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Biomedical subjects

R M Merion

Publications and source records attributed to R M Merion.

At least 73 records · Page 4Linked to original sources
PubMed1992

Selection for and outcome of liver transplantation in alcoholic liver disease.

It has been proposed that evaluation of alcoholic patients for liver transplantation should comprise a multidisciplinary program including medical, surgical, and psychiatric assessment. This article presents the outcome in 99 alcoholic persons evaluated from 1985 through 1989. Alcoholism was defined as alcohol dependence or abuse according to the DSM-III-R. Forty-five patients (43%) were considered suitable candidates and underwent transplantation. Actuarial survival in this group was 78% and 73% at 12 and 24 months, respectively, and did not differ from that observed in nonalcoholic recipients. Return to alcohol use after transplantation has been documented in 5 persons, 2 of whom have had episodes of uncontrolled drinking. Of 54 patients not selected for transplantation, 17 were considered too well and suitable for alternative therapy. Actuarial survival was 93% at 12 and 18 months but declined to 59% at 24 months. Nineteen patients were medically unsuitable and had very poor survival; survival was 35% at 3 months and 0% at 12 months. Seventeen patients were not selected on psychiatric grounds. Actuarial survival in this group (65% at 12 months, 43% at 18 months) was significantly less than that in alcoholics with transplants (P less than 0.05). There were no differences in age, sex ratio, degree of hepatic dysfunction, or duration of abstinence between alcoholics with transplants and those considered psychiatrically unsuitable. It was concluded that liver transplantation is successful in selected patients with alcoholic cirrhosis, that patients who are not selected because they are "too well" need continuing surveillance as a significant decline in survival can occur 18-24 months after initial evaluation and, finally, that patients not selected on psychiatric grounds have a significantly worse survival rate than those with transplants.

Adolescent↗
PubMed1992

Recurrence of hepatitis B and delta hepatitis after orthotopic liver transplantation.

The clinical course of 10 liver transplant recipients who had hepatitis B virus (HBV) and five recipients with HBV and D (delta) infection before transplantation is described. Six patients who underwent eight transplants died. The estimated one and two year survival rates in patients with HBV only before transplantation were 74% and 67% respectively. The estimated one and two year survival in patients with HBV and HDV infection beforehand was 100%. Graft infection by HBV occurred in 8 of 10 patients infected with HBV only; and in 4 of 5 patients with previous HBV and HDV infection. There was a widely variable time from transplantation to the appearance of HBV markers in liver or serum, ranging from 6-331 days. Hepatitis D antigen (HDAg) appeared in three grafts very rapidly after transplantation at 4, 8, and 37 days respectively. Graft infection by HBV was accompanied by significant liver injury in six allografts in five recipients. In particular, there was a striking morphological appearance in five infected livers in which the hepatocytes became progressively enlarged and distorted as they accumulated huge amounts of hepatitis B surface and core antigens (HBsAg, HBcAg). These features were accompanied by pericellular fibrosis and cholestasis but little associated inflammation. This syndrome carried a poor prognosis. A gradual progression to cirrhosis occurred in one additional liver. Finally, recurrent HBV infection was a principal or a contributing factor in all deaths. The presence of HBcAg and inflammation in he native liver increased the risk of HBV induced tissue damaged in the graft whereas HDV infection in the host liver seemed to reduce the risk of significant HBV induced tissue damage in the allograft. These data suggest that post transplant HBV infection is accompanied by a variety of changes in the liver allograft, some of which are unique to the transplanted liver and may result in impaired allograft function.

Adolescent↗
PubMed1992

Renal dysfunction in hepatic disease: early identification with renal duplex Doppler US in patients who undergo liver transplantation.

To improve early detection of renal dysfunction in patients who undergo liver transplantation, a prospective study was performed with intrarenal duplex Doppler sonography before and after liver transplantation in 42 patients. The duplex Doppler findings were compared with multiple clinical and laboratory findings; patients were grouped on the basis of preoperative renal resistive index (RI) and serum creatinine level. The mean initial renal RI was elevated (.73 +/- .07 [standard deviation]); after transplantation, it was lower (.60 +/- .06) (P less than .001). Thirty-six patients had a normal serum creatinine level at the preoperative Doppler examination. Patients with an elevated renal RI (n = 19) had a greater chance of subsequent renal dysfunction (P less than .001), hemodialysis (P less than .01), longer stays in the intensive care unit (P less than .05), and longer hospital stays after surgery (P less than .05) than those with a normal renal RI (n = 17). In 34 patients the RI fell 10% or more after surgery and none died, whereas five of eight patients (62%) whose RI fell less than 10% died. Doppler analysis enabled identification of patients without azotemia whose course of disease before and after surgery was similar to that of patients with clinically recognized renal disease.

