bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Airway Wall Motion on Surfactant Delivery
Authors: Halpern D. , Bull J. L. , Grotberg J. B.
Published: September 2004

Soluble surfactant and airway surface liquid transport are examined using a mathematical model of Marangoni flows which accounts for airway branching and for cyclic airway stretching. Both radial and longitudinal wall strains are considered. The model allows for variation of the amplitude and frequency of the motion, as may occur under a variety of ventilatory situations occurring during surfactant replacement therapy. The soluble surfactant dynamics of the thin fluid film are modeled by linear sorption. The delivery of surfactants into the lung is handled by setting the proximal boundary condition to a higher concentration compared to the distal boundary condition. Starting with a steady-state, nonuniform, surfactant distribution, we find that transport of surfactant into the lung is enhanced for increasing strain amplitudes. However, for fixed amplitude, increasing frequency has a smaller effect. At small strain amplitudes, increasing frequency enhances transport, but at large strain amplitudes, increasing cycling frequency has the opposite effect.
Wall Shear-Rate Estimation Within the 50cc Penn State Artificial Heart Using Particle Image Velocimetry
Authors: Hochareon Pramote , Manning Keefe B. , Fontaine Arnold A. , Tarbell John M. , Deutsch Steven
Published: September 2004

Particle image velocimetry (PIV) has been gaining acceptance as a routine tool to evaluate the flow fields associated with fluid mechanical devices. We have developed algorithms to investigate the wall shear-rates within the 50cc Penn State artificial heart using low magnification, conventional particle image velocimetry (PIV). Wall shear has been implicated in clot formation, a major post-implant problem with artificial hearts. To address the issues of wall scattering and incomplete measurement volumes, associated with near wall measurements, we have introduced a zero masking and a fluid centroid shifting technique. Simulations using different velocity fields were conducted with the techniques to assess their viability. Subsequently, the techniques were applied to the experimental data collected. The results indicate that the size of the interrogation region should be chosen to be as small as possible to maximize resolution while large enough to ensure an adequate number of particles per region. In the current study, a 16×16 interrogation window performed well with good spatial resolution and particle density for the estimation of wall shear rate. The techniques developed with PIV allow wall shear-rate estimates to be obtained from a large number of sites at one time. Because a planar image of a flow field can be determined relatively rapidly, PIV may prove useful in any preliminary design procedure.
Tetrapolar Measurement of Electrical Conductivity and Thickness of Articular Cartilage
Authors: Binette J. S. , Garon M. , Savard P. , McKee M. D. , Buschmann M. D.
Published: September 2004

A tetrapolar method to measure electrical conductivity of cartilage and bone, and to estimate the thickness of articular cartilage attached to bone, was developed. We determined the electrical conductivity of humeral head bovine articular cartilage and subchondral bone from a 1- to 2-year-old steer to be 1.14±0.11S/m(mean±sd,n=11) and 0.306±0.034S/m,(mean±sd,n=3), respectively. For a 4-year-old cow, articular cartilage and subchondral bone electrical conductivity were 0.88±0.08S/m(mean±sd,n=9) and 0.179±0.046S/m(mean±sd,n=3), respectively. Measurements on slices of cartilage taken from different distances from the articular surface of the steer did not reveal significant depth-dependence of electrical conductivity. We were able to estimate the thickness of articular cartilage with reasonable precision (<20% error) by injecting current from multiple electrode pairs with different inter-electrode distances. Requirements for the precision of this method to measure cartilage thickness include the presence of a distinct layer of calcified cartilage or bone with a much lower electrical conductivity than that of uncalcified articular cartilage, and the use of inter-electrode distances of the current injecting electrodes that are on the order of the cartilage thickness. These or similar methods present an attractive approach to the non-destructive determination of cartilage thickness, a parameter that is required in order to estimate functional properties of cartilage attached to bone, and evaluate the need for therapeutic interventions in arthritis.
Altered Mechanical Behavior of Epicardium Under Isothermal Biaxial Loading
Authors: Wells P. B. , Harris J. L. , Humphrey J. D.
Published: September 2004

Most soft tissues that are treated clinically via heating experience multiaxial states of stress and strain in vivo and are subject to complex constraints during treatment. Remarkably, however, there are no prior data on changes in the multiaxial mechanical behavior of a collagenous tissue subjected to isometric constraints during heating. This paper presents the first biaxial stress-stretch data on a collagenous membrane (epicardium) before and after heating while subjected to various biaxial isometric constraints. It was found that isometric heating does not allow the increase in stiffness at low strains that occurs following isotonic heating. Moreover, increasing the degree of stretch prior to heating increased the thermal stability of the tissue consistent with the concept that mechanical loading primarily affects the activation entropy, not the activation energy.
Measurement of Strain in Physical Models of Brain Injury: A Method Based on HARP Analysis of Tagged Magnetic Resonance Images (MRI)
Authors: Bayly, P. V. , Ji, S. , Song, S. K. , Okamoto, R. J. , Massouros, P. , Genin G. M.
Published: September 2004

