摘要:

Between 40% and 80% of patients treated with the monoclonal antibody OKT3 develop blocking antibody against its idiotypic region. Thus a major concern with the use of OKT3 as part of a baseline immunosuppressive regimen is that formation of blocking antibodies might preclude its subsequent use. Between 7/86 and 2/87, 32 patients received prophylactic OKT3 in addition to low-dose prednisone, azathioprine, and cyclosporine. Prophylactic OKT3 did not prevent rejection, as 21 of 32 patients studied developed rejection. Retreatment of 13 patients with OKT3 successfully reversed 12 rejections and lowered the number of T3-positive cells in spite of a low level of blocking antibody in two patients in this group. Of the patients analyzed, 38% developed blocking antibody on initial exposure to OKT3, but OKT3 reuse was denied only 4 patients due to the presence of these antibodies. Three of these had rejections reversed with steroids alone; the other patient lost the allograft. A high frequency of infectious complications occurred in the retreatment group, with viral infections predominating. Only one patient in the retreated group developed antibodies after the second use. Appearance of blocking antibodies after use of OKT3 as part of a baseline prophylactic immunosuppressive regimen did not significantly compromise access to OKT3 for treatment of subsequent rejection episodes, but multiple exposures to OKT3 did increase the frequency of infectious complications.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Donor pretreatment with antilymphocyte serum (ALS) effectively prevents graft-versus-host disease (GVHD) in a unidirectional (parent—to—F1hybrid) rat small bowel transplantation model. ALS must be administered prior to or at the time of transplantation, and the intraperitoneal route is more effective than subcutaneous administration. Donor pretreatment with ALS uniformly prevents GVHD without impairing subsequent allograft function as measured by absorption of dietary energy and nitrogen, weight gain, and bowel morphology. These rodent studies suggest that ALS treatment of donors as well as recipients in small bowel transplantation may be a highly effective, simple, and easily applicable method to prevent or ameliorate GVHD in human small bowel transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Thirty-nine canine segmental pancreatic autografts were preserved at 4°C for 48 hr prior to transplantation using five different preservation solutions: modified silica gel-filtered plasma (SGFP) (n=10); modified PPF (n=9); modified Collins' solution (n=8); partially modified plasma protein fraction (PPF) (n=6), and unmodified PPF (n=6). These modifications were with respect to osmolality, pH, protein, and potassium content. Graft function was assessed by daily fasting blood sugar and serum amylase, and by intravenous glucose tolerance test (IVGTT) and insulin output at 14–21 days. Viable preservation was deemed successful if normoglycemia was maintained for at least 5 days. Modified SGFP was successful in 80% of the animals, modified PPF in 100%, partially modified PPF in 60%, unmodified PPF in 50% and modified Collins' solution in 37%. The difference between modified PPF and the latter three solutions was significant (P<0.05). The causes of graft failure were primary nonfunction, graft pancreatitis, and focal necrosis in some of the grafts preserved by Collins' solution. Graft function in the surviving animals, as determined by the IVGTT and K value, was similar regardless of the method of preservation and was comparable to that previously obtained with fresh and unpreserved segmental pancreatic autografts. It is concluded that modified PPF solution is as effective as modified SGFP in the preservation of pancreatic grafts for 48 hr. The essential elements in this modification appear to be high pH and high oncotic pressure in a hyperosmolar and moderately hyperkalemic solution. Since PPF is readily available and is much cheaper than SGFP, it may be the solution of choice for clinical preservation of pancreas allografts for periods of 24–48 hr.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Uncontrolled pulmonary hypertension during auto-perfusion of the heart and lungs for preservation has been described, and it may result in extensive pulmonary injury and occasional early failure of the preparation. In order to investigate the neurohumoral mediators of the vasoconstrictor response in the pulmonary circulation of the autoperfused working heart-lung preparation, heart-lung organ blocks were harvested from calves, placed in a normothermic autoperfusion circuit, and studied. Effects of beta-adrenergic stimulation with isoproterenol, nonspecific vasodilatation with nitroglycerin, alpha-adrenergic blockade with phentolamine, phospholipase A2inhibition with methylprednisolone, cyclooxygenase inhibition with indomethacin, and white blood cell depletion were independently evaluated. Untreated animals,pre-and postexplant, served as controls. Multipoint pulmonary vascular pressure-cardiac output plots were constructed for each animal. An index of pulmonary vascular resistance was obtained from the linear relation: mean pulmonary artery pressure minus pulmonary capillary wedge pressure divided by cardiac output. An intense flow-dependent pulmonary vasoconstrictor response was confirmed to exist in the denervated bovine auto-perfused working heart-lung preparation. Isoproterenol afforded better protection against this response than the other agents studied. White blood cell depletion reduced postexplant pulmonary vasoconstriction, implying that circulating polymorphonuclear leukocytes mediate the response in the autoperfused working heart-lung preparation. White blood cell depletion and the administration of selected pharmacologic agents provide modalities for regulating the pulmonary vasoconstrictor response, and thus may enhance lung preservation in the autoperfusion model.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

