bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Remodeling as the Cause of Late Stent Malapposition
Authors: Mintz Gary S. , Shah Vivek M. , Weissman Neil J.
Published: June 2003

Background—

Late stent malapposition (LSM) is only detected if intravascular ultrasound (IVUS) is performed at implantation and follow-up. We used a novel “regional” IVUS analysis to assess the mechanism of LSM.

Methods and Results—

Corresponding image slices on postimplantation and follow-up IVUS studies of 11 malapposed stents were identified and electronically rotated until they were aligned. The geometric center of the stent was identified, and the angle of late malapposition measured. Radii were drawn from this center through the transition points between complete apposition and LSM. These two circumferences were divided into equal arcs, and radii were drawn to the external elastic membrane (EEM). Measurements included EEM radius and circumference, plaque and media (P&M=EEM minus stent radius) thickness and area, and stent-intima separation. Mean baseline EEM radius and P&M thickness were similar in apposed and malapposed circumferences. At follow-up, mean EEM radius increase within the malapposed circumference (0.57±0.34 mm) was larger than within the apposed circumference (0.16±0.18 mm;
P
=0.0004). ΔEEM for each malapposed radius was greater than for each apposed radius (
P
<0.05 for all comparisons). Stent-intima separation correlated with EEM radius increase within the malapposed circumference (
r
=0.83,
P
=0.0013). At follow-up, the mean P&M thickness decreased in the malapposed circumference (−0.31±0.22 mm;
P
<0.0001). However, the decrease in P&M thickness in the malapposed circumference occurred because the same P&M area was distributed over a larger circumference (4.1±1.6 mm to 5.4±3.0 mm;
P
=0.05), the result of positive remodeling.

Conclusion—

The main cause of LSM is a regional increase in EEM (regional positive remodeling).
Differential Regurgitation in Branch Pulmonary Arteries After Repair of Tetralogy of Fallot
Authors: Kang I-Seok , Redington Andrew N. , Benson Leland N. , Macgowan Christopher , Valsangiacomo Emanuela R. , Roman Kevin , Kellenberger Christian J. , Yoo Shi-Joon
Published: June 2003

Background—

The importance of pulmonary regurgitation (PR) after repair of tetralogy of Fallot (TOF) is increasingly recognized, but little is known regarding its underlying mechanisms. This phase-contrast cine magnetic resonance (PC MR) study was performed to evaluate the relative contribution of each lung to total regurgitant volume.

Methods and Results—

Twenty-two patients with significant PR underwent a PC MR 3 to 16 years after repair of TOF. Regurgitant fraction of the main pulmonary artery was 39±10%. Regurgitant fraction of the left pulmonary artery (LPA; 46±18%) was greater than that of the right pulmonary artery (34±16%;
P
=0.002). The average contribution of the LPA to the total regurgitant flow volume was 54±19%, whereas its average contribution to the total forward flow volume was 44±13% (
P
=0.002). In 4 patients, regurgitant flow in the LPA accounted for 75% to 100% of the total regurgitant flow. There was a linear relationship between regurgitant fraction and fraction of the regurgitant flow duration in the main pulmonary artery (
P
<0.001) and right pulmonary artery (
P
=0.001) but not in the LPA (
P
=0.129).

Conclusions—

PR after repair of TOF is commonly associated with differential regurgitation in the branch pulmonary arteries, which is usually greater in the LPA. Although the cause of this disparity requires further investigation, those patients with a significant unilateral contribution to total PR may be amenable to localized techniques to reduce regurgitation.
Targeting of Mitogen-Activated Protein Kinases and Phosphatidylinositol 3 Kinase Inhibits Hepatocyte Growth Factor/Scatter Factor–Induced Angiogenesis
Authors: Sengupta Shiladitya , Sellers Lynda A. , Li Rung-Chi , Gherardi Ermanno , Zhao Ganlin , Watson Nicki , Sasisekharan Ram , Fan Tai-Ping D.
Published: June 2003

Background—

Hepatocyte growth factor/scatter factor (HGF/SF) can sufficiently and independently induce pathophysiological angiogenesis. However, the treatment strategies have mostly been unsuccessful. The present study is the first to evaluate the possible targeting of downstream signals for the inhibition of HGF/SF-induced angiogenesis.

Methods and Results—

In a multichannel scratch assay with human endothelial cells (ECs), HGF/SF induced a strong and prolonged activation of MAPK and cell proliferation that was inhibited by PD98059 and LY294002/wortmannin, selective inhibitors of MAPK and PI3K signaling modules, respectively. Western blotting demonstrated a temporal relation between the activation of the two pathways. Chemical inhibition of the PI3K and MAPK signals inhibited HGF/SF-induced chemoinvasion of ECs in vitro and blocked the HGF/SF-induced neovascularization into a polymer scaffold in vivo, as quantified by vessel counts and the clearance of radioactive
133
Xe.

Conclusions—

These data indicate that MEK and PI3K inhibitors represent a promising approach to the clinical management of pathological conditions characterized by overt HGF/SF-induced angiogenesis.
Methylation of 2-Hydroxyestradiol in Isolated Organs
Authors: Zacharia Lefteris C. , Dubey Raghvendra K. , Mi Zaichuan , Jackson Edwin K.
Published: June 2003

