bluuebunny/crossref_metadata_2025 huggingface dataset:
Appropriateness of diagnostic strategies for evaluating suspected venous thromboembolism
Authors: Arnason Thomas , Wells Philip , Forster Alan
Published: June 2007

It was the objective of this study to determine the proportion of patients who undergo an appropriate diagnostic work-up following a D-dimer test performed to evaluate suspected pulmonary embolism (PE) or deep vein thrombosis (DVT). We performed a retrospective cohort study at a tertiary care hospital. We included patients if they underwent D-dimer testing between 2002 and 2005, if the D-dimer was performed for evaluation of VTE, and if the D-dimer test was successful. We classified: the patients’ clinical probability of DVT or PE according to theWells models,the imaging results,and the appropriateness of the testing algorithm. Of 1,000 randomly selected patients, 863 met our study criteria. Seven hundred nineteen patients (83%) had testing during an emergency department visit, while 144 were tested as inpatients (17%). Physicians performed the D-dimer test to evaluate DVT and PE in 238 (28%) and 625 (72%) patients, respectively. Overall, the testing strategy was appropriate in 69% (95% confidence interval [CI]: 66%–72%) of cases. The testing strategy was more likely to be appropriate for emergency department versus inpatients (75% vs. 39%, p < 0.05) and for DVT versus PE patients (84% vs. 63%, p < 0.05). Of all inappropriately tested patients, under-utilization of diagnostic imaging was more common than over-utilization (90% vs. 10%, p < 0.05). VTE was confirmed in 37 of 138 ‘DVT patients’ and 35 of 625 ‘PE patients’ (16% [95% CI: 11%–21%] and 6% [95% CI: 4%–8%], respectively). In conclusion, physicians often fail to use diagnostic testing strategies for VTE correctly following a D-dimer test.
Accuracy of compression ultrasound in screening for deep venous thrombosis in acutely ill medical patients
Authors: Davidson Bruce , Wisniewska Joanna , Malek Grzegorz , Kober Jaroslaw , Kuca Pawel , Burakowska Barbara , Oniszh Karina , Gallus Alexander , Lensing Anthonie , Tomkowski Witold
Published: June 2007

The value of vein ultrasonography for diagnosis of symptomatic deep vein thrombosis (DVT) is widely accepted. We are unaware of published data comparing ultrasonography with the “gold standard” of venography for DVT diagnosis in asymptomatic persons in the patient group of acutely ill medical patients. It was the objective of this study to evaluate sensitivity and specificity of compression ultrasound (CUS) examinations in the diagnosis of proximal and distal DVT in acutely ill medical patients [with congestive heart failure (NYHA class III and IV), exacerbations of respiratory disease, infectious disease, and inflammatory diseases] considered to be at moderate risk of venous thromboembolism (VTE). CUS examination was performed prior to ascending venography on day 6–15 of the hospital stay. Both investigations were done on the same day, each interpreted without knowledge of the other’s result. Proximal and calf veins were separately evaluated. Technically satisfactory venography was obtained in 160 patients. In 12 of 160 patients (7.5%, 95% CI = [4.0%-12.7%]), venography confirmed the presence of DVT, all of which was asymptomatic. Proximal DVT was detected in five patients (3.1%, 95% CI = [1.0%- 7.1%]) and distal DVT in seven patients (4.4%, 95% CI = [1.8% – 8.8%]). CUS of proximal veins was technically satisfactory in all 160 patients and CUS of distal veins in 150 patients. In three of five patients with veongraphically proven proximal DVT, the diagnosis was confirmed by CUS (sensitivity 60%, 95%CI = [23%-88%]). In one patient, the CUS was false positive (specificity 99.4%, 95%CI = [96%-99%]). Positive and negative predictive values (PPV and NPV) of CUS in the diagnosis of proximal DVT were 75% (95%CI = [30%-95%]) and 98% (95% CI = [95%-99%]), respectively. In two of seven patients with venographically proven calf DVT, the diagnosis was confirmed by CUS (sensitivity 28.6%, 95%CI = [8%-64%]) and in two patients, CUS was false positive (specificity 98.6, 95%CI = [95%-99%]). PPV and NPV of CUS in diagnosis of distal DVT were 50% (95%CI = [15–85%]) and 96% (95% CI = [92%-98%]), respectively. In conclusion, CUS underestimates the incidence of proximal and distal DVT compared to contrast venography in acutely ill medical patients without thrombosis symptoms.
Regulation by DDAH/ADMA pathway of lipopolysaccharideinduced tissue factor expression in endothelial cells
Authors: Jia Su-Jie , Song Kui , Wang Guang-Ping , Li Yuan-Jian , Xin Hong-Ya , Jiang De-Jian , Chen Fang-Ping
Published: June 2007

