Transplant information transfer and analysis in cyberspace.
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Computer Communication Networks↗
Biomedical subjects
R M Merion
Publications and source records attributed to R M Merion.
Update of the Adult and Pediatric Liver Transplant Program at the University of Michigan.
Significant technical innovations and improvements in immunosuppression have been introduced into our liver transplant program since its inception in 1985. The indications for transplantation have been extended to younger and older patients, and simultaneously more patients with comorbidities have been accepted for transplant. The net impact of these changes has been a continuing trend toward improved survival. Overall, patients with hepatitis B or malignancy have had poor survival rates. The introduction of prophylactic anti-hepatitis B immunoglobulin and lamivudine, and better selection of patients with malignancy may improve results for these patients in the future. As in other programs, our most vexing problem is the continuing scarcity of donor organs which has led to an ever-expanding waiting list, more deaths while awaiting transplant, and more suffering before transplantation. The introduction of living donor hepatic transplantation will be of some help in alleviating this shortage. We are confident that the evolution of our program into a joint multidisciplinary structure will provide more efficient, convenient and cost-effective care to our patients.
Adolescent↗
Usefulness of dobutamine stress echocardiography in detecting coronary artery disease in end-stage renal disease.
The cardiovascular evaluation of patients with end-stage renal disease (ESRD) has been hampered by the suboptimal sensitivity and specificity of currently employed diagnostic tests. Dobutamine stress echocardiography (DSE) is a recently developed technique which is accurate for the diagnosis of coronary artery disease (CAD) in general populations. The purpose of this study was to assess its diagnostic accuracy and prognostic implications in patients with ESRD. Patients with ESRD (n = 97) underwent DSE as part of a preoperative evaluation before being listed for renal transplantation. Patients were followed for 12 +/- 6 months (range 1 to 24) after the study. Rest and dobutamine stress echocardiograms were analyzed for regional and global function. Coronary angiography was performed in 30 patients, and 25 underwent renal transplantation in the follow-up period. DSE had a sensitivity of 95% (92% for 1-vessel, 100% for > or = 2-vessel disease), specificity of 86%, and accuracy of 90% for the detection of CAD. During the follow-up period, 6 patients died; DSE revealed inducible ischemia in 4, and catheterization before death revealed multivessel CAD in 2. Conversely, a normal DSE identified a very low risk population, with a 97% probability of being free of cardiac complications or death during the follow-up period. We conclude that DSE accurately identifies CAD in patients with ESRD and identifies a cohort of patients at low risk for cardiac complications.
Adult↗
Subtotal parathyroidectomy in dialysis-dependent and post-renal transplant patients. A 25-year single-center experience.
OBJECTIVE: To determine long-term results and durability of parathyroidectomy in patients with chronic renal failure and renal transplant recipients. DESIGN: Retrospective chart review and structured telephone interviews. SETTING: Tertiary-care academic medical center. PATIENTS: Ninety-one consecutive patients (80 undergoing long-term dialysis, 11 with posttransplant hyperparathyroidism). Mean follow-up was 8 years (minimum follow-up, 2 years; longest follow-up, 25 years). The most common indications for operation were bone pain (70% [56/80]) and weakness (46% [37/80]) in patients with renal failure and hypercalcemia (91% [10/11]) in renal transplant recipients. INTERVENTION: Subtotal parathyroidectomy without remnant gland implantation. MAIN OUTCOME MEASURES: Postoperative morbidity and mortality, relief and recurrence of symptoms. RESULTS: Symptoms were successfully ameliorated in 95% (86/91) of patients. Clinically significant complications occurred in 5% (5/91) of patients (one patient each with wound hematoma, wound infection, and permanent recurrent laryngeal nerve paralysis and two patients with permanent hypoparathyroidism). Recurrence occurred in five (5%) of 91 patients. Two of these patients required four operations each to eradicate all hyperfunctioning accessory glands. The other three recurrences were caused by hyperplasia of the remnant gland left in the neck. These were easily treated by simple excision, with no morbidity. The actuarial rate of recurrent hyperparathyroidism was 4.1% at 1 year and 11.7% at 20 years. Overall hospital mortality was 3% (3/91). None of the deaths was directly attributable to parathyroidectomy. CONCLUSIONS: We recommend subtotal parathyroidectomy without remnant implantation as a safe and durable intervention for hyperparathyroidism associated with renal failure and following renal transplantation. This intervention is associated with an acceptably low recurrence rate over extremely long periods of follow-up.
