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In vivo T cell depletion with low-dose rabbit antithymocyte globulin results in low transplant-related mortality and low relapse incidence following unrelated hematopoietic stem cell transplantation.

Stem cell transplantation from unrelated donors is associated with an increased risk of graft failure and graft-versus-host disease (GVHD). Addition of pretransplant antithymocyte globulin (ATG), although reducing the risk of graft rejection and GVHD, bears the risk of overimmunosuppression, resulting in an increased relapse rate and transplant-related mortality. Therefore, we evaluated in 21 consecutive patients receiving unrelated stem cell grafts from either HLA-matched (38%) or -mismatched (62%) donors whether low-dose rabbit ATG added to cyclosporin A and methotrexate at a total dose of 3.5 mg/kg for HLA-identical and 5.0 mg/kg for HLA-mismatched transplants given in two divided doses on days -2 and -1 provides sufficient immunosuppression for prevention of GVHD and graft rejection but is associated with an acceptable risk of relapse and transplant-related mortality. Stable leukocyte engraftment was achieved in all patients (100%). Overall survival after a median follow-up of 26 (median, range 14-42) months was 56 +/- 26% (95% confidence interval, CI) and the overall relapse rate at 3 years was 24 +/- 21%. Three-year survival for standard-risk patients, i.e., chronic myeloid leukemia (CML) in first chronic phase or acute leukemia in first complete remission, was 87% +/- 13% versus 40% +/- 31% for patients with more advanced disease. The incidence of acute GVHD II-IV degrees was 55 +/- 22%; that of severe acute GVHD III-IV degrees was 21 +/- 19%. Chronic GVHD was observed in 5/17 (29%) patients surviving more than 100 days post stem cell transplantation. Transplant-related mortality was 16 +/- 15% (95% CI) at day + 100 and 25 +/- 19% (95% CI) at 1 year after the transplant. The data presented show that pretransplant in vivo T cell depletion with low-dose rabbit ATG results in a low transplant-related mortality due to a low incidence of severe acute and chronic GVHD and a low relapse rate. To find out the optimal rabbit ATG dose in the unrelated stem cell transplantation setting, further dose-finding studies comparing high- and low-dose regimens are necessary.

Adolescent↗

Is renal transplantation involved in post-transplantation liver disease? A prospective study.

Various lesions of the liver commonly observed in renal transplant recipients are usually considered as a consequence of the transplantation procedures (immunosuppression, drug toxicity, alteration of immune responses to various viruses). A group of 64 patients all treated with corticosteroids and azathioprine was studied prospectively, and serial liver biopsies were performed on the day of transplantation and at 1 and 3 years after transplantation. Chronic hepatitis was already present in 40% of the patients on the day of transplantation and an increase of only 15% in the frequency of this condition was observed 3 years later. The presence of HBsAg in 45% of the patients at the time of transplantation was significantly associated with liver lesions. In about 3% of the cases, transplantation was directly responsible for a liver disease (peliosis hepatitis). During the followup period an evolution from chronic persistent hepatitis to chronic active hepatitis was observed with an abnormally high frequency (25%). We conclude that most of the liver diseases observed in transplant recipients are the consequence of events before transplantation and probably related to hemodialysis.

Alanine Transaminase↗

Pregnancy after pancreas transplantation in the cyclosporine era: report from the International Pancreas Transplant Registry.

BACKGROUND: As of December 31, 1996, a total of 9012 pancreas transplants have been reported to the International Pancreas Transplant Registry (IPTR). Over 75% of these recipients were < or = 40 years of age at the time of their transplant. With continued improvement in short- and long-term outcome after transplant, an increasing number of female recipients have become pregnant. However, outcome after pregnancy in pancreas transplant recipients has not been studied in detail. METHODS: To evaluate the risks of pregnancy after pancreas transplantation in the cyclosporine era, we surveyed the institutions reporting to the IPTR. RESULTS: Nineteen cases of pregnancy in 17 female recipients of simultaneous pancreas-kidney transplants resulted in 19 live births. Metabolic control during pregnancy was good in all cases. Mean duration of gestation was 35.2-2.2 weeks. Mean birth weight was 2150+/-680 g. Two congenital malformations were reported (one bilateral cataract and one double aortic arch). One child developed type I diabetes at age 3 years. Only one pancreas graft and one kidney graft were lost (in two different recipients). The pancreas graft was lost after delivery (because of acute rejection). The kidney graft was lost 3 months after delivery (impaired function due to previous amphotericin B treatment). One case of a worsened secondary complication (retinopathy) was reported. One recipient died of myocardial infarction 7 years after transplant and 5 years after delivery, in spite of a normal pretransplant coronary angiogram and good pancreas function. CONCLUSION: This study shows that simultaneous pancreas-kidney transplantation can restore fertility in uremic type I diabetic female recipients. Thus, both posttransplant contraception and fertility counseling are options for female recipients. However, our analysis demonstrates that, when discussing the possibility of pregnancy with female pancreas recipients, these potential risks must be considered: (1) graft loss, (2) progressive maternal morbidity and mortality even with good glycemic control, and (3) diabetes transmission to offspring.

Adult↗

Hepatocyte transplantation using biodegradable matrices in ascorbic acid-deficient rats: comparison with heterotopically transplanted liver grafts.

BACKGROUND: Hepatocyte transplantation using polymeric matrices is under investigation as an alternative therapy for metabolic liver diseases. Long-term engraftment of hepatocytes in polymers has been demonstrated. However, the metabolic activity of hepatocytes in such devices has never been assessed in direct comparison with liver grafts. METHODS: Hepatocyte and partial liver transplantation were evaluated in the scurvy-prone osteogenic disorder Shionogi rat model. Biodegradable poly glycolic acid matrices seeded with hepatocytes equivalent to 20% of the recipient's liver mass, or 20% liver grafts were heterotopically transplanted into ascorbic acid- (AsA) deficient recipients. Recipients of cell-free matrices or AsA-deficient liver grafts served as controls. Recipients were set on AsA-free diet after transplantation. Plasma AsA levels, AsA concentrations in liver and adrenal gland tissue, and body weight ratios were assessed and H&E histology was performed. RESULTS: Recipients from the control groups showed symptoms of scurvy at 1 month after cessation of AsA supply. Hepatocyte transplantation and auxiliary liver transplantation prevented symptoms of scurvy and increased plasma and tissue AsA levels and body weight ratios. AsA levels in recipients of 20% liver grafts were comparable to normal control animals. CONCLUSIONS: Hepatocytes transplanted in polymeric matrices are able to compensate for liver-based metabolic deficiencies. Hepatocyte transplantation improves plasma AsA levels in AsA-deficient recipients. However, auxiliary liver grafts are superior to hepatocyte grafts in improving metabolic parameters. Further research work is needed to increase the efficiency of liver cell transplantation with regard to a clinical application.

Animals↗

Reduced incidence of hyperuricemia, gout, and renal failure following liver transplantation in comparison to heart transplantation: a long-term follow-up study.

BACKGROUND: Hyperuricemia and gout are common complications of heart transplantation, reaching a prevalence of 84% and 30%, respectively, in heart transplant recipients. In contrast, they are seldom reported following orthotopic liver transplantation (OLT). METHODS: We retrospectively evaluated 75 consecutive liver transplant recipients and 47 consecutive heart transplant recipients, followed for at least 3 years after transplantation in a single transplantation center in Jerusalem, Israel. Data was collected on demographic and clinical variables, levels of uric acid, the occurrence of gout, renal function, and variables effecting hyperuricemia, such as weight and medications. RESULTS: Clinical gout was significantly more prevalent in heart recipients than in liver recipients (25.5% and 2.6%, respectively). Hyperuricemia was present in 100% of heart recipients, with an average uric acid level of 451 micromol/l, as compared with 85.7% and 403 micromol/l for liver recipients (P < 0.001 for both variables). Univariate analysis identified several parameters which significantly influenced the difference in hyperuricemia and gout among the two groups including age, gender, rejection episodes, hypertension, diabetes mellitus, the level of uric acid prior to transplantation, and the use of cyclosporine A, diuretics, steroids, and aspirin. Use of tacrolimus and azathioprine were associated with decreased incidence of hyperuricemia and gout. Multivariate analysis identified the type of transplantation as the only independent risk factor predicting the development of hyperuricemia and gout. CONCLUSION: Clinical gout and hyperuricemia were significantly more prevalent in heart recipients than in liver recipients. The disparity can be explained by differences in age, gender and renal function among the groups, as well as by the use of different medication regimens.