Vascular smooth muscle and glomerular mesangial cells in culture express a biochemical pathway that methylates 2-hydroxyestradiol (17β-estradiol metabolite) to produce 2-methoxyestradiol, a cell growth inhibitor that may mediate the cardiorenal protective effects of 17β-estradiol. Whether this pathway exists in intact organ systems is currently unclear. Accordingly, the purpose of the present investigation was to characterize the methylation of 2-hydroxestradiol in intact organs from both male and female rats. No significant differences were detected in the ability of male and female tissues to methylate 2-hydroxyestradiol. In isolated hearts, kidneys, and mesenteries perfused with Tyrode’s solution, K
m
values for 2-hydroxyestradiol methylation were 0.175±0.021, 0.387±0.054, and 0.495±0.089 μmol/L, respectively, and V
max
values were 21.0±1.58, 24.9±1.49, and 1.01±0.148 pmol 2-methoxyestradiol · min
−1
· ml
−1
per gram, respectively. The catalytic efficiency (V
max
/K
m
) was greatest in the heart compared with the kidney and mesentery (132±14.3, 78.4±15.1, and 2.30±0.263 pmol 2-methoxyestradiol · min
−1
· mL
−1
· μmol/L
−1
per gram, respectively). In the kidney, the catechol-O-methyltransferase inhibitor quercetin and norepinephrine (10 μmol/L) reduced methylation of 2-hydroxyestradiol by approximately 90% and 41%, respectively. Importantly, methylation in the kidney was inhibited by an average of 16.6±1.80% by endogenous norepinephrine released by renal artery nerve stimulation. Our results indicate that a robust 2-hydroxyestradiol methylation pathway exists in the kidney and heart, but not in the mesentery, and that this pathway is mediated by catechol-O-methyltransferase. Our findings also suggest that catecholamines may interfere with 2-hydroxyestradiol methylation and thereby attenuate the cardiorenal protective effects of 17β-estradiol.
GLUT-1 Overexpression
Authors: Gnudi Luigi , Viberti GianCarlo , Raij Leopoldo , Rodriguez Veronica , Burt Davina , Cortes Pedro , Hartley Barry , Thomas Stephen , Maestrini Sabrina , Gruden Gabriella
Published: June 2003

Mesangial matrix deposition is the hallmark of hypertensive and diabetic glomerulopathy. At similar levels of systemic hypertension, Dahl salt-sensitive but not spontaneously hypertensive rats (SHR) develop glomerular hypertension, which is accompanied by upregulation of transforming growth factor β
1
(TGF-β
1
), mesangial matrix expansion, and sclerosis. GLUT-1 is ubiquitously expressed and is the predominant glucose transporter in mesangial cells. In mesangial cells in vitro, GLUT-1 overexpression increases basal glucose transport, resulting in excess fibronectin and collagen production. TGF-β
1
has been shown to upregulate GLUT-1 expression. We demonstrated that in hypertensive Dahl salt-sensitive (S) rats fed 4% NaCl (systolic blood pressure [SBP]: 236±9 mm Hg), but not in similarly hypertensive SHR (SBP: 230±10 mm Hg) or their normotensive counterparts (Dahl S fed 0.5% NaCl, SBP: 145±5 mm Hg; and Wistar-Kyoto, SBP: 137±3 mm Hg), there was an 80% upregulation of glomerular GLUT-1 protein expression (
P
≤0.03). This was accompanied by a 2.7-fold upregulation of TGF-β
1
protein expression in glomeruli of DSH compared with DSN rats (
P
=0.02). TGF-β
1
expression was not upregulated and did not differ in the glomeruli of Wistar-Kyoto and SHR rats. As an in vitro surrogate of the in vivo hemodynamic stress imposed by glomerular hypertension, we used mechanical stretching of human and rat mesangial cells. We found that after 33 hours of stretching, mesangial cells overexpressed GLUT-1 (40%) and showed an increase in basal glucose transport of similar magnitude (both
P
≤0.01), which could be blocked with an anti TGF-β
1
–neutralizing antibody. These studies suggest a novel link between hemodynamic and metabolic factors that may cooperate in inducing progressive glomerular injury in conditions characterized by glomerular hypertension.
Sustained Activation of the Central Baroreceptor Pathway in Obesity Hypertension
Authors: Lohmeier Thomas E. , Warren Susan , Cunningham J. Thomas
Published: June 2003

The major goal of this study was to determine whether there is increased activation of medullary neurons that participate in the central baroreceptor reflex pathway in dogs with obesity-induced hypertension, a model of hypertension that is associated with increased sympathetic activity. We used Fos-like (Fos-Li) protein immunohistochemical methods to determine activation of neurons in the nucleus tractus solitarius (NTS), caudal ventrolateral medulla (CVLM), and rostral ventrolateral medulla (RVLM). Dogs were fed either a regular diet or an identical diet with the addition of 0.5 to 0.9 kg of cooked beef fat. After ≈6 weeks of the high fat diet, body weight (36.3±0.4 vs 21.5±0.5 kg), mean arterial pressure (105±4 vs 91±3 mm Hg), and heart rate (97±4 vs 70±3 bpm) were significantly greater in obese than in control dogs, respectively. There was little Fos-Li immunoreactivity in medullary neurons of control dogs but marked reactivity in obese dogs. Specifically, the number of Fos-Li–positive cells in the NTS and CVLM was 3 to 5 times greater in obese than in control dogs. Furthermore, despite sustained activation of these baroreceptor-sensitive neurons, there was a significantly greater number of Fos-Li positive cells in the RVLM of dogs fed the high fat diet. As baroreceptor suppression of sympathoexcitatory cells in the RVLM is mediated by activation of neurons in the NTS and CVLM, these results support recent findings indicating that baroreflex suppression of sympathetic activity is a long-term compensatory response in hypertension. However, sympathoexcitatory inputs onto RVLM neurons would appear to predominate over the inhibitory effects of the baroreflex in obesity hypertension.
Baroreflex Failure as a Late Sequela of Neck Irradiation
Authors: Sharabi Yehonatan , Dendi Raghuveer , Holmes Courtney , Goldstein David S.
Published: June 2003

Combined chemotherapy and radiotherapy increase long-term survival in patients with head and neck tumors. Late complications of treatment, however, are being recognized increasingly. Surgery or radiotherapy of the carotid sinuses or brain stem can evoke labile hypertension and orthostatic intolerance from acute or subacute baroreflex failure. Here we report cases in which chronic baroreflex failure appeared to develop as a late sequela of neck irradiation. Three patients referred for autonomic nervous system function testing had labile blood pressure and chronic orthostatic intolerance that developed years after neck irradiation for cancer. In each patient, heart rate remained constant during performance of the Valsalva maneuver, suggesting baroreflex-cardiovagal failure. All 3 patients had virtually zero baroreflex-cardiovagal gain, quantified by interbeat interval–systolic blood pressure relationships after intravenous phenylephrine or nitroglycerine. Ambulatory blood pressure monitoring revealed highly variable blood pressure, with sudden pressor and depressor episodes, a characteristic feature of baroreflex failure. Cardiovagal efferent function, assessed by power spectral analysis of heart rate variability during slow, deep respiration, was normal. Sympathetic noradrenergic efferent function, assessed by cold pressor testing and plasma catecholamine levels during supine rest and orthostasis, was also normal or increased. These findings indicated a primarily afferent lesion. Carotid ultrasonography revealed intimal thickening and atheromatous plaques in all 3 patients. We propose that labile hypertension and orthostatic intolerance can develop as a late sequela of neck irradiation, due to chronic carotid baroreflex failure, which in turn is due to radiation-induced accelerated development of carotid arteriosclerosis. Splinting of carotid sinus mechanoreceptors in rigidified arterial walls would impede detection of alterations in blood pressure and thereby disrupt baroreflex regulation of cardiovagal and sympathetic outflows.
Endothelin Antagonism on Aldosterone-Induced Oxidative Stress and Vascular Remodeling
Authors: Pu Qian , Neves Mario Fritsch , Virdis Agostino , Touyz Rhian M. , Schiffrin Ernesto L.
Published: June 2003

Endothelin A (ET
A
) receptor blockade has prevented vascular remodeling in aldosterone and salt-induced hypertension. To evaluate effects of the ET
A
receptor antagonist, BMS 182874, compared with the aldosterone antagonist, spironolactone, on vascular remodeling in aldosterone-infused rats not exposed to a high salt diet, Sprague-Dawley rats were infused subcutaneously with aldosterone (0.75 μg/h) and treated with BMS 182874 (40 mg · kg
−1
· d
−1
), spironolactone, or hydralazine (both 25 mg · kg
−1
· d
−1
) while receiving a normal salt diet for 6 weeks. Aldosterone increased systolic BP (
P
<0.01), plasma endothelin (3.33±0.32 versus 1.85±0.40 pmol/L in control,
P
<0.05), systemic oxidative stress as shown by plasma thiobarbituric acid–reacting substances and vascular nicotinamide adenine dinucleotide phosphate (NADPH) activity. Aldosterone increased small artery media thickness (17.7±0.9 versus 13.6±0.8 μm in control,
P
<0.05) and media/lumen ratio (7.6±0.4 versus 5.5±0.4% in control,
P
<0.05), with growth index of 21% indicating hypertrophic remodeling. Laser confocal microscopy showed increased collagen and fibronectin deposition and intercellular adhesion molecule-1 (ICAM-1) content in the vessel wall of aldosterone-infused rats. The 3 treatments lowered BP, although hydralazine was slightly less effective. BMS 182874 and spironolactone decreased oxidative stress, normalized the hypertrophic remodeling, decreased collagen and fibronectin deposition, and reduced ICAM-1 abundance in the vascular wall of aldosterone-infused rats, whereas hydralazine only reduced NADPH activity in aorta but did not affect the remaining parameters. Vascular remodeling of small arteries occurs in aldosterone-infused rats exposed to a normal salt diet and may be mediated in part by ET-1 via stimulation of ET
A
receptors. Endothelin blockade may exert beneficial effects on vascular remodeling, fibrosis, oxidative stress, and adhesion molecule expression in aldosterone-induced hypertension.
Immunomediated and Ischemia-Independent Inflammation of Coronary Microvessels in Unstable Angina
Authors: Neri Serneri Gian Gastone , Boddi Maria , Modesti Pietro Amedeo , Cecioni Ilaria , Coppo Mirella , Papa Maria Letizia , Toscano Thomas , Marullo Antonio , Chiavarelli Mario
Published: June 2003

This study investigated whether the myocardium is involved in the acute inflammatory reaction associated with bursts of unstable angina (UA). We looked for the presence of activated DR
+
inflammatory cells and the expression patterns, localization, and immunostaining identification of genes for cytokines (IL-1β, TNF-α, IL-6, and IFN-γ), MCP-1, and iNOS in the left ventricle biopsies from 2-vessel disease anginal patients, 24 with UA and 12 with stable angina (SA), who underwent coronary bypass surgery. Biopsy specimens from 6 patients with mitral stenosis who underwent valve replacement were examined as control hearts (CHs). Plasma levels of IL-2 soluble receptor (sIL-2R) were measured as a marker of systemic immune reaction. In CHs, DR
+
cells were undetectable, and cytokine and iNOS mRNA expression were negligible. UA patients had higher sIL-2R levels than SA patients (
P
<0.01), and their biopsy specimens showed both numerous DR
+
cells identified as lymphocytes, macrophages, endothelial cells, and elevated expression levels of cytokine and iNOS genes (from 2.4- to 6.1-fold vs SA;
P
<0.01). Cytokine and iNOS genes and proteins were localized in endothelial cells without involvement of myocytes. IL-1β and MCP-1 mRNAs were nearly undetectable. No significant differences were found in the number of DR
+
cells, levels of cytokine, and iNOS genes between potentially ischemic and nonischemic left ventricle areas. In SA specimens, DR
+
cells were very rare and only mRNAs for TNF-α and iNOS genes were overexpressed versus CHs. These results indicated that an acute immunomediated inflammatory reaction, essentially involving coronary microvessels, is demonstrable in UA patients.
Acute Inhibition of Myoglobin Impairs Contractility and Energy State of iNOS-Overexpressing Hearts
Authors: Wunderlich Carsten , Flögel Ulrich , Gödecke Axel , Heger Jacqueline , Schrader Jürgen
Published: June 2003

Elevated cardiac levels of nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS) have been implicated in the development of heart failure. The surprisingly benign phenotype of recently generated mice with cardiac-specific iNOS overexpression (TGiNOS) provided the rationale to investigate whether NO scavenging by oxymyoglobin (MbO
2
) yielding nitrate and metmyoglobin (metMb) is involved in preservation of myocardial function in TGiNOS mice.
1
H nuclear magnetic resonance (NMR) spectroscopy was used to monitor changes of cardiac myoglobin (Mb) metabolism in isolated hearts of wild-type (WT) and TGiNOS mice. NO formation by iNOS resulted in a significant decrease of the MbO
2
signal and a concomitantly emerging metMb signal in spectra of TGiNOS hearts only (ΔMbO
2
: −46.3±38.4 μmol/kg, ΔmetMb: +41.4±17.6 μmol/kg, n=6;
P
<0.05) leaving contractility and energetics unaffected. Inhibition of the Mb-mediated NO degradation by carbon monoxide (20%) led to a deterioration of myocardial contractility in TGiNOS hearts (left ventricular developed pressure: 78.2±8.2% versus 96.7±4.6% of baseline, n=6;
P
<0.005), which was associated with a profound pertubation of cardiac energy state as assessed by
31
P NMR spectroscopy (eg, phosphocreatine: 13.3±1.3 mmol/L (TGiNOS) versus 15.9±0.7 mmol/L (WT), n=6;
P
<0.005). These alterations could be fully antagonized by the NOS inhibitor
S
-ethylisothiourea. Our findings demonstrate that myoglobin serves as an important cytoplasmic buffer of iNOS-derived NO, which determines the functional consequences of iNOS overexpression.
Role of the Cytosolic Chaperones Hsp70 and Hsp90 in Maturation of the Cardiac Potassium Channel hERG
Authors: Ficker Eckhard , Dennis Adrienne T. , Wang Lu , Brown Arthur M.
Published: June 2003

The human
ether-a-gogo
–related gene (hERG) encodes the α subunit of the cardiac potassium current
I
Kr
. Several mutations in hERG produce trafficking-deficient channels that may cause hereditary long-QT syndrome and sudden cardiac death. Although hERG currents have been studied extensively, little is known about the proteins involved in maturation and trafficking of hERG. Using immunoprecipitations, we show that the cytosolic chaperones heat shock protein (Hsp) 70 and Hsp90, but not Grp94, interact with hERG wild type (WT) during maturation. The specific Hsp90 inhibitor geldanamycin prevents maturation and increases proteasomal degradation of hERG WT, while reducing hERG currents in heterologous expression systems. In ventricular myocytes, inhibition of Hsp90 also decreases
I
Kr
, whereas geldanamycin had no effect on
I
Ks
or heterologously expressed Kv2.1 and Kv1.5 currents. Both Hsp90 and Hsp70 interact directly with the core-glycosylated form of hERG WT present in the endoplasmic reticulum but not the fully glycosylated, cell-surface form. For the trafficking-deficient LQT2 mutants, hERG R752W and hERG G601S, interactions with Hsp90 and Hsp70 are increased as both mutants remained tightly associated with Hsp90 and Hsp70 in the endoplasmic reticulum. Incubation at lower temperature for R752W or with the hERG blocker astemizole for G601S dissociates channel-chaperone complexes and restores trafficking. In contrast, nonfunctional but trafficking-competent hERG G628S is released from chaperone complexes during maturation comparable to WT. We conclude that Hsp90 and Hsp70 are crucial for the maturation of hERG WT as well as the retention of trafficking-deficient LQT2 mutants. The full text of this article is available online at http://www.circresaha.org.
Hemodynamics Is a Key Epigenetic Factor in Development of the Cardiac Conduction System
Authors: Reckova Maria , Rosengarten Carlin , deAlmeida Angela , Stanley Chiffvon P. , Wessels Andy , Gourdie Robert G. , Thompson Robert P. , Sedmera David
Published: June 2003

The His-Purkinje system (HPS) is a network of conduction cells responsible for coordinating the contraction of the ventricles. Earlier studies using bipolar electrodes indicated that the functional maturation of the HPS in the chick embryo is marked by a topological shift in the sequence of activation of the ventricle. Namely, at around the completion of septation, an immature base-to-apex sequence of ventricular activation was reported to convert to the apex-to-base pattern characteristic of the mature heart. Previously, we have proposed that hemodynamics and/or mechanical conditioning may be key epigenetic factors in development of the HPS. We thus hypothesized that the timing of the topological shift marking maturation of the conduction system is sensitive to variation in hemodynamic load. Spatiotemporal patterns of ventricular activation (as revealed by high-speed imaging of fluorescent voltage-sensitive dye) were mapped in chick hearts over normal development, and following procedures previously characterized as causing increased (conotruncal banding, CTB) or reduced (left atrial ligation, LAL) hemodynamic loading of the embryonic heart. The results revealed that the timing of the shift to mature activation displays striking plasticity. CTB led to precocious emergence of mature HPS function relative to controls whereas LAL was associated with delayed conversion to apical initiation. The results from our study indicate a critical role for biophysical factors in differentiation of specialized cardiac tissues and provide the basis of a new model for studies of the molecular mechanisms involved in induction and patterning of the HPS in vivo.
Long-Term Angiographic Recurrences After Selective Endovascular Treatment of Aneurysms With Detachable Coils
Authors: Raymond Jean , Guilbert François , Weill Alain , Georganos Stavros A. , Juravsky Louis , Lambert Anick , Lamoureux Julie , Chagnon Miguel , Roy Daniel
Published: June 2003

Background and Purpose—

Our aim in this study was to assess the incidence and determining factors of angiographic recurrences after endovascular treatment of aneurysms.

Methods—

A retrospective analysis of all patients with selective endosaccular coil occlusion of intracranial aneurysms prospectively collected from 1992 to 2002 was performed. There were 501 aneurysms in 466 patients (mean±SD age, 54.20±12.54 years; 74% female). Aneurysms were acutely ruptured (54.1%) or unruptured (45.9%). Mean±SD aneurysm size was 9.67±5.91 mm with a 4.31±1.97-mm neck. The most frequent sites were basilar bifurcation (27.7%) and carotid ophthalmic (18.0%) aneurysms. Recurrences were subjectively divided into minor and major (ideally necessitating re-treatment). The most significant predictors of angiographic recurrence were determined by logistic regression. These results were confirmed by χ
2
,
t
tests, or ANOVAs followed, when appropriate, by Tukey’s contrasts.

Results—

Short-term (≤1 year) follow-up angiograms were available in 353 aneurysms (70.5%) and long-term (>1 year) follow-up angiograms, in 277 (55%), for a total of 383 (76.5%) followed up. Recurrences were found in 33.6% of treated aneurysms that were followed up and that appeared at a mean±SD time of 12.31±11.33 months after treatment. Major recurrences presented in 20.7% and appeared at a mean of 16.49±15.93 months. Three patients (0.8%) bled during a mean clinical follow-up period of 31.32±24.96 months. Variables determined to be significant predictors (
P
<0.05) of a recurrence included aneurysm size ≥10 mm, treatment during the acute phase of rupture, incomplete initial occlusions, and duration of follow-up.

Conclusions—

Long-term monitoring of patients treated by endosaccular coiling is mandatory.
Abdominal Obesity and Risk of Ischemic Stroke
Authors: Suk Seung-Han , Sacco Ralph L. , Boden-Albala Bernadette , Cheun Jian F. , Pittman John G. , Elkind Mitchell S. , Paik Myunghee C.
Published: June 2003

Background and Purpose—

Obesity is well recognized as a risk factor for coronary heart disease and mortality. The relationship between abdominal obesity and ischemic stroke remains less clear. Our aim was to evaluate abdominal obesity as an independent risk factor for ischemic stroke in a multiethnic community.

Methods—

A population-based, incident case-control study was conducted July 1993 through June 1997 in northern Manhattan, New York, NY. Cases (n=576) of first ischemic stroke (66% ≥65 years of age; 56% women; 17% whites; 26% blacks; 55% Hispanics) were enrolled and matched by age, sex, and race-ethnicity to stroke-free community controls (n=1142). All subjects were interviewed and examined and had measurements of waist-to-hip ratio (WHR). Odds ratios (ORs) of ischemic stroke were calculated with gender-specific quartiles (GQs) and gender-specific medians of WHR adjusted for stroke risk factors and body mass index (BMI).

Results—

Compared with the first quartile, the third and fourth quartiles of WHR had an increased risk of stroke (GQ3: OR, 2.4; 95% CI, 1.5 to 3.9; GQ4: OR, 3.0; 95% CI, 1.8 to 4.8) adjusted for other risk factors and BMI. Those with WHR equal to or greater than the median had an overall OR of 3.0 (95% CI, 2.1 to 4.2) for ischemic stroke even after adjustment for other risk factors and BMI. Increased WHR was associated with a greater risk of stroke in men and women and in all race-ethnic groups. The effect of WHR was stronger among younger persons (test for heterogeneity,
P
<0.0002) (<65 years of age: OR, 4.4; 95%CI, 2.2 to 9.0; ≥65 years of age: OR, 2.2; 95% CI, 1.4 to 3.2). WHR was associated with an increased risk among those with and without large-artery atherosclerotic stroke.

Conclusions—

Abdominal obesity is an independent, potent risk factor for ischemic stroke in all race-ethnic groups. It is a stronger risk factor than BMI and has a greater effect among younger persons. Prevention of obesity and weight reduction need greater emphasis in stroke prevention programs.
Comparison of Psychometric Properties of Three Mobility Measures for Patients With Stroke
Authors: Hsueh I-Ping , Wang Chun-Hou , Sheu Ching-Fan , Hsieh Ching-Lin
Published: June 2003

Background and Purpose—

This study compared the validity, responsiveness, and interrater reliability of 3 mobility measures in stroke patients from the acute stage up to 180 days after stroke onset. The 3 measures were the Rivermead Mobility Index (RMI), a modified RMI (MRMI), and the Mobility Subscale of the Stroke Rehabilitation Assessment of Movement (STREAM).

Methods—

The validity and responsiveness of the 3 mobility measures were prospectively examined by monitoring 57 stroke patients with the measures and the Barthel Index at 14, 30, 90, and 180 days after stroke onset. Two individual raters used the 3 measures to evaluate a different sample of 40 patients on 2 separate occasions to determine the interrater reliability.

Results—

The Spearman ρ between STREAM and MRMI was ≥0.92; the intraclass correlation coefficient (ICC, a measure of agreement) between them was ≥0.89, indicating high concurrent validity of both measures. RMI showed a moderate to high relationship and agreement with STREAM and MRMI (ρ≥0.78, ICC≥0.5). Responsiveness of the 3 measures was high before 90 days after stroke onset (standardized response mean ≥0.83) and low at 90 to 180 days after stroke onset (0.2≤standardized response mean≤0.4). The score changes of the 3 measures at each stage were significant (
P
≤0.05), except for RMI and MRMI at 90 to 180 days after stroke onset. The interrater agreement of the 3 measures was high (ICC≥0.92).

