bluuebunny/crossref_metadata_2025 huggingface dataset:
Tolerability and Efficacy of Multidose Epoetin Beta (Reco-Pen®) for Subcutaneous Administration in Patients with Anemia due to Renal Failure
Authors: Kleophas W. , Kult J. , Kreusser W. , Piper C. , Plache H. , Wunderle P. , Fiegel V. , Härtl W.
Published: July 2003

Aims: To assess the tolerability, safety and efficacy of the epoetin beta multidose cartridge formulation, self-administered subcutaneously via a pen device (Reco-Pen®), in adult patients with renal anemia. Methods: Patients receiving maintenance epoetin therapy were switched to the subcutaneous (SC) multidose formulation of epoetin beta (NeoRecormon®). The frequency of adverse events, local tolerability, and changes in blood pressure and laboratory variables were recorded. Hematologic parameters, transfusion requirements and epoetin beta dosage were also assessed. Results: A total of 406 patients were entered in the intention-to-treat analysis. Mean treatment duration was 82.3 days. Fifty patients (12.3%) withdrew from the study; 14 (3.4%) discontinued because of adverse events. Treatment was well tolerated, with adverse events considered probably related to treatment in only 5 cases, and 1 case of local intolerability. There were no clinically significant changes in blood pressure or laboratory variables, and no changes in hematologic parameters or transfusion requirements. Unexpectedly, the epoetin beta dose was reduced by almost one-third in patients previously maintained on SC epoetin. Conclusion: SC administration of this multidose epoetin beta formulation with the Reco-Pen® device was well tolerated and effective. It is possible that the improved capacity to individualize dose may have contributed to the considerable reduction in SC epoetin beta dosage requirement.
Is There Any Difference in Pregnancy and Implantation Rates when Nurses Perform Embryo Transfer in an IVF-ET Program?
Authors: Cheung Wai Man , Ng Ernest Hung Yu , Lau Estella Yee Lan , Yeung William Shu Biu , So William Wai Ki , Ho Pak Chung
Published: July 2003

A retrospective analysis of fresh in vitro fertilization treatment cycles and frozen embryo transfer (FET) cycles from mid-1995 to December 31, 1998, was undertaken. Nurses performed embryo transfer (ET) for government-funded cycles, whereas doctors performed ET for self-funded cycles. During the study period, fresh ET was performed in 1,165 treatment cycles. There were no significant differences in demographic data, ovarian responses and the number of embryos replaced between ET cycles performed by nurses and doctors. Pregnancy rates for ETs performed by nurses and doctors were 16.7 and 15.8% per transfer, respectively, whereas the corresponding implantation rates were 8.3 and 6.9%, respectively. Similar pregnancy and implantation rates were encountered in FET cycles whether ET was performed by nurses or doctors.
Does Cord Presentation on Ultrasound Predict Cord Prolapse?
Authors: Ezra Yossef , Strasberg Suzanne R. , Farine Dan
Published: July 2003

Objective: To study the association of umbilical cord presentation found on antenatal ultrasound and the incidence of cord prolapse in labor. Study Design: We reviewed the antenatal records of all deliveries in the Mount Sinai Hospital in a 5-year period and conducted two separate retrospective studies. In the first study we reviewed the antenatal sonograms of all women with proven cord prolapse for cord presentation (study A). In the second study we reviewed the obstetrical outcome of pregnancies where sonographic cord presentation was identified in the third trimester of pregnancy (study B). Results: In study A, 16,551 delivery records were reviewed and 42 patients were found to have had clinical cord prolapse (0.25%). Sonograms were available for 16 of these 42 patients. Only 2 of them (12.5%) had cord presentation on ultrasound scan. In study B, cord presentation was reported in 13 of 8,122 consecutive sonograms (0.16%). Six of these patients (6/13, 46%) had been scanned once. Three required cesarean delivery for malpresentation and cord presentation on ultrasound (3/13, 23%), while the other 3 had uncomplicated vaginal deliveries (23%). The remaining 7 patients had repeat scans which revealed persistent cord presentation in 3 (23%). All 3 underwent cesarean delivery, 1 following cord prolapse. The other 4 spontaneously converted to vertex with resolution of cord presentation as proven at delivery (31%). Conclusion: Cord presentation and cord prolapse are not synonymous. Documented cord presentation during the third trimester necessitates repeat scans and intrapartum sonographic assessment to determine the mode of delivery.
Genetic and Environmental Contributions to Severe Preeclampsia: Lack of Association with the Endothelial Nitric Oxide Synthase Glu298Asp Variant in a Developing Country
Authors: Yoshimura Toshihiro , Chowdhury Ferdous Ara , Yoshimura Michihiro , Okamura Hitoshi
Published: July 2003

Objective: We recently identified a missense variant (Glu298Asp) within exon 7 of the endothelial nitric oxide synthase (eNOS) gene that is associated with severe preeclampsia in the Japanese population. Our objective was to analyze the association between the Glu298Asp eNOS gene variant and severe preeclampsia in a developing country where the incidence of preeclampsia is more frequent. Methods: The study included 112 Bangladeshi women exhibiting severe preeclampsia and 119 control subjects. Screening for the Glu298Asp eNOS gene variant was carried out by analysis of the polymerase chain reaction-restriction fragment length polymorphism. Results: The analysis revealed that the frequencies of the Glu298Asp variant (Glu298Asp homozygotes and heterozygotes) in the preeclampsia (n = 40; 35%) and control (n = 42; 35%) groups were not significantly (p > 0.05) different. Conclusions: We conclude that the presence of the Glu298Asp eNOS gene is not a marker for the increased risk of preeclampsia in a population where the level of prenatal care is such that preeclampsia is still frequently seen.
The Duration of the Third Stage of Labor Is Subject to the Location of Placental Implantation
Authors: Lurie Samuel , Gomel Andrey , Sadan Oscar , Ginath Shimon , Rotmensch Sigi , Glezerman Marek
Published: July 2003

We evaluated the association between placental location and length of the third stage of labor in normal term singleton pregnancies. Two hundred consecutive singleton term live vaginal deliveries following uncomplicated pregnancies were included in a retrospective study. The mean maternal age was 27.5 ± 5.2 years, and the mean parity was 2.2 ± 1.4. Patients’ charts were reviewed in order to determine the placental implantation site. Anterior location of the placenta was noted in 96 women (48%), posterior in 66 (33%), fundal in 26 (13%), and lateral in 12 (6%). The duration of the third stage was 9.5 ± 5.5, 9.4 ± 5.3, 12.8 ± 9.5, and 7.6 ± 3.5 min in anterior, posterior, fundal, and lateral groups, respectively (p < 0.05). The duration of the third stage of labor is statistically significantly longer, if the placenta is located in the fundal area of the uterus. Therefore, we believe that the placental location may be important in managing the third stage of labor.
Association between Plasminogen Activator Inhibitor 1 Gene Polymorphisms and Preeclampsia
Authors: Fabbro Dora , D’Elia Angela V. , Spizzo Riccardo , Driul Lorenza , Barillari Giovanni , Di Loreto Carla , Marchesoni Diego , Damante Giuseppe
Published: July 2003

It is known that the plasminogen activator inhibitor 1 (PAI-1) protein levels are increased in placentas of preeclamptic subjects. Therefore, we assessed whether polymorphisms related to the transcriptional control of the PAI-1 gene (–675 4G/5G and –844G/A) are associated with mild preeclampsia. We compared 52 women with preeclampsia to 80 women with a normal pregnancy. None of the preeclamptic women suffered from the severe form of preeclampsia. DNA was extracted from blood, and –675 4G/5G and –844G/A genotypes of the PAI-1 gene were determined. Since it has been shown that the presence of factor V Leiden, prothrombin G20210A, and MTHFR C677T gene variants may be associated with preeclampsia, their frequency was also evaluated in our study groups. The factor V Leiden, PT G20210A, and MTHFR C677T gene variants were not associated with preeclampsia. In the case of the –675 4G/5G polymorphism, genotypes 4G/4G and 5G/5G were more prevalent in the preeclamptic and in the control group, respectively. In the case of –844 G/A polymorphism, genotypes A/A and G/G were more prevalent in the preeclamptic and in the control group, respectively. By using the χ2 test for trend, differences for both genotypes were significant (p = 0.0141 for the –675 genotypes and p = 0.0492 for the –844 genotypes). The frequency of the 4G and 5G alleles of the –675 gene polymorphism was significantly different between preeclamptic and normal women (p = 0.032). Differently, the allelic frequency of the –844 gene polymorphism did not show significant differences between preeclamptic and normal women (p = 0.083). In conclusion, the hypofibrinolytic genotypes 4G/4G and A/A at positions –675 and –844 of the PAI-1 gene are associated with the occurrence of mild preeclampsia independently of thrombophilic mutations of the factor V, prothrombin, and MTHFR genes.
Biofeedback and Pelvic Floor Exercises for the Rehabilitation of Urinary Stress Incontinence
Authors: Aksac Buket , Aki Semih , Karan Ayse , Yalcin Onay , Isikoglu Mete , Eskiyurt Nurten
Published: July 2003

We investigated the effectiveness of pelvic floor muscle (PFM) exercises or biofeedback for the treatment of urinary stress incontinence (USI). Fifty patients with USI were included in this randomized, controlled, prospective study. Twenty patients were taught PFM exercises via digital palpation and instructed to perform regularly as home program. The second group of 20 patients had PFM exercises via biofeedback three times a week for 2 months. The third group of 10 patients did not have any exercises. The patients were evaluated via pad test, perineometry, digital palpation based PFM strength, incontinence frequency, and visual analog scale based social activity index prior to and 8 weeks after the treatment. The first two groups had significant improvement in USI with respect to the control group (p < 0.001). The rise in PFM strength with perineometry of the biofeedback group was higher than in the digital palpation group after treatment (p < 0.001). PFM exercises are effective for the treatment of USI; the biofeedback method revealed better PFM strength results with respect to digital palpation.
Influence of Allogeneic Blood Transfusion on Clinical Outcome during Radiotherapy for Cancer of the Uterine Cervix
Authors: Santin A.D. , Bellone S. , Parrish R.S. , Coke C. , Dunn D. , Roman J. , Theus J.W. , Cannon M.J. , Parham G.P. , Pecorelli S.
Published: July 2003

Anemia has long been reported to adversely affect the efficacy of radiation treatment in cervical cancer. On the basis of these findings, many radiation oncologists routinely use blood transfusions with the intent to maintain hemoglobin above specified levels during radiation therapy. However, allogeneic blood transfusions have been previously linked with biological and clinical phenomena correlated with immune suppression. In this study we have analyzed the effects of blood transfusion on the outcome of 130 patients with stage-IIB and -III cervical carcinomas treated with external radiation and intracavitary brachytherapy with or without concomitant platinum administration at the University of Arkansas for Medical Sciences between 1990 and 1999. With the exception of hemoglobin and hematocrit levels at the onset of treatment between the transfused and untransfused groups (p < 0.001), the distribution of age, histology, total radiation dose and duration of treatment were not significantly different between the 2 groups of stage-IIB and -III patients. Among the 45 stage-IIB patients who received blood during radiation treatment, there were 31 deaths (68.8%), compared with 14 (31.8%) among the 44 patients who did not receive blood (p > 0.05). Among the 30 stage-III patients who received blood during radiation treatment, there were 27 deaths (90%), compared with 6 (54%) among the 11 patients who did not receive blood (p > 0.11). In multivariate analysis of survival, there was a significant difference due to transfusion with a risk ratio (RR) of 2.6 (95% CI 1.6, 4.2; p < 0.001) after adjusting for no chemotherapy (RR = 2.2, 95% CI 1.4, 3.5; p < 0.001), considering all patients collectively, stage-IIB patients only (RR = 1.9, 95% CI 1.1, 3.3; p < 0.01), and stage-III patients only (RR = 3.2, 95% CI 1.2, 8.7; p < 0.02). These results suggest that routine blood transfusion of anemic cervical cancer patients does not improve outcome and may represent an independent variable predictive of diminished survival during primary radiation treatment for cervical cancer. Prospective randomized studies are strongly warranted to confirm this hypothesis.
The Keeper®, a Menstrual Collection Device, as a Potential Cause of Endometriosis and Adenomyosis
Authors: Spechler Stacey , Nieman Lynnette K. , Premkumar Ahalya , Stratton Pamela
Published: July 2003

