bluuebunny/crossref_metadata_2025 huggingface dataset:
Undergraduate teaching in gerodontology in Austria, Switzerland and Germany
Authors: Nitschke Ina , Müller Frauke , Ilgner Alexander , Reiber Thomas
Published: August 2004

Objective:  To survey the present state of undergraduate teaching in the domain of gerodontology in Germany, Switzerland and Austria.

Study participants:  All universities of Austria (A), Germany (D) and Switzerland (CH).

Protocol:  A questionnaire on undergraduate teaching in gerodontology was mailed to all Deans (A: n = 3; CH: n = 4; D: n = 31) and all independent departments except paediatric dentistry and orthodontics (A: n = 11; CH: n = 15; D: n = 111).

Results:  The questionnaires were completed and returned by 29 Deans (A: n = 2; CH: n = 4; D: n = 23) and 102 departments (A: n = 7; CH: n = 8; D: n = 87). In Austria, gerodontology is a very small component of the dental curriculum and the Deans did not want this to be increased. Most German universities claimed to teach some aspects of gerodontology to undergraduate students and 87.4% of the Deans voted for separate lectures in gerodontology. In Switzerland, gerodontology seems well established. The results of questionnaires from the independent departments revealed that in all three countries lectures were more prevalent (A: n = 0; CH: n = 4; D: n = 6) than practical training in nursing homes (A: n = 0; CH: n = 3; D: n = 6).

Conclusion:  Considering the demographical shift which is leading to an increasing proportion of elderly in the population, the weighting of gerodontology in the undergraduate dental curriculum should be considered for revision in Austria and Germany.
Physiological regulation of hypothalamic IL-1β gene expression by leptin and glucocorticoids: implications for energy homeostasis
Authors: Wisse Brent E. , Ogimoto Kayoko , Morton Gregory J. , Wilkinson Charles W. , Frayo R. Scott , Cummings David E. , Schwartz Michael W.
Published: August 2004

Interleukin-1β (IL-1β) is synthesized in a variety of tissues, including the hypothalamus, where it is implicated in the control of food intake. The current studies were undertaken to investigate whether hypothalamic IL-1β gene expression is subject to physiological regulation by leptin and glucocorticoids (GCs), key hormones involved in energy homeostasis. Adrenalectomy (ADX) increased hypothalamic IL-1β mRNA levels twofold, measured by real-time PCR ( P < 0.05 vs. sham-operated controls), and this effect was blocked by subcutaneous infusion of a physiological dose of corticosterone. Conversely, hypothalamic IL-1β mRNA levels were reduced by 30% in fa/fa (Zucker) rats, a model of genetic obesity caused by leptin receptor mutation ( P = 0.01 vs. lean littermates), and the effect of ADX to increase hypothalamic IL-1β mRNA levels in fa/fa rats ( P = 0.02) is similar to that seen in normal animals. Moreover, fasting for 48 h (which lowers leptin and raises corticosterone levels) reduced hypothalamic IL-1β mRNA levels by 30% ( P = 0.02), and this decrease was fully reversed by refeeding for 12 h. Thus leptin and GCs exert opposing effects on hypothalamic IL-1β gene expression, and corticosterone plays a physiological role to limit expression of this cytokine in both the presence and absence of intact leptin signaling. Consistent with this hypothesis, systemic leptin administration to normal rats (2 mg/kg ip) increased hypothalamic IL-1β mRNA levels twofold ( P < 0.05 vs. vehicle), an effect similar to that of ADX. These data support a model in which expression of hypothalamic IL-1β is subject to opposing physiological regulation by corticosterone and leptin.
Generic uniqueness of minimal configurations with rational rotation numbers in Aubry‐Mather theory
Authors: Zaslavski Alexander J.
Published: August 2004

We study (h)‐minimal configurations in Aubry‐Mather theory, where h belongs to a complete metric space of functions. Such minimal configurations have definite rotation number. We establish the existence of a set of functions, which is a countable intersection of open everywhere dense subsets of the space and such that for each element h of this set and each rational number α, the following properties hold: (i) there exist three different (h)‐minimal configurations with rotation number α; (ii) any (h)‐minimal configuration with rotation number α is a translation of one of these configurations.
Local solvability of a constrainedgradient system of total variation
Authors: Giga Yoshikazu , Kashima Yohei , Yamazaki Noriaki
Published: August 2004

A 1‐harmonic map flow equation, a gradient system of total variation where values of unknowns are constrained in a compact manifold in ℝN, is formulated by the use of subdifferentials of a singular energy—the total variation. An abstract convergence result is established to show that solutions of approximate problem converge to a solution of the limit problem. As an application of our convergence result, a local‐in‐time solution of 1‐harmonic map flow equation is constructed as a limit of the solutions of p‐harmonic (p > 1) map flow equation, when the initial data is smooth with small total variation under periodic boundary condition.
Solutions for nonlinear variational inequalities with a nonsmooth potential
Authors: Filippakis Michael E. , Papageorgiou Nikolaos S.
Published: August 2004

First we examine a resonant variational inequality driven by the p‐Laplacian and with a nonsmooth potential. We prove the existence of a nontrivial solution. Then we use this existence theorem to obtain nontrivial positive solutions for a class of resonant elliptic equations involving the p‐Laplacian and a nonsmooth potential. Our approach is variational based on the nonsmooth critical point theory for functionals of the form φ = φ1 + φ2 with φ1 locally Lipschitz and φ2 proper, convex, lower semicontinuous.
Novel Method of Quantifying Pulmonary Vascular Resistance by Use of Simultaneous Invasive Pressure Monitoring and Phase-Contrast Magnetic Resonance Flow
Authors: Muthurangu Vivek , Taylor Andrew , Andriantsimiavona Rado , Hegde Sanjeet , Miquel Marc E. , Tulloh Robert , Baker Edward , Hill Derek L.G. , Razavi Reza S.
Published: August 2004

Background—

Pulmonary vascular resistance (PVR) quantification is important in the treatment of children with pulmonary hypertension. The Fick principle, used to quantify pulmonary artery flow, may be a flawed technique. We describe a novel method of PVR quantification by the use of magnetic resonance (MR) flow data and invasive pressure measurements.

Methods and Results—

In 24 patients with either suspected pulmonary hypertension or congenital heart disease requiring preoperative assessment, PVR was calculated by the use of simultaneously acquired MR flow and invasive pressure measurements (condition 1). In 19 of the 24 patients, PVR was also calculated at 20 ppm nitric oxide +30% (condition 2) and at 20 ppm nitric oxide +100% oxygen (condition 3), with the use of the MR method. This method proved safe and feasible in all patients. In 15 of 19 patients, PVR calculated by Fick flow was compared with the MR method. At condition 1, Bland-Altman analysis revealed a bias of 2.3% (MR > Fick) and limits of agreement of 50.2% to −45.5%. At condition 2, there was poorer agreement (bias was 28%, and the limits of agreement were 151.3% to 95.2%). At condition 3, there was very poor agreement (bias was 54.2%, and the limits of agreement were 174.4% to −66.0%).

Conclusions—

We have demonstrated the feasibility of using simultaneous invasive pressure measurements and MR flow data to measure PVR in humans.
Paclitaxel Balloon Coating, a Novel Method for Prevention and Therapy of Restenosis
Authors: Scheller Bruno , Speck Ulrich , Abramjuk Claudia , Bernhardt Ulrich , Böhm Michael , Nickenig Georg
Published: August 2004

Background—

Drug-eluting stents have shown promising antirestenotic effects in clinical trials. Non–stent-based local delivery of antiproliferative drugs may offer additional flexibility and also reach vessel areas beyond the immediate stent coverage. The aim of the present study was to evaluate a novel method of local drug delivery based on angioplasty balloons.

Methods and Results—

Stainless steel stents (n=40; diameter, 3.0 to 3.5 mm; length, 18 mm) were implanted in the left anterior descending and circumflex coronary arteries of domestic pigs. Both conventional uncoated and 3 different types of paclitaxel-coated, percutaneous transluminal coronary angioplasty balloons (contact with vessel wall for 1 minute) were used. No difference in short-term tolerance between coated and uncoated balloons and no signs of thrombotic events were observed. Quantitative angiography and histomorphometry of the stented arteries asserted the statistical equality of the baseline parameters between the control and the 3 treatment groups. Paclitaxel balloon coating led to a marked, dose-dependent reduction of parameters characterizing in-stent restenosis (reduction of neointimal area up to 63%). Despite the marked reduction in neointimal proliferation, endothelialization of stent struts was present in all samples. There was no evidence of a significant inflammatory response in the neighborhood of the stent struts.

Conclusions—

Paclitaxel balloon coating is safe, and it effectively inhibits restenosis after coronary angioplasty with stent implantation in the porcine model. The degree of reduction in neointimal formation was comparable to that achieved with drug-eluting stents.
Severe Aortic Stenosis and Myocardial Function
Authors: Bello Vitantonio Di , Giorgi Davide , Viacava Paolo , Enrica Talini , Nardi Carmela , Palagi Caterina , Donne Maria Grazia Delle , Verunelli Francesco , Mariani Massimo A. , Grandjean Jean , Dell’Anna Rita , Di Cori Andrea , Zucchelli Giulio , Romano Maria Francesca , Mariani Mario
Published: August 2004

Background—

The aim of this study was to assess the myocardial reflectivity pattern in severe aortic valve stenosis through the use of integrated backscatter (IBS) analysis. Patients with aortic stenosis (AS) were carefully selected in the Department of Cardiology.

Methods and Results—

Thirty-five subjects (AS: valve orifice ≤1 cm
2
; 12 female; mean age, 71.8±6.2 years) and 25 healthy subjects were studied. All subjects of the study had conventional 2D-Doppler echocardiography and IBS. Backscatter signal was sampled at the septum and posterior wall levels. Patients with AS were divided into 2 groups: 16 patients with initial signs of congestive heart failure and a depressed left ventricular systolic function (DSF) (ejection fraction [EF] range, 35% to 50%) and 19 asymptomatic patients with normal left ventricular systolic function (NSF) (EF >50%). Myocardial echo intensity (pericardium related) was significantly higher at the septum and posterior wall levels in DSF than in NSF and in control subjects. IBS variation, as an expression of variation of the signal, appeared to be significantly lower in AS with DSF than in NSF and in control subjects, at both the septum and posterior wall levels. Patients with DSF underwent aortic valve replacement, and, during surgical intervention, a septal myocardial biopsy was made for evaluation of myocardium/fibrosis ratio. Abnormally increased echo intensity was detected in left ventricular pressure overload by severe aortic stenosis and correlated with increase of myocardial collagen content (operating biopsy).

Conclusions—

One year after aortic valve replacement, we observed a significant reduction of left ventricular mass, and, only if pericardial indexed IBS value (reduction of interstitial fibrosis) decreased, it was possible to observe an improvement of EF and of IBS variation.
Bradycardia Induces Angiogenesis, Increases Coronary Reserve, and Preserves Function of the Postinfarcted Heart
Authors: Lei Li , Zhou Ruifeng , Zheng Wei , Christensen Lance P. , Weiss Robert M. , Tomanek Robert J.
Published: August 2004

Background—

We tested the hypothesis that induction of chronic bradycardia would trigger an upregulation of key growth factors and receptors, which would then lead to angiogenesis and improve coronary reserve in the left ventricle after myocardial infarction.

Methods and Results—

Bradycardia was induced in rats by administering alinidine via osmotic pumps beginning 1 day after coronary artery ligation. Echocardiographic analysis was conducted before and after treatment. Morphometric analysis was used in perfusion-fixed hearts to document arteriolar and capillary growth. Western blots were used to evaluate growth factor and receptor changes. During the first week of treatment, vascular endothelial growth factor (VEGF), VEGF receptor 1 (Flt-1), and basic fibroblast growth factor proteins were higher in the treated group, whereas VEGF receptor 2 (Flk-1), angiopoietin-1, and angiopoietin-2 were not affected by treatment. After 3 weeks, VEGF protein remained elevated, and bradycardia was associated with a higher capillary length density in the border (40%) and remote (14%) regions and a higher arteriolar length density in the septum (62%), despite a greater increase in left ventricular mass. Although arteriolar length density increased in all size classes, the greatest increase occurred in the smallest (terminal) arterioles. This vascular growth was associated with a 23% greater coronary reserve. Echocardiography revealed a smaller increase in ventricular volume and a greater preservation of ejection fraction in rats treated with bradycardia.

Conclusions—

Pharmacologic induction of bradycardia enhances vascularity and coronary reserve, preserves function of surviving myocardium, and therefore, is a noninvasive, therapeutic avenue that provides an alternative to gene therapy.
Endothelial β
3
-Adrenoceptors Mediate Vasorelaxation of Human Coronary Microarteries Through Nitric Oxide and Endothelium-Dependent Hyperpolarization
Authors: Dessy C. , Moniotte S. , Ghisdal P. , Havaux X. , Noirhomme P. , Balligand J.L.
Published: August 2004

Background—

Coronary vessel tone is modulated in part by β-adrenergic relaxation. However, the implication of specific β-adrenoceptor subtypes and their downstream vasorelaxing mechanism(s) in human coronary resistance arteries is poorly defined. β
3
-Adrenoceptors were recently shown to vasodilate animal vessels and are expressed in human hearts.

Methods and Results—

We examined the expression and functional role of β
3
-adrenoceptors in human coronary microarteries and their coupling to vasodilating nitric oxide (NO) and/or hyperpolarization mechanisms. The expression of β
3
-adrenoceptor mRNA and protein was demonstrated in extracts of human coronary microarteries. Immunohistochemical analysis revealed their exclusive localization in the endothelium, with no staining of vascular smooth muscle. In contractility experiments in which videomicroscopy was used, the nonspecific β-agonist isoproterenol and the β
3
-preferential agonist BRL37344 evoked an ≈50% relaxation of endothelin-1-preconstricted human coronary microarteries. Relaxations were blocked by the β
1
/β
2
/β
3
-adrenoceptor antagonist bupranolol but were insensitive to the β
1
/β
2
-adrenoceptor antagonist nadolol, confirming a β
3
-adrenoceptor-mediated pathway. Relaxation in response to BRL37344 was absent in human coronary microarteries devoid of functional endothelium. When human coronary microarteries were precontracted with KCl (thereby preventing vessel hyperpolarization), the relaxation to BRL37344 was reduced to 15.5% and totally abrogated by the NO synthase inhibitor
l
-ω-nitroarginine, confirming the participation of a NO synthase-mediated relaxation. The NO synthase-independent relaxation was completely inhibited by the Ca
2+
-activated K
+
channel inhibitors apamin and charybdotoxin, consistent with an additional endothelium-derived hyperpolarizing factor-like response. Accordingly, membrane potential recordings demonstrated vessel hyperpolarization in response to β
3
-adrenoceptor stimulation.

Conclusions—

β
3
-adrenoceptors are expressed in the endothelium of human coronary resistance arteries and mediate adrenergic vasodilatation through both NO and vessel hyperpolarization.
Electrophysiological Effects of Ranolazine, a Novel Antianginal Agent With Antiarrhythmic Properties
Authors: Antzelevitch Charles , Belardinelli Luiz , Zygmunt Andrew C. , Burashnikov Alexander , Di Diego José M. , Fish Jeffrey M. , Cordeiro Jonathan M. , Thomas George
Published: August 2004

Background—

Ranolazine is a novel antianginal agent capable of producing antiischemic effects at plasma concentrations of 2 to 6 μmol/L without reducing heart rate or blood pressure. The present study examines its electrophysiological effects in isolated canine ventricular myocytes, tissues, and arterially perfused left ventricular wedge preparations.

Methods and Results—

Transmembrane action potentials (APs) from epicardial and midmyocardial (M) regions and a pseudo-ECG were recorded simultaneously from wedge preparations. APs were also recorded from epicardial and M tissues. Whole-cell currents were recorded from epicardial and M myocytes. Ranolazine inhibited
I
Kr
(IC
50
=11.5 μmol/L), late
I
Na
, late
I
Ca
, peak
I
Ca
, and
I
Na-Ca
(IC
50
=5.9, 50, 296, and 91 μmol/L, respectively) and
I
Ks
(17% at 30 μmol/L), but caused little or no inhibition of
I
to
or
I
K1
. In tissues and wedge preparations, ranolazine produced a concentration-dependent prolongation of AP duration of epicardial but abbreviation of that of M cells, leading to reduction or no change in transmural dispersion of repolarization (TDR). At [K
+
]
o
=4 mmol/L, 10 μmol/L ranolazine prolonged QT interval by 20 ms but did not increase TDR. Extrasystolic activity and spontaneous torsade de pointes (TdP) were never observed, and stimulation-induced TdP could not be induced at any concentration of ranolazine, either in normal or low [K
+
]
o
. Ranolazine (5 to 20 μmol/L) suppressed early afterdepolarizations (EADs) and reduced the increase in TDR induced by the selective
I
Kr
blocker
d
-sotalol.

Conclusions—

Ranolazine produces ion channel effects similar to those observed after chronic amiodarone (reduced
I
Kr
,
I
Ks
, late
I
Na
, and
I
Ca
). The actions of ranolazine to suppress EADs and reduce TDR suggest that, in addition to its antianginal actions, the drug may possess antiarrhythmic activity.
Thin Filament-Based Modulation of Contractile Performance in Human Heart Failure
Authors: Noguchi Teruo , Hünlich Mark , Camp Phillip C. , Begin Kelly J. , El-Zaru Mohamed , Patten Richard , Leavitt Bruce J. , Ittleman Frank P. , Alpert Norman R. , LeWinter Martin M. , VanBuren Peter
Published: August 2004

Background—

The contribution of the sarcomere’s thin filament to the contractile dysfunction of human cardiomyopathy is not well understood.

Methods and Results—

We have developed techniques to isolate and functionally characterize intact (native) thin filaments obtained from failing and nonfailing human ventricular tissue. By use of in vitro motility and force assays, native thin filaments from failing ventricular tissue exhibited a 19% increase in maximal velocity but a 27% decrease in maximal contractile force compared with nonfailing myocardium. Native thin filaments isolated from human myocardium after left ventricular assist device support demonstrated a 37% increase in contractile force. Dephosphorylation of failing native thin filaments resulted in a near-normalization of thin-filament function, implying a phosphorylation-mediated mechanism. Tissue expression of the protein kinase C isoforms α, β
1
, and β
2
was increased in failing human myocardium and reduced after left ventricular assist device support.

Conclusions—

These novel findings demonstrate that (1) the thin filament is a key modulator of contractile performance in the failing human heart, (2) thin-filament function is restored to near normal levels after LVAD support, and (3) the alteration of thin-filament function in failing human myocardium is mediated through phosphorylation, most likely through activation of protein kinase C.
Low-Dose Therapy With the Long-Acting Erythropoietin Analogue Darbepoetin Alpha Persistently Activates Endothelial Akt and Attenuates Progressive Organ Failure
Authors: Bahlmann Ferdinand H. , Song Rong , Boehm Sascha M. , Mengel Michael , von Wasielewski Reinhard , Lindschau Carsten , Kirsch Torsten , de Groot Kirsten , Laudeley Robert , Niemczyk Eva , Güler Faikah , Menne Jan , Haller Hermann , Fliser Danilo
Published: August 2004

Background—

The hematopoietic cytokine erythropoietin has cytoprotective effects in endothelial cells in vitro that are mediated through direct activation of the pro-survival Akt tyrosine kinase signaling pathway. We tested the hypothesis that low-dose therapy with the long-acting recombinant human erythropoietin analogue darbepoetin alpha protects vascular endothelium in vivo in a classic remnant kidney rat model characterized by severe endothelial damage, progressive vascular sclerosis, and ischemia-induced tissue fibrosis.

Methods and Results—

Using a parallel group study design, we randomly assigned animals after 5/6 nephrectomy to treatment with either saline (n=36) or 0.1 μg/kg body wt darbepoetin (n=24) subcutaneously once weekly. We monitored hematocrit, blood pressure, and serum creatinine regularly and obtained renal tissue 6 weeks after nephrectomy for morphological and immunohistochemical analysis. Darbepoetin-treated animals had significantly improved survival compared with saline-treated controls (63% versus 33%;
P
<0.05), although hematocrit levels were similar in both groups. Darbepoetin treatment ameliorated endothelial damage; attenuated the composite tissue injury score (saline 1.9±0.4; darbepoetin 0.4±0.2;
P
<0.001), which included vascular sclerosis, glomerulosclerosis, and tubulointerstitial damage; and preserved renal function. We found persistent activation of the pro-survival Akt signaling pathway in endothelial and epithelial glomerular cells in darbepoetin-treated animals, accompanied by a significant reduction of apoptotic cell death in renal tissue.

Conclusions—

Low-dose darbepoetin treatment confers vascular and tissue protection that is associated with persistent stimulation of the pro-survival Akt signaling pathway. The use of recombinant human erythropoietin or analogues may have utility in preventing ischemia-related progressive vascular injury and organ failure.
Beating Heart Catheter-Based Edge-to-Edge Mitral Valve Procedure in a Porcine Model
Authors: Fann James I. , St. Goar Frederick G. , Komtebedde Jan , Oz Mehmet C. , Block Peter C. , Foster Elyse , Butany Jagdish , Feldman Ted , Burdon Thomas A.
Published: August 2004

Background—

Surgical edge-to-edge repair has been used in the treatment of mitral regurgitation. We evaluated the ability of a catheter-delivered clip (Evalve, Inc) to achieve edge-to-edge mitral valve approximation without cardiopulmonary bypass and the healing response of this technique.

Methods and Results—

Twenty-one pigs underwent general anesthesia and left thoracotomy. A 10F flexible delivery catheter with a clip was placed into the left atrium. With echocardiographic and fluoroscopic guidance, the clip grasped and approximated the mid portion of the anterior and posterior leaflets. After a double orifice had been confirmed, the clip was detached and the catheter withdrawn. All animals survived and had successful clip placement. Three animals were euthanized at 4 weeks, 9 at 12 weeks, 1 at 17 weeks, 7 at 24 weeks, and 1 at 52 weeks. The clip was well positioned, with leaflet approximation in all animals except 1, in which the clip separated from the posterior leaflet at 4 weeks without affecting valve function. The clip was modified and implanted in 4 pigs; all were intact at 12 to 24 weeks. Scanning electron microscopy showed clip encapsulation with complete endothelialization. Mitral stenosis and thromboembolism did not develop. Two animals developed endocarditis (1 at 12 weeks and 1 at 17 weeks). Progressive healing occurred in all other animals.