Previous studies have shown the regulatory effect of nitric oxide (NO) on endotoxin-induced tissue factor (TF) in endothelial cells. Asymmetric dimethylarginine (ADMA), a major endogenous NO synthase (NOS) inhibitor, could inhibit NO production in vivo and in vitro. ADMA and its major hydrolase dimethylarginine dimethylaminohydrolase (DDAH) have recently been thought of as a novel regulatory system of endogenous NO production. The aim of the present study was to determine whether the DDAH/ADMA pathway is involved in the effect of lipopolysaccharide (LPS) on TF expression in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were treated with LPS (1 µ g/ml) to induce TF expression. Exogenous ADMA significantly enhanced the increase in both TF mRNA level and activity induced by LPS, whereas L-arginine, the NOS substrate, markedly attenuated the LPS-induced TF increment. LPS markedly increased the level of ADMA in cultured medium and decreased DDAH activity in endothelial cells, and overexpression of DDAH2 could significantly suppress LPS-induced TF increment in endothelial cells. LPS could increase intracellular reactive oxygen species (ROS) production and activate nuclear factor-κ B, which were enhanced by exogenous ADMA and attenuated by either L-arginine or overexpression of DDAH2. Therefore, our present results for the first time suggest that the DDAH/ADMA pathway can regulate LPS-inducedTF expression via ROS-nuclear factor- κ B-dependent pathway in endothelial cells.
Multicentre ISI assignment and calibration of the INR measuring range of a new point-of-care system designed for home monitoring of oral anticoagulation therapy
Authors: Leichsenring Ingrid , Plesch Winfried , Unkrig Volker , Kitchen Steve , Kitchen Dianne , Maclean Rhona , Dikkeschei Bert , van den Besselaar Anton
Published: June 2007

The new CoaguChek XS system is designed for use in patient selftesting. It is the successor of the current CoaguChek S system. The detection principle is based on the amperometric measurement of the thrombin activity initiated by starting the coagulation cascade using a human recombinant thromboplastin. This study was performed to assign the International SEnsitivity Index (ISI) to the new test according to the WHO guidelines for thromboplastins and plasmas used to control anticoagulant therapy, and to establish the measuring range of the new system. At four study sites a total of 90 samples of normal donors and 291 samples of warfarin-, phenprocoumon- or acenocoumarol-treated patients were included in the study.The ISI value of the new test was assigned against the human recombinant reference thromboplastin rTF/95 at each site using the samples from stabilized patients in the International Normalized Ratio (INR) range between 1.5 and 4.5 only. The new point-of-care system’s measuring range between 0.8 and 8 INR was calibrated against the mean INR of rTF/95 and AD149 using polynomial regression. ISIs were (CV of the slope): Site 1: ISI 0.99 (1.1%); Site 2: ISI 1.02 (2.0%); Site 3: ISI 1.03 (1.1%); Site 4: ISI 1.00 (1.4%). All regression lines calculated from patient-only data pass through the normal donor data points.All CVs of the slopes of the orthogonal regression lines are well below 3%,thus fulfilling the requirements of the WHO guidelines. The mean ISI for the new CoaguChek XS PT Test is 1.01.
Vasa vasorum and atherosclerosis – Quid novi?
Authors: Kampschulte Marian , Buch Thomas , Bohle Rainer , Langheinrich Alexander
Published: June 2007

The role of vasa vasorum (VV) in atherosclerosis is hotly debated, and new experimental techniques have recently opened an opportunity to take a fresh look at this important topic. Although the proliferation of VV due to atherogenic stimuli is controversial, experimental and clinical evidence strongly suggest the potential of VV in vascular proliferative disorders. In the past, paradigms of atherosclerosis and restenosis have excluded the adventitia and VV in the artery wall due, in part, to a lack of i) appropriate animal models featuring adventitial VV neovascularization, ii) imaging technologies to quantitate adventitial VV and plaque neovascularization and iii) its consequences, concerning information on detectable plaque substrate in vulnerable lesions. VV proliferation is associated with increasing plaque burden and is linked to cellular processes which are critical during the development of atherosclerotic plaques such as inflammation, plaque perfusion and concomitant intraplaque hemorrhage – but the regulation and induction of VV based on pathological settings are poorly understood. This review discusses the current scientific status and its controversies and identifies open research questions.
Cellular and molecular mechanisms of hypoxia-inducible factor driven vascular remodeling
Authors: Weissmann Norbert , Grimminger Friedrich , Seeger Werner , Rose Frank , Hänze Jörg
Published: June 2007

Hypoxia-inducible factor (HIF) is an oxygen-dependent transcription factor that activates a diverse set of target genes, the products of which are involved in adaptive processes to hypoxia. Employing genetic manipulation of HIF expression, in-vivo and cellular studies have focused on HIF as a crucial factor affecting hypoxia-induced vascular remodeling.Vascular remodeling comprises processes which establish and improve blood vessel supply such as vasculogenesis, angiogenesis and arteriogenesis. These processes are observed during ontogenesis, tumor progression, ischemic disease or physical training. Furthermore, under hypoxic conditions, a pulmonary-specific type of vascular remodeling called pulmonary arterial remodeling occurs that is characterized by thickening of the vessel wall with a concomitant reduction in the vessel lumen area, thereby limiting blood flow.This response results in pulmonary hypertension with right ventricular hypertrophy, a lethal disease. In this review, we summarize and discuss mechanisms by which HIF interferes with the different vascular remodeling processes.
Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and venous thrombosis
Authors: Tsantes Argirios , Bagos Pantelis , Rapti Evdoxia , Mantzios Georgios , Kapsimali Violeta , Travlou Anthi , Nikolopoulos Georgios
Published: June 2007

The effect of the 675 insertion/deletion (4G/5G) polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene on the risk of venous thromboembolism (VTE) remains controversial. In this study, we performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out up until September 2006. A total of 22 articles were included in the analysis that was performed using random effects models. Eighteen papers, concerning patients without another known risk factor, comprised 2,644 cases and 3,739 controls. The alleles contrast (4G vs. 5G allele) yielded a statistically significant odds ratio (OR) of 1.153 (95% confidence interval [CI]: 1.068–1.246). In a sub-analysis of five studies that included 256 cases with another genetic risk factor and 147 controls, the combined per-allele OR was still significant (OR:1.833,95% CI:1.325–2.536). On the contrary, the analysis of five studies regarding cases with a non-genetic risk factor for VTE (antiphospholipid antibody syndrome, Behcet disease) provided insignificant results in all aspects. There was no evidence for heterogeneity and publication bias in all analyses. Based on our findings, the 4G allele appears to increase the risk of venous thrombosis, particularly in subjects with other genetic thrombophilic defects. Recommendation for detection of this polymorphism in evaluating thrombophilia in such patients might be considered.
Transmembrane chemokines: Versatile ‘special agents’ in vascular inflammation
Authors: Weber Christian , Ludwig Andreas
Published: June 2007

