bluuebunny/crossref_metadata_2025 huggingface dataset:
A Frequency Accurate Finite Difference Scheme for Burgers Equation
Authors: Orlin Peter A. , Perkins A. Louise
Published: August 2003

A method is presented for designing a one-step, explicit finite difference scheme for solving the inviscid Burgers equation based on an a priori specification of dissipation and phase accuracy requirements. Frequency accurate temporal and spatial approximations with undetermined coefficients are used, together with a set of constraints that ensure that the approximations converge as the spatial and temporal grid sizes approach zero and satisfy the Lax Equivalence Theorem. A practical design of the difference scheme using a heuristic zero placement method, combined with a stability requirement, results in a linear matrix problem which is solved to obtain the undetermined coefficients. The partial differential equation itself provides the relationship between the temporal and spatial frequency dependence in the numerical approximation.
Acoustic Scattering from Two- and Three-Dimensional Bodies
Authors: Chung Cathy , Morris Philip J.
Published: August 2003

In this paper we consider the scattering of sound by two- and three-dimensional bodies with arbitrary geometries. Particular emphasis is placed on the methodology for the implementation of solid wall boundary conditions for high-order, high-bandwidth numerical schemes. The Impedance Mismatch Method (IMM) is introduced to treat solid wall boundaries. In this method the solid wall is simulated using a wall region in which the characteristic impedance is set to a different value from that in the fluid region. This method has many advantages over traditional solid wall boundary treatments, including simplicity of coding, speed of computation and the ability to treat curved boundaries. This method has been used to solve a number of acoustic scattering problems to demonstrate its effectiveness. These problems include acoustic reflections from an infinite plate, acoustic scattering from a two-dimensional finite plate and a cylinder, and acoustic scattering by a sphere and a cylindrical shell.
Advances in Numerical Boundary Conditions for Computational Aeroacoustics
Authors: Tam Christopher K. W.
Published: August 2003

Advances in computational aeroacoustics (CAA) depend critically on the availability of accurate, nondispersive, least dissipative computation algorithm as well as high-quality numerical boundary treatments. This paper focuses on the recent developments of numerical boundary conditions. In a typical CAA problem, one often encounters two types of boundaries. Because a finite computation domain is used, there are external boundaries. On the external boundaries, boundary conditions simulating the solution outside the computation domain are to be imposed. Inside the computation domain, there may be internal boundaries. On these internal boundaries, boundary conditions simulating the presence of an object or surface with specific acoustic characteristics are to be applied. Numerical boundary conditions, both external or internal, developed for simple model problems are reviewed and examined. Numerical boundary conditions for real aeroacoustic problems are also discussed through specific examples. The paper concludes with a description of some of the much-needed research in numerical boundary conditions for CAA.
Acoustic Scattering by Two Submerged Spherical Shells
Authors: Everstine Gordon C. , Gaunaurd Guillermo C. , Huang Hanson
Published: August 2003

We validate, using a coupled finite element/boundary element computer code, a recently-developed1 series solution for the structural acoustics problem of scattering from two submerged spherical elastic shells. Although the general purpose computational tools for acoustic scattering have never been restricted to single scatterers, the availability of the series solution provides, for the first time, the mutual validation of both exact and numerical approaches for a multiple elastic scatterer problem. The excellent agreement between the two solutions presented thus allows this problem to be added to the short list of existing benchmark structural acoustics problems possessing an analytic solution. For the purposes of this comparison, the direction of incidence is taken as parallel with the axis joining the two shells. The numerical solution uses the NASHUA code, which couples a finite element shell model of the two shells with a boundary element model of the surrounding fluid. The exact solution is found by expanding in terms of classical modal series and uses the addition theorem for the spherical wave functions. The exact solution requires coupling coefficients that are expressed in terms of sums of products of Wigner 3-j symbols (or Clebsch-Gordan coefficients).
Imitation, Group Selection and Cooperation
Authors: Grégoire Philippe , Robson Arthur
Published: September 2003

A prior signalling stage is added to the Prisoner's Dilemma and the overall population involved is divided into a number of subpopulations. Evolution involves both local and global imitation — so that the process is formally one of "group selection". A subpopulation that is not signalling and defecting against one and all can be invaded by two "secret handshake" mutants. A subpopulation that is composed entirely of the secret handshake strategy can be invaded by a single "sucker punch" mutant. Nevertheless, if there are at least three subpopulations, the population cooperates always, in the limit as the mutation rate tends to zero.
Equilibrium Selection in the Two-Population KMR Model
Authors: Hehenkamp Burkhard
Published: September 2003

This paper shows that, for the class of individualistic adjustment dynamics, unique equilibrium selection is possible in the two-population model of evolution by Kandori, Mailath and Rob (1993). We establish that, for generic 2×2 co-ordination games, the evolutionary process always selects the mutation-dominant equilibrium. Though the concepts of mutation dominance and risk dominance yield different equilibrium predictions, we show that mutation dominance represents a natural extension of risk dominance that additionally captures the risk arising from the evolutionary environment.
An equivalence theorem concerning population growth in a variable environment
Authors: Redheffer Ray , Vance Richard R.
Published: August 2003

We give conditions under which two solutions x and y of the Kolmogorov equation satisfy limy(t)/x(t) = 1 as t → ∞. This conclusion is important for two reasons: it shows that the long‐time behavior of the population is independent of the initial condition and it applies to ecological systems in which the coefficients are time dependent. Our first application is to an equation of Weissing and Huisman for growth and competition in a light gradient. Our second application is to a nonautonomous generalization of the Turner‐Bradley‐Kirk‐Pruitt equation, which even before generalization, includes several problems of ecological interest.
The relation between Maxwell, Dirac, and the Seiberg‐Witten equations
Authors: Rodrigues Waldyr A.
Published: August 2003

