A discontinuous Galerkin method for approximating the Vlasov–Poisson system of equations describing the time evolution of a collisionless plasma is proposed. The method is mass conservative and, in ...the case that piecewise constant functions are used as a basis, the method preserves the positivity of the electron distribution function and weakly enforces continuity of the electric field through mesh interfaces and boundary conditions. The performance of the method is investigated by computing several examples and error estimates of the approximation are stated. In particular, computed results are benchmarked against established theoretical results for linear advection and the phenomenon of linear Landau damping for both the Maxwell and Lorentz distributions. Moreover, two nonlinear problems are considered: nonlinear Landau damping and a version of the two-stream instability are computed. For the latter, fine scale details of the resulting long-time BGK-like state are presented. Conservation laws are examined and various comparisons to theory are made. The results obtained demonstrate that the discontinuous Galerkin method is a viable option for integrating the Vlasov–Poisson system.
Avoidance of the clinical syndrome of acute right-sided heart failure after heart transplantation is, unfortunately, not possible. Clinical experience and the literature certainly suggest that a ...significant factor in the successful management of right ventricular (RV) failure is recipient selection. Moreover, threshold hemodynamic values beyond which RV failure is certain to occur and heart transplantation is contraindicated do not exist. Nor are there values below which RV failure is always avoidable. Acute RV failure will remain a difficult and ever-present clinical syndrome in the transplant recipient. Goals in the treatment of this clinical problem include: 1. Preserving coronary perfusion through maintenance of systemic blood pressure. 2. Optimizing RV preload. 3. Reducing RV afterload by decreasing pulmonary vascular resistance (PVR). 4. Limiting pulmonary vasoconstriction through ventilation with high inspired oxygen concentrations (100% Fio2), increased tidal volume and optimal positive end expiratory pressure ventilation. Inhaled nitric oxide is recommended before leaving the operating room in cases where the initial therapies have had little impact. Intra-aortic balloon counterpulsation is employed in patients with impaired left ventricular (LV) function and may be of benefit in patients with RV dysfunction resulting from ischemia, preservation injury or reperfusion injury. Optimal LV function reduces RV afterload and PVR. A proactive decision regarding RV assist device implantation is made before leaving the operating room and is highly dependent upon overall hemodynamics, size and function of the ventricles as seen on transesophageal echocardiography, renal function and surgical bleeding. Only through careful preoperative planning can this life-threatening condition be managed in the postoperative period.
A new type of computer-enhanced telemanipulator device for "robotic" laparoscopic surgery was recently approved. We prospectively evaluated the initial patients undergoing procedures with this new ...device at our institution.
Patient demographics, operative indications, port placement, operative time, robot time, complications, and hospital stay were recorded. Follow-up evaluation was appropriate for the individual procedure.
Initially, 35 cases were managed. There were 22 anti-reflux procedures, 9 Heller myotomies, 1 pyloroplasty, 1 distal pancreatectomy with splenectomy, 1 esophagectomy with intrathoracic anastomosis, and 1 diagnostic laparoscopy. The operative times ranged from 88 to 458 min. The robot use times were between 16 and 185 min. There were no device-related complications.
Computer-enhanced robotic telesurgery is a safe and effective treatment method for a variety of diseases of the proximal gastrointestinal tract. Further study is needed to determine the benefits of this approach as compared with current technology.
Objectives: Right-sided circulatory failure resulting from severe preoperative pulmonary hypertension is a source of mortality early after cardiac transplantation. We undertook the present study (1) ...to analyze the association of elevated pulmonary hemodynamic indices with 30-day mortality, (2) to define threshold ranges associated with an increase in 30-day mortality, and (3) to evaluate the effect of vasodilator reversibility on 30-day mortality.
Methods: Preoperative hemodynamic profiles were evaluated in 476 patients who ultimately underwent cardiac transplantation. From these data, receiver-operating characteristic curves and stratum-specific likelihood ratios were generated to compare the efficacy of each hemodynamic index. A subset of patients with elevated hemodynamic profiles at baseline additionally underwent graded sodium nitroprusside infusion.
Results: Analysis of receiver-operating characteristic curves demonstrated no statistically significant difference among the indices in their ability to predict 30-day mortality. Analysis of stratum-specific likelihood ratios demonstrated three risk strata that correlated with significant differences in 30-day mortality, with patients in the high-risk stratum having a 3.2 to 4.4 increase in odds of 30-day mortality when compared with patients in the low-risk stratum. Nitroprusside data demonstrated that although 30-day mortality was better in patients with reversible pulmonary hypertension than in those with fixed pulmonary hypertension, it was not comparable with that of patients without pulmonary hypertension at baseline.
Conclusions: Candidates for cardiac transplantation may be categorized into three risk strata on the basis of their preoperative pulmonary hemodynamic profile; the association of this profile with 30-day mortality is not linear. Reversibility with nitroprusside appears to confer some improvement in the risk of 30-day mortality, but it may not eliminate the risk entirely. (J Thorac Cardiovasc Surg 1997;114:627-34)
The posttransplantation lymphoproliferative disorders (PT-LPDs) are a morphologically heterogeneous group of Ep-stein-Barr virus (EBV)-driven lymphoid proliferations of varying clonal composition. ...Some PT-LPDs regress after a reduction in immunosuppression, while others progress in spite of aggressive therapy. Previously defined morphologic categories do not correlate with clonality, and neither morphology nor clonality has reliably predicted the clinical behavior of PT-LPDs. We investigated 28 PT-LPD lesions occurring in 22 patients for activating alterations involving the bcW, bcf-2, c-myc, and H-, K- and N-ras proto-oncogenes and for mutations involving the p53 tumor suppressor gene. We correlated the results of these studies with the morphology of the lesions, their clonality based on Ig heavy and light chain gene rearrangement analysis, and the presence and clonality of EBV infection. We found that the PT-LPDs are divisible into three distinct categories as follows: (1) plas-macytic hyperplasia: most commonly arise in the oropharynx or lymph nodes, are nearly always polyclonal, usually contain multiple EBV infection events or only a minor cell population infected by a single form of EBV, and lack oncogene and tumor suppressor gene alterations; (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma: may arise in lymph nodes or various extranodal sites, are nearly always monoclonal, usually contain a single form of EBV, and lack oncogene and tumor suppressor gene alterations; and (3) immunoblastic lymphoma or multiple myeloma: present with widely disseminated disease, are monoclonal, contain a single form of EBV, and contain alterations of one or more oncogene or tumor suppressor genes (N-ras gene codon 61 point mutation, p53 gene mutation, or c-myc gene rearrangement). The PT-LPDs are divisible into three categories exhibiting distinct morphologic and molecular genetic characteristics. Alterations involving the N-ras and c-myc proto-oncogenes and the p53 tumor suppressor gene may play an important role in the development and/or progression of the PT-LPDs.
The potential antiatherosclerotic actions of NO were investigated in four groups of mice (n = 10 per group) lacking functional LDL receptor genes, an animal model of familial hypercholesterolemia. ...Group 1 was fed a regular chow diet. Groups 2 through 4 were fed a 1.25% high-cholesterol diet. In addition, group 3 received supplemental L-arginine and group 4 received L-arginine and N omega-nitro-L-arginine (L-NA), an inhibitor of NO synthase (NOS).
Animals were killed at 6 months; aortas were stained with oil red O for planimetry and with antibodies against constitutive and inducible NOSs. Plasma cholesterol was markedly increased in the animals receiving the high-cholesterol diet. Xanthomas appeared in all mice fed the high-cholesterol diet alone but not in those receiving L-arginine. Aortic atherosclerosis was present in all mice on the high-cholesterol diet. The mean atherosclerotic lesion area was reduced significantly (P < .01) in the cholesterol-fed mice given L-arginine compared with those receiving the high-cholesterol diet alone. The mean atherosclerotic lesion area was significantly larger (P < .01) in cholesterol-fed mice receiving L-arginine + L-NA than in those on the high-cholesterol diet alone. Within the atherosclerotic plaques, endothelial cells immunoreacted for endothelial cell NOS; macrophages, foam cells, and smooth muscle cells immunostained strongly for inducible NOS and nitrotyrosine residues.
The data indicate that L-arginine prevents xanthoma formation and reduces atherosclerosis in LDL receptor knockout mice fed a high-cholesterol diet. The abrogation of the beneficial effects of L-arginine by L-NA suggests that the antiatherosclerotic actions of L-arginine are mediated by NOS. The data suggest that L-arginine may be beneficial in familial hypercholesterolemia.
Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and ...feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device (LVAD) implantation. In addition, we sought to gain preliminary information on graft survival and any associated changes in cardiac function.
Thirty patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twenty-four patients with a history of previous myocardial infarction and a left ventricular ejection fraction <40% were enrolled in the CABG arm. In a second arm, 6 patients underwent LVAD implantation as a bridge to heart transplantation, and patients donated their explanted native hearts for testing at the time of heart transplantation. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term, unexpected adverse events. Follow-up positron emission tomography scans showed new areas of glucose uptake within the infarct scar in CABG patients. Echocardiography measured an average change in left ventricular ejection fraction from 28% to 35% at 1 year and of 36% at 2 years. Histological evaluation in 4 of 6 patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium.
These results demonstrate the survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality offers a potential therapeutic treatment for end-stage heart disease.
Apoptosis is a distinct form of programmed cell death characterized by activation of endonucleases that cleave nuclear DNA, condensation and fragmentation of nuclear chromatin, blebbing of intact ...membranes, and cell shrinkage and fragmentation. The mechanisms responsible are unclear, but nitric oxide (NO) generated by inducible NO synthase (iNOS) has been demonstrated to induce apoptosis in macrophages in vitro. This study investigated whether apoptosis occurs during cardiac allograft rejection and examined the relationship of apoptosis to iNOS expression.
Heterotopic abdominal transplantation from Lewis to Wistar-Furth rats was used as a model of cardiac allograft rejection; Lewis-to-Lewis grafts served as controls. Apoptosis was identified by DNA ladders after electrophoresis on agarose gels and by in situ labeling of DNA fragments; cell types were determined by immunohistochemistry. The number of apoptotic cardiac myocytes increased sharply from day 3 (0.31/mm2 ventricular tissue) to day 5 (1.27/mm2) after transplantation. At day 5, allografts showed a significant increase (P < .01) in apoptotic cardiac myocytes, macrophages, and endothelial cells compared with syngeneic grafts. The expression of iNOS mRNA, protein, and enzyme activity paralleled in time and extent the apoptosis of cardiac myocytes. iNOS immunostaining of infiltrating macrophages and cardiac muscle fibers increased significantly in the allografts at days 3 to 5 and was accompanied by immunostaining of both cell types for nitrotyrosine, which is indicative of peroxynitrite formation.
Apoptosis of myocardial cells occurs during cardiac allograft rejection. Apoptosis during rejection parallels the expression of iNOS, which suggests that apoptosis may be triggered by NO and peroxynitrite.
To determine whether indirect allorecognition is involved in heart allograft rejection T cells obtained from peripheral blood and graft biopsy tissues were expanded in the presence of IL-2 and tested ...in limiting dilution analysis (LDA) for reactivity to synthetic peptides corresponding to the hypervariable regions of the mismatched HLA-DR antigen(s) of the donor. Serial studies of 32 patients showed that T cell reactivity to donor allopeptides was strongly associated with episodes of acute rejection. The frequency of allopeptide reactive T cells was 10-50-fold higher in the graft than in the periphery indicating that T cells activated via the indirect allorecognition pathway participate actively in acute allograft rejection. In recipients carrying a graft differing by two HLA-DR alleles the response appeared to target only one of the mismatched antigens of the donor. Indirect allorecognition was restricted by a single HLA-DR antigen of the host and directed against one immunodominant peptide of donor HLA-DR protein. However, intermolecular spreading was demonstrated in patients with multiple rejection episodes by showing that they develop allopeptide reactivity against the second HLA-DR antigen. These data imply that early treatment to suppress T cell responses through the indirect pathway of allorecognition, such as tolerance induction to the dominant donor determinant, may be required to prevent amplification and perpetuation of the rejection process.
Advances in surgical and medical management have greatly improved long-term survival rates in patients with congenital heart disease (CHD). As these patients reach adulthood, myocardial dysfunction ...can occur, leading to cardiac transplantation.
We reviewed the pretransplantation and posttransplantation courses of 24 patients >18 years old (mean age, 26 years; range, 18 to 56 years) with CHD who received a transplant between January 1985 and September 1998. The relation between preoperative and perioperative risk factors for complications and death was assessed. Single ventricle was the pretransplantation diagnosis for 12 patients (50%), and d-transposition of the great vessels was the diagnosis for 4 patients (16%). Twenty-two patients had a mean of 2 previous operations. At cardiac transplantation, additional surgical procedures were required to correct extracardiac lesions in 18 patients (75%). Refractory heart failure was present in 22 patients, significant cyanosis was present in 7, and protein-losing enteropathy was present in 4. There were 5 early deaths due to bleeding (n=3) and infection (n=2). The Kaplan-Meier survival rate after cardiac transplantation was 79% at 1 year and 60% at 5 years. No anatomic or surgical risk factor was predictive of death. The outcome of patients with CHD who received a transplant was compared with that for patients without CHD (n=788). Mean bypass and ischemic times were significantly longer in patients with CHD than in patients without CHD. Survival rates after transplantation did not differ significantly between patients with and those without CHD (P=0.83).
Successful cardiac transplantation is obtainable in adults with complex CHD, with an outcome similar to that of patients without CHD. A detailed assessment of cardiac anatomy and careful surgical planning are essential to the pretransplantation and posttransplantation management of these patients.
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