Two-dimensional (2-D) strain fields were estimated non-invasively in two simple experimental models of closed-head brain injury. In the first experimental model, shear deformation of a gel was induced by angular acceleration of its spherical container. In the second model the brain of a euthanized rat pup was deformed by indentation of its skull. Tagged magnetic resonance images (MRI) were obtained by gated image acquisition during repeated motion. Harmonic phase (HARP) images corresponding to the spectral peaks of the original tagged MRI were obtained, following procedures proposed by Osman, McVeigh and Prince [1]. Two methods of HARP strain analysis were applied, one based on the displacement of tag line intersections, and the other based on the gradient of harmonic phase. Strain analysis procedures were also validated on simulated images of deformed grids. Results show that it is possible to visualize deformation and to quantify strain efficiently in animal models of closed head injury.
A Method for Matching the Refractive Index and Kinematic Viscosity of a Blood Analog for Flow Visualization in Hydraulic Cardiovascular Models
Authors: Nguyen and T. T. , Biadillah Y. , Mongrain R. , Brunette, and J. , Tardif J.-C. , Bertrand O. F.
Published: September 2004

In this work, we propose a simple method to simultaneously match the refractive index and kinematic viscosity of a circulating blood analog in hydraulic models for optical flow measurement techniques (PIV, PMFV, LDA, and LIF). The method is based on the determination of the volumetric proportions and temperature at which two transparent miscible liquids should be mixed to reproduce the targeted fluid characteristics. The temperature dependence models are a linear relation for the refractive index and an Arrhenius relation for the dynamic viscosity of each liquid. Then the dynamic viscosity of the mixture is represented with a Grunberg-Nissan model of type 1. Experimental tests for acrylic and blood viscosity were found to be in very good agreement with the targeted values (measured refractive index of 1.486 and kinematic viscosity of 3.454 milli-m2/s with targeted values of 1.47 and 3.300 milli-m2/s).
Comorbidity and Myocardial Dysfunction Are the Main Explanations for the Higher 1-Year Mortality in Acute Myocardial Infarction With Left Bundle-Branch Block
Authors: Stenestrand Ulf , Tabrizi Fariborz , Lindbäck Johan , Englund Anders , Rosenqvist Mårten , Wallentin Lars
Published: September 2004

Background—

The purpose of this study was to assess the independent contribution of left bundle-branch block (LBBB) on cause-specific 1-year mortality in a large cohort with acute myocardial infarction (MI).

Methods and Results—

We studied a prospective cohort of 88 026 cases of MI from the Register of Information and Knowledge about Swedish Heart Intensive care Admissions in 72 hospitals in 1995 to 2001. Long-term mortality was calculated by Cox regression analysis, adjusted for multiple covariates that affect mortality by calculation of a propensity score. LBBB was present in 9% (8041 of 88 026) of the MI admissions. Patients with LBBB were older and had a higher prevalence of comorbid conditions than patients with no LBBB. The unadjusted relative risk of death within 1 year was 2.16 (95% CI, 2.08 to 2.24;
P
<0.001) for LBBB (42%, 3350 of 8041) compared with those with no LBBB (22%, 17 044 of 79 011). After adjustment for a propensity score that takes into account differences in risk factors and acute intervention, LBBB was associated with a relative risk of death of 1.19 (95% CI, 1.14 to 1.24;
P
<0.001). In a subgroup of 11 812 patients for whom left ventricular ejection fraction was available and could be added to the analysis, the contributing relative risk of LBBB for death was only 1.08 (95% CI, 0.93 to 1.25;
P
=0.33). The most common cause of death in both groups was ischemic heart disease.

Conclusions—

MI patients with LBBB have more comorbid conditions and an increased unadjusted 1-year mortality. When adjusted for age, baseline characteristics, concomitant diseases, and left ventricular ejection fraction, LBBB does not appear to be an important independent predictor of 1-year mortality in MI.
Impact of Prehospital Thrombolysis for Acute Myocardial Infarction on 1-Year Outcome
Authors: Danchin Nicolas , Blanchard Didier , Steg Philippe Gabriel , Sauval Patrick , Hanania Guy , Goldstein Patrick , Cambou Jean-Pierre , Guéret Pascal , Vaur Laurent , Boutalbi Youcef , Genès Nathalie , Lablanche Jean-Marc
Published: September 2004

Background—

Limited data are available on the impact of prehospital thrombolysis (PHT) in the “real-world” setting.

Methods and Results—

Of 443 intensive care units in France, 369 (83%) prospectively collected all cases of infarction (≤48 hours of symptom onset) in November 2000; 1922 patients (median age, 67 years; 73% men) with ST-segment–elevation infarction were included, of whom 180 (9%) received intravenous thrombolysis before hospital admission (PHT). Patients with PHT were younger than those with in-hospital thrombolysis, primary percutaneous interventions, or no reperfusion therapy. Median time from symptom onset to hospital admission was 3.6 hours for PHT, 3.5 hours for in-hospital lysis, 3.2 hours for primary percutaneous interventions, and 12 hours for no reperfusion therapy. In-hospital death was 3.3% for PHT, 8.0% for in-hospital lysis, 6.7% for primary percutaneous interventions, and 12.2% for no reperfusion therapy. One-year survival was 94%, 89%, 89%, and 79%, respectively. In a multivariate analysis of predictors of 1-year survival, PHT was associated with a 0.49 relative risk of death (95% CI, 0.24 to 1.00;
P
=0.05). When the analysis was limited to patients receiving reperfusion therapy, the relative risk of death for PHT was 0.52 (95% CI, 0.25 to 1.08;
P
=0.08). In patients with PHT admitted in ≤3.5 hours, in-hospital mortality was 0% and 1-year survival was 99%.

Conclusions—

The 1-year outcome of patients treated with PHT compares favorably with that of patients treated with other modes of reperfusion therapy; this favorable trend persists after multivariate adjustment. Patients with PHT admitted very early have a very high 1-year survival rate.
Microvolt T-Wave Alternans Distinguishes Between Patients Likely and Patients Not Likely to Benefit From Implanted Cardiac Defibrillator Therapy
Authors: Bloomfield Daniel M. , Steinman Richard C. , Namerow Pearila B. , Parides Michael , Davidenko Jorge , Kaufman Elizabeth S. , Shinn Timothy , Curtis Anne , Fontaine John , Holmes Douglas , Russo Andrea , Tang Chuen , Bigger J. Thomas
Published: September 2004

Background—

In 2003, the Centers for Medicaid and Medicare Services recommended QRS duration as a means to identify MADIT II–like patients suitable for implanted cardiac defibrillator (ICD) therapy. We compared the ability of microvolt T-wave alternans and QRS duration to identify groups at high and low risk of dying among heart failure patients who met MADIT II criteria for ICD prophylaxis.

Methods and Results—

Patients with MADIT II characteristics and sinus rhythm had a microvolt T-wave alternans exercise test and a 12-lead ECG. Our primary end point was 2-year all-cause mortality. Of 177 MADIT II–like patients, 32% had a QRS duration >120 ms, and 68% had an abnormal (positive or indeterminate) microvolt T-wave alternans test. During an average follow-up of 20±6 months, 20 patients died. We compared patients with an abnormal microvolt T-wave alternans test to those with a normal (negative) test, and patients with a QRS >120 ms with those with a QRS ≤120 ms; the hazard ratios for 2-year mortality were 4.8 (
P
=0.020) and 1.5 (
P
=0.367), respectively. The actuarial mortality rate was substantially lower among patients with a normal microvolt T-wave alternans test (3.8%; 95% confidence interval: 0, 9.0) than the mortality rate in patients with a narrow QRS (12.0%; 95% confidence interval: 5.6, 18.5). The corresponding false-negative rates are 3.5% and 10.2%, respectively.

Conclusion—

Among MADIT II–like patients, a microvolt T-wave alternans test is better than QRS duration at identifying a high-risk group and also better at identifying a low-risk group unlikely to benefit from ICD therapy.
ACAT2 Is Localized to Hepatocytes and Is the Major Cholesterol-Esterifying Enzyme in Human Liver
Authors: Parini Paolo , Davis Matthew , Lada Aaron T. , Erickson Sandra K. , Wright Teresa L. , Gustafsson Ulf , Sahlin Staffan , Einarsson Curt , Eriksson Mats , Angelin Bo , Tomoda Hiroshi , Ōmura Satoshi , Willingham Mark C. , Rudel Lawrence L.
Published: September 2004

Background—

Two acyl-coenzyme A:cholesterol acyltransferase (ACAT) genes,
ACAT1
and
ACAT2
, have been identified that encode 2 proteins responsible for intracellular cholesterol esterification.

Methods and Results—

In this study, immunohistology was used to establish their cellular localization in human liver biopsies. ACAT2 protein expression was confined to hepatocytes, whereas ACAT1 protein was found in Kupffer cells only. Studies with a highly specific ACAT2 inhibitor, pyripyropene A, in microsomal activity assays demonstrated that ACAT2 activity was highly variable among individual human liver samples, whereas ACAT1 activity was more similar in all specimens. ACAT2 provided the major cholesterol-esterifying activity in 3 of 4 human liver samples examined.

Conclusions—

The data suggest that in diseases in which dysregulation of cholesterol metabolism occurs, such as hypercholesterolemia and atherosclerosis, ACAT2 should be considered a target for prevention and treatment.
Genetically Determined Resistance to Collagenase Action Augments Interstitial Collagen Accumulation in Atherosclerotic Plaques
Authors: Fukumoto Yoshihiro , Deguchi Jun-o , Libby Peter , Rabkin-Aikawa Elena , Sakata Yasuhiko , Chin Michael T. , Hill Christopher C. , Lawler Patrick R. , Varo Nerea , Schoen Frederick J. , Krane Stephen M. , Aikawa Masanori
Published: September 2004

Background—

We hypothesized that collagenolytic activity produced by activated macrophages contributes to collagen loss and the subsequent instability of atheromatous lesions, a common trigger of acute coronary syndromes. However, no direct in vivo evidence links collagenases with the regulation of collagen content in atherosclerotic plaques.

Methods and Results—

To test the hypothesis that collagenases influence the structure of atheromata, we examined collagen accumulation in atherosclerotic lesions of apolipoprotein E-deficient mice (apoE
−/−
) that express collagenase-resistant collagen-I (Col
R/R
/apoE
−/−
, n=12) or wild-type collagen-expressing mice (Col
+/+
/apoE
−/−
, n=12). Aortic atheromata of both groups had similar sizes and numbers of macrophages, a major source of collagenases. However, aortic intimas from Col
R/R
/apoE
−/−
mice contained fewer smooth muscle cells, a source of collagen, probably because of decreased migration or proliferation or increased cell death. Despite reduced numbers of smooth muscle cells, atheromata of Col
R/R
/apoE
−/−
mice contained significantly more intimal collagen than did those of Col
+/+
/apoE
−/−
mice.

Conclusion—

These results establish that collagenase action regulates plaque collagen turnover and smooth muscle cell accumulation.
Natural History and Risk Stratification of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Hulot Jean-Sébastien , Jouven Xavier , Empana Jean-Philippe , Frank Robert , Fontaine Guy
Published: September 2004

Background—

Management of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is complicated by the incomplete information on the natural history of the disease and by the lack of risk stratification for cardiovascular death. The aim of the study was the identification of risk factors related to long-term prognosis.

Methods and Results—

Data were collected from 130 patients (100 men; age at onset of symptoms, 31.8±14.4 years) from a tertiary center between 1977 and 2000 who fulfilled the international standardized diagnostic criteria for ARVD/C. Risk factors for cardiovascular death were determined by a logistic regression model. After a mean follow-up of 8.1±7.8 years, 24 deaths were recorded, with a mean age at death of 54±19 years (annual mortality rate, 2.3%). There were 21 deaths with a cardiovascular origin (progressive heart failure for 14 patients and sudden death for the remaining 7 patients). All patients who died had a history of ventricular tachycardia. Multivariate analysis showed that after adjustment for sex, history of syncope, chest pain, inaugural ventricular tachycardia, recurrence of ventricular tachycardia, and QRS dispersion, clinical signs of right ventricular failure and left ventricular dysfunction both remained independently associated with cardiovascular mortality. The combined presence of one of these risk factors and ventricular tachycardia identifies high-risk subjects for cardiovascular mortality, whereas patients without ventricular tachycardia displayed the best prognosis.

Conclusions—

The information on the natural history of patients with ARVD allowed us to identify risks factors for cardiovascular mortality. An analysis of a large international registry is needed to refine these results.
Growth Factors in the Collateral Circulation of Chronic Total Coronary Occlusions
Authors: Werner Gerald S. , Jandt Enrico , Krack Andreas , Schwarz Gero , Mutschke Oliver , Kuethe Friedhelm , Ferrari Markus , Figulla Hans R.
Published: September 2004

Background—

Despite extensive animal experimental evidence, there are few data on the relation of growth factors and collateral function in humans.

Methods and Results—

In 104 patients with a chronic total coronary occlusion (CTO; >2 weeks’ duration), collateral function was assessed invasively during recanalization by intracoronary Doppler and pressure recordings. A collateral resistance index, R
Coll
, was calculated. Blood samples were drawn from the distal coronary bed supplied by the collaterals and from the aortic root to measure basic fibroblast growth factor (bFGF), monocytic chemotactic protein-1 (MCP-1), transforming growth factor-β (TGF-β), placenta growth factor (PlGF), and tumor necrosis factor-α (TNF-α). The bFGF concentration in the collateralized artery was higher than in the aortic root (34±20 versus 18±14 pg/mL;
P
<0.001). bFGF was highest in recent occlusions (2 to 12 weeks) with the highest R
Coll
. Higher collateral concentrations were also observed for MCP-1, TGF-β, and PlGF, but without a close relation to the duration of occlusion. TNF-α was not increased in collaterals compared with the systemic circulation. MCP-1, PlGF, and TGF-β were significantly increased in small collaterals with the highest shear stress. Diabetic patients had lower bFGF and higher MCP-1 levels than nondiabetics.

Conclusions—

In CTOs, the continuous release of bFGF into collaterals showed a close relation to the duration of occlusion and collateral function, which underscores its therapeutic potential. Other factors influencing growth factor release appeared to be shear stress for MCP-1, TGF-β, and PlGF and the presence of diabetes.
Critical Role of Macrophage 12/15-Lipoxygenase for Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Huo Yuqing , Zhao Lei , Hyman Matthew Craig , Shashkin Pavel , Harry Brian L. , Burcin Tracy , Forlow S. Bradley , Stark Matthew A. , Smith David F. , Clarke Sean , Srinivasan Suseela , Hedrick Catherine C. , Praticò Domenico , Witztum Joseph L. , Nadler Jerry L. , Funk Colin D. , Ley Klaus
Published: September 2004

Background—

Mice lacking leukocyte type 12/15-lipoxygenase (12/15-LO) show reduced atherosclerosis in several models. 12/15-LO is expressed in a variety of cells, including vascular cells, adipocytes, macrophages, and cardiomyocytes. The purpose of this study was to determine which cellular source of 12/15-LO is important for atherosclerosis.

Methods and Results—

Bone marrow from 12/15-LO
−/−
/apoE
−/−
mice was transplanted into apoE
−/−
mice and vice versa. Deficiency of 12/15-LO in bone marrow cells protected apoE
−/−
mice fed a Western diet from atherosclerosis to the same extent as complete absence of 12/15-LO, although plasma 8,12-
iso
-iPF
2α
-IV, a measure of lipid peroxidation, remained elevated. 12/15-LO
−/−
/apoE
−/−
mice regained the severity of atherosclerotic lesion typical of apoE
−/−
mice after replacement of their bone marrow cells with bone marrow from apoE
−/−
mice. Peritoneal macrophages obtained from wild-type but not 12/15-LO
−/−
mice caused endothelial activation in the presence of native LDL. Absence of 12/15-LO decreased the ability of macrophages to form foam cells when exposed to LDL.

Conclusions—

We conclude that macrophage 12/15-LO plays a dominant role in the development of atherosclerosis by promoting endothelial inflammation and foam cell formation.
Cardiorespiratory Fitness, Physical Activity, and Arterial Stiffness
Authors: Boreham Colin A. , Ferreira Isabel , Twisk Jos W. , Gallagher Alison M. , Savage Maurice J. , Murray Liam J.
Published: September 2004

Poor cardiorespiratory fitness and low physical activity have been identified as determinants of greater arterial stiffness, a mechanism that can partially explain the association of both variables with increased cardiovascular disease. However, the nature of these associations are not clear because cardiorespiratory fitness and physical activity can both mediate and confound the associations of one another with arterial stiffness. This issue was therefore examined in a population-based cohort of young adults. Subjects included 405 young men and women participating in an ongoing longitudinal study, the Northern Ireland Young Hearts Project. Pulse wave velocity was used to determine arterial stiffness in 2 arterial segments (aortoiliac and aortodorsalis pedis) using a noninvasive optical method. Cardiovascular fitness was estimated with a submaximal cycle test of physical work capacity and physical activity was estimated using a modified Baecke questionnaire. Associations were investigated with the use of multiple linear regression models with adjustment for potential confounders and/or intermediate variables. Cardiorespiratory fitness and sports-related physical activity (but not leisure- and work-related physical activity) were inversely associated with arterial stiffness in young adults. The associations between sports-related physical activity and arterial stiffness were strongly mediated by cardiorespiratory fitness, whereas physical activity levels did not disturb the associations between cardiopulmonary fitness and arterial stiffness. These findings suggest that arterial stiffness-related benefits of exercise are most likely to accrue if exercise prescription in young adults targets improvements in cardiorespiratory fitness.
Hypoxia Modulates Adenosine Receptors in Human Endothelial and Smooth Muscle Cells Toward an A
2B
Angiogenic Phenotype
Authors: Feoktistov Igor , Ryzhov Sergey , Zhong Hongyan , Goldstein Anna E. , Matafonov Anton , Zeng Dewan , Biaggioni Italo
Published: September 2004

We previously reported that adenosine A
2B
receptor activation stimulates angiogenesis. Because hypoxia is a potent stimulus for the release of both adenosine and angiogenic factors, we tested the hypothesis that hypoxia alters the expression of adenosine receptors toward an “angiogenic” phenotype. We used human umbilical vein endothelial cells (HUVECs) and bronchial smooth muscle cells (BSMCs) because, under normoxic conditions, adenosine does not release vascular endothelial growth factor (VEGF). HUVECs expressed a characteristic A
2A
phenotype (the selective A
2A
agonist CGS21680 was as potent as the nonselective agonist 5′-
N
-ethylcarboxamidoadenosine [NECA] in generating cAMP). Hypoxia (4.6% O
2
, 3 hours) decreased A
2A
mRNA from 1.56±0.3% to 0.16±0.01% of β-actin expression but increased A
2B
mRNA from 0.08±0.01% to 0.27±0.05%. Consistent with changes in receptor expression, CGS21680 failed to increase cAMP in hypoxic HUVECs, whereas NECA remained active (A
2B
phenotype), and NECA increased VEGF release from 9.5±1.0 to 14.2±1.2 pg/mL (
P
<0.05), indicating that increased A
2B
receptors were functionally coupled to upregulation of VEGF. Hypoxia had similar effects on BSMCs, increasing A
2B
mRNA by 2.4±0.3-fold, from 0.42±0.04% to 1.00±0.13% of β-actin. Whereas NECA had no effect on VEGF release in normoxic BSMCs, it increased VEGF release in hypoxic BSMCs, from 74.6±9.6 to 188.3±16.7 pg/mL (
P
<0.01), and a selective A
2B
antagonist, CVT-6694, inhibited this increase. A
2B
receptors activated a VEGF reporter made unresponsive to hypoxia by mutating its hypoxia-inducible factor-1 (HIF-1) binding element, indicating a mechanism independent of HIF-1. In conclusion, hypoxia modulates the expression of adenosine receptors in human endothelial and smooth muscle cells toward an A
2B
“angiogenic” phenotype.
Atrial Natriuretic Peptide Dose-Dependently Inhibits Pressure Overload-Induced Cardiac Remodeling
Authors: Franco Veronica , Chen Yiu-Fai , Oparil Suzanne , Feng Ji An , Wang Dajun , Hage Fadi , Perry Gilbert
Published: September 2004

We hypothesized that a single copy of the proatrial natriuretic peptide gene (
Nppa
+/−
) would not be adequate to protect heterozygous mice against exaggerated cardiac hypertrophy and remodeling after pressure-overload stress.
Nppa
+/+
,
Nppa
+/−
, and
Nppa
−/−
mice were subjected to sham surgery or transverse aortic constriction and fed a basal salt diet. Heart weight varied inversely with
Nppa
gene load by 1 week after either surgery. Fractional shortening did not differ among genotypes at baseline and fell in
Nppa
−/−
mice only after transverse aortic constriction. There was a graded response in collagen deposition related to atrial natriuretic peptide (ANP) expression after either surgery. A robust interstitial and perivascular fibrosis was noted in
Nppa
−/−
and
Nppa
+/−
but not in
Nppa
+/+
mice after transverse aortic constriction. Our findings are consistent with a growing body of evidence that ANP is an important modulator of cardiac hypertrophy and remodeling in response to hemodynamic stress. The observation that partial ANP deficiency results in exaggerated hypertrophy and remodeling after pressure overload suggests that genetic or environmental variation in ANP levels may play a role in the development of cardiac hypertrophy, remodeling, and failure in humans.
Pathophysiology of Hypertensive Renal Damage
Authors: Bidani Anil K. , Griffin Karen A.
Published: September 2004

Unlike the majority of patients with uncomplicated hypertension in whom minimal renal damage develops in the absence of severe blood pressure (BP) elevations, patients with diabetic and nondiabetic chronic kidney disease (CKD) exhibit an increased vulnerability to even moderate BP elevations. Investigations in experimental animal models have revealed that this enhanced susceptibility is a consequence of an impairment of the renal autoregulatory mechanisms that normally attenuate the transmission of elevated systemic pressures to the glomeruli in uncomplicated hypertension. The markedly lower BP threshold for renal damage and the steeper slope of relationship between BP and renal damage in such states necessitates that BP be lowered into the normotensive range to prevent progressive renal damage. When BP is accurately measured using radiotelemetry in animal models, the renal protection provided by renin-angiotensin system (RAS) blockade is proportional to the BP reduction with little evidence of BP-independent protection. A critical evaluation of the clinical data also suggests that the BP-independent renoprotection by RAS blockade has been overemphasized and that achieving lower BP targets is more important than the selection of antihypertensive regimens. However, achievement of such BP goals is difficult in CKD patients without aggressive diuresis, because of their proclivity for salt retention. The effectiveness of RAS blockers in lowering BP in patients who have been adequately treated with diuretics, along with their potassium-sparing and magnesium-sparing effects, provides a more compelling rationale for the use of RAS blockade in the treatment of CKD patients than any putative BP-independent renoprotective superiority.
Mapping the attainment of Black children in Britain
Authors: Mamon Saleh
Published: September 2004

The real facts that underlie what the media, educationalists and policy-makers term the underachievement of Black children are far more complex than is often realised. Only by developing a long-term and relative perspective on the statistics of educational performance and achievement, within a context that acknowledges class, social and local factors, as well as the differential impacts of current educational policy, can a true picture be obtained. Addressing the widespread concern in the Black community about education demands more than simplistically blaming either teacher racism or Black culture.
Patterns of Locoregional Failure in Patients With Operable Breast Cancer Treated by Mastectomy and Adjuvant Chemotherapy With or Without Tamoxifen and Without Radiotherapy: Results From Five National Surgical Adjuvant Breast and Bowel Project Randomized Clinical Trials
Authors: Taghian Alphonse , Jeong Jong-Hyeon , Mamounas Eleftherios , Anderson Stewart , Bryant John , Deutsch Melvin , Wolmark Norman
Published: September 2004

Purpose

To assess patterns of locoregional failure (LRF) in lymph node–positive (LN+) breast cancer patients treated with mastectomy and adjuvant chemotherapy (± tamoxifen) and without postmastectomy radiotherapy (PMRT) in five National Surgical Adjuvant Breast and Bowel Project trials.

Patients and Methods

We examined 5,758 patients enrolled onto the B-15, B-16, B-18, B-22, and B-25 trials. Median follow-up time was 11.1 years. Distribution of pathologic tumor size was ≤ 2 cm, 2.1 to 5 cm, and more than 5 cm in 30%, 52%, and 11% of patients, respectively. Distribution of the number of LN+ was one to three, four to nine, and ≥ 10 in 51%, 32%, and 16% of patients, respectively. Ninety percent of patients received doxorubicin-based chemotherapy.

Results

The overall 10-year cumulative incidences of isolated LRF, LRF with or without distant failure (DF), and DF alone as first event were 12.2%, 19.8%, and 43.3%, respectively. Cumulative incidences for LRF as first event with or without DF for patients with one to three, four to nine, and ≥ 10 LN+ were 13.0%, 24.4%, and 31.9%, respectively (P < .0001). For patients with a tumor size of ≤ 2 cm, 2.1 to 5.0 cm, and more than 5.0 cm, these incidences were 14.9%, 21.3%, and 24.6%, respectively (P < .0001). Multivariate analysis showed age, tumor size, premenopausal status, number of LN+, and number of dissected LN as significant predictors for LRF as first event.

Conclusion

In patients with large tumors and four or more LN+, LRF as first event remains a significant problem. Although PMRT is currently recommended for patients with four or more LN+, it may also have value in selected patients with one to three LN+. However, in the absence of a randomized trial examining the worth of radiotherapy in this group of patients, the value of PMRT remains unknown.
Phase III, Randomized, Double-Blind Study of Epoetin Alfa Compared With Placebo in Anemic Patients Receiving Chemotherapy
Authors: Witzig Thomas E. , Silberstein Peter T. , Loprinzi Charles L. , Sloan Jeff A. , Novotny Paul J. , Mailliard James A. , Rowland Kendrith M. , Alberts Steven R. , Krook James E. , Levitt Ralph , Morton Roscoe F.
Published: September 2004

Purpose

To determine whether weekly epoetin alfa could improve hemoglobin (HgB) levels, reduce RBC transfusions, and improve quality of life (QOL) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy.

Patients and Methods

This double-blind, placebo-controlled study randomly assigned patients to placebo or epoetin alfa (Ortho Biotech, Bridgewater, NJ) 40,000 U subcutaneous weekly for 16 weeks. QOL, HgB, and RBC transfusions were measured pretreatment and monthly.

Results

The study accrued 344 patients; 330 were assessable for efficacy and 305 were assessable for QOL. Placebo-treated patients had a mean increase in HgB of 0.9 g/dL (range, −3.8 to +5.3) compared with 2.8 g/dL (range, −2.2 to +7.5) for epoetin-treated patients (P < .0001). During the study, 31.7% of placebo-treated patients achieved a ≥ 2 g/dL HgB increase compared with 72.7% of epoetin-treated patients (P < .0001). The incidence of RBC transfusion for placebo and epoetin treatment arms was 39.6% and 25.3% (P = .005), respectively. The placebo group received 256 units of RBCs compared with 127 units in the epoetin group (P < .0001). The incidence of toxicity in the groups was similar. Changes in the average QOL scores from baseline to the end of the study were similar in the two groups (P = not significant). The HgB responders (irrespective of treatment arm) had a mean change in Functional Assessment of Cancer Therapy (FACT) fatigue score from a baseline of +5.1 compared with −2.1 for the nonresponders (P = .006).

Conclusion

Epoetin alfa significantly improved HgB and reduced transfusions in this patient population. These results support the use of weekly epoetin alfa as an ameliorative agent for cancer-related anemia.
Reflective and Impulsive Determinants of Social Behavior
Authors: Strack Fritz , Deutsch Roland
Published: September 2004

This article describes a 2-systems model that explains social behavior as a joint function of reflective and impulsive processes. In particular, it is assumed that social behavior is controlled by 2 interacting systems that follow different operating principles. The reflective system generates behavioral decisions that are based on knowledge about facts and values, whereas the impulsive system elicits behavior through associative links and motivational orientations. The proposed model describes how the 2 systems interact at various stages of processing, and how their outputs may determine behavior in a synergistic or antagonistic fashion. It extends previous models by integrating motivational components that allow more precise predictions of behavior. The implications of this reflective-impulsive model are applied to various phenomena from social psychology and beyond. Extending previous dual-process accounts, this model is not limited to specific domains of mental functioning and attempts to integrate cognitive, motivational, and behavioral mechanisms.
Peroxynitrite scavenging mode of alaternin isolated from Cassia tora
Authors: Park Tae Hyun , Kim Dae Hyun , Kim Chul Hong , Jung Hyun Ah , Choi Jae Sue , Lee Jae Won , Chung Hae Young
Published: September 2004

Peroxynitrite (ONOO−), formed from the reaction of superoxide (.O2−) and nitric oxide (.NO), is a potent oxidant that contributes to the oxidation of various cellular constituents, including lipids, amino acids, sulfhydryls and nucleotides. It can cause cellular injury, such as DNA fragmentation and apoptotic cell death. ONOO− toxicity is also reported to be involved in inflammatory and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and atherosclerosis. Moreover, the necessity for a strong ONOO− scavenger is important because of the lack of endogenous enzymes that protect against the damage caused by ONOO−. The aim of this study was to evaluate the ability of natural products to scavenge ONOO−. We tested various plant extracts for their ONOO− scavenging activity. Among them, extract from Cassia tora, which is well known as an oriental herb in traditional medicine, showed potent ONOO− scavenging activity. Further analysis identified the phenolic active components, alaternin and nor-rubrofusarin glucose, as potent ONOO− scavengers. Spectrophotometric analysis demonstrated that alaternin and nor-rubrofusarin glucose led to a decrease in the ONOO−-mediated nitration of tyrosine through electron donation. In bovine serum albumin, alaternin, but not nor-rubrofusarin glucose, showed significant inhibition of ONOO−-mediated nitration in a dose-dependent manner. We believe alaternin can be developed as an effective ONOO− scavenger for the prevention of ONOO−-associated diseases.
Inhibition of vascular smooth muscle cell migration by serum from rats treated orally with Saiko-ka-Ryukotsu-Borei-To, a traditional Chinese formulation
Authors: Chung Hwa-Jin , Maruyama Ikuro , Tani Tadato
Published: September 2004

Oral administration of Saiko-ka-Ryukotsu-Borei-To (SRB), a traditional Chinese formulation, has been found to prevent intimal thickening of the carotid artery after balloon endothelial denudation in cholesterol-fed rats. To clarify the mechanism of this effect, the present study investigated if SRB inhibits vascular smooth muscle cell (VSMC) migration, which plays an important role in the development of intimal thickening after endothelial injury. The serum (SRB serum) sampled from cholesterol-fed rats treated orally with SRB for 3 days before and 4 days after the injury dose-dependently inhibited the migration of cultured VSMCs. When added directly to cultured VSMCs, the SRB extract did not inhibit VSMC migration. It is remarkable that SRB serum, which may contain a much lower concentration of SRB ingredients compared with the SRB extract, inhibited cultured VSMC migration. The present testing system using serum obtained from animals treated orally with traditional Chinese formulations may be useful for clarifying the pharmacological efficacy of such drugs, including many non-absorbable components. Furthermore, it may be useful in the search for new active compounds in serum after oral administration of traditional Chinese formulations, the active metabolites of which have not been identified.
Hyperici herba extract interaction with artificial lipid bilayers
Authors: Neagoe Ioana , Macri Beatrice M , Flonta Maria Luisa
Published: September 2004

Hyperici herba (Hyp) is the aerial part collected during the flowering period from the well-known herb, Hypericum perforatum. Black lipid membrane experiments were performed to investigate the effect of the ethanolic Hyp extract on the electrical properties (capacitance and conductance) of artificial lipid bilayers. Hyp extract (1–10 μg mL−1) induced a concentration-dependent increase of both specific transmembrane capacitance and conductance in phosphatidylcholine (PC) membranes. The effect on conductance was enhanced when the Hyp extract (3 μg mL−1) was present on both sides of the membrane (Gm = 77.89 ± 8.81 nS cm−2, n = 5) compared with single-sided application (Gm = 36.48 ± 2.41 nS cm−2, n = 5). In bilayers containing PC and phosphatidylserine (PS), PC:PS, the Hyp extract effect was greater than on pure PC bilayers, although the surface charge was not the determining factor of this enhanced activity. Adding cholesterol to the PC:PS mixture reverted the conductance increase induced by the Hyp extract in a dose-dependent manner. The specific pattern of the Hyp extract interaction with lipid bilayers has possible consequences concerning its absorption and bioavailability, as well as its pharmacodynamic effects on neuronal excitability.
Developing indicators: issues in the use of quantitative data about poverty
Authors: Spicker Paul
Published: September 2004

English

Indicators are often confused with measures. This article argues that precise measurement is often inappropriate in relation to complex, multidimensional issues such as poverty. A good indicator should be understood as a pointer, not a measure. It should be accessible, robust and reinforced by other pointers. By treating indicators as quantities, summary indices conceal key issues, hide the values and concepts implicit in the exercise, and are vulnerable to mathematical accident. Using multiple indicators is sounder in principle, in methodological terms, and in practical application.
Rough sleeping in rural England: challenging a problem denied
Authors: Robinson David
Published: September 2004

English

Rough sleeping in rural England is a social problem denied. This neglect reflects the more general noncoupling of homelessness and rurality, with idyll-ised notions of rural England informing interpretations of social problems in rural spaces. This article contends that this non-coupling also stems from the inappropriate application of traditional methods for estimating rough sleeping in rural locations. The particular geography of problem recognition that has driven the policy response to rough sleeping is revealed and the insights provided by and challenges raised through the application of an alternative method of counting rough sleeping sensitive to the rural context are exposed.
The Madrigal and its Outcasts: Marenzio, Giovannelli, and the Revival of Sannazaro's Arcadia
Authors: Gerbino Giuseppe
Published: September 2004

In the 1580s Ruggero Giovannelli and Luca Marenzio published a series of madrigals drawn from the pastoral book Arcadia (1504) by the Neapolitan poet Jacopo Sannazaro. There was something unusual about this choice. The texts featured sdrucciolo lines, a verse type that was traditionally excluded from the Petrarchist canon and, consequently, from the repertory of the musical madrigal. In the dedication of his first book for four voices to Ferrante Penna, Giovannelli justified his decision to publish an entire collection of sdrucciolo as an homage to Sannazaro, to whom he referred as the pride of the kingdom of Naples. He clearly meant to capitalize on a distinctively southern sense of cultural identity that took pride in Sannazaro's poetic legacy. Why, in Rome in the 1580s, did it become so important, and potentially remunerative, to reaffirm the glory of a Neapolitan poet of the caliber and popularity of Sannazaro? Why did this celebratory act focus on such a specific aspect of his poetic output (namely the cultivation of sdrucciolo lines)? And above all, why did it take the form of a musical offering? By tracing the musical reception of Sannazaro's Arcadia in the 16th century, this article investigates the relationship between deviation from the norm and regional pride in the musical culture of the 1580s. Concomitantly, it aims at demonstrating that the study of the musical fortunes and misfortunes of Sannazaro's text has something distinctive to contribute to an understanding of the rhetoric of stylistic selection that surrounded the development of the Italian madrigal.
New Religious Movements and the "Acids" of Postmodernity
Authors: Lucas Phillip Charles
Published: September 2004

Most scholars of new religious movements (NRMs) have tended to ignore the critiques of contemporary culture offered by postmodern theorists. This article attempts to show how several of these critical perspectives can offer innovative conceptual tools with which to analyze growth, change and "distortion" in these movements. The specific elements of postmodernity considered include: 1) hyper-pluralism, globalization, and the radical relativization of truth claims characteristic of postmodernity; 2) postmodernity's "domination of simulation," by which human experience comes to be increasingly mediated by synthetic images produced and disseminated by the mass media; and 3) ephemerality and the contraction of time characteristic of postmodernity. Two NRMs, Christ the Savior Brotherhood and Church Universal and Triumphant, are used as case studies to demonstrate the utility of these three postmodern conditions in interpreting developments in new religions.
The human corpus luteum: which cells have progesterone receptors?
Authors: Maybin Jacqueline A , Duncan W Colin
Published: September 2004

Studies comparing the regressing corpus luteum with the rescued corpus luteum have demonstrated that human chorionic gonadotrophin (hCG) has effects on cell types that do not express hCG receptors. As progesterone synthesis is hCG dependent and the corpus luteum has been shown to express genomic progesterone receptors, progesterone is a candidate molecule for these paracrine effects. This study aimed to define the cellular localisation of progesterone receptors in the human corpus luteum using dual-staining immunohistochemistry for genomic progesterone receptors and specific cellular markers. Well-characterised corpora lutea (n = 12) from different stages of the luteal phase were studied. The same distribution was observed in all corpora lutea examined. The steroidogenic cells (3β-hydroxysteroid dehydrogenase positive) and both thecalutein (17α-hydroxylase positive) and granulosalutein (aromatase positive) express progesterone receptors, as do stromal fibroblasts (vimentin positive, fibroblast antigen positive). Vascular endothelial cells (CD31 positive), pericytes (α-smooth muscle actin positive), macrophages (CD68 positive) and fibroblasts within the central clot do not express nuclear progesterone receptors. Progesterone is a candidate messenger molecule for the effects of hCG on the matrix metalloproteinase-producing stromal fibroblasts. Some of the effects of hCG on steroidogenic cells may be mediated by progesterone, but its effects on blood vessels and macrophages require alternate paracrine signalling mechanisms. In addition, there appears to be at least two fibroblast populations in the corpus luteum.