bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymorphism of the Serotonin Transporter Gene and Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease
Authors: Eddahibi Saadia , Chaouat Ari , Morrell Nicholas , Fadel Elie , Fuhrman Claire , Bugnet Anne-Sophie , Dartevelle Philippe , Housset Bruno , Hamon Michel , Weitzenblum E. , Adnot Serge
Published: October 2003

Background—

The serotonin transporter (5-HTT) is involved in the pulmonary artery smooth muscle hyperplasia that leads to pulmonary hypertension (PH). Because hypoxia and 5-HTT gene polymorphism control 5-HTT expression, we examined 5-HTT gene polymorphism and PH in hypoxemic patients with advanced chronic obstructive pulmonary disease (COPD).

Methods and Results—

In 103 patients with COPD recruited in France (n=67) and the UK (n=36), we determined 5-HTT gene polymorphism and pulmonary artery pressure (PAP) measured during right heart catheterization (France) or Doppler echocardiography (UK). Ninety-eight subjects from the 2 countries served as control subjects. The distribution of 5-HTT gene polymorphism did not differ between patients and control subjects. In patients carrying the LL genotype, which is associated with higher levels of 5-HTT expression in pulmonary artery smooth muscle cells than the LS and SS genotypes, PH was more severe than in LS or SS patients. Mean PAP values in patients from France with the LL, LS, and SS genotypes were 34±3, 23±1, and 22±2 mm Hg (mean±SEM), respectively (
P
<0.01). Corresponding systolic PAP values in the UK were 40±3, 28±3, and 24±3 mm Hg, respectively (
P
<0.01). Compared with control subjects, platelet 5-HTT protein was increased in COPD patients in proportion to the hypoxemia level, and strong 5-HTT immunostaining was observed in remodeled pulmonary arteries from COPD patients.

Conclusions—

5-HTT gene polymorphism appears to determine the severity of PH in hypoxemic patients with COPD. Because PH is an important prognostic factor in this disease, recognition of patients at risk for PH should be helpful in managing COPD.
Immunoglobulin M Type of Autoantibodies to Oxidized Low-Density Lipoprotein Has an Inverse Relation to Carotid Artery Atherosclerosis
Authors: Karvonen Jarkko , Päivänsalo Markku , Kesäniemi Y. Antero , Hörkkö Sohvi
Published: October 2003

Background—

Lipoprotein oxidation plays an important part in atherogenesis. Autoantibodies to oxidation-specific epitopes of LDL occur in plasma and atherosclerotic lesions of humans and animals. The potential role of these autoantibodies in atherogenesis still remains unsolved. We studied the relationship between different isotypes of autoantibodies to copper-oxidized LDL and malondialdehyde-modified LDL (MDA-LDL) and carotid artery intima-media thickness (IMT) in a population-based cohort of 1022 middle-aged men and women. In addition, we studied the relation of C-reactive protein (CRP) to IMT.

Methods and Results—

The levels of IgM, IgG, and IgG2 autoantibodies binding to MDA-LDL and copper-oxidized LDL were determined in plasma samples by chemiluminescence-based ELISA. IMT and the number of plaques were measured ultrasonographically. The subjects were divided into tertiles for antibody titers. We found an inverse association between IMT and IgM autoantibody titers to MDA-LDL that remained statistically significant after adjusting for age, gender, LDL cholesterol, systolic blood pressure, CRP, and smoking. CRP was not independently associated with IMT.

Conclusions—

These results show that IgM autoantibodies to MDA-LDL have an inverse association with carotid atherosclerosis. The possible implications of this finding are discussed.
Health-Related Quality of Life Is Better for Cardiac Arrest Survivors Who Received Citizen Cardiopulmonary Resuscitation
Authors: Stiell Ian , Nichol Graham , Wells George , De Maio Valerie , Nesbitt Lisa , Blackburn Josée , Spaite Daniel
Published: October 2003

Background—

This study evaluated the prehospital factors associated with better health-related quality of life for survivors of out-of-hospital cardiac arrest.

Methods and Results—

This prospective, 20-community, cohort study involved consecutive, adult out-of-hospital cardiac arrest patients who survived to 1 year. Patients were contacted by telephone and evaluated for the Health Utilities Index Mark III (HUI3), which describes health as a utility score on a scale from 0 (dead) to 1.0 (perfect health). The 8091 cardiac arrest patients had overall survival rates of 5.2% to hospital discharge and 4.0% to 1 year. We successfully contacted and evaluated 268 of 316 (84.8%) of known 1-year survivors. The median HUI3 score was 0.80 (interquartile range, 0.50 to 0.97), which compares well with age-adjusted values for the general population (0.83). Logistic regression identified 2 factors independently associated with very good quality of life (HUI3 >0.90) and their odds ratios (95% CIs), as follows: age 80 years or older, 0.3 (0.1 to 0.84), and citizen-initiated cardiopulmonary resuscitation (CPR), 2.0 (1.2 to 3.4) (Hosmer-Lemeshow goodness-of-fit statistic, 0.74).

Conclusions—

This study is the largest ever conducted for out-of-hospital cardiac arrest survivors, clearly shows that these patients have good quality of life, and is the first to demonstrate that citizen-initiated CPR is strongly and independently associated with better quality of life. These results emphasize the importance of optimizing community citizen CPR readiness. Given the low rate of citizen-initiated CPR in many communities, we believe that local and national initiatives should vigorously promote the practice of bystander CPR.
Sulfatides
Authors: Merten M. , Motamedy S. , Ramamurthy S. , Arnett F.C. , Thiagarajan P.
Published: October 2003

Background—

Sulfatides are sulfated glycosphingolipids expressed on the surface of erythrocytes, leukocytes, and platelets. Sulfatides interact with several cell adhesion molecules involved in hemostasis. β
2
-Glycoprotein I is an anionic phospholipid-binding plasma protein, and the phospholipid-bound form is the target for most anti-phospholipid antibodies that are associated with recurrent thrombosis, miscarriages, and neurological symptoms. In this study, we examined whether β
2
-glycoprotein I forms a complex with sulfatides and thereby becomes a target for anti-phospholipid antibodies.

