bluuebunny/crossref_metadata_2025 huggingface dataset:
Electromechanical Mapping Identifies Improvement in Function and Retention of Contractile Reserve After Revascularization in Ischemic Cardiomyopathy
Authors: Samady Habib , Choi C. Joon , Ragosta Michael , Powers Eric R. , Beller George A. , Kramer Christopher M.
Published: October 2004

Background—

We hypothesized that (1) a significant proportion of ischemic dysfunctional segments that do not improve function will demonstrate postrevascularization contractile reserve and (2) electromechanical mapping (EMM) can identify segments that improve function as well as those with postrevascularization contractile reserve, a potential indicator of delayed functional improvement.

Methods and Results—

Eighteen patients with severe ischemic left ventricular dysfunction underwent EMM and dobutamine (D) cardiac magnetic resonance imaging (CMR) followed by revascularization. Four months after revascularization, all patients underwent a repeated D-CMR, and at 35 months, a subgroup (n=6) underwent a third CMR. Of 120 dysfunctional segments, 60 segments had improved rest function (IRF) and 60 did not. Twenty-eight of 60 segments (47%) that did not improve RF demonstrated postrevascularization contractile reserve (CR), and 32 of 60 segments (53%) that demonstrated neither IRF nor CR were persistently dysfunctional (PD). CR segments recovered significantly greater late function compared with IRF or PD: 14±12% vs 2±5% and 4±7%, respectively;
P
<0.05. EMM ratio, defined as the unipolar voltage divided by linear shortening, was significantly higher in IRF segments compared with segments that did not improve RF: 2.4±4.5 vs 0.7±3.5,
P
<0.05. Unipolar voltage was stepwise lower in normal, IRF, CR, and PD segments (10.5±4.7, 9.3±3.9, 8.8±3.2, and 7.4±2.3 mV, respectively;
P
<0.01 for trend).

Conclusions—

Almost half of dysfunctional myocardial segments in chronic ischemic heart disease that do not improve RF early after revascularization demonstrate early CR and delayed functional recovery. EMM parameters can identify segments that improve RF and retain CR early after revascularization.
Blockade of Vascular Endothelial Growth Factor Suppresses Experimental Restenosis After Intraluminal Injury by Inhibiting Recruitment of Monocyte Lineage Cells
Authors: Ohtani Kisho , Egashira Kensuke , Hiasa Ken-ichi , Zhao Qingwei , Kitamoto Shiro , Ishibashi Minako , Usui Makoto , Inoue Shujiro , Yonemitsu Yoshikazu , Sueishi Katsuo , Sata Masataka , Shibuya Masabumi , Sunagawa Kenji
Published: October 2004

Background—

Therapeutic angiogenesis by delivery of vascular endothelial growth factor (VEGF) has attracted attention. However, the role and function of VEGF in experimental restenosis (neointimal formation) after vascular intraluminal injury have not been addressed.

Methods and Results—

We report herein that blockade of VEGF by soluble VEGF receptor 1 (
sFlt-1
) gene transfer attenuated neointimal formation after intraluminal injury in rabbits, rats, and mice.
sFlt-1
gene transfer markedly attenuated the early vascular inflammation and proliferation and later neointimal formation.
sFlt-1
gene transfer also inhibited increased expression of inflammatory factors such as monocyte chemoattractant protein-1 and VEGF. Intravascular VEGF gene transfer enhanced angiogenesis in the adventitia but did not reduce neointimal formation.

Conclusions—

Increased expression and activity of VEGF are essential in the development of experimental restenosis after intraluminal injury by recruiting monocyte-lineage cells.
Engineered Zinc Finger–Activating Vascular Endothelial Growth Factor Transcription Factor Plasmid DNA Induces Therapeutic Angiogenesis in Rabbits With Hindlimb Ischemia
Authors: Dai Qunsheng , Huang Jianhua , Klitzman Bruce , Dong Chunming , Goldschmidt-Clermont Pascal J. , March Keith L. , Rokovich Joseph , Johnstone Brian , Rebar Edward J. , Spratt S. Kaye , Case Casey C. , Kontos Christopher D. , Annex Brian H.
Published: October 2004

Background—

Therapeutic angiogenesis seeks to promote blood vessel growth to improve tissue perfusion. Vascular endothelial growth factor (VEGF) exists in multiple isoforms. We investigated an engineered zinc finger–containing transcription factor plasmid designed to activate the endogenous VEGF gene (ZFP-VEGF).

Methods and Results—

New Zealand White rabbits (n=56) underwent unilateral femoral artery ligation and excision. At day 10 postoperatively, the ischemic muscle received ZFP treatment (500 μg ZFP-VEGF plasmid) or no ZFP treatment (β-galactosidase, empty, or no plasmid). Group 1 (n=13) was harvested 3 days after injection to examine VEGF mRNA by real-time polymerase chain reaction and protein by ELISA. Groups 2 (n=13) and 3 (n=10) were harvested 11 days after injection. Group 2 was studied by histology and group 3, by histology and changes in blood flow. Groups 4 and 5 (n=10 each) were harvested 22 and 32 days after injection, respectively, and studied for changes in blood flow. In group 1, VEGF mRNA copy numbers were significantly higher for VEGF
121
, VEGF
165
, VEGF
189
, and protein in the ZFP-VEGF-treatment versus no-ZFP-treatment arms. In groups 2 and 3, capillary density and proliferating cells were significantly greater and apoptosis significantly lower in the treatment versus no-treatment arms. Changes in the blood flow ratio of the ischemic to the nonischemic limb were significantly greater in the treatment versus no-ZFP-treatment groups (6.57±1.52% versus 3.38±0.87%,
P
<0.005; 13.15±1.77% versus 6.13±1.55%,
P
<0.001; and 20.16±2.84% versus 13.88±3.14%,
P
<0.01, for groups 3, 4, and 5, respectively).

Conclusions—

This engineered ZFP-VEGF–activating transcription factor may provide a novel approach to treat peripheral arterial disease.
Electroanatomic Substrate and Outcome of Catheter Ablative Therapy for Ventricular Tachycardia in Setting of Right Ventricular Cardiomyopathy
Authors: Marchlinski Francis E. , Zado Erica , Dixit Sanjay , Gerstenfeld Edward , Callans David J. , Hsia Henry , Lin David , Nayak Hemal , Russo Andrea , Pulliam Ward
Published: October 2004

Background—

To gain insight into the pathogenesis of right ventricular (RV) cardiomyopathy and ventricular tachycardia (VT), we determined the clinical and electroanatomic characteristics and outcome of ablative therapy in consecutive patients with (1) RV dilatation, (2) multiple left bundle-branch block (LBBB)–type VTs, and (3) an abnormal endocardial substrate defined by contiguous electrogram abnormalities.

Methods and Results—

All 21 patients had detailed RV bipolar electrogram voltage mapping. Eighteen patients had simultaneous left ventricular (LV) mapping, including all 4 patients with right bundle-branch block (RBBB) VT. VT was ablated in 19 patients by use of focal and/or linear lesions with irrigated-tip catheters in 10 of 19 patients. Eighteen patients were men, age 47±18 years, and none had a family history of RV dysplasia. RV volume was 223±89 cm
3
. Electrogram abnormalities extended from perivalvular tricuspid valves (5 patients), pulmonic valves (6 patients), or both valves (10 patients). Electrogram abnormalities always involved free wall, spared the apex, and included the septum in 15 patients (71%). The area of abnormality was 55±37 cm
2
(range, 12 to 130 cm
2
) and represented 34±19% of the RV. In 52 of 66 LBBB VTs, the origin was from the RV perivalvular region. LV perivalvular low-voltage areas noted in 5 patients were associated with a RBBB VT origin. No VT recurred after ablation in 17 patients (89%) during 27±22 months.

Conclusions—

In patients with RV cardiomyopathy and VT, (1) perivalvular electrogram abnormalities represent the commonly identified substrate and source of most VT, (2) LV perivalvular endocardial electrogram abnormalities and VT can occasionally be identified, and (3) aggressive ablative therapy provides long-term VT control.
Ongoing Myocardial Injury in Stable Severe Heart Failure
Authors: Perna Eduardo R. , Macin Stella M. , Canella Juan P. Cimbaro , Augier Natalia , Stival Jorge L. Riera , Cialzeta Jorge R. , Pitzus Ariel E. , Garcia Edgar H. , Obregón Ricardo , Brizuela Mónica , Barbagelata Alejandro
Published: October 2004

Background—

The progression of chronic heart failure (CHF) is related to ongoing myocyte loss, which can be detected by cardiac troponin T (cTnT). We examined the prevalence and prognostic value of increased cTnT concentrations in serial blood specimens from patients with severe CHF.

Methods and Results—

Clinical, echocardiographic, and 6-minute walk test data were collected prospectively at baseline and at 1 year in 115 outpatients (mean age, 61±11 years; 75% men; 62% coronary heart disease) with CHF and a left ventricular ejection fraction <40%. Blood samples were collected at baseline and at 3, 6, and 12 months of follow-up. cTnT concentrations ≥0.02 ng/mL were considered abnormal, and a Tn index (highest cTnT measurement/0.02 ng/mL) was calculated. In 62 patients (54%), cTnT was consistently <0.02 ng/mL (group 1); 28 (24%) had a single abnormal cTnT result (group 2); and 25 (22%) had ≥2 abnormal cTnT results (group 3). At 18 months, CHF hospitalization-free survival was 63%, 46%, and 17%, respectively (
P
=0.0001). In a Cox proportional-hazards model, hospitalization for worsening CHF in the previous year (HR=2.1; 95% CI, 1.1 to 4.1), functional class III–IV (HR=2.3; 95% CI, 1.1 to 4.6), and number of abnormal cTnT samples (HR=1.6; 95% CI, 1.1 to 2.4) were independently associated with prognosis. A cTnT rise of 0.020 ng/mL in any sample was associated with an excess of 9% (95% CI, 1% to 18%) in the incidence of combined end point.

Conclusions—

Abnormal cTnT concentrations were detected in >50% of outpatients with advanced CHF. This ongoing myocardial necrosis was a strong predictor of worsening CHF, suggesting a role of cTnT-based monitoring to identify high-risk patients.
Prostaglandin E
2
—Mediated Relaxation of the Ductus Arteriosus
Authors: Waleh Nahid , Kajino Hiroki , Marrache Anne Marilise , Ginzinger David , Roman Christine , Seidner Steven R. , Moss Timothy J.M. , Fouron Jean-Claude , Vazquez-Tello Alejandro , Chemtob Sylvain , Clyman Ronald I.
Published: October 2004

Background—

In the preterm newborn, a patent ductus arteriosus is in large part a result of the increased sensitivity of the immature ductus to prostaglandin E
2
(PGE
2
). PGE
2
acts through 3 G protein–coupled receptors (EP
2
, EP
3
, and EP
4
) that activate both adenyl cyclase and K
ATP
channels. We explored these pathways to identify the mechanisms responsible for the increased sensitivity of the immature ductus to PGE
2
.

Methods and Results—

We measured EP receptor content (mRNA and protein), receptor binding, cAMP production, and isometric tension in rings of ductus taken from immature (65% gestation) and mature (95% gestation) sheep and baboon fetuses. Ductus relaxation and cAMP generation were augmented in response to selective EP receptor agonists in the immature ductus. 8-Br-cAMP, a stable cAMP analogue, produced greater relaxation in the immature ductus. In the presence of a selective protein kinase A inhibitor, Rp-8-CPT cAMPS, the developmental differences in sensitivity to PGE
2
could no longer be demonstrated. EP
2
, EP
3
, and EP
4
receptor densities were higher in immature ductus, despite similar receptor mRNA and protein contents at the 2 gestational ages. In contrast, forskolin and NaF, direct activators of adenyl cyclase and G
s
, respectively, elicited comparable increases in cAMP in both age groups. K
ATP
channel inhibition also had similar effects on PGE
2
-induced relaxation in both age groups.

Conclusions—

Two mechanisms explain the increased sensitivity of the immature ductus to PGE
2
: (1) increased cAMP production because of increased binding of PGE
2
to the individual EP receptors and (2) increased potency of cAMP on protein kinase A–regulated pathways.
Increased Short-Term Variability of Repolarization Predicts
d
-Sotalol–Induced Torsades de Pointes in Dogs
Authors: Thomsen Morten B. , Verduyn S. Cora , Stengl Milan , Beekman Jet D.M. , de Pater Geert , van Opstal Jurren , Volders Paul G.A. , Vos Marc A.
Published: October 2004

Background—

Identification of patients at risk for drug-induced torsades de pointes arrhythmia (TdP) is difficult. Increased temporal lability of repolarization has been suggested as being valuable to predict proarrhythmia. The predictive value of different repolarization parameters, including beat-to-beat variability of repolarization (BVR), was compared in this serial investigation in dogs with chronic AV block.

Methods and Results—

In anesthetized dogs with electrically remodeled hearts, the dose-dependent difference in drug-induced TdP (
d
-sotalol, 2 and 4 mg/kg IV over 5 minutes, 25% and 75% TdP, respectively) could not be accounted for by prolongation of QT
c
(410±37 to 475±60 versus 415±47 to 484±52 ms, respectively). BVR was quantified by Poincaré plots at baseline and immediately before onset of
d
-sotalol–induced extrasystolic activity. TdP occurrence was associated with an increase in short-term variability (STV) of the left ventricular monophasic action potential duration (3.5±1.5 to 5.5±1.6 versus 3.0±0.7 to 8.6±3.8 ms, respectively), which was reversible when TdP was abolished by
I
K,ATP
activation. The absence of TdP despite QT
c
prolongation after chronic amiodarone treatment could also be explained by an unchanged STV. In experiments with isolated ventricular myocytes, STV increased after
I
Kr
block and was highest in cells that subsequently showed early afterdepolarizations.

Conclusions—

Proarrhythmia is not related to differences in prolongation of repolarization but corresponds to BVR, here quantified as STV of the left ventricle. STV could be a new parameter to predict drug-induced TdP in patients.
Effect of Simvastatin and Antioxidant Vitamins on Atrial Fibrillation Promotion by Atrial-Tachycardia Remodeling in Dogs
Authors: Shiroshita-Takeshita Akiko , Schram Gernot , Lavoie Joel , Nattel Stanley
Published: October 2004

Background—

There is evidence for a role of oxidant stress and inflammation in atrial fibrillation (AF). Statins have both antioxidant and antiinflammatory properties. We compared the effects of simvastatin with those of antioxidant vitamins on AF promotion by atrial tachycardia in dogs.

Methods and Results—

We studied dogs subjected to atrial tachypacing (ATP) at 400 bpm in the absence and presence of treatment with simvastatin, vitamin C, and combined vitamins C and E. Serial closed-chest electrophysiological studies were performed in each dog at baseline and 2, 4, and 7 days after tachypacing onset. Atrioventricular block was performed to control ventricular rate. Mean duration of induced AF was increased from 42±18 to 1079±341 seconds at terminal open-chest study after tachypacing alone (
P
<0.01), and atrial effective refractory period (ERP) at a cycle length of 300 ms was decreased from 117±5 to 76±6 ms (
P
<0.01). Tachypacing-induced ERP shortening and AF promotion were unaffected by vitamin C or vitamins C and E; however, simvastatin suppressed tachypacing-induced remodeling effects significantly, with AF duration and ERP averaging 41±15 seconds and 103±4 ms, respectively, after tachypacing with simvastatin therapy. Tachypacing downregulated L-type Ca
2+
-channel α-subunit expression (Western blot), an effect that was unaltered by antioxidant vitamins but greatly attenuated by simvastatin.

Conclusions—

Simvastatin attenuates AF promotion by atrial tachycardia in dogs, an effect not shared by antioxidant vitamins, and constitutes a potentially interesting new pharmacological approach to preventing the consequences of atrial tachycardia remodeling.
Associations of Parental, Birth, and Early Life Characteristics With Systolic Blood Pressure at 5 Years of Age
Authors: Lawlor Debbie A. , Najman Jake M. , Sterne Jonathan , Williams Gail M. , Ebrahim Shah , Smith George Davey
Published: October 2004

Background—

We examined the associations of a range of parental and early life characteristics with systolic blood pressure at 5 years of age.

Methods and Results—

Information from 3864 children who were followed up prospectively from their mother’s first antenatal clinic assessment was used. Maternal age, body mass index, and smoking during pregnancy were all positively associated with offspring systolic blood pressure at 5 years of age. The systolic blood pressure of children whose mothers had smoked throughout pregnancy was on average 0.92 mm Hg (95% CI 0.17 to 1.68) greater than that of children whose mothers had never smoked, after full adjustment. Children who had been breast fed until at least 6 months had lower systolic blood pressure than those who were breast fed for a shorter duration. Paternal body mass index and child’s weight, height, and body mass index were all positively associated with blood pressure at age 5.

Conclusions—

Because childhood blood pressure tracks into adulthood, interventions aimed at early life risk factors, such as quitting smoking during pregnancy, breast feeding, and prevention of obesity in all family members, may be important for reducing the population distribution of blood pressure and thus cardiovascular disease risk.
Statin-Induced Cholesterol Lowering and Plaque Regression After 6 Months of Magnetic Resonance Imaging–Monitored Therapy
Authors: Lima João A.C. , Desai Milind Y. , Steen Henning , Warren William P. , Gautam Sandeep , Lai Shenghan
Published: October 2004

Background—

Statin therapy reduces adverse outcomes, with a minimal decrease in vessel stenosis. Magnetic resonance imaging (MRI) noninvasively detects atherosclerotic plaque (AP) reduction. We hypothesized that statin-induced AP regression can be monitored by MRI and detected earlier than previously reported and is significantly associated with its lipid-lowering effect.

Methods and Results—

APs in thoracic aorta were measured by combined surface/transesophageal MRI in 27 patients (treated with simvastatin 20 to 80 mg daily) before and after 6 months of therapy. AP volume and luminal dimensions were measured from 6 cross sections used to construct a 2.4-cm 3D volume of the aorta that included plaque and lumen. Method reproducibility was studied in 10 patients imaged twice, 1 week apart. AP volume was reduced from 3.3±0.1.4 to 2.9±1.4 cm
3
at 6 months (
P
<0.02), whereas luminal volume increase was less accentuated (from 12.0±3.9 to 12.2±3.7 cm
3
,
P
<0.06). LDL cholesterol decreased by 23% (from 125±32 to 97±27 mg/dL,
P
<0.05) in 6 months. AP regression (plaque volume/area reduction) was significantly related to LDL cholesterol reduction (
P
<0.02 and
P
<0.005, respectively), and luminal volume increase was inversely related to LDL cholesterol reduction (
P
<0.04). Plaque volume measurement was highly reproducible (intraclass correlation
R
=0.98 and variability=4.8%). Intraobserver (0.91) and interobserver (0.81) concordances were documented for plaque volume assessment.

Conclusions—

AP regression and reverse remodeling can be detected accurately by MRI 6 months after statin therapy initiation, and it is strongly associated with LDL cholesterol reduction.
NaCl Restriction Upregulates Renal
Slc26a4
Through Subcellular Redistribution
Authors: Wall Susan M. , Kim Young Hee , Stanley Lorraine , Glapion Dawn M. , Everett Lorraine A. , Green Eric D. , Verlander Jill W.
Published: October 2004

Slc26a4 (Pds
, pendrin) is an anion transporter expressed in the apical region of type B and non-A, non-B intercalated cells of the distal nephron. It is upregulated by aldosterone analogues and is critical in the development of mineralocorticoid-induced hypertension. Thus,
Slc26a4
expression and its role in blood pressure and fluid and electrolyte homeostasis was explored during NaCl restriction, a treatment model in which aldosterone is appropriately increased. Ultrastructural immunolocalization, balance studies, and cortical collecting ducts (CCDs) perfused in vitro were used. With moderate physiological NaCl restriction,
Slc26a4
expression in the apical plasma membrane increased 2- to 3-fold in type B intercalated cells. Because
Slc26a4
transports Cl
−
, we tested whether NaCl balance differs in
Slc26a4
(+/+)
and
Slc26a4
(−/−)
mice during NaCl restriction. Cl
−
absorption was observed in CCDs from
Slc26a4
(+/+)
but not from
Slc26a4
(−/−)
mice. After moderate NaCl restriction, urinary volume and Cl
−
excretion were increased in
Slc26a4
(−/−)
relative to
Slc26a4
(+/+)
mice. Moreover,
Slc26a4
(−/−)
mice had evidence of relative vascular volume depletion because they had a higher arterial pH, hematocrit, and blood urea nitrogen than wild-type mice. With moderate NaCl restriction, blood pressure was similar in
Slc26a4
(+/+)
and
Slc26a4
(−/−)
mice. However, on a severely restricted intake of NaCl,
Slc26a4
(−/−)
mice were hypotensive relative to wild-type mice. We conclude that
Slc26a4
is upregulated with NaCl restriction and is critical in the maintenance of acid-base balance and in the renal conservation of Cl
−
and water during NaCl restriction.
Hormone Replacement Therapy and Cardiovascular Disease
Authors: Dubey Raghvendra K. , Imthurn Bruno , Zacharia Lefteris C. , Jackson Edwin K.
Published: October 2004

Observational studies in humans and experimental studies in animals and isolated cells supported the widely held belief that hormone replacement therapy protects the cardiovascular system from disease. To nearly everyone’s astonishment, the Women’s Health Initiative Study and the Heart and Estrogen/Progestin Replacement Study overturned the conclusion that hormone replacement therapy protects the cardiovascular system and, in fact, supported the opposite view that such therapy may actually increase the risk of cardiovascular disease. This review addresses 2 questions: what went wrong and where do we go from here?
Upregulation of Angiotensin-Converting Enzyme 2 by All-
trans
Retinoic Acid in Spontaneously Hypertensive Rats
Authors: Zhong Jiu-Chang , Huang Dong-Yang , Yang Yan-Mei , Li Yi-Fan , Liu Ge-Fei , Song Xu-Hong , Du Kun
Published: October 2004

There is increasing evidence that all-
trans
retinoic acid (atRA) influences gene expression of components of renin-angiotensin system (RAS), which plays a pivotal role in the pathophysiology of essential hypertension. To further validate effects of atRA on the RAS and to assess the possibility that atRA affects the activity of angiotensin-converting enzyme 2 (ACE2), gene, and protein expression of ACE2 have been examined by real-time polymerase chain reaction and Western blot methods in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Rats were treated with atRA (10 or 20 mg · kg
−1
· day
−1
) or placebo given as daily intraperitoneal injection for 1 month. ACE2 expression was markedly decreased in placebo-treated SHR when compared with WKY rats. However, in atRA-treated SHR, a significant upregulation of ACE2 expression was observed in heart and kidney. In conclusion, chronic atRA treatment increases gene and protein expressions of ACE2, resulting in the reduction of blood pressure and the attenuation of myocardial damage in SHR, which suggests that atRA may be an attractive candidate for the potential prevention and treatment of human essential hypertension.
Magnesium Inhibits Norepinephrine Release by Blocking N-Type Calcium Channels at Peripheral Sympathetic Nerve Endings
Authors: Shimosawa Tatsuo , Takano Koji , Ando Katsuyuki , Fujita Toshiro
Published: October 2004

Although Mg
2+
contributes to blood pressure regulation partly in terms of vasodilator action, its sympatholytic effect may also play an important role to control blood pressure. Thus, in the present study, we investigated the effect of Mg
2+
on sympathetic tone and blood pressure. We studied its actions on the blood pressure response to hydralazine, a direct vasodilator, in conscious spontaneously hypertensive rats (SHRs), and to electrical stimulation in the pithed Sprague–Dawley rat; catecholamine release by peripheral sympathetic nerve endings; and the N-type Ca
2+
channels of cultured neural cells. Intravenous Mg
2+
infusion (MgSO
4
: 3×10
−6
mol/kg body weight/min) induced the greater hypotensive response to hydralazine with attenuated reflex tachycardia in SHRs. In pithed rats, Mg
2+
infusion significantly attenuated the blood pressure elevation (2±2 mm Hg versus 27±6 mm Hg,
P
<0.01) in response to spinal electrical stimulation. In the perfused mesenteric arteries system, norepinephrine release was significantly attenuated (51±2%,
P
<0.01) by high Mg
2+
concentration solution (4.8 mmol/L) compared with normal Mg
2+
solution (1.2 mmol/L). When we applied the perforated whole-cell patch clamp method to nerve growth factor-treated PC12 cells, Mg
2+
blocked voltage-gated Ca
2+
currents in a concentration-dependent manner. The majority of the voltage-gated Ca
2+
currents were carried through N-type channels, followed by
l-
type channels. Mg
2+
blocked both of these channels. These findings suggest that Mg
2+
blocks mainly N-type Ca
2+
channels at nerve endings, and thus inhibits norepinephrine release, which decreases blood pressure independent of its direct vasodilating action.
Do Tongue Ties Affect Breastfeeding?
Authors: Griffiths D. Mervyn
Published: October 2004

This study assessed indications for and safety and outcome of simple division of tongue tie without an anesthetic. There were 215 infants younger than 3 months (mean 0-19 days) who had major problems breastfeeding, despite professional support. Symptoms, tongue tie details, safety of division, and complications were recorded. Feeding was assessed by the mothers immediately, at 24 hours, and 3 months after division. Prior to division, 88% had difficulty latching, 77% of mothers experienced nipple trauma, and 72% had a continuous feeding cycle. During division, 18% slept throughout; 60% cried more after division (mean 0-15 seconds). There were no significant complications. Within 24 hours, 80% were feeding better. Overall, 64% breastfed for at least 3 months (UK national average is 30%). Initial assessment, diagnosis, and help, followed by division and subsequent support by a qualified lactation consultant, might ensure that even more mothers and infants benefit from breastfeeding.
Teenage Mothers and Breastfeeding: Does Paternal Age Make a Difference?
Authors: Harner Holly M. , McCarter-Spaulding Deborah
Published: October 2004

This descriptive investigation explores the impact of paternal age on a teenage mother’s decision regarding infant-feeding method during the postpartum hospital stay. Eighty-six teenagers who delivered a live birth were asked the age of the fathers of their babies and what, if any, influence the fathers had on infant feeding. Although the fathers of the babies frequently voiced an opinion regarding infant feeding, teenage mothers partnered with older men were less likely to breastfeed during the postpartum hospital stay than were teenagers partnered with male peers. Implications for future research and clinical nursing practice are presented.
Differential Response to Breastfeeding Peer Counseling Within a Low-Income, Predominantly Latina Population
Authors: Chapman Donna J. , Damio Grace , Pérez-Escamilla Rafael
Published: October 2004

This study aims to identify those most responsive to breastfeeding peer counseling (PC) using data from a US-based randomized trial. The authors ran a series of logistic regression models to identify differential responses to PC, using breastfeeding status at 0, 1, 3, and 6 months postpartum as the dependent variables. Three subgroups were found to be most responsive to breastfeeding PC. Multiparae receiving PC were 6 times more likely to initiate breastfeeding than were multiparous controls (odds ratio [OR] = 6.4; 95% confidence interval [CI] = 1.9-20.8). Similarly, those with uncertain prenatal breastfeeding intentions in the PC group were 7 times (OR = 7.4; 95% CI = 1.5-37.0) more likely to initiate breastfeeding than their control group counterparts. Among subjects partially breastfeeding on day 1 postpartum, those receiving PC were 12 times (OR = 11.9; 95% CI = 1.2-111.1) more likely to breastfeed through 3 months postpartum than were controls. These findings have important implications to the Supplemental Food Program for Women, Infants and Children.
Transfer of Celecoxib into Human Milk
Authors: Hale Thomas W. , McDonald Rose , Boger James
Published: October 2004

The aim of this study was to investigate the transfer of celecoxib into human milk. In one group of 3 breastfeeding patients on celecoxib at steady state, milk levels were determined at set intervals over 24 hours. Plasma levels were determined in 2 of their infants, age 17 and 22 months. In a second group of 2 subjects, intravenous lines were placed and a single 200-mg dose of celecoxib was followed by multiple paired plasma and milk samples over 8 hours. The mean milk-to-plasma ratio for celecoxib was 0.23 (95% confidence interval [CI]: 0.15-0.31). The average concentration of celecoxib in milk during the 8-hour dosing interval was 66 μg/L (95% CI: 41-89). The absolute infant dose averaged 9.8 μg/kg/d (95% CI: 6.2-13.4); the mean relative infant dose was 0.30%. Therefore, the average clinical dose transferred to the infant daily would be approximately 0.3% of the weight-adjusted maternal dose. The authors suggest that the use of celecoxib in breastfeeding mothers at these doses is very unlikely to cause untoward effects in breastfed infants.
Born to be king
Authors: Hagerty Bill
Published: October 2004

