Biomedical subjects
Alfred J Tector
Publications and source records attributed to Alfred J Tector.
CTLA-4 is important in maintaining long-term survival of cardiac allografts.
INTRODUCTION: CTLA-4 is a negative regulatory molecule upregulated on activated T cells; however, its role in induction and maintenance of transplant tolerance is not well understood. METHODS: The characteristics and effects of a novel mouse anti-rat CTLA-4 antibody (Ab) (242B58) were examined using fluorescence-activated cell sorter, mixed lymphocyte reaction, enzyme-linked immunospot, signaling studies, and a rat model of cardiac transplant tolerance induced by administration of anti-CD28 Ab and cyclosporine. RESULTS: The anti-CTLA4 Ab was shown to bind to CTLA-4 but not prevent subsequent binding of B7 to CTLA-4. Binding to CTLA-4 did not result in phosphorylation of early cytoplasmic tyrosine kinases, suggesting that this is not a signaling Ab. However, its in vitro function was compatible with antagonization of the effects of CTLA-4, thereby increasing T-cell proliferation and interferon-gamma production in mixed lymphocyte reaction and enzyme-linked immunospot assays, respectively. Administration of 242B58 to animals treated with anti-CD28 Ab and cyclosporine either at the time of transplantation or various time-points up to 33 days posttransplantation did not result in immediate rejection, but rather caused a delayed severe acute allograft rejection at approximately 45 days posttransplant. CONCLUSIONS: Our results seem to be a reflection of the unique properties of the 242B58 Ab, which does not antagonize B7 binding to CTLA-4 and affect its ability to out-compete CD28 for B7 binding. It does, however, seem to interfere with CTLA-4 signaling, suggesting that competition for B7 may be important in induction of tolerance, but signaling through CTLA-4 is more important in maintaining a tolerant phenotype.
Comparison of Novacor and HeartMate vented electric left ventricular assist devices in a single institution.
We compared the survival outcomes, left ventricular assist device (LVAD)-related hospitalization, stroke, infection, panel reactive antibody, and blood product use data among 13 Novacor and 51 HeartMate system recipients. Stroke was significantly higher in Novacor patients, as was blood product use at the time of heart transplantation, likely due to long-term anti-coagulation, while the LVAD-related hospitalization and infections did not differ between the 2 groups. A positive panel reactive antibody was seen more among the HeartMate patients, but did not have a significant clinical impact and may not represent a true allosensitization.
Left ventricular assist device performance with long-term circulatory support: lessons from the REMATCH trial.
BACKGROUND: Left ventricular assist device (LVAD) failure and malfunction rates are critical gauges for establishing LVADs as a long-term therapy for end-stage heart failure patients. These device performance measures, however, have been inadequately characterized in the bridge-to-transplantation literature. METHODS: REMATCH is a randomized trial that compares optimal medical management with LVAD implantation for patients with end-stage heart failure. An independent committee adjudicated patient outcomes. The primary endpoint--survival--was analyzed by intention to treat using the log-rank statistic. Frequency of event occurrence was analyzed by Poisson regression. The time to first event was analyzed by the product limit method. Device performance was disaggregated into confirmed malfunctions and system failures. The latter were events in which patients could not be rescued with backup circulatory support measures. RESULTS: The 1-year survival rate was 52% (95% confidence limit [CL]; 40%-63%) for LVAD patients versus 28% (95% CL; 17%-39%) for medical patients and the 2-year survival rate was 29% (95% CL; 19%-40%) for LVAD patients versus 13% (95% CL; 5%-22%) for medical patients. System failure was 0.13 per patient per year and the confirmed LVAD malfunction rate was 0.90. Freedom from device replacement was 87% at 1 year and 37% at 2 years. CONCLUSIONS: Despite the observed rates of device malfunction and replacement, LVAD implantation confers clinically significant improvement with regard to survival as compared with medical management. Device modifications and innovations for infection management exhibit great promise of improving device performance in the near future.
Evolution of a pheochromocytoma.
OBJECTIVE: To present a case that demonstrates the evolution of a pheochromocytoma over a several-year period and to emphasize the importance of a thorough work-up for pheochromocytoma in patients with neurofibromatosis type 1 (NF1) and hypertension. METHODS: We review the long-term clinical, biochemical, and imaging findings in a man with a complex medical history of hypertension, NF1, and cardiomyopathy. RESULTS: A 44-year-old man, with a well-documented history of headaches, hypertension, and NF1, was referred for evaluation of a right adrenal enlargement. He had developed cardiomyopathy and undergone an evaluation for cardiac transplantation. Initial computed tomography revealed subtle asymmetry in the upper right adrenal gland. Biochemical studies for pheochromocytoma yielded equivocal findings, with a 1.5-fold elevation in the urinary norepinephrine and near-normal urinary metanephrine level. Because 131I-metaiodobenzylguanidine imaging showed no tracer uptake in the area of the right adrenal gland, the patient was thought not to have a pheochromocytoma. The patient eventually underwent cardiac transplantation and did well. On reassessment 3 1/2 years later, he was found to have a larger right adrenal mass. The second endocrine evaluation demonstrated substantial elevation in the urinary metanephrine level, and the patient underwent laparoscopic right adrenalectomy to remove the tumor (3.5 by 3.0 by 2.5 cm), which proved to be a pheochromocytoma. CONCLUSION: This case shows that a pheochromocytoma can be difficult to diagnose and can evolve to become a large, biochemically active tumor. It is imperative that patients with an adrenal tumor undergo periodic reevaluation to ensure that the tumor remains stable in size. If the tumor enlarges, further biochemical testing is warranted.