bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intranasal sufentanil for cancer-associated breakthrough pain
Authors: Good P , Jackson K , Brumley D , Ashby M 
Published: January 2009

The objective of this study was to demonstrate the efficacy, safety and patient acceptability of the use of intranasal sufentanil for cancer-associated breakthrough pain. This was a prospective, open label, observational study of patients in three inpatient palliative care units in Australia. Patients on opioids with cancer-associated breakthrough pain and clinical evidence of opioid responsiveness to their breakthrough pain were given intranasal (IN) Sufentanil via a GO Medical™ patient controlled IN analgesia device. The main outcome measures were pain scores, need to revert to previous breakthrough opioid after 30 min, number of patients who chose to continue using IN sufentanil, and adverse effects. There were 64 episodes of use of IN sufentanil for breakthrough pain in 30 patients. There was a significant reduction in pain scores at 15 ( P < 0.0001) and 30 min ( P < 0.0001). In only 4/64 (6%) episodes of breakthrough pain did the participants choose to revert to their prestudy breakthrough medication. Twenty-three patients (77%) rated IN sufentanil as better than their prestudy breakthrough medication. The incidence of adverse effects was low and most were mild. Our study showed that IN sufentanil can provide relatively rapid onset, intense but relatively short lasting analgesia and in the palliative care setting it is an effective, practical, and safe option for breakthrough pain.
Prevalence of hypoechoic carotid plaques in coronary artery disease: relationship with coexistent peripheral arterial disease and leukocyte number
Authors: Brevetti Gregorio , Sirico Giusy , Giugliano Giuseppe , Lanero Simona , De Maio Julieta Isabel , Luciano Rossella , Laurenzano Eugenio , Chiariello Massimo 
Published: January 2009

Abstract In coronary artery disease (CAD), a concomitant peripheral arterial disease (PAD) entails a more severe coronary atherosclerosis. We hypothesized that the severity of carotid artery disease is greater in CAD+PAD than in CAD alone. In 90 CAD and 79 CAD+PAD patients, carotid plaque echolucency was measured by gray-scale median (GSM), and the degree of carotid stenosis by routine Doppler criteria. Plaques were absent in 20 (22.2%) CAD and 8 (10.1%) CAD+PAD patients ( p = 0.035), while the prevalence of carotid stenosis ≥ 50% was 16.7% and 25.3%, respectively ( p = 0.166). The GSM score was 45.1 [21.7–67.7] in CAD+PAD vs 60.1 [44.9–83.1] in CAD alone ( p < 0.001). Consistently, hypoechoic plaques (GSM < 25th percentile) were more common in CAD+PAD than in CAD patients (38.0% vs 11.4%, p < 0.001). On multivariate analysis, CAD+PAD was the only variable significantly associated with hypoechoic plaques (OR = 4.16, 95% CI 1.68–10.28). However, when the leukocyte count was added to the model, it showed the strongest association with hypoechoic plaques (OR = 6.70, 95% CI 2.13–21.10). In conclusion, compared with CAD alone patients, those with concomitant PAD showed a greater prevalence of plaques with characteristics of instability. Thus, our data suggest that in CAD+PAD, evaluation of carotid plaque echogenicity could contribute to improve clinical decision-making and differentiate treatments for individual patients.
Multidetector computed tomographic angiography of aberrant subclavian arteries
Authors: Türkvatan Aysel , Büyükbayraktar Fatma Gül , Ölçer Tülay , Cumhur Turhan 
Published: January 2009

Abstract The purpose of this study was to evaluate the utility of 16-slice multidetector computed tomographic (MDCT) angiography for identifying anatomic features of aberrant subclavian arteries. Seventeen patients with aberrant subclavian arteries were assessed by MDCT angiography. The aortic arch position, the presence of a Kommerell’s diverticulum, aneurysm, vascular compression of trachea and oesophagus and associated cardiovascular abnormalities were evaluated. MDCT findings were confirmed by surgery in eight patients but in the other nine patients no further evaluation or management was warranted as the aberrant subclavian artery had no significant clinical consequence. Eleven patients had an aberrant right subclavian artery arising from the left aortic arch and six patients had an aberrant left subclavian artery arising from the right aortic arch. Kommerell’s diverticulum was identified in three patients with an aberrant right subclavian artery and in five patients with an aberrant left subclavian artery. In two patients it was aneurysmal. Oesophageal compression was detected in eight patients, and tracheal compression was identified in only one paediatric patient. An aberrant subclavian artery was associated with complex congenital heart disease in one patient, intracardiac defects in two patients, aortic coarctation in two patients, patent ductus arteriosus in two patients and an aberrant vertebral artery in one patient. In conclusion, MDCT angiography is superior to digital subtraction angiography for the assessment of aberrant subclavian arteries since digital subtraction angiography has only a poor ability to visualize adjacent structures completely and is invasive in nature. MDCT angiography or magnetic resonance angiography are the current standard in the initial evaluation of thoracic vascular anomalies.
Lipid goal achievement and trends in lipid-lowering therapy in veterans undergoing carotid endarterectomy
Authors: Fitzgerald Tamara N , Popp Cathy , Dardik Alan , Federman Daniel G 
Published: January 2009

Abstract Secondary prevention of cardiovascular disease after carotid endarterectomy should include management of low-density lipoprotein (LDL) levels, but increased LDL levels are undertreated in these patients. We examined trends in statin use and LDL goal achievement in veterans undergoing carotid endarterectomy (CEA), a medically high-risk group with high rates of cardiovascular morbidity and mortality. The records of all CEA performed between 1995 and 2005 in the Connecticut Veterans’ Affairs (VA) hospital were reviewed. Kaplan-Meier analysis was used to analyze long-term outcomes. ANOVA was used for comparisons between groups. A total of 309 CEA procedures were performed in 298 patients. The mean follow-up was 4.1 years. Statin use increased over time (12% in 1995, 84% in 2005) and mean LDL levels decreased (105 mg/dl in 1997, 90 mg/dl in 2007). The number of patients achieving LDL goals of 100 mg/dl or 70 mg/dl increased. Mean HDL levels decreased (53 mg/dl in 1997 and 38 mg/dl in 2007). Patients with three or more comorbid medical conditions were more likely to achieve LDL goals. At 12 years, freedom from stroke was 91%, freedom from myocardial infarction was 46% and survival was 12%. In conclusion, over the last decade, among patients who have undergone CEA, statin use has increased and LDL levels have improved.
Early identification and management of chronic kidney disease in adults in primary and secondary care: a commentary on NICE Guideline No 73, Sept 2008
Authors: Andrews Peter A 
Published: January 2009

Chronic kidney disease (CKD) is common, but more than 30% of people with CKD are referred late, leading to increased morbidity and mortality. An updated classification of CKD, using estimated glomerular filtration rate (eGFR) allows the severity of CKD to be determined and when it is appropriate to refer to a consultant nephrologist. New approaches to the measurement of protein excretion are stressed with particular reference to using urine albumin:creatinine ratio or urine protein:creatinine ratio. Annual measurement of serum creatinine in at-risk patients is clearly outlined as are the indications for renal ultrasound examination. Two algorithms for the management of newly detected abnormal eGFR and for the management of CKD, Stages 3—5, are not in the NICE Guideline No 73 document but reflect the author's clinical experience of working in this area, with the aim of simplifying these two important topics. The safe use of angiotensin-converting-enzyme (ACE) inhibitors and angiotensin blocking agents in the everyday clinical work place is outlined. The management of CKD due to diabetic nephropathy and hypertension is an important part of diabetes management and this review of NICE Guideline No 73 on the early identification and management of CKD in adults in both primary and secondary care settings will further enable the better care of type 1 and type 2 diabetic subjects with renal impairment. Br J Diabetes Vasc Dis 2008; 8: 257—262
Genetic variants in the candidate genes of the apoptosis pathway and susceptibility to chronic myeloid leukemia
Authors: Kim Dong Hwan (Dennis) , Xu Wei , Ma Clement , Liu Xiangdong , Siminovitch Katherine , Messner Hans A. , Lipton Jeffrey H. 
Published: January 2009

AbstractChronic myeloid leukemia (CML) is a clonal myeloproliferative disorder, characterized by the presence of BCR/ABL fusion gene. It is unclear which cellular events drive BCR/ABL gene translocation or initiate leukemogenesis in CML. Bcl-2 promotes survival of hematopoietic stem cells. Accordingly, apoptosis-related pathway may involve in the leukemogenesis of CML. In the current study, we evaluated 80 single nucleotide polymorphism (SNP) markers involved in the pathways of apoptosis (n = 30), angiogenesis (n = 7), myeloid cell growth (n = 14), xenobiotic metabolism (n = 13), WT1 signaling (n = 7), interferon signaling (n = 4), and others (n = 5) in 170 CML patients and 182 healthy controls. In a single-marker analysis, the following SNPs were identified including VEGFA, BCL2, CASP7, JAK3, CSF3, and HOCT1. In the multivariate logistic model with these SNPs and covariates, only BCL2 (rs1801018) was significantly associated with the susceptibility to CML (P = .05; odds ratio [OR] 2.16 [1.00-4.68]). In haplotype analyses, haplotype block of BCL2 consistently showed significant association with the susceptibility to CML. Risk allele analysis showed that a greater number of risk alleles from BCL2 SNP correlated to increasing risk of CML (overall P = .1, OR 1.84 [1.06-3.22] for 3-4 risk alleles vs 0-1 risk alleles). The current study indicated that BCL2 SNP seemed to be associated with increasing susceptibility to CML.
Endogenous EPCR/aPC-PAR1 signaling prevents inflammation-induced vascular leakage and lethality
Authors: Niessen Frank , Furlan-Freguia Christian , Fernández José A. , Mosnier Laurent O. , Castellino Francis J. , Weiler Hartmut , Rosen Hugh , Griffin John H. , Ruf Wolfram 
Published: January 2009

AbstractProtease activated receptor 1 (PAR1) signaling can play opposing roles in sepsis, either promoting dendritic cell (DC)–dependent coagulation and inflammation or reducing sepsis lethality due to activated protein C (aPC) therapy. To further define this PAR1 paradox, we focused on the vascular effects of PAR1 signaling. Pharmacological perturbations of the intravascular coagulant balance were combined with genetic mouse models to dissect the roles of endogenously generated thrombin and aPC during escalating systemic inflammation. Acute blockade of the aPC pathway with a potent inhibitory antibody revealed that thrombin-PAR1 signaling increases inflammation-induced vascular hyperpermeability. Conversely, aPC-PAR1 signaling and the endothelial cell PC receptor (EPCR) prevented vascular leakage, and pharmacologic or genetic blockade of this pathway sensitized mice to LPS-induced lethality. Signaling-selective aPC variants rescued mice with defective PC activation from vascular leakage and lethality. Defects in the aPC pathway were fully compensated by sphingosine 1 phosphate receptor 3 (S1P3) deficiency or by selective agonists of the S1P receptor 1 (S1P1), indicating that PAR1 signaling contributes to setting the tone for the vascular S1P1/S1P3 balance. Thus, the activating proteases and selectivity in coupling to S1P receptor subtypes determine vascular PAR1 signaling specificity in systemic inflammatory response syndromes in vivo.
Lentivirus-mediated transgene delivery to the hippocampus reveals sub-field specific differences in expression
Authors: van Hooijdonk Lenneke WA , Ichwan Muhammad , Dijkmans Thomas F , Schouten Theo G , de Backer Marijke WA , Adan Roger AH , Verbeek Fons J , Vreugdenhil Erno , Fitzsimons Carlos P 
Published: January 2009

AbstractBackgroundIn the adult hippocampus, the granule cell layer of the dentate gyrus is a heterogeneous structure formed by neurons of different ages, morphologies and electrophysiological properties. Retroviral vectors have been extensively used to transduce cells of the granule cell layer and study their inherent properties in an intact brain environment. In addition, lentivirus-based vectors have been used to deliver transgenes to replicative and non-replicative cells as well, such as post mitotic neurons of the CNS. However, only few studies have been dedicated to address the applicability of these widespread used vectors to hippocampal cells in vivo. Therefore, the aim of this study was to extensively characterize the cell types that are effectively transduced in vivo by VSVg-pseudotyped lentivirus-based vectors in the hippocampus dentate gyrus.ResultsIn the present study we used Vesicular Stomatitis Virus G glycoprotein-pseudotyped lentivirual vectors to express EGFP from three different promoters in the mouse hippocampus. In contrast to lentiviral transduction of pyramidal cells in CA1, we identified sub-region specific differences in transgene expression in the granule cell layer of the dentate gyrus. Furthermore, we characterized the cell types transduced by these lentiviral vectors, showing that they target primarily neuronal progenitor cells and immature neurons present in the sub-granular zone and more immature layers of the granule cell layer.ConclusionOur observations suggest the existence of intrinsic differences in the permissiveness to lentiviral transduction among various hippocampal cell types. In particular, we show for the first time that mature neurons of the granule cell layer do not express lentivirus-delivered transgenes, despite successful expression in other hippocampal cell types. Therefore, amongst hippocampal granule cells, only adult-generated neurons are target for lentivirus-mediated transgene delivery. These properties make lentiviral vectors excellent systems for overexpression or knockdown of genes in neuronal progenitor cells, immature neurons and adult-generated neurons of the mouse hippocampus in vivo.
Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease
Authors: Marsillach Judit , Camps Jordi , Ferré Natàlia , Beltran Raul , Rull Anna , Mackness Bharti , Mackness Michael , Joven Jorge 
Published: January 2009

Abstract

Background
Paraoxonase-1 (PON1) is an antioxidant enzyme synthesized by the liver. It protects against liver impairment and attenuates the production of the pro-inflammatory monocyte chemoattractant protein-1 (MCP-1). We investigated the relationships between hepatic PON1 and MCP-1 expression in rats with liver disease and explored the possible molecular mechanisms involved.

Methods
CCl4 was administered for up to 12 weeks to induce liver damage. Serum and hepatic levels of PON1 and MCP-1, their gene and protein expression, nuclear transcription factors, and histological and biochemical markers of liver impairment were measured.

Results
High levels of PON1 and MCP-1 expression were observed at 12th week in the hepatocytes surrounding the fibrous septa and inflammatory areas. CCl4-administered rats had an increased hepatic PON1 concentration that was related to decreased gene transcription and inhibited protein degradation. Decreased PON1 gene transcription was associated with PPARδ expression. These changes were accompanied by increased hepatic MCP-1 concentration and gene expression. There were significant direct relationships between hepatic PON1 and MCP-1 concentrations (P = 0.005) and between PON1 and the amount of activated stellate cells (P = 0.001).

Conclusion
Our results from this experimental model suggest a hepato-protective role for PON1 against inflammation, fibrosis and liver disease mediated by MCP-1.
Cured meat, vegetables, and bean-curd foods in relation to childhood acute leukemia risk: A population based case-control study
Authors: Liu Chen-yu , Hsu Yi-Hsiang , Wu Ming-Tsang , Pan Pi-Chen , Ho Chi-Kung , Su Li , Xu Xin , Li Yi , Christiani David C ,   the Kaohsiung Leukemia Research Group
Published: January 2009

AbstractBackgroundConsumption of cured/smoked meat and fish leads to the formation of carcinogenicN-nitroso compounds in the acidic stomach. This study investigated whether consumed cured/smoked meat and fish, the major dietary resource for exposure to nitrites and nitrosamines, is associated with childhood acute leukemia.MethodsA population-based case-control study of Han Chinese between 2 and 20 years old was conducted in southern Taiwan. 145 acute leukemia cases and 370 age- and sex-matched controls were recruited between 1997 and 2005. Dietary data were obtained from a questionnaire. Multiple logistic regression models were used in data analyses.ResultsConsumption of cured/smoked meat and fish more than once a week was associated with an increased risk of acute leukemia (OR = 1.74; 95% CI: 1.15–2.64). Conversely, higher intake of vegetables (OR = 0.55; 95% CI: 0.37–0.83) and bean-curd (OR = 0.55; 95% CI: 0.34–0.89) was associated with a reduced risk. No statistically significant association was observed between leukemia risk and the consumption of pickled vegetables, fruits, and tea.ConclusionDietary exposure to cured/smoked meat and fish may be associated with leukemia risk through their contents of nitrites and nitrosamines among children and adolescents, and intake of vegetables and soy-bean curd may be protective.
Luteal blood flow and luteal function
Authors: Takasaki Akihisa , Tamura Hiroshi , Taniguchi Ken , Asada Hiromi , Taketani Toshiaki , Matsuoka Aki , Yamagata Yoshiaki , Shimamura Katsunori , Morioka Hitoshi , Sugino Norihiro 
Published: January 2009

Abstract

Background
Blood flow in the corpus luteum (CL) is associated with luteal function. The present study was undertaken to investigate whether luteal function can be improved by increasing CL blood flow in women with luteal phase defect (LFD).

Methods
Blood flow impedance in the CL was measured by transvaginal color-pulsed-Doppler-ultrasonography and was expressed as a resistance index (RI). The patients with both LFD [serum progesterone (P) concentrations < 10 ng/ml during mid-luteal phase] and high CL-RI (≥ 0.51) were given vitamin-E (600 mg/day, n = 18), L-arginine (6 g/day, n = 14) as a potential nitric oxide donor, melatonin (3 mg/day, n = 13) as an antioxidant, or HCG (2,000 IU/day, n = 10) during the subsequent menstrual cycle.