We discuss unsuspected relations between Maxwell, Dirac, and the Seiberg‐Witten equations. First, we present the Maxwell‐Dirac equivalence (MDE) of the first kind. Crucial to that proposed equivalence is the possibility of solving for ψ (a representative on a given spinorial frame of a Dirac‐Hestenes spinor field) the equation , where F is a given electromagnetic field. Such task is presented and it permits to clarify some objections to the MDE which claim that no MDE may exist because F has six (real) degrees of freedom and ψ has eight (real) degrees of freedom. Also, we review the generalized Maxwell equation describing charges and monopoles. The enterprise is worth, even if there is no evidence until now for magnetic monopoles, because there are at least two faithful field equations that have the form of the generalized Maxwell equations. One is the generalized Hertz potential field equation (which we discuss in detail) associated with Maxwell theory and the other is a (nonlinear) equation (of the generalized Maxwell type) satisfied by the 2‐form field part of a Dirac‐Hestenes spinor field that solves the Dirac‐Hestenes equation for a free electron. This is a new result which can also be called MDE of the second kind. Finally, we use the MDE of the first kind together with a reasonable hypothesis to give a derivation of the famous Seiberg‐Witten equations on Minkowski spacetime. A physical interpretation for those equations is proposed.
Pseudoinverse formulation of Rayleigh‐Schrödinger perturbationtheory for the symmetric matrix eigenvalue problem
Authors: McCartin Brian J.
Published: August 2003

A comprehensive treatment of Rayleigh‐Schrödinger perturbation theory for the symmetric matrix eigenvalue problem is furnished with emphasis on the degenerate problem. The treatment is simply based upon the Moore‐Penrose pseudoinverse thus distinguishing it from alternative approaches in the literature. In addition to providing a concise matrix‐theoretic formulation of this procedure, it also provides for the explicit determination of that stage of the algorithm where each higher‐order eigenvector correction becomes fully determined. The theory is built up gradually with each successive stage appended with an illustrative example.
Role of Alimentation in Irritable Bowel Syndrome
Authors: Dapoigny M. , Stockbrügger R.W. , Azpiroz F. , Collins S. , Coremans G. , Müller-Lissner S. , Oberndorff A. , Pace F. , Smout A. , Vatn M. , Whorwell P.
Published: September 2003

Background: Different food items are made responsible for irritable bowel syndrome (IBS) symptoms, but the physiopathology of IBS remains unclear. Aims: During a meeting in Nice, France, experts of the European Working Team of the IBiS Club discussed selected data regarding the relationships between alimentation, food items (including fibers) and IBS symptoms. Methods/Results: Food allergy remains a difficult diagnosis, but medical and general history, presence of general symptoms such as skin rash, and hypersensitivity tests may help in achieving a positive diagnosis. On the other hand, food intolerance is more confusing because of the subjectivity of the relationship between ingestion of certain foods and the appearance of clinical symptoms. Different food items which are commonly implicated in adverse reactions mimicking IBS were found to be stimulants for the gut, suggesting that patients with predominant diarrhea IBS have to be carefully questioned about consumption of different kinds of food (i.e., coffee, alcohol, chewing gum, soft drinks) and not only on lactose ingestion. Gas production is discussed on the basis of retention of intestinal gas as well as on malabsorption of fermentable substrates. The role of a large amount of this kind of substrate reaching the colon is suggested as a potential mechanism of IBS-type symptoms in overeating patients. Regarding the role of fiber in IBS, the expert group concluded that fibers are not inert substances and that they could trigger pain or bloating in some IBS patients. Conclusion: Despite numerous reviews on this subject, it is very difficult to give general dietary advice to IBS patients, but dieteticians may have a positive role in managing such patients.
Guillain-Barré Syndrome in a Case of Acute Lymphoblastic Leukaemia
Authors: Vembu Periasamy , Al-Shubaili Asmahan , Al-Khuraibet Adnan , Kreze Olivia , Pandita Ramesh
Published: September 2003

Objective: To report a case of severe Guillain-Barré syndrome in a 32-year old female patient diagnosed with acute lymphoblastic leukaemia who was on chemotherapy. Clinical Presentation and Intervention: The patient received chemotherapy including vincristine and steroids according to the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia-12 (MRC UKALL-12) protocol. On the 21st day of the first induction course she developed acute fulminant quadriparesis with total areflexia. The clinical features, nerve conduction and the cerebrospinal fluid studies were consistent with acute Guillain-Barré syndrome. She was treated with a 5-day course of intravenous immunoglobulins (IVIG) that resulted in only partial improvement. A second course of IVIG was given 2 weeks later that improved her condition slowly and steadily over a period of 12–16 weeks; the patient was able to walk with minimal support. Conclusion: The fulminant neuropathy was most likely due to the association between Guillain-Barré syndrome and leukaemia rather than vincristine neurotoxicity. IVIG was an effective and non-invasive treatment for Guillain-Barré syndrome associated with the malignancy.
Pre-Dilution vs. Post-Dilution during Continuous Veno-Venous Hemofiltration: Impact on Filter Life and Azotemic Control
Authors: Uchino Shigehiko , Fealy Nigel , Baldwin Ian , Morimatsu Hiroshi , Bellomo Rinaldo
Published: September 2003