Within the chemokine family of small chemotactic polypeptides CX3CL1 (fractalkine) and CXCL16 (SR-PSOX) are exceptional in that they are synthesized as transmembrane molecules and can be cleaved from the cell surface to produce a soluble chemoattractant. As transmembrane molecules on the surface of endothelial cells, CX3CL1 and CXCL16 can interact with their receptors CX3CR1 and CXCR6, respectively, which are expressed on leukocyte subtypes.This interaction leads to cell-cell adhesion that is resistant to shear forces. Transmembrane CX3CL1 and CXCL16 are constitutively shed from the cell surface by the activity of a disintegrin and metalloproteinase (ADAM) 10, and cleavage can be rapidly enhanced by activation of the closely related enzyme ADAM17. This cleavage leads to the downregulation of adhesive properties and may even result in the detachment of bound cells. Functionally, both chemokines appear to exert homeostatic and inflammatory activities. Basal expression of CX3CL1 or CXCL16 may be relevant for positioning and survival of tissue-homing leukocytes. Upregulated expression is found under inflammatory conditions such as atherosclerosis where CXCL16 may have a dual function by acting as an adhesion molecule and by promoting uptake of oxidized LDL as a scavenger receptor. Accumulating evidence from knockout mice and genetic polymorphisms in humans points towards a differential contribution of CX3CL1 and CXCL16 in atherosclerosis, where shedding may serve to further regulate their biological functions. Small molecules that block either the receptors or the shedding enzymes of transmembrane chemokines need to be tested in animal models of vascular inflammation.
The specific role of chemokines in atherosclerosis
Authors: Braunersreuther Vincent , Mach François , Steffens Sabine
Published: June 2007

Atherosclerosis is a chronic inflammatory disease that represents the primary cause of heart disease and stroke.The recruitment of inflammatory cells in the intima is an essential step in the development and progression of atherosclerosis.This process is triggered by local production of chemokines and chemokine receptors from activated endothelial cells and inflammatory cells. Various members of the CC chemokine family (e.g. MCP- 1/CCL2) as well as CXC family (e.g. IL-8/CCL8, IP-10/CXCL10, SDF-1/CXCL12) and, more recently, fractalkine/CX3CL1 have been implicated in atherosclerosis development. Latest findings in animal models suggest that blocking chemokine/chemokine receptor interactions may serve as a suitable approach to treat atherosclerosis. Likewise, chemokine antagonists that inhibit leukocyte recruitment could particularly be interesting to treat inflammation in response to myocardial infarction, the major consequence of atherosclerosis.
Nuclear factor of activated T cells and early growth response-1 cooperate to mediate tissue factor gene induction by vascular endothelial growth factor in endothelial cells
Authors: Schabbauer Gernot , Schweighofer Bernhard , Mechtcheriakova Diana , Lucerna Markus , Binder Bernd , Hofer Erhard
Published: June 2007

Based on the finding that tissue factor belongs to a group of genes upregulated in endothelial cells by VEGF, but not by EGF, we investigated signals selectively triggered by VEGF. Whereas the transcription factor early growth response (EGR)-1, which has previously been shown by us to be essentially involved in tissue factor gene regulation, was similarly induced by both factors, one major difference between VEGF and EGF signaling was the activation of the Ca++-mediated calcineurin/nuclear factor of activated T cells (NFAT) pathway by VEGF. Consistent with the importance of this pathway for tissue factor induction, treatment of endothelial cells with the Ca++ chelator BAPTA-AM, as well as the calcineurin inhibitor cyclosporin A, partially inhibited VEGF induced tissue factor upregulation. Furthermore, tissue factor reporter gene assays revealed a synergistic cooperation of NFAT and EGR-1 in the induction of the TF promoter, and a physical interaction between the two factors was indicated by co-immunoprecipitation assays. Another gene upregulated by VEGF predominantly via NFAT, which is not induced by EGF, is the DSCR-1 gene. The calcineurin inhibitor DSCR-1 seems to be induced by VEGF in a negative feed-back loop to limit NFAT activation. When we tested adenoviral overexpression of DSCR-1, VEGF-mediated induction of tissue factor mRNA was reduced, and complete suppression could be achieved by a combination of viruses expressing DSCR-1 and NAB2, a corepressor of EGR-1. These findings support that both, NFAT and EGR-1, are required for tissue factor upregulation in response to VEGF.
Chemokines and thrombogenicity
Authors: Lambert Michele , Sachais Bruce , Kowalska M.
Published: June 2007

Thrombosis is an important clinical entity, and pathologic thrombosis, in the form of atherosclerosis, is a major cause of morbidity and mortality. Recent research points to the role of chemokines, normally key factors in inflammation, in thrombogenesis. Many recent studies in murine transgenic and knockout models show that chemokines and their receptors are important modulators of the process of thrombus formation, particularly in atherosclerosis. Platelet-released chemokines can potentiate or inhibit thrombosis and inflammation.This review focuses on the role of chemokines in platelet activation and thrombosis, particularly as it relates to atherosclerosis. Further studies to define this complex interaction are underway.
Platelet-derived chemokines in vascular biology
Authors: Hundelshausen Philipp , Petersen Frank , Brandt Ernst
Published: June 2007

Undoubtedly, platelets are key elements in the regulation of thrombosis and haemostasis. Along with their primary task to prevent blood loss from injured vessels, platelets have emerged as regulators of a variety of processes in the vasculature. Multiple challenges, from the contact and adhesion to subendothelial matrix after injury of the vessel wall, to interactions with blood cells in inflammatory conditions, result in platelet activation with concomitant shape change and release of numerous substances. Among these, chemokines have been found to modulate several processes in the vasculature, such as atherosclerosis and angiogenesis. In particular, the chemokines connective tissue activating protein III (CTAP-III) and its precursors, or truncation products (CXCL7), platelet factor 4, (PF4, CXCL4) and its variant PF4alt (CXCL4L1) or regulated upon activation and normal T cell expressed and secreted (RANTES, CCL5), have been investigated thoroughly. Defined common properties as their aptitude to bind glycosaminoglycans or their predisposition to associate and form homooligomers are prerequisites for their role in the vasculature and function in vivo. The current review summarizes the development of these single chemokines, and their cooperative effects that may in part be dependent on their physical interactions.
Chemokines in vascular remodeling
Authors: Zernecke Alma , Schober Andreas
Published: June 2007

The arterial vessel wall response to a variety of injuries consists in structural changes, which can result in luminal narrowing and aggravation of the underlying disease.This arterial remodeling is characterized by neointima formation and medial thickening, inflammatory cell recruitment and endothelial dysfunction. Chemokines and the corresponding receptors have been shown to participate at every step of the remodeling process.The monocyte chemotactic protein (MCP)-1/CC motif receptor 2 (CCR2) axis induces monocyte infiltration of the injured vessel wall and can stimulate proliferation of smooth muscle cells (SMCs) in models of restenosis, cardiac allograft vasculopathy (CAV), pulmonary hypertension, and systemic hypertension. In contrast, stromal cell-derived factor (SDF)-1α and its receptor CXC motif receptor 4 (CXCR4) are centrally involved in the neointimal recruitment of SMC progenitor cells (SPCs), presumably in response to SMC apoptosis, in restenosis and CAV.The RANTES (Regulated upon activation, normally T-cell expressed,and presumably secreted) receptors CC motif receptor 1 (CCR1) and CC motif receptor 5 (CCR5) affect intimal monocyte infiltration and neointimal growth, which could be due to the deposition of platelet-derived RANTES on activated endothelial cells. Fractalkine is expressed on neointimal SMCs and thus mediates the arrest of monocytes. Interestingly, reendothelialization of injured vessels appears to primarily depend on CXC motif ligand 1 (CXCL1).These chemokine effects form a complex network, which operates in all mechanisms of vascular remodeling.The detailed understanding of the function of the chemokine network in the remodeling process may allow specific disease intervention.
Acquired muscle contractures in the dog and cat. A review of the literature and case report
Authors: Tangner C. H. , Taylor J.
Published: June 2007

Canine and feline muscle contracture is reported to affect several different muscles, is associated with a number of predisposing factors, and a varying prognosis depending upon which muscle is affected. Most patients suffer some form of trauma weeks to months before the contracture is present. The clinical signs include: lameness, pain, weakness, decreased range of motion, a firmness noted throughout the entire muscle, and usually a characteristic gait. Pre-disposing factors for muscle contracture include: compartment syndrome, infection, trauma, repetitive strains, fractures, infectious diseases, immune-mediated diseases, neoplasia, and ischaemia . There does appear to be some breed and age predilection, however, the sex of the animal does not have an appreciable influence. In general, muscle contractures of the forelimb respond better to treatment and carry a better prognosis than muscle contractures of the hindlimb.
Evaluation of three approaches to meniscal release
Authors: Montgomery R. D. , Wright J. , Bellah J. R. , Tonks C. , Austin B.
Published: June 2007

Three approaches to medial meniscal release (MMR) were compared using 48 canine cadaver stifles. The approaches included a caudomedial arthrotomy approach, a blind stab incision based on anatomic landmarks, and an arthroscopic guided approach. The cranial cruciate ligament was intact in all specimens. The time required to perform the meniscal release and joint capsule closure was recorded, as well as completeness and location of the meniscal transection. Damage to the caudal cruciate ligament, femoral cartilage, and medial collateral ligament were recorded. The mini-arthrotomy was 81% successful in accomplishment of MMR with a 4% rate of iatrogenic damage. The blind technique was 56% successful in the accomplishment of MMR with a 4% rate of iatrogenic damage. The arthroscopic guided approach was 62.5% successful in accomplishment of MMR, with a 10% rate of iatrogenic damage. Accomplishment and iatrogenic damage rates were not significantly different among procedures (p>0.05). Significantly less time was required to perform the blind technique, and significantly greater time was required to perform the arthroscopic guided technique (p>0.05). Significant differences were not noted among the procedures regarding the ability to accomplish the meniscal release or damage surrounding structures. None of the evaluated approaches for meniscal release resulted in a complete and accurate meniscal release for over 81% of the time.
Treatment of a shoulder luxation in a forelimb amputee dog
Authors: Owen M. R. , Burton N. J.
Published: June 2007

An eight-year-old, male, thoracic limb amputee Whippet presented with a traumatic lateral luxation of the scapulohumeral joint. Surgical reduction and stabilisation of the shoulder joint by means of a modified Campbell scapulohumeral prosthesis and capsulorrhaphy was unsuccessful and reluxation of the shoulder joint occurred. Subsequent surgical stabilisation using bicipital tendon transposition and a modified Campbell scapulohumeral encircling prosthesis in combination with a novel body cast / Spica splint resulted in a return to satisfactory function of this limb.
Carpal laxity syndrome in forty-three puppies
Authors: Yardimci C. , Sağlam M. , Çetinkaya M. A.
Published: June 2007

Forty-three dogs with carpal laxity syndrome were included in the study. The cases were assessed with clinical and radiographical examinations. The case histories were obtained from patient owners. We recommended exercise and commercially available balanced diets for the treatment. In all cases, the clinical recovery period varied between one to four weeks. Healing occured by the second week in the majority of cases (65.11%). The deformity was observed more frequently in male dogs (n=30) than in female dogs (n=13), and in six- to eight-week-old dogs.

Carpal Laxity Syndrome is a more general term, used for both hyperextension and hyperflexion deformity. Malnutrition or over-nutrition of rapidly growing large breed puppies causes weakness and irregular tension between extensor and flexor muscle groups, which leads to laxity of the carpal joint. Exercise and commercially available balanced diets without any other treatment is usually enough to achieve physical and functional recovery.
Pilot Randomized Clinical Trial of Prehospital Induction of Mild Hypothermia in Out-of-Hospital Cardiac Arrest Patients With a Rapid Infusion of 4°C Normal Saline
Authors: Kim Francis , Olsufka Michele , Longstreth W.T. , Maynard Charles , Carlbom David , Deem Steven , Kudenchuk Peter , Copass Michael K. , Cobb Leonard A.
Published: June 2007

Background—

Although delayed hospital cooling has been demonstrated to improve outcome after cardiac arrest, in-field cooling started immediately after the return of spontaneous circulation may be more beneficial. The aims of the present pilot study were to assess the feasibility, safety, and effectiveness of in-field cooling.

Methods and Results—

We determined the effect on esophageal temperature, before hospital arrival, of infusing up to 2 L of 4°C normal saline as soon as possible after resuscitation from out-of-hospital cardiac arrest. A total of 125 such patients were randomized to receive standard care with or without intravenous cooling. Of the 63 patients randomized to cooling, 49 (78%) received an infusion of 500 to 2000 mL of 4°C normal saline before hospital arrival. These 63 patients experienced a mean temperature decrease of 1.24±1°C with a hospital arrival temperature of 34.7°C, whereas the 62 patients not randomized to cooling experienced a mean temperature increase of 0.10±0.94°C (
P
<0.0001) with a hospital arrival temperature of 35.7°C. In-field cooling was not associated with adverse consequences in terms of blood pressure, heart rate, arterial oxygenation, evidence for pulmonary edema on initial chest x-ray, or rearrest. Secondary end points of awakening and discharged alive from hospital trended toward improvement in ventricular fibrillation patients randomized to in-field cooling.

Conclusions—

These pilot data suggest that infusion of up to 2 L of 4°C normal saline in the field is feasible, safe, and effective in lowering temperature. We propose that the effect of this cooling method on neurological outcome after cardiac arrest be studied in larger numbers of patients, especially those whose initial rhythm is ventricular fibrillation.
N-Terminal Pro–B-Type Natriuretic Peptide Testing Improves the Management of Patients With Suspected Acute Heart Failure
Authors: Moe Gordon W. , Howlett Jonathan , Januzzi James L. , Zowall Hanna
Published: June 2007

Background—

The diagnostic utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure has been documented. However, most of the data were derived from countries with high healthcare resource use, and randomized evidence for utility of NT-proBNP was lacking.

Methods and Results—

We tested the hypothesis that NT-proBNP testing improves the management of patients presenting with dyspnea to emergency departments in Canada by prospectively comparing the clinical and economic impact of a randomized management strategy either guided by NT-proBNP results or without knowledge of NT-proBNP concentrations. Five hundred patients presenting with dyspnea to 7 emergency departments were studied. The median NT-proBNP level among the 230 subjects with a final diagnosis of heart failure was 3697 compared with 212 pg/mL in those without heart failure (
P
<0.00001). Knowledge of NT-proBNP results reduced the duration of ED visit by 21% (6.3 to 5.6 hours;
P
=0.031), the number of patients rehospitalized over 60 days by 35% (51 to 33;
P
=0.046), and direct medical costs of all ED visits, hospitalizations, and subsequent outpatient services (US $6129 to US $5180 per patient;
P
=0.023) over 60 days from enrollment. Adding NT-proBNP to clinical judgment enhanced the accuracy of a diagnosis; the area under the receiver-operating characteristic curve increased from 0.83 to 0.90 (
P
<0.00001).

Conclusions—

In a universal health coverage system mandating judicious use of healthcare resources, inclusion of NT-proBNP testing improves the management of patients presenting to emergency departments with dyspnea through improved diagnosis, cost savings, and improvement in selected outcomes.
Long-Term Prognostic Value of Neopterin
Authors: Ray Kausik K. , Morrow David A. , Sabatine Marc S. , Shui Amy , Rifai Nader , Cannon Christopher P. , Braunwald Eugene
Published: June 2007

Background—

Monocyte activation is believed to play an important role in the pathogenesis of acute coronary syndromes (ACS). Neopterin is a soluble marker of monocyte activation, and elevated levels are of prognostic value in patients with stable coronary artery disease.

Methods and Results—

Neopterin levels were measured on average at 7 days (in 3946 patients) and at 4 months (in 3369 patients) after ACS in the PRavastatin Or atorVastatin Evaluation Infection Therapy–Thrombolysis In Myocardial Infarction (PROVE IT–TIMI 22) trial. We assessed the relationship between plasma neopterin levels and the risk of death and death or acute coronary events (nonfatal myocardial infarction or unstable angina) over 2 years. Seven days after an ACS event, neopterin levels ≥12.11 nmol/L (upper quartile, derived from a post hoc analysis) were associated with an increased risk of death and an increased risk of death or acute coronary events after adjustment for age, gender, history of diabetes mellitus, history of hypertension, history of smoking, type of ACS presentation, use of percutaneous coronary intervention for the index event, statin regimen, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein (hazard ratio, 1.86 [95% CI, 1.24 to 2.77],
P
=0.003; and hazard ratio, 1.33 [95% CI, 1.09 to 1.63]
P
=0.006, respectively). Neopterin levels ≥12.11 nmol/L at 4 months remained a predictor of death alone and of death or acute coronary events after multivariable adjustment that included adjustment for month 4 low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and statin regimen (hazard ratio, 2.39 [95% CI, 1.43 to 3.99],
P
=0.001; and hazard ratio, 1.60 [95% CI, 1.21 to 2.11],
P
=0.001). High-dose atorvastatin significantly attenuated the risk among subjects with neopterin levels ≥12.11 nmol/L at baseline (interaction
P
for death or acute coronary event, 0.018).

Conclusions—

Increased monocyte activation detected by an elevated plasma neopterin level identifies patients at long-term risk of death or recurrent acute coronary events after ACS. Intensive statin therapy significantly attenuates the risk of recurrent events among patients with an elevated neopterin level.
Exercise Training Normalizes Sympathetic Outflow by Central Antioxidant Mechanisms in Rabbits With Pacing-Induced Chronic Heart Failure
Authors: Gao Lie , Wang Wei , Liu Dongmei , Zucker Irving H.
Published: June 2007

Background—

In a recent study, we demonstrated that an increase in oxidative stress in the rostral ventrolateral medulla plays a critical role in the sympathoexcitation observed in chronic heart failure (CHF). Growing evidence indicates that exercise training evokes an antioxidative effect in CHF. In the present study, we therefore hypothesized that long-term exercise exerts its beneficial effect on autonomic activity in CHF via central antioxidative mechanisms.

Methods and Results—

Experiments were performed on New Zealand White rabbits. All rabbits were instrumented to measure mean arterial pressure, heart rate, and renal sympathetic nerve activity and to test baroreflex sensitivity. Exercise training significantly decreased baseline renal sympathetic nerve activity (65.8±5.2% to 41.3±3.9% of Max [where “Max” is the maximum renal sympathetic nerve activity induced by a 50-mL puff of smoke directed to the external nares of the rabbit],
P
<0.05) and increased the maximal gain of the baroreflex curves for heart rate (2.2±0.2 to 4.6±0.7 bpm per mm Hg,
P
<0.01) and renal sympathetic nerve activity (1.9±0.2% to 4.5±0.4% of Max per mm Hg,
P
<0.01) in CHF rabbits. Exercise training increased expression of CuZn superoxide dismutase (0.3±0.1 to 1.5±0.3 [ratio of CuZn superoxide dismutase to tubulin],
P
<0.01) and decreased NAD(P)H oxidase subunit gp91
phox
protein expression (1.9±0.2 to 1.2±0.1 [ratio of gp91
phox
to tubulin],
P
<0.05) in the rostral ventrolateral medulla of CHF rabbits. Central overexpression of CuZn superoxide dismutase dose-dependently decreased baseline renal sympathetic nerve activity (control, 68.5±7.1% of Max; 10
10
particles of adenovirus, 53.2±4.4% of Max; and 10
11
particles of adenovirus, 33.7±3.5% of Max;
P
<0.05) in CHF rabbits.

Conclusions—

These results suggest that an upregulation in central antioxidative mechanisms and suppressed central prooxidant mechanisms may contribute to the exercise training–induced beneficial effects on autonomic activity in CHF.
Food Omega-3 Fatty Acid Intake of Individuals (Total, Linolenic Acid, Long-Chain) and Their Blood Pressure
Authors: Ueshima Hirotsugu , Stamler Jeremiah , Elliott Paul , Chan Queenie , Brown Ian J. , Carnethon Mercedes R. , Daviglus Martha L. , He Ka , Moag-Stahlberg Alicia , Rodriguez Beatriz L. , Steffen Lyn M. , Van Horn Linda , Yarnell John , Zhou Beifan
Published: June 2007

Findings from short-term randomized trials indicate that dietary supplements of omega-3 polyunsaturated fatty acids (PFA) lower blood pressure of hypertensive persons, but effect size in nonhypertensive individuals is small and nonsignificant. Data are lacking on food omega-3 PFA and blood pressure in general populations. The International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP) is an international cross-sectional epidemiologic study of 4680 men and women ages 40 to 59 from 17 population-based samples in China, Japan, United Kingdom, and United States. We report associations of food omega-3 PFA intake (total, linolenic acid, long-chain) of individuals with blood pressure. Systolic and diastolic blood pressure were measured 8 times at 4 visits. With several models to control for possible confounders (dietary, other), linear regression analyses showed inverse relationship of total omega-3 PFA from food (percent kilocalories, from four 24-hour dietary recalls) to systolic and diastolic blood pressures. With adjustment for 17 variables, estimated systolic blood pressure/diastolic blood pressure differences with 2 standard deviation higher (0.67% kcal) omega-3 PFA were −0.55/−0.57 mm Hg (Z-score −1.33, −2.00); for 2238 persons without medical or dietary intervention, −1.01/−0.98 mm Hg (Z −1.63, −2.25); for 2038 nonhypertensive persons from this sub-cohort, −0.91/−0.92 mm Hg (Z −1.80, −2.38). For linolenic acid (largely from vegetable foods), blood pressure differences were similar, eg, for the 2238 “nonintervened” individuals, −0.97/−0.87 mm Hg (Z −1.52, −1.95); blood pressure differences were −0.32/−0.45 mm Hg for long-chain omega-3 PFA (largely from fish). In summary, food omega-3 PFA intake related inversely to blood pressure, including in nonhypertensive persons, with small estimated effect size. Food omega-3 PFA may contribute to prevention and control of adverse blood pressure levels.
School Dress Codes in Post-Scarcity Japan
Authors: Tamura Yuichi
Published: June 2007

