bluuebunny/crossref_metadata_2025 huggingface dataset:
Observation of Polymer Conformation Hysteresis in Extensional Flow
Authors: Schroeder Charles M. , Babcock Hazen P. , Shaqfeh Eric S. G. , Chu Steven
Published: September 2003

Highly extensible
Escherichia coli
DNA molecules in planar extensional flow were visualized in dilute solution by fluorescence microscopy. For a narrow range of flow strengths, the molecules were found in either a coiled or highly extended conformation, depending on the deformation history of the polymer. This conformation hysteresis persists for many polymer relaxation times and is due to conformation-dependent hydrodynamic forces. Polymer conformational free-energy landscapes were calculated from computer simulations and show two free-energy minima for flow strengths near the coil-stretch transition. Hysteresis cycles may directly influence bulk-solution stresses and the development of stress-strain relations for dilute polymer flows.
Resistance to Enediyne Antitumor Antibiotics by CalC Self-Sacrifice
Authors: Biggins John B. , Onwueme Kenolisa C. , Thorson Jon S.
Published: September 2003

Antibiotic self-resistance mechanisms, which include drug elimination, drug modification, target modification, and drug sequestration, contribute substantially to the growing problem of antibiotic resistance among pathogenic bacteria. Enediynes are among the most potent naturally occurring antibiotics, yet the mechanism of resistance to these toxins has remained a mystery. We characterize an enediyne self-resistance protein that reveals a self-sacrificing paradigm for resistance to highly reactive antibiotics, and thus another opportunity for nonpathogenic or pathogenic bacteria to evade extremely potent small molecules.
The extended hyper-Wiener index
Authors: Li X H
Published: September 2003

According to the definition of molecular connectivity and the definition of a hyper-Wiener index, a novel set of hyper-Wiener indexes (Rn, mRn) are defined and are named the extended hyper-Wiener indexes. Where n = 1, 2, 3, 4,... represents the type of subgraph units and is the number of endmost atoms of the subgraph unit, m is the number of atoms of the subgraph unit. Here n = 1 means the subgraph unit is an atom, n = 2 means the subgraph units are straight-line combinations of m atoms (m = 2, 3, 4, 5, 6,...), and n = 3 means the subgraph units are Y types of combinations of m atoms (m = 4, 5, 6, 7, 8,...), and so on. The potential usefulness of the extended hyper-Wiener index in QSAR and (or) QSPR is evaluated by its correlation with a number of C3C8 alkanes and by a favorable comparison with models based on the molecular connectivity index and the overall Wiener index. To verify the robustness and the predictive ability of the models, a cross-validation procedure, leave-one-out, and a random test were also performed. The results show that the extended hyper-Wiener indexes examined demonstrate a good potential for QSAR and QSPR studies. Considerably better statistics are obtained when extending the hyper-Wiener index to the extended hyper-Wiener index. The extended hyper-Wiener indexes provided statistical results as good as the molecular connectivity indexes and the overall Wiener index in all models, and the standard deviations provided by these three sets of indexes are rather close. Moreover, this method may provide a better way to apply the Wiener number and the hyper-Wiener index to the system of unsaturated hydrocarbons and organic compounds, including heteroatoms, according to the method of the molecular connectivity index. This can extend the usefulness of the Wiener number and hyper-Wiener index and can make them a kind of widely used topological index in practice.Key words: hyper-Wiener index (R), extended hyper-Wiener index, molecular connectivity index.
Prostaglandin E Receptor EP1 Subtype but Not Prostacyclin IP Receptor Involved in Mucosal Blood Flow Response of Mouse Stomachs following Barrier Disruption
Authors: Komoike Yusuke , Nakashima Masato , Nakagiri Akari , Takeuchi Koji
Published: September 2003

Aim: We investigated the role of prostacyclin IP receptors in gastric mucosal protection as well as functional responses induced by taurocholate Na (TC) as a mild irritant using IP receptor knockout mice, in comparison with prostaglandin (PG) E receptor EP1 subtype knockout animals. Methods: Male C57/BL6 mice fasted for 18 h were used under urethane anesthesia. The stomach mounted on an ex vivo chamber was perfused with 20 mM HCl, and the transmucosal potential difference (PD), luminal acid loss, and gastric blood flow (GMBF) were simultaneously measured before and after exposure of the stomach to 20 mM TC for 20 min. Results: Mucosal exposure to TC in wild-type mice caused a marked decrease in PD, followed by an increase in H+ loss and GMBF. The PD gradually normalized after removal of TC from the chamber, with minimal damage in the mucosa 1 h later. The increase of GMBF following TC treatment was inhibited by indomethacin with no change in PD reduction or H+ loss, resulting in severe lesions in the mucosa. None of these responses induced by TC were significantly altered in IP receptor knockout mice. However, in mice lacking EP1 receptors, TC did not increase GMBF, despite causing PD reduction and acid loss, and resulted in severe damage in the mucosa. Mucosal PGE2 levels were significantly increased after TC, similarly, in all groups of mice, while levels of 6-keto-PGF1α showed a slight but not significant increase in all groups. Conclusion: We confirmed the importance of endogenous PGs and EP1 receptors in the adaptive protection and functional responses induced by a mild irritant in mouse stomach and further suggested that IP receptors are not actively involved in maintaining the gastric mucosal integrity under adverse conditions.
Expression of FGF Receptors 1, 2, 3 in the Embryonic and Postnatal Mouse Brain Compared with Pdgfrα, Olig2 and Plp/dm20: Implications for Oligodendrocyte Development
Authors: Bansal Rashmi , Lakhina Vanisha , Remedios Ryan , Tole Shubha
Published: September 2003