Methods and Results—

β
2
-Glycoprotein I binds to surface-bound sulfatides but not to other glycolipids, such as ceramide, cerebrosides, sphingomyelin, or ganglioside. At a sulfatide coating density of 1 μg/well, β
2
-glycoprotein I reaches half-maximal binding at 2.5 μg/mL, and the binding is saturated at 10 μg/mL. The binding of β
2
-glycoprotein I also depends on the coating density of sulfatides in the well. At a constant β
2
-glycoprotein I concentration of 5 μg/mL, maximal binding of β
2
-glycoprotein I is observed at a coating density of 1 μg/well. The serum from 14 patients with anti-cardiolipin antibodies, a subset of anti-phospholipid antibodies, bound to sulfatide-bound β
2
-glycoprotein I and previous absorption on cardiolipin-coated surfaces decreased the immunoreactivity toward sulfatide-β
2
-glycoprotein I complex by >50% in 12 of 14 patients. Furthermore, immunoaffinity-purified anti-cardiolipin antibodies from 4 of 5 patients reacted with sulfatide-bound β
2
-glycoprotein I.

Conclusions—

These results show that not only anionic phospholipids, as commonly known, but also sulfatides are targets for most anti-phospholipid antibodies. We therefore postulate that interactions of these antibodies with sulfatides may contribute to some of the clinical symptoms of the anti-phospholipid antibody syndrome.
Catheter Ablation for Paroxysmal Atrial Fibrillation
Authors: Oral Hakan , Scharf Christoph , Chugh Aman , Hall Burr , Cheung Peter , Good Eric , Veerareddy Srikar , Pelosi Frank , Morady Fred
Published: October 2003

Background—

Segmental ostial catheter ablation (SOCA) to isolate the pulmonary veins (PVs) and left atrial catheter ablation (LACA) to encircle the PVs both may eliminate paroxysmal atrial fibrillation (PAF). The relative efficacy of these 2 techniques has not been directly compared.

Methods and Results—

Of 80 consecutive patients with symptomatic PAF (age, 52±10 years), 40 patients underwent PV isolation by SOCA and 40 patients underwent LACA to encircle the PVs. During SOCA, ostial PV potentials recorded with a ring catheter were targeted. LACA was performed by encircling the left- and right-sided PVs 1 to 2 cm from the ostia and was guided by an electroanatomic mapping system; ablation lines also were created in the mitral isthmus and posterior left atrium. The mean procedure and fluoroscopy times were 156±45 and 50±17 minutes for SOCA and 149±33 and 39±12 minutes for LACA, respectively. At 6 months, 67% of patients who underwent SOCA and 88% of patients who underwent LACA were free of symptomatic PAF when not taking antiarrhythmic drug therapy (
P
=0.02). Among the variables of age, sex, duration and frequency of PAF, ejection fraction, left atrial size, structural heart disease, and the ablation technique, only an increased left atrial size and the SOCA technique were independent predictors of recurrent PAF. The only complication was left atrial flutter in a patient who underwent LACA.

Conclusions—

In patients undergoing catheter ablation for PAF, LACA to encircle the PVs is more effective than SOCA.
Endovascular Edge-to-Edge Mitral Valve Repair
Authors: St. Goar Frederick G. , Fann James I. , Komtebedde Jan , Foster Elyse , Oz Mehmet C. , Fogarty Thomas J. , Feldman Ted , Block Peter C.
Published: October 2003

Background—

The edge-to-edge technique is an accepted method for the surgical repair of a regurgitant mitral valve. This study reports the initial use of an endovascular technology that enables a double-orifice edge-to-edge mitral valve repair without cardiopulmonary bypass in an animal model.

Methods and Results—

Adult pigs (n=14) were anesthetized, and left thoracotomy was performed for epicardial echo imaging. Using femoral vein access, a steerable guide catheter was placed transseptally into the left atrium. An implantable clip designed to grasp and approximate the middle scallops of the anterior and posterior mitral leaflets was introduced through the guide catheter. The clip was opened in the left atrium, advanced through the mitral orifice, and retracted to grasp the leaflet edges. When a functional double-orifice valve was confirmed by echo, the clip was closed to coapt the leaflets and detached from the delivery catheter. Before final clip detachment, echo demonstrated a double orifice in all 14 animals. In 2 studies, the clip released from the anterior mitral leaflet. Retrospective analysis of echo images indicated an incomplete grasp of the anterior leaflet. Immediate postmortem examination revealed that the clip successfully approximated the middle scallops of the anterior and posterior leaflets in all 12 double-orifice studies.

Conclusions—

This study demonstrates for the first time that an endovascular system can be successfully used to perform the edge-to-edge repair technique in a nondiseased porcine model. This technique is potentially applicable as a percutaneous catheterization laboratory procedure for the treatment of mitral regurgitation in humans.
Circulating Pregnancy-Associated Plasma Protein A Predicts Outcome in Patients With Acute Coronary Syndrome but No Troponin I Elevation
Authors: Lund Juha , Qin Qiu-Ping , Ilva Tuomo , Pettersson Kim , Voipio-Pulkki Liisa-Maria , Porela Pekka , Pulkki Kari
Published: October 2003

Background—

Risk stratification in troponin (cTn)-negative acute coronary syndrome (ACS) remains a clinical challenge. We investigated the predictive value of circulating pregnancy-associated plasma protein A (PAPP-A), a novel marker of atherosclerotic plaque activity, in these patients.

Methods and Results—

Two hundred consecutive hospitalized ACS patients were included, of whom 136 (69 men and 67 women; mean±SD age, 66±16 years) remained cTnI-negative for up to 24 hours. PAPP-A was measured at admission, 6 to 12 hours, and 24 hours. During 6-month follow-up, 26 (19.1%) of the cTnI-negative patients reached a primary end point (cardiovascular death, myocardial infarction, or revascularization). At a cutoff level of 2.9 mIU/L, elevated PAPP-A was an independent predictor of adverse outcome (adjusted risk ratio [RR], 4.6; 95% confidence interval, 1.8 to 11.8;
P
=0.002). Another independent predictor was admission CRP >2.0 mg/L (RR, 2.6;
P
=0.03).

Conclusions—

Measurement of plasma PAPP-A, a zinc-binding matrix metalloproteinase, is a strong independent predictor of ischemic cardiac events and need of revascularization in patients who present with suspected myocardial infarction but remain troponin negative.
Celiprolol Activates eNOS Through the PI3K-Akt Pathway and Inhibits VCAM-1 Via NF-κB Induced by Oxidative Stress
Authors: Kobayashi Naohiko , Mita Shin-ichiro , Yoshida Kohtaro , Honda Takeaki , Kobayashi Tsutomu , Hara Kazuyoshi , Nakano Shigefumi , Tsubokou Yusuke , Matsuoka Hiroaki
Published: October 2003

Vascular cell adhesion molecule-1 (VCAM-1) and reactive oxygen species play critical roles in early atherogenesis, and nitric oxide (NO) is an important regulator of the cardiovascular system. Although celiprolol, a specific β
1
-antagonist with weak β
2
-agonistic action, stimulates endothelial nitric oxide synthase (eNOS) production, the mechanisms remain to be determined. Because it was recently reported that phosphatidylinositol 3-kinase (PI3K) and its downstream effector Akt are implicated in the activation of eNOS and that regulation of VCAM-1 expression is mediated via nuclear factor-κB (NF-κB), we hypothesized that celiprolol activates phosphorylation of eNOS through the PI3K-Akt signaling pathway; that celiprolol modulates VCAM-1 expression, which is associated with inhibiting NF-κB phosphorylation; and that celiprolol suppresses NAD(P)H oxidase p22phox, p47phox, gp91phox, and nox1 expression in the left ventricle of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. eNOS and Akt phosphorylation upregulated by celiprolol alone were suppressed by treatment with celiprolol plus wortmannin. Increased expression of VCAM-1, p22phox, p47phox, gp91phox, nox1, activated p65 NF-κB, c-Src, p44/p42 extracellular signal-regulated kinases, and their downstream effector p90 ribosomal S6 kinase phosphorylation in DOCA rats was inhibited by celiprolol. Celiprolol administration resulted in a significant improvement in cardiovascular remodeling and suppression of transforming growth factor-β1 gene expression. In conclusion, celiprolol suppresses VCAM-1 expression because of inhibition of oxidative stress, NF-κB, and signal transduction, while increasing eNOS via stimulation of the PI3K-Akt signaling pathway and improving cardiovascular remodeling.
Short-Term Blood Pressure, Noradrenergic, and Vascular Effects of Nocturnal Home Hemodialysis
Authors: Chan Christopher T. , Harvey Paula J. , Picton Peter , Pierratos Andreas , Miller Judith A. , Floras John S.
Published: October 2003

Long-term nocturnal hemodialysis, which uses longer and more frequent sessions than conventional hemodialysis, lowers clinic blood pressure and left ventricular mass. We tested the hypotheses that short-term nocturnal hemodialysis would (1) reduce ambulatory blood pressure; (2) cause peripheral vasodilation; (3) lower plasma norepinephrine concentration; and (4) improve the arterial response to reactive hyperemia (a marker of endothelium-dependent vasodilation). We studied 18 consecutive patients (age, 41±2; [mean±SEM]) before and 1 and 2 months after conversion from conventional (three 4-hour sessions per week) to nocturnal (six 8-hour sessions per week) hemodialysis. As the dialysis dose per session (Kt/V) increased from 1.24±0.06 to 2.04±0.08 after 2 months (
P
=0.02), symptomatic hypotension developed and most antihypertensive medications were withdrawn. Nocturnal hemodialysis nonetheless lowered 24-hour mean arterial pressure (from 102±3 to 90±2 mm Hg after 2 months;
P
=0.01), total peripheral resistance (from 1967±235 to 1499±191 dyne · s · cm
−5
;
P
<0.01) and plasma norepinephrine (from 2.66±0.4 to 1.96±0.2 nmol;
P
=0.04). Endothelium-dependent vasodilation could not be elicited during conventional hemodialysis (−2.7±1.8%) but was restored (+8.0±1.0%;
P
=0.001) after 2 months of nocturnal hemodialysis. The brachial artery response to nitroglycerin also improved (from 6.9±2.8 to 15.7±1.6%;
P
<0.05). Nocturnal hemodialysis had no effect on weight or on stroke volume. Rapid reversal of these markers of adverse cardiovascular events with more intense hemodialysis may translate into improved outcome in this high-risk group of patients.
Paracrine Regulation of Angiogenesis and Adipocyte Differentiation During In Vivo Adipogenesis
Authors: Fukumura Dai , Ushiyama Akira , Duda Dan G. , Xu Lei , Tam Joshua , Krishna V. , Chatterjee K. , Garkavtsev Igor , Jain Rakesh K.
Published: October 2003