Focusing on dress codes, this article aims at providing a better understanding of current practices of youth socialization in Japanese schools and of cultural consequences of post-scarcity on schools. Since the late 1980s, there has been a national trend among Japanese secondary schools granting students more freedom of individual expression through attire and hairstyle. Using contradiction as a sensitizing concept, the author identifies several emerging cultural themes such as individuality and human rights that became incongruent with the uniformity of student appearance prescribed by dress codes. This Japanese case study suggests that, in times of post-scarcity in which economic affluence permits wide participation in the culture of individualism and consumerism, a new educational paradigm that emphasizes individuality emerges, and schools' management of youth lifestyles may shift toward deregulation and permissiveness.
Participation in Structured Youth Programs
Authors: Perkins Daniel F. , Borden Lynne M. , Villarruel Francisco A. , Carlton-Hug Annelise , Stone Margaret R. , Keith Joanne G.
Published: June 2007

This study examines the cultural and contextual factors that influence the decisions of underrepresented urban youth, who identify themselves as Black/ African American, Latino, Arab, or Chaldean, to participate in youth programs. Although youth programs are increasingly recognized for their positive influences, little is known about the factors that influence a young person's decision to participate. Using the concept systems method, participants engaged in “brainstorming sessions” that led to more in-depth discussions about why youth participate in youth programs. Overall, youth emphasized how youth programs help young people stay off the streets, learn new skills, avoid boredom, and provide opportunities for fun and enjoyable activities. The perceived barriers preventing young people from participating differed between genders and ethnicities and included barriers related to personal decisions, peer influence, and parental restrictions.
Cytotoxic T lymphocytes carrying a pattern recognition protein Tag7 can detect evasive, HLA-negative but Hsp70-exposing tumor cells, thereby ensuring FasL/Fas-mediated contact killing
Authors: Sashchenko Lidia P. , Dukhanina Elena A. , Shatalov Yury V. , Yashin Denis V. , Lukyanova Tamara I. , Kabanova Olga D. , Romanova Elena A. , Khaidukov Sergei V. , Galkin Alexander V. , Gnuchev Nikolai V. , Georgiev Georgii P.
Published: June 2007

Within the broad problem of host immune surveillance versus tumor immune evasion, a most intriguing question is how the cellular immunity can cope with cancerous cells that have gotten rid of the classical antigen-presenting machinery. One such option stems from (1) the fact that HLA loss is often attended with expression of Hsp70 on the tumor cell surface, and (2) our findings that human lymphocytes express a protein Tag7 (also known as PGRP-S) capable of tight and specific interaction with cognate Hsp70. Here we show that a subpopulation of human CD4+CD25+ lymphocytes, obtained either in culture as lymphokine-activated killers or directly from healthy donors, carry Tag7 and FasL on their surface and can indeed kill the HLA-negative tumor-derived cells K562 and MOLT-4 that expose Hsp70 and Fas. The primary binding of lymphocyte Tag7 to target-cell Hsp70 is very specific (eg, it is blocked by preincubating either cell with minimal peptides from the “partner” protein), and secures cell contact indispensable for subsequent FasL/Fas-triggered apoptosis. Unrelated to natural killer cell action or the putative role of Hsp as an antigen-presenting substitute, this novel mechanism is rather a backup analog of orthodox (CD8+) target recognition (Tag7 acting as built-in T-cell receptor and Hsp70 itself as ligand).
Response to B-cell–depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura
Authors: Stasi Roberto , Del Poeta Giovanni , Stipa Elisa , Evangelista Maria Laura , Trawinska Margherita M. , Cooper Nichola , Amadori Sergio
Published: June 2007

Rituximab, an anti-CD20 monoclonal antibody, has been used to treat autoimmune disorders such as idiopathic thrombocytopenic purpura (ITP). However, its mechanisms of action as well as the effects on cellular immunity remain poorly defined. We investigated the changes of different peripheral blood T-cell subsets, the apoptosis profile, as well as the changes of T-cell receptor (TCR) β-variable (VB) region gene usage of CD4+ and CD8+ T-cell subpopulations following rituximab therapy. The study involved 30 patients with chronic ITP who received rituximab, of whom 14 achieved a durable (> 6 months) response. Compared with the control group, pretreatment abnormalities of T cells in ITP patients included an increase of the Th1/Th2 ratio and of the Tc1/Tc2 ratios (P < .001), increased expression of Fas ligand on Th1 and Th2 cells (P < .001), increased expression of Bcl-2 mRNA (P = .003) and decreased expression of bax mRNA (P = .025) in Th cells, and expansion of oligoclonal T cells with no preferential use of any TCR VB subfamily. These abnormalities were reverted in responders at 3 and 6 months after treatment, whereas they remained unchanged in nonresponders. Our findings indicate that in patients with ITP, response to B-cell depletion induced by rituximab is associated with significant changes of the T-cell compartment.
Dietary n-3 fatty acids have suppressive effects on mucin upregulation in mice infected with Pseudomonas aeruginosa
Authors: Tetaert Daniel , Pierre Maud , Demeyer Dominique , Husson Marie-Odile , Béghin Laurent , Galabert Claude , Gottrand Frédéric , Beermann Christopher , Guery Benoit , Desseyn Jean-Luc
Published: June 2007