Conclusions—

Edge-to-edge mitral valve approximation can be successfully and reliably achieved with a catheter-delivered clip without cardiopulmonary bypass, resulting in durable healing. The success of this device supports the development of a percutaneous catheter-based system for mitral valve repair.
Involvement of the Serotonin 5-HT
2B
Receptor in Cardiac Hypertrophy Linked to Sympathetic Stimulation
Authors: Jaffré Fabrice , Callebert Jacques , Sarre Alexandre , Etienne Nelly , Nebigil Canan G. , Launay Jean-Marie , Maroteaux Luc , Monassier Laurent
Published: August 2004

Background—

The serotonergic 5-HT
2B
receptor regulates cardiomyocyte development and growth. A putative contribution of this receptor to fibroblast-dependent cardiac function has not been identified.

Methods and Results—

By mimicking sympathetic stimulation with chronic isoproterenol perfusion in vivo, we found that mice developed a cardiac hypertrophy, which was prevented by exposure to the 5-HT
2B
receptor antagonists SB206553 or SB215505 or in 5-HT
2B
receptor–knockout mice. The isoproterenol-induced hypertrophy was associated with an increase in the plasma levels of interleukin-1β and tumor necrosis factor-α but not interleukin-6. In contrast, the plasma isoproterenol-induced cytokine increase was not observed in either 5-HT
2B
receptor–mutant or wild-type mice perfused with isoproterenol+SB206553. We demonstrated that stimulation of wild-type cardiac fibroblasts by isoproterenol markedly increased the production of the interleukin-6, interleukin-1β, and tumor necrosis factor-α cytokines. Strikingly, we found that this isoproterenol-induced cytokine production was abolished by SB206553 or in 5-HT
2B
receptor–knockout fibroblasts. Serotonin also stimulated production of the 3 cytokines in wild-type fibroblasts, which was effectively reduced in 5-HT
2B
receptor–knockout fibroblasts.

Conclusions—

Our results demonstrate for the first time that 5-HT
2B
receptors are essential for isoproterenol-induced cardiac hypertrophy, which involves the regulation of interleukin-6, interleukin-1β, and tumor necrosis factor-α cytokine production by cardiac fibroblasts.
Albuminuria, a Therapeutic Target for Cardiovascular Protection in Type 2 Diabetic Patients With Nephropathy
Authors: de Zeeuw Dick , Remuzzi Giuseppe , Parving Hans-Henrik , Keane William F. , Zhang Zhongxin , Shahinfar Shahnaz , Snapinn Steve , Cooper Mark E. , Mitch William E. , Brenner Barry M.
Published: August 2004

Background—

Albuminuria is an established risk marker for both cardiovascular and renal outcomes. Albuminuria can be reduced with drugs that block the renin-angiotensin system (RAS). We questioned whether the short-term drug-induced change in albuminuria would predict the long-term cardioprotective efficacy of RAS intervention.

Methods and Results—

We analyzed data from Reduction in Endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL), a double-blind, randomized trial in 1513 type 2 diabetic patients with nephropathy, focusing on the relationship between the prespecified cardiovascular end point (composite) or hospitalization for heart failure and baseline or reduction in albuminuria. Patients with high baseline albuminuria (≥3 g/g creatinine) had a 1.92-fold (95% CI, 1.54 to 2.38) higher risk for the cardiovascular end point and a 2.70-fold (95% CI, 1.94 to 3.75) higher risk for heart failure compared with patients with low albuminuria (<1.5 g/g). Among all available baseline risk markers, albuminuria was the strongest predictor of cardiovascular outcome. The association between albuminuria and cardiovascular outcome was driven by those patients who also had a renal event. Modeling of the initial 6-month change in risk parameters showed that albuminuria reduction was the only predictor for cardiovascular outcome: 18% reduction in cardiovascular risk for every 50% reduction in albuminuria and a 27% reduction in heart failure risk for every 50% reduction in albuminuria.

Conclusions—

Albuminuria is an important factor predicting cardiovascular risk in patients with type 2 diabetic nephropathy. Reducing albuminuria in the first 6 months appears to afford cardiovascular protection in these patients.
β-Radiation for the Creation of Linear Lesions in the Canine Atrium
Authors: Guerra Peter G. , Talajic Mario , Thibault Bernard , Dubuc Marc , Roy Denis , Macle Laurent , Leung Tack Ki , Arsenault André , Harel François , Grégoire Jean , Bonan Raoul
Published: August 2004

Background—

Creating linear lesions is important for the treatment of arrhythmias such as atrial flutter and fibrillation. Making these lesions with standard radiofrequency catheters can be difficult and may result in charring and thrombosis. The purpose of this study was to evaluate β-radiation as a novel energy source for creating linear myocardial lesions.

Methods and Results—

Eight dogs with intact conduction across the cavotricuspid isthmus were studied. The isthmus was irradiated (25 to 50 Gy) with strontium/yttrium-90 delivered via a deflectable 7F catheter (Novoste Corporation). There were no immediate effects, but bidirectional conduction block developed during follow-up studies in 7 of 8 dogs. The dog without conduction block received 25 Gy. After the animals were euthanized, histology revealed transmural, linear areas of fibrosis without any thrombus.

Conclusions—

β-Radiation can safely and effectively create linear lesions that are contiguous and nonthrombogenic. This energy source may become an interesting adjunct to radiofrequency for the treatment of atrial flutter and fibrillation.
Relationship Between Activated Clotting Time and Ischemic or Hemorrhagic Complications
Authors: Brener Sorin J. , Moliterno David J. , Lincoff A. Michael , Steinhubl Steven R. , Wolski Kathy E. , Topol Eric J.
Published: August 2004

Background—

Unfractionated heparin (UFH) is the most widely used antithrombin during percutaneous coronary intervention (PCI). Despite significant pharmacological and mechanical advancements in PCI, uncertainty remains about the optimal activated clotting time (ACT) for prevention of ischemic or hemorrhagic complications.

Methods and Results—

We analyzed the outcome of all UFH-treated patients enrolled in 4 large, contemporary PCI trials with independent adjudication of ischemic and bleeding events. Of 9974 eligible patients, maximum ACT was available in 8369 (84%). The median ACT was 297 seconds (interquartile range 256 to 348 seconds). The incidence of death, myocardial infarction, or revascularization at 48 hours, by ACT quartile, was 6.2%, 6.8%, 6.0%, and 5.7%, respectively (
P
=0.40 for trend). Covariate-adjusted rate of ischemic complications was not correlated with maximal procedural ACT (continuous value,
P
=0.29). Higher doses of UFH (>5000 U, or up to 90 U/kg) were independently associated with higher rates of events. The incidence of major or minor bleeding at 48 hours, by ACT quartile, was 2.9%, 3.5%, 3.8%, and 4.0%, respectively (
P
=0.04 for trend). In a multivariable logistic model with a spline transformation for ACT, there was a linear increase in risk of bleeding as the ACT approached 365 seconds (
P
=0.01), which leveled off beyond that value. Increasing UFH weight-indexed dose was independently associated with higher bleeding rates (OR 1.04 [1.02 to 1.07] for each 10 U/kg,
P
=0.001).

Conclusions—

In patients undergoing PCI with frequent stent and potent platelet inhibition use, ACT does not correlate with ischemic complications and has a modest association with bleeding complications, driven mainly by minor bleeding. Lower values do not appear to compromise efficacy while increasing safety.
Phase 2 Reentry as a Trigger to Initiate Ventricular Fibrillation During Early Acute Myocardial Ischemia
Authors: Yan Gan-Xin , Joshi Ajay , Guo Donglin , Hlaing Thinn , Martin Jack , Xu Xiaoping , Kowey Peter R.
Published: August 2004

Background—

Phase 2 reentry caused by heterogeneous loss of the transient outward potassium current (
I
to
)–mediated epicardial action potential (AP) dome can produce a closely coupled R-on-T extrasystole leading to ventricular fibrillation (VF) under conditions of ST-segment elevation unrelated to ischemia. The present study examined the role of phase 2 reentry in the initiation of VF during early myocardial ischemia.

Methods and Results—

Regional myocardial ischemia was produced in an isolated, arterially perfused canine right ventricular wedge preparation. Transmembrane APs from 2 epicardial sites at each side of the ischemic border were simultaneously recorded together with measurements of extracellular potassium concentration ([K
+
]
o
) and a transmural ECG. Loss of the
I
to
-mediated epicardial AP dome in the ischemic zone but not in the perfused tissue resulted in phase 2 reentry and associated R-on-T extrasystoles capable of initiating VF in 7 of 15 preparations during the first 3 to 9 minutes of myocardial ischemia, with marked ST-segment elevation and [K
+
]
o
accumulation. The
I
to
and phase 1 magnitude of epicardium contributed importantly to the onset of VF. Phase 1 magnitude and
I
to
density at +30 mV in the group with phase 2 reentry–related R-on-T extrasystoles were 32.2±1.3 mV and 30.3±0.5 pA/pF (n=7), respectively, significantly greater than those (24.0±1.8 mV and 23.2±1.0 pA/pF) in the group without the extrasystoles (n=8,
P
<0.01).

Conclusions—

Acute regional myocardial ischemia results in markedly heterogeneous loss of
I
to
-mediated epicardial AP domes across the ischemic border, leading to phase 2 reentry. Phase 2 reentry can in turn produce an R-on-T extrasystole capable of initiating VF.
Plasma Surfactant Protein-B
Authors: De Pasquale Carmine G. , Arnolda Leonard F. , Doyle Ian R. , Aylward Philip E. , Chew Derek P. , Bersten Andrew D.
Published: August 2004

Background—

In chronic heart failure (CHF), elevated pulmonary microvascular pressure (P
mv
) results in pulmonary edema. Because elevated P
mv
may alter the integrity of the alveolocapillary barrier, allowing leakage of surfactant protein-B (SP-B) from the alveoli into the circulation, we aimed to determine plasma levels of SP-B in CHF and their relation to clinical status.

Methods and Results—

Fifty-three outpatients with CHF had plasma SP-B and N-terminal proBNP (NT-proBNP) assayed, in addition to a formalized clinical assessment at each clinic review over a period of 18 months. The control group comprised 19 normal volunteers. Plasma SP-B was elevated in CHF (
P
<0.001), and levels increased with New York Heart Association classification (
P
<0.001). SP-B correlated with objective clinical status parameters and NT-proBNP. During follow-up, major cardiovascular events occurred in patients with higher plasma SP-B (
P
<0.01) and NT-proBNP (
P
<0.05). Furthermore, on conditional logistic regression analysis, only SP-B was independently associated with CHF hospitalization (
P
=0.005). The 53 patients underwent a total of 210 outpatient visits. When the diuretic dosage was increased on clinical grounds, SP-B had increased 39% (
P
<0.001) and NT-proBNP had increased 32% (
P
<0.001). Conversely, at the next visit, SP-B fell 12% (
P
<0.001), whereas NT-proBNP fell 39% (
P
<0.001).

Conclusions—

Plasma SP-B is increased in CHF, and levels are related to clinical severity. Furthermore, within individual patients, SP-B levels vary with dynamic clinical status and NT-proBNP levels. Because plasma SP-B is independently associated with CHF hospitalization, it may, by virtue of its differing release mechanism to NT-proBNP, be a clinically useful biomarker of the pulmonary consequences of raised P
mv
.
Endothelial Cells Promote Cardiac Myocyte Survival and Spatial Reorganization
Authors: Narmoneva Daria A. , Vukmirovic Rada , Davis Michael E. , Kamm Roger D. , Lee Richard T.
Published: August 2004

Background—

Endothelial–cardiac myocyte (CM) interactions play a key role in regulating cardiac function, but the role of these interactions in CM survival is unknown. This study tested the hypothesis that endothelial cells (ECs) promote CM survival and enhance spatial organization in a 3-dimensional configuration.

Methods and Results—

Microvascular ECs and neonatal CMs were seeded on peptide hydrogels in 1 of 3 experimental configurations: CMs alone, CMs mixed with ECs (coculture), or CMs seeded on preformed EC networks (prevascularized). Capillary-like networks formed by ECs promoted marked CM reorganization along the EC structures, in contrast to limited organization of CMs cultured alone. The presence of ECs markedly inhibited CM apoptosis and necrosis at all time points. In addition, CMs on preformed EC networks resulted in significantly less CM apoptosis and necrosis compared with simultaneous EC-CM seeding (
P
<0.01, ANOVA). Furthermore, ECs promoted synchronized contraction of CMs as well as connexin 43 expression.

Conclusions—

These results provide direct evidence for a novel role of endothelium in survival and organization of nearby CMs. Successful strategies for cardiac regeneration may therefore depend on establishing functional CM–endothelium interactions.
Visceral Periadventitial Adipose Tissue Regulates Arterial Tone of Mesenteric Arteries
Authors: Verlohren Stefan , Dubrovska Galyna , Tsang Suk-Ying , Essin Kirill , Luft Friedrich C. , Huang Yu , Gollasch Maik
Published: August 2004

Periadventitial adipose tissue produces vasoactive substances that influence vascular contraction. Earlier studies addressed this issue in aorta, a vessel that does not contribute to peripheral vascular resistance. We tested the hypothesis that periadventitial adipose tissue modulates contraction of smaller arteries more relevant to blood pressure regulation. We studied mesenteric artery rings surrounded by periadventitial adipose tissue from adult male Sprague-Dawley rats. The contractile response to serotonin, phenylephrine, and endothelin I was markedly reduced in intact vessels compared with vessels without periadventitial fat. The contractile response to U46619 or depolarizing high K
+
-containing solutions (60 mmol/L) was similar in vessels with and without periadventitial fat. The K
+
channel opener cromakalim induced relaxation of vessels precontracted by serotonin but not by U46619 or high K
+
-containing solutions (60 mmol/L), suggesting that K
+
channels are involved. The intracellular membrane potential of smooth muscle cells was more hyperpolarized in intact vessels than in vessels without periadventitial fat. Both the anticontractile effect and membrane hyperpolarization of periadventitial fat were abolished by inhibition of delayed-rectifier K
+
(K
v
) channels with 4-aminopyridine (2 mmol/L) or 3,4-diaminopyridine (1 mmol/L). Blocking other K
+
channels with glibenclamide (3 μmol/L), apamin (1 μmol/L), iberiotoxin (100 nmol/L), tetraethylammonium ions (1 mmol/L), tetrapentylammonium ions (10 μmol/L), or Ba
2+
(3 μmol/L) had no effect. Longitudinal removal of half the perivascular tissue reduced the anticontractile effect of fat by almost 50%, whereas removal of the endothelium had no effect. We suggest that visceral periadventitial adipose tissue controls mesenteric arterial tone by inducing vasorelaxation via K
v
channel activation in vascular smooth muscle cells.
Endogenous Angiotensin II Induces Atherosclerotic Plaque Vulnerability and Elicits a Th1 Response in ApoE
−/−
Mice
Authors: Mazzolai Lucia , Duchosal Michel A. , Korber Martine , Bouzourene Karima , Aubert Jean François , Hao Hiroyuki , Vallet Veronique , Brunner Hans- R. , Nussberger Jürg , Gabbiani Giulio , Hayoz Daniel
Published: August 2004

Rupture of vulnerable plaques is the main cause of acute cardiovascular events. However, mechanisms responsible for transforming a stable into a vulnerable plaque remain elusive. Angiotensin II, a key regulator of blood pressure homeostasis, has a potential role in atherosclerosis. To study the contribution of angiotensin II in plaque vulnerability, we generated hypertensive hypercholesterolemic ApoE
−/−
mice with either normal or endogenously increased angiotensin II production (renovascular hypertension models). Hypertensive high angiotensin II ApoE
−/−
mice developed unstable plaques, whereas in hypertensive normal angiotensin II ApoE
−/−
mice plaques showed a stable phenotype. Vulnerable plaques from high angiotensin II ApoE
−/−
mice had thinner fibrous cap (
P
<0.01), larger lipid core (
P
<0.01), and increased macrophage content (
P
<0.01) than even more hypertensive but normal angiotensin II ApoE
−/−
mice. Moreover, in mice with high angiotensin II, a skewed T helper type 1-like phenotype was observed. Splenocytes from high angiotensin II ApoE
−/−
mice produced significantly higher amounts of interferon (IFN)-γ than those from ApoE
−/−
mice with normal angiotensin II; secretion of IL4 and IL10 was not different. In addition, we provide evidence for a direct stimulating effect of angiotensin II on lymphocyte IFN-γ production. These findings suggest a new mechanism in plaque vulnerability demonstrating that angiotensin II, within the context of hypertension and hypercholesterolemia, independently from its hemodynamic effect behaves as a local modulator promoting the induction of vulnerable plaques probably via a T helper switch.
Retinal Arteriolar Narrowing Is Associated With 5-Year Incident Severe Hypertension
Authors: Smith Wayne , Wang Jie Jin , Wong Tien Yin , Rochtchina Elena , Klein Ronald , Leeder Stephen R. , Mitchell Paul
Published: August 2004

