Freshly isolated allogenic pancreatic islets transplanted into the thymus of transiently immunosuppressed rats are not rejected but survive indefinitely while also inducing a state of specific unresponsiveness that permits survival of secondary donor-strain islets transplanted extrathymically. Since freshly isolated pancreatic islets contain intraislet antigen-presenting cells as well as endocrine cells it is unclear which cellular component is primarily responsible for mediating unresponsiveness. We therefore examined the impact of pretransplant in vitro culture (a maneuver which selectively depletes intraislet APCs) on the capacity of islet allografts to induce unresponsiveness after intrathymic implantation. APC-depleted pancreatic islets, which are known to have reduced immunogenicity, survived indefinitely in the thymus of allogeneic hosts whether or not brief immunosuppression was employed, but failed to promote survival of subsequent donor-strain islets transplanted to an extrathymic site. These findings emphasize the central role of APCs in the induction of transplantation tolerance in this model, and are consistent with the established role of this population in the development of T cell tolerance in the thymus.

Animals↗

PubMed1994

Basic and clinical considerations in the use of xenografts.

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Animals↗

PubMed1994

Peripheral vascular surgery with magnetic resonance angiography as the sole preoperative imaging modality.

PURPOSE: Magnetic resonance angiography (MRA) is a developing technique that provides arteriograms without the risks associated with iodinated contrast and arterial puncture or the expense of hospitalization. Prior reports have demonstrated the accuracy of peripheral vessel MRA for evaluation of the aorta through pedal vessels. This study sought to determine whether vascular reconstructions could be planned and accomplished on the basis of MRA alone. METHODS: Eighty consecutive candidates for bypass with ischemic rest pain or tissue loss were studied with preoperative outpatient MRA of the juxtarenal aorta through the foot. Confirmation of MRA findings was provided by intraoperative intraarterial pressure measurements for proximal vessels and postbypass arteriography for the runoff. Life-table analysis of graft patency and limb salvage was performed. RESULTS: Two patients could not tolerate MRA and required contrast arteriography, but all others underwent reconstructive procedures on the basis of MRA alone (11 aortobifemoral, 67 infrainguinal). Intraoperative findings regarding suitability of inflow and outflow vessels confirmed the accuracy of the MRAs in every case. MRA indicated that none of the patients undergoing infrainguinal bypass had significant inflow occlusive disease, and this was confirmed at operation with pressure measurements of inflow vessels that were always within 10 mm Hg (peak systolic) of systemic pressure. The results of intraoperative completion arteriography and preoperative MRAs were identical for all but two patients who had minor discrepancies. All aortobifemoral reconstructions remained patent, and all limbs remained intact. The infrainguinal reconstructions had an 84% limb salvage rate and 78% primary graft patency rate at 21 months. Comparison of charges for patients undergoing preoperative MRA versus contrast angiography showed a cost savings of $1288 for each patient treated with preoperative MRA alone. CONCLUSIONS: MRA is a noninvasive, cost-effective outpatient imaging technique that, if properly performed and interpreted, is sufficient for planning peripheral bypass procedures. Its use may supplant contrast arteriography in many patients.

Adult↗

PubMed1994

Popliteal artery aneurysms: current management and outcome.

PURPOSE: Thrombosis of popliteal artery aneurysms can produce limb-threatening ischemia. In this setting we have found preoperative thrombolytic therapy to be beneficial. METHODS: Thirty-three patients with 54 popliteal artery aneurysms were studied (mean follow-up 62 months). Twenty-one patients (62%) had bilateral popliteal artery aneurysms, and 20 patients (61%) had extrapopliteal arterial aneurysms. Thirty-three (61%) aneurysms had symptoms of compression or ischemia, and 21 (39%) aneurysms had thrombosis. A trend toward thrombosis for larger aneurysms was noted (p < 0.068). RESULTS: Forty-five aneurysms were treated with bypass grafting. Five-year graft patency and limb salvage rates were 71% and 90%, respectively. Factors favoring graft patency and limb salvage included presence of two- or three-vessel runoff compared with patients with single- or no-vessel runoff (p < 0.025 graft patency; p < 0.003 limb salvage) and presence of a patent aneurysm (p < 0.005 graft patency and limb salvage). Seven patients diagnosed with thrombosis of their aneurysm and all runoff vessels were treated with preoperative thrombolytic therapy. Complete clearing of thrombus from these arteries was achieved in six of these patients (and from two of these runoff vessels in the remaining patient). These patients had better graft patency (p < 0.005) and limb salvage (p < 0.01) than comparable patients treated with emergency operations. Six amputations were performed in the follow-up interval, none of which were performed in patients having undergone thrombolytic therapy. CONCLUSIONS: It is concluded that popliteal aneurysms are managed best by elective repair of patent aneurysms with good runoff. In that difficult situation of the thrombosed popliteal artery aneurysm associated with acute leg ischemia, thrombolytic therapy safely and effectively provides patients with a more favorable alternative than emergency surgery.

Adult↗

PubMed1994

Is induction therapy necessary for successful simultaneous pancreas and kidney transplantation in the cyclosporine era?

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Adult↗

PubMed1994

Magnetic resonance angiography of the aorta, iliac, and femoral arteries.

BACKGROUND: Successful management of patients with peripheral vascular disease requires detailed vascular imaging, usually performed by contrast arteriography. Recently, magnetic resonance angiography (MRA) has been shown to be a noninvasive technique with greater sensitivity than contrast arteriography for detecting distal runoff vessels in patients with peripheral arterial occlusive disease. However, to supplant the need for contrast arteriography and provide a completely noninvasive evaluation of patients with occlusive disease, accurate imaging of the inflow vessels and the runoff vessels is necessary. METHODS: We used both conventional arteriography and MRA in preoperative studies of the aorta, iliac, and femoral vessels of 47 patients. Conventional arteriography and MRA studies were compared for their ability to detect vessel patency and the presence of hemodynamically significant stenoses. Independent interventional plans were developed based on the information provided by each technique. The findings of conventional and MRA studies were verified by intraoperative arteriography or direct operative exploration. RESULTS: Results of the two studies were identical in 41 (87%) of 47 patients or 600 (98%) of 614 segments imaged. MRA accurately detected patent and occluded arterial segments (sensitivity 99.6%, specificity 100%, positive predictive value 100%, negative predictive value 98.6%) and hemodynamically significant stenoses. Therapeutic plans based on either MRA or conventional arteriography were identical for each patient. CONCLUSIONS: MRA provides comparable results to contrast arteriography in the proximal arterial system and superior results for imaging the distal vasculature. This noninvasive technique may replace contrast arteriography in a large number of patients in the future.

Adult↗

PubMed1994

Genetically engineered grafts to study xenoimmunity: a role for indirect antigen presentation in the destruction of major histocompatibility complex antigen deficient xenografts.

BACKGROUND: The genetic engineering of xenogeneic donor species for transplantation may provide a means of attenuating the potent immune response elicited by tissues from foreign species. Because of their well-established role in allograft rejection, a logical target for genetic manipulation is the genes encoded by the major histocompatibility complex (MHC). In the current study we examined whether skin, heart, or pancreatic islet xenografts harvested from lines of transgenic mice rendered deficient in MHC antigen expression by gene disruption would exhibit a survival benefit when transplanted to xenogeneic rat recipients. In addition, we characterized the in vitro response of rat T cells to normal and MHC-deficient mouse cells. METHODS: Skin, heart, and pancreatic islet grafts were harvested from control C57Bl/6 and each of three lines of mice deficient in MHC antigen expression. MHC-deficient lines included (1) mice selectively lacking MHC class I antigens (CID), produced by disruption of the beta-2 microglobulin gene; (2) mice lacking MHC class II expression (CIID), produced by targeting the I-A beta-chain gene; and (3) mice devoid of both class I and class II molecules (CI,IID). RESULTS: In contrast to the prolonged survival that has been observed for certain allografts deficient in MHC antigen expression, we did not detect significant extension of survival in the case of xenografts. Using in vitro assays of T-cell function, we demonstrated that rats that rejected grafts lacking MHC expression evidenced sensitization of T cells specific for graft antigens presented by rat antigen-presenting cells. CONCLUSIONS: The strategies of gene targeting of donor species to produce less immunogenic xenografts may be hampered by the presence of a strong response through the indirect pathway of immunity. Immune intervention directed at the indirect antigen presentation pathway may be of benefit in xenotransplantation.

Animals↗

PubMed1994