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Vein graft stenosis remains an important contributing factor to the failure of infrainguinal arterial reconstruction. Repair of these lesions before graft occlusion provides sustained patency, yet the optimal method of repair has not been established. Percutaneous transluminal balloon angioplasty of these vein graft lesions has been repeatedly advocated as an alternative to surgical revision. Balloon angioplasty was used in 30 patients with 54 stenotic lesions occurring in autogenous vein grafts after infrainguinal reconstruction. The primary 5-year cumulative patency rate was 18% overall, with no significant differences observed among patency rates based on initial indication, length of stenotic lesion, or requirement for preliminary thrombolytic therapy. The 3-year patency rate associated with vein graft lesions requiring only a single angioplasty proved significantly higher (59%) than those requiring repetitive dilations (6%). It is our conclusion that balloon angioplasty for vein graft stenosis has significant limitations in providing sustained secondary patency.

We attempt to elucidate the mechanisms of neutrophil (PMN) activation after burn injury. We previously reported prolonged elevations of PMN cell surface complement (C) opsonin receptor levels after burn trauma with a corresponding period of depressed PMN chemotaxis to C5a, which suggests that the C product, C5a, was responsible for PMN activation. However, a lack of direct correlation of C activation with C receptor levels soon after injury raised the possibility of a second PMN-activating substance. We therefore investigated the effect of endotoxin (LPS) on the expression of the C receptors (CR1 and CR3) by normal human PMNs. Concentrations from 0 to 50 ng/ml of LPS 026:B6 caused a dose response increase in the PMN surface expression of CR1 and CR3 as assessed by monoclonal antibody binding and indirect immunofluorescence. The relative CR1-dependent fluorescence rose from a mean of 50 to 385 and CR3 from 50 to 300. Chelation by ethylenediaminetetra acetic acid (EDTA) did not influence this dose response, thus ruling out the possibility of C activation by LPS--an inference supported by the lack of complement activation observed with these concentrations of LPS in normal serum. A similar dose response was obtained in the absence of other cell types or serum, which implies a direct effect that mimicked that of C5a. To determine the mechanism of the later, prolonged C activation after burn injury, we next examined C activation products in 22 patients with burn injuries. Elevations of plasma C3a desArg were present and persisted for 50 days. Elevations were at maximum levels on days 9 through 13 postburn (mean +/- standard error of mean [SEM], 496 +/- 47 ng/ml versus normal 113 +/- 32; p less than 0.01). These were accompanied by elevations of C4a desArg (917 +/- 154 ng/ml versus normal 424 +/- 50; p less than 0.01), which are indicative of classic pathway activation. Finally, we examined PMN function, phagocytosis and percentage killing of Staphylococcus aureus, and found PMN function to be unaltered in the 22 patients. Thus PMN activation after burn injury appears to be caused by LPS soon after injury and by C5a later after injury and affects only selected PMN functions.

Patients who have sustained a large hemispheric stroke are not candidates for early carotid endarterectomy, but there is less agreement regarding the role of carotid endarterectomy in patients with small, fixed neurologic deficits. Accepted practice in many centers is to wait 4 to 6 weeks after the onset of the deficit before proceeding with carotid endarterectomy because of the fear that early revascularization will increase the size of the infarct. Earlier endarterectomy, however, in patients with significant residual ipsilateral carotid territory at risk may prevent repeated infarctions. For the past 5 years our approach to patients with a small stable stroke and significant stenosis (greater than 75%) has been prompt ipsilateral endarterectomy. Of the 337 carotid endarterectomies at our institution since 1979, a subset of 28 patients with hemodynamically significant carotid lesions presented with a small, fixed stroke. The period of time between the appearance of the stroke and carotid endarterectomy averaged 11 days, but 53% of patients were operated on within 7 days of the onset of symptoms. Selective shunting based on intraoperative EEG monitoring was utilized and 40% of the 28 patients required shunts. Operative mortality consisted of one death from a pulmonary embolus, and no patient sustained a new postoperative deficit. Long-term follow-up was available for 96% of patients over a mean of 2 years. During this time two new neurologic events occurred: one fatal stroke and one transient deficit. This experience indicates that patients with small, fixed neurologic deficits who continue to have carotid territory at risk may safely undergo carotid endarterectomy without waiting 4 to 6 weeks.

The immunoreactivity of lymphocytes from mice bearing large tumors was investigated. As compared to normal lymphocytes, lymphocytes from tumor bearers manifested a lessened proliferative response to T-cell mitogens and were less capable of destroying syngeneic tumor target cells. However, the impaired reactivity of these lymphocytes was improved significantly after washing repeatedly in tissue culture medium in vitro. The increase in cytolytic activity was tumor specific. A membrane-associated suppressive substance was detected in the washing medium which inhibited the cytotoxicity of washed lymphocytes. The effect of suppressive substance was tumor specific and sensitive to treatment with protein A and anti-immunoglobulin antibody, indicating that the suppressive substance contained immunoglobulin. The present findings suggest that a membrane-associated suppressive substance(s) may be in part responsible for the diminished immune responsiveness of lymphocytes from animals bearing large tumors.

The suppression of tumor-specific cell-mediated cytotoxicity by human immunoregulatory alpha-globulin (IRA), by a peptide fraction derived from IRA, and by IRA-like peptides from the serum of cancer patients was studied in a syngeneic murine tumor-host system. Splenic lymphocytes from tumor-immunized mice were cytotoxic specific tumor cells in vitro as measured by the [125]-iododeoxyuridine release microcytotoxicity assay. However, this effect was significantly depressed if 1.25 to 5 mg of IRA per ml were added to the cultures. Pooled lyophilized normal human serum protein was inactive. IRA peptide and IRA-like peptide fractions from cancer patients were also highly suppressive of cell-mediated cytotoxicity at much lower concentrations (0.05 to 0.5 mg/ml). Control human serum peptide, which failed to inhibit the induction of hemolytic plaque-forming cells in sheep erythrocyte-injected mice, had no effect on cell-mediated cytotoxicity. IRA and IRA-like peptide fractions were not cytotoxic to the effector lymphocytes or to the target cells at the concentrations used.

Thirty-four patients undergoing elective abdominal aortic aneurysmectomy were studied, and they were randomly allocated to a "fed group receiving amino acid dextrose solutions intravenously and fat emulsions or an "unfed" group receiving standard postoperative care. Cell-mediated immunity was measured by lymphocyte count, the in vitro response to the T-cell mitogen PHA and determination of T-cell subsets using monoclonal antibodies. Serum suppressive activity was measured by the ability of the sera of the patient to suppress the response of normal lymphocytes to PHA. Feeding was continued for three to five days postoperatively until satisfactory oral intake was achieved. There was no significant improvement in lymphocyte count or blastogenesis postoperatively in the "fed" group, and operation did not lead to any alteration in the ratio of T-cell subsets, although there was a fall in T-cell count (OKT3 positive cells). We conclude that short term parenteral nutrition in well nourished patients, postoperatively, does not abrogate the depression of cell-mediated immunity which occurs after extensive operative procedures.

The alpha-globulin-rich fraction of Cohn Fraction IV, designated IRA, suppresses the in vitro antibody response to sheep red blood cells (SRBC) without cytotoxicity. IRA was effective if added before or up to 24 hr after antigen exposure. The suppression could be reversed after 24-hr treatment by washing the cells two to three times; after 48 hr of IRA treatment, however, suppression could only be partially reversed. The addition of a population of thymus-derived cells educated to the antigen SRBC could effectively reverse the IRA-induced inhibition of antibody production, whereas BSA-educated T cells could not.

This study reports our experience with 10 patients who underwent the emergent construction of a femorofemoral bypass graft to salvage an acutely ischemic lower extremity following the insertion of a transfemoral intra-aortic balloon pump catheter. All patients had excellent resolution of the ischemia and salvage of the extremity. Half of the procedures were done at the bedside with the remainder performed in the operating room. No long-term infections or ischemic sequelae resulted from the procedures in the nine patients available for long-term follow-up. The use of femorofemoral bypass grafting is, therefore, recommended in patients with severe ipsilateral limb ischemia who are dependent on an intra-aortic balloon pump to prevent extremity tissue loss as well as the systemic metabolic manifestations of ongoing tissue ischemia and necrosis. Patient selection, technical considerations, and postoperative management are discussed.

Recent clinical studies indicate that the use of aspirin and dipyridamole improves graft patency rates in patients with infrainguinal polytetrafluoroethylene (PTFE) grafts and aortocoronary vein grafts. We undertook a prospective, double-blind, randomized study to determine whether these drugs administered postoperatively to patients with PTFE or autologous vein infrainguinal bypasses would improve graft patency during the first 24 months after operation. Patients received either aspirin 325 mg and dipyridamole 75 mg or identical placebo tablets three times a day, taken orally. Patency rates were compared by computing standard life tables and comparing cumulative patency rates. One hundred patients with 102 grafts were studied. The cumulative patency rate at 24 months was not significantly different for the treatment (57%) versus control (67%) groups or for any subgroup. We conclude that aspirin and dipyridamole administered postoperatively in the doses used in this study do not improve the overall patency rates of vein or PTFE infrainguinal bypass grafts.

Despite the recent popularity of the in situ saphenous vein graft for infrainguinal arterial reconstruction, considerable doubt exists as to whether this approach offers any real advantage over conventional reversed vein grafts. Therefore we have reviewed our experience with 675 infrainguinal vein grafts undertaken during the past 10 years. There have been no substantial modifications in the technique used for 535 reversed vein grafts over the 10-year period. During the past 3 years, 140 in situ vein grafts have been carried out with the Leather valvulotome used to incise the venous valves. Life-table analysis of 449 femoropopliteal reversed saphenous vein grafts demonstrated 1- and 3-year cumulative patency rates of 81% and 73%, respectively, and a 5-year patency rate of 63%. Seventy-five femoropopliteal in situ bypasses demonstrated a patency rate of 85% at both 1- and 3-year intervals. Cumulative patency rates for 86 femoroinfrapopliteal reversed saphenous vein grafts were 64% and 62% at 1 and 3 years, respectively. Comparable patency rates for 65 infrapopliteal in situ saphenous vein grafts remained stable at 87% for 3 years. Fifteen of the in situ bypasses were anastomosed to vessels at the ankle or foot level, whereas none of the reversed bypasses was carried that far distally. This experience with both in situ and reversed techniques on one service by the same surgeons demonstrates a clear superiority of the in situ saphenous vein graft for infrapopliteal reconstruction at the 3-year interval.

Two antigenically distinct fibrosarcomas, designated BP-8 and BP-9, induced in syngeneic C3H/HeN mice by 3,4-benzo(a)pyrene were used to study tumor-specific immunity, concomitant tumor immunity and the effect of large tumor volumes on the loss of immunological reactivity. Two groups of mice were immunized to the BP-8 tumor by amputation of growing BP-8 isografts. One group was rechallenged with the BP-8 cells, and tumor growth was not noted. Both groups of mice then received an inoculum of BP-9 cells that grew to palpable tumors to the same extent as in control mice. BP-8-immunized mice bearing progressively larger PB-9 tumors were sacrified at varying intervals after the BP-9 isograft. Tumor weight was recorded as a percentage of total body weight and viable spleen cells from these animals were tested in vitro for cytotoxicity against BP-8 and BP-9 cells in the [125I]iododeoxyuridine microcytotoxicity assay. Spleen cells from untreated mice were used as controls. The mice with growing BP-9 tumors developed an immune reaction against the tumor antigens which increased with time from initial tumor isograft and with increasing tumor size up to a definite but variable limit. Cytotoxicity to BP-9 cells rose from 18% when the BP-9 tumor was not palpable to a maximum of 77% when the tumor represented 5 to 10% of the total body weight. Cytotoxicity to BP-9 fell progressively as tumor size exceeded 15% of the total body weight and approached the 10% background cytotoxicity of control lymphocytes to BP-9 cells, when the tumor weight achieved 25% of the animal's weight. Conversely, cytotoxicity of lymphocytes against the BP-8 tumor did not vary significantly and remained about 41 to 44% over the same interval even while specific reactivity to BP-9 cells significantly decreased. In addition, with time, lymphocyte-mediated cytotoxicity to the BP-8 tumor increased from 41 to 70% if the BP-8-immunized mice had been rechallenged with antigenically identical BP-8 cells prior to the BP-9 isograft. These data suggest that loss of immunoreactivity at large tumor volumes is tumor and, presumably, antigen specific. No evidence of a generalized immune paralysis was demonstrated, since the mice always maintained immunity to the BP-8 tumor despite progressive and lethal growth of the antigenically distinct BP-9 tumor.