Results
In the control group (n = 11), who received no medication to increase CL blood flow, only one patient (9%) improved in CL-RI and 2 patients (18%) improved in serum P. Vitamin-E improved CL-RI in 15 patients (83%) and improved serum P in 12 patients (67%). L-arginine improved CL-RI in all the patients (100%) and improved serum P in 10 patients (71%). HCG improved CL-RI in all the patients (100%) and improved serum P in 9 patients (90%). Melatonin had no significant effect.

Conclusion
Vitamin-E or L-arginine treatment improved luteal function by decreasing CL blood flow impedance. CL blood flow is a critical factor for luteal function.
Egr-1 inhibits the expression of extracellular matrix genes in chondrocytes by TNFα-induced MEK/ERK signalling
Authors: Rockel Jason S , Bernier Suzanne M , Leask Andrew 
Published: January 2009

Abstract
Introduction
TNFα is increased in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis. TNFα activates mitogen-activated kinase kinase (MEK)/extracellular regulated kinase (ERK) in chondrocytes; however, the overall functional relevance of MEK/ERK to TNFα-regulated gene expression in chondrocytes is unknown.

Methods
Chondrocytes were treated with TNFα with or without the MEK1/2 inhibitor U0126 for 24 hours. Microarray analysis and real-time PCR analyses were used to identify genes regulated by TNFα in a MEK1/2-dependent fashion. Promoter/reporter, immunoblot, and electrophoretic mobility shift assays were used to identify transcription factors whose activity in response to TNFα was MEK1/2 dependent. Decoy oligodeoxynucleotides bearing consensus transcription factor binding sites were introduced into chondrocytes to determine the functionality of our results.

Results
Approximately 20% of the genes regulated by TNFα in chondrocytes were sensitive to U0126. Transcript regulation of the cartilage-selective matrix genes Col2a1, Agc1 and Hapln1, and of the matrix metalloproteinase genes Mmp-12 and Mmp-9, were U0126 sensitive – whereas regulation of the inflammatory gene macrophage Csf-1 was U0126 insensitive. TNFα-induced regulation of Sox9 and NFκB activity was also U0126 insensitive. Conversely, TNFα-increased early growth response 1 (Egr-1) DNA binding was U0126 sensitive. Transfection of chondrocytes with cognate Egr-1 oligodeoxynucleotides attenuated the ability of TNFα to suppress Col2a1, Agc1 or Hapln1 mRNA expression.

Conclusions
Our results suggest that MEK/ERK and Egr1 are required for TNFα-regulated catabolic and anabolic genes of the cartilage extracellular matrix, and hence may represent potential targets for drug intervention in osteoarthritis or rheumatoid arthritis.
Macrophage fusion, giant cell formation, and the foreign body response require matrix metalloproteinase 9
Authors: MacLauchlan Susan , Skokos Eleni A , Meznarich Norman , Zhu Dana H , Raoof Sana , Shipley J Michael , Senior Robert M , Bornstein Paul , Kyriakides Themis R 
Published: January 2009

AbstractMacrophages undergo fusion to form multinucleated giant cells in several pathologic conditions, including the foreign body response (FBR). We detected high levels of matrix metalloproteinase (MMP)-9 during macrophage fusion in vitro and in foreign body giant cells (FBGCs) in vivo. Wild-type (WT) bone marrow-derived macrophages were induced to fuse with IL-4 in the presence of MMP-9 function-blocking antibodies and displayed reduced fusion. A similar defect, characterized by delayed shape change and abnormal morphology, was observed in MMP-9 null macrophages. Analysis of the FBR in MMP-9 null mice was then pursued to evaluate the significance of these findings. Specifically, mixed cellulose ester disks and polyvinyl alcohol sponges were implanted s.c. in MMP-9 null and WT mice and excised 2–4 weeks later. Histochemical and immunohistochemical analyses indicated equal macrophage recruitment between MMP-9 null and WT mice, but FBGC formation was compromised in the former. In addition, MMP-9 null mice displayed abnormalities in extracellular matrix assembly and angiogenesis. Consistent with a requirement for MMP-9 in fusion, we also observed reduced MMP-9 levels in MCP-1 null macrophages, previously shown to be defective in FBGC formation. Collectively, our studies show abnormalities in MMP-9 null mice during the FBR and suggest a role for MMP-9 in macrophage fusion.