Fibroblast growth factors (FGF) receptors FgfR1, FgfR2 and FgfR3 are differentially regulated during oligodendrocyte (OL) maturation in vitro: FgfR3 is expressed by OL progenitors whereas FgfR2 is expressed by differentiated OLs[Mol Cell Neurosci 1996;7:263–275], and we have recently shown that FgfR3 is required for the timely differentiation of OLs in vivo [J Neurosci 2003;23:883–894].Here we have used in situhybridization to investigate the expression patterns of FgfR1–3 and compare them to the putative OL progenitor markers Olig2, Pdgfrαand Plp/dm20 as a function of development in vivo, in particular at sites of OL specification, migration or differentiation in the mouse forebrain and cerebellum. We show that at early stages FgfR1–3 expression overlaps with that of Olig2 in the embryonic ventricular zone of the lateral and medial ganglionic eminences. Further, a scattered population of cells expressing FgfR3 (but not FgfR1 or FgfR2) in the ventral telencephalon appear to arise from the ventricular zone, and at later stages are found more dorsally in the cortex, in an overall pattern similar to Olig2 and/or Pdgfrα. Postnatal expression of FgfR2 increases with age, more prominently in specific regions, including the cortical and cerebellar white matter and optic nerve. Thus, the differential expression pattern of FgfR2 and FgfR3 observed in vivo suggests that their expression is developmentally regulated in a manner consistent with the pattern of their expression in culture. These data provide further insights into role of FgfRs in OL development, and they emphasize that these receptors are positioned both spatially and temporally to impact OL generation in vivo.
Serotonergic Regulation of Somatosensory Cortical Development: Lessons from Genetic Mouse Models
Authors: Luo Xiaoyan , Persico Antonio M. , Lauder Jean M.
Published: September 2003

Monoaminergic neurotransmitter systems appear early during embryogenesis, suggesting that they could play important roles in brain development. Accumulated evidence indicates that serotonin (5-hydroxytryptamine, 5-HT) regulates neural as well as nonneural development, including early aspects of embryonic development, differentiation of neuronal progenitors, and morphogenesis of the craniofacial region, heart and limb. Recent studies using monoamine oxidase-A (MAO-A), 5-HT transporter, vesicular monoamine transporter-2 (VMAT2) and 5-HT1B receptor single, double and triple knockout mice have provided evidence that the serotonergic system plays important roles in barrel field formation in the developing somatosensory cortex. Here we review evidence from these genetic mouse models and, based on the accumulated evidence, propose a testable model for future studies of mechanisms underlying serotonergic regulation of cortical development.
Dynamic Patterned Expression of Orphan Nuclear Receptor Genes RORα and RORβ in Developing Mouse Forebrain
Authors: Nakagawa Yasushi , O’Leary Dennis D.M.
Published: September 2003

As a step toward using two closely related members of the nuclear receptor family, RORα and RORβ, as markers and tools for genetic manipulations in mouse forebrain, we have used in situ hybridization to analyze their expression from E10.5 to P7. At later embryonic and early postnatal ages, RORα expression in dorsal thalamus is mainly limited to robust expression throughout the principal sensory nuclei. RORβ is expressed in a similar set of dorsal thalamic nuclei as RORα, but exhibits a more limited expression within the principal sensory nuclei. RORα is expressed as early as E12.5 in dorsal thalamus by presumptive ventroposterior neurons, whereas RORβ expression is not detected until later embryonic ages. RORβ is highly expressed in embryonic neocortex, and exhibits strongly graded rostrocaudal and lateromedial patterns of expression. Over the first postnatal week, the graded expression of RORβ gradually acquires a disjunctive pattern largely restricted to layers 4 and 5 of the primary sensory areas. In contrast, very weak RORα expression is first detected in the neocortex just around birth, and is limited to the middle layer of the cortical plate of the putative somatosensory area. Later, a limited and very weak RORα expression is evident mainly in layer 4 of more caudal areas. To determine whether patterned retinal input is required for the proper postnatal expression and patterning of RORα and RORβ, we performed neonatal bilateral enucleations. We did not detect any significant differences between normal and enucleated mice in expression in visual areas. Although TCA input may be required for proper regulation of the postnatal expression of RORα and RORβ, these findings suggest that aspects of the dynamic postnatal expression and patterning of these genes are regulated independently of patterned visual activity relayed by geniculocortical afferents. The patterned expression of RORα in dorsal thalamus suggests that this gene locus may be useful to genetically modify the development of dorsal thalamus and thalamocortical projections.
Ontogeny and Plasticity of Adult Hippocampal Neural Stem Cells
Authors: Sieber-Blum Maya
Published: September 2003

We have investigated the ontogenetic origin and the degree of plasticity of adult hippocampal neural stem cells. Wnt1-expressing cells are located at the dorsal aspect of the embryonic neural tube and some of them are predestined to give rise to neural crest stem cells. Whereas the majority of adult hippocampal neural stem cells do not originate from cells that express Wnt1, a subset does express Wnt1 transiently during embryogenesis, as determined in the double transgenic mouse, Wnt1-cre/R26R. Hippocampal stem cells from adult ROSA 26 mice differentiate into chondrocytes, melanocytes (pigment cells) and smooth muscle cells when cocultured with neural crest cells from quail embryos. Neural crest cell-generated stimuli have a short-range of action and are recognized across species. These observations provide evidence for the heterogeneity in the hippocampal neural stem cell pool with regard to Wnt1 expression. Furthermore, they show plasticity and a remarkably wide range of developmental options of adult hippocampal stem cells.
Relationship between Insulin-Like Growth Factor 1 and Bone Mineral Density in Men Aged over 65 Years
Authors: Ertuğrul İbrahim , Karan M. Akif , Karan Ayşe , Erten Nilgün , İşsever Halim , Çefle Kıvanç , Sindel Dilşad
Published: September 2003

Objective: To determine the association between insulin growth factor 1 (IGF-1) and bone mineral density (BMD) in men over 65 years of age. Subjects and Methods: Forty-one male patients aged 65–88 years without a history of drug use or illness which is known to affect BMD were enrolled in the study. The control group consisted of 20 healthy men (19–62 years old). An immunoradiometric assay was used to measure IGF-1 levels. Dual-energy X-ray absorptiometry was used to determine BMD at the proximal femur and lumbar spine. A detailed questionnaire was used to assess the epidemiological findings. Results: The men over 65 years of age had a lower mean IGF-1 level (102.04 ± 36.65 vs. 196.62 ± 84.86 ng/ml) and a lower mean BMD at the femoral neck, trochanter and intertrochanteric zones, Ward’s triangle and total hip than the controls. No statistically significant association was observed in the BMD of the lumbar vertebrae between the patients and controls. IGF-1 levels were strongly and negatively correlated with age (p < 0.0001, r = –0.82). Logistic regression analysis showed that low IGF-1 levels were strongly associated with osteopenia of the total hip, femoral neck, trochanter and intertrochanteric zone. Conclusion: The finding shows that low serum IGF-1 levels were associated with an increased risk of hip osteopenia and, hence, at least partly responsible for the osteopenia observed in men aged 65 years or over.
A Community Study of Depression in Adolescent Girls: Prevalence and Its Relation to Age
Authors: Shaaban K.M.A. , Baashar T.A.
Published: September 2003

Objective: To conduct a two-stage epidemiological survey in order to measure the prevalence rate of major depressive disorder in girls 12–19 years of age and to relate it to age. Subjects and Methods: The Beck Depression Inventory (BDI) questionnaire was administered to 1,107 girls from 3 elementary and 3 secondary schools in Khartoum, Sudan, 272 of whom were selected for intensive interviews. Results: The estimated prevalence of major depressive disorder for the population was 4.2%. Using a cutoff point of 15 on a short BDI, 11% of the adolescent girls reported severe depression. The BDI scores increased with age. A proportion of girls interviewed reported depressive symptoms which did not meet the criteria of Diagnostic and Statistical Manual IV (DSM-IV) for major depressive disorder, and the estimated prevalence of this ‘partial syndrome’ was 8.6%. Conclusion: The findings indicate a high rate of depression. Considering the fact that none of the girls who were identified with major depression reported to the health system, a surveillance system is recommended to identify depression among adolescent girls.
Novel Pharmacological Strategies in Amyloidosis
Authors: Lachmann Helen J. , Hawkins Philip N.
Published: September 2003

Amyloidosis is a disorder of protein folding in which normally soluble plasma proteins are deposited as insoluble fibrils that disrupt tissue structure. Over 20 unrelated proteins form amyloid in vivo, with fibrils sharing a cross-β-sheet structure composed of non-covalently associated protein or peptide subunits. Glycosaminoglycans and serum amyloid P component are universal non-fibrillar constituents of amyloid, contributing to fibrillogenesis and the stability of amyloid deposits. Amyloidosis may be acquired or hereditary and local or systemic, and is classified according to the precursor protein. Current treatment consists of support or replacement of impaired organ function and measures to reduce the production of amyloidogenic precursor proteins. Potential novel therapeutic strategies include stabilisation of the native fold of precursor proteins, reversion of misfolded proteins to their native state, inhibition of fibril propagation and enhancement of amyloid clearance either through immunotherapy or by reducing the stability of deposits through depletion of serum amyloid P component.
Bone Mineral Density in Girls and Their Mothers with Idiopathic Hypercalciuria
Authors: García-Nieto Victor , Navarro Juan F. , Monge Margarita , García-Rodríguez Victoria E.
Published: September 2003

Background/Aims: Idiopathic hypercalciuria (IH) is associated with a decreased bone mineral density (BMD) both in children and adults. It is being increasingly recognized that IH may be a contributing factor to osteopenia and/or osteoporosis in adults. We studied BMD in girls with IH and in their mothers, also affected with IH, in order to evaluate the influence of genetic background on bone mass in the setting of IH. Methods: BMD was evaluated in 40 girls with IH and in their premenopausal mothers from whom they had inherited this disease. Urinary creatinine and calcium were measured by standard laboratory methods. BMD was determined by dual X-ray absorptiometry scanning of the lumbar spine (LS) and the femoral neck (FN), and values are expressed as Z- and T-scores. Results: A Z-score of <–1 at the LS was found in 42.5% of the girls, whilst in the mothers, a Z score of <–1 at the LS and/or FN was observed in 47.5% and a T-score of <–1 at the LS and/or FN in 62.5%. The Z-score at the LS was significantly lower in girls and their mothers compared to controls, although this finding did not apply for the Z-score at the FN in the mothers. Z-scores in the girls of mothers with osteopenia were significantly lower or there was a trend for the score to be lower than in the girls of mothers with normal BMD. There was a significant relationship between the Z-score of the girls and the T-score at the LS in the mothers (r = 0.32, p < 0.05). Conclusion: We have observed a high prevalence of osteopenia in our population affected by IH, both in girls and in their mothers. We suggest that BMD should be measured during the third or fourth decades of life in those individuals with nephrolithiasis or with children diagnosed as having IH.
Zaleplon Improves Sleep Quality in Maintenance Hemodialysis Patients
Authors: Sabbatini Massimo , Crispo Anna , Pisani Antonio , Ragosta Annalisa , Cesaro Antonio , Mirenghi Francesco , Cianciaruso Bruno , Federico Stefano
Published: September 2003

Background/Aim: A recent survey has shown that insomnia is still a very common problem in maintenance hemodialysis (MHD) patients. The aim of the present study was to test the effects of zaleplon (ZAL), a new nonbenzodiazepine hypnotic drug, on the sleep quality of MHD patients with insomnia. Methods: The sleep quality was assessed by the Pittsburgh questionnaire in 10 patients (6 males/4 females) with insomnia on MHD; these patients underwent a randomized double-blind crossover study versus placebo (PLA). The main exclusion criterion was the presence of any possible cause of insomnia related to other concurrent diseases. Results: Treatment with ZAL significantly improved the total score of sleep quality (p < 0.03 vs. PLA). The analysis of the single components revealed that treatment with ZAL was associated with a higher subjective sleep quality (p < 0.01 vs. PLA) and a reduced sleep latency (p < 0.01 vs. PLA). The duration of sleep was not modified by ZAL, whereas a significant improvement was detected in habitual sleep efficacy (p < 0.05 vs. PLA). No peculiar side effect was recorded on ZAL. Blood parameters did not change, nor were differences recorded in the dialysis parameters (body weight gain, blood pressure) throughout the study. Conclusions: This study suggests that ZAL has a positive effect on the sleep quality in MHD patients. The absence of side effects and its pharmacodynamic properties make ZAL a useful drug in uremic patients.
A New Scoring System to Determine Thromboembolic Risk After Heart Valve Replacement
Authors: Butchart Eric G. , Ionescu Adrian , Payne Nicola , Giddings John , Grunkemeier Gary L. , Fraser Alan G.
Published: September 2003

Objective—

To determine the most important inflammatory and hematologic predictors of thromboembolism (TE) in patients undergoing valve replacement (VR) to be used in conjunction with clinical risk factors for preoperative risk profiling.

Methods and Results—

Preoperative and immediately postoperative clinical, echocardiographic, hematologic, biochemical and microbiological parameters were examined prospectively in 370 patients undergoing VR (249 AVR, 93 MVR, 28 DVR). Mean follow-up was 4.4 years (max 6.6 years; total 1566 pt/yrs), and 96 TE events were documented (28 major and 68 minor). INR data were collected on all patients. Laboratory values were considered elevated if they exceeded the 80
th
percentile of those of 70 controls with the same distribution of age and gender. IgA antibody to Chlamydia pneumoniae (CP)≥1:64 was considered indicative of significant infection. Predictors of TE on multivariate analysis following AVR were (hazard ratios): CP infection (2.6), previous TE (2.5), raised eosinophils (2.4), cancer history (2.1), postoperative infection (2.0), hypertension (2.0), CABG × 3/4 (2.0), and diabetes (1.9). Predictors of TE following MVR/DVR were raised mean platelet volume (4.0), raised factor VII (3.1), CP infection (2.7), previous mitral valvotomy (2.5), raised fibrinogen (2.2), and raised reticulocytes (2.0). These risk factors were additive when present in the same patient, enabling a scoring system to be developed that accurately predicted risk of TE based on number of risk factors.

Conclusions—

Selected blood tests and clinical risk factors provide a scoring system that accurately predicts TE risk and may guide prosthesis choice and antithrombotic management.
Gene Transfer of Hepatocyte Growth Factor Attenuates Postinfarction Heart Failure
Authors: Jayasankar Vasant , Woo Y. Joseph , Bish Lawrence T. , Pirolli Timothy J. , Chatterjee Subhasis , Berry Mark F. , Burdick Jeffrey , Gardner Timothy J. , Sweeney H. Lee
Published: September 2003

Background—

Despite advances in surgical and percutaneous coronary revascularization, ongoing ischemia that is not amenable to standard revascularization techniques is a major cause of morbidity and mortality. Hepatocyte Growth Factor (HGF) has potent angiogenic and anti-apoptotic activities, and this study evaluated the functional and biochemical effects of HGF gene transfer in a rat model of postinfarction heart failure.

Methods and Results—

Lewis rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of replication-deficient recombinant adenovirus encoding HGF (n=10) or empty null virus as control (n=9), and animals were analyzed after six weeks. Pressure-volume conductance catheter measurements demonstrated significantly preserved contractile function in the HGF group compared with Null control animals as measured by maximum developed LV pressure (79±5 versus 56±4 mm Hg,
P
<0.001) and maximum dP/dt (2890±326 versus 1622±159 mm Hg/sec,
P
<0.01). Significant preservation of LV geometry was associated with HGF treatment (LV Diameter HGF 13.1±0.54 versus Null 14.4±0.15 mm
P
<0.01; LV wall thickness 1.73±0.10 versus 1.28±0.07 mm
P
<0.01). Angiogenesis was significantly enhanced in HGF treated animals as measured by both Von Willebrand’s Factor immunohistochemical staining and a microsphere assay. TUNEL analysis revealed a significant reduction in apoptosis in the HGF group (3.42±0.83% versus 8.36±1.16%,
P
<0.01), which correlated with increased Bcl-2 and Bcl-x
L
expression in the HGF animals.

Conclusions—

Hepatocyte Growth Factor gene transfer following a large myocardial infarction results in significantly preserved myocardial function and geometry, and is associated with significant angiogenesis and a reduction in apoptosis. This therapy may be useful as an adjunct or alternative to standard revascularization techniques in patients with ischemic heart failure.
Minimally Invasive Aortic Valve Surgery in the Elderly: A Case-Control Study
Authors: Sharony Ram , Grossi Eugene A. , Saunders Paul C. , Schwartz Charles F. , Ribakove Greg H. , Culliford Alfred T. , Ursomanno Patricia , Baumann F. Gregory , Galloway Aubrey C. , Colvin Stephen B.
Published: September 2003

Introduction—

Although minimally invasive aortic valve surgery (MIAVR) is performed in many centers, few studies have compared its results to a standard sternotomy (SS) approach. We assessed the hypothesis that, when compared with SS in the elderly population, MIAVR has similar morbidity and mortality and allows faster hospital recovery.

Methods and Results—

From January 1995 through February 2002, 515 patients over age 65 underwent isolated aortic valve replacement. Using data gathered prospectively, 189 MIAVR patients were matched with 189 SS patients by age, ventricular function, valvular pathology, urgency of operation, diabetes, previous cardiac surgery, renal disease, and history of stroke. In each group, 56.1% of patients underwent non-elective procedures, and 28% were ≥80 years old. Hospital mortality (6.9%) and freedom from postoperative morbidity (82.5% versus 81.5%,
P
=0.79) were similar. Multivariate analysis revealed that urgent procedures [Odds Ratio (OR)=3.97;
P
=0.03], congestive heart failure (OR=3.94;
P
=0.03), and ejection fraction <30% (OR=4.16;
P
=0.03) were significant predictors of hospital mortality. Prolonged length of stay was associated with age (
P
=0.05), preoperative stroke (OR=3.5,
P
=0.001), CHF (OR=2.2,
P
=0.004), and sternotomy approach (OR=2.3,
P
=0.002) by multivariate analysis. More MIAVR patients were discharged home (52.6% versus 38.6%,
P
=0.03) rather than to rehabilitation facilities. Three year actuarial survival revealed no difference between groups.

Conclusions—

Minimally invasive aortic valve surgery is safe in elderly patients, with morbidity and mortality comparable to sternotomy approach. The shorter hospital stay and greater percentage of patients discharged home after MIAVR reflect enhanced recovery with this technique.
Coronary Events After Arterial Switch Operation for Transposition of the Great Arteries
Authors: Legendre A. , Losay J. , Touchot-Koné A. , Serraf A. , Belli E. , Piot J. D. , Lambert V. , Capderou A. , Planche C.
Published: September 2003

Background—

Transfer of the coronary arteries is a crucial step during the arterial switch operation (ASO) for transposition of the great arteries. This retrospective study aims to assess the incidence and risk factors of coronary events after ASO and sensitivity of noninvasive tests in the diagnosis of the coronary obstruction.

Methods and Results—

Between 1982 and 2001, 1304 newborn and infants had an ASO and the 1 198 hospital survivors had a 59-month mean follow-up. Coronary events occurred in 94 patients (7.2%; 95% CI, 6 to 9). Survival without coronary events were 92.7, 91, and 88.2% at 1, 10, and 15 years, respectively. The incidence was bimodal: high early and slow later. Multivariate analysis showed correlation with type B or C coronary pattern and major operative events (
P
<0.0001 and
P
=0.0024). In a subset of 324 patients who underwent a coronary artery angiography, lesions were observed in 22 patients (6.8%; 95% CI, 5 to 10). Multivariate analysis showed correlation with only type B or C coronary pattern (OR=20.8,
P
=0.0002). All of these patients had electrocardiogram and echocardiogram, 174 patients also had a treadmill test, and 115 patients had a myocardial scintigraphy. The association of these tests had the highest diagnosis sensitivity, 75%.

Conclusion—

After ASO, coronary events are not rare, occurring most often early and are an important cause of death. Coronary repair can be needed lately. Noninvasive tests are not sensitive enough to detect significant delayed coronary artery stenosis and coronary artery angiography should be performed.
Paneth Suture Annuloplasty Abolishes Acute Ischemic Mitral Regurgitation but Preserves Annular and Leaflet Dynamics
Authors: Tibayan Frederick A. , Rodriguez Filiberto , Liang David , Daughters George T. , Ingels Neil B. , Miller D. Craig
Published: September 2003

Background

Ring annuloplasty, the standard treatment for ischemic mitral regurgitation (IMR), abolishes normal annular dynamics and freezes the posterior leaflet. We examined the impact of Paneth suture annuloplasty during acute IMR on motion of the mitral annulus and leaflets in an ovine model.

Methods and Results

Eight sheep had radiopaque markers placed on the left ventricle, anterior mitral leaflet, posterior mitral leaflet, and mitral annulus. A Paneth suture annuloplasty that could be reversibly tightened was anchored to each fibrous trigone and externalized through the mid-lateral mitral annulus. Acute IMR was induced by proximal circumflex artery occlusion. Transesophageal echocardiography assessed the degree of IMR, and biplane cinefluoroscopy measured 3-dimensional marker coordinates before and during circumflex ischemia, and tightening of the Paneth suture. Paneth suture annuloplasty eliminated acute IMR, and reduced septal-lateral and commissure-commissure mitral annular dimensions. Tightening of the annuloplasty sutures, even beyond the degree necessary to eliminate mitral regurgitation (MR), did not reduce septal-lateral or commissure-commissure annular shortening, shortening of the muscular annular perimeter, annular flexion, or angular excursion of the anterior or posterior leaflets relative to ischemic conditions.

Conclusions

In contrast to ring annuloplasty, annular reduction sufficient to restore mitral competence during acute IMR can be achieved with a Paneth suture annuloplasty while simultaneously maintaining normal annular and leaflet dynamic motion. These findings should prompt additional investigation and design of repair methods that preserve the mobility of the mitral apparatus.
Transplantation of Autologous Fresh Bone Marrow Into Infarcted Myocardium: A Word of Caution
Authors: Bel Alain , Messas Emmanuel , Agbulut Onnik , Richard Patrice , Samuel Jane- Lyse , Bruneval Patrick , Hagège Albert A. , Menasché Philippe
Published: September 2003

Background—

As the benefits of extemporaneous transplantation (Tx) of fresh (unfractionated) autologous bone marrow (BM) have been primarily studied in the setting of acute myocardial infarction, we assessed whether this approach could be effective for regenerating chronically infarcted myocardium.

Methods and Results—

Myocardial infarction was created in 18 sheep by ligation of circumflex arterial branches. Three weeks later, BM was aspirated from the iliac crest, washed, labeled with the fluorescent dye Dil and reinjected (mean: 422×10
6
cells in 3 mL) in 10 sites across the infarcted area through the reopened thoracotomy (n=9). Nine controls received culture medium. Left ventricular (LV) function was assessed before and 2 months after Tx by two-dimensional echocardiography whereas transmural velocity gradients were measured using M-mode tissue Doppler imaging at the center of the infarcted/grafted area. Formalin-fixed hearts were processed for the detection of grafted cells and angiogenesis. LV ejection fraction deteriorated similarly in the Tx and control groups (from 42±5% to 30±4% and from 40±4% to 31±1%, respectively;
P
=0.86). Likewise, BM Tx failed to prevent LV dilatation and impairment of the global wall motion score. The decrease in regional systolic velocity gradients (s
−1
) featured a similar pattern (Tx group: from 0.77±0.11 to 0.31±0.07; control group: from 0.73±0.10 to 0.50±0.07;
P
=0.06). Histologically, there was neither BM tissue engraftment, except for a few scattered Dil-positive macrophages in the infarcted fibrotic areas nor transdifferentiation of BM cells into endothelial cells.

Conclusion—

These data caution against the functional efficacy of extemporaneous Tx of fresh unfractionated BM into postinfarction scars.
Midterm Clinical and Echocardiographic Results With Patch Glue Repair of Left Ventricular Free Wall Rupture
Authors: Canovas Sergio J. , Lim Eric , Dalmau Maria J. , Bueno Maria , Buendía Jose , Hornero Fernando , Gil Oscar , Garcia Rafael , Paya Rafael , Perez Jose , Echanove Ildefonso , Montero Jose
Published: September 2003

Background—

Left ventricular free wall rupture (LVFWR) is a dramatic complication after myocardial infarction. We present our mid-term clinical and echocardiographic results of LVFWR with an epicardial patch without cardiopulmonary bypass.

Methods—

From February 1993 to May 2001, 17 patients underwent surgery for LVFWR. The mean age±SD of 12 males and 5 females was 68±10 years. All patients presented for emergency surgery with cardiac tamponade confirmed on echocardiography. After opening the chest and identification of the site of rupture, a Goretex patch was fashioned and applied with enbucrilate surgical glue.

Results—

Effective control of bleeding was achieved in all cases. There were no on-table deaths. The operative (30 day) mortality was 23.5% (4/17). One death occurred because of patch failure, two because of cardiogenic shock, and one from pneumonia. On follow-up at a median of 2.2 years (interquartile range, 1.1 to 4.3 years), two further deaths occurred, one from myocardial infarction and another of undetermined etiology. Echocardiography did not reveal any evidence of restriction to left ventricular free wall motion.

Conclusions—

Patch glue repair is expedient, simple and effective; with no adverse effects on mid-term ventricular dynamics. In view of superior published results to infarctectomy and repair with extra corporeal circulation, it should be considered to be the initial procedure of choice for the surgical repair of LVFWR.
INR Self-Management Permits Lower Anticoagulation Levels After Mechanical Heart Valve Replacement
Authors: Koertke H. , Minami K. , Boethig D. , Breymann Th. , Seifert D. , Wagner O. , Atmacha N. , Krian A. , Ennker J. , Taborski U. , Klövekorn W.P. , Moosdorf R. , Saggau W. , Koerfer R.
Published: September 2003

Background—

The Early Self Controlled Anticoagulation Trial (ESCAT I) showed that anticoagulation self-management after mechanical heart valve replacement decreased complication rates by maintaining INR levels closer to the target range than International Normalized Ratio (INR) home doctor management. The therapeutic range for the INR in that study was between 2.5 and 4.5 for all positions of prosthetic valves. ESCAT II should find out whether lowering the target range for INR self-management would further reduce complication rates.

Methods—

ESCAT II is a prospective controlled randomized (valves: St. Jude Medical Standard or Medtronic Hall, treatment: conventional/low-dose) multicenter study with 3 300 patients. We present interim results of 1 818 patients. 908 were categorized as having a low-dose target range, which was INR 1.8 to 2.8 for prostheses in aortic position and 2.5 to 3.5 for prostheses in mitral position or in combined valve replacement. The control group (conventional group) with 910 patients aimed at an INR of 2.5 to 4.5 for all valve positions.

Results—

In the conventional group, 74% of INR values measured were within the therapeutic range. In the low-dose group, 72% of the values were within that range. The linearized thromboembolism rate (% per patient year) was 0.21% for both groups. The bleeding complication rate was 0.56% in the low-dose regimen group versus 0.91% in the conventional group.

Conclusions—

Early onset INR self-management under oral anticoagulation after mechanical heart valve replacement enables patients to keep within a lower and smaller INR target range. The reduced anticoagulation level resulted in fewer grade III bleeding complications without increasing thromboembolic event rates.
Mesenchymal Progenitor Cells Differentiate into an Endothelial Phenotype, Enhance Vascular Density, and Improve Heart Function in a Rat Cellular Cardiomyoplasty Model
Authors: Davani Siamak , Marandin Aliette , Mersin Nursen , Royer Bernard , Kantelip Bernadette , Hervé Patrick , Etievent Joseph-Philippe , Kantelip Jean-Pierre
Published: September 2003

Background—

Cellular cardiomyoplasty is a promising approach to improve postinfarcted cardiac function. The differentiation pathways of engrafted mesenchymal progenitor cells (MPCs) and their effects on the left ventricular function in a rat myocardial infarct heart model were analyzed.

Methods and Results—

A ligation model of left coronary artery of Lewis rats was used. MPCs were isolated by bone marrow cell adherence. Seven days after ligation, MPCs labeled with 4′,6-diamidino-2′-phenylindole were injected into the infarcted myocardium (n=8). Culture medium was injected in the infarcted myocardium of control animals (n=8). Thirty days after implantation, immunofluorescence studies revealed some engrafted cells expressing a smooth muscle phenotype (α SM actin
+
), as similarly observed in culture. Other engrafted cells lost their smooth muscle phenotype and acquired an endothelial phenotype (CD31
+
). Furthermore, vessel density was augmented in the MPC group in comparison with the control group. After 30 days, echocardiography showed an improvement on left ventricular performance in the MPCs compared with the control group.

Conclusions—

In vivo administration of syngenic MPCs into a rat model of myocardial infarcted heart was safety demonstrated. Some engrafted cells appeared to differentiate into endothelial cells and loss their smooth muscle phenotype. MPC engraftment might to contribute to the improvement on the cardiac function in such a setting.
Patient Selection and Current Practice Strategy for Off-pump Coronary Artery Bypass Surgery
Authors: Magee Mitchell J. , Coombs Laura P. , Peterson Eric D. , Mack Michael J.
Published: September 2003

Objective—

Previous studies comparing off-pump coronary artery bypass surgery (OPCABG) to conventional techniques utilizing cardiopulmonary bypass (CABG-CPB) have failed to provide patient selection guidelines. We sought to determine guidelines, attempting to rectify the limitations of previous studies.

Methods and Results—

A retrospective analysis of prospectively collected data from the Society of Thoracic Surgeons National Database, from January 1999 through December 2000, identified 204 602 multivessel coronary artery bypass (CABG) patients. Unadjusted and risk-adjusted odds ratios (OR) were calculated to compare OPCABG and CABG-CPB morbidity and mortality. A propensity model was developed to identify factors associated with selection for OPCABG. All off-pump patients were pair-matched with on-pump patients based on their propensity to receive an off-pump procedure. Off-pump patients, 8.8% of the total, had significantly different patient characteristics than the on-pump group. Characteristics associated with OPCABG selection included fewer diseased vessels, absence of left main disease, fewer bypass grafts, no previous CABG, older age, chronic lung disease, and renal failure. Unadjusted and risk-adjusted odds ratios indicate a significant off-pump survival benefit and decreased morbidity including stroke and renal failure in the overall group. Propensity matching also showed a significant OPCABG survival benefit [OR (95% CI) 0.83 (0.72, 0.96)]. Subgroup analysis of propensity-matched groups identified off-pump survival benefits in patients with previous CABG (OR=0.53), diabetics (OR=0.66), LVEF between 30% to 50% (OR=0.75), females (OR=0.79), and age 66 to 75 years (OR=0.80).

Conclusion—

OPCABG imparts some survival benefit to most patient subgroups. Higher risk patients including those undergoing reoperative CABG, diabetics, and the elderly may gain the most benefit.
Incidence and Clinical Consequences of Atrial Fibrillation Within 1 Year of First-Time Isolated Coronary Bypass Surgery
Authors: Elahi Maqsood , Hadjinikolaou Leonidas , Galiñanes Manuel
Published: September 2003

Background—

Atrial fibrillation (AF) is the commonest complication during cardiac surgery, however, the long-term prevalence of AF following surgery and its clinical consequences remain unclear.

Patients and Methods—

To investigate this, 877 consecutive patients undergoing first time CABG were followed for 1 year. Rhythm disturbances were diagnosed from serial ECGs and documented notes. The arrhythmia was treated medically and/or by cardioversion.

Results—

Out of 877, 17 patients (1.9%) died in the hospital and out of the remaining 860 patients 844 (98.1%) had a complete 1-year follow-up. Patients were divided according to their age: Group I (50 to 59 years), Group II (60 to 69 years) and Group III (70 to 79 years). The prevalence of AF in the general population was taken from the Framingham Heart Study. Patients in groups I and II had a higher incidence of AF before the operation than the general population (1.5% versus 0.4% and 3.1% versus 1.6%, respectively,
P
<0.05) and also higher incidence of AF at the 1-year follow-up (2% versus 0.4% and 4.6% versus 1.6% respectively,
P
<0.05). The incidence of AF in group III did not differ from the general population before operation, at the 6-week and 1-year follow-ups. As expected most of the patients with preoperative AF remained in AF after 1-year of CABG surgery. Importantly, the incidence of newly developed AF was higher in patients that developed infection and renal dysfunction in the postoperative period. AF did not predict embolic events at any stage of the study.

Conclusion—

In conclusion, the incidence of AF for the first year following CABG is higher in patients <70 years but not in those >70 years when compared with the general population. AF was also associated to the occurrence of postoperative infection and renal dysfunction. Patients in this study were closely monitored and received timely appropriate treatment, and this may account for the absence of a relationship between AF and embolic events.
Modulation of Circulating Endothelin-1 and Big Endothelin by Nitric Oxide Inhalation Following Left Ventricular Assist Device Implantation
Authors: Wagner Frank D. , Buz Semih , Knosalla Christoph , Hetzer Roland , Hocher Berthold
Published: September 2003

Background—

Inhaled nitric oxide (iNO) is an established therapy in the treatment of pulmonary hypertension and right ventricular dysfunction following left ventricular assist device implantation. Since it is known that endothelin-1 contributes to pulmonary hypertension, and nitric oxide modulates endothelin-1 synthesis in vitro, we investigated the effects of iNO on circulating endothelin-1 and big endothelin following left ventricular assist device implantation.

Methods and Results—

On weaning from cardiopulmonary bypass, 15 consecutive patients with secondary pulmonary hypertension after implantation of a left ventricular assist device were treated with iNO. Endothelin-1 and big endothelin plasma levels were measured preoperatively, on cardiopulmonary bypass prior to iNO, 12, 24, and 48 hour postoperatively, and 72 hour after cessation of iNO. Endothelin-1 levels were increased preoperatively (1.05±0.20 fmol/L), and were highest on cardiopulmonary bypass (1.65±0.27 fmol/L). During iNO therapy endothelin-1 and big endothelin decreased significantly (endothelin-1: 12 hour 1.24±0.18, 24 hour 0.93±0.20, and 48 hour 0.81±0.14 fmol/L); they were lowest 72 hour post-iNO (endothelin-1: 0.56±0.09 fmol/L). Plasma endothelin-1 concentrations and iNO dose were inversely correlated (
r
=−0.657,
P
<0.015). A significant correlation was also found between endothelin-1 versus PA pressures and PVR/SVR ratio, but not with CI and SVR.

Conclusions—

Since it is known that endothelin-1 mediates pulmonary hypertension, we suggest a 2-fold effect of iNO therapy: firstly, a selective vasodilation of the pulmonary vasculature; and secondly, iNO mediated modulation of endothelin-1.
Incidence of Non–AIDS-Defining Cancers Before and During the Highly Active Antiretroviral Therapy Era in a Cohort of Human Immunodeficiency Virus–Infected Patients
Authors: Herida Magid , Mary-Krause Murielle , Kaphan Régis , Cadranel Jacques , Poizot-Martin Isabelle , Rabaud Christian , Plaisance Nathalie , Tissot-Dupont Hervé , Boue François , Lang Jean-Marie , Costagliola Dominique
Published: September 2003

Purpose: To determine incidence of non–AIDS-defining cancers (NADC) in HIV–infected patients before (P1) and during (P2) the use of highly active antiretroviral therapy (HAART) relative to that observed in the French general population (FGP) of the same age and sex.

Patients and Methods: Sex- and age-adjusted NADC standardized incidence ratios (SIR), with FGP as reference, were estimated in 1992 to 1995 (P1) and in 1996 to 1999 (P2) in a French Hospital Database on HIV prospective hospital cohort study.

Results: NADCs were diagnosed in 260 patients during P1 and 391 patients during P2 among the 77,025 patients included in the database between January 1, 1992, and December 31, 1999. Estimated incidence of all cancers was higher in HIV-infected men than in FGP during both periods (P1 SIR = 2.36 and P2 SIR = 1.91). No excess of cancers was observed among HIV-infected women in either period. Incidence of all cancers did not change from P1 to P2 in either sex (SIR = 0.96 for men and 1.00 for women). In contrast, incidence of Hodgkin’s disease (HD) was higher than in FGP in both sexes and both periods and increased in P2 as compared with P1; incidence of lung cancer was higher in both sexes during P2.

Conclusion: Relative to FGP, the overall incidence of NADCs was increased in HIV-infected men but not in women and did not differ between P1 and P2. Only HD was much more common in HIV infection, and the potential role of HAART on HD cannot be excluded.
Small-Cell Carcinoma of the Cervix: Fourteen Years of Experience at a Single Institution Using a Combined-Modality Regimen of Involved-Field Irradiation and Platinum-Based Combination Chemotherapy
Authors: Hoskins P.J. , Swenerton K.D. , Pike J.A. , Lim P. , Aquino-Parsons C. , Wong F. , Lee N.
Published: September 2003

Purpose: To determine the efficacy and toxicity of a combined-modality regimen of irradiation with platinum-based combination chemotherapy in small-cell carcinoma of the cervix (SCCC).

Patients and Methods: Thirty-four patients with SCCC were seen and treated at the British Columbia Cancer Agency between May 1988 and November 2002. Two protocols were used, SMCC (May 1988 to December 1995) and SMCC2 (January 1996 to November 2002). Both protocols used cisplatin, etoposide, and involved-field irradiation (essentially pelvis plus or minus para-aortics) with concurrent chemotherapy. In addition, SMCC2 included carboplatin and paclitaxel, and the para-aortics were irradiated routinely.

Results: Thirty-one patients received either SMCC (n = 17) or SMCC2 (n = 14), and three patients did not (disease too extensive, n = 1; patient refusal, n = 1; and alternative regimen, n = 1). For the 31 patients treated on one of the protocols, the 3-year overall and failure-free survival (FFS) rates were 60% and 57%, respectively. The results were equivalent for SMCC and SMCC2. Radiologic stage was the only independent predictor for FFS (80% at 3 years for stage I and II patients v 38% at 3 years for stage III and IV patients). Distant failure (28%) was the most common cause of failure, with local failure occurring in 13% of patients. The switch to SMCC2 did not improve efficacy but did lessen the toxicity.

Conclusion: SCCC can be successfully treated in approximately 55% of patients with a combination of irradiation and platinum-based chemotherapy. Disease extent predicts for chance of curability.