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Biomedical subjects

J C Pierce

Publications and source records attributed to J C Pierce.

At least 37 records · Page 2Linked to original sources

Persistent hypophosphatemia following parathyroidectomy in end-stage renal disease: report of three patients.

Immediate and persistent hypophosphatemia following subtotal parathyroidectomy, despite discontinuation of phosphate binders, developed in three chronic hemodialysis patients. Although the serum phosphorous level is regularly reduced by parathyroidectomy in such patients, prolonged hypophosphatemia has not previously been reported. This observation supports the concept that parathyroid overactivity in end-stage renal disease is a major determinant of hyperphosphatemia.

Adult↗

Restrospective correlation of clinical and histologic findings of 189 exchanged kidneys.

Tissues samples from 189 unsuccessful renal allografts, 47 recovered at autopsy and the others removed surgically, were examined histologically by light microscopy. Tissues samples were obtained from cadaver kidneys that had been exchanged regionally for transplantation. Each allograft tissue sample was rated as to extent of pathologic changes denoting rejection and was classified accordingly. Surgical and autopsy reports, as well as clinical data, were then obtained and these were compared with the retrospective pathologic findings of this study. Our pathologic findings agreed with the original pathologic diagnosis as to presence or absence of rejection changes in 180 cases, but disagreed with the clinical diagnosis of rejection in 28 of the 63 cases with minimal or no histologic evidence of rejection. There was less disagreement with the clinical diagnosis for the 87 cases with histologic evidence of rejection which had been judged as sufficient to cause allograft loss, 70 having been clinically diagnosed as rejected. Disagreement occurred most often where the allograft had never functioned or had been lost within 3 months. Retrospective analysis did not disclose any association between rejection histology and preformed antibodies or length of kidney perfusion time. Sufficient allografts appeared to have been lost for reasons other than rejection to cast doubt on the validity of interpreting renal allograft data only by graft survival statistics.

Diagnosis, Differential↗

A mixed antiglobulin test for the detection of immunoglobulin G antibody to lymphocytes.

A mixed antiglobulin test with lymphocytes as test antigens has been developed for the detection of IgG antibodies. Free lymphocytes were counted before and after the addition of anti-D-coated indicator erythrocytes to quantitate the test. The optimal ratio of lymphocytes to indicator erythrocytes was 1: 30. Both anti-T and anti-B lymphocyte antibodies were detected by the test. Nonspecific agglutination of B lymphocytes and detector erythrocytes was avoided by the use of an appropriate dilution of the goat anti-human gamma chain reagent. Unlike cytotoxicity tests it could be used with dead lymphocytes that were frozen and stored intact as well as with live lymphocytes. Lymphocytes were better test antigens than were kidney cells from the same donors in the test. The mixed antiglobulin test with lymphocytes was also more sensitive in the detection of antibodies in hemodialysis patients than was the microlymphocytotoxicity test.

Antibodies, Anti-Idiotypic↗

Myelin basic protein-stimulated rosette-forming T cells in multiple sclerosis.

A subpopulation of T lymphocytes sensitized to human myelin basic protein in peripheral blood of patients with multiple sclerosis, central nervous system (CNS) tumors, and cerebrovascular accidents was demonstrated by the antigen-stimulated, rosette-forming T-cell assay. A significant increase in the percent of active rosette-forming T cells was detected after in vitro exposure of peripheral blood lymphocytes to human myelin basic protein but not to histones. In contrast, peripheral blood lymphocytes from healthy controls and from patients with benign and malignant breast diseases were unresponsive to stimulation by either antigen. These results demonstrate a functionally active T-lymphocyte subpopulation sensitized to myelin basic protein in patients with multiple sclerosis and in patients with certain other CNS diseases.

Adult↗

Kidney transplantation.

Since 1954, more than 26,000 kidney transplants have been performed and transplantation is now an accepted method for the treatment of end-stage renal disease. Recent advances in transplantation include operation not only on ideal recipients, but also on a much broader group of patients; an improved understanding of rejection mechanisms; better employment of standard immunosuppressive drugs; identification of an additional major histocompatibility antigen system; appreciation that blood transfusions prior to transplantation may facilitate acceptance of cadaver kidneys; and development of intracellular washout solutions for kidney preservation. Although the overall functional survival rates of kidney transplants have not improved recently, there has been a significant improvement in patient survival, especially after transplantation of cadaver kidneys.

Graft Rejection↗

Computed tomography in renal transplant problems.

