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Randall C Starling

Publications and source records attributed to Randall C Starling.

80 records · Page 5Linked to original sources

Acute cellular rejection following human heart transplantation is associated with increased expression of vitronectin receptor (integrin alphavbeta3).

The vitronectin receptor (integrin alphavbeta3), a cell-surface adhesion receptor, has been shown to play a significant role in endothelial cell migration, apoptosis, atherosclerosis, and T-lymphocyte activation. This study was undertaken to test the hypothesis that cardiac allograft rejection is associated with increased expression of alphavbeta3. We also determined whether fibronectin receptor (alpha5beta1) and tissue factor are up-regulated in the presence of acute cellular rejection. We evaluated endomyocardial biopsy specimens with histologic evidence of different degrees of acute cellular rejection (grade 0, n = 10; grade 1A, n = 10; grade 2, n = 10; grade 3A, n = 10). Biopsies were obtained 2-4weeks after cardiac transplantation. Immunoperoxidase staining was performed for alphavbeta3, tissue factor, and alpha5beta1, and protein levels were further determined by Western blot analysis. Specimens with grade 2 and grade 3A rejection showed positive staining of alphavbeta3 in lymphocytic aggregates and vascular endothelial cells. By immunoblotting, we identified significantly increased expression of alphavbeta3 in the presence of acute rejection, grade 2 (3-fold, p = 0.01) and grade 3A (3.6-fold, p = 0.005) compared to grade 0 and 1 A specimens. There was no evidence of increased expression of alpha5beta1 or tissue factor. Acute cellular rejection, a process characterized by T-lymphocyte activation and release of inflammatory cytokines, is associated with increased expression of alphavbeta3.

Acute Disease↗

Increased beta-myosin heavy chain in acute cellular rejection following human heart transplantation.

BACKGROUND: Increased expression of smooth muscle and nonmuscle myosin heavy chains has been previously reported in animal models of cardiac allograft rejection. However, altered expression of beta-myosin heavy chain in human cardiac rejection has not been determined. METHODS: Two-dimensional (2D)-gel electrophoresis of endomyocardial biopsies taken from patients with (Grade 3A, n = 6) and without (Grade 0, n = 6) acute rejection were analyzed. Increased expression of two protein spots (MW approximately 12 kDa) were identified in the presence of acute rejection and were further characterized by mass spectrometry analysis. In patients who had acute rejection, protein expression was subsequently analyzed by immunoblotting on biopsies preceding, during, and following treatment of rejection. RESULTS: Mass spectrometric analysis of the protein spots detected 6 and 22 tryptic peptides, respectively. Protein sequence database search analysis identified the first protein as beta-myosin heavy chain and the second spot consisted of proteins of unidentified nature that may represent novel proteins. Immunoblotting analysis showed 1.4 x fold increase (p < 0.01) of protein expression of beta-myosin heavy chain expression in the presence of acute rejection. CONCLUSIONS: To our knowledge, this is the first 2D-gel study to describe increased expression of beta-myosin heavy chain and other proteins of unidentified nature in association with human cardiac allograft rejection.

Adult↗

Management of the waiting list for cadaveric kidney transplants: report of a survey and recommendations by the Clinical Practice Guidelines Committee of the American Society of Transplantation.

The Clinical Practice Guidelines Committee of the American Society of Transplantation developed a survey to review the policies of kidney transplant programs in the United States with respect to the management of the steadily expanding waiting list for cadaveric kidneys. The survey was sent to 287 centers, and 192 (67%) responded. The survey indicated that regular follow-up monitoring, most frequently on an annual basis, is required by the majority (71%) of programs. Patients considered to be at high risk and candidates for combined kidney-pancreas transplantation may be monitored more frequently. Annual screening for coronary artery disease is typically required for asymptomatic patients considered to be at high risk for covert disease. Noninvasive techniques are typically used, and a designated cardiologist is usually available to the transplant program. The dialysis nephrologist or the potential transplant recipient is expected to inform the transplant program of intercurrent events that may affect transplant candidacy. Standard health maintenance screening is required, together with the routine updating of serologic and other blood tests that may be relevant to the posttransplant course. Smaller transplant programs (<100 patients on the waiting list) are more likely to maintain closer contact with the wait-listed patients and to attempt to influence their treatment during dialysis and are less likely to cancel transplants because of unanticipated pretransplant medical problems. The work load necessitated by the follow-up monitoring of wait-listed patients was assessed and, in the absence of specific evidence-based information, a series of recommendations were developed to reflect current standards of practice and to suggest future research initiatives.

Cadaver↗

Regional referral system for patients with acute mechanical support: experience at the Cleveland Clinic Foundation.

Regional referral networks ("hub and spoke") have been created to facilitate the transfer of patients on mechanical circulatory support. Although individual centers report good success, overall outcomes have remained poor. We investigated whether preoperative variables influenced survival and could be used to help select patients best served by referral. A retrospective chart review was conducted on all patients transferred to our institution supported on cardiac assist devices. Between January 1995 and September 2003, 39 patients were received in transfer for continued care after the implantation of a cardiac assist device. Eighty-five percent of patients had the ABIOMED BVS 5000 implanted. The most common indication was postcardiotomy shock. Sixty-four percent of patients were not candidates for heart transplantation due to medical or social contraindications. The 30-day mortality of this group was 62%. Survivors had less comorbidity and were less likely to have complex surgeries, neurologic impairment, and multisystem organ failure when presenting to our center. Devices were weaned in 30% of cases. Only six patients (15%) were successfully transplanted, and five of these patients have done well at follow-up. Based on our experience, we believe that cardiogenic shock patients benefit from a regional referral system if they have not had complex cardiac surgical procedures or developed multisystem organ failure. Furthermore, there is a survival advantage when using long-term devices because this allows possible recovery or transplantation.

Adult↗

Management of acute decompensated heart failure in the emergency department.

Heart failure, a disease of epidemic proportions, has a tremendous clinical and financial impact on the US health care system. With more than 5 million Americans diagnosed with heart failure and 5-year mortality approaching 50%, it is the most common cause of hospitalization in patients older than 65 years and is the single most expensive diagnosis in the US health care system. Because the average US hospital loses more than 1000 dollars per heart failure admission, effective therapies that decrease length of stay, reduce hospital costs, and prevent 30-day readmissions are needed. This article reviews the relevant pathophysiology of heart failure, discusses the newest diagnostic strategies for emergency department diagnoses, evaluates recent advances and effects of early aggressive therapies, and presents a suggested algorithm for the treatment of acutely decompensated heart failure in emergency departments.

Aged↗