Conclusions—

All 3 measures examined showed acceptable levels of reliability, validity, and responsiveness in stroke patients. The psychometric characteristics of STREAM were slightly superior to those of the other 2 measures among our patients. We prefer and recommend STREAM for measuring mobility disability in stroke patients.
Central Retinal Artery Doppler Flow Parameters Reflect the Severity of Cerebral Small-Vessel Disease
Authors: Hiroki Masahiko , Miyashita Kotaro , Yoshida Hiroshi , Hirai Shunsaku , Fukuyama Hidenao
Published: June 2003

Background and Purpose—

We investigated the usefulness of central retinal artery (CRA) Doppler flowmetry in patients with cerebral small-vessel disease (SVD).

Methods—

CRA Doppler flowmetry was performed in 103 SVD patients who underwent MRI. Sixty-four adjusted control subjects were also registered. We assessed average CRA flow parameter values for both eyes with the clinical and MRI findings.

Results—

Each Doppler flowmetry was performed within 5 minutes. Patients with SVD had significantly lower end-diastolic and mean velocities of the CRA than control subjects; they also had higher pulsatility and resistive indexes. Multivariate analysis showed that the number of small infarcts was an independent predictor of peak systolic and mean velocities. Grade of periventricular hyperintensities was an additional independent predictor of peak systolic and mean velocities, whereas the number of small infarcts was predictive of end-diastolic velocity.

Conclusions—

Flow parameters may be useful for the quantitative assessment of SVD severity.
Association of Methylenetetrahydrofolate Reductase Gene Polymorphism With Carotid Atherosclerosis Depending on Smoking Status in a Japanese General Population
Authors: Inamoto Nozomu , Katsuya Tomohiro , Kokubo Yoshihiro , Mannami Toshifumi , Asai Takashi , Baba Shunroku , Ogata Jun , Tomoike Hitonobu , Ogihara Toshio
Published: June 2003

Background and Purpose—

The association of the
methylenetetrahydrofolate reductase
gene (
MTHFR
) with carotid atherosclerosis remains inconsistent. This may be due to small sample size and inappropriate analysis. We investigated the association of
C677T/MTHFR
with blood pressure and carotid atherosclerosis in a Japanese general population.

Methods—

Subjects (30 to 89 years of age; 1693 women, 1554 men) who gave informed consent were randomly selected from a general population in Suita, Japan.
MTHFR
genotypes were determined by TaqMan polymerase chain reaction. Carotid atherosclerosis was evaluated by high-resolution ultrasonography with atherosclerotic indexes of intimal-medial thickness (IMT), maximum IMT in the common carotid artery (CCA), plaque score, and stenosis (>50%).

Results—

Age-adjusted diastolic blood pressure was significantly higher in women with the
TT
genotype than in those with the
CC
genotype. In a recessive model (
CC
+
CT
versus
TT
), all adjusted odds ratios for hypertension and >50% stenosis in women were 1.42 and 3.42 (95% confidence intervals, 1.01 to 1.99 and 1.23 to 9.53), respectively. In women, maximum IMT in CCA for smokers with the
TT
genotype was significantly higher than for smokers with the
CC
genotype and nonsmokers with the
TT
genotype (
P
<0.05).

Conclusions—

Our study suggests that the
MTHFR TT
genotype is a risk factor for hypertension and carotid stenosis in women. Significant interactions between
C677T/MTHFR
and smoking on maximum IMT in CCA were observed in women but not in men. Smoking cessation for subjects with the
TT
genotype is important in the prevention of cerebrovascular disease.
Endoglin Is Not a Major Susceptibility Gene for Intracranial Aneurysm Among Japanese
Authors: Onda Hideaki , Kasuya Hidetoshi , Yoneyama Taku , Hori Tomokatsu , Nakajima Toshiaki , Inoue Ituro
Published: June 2003

Background and Purpose—

A 6-base insertion (6bINS) polymorphism in intron 7 of the endoglin gene (
ENG
), which codes for a component of the transforming growth factor-β receptor complex, was reported to be associated with intracranial aneurysm (IA) in a Japanese population. A recent report using a white population could not replicate the association. We tested for this association with high statistical power in our independent Japanese subjects and evaluated the linkage between markers on chromosome 9, which contains
ENG
, and IA.

Methods—

The sample for the linkage study comprised 179 individuals with IA in 85 nuclear families, with 104 possible affected sibpairs. For the association study of the 6bINS polymorphism and 4 single nucleotide polymorphisms (SNPs) in
ENG
, 172 Japanese patients with IA and 192 control subjects were examined.

Results—

There was no evidence of linkage in the vicinity of
ENG
by analysis of affected sibpairs. The allele frequency of the 6bINS polymorphism was 104 of 344 (30.2%) in the total IA group and 122 of 382 (31.9%) in the control group. The statistical difference in allele frequency between the 2 groups was not significant (χ
2
=0.245,
df
=1,
P
=0.620). The power of the present association study was 98.3% at a significance level of 0.05 on the basis of the allele frequencies in the previous study. In addition, no associations between the 4 SNPs in
ENG
and IA were detected.

Conclusions—

We provide evidence that there is no association between the 6bINS polymorphism or 4 SNPs in
ENG
and IA and that there is no linkage between the
ENG
locus and IA, indicating that
ENG
is not a major susceptibility gene for IA in Japanese.
Smokeless Tobacco as a Possible Risk Factor for Stroke in Men
Authors: Asplund Kjell , Nasic Salmir , Janlert Urban , Stegmayr Birgitta
Published: June 2003

Background and Purpose—

Snuff and other forms of smokeless tobacco are widely used in some populations. Whereas the detrimental cardiovascular effects of smoking are well documented, possible health hazards associated with the use of smokeless tobacco remain controversial. The purpose of this study was to explore whether the use of snuff, a smokeless tobacco product, increases the risk of stroke in men.

Methods—

In a nested case-control study (1 case and 2 matched controls without cardiovascular disease), information on tobacco habits was collected through population risk factor surveys. During follow-up, first-ever fatal and nonfatal strokes occurring among 25- to 74-year-old participants were identified in a population-based stroke register. The study was restricted to men (276 cases, 551 controls).

Results—

The unadjusted odds ratio for stroke in regular cigarette smokers compared with men who never used tobacco was 2.21 (95% CI, 1.29 to 3.79). When never-smoking regular snuff dippers (excluding ex-smokers) were compared with men who never used tobacco, the unadjusted odds ratio was 1.05 (95% CI, 0.37 to 2.94). The odds ratio for never-snuffing smokers versus never-smoking snuff users was 2.90 (95% CI, 0.92 to 9.1). After adjustment for multiple cardiovascular risk factors, the odds ratio for having a stroke was 1.74 (95% CI, 0.85 to 3.54) in regular smokers and 0.87 (95% CI, 0.41 to 1.83) in regular snuff users.

Conclusions—

Whereas regular smoking doubles the risk of stroke in men, snuff use is not associated with any apparent excess risk. Chemical moieties produced by burning tobacco are probably the most important contributors to smokers’ excess risk of atherothrombotic disease, including stroke.
Effect of Carotid Endarterectomy on Primary Collateral Blood Flow in Patients With Severe Carotid Artery Lesions
Authors: Hendrikse Jeroen , Rutgers Dirk R. , Klijn Catharina J.M. , Eikelboom Bert C. , van der Grond Jeroen
Published: June 2003

Background and Purpose—

In patients with severe obstruction of the internal carotid artery (ICA), it is recognized that the preoperative failure to visualize collaterals of the circle of Willis increases the risk of hemispheric ischemia before, during, and after carotid endarterectomy (CEA). The purpose of the present study was to assess the effect of CEA on the anatomy and function of the circle of Willis.

Methods—

Time-of-flight and phase-contrast MR angiography were used to study changes in vessel diameter and collateral flow of the circle of Willis in 48 patients with 70% to 99% ICA stenosis before and after CEA.

Results—

In patients with unilateral ICA stenosis, all preoperative vessel diameters on both sides of the circle of Willis were larger than in control subjects. All demonstrated a significant diameter decrease to reach normal values after CEA. Furthermore, preoperative collateral flow patterns normalized after CEA (
P
=0.03). In patients with stenosis and contralateral ICA occlusion, CEA resulted in a significant increase in the prevalence of collateral flow via the anterior communicating artery (33% to 83%,
P
<0.01) and a significant increase in diameter of both A1 segments (
P
<0.05) in patients in whom collateral flow developed after CEA.

Conclusions—

CEA reduces the caliber of compensatory collateral channels to normal levels by MR angiography measurements in the presence of severe unilateral stenosis; when the opposite side is occluded and the stenosis is removed ipsilaterally, a greater amount of compensatory collateral circulation can be measured on both the occluded side and the fully opened side.
Neither Arm nor Face Warming Reduces the Shivering Threshold in Unanesthetized Humans
Authors: Doufas Anthony G. , Wadhwa Anupama , Lin Chun-Ming , Shah Yunus M. , Hanni Keith , Sessler Daniel I.
Published: June 2003

Background and Purpose—

Hand warming and face warming, combined with inhalation of heated air, are reported to suppress shivering. However, hand or face temperature contributes only a few percent to control of shivering. Thus, it seems unlikely that manipulating hand or facial skin temperature alone would be sufficient to permit induction of therapeutic hypothermia. We tested the hypothesis that focal arm (forearm and hand) warming or lower facial warming, combined with inhalation of heated and humidified gas, only minimally reduces the shivering threshold (triggering core temperature).

Methods—

We studied 8 healthy male volunteers (18 to 40 years of age) on 3 days: (1) control (no warming), (2) arm warming with forced air at ≈43°C, and (3) face warming with 21 L/min of air at ≈42°C at a relative humidity of 100%. Fluid at ≈4°C was infused via a central venous catheter to decrease tympanic membrane temperature 1°C/h to 2°C/h; mean skin temperature was maintained at 31°C. A sustained increase in oxygen consumption quantified the shivering threshold.

Results—

Shivering thresholds did not differ significantly between the control (36.7±0.1°C), arm-warming (36.5±0.3°C), or face-warming (36.5±0.3°C; analysis of variance,
P
=0.34) day. The study was powered to have a 95% probability of detecting a difference of 0.5±0.5°C (mean±SD) between control and either of the 2 treatments at α=0.05.

Conclusions—

Focal arm or face warming did not substantially reduce the shivering threshold in unanesthetized volunteers. It thus seems unlikely that these nonpharmacological modalities will substantially facilitate induction of therapeutic hypothermia.
Triggers of Subarachnoid Hemorrhage
Authors: Anderson Craig , Ni Mhurchu Cliona , Scott David , Bennett Derrick , Jamrozik Konrad , Hankey Graeme
Published: June 2003

Background and Purpose—

Unaccustomed strenuous physical exertion can trigger myocardial infarction, but little is known about the mechanisms precipitating subarachnoid hemorrhage (SAH).

Methods—

We identified all cases of first-ever SAH among the combined populations (2.8 million) of 4 urban centers in Australia and New Zealand. Information on the type, time, and intensity of exposures in the 26 hours before the onset of SAH was ascertained by structured interviews. We used the case-crossover technique to assess the risk of SAH associated with transient exposures of moderate to extreme physical exertion, heavy cigarette smoking, and binge alcohol consumption.

Results—

We registered 432 first-ever cases of SAH (62% women; mean age, 56.5 years). A definite time of onset of SAH was established for 393 patients (91%), and information on the levels of physical activity in the preceding 26 hours was obtained in 338 (78%). Of these patients, 19% engaged in moderate to extreme exertion (≥5 metabolic equivalents) in the 2 hours before SAH, which was associated with a tripling in the risk of SAH (odds ratio [OR], 2.7; 95% CI, 1.6 to 4.6). There was no evidence of any association between heavy cigarette smoking or binge drinking and risk of SAH in the subsequent 2 hours (OR, 1.1; 95% CI, 0.4 to 3.7; and OR, 0.41; 95% CI, −∞ to 5.3). Habitual exercise did not appear to alter the risk of SAH associated with moderate to extreme exertion.

Conclusions—

Moderate to extreme physical exertion tripled the risk of SAH, but there was no association between transient heavy smoking or binge drinking and risk of SAH. These data suggest that heavy physical activity may trigger SAH.
'The Roman Family' in Recent Research: State of the Question
Authors: Rawson Beryl
Published: June 2003

In the past two decades of rapid expansion,the study of ‘the Roman family’ has developed from its early focus on the city of Rome and on legal, literary and epigraphical sources to a wider geographical canvas and to more extensive use of archaeological material. The whole range of sources is now being applied to particular problems, providing different perspectives and a better chance of contextualising specific details. Of the new methodologies available, demography and the archaeology of domestic space are proving most productive. Questions most frequently debated are the Romans’ concept of ‘the family’ and the nature of family relationships. There is a growing recognition that regional and cultural differentiation must be taken into account: generalisations about ‘the Mediterranean world’ or even ‘Greco-Roman culture’ are seldom useful. Similarly, regional differentiations in early Christianity are being recognised: Christian communities were likely to share many of the characteristics of the city or area in which they were developing. This makes the growing dialogue between Romanists and Early Christian scholars profitable and stimulating, and topics of particular fertilisation are those of family relationships and domestic space.
Ευσεβεια: Roman Imperial Family Values and the Sexual Politics of 4 Maccabees and the Pastorals
Authors: D'Angelo Mary
Published: June 2003

Early Christian and Jewish texts responded to the “family values” campaigns mounted by successive emperors from Augustus and Hadrian with varying combinations of accommodation and resistance. This dialectic of resistance and accommodation appears in central aspects of 4 Maccabees and the Pastorals, texts that have frequently been assigned to the earlier part of the second century, that is, to the reigns of Trajan and Hadrian, and that foreground martyrs as the exemplars of their teaching. Both the Jewish and the Christian text give the virtue ευσεβεια a central role, constructing that virtue along the lines of the Roman virtue pietas, that is, as duty and devotion not only to the divine, but also to those of one’s household and family. The specifically post-Augustan character of this virtue is manifest in their displays of an a ideal of chastity for women that responds to the Julian laws—not only the avoidance of adultery and stuprum, but also a commitment to marriage and remarriage as long as the woman can bear children. Both likewise espouse the long term Roman idealization of the univira and both are insistent that the husband must be the teacher of the wife. Among the most significant aspects of this comparison are the close correspondences between the exegeses of Genesis 2-3 in 4 Macc.18:7-10 and 1 Tim. 2:13-15.
Pietas in and out of the Frying Pan
Authors: Osiek Carolyn
Published: June 2003

The importance of research in the Roman family for understanding the early Christian family in context is underlined, and some difficulties and challenges for interrelating the two areas are summarized.
The Jesus Movement Was Not Egalitarian but Family-oriented
Authors: Elliott John
Published: June 2003

The theory that Jesus founded a "discipleship of equals" that after his death assumed the shape of egalitarian structured house churches, which by the end of the first century abandoned their egalitarian ethos and organization and assimilated to the conventional patriarchal household pattern of their Greco-Roman environment, fails to stand up under close scrutiny. The theory lacks probative textual and historical support, is sociologically implausible, conceptually anachronistic, and appears ideologically driven.
Fathers and Householders in the Jesus Movement: The Perspective of the Gospel of Luke
Authors: Pesce Mauro , Destro Adriana
Published: June 2003

The Jesus' movement has in Luke a structural relation with the households. The relation between household and discipleship is dialectical, because it assigns external and internal roles to those that belong to both social forms. The itinerant followers of Jesus seem to belong to an emerging middle generation in their households, and have some experience in choosing to adhere to voluntary associations. Most (both married and unmarried, both men and women) belong to the households of their fathers. Some are themselves householders, who can freely dispose of their property, and who have an important function in their own household. This creates strong conflicts between the followers and the other members of the household because of the function they fulfilled before their becoming part of the movement. On the other hand, Jesus and his movement depend on the household structure. The householders offer Jesus' movement the required support through hospitality. Furthermore, Luke's Jesus denounces the mechanism of exchange between householders that excludes all social classes that have no chance whatsoever of entering into it and cannot benefit from the mechanisms of patronage. Jesus asks the householders to open their homes and offer a different kind of hospitality without reciprocity and social compensation. The double challenge to the itinerant followers and to the householders differentiates the kind of participation of individuals to Jesus movement, and put all of them into a close interrelation within which the model of discipleship tends to transform the model of the household.
Gender, Judaism, and Literature: Unwelcome Guests in Household Configurations
Authors: Levine Amy-Jill
Published: June 2003

Investigation of the early Christian household, frequently based on social-science models, can benefit by attending more formally to gender constructs, Jewish sources, and literary-critical observations. The category of 'householder' should be expanded to include independent women; the role of women and slaves in Jewish environs should be examined in light not only of Greek and Roman political and philosophical ideals but also of early Rabbinic thought; social models applied to and/or gleaned from the Gospels should be checked against the evangelists' narrative art.