To date, it has not been possible to reliably prevent intestinal allograft rejection in large animals. This study was undertaken to determine if continuous i.v. cyclosporine (CsA) followed by p.o. CsA would prevent rejection in outbred piglets with orthotopic, in-continuity intestinal allografts. Untreated recipients (n=7) died of rejection (2), interstitial pnuemontitis (3), or technical complications (2) at 5.3±1 days. Intestinal recipients treated with i.v. CsA 8 mg/kg/day and i.v. steroids (n=3) died of rejection (mean survival 11.3±3.2 days). CsA 20 mg/kg/day i.v. plus i.v. steroids for 21 days, followed by p.o. CsA 25 mg/kg/day (n=6) prevented rejection; however, most of the recipients developed fatal infections (mean survival 28±8 days). Intravenous CsA 15 mg/kg/day for 7–10 days (n=16), followed by p.o. CsA 30 mg/ kg/day in tapering doses reliably prevented graft rejection, permitting long-term survival (mean survival 121±32 days). Rejection did not occur in 7 animals when CsA was discontinued at 97±11 days. Seven animals surviving more than 100 days maintained normal nutritional indices and gained weight at the same rate as control animals. This study provides a rationale for further experimentation to determine the feasibility of intestinal transplantation in man.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Postischemic renal failure is a severe problem following cadaveric renal transplantation, especially if the kidney has been harvested from a non-heartbeating donor, and thereby subjected to periods of both warm and cold ischemia. It is well established that a substantial component of postischemic injury is produced by oxygen-derived free radicals generated from xanthine oxidase at reperfusion. However, the clinical potential of free radical ablative therapy is dependent upon the proportion of the total injury caused by this reperfusion mechanism, compared with the proportion resulting from ischemic injury per se. Therefore, we quantitatively evaluated these proportions in porcine kidneys subjected to various periods of warm (renal artery occlusion in situ), cold (harvest, cold preservation, and allotransplantation), and combined warm and cold ischemia. Experiments were paired, one kidney treated

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Canine small bowel was harvested and stored by simple hypothermic technique. After 12-and 24-hr storage, respectively, the small bowel graft was allotransplanted into recipients. All animals receiving 12-hr stored grafts (n=9) survived beyond 5 days. In the 24-hr storage group, 67% of the animals (n=9) survived beyond 5 days. Successful storage for such extended periods by simple hypothermia has not been achieved previously. Donor pretreatment with antibiotics as well as extensive intra-luminal irrigation of the harvested small bowel are considered to be important technical features in this successful preservation.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

We have previously demonstrated that pretreatment of ACI recipients with ultraviolet-irradiated donor-specific blood transfusion (UV-DST) leads to permanent cardiac allograft survival without further host immunosuppression (ACI rats are weak responders to Lewis lymphocytes in mixed-lymphocyte reaction). This study examines the effect of UV-DST and the timing of transfusions on ACI cardiac allograft survival in Lewis recipients with and without the addition of peritransplant cyclosporine (CsA) (20 mg/kg i.m.) given on days 0, +1, and +2 in relation to the time of transplantation. The mean survival time (MST) of ACI cardiac allografts in Lewis recipients was significantly increased to 33.6±5.7 days (P<0.001) by CsA treatment alone as compared to 6.5±0.5 days survival in control. When DST was given on day-3 combined with CsA, graft survival was increased to 42.0±9.3 days (P<0.01), as compared to 5.8±1.3 days when DST alone was used. When DST was irradiated with ultraviolet B (UV-DST) and administered on day-3 combined with peritransplant CsA, the MST was increased to 68.83±16.1 days as compared to an MST of 10.0±1.0 days in controls treated with UV-DST alone. When UV-DST was given on day-7 and combined with peritransplant CsA immunosuppression, the results were similar. However, when UV-DST was peritransplant CsA course, 4 of 6 recipients maintained their ACI heart allografts indefinitely (>300 days) in contrast to the effect of UV-DST alone (MST of 13.5 days). Third-party (W/F) UV-irradiated blood transfusions were ineffective in prolonging ACI cardiac allografts in Lewis rats, regardless of whether the transfusions were given alone or in combination with peritransplant immunosuppression with CsA. In conclusion, these results demonstrate that UV-DST combined with a brief peritransplant immunosuppression with CsA induces prolonged heart allograft survival in a histoincompatible, strong responder host, and that such effect is donor specific. The use of UV-DST combined with peritransplant CsA immunosuppression offers a promising approach to achieving organ transplant unresponsiveness, and decreased sensitization to the donor blood elements, which eventually may have important clinical implications.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

An immune—reduction-suppression protocol using spleen cell infusion followed by cyclophosphamide (CP) or azathioprine (AZ) to reduce the immunocompetent cells and maintenance suppression with low-dose cyclosporine (CsA) was highly effective in a rat cardiac transplant model. Following one or two spleen cell infusions, AZ or CP treatment was given before transplantation. After transplantation the animals were maintained with low-dose CsA. Among those treated with AZ, five of eight survived >100 days, and among those treated with CP, six of eight survived >100. These two protocols were far superior to 28 other permutations of treatment consisting of 164 transplants, such as infusions plus AZ without CsA and infusions without AZ but with CsA.We conclude that CsA can most effectively be used in low dose as a maintenance drug and that immunoreduction therapy is optimized by prestimulation and expansion of reactive cells. Another important feature of this proposal is that the immunoreductive risk phase, performed before transplantation, can be separated from the operative risk period. This avoids the conventional superimposition of the two risks.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID