摘要:

The correction of lysosomal enzyme deficiency was investigated for various organs of β-glucuronidase-deficient C3H/Rij mice after allogeneic bone marrow transplantation from an enzymatically normal donor strain (C57BL/Rij). In the hemopoietic organs, the enzyme level increased to levels found in donor mice. In lung, kidney, liver, and peripheral nervous tissue, a significant increase in enzyme activity was seen to levels intermediate between those of donor and recipient. Increased enzyme activity was maintained throughout the observation period of 150 days. In skeletal muscle tissue, enzyme levels tended to be higher in recipient mice, but this increase was not significant for all data points. Bone marrow transplantation failed to significantly affect enzyme activity in central nervous system tissue. These data suggest that beneficial effects expected from bone marrow transplantation for lysosomal enzyme deficiencies depend on the type of tissue involved in the disease. In diseases severely affecting the central nervous system, cure may not be expected from bone marrow transplantation alone, whereas in diseases with only minimal central nervous system involvement, alleviation or prevention of clinical symptoms may occur.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Recently, we developed two techniques for the combined transplantation of heart and the left lung into the left hemithorax of rats. One technique, with two vessel anastomoses, comprised the microsurgical repair of aorta, anterior vena cava, and left main bronchus. With the other, single vessel technique, only the aorta and bronchus were anastomosed. In this study, we determined the function and histology of syngeneic and cy-closporine (CsA)-treated allogeneic grafts transplanted with both techniques, and compared the results with those of heterotopic heart-lung grafts transplanted with a. previously described technique for transplantation into the rat's abdomen.The survival rate of rats operated with either of the thoracic transplantation techniques was high (83%). Lungs and hearts of the grafts functioned well for over two months and had normal morphology when the double vessel technique was used. With the single vessel technique, the function of the lungs started to deteriorate from the third postoperative week onward, probably secondary to congestion. The results of thoracic grafts were superior to those of abdominal transplants, where the nonventilated lungs–especially during immunosuppression–wesre frequently infected. We conclude that these new techniques for thoracic transplantation are most suitable for research of combined heart-lung transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The pressure within rat cardiac and renal allografts has been observed to rise during rejection. We wished to see if this pressure rise could be prevented or reversed with immunosuppression. Transplants were performed from Lewis or DA donors to Lewis recipients. The rats received either a heterotopic cardiac transplant or an orthotopic renal transplant and were then treated with different immunosuppressive protocols. Intramyocardial pressure was recorded using a fine-gauge needle connected to an air pressure manometer. In the case of the renal transplants, a pressure transducer was used as well and the two methods compared.Intramyocardial and intrarenal pressures rose dramatically in unimmunosuppressed recipients of DA allografts. No such rise was seen in isografted organs, although the pressures recorded remained significantly higher than those found in untransplanted hearts and kidneys. Cyclosporine 20 mg/kg/day was effective in suppressing rejection in both models, and inhibited any rise in intraorgan pressure. Cyclosporine 10 mg/kg/day was less effective, and with 2 mg/kg/day allograft function was considerably impaired, one-third of the cardiac grafts being rejected by 16 days. In both models intraorgan pressures became raised. The addition of methyl-prednisolone 16 mg/kg i.p. on days 7 and 8 to this low dose regimen of cyclosporine 2 mg/kg/day rapidly reversed the rise in pressure and restored graft function to normal.Intraorgan pressure levels therefore accurately reflected the state of function of transplanted hearts and kidneys. When a manometer and a transducer were compared as a means of measuring the pressure in the renal transplants, the manometer method was found to be superior.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Three agents that significantly prolong cardiac allograft survival were tested in Lewis rats that were recipients of hearts from Lewis x Brown-Norway F1hybrid donors. In the presence of azathioprine, the effects of daily administration of either the thromboxane antagonist (L 640,035), the platelet-activating factor (PAF) antagonist (BN 52021) or prednisolone were evaluated on the infiltration of cardiac allografts by syngeneic lymphocytes and platelets labeled with111indium. As anticipated, platelet deposition was reduced by the thromboxane antagonist and unaffected by the PAF antagonist; the latter is likely due to the known absence of PAF receptors in rat platelets. In addition prednisolone had no effect. The increased accumulation of lymphocytes on days 4–5 was also unaffected by all three drugs. These experiments indicate that, in this model, graft survival is not necessarily related to lymphocyte and platelet infiltration of the graft. The data also provide evidence for the efficacy of the thromboxane receptor antagonist L 640,035 in preventing platelet deposition in vivo.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Preservation of cadaveric pancreas allografts has been a difficult problem in clinical pancreas transplantation; most institutions use Collins solution and limit preservation time to less than 6 hr. Longer preservation times have been used at the University of Minnesota. Between August 1983, and December 1985, 47 human cadaveric pancreas grafts were transplanted into Type I diabetic recipients after cold storage at 4°C in a modified, hyperosmolar silica-gel filtered plasma (SGFP),*a solution previously found to allow dog pancreas grafts to be successfully preserved for up to 48 hr. Ten grafts were preserved for 2–5 hr (group 1); 20 for 6–11 hr (group 2; 17 for 12–26 hr (group 3). Graft function and late outcome were compared between these groups and another group of 7 cadaveric grafts (group 4), which were transplanted immediately and without any preservation. Analysis of exocrine pancreatic function early after transplantation showed a maximum mean serum amylase (IU/L) of 557, 440, 429, and 307 in groups 1, 2, 3, and 4, respectively. Primary preservation failure rates of 0, 5%, 5.8%, and 0%, and endocrine graft function rates at 1 month of 80%, 80%, 78%, and 88% were obtained for groups 1, 2, 3, and 4, respectively (P=NS). Only patients who were insulin-independent were counted as having functioning grafts. Detailed functional studies at 1 month showed that mean plasma glucose levels during 24-hr metabolic profiles were in the normal range in 71%, 68%, 72%, and 50%, while oral glucose tolerance test results were within the normal range in 38%, 81%, 76%, and 68% of groups 1, 2, 3, and 4, respectively (P=NS). At 1 year, patient survival rates were 57%, 88%, 75%, and 100% (P=NS), and the graft functional survival rates were 0, 25%, 33%, and 29% (P=NS) in the respective groups. Five patients in group 2, and 8 in group 3 have currently functioning grafts at 4 to 37 months after transplantation. We conclude that cadaver pancreas grafts can be safely preserved for 12–24 hr in modified SGFP solution, thus making the sharing of these organs between different centers practical and the transplant operation less of an emergency procedure.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The effect of HLA matching on one-year first cadaver donor graft survival rates between best and worst matches was 6% (P< 0.001) for A, B; 7% (P< 0.001) for DR; 9% (P< 0.001) for A, DR; 15% (P< 0.001) for B, DR; and 17% (P< 0.001) for A, B, DE. For second cadaver donor grafts, the differences were comparable. Analysis of the cyclosporine-treated patients separately yielded similar results: 5% (NS) for A, B; 7% (P< 0.001) for DR; 13% (P< 0.001) for A, DR; 16% (P< 0.001) for B, DR; and 18% (P< 0.001) for A, B, DR. The most significant effect of matching was achieved by zero mismatching B and DR antigens. The one-year graft survival for patients with zero A, B, DR mismatch was 88% with cyclosporine. Without cyclosporine, zero mismatched A, B, DR grafts survive at 84%; this difference is not statistically significant. Zero mismatching for class I and II antigens (that is, A, DR or B, DR with cyclosporine) gives one-year graft survivals of 84% and 87%, respectively. The zero mismatching HLA class I and II antigen effect is lost ‘when even one antigen is mismatched. Transfusions improved the one-year graft survival 10% in cyclosporine-treated patients, but not in those “who were not treated with cyclosporine. Seventy-one patients transfused with more than 4 units of blood, zero B, DR mismatched, and treated with cyclosporine had a 91% one-year graft survival. Recipient pool sizes for obtaining zero A, B, DR or B, DR mismatched donors are calculated. Zero A, B, DR mismatched patients can be transplanted at a 19% frequency with a 10,000 recipient pool. The success rate for zero mismatching of class I and class II antigens indicates that kidney sharing and large recipient pool sizes are a reasonable policy.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The long-term effects of cyclosporine on renal function were evaluated in eleven liver transplant recipients over a 6–26-month follow-up period. Renal hemodynamic function (glomerular filtration rate [GFR], effective renal plasma flow [ERPF])*fell 60% postoperatively, subsequently improved, and stabilized at 45–60% of normal despite continued drug administration. Tubular sodium transport studies during water diuresis suggested that the proximal tubule is a major site of cyclosporine nephrotoxicity. In contrast to the acute effects of cyclosporine on renal function, the fraction of glomerular filtrate reabsorbed in the proximal tubule was less in the patient group 'while the fractional excretion of sodium, potassium, and phosphate was increased. When the fraction of filtered sodium reabsorbed in the diluting segment was examined as a function of sodium delivery, functional impairment occurred in the diluting segment as well. Eight renal biopsies performed in six patients 4–29 months posttransplantation showed only mild to moderate changes, predominantly vascular, which correlated poorly with corresponding renal function. These data showed that long-term cyclosporine administration produced early and persistent depression of both hemodynamic and tubular function. A functional rather than structural mechanism appears to be more significant during this period of observation.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

In this prospective study the frequency of deep venous thrombosis during the first three weeks after renal transplantation was determined using a combination of strain gauge plethysmography and thermography for objective diagnosis. Ninety-seven consecutive patients were studied, 30 patients having juvenile diabetes mellitus. As immunosuppression cyclosporine and low-dose steroids were used. The series was compared with a similar group of 83 patients, 33 having juvenile diabetes mellitus treated with azathioprine and high-dose steroids as immunosuppression, in which the diagnosis of deep venous thrombosis was made with an identical technique. The overall frequency of thrombosis was 9.3% in the cyclosporine-treated group, which is a significant reduction in comparison with the azathioprine group (24.1%). It is concluded that the combination of cyclosporine and low-dose steroids does not increase the frequency of deep venous thrombosis in comparison with azathioprine and high-dose steroids in renal transplanted patients.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Sixty-nine patients with acute nonlymphocytic leukemia in first remission received total-body irradiation and chemotherapy followed by allogeneic bone marrow transplantation from Mstocompatible sibling donors, Patient age was between 1 and 41 years: 20 patients 1– 19 years (group 1); 27 patients 20–29 years (group 2); and 22 patients 30–41 years (group 3). Two pretrans-plant radiochemotherapy regimens were employed: The first 45 patients received total-body irradiation (in a single dose) with cytosine arabinoside and cyclophosphamide; the next 24 patients received total-body irradiation (in a fractionated schedule) with cyclophosphamide alone. For all patients, actuarial disease-free survival is 51% (37 of 69 patients are alive and in continuous remission between 5 months and 9.3 years, median 3.7 years). For group 1 actuarial survival is 56%, group 2 48%, and group 3 48%. When analyzed for pretransplant factors that might predict disease-free survival after bone marrow transplantation neither patient age, white cell count at the time of diagnosis, FAB leukemic subtype, length of time before achieving remission, nor length of time between remission and bone marrow transplantation were established as prognostic.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

To define an effective and convenient means for providing extended prophylaxis of herpes simplex virus (HSV) infection to chronically immunocompromised patients, we studied a two-part regimen of intravenous, followed by oral, acyclovir after marrow transplantation. Seropositive patients were first given intravenous acyclovir until day 30 after transplant. Intravenous acyclovir (250 mgm/m2) given twice daily to 34 patients during this period was 90% viroiogicaily effective among those completing the prophylactic course. A randomized, double-blind comparison of twice-daily oral acyclovir (800 mg) and placebo was then conducted from day 31 to day 75 after transplant in 51 patients. Oral acyclovir significantly delayed the median time to first excretion of HSV when compared with placebo (> 100 vs. 70 days after transplant,P=0.0006) and was completely effective in all patients for the duration of drug administration. Patients receiving extended prophylaxis appeared to have less-severe HSV infection when later recurrences did occur. Sequential intravenous and oral acyclovir given twice daily is an effective and convenient regimen for extended prophylaxis of HSV infection following marrow transplantation, and should be useful in other transplant patients or other chronically immunosuppressed patients as well.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID