bluuebunny/crossref_metadata_2025 huggingface dataset:
National Patterns of Use and Effectiveness of Angiotensin-Converting Enzyme Inhibitors in Older Patients With Heart Failure and Left Ventricular Systolic Dysfunction
Authors: Masoudi Frederick A. , Rathore Saif S. , Wang Yongfei , Havranek Edward P. , Curtis Jeptha P. , Foody JoAnne Micale , Krumholz Harlan M.
Published: August 2004

Background—

Although ACE inhibitors are underprescribed for heart failure, factors associated with their use are not well described. Furthermore, the effectiveness of ACE inhibitors has been questioned in some populations, potentially contributing to underuse. Our objectives were to assess the correlates of ACE inhibitor use and the relationship between ACE inhibitor prescription and mortality in older patients with heart failure.

Methods and Results—

We studied a national sample aged ≥65 years who had survived hospitalization for heart failure between April 1998 and March 1999 or July 2000 and June 2001, restricting the analysis to patients with left ventricular systolic dysfunction and without a documented contraindication to use of ACE inhibitors (n=17 456). Factors associated with ACE inhibitor prescription at discharge and the relationship between ACE inhibitor prescription and death within 1 year were assessed with hierarchical logistic models. Secondary analyses assessed therapeutic substitution with angiotensin receptor blockers (ARBs). ACE inhibitors were prescribed to only 68% of this ideal cohort, and 76% received either an ACE inhibitor or an ARB. Patient, physician, and hospital factors were weak predictors of prescription, except for serum creatinine (RR for 133 to 221 μmol/L=0.87, 95% CI 0.85 to 0.89; RR for ≥222 μmol/L=0.53, 95% CI 0.49 to 0.57 compared with ≤132 μmol/L). ACE inhibitor prescription was associated with lower crude 1-year mortality (33.0% versus 42.1%,
P
<0.001), lower risk of death after adjustment (RR 0.86, 95% CI 0.82 to 0.90), and lower mortality regardless of patient gender, age, race, or serum creatinine level.

Conclusions—

ACE inhibitors were widely underprescribed despite evidence of a favorable impact on survival in a broad range of patients with heart failure. These results emphasize the importance of ongoing efforts to translate clinical trial results into practice.
Randomized, Double-Blind, Placebo-Controlled Trial of Oral Sirolimus for Restenosis Prevention in Patients With In-Stent Restenosis
Authors: Hausleiter Jörg , Kastrati Adnan , Mehilli Julinda , Vogeser Michael , Zohlnhöfer Dietlind , Schühlen Helmut , Goos Christoph , Pache Jürgen , Dotzer Franz , Pogatsa-Murray Gisela , Dirschinger Josef , Heemann Uwe , Schömig Albert
Published: August 2004

Background—

Despite recent advances in interventional cardiology, including the introduction of drug-eluting stents for de novo coronary lesions, the treatment of in-stent restenosis (ISR) remains a challenging clinical issue. Given the efficacy of systemic sirolimus administration to prevent neointimal hyperplasia in animal models and to halt and even reverse the progression of allograft vasculopathy, the aim of the present double-blind, placebo-controlled study was to evaluate the efficacy of a 10-day oral sirolimus treatment with 2 different loading regimens for the prevention of recurrent restenosis in patients with ISR.

Methods and Results—

Three hundred symptomatic patients with ISR were randomly assigned to 1 of 3 treatment arms: placebo or usual-dose or high-dose sirolimus. Patients received a cumulative loading dose of 0, 8, or 24 mg of sirolimus 2 days before and the day of repeat intervention followed by maintenance therapy of 2 mg/d for 7 days. Angiographic restenosis at 6-month angiography was the primary end point of the study. Restenosis was significantly reduced from 42.2% to 38.6% and to 22.1% in the placebo, usual-dose, and high-dose sirolimus groups, respectively (
P
=0.005). Similarly, the need for target vessel revascularization was reduced from 25.5% to 24.2% and to 15.2% in the placebo, usual-dose, and high-dose groups, respectively (
P
=0.08). The sirolimus blood concentration on the day of the procedure correlated significantly with the late lumen loss at follow-up (
P
<0.001).

Conclusions—

In patients with ISR, an oral adjunctive sirolimus treatment with an intensified loading regimen before coronary intervention resulted in a significant improvement in the angiographic parameters of restenosis.
Mineralocorticoid Receptor Antagonism Prevents the Electrical Remodeling That Precedes Cellular Hypertrophy After Myocardial Infarction
Authors: Perrier Emeline , Kerfant Benoît-Gilles , Lalevee Nathalie , Bideaux Patrice , Rossier Michel F. , Richard Sylvain , Gómez Ana María , Benitah Jean-Pierre
Published: August 2004

Background—

Cardiac hypertrophy underlies arrhythmias and sudden death, for which mineralocorticoid receptor (MR) activity has recently been implicated. We sought to establish the sequence of ionic events that link the initiating insult and MR to hypertrophy development.

Methods and Results—

Using whole-cell, patch-clamp and quantitative reverse transcription–polymerase chain reaction techniques on right ventricular myocytes of a myocardial infarction (MI) rat model, we examined the cellular response over time. One week after MI, no sign of cellular hypertrophy was found, but action potential duration (APD) was lengthened. Both an increase in Ca
2+
current (
I
Ca
) and a decrease in K
+
transient outward current (
I
to
) underlay this effect. Consistently, the relative expression of mRNA coding for the Ca
2+
channel α1C subunit (Ca
v
1.2) increased, and that of the K
+
channel K
v
4.2 subunit decreased. Three weeks after MI, AP prolongation endured, whereas cellular hypertrophy developed.
I
Ca
density, Ca
v
1.2, and K
v
4.2 mRNA levels regained control levels, but
I
to
density remained reduced. Long-term treatment with RU28318, an MR antagonist, prevented this electrical remodeling. In a different etiologic model of abdominal aortic constriction, we confirmed that APD prolongation and modifications of ionic currents precede cellular hypertrophy.

Conclusions—

Electrical remodeling, which is triggered at least in part by MR activation, is an initial, early cellular response to hypertrophic insults.
Electrocardiographic Predictors of Arrhythmic Death and Total Mortality in the Multicenter Unsustained Tachycardia Trial
Authors: Zimetbaum Peter J. , Buxton Alfred E. , Batsford William , Fisher John D. , Hafley Gail E. , Lee Kerry L. , O’Toole Michael F. , Page Richard L. , Reynolds Matthew , Josephson Mark E.
Published: August 2004

Background—

Stratifiers of sudden and total mortality risk are needed to optimally target preventive therapies in patients with coronary artery disease and impaired ventricular function. We assessed the prognostic significance of ECG markers of conduction abnormalities and left ventricular hypertrophy in the Multicenter Unsustained Tachycardia Trial (MUSTT).

Methods and Results—

We analyzed the ECGs of 1638 patients from MUSTT who did not receive antiarrhythmic therapy (antiarrhythmic medication or implantable cardioverter-defibrillator). After adjustment for other significant factors, left bundle-branch block and intraventricular conduction delay were associated with a 50% increase in the risk of both arrhythmic and total mortality. Right bundle-branch block was not associated with arrhythmic or total mortality. Left ventricular hypertrophy was the only ECG predictor of arrhythmic (hazard ratio, 1.35; 95% CI, 1.08 to 1.69) but not total mortality.

Conclusions—

In patients with coronary artery disease, depressed left ventricular function, and nonsustained ventricular tachycardia, QRS prolongation resulting from left bundle-branch block or intraventricular conduction delay but not right bundle-branch block provided prognostic information about the risk of arrhythmic and total mortality independently of electrophysiological evaluation and ejection fraction. Left ventricular hypertrophy was associated with increased arrhythmic but not total mortality.
Impact of Prolonged Cyclooxygenase-2 Inhibition on Inflammatory Markers and Endothelial Function in Patients With Ischemic Heart Disease and Raised C-Reactive Protein
Authors: Bogaty Peter , Brophy James M. , Noel Martin , Boyer Luce , Simard Serge , Bertrand Fernand , Dagenais Gilles R.
Published: August 2004

Background—

The impact of cyclooxygenase (COX)-2 antagonist treatment on acute coronary risk is controversial. We investigated the effect of prolonged COX-2 inhibition on inflammatory profile and endothelial function in patients with ischemic heart disease and high serum C-reactive protein (CRP) values.

Methods and Results—

In a double-blind study, 35 stable subjects on low-dose aspirin with ≥2 previous acute coronary events and 2 of 2 screening CRP values >2.0 mg/L were randomized to the COX-2 inhibitor rofecoxib (25 mg) or placebo daily for 6 months. Serum CRP, interleukin-6 (IL-6), P-selectin, matrix metalloproteinase-9 (MMP-9), and brachial artery endothelial function were evaluated. In the placebo group, CRP (median) was 3.16 mg/L (25% and 75% quartiles, 1.90 and 5.78 mg/L) at baseline and 4.22 mg/L (25% and 75% quartiles, 2.04 and 6.25 mg/L) at 6 months; in the rofecoxib group, CRP was 3.45 mg/L (25% and 75% quartiles, 2.08 and 5.78 mg/L) at baseline and 1.41 mg/L (25% and 75% quartiles, 1.17 and 4.81 mg/L) at 6 months (
P
=0.03). Rofecoxib compared with placebo also lowered IL-6 at 6 months (
P
=0.0002). There was a significant off-drug effect on CRP and IL-6 levels in the rofecoxib group 3 months after treatment (
P
=0.005 and
P
=0.009, respectively). Rofecoxib did not significantly affect P-selectin, MMP-9, and brachial artery vasoreactivity.

Conclusions—

Prolonged COX-2 inhibition attenuates CRP and IL-6, does not modify P-selectin and MMP-9, and has no deleterious effect on endothelial function in stable patients with a history of recurrent acute coronary events and raised CRP. These results strengthen the rationale for evaluating the clinical benefit of COX-2 inhibition in patients with ischemic heart disease.
Soluble CD40 Ligand in Pulmonary Arterial Hypertension
Authors: Damås Jan K. , Otterdal Kari , Yndestad Arne , Aass Halfdan , Solum Nils O. , Frøland Stig S. , Simonsen Svein , Aukrust Pål , Andreassen Arne K.
Published: August 2004

Background—

Inflammatory processes seem to be involved in pulmonary arterial hypertension (PAH). CD40 ligand (L) may promote inflammation and thrombus formation, and we hypothesized that CD40L could be involved in the pathogenesis of PAH.

Methods and Results—

Several significant findings were revealed when examining the possible role of CD40L in PAH. (1) Patients with primary (n=13) and secondary (n=11) PAH but not those with chronic thromboembolic pulmonary hypertension (n=8) had increased plasma levels of soluble (s) CD40L compared with control subjects (n=8). (2) PAH patients using warfarin had markedly lower sCD40L levels than those without such therapy. (3) sCD40L levels were higher in arterial (femoral artery) compared with mixed venous blood (pulmonary artery), suggesting enhanced release or reduced clearance in the pulmonary vasculature. (4) Platelets from PAH patients showed enhanced spontaneous and SFLLRN-stimulated release of sCD40L compared with control subjects. (5) In vitro, recombinant sCD40L induced monocyte chemoattractant protein (MCP)-1 and interleukin-8 gene expression in endothelial cells, and plasma levels of these chemokines were raised in all PAH groups, significantly correlated to sCD40L and hemodynamic parameters. (6) Although prostacyclin therapy (3 months) showed clinical benefit, this therapy had no effect on sCD40L and increased MCP-1 levels in PAH patients, and prostacyclin enhanced MCP-1 in CD40L-stimulated endothelial cells.

Conclusions—

Our findings suggest a role for CD40L in the pathogenesis of PAH, possibly operating through an interaction between platelets and endothelial cells involving chemokine-related mechanisms.
Hypertensive Response to Acute Stress Is Attenuated in Interleukin-6 Knockout Mice
Authors: Lee Dexter L. , Leite Romulo , Fleming Cassandra , Pollock Jennifer S. , Webb R. Clinton , Brands Michael W.
Published: August 2004

This study tested the hypothesis that the inflammatory cytokine, interleukin-6, contributes to the hypertensive response to acute psychosocial stress, caused by switching male mice to a cage previously occupied by a different male mouse. Male C57BL6 (WT) and interleukin-6 (IL-6) knockout (KO) mice were implanted with biotelemetry devices to monitor mean arterial pressure, heart rate, and motor activity in the unrestrained state. Baseline mean arterial pressure was 98±1 and 103±1 for WT and IL-6 KO mice. Cage switch increased mean arterial pressure by 42±2 mm Hg in WT mice, but this was blunted significantly in KO mice (31±3 mm Hg peak increase). Area under the curve for the first 90 minutes also was significantly less. Heart rate and motor activity increased similarly, and there also were no differences in the increases in plasma renin activity or plasma norepinephrine concentration between WT and KO mice. Thus, the acute hypertensive response to psychosocial stress depends significantly on IL-6, and the effect appears to be specific for blood pressure rather than to a global impairment in the response to stress. However, because perfusion of the isolated mesenteric bed with phenylephrine and chronic infusion of angiotensin II caused similar responses in WT and IL-6 KO mice, it is clear that future studies are needed to determine to what extent the acute blood pressure effect of IL-6 is stress-specific.
Intracellular and Extracellular Angiotensin II Enhance the L-Type Calcium Current in the Failing Heart
Authors: De Mello Walmor C. , Monterrubio Jose
Published: August 2004

The influence of intracellular and extracellular angiotensin II (Ang II) on the L-type calcium current of cardiomyocytes isolated from cardiomyopathic hamsters was investigated. The results indicated that Ang II (10
−8
mmol/L), added to the bath, increased the peak inward calcium current (I
Ca
) density by 37±3.4% (
P
<0.05), an effect that depends on the activation of protein kinase C. Intracellular administration of the same dose of Ang II (10
−8
mmol/L) also elicited an increase of peak I
Ca
density but enhanced the rate of I
Ca
inactivation, an effect not seen with extracellular Ang II. Moreover, in control animals, no change in the rate of I
Ca
inactivation was seen with intracellular Ang II. Thapsigargin (1 μmol/L), a potent inhibitor of sarcoplasmic reticulum (SR) ATPase, which depletes the SR, decreased the rate of I
Ca
inactivation elicited by intracellular Ang II, although the cytoplasmic calcium concentration was highly buffered with 10 mmol/L EGTA. These findings might indicate that intracellular Ang II releases calcium from the SR and inactivates I
Ca
. The effect of intracellular Ang II on peak I
Ca
was not altered by extracellular losartan (10
−7
mmol/L), supporting the notion that the peptide acted intracellularly. Other studies showed that intracellular Ang I administration (10
−8
mmol/L) enhanced the peak I
Ca
density and the rate of I
Ca
inactivation, an effect that was reduced by intracellular enalaprilat (10
−8
mmol/L). Moreover, intracellular enalaprilat by itself reduced the peak I
Ca
density. These observations might indicate that endogenous Ang II is contributing to I
Ca
modulation in the failing heart.
Differences in Circadian Pattern of Ambulatory Pulse Pressure Between Healthy and Complicated Pregnancies
Authors: Hermida Ramón C. , Ayala Diana E. , Iglesias Manuel
Published: August 2004

With the use of ambulatory monitoring, a circadian blood pressure pattern has been shown to characterize normotensive as well as hypertensive pregnant women. However, the potential differences between healthy and complicated pregnancies in pulse pressure, an independent marker of cardiovascular risk in the general population, have not yet been investigated. We analyzed 2523 blood pressure series sampled for 48 hours once every 4 weeks from the first obstetric visit until delivery in 245 women with uncomplicated pregnancies, 140 with gestational hypertension, and 49 who developed preeclampsia. Compared with uncomplicated pregnancies, a statistically significant elevation in the 24-hour mean of pulse pressure is found in complicated pregnancies in all trimesters (
P
<0.001). Results further indicate similar 24-hour mean of pulse pressure between gestational hypertension and preeclampsia in the first trimester of pregnancy (
P
=0.158). The increase in pulse pressure among women who developed preeclampsia compared with women with gestational hypertension, although small, was statistically significant in the second trimester (1.4 mm Hg;
P
=0.010) and, to a larger extent, in the third trimester of pregnancy (1.8 mm Hg;
P
<0.001). The differences in pulse pressure between healthy and complicated pregnancies, observed already in the first trimester of gestation, are found when systolic and diastolic blood pressure for women with a later diagnosis of gestational hypertension or preeclampsia are within the accepted range of normotension. Moreover, ambulatory pulse pressure provides higher sensitivity than clinic measurements for the diagnosis of hypertension in pregnancy.
Treatment of Dilated Cardiomyopathy With Electroporation of Hepatocyte Growth Factor Gene Into Skeletal Muscle
Authors: Komamura Kazuo , Tatsumi Rie , Miyazaki Jun-ichi , Matsumoto Kunio , Yamato Eiji , Nakamura Toshikazu , Shimizu Yoshito , Nakatani Takeshi , Kitamura Soichiro , Tomoike Hitonobu , Kitakaze Masafumi , Kangawa Kenji , Miyatake Kunio
Published: August 2004

Hepatocyte growth factor (HGF) is a potent angiogenic and antifibrotic factor. Cardioprotective effects of HGF for idiopathic dilated cardiomyopathy were examined in hamsters with electroporation of plasmid DNA into skeletal muscle. We used hamster skeletal muscle as a protein producer of HGF gene. A plasmid vector encoding HGF (HGF group, n=12) or empty plasmid (placebo group, n=12) was transferred with in vivo electroporation into tibialis anterior muscles of hamsters with inherited dilated cardiomyopathy (TO-2 strain). The HGF group had greater serum HGF levels (21.6±2.2 versus 0.11±0.07 ng/mL,
P
<0.05), higher left ventricular ejection fraction (47.9±9.4% versus 28.8±11.2%,
P
<0.05), and greater wall thickening (31.6±6.3% versus 19.7±6.1%,
P
<0.05) when compared with the placebo group. The HGF group had smaller areas of ventricular fibrosis (11.8±3.4% versus 17.1±3.5%,
P
<0.05) and lower hydroxyproline content (3.7±0.7 versus 5.1±0.9 μmol/g,
P
<0.05) than did the placebo group. The HGF group also had higher capillary density (1885±232 versus 1447±182 vessel/mm
2
,
P
<0.05) and higher matrix metalloprotease-1 activity (13.1±3.5 versus 8.1±3.6 μg/collagen degraded per hour per gram tissue,
P
<0.05) than did the placebo group. Exogenous HGF might improve the deleterious changes in myocardial function and structure in the hamster with dilated cardiomyopathy. Systemic delivery of gene products with in vivo electroporation into skeletal muscle seemed to be an alternative means of direct gene delivery.
Mechanism for Aldosterone Potentiation of Angiotensin II–Stimulated Rat Arterial Smooth Muscle Cell Proliferation
Authors: Xiao Fang , Puddefoot John R. , Barker Stewart , Vinson Gavin P.
Published: August 2004

After earlier studies in which secretion of aldosterone was demonstrated to be important in rat arterial smooth muscle cell (RASMC) proliferation in vitro, the presence of both 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) gene transcription were shown in these cells by real-time reverse transcription–polymerase chain reaction (RT-PCR). In proliferation studies, tritiated thymidine incorporation into RASMC and RASMC cell number were both significantly increased by angiotensin II (Ang II) (10
−7
mol/L) compared with controls (
P
<0.01), but this effect was inhibited by the 3β-hydroxysteroid-dehydrogenase inhibitor trilostane (10
−6
mol/L and 10
−5
mol/L,
P
<0.05). Aldosterone alone added to RASMC did not significantly change tritiated thymidine incorporation when compared with controls, but the Ang II–induced increase was significantly enhanced by aldosterone at 10
−10
mol/L and 10
−8
mol/L (
P
<0.05). Neither corticosterone nor 18-hydroxydeoxycorticosterone had any such potentiating effect. RT-PCR analysis and real-time quantitative RT-PCR revealed an increase of Ang II type-1 (AT
1
) receptor mRNA in RASMC treated by aldosterone (10
−8
mol/L) compared with untreated controls, and this was correlated with a small but significant increase in AT
1
receptor protein (
P
<0.05), as assessed by immunoblotting analysis. These data confirm that steroid production by RASMC is critical in the response to Ang II, and the data support the view that aldosterone specifically is required for the full proliferative response to Ang II in RASMC. One way it may act is by modulating the expression and functions of the AT
1
receptor.
Increased Insulin Receptor Substrate 1 Serine Phosphorylation and Stress-Activated Protein Kinase/c-Jun N-Terminal Kinase Activation Associated With Vascular Insulin Resistance in Spontaneously Hypertensive Rats
Authors: Sugita Michiko , Sugita Hiroki , Kaneki Masao
Published: August 2004

Insulin resistance is associated with cardiovascular disease. Impaired insulin receptor substrate (IRS)–mediated signal transduction is a major contributor to insulin resistance. Recently, IRS-1 phosphorylation at serine 307 by stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) has been highlighted as a molecular event that causes insulin resistance. We investigated IRS-1–mediated insulin signaling, IRS-1 phosphorylation at serine 307, and SAPK/JNK activation status in the aorta of spontaneously hypertensive rats (SHR) by immunoprecipitation and immunoblotting. Insulin-stimulated tyrosine phosphorylation of insulin receptor and IRS-1 in SHR was decreased to 55% (
P
<0.01) and 40% (
P
<0.01) of the levels in Wistar-Kyoto rats (WKY), respectively. Insulin-stimulated IRS-1–associated phosphatidylinositol 3-kinase activation in SHR was reduced to 28% of the level in WKY (
P
<0.0001). Immunoblot analysis revealed that phosphorylated IRS-1 at serine 307 in SHR was increased to 261% (
P
<0.001) of the level in WKY. Phosphorylated (activated) SAPK/JNK in SHR was increased to 223% of the level in WKY (
P
<0.01). Serine-phosphorylated IRS-1 that was immunoprecipitated from the aorta of SHR was capable of inhibiting in vitro tyrosine phosphorylation by recombinant insulin receptor compared with WKY-derived IRS-1. These findings demonstrate that insulin resistance in the aorta of SHR was associated with elevated IRS-1 phosphorylation at serine 307 and increased SAPK/JNK activation. The present study suggests that increased SAPK/JNK activation may play an important role in the pathogenesis of vascular insulin resistance via inhibitory serine phosphorylation of IRS-1.
The Structure of French Romantic Histories of Religions
Authors: McCalla Arthur
Published: August 2004

This article analyzes the histories of religions of Louis de Bonald, Antoine Fabre d'Olivet, Pierre-Simon Ballanche, and Ferdinand d'Eckstein. Rather than offer yet another definition of Romanticism, it seeks to establish a framework by which to render intelligible a set of early nineteenth-century French histories of religions that have been largely ignored in the history of the study of religion. It establishes their mutual affinity by demonstrating that they are built on the common structural elements of an essentialist ontology, an epistemology that eludes Kantian pessimism, and a philosophy of history that depicts development as the unfolding of a preexistent essence according to an a priori pattern. Consequent upon these structural elements we may identify five characteristics of French Romantic histories of religions: organic developmentalism; reductionism; hermeneutic of harmonies; apologetic intent; and reconceptualization of Christian doctrine. Romantic histories of religions, as syntheses of traditional faith and historical-mindedness, are at once a chapter in the history of the study of religion and in the history of religious thought.
Contradiction and the Merit of Giving in Indian Religions
Authors: Brekke Torkel
Published: August 2004

The gift has been an important focus of research on Indian sociology and religion. However, almost all research has been confined to the Hindu tradition. I believe we can shed new light on religious giving if we focus on common themes in the main religions of the sub-continent. In this article I look at the textual traditions on giving in Hinduism, Buddhism and Jainism. My thesis is that these traditions share basic contradictions in their ideas of giving. There is, firstly, a contradiction between the gift as a sacrifice and a charitable gift and, secondly, a contradiction between the merit associated with giving as originating from the qualitites of the recipient and from the intention of the donor. These two contradictions are interlinked. Initially, they seem to threaten the institution of giving to the religious renouncer. If giving can be perceived as an act of charity where the merit accrues from the right intentions behind the act, there is no more reason to give to the renouncer than to anybody else. However, it seems that the contradiction also has been used to make giving to renouncers a priori meritorious. When the gift is perceived as a sacrifice to a worthy monk the merit accrues from the qualities of the recipient, but when there are no worthy recipients around the merit accrues from the right intention of the donor.
Observations on the Scolarly Study of Religions as Pursued in some Muslim Countries
Authors: Waardenburg Jacques
Published: August 2004

The article examines the study of religions at scholarly institutions in Muslim countries. As far as Islam and Islamic thought is concerned, both traditional and overly ideological approaches are problematic from a scholarly point of view. With regard to the study of religions other than Islam, interesting initiatives have been taken in several countries. Difficulties on a practical level include a lack of good handbooks in the “Islamic” languages, while books published in the West are mostly too expensive to acquire. Training in the languages of the various religious Scriptures is virtually absent. History of religions or religious studies have rarely been institutionalized. The study of some religions is seriously handicapped by political conflicts.Among the positive developments at present is, first, the increased interest in “religions” among students and the general public. The historical, anthropological and sociological research carried out in several Muslim countries pays attention to the social role of religion. A number of Muslim students enrolled at Western universities take courses in religions.The conclusion contends that the medieval tradition of Muslim studies of other religions could be a source of inspiration for the future. What is still much needed are competent staff, material facilities, a positive climate for intellectual pursuits, technical training in the study of texts, facts and meanings, and mental training for the pursuit of scholarly truth are needed. While perhaps acting as catalysts, Western models should not enjoy absolute authority. The author considers the pursuit of knowledge which is useful both to Muslims and to the scholarly community at large as most important.
Samaritan Tabernacle Drawings
Authors: Pummer Reinhard
Published: August 2004

Drawings of the Israelite tent sanctuary, the Tabernacle, and its implements are the main expression of representional art among the Samaritans. They are based on the descriptions in Exodus and are expressions of central tenets of the Samaritan faith—belief in the special status of Moses, in the Tabernacle as the only legitimate sanctuary in the history of Israel, and in the end times for which the restoration of the Tabernacle is expected. The paper is an attempt to probe the question of the age of the Samaritan tradition of depicting the Tabernacle in different media.Archaeological excavations have revealed synagogue mosaics and clay lamps from the Byzantine period that represent various elements of this artistic tradition. However, the main specimens date from the early sixteenth to the early twentieth century. It is these representations, executed on metal, cloth, parchment and paper, which are the focus of this article. The discussion is based on an examination of all extant and publicly accessible samples (see the Inventory at the end of this article).A great chronological and artistic gap separates the representations on the mosaics and oil lamps of the Byzantine period from the drawings of modern times. No continuous line exists between the two groups. The parchment in Moscow that allegedly dates from 32 A.H., i.e., 652/653 C.E., must be assigned to a much later period.There are obvious similarities of the Samaritan drawings with Jewish representations of the Tabernacle/Temple, yet it is impossible to identify a time or place where cross-fertilization may have taken place.At the present state of our knowledge, therefore, neither the mosaics from the Byzantine period nor the similarities with Jewish representations enable us to determine the time at which the Samaritan tradition of making Tabernacle drawings may have originated. It is probable, though, that the tradition had its beginnings well before the oldest extant samples from the early sixteenth century.
"Yahweh and His Asherah": the Goddess or Her Symbol?
Authors: Emerton J.A.
Published: August 2004

This article discusses whether 'srth in the phrase lyhwh ... wl'srth in inscriptions at Kuntillet 'Ajrud and Khirbet el-Qom refers to the goddess Asherah or her wooden symbol (here rendered "asherah"). First, it is argued that the drawing on pithos A from Kuntillet 'Ajrud does not illustrate the inscription, and that the figures in it probably do not represent Yahweh and Asherah. Second, although our knowledge of the Hebrew used in ancient Israel and Judah is far from complete, it is best, if possible, to interpret inscriptions in the light of usage in the Hebrew Bible. Since pronominal suffixes are not attached to personal names in the Hebrew Bible, it is better to translate 'srth "his asherah", rather than "his Asherah". Third, there is no difficulty in supposing that someone could utter a blessing by Yahweh and by a cultic object.
Scribal Errors or Phonetic Spellings? Samuel as an Aural Text
Authors: Tsumura David Toshio
Published: August 2004

The purpose of this paper is to establish the "phonic" nature of some of the socalled "corrupt" passages in the MT of Samuel. We are particularly interested in Samuel's "aural" characteristics which might be represented in the phonetic spellings. This aural aspect of the narrative is clearly attested in cases where the Ketib and the Qere give two variant forms of the same word or phrase. In such cases, the K. usually represent "phonic" reality by a phonetic spelling. By contrast, the Q. points to the "correct" historical spelling. Such aural features can be demonstrated in other ways in the MT of Samuel, especially when 2 Sam. xxii is compared with its duplicate text, Ps. xviii. These variant forms are caused by phonological phenomena such as assimilation, metathesis, palatalization, vowel sandhi, consonantal sandhi, and glide. These examples are not exhaustive, but they are sufficient to show that many of the often-asserted "scribal errors" are actually rather phonetic spellings and do reflect the "economy" of pronunciation. Such phonic realization in writing is attested not simply in poetic texts but also in prose sections of 1-2 Samuel. Hence, our topic is not so much a problem of literary-linguistic composition as a matter of the method of writing, i.e. graphic and graphemic representation of an aural text.
Increased and pathologic emperipolesis of neutrophils within megakaryocytes associated with marrow fibrosis in GATA-1low mice
Authors: Centurione Lucia , Di Baldassarre Angela , Zingariello Maria , Bosco Domenico , Gatta Valentina , Rana Rosa Alba , Langella Vincenzo , Di Virgilio Antonio , Vannucchi Alessandro M. , Migliaccio Anna Rita
Published: August 2004

Deletion of megakaryocytic-specific regulatory sequences of GATA-1 (Gata1tm2Sho or GATA-1low mutation) results in severe thrombocytopenia, because of defective thrombocytopoiesis, and myelofibrosis. As documented here, the GATA-1low mutation blocks megakaryocytic maturation between stage I and II, resulting in accumulation of defective megakaryocytes (MKs) in the tissues of GATA-1low mice. The block in maturation includes failure to properly organize α granules because von Willebrand factor is barely detectable in mutant MKs, and P-selectin, although normally expressed, is found frequently associated with the demarcation membrane system (DMS) instead of within granules. Conversely, both von Willebrand factor and P-selectin are barely detectable in GATA-1low platelets. Mutant MKs are surrounded by numerous myeloperoxidase-positive neutrophils, some of which appear in the process to establish contact with MKs by fusing their membrane with those of the DMS. As a result, 16% (in spleen) to 34% (in marrow) of GATA-1low MKs contain 1 to 3 neutrophils embedded in a vacuolated cytoplasm. The neutrophil-embedded GATA-1low MKs have morphologic features (high electron density and negativity to TUNEL staining) compatible with those of cells dying from para-apoptosis. We suggest that such an increased and pathologic neutrophil emperipolesis may represent one of the mechanisms leading to myelofibrosis by releasing fibrogenic MK cytokines and neutrophil proteases in the microenvironment.
Low-dose thalidomide and donor lymphocyte infusion as adoptive immunotherapy after allogeneic stem cell transplantation in patients with multiple myeloma
Authors: Kröger Nicolaus , Shimoni Avichai , Zagrivnaja Maria , Ayuk Francis , Lioznov Michael , Schieder Heike , Renges Helmut , Fehse Boris , Zabelina Tatjana , Nagler Arnon , Zander Axel R.
Published: August 2004

To improve the antimyeloma effect of donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation in multiple myeloma, we investigated in a phase 1/2 study the effect of low-dose thalidomide (100 mg) followed by DLI in 18 patients with progressive disease or residual disease and prior ineffective DLI after allografting. The overall response rate was 67%, including 22% complete remission. Major toxicity of thalidomide was weakness grade I/II (68%) and peripheral neuropathy grade I/II (28%). Only 2 patients experienced mild grade I acute graft versus host disease (aGvHD) of the skin, while no grades II to IV aGvHD was seen. De novo limited chronic GvHD (cGvHD) was seen in 2 patients (11%). The 2-year estimated overall and progression-free survival were 100% and 84%, respectively. Adoptive immunotherapy with low-dose thalidomide and DLI induces a strong antimyeloma effect with low incidence of graft versus host disease. (Blood. 2004;104:3361-3363)
A multilocus likelihood approach to joint modeling of linkage, parental diplotype and gene order in a full-sib family
Authors: Lu Qing , Cui Yuehua , Wu Rongling
Published: August 2004

Background

Unlike a pedigree initiated with two inbred lines, a full-sib family derived from two outbred parents frequently has many different segregation types of markers whose linkage phases are not known prior to linkage analysis.

Results

We formulate a general model of simultaneously estimating linkage, parental diplotype and gene order through multi-point analysis in a full-sib family. Our model is based on a multinomial mixture model taking into account different diplotypes and gene orders, weighted by their corresponding occurring probabilities. The EM algorithm is implemented to provide the maximum likelihood estimates of the linkage, parental diplotype and gene order over any type of markers.

Conclusions

Through simulation studies, this model is found to be more computationally efficient compared with existing models for linkage mapping. We discuss the extension of the model and its implications for genome mapping in outcrossing species.
The Retinome – Defining a reference transcriptome of the adult mammalian retina/retinal pigment epithelium
Authors: Schulz Heidi L , Goetz Thomas , Kaschkoetoe Juergen , Weber Bernhard HF
Published: August 2004

Background

The mammalian retina is a valuable model system to study neuronal biology in health and disease. To obtain insight into intrinsic processes of the retina, great efforts are directed towards the identification and characterization of transcripts with functional relevance to this tissue.

Results

With the goal to assemble a first genome-wide reference transcriptome of the adult mammalian retina, referred to as the retinome, we have extracted 13,037 non-redundant annotated genes from nearly 500,000 published datasets on redundant retina/retinal pigment epithelium (RPE) transcripts. The data were generated from 27 independent studies employing a wide range of molecular and biocomputational approaches. Comparison to known retina-/RPE-specific pathways and established retinal gene networks suggest that the reference retinome may represent up to 90% of the retinal transcripts. We show that the distribution of retinal genes along the chromosomes is not random but exhibits a higher order organization closely following the previously observed clustering of genes with increased expression.

Conclusion

The genome wide retinome map offers a rational basis for selecting suggestive candidate genes for hereditary as well as complex retinal diseases facilitating elaborate studies into normal and pathological pathways. To make this unique resource freely available we have built a database providing a query interface to the reference retinome [1].
Assessment of genetic diversity in Trigonella foenum-graecum and Trigonella caeruleausing ISSR and RAPD markers
Authors: Dangi Rakhee S , Lagu Meena D , Choudhary Lal B , Ranjekar Prabhakar K , Gupta Vidya S
Published: August 2004

Background

Various species of genus Trigonella are important from medical and culinary aspect. Among these, Trigonella foenum-graecum is commonly grown as a vegetable. This anti-diabetic herb can lower blood glucose and cholesterol levels. Another species, Trigonella caerulea is used as food in the form of young seedlings. This herb is also used in cheese making. However, little is known about the genetic variation present in these species. In this report we describe the use of ISSR and RAPD markers to study genetic diversity in both, Trigonella foenum-graecum and Trigonella caerulea.

Results

Seventeen accessions of Trigonella foenum-graecum and nine accessions of Trigonella caerulea representing various countries were analyzed using ISSR and RAPD markers. Genetic diversity parameters (average number of alleles per polymorphic locus, percent polymorphism, average heterozygosity and marker index) were calculated for ISSR, RAPD and ISSR+RAPD approaches in both the species. Dendrograms were constructed using UPGMA algorithm based on the similarity index values for both Trigonella foenum-graecum and Trigonella caerulea. The UPGMA analysis showed that plants from different geographical regions were distributed in different groups in both the species. In Trigonella foenum-graecum accessions from Pakistan and Afghanistan were grouped together in one cluster but accessions from India and Nepal were grouped together in another cluster. However, in both the species accessions from Turkey did not group together and fell in different clusters.

Conclusions

Based on genetic similarity indices, higher diversity was observed in Trigonella caerulea as compared to Trigonella foenum-graecum. The genetic similarity matrices generated by ISSR and RAPD markers in both species were highly correlated (r = 0.78 at p = 0.001 for Trigonella foenum-graecum and r = 0.98 at p = 0.001 for Trigonella caerulea) indicating congruence between these two systems. Implications of these observations in the analysis of genetic diversity and in supporting the possible Center of Origin and/or Diversity for Trigonella are discussed.
A randomised controlled trial and cost effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in the over 65s: (SAFE) [ISRCTN19633732]
Authors: Swancutt Dawn , Hobbs Richard , Fitzmaurice David , Mant Jonathan , Murray Ellen , Jowett Sue , Raftery James , Bryan Stirling , Davies Michael , Lip Gregory
Published: August 2004

Background

Atrial fibrillation (AF) has been recognised as an important independent risk factor for thromboembolic disease, particularly stroke for which it provides a five-fold increase in risk. This study aimed to determine the baseline prevalence and the incidence of AF based on a variety of screening strategies and in doing so to evaluate the incremental cost-effectiveness of different screening strategies, including targeted or whole population screening, compared with routine clinical practice, for detection of AF in people aged 65 and over. The value of clinical assessment and echocardiography as additional methods of risk stratification for thromboembolic disease in patients with AF were also evaluated.

Methods

The study design was a multi-centre randomised controlled trial with a study population of patients aged 65 and over from 50 General Practices in the West Midlands. These purposefully selected general practices were randomly allocated to 25 intervention practices and 25 control practices. GPs and practice nurses within the intervention practices received education on the importance of AF detection and ECG interpretation. Patients in the intervention practices were randomly allocated to systematic (n = 5000) or opportunistic screening (n = 5000). Prospective identification of pre-existing risk factors for AF within the screened population enabled comparison between high risk targeted screening and total population screening. AF detection rates in systematically screened and opportunistically screened populations in the intervention practices were compared to AF detection rate in 5,000 patients in the control practices.
Outcome after acute myocardial infarction: a comparison of patients seen by cardiologists and general physicians
Authors: Abubakar Ibrahim , Kanka David , Arch Barbara , Porter Jo , Weissberg Peter
Published: August 2004

Background

The management of acute myocardial infarction (AMI) has improved over the last 50 years with the more frequent use of effective medicines and procedures. The clinical benefit of the speciality of the attending physician is less clear. The United Kingdom National Service Framework for coronary heart disease (CHD) suggested that patients with CHD are likely to benefit from cardiological supervision. We set out to assess the effect of access to cardiologists on survival among AMI patients admitted in two UK hospitals.

Methods

The study was conducted in a university hospital and a district general hospital in England. Information was obtained on age, sex, ethnicity, Carstairs socioeconomic deprivation category derived from postcode of residence, comorbidity, distance from hospital and medication from all patients admitted with acute myocardial infarction in two acute trusts between July 1999 and June 2000. Record linkage to subsequent Hospital Episode Statistics and Registrar General's death records provided follow up information on procedures and mortality up to eighteen months after admission. Cox proportional hazard models were used to investigate the main hypothesis controlling for confounding. The main outcome measure was 18-month survival after myocardial infarction.

Results

Access to a cardiologist was univariately associated with improved survival (hazard ratio 0.16, 95% CI 0.10 to 0.25). This effect remained after controlling for the effect of patient characteristics (hazard ratio 0.22, 95% CI 0.14 to 0.25). The effect disappeared after controlling for access to effective medication (hazard ratio 0.70, 95% CI 0.33 to 1.46).

Conclusions

Access to a cardiologist is associated with better survival compared to no access to a cardiologist among a cohort of patients already admitted with AMI. This effect is mainly due to the more frequent use of effective medicines by the group referred to cardiologists. Hospitals may improve survival by improving access to effective medicines and by coordinating care between cardiologists and general physicians.
Chronic pain self-management for older adults: a randomized controlled trial [ISRCTN11899548]
Authors: Ersek Mary , Turner Judith A , Cain Kevin C , Kemp Carol A
Published: August 2004

Background

Chronic pain is a common and frequently disabling problem in older adults. Clinical guidelines emphasize the need to use multimodal therapies to manage persistent pain in this population. Pain self-management training is a multimodal therapy that has been found to be effective in young to middle-aged adult samples. This training includes education about pain as well as instruction and practice in several management techniques, including relaxation, physical exercise, modification of negative thoughts, and goal setting. Few studies have examined the effectiveness of this therapy in older adult samples.

Methods/Design

This is a randomized, controlled trial to assess the effectiveness of a pain self-management training group intervention, as compared with an education-only control condition. Participants are recruited from retirement communities in the Pacific Northwest of the United States and must be 65 years or older and experience persistent, noncancer pain that limits their activities. The primary outcome is physical disability, as measured by the Roland-Morris Disability Questionnaire. Secondary outcomes are depression (Geriatric Depression Scale), pain intensity (Brief Pain Inventory), and pain-related interference with activities (Brief Pain Inventory). Randomization occurs by facility to minimize cross-contamination between groups. The target sample size is 273 enrolled, which assuming a 20% attrition rate at 12 months, will provide us with 84% power to detect a moderate effect size of .50 for the primary outcome.

Discussion

Few studies have investigated the effects of multimodal pain self-management training among older adults. This randomized controlled trial is designed to assess the efficacy of a pain self-management program that incorporates physical and psychosocial pain coping skills among adults in the mid-old to old-old range.
Adenoid cystic carcinoma of the parotid metastasizing to liver: case report
Authors: Harish K , Mangala Gouri SR
Published: August 2004

Background

Adenoid cystic carcinoma is a rare malignant parotid tumor. Metastasis can occur even a decade or more after initial treatment of the primary.

Case presentation

We report a 60 year old female patient who presented with adenoid cystic carcinoma of the parotid gland. She underwent a total conservative parotidectomy followed by adjuvant radiotherapy. While on follow up, patient developed multiple liver metastases which manifested three years later. Patient lived for another two years before she died of her disease.

Conclusions

Although distant metastases of adenoid cystic carcinoma develop frequently, isolated metastasis to liver is unusual. Even after manifestation of distant metastasis, patients can be expected to live for a number of years. Palliative chemotherapy can be considered in symptomatic cases while the usefulness of metastatectomy is controversial.