Marked histoincompatibility between and within sublines of AKR mice used in a syngeneic leukemia model.

Sublines of AKR mice differed significantly in their histoincompatibility to AKR/J mice, as indicated by their ability to reject AKR/J skin grafts and an AKR transplantable leukemia. Further, all sublines tested demonstrated some degree of heterogeneity, because isografts were rejected in 5-97% of the mice, depending on the subline. The presence of excessive heterogeneity among and within sublines poses a serious problem for experimental oncologists using these sublines in their tumor models.

Prolongation of murine skin allografts by prostaglandin E1.

The effects of 16,16-dimethyl prostaglandin E2 methyl ester (di-M-PGE2) and indomethacin (an inhibitor of endogenous prostaglandin biosynthesis) on mouse skin allograft survival were studies in B10.D2 female mice receiving skin allografts from (B10.BR X B10.D2)F1 mice. Control animals with and without i.p. diluent injections had a mean allograft survival of 13.8+/-0.6 and 13.5+/-0.5 days, respectively. Daily administration of di-M-PGE2 (200 microng/kg) prolonged mean allograft survival, both when administered alone, 16.7+/-0.6 days (P less than 0.001), or with indomethacin, 4 mg/kg thrice weekly, 16.0+/0.6 days (P less than 0.005). Increasing concentrations of indomethacin (4, 6, and 8 mg/kg thrice weekly) were inversely corrleated with allograft survival ((12.7+/-0.2, 11.8+/-0.2, and 10.9+/-0.4 days, respectively), coefficient of correlation=-0.6986; P less than 0.001. Mean plasma PGE levels at the time of total allograft rejection were 879+/-80 pg/ml in control, 717+/-59 pg/ml in 100 micron g of indomethacin-treated mice, and 654+/-59 pg/ml in 200 microng of indomethacin-treated mice (P less than 0.05). Exogenous di-M-PGE2 prolonged skin allograft survival in mice. Inhibition of endogenous prostaglandin biosynthesis by indomethacin chortened allograft survival, but this effect was completely abrogated by concurrent injection of di-M-PGE2.

Time-response studies of the cellular immune response to cell membrane antigens.

It was the objective of these experiments to study the time-related changes in the responsiveness of the cellular elements of the immune system following contact with single non-H-2 or multiple H-2 histocompatibility antigens. The reactivity of spleen cells from mice that received injections of spleen cells bearing H-1c, H-3c, H-13a, or H-2b cell membrane alloantigens was characterized at intervals following antigen contact. Spleen cells taken from mice not receiving injections showed no in vitro proliferative or cytolytic responsiveness to cells bearing individual non-H-2 antigens; after in vivo antigen contact with single non-H-2 antigens there was an interval of specific cellular unresponsiveness followed by alternating periods of responsiveness and unresponsiveness. The duration of the unresponsiveness immediately following injection correlated with the strength of the injected antigen--specifically, the stronger the antigen, the shorter the period of unresponsiveness. The data indicate fluctuation in the level of helper T lymphocyte activity, as well as cytotoxic T lymphocyte activity. In contrast, in vitro responsiveness elicited by H-2b antigens with and without prior in vivo antigen contact was of a similar magnitude, and both persisted at a relatively constant level. Suppressor mechanisms were not studied. Of particular interest was the observation that in vivo contact with non-H-2 antigens resulted in suppression of spleen cell production of IL-2 in response to lectin stimulation and fluctuation in the magnitude of the primary response of cytotoxic T lymphocytes to H-2 antigens.

Blood flow measurements in arteriovenous dialysis fistulas.

Blood flows were measured in 75 arteriovenous dialysis fistulas (AVF) at the time of fistula construction. End cephalic vein to side of radial artery AVF had a mean flow of 242 +/- 89 ml. per minute which was similar to bovine heterograft AVF that also originated from the radial artery (291 +/- 67 ml. per minute). AVF originating from the brachial artery had flow rates twice those originating from the radial artery (599 +/- 163 vs. 251 +/- 89 ml. per minute), respectively). Flow rates were similar for straight arm (641 +/- 111 ml. per minute), curved forearm (561 +/- 187 ml. per minute), and curved thigh (592 +/- 134 ml. per minute) bovine AVF. Initial blood flow through arteriovenous dialysis fistulas is too low to cause heart failure, except in patients with previously compromised cardiac function. In such patients AVF from the radial artery theoretically would be preferred over brachial or femoral artery AVF.

Serum lactic dehydrogenase and irreversible renal allograft rejection.

The relationship between serum lactic dehydrogenase (SLDH) values and renal allograft rejection was examined in the dog and in man. Nine dogs with renal allografts and four with autografts had similar maximal elevations of SLDH during the first five postoperative days (mean, 420 +/- 213 and 433 +/- 80 I.U. per liter, respectively). During rejection of the allografts between days 7 and 14 the maximum SLDH was 810 +/- 285 I.U. per liter, and in autografts the peak SLDH was 233 +/- 22 I.U. per liter (p less than 0.01). The isoenzyme pattern of maximum SLDH during rejection was prominent in LDH5 and corresponded with renal tissue LDH isoenzyme composition. In 93 episodes of initial acute human renal allograft rejection reactions, the SLDH peaked above 500 I.U. per liter in 23 cases and remained below 500 I.U. per liter in 70 cases. SLDH levels above 500 I.U. per liter were associated with complete rejection of the kidney in 91 percent of patients and SLDH levels persistently below 500 I.U. per liter corresponded with reversal of rejection reaction in 99 percent of patients (p less than 0.01). Marked SLDH elevation is associated with severe, usually complete renal allograft rejection and may be useful in identifying patients with irreversible rejection reactions.

Colorectal complications of renal allograft transplantation.

The occurrence of perforated sigmoid diverticulitis in a renal transplant recipient stimulated a review of colorectal complications in renal allograft recipients. One hundred twenty-five renal transplantations were performed in 113 patients between January 1968 and December 1975. Six patients (5%) were identified as having colorectal complications and five of these patients died as a direct result. Chart analysis of these 113 transplant recipients identified 55 patients as having undergone colonic evaluation (contrast enema, postmortem examination), with seven of these 55 (13%) found to have diverticulosis and major colonic complications eventually developing in four of these seven. Since the mortality from the complications of colorectal diseases in immunosuppressed patients is so prohibitive, in patients with diverticulosis and a previous history suggestive of diverticulitis, consideration should be given to exclusion from transplantation or elective segmental colectomy prior to transplantation.

Saphenous vein-popliteal artery fistula for chornic hemodialysis.

A saphenous vein arteriovenous fistula for chronic hemodialysis can be formed in the thigh by tunneling the vein subcutaneously, anastomosing the distal end to the popliteal artery, and leaving the proximal end attached to the femoral vein. Of seven fistulas, only one has thrombosed spontaneously. There were no instances of infection, vascular insufficiency, or high output cardiac failure. A saphenous vein-popliteal artery fistula can be a satisfactory method of maintaining vascular access in those patients who require chronic hemodialysis but who have no available sites in the upper extremities for construction of a fistula.

The clinical importance of flow cytometry crossmatch in the context of CDC crossmatch results.

BACKGROUND: The complement-dependent microcytotoxicity crossmatch (CDCXM) is a standard method for evaluating the presence of preformed antibodies before transplantation. The flow cytometry crossmatch (FCXM) is more sensitive, but there is controversy regarding translation of its increased sensitivity to clinically relevant graft outcomes. METHODS: We analyzed Organ Procurement and Transplant Network registry data for living and deceased donor kidney transplants performed in 1995 to 2009 after both CDCXM and FCXM testing. Transplants with negative CDCXM (CDCXM(-)) and with T-cell positive (T(+)), T-cell negative/B-cell positive (T(-)B(+)), or T- and B-cell negative (T(-)B(-)) FCXM results were included. Graft survival according to crossmatch results was compared by survival analysis. RESULTS: Among patients transplanted with negative CDCXM (CDCXM(-)), deceased and living donor graft recipients with T(+) FXCM experienced significant absolute reductions in 5-year graft survival of 11.5% and 8.8% compared to those with T(-) FCXM (P < .0001). Compared to patients with FCXM(-)/CDCXM(-) deceased and living donor recipients with T(-)B(+) FCXM/CDCXM(-) had absolute reductions in 5-year graft survival of 9.6% and 7.6%, respectively (P < .0001). Upon multivariate adjustment with Cox regression, T(+) FCXM/CDCXM(-) deceased donor transplantation was associated with 51% higher adjusted relative risk of 1-year graft loss than FCXM(-)/CDCXM(-). Relative risks were more marked at 1 year for the T(+) groups but stronger in the 1- to 5-year interval for the T(-)B(+) groups. CONCLUSION: Positive FCXM has important prognostic implications even when CDCXM is negative. Thus, positive FCXM should not routinely be dismissed as "overly sensitive" when CDCXM is negative.