摘要:

Cyclophosphamide was tested for its interaction with passive enhancement in suppressing the rejection of kidney allografts in the (DA x Lewis) F, to Lewis rat strain. Dose response studies with cyclophosphamide showed that 10 mg/kg/day for 14 days was necessary for complete suppression of rejection and indefinite graft survival. Doses of 5 and 3.5 mg/kg/day had only a marginal effect on graft function and survival, although the lymphocytotoxin response to the graft was completely or very substantially suppressed by these smaller doses. The use of passive enhancement with cyclophosphamide at the 5− and 3.5-mg/kg/day doses resulted in a favourable interaction with improved graft function and survival. Interestingly, passive enhancement in combination with 5 mg/kg/day of cyclophosphamide resulted in indefinite graft survival only if cyclophosphamide was given for 28 days. If cyclophosphamide was given for 14 days, rejection was suppressed only during the period of cyclophosphamide treatment.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The in vitro response of human lymphocytes to phytohaemagglutinin was inhibited in a dose-related fashion by methyl-prednisolone added to the cell culture. The inhibition by steroid was 100-fold less than expected from published values of human lymphocyte receptor affinity. The dose response curve for inhibition was complex, frequently featuring a plateau region suggestive of a heterogeneous system, possibly caused by the presence of more than one subpopulation of cells. When lymphocytes were separated by unit velocity sedimentation, slow sedimenting lymphocytes were found to be highly steroid sensitive whereas rapidly sedimenting lymphocytes were steroid resistant. However, the addition of cultured macrophages rendered the steroid-sensitive fractions relatively steroid resistant. Similarly, unseparated peripheral blood lymphocytes at low concentrations were found to be highly steroid sensitive despite the addition of 2-mercaptoethanol. This sensitivity was lost by the addition of culture macrophages. Thus, macrophages play a vital role in the relative steroid resistance of human lymphocytes. No evidence was found that macrophages actually reduced steroid concentration in culture, and it is suggested that a cellular interaction is required to increase resistance to steroids.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Matching for HLA haplotypes as well as for HLA-A and B antigens improved graft survival in 112 living related first transplants. In cadaveric first transplants, matching for HLA-A and B antigens had a beneficial effect on the fate of 373 grafts, while matching for HLA-C antigens had no predictive value. One hundred seventeen cadaveric transplants and their recipients were prospectively typed for the HLA-DR antigens. Compatibility for HLA-DR was found to be prognostically beneficial irrespective of matching for HLA-A and B antigens, and with no difference between transfused and nontransfused patients. Matching both for HLA-A, B and D/DR was thus found to influence the outcome of renal transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Osteopetrotic microphthalmic mice (mi/mi) were treated by injections of suspensions of myeloid tissue, newborns i.p., and weanlings i.v. Donated syngeneic material effected permanent cure of oteopetrosis provided that the dose was large enough (108cells of bone marrow). H-2-compatible allogeneic bone marrow was initially as effective, but relapse ensued in immunocompetent mice. H-2-incompatible marrow was ineffective except in one set of newborn tolerant mice. Total body X-radiation in sublethal doses to recipients allowed permanent cure with H-2-compatible, and, in one circumstance, with H-2-incompatible marrow in smaller doses. The best results were obtained after lethal irradiation and the smaller dose of marrow. Results were checked by chromosome assay demonstrating that cure or relapse was correlated with permanent take or rejection, respectively, of a transplant in a recipient's bone marrow. Retention of donor lymphocytes alone was not associated with effective bony resorption; the candidate cell line for effectiveness remains the haematopoietic stem cell-monocyte-tissue phagocyte.Mammalian osteopetrosis is a disease characterised by deficient resorption of bone because of a failure of osteoclastic activity. This subject was recently reviewed by Marks and Walker (7). The injection of myeloid tissue from phenotypically normal donors resolves the osteopetrosis in microphthalmic mice which suffer from the disease (2, 3). Walker (2) reported that murine osteopetrosis based on a C57BL/6 background required lethal X-irradiation before cellular restoration, but in several Harwell stocks of newborn and weanling (17− to 22-day -old) microphthalmic mice, Loutit and Sansom (3) found that irradiation was unnecessary. Syngeneic and hemisyngeneic myeloid material was also effective in adult mice (4). This report confirms that maintained resolution depends on histo-compatibility of the donated material (5) and on the persistence of a detectable transplant in the bone marrow (6).