Adult↗
Corticosteroid withdrawal after liver transplantation.
BACKGROUND: Long-term side effects of corticosteroids (CSs) result in > major morbidity for recipients of orthotopic liver transplants (OLT). We instituted a program of CS withdrawal among OLT recipients to quantify the contribution of CS to adverse clinical sequelae and to determine whether long-term CS administration is necessary to avoid rejection. METHODS: Recipients who had normal allograft function on CS, cyclosporine, and azathioprine more than 1 year after OLT were offered CS withdrawal during 12 to 22 weeks. Patients underwent routine clinical monitoring and laboratory studies. Continuous variables were compared by paired t test analysis. RESULTS: CSs were discontinued in 51 recipients; 45 (88%) of 51 patients remain steroid-free after a mean follow-up of 13.8 months (range, 4 to 36). CS therapy was reinstituted in 6 patients who had abnormal transaminase levels during routine follow-up. Among the patients who remain off CS, there were no significant changes in blood pressure, transaminase, alkaline phosphatase, bilirubin, or glucose levels during the study period. Mean number of blood pressure medications decreased from 0.7 +/- 0.1 to 0.4 +/- 0.1 (p = 0.007). Cholesterol decreased from 217 +/- 8 mg/dl on CS to 204 +/- 9 mg/dl at 1 month (p = 0.0001), 183 +/- 10 mg/dl at 3 months (p = 0.0001), 198 +/- 8 mg/dl at 6 months (p = 0.04), 213 +/- 11 mg/dl at 12 months (p = 0.01), 209 mg/dl +/- 16 at 18 months (p = 0.02), and 183 +/- 19 mg/dl at 24 months (p = 0.2) off CS. Weight loss occurred in 88% of patients and averaged 9.5 pounds. CONCLUSIONS: CS therapy can be successfully withdrawn without precipitating rejection in liver transplant recipients who have stable graft function 1 year after OLT. The incidence and severity of hypertension and hypercholesterolemia are reduced in patients whose CSs have been withdrawn.
Adrenal Cortex Hormones↗
Inhibitory activity of intestinal intraepithelial lymphocytes.
BACKGROUND: Intestinal intraepithelial lymphocytes (iIEL) are the first line of lymphoid cells exposed to orally absorbed foreign antigen. Because of this unique position, we hypothesized that the iIEL down-regulates the immune response to foreign antigen to prevent broad sensitization. METHODS: One-way mixed lymphocyte cultures (MLCs) were performed with Brown Norway (BN) as the responder and irradiated Lewis rats as the stimulator. BN iIEL or control cells (irradiated BN spleen-thymus cells) were added to the MLCs to assess their inhibitory function. RESULTS: When iIEL cells comprised 0.63% of well volumes, a significant (p < 0.05) decline in MLC proliferation was seen. To determine whether this inhibitory action was mediated by a soluble factor, supernatant from iIEL cultured with irradiated Lewis spleen-thymus cells was added to MLCs and was compared with the addition of culture medium as the control group. The iIEL group proliferated significantly less (p < 0.05) than the control group. To further define the mechanism of action, iIEL-conditioned supernatant was treated with neutralizing antibody to transforming growth factor-beta (25 micrograms/ml) or control immunoglobulin. Treated supernatant was then added to an MLC, resulting in a partial loss of inhibitory action. CONCLUSIONS: The iIEL appears to significantly suppress a response to allogeneic stimuli via a mechanism mediated by the action of one or more soluble factors. Transforming growth factor-beta may well be one of the mediators of this inhibitory action.
Animals↗
A double-blind, randomized, placebo-controlled trial of prostaglandin E1 in liver transplantation.
A double-blind placebo-controlled trial of intravenous prostaglandin PGE1 (40 micrograms/h) was conducted in adult orthotopic liver transplant recipients. Infusion was started intraoperatively and continued for up to 21 days. Patients were followed up for 180 days postoperatively. Among 172 patients eligible for treatment in the study, 160 could be evaluated (78 PGE1; 82 placebo). Patient and graft survival were similar (PGE1: 16 deaths, 9 retransplantations [7 survivors]; controls: 15 deaths, 6 retransplantations [3 survivors]). In patients with surviving grafts, however, PGE1 administration resulted in a 23% shorter mean duration of hospitalization following transplantation (PGE1: 24.4 days; controls: 31.8 days; P = .02) and a 40% shorter length of time postoperatively in the intensive care unit (PGE1: 8.2 days; controls 13.7 days; P = .05). Reduced needs for renal support (P = .03) or surgical intervention other than retransplantation (P = .02) were also noted with PGE1 use. Further, PGE1 administration resulted in a trend toward improved survival rates in patients with mild renal impairment (preoperative serum creatinine 1.5 mg percent or greater; P = .08). Neither the incidence of acute cellular rejection nor of primary nonfunction was significantly different in the two groups. Phlebitis was the only complication that was more common during PGE1 administration, (PGE1: 9; controls: 4). These results suggest that PGE1 use in hepatic allograft recipients reduces morbidity and may result in sizable cost reductions.
Adult↗
Mechanisms of hyperacute rejection in porcine liver transplantation. Antibody-mediated endothelial injury.
Hyperacute rejection after OLT is an unusual event. We have demonstrated previously that hepatic hyperacute rejection can occur in the presence of high titers of donor-specific cytotoxic antibody. This study addresses the issues of antibody localization within the allograft and the consequences of antibody deposition and complement activation within the transplanted organ. A porcine model of liver transplantation was used and 3 experimental groups were studied. Group I recipients (n = 6) were specifically sensitized to their liver donors with skin grafts from their liver donors before hepatic grafting. Group II recipients (n = 6) underwent third-party skin graft sensitization before liver transplantation. Group III recipients (n = 6) underwent liver grafting without prior sensitization. After liver transplantation, serum complement (CH50) levels declined promptly in all groups; a statistically significant drop as compared with control animals was seen only in group I (P < 0.05). Liver biopsies from donor-specific sensitized recipients showed massive injury by light microscopy within 30 min of revascularization, demonstrating fibrinoid necrosis of vessels and neutrophil influx. On immunofluorescent examination, liver specimens from donor-specific sensitized animals showed intense IgG, IgM, and C3 deposition in the vessels of the portal triads. Antibody deposition was not seen in third-party sensitized animals or control animals. On electron microscopy, control animals and third-party sensitized animals showed minimal ultrastructural alterations. In comparison, livers from donor-specific sensitized animals showed severe microvascular injury with destruction of endothelial cells, edema, hemorrhage, and hepatocyte necrosis. In a passive serum transfer experiment carried out by infusing serum from a skin graft-sensitized pig directly into the portal vein of the skin graft donor, severe liver injury was evident, with identification of antibody deposition by light and electron microscopy and by immunofluorescence. These studies demonstrate that tissue injury in hyperacute hepatic rejection is mediated by antibody deposition within the grafted liver and is associated with systemic activation of the complement cascade.
Acute Disease↗
P450 3A activity and cyclosporine dosing in kidney and heart transplant recipients.
Interpatient differences in the kinetics of cyclosporine appear to result in part from interindividual differences in the catalytic activity of an enzyme termed P450 3A. We investigated the relationship between P450 3A activity, as measured by the erythromycin breath test (ERMBT), and the appropriate stable daily dose of cyclosporine as currently determined by physicians at our institution. The ERMBT was administered to kidney and heart allograft recipients who had attended at least two monthly clinic visits without having their daily cyclosporine dose changed. There was a significant positive correlation between the ERMBT result and the daily cyclosporine doses (in milligrams per kilogram) in both the heart (r = 0.68; p = 0.04; n = 9) and kidney (r = 0.68; p = 0.03; n = 10) recipients. To confirm our findings, we prospectively administered the ERMBT on multiple occasions to 20 patients who were undergoing kidney transplantation. Although the transplant physicians were blinded to the ERMBT results, the test predicted the stable daily doses of cyclosporine that they ultimately prescribed to the patients (r = 0.54; p = 0.015). When data from all 39 patients were pooled and subjected to multiple regression analysis, the ERMBT was the only variable examined that significantly correlated with the stable daily cyclosporine dose (r = 0.63; p < 0.001; n = 39). In the 20 patients prospectively studied, the prescribed daily dose of cyclosporine generally decreased during the months after surgery and the percentage changes in cyclosporine daily dose correlated with changes in P450 3A activity during this period (r = 0.47; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
CYP3A gene expression in human gut epithelium.