Background

Mucin hypersecretion and mucus plugging in the airways are characteristic features of chronic respiratory diseases like cystic fibrosis (CF) and contribute to morbidity and mortality. In CF, Pseudomonas aeruginosa superinfections in the lung exacerbate inflammation and alter mucus properties. There is increasing evidence that n-3 polyunsaturated fatty acids (PUFAs) exhibit anti-inflammatory properties in many inflammatory diseases while n-6 PUFA arachidonic acid (AA) favors inflammatory mediators such as eicosanoids prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) that may enhance inflammatory reactions. This suggests that n-3 PUFAs may have a protective effect against mucus over-production in airway diseases. Therefore, we hypothesized that n-3 PUFAs may downregulate mucins expression.

Methods

We designed an absolute real-time PCR assay to assess the effect of a 5-week diet enriched either with n-3 or n-6 PUFAs on the expression of large mucins in the lungs of mice infected by P. aeruginosa.

Results

Dietary fatty acids did not influence mucin gene expression in healthy mice. Lung infection induced an increase of the secreted gel-forming mucin Muc5b and a decrease of the membrane bound mucin Muc4. These deregulations are modulated by dietary fatty acids with a suppressive effect of n-3 PUFAs on mucin (increase of Muc5b from 19-fold up to 3.6 × 105-fold for the n-3 PUFAs treated group and the control groups, respectively, 4 days post-infection and decrease of Muc4 from 15-fold up to 3.2 × 104-fold for the control and the n-3 PUFAs treated groups, respectively, 4 days post-infection).

Conclusion

Our data suggest that n-3 PUFAs enriched diet represents an inexpensive strategy to prevent or treat mucin overproduction in pulmonary bacterial colonization.
A new advance in alternative splicing databases: from catalogue to detailed analysis of regulation of expression and function of human alternative splicing variants
Authors: de la Grange Pierre , Dutertre Martin , Correa Margot , Auboeuf Didier
Published: June 2007

Background

Most human genes produce several transcripts with different exon contents by using alternative promoters, alternative polyadenylation sites and alternative splice sites. Much effort has been devoted to describing known gene transcripts through the development of numerous databases. Nevertheless, owing to the diversity of the transcriptome, there is a need for interactive databases that provide information about the potential function of each splicing variant, as well as its expression pattern.

Description

After setting up a database in which human and mouse splicing variants were compiled, we developed tools (1) to predict the production of protein isoforms from these transcripts, taking account of the presence of open reading frames and mechanisms that could potentially eliminate transcripts and/or inhibit their translation, i.e. nonsense-mediated mRNA decay and microRNAs; (2) to support studies of the regulation of transcript expression at multiple levels, including transcription and splicing, particularly in terms of tissue specificity; and (3) to assist in experimental analysis of the expression of splicing variants. Importantly, analyses of all features from transcript metabolism to functional protein domains were integrated in a highly interactive, user-friendly web interface that allows the functional and regulatory features of gene transcripts to be assessed rapidly and accurately.

Conclusion

In addition to identifying the transcripts produced by human and mouse genes, fast DB http://www.fast-db.com provides tools for analyzing the putative functions of these transcripts and the regulation of their expression. Therefore, fast DB has achieved an advance in alternative splicing databases by providing resources for the functional interpretation of splicing variants for the human and mouse genomes. Because gene expression studies are increasingly employed in clinical analyses, our web interface has been designed to be as user-friendly as possible and to be readily searchable and intelligible at a glance by the whole biomedical community.
Computerized acoustic assessment of treatment efficacy of nebulized epinephrine and albuterol in RSV bronchiolitis
Authors: Beck Raphael , Elias Nael , Shoval Shay , Tov Naveh , Talmon Gil , Godfrey Simon , Bentur Lea
Published: June 2007

Aim

We evaluated the use of computerized quantification of wheezing and crackles compared to a clinical score in assessing the effect of inhaled albuterol or inhaled epinephrine in infants with RSV bronchiolitis.

Methods

Computerized lung sounds analysis with quantification of wheezing and crackles and a clinical score were used during a double blind, randomized, controlled nebulized treatment pilot study. Infants were randomized to receive a single dose of 1 mgr nebulized l-epinephrine or 2.5 mgr nebulized albuterol. Computerized quantification of wheezing and crackles (PulmoTrack®) and a clinical score were performed prior to, 10 minutes post and 30 minutes post treatment. Results were analyzed with Student's t-test for independent samples, Mann-Whitney U test and Wilcoxon test.

Results

15 children received albuterol, 12 received epinephrine. The groups were identical at baseline. Satisfactory lung sounds recording and analysis was achieved in all subjects. There was no significant change in objective quantification of wheezes and crackles or in the total clinical scores either within the groups or between the groups. There was also no difference in oxygen saturation and respiratory distress.

Conclusion

Computerized lung sound analysis is feasible in young infants with RSV bronchiolitis and provides a non-invasive, quantitative measure of wheezing and crackles in these infants.

Trial registration number: ClinicalTrials.gov NCT00361452