With an increasing incidence of obesity worldwide, rational strategies are needed to control adipogenesis. Growth of any tissue requires the formation of a functional and mature vasculature. To gain mechanistic insight into the link between active adipogenesis and angiogenesis, we developed a model to visualize noninvasively and in real time both angiogenesis and adipogenesis using intravital microscopy. Implanted murine preadipocytes induced vigorous angiogenesis and formed fat pads in a mouse dorsal skin-fold chamber. The newly formed vessels subsequently remodeled into a mature network consisting of arterioles, capillaries, and venules, whereas the preadipocytes differentiated into adipocytes as confirmed by increased aP2 expression. Inhibition of adipocyte differentiation by transfection of preadipocytes with a peroxisome proliferator-activated receptor γ dominant-negative construct not only abrogated fat tissue formation but also reduced angiogenesis. Surprisingly, inhibition of angiogenesis by vascular endothelial growth factor receptor-2 (VEGFR2) blocking antibody not only reduced angiogenesis and tissue growth but also inhibited preadipocyte differentiation. We found that part of this inhibition stems from the paracrine interaction between endothelial cells and preadipocytes and that VEGF–VEGFR2 signaling in endothelial cells, but not preadipocytes, mediates this process. These findings reveal a reciprocal regulation of adipogenesis and angiogenesis, and suggest that blockade of VEGF signaling can inhibit in vivo adipose tissue formation. The full text of this article is available online at http://www.circresaha.org.
Neuropeptide Y Is an Essential In Vivo Developmental Regulator of Cardiac
I
Ca,L
Authors: Protas Lev , Barbuti Andrea , Qu Jihong , Rybin Vitalyi O. , Palmiter Richard D. , Steinberg Susan F. , Robinson Richard B.
Published: October 2003

Cell culture studies demonstrate an increase in cardiac L-type Ca
2+
current (
I
Ca,L
) density on sympathetic innervation in vitro and suggest the effect depends on neurally released neuropeptide Y (NPY). To determine if a similar mechanism contributes to the postnatal increase in
I
Ca,L
in vivo, we prepared isolated ventricular myocytes from neonatal and adult mice with targeted deletion of the NPY gene (
Npy
−/−
) and matched controls (
Npy
+/+
). Whole-cell voltage clamp demonstrates
I
Ca,L
density increases postnatally in
Npy
+/+
(by 56%), but is unchanged in
Npy
−/−
. Both
I
Ca,L
density and action potential duration are significantly greater in adult
Npy
+/+
than
Npy
−/−
myocytes, whereas
I
Ca,L
density is equivalent in neonatal
Npy
+/+
and
Npy
−/−
myocytes. These data indicate NPY does not influence
I
Ca,L
prenatally, but the postnatal increase in
I
Ca,L
density is entirely NPY-dependent. In contrast, there is a similar postnatal negative voltage shift in the
I
-V relation in
Npy
+/+
and
Npy
−/−
, indicating NPY does not influence the developmental change in
I
Ca,L
voltage-dependence. Immunoblot analyses and measurements of maximally activated
I
Ca,L
(in presence of forskolin or BayK 8644) show that the differences in current density between
Npy
+/+
and
Npy
−/−
cannot be attributed to altered Ca
2+
channel α
1C
subunit protein expression. Rather, these results suggest that the in vivo NPY-dependent postnatal increase in
I
Ca,L
density in cardiac myocytes results from regulation
I
Ca,L
properties by NPY.
Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in a Monocyte Chemoattractant Protein-1–Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells
Authors: Fujiyama Soichiro , Amano Katsuya , Uehira Kazutaka , Yoshida Masayuki , Nishiwaki Yasunobu , Nozawa Yoshihisa , Jin Denan , Takai Shinji , Miyazaki Mizuo , Egashira Kensuke , Imada Takayuki , Iwasaka Toshiji , Matsubara Hiroaki
Published: October 2003

Peripheral blood (PB)-derived CD14
+
monocytes were shown to transdifferentiate into endothelial cell (EC) lineage cells and contribute to neovascularization. We investigated whether bone marrow (BM)- or PB-derived CD34
−
/CD14
+
cells are involved in reendothelialization after carotid balloon injury. Although neither hematopoietic nor mesenchymal stem cells were included in human BM-derived CD34
−
/CD14
+
monocyte lineage cells (BM-MLCs), they expressed EC-specific markers (Tie2, CD31, VE-cadherin, and endoglin) to an extent identical to mature ECs. When BM-MLCs were cultured with vascular endothelial growth factors, hematopoietic markers were drastically decreased and new EC-specific markers (Flk and CD34) were induced. BM-MLCs were intra-arterially transplanted into balloon-injured arteries of athymic nude rats. When BM-MLCs were activated by monocyte chemoattractant protein-1 (MCP-1) in vivo or in vitro, they adhered onto injured endothelium, differentiated into EC-like cells by losing hematopoietic markers, and inhibited neointimal hyperplasia. Ability to prevent neointimal hyperplasia was more efficient than that of BM-derived CD34
+
cells. MCP-dependent adhesion was not observed in PB-derived CD34
−
/CD14
+
monocytes. Regenerated endothelium exhibited a cobblestone appearance, blocked extravasation of dye, and induced NO-dependent vasorelaxation. Basal adhesive activities on HUVECs under laminar flow and β
1
-integrin expression (basal and active forms) were significantly increased in BM-MLCs compared with PB-derived monocytes. MCP-1 markedly enhanced adhesive activity of BM-MLCs (2.8-fold) on HUVECs by activating β
1
-integrin conformation. Thus, BM-MLCs can function as EC progenitors that are more potent than CD34
+
cells and acquire the ability to adhere on injured endothelium in a MCP-1–dependent manner, leading to reendothelialization associated with inhibition of intimal hyperplasia. This will open a novel window to MCP-1–mediated biological actions and vascular regeneration strategies by cell therapy.
Rapid Effect of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibition on Coronary Endothelial Function
Authors: Wassmann Sven , Faul Anna , Hennen Benno , Scheller Bruno , Böhm Michael , Nickenig Georg
Published: October 2003

Treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decreases cardiovascular event rates in hypercholesterolemic patients. Whether statins exert effects within 24 hours on the coronary vasculature in patients with endothelial dysfunction has not been elucidated. Twenty-seven patients with stable angina pectoris and average low-density lipoprotein cholesterol concentrations of 138±9 mg/dL at baseline were allocated to treatment with placebo (14 patients) or 40 mg/d pravastatin (13 patients) in a randomized, double-blind, prospective trial. Coronary endothelial function was assessed before and 24 hours after single treatment by quantitative coronary angiography during intracoronary infusion of nitroglycerin or increasing concentrations of acetylcholine (0.01, 0.1, and 1 μmol/L). Coronary blood flow reserve was measured by Doppler velocimetry during adenosine infusion. Intracoronary acetylcholine infusion induced abnormal vasoconstriction in both groups before treatment, indicating coronary endothelial dysfunction. Treatment with a single oral 40-mg dose of pravastatin significantly attenuated acetylcholine-mediated vasoconstriction after 24 hours (mean±SE decrease in luminal diameter before and after treatment: 0.01 μmol/L, 6.1±2.2% versus 3.0±1.2%; 0.1 μmol/L, 15.6±2.6% versus 7.4±1.8%;
P
<0.05; 1 μmol/L, 22.9±2.9% versus 13.2±2.6%;
P
<0.05). There was no significant difference in the response to acetylcholine in the placebo group (8.1±2.4% versus 9.7±2.4%, 16.1±2.9% versus 16.8±3.2%, and 21.4±3.9% versus 23.3±4.2%). The response to nitroglycerin infusion was not altered in both groups. Increase in coronary blood flow in response to adenosine and coronary flow reserve remained unchanged during placebo and statin treatment. Serum concentrations of blood lipids and high-sensitive C-reactive protein were not significantly altered after 24 hours in response to placebo or pravastatin therapy. Statin treatment improves endothelium-dependent coronary vasomotion within 24 hours in the absence of significant cholesterol reduction. The full text of this article is available online at http://www.circresaha.org.
C-Terminal Truncation of Cardiac Troponin I Causes Divergent Effects on ATPase and Force
Authors: Foster D. Brian , Noguchi Teruo , VanBuren Peter , Murphy Anne M. , Van Eyk Jennifer E.
Published: October 2003

Myocardial stunning is a form of reversible myocardial ischemia/reperfusion injury associated with systolic and diastolic contractile dysfunction. In the isolated rat heart model, myocardial stunning is characterized by specific C-terminal proteolysis of the myofilament protein, troponin I (cTnI) that yields cTnI
1-193
. To determine the effect of this particular C-terminal truncation of cTnI, without the confounding factor of other stunning-induced protein modifications, a series of solution biochemical assays has been undertaken using the human homologue of mouse/rat cTnI
1-193
, cTnI
1-192
. Affinity chromatography and actin sedimentation experiments detected little, or no, difference between the binding of cTnI (cTnI
1-209
) and cTnI
1-192
to actin-tropomyosin, troponin T, or troponin C. Both cTnI and cTnI
1-192
inhibit the actin-tropomyosin–activated ATPase activity of myosin subfragment 1 (S1), and this inhibition is released by troponin C in the presence of Ca
2+
. However, cTnI
1-192
, when reconstituted as part of the troponin complex (cTn
1-192
), caused a 54±11% increase in the maximum Ca
2+
-activated actin-tropomyosin-S1 ATPase activity, compared with troponin reconstituted with cTnI (cTn). Furthermore, cTn
1-192
increased Ca
2+
sensitivity of both the actin-tropomyosin-activated S1 ATPase activity and the Ca
2+
-dependent sliding velocity of reconstituted thin filaments, in an in vitro motility assay, compared with cTn. In an in vitro force assay, the actin-tropomyosin filaments bearing cTn
1-192
developed only 76±4% (
P
<0.001) of the force obtained with filaments composed of reconstituted cTn. We suggest that cTnI proteolysis may contribute to the pathophysiology of myocardial stunning by altering the Ca
2+
-sensing and chemomechanical properties of the myofilaments.
Downregulation of the BK Channel β1 Subunit in Genetic Hypertension
Authors: Amberg Gregory C. , Santana L. Fernando
Published: October 2003

The molecular mechanisms underlying increased arterial tone during hypertension are unclear. In vascular smooth muscle, localized Ca
2+
release events through ryanodine-sensitive channels located in the sarcoplasmic reticulum (Ca
2+
sparks) activate large-conductance, Ca
2+
-sensitive K
+
(BK) channels. Ca
2+
sparks and BK channels provide a negative feedback mechanism that hyperpolarizes smooth muscle and thereby opposes vasoconstriction. In this study, we examined Ca
2+
sparks and BK channel function in Wistar-Kyoto (WKY) rats with borderline hypertension and in spontaneously hypertensive rats (SHR), a widely used genetic model of severe hypertension. We found that the amplitude of spontaneous BK currents in WKY and SHR cells were smaller than in normotensive cells even though Ca
2+
sparks were of similar magnitude. BK channels in WKY and SHR cells were less sensitive to physiological changes in intracellular Ca
2+
than normotensive cells. Our data indicate that decreased expression of the BK channel β1 subunit underlies the lower Ca
2+
sensitivity of BK channels in SHR and WKY myocytes. We conclude that the lower expression of the β1 subunit during genetic borderline and severe hypertension reduced BK channel activity by decreasing the sensitivity of these channels to physiological changes in Ca
2+
. These results support the view that changes in the molecular composition of BK channels may be a fundamental event contributing to the development of vascular dysfunction during hypertension.
Risk of Ischemic Stroke in Patients With Symptomatic Vertebrobasilar Stenosis Undergoing Surgical Procedures
Authors: Blacker David J. , Flemming Kelly D. , Wijdicks Eelco F.M.
Published: October 2003

Background and Purpose—

There is little information to provide an estimate for stroke risk in patients with established stenosis or occlusion in the basilar or intracranial vertebral arteries undergoing surgical procedures. The objective of this study was to determine the ischemic stroke risk in this specific patient population.

Methods—

A medical records linkage system retrospectively identified patients with a diagnosis of symptomatic vertebrobasilar stenosis or occlusion matched with surgical procedures. Patients were selected if they had stenosis or occlusion of the basilar or intracranial vertebral arteries identified on vascular imaging before undergoing surgical procedures under general anesthesia. Clinical and radiographic features were reviewed, along with the nature of the surgeries and details of the perioperative management. Records were reviewed for the diagnosis of stroke occurring within 1 month of surgery.

Results—

Thirty-eight patients with a history of symptomatic vertebrobasilar ischemia underwent 50 operations under general anesthesia, and 3 had ischemic strokes in the vertebrobasilar territory immediately after surgery, a per-procedure rate of 6.0% (95% confidence interval, 1.2 to 16.6) All 3 had episodes of prolonged hypotension (systolic blood pressure <100 mm Hg for >10 minutes) during surgery.

Conclusions—

The risk of perioperative stroke in patients with vertebrobasilar stenosis undergoing surgery under general anesthesia is 6.0%, which is notably higher than the risk for patients with other patterns of cerebrovascular disease.
Evidence for an Association Between Air Pollution and Daily Stroke Admissions in Kaohsiung, Taiwan
Authors: Tsai Shang-Shyue , Goggins William B. , Chiu Hui-Fen , Yang Chun-Yuh
Published: October 2003

Background and Purpose—

Many studies have reported increases in daily cardiovascular mortality and hospital admissions associated with increases in levels of air pollutants. However, little is known about the relationship between hospital admissions for stroke and air pollution. This study was undertaken to determine whether there is an association between air pollution and hospital admissions for stroke in Kaohsiung, Taiwan.

Methods—

Data on a total of 23 179 stroke admissions were obtained for the period 1997 through 2000. The relative risk of hospital admissions was estimated with a case-crossover approach.

Results—

In the single-pollutant models, on warm days (≥20°C), significant positive associations were found between levels of PM
10
, NO
2
, SO
2
, CO, and O
3
and both primary intracerebral hemorrhage and ischemic stroke admissions. On cool days (<20°C), only CO levels and ischemic stroke admissions were significantly associated. For the 2-pollutant models, PM
10
and NO
2
remained consistently and significantly associated with admissions for both types of stroke on warm days. We observed estimated relative risks of 1.54 (95% confidence interval [95%], 1.31 to 1.81) and 1.56 (95% CI, 1.32 to 1.84) for primary intracerebral hemorrhage for each interquartile range increase in PM
10
and NO
2
. The values for ischemic stroke were 1.46 (95% CI, 1.32 to 1.61) and 1.55 (95% CI, 1.40 to 1.71), respectively. The effects of CO, SO
2
, and O
3
were mostly nonsignificant when either NO
2
or PM
10
was controlled for.

Conclusions—

This study provides an association between exposure to air pollution and hospital admissions for stroke.
Interactions Between p38 Mitogen-Activated Protein Kinase and Caspase-3 in Cerebral Endothelial Cell Death After Hypoxia-Reoxygenation
Authors: Lee Sun-Ryung , Lo Eng H.
Published: October 2003

Background and Purpose—

The emerging concept of the neurovascular unit in stroke reemphasizes the need to focus on endothelial responses in brain. In this study we examined the role of mitogen-activated protein (MAP) kinase signaling in the regulation of hypoxic cell death in cerebral endothelial cells.

Methods—

Human cerebral microvascular endothelial cells were exposed to 4 to 12 hours of hypoxia followed by 12 to 24 hours of reoxygenation. Cytotoxicity was measured by quantifying lactate dehydrogenase release. DNA laddering and caspase-3 activity were assessed to document a role for caspase-dependent cell death. zVAD-fmk and zDEVD-fmk were used to inhibit caspases. Activation of extracellular signal–regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) was assessed with Western blotting and kinase activity assays. U0126, SB203580, and SP600125 were used to interrupt the ERK, p38, and JNK pathways, respectively.

Results—

Endothelial cell death occurred primarily during reoxygenation. DNA laddering and caspase activation were observed, and cytotoxicity was ameliorated by caspase inhibitors (20 μmol/L of zVAD-fmk or zDEVD-fmk). Among the 3 major MAP kinases, only p38 was transiently activated during reoxygenation, and inhibition with 10 μmol/L of SB203580 significantly reduced cytotoxicity. No effects were observed with other MAP kinase inhibitors. Cytoprotection with SB203580 was not accompanied by caspase downregulation. In contrast, cytoprotection with zVAD-fmk was associated with a decrease in p38 activation. Furthermore, cleavage of MEKK1 (an upstream kinase of p38) was significantly reduced by zVAD-fmk.

