bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Systematic Review of Measures of End‐of‐Life Care and Its Outcomes
Authors: Mularski Richard A. , Dy Sydney M. , Shugarman Lisa R. , Wilkinson Anne M. , Lynn Joanne , Shekelle Paul G. , Morton Sally C. , Sun Virginia C. , Hughes Ronda G. , Hilton Lara K. , Maglione Margaret , Rhodes Shannon L. , Rolon Cony , Lorenz Karl A. 
Published: April 2007

Objective. To identify psychometrically sound measures of outcomes in end‐of‐life care and to characterize their use in intervention studies.Data Sources. English language articles from 1990 to November 2005 describing measures with published psychometric data and intervention studies of end‐of‐life care.Study Design. Systematic review of end‐of‐life care literature.Extraction Methods. Two reviewers organized identified measures into 10 major domains. Eight reviewers extracted and characterized measures from intervention studies.Principal Findings. Of 24,423 citations, we extracted 200 articles that described 261 measures, accepting 99 measures. In addition to 35 measures recommended in a prior systematic review, we identified an additional 64 measures of the end‐of‐life experience. The most robust measures were in the areas of symptoms, quality of life, and satisfaction; significant gaps existed in continuity of care, advance care planning, spirituality, and caregiver well‐being. We also reviewed 84 intervention studies in which 135 patient‐centered outcomes were assessed by 97 separate measures. Of these, 80 were used only once and only eight measures were used in more than two studies.Conclusions. In general, most measures have not undergone rigorous development and testing. Measure development in end‐of‐life care should focus on areas with identified gaps, and testing should be done to facilitate comparability across the care settings, populations, and clinical conditions. Intervention research should use robust measures that adhere to these standards.
Differences in the Implementation of Diagnosis‐Related Groups across Clinical Departments: A German Hospital Case Study
Authors: Ridder Hans‐Gerd , Doege Vanessa , Martini Susanne 
Published: April 2007

Objective. This article aims to examine the implementation process of diagnosis‐related groups (DRGs) in the clinical departments of a German hospital group and to explain why some gain competitive advantage while others do not.Study Setting. To investigate this research question, we conducted a qualitative study based on primary data obtained in six clinical departments in a German hospital group between 2003 and 2005.Study Design. We chose the case study method in order to gain deep insights into the process dynamics of the implementation of DRGs in the six clinical departments. The dynamic capability approach is used as a theoretical foundation. Employing theory‐driven categories we focused on idiosyncratic and common patterns of “successful coders” and “unsuccessful coders.”Data Collection. To observe the implementation process of DRGs, we conducted 43 semistructured interviews with key persons, carried out direct observations of the monthly meetings of the DRG project group, and sampled written materials.Principal Findings. “Successful coders” invest into change resources, demonstrate a high level of acceptance of innovations, and organize effective processes of coordination and learning.Conclusions. All clinical departments only put an emphasis on the coding aspects of the DRGs. There is a lack of vision regarding the optimization of patient treatment processes and specialization. Physicians are the most important key actors, rather than the main barriers.
Comprehensive genetic analysis of cancer cells
Authors: Popescu Nicholas C. 
Published: May 2007

AbstractHuman cancer is viewed as a disorder of genes originating from the progeny of a single cell that has accumulated multiple genetic alterations. The genetic alterations include point mutation, chromosomal rearrangements and imbalances. Amplifications primarily involve oncogenes whose overexpression leads to growth deregulation, while deletions commonly target tumor suppressor genes that control cell cycle checkpoints and DNA repair mechanisms. With the advent of molecular cytogenetics procedures for global detection of genomic imbalances and for multicolor visualization of structural chromosome changes, as well as the completion of human genome mapping and the development of microarray technology for serial gene expression analysis of the entire genomes, a significant progress has been made in uncovering the molecular basis of cancer. The major challenge in cancer biology is to decipher the molecular anatomy of various cancers and to identify cancer‐related genes that now comprise only a fraction of human genes. The complete genetic anatomy of specific cancers would allow a better understanding of the role of genetic alterations in carcinogenesis, provide diagnostic and prognostic markers and discriminate between cells at different stages of progression toward malignancy. This review highlights current technologies that are available to explore cancer cells and outlines their application to investigations in human hepatocellular carcinoma.
Messenger molecules of the phospholipase signaling system have dual effects on vascular smooth muscle contraction
Authors: Vidulescu Cristina , Mironneau J. , Mironneau Chantal , Popescu L.M. 
Published: May 2007

Abstract Background and methods. In order to investigate the role of phospholipases and their immediately derived messengers in agonist‐induced contraction of portal vein smooth muscle, we used the addition in the organ bath of exogenous molecules such as: phospholipases C, A2, and D, diacylglycerol, arachidonic acid, phosphatidic acid, choline. We also used substances modulating activity of downstream molecules like protein kinase C, phosphatidic acid phosphohydrolase, or cyclooxygenase. Results. a) Exogenous phospholipases C or A2, respectively, induced small agonist‐like contractions, while exogenous phospholipase D did not. Moreover, phospholipase D inhibited spontaneous contractions. However, when added during noradrenaline‐induced plateau, phospholipase D shortly potentiated it. b) The protein kinase C activator, phorbol dibutyrate potentiated both the exogenous phospholipase C‐induced contraction and the noradrenaline‐induced plateau, while the protein kinase C inhibitor 1‐(‐5‐isoquinolinesulfonyl)‐2‐methyl‐piperazine relaxed the plateau. c) When added before noradrenaline, indomethacin inhibited both phasic and tonic contractions, but when added during the tonic contraction shortly potentiated it. Arachidonic acid strongly potentiated both spontaneous and noradrenaline‐induced contractions, irrespective of the moment of its addition. d) In contrast, phosphatidic acid inhibited spontaneous contractile activity, nevertheless it was occasionally capable of inducing small contractions, and when repetitively added during the agonist‐induced tonic contraction, produced short potentiations of the plateau. Pretreatment with propranolol inhibited noradrenaline‐induced contractions and further addition of phosphatidic acid augmented this inhibition. Choline augmented the duration and amplitude of noradrenaline‐induced tonic contraction and final contractile oscillations. Conclusions. These data suggest that messengers produced by phospholipase C and phospholipase A2 contribute to achieve the onset and maintenance of contraction, while phospholipase D‐yielded messengers appear to provide a delayed “on/off switch” that ultimately brings relaxation.
Stem cell generation and choice of fate: role of cytokines and cellular microenvironment
Authors: Constantinescu S.N. 
Published: May 2007

AbstractHematopoietic stem cells (HSC) have provided a model for the isolation, enrichment and transplantation of stem cells. Gene targeting studies in mice have shown that expression of the thrombopoietin receptor (TpoR) is linked to the accumulation of HSCs capable to generate long‐term blood repopulation when injected into irradiated mice. The powerful increase in vivo in HSC numbers by retrovirally transduced HOX4B, a homeotic gene, along with the role of the TpoR, suggested that stem cell fate, renewal, differentiation and number can be controlled. The discovery of the precise region of the mouse embryo where HSCs originate and the isolation of supporting stromal cell lines open the possibility of identifying the precise signals required for HSC choice of fate. The completion of human genome sequencing coupled with advances in gene expression profiling using DNA microarrays will enable the identification of key genes deciding the fate of stem cells. Downstream from HSCs, multipotent hematopoietic progenitor cells appear to co‐express a multiplicity of genes characteristic of different blood lineages. Genomic approaches will permit the identification of the select group of genes consolidated by the commitment of these multipotent progenitors towards one or the other of the blood lineages. Studies with neural stem cells pointed to the unexpected plastic nature of these cells. Isolation of stem cells from multiple tissues may suggest that, providing the appropriate environment/signal, tissues could be regenerated in the laboratory and used for transplantation. A spectacular example of influence of the environment on cell fate was revealed decades ago by using mouse embryonic stem cells (ES). Injected into blastocysts, ES cells contribute to the formation of all adult tissues. Injected into adult mice, ES cells become cancer cells. After multiple passages as ascites, when injected back into the blastocyst environment, ES‐ derived cancer cells behaved again as ES cells. More recently, the successful cloning of mammals and reprogramming of transferred nuclei by factors in the cytoplasm of oocytes turned back the clock by showing that differentiated nuclei can be “re‐booted” to generate again the stem cells for different tissues.
Neurons bearing presenilins: weapons for defense or suicide?
Authors: Popescu B.O. , Ankarcrona Maria 
Published: May 2007

