What's new in transplantation.
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Animals↗
Biomedical subjects
J F Burdick
Publications and source records attributed to J F Burdick.
Induction of heat-shock gene expression in postischemic pig liver depends on superoxide generation.
BACKGROUND/AIMS: Both hemorrhagic and cardiogenic shock are associated with hepatic shock gene expression at resuscitation. This study investigated the potential role of intravascular superoxide anion as a proximal trigger of heat shock protein gene expression. METHODS: Preanesthetized pigs were subjected to 120 m of total warm hepatic ischemia. The survival model consisted of warm, total hepatic ischemia and reperfusion (with active portal-systemic bypass) followed by reperfusion and survival for 3 days. Serial hepatic biopsy samples were evaluated for the expression of heat shock protein 72 (HSP-72) messenger RNA (mRNA) by Northern and Western analysis and by in situ RNA hybridization. The possible role of intravascular O2- as a mediator of heat shock response was evaluated by its specific inhibition by the intravenous infusion of recombinant human superoxide dismutase (SOD). RESULTS: Ischemia for 120 minutes followed by 60 minutes of reperfusion caused accumulation of HSP-72 mRNA. Transcripts were localized to hepatocytes. HSP-72 mRNA was detected neither following ischemia alone nor when SOD was infused for 15 minutes at reperfusion. Three days later, transcripts were not detectable, but HSP-72 protein accumulated irrespective of SOD administration. CONCLUSIONS: Warm hepatic ischemia induces the hepatocyte expression of HSP-72 at reperfusion by a mechanism that is dependent upon the superoxide anion, probably generated intravascularly. However, the transient dismutation of superoxide is insufficient to suppress subsequent accumulation of HSP-72.
Animals↗
Visceral lipid peroxidation occurs at reperfusion after supraceliac aortic cross-clamping.
PURPOSE: Recently, we have reported that lipid peroxidation specific to oxygen free radical-mediated injury increased immediately after reperfusion of human liver allografts. However, in the human liver transplantation setting it was impossible to disassociate the contributions to lipid peroxidation caused by the warm and cold ischemic phases from those caused by reperfusion. Therefore we now have studied lipid peroxidation at reperfusion after supraceliac aortic cross-clamping in patients with normal livers. METHODS: Ethane, a noninvasive biomaker of lipid peroxidation, was measured in exhaled breath of patients before and during cross-clamping of the thoracic aorta and at sequential time intervals after visceral reperfusion. RESULTS: Approximately a two-fold transient increase in the ethane level was observed at around 15 minutes after reperfusion in those patients whose aortas were cross-clamped for more than 18 minutes. CONCLUSIONS: These results indicate that free radical-mediated lipid peroxidation occurs at reperfusion of warm ischemic viscera in the clinical setting of aortic repair. This observation supports the hypothesis that substantial lipid peroxidation occurs when tissues are subjected to cold or warm ischemia followed by reperfusion.
Aged↗
Oligoclonal V beta usage in vitro after in vivo exposure to pig xenoantigen extracorporeal pig liver perfusion.
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Animals↗
Role of naturally occurring xenoantibodies in hyperacute rejection strengthened by their avid binding to ex vivo pig to human liver xenografts and to isolated pig liver preparations.
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Animals↗
Morphology of ischemic acute renal failure, normal function, and cyclosporine toxicity in cyclosporine-treated renal allograft recipients.
To characterize morphologic changes in the early post-transplant period in cyclosporine-treated renal allograft recipients, we examined biopsies from three groups of cyclosporine-treated patients: normal function (N = 9), ischemic acute renal failure or "acute tubular necrosis" (N = 12), and cyclosporine toxicity (N = 7). Groups were compared with each other and with previously studied groups of azathioprine-treated patients and native kidney patients. The interstitial infiltrate commonly observed in normally functioning azathioprine-treated grafts was not observed in normally functioning cyclosporine-treated grafts, but two of nine such grafts had a significant venulitis, a change also seen in three of the patients with cyclosporine nephrotoxicity. "Acute tubular necrosis" (ATN) in cyclosporine-treated graft recipients was characterized by focal necrosis of complete tubular cross sections, a finding normally rare in other types of ATN, and by shedding into the tubular lumen of tubular cells with non-pyknotic nuclei, a finding supporting our previous observation of detachment of viable tubular cells in ATN but not in the normal kidney. Hyaline arteriolar thickening was the only morphologic finding on biopsy which distinguished patients with cyclosporine nephrotoxicity from other groups. In summary, the morphologic changes observed in cyclosporine-treated renal allograft recipients with ATN or normal function are quite different from those observed in azathioprine-treated patients. Cyclosporine appears to enhance the tubular injury observed in ATN. Hyaline arteriolar thickening is the main distinguishing feature of cyclosporine nephrotoxicity.
Adult↗
International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology.
