Geomorphology of the Mirador-Calakmul Karst Basin: A GIS-based approach to hydrogeologic mapping.

This paper classifies the karst landscapes of the Petén Plateau and defines the Mirador-Calakmul Karst Basin by illustrating the distribution of its karst hydrologic features. Archaeological and spatial research of the Mirador-Calakmul area of Guatemala and Mexico has shown it to be a karst basin with geopolitical implications. Current research characterizes the karst landscapes of the Petén Plateau, maps the distribution of karst hydrologic features, and delineates the basin in geomorphological terms.

Exercise capacity after heart transplantation: influence of donor and recipient characteristics.

Background: For incompletely understood reasons, cardiac transplant recipients achieve only 60% to 70% of predicted values for maximal exercise capacity. The objective was to determine the characteristics of cardiac transplant recipients that are predictive of exercise capacity.

Methods: One hundred ten patients underwent maximal exercise testing using a modified Naughton protocol 26 +/- 1 months after transplantation.

Methotrexate for rejection prophylaxis after heart transplantation.

Background: The addition of vincristine to "quadruple-drug" induction immunotherapy (OKT3, cyclosporine, azathioprine, prednisone) after heart transplantation decreases the incidence of rejection but is limited by neurotoxicity. We hypothesized that methotrexate, when added to quadruple therapy, may also decrease the incidence of rejection but with less toxicity.

Methods: We randomized 36 heart transplant recipients to receive either quadruple therapy (OKT3, cyclosporine, azathioprine, corticosteroids) (n = 19) or quadruple therapy plus methotrexate (n = 17).

Effects of alloimmune injury on contraction and relaxation in cultured myocytes and intact cardiac allografts.

Objectives: This study was performed to determine the mechanisms by which allosensitized lymphocytes cause contractile dysfunction in cultured ventricular myocytes and to compare the effects on isolated myocytes with those observed in an intact heart preparation during allograft rejection.

Background: Allograft rejection may be associated with reversible abnormalities of both systolic and diastolic function. The immunologic mechanisms that cause ventricular dysfunction are poorly understood.

A prospective, randomized comparison of cyclophosphamide and azathioprine for early rejection prophylaxis after cardiac transplantation. Decreased sensitization to OKT3.

Humoral immune responses have been implicated in the pathogenesis of vascular rejection, allograft coronary artery disease, and sensitization to OKT3. Because cyclophosphamide (CP) is a potent suppressor of humoral immunity, we postulated that substituting cyclophosphamide for azathioprine (AZA) would be associated with a decrease in acute vascular rejection and sensitization to OKT3 in cardiac transplant recipients also receiving cyclosporine, corticosteroids, and perioperative OKT3. We prospectively randomized 119 patients to receive azathioprine (n = 61) or cyclophosphamide (n = 58) from the time of transplantation.

Helper T lymphocyte unresponsiveness to cardiac allografts following transient depletion of CD4-positive cells. Implications for cellular and humoral responses.

Initial treatment of heterotopic cardiac transplant recipients with anti-CD4 mAb promotes long-term (> 60 days) allograft survival. We have used modified limiting dilution analysis to quantitate donor alloantigen-reactive helper T lymphocytes (HTL) and CTL in mice bearing long-term cardiac allografts. Despite repopulation of lymphoid tissues with CD4+ T cells, donor alloantigen-reactive IL-2 producing and IL-4-producing HTL were rare or not detectable in lymphoid tissues or in the graft.

Mycophenolate mofetil (RS-61443): preclinical, clinical, and three-year experience in heart transplantation.

Mycophenolate mofetil (formerly known as RS-61443) is a morpholinoethyl ester of mycophenolic acid. Mycophenolic acid is a unique immunosuppressive agent because of its mechanism of action. By inhibiting the de novo pathway of purine synthesis, mycophenolic acid suppresses lymphocyte function much more than that of neutrophil, erythrocyte, and other rapidly dividing cell lines which can use the salvage purine synthesis pathway.

CD4-positive helper T lymphocytes mediate mouse cardiac allograft rejection independent of donor alloantigen specific cytotoxic T lymphocytes.

Mouse heterotopic cardiac allograft recipients were depleted of CD4+ or CD8+ T lymphocytes in vivo to assess cellular requirements for graft infiltration, tissue damage, and acute allograft rejection. Modified limiting dilution analysis was employed to quantitate IL-2-producing Th lymphocytes (HTL) and CTL infiltrating the graft. Results were correlated with graft function and histologic evidence of tissue damage.

Increased frequency of alloantigen-reactive helper T lymphocytes is associated with human cardiac allograft rejection.

Endomyocardial biopsy (EMB) is the standard method of monitoring heart transplant recipients for the development of allograft rejection. To date, noninvasive methods to detect cardiac allograft rejection have lacked adequate sensitivity and specificity for wide clinical application. In this study, limiting dilution analysis (LDA) was used to quantitate the number of donor alloantigen-reactive helper T lymphocytes (HTLs) in the peripheral blood of cardiac transplant recipients.

The use of mycophenolate mofetil (RS-61443) in human heart transplant recipients.

Mycophenolate mofetil is a potent inhibitor of de novo guanine nucleotide synthesis that selectively blocks lymphocyte proliferative responses. In animal models, mycophenolate mofetil has been shown to prolong allograft survival, reverse ongoing rejection, and induce strain-specific tolerance. To assess the safety and efficacy of mycophenolate mofetil in cardiac transplantation, 30 recipients with mild rejection were enrolled in an 8-week phase I trial.

Vascular rejection in heart transplantation: clinical correlation, treatment options, and future considerations.

Vascular rejection injures the vascular endothelium in cardiac allografts in the absence of significant intramyocardial lymphocytic infiltration. When compared with cellular rejection, vascular rejection occurs earlier after transplantation, is more resistant to immunosuppressive augmentation, causes more allograft dysfunction, and is associated with a higher frequency of allograft loss. Between January 1990 and October 1992, acute hemodynamically significant vascular rejection developed in 13 of 170 patients (8%).

Cardiac retransplantation: a viable option? The Registry of the International Society for Heart and Lung Transplantation.

To evaluate cardiac retransplantation as an appropriate utilization of scarce donor organs we analyzed data from the registry of the International Society for Heart and Lung Transplantation (ISHLT) (n = 449) and the Utah Cardiac Transplant Program (n = 20). Actuarial survival among retransplants was lower than in patients who received only one transplant in both the ISHLT registry patients (1 year survival, 48% versus 78%; p = 0.001) and the Utah series (1 year survival, 74% versus 88%; p = 0.

Predictors of survival after repeat heart transplantation. The Registry of the International Society for Heart and Lung Transplantation, and Contributing Investigators.

To examine factors potentially predictive of outcome after repeat heart transplantation, data were analyzed for 449 recipients of second allografts reported to the registry of the International Society for Heart and Lung Transplantation and a matched group of 421 primary transplant recipients. Survival was markedly decreased in repeat transplantation patients (1 year actuarial survival rate, 48% vs 79%; p less than 0.001).

Myocyte injury and contraction abnormalities produced by cytotoxic T lymphocytes.

Background: The mechanisms by which ventricular function is altered during cardiac transplant rejection are not well understood. Therefore, an in vitro model system has been developed to facilitate investigation of lymphocyte-mediated myocyte injury.

Methods And Results: Splenic lymphoid cells were obtained from mice 8-10 days after placement of a vascularized abdominal cardiac allograft and were restimulated in vitro with irradiated donor-type splenocytes for 5 days.

Nafazatrom (Bay g 6575) blunts canine hypoxic pulmonary vasoconstriction: evidence for a prostaglandin-mediated mechanism.

The eicosanoids are circulating vasoactive substances which may serve as modulators of pulmonary vasomotor tone. Nafazatrom (Bay g 6575) has been reported to raise circulating levels of prostaglandin I2 (PGI2) either by stimulating its synthesis or inhibiting its metabolism, and may also decrease leukotriene synthesis by inhibiting lipoxygenase. We evaluated the hemodynamic effects of nafazatrom administered intravenously in doses of 2,5, and 10 mg/kg in intact, anesthetized dogs ventilated with 21% and 10% oxygen.