Nineteen patients were studied with computed tomography immediately after kidney transplantation and subsequently if declining renal function was noted. Abscess formation, hematoma and lymphocele were satisfactorily demonstrated. Of 8 diagnosed abnormal densities, 5 were proved correct (abscess 2; serous collection and old blood 1; lymphocele 1; and hematoma (fresh) 1). Two were not proved but abnormalities resolved on medical therapy. There was one incorrect diagnosis: what was thought to be an abnormal fluid collection was really a markedly enlarged edematous rejected kidney. Computed tomography represents an excellent method of following the course of therapy, whether surgical or conservative.

Abscess↗

Cell-mediated immunity to donor antigens in renal allograft recipients.

The antigen-stimulated active rosette-forming T-cell (AgARFC) assay was adapted for the preoperative study of 21 consecutive kidney transplants (17 cadaver donors and four living related donors; five retransplants). Recipient peripheral blood lymphocytes were incubated for 15 minutes with donor histocompatibility antigens preparaed by sonication of donor peripheral blood or splenic lymphocytes. Recipient presensitization to donor antigens was expressed as the difference between active rosette formation in the presence (%AgARFC) and in the absence (%ARFC) of donor antigens. This antigen-induced difference is rosette formation (%AgARFC - %ARFC) for all patients ranged from - 7.0% to 24.2%. Of those patients with pretransplant sensitization greater than 6.3% (group I: mean, 13.2 +/- 3.0; n = 7), 71% had severe acute rejection requiring dialysis within the first 2 weeks of transplantation. In contrast, none of the patients with pretransplant values below 6.3% (group II: mean, -0.8 +/- 1.0; n = 14) had rejection requiring dialysis within the first 2 weeks. Group I patients had 43% graft survival at 1 month and 14% survival at 2 months, whereas group II had 86% graft survival at 1 month and 71% at 2 months. The AgARFC assay provided a rapid means of measuring recipient T-cell presensitization to donor alloantigens, which was correlated with the accelerated rejection of renal allografts.

Antigen-Antibody Reactions↗

Renal artery occlusion in transplant recipients.

Five cases of renal artery occlusion occurring in kidney transplant recipients are reported--an incidence of 1.4%. Two patients recovered moderate renal function after thrombectomy in spite of the estimated occlusion time of four hours and 12 hours, respectively, under normothermic conditions. Three cases of occlusion were associated with pre-existing renal artery stenosis. This experience reinforced the optimistic and aggressive approach to treatment of renal artery thrombosis. Renal artery occlusion may simulate acute rejection in the transplant recipient.

Adult↗

A new assay for T-cell mediated immunity to transplantation antigens.

The kinetics of circulating antigen sensitive T-cells were studied in Hartley strain guinea pig recipients of Shorthair strain first- and second-set skin allografts. Peripheral blood donor antigen sensitive T-cells (AST) were quantitated by the antigen-stimulated active rosette-forming T-cell (AgARFC) assay by incubating lymphocytes in the presence and in the absence of soluble transplantation antigens. The number of circulating AST/cu mm rose to maximum levels (1,165 +/- 272 SEM) by day 3 and fell sharply before first-set graft rejection (453 +/- 117 SEM) on day 7 after transplant. In contrast, there were no detectable antigen-sensitive cells when lymphocytes from both recipient and control guinea pigs were stimulated with soluble recipient-strain antigen. Significant numbers (212 +/- 159 SEM) of circulating AST remained through day 68 after first-set grafts. Following placement of sencon-set allografts on day 73, the AST disappeared from the circulation for 2.5 days and then rose to peak levels (825 +/- 167 SEM) in circulating AST (579 +/- 327 SEM) preceded rejection of second-set skin allografts. When control guinea pigs were immunized with a single dose of soluble donor antigens, a progressive increase in circulating AST (579 +/- 327 SEM) was found through day 17 after sensitization without the fall associated with graft rejection. The antigen-stimulated, rosette-forming T-cell assay may prove useful in the detection of cellular presensitization and in the monitoring of graft rejection in clinical transplantation.

Animals↗

The angiographic evaluation of human renal allotransplants. Functional graft deterioration and hypertension.

The renal arteriogram is a highly reliable test in the differential diagnosis of early transplant anuria, graft rejection, and hypertension. The reliability of the renal arteriogram was 97.8% in either substantiating or disproving the presence of a suspected episode of graft rejection or renal artery stenosis. The earliest signs of acute humoral and acute rejection were a prolongation of arterial clearance time, diffuse edema with enlargement of the kidney, and progressive deterioration of the nephrogram. Renal artery stenosis may be a sharply localized septum or an elongated narrowing at or distal to the actual site of anastomosis. This was seen primarily in patients' arteriograms more than 60 days after transplantation, and it is important because it is a surgically correctable cause of hypertension.

Adolescent↗

Use of plasma protein fraction in preservation of cadaveric kidneys.

We have compared 23 cadaver kidneys preserved with cryoprecipitated plasma (CPP) with 23 consecutive cadaver kidneys preserved with plasma protein fractions (PPF). In both groups the MOX-100 Waters machine was used. The PPF solution does not contain any fibrinogen or gamma globulin. The harvesting characteristics of both groups were comparable. Pulsatile perfusion time in the PPF group was up to 46 hours and in the CPP group was up to 44 hours. In the PPF group, 20 kidneys achieved immediate function upon transplant (85 percent). Two underwent periods of acute tubular necrosis (ATN) and one kidney never worked. In the CPP group, 18 kidneys achieved immediate function (78 percent). Two underwent periods of ATN and three never achieved satisfactory function. From this clinical experience, PPF is as effective as CPP for the preservation of kidneys up to 44 hours prior to transplant. The advantages of the PPF are easy availability, long shelf life, simple preparation, low cost, freedom from risk of hepatitis, and theoretical absence of antibody against the kidney. Graft and patient survival at 6 months showed no statistical difference.

Adolescent↗

Humoral antibody responses following transplantation in man.

Sequential titers of five different humoral antibodies (antirat erythrocyte, antisheep erythrocyte, isoantibodies, rheumatoid factors, and serum agglutinators) were simultaneously performed on 20 patients with renal transplants, 12 patients with skin transplants, and 2 patient populations (one hospitalized and one ambulatory). The results suggested that rises in titer of any of these antibodies could not be used as an indicator of acute rejection. Nevertheless, patients who lacked rejection episodes were unlikely to show humoral responses and always lacked antiglobulin responses. Heterophil responses always preceeded antiglobulin responses. These results suggest that heterophils are cross reacting antibodies and antiglobulins are auxillary immune responses.

Absorption↗

A mixed antiglobulin test with kidney cells in suspension for IgG antibody in human allograft recipients.

A modification of the mixed antiglobulin test for the detection of IgG antibodies directed against human kidney cells has been devised which uses a suspension of individual kidney cells rather than a monolayer culture as antigen so that it may be enployed clinically as a prospective crossmatch for organ transplantation. The antiglobulin reagent is added to the sensitized kidney cells rather than to the indicator erythrocytes, which reduces the background of nonspecific reations almost to zero. It is reproducible. The mixed antiglobulin test detected antibody in the sera of patients on chronic dialysis two to four times more frequently than did either the immune adherence test or the most sensitive modification of the microlymphocytotoxicity test which was utilized. It detected the development of antibody specific for donor kidney cells in the sera of 5 of 10 allograft receipients during periods of good to moderate renal transplant function several months before rejection.

Animals↗

Donor-specific IgG antibody and the chronic rejection of human renal allografts.

Although many investigators have felt that humoral antibody was responsible for chronic rejection, attempts to detect it in the sera of recipients in the presence of functioning renal allografts have been largely unsuccessful. A modification of the mixed antiglobulin reaction has increased its sensitivity so that the development of low titers of immunoglobulin (IgG) antibody antibody specific for donor kidney cells can be detected in renal allograft recipients while renal function is still good. Donor-specific antibody was detected in the sera of 11 of 13 patients whose transplants had ceased to function from 5 to 43 months after transplantation. In five recipients the antibody was present prior to as well as after transplantation and in six recipients antibody developed after transplantation from 3 to 25 months prior to the cessation of function. In the patients with antibody, chronic rejection was characterized by hypertension which required treatment with multiple drugs, by proteinuria of greater than one gram per day, by a gradual, progressively rising serum creatinine, and by an absence of acute ologuric rejection episodes. Pathologically there was extensive intimal proliferation and occlusion of the intrarenal arteris. There also was significant glomerulonephritis which consisted of thickening of the basement membranes, mesangial cell proliferation, simplification of the capillary loops, and in some patients fibroepithelial crescent formation. These findings suggest that IgG antibodies directed against cell-surface antigens of the donor are the chief cause of chronic renal allograft rejection.

Adult↗