Barrier contraceptive devices like the cervical cap and diaphragm and menstrual collecting devices may block menstrual flow, increase retrograde menstruation, and thus theoretically increase the likelihood of developing endometriosis or adenomyosis. We describe the case of a woman with a prior tubal ligation who after 4 years of regular use of the Keeper®, a menstrual collecting device, developed adenomyosis and endometriosis.
Accuracy of Clinical Diagnostic Methods of Threatened Abortion
Authors: Yip Shing-Kai , Sahota Daljit , Cheung Lai-Ping , Lam Peggo , Haines Christopher John , Chung Tony Kwok-Hung
Published: July 2003

Objective: To examine the accuracy of clinical diagnostic methods in assessing vaginal bleeding in pregnant women before 28 weeks’ gestation. Methods: 772 consecutive women who presented with threatened abortion before 28 weeks’ gestation were studied. Structured history and physical examination were performed on each woman as initial clinical assessment. This was followed by transvaginal sonography to determine the status of pregnancy. The accuracy of diagnoses at different clinical stages (history, physical examination, and transvaginal sonography) relative to the final diagnosis was compared using the kappa coefficient (ĸ). Results: Clinicians were unable to accurately diagnose or predict the status of the pregnancy from history alone (ĸ = 0.33; 95% CI 0.28, 0.38) or after physical examination (ĸ = 0.57; 95% CI 0.52, 0.62). Transvaginal sonography led to an accurate diagnosis of pregnancy status (ĸ = 0.96; 95% CI 0.95, 0.98) in most cases, except where an ectopic pregnancy existed. Absence of abdominal tenderness (p = 0.04), cervical excitation (p = 0.02), and incorrect identification of retained products of conception on transvaginal sonography (p = 0.01) were features of missed ectopic pregnancy. Conclusions: The clinical assessment of threatened abortion by history and physical examination is unreliable in most cases. The diagnostic accuracy is improved by the addition of transvaginal sonography. Even with the help of transvaginal sonography, a small proportion of ectopic pregnancies will be missed.
Turbulent Times for Hormone Replacement Therapy: Is There a Way Out?
Authors: Verhaeghe Johan
Published: July 2003

The long-awaited results of the large Women’s Health Initiative (WHI) trial on the effects of combined estrogen-progestin hormone replacement therapy (HRT) in postmenopausal women show that the overall benefits are smaller than the risks. Herein I argue that many of the findings could be predicted from earlier observational studies. Although the WHI trial will rightly reverse the soaring HRT use of the last decades, there is unquestionably a future for HRT. A consensus is growing that postmenopausal women may be treated with HRT only when seeking help for disturbing symptoms of the ovarian hormone insufficiency syndrome, rather than be treated for menopause per se. The ovarian hormone insufficiency syndrome comprises conditions of estrogen and/or androgen insufficiency; at this time, the diagnosis of these clinical entities is based largely on symptomatology. Future research should disclose why the deprivation of ovarian hormones has a variable impact on women’s functioning, and further trials ought to reveal effective and safe treatments for women suffering from this syndrome.
Peritoneal Fluid Concentrations of Ciliary Neurotrophic Factor, a gp130 Cytokine, in Women with Endometriosis
Authors: Suzumori Nobuhiro , Suzumori Kaoru
Published: July 2003

Ciliary neurotrophic factor (CNTF) is a gp130 neuroregulatory cytokine belonging to the interleukin-6-type cytokine superfamily. Several lines of evidence suggest that the concentrations of interleukin-6 are elevated in the peritoneal fluid of endometriosis patients. To our knowledge, no study on whether this might also be the case for CNTF levels has been published previously. The CNTF concentrations in the peritoneal fluid were measured by ELISA in 51 women with (n = 31) and without (n = 20) endometriosis. Surgery was scheduled during the proliferative or the secretory phase of the menstrual cycle. CNTF was detectable in the peritoneal fluid of 43% of the women tested. The concentrations of CNTF showed no correlation with the presence of endometriosis or the phase of the menstrual cycle. We found no evidence to suggest that CNTF is involved in the pathogenesis of pelvic endometriosis.
Impairment of Thermoregulatory Control of Skin Sympathetic Nerve Traffic in the Elderly
Authors: Grassi Guido , Seravalle Gino , Turri Carlo , Bertinieri Giovanni , Dell’Oro Raffaella , Mancia Giuseppe
Published: July 2003

Background—

Human aging is characterized by a marked increase in muscle sympathetic nerve traffic (MSNA). No information exists, however, on the effects of aging on skin sympathetic nerve traffic (SSNA) and on its reflex modulation by thermoregulatory mechanisms.

Methods and Results—

In 13 young, 11 middle-aged, and 12 elderly healthy subjects, we measured arterial blood pressure (Finapres), skin temperature (thermocouples), and resting MSNA and SSNA (microneurography). Measurements also included the SSNA responses to (1) an acute increase and reduction (±8°C) in room temperature, each lasting 45 minutes and (2) an acoustic stimulus capable to trigger an emotional arousal. Although resting MSNA was progressively and significantly (
P
<0.05) increased from young to middle-aged and elderly groups, SSNA was significantly (
P
<0.05) reduced in the latter compared with the former 2 groups. Cold exposure induced a SSNA increase that was significantly (
P
<0.01) smaller in the elderly than in young and middle-aged subjects. Conversely, heat exposure induced a SSNA reduction that was significantly (
P
<0.05) smaller in elderly than in young and middle-aged subjects. Compared with SSNA in young individuals, the SSNA change from cold to warm temperature was reduced by 61% in the elderly group. This was not the case, however, for the SSNA responses to the arousal stimulus, which were superimposable in the 3 groups.

Conclusions—

These data provide the first demonstration of a dichotomy in the MSNA and SSNA responses to aging. They also show that aging markedly impairs thermoregulatory control of SSNA and that this impairment might participate at the age-related SSNA decrease.
Subtype-Selective Antagonists of Lysophosphatidic Acid Receptors Inhibit Platelet Activation Triggered by the Lipid Core of Atherosclerotic Plaques
Authors: Rother Enno , Brandl Richard , Baker Daniel L. , Goyal Pankaj , Gebhard Harry , Tigyi Gabor , Siess Wolfgang
Published: July 2003

Background—

Lysophosphatidic acid (LPA) is a platelet-activating component of mildly oxidized LDL (mox-LDL) and lipids isolated from human atherosclerotic plaques. Specific antagonists of platelet LPA receptors could be useful inhibitors of thrombus formation in patients with cardiovascular disease.

Methods and Results—

Short-chain analogs of phosphatidic acid (PA) were examined for their effect on two initial platelet responses, platelet shape change and Ca
2+
mobilization. Dioctylglycerol pyrophosphate [DGPP(8:0)] and dioctylphosphatidic acid [PA(8:0)], recently described selective antagonists of the LPA
1
and LPA
3
receptors, inhibited platelet activation evoked by LPA but not by other platelet stimuli. DGPP(8:0) was more potent than PA(8:0). DGPP(8:0) also inhibited platelet shape change induced by mox-LDL and lipid extracts from human atherosclerotic plaques. Notably, we demonstrate for the first time that the lipid-rich core isolated from soft plaques was able to directly induce shape change. This effect was completely abrogated by prior incubation of platelets with DGPP(8:0). Moreover, coapplication of the lipid-rich core or LPA together with subthreshold concentrations of ADP or epinephrine synergistically induced platelet aggregation; this effect was inhibited by DGPP(8:0). Analysis by liquid chromatography-mass spectrometry revealed the presence of LPA alkyl- and acyl-molecular species with high platelet-activating potency (16:0-alkyl-LPA, 20:4-acyl-LPA).

Conclusions—

LPA molecules present in the core region of atherosclerotic plaques trigger rapid platelet activation through the stimulation of LPA
1
and LPA
3
receptors. Antagonists of platelet LPA receptors might provide a new strategy to prevent thrombus formation in patients with cardiovascular diseases.
Disruption of Leptin Signaling Contributes to Cardiac Hypertrophy Independently of Body Weight in Mice
Authors: Barouch Lili A. , Berkowitz Dan E. , Harrison Robert W. , O’Donnell Christopher P. , Hare Joshua M.
Published: July 2003

Background—

Whether left ventricular hypertrophy (LVH) in obesity results from increased hemodynamic load or altered neurohormonal signaling remains controversial. Dysregulation of leptin, a neurohormone essential to energy homeostasis, is implicated in the pathogenesis of obesity. Because leptin has cardiovascular bioactivity, we hypothesized that disruption of leptin signaling mediates the development of obesity-associated LVH.

Methods and Results—

We measured left ventricular (LV) wall thickness and LV mass with echocardiography in mice lacking leptin (
ob/ob
, n=15) or functional receptor (
db/db
, n=10) and controls at 2, 4, and 6 months of age. None of the mice had LVH at 2 months. Progressive obesity developed in
ob/ob
and
db/db
mice. At 6 months, LVH occurred in
ob/ob
and
db/db
compared with controls. We observed corresponding myocyte hypertrophy by light microscopy. To separate the direct contribution of leptin deficiency from mechanical effects of obesity, we induced weight loss in 6- to 8-month-old
ob/ob
mice either by leptin infusion or caloric restriction. Mice in both groups lost similar weight compared with placebo-treated controls. Leptin infusion completely reversed the increase in wall thickness with partial resolution of myocyte hypertrophy, whereas calorie-restricted mice had no decrease in wall thickness and a lesser change in myocyte size.

Conclusions—

Together these data show that the effect of leptin on LV remodeling is not attributable to weight loss alone, indicating that leptin has antihypertrophic effects on the heart, either directly or through a leptin-regulated neurohumoral pathway. Disruption of leptin signaling may represent a novel mechanism in LVH and related cardiovascular disorders.
Prophylactic Efficacy of Topical Temporin A and RNAIII-Inhibiting Peptide in a Subcutaneous Rat Pouch Model of Graft Infection Attributable to Staphylococci With Intermediate Resistance to Glycopeptides
Authors: Cirioni Oscar , Giacometti Andrea , Ghiselli Roberto , Dell’Acqua Giorgio , Gov Yael , Kamysz Wojciech , Łukasiak Jerzy , Mocchegiani Federico , Orlando Fiorenza , D’Amato Giuseppina , Balaban Naomi , Saba Vittorio , Scalise Giorgio
Published: July 2003

Background—

Bacteria that adhere to implanted medical devices play an important role in industry and in modern medicine. Staphylococci are among the most common pathogens that cause biomaterial infections. Vascular prosthetic graft infection is one of the most feared complications that the vascular surgeon treats, frequently resulting in prolonged hospitalization, organ failure, amputation, and death. A rat model was used to investigate the topical efficacies of temporin A and the quorum-sensing inhibitor RNAIII-inhibiting protein (RIP) as prophylactic agents of vascular prosthetic graft infections caused by
Staphylococcus aureus
and
Staphylococcus epidermidis
with intermediate resistance to glycopeptides.

Methods and Results—

Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses 1 cm
2
followed by topical inoculation with 2×10
7
colony-forming units of bacterial strains. The study included, for each staphylococcal strain, a control group (no graft contamination), a contaminated group that did not receive antibiotic prophylaxis, and 6 contaminated groups that received grafts soaked with temporin A, RIP, rifampin, temporin A plus RIP, RIP plus rifampin, or temporin A plus RIP. The infection was evaluated by quantitative agar culture. When tested alone, temporin A and RIP showed comparable efficacies, and their efficacies were significantly higher than that of rifampin against both strains. All combinations showed efficacies significantly higher than that of each single compound. The combinations of temporin A and RIP exerted the strongest antistaphylococcal efficacies, eliminating infection by 100%.

Conclusions—

The results of the present study make these molecules potentially useful for antimicrobial chemoprophylaxis in vascular surgery.
A20 Protects From CD40-CD40 Ligand-Mediated Endothelial Cell Activation and Apoptosis
Authors: Longo Christopher R. , Arvelo Maria B. , Patel Virendra I. , Daniel Soizic , Mahiou Jerome , Grey Shane T. , Ferran Christiane
Published: July 2003

Background—

CD40/CD40 ligand (CD40L) signaling is a potent activator of endothelial cells (ECs) and promoter of atherosclerosis. In this study, we investigate whether A20 (a gene we have shown to be antiinflammatory and antiapoptotic in ECs) can protect from CD40/CD40L-mediated EC activation.

Methods and Results—

Overexpression of CD40, in a transient transfection system, activates the transcription factor NF-κB and upregulates IκBα, E-selectin, and tissue factor (TF) reporter activity. Coexpression of A20 inhibits NF-κB and upregulation of IκBα and E-Selectin but not TF, suggesting that CD40 induces TF in a non–NF-κB–dependent manner. In human coronary artery ECs (HCAECs), adenovirus-mediated overexpression of A20 blocks physiological, CD40-induced activation of NF-κB, upstream of IκBα degradation (Western blot) and subsequently upregulation of ICAM-1, VCAM-1, and E-selectin (flow cytometry). Although A20 does not block TF transcription its expression in HCAECs inhibits TF induction (colorimetric assay and RT-PCR) by blunting CD40 upregulation. We demonstrate that CD40 signaling induces apoptosis in a proinflammatory microenvironment. A20 overexpression protects from CD40-mediated EC apoptosis (DNA content analysis and trypan blue exclusion). We also demonstrate that signaling through CD40L activates NF-κB and induces apoptosis in ECs, both of which are inhibited by A20 overexpression.

Conclusion—

A20 works at multiple levels to protect ECs from CD40/CD40L mediated activation and apoptosis. A20-based therapy could be beneficial for the treatment of vascular diseases such as atherosclerosis and transplant-associated vasculopathy.
Ionic Remodeling of Sinoatrial Node Cells by Heart Failure
Authors: Verkerk Arie O. , Wilders Ronald , Coronel Ruben , Ravesloot Jan H. , Verheijck E. Etienne
Published: July 2003

Background—

In animal models of heart failure (HF), heart rate decreases as the result of an increase in intrinsic cycle length of the sinoatrial node (SAN). In this study, we evaluate the HF-induced remodeling of membrane potentials and currents in SAN cells.

Methods and Results—

SAN cells were isolated from control rabbits and rabbits with volume and pressure overload–induced HF and patch-clamped to measure their electrophysiological properties. HF cells were not hypertrophied (capacitance, mean±SEM, 52±3 versus 50±4 pF in control). HF increased intrinsic cycle length by 15% and decreased diastolic depolarization rate by 30%, whereas other action potential parameters were unaltered. In HF, the hyperpolarization-activated “pacemaker” current (
I
f
) and slow component of the delayed rectifier current (
I
Ks
) were reduced by 40% and 20%, respectively, without changes in voltage dependence or kinetics. T-type and L-type calcium current, rapid and ultrarapid delayed rectifier current, transient outward currents, and sodium-calcium exchange current were unaltered.

Conclusions—

In single SAN cells of rabbits with HF, intrinsic cycle length is increased as the result of a decreased diastolic depolarization rate rather than a change in action potential duration. HF reduced both
I
f
and
I
Ks
density. Since
I
Ks
plays a limited role in pacemaker activity, the HF-induced decrease in heart rate is attributable to remodeling of
I
f
.
Decline in Out-of-Hospital Coronary Heart Disease Deaths Has Contributed the Main Part to the Overall Decline in Coronary Heart Disease Mortality Rates Among Persons 35 to 64 Years of Age in Finland
Authors: Salomaa V. , Ketonen M. , Koukkunen H. , Immonen-Räihä P. , Jerkkola T. , Kärjä-Koskenkari P. , Mähönen M. , Niemelä M. , Kuulasmaa K. , Palomäki P. , Mustonen J. , Arstila M. , Vuorenmaa T. , Lehtonen A. , Lehto S. , Miettinen H. , Torppa J. , Tuomilehto J. , Kesäniemi Y.A. , Pyörälä K.
Published: July 2003

Background—

Out-of-hospital deaths constitute the majority of all coronary heart disease (CHD) deaths and are therefore of considerable public health significance.

Methods and Results—

We used population-based myocardial infarction register data to examine trends in out-of-hospital CHD deaths in Finland during 1983 to 1997. We included in out-of-hospital deaths also deaths in the emergency room and all deaths within 1 hour after the onset of symptoms. Altogether, 3494 such events were included in the analyses. The proportion of out-of-hospital deaths of all CHD deaths depended on age and gender. In the age group 35 to 64 years, it was 73% among men and 60% among women. These proportions did not change during the study. The annual average decline in the age-standardized out-of-hospital CHD death rate was 6.1% (95% CI, −7.3, −5.0%) among men and 7.0% (−10.0, −4.0%) among women. These declines contributed among men 70% and among women 58% to the overall decline in CHD mortality rate. In all, 58% of the male and 52% of the female victims of out-of-hospital CHD death had a history of symptomatic CHD. Among men with a prior history of myocardial infarction, the annual average decline in out-of-hospital CHD deaths was 5.3% (−7.2, −3.2%), and among men without such history the decline was 2.9% (−4.4, −1.5%). Among women, the corresponding changes were −7.8% (−14.2, −1.5%) and −4.5% (−8.0, −1.0%).

Conclusions—

The decline in out-of-hospital CHD deaths has contributed the main part to the overall decline in CHD mortality rates among persons 35 to 64 years of age in Finland.
Norepinephrine Precursor Therapy in Neurogenic Orthostatic Hypotension
Authors: Kaufmann Horacio , Saadia Daniela , Voustianiouk Andrei , Goldstein David S. , Holmes Courtney , Yahr Melvin D. , Nardin Rachel , Freeman Roy
Published: July 2003

Background—

In patients with neurogenic orthostatic hypotension (NOH), the availability of the sympathetic neurotransmitter norepinephrine (NE) in the synaptic cleft is insufficient to maintain blood pressure while in the standing posture.

Methods and Results—

We determined the effect of oral administration of the synthetic amino acid L-threo-3,4-dihydroxyphenylserine (L-DOPS), which is decarboxylated to NE by the enzyme L–aromatic amino acid decarboxylase (L-AADC) in neural and nonneural tissue, on blood pressure and orthostatic tolerance in 19 patients with severe NOH (8 with pure autonomic failure and 11 with multiple-system atrophy). A single-blind dose-titration study determined the most appropriate dose for each patient. Patients were then enrolled in a double-blind, placebo-controlled, crossover trial. L-DOPS significantly raised mean blood pressure both supine (from 101±4 to 141±5 mm Hg) and standing (from 60±4 to 100±6 mm Hg) for several hours and improved orthostatic tolerance in all patients. After L-DOPS, blood pressure increases were closely associated with increases in plasma NE levels. Oral administration of carbidopa, which inhibits L-AADC outside the blood-brain barrier, blunted both the increase in plasma NE and the pressor response to L-DOPS in all patients

Conclusions—

Acute administration of L-DOPS increases blood pressure and improves orthostatic tolerance in patients with NOH. The pressor effect results from conversion of L-DOPS to NE outside the central nervous system.
Increasing Trends in Hospitalization for Atrial Fibrillation in the United States, 1985 Through 1999
Authors: Wattigney Wendy A. , Mensah George A. , Croft Janet B.
Published: July 2003

Background—

Atrial fibrillation, the most common sustained disturbance of heart rhythm, is associated with a 5-fold increase in the incidence of ischemic stroke.

Methods and Results—

The National Hospital Discharge Survey was used to estimate the annual number and prevalence of hospitalizations with atrial fibrillation among men and women 35 years of age or older. From 1985 through 1999, hospitalizations increased from 154 086 to 376 487 for a first-listed diagnosis and from 787 750 to 2 283 673 for any diagnosis. Prevalence was higher among successive age groups. Age-standardized prevalence was consistently higher among men than women. In 1999, essential hypertension, ischemic heart disease, congestive heart failure, and diabetes were prominent coexisting conditions. The number of male patients discharged home decreased from 77% to 63%, whereas the number of discharges to long-term care increased from 9% to 15%; the corresponding values for women were 72% to 56% and 15% to 23%. A slight increase in discharges to short-term care was indicated, whereas no trends were noted for in-hospital mortality.

Conclusions—

Hospitalizations for atrial fibrillation have increased dramatically (2- to 3-fold) in recent years. The public health burden of atrial fibrillation is enormous and expected to continue to increase over the next decades. Primary prevention of atrial fibrillation must be recognized and pursued as a complementary management strategy for reducing cardiovascular morbidity and mortality.
Effect of 7-Year Infancy-Onset Dietary Intervention on Serum Lipoproteins and Lipoprotein Subclasses in Healthy Children in the Prospective, Randomized Special Turku Coronary Risk Factor Intervention Project for Children (STRIP) Study
Authors: Kaitosaari Tuuli , Rönnemaa Tapani , Raitakari Olli , Talvia Sanna , Kallio Katariina , Volanen Iina , Leino Aila , Jokinen Eero , Välimäki Ilkka , Viikari Jorma , Simell Olli
Published: July 2003

Background—

We previously showed that low-saturated-fat dietary intervention from infancy until 5 years of age safely and effectively reduced serum cholesterol concentration. We now report how such intervention influenced serum lipids, LDL particle size, and HDL subfractions in children when they reached the age of 7 years.

Methods and Results—

Healthy 7-month-old infants (n=1062) were randomized to the intervention (n=540) and control (n=522) groups. Each year, two individualized counseling sessions were organized to the intervention families. Serum lipid values were measured annually. The intervention boys had 0.20 to 0.39 mmol/L lower serum cholesterol values than the control boys throughout the follow-up (always
P
<0.05), but the values of the intervention and control girls did not differ. The LDL particle sizes and HDL subfractions were determined in a random subgroup of 96 intervention and 101 control children at the age of 7 years. The mean particle diameter of major LDL peak was 262.6 Å in the intervention boys and 258.5 Å in the control boys (
P
=0.05), and 259.2 Å in the intervention girls and 261.3 Å in the control girls (
P
=0.30). HDL
2
and HDL
3
cholesterol concentrations did not differ between the intervention and control children or between the two genders.

Conclusions—

The 7-year intervention favorably influenced not only the serum total and LDL cholesterol concentrations but also the LDL particle size in boys. LDL particle size remained unchanged in girls, as did HDL
2
and HDL
3
concentrations in both genders.
Regression of Electrocardiographic Left Ventricular Hypertrophy by Losartan Versus Atenolol
Authors: Okin Peter M. , Devereux Richard B. , Jern Sverker , Kjeldsen Sverre E. , Julius Stevo , Nieminen Markku S. , Snapinn Steven , Harris Katherine E. , Aurup Peter , Edelman Jonathan M. , Dahlöf Björn
Published: July 2003

Background—

Electrocardiographic left ventricular hypertrophy (LVH) predicts cardiovascular morbidity and mortality, and regression of ECG LVH may predict improved prognosis in hypertensive patients. However, uncertainty persists as to how best to regress ECG LVH.

Methods and Results—

Regression of ECG LVH with losartan versus atenolol therapy was assessed in 9193 hypertensive patients with ECG LVH by Sokolow-Lyon voltage or Cornell voltage-duration product criteria enrolled in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) Study. Patients had ECGs at study baseline and after 6 months, 1, 2, 3, 4, and 5 years of blinded losartan-based or atenolol-based therapy. After 6 months’ follow-up, adjusting for baseline ECG LVH levels, baseline and in-treatment systolic and diastolic pressures, and for diuretic therapy, losartan-based therapy was associated with greater regression of both Cornell product (adjusted means, −200 versus −69 mm · ms,
P
<0.001) and Sokolow-Lyon voltage (−2.5 versus −0.7 mm,
P
<0.001) than was atenolol-based therapy. Greater regression of ECG LVH persisted at each subsequent annual evaluation in the losartan-treated group, with between 140 and 164 mm · ms greater mean reductions in Cornell product and from 1.7 to 2.2 mm greater mean reductions in Sokolow-Lyon voltage (all
P
<0.001). The effect of losartan was consistent across subgroups defined by gender, age, ethnicity, and diabetes.

Conclusions—

After adjusting for baseline and in-treatment blood pressure and baseline severity of ECG LVH, losartan-based antihypertensive therapy resulted in greater regression of ECG LVH by Cornell voltage-duration product and Sokolow-Lyon voltage criteria than did atenolol-based therapy. These findings support the value of angiotensin receptor blockade with losartan for reversing ECG LVH.
Characterization of Endocardial Electrophysiological Substrate in Patients With Nonischemic Cardiomyopathy and Monomorphic Ventricular Tachycardia
Authors: Hsia Henry H. , Callans David J. , Marchlinski Francis E.
Published: July 2003

Background—

Although catheter mapping has been used to define the endocardial electrogram characteristics in patients with ventricular tachycardia (VT) and coronary disease, characterization of the electrophysiological substrate in patients with VT and nonischemic cardiomyopathy is limited.

Methods and Results—

Left ventricular endocardial electroanatomical mapping was performed in 19 patients with nonischemic cardiomyopathy and monomorphic VT with an average of 178±83 sites per chamber mapped. Abnormal bipolar electrogram was defined as endocardial voltage signal amplitude of <1.8 mV. The extent and location of abnormal endocardium was estimated by measuring areas of abnormal electrogram recordings from 3D voltage maps. The origin of VT was approximated by identifying sites of entrainment with concealed fusion or early presystolic activity and/or by pace mapping. Abnormal electrograms were recorded over a 41±28 cm
2
area that represented 20±12% of total endocardial surface. The majority of patients (14/19 patients) had only a modest area (<25%) of endocardial abnormality. All patients had abnormal low-voltage endocardial areas located near the ventricular base in the perivalvular region. There were 3±1 VT morphologies per patient. The majority (88%) of the 57 mapped VTs originated from the ventricular base, corresponding to regions with abnormal endocardial electrograms.

Conclusions—

Electroanatomical mapping in patients with monomorphic VT and nonischemic cardiomyopathy typically demonstrates a modest-sized basal area of endocardial electrogram abnormalities. The VT site of origin corresponds to these basal electrogram abnormalities. These findings have important implications regarding strategies for VT ablation in this setting.
Short-Term Statin Therapy Improves Cardiac Function and Symptoms in Patients With Idiopathic Dilated Cardiomyopathy
Authors: Node Koichi , Fujita Masashi , Kitakaze Masafumi , Hori Masatsugu , Liao James K.
Published: July 2003

Background—

Chronic heart failure is associated with inflammation and neurohormonal imbalance. The 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, or statins, exert anti-inflammatory and vascular protective effects. We hypothesized that short-term statin therapy may have beneficial effects in patients with nonischemic heart failure.

Methods and Results—

Sixty-three patients with symptomatic, nonischemic, dilated cardiomyopathy were randomly divided into 2 groups. One group received simvastatin (n=24), and the other group received placebo (n=27). The initial dose of simvastatin was 5 mg/d, which was increased to 10 mg/d after 4 weeks. After 14 weeks, patients receiving simvastatin exhibited a modest reduction in serum cholesterol level compared with patients receiving placebo (130±13 versus 148±18,
P
<0.05). Patients treated with simvastatin had a lower New York Heart Association functional class compared with patients receiving placebo (2.04±0.06 versus 2.32±0.05,
P
<0.01). This corresponded to improved left ventricular ejection fraction in the simvastatin group (34±3 to 41±4%,
P
<0.05) but not in the placebo group. Furthermore, plasma concentrations of tumor necrosis factor-α, interleukin-6, and brain natriuretic peptide were significantly lower in the simvastatin group compared with the placebo group.

Conclusions—

Short-term statin therapy improves cardiac function, neurohormonal imbalance, and symptoms associated with idiopathic dilated cardiomyopathy. These findings suggest that statins may have therapeutic benefits in patients with heart failure irrespective of serum cholesterol levels or atherosclerotic heart disease.
Percutaneous Balloon Valvotomy in Pulmonary Atresia With Intact Ventricular Septum
Authors: Humpl Tilman , Söderberg Björn , McCrindle Brian W. , Nykanen David G. , Freedom Robert M. , Williams William G. , Benson Lee N.
Published: July 2003

Background—

Pulmonary atresia with intact ventricular septum (PA-IVS) is a rare congenital lesion with high mortality. Therapy was exclusively surgical until recently, when the use of radiofrequency-assisted perforation of the atretic valve was introduced as a treatment option. This study analyzes the outcomes and morphological changes to right heart structures after percutaneous perforation and balloon dilation of the atretic valve.

Methods and Results—

Between April 1992 and August 2000, 30 patients with PA-IVS underwent attempted percutaneous valve perforation and balloon dilation of the pulmonary valve. Longitudinal echocardiographic measurements of the tricuspid valve diameter, right ventricular length and area were recorded.
Z
scores were calculated according to published formulas. Perforation was achieved in 27 patients. In 14 patients a modified Blalock-Taussig shunt was performed between 2 and 24 days after valve dilation. There were 3 early and 2 late deaths. Among the survivors (follow-up time of 1 to 87 months), 16 patients had a biventricular circulation, 3 a 1 ½-ventricle circulation, and 1 a Fontan operation. Four patients are awaiting further palliation. There was no significant change of the tricuspid valve
Z
score or right ventricular length
Z
score with time.

Conclusions—

Percutaneous balloon valvotomy is an effective treatment strategy for patients with PA-IVS provided that there is a patent infundibulum and a lack of a right ventricle–dependent coronary circulation. Despite the observation that right heart growth does not increase with body growth in early follow-up, it appears adequate to maintain a biventricular circulation in many patients.
Do Hospitals and Surgeons With Higher Coronary Artery Bypass Graft Surgery Volumes Still Have Lower Risk-Adjusted Mortality Rates?
Authors: Hannan Edward L. , Wu Chuntao , Ryan Thomas J. , Bennett Edward , Culliford Alfred T. , Gold Jeffrey P. , Hartman Alan , Isom O. Wayne , Jones Robert H. , McNeil Barbara , Rose Eric A. , Subramanian Valavanur A.
Published: July 2003

Background—

Studies that are the basis of recommended volume thresholds for CABG surgery are outdated and not reflective of recent advances in the field. This study examines both hospital and surgeon volume-mortality relations for CABG surgery through the use of a population-based clinical data set.

Methods and Results—

Data from New York’s clinical CABG surgery registry from 1997 to 1999 (total number of procedures, 57 150) were used to examine the individual and combined impact of annual hospital volume and annual surgeon volume on in-hospital mortality rates after adjusting for differences in severity of illness. Significantly lower risk-adjusted mortality rates occurred above all annual hospital volume thresholds between 200 and 800 and above all surgeon volume thresholds between 50 and 200. The number needed to treat (NNT) at higher-volume providers to avoid a death was minimized for a hospital threshold volume of 100 (NNT=50) and a surgeon threshold volume of 50 (NNT=118). The risk-adjusted mortality rate (RAMR) for patients undergoing surgery performed by surgeons with volumes of ≥125 in hospitals with volumes of ≥600 was 1.89%. The RAMR was significantly higher (2.67%) for patients undergoing surgery performed by surgeons with volumes of <125 in hospitals with volumes of <600.

Conclusions—

Higher-volume surgeons and hospitals continue to have lower risk-adjusted mortality rates, and patients undergoing surgery performed by higher-volume surgeons in higher-volume hospitals have the lowest mortality rates.
Prognostic Value of Lead aVR in Patients With a First Non–ST-Segment Elevation Acute Myocardial Infarction
Authors: Barrabés José A. , Figueras Jaume , Moure Cristina , Cortadellas Josefa , Soler-Soler Jordi
Published: July 2003

Background—

ST-segment elevation in lead aVR has been associated with severe coronary artery lesions in patients with acute coronary syndromes, but the prognostic significance of this finding is unknown.

Methods and Results—

We analyzed the initial ECG in 775 consecutive patients admitted to our center with a first acute myocardial infarction without ST-segment elevation in leads other than aVR or V
1
. The rates of in-hospital death in patients without (n=525) and with 0.05 to 0.1 mV (n=116) or ≥0.1 mV (n=134) of ST-segment elevation in lead aVR were 1.3%, 8.6%, and 19.4%, respectively (
P
<0.001). After adjustment for the baseline clinical predictors and for ST-segment depression on admission, the odds ratios for death in the last 2 groups were, respectively, 4.2 (95% CI, 1.5 to 12.2) and 6.6 (95% CI, 2.5 to 17.6). The rates of recurrent ischemic events and heart failure during hospital stay also increased in a stepwise fashion among the groups, whereas creatine kinase–MB levels were similar. Among the 437 patients that were catheterized within 6 months, the prevalence of left main or 3-vessel coronary artery disease in the 3 groups was 22.0%, 42.6%, and 66.3%, respectively (
P
<0.001).

Conclusions—

Lead aVR contains important short-term prognostic information in patients with a first non–ST-segment elevation acute myocardial infarction. Because the poorer outcome predicted by ST-segment elevation in lead aVR seems to be related to a more severe coronary artery disease, an early invasive approach might be especially beneficial in patients presenting with this finding.