Conclusions—

Cerebral endothelial cell death after hypoxia-reoxygenation is mediated by interactions between caspases and p38 MAP kinase. Surprisingly, p38 pathways lie downstream of caspase mechanisms in this model system.
The Use of Harmful to Others-Criterion for Involuntary Treatment in Finland
Authors: Lehtinen  , Korkeila  , Tuohimäki  , Joukamaa  , Tuori  , Kaltiala-Heino
Published: October 2003

During the past decades the Western countries have paid attention to their Mental Health legislation, in particular, by making changes concerning involuntary treatment. In Western countries legislation allows involuntary treatmentof the mentally ill. Involuntary psychiatric treatment is motivated by either potential harm to others (for the good of society) or by need for treatment and/or potential self-harm (for the good of the patient). The aims of this study were to describe to what extent the danger to others criterion is used as a motivation for involuntary hospitalization and detainment in Finland, and to what kind of patients this criterion is applied. The study involves a retrospective chart review of all the treatment periods of a six month admission sample in three Finnish university hospitals. We found that potential harm to others has been rarely used as a motivation for involuntary referral or detainment together with other motivations, and virtually never as the sole motivation. With the exception of gender, which was most often male, patients with potential harm to others did not differ significantly from other involuntarily treated patients. Coercion (defined as seclusion, the use of restraints, forced medication, physical restraint or restrictions in leaving the ward) was not used with these patients more regularly than with the patients motivated by the other criteria. Length of stay (LOS) in a psychiatric hospital did not differ between the patients determined harmful to others and the other involuntarily treated patients.
Turkey
Authors: Büken Erhan , Büken Nüket Örnek
Published: October 2003

The issue of patients' rights is relatively unknown in our country but it is often recalled when an incident of death or disability is suspected as being caused by a physician's error. However patients' rights are being violated thousands of times every day in our country. More than these patients' rights' violations, the essential point is the lack of a mechanism to claim those rights and to complain about the practices which violate them. In our country, patients and their relatives are uninformed, powerless and unprotected against physicians and health organizations, and they typically accept whatever happens to them without complaint. Some of the reasons for this are, presumably, an underdeveloped consciousness of patients' rights, an absence of patient organizations, and insufficient ethical and legal regulations on patients' rights. These deficiencies were diminished somewhat by the "Regulation on Patients' Rights," which was prepared by the Ministry of Health in1998. Another legal draft law referred to as "Responsibilities Due to Malpractice in Medical Services" has been prepared and is in the process of becoming law. This draft law and the general conditions of the country on this subject are evaluated in this article.
Ultrastructure of last larval instar fat body cells of Pachycondyla (= Neoponera) villosa (Formicidae: Ponerinae): cytochemical and chemical analysis
Authors: Zara Fernando José , Caetano Flávio Henrique , Cabrera Aivlé Cecilia , Jaffé Klaus
Published: October 2003

The ultrastructure of the fat body cells (trophocytes) of the last larval instar of Pachycondyla (= Neoponera) villosa is presented. The cytoplasm is restricted to the cell periphery and to the smaller strips among the vacuoles, protein granules, lipid droplets, and around the nucleus. Cytochemically, the presence of basic amino acids in the protein granules and in the nuclei was observed by using the ethanolic phosphotungstic acid technique (EPTA). The lipid droplets stained for unsaturated lipids. This result was further confirmed by gas chromatography and mass spectrometry, where the unsaturated fatty acids were identified as oleic and linoleic acids together with saturated fatty acids such as palmitic and stearic acid. Carbohydrates (glycogen) were also detected in the fat body. The glycogen is present as β particles distributed among the lipid droplets and sometimes attached to them.
Population density of Lepidoptera in a plantation of Eucalyptus urophylla in the state of Minas Gerais, Brazil
Authors: Zanuncio José Cola , Zanuncio Teresinha Vinha , de Freitas Fernando Azevedo , Pratissoli Dirceu
Published: October 2003

A monitoring programme was developed from July 1992 to June 1993 using light traps in a plantation of Eucalyptus urophylla in the municipality of Tres Marias, State of Minas Gerais, Brazil. A total of 437 species of the Lepidoptera order was collected and divided into the following groups: primary pests: 11; secondary pests: 18; species without defined importance to eucalyptus culture: 65; and non-identified species: 343. These four groups had 1295.35, 24.40, 127.20 and 1030.55 individuals per light trap, respectively, with a total of 2477.50 Lepidoptera individuals collected per light trap during this period. Most frequent primary pests were Psorocampa denticulata (Notodontidae), Stenalcidia grosica (Geometridae) and Eupseudosoma aberrans (Arctiidae) which were constant species (present in more than 50% of the collections) with a higher number of individuals during the driest and coldest periods, except P. denticulata, which showed more individuals during the hottest and most humid periods of the year. Faunistic analysis of this area showed a possibility of outbreaks of these primary pests, and mainly of P. denticulata.
The effect of incubation temperature on egg survival, hatchling traits and embryonic use of energy in the blue-tailed skink, Eumeces elegans
Authors: Du Wei-Guo , Shou Lu , Liu Ji-Ke
Published: October 2003

Eggs of the skink, Eumeces elegans were incubated at 24, 27, 30 and 33°C to assess the effect of temperature on hatchling traits and embryonic use of energy. The mean incubation periods of eggs incubated at 24, 27, 30 and 33°C were 44.1, 28.0, 23.6 and 20.0 days, respectively. The mortality of embryos incubated at these temperatures did not differ significantly. The mean snoutvent lengths of hatchlings from 30 and 33°C were smaller than those of hatchlings from 24°C. In contrast, the body masses of hatchlings were not affected by temperature. Incubation temperature can also modify limb lengths of hatchlings. The fore and hind limb lengths of hatchlings from 24°C were longer than those of hatchlings from 33°C. However, tail length and head size (length and width) for hatchlings from different temperatures were similar. The locomotor capacity of hatchlings incubated at 33°C was completely destroyed, whereas that of hatchlings from the other three temperatures did not differ significantly in spite of the existence of differences in hatchling size. Moreover, incubation temperature affected the allocation of energy between carcass and yolk sac in the hatchling, although the overall conversion of energy from eggs to hatchlings was not influenced by temperature. Hatchlings from 30 and 33°C had a less developed carcass and more energy in yolk sac than those from 24°C. Thus, we can conclude that 33°C is not suitable for the incubation of E. elegans eggs, due to damage to the embryo.
Observations on rearing damselflies under laboratory conditions
Authors: van Gossum Hans , Sánchez Rosana , Rivera Adolfo Cordero
Published: October 2003

Rearing damselflies under laboratory conditions is a promising means of solving a variety of biological questions. Therefore, in order to improve the success of future researchers we felt the need to indicate potential difficulties in carrying out rearing experiments. Laboratory crosses were obtained using virgin animals originating from natural populations in Belgium and Spain. Resulting offspring was maintained, under laboratory conditions, in small aquaria until emergence and in insectaries as adults. Our results show that keeping damselflies during their entire life cycle under artificial conditions can be very difficult. We suggest that future researchers should change water regularly, supply sufficient food, and rear animals at low density or even individually. Furthermore, suggestions are given on type of food, advisable laboratory conditions and female oviposition methodology.
Life-history strategies of native and introduced fish species from a Mediterranean lake
Authors: Vila-Gispert  , Moreno-Amich
Published: October 2003

Seven life-history traits were used to describe the life-history strategies of 12 native and introduced species from a permanent lake in Spain. Multivariate analysis identified a continuum of life-history patterns between two extremes: 1) species with one or few spawnings per year, short breeding season, long generation time, large size, high fecundity, and no parental care. This set of life-history traits corresponded to the periodic life-history strategy described by Winemiller (1989) and Winemiller and Rose (1992); and 2) species with multiple spawnings per year, prolonged breeding season, short generation time, small size, low fecundity, parental care, and small to medium size of eggs. This association of life-history traits corresponded to the opportunistic life-history strategy described by Winemiller (1989) and Winemiller and Rose (1992). It seems that there were no apparent differences in life-history strategies between native and introduced species in Lake Banyoles. Native and introduced species were found among periodic and opportunistic strategists. Observed differences in the success of native and introduced species with comparable life-history strategies seems to suggest that the success of fish species in Lake Banyoles could not be explained on the basis of life-history features. Nevertheless, it seems that successful invasive species in Lake Banyoles display a suite of traits such as high fecundity, late maturity, and large body size. These characteristics may perhaps be viewed as biological predictors of successful invaders but more information is needed about life-history features of successful introduced species from other ecosystems.
Body shape variation in relation to resource partitioning within cichlid trophic guilds coexisting along the rocky shore of Lake Malawi
Authors: Kassam Daud , Adams Dean , Ambali Aggrey , Yamaoka Kosaku
Published: October 2003

To appreciate better how cichlids segregate along the trophic, spatial and temporal dimensions, it is necessary to understand the cichlids' body design, and its role in resource partitioning. We investigated body shape variation, quantified using landmark-based geometric morphometrics, among cichlid species belonging to algal and zooplankton feeders coexisting along the rocky shores of Lake Malawi, in order to elucidate the adaptive significance of body shape. Significant differences were found within zooplankton feeders in which Copadichromis borleyi had a shorter gape, smaller eyes and shorter caudal peduncle relative to Ctenopharynx pictus and, within algal feeders, Labeotropheus fuelleborni had a shorter and inferior subterminal gape, and shorter head relative to Petrotilapia genalutea. Variation among species is discussed with reference to trophic and feeding microhabitat differentiation which enables us to appreciate the role of body shape in enhancing ecological separation, and thus leads to coexistence among cichlid species.
Public Response to Cost-Quality Tradeoffs in Clinical Decisions
Authors: Beach Mary Catherine , Asch David A. , Jepson Christopher , Hershey John C. , Mohr Tara , McMorrow Stacey , Ubel Peter A.
Published: October 2003

Purpose. To explore public attitudes toward the incorporation of cost-effectiveness analysis into clinical decisions. Methods. The authors presented 781 jurors with a survey de-scribing 1 of 6 clinical encounters in which a physician has to choose between cancer screening tests. They provided cost-effectiveness data for all tests, and in each scenario, the most effective test was more expensive. They instructed respondents to imagine that he or she was the physician in the scenario and asked them to choose which test to recommend and then explain their choice in an open-ended manner. The authors then qualitatively analyzed the responses by identifying themes and developed a coding scheme. Two authors separately coded the statements with high overall agreement(kappa = 0.76). Categories were not mutually exclusive. Results. Overall, 410 respondents (55%) chose the most expensive option, and 332 respondents (45%) choose a less expensive option. Explanatory comments were given by 82% respondents. Respondents who chose the most expensive test focused on the increased benefit (without directly acknowledging the additional cost) (39%), a general belief that life is more important than money (22%), the significance of cancer risk for the patient in the scenario (20%), the belief that the benefit of the test was worth the additional cost (8%), and personal anecdotes/preferences (6%). Of the respondents who chose the less expensive test, 40% indicated that they did not believe that the patient in the scenario was at significant risk for cancer, 13% indicated that they thought the less expensive test was adequate or not meaningfully different from the more expensive test, 12% thought the cost of the test was not worth the additional benefit, 9% indicated that the test was too expensive (without mention of additional benefit), and 7% responded that resources were limited. Conclusions. Public response to cost-quality tradeoffs is mixed. Although some respondents justified their decision based on the cost-effectiveness information provided, many focused instead on specific features of the scenario or on general beliefs about whether cost should be incorporated into clinical decisions.