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Total rosette-forming cells (TRFCs) and percentage of rosette-forming cell (RFC) levels were measured in patients undergoing dialysis and in recipients following renal transplantation. The percentage of RFCs of the dialysis patients was not different from the percentage of RFCs of normal subjects, whereas the TRFCs were significantly lower in the dialysis patients. After transplantation, the percentage of RFCs and TRFCs was significantly lower in recipients treated with anti-thymocyte globulin (ATG) than in those of the control group; however, there was no difference in allograft survival between the ATG-treated and control recipients when using ATG in the dose by rosette protocol.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Antithymocyte globulin (ATG, ATGAM; The Upjohn Company) was tested for efficacy and safety in controlled studies in 358 renal allograft recipients. A total of 183 patients were treated according to protocols prescribing 14 daily doses of ATG in addition to standard immunosuppressive therapy with azathioprine and prednisone, while 175 controls received no ATG. Four ATG lots were tested; results with each lot were analyzed separately, and the data were also pooled to obtain an overall impression.ATG delayed the onset of the first rejection episode during the prescribed treatment period (2 weeks). Concurrently, less i.v. steroid was required, but the steroid dosage requirement then rebounded in the 2 weeks after the end of the prescribed treatment period. ATG did not significantly improve the proportion of patients alive with functioning grafts 6 months after transplant, except with one of the four lots.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Methods are described for preparing large amounts of horse anti-human thymocyte globulin (ATG, ATGAM; The Upjohn Company) for clinical use. These methods have been used since 1968 to provide material for clinical trials. Characteristics of 40 lots of ATG are summarized.Since 1968 The Upjohn Company has been supplying ATG for clinical trials. These trials have included both pilot studies and prospective controlled studies of this immunosuppressive agent in patients undergoing transplantation of kidneys (1–6), heart (7), bone marrow (8–10), lung (F. Veith, unpublished studies), and liver (R. N. Taub, unpublished studies), and also in skin transplantation in extensively burned patients (11). Our companion paper (6) describes results in our first reported multicenter studies of ATG in renal allograft recipients. This paper serves in part as a materials and methods section of that paper.Russell's review (12) summarizes data on preparation of antilymphocyte sera as well as published results of clinical trials through 1975. Most of our own views on preparing an ideal antiserum (13) have persisted. We believe that single-cell suspensions from human thymus are the ideal antigen source. Because of production logistics, we have opted for the horse as the antibody source. It takes a few more cells to immunize a horse than to immunize a rabbit, but a horse can supply up to 90 liters of crude plasma. Our early attempts to use lymphoblasts as antigen and goats as antibody source proved disappointing and were abandoned.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

In human kidney transplantation, a high blood flow established through the graft immediately upon clamp release is usually associated with immediate satisfactory renal function. One hundred consecutive kidney transplant patients were thus provided with a large volume of fluid during surgery. To avoid pulmonary edema, fluid load was given under mean pulmonary arterial pressure (PAP) monitoring, and controlled ventilation was maintained during the early postoperative period. Whether initial PAP value was within normal range or elevated, all patients required an equivalent fluid load to reach the best hemodynamic condition upon clamp removal. The mean intra-operative fluid load consisted of 2406 ± 968 ml of water with 22.8 ± 9.4 g of sodium chloride, 5.9 ± 1.8 units of albumin, and 2.6 ± 1.8 units of packed red blood cells. Immediately before clamp release patients were given furosemide and mannitol. During the postoperative period, i.v. infusions consisted of water and sodium chloride (6 g/liter) to match urine output, provided that diuresis was equal to or above 400 ml/hr. If diuresis remained or decreased below this level, diuresis replacement was associated with PAP-controlled infusion of saline, albumin, and red blood cells if needed. Furosemide was eventually given if diuresis did not increase above 400 ml/hr with fluid loading. With this protocol a good early diuresis was established in 95% of the cases. Ten patients required dialysis before the 5th postoperative day, one of them because of fluid overload and anuria. Concurrently, a decreased mortality rate and an increased graft survival rate were observed.In human kidney transplantation, immediate efficient diuresis avoids the many problems associated with postoperative dialysis and the difficulties encountered for rejection diagnosis in patients with a nonfunctioning kidney. Among the many factors difficult to control which may induce postoperative oliguria are those related to the donor's hemodynamic condition, as well as harvesting and preservation management. Conversely, the importance of good hemodynamic conditions in the recipient to get immediate maximum renal function has been suggested in work from several authors(1–6).Obtaining the patient's best cardiac performance through fluid loading upon graft revascularization and during the subsequent hours was the goal of this study.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The survival rate among 458 cadaver kidney grafts with “full-house” four HLA-A,B antigens detected in the donor, three being identical to those of the recipient and only one mismatched, was studied specifically in relation to antigen incompatibility. At theAlocus, the A3 incompatibility was associated with a lower transplant survival (44% at 2 years) than all of the others, and particularly more than the All (80% at 2 years) (P< 0.003 but without significance after correction multiplying by the number of tested alleles). At theBlocus, there was no significant difference in survival rate among the alleles.These results are only preliminary and need confirmation based on longer series permitting possible cross-reactions which exit between donor and recipient antigens to be taken into consideration.It is well known that in a given immunogenetic system the antigenic strength of each allele can be variable. A good example of this being antibodies formed in pregnancy because of rhesus incompatibility whose frequency appears to be quite dependent on the relative potency of the antigens concerned: D, for instance, being estimated to be 25 times as potent as the c rhesus allele(1).Most of the studies analysing the survival rate of kidney grafts in relation to the HLA matching (number of HLA-A,B identities) in donor and recipient were based upon the hypothesis that all of the alleles were of the same antigenic weight.However theBlocus appeared to be of greater importance for graft survival in several studies(2–5)but was not confirmed by others (6).The following preliminary results of antigen incompatibility were based on an analysis of kidney grafts performed with the framework of France Transplant.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

End stage renal failure in a patient with congenital hemolytic anemia attributable to glucose phosphate isomerase deficiency was treated successfully with maintenance hemodialysis and renal transplantation. Increased transfusion requirements, intolerance to immunosuppressive agents, and frequent infections were not encountered. Induction of the deficient erythrocyte enzyme by renal transplantation was not expected or realized.Anemia is a common accompaniment of end stage renal disease (ESRD) and remains a problem in most patients even after initiation of chronic hemodialysis. The hemodialysis procedure itself may exacerbate this problem through loss of blood in the dialysis membrane, oxidative injury to the erythrocytes from drugs, impurities in the water supply, and the production of endogenous plasma factors which inhibit the red blood cell hexose monophosphate shunt (1–4). Successful renal transplantation does substantially restore normal erythropoiesis, although azathioprine can produce marked bone marrow suppression. We encountered a patient with severe congenital hemolytic anemia and ESRD and anticipated problems with severe anemia, access thrombosis, or congestive heart failure during hemodialysis and transplantation. Review of the literature showed that the experience with dialysis and transplantation in patients with nonspherocytic congenital hemolytic anemia has been limited to sickle cell disease. A recent report of hemodialysis (5) in these patients has noted poor rehabilitation because of limited cardiac reserve, and successful renal transplantation has been associated with an exacerbation of painful crises (6). We wish to report successful hemodialysis and transplantation in a patient with severe chronic hemolytic anemia attributable to glucose phosphate isomerase (GPI) deficiency. Despite the severe hemolytic process, the blood loss associated with hemodialysis and the immunosuppression associated with transplantation were tolerated without difficulty.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID