temperature is associated with large lesion volumes, high case fatality, and poor functional outcome. A 1°C increase in body temperature may double the odds of poor outcome. Two randomized double-blind clinical trials in patients with acute ischemic stroke have shown that treatment with a daily dose of 6 g acetaminophen (paracetamol) results in a small but rapid and potentially worthwhile reduction of 0.3°C (95% CI: 0.1–0.5) in body temperature. We set out to test the hypothesis that early antipyretic therapy reduces the risk of death or dependency in patients with acute stroke, even if they are normothermic.

Methods/design
Paracetamol (Acetaminophen) In Stroke (PAIS) is a randomized, double-blind clinical trial, comparing high-dose acetaminophen with placebo in 2500 patients. Inclusion criteria are a clinical diagnosis of hemorrhagic or ischemic stroke and the possibility to start treatment within 12 hours from onset of symptoms. The study will have a power of 86% to detect an absolute difference of 6% in the risk of death or dependency at three months, and a power of 72% to detect an absolute difference of 5%, at a 5% significance level.

Discussion
This is a simple trial, with a drug that only has a small effect on body temperature in normothermic patients. However, when lowering body temperature with acetaminophen does have the expected effectiveness, 20 patients will have to be treated to prevent dependency or death in one.
Psoriasis vulgaris flare during efalizumab therapy does not preclude future use: a case series
Authors: Lowes Michelle A , Turton James A , Krueger James G , Barnetson Ross StC 
Published: August 2005

Abstract

Background
Severe psoriasis vulgaris can be extremely difficult to treat in some patients, even with the newer biological therapies available today.

Case presentations
We present two patients with severe chronic plaque psoriasis who received numerous systemic anti-psoriatic therapies with varied results. Both responded well to initial treatment with efalizumab (anti-CD11a), but then experienced a flare of their disease after missing a dose. However, after disease stablization, both patients responded well to re-introduction of efalizumab, one patient requiring concurrent treatment with infliximab (anti-TNF-α).

Conclusion
These cases are presented to characterize this "flare" reaction, and to inform health care providers that efalizumab can still be administered after disease flare, and again may be a successful therapy.
Effect of the degree of ischaemic injury and reoxygenation time on the type of myocardial cell death in man: role of caspases
Authors: Vohra Hunaid A , Galiñanes Manuel 
Published: August 2005

Abstract

Background
The importance of apoptosis in the injury sustained by the human myocardium during ischaemia and reoxygenation and the underlying mechanisms remain unclear. To quantify apoptosis and necrosis induced by simulated ischaemia/reoxygenation in the human atrial myocardium, free-hand sections of right atrial appendage (n = 8/group) were subjected to 90 minutes simulated ischaemia followed by 2, 8 and 24 hours reoxygenation.

Results
Apoptosis, as assessed by TUNEL, was greater than necrosis after 90 minutes simulated ischaemia and 2 hours reoxygenation (35.32 ± 3.22% vs 13.55 ± 1.3%; p < 0.05) but necrosis was greater than apoptosis by 24 hours reoxygenation (45.20 ± 2.75% vs 4.82 ± 0.79%; p < 0.05). Total caspase activation was similar after 90 minutes simulated ischaemia followed by 2 hours and 24 hours reoxygenation (515270 ± 99570 U vs 542940 ± 95216 U; p = NS). However, caspase-3 like activation was higher at 2 hours than at 24 hours reoxygenation (135900 ± 42200 U vs 54970 ± 19100 U; p < 0.05). Inhibition of caspase-3 by z.DEVD.fmk (70 nM) almost completely abolished apoptosis from 23.26 ± 2.854% to 0.73 ± 0.28 % (p < 0.05), without affecting necrosis.

Conclusion
Cell death by apoptosis and necrosis in the human myocardium subjected to simulated ischaemia/reoxygenation depends on the degree of the ischaemic insult and have a different time-course with apoptosis happening early during reoxygenation and necrosis becoming more important later. Importantly, the apoptosis induced by simulated ischaemia/reoxygenation is mainly mediated by activation of caspase-3 but it does not affect necrosis.
CXCR4 and CCR5 shRNA transgenic CD34+ cell derived macrophages are functionally normal and resist HIV-1 infection
Authors: Anderson Joseph , Akkina Ramesh 
Published: August 2005

AbstractBackgroundStable simultaneous knock down of the HIV-1 coreceptors CCR5 and CXCR4 is a promising strategy to protect cells from both R5 macrophage tropic and X4 T cell tropic as well as dual tropic viral infections. The potency of shRNAs in targeted gene silencing qualifies them as powerful tools for long term HIV gene therapy. Our previous work with a bispecific lentiviral vector containing CXCR4 and CCR5 shRNAs showed efficacy in down regulating both coreceptors and conferring viral resistance to both X4 and R5-tropic strains of HIV-1 in cultured cell lines. To extend these results to a stem cell gene therapy setting, here we show transduction of primary CD34+ hematopoietic progenitor cells to derive normal end stage cells that are resistant to HIV-1 infection.ResultsThe bispecific XHR lentiviral vector harboring CXCR4 and CCR5 shRNA expression cassettes was efficient in transducing CD34+ cells. The transduced cells gave rise to morphologically normal transgenic macrophages when cultured in cytokine media. There was a marked down regulation of both coreceptors in the stably transduced macrophages which showed resistance to both R5 and X4 HIV-1 strains uponin vitrochallenge. Since off target effects by some shRNAs may have adverse effects on transgenic cells, the stably transduced macrophages were further analyzed to determine if they are phenotypically and functionally normal. FACS evaluation showed normal levels of the characteristic surface markers CD14, CD4, MHC class II, and B7.1. Phagocytic functions were also normal. The transgenic macrophages demonstrated normal abilities in up-regulating the costimulatory molecule B7.1 upon LPS stimulation. Furthermore, IL-1 and TNFα cytokine secretion in response to LPS stimulation was also normal. Thus, the transgenic macrophages appear to be phenotypically and functionally normal.ConclusionThese studies have demonstrated for the first time that a bispecific lentiviral vector could be used to stably deliver shRNAs targeted to both CCR5 and CXCR4 coreceptors into CD34+ hematopoietic progenitor cells and derive transgenic macrophages. Transgenic macrophages with down regulated coreceptors were resistant to both R5 and X4 tropic HIV-1 infections. The differentiated cells were also phenotypically and functionally normal indicating no adverse effects of shRNAs on lineage specific differentiation of stem cells. It is now possible to construct gene therapeutic lentiviral vectors incorporating multiple shRNAs targeted to cellular molecules that aid in HIV-1 infection. Use of these vectors in a stem cell setting shows great promise for sustained HIV/AIDS gene therapy.
Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin: a prospective, clinical study
Authors: Jochberger Stefan , Mayr Viktoria , Luckner Günter , Fries Dietmar R , Mayr Andreas J , Friesenecker Barbara E , Lorenz Ingo , Hasibeder Walter R , Ulmer Hanno , Schobersberger Wolfgang , Dünser Martin W 
Published: August 2005

Abstract
Introduction
Deep venous thrombosis with subsequent pulmonary embolism or post-thrombotic syndrome is a feared complication in the intensive care unit. Therefore, routine prophylactic anticoagulation is widely recommended. Aside from unfractionated heparin, low molecular weight heparins, such as certoparin, have become increasingly used for prophylactic anticoagulation in critically ill patients. In this prospective study, we evaluated the potency of 3,000 IU certoparin administered once daily to reach antithrombotic antifactor Xa (aFXa) levels of 0.1 to 0.3 IU/ml in 62 critically ill patients.

Methods
AFXa levels were determined 4, 12 and 24 h after injection of certoparin. Prothrombin time, activated partial thromboplastin time, antithrombin, fibrinogen, hemoglobin, platelet count, serum urea and creatinine concentrations were documented before and 12 and 24 h after injection of certoparin.

Results
Four hours after certoparin injection (n = 32), 28% of patients were within the antithrombotic aFXa range. After 12 and 24 h, 6% achieved antithrombotic aFXa levels. Because of a severe pulmonary embolism in one study patient, an interim analysis was performed, and the dosage of certoparin was increased to 3,000 IU twice daily. This regime attained recommended antithrombotic aFXa levels in 47%, 27%, 40% and 30% of patients at 4, 12, 16 and 24 h, respectively, after twice daily certoparin injection (n = 30). Antithrombin and fibrinogen concentrations slightly increased during the observation period. Low antithrombin concentrations before certoparin were independently correlated with underdosing of certoparin. Patients with aFXa levels <0.1 IU/ml 4 h after certoparin injection required vasopressors more often and had lower serum concentrations of creatinine and urea than patients with antithrombotic aFXa levels.

Conclusion
Standard dosages of certoparin of 3,000 IU given once or twice daily are ineffective for attaining the recommended aFXa levels of 0.1 to 0.3 IU/ml in critically ill patients. Low antithrombin levels before certoparin administration were independently associated with low aFXa levels. Renal function and vasopressor therapy may further influence the effectiveness of certoparin in ensuring adequate antithrombotic prophylaxis.
Does cardiac surgery in newborn infants compromise blood cell reactivity to endotoxin?
Authors: Schumacher Kathrin , Korr Stefanie , Vazquez-Jimenez Jaime F , von Bernuth Götz , Duchateau Jean , Seghaye Marie-Christine 
Published: August 2005

Abstract
Introduction
Neonatal cardiac surgery is associated with a systemic inflammatory reaction that might compromise the reactivity of blood cells against an inflammatory stimulus. Our prospective study was aimed at testing this hypothesis.

Methods
We investigated 17 newborn infants with transposition of the great arteries undergoing arterial switch operation. Ex vivo production of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), of the regulator of the acute-phase response IL-6, and of the natural anti-inflammatory cytokine IL-10 were measured by enzyme-linked immunosorbent assay in the cell culture supernatant after whole blood stimulation by the endotoxin lipopolysaccharide before, 5 and 10 days after the operation. Results were analyzed with respect to postoperative morbidity.

Results
The ex vivo production of TNF-α and IL-6 was significantly decreased (P < 0.001 and P < 0.002, respectively), whereas ex vivo production of IL-10 tended to be lower 5 days after the operation in comparison with preoperative values (P < 0.1). Ex vivo production of all cytokines reached preoperative values 10 days after cardiac surgery. Preoperative ex vivo production of IL-6 was inversely correlated with the postoperative oxygenation index 4 hours and 24 hours after the operation (P < 0.02). In contrast, postoperative ex vivo production of cytokines did not correlate with postoperative morbidity.

Conclusion
Our results show that cardiac surgery in newborn infants is associated with a transient but significant decrease in the ex vivo production of the pro-inflammatory cytokines TNF-α and IL-6 together with a less pronounced decrease in IL-10 production. This might indicate a transient postoperative anti-inflammatory shift of the cytokine balance in this age group. Our results suggest that higher preoperative ex vivo production of IL-6 is associated with a higher risk for postoperative pulmonary dysfunction.
Differential gene expression in anatomical compartments of the human eye
Authors: Diehn Jennifer J , Diehn Maximilian , Marmor Michael F , Brown Patrick O 
Published: August 2005

Abstract
Background
The human eye is composed of multiple compartments, diverse in form, function, and embryologic origin, that work in concert to provide us with our sense of sight. We set out to systematically characterize the global gene expression patterns that specify the distinctive characteristics of the various eye compartments.

Results
We used DNA microarrays representing approximately 30,000 human genes to analyze gene expression in the cornea, lens, iris, ciliary body, retina, and optic nerve. The distinctive patterns of expression in each compartment could be interpreted in relation to the physiology and cellular composition of each tissue. Notably, the sets of genes selectively expressed in the retina and in the lens were particularly large and diverse. Genes with roles in immune defense, particularly complement components, were expressed at especially high levels in the anterior segment tissues. We also found consistent differences between the gene expression patterns of the macula and peripheral retina, paralleling the differences in cell layer densities between these regions. Based on the hypothesis that genes responsible for diseases that affect a particular eye compartment are likely to be selectively expressed in that compartment, we compared our gene expression signatures with genetic mapping studies to identify candidate genes for diseases affecting the cornea, lens, and retina.

Conclusion
Through genome-scale gene expression profiling, we were able to discover distinct gene expression 'signatures' for each eye compartment and identified candidate disease genes that can serve as a reference database for investigating the physiology and pathophysiology of the eye.
Favorable Prognosis for Patients 12 to 18 Months of Age With Stage 4 Nonamplified MYCN Neuroblastoma: A Children's Cancer Group Study
Authors: Schmidt Mary Lou , Lal Ashutosh , Seeger Robert C. , Maris John M. , Shimada Hiroyuki , O'Leary Maura , Gerbing Robert B. , Matthay Katherine K. 
Published: August 2005

Purpose The long-term survival of children between age 12 and 24 months with stage 4 neuroblastoma and nonamplified MYCN (MYCN-NA) has not been defined previously. Patients and Methods Survival for stage 4 MYCN-NA neuroblastoma patients enrolled onto Children's Cancer Group (CCG) protocols 321P2 (1986 to 1991) and 3891 (1991 to 1996) was analyzed. Treatment consisted of intensive alkylator-based induction chemotherapy with or without autologous bone marrow transplantation (ABMT) with or without 13 cis-retinoic acid. Survival was analyzed by age strata less than 12, 12 to 18, 18 to 24, and more than 24 months at diagnosis. Patients younger than 12 months were treated on the moderate-intensity CCG protocol 3881. Results Forty-three patients with stage 4 MYCN-NA disease enrolled onto CCG-321P2 (n = 17) or CCG-3891 (n = 26) were between 12 and 24 months of age at diagnosis. After a median follow-up of 94 months (range, 4 to 140 months), the 6-year event-free survival (EFS) for the 12- to 18-month age group was superior to that of the 18- to 24-month age group (74% ± 8% v 31% ± 12%; P = .008). The EFS for children older than 24 months with stage 4 MYCN-NA neuroblastoma was 23% ± 3%, and for children younger than 12 months was 92% ± 3%. Conclusion Children diagnosed with stage 4 MYCN-NA neuroblastoma in the second year of life form a transitional group between infants and older children in terms of prognosis. Patients between 12 and 18 months of age have significantly better long-term survival than that of older children treated with intensive chemotherapy with or without ABMT. These patients may not benefit from additional intensification of therapy beyond that provided in earlier clinical trials and may even maintain this high survival rate with less intensive therapy.
Euthanasia and Depression: A Prospective Cohort Study Among Terminally Ill Cancer Patients
Authors: van der Lee Marije L. , van der Bom Johanna G. , Swarte Nikkie B. , Heintz A. Peter M. , de Graeff Alexander , van den Bout Jan 
Published: August 2005

Purpose To study the association between depression and the incidence of explicit requests for euthanasia in terminally ill cancer patients. Patients and Methods A prospective cohort study was conducted on 138 consecutive cancer patients with an estimated life expectancy of 3 months or less, in the period between September 1999 and August 2003. At inclusion, participants completed the Hospital Anxiety and Depression Scale. To identify “depressed mood” we used a cutoff score of 20. Kaplan-Meier curves and Cox regression analyses were used to assess the association between depressed mood and the risk of a request for euthanasia. Results Of 138 patients, 32 patients had depressed mood at inclusion. Thirty patients (22%) made an explicit request for euthanasia. The risk to request euthanasia for patients with depressed mood was 4.1 times higher than that of patients without depressed mood at inclusion (95% CI, 2.0 to 8.5). Conclusion Depression in cancer patients with an estimated life expectancy of less than 3 months is associated with a higher likelihood to request for euthanasia. The question of whether depressed mood can adequately be treated in this terminally ill population, and if so, whether it would lower the incidence of requests for euthanasia needs further investigation.
Novel applications of the intraoperative parathyroid hormone assay Neue Anwendungen des intraoperativen Parathormon-Assays
Authors: Richards Melanie L. , Bingener Juliane 
Published: August 2005

Abstract
The development of an accurate and rapid method to measure parathyroid hormone (PTH) utilizing a two-site immunochemiluminometric assay (ICMA) has expanded its use to point-of-care testing. Measuring parathyroid hormone can be utilized to determine the completeness of parathyroid resection, to regionalize hypersecreting parathyroid glands, to identify parathyroid glands on fine-needle aspiration, and as a predictor of postoperative hypocalcemia following thyroidectomy and parathyroidectomy. This review addresses the current utilization of these techniques in patients with thyroid and parathyroid disease.