Faculty Bibliography

In patients with delayed graft function (DGF), the use of cyclosporine (CsA) has been reported to prolong DGF, increase the number of required dialyses, increase the duration of hospitalization, and be associated with decreased graft survival. Routine postoperative antilymphocyte globulin (ALG) use has been advocated, but ALG is associated with increased viral infection. We studied outcome of individualization of immunosuppression. Between 11/84 and 8/86, first-cadaver transplant recipients whose serum creatinine (Cr) fell greater than or equal to 30% in the first 24 hr (immediate function) were started on CsA and prednisone (P) (group 1, n = 26). The remainder were randomized to P and azathioprine (group 2, n = 32) or P and ALG (group 3, n = 26), and switched to CsA when serum Cr fell greater than 30% (minimum 5 days ALG for the ALG group). P taper was the same in all groups. Patients with DGF (groups 2 and 3) had longer preservation time and higher peak PRA (P less than .05) than group 1. Groups were otherwise equivalent. One and 2-year patient survival was 96% (3 cardiovascular deaths; all with functioning grafts). One-year graft survival was 87% for group 1, 87% for group 2, and 82% for group 3(NS). In patients requiring dialysis, mean day off dialysis was 12 +/- 3 in both groups 2 and 3. Mean hospital stay was 12.5 +/- 1.3 days for group 1, 21.6 +/- 2.1 days for group 2 (P less than .05 vs. 1 & 3), and 14.5 +/- 1.2 days for group 3 (NS vs. 1). The increased hospital stay for group 2 patients was mainly due to increased in-hospital rejections: 75% for group 2, (P less than .05 vs. group 1 [35%], and group 3 [11.5%]). In addition, more group 2 in-hospital 1st rejections were steroid resistant as compared to group 1; 46% group 1 patients have remained rejection free as compared to 0% group 2 (P less than .05 vs. 1 and 3) and 35% of group 3 (P less than .05 vs. 1 and 2). Mean serum creatinine at 6-12 months remained higher in patients with DGF (group 1 P less than .05 vs. 2 and 3). Rejection was the major cause of graft loss in all groups.(ABSTRACT TRUNCATED AT 400 WORDS)

To determine whether vein graft length is a factor that influences infrapopliteal bypass patency, we reviewed 237 consecutive reversed saphenous vein bypasses performed because of critical ischemia during a 5-year period. One hundred seventeen long vein grafts (LVGs) were longer than 40 cm (42 to 92 cm, mean 60.9 +/- 9 cm) and 120 short vein grafts (SVGs) were 40 cm or shorter (6 to 40 cm, mean 24.7 +/- 8 cm). Ninety-three percent of the LVGs originated from or were proximal to the superficial femoral artery (SFA) whereas all of the SVGs originated at or distal to the SFA. The cumulative patency rate for LVGs at 3 years was 45% and for SVGs was 63% (p less than 0.025). In the absence of an intact pedal arch, 3-year patency rates for LVGs (51 cases) and SVGs (78 cases) were 22% and 53%, respectively (p less than 0.01). High intraoperative outflow resistance measurements (greater than 0.7 mm Hg/ml/min) were encountered in 25 cases. Of these, occlusion within 6 months occurred in six of seven cases with LVGs and in only 8 of 18 cases with SVGs (p less than 0.05). Wound complications at vein harvest sites occurred in 17% of LVGs and in only 6% of SVGs (p less than 0.01). Of 16 additional cases in which a proximal patch angioplasty or percutaneous transluminal angioplasty was performed tandem with a short distal vein graft, four occluded (less than 6 months) and 12 remained patent from 3 to 43 months (mean 12.6 months).(ABSTRACT TRUNCATED AT 250 WORDS)

In selected patients with localized infection of polytetrafluoroethylene graft arteriovenous fistulas, the access route can be preserved by treatment with antibiotics and surgical drainage. However, such treatment may result in exposure of the graft, which in itself is a threat to continued survival of the graft. This article describes a simple method that has been successfully used to achieve skin coverage of such grafts

Cyclosporine in renal transplant recipients with delayed graft function (DGF) has been reported to decrease graft survival and prolong both DGF and hospitalization. In some centers, antilymphocyte globulin (ALG) has been used perioperatively to obviate these problems, but ALG is associated with increased viral infections. In this study, first cadaver transplant recipients with a fall in serum creatinine level of greater than or equal to 30% in the first 24 hr were started on prednisone (P) and cyclosporine (Group 1, n = 18). Those whose creatinine level did not fall were started on P and azathioprine (Group 2, n = 23) and switched to P and cyclosporine when serum creatinine fell 30%. One-year patient survival was 98%. One-year graft survival was 83% for both Groups 1 and 2 (NS). Results were compared to historical controls with DGF who received P and cyclosporine (Group 3, n = 19). Patients with DGF and requiring dialysis had fewer dialyses (P less than 0.05) and a shorter hospital stay (P less than 0.05) if started on azathioprine, as compared to those started on cyclosporine. Patients with DGF had a higher serum creatinine at 12 months than those with immediate function (P less than 0.05). We conclude that withholding cyclosporine until DGF is resolving decreases the duration of dialysis, decreases hospital stay, and without the use of prophylactic ALG, is associated with graft survival equivalent to that in patients with immediate function

Immunologic, morphologic, and functional evaluations were performed in beagle dogs with single lung allografts surviving 3-13 years after transplantation. Immunosuppressive treatment included lethal total-body irradiation, autologous bone marrow reconstitution, and three doses of methotrexate. Three beagle recipients with full DLA-haplotype-matched grafts and five recipients with one-haplotype-mismatched grafts were studied. Evidence of rejection--i.e., infiltrates on chest roentgenograms, hypoperfusion on radionuclide lung scans, and histopathologic changes--were absent in the matched recipients and in three of the five mismatched recipients. Two of the mismatched recipients had decreased perfusion to their allografted lungs, and open-lung biopsy specimens revealed diffuse fibrotic blood vessels with narrowed lumina but no other abnormalities. Decreased fractional blood flow to the lung allograft of the five one-haplotype-mismatched recipients was correlated (r = -0.92) with the level of donor-specific cytolytic lymphocyte activity generated in mixed lymphocyte cultures (MLC). In contrast, the level of proliferative activity in donor-specific MLC did not correlate well with graft function. These findings suggest that the mechanism of tolerance to these lung allografts (with particular regard to vascular integrity) involves attenuation of the response against major histocompatibility complex (MHC) class I alloantigen since the induction of cytolytic T lymphocytes in MLC is directed primarily against these molecules. Though all of the mismatched recipients had the ability to react against MHC class II alloantigens in vitro (as demonstrated by proliferative responses in MLC), in vivo responses to class II gene products may not occur because of the lack of expression of these molecules on long-term surviving grafts

Techniques for exposure of the popliteal artery via lateral approaches above and below the knee are described. These techniques were used successfully in 21 patients who required secondary arterial reconstructions in the presence of extensive scarring, infection, or both in the standard medial access routes

Criteria for abandoning infrainguinal arterial reconstructions in favor of major amputations should include reliable predictors not only of graft patency, but more importantly, of limb salvage. To evaluate the efficacy of intraoperative outflow resistance measurements in predicting limb salvage after infrainguinal bypasses, we have reviewed 134 such operations (64 femoropopliteal and 70 femorodistal bypasses) performed for critical ischemia. Outflow resistance measurements were divided into quartiles for femoropopliteal bypasses (Group A 0.17 mm Hg/ml/min or less, Group B 0.18 to 0.24 mm Hg/ml/min, Group C 0.25 to 0.4 mm Hg/ml/min, and Group D greater than 0.4 mm Hg/ml/min) and femorodistal bypasses (Group A 0.4 mm Hg/ml/min or less, Group B 0.4 to 0.58 mm Hg/ml/min or less, Group C 0.6 to 1 mm Hg/ml/min, and Group D 1 mm Hg/ml/min or greater). One year limb salvage rates for patients who underwent femoropopliteal bypass were 95 percent, 92 percent, 87 percent, and 67 percent from the lowest to the highest quartile (difference not statistically significant), and for those who had femorodistal bypass, they were 51 percent, 75 percent, 48 percent, and 0, respectively (p less than 0.05). Interestingly, 12 month graft patency and limb salvage rates for patients who underwent femorodistal bypass with outflow resistances between 0.59 and 1 mm Hg/ml/min did not correlate well (22 percent and 48 percent, respectively), whereas for those with outflow resistance greater than 1 mm Hg/ml/min, they were 22 percent and 22 percent, respectively. Thus, measurement of intraoperative outflow resistance is a very accurate predictor of limb salvage after infrainguinal bypass operations

Alloreactivity of intragraft and peripheral blood lymphocytes from tolerant canine lung allograft recipients was examined. Tolerance was induced by variable periods of treatment with cyclosporine. Analysis of effector cells from lung allografts (obtained by bronchoalveolar lavage) revealed the absence of specific cytolytic T lymphocyte (CTL) activity and the presence of a low level of cytolytic activity detected in a lectin-dependent cell-mediated cytotoxicity assay. In contrast, high levels of specific CTL activity and lectin-dependent activity were detected in cell preparations from lung allografts undergoing rejection. Tolerant recipients retained normal ability to generate specific CTL activity to third party alloantigens in mixed lymphocyte cultures (MLC) but had diminished ability to generate CTL to donor alloantigens in recipient X donor MLC. Addition of exogenous interleukin 2 to these MLC was unable to restore donor-specific CTL activity. Lymphocytes from tolerant recipients were, however, capable of generating proliferative responses and lectin-dependent cytotoxicity on exposure to donor alloantigens in MLC. Evidence presented in this report suggests that the lectin-dependent cytolytic activity generated in these MLC is mediated by lymphokine-activated killer cells. Such cells are likely to be activated by interleukin 2 released in the proliferative response. The results support the proposal that the cyclosporine-induced tolerant state is characterized by the relative inability to respond against major histocompatibility complex class I antigens in contrast to class II antigens and/or minor histocompatibility antigens since MLC-induced CTL are directed, for the most part, against class I molecules