AbstractApoptotic machinery designed for cell's organized self‐destruction involve different systems of proteases which cleave vital proteins and disassemble nuclear and cytoplasmic structures, committing the cell to death. The most studied apoptotic proteolytic system is the caspase family, but calpains and the proteasome could play important roles as well. Alzheimer's disease associated presenilins showed to be a substrate for such proteolytic systems, being processed early in several apoptotic models, and recent data suggest that alternative presenilin fragments could regulate cell survival. Mutations in genes encoding presenilins proved to sensitize neurons to apoptosis by different mechanisms e.g. increased caspase‐3 activation, oxyradicals production and calcium signaling dysregulation. Here we review the data involving presenilins in apoptosis and discuss a possible role of presenilins in the regulation of apoptotic biochemical machinery.
Cell death mechanisms in neurodegeneration
Authors: Jellinger K. A. 
Published: May 2007

AbstractProgressive cell loss in specific neuronal populations often associated with typical cytoskeletal protein aggregations is a pathological hallmark of neurodegenerative disorders, but the nature, time course and molecular causes of cell death and their relation to cytoskeletal pathologies are still unresolved. Apoptosis or alternative pathways of cell death have been discussed in Alzheimer's disease and other neurodegenerative disorders. Apoptotic DNA fragmentation in human brain as a sign of neuronal injury is found too frequent as to account for continous neuron loss in these slowly progressive processes. Morphological studies revealed extremely rare apoptotic neuronal death in Alzheimer's disease but yielded mixed results for Parkinson's disease and other neurodegenerative disorders. Based on recent data in human brain, as well as in animal and cell culture models, a picture is beginning to emerge suggesting that, in addition to apoptosis, other forms of programmed cell death may participate in neurodegeneration. Better understanding of the molecular players will further elucidate the mechanisms of cell death in these disorders and their relations to cytoskeletal abnormalities. Susceptible cell populations in a proapoptotic environment show increased vulnerability towards multiple noxious factors discussed in the pathogenesis of neurodegeneration. In conclusion, although many in vivo and in vitro data are in favor of apoptosis involvement in neurodegenerative processes, there is considerable evidence that very complex events may contribute to neuronal death with possible repair mechanisms, the elucidation of which may prove useful for future prevention and therapy of neurodegenerative disorders.
Problems and solutions in myoblast transfer therapy
Authors: Smythe Gayle M. , Hodgetts Stuart I. , Grounds Miranda D. 
Published: May 2007

AbstractDuchenne muscular dystrophy is a severe X‐linked neuromuscular disease that affects approximately 1/3500 live male births in every human population, and is caused by a mutation in the gene that encodes the muscle protein dystrophin. The characterization and cloning of the dystrophin gene in 1987 was a major breakthrough and it was considered that simple replacement of the dystrophin gene would ameliorate the severe and progressive skeletal muscle wasting characteristic of Duchenne muscular dystrophy. After 20 years, attempts at replacing the dystrophin gene either experimentally or clinically have met with little success, but there have been many significant advances in understanding the factors that limit the delivery of a normal dystrophin gene into dystrophic host muscle. This review addresses the host immune response and donor myoblast changes underlying some of the major problems associated with myoblast‐mediated dystrophin replacement, presents potential solutions, and outlines other novel therapeutic approaches.
Abnormalities of platelet aggregation in chronic myeloproliferative disorders
Authors: Avram Simona , Lupu Anca , Angelescu Silvana , Olteanu Nicoleta , Mut‐Popescu Delia 
Published: May 2007

AbstractA large variety of platelet dysfunctions has been described in chronic myeloproliferative disorders. These abnormalities may be due to deficiency of platelet granules, arahidonic acid metabolism defects or platelet membrane glycoproteins abnormalities. In this study we intend to detect the incidence of platelet function defects in 76 patients with various types of chronic myeloproliferative disorders. The platelet activity was studied in vitro by measuring platelet aggregation in response to ADP, epinephrine, collagen, arachidonic acid and ristocetin. These results were subsequently correlated with bleeding time and clinical aspects (bleeding or thrombosis). We found complex changes in platelet response with all agonists, in varied proportions. These abnormalities include absent, decreased or abnormal platelet aggregation response. In a few cases we found a markedly decreased, almost absent platelet response to all agonists while in some patients a normal platelet aggregation was noted. The correlation between these results and template bleeding time, thrombotic or hemorrhagic events and the type of diseases was difficult to establish and sometimes conflictual. Despite this fact, we consider that investigating platelet aggregation may be useful not only for the assesment of the hemostatic balance in chronic myeloproliferative disorders but also for a better insight into cell abnormalities occuring in these pathologic conditions.
Fibroblast growth factors in myocardial ischemia / reperfusion injury and ischemic preconditioning
Authors: Cuevas P. , Carceller F. , Giménez‐Gallego G. 
Published: May 2007

AbstractAngiogenic growth factors such as fibroblast growth factors (FGFs) are currently in clinical trials for accelerating blood vessel formation in myocardial and limb ischemic conditions. However, recent experimental evidence suggests that FGFs can also participate as endogenous cardioprotective agents. In this report, the current knowledge for FGFs implication in myocardial ischemic tolerance will be summarized. Pharmacologic preconditioning with drugs as FGFs that mimic the beneficial effects of ischemic preconditioning could lead to novel therapeutic approaches for the treatment of ischemic disorders including myocardial infarction and stroke.
Cardiac apoptosis: from organ failure to allograft rejection
Authors: Hinescu M. E. 
Published: May 2007

AbstractCardiac myocyte apoptosis has been extensively studied in the last few years. Increased interest in the field stems from the hope that pharmacological manipulation of apoptosis may become a valuable tool for preventing excessive cell death observed in different pathological conditions. This paper is not intended as a comprehensive overview of current research about life and death in the cardiovascular system, but rather as a concise update on new developments in areas that were highlighted in a recent series of excellent reviews. A short inventory of unsolved issues concerning the significance of cardiac myocyte loss through apoptosis in both physiological and pathological circumstances is addressed.
Can a mixed damage interfere with DNA‐prottein cross‐links repair?
Authors: Marzano Christine , Severin Emilia , Bordin Franco 
Published: May 2007

AbstractSome photochemical and photobiological properties of 4,5′,8‐trimethylpsoralen (TMP) have been studied in comparison with 1,4,6,8‐tetramethyl‐2H‐furo[2,3‐h]quinolin‐2 one (FQ) and 8‐methoxypsoralen (8‐MOP). TMP and FQ can photobind to mammalian cell DNA in vivo, by UVA irradiation, forming DNA‐protein cross‐links (DPC), but only TMP shows a strong capacity of inducing interstrand cross‐links (ISC). The mechanism of DPC formation was studied using the double irradiation method in Chinese hamster ovary (CHO) cells, and DPC were detected by alkaline elution. Both TMP and FQ induce covalent diadducts linking together DNA and proteins. Studying the formation of double strand breaks (DSB) in CHO cells we observed that TMP induced a low amount of DSB, similar to 8‐MOP. TMP and 8‐MOP induced chromosomal aberrations in CHO cells to the same extent, while FQ appeared to be more active. Our data suggest that the ISC induced by TMP could trap enzymes involved in DPC repair.
Effects of synovial fluid on the respiratory burst of granulocytes in rheumatoid arthritis
Authors: Bostan M. , Brasoveanu L. I. , Livescu A. , Manda G. , Neagu M. , Iordachescu D. 
Published: May 2007

AbstractNeutrophil infiltration in the synovia is an important feature of the local inflammatory process associated with rheumatoid arthritis. The present study is focused on the effects exerted in vitro by the synovial fluid versus serum on the respiratory burst of granulocytes isolated either from blood or synovial fluid of rheumatoid arthritis patients. The respiratory burst was evaluated as superoxide anion release, by lucigenin‐amplified chemiluminescence. Our data show that the respiratory burst of granulocytes isolated from rheumatoid arthritis patients might trigger a significant oxidative stress both in periphery and the inflamed joint. These cells show no pathological pattern when activated in vitro by the chemotactic peptide fMLP, heterologous synovial fluid or serum. Acellular synovial fluid amplifies the superoxide anion release induced by fMLP more than the corresponding serum, indicating that a bacterian infection in the joint might enhance the oxidative damage in the inflamed synovium.
Apolipoprotein E: a major piece in the Alzheimer's disease puzzle
Authors: Cedazo‐Mínguez A. , Cowburn R. F. 
Published: May 2007

AbstractAlzheimer's disease (AD) is a complex neurodegenerative disorder with multiple etiologies. The presence of the E4 isoform of apolipoprotein E (apoE) has been shown to increase the risk and to decrease the age of onset for AD and is the major susceptibility factor known for the disease. ApoE4 has been shown to intensify all the biochemical distrubances characteristic of AD, including beta amyloid (Aβ) deposition, tangle formation, neuronal cell death, oxidative stress, synaptic plasticity and dysfunctions of lipid homeostasis and cholinergic signalling. In contrast, other apoE isoforms are protective. Here we review and discuss these major hypotheses of the apoE4‐AD association.
The total peroxyl radical trapping potential in serum ‐ an assay to define the stage of atherosclerosis
Authors: Niculescu L. , Stancu Camelia , Sima Anca , Toporan Daniela , Simionescu Maya 
Published: May 2007

AbstractLipid peroxides were identified among the factors that contribute to the atherosclerotic plaque formation in the arterial wall. We hypothesised that a correlation may exist between the content of antioxidant constituents in the serum and the gravity of atherosclerosis. To this purpose, we have determined the serum total peroxyl radical‐ trapping potential (TRAP), which is the combined capacity of all antioxidants to neutralize free radicals in serum and followed its variation in hyperlipemic animals in correlation with the stage of atherosclerosis. In addition, we compared TRAP values in the sera of coronary heart disease (CHD) patients, with or without type II diabetes mellitus. Results showed that after 18 weeks of hyperlipemic diet, the mean TRAP values measured in sera isolated from hyperlipemic hamsters exhibited an about 44% decrease, in good agreement with the increase of serum cholesterol and triglycerides. In the 3 groups of CHD patients, TRAP values decreased with about 10% in sera of stable angina patients, 20% in unstable patients, as compared with normal subjects. The lowest TRAP values were detected in the sera of patients with acute myocardial infarction. The results obtained for different experimental animals and for CHD patients sera indicate that the TRAP method, as adapted in our laboratory, is a reliable and reproducible assay, fit to be used in clinical studies as an ex vivo measurable parameter that correlates with the stage of the atherosclerosis.
Cell viability of retinal photoreceptor evaluated by polar distribution of Ca2+ and electrical charge
Authors: Kovács Eugenia , Pilarczyk G. , Monajembashi Shamci , Moraru Roxana Pologea , Greulich K. O. 
Published: May 2007

AbstractThe polar organisation is characteristic to the living cell and disappears with the cell functional decay. Here we report experimental evidence that frog retinal photoreceptor rod cell shows a polar distribution of the electrical charge and of free cytosolic Ca2+ along its length. Retinal rod cells were loaded with Calcium sensitive dye (Green 1) and examined under fluorescence microscopy coupled with an image analysis system. In addition, suspension of rod cells was placed in direct current electric field for electrical polarity assessment. Both polar Ca2+ and electrical charge distribution can be objectively measured and quantified providing thus a fine test for cell viability. Such a test is required in checking the functional integrity of photoreceptors used in rentinal transplant.