bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in blood carnitine and acylcarnitine profiles of very long‐chain acyl‐CoA dehydrogenase‐deficient mice subjected to stress
Authors: Spiekerkoetter U. , Tokunaga C. , Wendel U. , Mayatepek E. , Exil V. , Duran M. , Wijburg F. A. , Wanders R. J. A. , Strauss A. W. 
Published: March 2004

AbstractBackground  In humans with deficiency of the very long‐chain acyl‐CoA dehydrogenase (VLCAD), C14–C18 acylcarnitines accumulate. In this paper we have used the VLCAD knockout mouse as a model to study changes in blood carnitine and acylcarnitine profiles under stress.Design  VLCAD knockout mice exhibit stress‐induced hypoglycaemia and skeletal myopathy; symptoms resembling human VLCADD. To study the extent of biochemical derangement in response to different stressors, we determined blood carnitine and acylcarnitine profiles after exercise on a treadmill, fasting, or exposure to cold.Results  Even in a nonstressed, well‐fed state, knockout mice presented twofold higher C14–C18 acylcarnitines and a lower free carnitine of 72% as compared to wild‐type littermates. After 1 h of intense exercise, the C14–C18 acylcarnitines in blood significantly increased, but free carnitine remained unchanged. After 8 h of fasting at 4 °C, the long‐chain acylcarnitines were elevated 5‐fold in knockout mice in comparison with concentrations in unstressed wild‐type mice (P < 0·05), and four out of 12 knockout mice died. Free carnitine decreased to 44% as compared with unstressed wild‐type mice. An increase in C14–C18 acylcarnitines and a decrease of free carnitine were also observed in fasted heterozygous and wild‐type mice.Conclusions  Long‐chain acylcarnitines in blood increase in knockout mice in response to different stressors and concentrations correlate with the clinical condition. A decrease in blood free carnitine in response to severe stress is observed in knockout mice but also in wild‐type littermates. Monitoring blood acylcarnitine profiles in response to different stressors may allow systematic analysis of therapeutic interventions in VLCAD knockout mice.
Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey
Authors: Mehta A. , Ricci R. , Widmer U. , Dehout F. , Garcia de Lorenzo A. , Kampmann C. , Linhart A. , Sunder‐Plassmann G. , Ries M. , Beck M. 
Published: March 2004

AbstractBackground  Fabry disease is a rare X‐linked disorder caused by deficient activity of the lysosomal enzyme α‐galactosidase A. Progressive accumulation of the substrate globotriaosylceramide in cells throughout the body leads to major organ failure and premature death. In response to the recent introduction of enzyme replacement therapy, the Fabry Outcome Survey (FOS) was established to pool data from European clinics on the natural history of this little‐known disease and to monitor the long‐term efficacy and safety of treatment. This paper presents the first analysis of the FOS database and provides essential baseline data against which the effects of enzyme replacement can be measured.Design  Baseline data from a cohort of 366 patients from 11 European countries were analysed in terms of demography and clinical manifestations of Fabry disease.Results  Misdiagnosis of Fabry disease is common, and the mean delay from onset of symptoms to correct diagnosis was 13·7 and 16·3 years in males and females, respectively. Although previously thought to have serious manifestations only in hemizygous men, the FOS database has confirmed that females heterozygous for Fabry disease are similarly affected. Furthermore, signs and symptoms of Fabry disease may be present from early childhood.Conclusions  With the advent of enzyme replacement therapy, it is important that general practitioners and physicians in a range of specialties recognize the signs and symptoms of Fabry disease so that effective treatment can be given. Baseline data from FOS demonstrate that enzyme replacement therapy should not be restricted to hemizygous men, but should be considered for both heterozygous females and children.
Gender, age and seasonal effects on IgA deficiency: a study of 7293 Caucasians
Authors: Weber‐Mzell D. , Kotanko P. , Hauer A. C. , Goriup U. , Haas J. , Lanner N. , Erwa W. , Ahmaida I. A. , Haitchi‐Petnehazy S. , Stenzel M. , Lanzer G. , Deutsch J. 
Published: March 2004

AbstractBackground  The frequency of serum IgA deficiency (SIgAD) differs between populations. We examined the prevalence of SIgAD in healthy Caucasians.Materials and methods  Serum immunoglobulin A (SIgA) was measured in 7293 volunteers (2264 women, 5029 men) aged 30 ± 14·2 years (mean ± SD; range: 12–66). Serum immunoglobulin A and subnormal SIgA levels were defined by a SIgA level < 0·07 g L−1, and between 0·07 and 0·7 g L−1, respectively. Means were compared by analysis of variance (anova) and analysis of covariance (ancova); frequencies by the χ2 test.Results  Fifteen subjects (0·21%; one woman, 14 men) had SIgAD. Subnormal SIgA levels were found in 155 persons (2·13%): 21 females (0·93% of the females) and 134 males (2·66% of the males; difference: 1·74%; 95% CI: 1·12–2·33%; P < 0·001). Males were more likely to have subnormal SIgA levels or SIgAD (odds ratio 3·09, 95% CI: 1·97–4·85). The prevalence of SIgAD and subnormal SIgA was lowest in winter (χ2 = 14·8; P = 0·002; 3 d.f.; and χ2 = 43·2; P < 0·001; 3 d.f., respectively).Serum immunoglobulin A concentrations were significantly higher during winter. Serum immunoglobulin A levels increased with age on average by 0·2 ± 0·06 g L−1 per decade of life (P < 0·001). Taking into account the influence of age, SIgA concentration was lower in females as compared with males.Conclusion  The prevalence of SIgAD and subnormal SIgA levels is increased in males. There exists a significant influence of gender, age and seasons on SIgA levels.
Intracellular lipid accumulation, low‐density lipoprotein receptor‐related protein expression, and cell survival in vascular smooth muscle cells derived from normal and atherosclerotic human coronaries
Authors: Llorente‐Cortés V. , Otero‐Viñas M. , Berrozpe M. , Badimon L. 
Published: March 2004

AbstractBackground  Vascular smooth muscle cell (VSMC) regulation during atherosclerotic plaque progression is determinant for plaque stability.Aims  To study lipid accumulation, low‐density lipoprotein receptor‐related protein (LRP) expression, and cell survival in VSMCs isolated from nonatherosclerotic areas (normal VSMCs) and advanced atherosclerotic plaques (plaque‐VSMCs) of human coronaries.Design  Normal or plaque‐VSMCs were obtained from the intima by modification of the explant technique.Results  Aggregated low‐density lipoprotein (agLDL) (100 µg mL−1) internalization induced higher intracellular cholesteryl ester (CE) accumulation in plaque‐VSMC compared with normal VSMCs (89·28 ± 6·1 vs. 60·34 ± 4·1 µg CE mg−1 of protein; P < 0·05). This internalization was associated with LRP expression, as plaque‐VSMCs show higher levels of LRP mRNA (6·06 ± 0·55 vs. 3·87 ± 0·28; P < 0·05) and LRP protein expression than normal VSMCs. However, plaque‐VSMCs showed a lower proliferative response than normal VSMCs (6536 ± 636 vs. 11151 ± 815 c.p.m. [3H]thymidine; P < 0·05) and did not respond to platelet‐derived growth factor BB (PDGF‐BB) stimulus. In agreement, the Bcl2/BAX ratio was significantly lower in plaque‐VSMCs compared with normal VSMCs (0·14 ± 0·05 vs. 0·51 ± 0·07; P < 0·05) and it was independent of lipid loading.Conclusions  These results indicate that higher intracellular lipid deposition in plaque‐VSMCs is related to higher LRP expression levels. However, LRP‐mediated agLDL internalization is not directly related to the reduced survival of plaque‐VSMCs.
Association between human‐Pneumocystis infection and small‐cell lung carcinoma
Authors: De La Horra C. , Varela J. M. , Fernández‐Alonso J. , Medrano F. J. , Respaldiza N. , Montes‐Cano M. A. , Calderón E. J. 
Published: March 2004

AbstractBackground  Tobacco smoking is the most important but not the only risk factor in lung carcinoma. There is evidence that certain infections, which cause chronic inflammatory reactions, can also induce tumour development. It has recently been shown that patients with chronic pulmonary diseases present a high rate of subclinical Pneumocystis infection, and that the latter is able to induce inflammatory responses and alveolar cell alterations. The possible role of Pneumocystis infection in the development of lung neoplasms thus deserves consideration.Material and methods  Polymerase chain reaction has been used to analyze the presence of DNA of two independent loci of the Pneumocystis genome: the mitochondrial region (mtLSU rRNA) and the gene encoding for the dihydropteroate synthase enzyme, in paraffin‐embedded tissue blocks of 10 cases of small cell lung carcinoma (SCLC) and 10 cases of nonsmall cell lung carcinoma (NSCLC) with similar demographic and clinical characteristics. Five cases without lung pathology, and two cases of Pneumocystis pneumonia were also analyzed as controls.Results  DNA of the microorganism was found in all the cases of SCLC but in only two of the NSCLC, and in none of the controls without pulmonary disease – thus implying a statistically significant association (P < 0·0001) between subclinical Pneumocystis infection and SCLC.Conclusions  While the nature of this association is not clear, it nevertheless constitutes an important finding – either the infection is specifically facilitated by this tumour or induces the development of this type of neoplasm in combination with other factors.
Use of an artificial neural network to predict Graves’ disease outcome within 2 years of drug withdrawal
Authors: Orunesu E. , Bagnasco M. , Salmaso C. , Altrinetti V. , Bernasconi D. , Del Monte P. , Pesce G. , Marugo M. , Mela G. S. 
Published: March 2004

AbstractBackground  Graves’ disease (GD) is an autoimmune disorder characterized by hyperthyroidism, which can relapse in many patients after antithyroid drug treatment withdrawal. Several studies have been performed to predict the clinical course of GD in patients treated with antithyroid drugs, without conclusive results. The aim of this study was to define a set of easily achievable variables able to predict, as early as possible, the clinical outcome of GD after antithyroid therapy.Methods  We studied 71 patients with GD treated with methimazole for 18 months: 27 of them achieved stable remission for at least 2 years after methimazole therapy withdrawal, whereas 44 patients relapsed. We used for the first time a perceptron‐like artificial neural network (ANN) approach to predict remission or relapse after methimazole withdrawal. Twenty‐seven variables obtained at diagnosis or during treatment were considered.Results  Among different combinations, we identified an optimal set of seven variables available at the time of diagnosis, whose combination was useful to efficiently predict the outcome of the disease following therapy withdrawal in approximately 80% of cases. This set consists of the following variables: heart rate, presence of thyroid bruits, psycological symptoms requiring psychotropic drugs, serum TGAb and fT4 levels at presentation, thyroid‐ultrasonography findings and cigarette smoking.Conclusions  This study reveals that perceptron‐like ANN is potentially a useful approach for GD‐management in choosing the most appropriate therapy schedule at the time of diagnosis.
Bradycardia and sinus arrest during percutaneous ethanol injection therapy for hepatocellular carcinoma
Authors: Ferlitsch A. , Kreil A. , Bauer E. , Schmidinger H. , Schillinger M. , Gangl A. , Peck‐Radosavljevic M. 
Published: March 2004

AbstractBackground  Percutaneous ethanol injection (PEI) is an established method in the treatment of hepatocellular carcinoma (HCC) and considered a safe procedure, with severe complications occurring rarely. Cardiac arrhythmias have not been reported to date. Aim of the study was to investigate the occurrence of dysrhythmias during PEI.Patients and methods  Twenty‐six consecutive patients with inoperable HCC were included. During ultrasound‐guided PEI with 95% ethanol, electrocardiogram (ECG) monitoring was performed before starting and continuously during PEI.Results  During PEI a significant reduction in mean heart rate (> 20%) was seen in 15 of 26 (58%) patients. In 11 of 26 patients (42%) occurrence of sinuatrial block (SAB) or atrioventricular block (AVB) was observed after a median time of 9 s (range 4–50) from the start of PEI with a median length of 24 s (range 12–480). Clinical symptoms were seen in two patients, including episodes of unconsciousness, seizure‐like symptoms in both and a respiratory arrest during PEI in one patient, requiring mechanical ventilation. In four of 12 patients with repeat interventions, dysrhythmias were reproducible during monthly performed procedures. There was a significant association between the occurrence of SAB or AVB and the amount of instilled alcohol (P = 0·03) and post‐PEI serum ethanol levels (P = 0·03).Conclusions  Bradycardia and block formation occur frequently during PEI. These symptoms could be explained by a vasovagal reaction and/or the direct effect of ethanol on the sinus node or the right atrial conduction system. Ethanol dose is an important factor for the occurrence of SAB/AVB. ECG‐monitoring seems mandatory during PEI. Prophylactic use of intravenously administered Atropine might be useful.
Strategic Collaborative Model for Evidence‐Based Nursing Practice
Authors: Olade Rosaline A. 
Published: March 2004

ABSTRACT Purpose: To describe a model that has been developed to guide nurses and other health professionals in collaborative efforts toward evidence‐based nursing practice. Method: A review of literature was conducted using MEDLINE and CINAHL to search for articles on research utilization for evidence‐based practice in health care delivery. Empirical studies; reviews; and theoretical, opinion, and information articles were included in the review in order to provide a more comprehensive view of the state of evidence‐based nursing internationally. Findings: Findings revealed a number of barriers to evidence‐based nursing practice, which have persisted over the last two decades, including inadequate knowledge of research among practicing nurses, lack of administrative support for research activities in clinical settings, lack of empowerment of nurses, and lack of needed mentoring from nursing research consultants. Conclusions: Barriers in the areas of nursing education and administrative support appear to be major. A need was identified for a pragmatic model that encourages cooperation and collaboration between educators/researchers in academia and the administrative leaders in the clinical facilities if evidence‐based nursing practice is to become the norm. Framework of Model: The Tyler Collaborative Model is based on an eclectic approach to planned change for creating evidence‐based practice. This model identifies a step‐by‐step process for change, while allowing for the opportunity to integrate any of the previously available methods of critical appraisal to determine the best evidence for practice in each clinical setting.
Fortuitous Phenomena: On Complexity, Pragmatic Randomised Controlled Trials, and Knowledge for Evidence‐Based Practice
Authors: Thompson Carl 
Published: March 2004

ABSTRACT Context: Many of the interventions that nurses develop and implement are in themselves complex and have to operate in situations of irreducible complexity and uncertainty. Main Argument: This article argues that the primary means of generating knowledge for the evidence‐based deployment of complex interventions should be the pragmatic randomised controlled trial. Randomised controlled trials represent the only research design to adequately deal with that which we know and (far more importantly) that which we do not. Literary Method: Using the example of practice development as an exemplar for complexity, and drawing on the objections often voiced as a response to calls to make use of randomised controlled trials in nursing and nursing research, the article presents a developmental framework and some methodological solutions to problems often encountered. Conclusion: Randomised controlled trials, whilst undoubtedly methodologically and strategically challenging, offer the most robust basis for developing primary research knowledge on the effects of complex interventions in nursing and their active components.
Conducting Translation Research in the Home Care Setting: Lessons from a Just‐in‐Time Reminder Study
Authors: Feldman Penny Hollander , McDonald Margaret V. 
Published: March 2004

ABSTRACT Background: Home care organizations are relatively isolated from academic health centers, university‐based schools of nursing, and centers of health services research that have advanced the knowledge base for quality improvement. Thus limited information exists about how best to promote evidence‐based practice in this setting. Aims: This article examines research and translation issues posed by the decentralized home care setting and considers how these issues compare to issues in other settings. Methods: A case study approach is used to frame a discussion of the contextual and practical factors that can influence the design and future acceptance of different translation strategies in the home care setting. Use of a recently concluded randomized trial that tested the effectiveness of two interventions designed to improve the adoption of evidence‐based practices by home health nurses has been made to inform this discussion. Discussion: Effective translation interventions in home health care need to address the unique nature of this setting including the dispersed, generalist workforce that serves a diverse patient population and lacks strong peer contact or on‐site support and supervision. Proactive push translation strategies such as reminders that have been effective in other settings show promise in this service area but had a differential effect across conditions. Significantly, the cost‐effectiveness analysis of this intervention showed that net patient care costs actually increased for one condition. Implications: The study described in this article demonstrates that rigorous translation research can be conducted in highly decentralized practice settings. It also points to the value of assessing different levels of intensity of interventions in a single study, looking at process measures and patient outcomes, and conducting a cost‐effectiveness analysis. To encourage broader adoption of translation strategies, additional incentives from purchasing or regulatory agencies may be needed.
Methods in Translation Science
Authors: Titler Marita G. 
Published: March 2004

ABSTRACT Background: The gap between research findings and practice has been, and continues to be, a concern for the international community. A number of descriptive studies have elucidated barriers and facilitators of evidence‐based practice in nursing. It is argued that it is now time to use findings from these studies to design and test interventions that explicitly target barriers to the use of evidence in practice rather than doing further research to describe generic barriers and facilitators to evidence‐based practice. This article discusses research methods to advance our knowledge regarding the efficacy of translating research into practice (TRIP) interventions that promote and hasten adoption of evidence in practice. Approach: Published research is reviewed and used as exemplars of translation studies. The benefits and challenges in studying natural experiments are addressed as are the benefits and challenges in conducting TRIP studies using experimental designs. Discussion: The article discusses factors such as sample attainment, unit of analysis, intervention characteristics, outcome measurement, and sustainability. Although there are a myriad of initiatives aimed at increasing use of evidence in practice, there is little systematic evidence of the effectiveness of these initiatives. In order to advance knowledge, translation research needs more experimental studies that test TRIP interventions through, for example, partnership models.
Evidence Review on Older People's Views and Experiences of Falls Prevention Strategies
Authors: McInnes Elizabeth , Askie Lisa 
Published: March 2004

ABSTRACT Background: A systematic review was undertaken of qualitative and quantitative studies and reviews that focus on older people's views and experiences of falls prevention. The review was undertaken to provide an additional dimension to the clinical effectiveness evidence provided by a Cochrane review on falls prevention (Gillespie et al. 2003) to inform the development of a national guideline on falls prevention in older people. As guideline recommendations or policies relating to preventive strategies have the potential to increase health care costs, it is important that all sources of evidence are reviewed by guideline development groups so that an understanding is achieved of the acceptability and sustainability of interventions in relation to different groups and settings. Method: Accordingly, this review examined the literature on the views, preferences, and experiences of older people in relation to falls prevention strategies. Twenty‐four studies meeting the inclusion criteria were critically reviewed and were then summarized into evidence tables. The key facilitators and barriers to participation in falls prevention programs were derived from the commonly occurring and consistent themes arising from the reviewed studies. The implications of these findings for the clinical effectiveness review conclusions were then taken into account. Findings: Several important findings emerged. These included preferences for falls prevention strategies not involving behaviour change among some groups, the need to promote the social value of falls prevention programs, and the importance of identifying and addressing factors associated with activity avoidance. Conclusions and Implications: In terms of the impact of these findings on the Cochrane review, the most important implication is that although trials of multifactorial falls prevention packages have reported beneficial results, in clinical practice it is important to consult with individual potential participants and find out what characteristics they are willing to modify, and what changes they are prepared to make to reduce their risk of falling. Otherwise, there is the risk that expensive programs are not properly targeted or fail to achieve maximum participation rates. Further work on the most robust and pragmatic methods of synthesizing disparate studies on patients' views and preferences to inform evidence‐based guideline recommendations is needed.