A group of renal pathologists, nephrologists, and transplant surgeons met in Banff, Canada on August 2-4, 1991 to develop a schema for international standardization of nomenclature and criteria for the histologic diagnosis of renal allograft rejection. Development continued after the meeting and the schema was validated by the circulation of sets of slides for scoring by participant pathologists. In this schema intimal arteritis and tubulitis are the principal lesions indicative of acute rejection. Glomerular, interstitial, tubular, and vascular lesions of acute rejection and "chronic rejection" are defined and scored 0 to 3+, to produce an acute and/or chronic numerical coding for each biopsy. Arteriolar hyalinosis (an indication of cyclosporine toxicity) is also scored. Principal diagnostic categories, which can be used with or without the quantitative coding, are: (1) normal, (2) hyperacute rejection, (3) borderline changes, (4) acute rejection (grade I to III), (5) chronic allograft nephropathy ("chronic rejection") (grade I to III), and (6) other. The goal is to devise a schema in which a given biopsy grading would imply a prognosis for a therapeutic response or long-term function. While the clinical implications must be proven through further studies, the development of a standardized schema is a critical first step. This standardized classification should promote international uniformity in reporting of renal allograft pathology, facilitate the performance of multicenter trials of new therapies in renal transplantation, and ultimately lead to improvement in the management and care of renal transplant recipients.
Graft Rejection↗
Breath ethane: a specific indicator of free-radical-mediated lipid peroxidation following reperfusion of the ischemic liver.
A major component of the organ injury mediated by toxic oxidants, such as seen following reperfusion of the ischemic liver, is due to the peroxidation of polyunsaturated fatty acids, especially of cell membranes. We utilized the measurement of exhaled breath ethane, a metabolic product unique to oxidant-mediated lipid peroxidation, as a noninvasive indicator of this process in swine liver subjected to warm ischemia/reperfusion. Under rigorously controlled anesthesia conditions, pig livers were subjected to 2 h of warm total ischemia, followed by reperfusion in situ. Expired air was collected and its ethane content quantitated by a novel gas chromatographic technique. The time course of breath ethane generation correlated closely with the appearance of hepatocellular injury as measured by impairment of Factor VII generation and other measures of liver integrity. Moreover, the administration of the specific superoxide free radical scavenger, superoxide dismutase (SOD), significantly attenuated both the elaboration of ethane and the hepatocellular injury. These findings not only provide confirmation of the previously reported link between hepatocellular injury by free radicals generated at reperfusion, but also establish the use of expired breath ethane analysis as a sensitive, specific, and noninvasive indicator of the injury process in real time.
Alanine Transaminase↗
A pilot study to assess the ability of an orally available selective thromboxane synthase inhibitor to improve renal function in cyclosporine-treated renal transplant recipients.
Six cyclosporine (cyclosporine A [CsA])-treated renal transplant patients (4.3 +/- 0.6 months posttransplantation) were studied to see if selective urinary thromboxane (TX) inhibition with CGS 12970 (TX synthase inhibitor) would improve renal function and lessen CsA-induced decrements in RPF and GFR as measured by [99Tc]DTPA and [131I]hippuran clearances. The baseline trough CsA levels of the patients were 208 +/- 92 ng/mL. Before treatment with CGS 12970 (100 mg twice a day for 7 days), all drugs known to affect renal function or CsA pharmacokinetics were stopped. CGS 12970 therapy did not alter RPF (203 +/- 17 pre versus 200 +/- 15 mL/min post), GFR (38.5 +/- 3.2 pre versus 38.2 +/- 3.9 mL/min post), or serum creatinine (creat) (1.9 +/- .06 pre versus 1.8 +/- 0.18 mg/dL post), despite an average of 81% suppression of urine TX (65 +/- 14 pg/mg of creat pre versus 12 +/- 4 pg/mg of creat post); P less than 0.01), as measured by gas chromatography/mass spectrometry. CGS 12970 had no significant effect on urinary 6-keto-prostaglandin F1 alpha levels (63 +/- 4 pg/mg of creat pre versus 85 +/- 25 pg/mg of creat post). CGS 12970 did not alter CsA pharmacokinetics or drug levels, blood pressure, weight, or serum electrolytes of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Does contralateral internal carotid artery occlusion increase the risk of carotid endarterectomy?
The results of every carotid endarterectomy performed contralateral to an internal carotid artery occlusion (n = 36) (group I) were compared with those performed contralateral to a patent internal carotid artery (n = 169) (group II) over the last 10 years. The patients in each group were evenly matched with respect to male gender (66% vs 69%); mean age (66.7 vs 65.9 years); and incidence of hypertension (55.6% vs 53.2%), diabetes (16.7% vs 20.1%), and hyperlipidemia (8.3% vs 11.8%). Patients in group I had a higher incidence of previous myocardial infarction (25% vs 11.8%, p less than 0.05) and exertional angina (55.6% vs 29.6%, p less than 0.01). Indications for carotid endarterectomy were equivalent, including stroke (19.4% vs 21.9%), transient ischemic attacks (36.1% vs 35.5%), amaurosis fugax (16.7% vs 11.8%), nonhemispheric symptoms (5.6% vs 8.3%), and asymptomatic stenoses (22.2% vs 22.5%), respectively. Perioperative strokes occurred in one (2.8%) patient in group I and seven (4.1%) patients in group II (NS). Among the patients in group II the incidence of perioperative stroke did not correlate directly with the degree of contralateral ICA stenosis: greater than 90% (4%); 70% to 90% (6.7%); 50% to 70% (8.7%); and less than 50% (2.8%). The operative mortality rate was 0% among patients in group I and 1.2% among patients in group II (NS). Cardiac complications occurred in two (5.6%) patients in group I and nine (5.3%) patients in group II (NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Graft-specific MHC class II gene expression in response to allogeneic stimulus in heterotopic murine cardiac allografts.
Although, major histocompatibility complex (MHC) class II antigen expression in allografts is thoroughly studied, regulation of the genes for these antigens is not fully understood. The graft-specific MHC class II genes are potentially important in determining the immunogenicity of graft but their detection in a mixed-cell population such as in the allograft would require unambiguous differentiation of graft-specific class II expression from those in host lymphoid cells. With an oligonucleotide probe that specifically hybridizes to I-Ab mRNA from H-2k haplotype mice, we have studied I-A gene expression in cardiac allografts heterotopically transplanted from B10.Br (H-2k) to B10.D2 (H-2d) mice. Normal B10.Br hearts do not have appreciable I-Ab transcripts as determined with this probe, but 4 days after allografting, a substantial increase in I-Abk messenger RNA (mRNA) content was noted in the allografted hearts which persisted for the next 2 days and then decreased concomitant with destruction of the heart. The increase in I-Abk mRNA preceded the expression of surface Iak antigens on dendritic and endothelial cells in the allograft. These data indicate increased transcription of the I-Ab gene in cells of graft origin suggesting that transcriptional regulation is the initial mechanism for expression of class II genes in allografts. The sustained rise in graft-specific class II mRNA also seen in these allografts suggests that increased mRNA stability may be another mechanism for the increased density of class II antigens in allografts undergoing rejection.
Animals↗
Liver transplantation after hepatic failure during pregnancy.
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Female↗
Reduction of morbidity and mortality from biliary complications after liver transplantation.
Over a 4-yr period that began October 1, 1986, 103 orthotopic liver transplants were performed on 91 patients at the Johns Hopkins Hospital. Biliary reconstruction at the time of transplantation was performed in standard fashion by an appropriately trained member of the surgical team. Six (7%) patients developed biliary complications, which included three cases of common bile duct stricture and one case each of bile duct obstruction caused by biopsy-related hemobilia, biloma and a retained fragment of a T tube after removal. Five of the six patients were treated successfully by nonoperative interventional radiological procedures performed under local anesthesia with light intravenous sedation. Reoperative surgery (to remove the T-tube fragment from subcutaneous tissue) was required for only one patient, and no deaths (0 of 91) were attributable to biliary complications. All six patients are alive and well 6 to 33 mo after the operation with excellent liver function. Our findings would suggest that most biliary complications of orthotopic liver transplants are avoidable and that the few that do appear can usually be managed both safely and effectively by an interventional radiological approach.
Adult↗
Femoro-femoral or ilio-femoral bypass for unilateral inflow reconstruction?
Femoro-femoral and ilio-femoral bypass are two popular options for unilateral inflow reconstruction. In order to evaluate these alternative approaches, the records of 70 consecutive patients who underwent either femoro-femoral (n = 50) or ilio-femoral (n = 22) grafts were retrospectively reviewed. There were 46 men and 24 women, ranging in age from 27 to 84 years (mean: 66 years). Operative mortality was 10% for all femoro-femoral procedures, including 50% for emergent, 14% for synchronous, and 0% for solitary procedures; mortality was 9% for all ilio-femoral grafts including 20% for synchronous and 6% for solitary procedures. Among the elective solitary procedures, there was no significant difference with respect to operative time, blood loss, fluid requirement, time until resuming an oral diet, or duration of postoperative course for the two procedures. Five-year patency was 93% for all ilio-femoral and 57% for all femoro-femoral grafts. Although femoro-femoral bypass has been the more popular option for unilateral inflow reconstruction in this and other institutions, these findings justify the more widespread use of ilio-femoral bypass.
Adult↗
Angiographic localization of spinal cord blood supply and its relationship to postoperative paraplegia.
Forty-seven patients underwent selective catheterization of middle and lower thoracic intercostal and upper lumbar arteries to define the origin of the artery of Adamkiewicz. One patient had significant atheroembolism, and a second had transient lower extremity paresthesias. No other complications occurred. The origin was found in 26 (55%), and 21 patients underwent thoracoabdominal aneurysm repair with this knowledge. When the critical lumbar or intercostal artery could be included as part of a long proximal or distal anastomosis, all 12 patients could be included as part of a long proximal or distal anastomosis, all 12 patients survived, and one was paralyzed. However, if the aneurysm repair mandated a midgraft anastomosis to intercostal arteries critical to spinal cord perfusion, seven of nine patients either died or were paralyzed (p less than 0.05). In the group of 19 patients operated on in whom spinal cord blood supply was not identified three patients had a technically unsuccessful operation; two died, and one was paralyzed. Twelve of 16 patients who had an adequate, but unsuccessful attempt at localization were treated by intercostal "neglect" and survived. Late paresis developed in two patients, but they are walking now. One of the patients who died had multiple systems failure and awakened paraplegic. She had a patent, enlarged, thoracic radicular artery at T-5 which probably supplied to spinal cord and which was missed angiographically. Paralysis was associated with aneurysm extent (group 2 and III B, dissections vs group 1 & 3, p less than 0.05). Selective intercostal angiography requires further refinement, but it is safe and offers the promise of understanding the mechanisms and risks of spinal cord complications after repair of extensive thoracoabdominal aneurysms.
Adult↗
Progression to total occlusion is an underrecognized complication of the medical management of carotid disease.
One potential complication of carotid disease is progression to total occlusion while under medical management. To investigate this important issue, 44 patients (31 men; 13 women) ranging in age from 44 to 83 (mean, 65.9) years with internal carotid artery occlusions as a result of arteriosclerosis were identified among 993 patients undergoing carotid angiography from Jan. 1, 1985 to Dec. 31, 1989, and their prior medical records were reviewed. Clinical presentations included stroke in 9 (20.5%), retinal infarct in 8 (18.2%), transient ischemic attacks in 10 (22.7%), amaurosis fugax in 4 (9.1%), nonhemispheric symptoms in 3 (6.8%), and 10 (22.7%) were asymptomatic. A review of these patients' medical records documented that prior hemispheric symptoms referrable to the now occluded internal carotid artery had occurred in five (55%) of the nine patients who were admitted with stroke, five (62%) of the eight patients with a retinal infarct, six (60%) of the 10 patients who were admitted with a transient ischemic attack, all four (100%) patients who were admitted with amaurosis fugax, one (33%) of three patients with nonhemispheric symptoms, and in seven (70%) of the 10 patients who were asymptomatic when the internal carotid artery occlusion was identified angiographically. In summary, 28 (64%) of the 44 patients had experienced ipsilateral symptoms from 2 to 120 (mean, 30) months before the diagnosis of internal carotid artery occlusion; only eight (28%) had undergone noninvasive or angiographic evaluation, and all were placed on antiplatelet therapy when prior hemispheric symptoms developed.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Factors affecting early diagnosis of organ allograft rejection.
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Biopsy↗
Vascularized bone allografts: in vitro assessment of cell-mediated and humoral responses.
The immunologic consequences of transplantation of vascularized bone allografts have not been previously characterized. In this study, knee allografts, both vascularized and nonvascularized, were transplanted from Lewis rats to Brown Norway rats across a strong histocompatibility barrier. A total of 66 transplants and 8 control animals were evaluated. The vascularized knee grafts consisted of 1 cm of proximal tibia and distal femur with a minimal muscular cuff isolated on the femoral vessels, and these were transplanted to a heterotopic, subcutaneous position on the abdominal wall of the recipient rat. Nonvascularized allografts (identical but without anastomoses) were transplanted for comparison. The cell-mediated response was measured by lymphocytotoxicity assay, and the humoral response was measured by cytotoxic antibody assay, both employing 51Cr-labeled target cells. The timing and intensity of the immune response differed according to the type of graft. The vascularized bone allografts generated significant cell-mediated and humoral responses as early as 5 days posttransplant. A significant humoral response in nonvascularized bone allografts was not apparent until day 14, while cell-mediated response in these grafts was variable. These findings were correlated with the histologic appearance of the grafted tissue. Cyclosporine, which was administered to one group of vascularized bone allografts, resulted in the suppression of both types of immune responses. The histologic appearance of this group resembled that of isografts transplanted as controls. The clinical application of vascularized bone allografts may offer significant advantages over nonvascularized allografts in the reconstruction of massive bone defects. Complications such as nonunion, fracture, and collapse of articular segments seen in nonvascularized allograft transplantation may be avoided by preservation of the blood supply to the graft. Characterization of the immune response to vascularized bone allografts may subsequently allow the manipulation of the host and/or graft tissue and promote graft incorporation.
Analysis of Variance↗