We assessed whether retinal arteriolar narrowing and structural abnormalities independently predicted 5-year incident severe (grade 2 or 3) hypertension in an older population-based cohort. The Blue Mountains Eye Study baseline (1992 to 1994) examined 3654 residents aged 49 and older in 2 postal code areas, west of Sydney. Of the 2335 participants (75.1% of survivors) who returned at the 5-year examinations, 1319 were normotensive or had mild (grade 1) hypertension at baseline. Baseline retinal photographs were graded for focal retinal vessel wall signs and vessel diameters were measured. Participants were classified as having normal, high-normal blood pressure [BP] (systolic BP 121 to 139 mm Hg and/or diastolic BP 81 to 89 mm Hg), mild hypertension (systolic BP 140 to 159 mm Hg and/or diastolic BP 90 to 99 mm Hg), or severe hypertension if they had a previous diagnosis of hypertension and were receiving antihypertensive medications or had systolic BP ≥160 mm Hg and/or diastolic BP ≥100 mm Hg at examination. Incident severe hypertension was defined in persons who were free of severe hypertension at baseline but classified as having severe hypertension at the 5-year examinations. Of the 1319 baseline subjects at risk, 390 (29.6%) developed severe hypertension. After adjusting for age, sex, body mass index, smoking, glucose, and total cholesterol, generalized retinal arteriolar narrowing at baseline was associated with increased risk of incident severe hypertension (odds ratio 2.6; 95% confidence interval, 1.7 to 3.9) when comparing the narrowest versus widest quintile. This association remained significant after further adjustment for baseline mean arterial BP or BP status. Our findings support the hypothesis that small vessel structural changes may precede the development of severe hypertension.
The Religious System of Global Society: A Sociological Look at Contemporary Religion and Religions
Authors: Beyer Peter
Published: August 2004

Controversies within religious studies over the categories of religion and religions are reflective of changes in religion that correspond to the historical development of global society in recent centuries. The globalization of society has created social conditions that encourage the differentiation of religion as a distinct modality of social communication based on binary codes and centred on institutionalized programmes that flow from these. The result has been the gradual construction and imagining of an ambiguous but nonetheless observable and operative global religious system. From its beginnings in early modern Western Christianity, the system has spread haltingly and gradually to the rest of the world. Similar to the way the spread of the global political system brought about the discovery and construction of nations, the development of the religious system has resulted in the crystallization of ‘religions’, especially but not exclusively what we now call the world religions. The examples of Christianity, Hinduism, Islam, and Chinese religion are discussed briefly as illustration.
The Politics of Pure Land Buddhism in India
Authors: Amstutz Galen
Published: August 2004

Pure Land Buddhism achieved its primary influence in East Asia because it supplied a nonmonastic, autonomous source of religious authority and practice to middle elites in those cultural regions. In contrast Pure Land failed to achieve any success in India. The explanation for the marginalization of Indian Pure Land is probably sociopolitical: Pure Land teachings tended to bypass not only the authority of the Hindu brahmins, but even the authority of Buddhist renunciate orders. Indian social history did not produce any significant middle elites concerned with such non-gurucentric religious authority. As a result, Buddhist India did not produce any innovations in the upâya of religious institutionalization in Buddhism.
Exodus III 19B and the Interpretation of Biblical Narrative
Authors: Addinall Peter
Published: August 2004

God tells Moses that the king of Egypt will not let the Hebrews go, not even by a mighty hand. It is, however, a basic theme of the Exodus narrative that the king of Egypt is in fact compelled to let the Hebrews go by the mighty hand of Yahweh. From ancient times to the present commentators and translators have in general either eliminated the contradiction by re-writing the text or adopting a forced interpretation of it. A different but by no means novel approach to the text removes the contradiction and at the same time poses a challenge to much generally accepted analysis of biblical narrative.
Jesaja X 18
Authors: Dafni Evangelia
Published: August 2004

Der Wortkomplex (Jes. x 18) ist ein hapax legomenon und wird im allgemeinen als sprichwörtliche Redewendung betrachtet, die das "ganz und gar" zum Ausdruck bringt. Dieser Wortkomplex ist m.E. mit (1 Sam. xv 3 u.a.) und (Nu. v 3) zu vergleichen, weil alle drei aus Einzelwörtern bestehen, die vor allem und grundsätzlich der at.lichen Anthropologie angehören. Jedoch beachtenswert ist, daß bei den bisherigen Jesaja-Kommentatoren keine anthropologische Bewertung der an der betreffenden Stelle vorhandenen Kombination von und gibt. Das Gleiche gilt ebenso auch für die at.liche anthropologische Forschung, die m.W. die Jesaja-Stelle nicht gebührend beachtet hat. In meinem Aufsatz versuche ich durch eingehende Untersuchung a) der Textzusammenhänge, b) der im Alten Testament vorhandenen ähnlichen und im allgemenen vergleichbaren Wortkomplexe sowie c) der Evidenz der alten Übersetzungen dem eigentlichen Sinn von näherzukommen.
Biblical Historiography and Literary History: A Programmatic Survey
Authors: Kallai Zecharia
Published: August 2004

The issue addressed concerns relative literary chronology, involving the quest for historicity of literary witnesses and their literary history. The question of historicity was elsewhere shown to be bound up with the basic historiographical concepts embodied in the literary compositions. The manifestation of these concepts facilitates observations concerning literary relativity. The study of the literary history based on historiographical data and considerations pertains to two important facets. One is the primary and dependent formulation of historiographical concepts and the other is the changing manner of application of these patterns. Historiographical and geographical features that reflect the early monarchy figure in a specific manner up to the end of the first commonwealth, and as of Ezekiel, in Ezra and Nehemiah, as well as in Chronicles, a change in the application of these motifs is to be noted. The exilic period is, therefore, an incisive stylistic boundary.