Bill Hagerty meets the chairman of the board and publisher of The New York Times, who discusses the Jayson Blair episode and beyond. When it was discovered that the reporter, had blatantly been faking stories, it was, says Sulzberger, "a huge black eye. I can't speak for anybody else, but there were shock waves...for me it was very traumatic. It came at a remarkable time, when we had just won seven Pulitzer prizes and were riding reasonably high. It was a bolt out of the blue. And it wasn't just Jayson Blair. To be fair, the events than transpired here had deeper roots than that. It was a wake-up call for us, it was a wake-up call for the industry."
For many, British is better
Authors: Christensen Christian
Published: October 2004

Since the start of the war in Iraq, much has been made of the fact that a significant number of Americans are turning to British news sources (such as The Guardian and the BBC) for information regarding the conflict, writes Christensen. Figures from The Guardian indicate that approximately 40 per cent of the newspaper's online readers are located in the United States. Similarly, audiences for BBC World News bulletins aired on the US Public Broadcasting System (PBS) increased by almost 30 per cent during the first weeks of the war. The BBC website has also seen a dramatic increase in the number of users from the United States. These developments have been cited by media critics as evidence of a broader dissatisfaction on the part of the American public with the state of the press in the United States. The highly commercialised and nationalistic nature of the US news media, so the argument goes, in addition to an uncomfortably close relationship between the press and the military, has made it impossible for the average citizen to get "objective" or "unbiased" information about events in Iraq.
The last scandal?
Authors: Winston Brian
Published: October 2004

In the wake of the Daily Mirror's publication of "fake" pictures that led to the departure of editor Piers Morgan, Winston examines the history of photographic trickery and concludes: "The digital camera has fatally undercut the promise of photography as scientific evidence and editors cannot any longer totally rely on a photograph to bolster the veracity of a written story. Reporting, while claiming less authenticity, can, in effect, achieve more of it than photographs. Had Morgan stuck with the words, he would quite probably still have his job. Perhaps not many more journalists will be willing to go to the wall for an image? The Mirror's faked "Iraqi" photos splash could be the last scandal of its kind."
The four horsemen
Authors: Dennis Felix
Published: October 2004

"In no way do I imagine myself to be a clairvoyant or a man who can see further than others into the future," writes magazines publisher Dennis. "Nevertheless, the news I bring from our industry is not what I would wish it to be. Frankly, it is not good... It is my belief that four major forces are converging on the magazine industry. These four threats, which I refer to as the four horsemen, pose a grave menace to the magazine industry's future growth, and perhaps to its very survival... We have lived, all but the youngest of us, through a golden age of magazine publishing... But I predict that we have already unknowingly entered the autumn of ink-on-paper periodicals after a glorious summer that has lasted for nearly 50 years. I fear that the four horseman are the harbingers of a long, slow, inevitable and, to me, immensely sad decline in the fortunes of newspapers and magazines; as our readers mutate into viewers; as our distribution, sales channels and margins shrink; as the environmentalists batter us with claims of social irresponsibility and as our advertisers, slowly at first, but in growing numbers, migrate to the electronic sea."
The secret: sex and celebs
Authors: Johnson Jane
Published: October 2004

Award-winning editor Johnson explains the success of Closer, the magazine she launched to instant success. The public has an insatiable appetite for sex and celebrity gossip, she claims: "In a world where people don't necessarily know, or want to know, who their next door neighbours are, women turn to Closer to find out the truth about their neighbour-substitutes - EastEnders' Jessie Wallace, Ulrika, Jade Goody. Reality TV and soap stars all have problems shared by our readers and their neighbours: love affairs, baby trouble, cheating boyfriends." Do Closer and its imitators have the formula to buck the industry's downward trend?
Hot news for the Barclays
Authors: Berry Don
Published: October 2004

A former senior editorial executive at the Daily Telegraph explains why he thinks maintaining a superior news service is the way forward for the paper and delivers this message to the paper's new proprietors, the Barclay brothers: "I am not suggesting that the Telegraph should ditch or even reduce any of its non-news ingredients - no paper can live on news alone these days - but simply that it focuses its attention and best journalistic skills on news coverage. Yes, it is an old-fashioned idea, but sometimes those do work. During my decade on The Daily Telegraph I had to fight over and over again to preserve the paper's gothic titlepiece or masthead, which was highly distinctive and itself stood for integrity. It has survived, although slightly tweaked, and in my view the paper's reputation has benefited from this. If the Barclays drop the gothic, we will know the paper is heading for real trouble."
Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells
Authors: Levings Megan K. , Gregori Silvia , Tresoldi Eleonora , Cazzaniga Sabrina , Bonini Chiara , Roncarolo Maria Grazia
Published: October 2004

Dendritic cells (DCs) are specialized antigen-presenting cells that monitor the antigenic environment and activate naive T cells. The role of DCs is not only to sense danger but also to tolerize the immune system to antigens encountered in the absence of maturation/inflammatory stimuli. Indeed, if a naive T cell encounters its antigen on immature DCs (iDCs), it may differentiate into a T-regulatory (Tr) rather than a T-effector cell. However, little is known about the mechanisms by which iDCs differentiate Tr cells. We developed a standardized and highly reproducible protocol to differentiate Tr cells by repetitive exposure of naive peripheral blood CD4+ T cells to allogeneic iDCs. The resultant Tr cells are phenotypically and functionally identical to type 1 Tr (Tr1) cells because their generation requires production of IL-10 by iDCs, and they suppress T-cell responses through an interleukin-10 (IL-10)– and a transforming growth factor β (TGF-β)–dependent mechanism. In addition, Tr1 cells induced by iDCs do not require the presence of CD4+CD25+ Tr cells for their generation, nor do they express high constitutive levels of CD25 or the transcription factor FoxP3. Thus, iDCs can drive the differentiation of Tr1 cells and can be used to generate large numbers of alloantigen-specific Tr1 cells for clinical use as a cellular therapy to restore peripheral tolerance.
The birth of Emerging Themes in Epidemiology: a tale of Valerie, causality and epidemiology
Authors: Tam Clarence C
Published: October 2004

Emerging Themes in Epidemiology (ETE) is a new, online, Open Access peer-reviewed journal. The Journal is unique in that it was conceived and is managed by research degree students in epidemiology and related public health fields. The Journal's management is overseen by its Editor-in-Chief and Associate Faculty Editors, all of whom are senior members of faculty. ETE aims to encourage debate and discussion on the theoretical, methodological and practical aspects of epidemiologic research and practice. In addition, ETE is dedicated to the promotion of Open Access publication and the training of research students in the scientific publishing process. This editorial, to coincide with the launch of ETE, sets out the Journal's philosophy and aims. Epidemiology is a rich and innovative science that has much to gain from broader discussion of the causal frameworks that underpin it. ETE aims to be a major forum for such discussion.
Trade Costs
Authors: Anderson James E , van Wincoop Eric
Published: October 2004

This paper surveys the measurement of trade costs: what we know and don't know but may usefully attempt to learn. Partial and incomplete data on direct measures of costs go with inference on implicit costs from trade flows and prices. Total trade costs in rich countries are large. The ad valorem tax equivalent is about 170 percent when pushing the data hard. Poor countries face even higher trade costs. There is a lot of variation across countries and across goods within countries, much of which makes economic sense. In our survey, theory provides interpretation and perspective and suggests improvements for the future. Some new results are presented to properly apply and interpret gravity theory and handle aggregation.
Review of Mokyr's Gifts of Athena
Authors: Varian Hal R
Published: October 2004

This is a review article of the book The Gifts of Athena: Historical Origins of the Knowledge Economy, by Joel Mokyr, published in 2002.
International Technology Diffusion
Authors: Keller Wolfgang
Published: October 2004

This paper surveys what is known about the extent of international technology diffusion and channels through which technology spreads. Productivity differences explain much of the variation in incomes across countries, and technology plays a key role in determining productivity. The pattern of worldwide technical change is determined largely by international technology diffusion because a few rich countries account for most of the world's creation of new technology. Cross-country income convergence turns on whether technology diffusion is global or local. There is no indication that international diffusion is inevitable or automatic, but rather, domestic technology investments are necessary. Better understanding of what determines the effectiveness of technology diffusion sheds light on the pace at which the world's technology frontier may expand.
Topology Studies of the Chloroplast Protein Import Channel Toc75
Authors: Sveshnikova N. , Grimm R. , Soll J. , Schleiff E.
Published: October 2004

A major goal in understanding protein transport across membranes is the investigation of the structure and regulation of the translocon subunits. We analysed Toc75, a pore-forming subunit of the translocon of the outer envelope of chloroplasts. Toc75 was over-expressed and reconstituted into liposomes. Immunoprecipitation of liposome-reconstituted Toc75 indicates an Nin-Cin orientation of Toc75. Limited proteolytic digestion of Toc75 present in outer envelope vesicles with specific proteases combined with amino acid sequencing was used to study the topology of Toc75. Finally, computer modelling based on known protein structures indicates that Toc75 traverses the outer envelope with 16 amphiphilic beta sheets and the topology model is presented.
Different Signaling Pathways Are Involved in CCKB Receptor-Mediated MAP Kinase Activation in COS-7 Cells
Authors: Zieger M. , Oehrl W. , Wetzker R. , Henklein P. , Nowak G. , Kaufmann R.
Published: October 2004

Recently, the involvement of the MAP kinase ERK in mitogenic signaling of cholecystokininB (CCKB) receptors has been shown. However, the intracellular effector systems involved in this signaling pathway are poorly defined. In this study, we used COS-7 cells transiently transfected with the human CCKB receptor to investigate cholecystokinin-induced MAP kinase activation. CCK-8 induced activation of ERK2 which is associated with its phosphorylation and localization in the nucleus. The CCK-8-dependent ERK stimulation is sensitive to wortmannin an inhibitor of phosphoinositide 3-kinases (PI3Ks) indicating the involvement of PI3K activity. To identify the PI3K species involved in mitogenic signaling of the CCKB receptor several dominant-negative mutants of PI3K regulatory and catalytic subunits were transiently expressed. Surprisingly, different catalytically inactive mutants of the G protein-sensitive PI3Kγ did not affect ERK stimulation induced by CCK, whereas a dominant-negative mutant of the regulatory p85 subunit induced significant inhibition of CCK-dependent ERK activity. These results indicate an involvement of PI3K class 1A species α, β or/and δ in signal transduction via CCKB receptors. In addition, protein kinase C (PKC)-dependent signaling pathways contribute to CCKB-mediated MAP kinase signaling as shown by inhibition of CCK-8-induced ERK activation by the PKC inhibitor bisindolylmaleimide.
Photo-CIDNP 13C Magic Angle Spinning NMR on Bacterial Reaction Centres: Exploring the Electronic Structure of the Special Pair and Its Surroundings
Authors: Matysik Jörg , Schulten Els , Alia Alia , Gast Peter , Raap Jan , Lugtenburg Johan , Hoff Arnold J. , Groot Huub J. M. de
Published: October 2004

Photochemically induced dynamic nuclear polarisation
(photoCIDNP) in intact bacterial reaction centres has been observed by 13Csolid
state NMR under continuous illumination with white light. Strong intensity
enhancement of 13C NMR signals of the aromatic rings allows probing the
electronic ground state of the two BChl cofactors of the special pair at the
molecular scale with atomic selectivity. Differences between the two BChl
cofactors are discussed. Several aliphatic 13C atoms of cofactors, as well as
13C atoms of the imidazole ring of histidine residue(s), show nuclearspin
polarisation to the same extent as the aromatic nuclei of the cofactors.
Mechanisms and applications of polarisation transfer are discussed.
Determination of Free Apolipoprotein(a) in Serum by Immunoassay and Its Significance for Risk Assessment in Patients with Coronary Artery Disease
Authors: Herrmann Wolfgang , Quast Sabine , Wolter Kai , Eger Hartmut , Kießig Stefan T. , Hahmann Harry , Kreuter Jörg , Molinari Ewald
Published: October 2004

This paper describes a new enzyme-linked ligand sorbent assay (ELLSA) to quantify free apolipoprotein(a) (apo(a)). The new test immobilizes free apo(a) utilizing a specific peptide that carries the amino acid sequence of a non-covalent apo(a) binding site on apoB3375–3405 (ligand-peptide). The ligand-peptide coupled to Sepharose was used in affinity chromatography to separate free apo(a) from whole serum. Isolated free apo(a) consisted of full length apo(a) and smaller apo(a). Additionally, free apo(a) levels determined by ELLSA as well as by electroimmunodiffusion correlated moderately well. Significantly increased serum concentrations of free apo(a) were found in coronary artery disease. The mean value of free apo(a) was three times higher in patients than in controls while the lipoprotein(a) (Lpla)) concentration was doubled. Utilizing receiver operating characteristic diagrams, it was shown that the free apo(a)-ELLSA had a better diagnostic test performance in atherosclerotic risk assessment than the Lp(a)-test: specificity free apo(a)-ELLSA 0.77, Lp(a)-test 0.81 [with (a:a)-enzyme immunoassay (EIA)] to 0.83 [with (a:B)-EIA]; sensitivity free apo(a)-ELLSA 0.57, Lp(a)-test 0.36 to 0.40. In conclusion, the new free apo(a)-ELLSA allows for the specific quantification of free apo(a). This provides an interesting indicator for atherosclerotic risk assessment.
Current System of Undergraduate and Postgraduate Education in Clinical Chemistry in Croatia
Authors: Juretić Dubravka , Žanić-Grubišić Tihana
Published: October 2004

We present here a specific model of education and practice in clinical chemistry that is almost exclusively based on the medical biochemists academically educated at the Faculty of Pharmacy and Biochemistry. This model has been successfully used for 35 years in Croatian Health Care System. Undergraduate education in clinical chemistry consists of four years of specific university education which provides for all requirements to maintain the high quality of our profession. Postgraduate education leading to more specific scientific and professional expertise is further regulated by the laws issued by The Ministry of Health and The Ministry of Science and Technology. At present there is a compulsory programme of lifelong continuing education recognised by Croatian Chamber of Medical Biochemists.
A Rapid and Sensitive Automated Light Scattering Immunoassay for Serum C-Reactive Protein and the Definition of a Reference Range in Healthy Blood Donors
Authors: Price Christopher P. , Calvin Jacqui , Walker Susan A. , Trull Andrew , Newman David J. , Gorman Eileen G.
Published: October 2004

The increasing interest in the measurement of serum C-reactive protein in relation to the risk stratification of patients with chest pain has demonstrated the need for more sensitive routine methods of measurement, and an accurate definition of the reference range. We report the determination of a reference range in serum samples from 491 blood donors using a particle enhanced turbidimetric immunoassay that has been modified to offer better imprecision within the reference range. The median values were found to be 2.40 and 2.20 mg/l for males and females, respectively, with 95th percentile range of 1.20–5.20 and 0.40–5.40 mg/l respectively.
Photodynamic Effects In Vitro in Fresh GynecologicTumors Analyzed with a Bioluminescence Method
Authors: Schlosser Viola , Koechli Ossi R. , Cattaneo Rosanna , Jentsch Brigitte , Haller Urs , Walt Heinrich
Published: October 2004

Photodynamic therapy (PDT) is a promising alternative method for clinical cancer treatment. In the present study, cells from four breast carcinomas, seven ovarian carcinomas of various stages of differentiation, and ascites from a diffuse metastatic tumor were treated by PDT in vitro. Tetra(m-hydroxyphenyl)-chlorin (m-THPC) was used as the photosensitizer. Surviving cell rate was evaluated by the ATP-Cell-Viability-Assay (ATP-CVA), which measures light production as an interaction of intracellular ATP with the luciferin-luciferase complex. The most effective PDT of the tumor cells was achieved at an m-THPC concentration of 0.2 μg/ml following incubation of the cells with photosensitizer for 24 hours. PDT toxicity resulted in a cell survival rate of 1 % to 42 % compared to untreated control cells (survival rate of control = 100 %). The inhibitor concentration IC50 of m-THPC was determined both in the dark (dark toxicity) and in combination with laser irradiation. IC50 was defined as the concentration of photosensitizer which caused 50 % of cell death. The IC50 values were heterogeneous in all tumor specimens examined. IC50 values for dark toxicity were on average 0.14 μg m-THPC/ml for primary ovarian carcinoma, 2.16 μg m-THPC ml for refractory ovarian carcinoma and 0.3 μg m-THPC/ml for breast carcinoma. After PDT, average IC50 value for refractory ovarian carcinoma was 0.04 μg m-THPC/ml, for primary ovarian carcinoma 0.05 μg m-THPC/ml and for breast carcinoma 0.03 μg m-THPC/ml. These data might indicate that clinical PDT of gynecological carcinoma requires individual treatment conditions to achieve optimal results.