CYP3A4, a major Phase I xenobiotic metabolizing enzyme present in liver, is also present in human small bowel epithelium where it appears to catalyse significant 'first pass' metabolism of some drugs. To determine whether CYP3A4 or the related enzymes CYP3A3, CYP3A5, and CYP3A7 are present in other regions of the digestive tract, we used CYP3A-specific antibodies to examine histological sections and epithelial microsomes obtained from a human organ donor. CYP3A-related proteins were detected in epithelia throughout the digestive tract and in gastric parietal cells, in pericentral hepatocytes, and in ductular cells of the pancreas. Immunoblot analysis suggested that the major CYP3A protein present in liver, jejunum, colon, and pancreas was CYP3A4 or CYP3A3, whereas CYP3A5 was the major protein present in stomach. Both CYP3A4 and CYP3A5 mRNA were detectable in all regions of the digestive tract using the polymerase chain reaction (PCR); however, only CYP3A4 could be detected by Northern blot analysis. CYP3A7 mRNA was consistently detected only in the liver by PCR and CYP3A3 mRNA was not detected in any of the tissues. We conclude that CYP3A4 and CYP3A5 are present throughout the human digestive tract and that differences in the expression of these enzymes may account for inter-organ differences in the metabolism of CYP3A substrates.
Adult↗
Lymphocyte immunologic interactions in intestinal transplantation.
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Animals↗
Renal duplex Doppler ultrasonography: a noninvasive predictor of kidney dysfunction and hepatorenal failure in liver disease.
Hepatorenal failure, a well-recognized complication of established liver disease, is characterized by early renal hemodynamic changes (vasoconstriction) before clinically recognized kidney disease. This renal vasoconstriction (increased renal vascular resistance) should be detectable noninvasively by Doppler ultrasonography. We studied whether renal Doppler ultrasonography detects abnormalities in patients with nonazotemic liver disease and its prognostic value for subsequent kidney status. We observed by renal Doppler ultrasonography 180 patients who had liver disease without azotemia. A simple parameter, resistive index, was derived for each subject on the basis of Doppler waveform analysis. Traditional parameters used to assess patients with liver disease were also recorded at the time of Doppler ultrasonography. Subsequent kidney outcomes were kidney dysfunction (doubling of initial creatinine level to 1.5 mg/dl [133 mumol/L]) or more and the presence or absence of the hepatorenal syndrome. Abnormal results of Doppler examinations (elevated resistive index) were seen in 76 (42%) of the 180 patients. Kidney dysfunction developed in 55% (42/76) of the patients with an elevated resistive index and 6% (6/104) of those with normal results of Doppler study (p < 0.00005). Hepatorenal syndrome developed in 26% (20/76) of subjects with an elevated resistive index and 1% (1/104) of those with a normal resistive index (p < 0.00005). Cox regression analysis identified resistive index as a significant independent predictor of subsequent hepatorenal syndrome (p < 0.00005) and kidney dysfunction (p < 0.00005). Renal duplex Doppler ultrasonography can noninvasively identify a subgroup of nonazotemic patients with liver disease that is at significantly higher risk for subsequent development of kidney dysfunction and the hepatorenal syndrome.
Adolescent↗
Cytomegalovirus and Epstein-Barr virus-acquired immunity after Sandoglobulin prophylaxis in the pediatric renal transplant population.
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Adolescent↗
Superior allograft survival in pediatric renal transplant recipients.
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Adolescent↗
Aortic revascularization of orthotopic liver allografts: indications and long-term follow-up.
BACKGROUND: Occasionally because of certain conditions that would imperil arterial supply to a hepatic graft, it is necessary to base the arterial supply on the aorta. METHODS: Twenty orthotopic liver transplants (OLTs) in 19 patients were performed with arterial revascularization based on the aorta (Ao-OLT). In two patients the donor celiac axis was anastomosed directly to the aorta and in 18 to a conduit anastomosed to either the supraceliac (n = 10) or infrarenal (n = 8) aorta. RESULTS: One thrombosis occurred 2 months after the placement of a supraceliac conduit in an adult patients, accounting for a cumulative 1-year hepatic artery patency rate of 91.7% +/- 8.0% for 16 grafts placed in 15 adults and 100% for four grafts placed in four children. In comparison, hepatic artery-based transplantation was associated with a 1-year patency rate of 92.6% +/- 1.9% for 245 adults and 94.7% +/- 5.1% for 19 children (difference not significant compared with Ao-OLT). By logistic regression analysis, the only factor independently associated with hepatic artery thrombosis was retransplantation (1-year hepatic artery patency rate 85.7% +/- 5.9% [n = 38] for retransplants vs 93.9% +/- 1.7% for primary transplantation [n = 246]; p < 0.05). For retransplantation, Ao-OLT revascularizations were superior to those based on the hepatic artery (1-year patency rate 100% [n = 11] vs 79.9% +/- 8.1% [n = 27]; p < 0.05). CONCLUSIONS: Indications for Ao-OLT include poor hepatic arterial inflow, small or anomalous recipient hepatic arteries, friable or attenuated native hepatic arteries as may be present during retransplantation, and recipient age less than 1 year, especially those less than 15 kg or in whom the recipient artery is less than 3 mm in diameter. In these more precarious situations, Ao-OLT achieves patency rates similar to those of primary, uncomplicated OLT, is superior for retransplantation, and has technical advantages in the small pediatric liver recipient.
Adolescent↗
T cell subset analysis by flow cytometry during MALG induction for pediatric renal transplantation.
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Adolescent↗
Resource utilization and outcome of liver transplantation for alcoholic cirrhosis. A case-control study.
Liver transplantation for alcoholic cirrhosis remains controversial at some transplantation centers. We compared resource utilization and outcome in alcoholic and nonalcoholic cirrhotic patients undergoing liver transplantation. Data were collected from 56 patients who underwent transplantation for alcohol-related cirrhosis from August 1985 to February 1991 and compared with data from a control group matched for age, sex, Child-Pugh class, and date of transplantation. No significant differences were noted in the resource utilization variables examined or in outcome (as assessed by indicators of early graft function, frequency of sepsis, incidence of rejection, renal function, and retransplantation rate). One-year survival was not significantly different (75% for the alcoholic cirrhotic group vs 76% for the nonalcoholic cirrhotic group). We conclude that liver transplantation for end-stage alcohol-related cirrhosis provides excellent results and that resource utilization appears to be equivalent to that for patients undergoing transplantation for non-alcohol-related cirrhosis.
Actuarial Analysis↗
Biochemical and histopathological correlation in liver transplant: the first 180 days.
It is not known whether the histopathology of the liver allograft can be predicted from biochemical measurements in serum with the same confidence as in the native liver. To answer this question we compared the histopathological diagnoses in 170 biopsy specimens from 70 adult transplant recipients obtained during the first 180 days, with the concentrations of the serum bilirubin and the activities of AST, ALT and alkaline phosphatase measured at the same time. The most frequent diagnosis was cholestasis (n = 45), which was mild, moderate or severe and which may have been complicated by rejection (n = 28) or ischemia (n = 14). Hepatitis (n = 14), ischemia with rejection (n = 6) and spotty focal necrosis (n = 6) were diagnosed less frequently. Fifteen biopsy specimens were reported as histopathologically normal. In general, biochemical measurements discriminated poorly between different histopathological diagnoses. The histopathologically normal liver often showed an abnormal pattern of enzymes and an increase in the serum bilirubin level. As a result histopathologically normal biopsy specimens were indistinguishable biochemically from those with hepatitis. When two pathological conditions were found to coexist (e.g., cholestasis with either rejection or ischemic necrosis, or ischemic necrosis with rejection), the effect on the serum biochemistry was usually not additive and in some instances returned the biochemical abnormalities toward normal. With the exception of the serum bilirubin level, which increased with the severity of uncomplicated cholestasis, we could not identify a specific pattern of biochemical changes corresponding to a given histopathological diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