Vascular access complications are a major problem in hemodialysis patients. Native arteriovenous fistulae, historically the preferred mode of access, have a patency rate of only 60% at 1 year. The most common mode of failure is due to progressive stenosis at the anastomotic site. We have previously demonstrated that perivascular endothelial cell implants inhibit intimal thickening following acute balloon injury in pigs and now seek to determine if these implants provide a similar benefit in the chronic and more complex injury model of arteriovenous anastomoses. Side-to-side femoral artery-femoral vein anastomoses were created in 24 domestic swine and the toxicological, biological and immunological responses to allogeneic endothelial cell implants were investigated 3 days and 1 and 2 months postoperatively. The anastomoses were wrapped with polymer matrices containing confluent porcine aortic endothelial cells (PAE; n = 14) or control matrices without cells (n = 10). PAE implants significantly reduced intimal hyperplasia at the anastomotic sites compared to controls by 68% (p < 0.05) at 2 months. The beneficial effects of the PAE implants were not due to differences in the rates of reendothelialization between the groups. No significant immunological response to the allogeneic endothelial cells that impacted on efficacy was detected in any of the pigs. No apparent toxicity was observed in any of the animals treated with endothelial implants. These data suggest that perivascular endothelial cell implants are safe and reduce early intimal hyperplasia in a porcine model of arteriovenous anastomoses.

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Analysis of the serological and cellular sensitization induced by encapsulated human islets transplantation in type I and type II diabetes patients.

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Adult↗

PubMedDate not supplied

Expression of transferrin receptors on lymphocytes: its correlation with T-helper/T-suppressor cytotoxic ratio and rejection in heart transplant recipients.

Forty-one heart transplant recipients were monitored serially for the expression of transferrin receptors and T-helper/T-suppressor cytotoxic ratios on circulating lymphocytes during the hospitalization periods after heart transplantations (60.5 +/- 18.9 days). These values were retrospectively correlated with the patients' clinical status with respect to rejection and infection. During clinically stable periods the average values of percentage of transferrin receptor-positive lymphocytes and T-helper/T-suppressor cytotoxic ratios were 5.9 +/- 4.3 and 1.5 +/- 1.0, respectively. The percentage of transferrin receptor-positive lymphocytes increased to a level of 12.0 +/- 5.4 (p less than 0.001) during the early prerejection phase and remained at this level throughout the rejection period. T-helper/T-suppressor cytotoxic ratios increased to 1.96 +/- 0.92 during the early prerejection phase (p less than 0.05), peaked at 2.30 +/- 1.21 during the late prerejection phase (p less than 0.01), but began to decline by the rejection period. After rejection treatment percentage of transferrin receptor-positive lymphocytes decreased to 8.4 +/- 5.3 (p less than 0.05), and T-helper/T-suppressor cytotoxic ratios decreased to normal levels. In contrast, in patients with infectious complications, a remarkably elevated percentage of transferrin receptor-positive lymphocytes (20.7 +/- 11.7) and relatively low T-helper/T-suppressor cytotoxic ratios (1.3 +/- 0.5) were noted. The data show an association between the clinical status, such as rejection and infection, and these immunologic measurements as transferrin receptor-positive lymphocytes and T-helper/T-suppressor cytotoxic ratios in heart transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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Effects of prophylactic rabbit antithymocyte globulin in cardiac allograft recipients treated with cyclosporine.

The prophylactic use of rabbit antithymocyte globulin (RATG) was evaluated in 13 cardiac allograft recipients who received a low-dose of RATG (175 +/- 32 mg) after transplantation (group 1). The patients were retrospectively compared with 13 parallel cases receiving the same treatment except for the initial RATG (group 2). There were no differences in the patient composition and the level of the basic immunosuppression therapy with cyclosporine. The patients treated with RATG (group 1) showed substantially greater suppression of T helper and total T cells up to 10 and 20 days after surgery, respectively. The incidence of rejection episodes during the initial admission seemed lower in patients receiving RATG, with a borderline significance (1.4 versus 2.4, p = 0.06). This accounts for the reduced requirement of methylprednisolone in treating rejection in patients in group 1 (1.3 gm versus 4.0 gm, p less than 0.02). Moreover, the patients without initial doses of RATG (group 2) more frequently experienced recurrent rejection (five of 12 versus nine of 10, p less than 0.05), which necessitated rescue RATG; the initial difference in the RATG usage disappeared by the time of discharge. Serious infection occurring after antirejection therapy was common in the group 2 patients without initial doses of RATG, although the overall incidence of infection was not statistically different. Prophylactic use of RATG at the dosage used appeared to reduce the incidence of rejection and the requirement for intravenous steroids and other immunosuppressants. It seems warranted to test this approach in a prospective randomized manner.

Adult↗

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Improved results of secondary cadaver retransplantation.

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Adult↗

PubMedDate not supplied

Comparison of immunosuppression therapy following heart transplantation: pretransfusion/azathioprine/ATG/prednisone versus cyclosporine/prednisone.

Since the introduction of cyclosporine in heart transplantation, the search for the ideal combination of immunosuppressive agents continues. Between January 1983 and February 1985, 32 patients have been randomized prospectively to either one of two immunosuppressive regimens: one includes pretransplant transfusion, prednisone, azathioprine and rabbit anti-thymocyte globulin [Group I, n = 14], the other includes cyclosporine and prednisone [Group II, n = 18]. There were no differences between Group I and II in relation to age distribution, indications for transplantation, preoperative serum creatinine, length of follow-up, mortality or number of rejection episodes per patient. However, there was a statistically significant increase in the incidence of serious infections in Group I compared to Group II patients, and also in Group II of the incidence of systemic hypertension (p less than 0.001), of symptomatic pericardial effusion (p less than 0.05) and impaired renal function (p less than 0.02). Adding cyclosporine to azathioprine immunosuppression is effective in treating ongoing rejection in patients not previously treated with cyclosporine. In conclusion, patients treated with azathioprine and prednisone (Group I) develop a greater number of serious infections, but both groups had a similar incidence of rejection. The development of renal dysfunction and hypertension in patients treated with cyclosporine continues to be of concern and may preclude its use as an effective long-term immunosuppressive agent in heart transplant recipients.

Adult↗

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Cytokine gene transcripts for tumor necrosis factor-alpha, interleukin-2, and interferon-gamma in human pulmonary allografts.

BACKGROUND: Cytokines participate in host responses to allografts, largely through recruiting and activating various regulatory and effector cells. We performed this study to determine the feasibility of using polymerase chain reaction methodology to define the expression of three important cytokines (tumor necrosis factor-alpha, interleukin-2, and interferon-gamma) in human pulmonary allografts. METHODS: Twenty-six graft-derived samples (11 transbronchial biopsy and 8 macrophage and 7 lymphocyte cell pellets isolated from bronchoalveolar lavage) were obtained from 13 lung transplant recipients and treated as follows: extraction of RNA; reverse transcription of RNA to complementary DNA; polymerase chain reaction amplification of cDNA with oligonucleotide primers specific for the three cytokines; gel electrophoresis of the polymerase chain reaction products; and verification of correct cytokine message by Dot blot technique (with specific 32P-labeled oligonucleotide probes). RESULTS: Concomitant pathologic evaluation of biopsy specimens from these 13 recipients showed five diagnostic groups: "normal" (no rejection/infection), n = 2; acute rejection, n = 4; nonspecific inflammation, n = 3; infection, n = 3; and obliterative bronchiolitis, n = 1. Interleukin-2 was expressed predominantly in acute rejection and infection (seven of ten and five of six samples positive, respectively), whereas tumor necrosis factor-alpha was expressed mainly in nonspecific inflammation (four of five samples) and somewhat less in rejection (six of ten). Interferon-gamma was expressed less frequently (in two of six samples with infection, but in none of ten with rejection and none of five with nonspecific inflammation). Serial data from one patient (6 months apart) showed considerable increase in interleukin-2 and interferon-gamma expression as she progressed from normal histologic status to obliterative bronchiolitis. CONCLUSIONS: Cytokine gene transcripts can be determined from minute samples derived directly from pulmonary allografts. Although our data are insufficient to make definitive conclusions, the suggestion of trends of cytokine expression in different posttransplantation pathologic conditions may indicate a useful role for this approach in the clinical evaluation of the lung transplant recipient.

Adult↗

PubMedDate not supplied

Expression of intercellular and vascular cell adhesion molecules and class II major histocompatibility antigens in human lungs: lack of influence by conditions of organ preservation.

BACKGROUND: The expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and class II major histocompatibility complex antigens was studied in control lung tissue and preserved human donor lungs. The three controls were represented by wedge biopsy specimens taken from non-neoplastic lung surrounding bronchogenic carcinomas. METHODS: Nine lungs were harvested from six brain-dead donors, flushed with Euro-Collins solution or low potassium-dextran-glucose solution, and stored at 1 degree C or 10 degrees C. Samples of the latter organs were taken at the time of surgical harvest (baseline) and after 2, 12, 24, and 48 hours of preservation time. Immunostains with monoclonal antibodies against intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and class II major histocompatibility complex molecules were performed on all samples, and the relative presence of these determinants was evaluated. RESULTS: In both the controls and preserved lungs, intercellular adhesion molecule-1 expression was intense in the septal capillary endothelium and alveolar pneumocytes, but essentially absent in bronchial epithelium. Vascular cell adhesion molecule-1 was moderately to strongly labeled in the endothelia of large and small blood vessels of all types, and it was not seen in other cell types. Class II major histocompatibility complex antigens were variably observed in pulmonary epithelial cells, but they were not expressed by endothelia. There appeared to be no significant difference in the immunohistologic density of intercellular adhesion molecule-1 or vascular cell adhesion molecule-1 immunostaining in allografts at the specified time points of preservation; this conclusion was confirmed by Western blot analysis. Similar findings pertained to staining results for human leukocyte DR antigens. There was likewise no significant difference in the expression of the three analytes when donor lungs perfused with Euro-Collins solution versus low potassium-dextran-glucose solution were compared; this was also true of organs preserved at 1 degree C versus 10 degrees C. CONCLUSIONS: These results suggest that, in the immediate post-harvest period, modulations in the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, or class II major histocompatibility complex antigens in pulmonary allografts are not attributable to the influences of preservation conditions.

Adolescent↗