Adult↗

The effect of blood transfusions on renal transplantation. Studies of 395 patients registered for transplantation with a first cadaveric kidney.

Three-hundred-and-ninety-five candidates registered for a first cadaveric renal transplant have been analyzed for the effect of pre-graft blood transfusions. Of these, 348 patients were transplanted, 45 died prior to transplantation and two patients have not yet received a transplant. Slightly less than half of the transplanted patients had been transfused, and those received five or more transfusions demonstrated a superior graft survival. This was pronounced in all HLA incompatible transplants who had received five or more transfusions. In patients who received less than five transfusions, only one-two HLA antigen incompatible transplants demonstrated increased graft survival. The frequency of rejection episodes was significantly decreased in all transfused compared to non-transfused groups. Among the patients dying while waiting for a transplant, the majority had been transfused, and a significantly higher proportion of them had cytotoxic HLA antibodies, compared to those who were transplanted.

Adult↗

BEAM+autologous stem cell transplantation in malignant lymphoma: 100 consecutive transplants in a single centre. Efficacy, toxicity and engraftment in relation to stem-cell source and previous treatment.

One hundred consecutive patients with malignant lymphoma treated with high-dose chemotherapy and autologous stem cell transplantation, followed at least 1 yr post-transplant, are reported, 68 with non-Hodgkin's lymphoma and 32 with Hodgkin's disease. At transplant, 23 patients were in first remission, 69 in later chemosensitive disease and 8 were chemotherapy resistant. Based on previous treatment and stem-cell source, the patients were subdivided into 3 cohorts: BMT1: bone-marrow harvest and transplant after > or =3 treatment regimens (38 patients); BMT2: bone marrow harvest and transplant after less than 3 treatment regimens (24 patients); PBSCT: peripheral-blood stem cell transplant (38 patients, 5 of these with CD34+ cell selected PBSC). The 4-yr survival and progression-free survival of all patients was 45 and 40%, respectively. Forty-one patients have died, 27 of lymphoma, evenly distributed in the cohorts. Fourteen treatment-related deaths occurred, 13 of these in the BMT1 cohort, significantly more than in the other cohorts (p=0.001). In univariate survival analysis cohort, age, disease status at transplant and number of previous treatment regimens were significant. In multivariate survival analysis cohort, age and sex were independently significant, women having a shorter survival. The patients transplanted with unselected PBSC had significantly shorter duration of pancytopenia and hospital stay than the otherwise comparable BMT2 patients, but their progression-free survival was identical. We confirm that high-dose therapy with autologous stem cell transplant from blood or bone marrow in not-too-heavily pretreated patients is a safe procedure but will cure only half the patients.

Adult↗

Second allogeneic marrow transplantation for patients with recurrent leukemia after initial transplant with total-body irradiation-containing regimens.

PURPOSE: The impact of a second marrow transplant on long-term disease-free survival (DFS) was evaluated for 77 consecutive patients aged 2 to 51 years who relapsed subsequent to allogeneic marrow transplantation after high-dose chemotherapy and total-body irradiation (TBI). PATIENTS AND METHODS: Patients received a second transplant for recurrent chronic myelogenous leukemia (CML) (n = 28), acute myelogenous leukemia (AML) (n = 32), and acute lymphoblastic leukemia (ALL) (n = 15) or lymphoma (n = 2) that used the same marrow donor as the initial transplant. High-dose chemotherapy of busulfan (BU) and cyclophosphamide (CY), or CY, carmustine (BCNU), and etoposide (VP-16), was used as a preparative regimen for the second transplant. Graft-versus-host disease (GVHD) prophylaxis consisted of the following: no prophylaxis (n = 8), T-cell depletion (n = 36), methotrexate (MTX) only (n = 21), cyclosporine (CSP) only (n = 1), MTX and CSP (n = 9), or anti-thymocyte globulin (ATG) and prednisone (n = 2). RESULTS: Engraftment occurred in the 74 assessable patients. Severe veno-occlusive disease (VOD) was the most frequent cause of grades 3 and 4 regimen-related toxicity (RRT); it occurred in 20 patients. The probability of death before day 100 from nonleukemic causes was 36%. The probability of relapse after second transplant was 70%, and the DFS rate was 14% (median DFS, 36 months; range, 22 to 87). The DFS rates for ALL, AML, and CML were 8%, 10%, and 25%, respectively. Multivariate analysis showed that the risk of relapse was inversely associated with acute GVHD (relative risk [RR] of relapse = 0.2; P = .0009). No other factor was associated with relapse. DFS was associated with the presence of acute GVHD (RR of treatment failure = 0.5; P = .0085), and a reduction of DFS was associated with severe VOD (RR = 10.6; P = .0001) and those patients older than 10 years (RR = 2.5; P = .0337). CONCLUSION: These data show that some patients may benefit from a second marrow transplant for recurrent leukemia after an initial marrow transplant. Younger patients and patients with CML especially should be considered as potential candidates for a second transplant.

Adolescent↗

Hepatocyte growth factor gene therapy for pancreatic islets in diabetes: reducing the minimal islet transplant mass required in a glucocorticoid-free rat model of allogeneic portal vein islet transplantation.

Islet transplantation for diabetes is limited by the availability of human islet donors. Hepatocyte growth factor (HGF) is a potent beta-cell mitogen and survival factor and improves islet transplant outcomes in a murine model. However, the murine model employs renal subcapsular transplant and immunodeficient mice, features not representative of human islet transplantation protocols. Therefore, we have developed a more rigorous, marginal-mass rat islet transplant model that more closely resembles human islet transplantation protocols: islet donors are allogeneic Lewis islets; recipients are normal Sprague Dawley rats; islets are delivered intraportally; and immunosuppression is accomplished using the same immunosuppressants employed by the Edmonton group. We demonstrate that 1) surprisingly, the Edmonton immunosuppression regimen induces marked insulin resistance and beta-cell toxicity in rats, 2) adenovirus does not adversely affect islet transplant outcomes, 3) the Edmonton immunosuppressants may delay or block rejection of adenovirally transduced islets, and more importantly, 4) pretransplant islet adenoviral gene therapy with HGF markedly improves islet transplant outcomes, 5) this enhanced function persists for months, and 6) HGF enhances islet function and survival even in the setting of immunosuppressant-induced insulin resistance and beta-cell toxicity. This approach may enhance islet transplantation outcomes in humans.

Adenoviridae↗

Behavior of transplanted bone marrow-derived GFP mesenchymal cells in osteochondral defect as a simulation of autologous transplantation.

To elucidate the behavior of autologously transplanted mesenchymal cells in osteochondral defects, we followed transplanted cells using green fluorescent protein (GFP) transgenic rats, in which all cells express GFP signals in their cytoplasm and nuclei as transplantation donors. Bone marrow-derived mesenchymal cells, which contain mesenchymal stem cells (MSCs), were obtained from transgenic rats. Then, dense mesenchymal cell masses created by hanging-drop culture were transplanted and fixed with fibrin glue into osteochondral defects of wild-type rats. At 24 weeks after surgery, the defects were repaired with hyaline-like cartilage and subchondral bone. GFP positive cells, indicating transplanted mesenchymal-derived cells, were observed in the regenerated tissues for 24 weeks although GFP positive cells decreased in number with time. Because GFP causes no immunological rejection and requires no chemicals for visualization, transplantation between transgenic and wild-type rats can be regarded as a simulation of autologous transplantation, and the survivability of transplanted cells are able to be followed easily and reliably. Thus, the behavior of transplanted mesenchymal cells was able to be elucidated in vivo by this strategy, and the results could be essential in future tissue engineering for the regeneration of osteochondral defects with original hyaline cartilage and subchondral bone.

Animals↗

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↗

Ten years of experience with liver transplantation for familial amyloid polyneuropathy in Japan: outcomes of living donor liver transplantations.

OBJECTIVE: We summarize 10 years of experience with liver transplantation for FAP patients in Japan and review the current opinions regarding this treatment for FAP. METHODS AND PATIENTS: All basic report data on patients at the time of transplantation were registered with the Japanese Liver Transplantation Society (JLTS). Based on the JLST report data, more detailed information on FAP patients was requested from each center. RESULTS: Living donor liver transplantation (LDLT) for FAP patients was first performed in Japan in 1993. LDLT has since been performed in 41 FAP patients, including nine cases of temporary auxiliary partial orthotopic liver transplantation (APOLT). Orthotopic liver transplantation (OLT) from cadaveric donors for FAP patients began in 1999, but only one FAP patient has subsequently undergone this procedure. Of these total of 43 FAP patients, 36 are currently alive: the one-year survival rate of patients after transplantation was 93%, and the five-year survival rate of these cases was 77%. Preoperative clinical severity and the nutritional status of patients are correlated with their outcome after liver transplantation. Domino (sequential) liver transplantation has been carried out in 20 domino recipients with end-stage liver diseases. Of the 20 domino recipients, 12 are currently alive. CONCLUSION: For FAP patients, these outcomes after the operation were very similar to those of OLT from cadaveric donors reported in other countries. Therefore, we concluded that for the treatment of FAP, LDLT from a living donor is equally effective as OLT from a cadaveric donor.

Adult↗

Effects of intraportal islet transplantation on the transplanted tissue and the recipient pancreas. I. Functional studies.

It is well known that, in diabetes, there is an abnormality of both pancreatic beta and alpha cell secretion. Since islet transplantation can markedly improve the diabetic state in streptozotocin-treated rats, we investigated the effects of intraportal transplantation on the beta and alpha cell secretion of the transplanted tissue. In addition we examined the effects of transplantation on the hormone content of both the transplanted tissue and the endogenous pancreas. Animals were examined 6 and 20 wk after transplantation. Isolated perfusions of the perfusions of the islet-containing livers showed that both glucagon and insulin secretion could be promptly stimulated by arginine. The hormone content of the livers at death revealed that, while the insulin content of transplanted tissue was well maintained, there was a marked reduction in glucagon content. An increase in pancreatic glucagon content was found in rats with untreated diabetes of five months' duration; this was partially or fully prevented by islet transplantation. There was also a moderate increase in insulin content of the pancreases of animals that received islet transplants.

Animals↗

Pancreatic transplantation. Impact on the quality of life of diabetic renal transplant recipients.

OBJECTIVE: To determine the impact of pancreas transplantation on the quality of life of renal transplant recipients with diabetes. RESEARCH DESIGN AND METHODS: In this quasi-experimental comparative study of 41 successful pancreas transplant (SP) recipients, 13 failed pancreas transplant (FP) recipients, and 28 kidney alone (KA) transplant recipients, we collected data from individuals who had their pancreas/kidney or kidney alone transplants > or = 6 months before at a university tertiary care center. This study was an extension of a 1992 study of SP and FP recipients. The subject group was enlarged with additional pancreas/kidney recipients and a control group of KA recipients. Five dimensions of life quality were measured. RESULTS: Groups did not differ significantly regarding age, gender, marital status, comorbidity, type of prior dialysis, current kidney function, length of time since transplant, physical activity, symptom burden, emotional state, and feelings of well-being. A significant time by group interaction occurred for quality of life (P = 0.0023) and health (P = 0.0001). Patients in the SP and KA groups perceived their past life and health quality to be significantly lower and their present and future life and health quality to be significantly better than did the FP group. The groups' major concerns differed significantly. The FP group's concern related to diabetes, the SP group's to immunosuppression, and the KA group's to graft rejection. CONCLUSION: Patients with failed pancreas but successful kidney transplants see less improvement in their quality of life than do patients who meet their transplant goals, irrespective of whether they receive a pancreas.

Cohort Studies↗

Orthotopic liver transplantation for life-threatening veno-occlusive disease of the liver after allogeneic bone marrow transplant.

Veno-occlusive disease (VOD) of the liver is a serious and often lethal sequela to bone marrow transplantation. Although a history of prior hepatitis moderately increases the risk of VOD, reliable screening methods for identifying high risk patients are not available. New approaches to managing patients who develop serious VOD are needed. One approach may be the use of orthotopic liver transplantation in selected patients who are likely to die of the disease. In this report we describe a patient who underwent liver transplantation for life-threatening VOD following allogeneic transplantation for CML. Although this patient died early from interstitial pneumonitis, the orthotopic liver functioned well up to her death. Other reports describing successful liver transplants in patients with advanced VOD or graft-versus-host disease of the liver are discussed and the possible indications for liver transplantation for VOD after marrow transplantation are considered. Taken together, these reports suggest that orthotopic liver transplantation may be a feasible and potentially effective approach to managing select patients with life-threatening liver dysfunction after marrow transplantation.

Adult↗

Left lung allotransplantation in pig feasibility and transplanted lung function. Experimental Lung Transplant Group of Ospedale Maggiore of Milan.

Changing attitudes to animals in research and practical considerations prompted the authors to evaluate whether the pig might be a suitable substitute for dog and baboons for single left lung transplants. Twenty-nine paired pigs were used. The first transplants on 13 pairs (group 1) were done to adapt the lung transplant technique to pigs; later transplants on 16 pig pairs (group 2) were done to evaluate operative survival, and function and histological modifications of the transplanted lung in the absence of immunosuppressive treatment. Surgical and anesthetic techniques for both donor and recipient are described in detail. The survival rate in group 2 was 68%. Hemodynamic and blood gas changes were assessed during operation. PaO2 did not drop significantly after occluding the right pulmonary artery by an inflatable cuff placed around it; this suggests that the function of the transplanted lung was preserved. The pigs were put down on the third postoperative day. Vascular and bronchial anastomoses were patent and intact, but the transplanted lung was macroscopically and microscopically altered. Lung transplants can be performed in pigs and the transplanted lung seems to be capable of functioning immediately after the operation. Alteration in the lung after 3 days is probably due to rejection.

Animals↗

Transplantable primate tumors induced by Rous sarcoma virus. I. Induction of tumors transplantable into young marmosets.

The tumors induced in white-lipped marmosets (Saguinus fuscicollis, S. nigricollis) by Rous sarcoma virus (RSV) of chicken origin (RSV-SR) were not transplantable to allogeneic hosts. In contrast, RSV rescued from these tumors (RSV-M) induced sarcomas that were transplantable to young but not to adult marmosets. The tumors induced by RSV-M and the transplants rapidly enlarged, metastasized to various organs, and killed the recipients 29-59 days post inoculation. Cell lines were readily established from all transplantable sarcomas. No virus expression was detected in transplantable tumor cell lines by electron microscopy or by biochemical and biological assays. However, RSV of the same subgroup as RSV-SR was rescued from both short-term and long-term tumor cell cultures by cocultivation with chicken embryo fibroblasts (CEF). The rescued viruses transformed marmoset cells 100-fold more efficiently than CEF cells, although CEF cells remained permissive for virus replication. Cytogenetic studies revealed extensive chromosome abnormalities in tumor transplants but not in RSV-M-induced sarcomas. All cell lines were hyperploid and contained structurally abnormal, large metacentric and telocentric chromosomes. Immunologic studies failed to detect group-specific (gs) antigen of the avian sarcoma-leukemia complex in either RSV-M-induced, transformed cells or tumor transplants. By complement-dependent cytotoxicity assays, with the use of marmoset anti-gs serum, RSV-associated antigen could be detected on the surfaces of tumor cells. No differences in the expression of this antigen existed between transplantable and nontransplantable marmoset sarcomas. All transplantable cell lines contained abnormal amounts of lipids and glycogen in comparison to RSV-SR-induced tumors and normal marmoset cell lines. The glycogen was associated with unique cytoplasmic membrane complexes and was surrounded by either single- or double-membraned vesicles.

Animals↗

Renal response to volume expansion in heart-transplant and kidney-transplant recipients.

The renal excretion of an intravenous sodium load by ten heart-transplant recipients with (five patients) or without (five patients) moderate renal failure was compared with the results obtained in two matched control groups of ten kidney-transplant recipients with similar renal function. All patients were treated with prednisone and cyclosporine except, for the latter treatment, the kidney-transplant recipients without renal failure. A supplementary control group of five healthy subjects who did not receive any treatment was also included in the study. Fractional sodium and osmolal clearances were greater in heart-transplant than in kidney-transplant recipients for both the patients with and the patients without renal failure. These two parameters were also greater in heart-transplant recipients without renal failure than in healthy subjects. Free water clearance was smaller in the heart-transplant recipients than in the corresponding control patients. Fractional potassium clearance was not different from group to group. These results demonstrate that heart-transplant recipients excrete a greater fraction of the filtered sodium load than their controls. This increased fractional excretion of sodium cannot be attributed to the cyclosporine treatment or the moderate chronic renal failure which both have been taken into account in the comparisons. The unchanged blood pressure during the saline load and the high or normal plasma renin activity levels in the heart-transplant recipients make it also unlikely that the exaggerated natriuresis was the consequence of the higher blood pressure observed in these patients. The chronic cardiac denervation which is the consequence of surgery in these patients could play a role in the mechanism of the saline diuresis.

Adult↗