bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of haematopoietic malignancies in US radiologic technologists
Authors: Linet M S , Freedman D M , Mohan A K , Doody M M , Ron E , Mabuchi K , Alexander B H , Sigurdson A , Hauptmann M
Published: November 2005

Background:There are limited data on risks of haematopoietic malignancies associated with protracted low-to-moderate dose radiation.

Aims:To contribute the first incidence risk estimates for haematopoietic malignancies in relation to work history, procedures, practices, and protective measures in a large population of mostly female medical radiation workers.

Methods:The investigators followed up 71 894 (77.9% female) US radiologic technologists, first certified during 1926–80, from completion of a baseline questionnaire (1983–89) to return of a second questionnaire (1994–98), diagnosis of a first cancer, death, or 31 August 1998 (731 306 person-years), whichever occurred first. Cox proportional hazards regression was used to compute risks.

Results:Relative risks (RR) for leukaemias other than chronic lymphocytic leukaemia (non-CLL, 41 cases) were increased among technologists working five or more years before 1950 (RR = 6.6, 95% CI 1.0 to 41.9, based on seven cases) or holding patients 50 or more times forxray examination (RR = 2.6, 95% CI 1.3 to 5.4). Risks of non-CLL leukaemias were not significantly related to the number of years subjects worked in more recent periods, the year or age first worked, the total years worked, specific procedures or equipment used, or personal radiotherapy. Working as a radiologic technologist was not significantly linked with risk of multiple myeloma (28 cases), non-Hodgkin’s lymphoma (118 cases), Hodgkin’s lymphoma (31 cases), or chronic lymphocytic leukaemia (23 cases).

Conclusion:Similar to results for single acute dose and fractionated high dose radiation exposures, there was increased risk for non-CLL leukaemias decades after initial protracted radiation exposure that likely cumulated to low-to-moderate doses.
The effect of asbestosis on lung cancer risk beyond the dose related effect of asbestos alone
Authors: Reid A , de Klerk N , Ambrosini G L , Olsen N , Pang S C , Berry G , Musk A W
Published: November 2005

Aims:To determine if the presence of asbestosis is a prerequisite for lung cancer in subjects with known exposure to blue asbestos (crocidolite).

Methods:Former workers and residents of Wittenoom with known amounts of asbestos exposure (duration, intensity, and time since first exposure), current chestxray and smoking information, participating in a cancer prevention programme (n = 1988) were studied. The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was examined for radiographic evidence of asbestosis according to the UICC (ILO) classification. Cox proportional hazards modelling was used to relate asbestosis, asbestos exposure, and lung cancer.

Results:Between 1990 and 2002 there were 58 cases of lung cancer. Thirty six per cent of cases had radiographic evidence of asbestosis compared to 12% of study participants. Smoking status was the strongest predictor of lung cancer, with current smokers (OR = 26.5, 95% CI 3.5 to 198) having the greatest risk. Radiographic asbestosis (OR = 1.94, 95% CI 1.09 to 3.46) and asbestos exposure (OR = 1.21 per f/ml-year, 95% CI 1.02 to 1.42) were significantly associated with an increased risk of lung cancer. There was an increased risk of lung cancer with increasing exposure in those without asbestosis.

Conclusion:In this cohort of former workers and residents of Wittenoom, asbestosis is not a mandatory precursor for asbestos related lung cancer. These findings support the hypothesis that it is the asbestos fibres per se that cause lung cancer, which can develop with or without the presence of asbestosis.
The threat to scientific integrity in environmental and occupational medicine
Authors: Tong S , Olsen J
Published: November 2005

Over the last century, environmental and occupational medicine has played a significant role in the protection and improvement of public health. However, scientific integrity in this field has been increasingly threatened by pressure from some industries and governments. For example, it has been reported that the tobacco industry manipulated eminent scientists to legitimise their industrial positions, irresponsibly distorted risk and deliberately subverted scientific processes, and influenced many organisations in receipt of tobacco funding. Many environmental whistleblowers were sued and encountered numerous personal attacks. In some countries, scientific findings have been suppressed and distorted, and scientific advisory committees manipulated for political purposes by government agencies. How to respond to these threats is an important challenge for environmental and occupational medicine professionals and their societies. The authors recommend that professional organisations adopt a code of ethics that requires openness from public health professionals; that they not undertake research or use data where they do not have freedom to publish their results if these data have public health implications; that they disclose all possible conflicts; that the veracity of their research results should not be compromised; and that their research independence be protected through professional and legal support. The authors furthermore recommend that research funding for public health not be directly from the industry to the researcher. An independent, intermediate funding scheme should be established to ensure that there is no pressure to analyse data and publish results in bad faith. Such a funding system should also provide equal competition for funds and selection of the best proposals according to standard scientific criteria.
THERMODYNAMIC AND MAGNETIC PROPERTIES OF THE ARCHIMEDEAN LATTICES
Authors: ZHANG Q. L.
Published: November 2005

We numerically study the thermodynamic properties of two Archimedean lattices1 with Ising spins using Wang–Landau algorithm of the Monte Carlo simulation. The two Archimedean lattices are of the type (3, 122) and Kagomé, for which we are particularly interested in the frustration effects. The internal energy, specific heat, free energy, entropy, magnetization and spin susceptibility are calculated.
LASER FIELD INDUCED AZIMUTHAL ANCHORING GLIDING IN DYE DOPED NEMATIC LIQUID CRYSTALS
Authors: PĂLĂRIE ION , EŞEANU NICOLETA
Published: November 2005

We have analyzed the rotating effect of an Ar+linearly polarized laser beam on a dye-doped nematic liquid crystal (DDNLC) in a pump-probe experiment. An asymmetric capillary cell with two polymer coated glasses was used. An easy axis was induced by rubbing one surface, the other one remained non-oriented. The exciting laser beam entering the orienting surface has the polarization direction perpendicular to the easy axis. The time dependent transmitted intensity of a probe He – Ne laser beam (polarization direction parallel to the easy axis) has been measured. For large enough Ar+laser power a non-monotonous curve (having one or even two maxima) has been observed. We develop a model which explains our experimental data by taking into account the gliding of the easy axis on the orienting surface. The azimuthal anchoring gliding angle has been estimated.
GROWTH, OPTICAL AND THERMAL PROPERTIES OF ZINC OXIDE NANO WIRES
Authors: RAJI P. , SIVAKANTH S. , UMESH K. K. , RAMAKRISHNAN S. K. , RAMACHANDRAN K.
Published: November 2005

ZnO nano wire synthesized by microemulsion mediated hydrothermal process is characterized by X-ray diffraction, scanning electron microscope, UV–VIS and photoluminescence. The optical and thermal properties are then studied by photoacoustics. These studies reveal that the ZnO nano wires exhibit a strong ultra violet absorption and a relatively weak defect emission.
EXACT SOLUTIONS, LADDER OPERATORS AND BARUT–GIRARDELLO COHERENT STATES FOR A HARMONIC OSCILLATOR PLUS AN INVERSE SQUARE POTENTIAL
Authors: DONG SHI-HAI , LOZADA-CASSOU M.
Published: November 2005

We present exact solutions of the one-dimensional Schrödinger equation with a harmonic oscillator plus an inverse square potential. The ladder operators are constructed by the factorization method. We find that these operators satisfy the commutation relations of the generators of the dynamical group SU(1, 1). Based on those ladder operators, we obtain the analytical expressions of matrix elements for some related functions ρ and [Formula: see text] with ρ=x2. Finally, we make some comments on the Barut–Girardello coherent states and the hidden symmetry between E(x) and E(ix) by substituting x→ix.
LOW BIT-RATE IMAGE COMPRESSION SCHEMES BASED ON VECTOR QUANTIZATION
Authors: HU YU-CHEN
Published: November 2005

Three image compression schemes based on vector quantization are proposed in this paper. The block similarity property among neighboring image blocks is exploited in these schemes to cut down the bit rate of the vector quantization scheme. For the first scheme, the correlation among the encoded block to the left and the encoded block directly above the current processing block is exploited. In the second scheme, the relative addressing technique is incorporated into the encoding procedure. Finally, the third scheme introduces a simple technique to reduce the required bit rate with only a slight reduction in image quality. According to the experimental results, it is shown that these proposed schemes not only reduce storage costs but also achieve good reconstructed image quality. Furthermore, the required computational cost for the encoding/decoding procedures of these schemes is less than that of the conventional vector quantization scheme. In other words, these schemes are suitable for the compression of digital images.
Effectiveness of Communication Channels for Knowledge Sharing: A Study of Kuwaiti Companies
Authors: Rehman Sajjad ur
Published: November 2005

Different theories have been advanced and tested about the choice of communication media/channels. These theories deal with information richness, task orientation and relevance of social and organisational contexts in developed nations. Communication media are distinctly important to knowledge sharing. This study will investigate the effectiveness of communication channels in the private companies of Kuwait, a developing nation, so as to ascertain whether these theories are valid in the setting of a developing nation. A research instrument was developed with ten communication channels, and 526 participants from nine Kuwaiti companies indicated the perceived degree of effectiveness of ten media for sharing information/knowledge. It was found that the employees of Kuwaiti companies perceived documented knowledge to be more effective than other media. Face-to-face informal communications, the richest medium found in the earlier studies, was perceived to be less effective than memos, letters and written pronouncements. The telephone was perceived to be a significantly less effective medium. Electronic channels were also not perceived to be as effective. Differences in these results have been explained in the sociocultural and organisational context of Kuwait.
Corporate E-Learning: An Empirical Evaluation
Authors: Handzic Meliha , Ho-Hur Joon
Published: November 2005

This paper explores user views of the current e-learning practices in an organisational setting. Eighty employees of Korean Air, who were enrolled in an e-learning course, participated in the study on a voluntary basis. Data on employees' perceptions of importance and satisfaction with their course portal were gathered by administering a survey questionnaire. The study revealed that employees considered all portal features as quite important and satisfying, although some more than others. They also agreed that there was scope for further improvement through adding extra functionality. These findings have important implications for improving the effectiveness of corporate e-learning.
From Library Management to Knowledge Management: A Conceptual Change
Authors: Malhan I. V. , Rao Shivarama
Published: November 2005

In the knowledge economy era, the library will play a very crucial role in the further extension and modification of knowledge. The growing need for knowledge management has influenced every component and operation of a library. Knowledge management requires more effective methods of information handling, speedy transfer of information and linking of information with individuals and their activities. It demands library patron centred development of information systems and services and customisation of information at the individual level. This opinion paper briefly outlines the nature and significance of conceptual changes involved in the practices of library management to their transition of knowledge management and discusses the competencies required for managing knowledge resources.
Communication Climate and Organisational Knowledge Sharing
Authors: Pascoe Celina , More Elizabeth
Published: November 2005

This paper reports research on the role of communication in knowledge management, examined through the lens of communication climate. The research is being undertaken in a major public sector organisation. The organisation wishes to shift its culture to one characterised by internal information sharing and, to this end, it has undertaken a 3-year knowledge management initiative that comprises an integrated suite of formal and informal knowledge sharing activities. The research is being conducted on a longitudinal basis between 2003 and 2005, and results of the first survey of the organisation's communication climate are reported in this paper. It is proposed that communication audits can be used to gauge whether knowledge and information sharing are likely to occur by providing data on two antecedents to such sharing: perceptions of other organisational members' openness to the receiving as well as the sending aspects of sharing.
Collaborative Knowledge Management Systems for Learning Organisations
Authors: Abdullah Rusli , Sahibudin Shamsul , Alias Rose Alinda , Selamat Mohd Hasan
Published: November 2005

A knowledge management system (KMS) is a concept that can be used for creating knowledge repositories, improving knowledge access and sharing as well as communicating through collaboration, enhancing the knowledge environment and managing knowledge as an asset for an institution or organisation. In this paper, we propose a collaborative KMS framework for learning organisations (LOs) and discuss components in the framework that will help organisations to increase productivity and quality as well as to gain return on investment from a KMS. These components are KMS functionality, architecture, taxonomy, psychological, sociocultural and audit.
An Information Retrieval Model Based on Latent Semantic Indexing with Intelligent Preprocessing
Authors: AswaniKumar Ch. , Gupta Ankush , Batool Mahmooda , Trehan Shagun
Published: November 2005

The primary goal of an information retrieval system is to retrieve all the documents that are relevant to the user query. Disparities between the vocabulary of the system's authors and that of their users pose difficulties when information is processed without human intervention. Preprocessing the documents and user queries using intelligence techniques to remove the ambiguities in representation and indexing is the current area of research. In this paper, we present a novel intelligent method that has been appended to existing stemming and stopword removal processes. We designed an information retrieval system based on the proposed method using latent semantic indexing. The experimental results of the system using the proposed method exhibits the superiority over other systems based on traditional preprocessing methods.
Differential cytokine response from dendritic cells to commensal and pathogenic bacteria in different lymphoid compartments in humans
Authors: O’Mahony Liam , O’Callaghan Louise , McCarthy Jane , Shilling David , Scully Paul , Sibartie Shomik , Kavanagh Eamon , Kirwan William O. , Redmond Henry Paul , Collins John Kevin , Shanahan Fergus
Published: November 2005

Resident host microflora condition and prime the immune system. However, systemic and mucosal immune responses to bacteria may be divergent. Our aim was to compare, in vitro, cytokine production by human mononuclear and dendritic cells (DCs) from mesenteric lymph nodes (MLNs) and peripheral blood mononuclear cells (PBMCs) to defined microbial stimuli. Mononuclear cells and DCs isolated from the MLN ( n = 10) and peripheral blood ( n = 12) of patients with active colitis were incubated in vitro with the probiotic bacteria Lactobacillus salivarius UCC118 or Bifidobacterium infantis 35624 or the pathogenic organism Salmonella typhimurium UK1. Interleukin (IL)-12, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and IL-10 cytokine levels were quantified by ELISA. PBMCs and PBMC-derived DCs secreted TNF-α in response to the Lactobacillus, Bifidobacteria, and Salmonella strains, whereas MLN cells and MLN-derived DCs secreted TNF-α only in response to Salmonella challenge. Cells from the systemic compartment secreted IL-12 after coincubation with Salmonella or Lactobacilli, whereas MLN-derived cells produced IL-12 only in response to Salmonella. PBMCs secreted IL-10 in response to the Bifidobacterium strain but not in response to the Lactobacillus or Salmonella strain. However, MLN cells secreted IL-10 in response to Bifidobacteria and Lactobacilli but not in response to Salmonella. In conclusion, commensal bacteria induced regulatory cytokine production by MLN cells, whereas pathogenic bacteria induce T cell helper 1-polarizing cytokines. Commensal-pathogen divergence in cytokine responses is more marked in cells isolated from the mucosal immune system compared with PBMCs.
Effects of pancreatic duct ligation on pancreatic response to bombesin
Authors: Otani Taiichi , Matsukura Akira , Takamoto Takeshi , Seyama Yasuji , Shimizu Yasuhito , Shinomiya Michiyo , Usui Hiroshi , Gorelick Fred S. , Makuuchi Masatoshi
Published: November 2005

To examine mechanisms that might be related to biliary pancreatitis, we examined the effects of pancreatic duct ligation (PDL) with pancreatic stimulation in vivo. PDL alone caused no increase in pancreatic levels of trypsinogen activation peptide (TAP), trypsin, or chymotrypsin and did not initiate pancreatitis. Although bombesin caused zymogen activation within the pancreas, the increases were slight and it did not cause pancreatitis. However, the combination of PDL with bombesin resulted in prominent increases in pancreatic TAP, trypsin, chymotrypsin, and the appearance of TAP in acinar cells and caused pancreatitis. Disruption of the apical actin network in the acinar cell was observed when PDL was combined with bombesin but not with PDL or bombesin alone. These studies suggest that when PDL is combined with pancreatic acinar cell stimulation, it can promote zymogen activation, the retention of active enzymes in acinar cells, and the development of acute pancreatitis.
VEGF-A stimulation of leukocyte adhesion to colonic microvascular endothelium: implications for inflammatory bowel disease
Authors: Goebel Stephen , Huang Meng , Davis William C. , Jennings Merilyn , Siahaan Teruna J. , Alexander J. Steven , Kevil Christopher G.
Published: November 2005

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder characterized by increased leukocyte recruitment and subsequent tissue damage. An increase in the density of the microvasculature of the colon during IBD has been suggested, leading to the concept that angiogenesis may play a pathological role in IBD. Increased tissue and serum levels of the angiogenic cytokine VEGF-A have been reported in cases of active IBD. In this study, we examined the hypothesis that VEGF-A exerts a proinflammatory effect on colon microvascular endothelium that contributes to colonic inflammation. Leukocyte adhesion to VEGF-A-stimulated colon microvascular endothelial cells was examined using a parallel-plate hydrodynamic flow chamber. ICAM-1 adhesion molecule expression on colonic microvascular endothelium also was determined in response to VEGF-A stimulation, along with characterization of leukocyte adhesion molecule expression. High-dose VEGF-A (50 ng/ml) stimulation increased neutrophil and T cell adhesion to and decreased rolling velocities on activated endothelium, whereas low-dose VEGF-A (10 ng/ml) was without effect. Colonic endothelium constitutively expressed ICAM-1, which was significantly increased by treatment with 50 ng/ml VEGF-A or 10 ng/ml TNF-α but not 10 ng/ml VEGF-A. T cells expressed CD18 and CD11a with no expression of CD11b, whereas neutrophils expressed CD18, CD11a, and CD11b. Finally, VEGF-A-dependent leukocyte adhesion was found to occur in a CD18-dependent manner. These results demonstrate that VEGF-A levels found in IBD exert a proinflammatory effect similar to other inflammatory agents and suggest that this cytokine may serve as an intermediary between angiogenic stimulation and cell-mediated immune responses.
Hypertonic saline dextran after burn injury decreases inflammatory cytokine responses to subsequent pneumonia-related sepsis
Authors: Horton Jureta W. , Maass David L. , White D. Jean
Published: November 2005

The present study examined the hypothesis that hypertonic saline dextran (HSD), given after an initial insult, attenuates exaggerated inflammation that occurs with a second insult. Adult rats ( n = 15 per group) were divided into groups 1 (sham burn), 2 [40% total body surface area burn + 4 ml/kg isotonic saline (IS) + 4 ml·kg−1·% burn−1 lactated Ringer solution (LR)], and 3 (burn + 4 ml/kg HSD + LR), all studied 24 h after burns. Groups 4 (sham burn), 5 (burn + IS + LR), and 6 (burns + HSD + LR) received intratracheal (IT) vehicle 7 days after burns; groups 7 (burn + IS + LR) and 8 (burn + HSD + LR) received IT Streptococcus pneumoniae (4 × 106 colony-forming units) 7 days after burn. Groups 4–8 were studied 8 days after burn and 24 h after IT septic challenge. When compared with sham burn, contractile defects occurred 24 h after burn in IS-treated but not HSD-treated burns. Cardiac inflammatory responses (pg/ml TNF-α) were evident with IS (170 ± 10) but not HSD (45 ± 5) treatment vs. sham treatment (80 ± 15). Pneumonia-related sepsis 8 days after IS-treated burns ( group 7) exacerbated TNF-α responses/contractile dysfunction vs. IS-treated burns in the absence of sepsis ( P < 0.05). Sepsis that occurred after HSD-treated burns ( group 8) had less myocyte TNF-α secretion/better contractile function than IS-treated burns given septic challenge ( group 7, P < 0.05). We conclude that an initial burn injury exacerbates myocardial inflammation/dysfunction occurring with a second insult; giving HSD after the initial insult attenuates myocardial inflammation/dysfunction associated with a second hit, suggesting that HSD reduces postinjury risk for infectious complications.
Noninvasive Doppler-derived myocardial performance index in rats with myocardial infarction: validation and correlation by conductance catheter
Authors: Jegger David , Jeanrenaud Xavier , Nasratullah Mohammad , Chassot Pierre-Guy , Mallik Ajit , Tevaearai Hendrik , von Segesser Ludwig K. , Segers Patrick , Stergiopulos Nikolaos
Published: November 2005

The rodent model of myocardial infarction (MI) is extensively used in heart failure studies. However, long-term follow-up of echocardiographic left ventricular (LV) function parameters such as the myocardial performance index (MPI) and its ratio with the fractional shortening (LVFS/MPI) has not been validated in conjunction with invasive indexes, such as those derived from the conductance catheter (CC). Sprague-Dawley rats with left anterior descending coronary artery ligation (MI group, n = 9) were compared with a sham-operated control group ( n = 10) without MI. Transthoracic echocardiography (TTE) was performed every 2 wk over an 8-wk period, after which classic TTE parameters, especially MPI and LVFS/MPI, were compared with invasive indexes obtained by using a CC. Serial TTE data showed significant alterations in the majority of the noninvasive functional and structural parameters (classic and novel) studied in the presence of MI. Both MPI and LVFS/MPI significantly ( P < 0.05 for all reported values) correlated with body weight ( r = −0.58 and 0.76 for MPI and LVFS/MPI, respectively), preload recruitable stroke work ( r = −0.61 and 0.63), LV end-diastolic pressure (LVEDP) ( r = 0.82 and −0.80), end-diastolic volume ( r = 0.61 and −0.58), and end-systolic volume ( r = 0.46 and −0.48). Forward stepwise linear regression analysis revealed that, of all variables tested, LVEDP was the only independent determinant of MPI ( r = 0.84) and LVFS/MPI ( r = 0.83). We conclude that MPI and LVFS/MPI correlate strongly and better than the classic noninvasive TTE parameters with established, invasively assessed indexes of contractility, preload, and volumetry. These findings support the use of these two new noninvasive indexes for long-term analysis of the post-MI LV remodeling.
Tubuloglomerular feedback-dependent modulation of renal myogenic autoregulation by nitric oxide
Authors: Shi Ying , Wang Xuemei , Chon Ki H. , Cupples William A.
Published: November 2005