Background/Aims: To determine the impact of replacement fluid infusion site on filter life and azotemic control during continuous veno-venous hemofiltration (CVVH). Methods:Pre-dilution CVVH was conducted from February 2001 to December 2001 and then practice was changed to post-dilution (from January 2002 to July 2002). Filter life was prospectively observed and the following data obtained for each filter: starting date and time, ending date and time, heparin use, heparin dose and protamine use. Daily creatinine, urea, INR, APTT and platelet count were also collected. Results: Forty-eight patients were studied (33 in pre-dilution and 15 in post-dilution) for a total of 309 filters (202 in pre-dilution and 107 in post-dilution). The median filter life was significantly shorter in the post-dilution period (18.0 vs. 13.0 h, p = 0.021). Multivariate linear regression analysis showed that pre-dilution was a significant independent predictor of increased filter life (p = 0.029), together with platelet count (p = 0.0035) and heparin dose (p = 0.046). There was no significant improvement in daily creatinine and/or urea reduction in the post-dilution period (% Δ creatinine: 7.9 vs. 10.2%/day, p = 0.99, urea: 5.4 vs. 9.7%/ day, p = 0.78). Conclusions: Post-dilution was associated with reduced filter life without any beneficial effect on daily changes in urea and creatinine levels. Pre-dilution appears a preferable technical approach to CVVH.
Low Molecular Weight Heparin and Unfractionated Heparin Are Both Effective at Accelerating Pulmonary Vascular Maturation in Neonatal Rabbits
Authors: O’Blenes Stacy B. , Merklinger Sandra L. , Jegatheeswaran Anusha , Campbell Andrew , Rabinovitch Marlene , Rebeyka Ivan , Van Arsdell Glen
Published: September 2003

Background—

Creation of a bi-directional cavopulmonary shunt after the Norwood procedure for hypoplastic left heart syndrome is delayed to allow pulmonary vascular resistance to fall with maturation of the pulmonary vascular bed. We hypothesized that unfractionated heparin (UFH) and low molecular weight heparin (LMWH), which promote angiogenesis and inhibit smooth muscle cell growth, could accelerate this process.

Methods and Results—

Fifty-six newborn rabbits were randomly selected to receive UFH 225U/kg (n=12), LMWH 1 mg/kg (n=14), LMWH 10 mg/kg (n=16), or saline (n=14) by subcutaneous injection every 12 hours for 14 days. Treatment with heparin reduced mean pulmonary artery (PA) pressure by 12% to 16% relative to controls [9.0±0.2 (UFH), 9.4±0.1 (LMWH 1 mg/kg), 9.2±0.2 (LMWH 10 mg/kg) versus 10.7±0.2 mm Hg (saline),
P
=0.0001]. Lower PA pressures were associated with reduced alveolar:arterial ratio consistent with enhanced pulmonary angiogenesis in heparin treated animals [8±1 (UFH), 13±2 (LMWH 1 mg/kg), 12±2 (LMWH 10 mg/kg) versus 23±5 (saline),
P
<0.03]. Reduced PA medial wall thickness and muscularization, two additional features of pulmonary vascular maturation, were also more evident in heparin treated animals. Mean PA pressures in 14-day-old rabbits treated with heparin were lower than those measured in control rabbits less than 7 weeks of age suggesting that heparin shortens the pulmonary vascular maturation process by over 60%.

Conclusions—

These results indicate that both UFH and LMWH are effective at accelerating pulmonary vascular maturation in newborn rabbits. This raises the possibility that administration of heparin to children after the Norwood procedure might allow for earlier conversion to a bi-directional cavopulmonary shunt.
Worldwide Experience With the MicroMed DeBakey Ventricular Assist Device® as a Bridge to Transplantation
Authors: Goldstein Daniel J.
Published: September 2003

Background—

Ventricular assist device (VAD) support with pulsatile first generation pumps is a well-established therapy for bridging to transplantation. Shortcomings of this technology include limited applicability to small patients, noise, and high incidence of infection and pump malfunction. A second generation of pumps, spearheaded by the axial flow MicroMed DeBakey VAD®, is in clinical trials and potentially will address these shortcomings.

Methods and Results—

Between November 13, 1998 and May 7, 2002, 150 patients worldwide underwent placement of the Micromed DeBakey VAD® as a bridge to transplantation. Prospectively acquired data including demographics, adverse events and outcomes was collected. Follow up is 100% with 30.4 patient-years of cumulative support time. Mean age was 48±4 years and 18% were female. Twenty-three percent had prior sternotomy. Preoperatively, 25% were on balloon pump support, 20% had renal insufficiency, and 40% were on at least two inotropes with a mean cardiac index of 1.8 L/min/m
2
. Mean support time was 75±81 days. Linearized rates (events/patient-year) were: reoperation for bleeding 2.03, hemolysis 0.61, device infection 0.16, thromboembolic event 0.61, pump thrombus 0.61, and pump failure 0.13. Eight-two patients (55%) were either bridged to transplantation, recovery or are ongoing and 68 (45%) have died. Several patients have been supported as outpatients.

Conclusions—

This initial experience suggests that bridging to transplantation can be successfully approached with a small and quiet axial flow pump that provides low incidence of device infection and pump failure. The incidence of pump thrombus and thromboembolism is being addressed by incorporation of heparin coating to all device surfaces.
Transplanted Skeletal Myoblasts Can Fully Replace the Infarcted Myocardium When They Survive in the Host in Large Numbers
Authors: Tambara Keiichi , Sakakibara Yutaka , Sakaguchi Genichi , Lu Fanglin , Premaratne Goditha U. , Lin Xue , Nishimura Kazunobu , Komeda Masashi
Published: September 2003

Background—

It is not clear how many skeletal myoblsts (SM) can survive and exert beneficial effects in the host myocardial infarction (MI) area. We assessed the hypothesis that a large number of SM can replace the MI area with reverse left ventricular (LV) remodeling.

Methods and Results—

MI was created by left coronary artery ligation in male Lewis rats. Four weeks after ligation, 45 rats had skeletal myoblast transplantation in the MI area. They were randomized into 3 groups according to the number of SM: group I (n=15), 5×10
7
; group II (n=15), 5×10
6
; and group III (n=15), 5×10
5
cells. Donor SM were obtained from neonatal Lewis rats and directly used without expansion. Another four weeks later, all rats were sacrificed following hemodynamic assessment. All heart sections were stained with anti-fast skeletal myosin heavy chain (FSMHC) antibody to determine the spacial extent of donor myocytes.

Results—

Four weeks after transplantation, LV diastolic dimension was decreased, fractional area change was increased, and MI size was decreased maximally in group I. Histological study showed that donor cells positive for FSMHC occupied the MI area with nearly normal wall thickness in group I, in which estimated volume of donor-derived muscle tissue was 40 mm
3
. In the other groups, FSMHC-positive cells were found only partly in the MI area.

Conclusions—

A large number of freshly isolated neonatal SM can survive in the host and fully replace the infarcted myocardium with reverse LV remodeling in rats with MI.
The −174G/C Interleukin-6 Polymorphism Influences Postoperative Interleukin-6 Levels and Postoperative Atrial Fibrillation. Is Atrial Fibrillation an Inflammatory Complication?
Authors: Gaudino Mario , Andreotti Felicita , Zamparelli Roberto , Di Castelnuovo Augusto , Nasso Giuseppe , Burzotta Francesco , Iacoviello Licia , Donati Maria Benedetta , Schiavello Rocco , Maseri Attilio , Possati Gianfederico
Published: September 2003

Background—

It has been suggested that inflammation can have a role in the development of atrial arrhythmias after cardiac surgery and that a genetic predisposition to develop postoperative complications exists. This study was conceived to verify if a potential genetic modulator of the systemic inflammatory reaction to cardiopulmonary bypass (the −174 G/C polymorphism of the promoter of the Interleukin-6 gene) has a role in the pathogenesis of postoperative atrial fibrillation (AF).

Patients and Results—

In 110 primary isolated coronary artery bypass patients the −174G/C Interleukin-6 promoter gene variant was determined. Interleukin-6, fibrinogen and C-reactive protein plasma levels were determined preoperatively, 24, 48, and 72 hours after surgery and at discharge. Heart rate and rhythm were continuously monitored for the first 36 to 48 hours; daily 12-lead electrocardiograms were performed thereafter until discharge. GG, CT, and CC genotypes were found in 62, 38, and 10 patients, respectively. Multivariate analysis (which included genotype, age, sex, and classical risk factors for AF) identified the GG genotype as the only independent predictor of postoperative AF. The latter occurred in 33.9% of GG versus 10.4% of non-GG patients (hazard ratio 3.25, 95%CI 1.23 to 8.62). AF patients had higher blood levels of Interleukin-6 and fibrinogen after surgery (
P
<0.001 for difference between the area under the curve).

Conclusion—

The −174G/C Interleukin-6 promoter gene variant appears to modulate the inflammatory response to surgery and to influence the development of postoperative AF. These data suggest an inflammatory component of postoperative atrial arrhythmias and a genetic predisposition to this complication.
Intravenous Plus Oral Amiodarone, Atrial Septal Pacing, or Both Strategies to Prevent Post-Cardiothoracic Surgery Atrial Fibrillation: The Atrial Fibrillation Suppression Trial II (AFIST II)
Authors: White C. Michael , Caron Michael F. , Kalus James S. , Rose Heidi , Song Jessica , Reddy Prabashni , Gallagher Robert , Kluger Jeffrey
Published: September 2003

Background—

The effect of a hybrid intravenous and oral prophylactic amiodarone regimen on postcardiothoracic surgery (CTS) atrial fibrillation (AF) is unknown. The impact of active atrial septal pacing on post-CTS AF has not been well characterized. In addition, the effect of using both amiodarone and atrial septal pacing together to prevent atrial fibrillation is unknown.

Methods and Results—

Patients (n=160) were randomized to amiodarone or placebo and then to pacing or no pacing using a 2×2 factorial design. All therapies began within 6 hours post-CTS. Amiodarone was given by intravenous infusion for the first 24 hours (1050 mg total) followed by oral therapy for 4 postoperative days (4800 mg total). Atrial septal pacing was given for 96 hours. Amiodarone reduced the risk of AF by 43% and the risk of symptomatic AF by 68% (
P
=0.037 and
P
=0.019) versus placebo. Atrial septal pacing did not reduce AF or symptomatic AF incidence versus no pacing. The risk of post-CTS AF in the patients receiving amiodarone+pacing was lower than the placebo+no pacing and the placebo+pacing groups (57.9% and 60.5% reductions,
P
=0.047 and
P
=0.040, respectively).

Conclusions—

Amiodarone given as both an intravenous and oral regimen is effective at reducing post-CTS AF but atrial septal pacing is ineffective. Combining amiodarone and pacing is better than placebo with or without pacing but not amiodarone alone.
Improved Left Ventricular Aneurysm Repair With Bioengineered Vascular Smooth Muscle Grafts
Authors: Matsubayashi Keiji , Fedak Paul W.M. , Mickle Donald A.G. , Weisel Richard D. , Ozawa Tsukasa , Li Ren-Ke
Published: September 2003

Background—

Recurrent ventricular dilatation can occur after surgical repair of a left ventricular (LV) aneurysm. Use of an autologous bioengineered muscle graft to replace resected scar tissue may prevent recurrent dilatation and improve cardiac function.

Methods—

Vascular smooth muscle cells (SMCs, 5×10
6
cells) from rat aortas were seeded onto synthetic PCLA (sponge polymer of ε-caprolactone-co-L-lactide reinforced with knitted poly-L-lactide fabric) patches and cultured for 2 weeks to allow tissue formation. Syngenic rats underwent proximal left coronary artery ligation to create a transmural myocardial scar. Four weeks after coronary ligation, cell-seeded patches (n=15) or unseeded patches (n=12) were used for a modified endoventricular circular patch plasty (EVCPP) repair of the infarct area. Ligated controls (n=14) and nonligated normal rats (n=10) had sham surgeries without EVCPP. Cardiac function was assessed by echocardiography and isolated Langendorff heart perfusion. Graft histology and morphology was also assessed.

Results—

After 8 weeks in vivo, seeded patches were thicker (
P
<0.05) and smaller in area (
P
<0.003) than unseeded patches. Only seeded patches had prominent elastic tissue formation (
P
<0.001) in association with SMCs. LV systolic function by echocardiography was improved in the seeded group compared with both unseeded (
P
<0.002) and control groups (
P
<0.0001). LV volumes in both patch repair groups were comparable but were significantly smaller (
P
<0.05) than controls. LV distensibility tended toward improvement in the seeded group as compared with unseeded hearts, but the difference did not achieve statistical significance (
P
=0.06).

Conclusions—

Surgical repair with muscle-cell seeded grafts reduced abnormal chamber distensibility and improved LV function after myocardial infarction as compared with unseeded grafts. Bioengineered muscle grafts may be superior to synthetic materials for the surgical repair of LV scar.
Survival After Coronary Revascularization, With and Without Mitral Valve Surgery, in Patients With Ischemic Mitral Regurgitation
Authors: Trichon Benjamin H. , Glower Donald D. , Shaw Linda K. , Cabell Christopher H. , Anstrom Kevin J. , Felker G. Michael , O’Connor Christopher M.
Published: September 2003

Background—

The most appropriate treatment for patients with ischemic mitral regurgitation (IMR) is often debated. We compared the survival rates of patients with IMR undergoing different treatment strategies, namely: medical therapy, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and CABG + mitral valve (MV) surgery.

Methods and Results—

Patients undergoing catheterization between 1986 and 2001 were included. IMR was defined as: ≥grade 2+ mitral regurgitation (MR) and significant coronary artery disease (CAD) without primary mitral valve disease. Patients undergoing catheterization for the evaluation of congenital or other valvular heart disease were excluded. Multivariable Cox proportional hazards modeling was utilized to assess the independent relation between treatment and survival. Propensity score methods were used to correct for the nonrandom assignment of treatment. Of the 2,757 patients who met study criteria: 1,305 were treated medically, 537 underwent PCI, 687 underwent CABG, and 228 underwent CABG + MV surgery. The median duration of follow-up was 3.2 (0.9, 7.1) years. Patients undergoing CABG + MV surgery had more severe MR and more severe heart failure than those treated by other modalities. After adjusting for differences in baseline characteristics, patients undergoing PCI, CABG, and CABG + MV surgery had a 31% (hazards ratio [HR]=0.69;
P
=0.0001), 42% (HR=0.58;
P
=0.0001), and 42% (HR=0.58;
P
=0.0001) reduction in the risk of death, respectively, compared with those undergoing medical therapy. The performance of mitral valve surgery with CABG was not associated with improved survival versus CABG alone (
P
=0.258).

Conclusions—

Among patients with IMR, treatment with PCI, CABG, or CABG + MV surgery is associated with improved survival compared with medical therapy.
Comparison of Intracardiac Cell Transplantation: Autologous Skeletal Myoblasts Versus Bone Marrow Cells
Authors: Thompson Richard B. , Emani Sitaram M. , Davis Bryce H. , van den Bos Ewout J. , Morimoto Yoshihisa , Craig Damian , Glower Donald , Taylor Doris A.
Published: September 2003

Background—

Multiple cell types are being proposed for cardiac repair, but side-by-side comparisons are lacking. We tested the hypothesis that intracardiac transplantation of autologous bone marrow- or skeletal muscle-derived progenitor cells improve regional heart function to a similar degree.

Methods and Results—

Thirty-nine New Zealand White rabbits underwent cryoinjury of the left ventricle and simultaneous hind limb bone marrow aspiration or soleus muscle biopsy. Both muscle and bone marrow cells were expanded in vitro. After 2 weeks, 10
8
skeletal muscle (SM group) or bone marrow-derived progenitor cells (BM group) were injected into the cryoinjured region (SM: n=12; BM: n=8). Medium alone was injected into the remaining animals (Control: n=16). Regional systolic function was measured using micromanometry and sonomicrometry at baseline, before, and 4 weeks after cell injection. Cell treatment resulted in a similar degree of improvement in a derivative of stroke work in the SM and BM groups (
P
=0.0026 and
P
=0.0085 versus Control, respectively). No significant difference was seen between BM and SM groups (
P
=0.9). On histology, engrafted cells were found in all of the cell treated animals. Injected myoblasts formed myotubes or muscle cells throughout the scar that expressed slow and fast myosin heavy chain. A subset of bone marrow cells differentiated toward a myogenic phenotype, as indicated by expression of desmin and α-sarcomeric actin in the engrafted areas.

Conclusion—

Transplantation and myogenic differentiation of bone marrow-derived progenitor cells increased regional systolic heart function after myocardial injury to a similar degree as skeletal myoblasts.
Abnormal Extracellular Matrix Protein Transport Associated With Increased Apoptosis of Vascular Smooth Muscle Cells in Marfan Syndrome and Bicuspid Aortic Valve Thoracic Aortic Aneurysm
Authors: Nataatmadja Maria , West Malcolm , West Jenny , Summers Kim , Walker Philip , Nagata Michio , Watanabe Teruo
Published: September 2003

Background—

Marfan syndrome (MS) is a genetic disorder caused by a mutation in the fibrillin gene FBN1. Bicuspid aortic valve (BAV) is a congenital heart malformation of unknown cause. Both conditions are associated with ascending aortic aneurysm and premature death. This study examined the relationship among the secretion of extracellular matrix proteins fibrillin, fibronectin, tenascin, and vascular smooth muscle cell (VSMC) apoptosis. The role of matrix metalloproteinase (MMP)-2 in VSMC apoptosis was studied in MS aneurysm.

Methods and Results—

Aneurysm tissue was obtained from patients undergoing surgery (MS: 4 M, 1 F, age 27–45 years; BAV: 3 M, 2 F, age 28–65 years). Normal aorta from subjects with nonaneurysm disease was also collected (4 M, 1 F, age 23–93 years). MS and BAV aneurysm histology showed areas of cystic medial necrosis (CMN) without inflammatory infiltrate. Immunohistochemical study of cultured MS and BAV VSMC showed intracellular accumulation and reduction of extracellular distribution of fibrillin, fibronectin, and tenascin. Western blot showed no increase in expression of fibrillin, fibronectin, or tenascin in MS or BAV VSMC and increased expression of MMP-2 in MS VSMCs.

There was 4-fold increase in loss of cultured VSMC incubated in serum-free medium for 24 hours in both MS (27±8%) and BAV (32±14%) compared with control (7±5%).

Conclusions—

In MS and BAV there is alteration in both the amount and quality of secreted proteins and an increased degree of VSMC apoptosis. Up-regulation of MMP-2 might play a role in VSMC apoptosis in MS VSMC. The findings suggest the presence of a fundamental cellular abnormality in BAV thoracic aorta, possibly of genetic origin.
Inhibition of the Cardiac Angiogenic Response to Surgical FGF-2 Therapy in a Swine Endothelial Dysfunction Model
Authors: Ruel Marc , Wu Gui Fu , Khan Tanveer A. , Voisine Pierre , Bianchi Cesario , Li Jianyi , Li Jian , Laham Roger J. , Sellke Frank W.
Published: September 2003

Background—

Discrepancy exists between the potent effects of therapeutic angiogenesis in laboratory animals and the marginal results observed in patients with advanced coronary artery disease. In vitro and small animal data suggest that angiogenesis may depend on locally available nitric oxide (NO), but the impact of endothelial dysfunction on therapeutic angiogenesis in the myocardium has been unclear. We compared the effects of clinically applicable angiogenesis methods in swine in which endothelial dysfunction was experimentally induced to that observed in normal swine.

Methods and Results—

Miniswine were fed either a regular (N=13) or hypercholesterolemic diet (N=13) for 20 weeks. Hypercholesterolemic swine showed coronary endothelial dysfunction on videomicroscopy. Animals from both groups received 100 μg of perivascular sustained-release fibroblast growth factor (FGF)-2 in the lateral myocardial territory, previously made ischemic by placement of an ameroid constrictor around the circumflex artery. After 4 weeks of FGF-2 therapy, lateral myocardial perfusion was significantly lower in hypercholesterolemic than in normocholesterolemic swine, both at rest and during pacing (0.44±0.04 versus 0.81±0.15 mL/min/g at rest, respectively;
P
=0.006; and 0.50±0.06 versus 0.71±0.10 mL/min/g during pacing;
P
=0.02). Hypercholesterolemic swine showed no net increase in perfusion from FGF-2 treatment. Endothelial cell density and FGF receptor-1 expression were significantly lower in the lateral territory of hypercholesterolemic versus normocholesterolemic animals.

Conclusions—

The cardiac angiogenic response to FGF-2 treatment using clinically applicable methods was markedly inhibited in hypercholesterolemic swine with coronary endothelial dysfunction. These findings suggest that coronary endothelial dysfunction is major obstacle to the efficacy of clinical angiogenesis protocols and constitutes a target toward making angiogenesis more effective in patients with advanced coronary disease.
Midterm Results After Stentless Mitral Valve Replacement
Authors: Walther Thomas , Lehmann Sven , Falk Volkmar , Walther Claudia , Doll Nico , Rastan Ardawan , Metz Sebastian , Schneider Johannes , Gummert Jan , Mohr Friedrich W.
Published: September 2003

Background—

To analyze the midterm clinical results after stentless mitral valve (SMV) replacement.

Methods and Results—

Fifty one patients (68.3±8.4 years, 35 female) with severe mitral valve disease (stenosis 25, incompetence 17, mixed lesion 9) received a chordally supported SMV (Quattro™, St. Jude Medical Inc.) since August 1997. Preoperative New York Heart Association class was 3.1±0.6; left ventricular ejection fraction 64±13%, and cardiac index 2.1±0.8 l/min/m
2
. Additional intraoperative ablation therapy was performed on 19 patients with chronic atrial fibrillation. Mean follow-up is 35.4±19.2 months (range 5 to 63).

SMV implantation was performed using a conventional (32) or a minimally invasive (19) approach, valve size was 29±1.5 mm, cross-clamp duration was 81±33 minutes. Atrial rhythm was reestablished in 16 of 19 patients. Five patients required reoperation early in this series, two for paravalvular leakage, two for functional stenosis, and one with underlying rheumatoid disease. Mortality was one perioperative (1.96%, non-valve-related), one after reoperation as a result of multiple organ failure (MOF), and five during late follow-up (30±7 months postoperatively) for noncardiac causes. Regular echocardiographic control revealed good SMV function (V
max
1.7±0.2m/s, P
mean
3.9±1.2 mm Hg) and well-preserved ejection fraction postoperatively and at most recent follow-up.

Conclusions—

Midterm results after SMV implantation are promising. Preservation of the annuloventricular continuity leads to stable left ventricular function and combined with ablation therapy to physiological hemodynamics. Long-term durability remains to be proven.
Total Arterial Myocardial Revascularization With Composite Grafts Improves Results of Coronary Surgery in Elderly: A Prospective Randomized Comparison With Conventional Coronary Artery Bypass Surgery
Authors: Muneretto Claudio , Bisleri Gianluigi , Negri Alberto , Manfredi Jacopo , Metra Marco , Nodari Savina , Culot Lidia , Dei Cas Livio
Published: September 2003

Background

Total arterial myocardial revascularization with composite grafts proved to enhance the long-term benefits of coronary surgery. We assessed the hypothesis that full arterial revascularization (FAR) may improve clinical outcome even in elderly and at short term.

Methods and Results

A prospective randomized study was designed to compare FAR with conventional coronary artery bypass grafting (CABG) surgery [left interval thoracic artery (LITA) on left anterior descending (LAD) plus additional saphenous vein grafts] with the following end points: early and late death, graft occlusion, reintervention, angina recurrence, and acute myocardial infarction (AMI). We enrolled 200 consecutive patients >70 years of age; population was equally divided at random in Group 1 (G1, FAR) and Group 2 (G2, Conventional). The groups resulted comparable with respect to all preoperative continuous and discrete variables and risk factors (Euroscore: G1=8.4 versus G2=8.1). No differences between G1 versus G2 were observed in terms of postoperative complications (perioperative AMI:2% versus 3%), mean intensive care unit (ICU) (hours: 39±11 versus 40±9) and hospital stay (days: 6±2 versus 7±3) nor were there any differences in hospital mortality(G1=5% versus G2=4%). At the mean follow-up of 14±5 months the incidence of angina recurrence was 3% in G1 versus 12% in G2. Angiographic controls of grafts showed a superior graft patency rate of all the arterial grafts when compared with saphenous vein grafts. Conventional CABG surgery was identified as incremental risk factor for angina recurrence and as predictor for graft occlusion.

Conclusions

Total arterial myocardial revascularization improved clinical outcome of patients undergoing coronary surgery in the elderly, whereas saphenous vein grafts negatively affected patient prognosis in terms of graft patency and freedom from late cardiac events.
Totally Endoscopic Atrial Septal Defect Repair With Robotic Assistance
Authors: Argenziano Michael , Oz Mehmet C. , Kohmoto Takushi , Morgan Jeffrey , Dimitui Jaina , Mongero Linda , Beck James , Smith Craig R.
Published: September 2003

Background—

Computer (robotic) enhancement had emerged as a facilitator of minimally invasive cardiac surgery, and has been used to perform portions of intracardiac procedures via thoracotomy incisions. This report describes the next step in this progression—the first U.S. application of robotic technology for totally endoscopic open heart surgery.

Methods and Results—

Seventeen patients underwent repair of a secundum-type atrial septal defect (n=12) or patent foramen ovale (n=5) by a totally endoscopic approach, utilizing the Da Vinci robotic system. Cardiopulmonary bypass (CPB) was achieved peripherally. Cardioplegia was administered via the distal port of the arterial cannula after endo-balloon inflation. Via three port incisions in the right chest, pericardiotomy, bicaval occlusion, atriotomy, atrial septopexy, and atrial closure were performed by a surgeon seated at a computer console. A fourth 15-mm port was utilized for suction and suture passage by a patient-side assistant. The mean age of the patients was 47 years (range, 22 to 68). Aortic crossclamp time was 32 minutes (median), and CPB time was 122 minutes. In 16 patients, transesophageal echocardiography after 30 days confirmed successful repair. In one patient, a recurrent shunt was identified and repaired on postoperative day 5. Median length of stay (LOS) in the intensive care unit was 20 hours, and median hospital length of stay was 4 days.

Conclusions—

Robotic technology can be utilized to perform open heart procedures safely and effectively via totally endoscopic approaches. This technique represents an option for patients seeking a reliable ASD repair but wishing to avoid sternotomy or thoracotomy.
JunB inhibits proliferation and transformation in B-lymphoid cells
Authors: Szremska Agnieszka P. , Kenner Lukas , Weisz Eva , Ott Rene G. , Passegué Emmanuelle , Artwohl Michaela , Freissmuth Michael , Stoxreiter Renate , Theussl Hans-Christian , Parzer Sabina Baumgartner , Moriggl Richard , Wagner Erwin F. , Sexl Veronika
Published: August 2003

The activator protein 1 (AP-1) member JunB has recently been implicated in leukemogenesis. Here we surveyed human lymphoma samples for expression of JunB and other AP-1 members (c-Jun, c-Fos, Fra1, JunD). JunB was strongly expressed in T-cell lymphomas, but non-Hodgkin B-cell lymphomas do not or only weakly express JunB. We therefore asked whether JunB acted as a negative regulator of B-cell development, proliferation, and transformation. We used transgenic mice that expressed JunB under the control of the ubiquitin C promoter; these displayed increased JunB levels in both B- and T-lymphoid cells. JunB transgenic cells of B-lymphoid, but not of T-lymphoid, origin responded poorly to mitogenic stimuli. Furthermore, JunB transgenic cells were found to be less susceptible to the transforming potential of the Abelson oncogene in vitro. In addition, overexpression of JunB partially protected transgenic mice against the oncogenic challenge in vivo. However, transformed B cells eventually escaped from the inhibitory effect of JunB: the proliferative response was similar in explanted tumor-derived cells from transgenic animals and those from wild-type controls. Our results identify JunB as a novel regulator of B-cell proliferation and transformation. (Blood. 2003;102:4159-4165)
Quantitative Tumor Apoptosis Imaging Using Technetium-99m–HYNIC Annexin V Single Photon Emission Computed Tomography
Authors: Van de Wiele Christophe , Lahorte Christophe , Vermeersch Hubert , Loose D. , Mervillie Kris , Steinmetz Neil D. , Vanderheyden Jean-Luc , Cuvelier Claude A. , Slegers Guido , Dierck Rudi A.
Published: September 2003

Purpose: Radiolabeled annexin V may allow for repetitive and selective in vivo identification of apoptotic cell death without the need for invasive biopsy. This study reports on the relationship between quantitative technetium-99m– (99mTc-) 6-hydrazinonicotinic (HYNIC) radiolabeled annexin V tumor uptake, and the number of tumor apoptotic cells derived from histologic analysis.

Patients and Methods: Twenty patients (18 men, two women) suspected of primary (n = 19) or recurrent (n = 1) head and neck carcinoma were included. All patients underwent a spiral computed tomography (CT) scan, 99mTc-HYNIC annexin V tomography, and subsequent surgical resection of the suspected primary or recurrent tumor. Quantitative 99mTc-HYNIC annexin V uptake in tumor lesions divided by the tumor volume, derived from CT, was related to the number of apoptotic cells per tumor high-power field derived from terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assays performed on sectioned tumor slices.

Results: Diagnosis was primary head and neck tumor in 18 patients, lymph node involvement of a cancer of unknown primary origin in one patient, and the absence of recurrence in one patient. Mean percentage absolute tumor uptake of the injected dose per cubic centimeter tumor volume derived from tomographic images was 0.0003% (standard deviation [SD], 0.0004%) at 1 hour postinjection (PI) and 0.0001% (SD, 0.0000%) at 5 to 6 hours PI (P = .012). Quantitative 99mTc-HYNIC annexin V tumor uptake correlated well with the number of apoptotic cells if only tumor samples with no or minimal amounts of necrosis were considered.

Conclusion: In the absence of necrosis, absolute 99mTc-HYNIC annexin V tumor uptake values correlate well with the number of apoptotic cells derived from TUNEL assays.
Angiotensin II Receptor Blocker Valsartan Suppresses Reactive Oxygen Species Generation in Leukocytes, Nuclear Factor-κB, in Mononuclear Cells of Normal Subjects: Evidence of an Antiinflammatory Action
Authors: Dandona Paresh , Kumar Vikramjeet , Aljada Ahmad , Ghanim Husam , Syed Tufail , Hofmayer Debborah , Mohanty Priya , Tripathy Devjit , Garg Rajesh
Published: September 2003

In view of the pro-oxidant and proinflammatory effects of angiotensin II, we have tested the hypothesis that valsartan, an angiotensin receptor blocker, may exert a suppressive action on reactive oxygen species (ROS) generation, nuclear factor κB (NF-κB) in mononuclear cells. Four groups of eight normal subjects were given 1) 160 mg daily of valsartan, 2) 80 mg daily of simvastatin, 3) 40 mg quinapril, or 4) no treatment. Fasting blood samples were obtained before treatment and at d 1, 8, and 14 (7 d after the cessation of the drug). After valsartan, ROS generation by polymorphonuclear cells and mononuclear cells fell significantly by more than 40% (P < 0.01). NF-κB binding activity and the expression of total cellular p65, a protein component of NF-κB, fell significantly (P < 0.01). The expression of inhibitor κB (IκB) increased significantly (P < 0.05). Plasma C-reactive protein (CRP) concentration fell significantly (P < 0.01). All indices, except IκB, reverted toward baseline, 7 d after the cessation of the drug. IκB persisted in an elevated state. Neither quinapril nor simvastatin given for 7 d produced a suppression of ROS generation, intranuclear NF-κB, p65, or CRP, and these two agents did not alter cellular IκB either. The untreated controls also did not demonstrate a change in their ROS generation or NF-κB binding activity or plasma CRP concentration. We conclude that valsartan at a modest dose exerts a profound and rapid ROS and inflammation-suppressive effect that may be relevant to its potential beneficial effects in atherosclerosis, diabetes, and congestive cardiac failure. In contrast, quinapril and simvastatin produced no similar effect over the period of 1 wk. Our observations may also have implications to clinical situations in which a rapid antiinflammatory effect is required.