Nonselective inhibition of nitric oxide (NO) synthase (NOS) augments myogenic autoregulation, an action that implies enhancement of pressure-induced constriction and dilatation. This pattern is not explained solely by interaction with a vasoconstrictor pathway. To test involvement of the Rho-Rho kinase pathway in modulation of autoregulation by NO, the selective Rho kinase inhibitor Y-27632 and/or the NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) were infused into the left renal artery of anesthetized rats. Y-27632 and l-NAME were also infused into isolated, perfused hydronephrotic kidneys to assess myogenic autoregulation over a wide range of perfusion pressure. In vivo, l-NAME reduced renal vascular conductance and augmented myogenic autoregulation, as shown by increased slope of gain reduction and associated phase peak in the pressure-flow transfer function. Y-27632 (10 μmol/l) strongly dilated the renal vasculature and profoundly inhibited autoregulation in the absence or presence of l-NAME in vivo and in vitro. Afferent arteriolar constriction induced by 30 mmol/l KCl was reversed (−92 ± 3%) by Y-27632. Phenylephrine caused strong renal vasoconstriction but did not affect autoregulation. Inhibition of neuronal NOS by N5-(1-imino-3-butenyl)-l-ornithine (l-VNIO) did not cause significant vasoconstriction but did augment myogenic autoregulation. Thus vasoconstriction is neither necessary (l-VNIO) nor sufficient (phenylephrine) to explain the augmented myogenic autoregulation induced by l-NAME. The effect of l-VNIO implicates tubuloglomerular feedback (TGF) and neuronal NOS at the macula densa in regulation of the myogenic mechanism. This conclusion was confirmed by the demonstration that systemic furosemide removed the TGF signature from the pressure-flow transfer function and significantly inhibited myogenic autoregulation. In the presence of furosemide, augmentation of myogenic autoregulation by l-NAME was significantly reduced. These results provide a potential mechanism to explain interaction between myogenic and TGF-mediated autoregulation.
Reduced forearm α1-adrenergic vasoconstriction is associated with enhanced heart rate fluctuations in humans
Authors: Masuki Shizue , Eisenach John H. , Dinenno Frank A. , Joyner Michael J.
Published: November 2005

In the present study, we assessed whether heart rate (HR) or arterial pressure fluctuations are enhanced in healthy young humans with reduced α-adrenergic vasoconstrictor responses and, if so, whether this occurs for both α1- and α2-adrenergic receptor-mediated vasoconstriction. Arterial pressure (brachial artery catheter) and HR (ECG) were monitored continuously, and α1- and α2-adrenergic responsiveness was determined by assessing the effects of brachial artery infusions of phenylephrine (α1-adrenergic agonist) and dexmedetomidine (α2-adrenergic agonist), respectively, on forearm blood flow (strain gauge plethysmography). α1-Adrenergic responsiveness varied markedly among the subjects ( n = 20) and was inversely correlated with coefficient of variation for HR ( R2 = 0.37, P < 0.01), whereas the responsiveness was not correlated with the coefficient of variation for either systolic or diastolic arterial pressure. α1-Adrenergic responsiveness was inversely and more strongly correlated with baroreflex sensitivity ( R2 = 0.62, P < 0.0001), determined from beat-to-beat changes in HR and systolic arterial pressure, than the coefficient of variation for HR. On the other hand, α2-adrenergic responsiveness was not correlated with any of the parameters determined above. These results suggest that, in healthy young subjects, the enhanced HR response to changes in systolic pressure helps maintain the stability of arterial blood pressure when α1-adrenergic responsiveness is reduced.
Near-infrared spectroscopy measurements of cerebral blood flow and oxygen consumption following hypoxia-ischemia in newborn piglets
Authors: Tichauer Kenneth M. , Brown Derek W. , Hadway Jennifer , Lee Ting-Yim , Lawrence Keith St.
Published: November 2005

Impaired oxidative metabolism following hypoxia-ischemia (HI) is believed to be an early indicator of delayed brain injury. The cerebral metabolic rate of oxygen (CMRO2) can be measured by combining near-infrared spectroscopy (NIRS) measurements of cerebral blood flow (CBF) and cerebral deoxy-hemoglobin concentration. The ability of NIRS to measure changes in CMRO2 following HI was investigated in newborn piglets. Nine piglets were subjected to 30 min of HI by occluding both carotid arteries and reducing the fraction of inspired oxygen to 8%. An additional nine piglets served as sham-operated controls. Measurements of CBF, oxygen extraction fraction (OEF), and CMRO2 were obtained at baseline and at 6 h after the HI insult. Of the three parameters, only CMRO2 showed a persistent and significant change after HI. Five minutes after reoxygenation, there was a 28 ± 12% (mean ± SE) decrease in CMRO2, a 72 ± 50% increase in CBF, and a 56 ± 19% decrease in OEF compared with baseline ( P < 0.05). By 30 min postinsult and for the remainder of the study, there were no significant differences in CBF and OEF between control and insult groups, whereas CMRO2 remained depressed throughout the 6-h postinsult period. This study demonstrates that NIRS can measure decreases in CMRO2 caused by HI. The results highlight the potential for NIRS to be used in the neonatal intensive care unit to detect delayed brain damage.
Slower skeletal muscle phenotypes are critical for constitutive expression of Hsp70 in overloaded rat plantaris muscle
Authors: O'Neill David E. T. , Aubrey F. Kris , Zeldin David A. , Michel Robin N. , Noble Earl G.
Published: November 2005

Heat shock protein 72 (Hsp70) is constitutively expressed in rat hindlimb muscles, reportedly in proportion to their content of type I myosin heavy chain. This distribution pattern has been suggested to result from the higher recruitment and activity of such muscles and/or a specific relationship between myosin phenotype and Hsp70 content. To differentiate between these possibilities, the fiber-specific distribution of Hsp70 was examined in male Sprague-Dawley rat plantaris under control conditions, following a fast-to-slow phenotypic shift in response to surgically induced overload (O) and in response to O when the phenotypic shift was prevented by 3,5,3′-triiodo-dl-thyronine administration. Constitutive expression of Hsp70 was restricted to type I and IIa fibers in plantaris from control rats, and this fiber-specific pattern of expression was maintained following O of up to 28 days, although Hsp70 content in the O muscle doubled. When O (for 40 days) of the plantaris was combined with 3,5,3′-triiodo-dl-thyronine administration, despite typical hypertrophy in the overloaded plantaris, prevention of the normal phenotypic transformation also blocked the increased expression of Hsp70 observed in euthyroid controls. Collectively, these data suggest that chronic changes in constitutive expression of Hsp70 with altered contractile activity appear critically dependent on fast-to-slow phenotypic remodeling.
Upregulation of vascular inducible nitric oxide synthase mediates the hypotensive effect of ethanol in conscious female rats
Authors: El-Mas Mahmoud M. , Zhang Jian , Abdel-Rahman Abdel A.
Published: November 2005

Previous reports from our laboratory have shown that ethanol elicits hypotension in female but not in male rats and that this effect of ethanol is estrogen dependent (El-Mass MM and Abdel-Rahman AA. Alcohol Clin Exp Res 23: 624–632, 1999; El-Mass MM and Abdel-Rahman AA. Clin Exp Hypertens 21: 1429–1445, 1999). In the present study, we tested the hypothesis that ethanol lowers blood pressure in female rats via upregulation of the inducible nitric oxide synthase (iNOS) in vascular tissues. The effects of pretreatment with NG-nitro-l-arginine (NOARG; nonselective nitric oxide synthase inhibitor) or aminoguanidine (selective iNOS inhibitor) on hemodynamic responses elicited by intragastric (ig) ethanol were determined in conscious female rats. Changes in vascular (aortic) iNOS protein expression evoked by ethanol in the presence and absence of aminoguanidine were also measured by immunohistochemistry. Compared with control (water treated) female rats, ethanol (1 g/kg ig) elicited hypotension that was associated with a significant increase in the aortic iNOS activity. The hypotensive effect of ethanol was virtually abolished in rats infused with the nitric oxide synthase inhibitor NOARG, suggesting a role for nitric oxide in ethanol hypotension. The inability of ethanol to lower blood pressure in NOARG-treated rats cannot be attributed to the presence of elevated blood pressure in these rats because ethanol produced hypotension when blood pressure was raised to comparable levels with phenylephrine infusion. Selective inhibition of iNOS by aminoguanidine (45 mg/kg ip), which had no effect on baseline blood pressure, abolished both the hypotensive action of subsequently administered ethanol and the associated increases in aortic iNOS content. These findings implicate vascular iNOS, at least partly, in the acute hypotensive action of ethanol in female rats.
The effect of long term, low-dose tranexamic acid treatment on platelet dysfunction and haemoglobin levels in haemodialysis patients
Authors: Zupan Irena Preložnik , Salobir Barbara , Zupan Igor , Černelã Peter , Lavre Janez , Vujkovac Bojan , Šaboviã Mišo
Published: November 2005

Some previous studies suggest that activation of the fibrinolytic system may induce platelet dysfunction in haemodialysis patients. Accordingly, inhibition of fibrinolysis may improve platelet dysfunction, and speculatively increase haemoglobin levels. We tested this hypothesis. The study group comprised 22 patients (14 male, 8 female, median age 62), who had been on maintenance haemodialysis for more than one year. Patients were treated for three months with low-dose tranexamic acid (TXA), a potent anti-fibrinolytic agent. The dosages of erythropoietin and the haemodialysis procedure were not changed significantly during the study. We primarily followed platelet function (by in vitro closure time test) and haemoglobin values. Patients were divided into those with substantially prolonged (N=9) and those with slightly delayed or normal (N=13) in vitro closure time. Treatment with TXA resulted in a significant improvement of platelet function and increased levels of haemoglobin in the first group, and no changes in either platelet function or haemoglobin values in the second group. TXA in the dosage used was biologically active, since a significant decrease in plasminogen and D-dimer were found in both groups. No significant changes in other fibrinolytic parameters or von Willebrand factor were found. No complications in terms of arterial or venous thrombosis were observed. Our pilot study suggests that long term, low-dose TXA treatment of haemodialysis patients with substantially prolonged in vitro closure time results in a significant improvement of platelet dysfunction and a significant increase in haemoglobin values. These new, promising results merit further investigation in larger studies.
Chorioamnionitis is associated with increased CD40L expression on cord blood platelets
Authors: Sitaru Ana-Gabriela , Speer Christian P. , Holzhauer Susanne , Obergfell Achim , Walter Ulrich , Grossmann Ralf
Published: November 2005

Chorioamnionitis (CA) is a severe infection responsible not only for premature birth but also for many severe neonatal diseases. The aim of the present study was to investigate the expression of CD40L and P-selectin on platelets and the plasma levels of their soluble forms in the umbilical cord blood in infants with documented chorioamnionitis. Umbilical cord blood samples were obtained from 10 healthy term newborns,10 noninfected preterm infants, 10 preterm infants with premature rupture of membranes and 9 preterm infants with clinical and histological CA. The expression of CD40L and P-selectin on platelets was analyzed by flow cytometry. Soluble P-selectin (sCD62P), soluble CD40L (sCD40L) and interleukine-6 (IL-6) were measured in plasma by ELISA assays. Neonates with CA had significantly higher percentages of platelets expressing CD40L in basal conditions (5.3 ± 2.9% vs. 1.6 ± 0.7% in non- infected preterm infants p < 0.05), while the percentages of Pselectin positive platelets were similar among all groups. In contrast, the level of sP-selectin was higher in infants with CA (222 ± 128 ng/ml vs. 104 ± 71 ng/ml in non-infected preterm infants, p < 0.05) but no differences were found in the levels of sCD40L. As expected, the levels of IL-6, a pro-inflammatory cytokine were significantly higher in samples obtained from preterm neonates whose mothers had also elevated inflammatory parameters. Our observations suggest that platelets are involved in the complex inflammatory pathogenesis of CA. Neither P-selectin expression on cord blood platelets nor plasma sP-selectin or sCD40L were suitable platelet markers in CA, whereas CD40L was significantly elevated in histologically proven CA.
Homocysteine rapidly increases matrix metalloproteinase-2 expression and activity in cultured human vascular smooth muscle cells
Authors: Doronzo Gabriella , Russo Isabella , Mattiello Luigi , Trovati Mariella , Anfossi Giovanni
Published: November 2005

In this study we aimed to test the hypothesis that in human vascular smooth muscle cells (VSMC) homocysteine influences synthesis and release of matrix metalloproteinase-2 (MMP-2), which is deeply involved in vascular remodeling and atherosclerotic plaque instabilization. Experiments were carried out in cultured human VSMC exposed to 50–500 μmol/l homocysteine after a 24-hour culture with MEM containing 0.1% BSA. Both in supernatants and cell lysates we evaluated MMP-2 activity (gelatin zimography), MMP-2 and TIMP-2 protein synthesis (Western immunoblotting). Homocysteine effects were investigated also after cell exposure to i) specific MEK inhibitor PD98059 (30 μmol/l) to evaluate the involvement of Mitogen-Activated Protein Kinase (MAPK) and ii) specific phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 (100 μmol/l) to evaluate the involvement of PI3-K pathway. Gelatin zimography evidenced that MMP-2 activity is increased both in conditioned media and in cell lysates starting from 8-hour incubation with 100 μmol/l homocysteine. Western blot analysis evidenced increased MMP-2 levels in both conditioned media and cell lysates. Cell exposure to PD98059 and LY294002 prevented homocysteine effects on MMP-2 synthesis. Homocysteine, at concentrations associated with increased risk of cardiovascular events, increases MMP-2 activity, synthesis and secretion in VSMC through a mechanism involving the activation of MAPK and PI3-K pathways. These data suggest that homocysteine is directly involved in mechanisms leading to remodelling and instabilization of atherosclerotic plaques.
Intermittent pneumatic compression and deep vein thrombosis prevention
Authors: Urbankova Jana , Quiroz Rene , Kucher Nils , Goldhaber Samuel Z.
Published: November 2005

Our objective was to overview the effectiveness of intermittent pneumatic compression (IPC) devices to prevent deep vein thrombosis (DVT) in postoperative patients, using meta-analysis methodology. We searched the Medline, metaRegister of Controlled Trials, and Cochrane database for studies published between 1970 and October 2004. Our inclusion criteria were: 1) randomized controlled trial of IPC versus no prophylaxis, 2) at least 20 patients per group, 3) at least one diagnostic DVT imaging test in all patients, and 4) clinical follow-up for at least the duration of hospitalization. A total of 2,270 patients were included in 15 eligible studies: 1,125 and 1,145 in the IPC and no prophylaxis group, respectively. The included studies formed a total of 16 treatment groups and were conducted in orthopedic (5), general surgical (4), oncologic (3), neurosurgical (3) and urologic (1) patient populations. In comparison to no prophylaxis, IPC devices reduced the risk of DVT by 60% (relative risk 0.40, 95% CI 0.29 – 0.56; p< 0.001). Contemporary randomized trials should be undertaken to test the utility of IPC in hospitalized medical patients as well as combined pharmacological plus IPC prophylaxis in both medical and surgical patients.
Continuous infusion of recombinant factor VIIa for surgery in patients with deficiency of factor VII
Authors: Tjønnfjord Geir E. , Wallensten Richard , Martinowitz Uri , Kenet Gili , Schulman Sam
Published: November 2005

The administration of recombinant activated factor VII (rFVIIa) by continuous infusion has provided a safe and convenient alternative to bolus injections in haemophiliacs with inhibitors, but it has only been reported in a single case with congenital factorVII (FVII) deficiency. The results of 12 consecutive surgical procedures in 7 patients with congenital FVII deficiency are reported here. rFVIIa was always given in continuous infusion, aiming at plasma FVII activity of 0.5 IU/mL. Treatment was given for 2 to 7 days with a mean total dose of 7.8 mg rFVIIa. Blood loss was as expected from the different types of procedures and the only thromboembolic complication was a superficial thrombophlebitis at the infusion site. This mode of substitution was therefore safe, effective and well tolerated.
Neutrophil P-selectin-glycoprotein-ligand-1 binding to platelet P-selectin enhances metalloproteinase 2 secretion and platelet-neutrophil aggregation
Authors: Abou-Saleh Haissam , Théorêt Jean-François , Yacoub Daniel , Merhi Yahye
Published: November 2005

Platelets and neutrophils constitute a high source of metalloproteinases (MMPs), and their interactions via P-selectin and Pselectin- glycoprotein-ligand-1 (PSGL-1) are involved in thrombosis, vascular remodelling, and restenosis. We investigated the impact of these interactions on platelet MMP-2 secretion and function in platelet and neutrophil aggregation. The secretion of MMP-2 from human platelets was significantly increased threefold after thrombin activation, and enhanced two-fold in the presence of neutrophils. Neutrophil supernatant had no effect on platelet MMP-2 secretion. While no MMP-2 was detected in the supernatant of neutrophils, a high amount of MMP-9 was released by neutrophils, and remained unchanged upon thrombin activation or in the presence of platelets. Platelet P-selectin, which increased significantly after activation, triggered platelet binding to neutrophils that was completely inhibited by P-selectin or PSGL-1 antagonists, and was reduced by 50% with a GPIIb/ IIIa antagonist. P-selectin or PSGL-1 antagonism abolished the enhanced secretion of platelet MMP-2 in the presence of neutrophils and reduced platelet-neutrophil aggregation. Platelet activation and binding to neutrophils enhance the secretion of platelet MMP-2 via an adhesive interaction between P-selectin and PSGL-1, which contribute to increase platelet-neutrophil aggregation.
Anti-thrombotic action of clopidogrel and PlA1/A2 polymorphism of β3 integrin in patients with coronary artery disease not being treated with aspirin
Authors: Dropinski Jerzy , Musial Jacek , Jakiela Bogdan , Wegrzyn Wojciech , Sanak Marek , Szczeklik Andrew
Published: November 2005

Individual variability in response to clopidogrel is known but its mechanism is poorly understood. We examined the relationship between glycoprotein IIIa polymorphism PlA1/A2 and anti-thrombotic actions of clopidogrel. Clopidogrel (75 mg/d; 2 weeks) was administered to 48 normolipemic patients with coronary artery disease. Bleeding time, thrombin generation at the site of microvascular injury, platelet function under high shear, using PFA-100 with ADP cartridge, and platelet surface activation markers (P-selectin and fibrinogen binding sites on GPIIb/IIIa complex detected by PAC-1 antibody), were studied both before and after clopidogrel treatment. Both unstimulated and low-dose (0.02 μM and 1 μM) in vitro ADP-stimulated platelets were examined. GP IIIa polymorphism was assessed by polymerase chain reaction and restriction fragment length polymorphism analysis. We identified 32 PlA1/A1 homozygotes, 15 PlA1/A2 heterozygotes and one PlA2/A2 homozygote. Clopidogrel significantly prolonged bleeding time in all subjects, but this effect was greater in PlA2 carriers (p<0.01). Furthermore, clopidogrel only depressed thrombin generation at the site of microvascular injury (p<0.01) in PlA2 patients and prolonged closure time measured in vitro by PFA-100 (p<0.05). At baseline spontaneous expression of PAC-1 and P-selectin was higher in PlA2 subjects as compared to PlA1 homozygotes (p<0.05 for both antigens). Clopidogrel lowered the expression of both markers affecting more PlA2 carriers, so that the difference in binding PAC-1 antibody between platelets from PlA1 and PlA2 carriers disappeared, while the difference in P-selectin expression slightly diminished. Anti-thrombotic effects of clopidogrel are more pronounced in CAD patients carrying the PlA2 allele than in PlA1 homozygotes.
Platelet integrin α2 I-domain specific antibodies produced via domain specific DNA vaccination combined with variable gene phage display
Authors: Hughes Darren L. , Stafford Prachi , Hamaia Samir W. , Schoolmeester Anne , Deckmyn Hans , Farndale Richard W. , Ouwehand Willem H. , Harmer Ian J. , Watkins Nicholas A.
Published: November 2005

Antibodies are a powerful tool for structure/function studies of platelet proteins. However, classic immunisation frequently elicits antibody responses against domains of minor functional interest. Robust strategies to generate antibodies against defined domains would be of significant interest in post-genome research. In this study, we report a new strategy using a combination of DNA vaccination and V gene phage display that allows the rapid generation of domain specific single-chain Fv antibodies (scFvs).This system was validated using the I-domain of α2 integrin as a model. The α2β1 integrin, which is expressed on many cell types, is the dominant collagen attachment receptor on platelets, functioning in close interplay with the collagen signalling receptor glycoproteinVI. A novel set of I-domain specific antibodies was obtained by a DNA vaccination/V gene repertoire cloning approach. Mice were first immunized with a DNA vaccine in which the α2 I-domain is expressed as a fusion protein with fragment C of tetanus toxoid (FrC-TT).Then the heavy and kappa light chain variable gene repertoires were rescued from immune splenocytes using antibody phage display. A total of four α2 I-domain specific scFvs were isolated by selection on recombinant I-domain or native platelet α2β1 integrin. Characterisation of the scFvs indicated that they recognised distinct epitopes that had profound differences in accessibility between native and recombinant I-domain. Our data suggest DNA immunisation and phage display represent versatile alternatives to protein immunisation and hybridoma-fusion techniques for the isolation of recombinant antibody reagents. This approach will be particularly useful for the generation of domain or splicevariant specific antibodies that recognise native protein.