Adolescent↗
PubMed1992

Preoperative risk factor assessment in liver transplantation.

BACKGROUND: Despite the increasing success of liver transplantation, there is lack of objective data defining appropriate candidate suitability. This study was undertaken to determine preoperative risk factors that independently or in combination affected outcome after orthotopic liver transplantation. METHODS: We reviewed data on 229 consecutive adult liver transplant recipients. Thirty-one preoperative risk factors recorded at the time of listing and immediately before transplantation were analyzed. Outcome variables included hospital mortality rates, bacterial or fungal sepsis, and the need for renal support. RESULTS: The overall hospital mortality rate was 15.7%. Patients who were in the intensive care unit immediately before transplantation had the highest hospital mortality rate (32.6%; p = 0.006), incidence of bacterial sepsis (51%; p = 0.001), fungal infection rate (27.6%; p = 0.001), and need for renal support (38.7%; p = 0.001). Preoperative renal dysfunction was significantly associated with sepsis and was reflected in higher hospital mortality rates (29.5%; p = 0.011). Child-Pugh class C was associated with higher mortality rates (23.9%; p = 0.017), an increased incidence of bacterial (37.2%; p = 0.020) and fungal infection (20.3%; p = 0.049), and a 30.4% requirement for postoperative renal support (p = 0.004). CONCLUSIONS: These results emphasize the need for earlier referral and transplantation in patients with advanced liver disease. Further studies are needed to refine identified risk profiles and devise strategies to decrease morbidity and mortality rates.

Adult↗
PubMed1991

First-pass metabolism of cyclosporin by the gut.

Cyclosporin is thought to be exclusively metabolised in the liver. We instilled cyclosporin into the small bowel of 2 patients during the anhepatic phase of liver transplantation; cyclosporin metabolites were readily detected in portal venous blood. Our findings indicate that the small intestine is a major site of cyclosporin breakdown: such intestinal metabolism might help to explain the poor oral bioavailability and drug interactions of cyclosporin.

Biological Availability↗
PubMed1991

Liver transplant for fulminant hepatic failure.

Fulminant hepatic failure is a challenging indication for liver transplantation because of associated multiple organ failure, profound neurologic abnormalities and coagulopathy. Sixteen patients have undergone emergent orthotopic liver transplantation for this indication at the University of Michigan, Ann Arbor, Michigan. Despite the associated problems, patient survival (68.2% at 2 years), intra-operative blood product utilization and duration of surgery were comparable to patients receiving liver transplants for other indications. All patients experienced complete recovery from preoperative neurologic abnormalities. Recurrent viral hepatitis did occur but did not result in allograft loss. For selected patients, orthotopic liver transplantation is excellent therapy for patients presenting with fulminant hepatic failure.

Adolescent↗
PubMed1991

Combined hepatic and renal transplantation in primary hyperoxaluria type I: clinical report of nine cases.

PURPOSE AND PATIENTS AND METHODS: The purpose of this article is to report the experience of three centers with combined hepatic and renal transplantation for pyridoxine-resistant primary hyperoxaluria type I (alanine:glyoxylate aminotransferase [EC 2.6.1.44] deficiency), with particular emphasis on the selection criteria and timing of the operation. Nine patients with this inherited disease were treated by combined hepatic and renal transplantation. The former replaces the enzyme-deficient organ while the latter replaces the functionally affected organ. RESULTS: One patient with gross systemic oxalosis died in the immediate postoperative period and another died 8 weeks postoperatively of a generalized cytomegalovirus infection, having shown evidence of biochemical correction. One patient with particularly severe osteodystrophy at the time of the operation died 14 months postoperatively from renal failure due to progressive calcium oxalate nephrocalcinosis involving the transplanted kidney, plus thromboembolic disease. He also had very extensive systemic oxalosis. An additional patient with severe osteodystrophy died 9 months postoperatively. One patient developed hyper-rejection of the kidney and died later of gastrointestinal hemorrhage. The four long-term survivors (22 to 38 months) have remained asymptomatic from the standpoint of their renal disease, with resolution of any manifestations of systemic oxalosis that they may have had. They are either employed or continuing their education. CONCLUSIONS: A prolonged period of end-stage renal failure treated by dialysis regimens that are suitable for non-hyperoxaluric renal failure and extensive systemic oxalosis, particularly oxalotic osteodystrophy, are poor prognostic features. We propose that hepatic transplantation should be considered as definitive treatment before end-stage renal failure develops. This should be supplemented by renal transplantation with vigorous pre- and perioperative hemodialysis to deplete the body stores of oxalate. Although some authorities would reserve hepatic transplantation for patients in whom renal transplantation has failed, we suggest that combined liver and kidney transplantation is appropriate in patients who have never had a renal graft. Furthermore, the time has come to consider hepatic transplantation before any irreversible renal damage has occurred in these patients.

Adolescent↗
PubMed1991

Obesity and renal transplantation.

In this study, we examined the influence of pre-existing obesity (weight more than 120 per cent of ideal body weight) on outcome after renal transplantation. Among 263 cyclosporine-treated recipients of renal allografts, 223 (85 per cent) were nonobese and 40 (15 per cent) were obese prior to transplantation. Obese and nonobese recipients were similar with regard to age, sex, renal diagnosis, history of prior transplant, donor source, pretransplant blood pressure, pretransplant antihypertensive agents, diabetic recipients with insulin requirements more than 40 units per day and pretransplant serum cholesterol. Duration of hospitalization was similar (26 +/- 25 versus 25 +/- 14 days; p = NS). There was a significantly higher incidence of wound infections in obese recipients (17.5 versus 6.3 per cent; p = 0.036); other complications occurred with similar incidence. Preoperative per cent of ideal body weight correlated with post-transplant weight gain during the first post-transplant year (p = 0.00002). After one year, obese recipients had gained 14.2 +/- 2.2 kilograms compared with 8.9 +/- 0.6 kilograms for nonobese patients (p = 0.002). Mean doses of prednisone, azathioprine and cyclosporine were similar at three, six and 12 months post-transplant. There were no differences in blood cyclosporine, serum cholesterol or blood glucose levels at any time. Blood pressure measurements were similar throughout the first post-transplant year. There was no difference in the incidence or number of rejection episodes. Actuarial patient survival rate for nonobese patients was 93 per cent at three years. For obese patients, three year actuarial patient survival rate was 90.5 per cent (p = NS). Actuarial graft survival rate among nonobese patients was 71.8 per cent at three years. For obese patients, three year actuarial graft survival rate was 64.5 per cent (p = NS). In conclusion, obese patients with end stage renal disease are good candidates for renal transplantation. Obesity does not seem to constitute a major risk factor, the most notable adverse outcomes being an increased incidence of wound infection and continued weight gain through the first post-transplant year.

Actuarial Analysis↗
PubMed1990

Cyclosporin toxicity at therapeutic blood levels and cytochrome P-450 IIIA.

A 40-year-old male liver allograft recipient had neurological dysfunction and renal failure while his cyclosporin blood levels were in the therapeutic range; these features recurred on rechallenge. The hypothesis that this toxic effect might have resulted from abnormal metabolism of cyclosporin by liver cytochrome P-450 IIIA was investigated with the [14C]erythromycin breath test, which is a measure of this enzyme's activity. P-450 IIIA activity was decreased compared with that in controls, including other liver transplant recipients. Pretreatment with rifampicin, an inducer of P-450 IIIA, increased enzyme activity. After treatment with rifampicin the patient could be rechallenged with cyclosporin at a dose almost twice that which had previously been toxic. The patient died during a second transplantation and the microsomal content of P-450 IIIA was found to be low in the first transplant.

Administration, Oral↗
PubMed1990

Estimation of in vivo reticuloendothelial system phagocytic activity in rats by direct blood clearance techniques and nuclear scintigraphy.

There has been considerable interest in the examination of reticuloendothelial system phagocytic blockade. In this study, the kinetics of phospholipid liposome-mediated and intraperitoneal silica-mediated phagocytic blockade were examined using five methods of analysis of in vivo 99mTc-labeled albumin clearance and reticuloendothelial cell uptake. Two direct blood sampling techniques revealed significant impairment in 99mTc-labeled albumin clearance after treatment with silica (P less than 0.05), while liposome treatment was not associated with such impairment. A method utilizing nuclear scintigraphy for the determination of blood clearance was incapable of detecting silica-mediated blockade but demonstrated significant impairment by liposomes at 2 hr (P less than 0.001), 6 hr (P less than 0.05), and 24 hr (P less than 0.001). Gamma camera imaging methods for determination of hepatic uptake demonstrated significant (P less than 0.05) and reversible impairment of 99mTc-labeled albumin uptake by liposomes. The most promising of these techniques utilizes deconvolutional analysis of liver region of interest time-activity curves to correct for continuously changing blood concentrations of tracer and for intracellular tracer processing and catabolism. Measurements of reticuloendothelial system phagocytic activity should include methods that take into account the observed discrepancies between blood clearance determinations and reticuloendothelial cell uptake.

Albumins↗
PubMed1990

A prospective controlled trial of cold-storage versus machine-perfusion preservation in cadaveric renal transplantation.

A prospective controlled study was carried out in 60 consecutive cadaver renal donors comparing cold storage to pulsatile machine-perfusion preservation. Each donor served as its own control, by allocating one of the kidneys to each of the two preservation methods. There were 51 evaluable pairs of kidneys. Recipient age, panel-reactive antibody level, history of prior renal transplant, and immunosuppressive regimen were similar in the two preservation groups. Almost all recipients were treated with cyclosporine, and over 50% received antilymphoblast globulin. Total cold ischemic time was 1262 +/- 387 min in the machine-perfused group and 1309 +/- 426 min in the cold-storage group (P = NS). Prolonged ischemia (greater than 24 hr) occurred in 31% of machine-perfused and 22% of cold-stored kidneys (P = NS). Post-operative serum creatinine levels at 1, 7, and 30 days posttransplant were similar in both groups. Dialysis requirements were also similar, with 21 recipients of machine-perfused kidneys (41%) requiring at least one dialysis treatment compared to 16 patients (31%) in the cold-stored group (P = NS); the mean number of dialysis treatments required was 3.14 +/- 1.46 and 3.06 +/- 1.29, respectively (P = NS). Long ischemic time (greater than 24 hr) was associated with a higher rate of dialysis requirement in both groups, but in neither case did this achieve statistical significance. The distribution of graft losses within the first 30 days was similar in both groups, and the incidence of preservation-related graft failure was not significantly different. These results demonstrate that, in the cyclosporine era, machine perfusion offers no significant advantages over cold storage for cadaver renal preservation. Because machine perfusion is considerably more expensive and cold storage is simpler and facilitates the logistics of organ sharing, we recommend simple hypothermic storage of renal allografts as the preservation method of choice.

Analysis of Variance↗
PubMed1990

Hyperacute rejection in porcine liver transplantation. I. Clinical characteristics, histopathology, and disappearance of donor-specific lymphocytotoxic antibody from serum.

Hyperacute rejection following orthotopic liver transplantation remains an extremely unusual occurrence. In this study, we examined a porcine model of liver transplantation in which recipient animals were sensitized prior to transplantation with three serial full-thickness skin grafts. Three experimental groups were studied. Group I recipients (n = 6) were specifically sensitized against their liver donors with biweekly skin grafts followed by hepatic grafting. Group II recipients (n = 6) underwent third-party skin graft sensitization prior to liver transplantation. Group III recipients (n = 6) underwent liver grafting without sensitization. Mixed lymphocyte cultures were done before each skin graft and prior to transplantation. Lymphocytotoxic antibody (LCTA) titers were measured before the first skin graft, at weekly intervals thereafter, intraoperatively, and daily postoperatively until death. Intraoperative and postmortem liver biopsies were obtained in all recipients. Five of six recipients in Group I died within 4 hr of hepatic revascularization. The remaining animal survived for four days. Mean survival time in group I was 0 +/- 0.7 days. In contrast, MST in groups II and III were 4.0 +/- 1.2 and 6.2 +/- 1.3 days, respectively. The MST in group I was significantly shorter than in groups II and III (P less than 0.026 and P less than 0.005, respectively). There was no significant difference in survival between groups II and III. MLC reactivity between recipients and skin donors increased progressively following each skin graft, reaching a peak just prior to liver transplantation. LCTA titers also increased following each skin graft, reaching peak levels immediately prior to hepatic grafting. Intraoperative LCTA titers decreased within 2 min of graft revascularization and were undetectable within 4 hr. In group III (unsensitized recipients), MLC reactivity was low and at no time was LCTA detectable. Histologic examination of the livers from group I recipients showed parenchymal hemorrhage, endophlebitis, and neutrophil infiltration. Histologic examination of postmortem liver biopsies from animals in groups II and III revealed acute cellular rejection. In conclusion, hyperacute rejection resulting in graft failure and recipient death can be consistently produced in a porcine model of hepatic transplantation by donor-specific sensitization of the recipient. It is postulated that high titers of donor-specific antibody are required to exceed the liver's capacity for antibody absorption and elimination and produce the clinical picture of hyperacute rejection.

Animals↗
PubMed1989

Amelioration of chronic renal allograft dysfunction in cyclosporine-treated patients by addition of azathioprine.

Management of chronic renal allograft dysfunction in cyclosporine-prednisone treated renal allograft recipients remains problematic. We therefore initiated a protocol of azathioprine addition (1.0-1.5 mg/kg/day) to ongoing CsA/Pred therapy. Three groups were treated. Group A (n = 21) had chronic progressive renal dysfunction (serum creatinine greater than or equal to 2.5 mg/dl or more than 15% above baseline) four or more months after transplantation. Group B (n = 8) had frequent or severe rejection episodes occurring despite adequate CsA levels. Group C (n = 7) had constitutional side effects of CsA with or without renal dysfunction persisting despite drug taper or financial difficulty in affording CsA. Aza was initiated 17.8 +/- 2.8 months after transplantation in group A, the mean serum creatinine having risen from 2.55 +/- 27 mg/dl to 3.04 +/- .20 mg/dl (P = .07) over the six months preceding Aza initiation, despite stable and low therapeutic range HPLC whole-blood CsA levels (118 +/- 10 ng/ml vs. 133 +/- 11 ng/ml, P = NS). Renal function declined at a rate of -0.20 +/- .06 Cr1/year in the six-month period before addition of Aza, and then improved at a rate of 0.09 +/- .04 Cr-1/year after addition of Aza (P = .002). These changes in renal function occurred without a decrease in CsA levels (118 +/- 10 six months before Aza vs. 126 +/- 26 six months after Aza, P = NS). In group B Aza was initiated at 58 +/- 8 days after transplantation when mean sCr was 3.56 +/- .29 mg/dl and mean CsA level was 222 +/- 17 ng/ml. At least follow-up 12.7 +/- 2.0 months after addition of Aza, all group B grafts were functioning, mean sCr was 2.69 +/- .31 mg/dl (P = .09 compared with baseline), and mean CsA level was 128 +/- 34 ng/ml (P = .07 compared with baseline). Group C patients had addition of Aza at 43 +/- 19 months after transplantation when mean sCr was 2.97 +/- .60 and mean CsA level was 125 +/- 30 ng/ml; addition of Aza had no influence on the rate of decline in renal function in this group. Of these 36 patients, 6 received therapy for acute rejection over the entire follow-up period of 12.3 +/- 1.4 months after addition of Aza; 4 of these retain graft function. Infectious complications consisted of 2 urinary tract infections, 1 bacterial pneumonia, and one case of otitis media.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗
PubMed1989

No improvement of pancreas transplant endocrine function by exogenous insulin infusion (islet rest) in the postoperative period.

The concept of islet exhaustion maintains that exposure of pancreatic islets to hyperglycemia and other stresses leads to islet dysfunction and irreparable damage. The process of pancreatic transplantation places many stresses on islets (e.g., counter-regulatory hormones, steroids, cyclosporine toxicity). As practiced by some centers, it may be important to administer exogenous insulin in the postoperative period to provide islet rest. Using a porcine pancreas transplant model that simulates clinical transplantation, we studied 2 groups: 1 group (n = 8) received constant insulin infusion for 7 days after transplantation; the control group (n = 5) received vehicle only. The islets in the insulin infusion group were rested as evidenced by a significantly decreased mean C-peptide level (0.27 +/- 0.04 ng/ml) as compared to the control group (0.66 +/- 0.08 ng/ml) (P less than 0.05). After insulin infusion was discontinued, intravenous glucose tolerance testing found insulin, C-peptide and glucagon responses were not different between groups. Glucose clearance was also comparable; K values were -1.79 and -1.60 in the insulin infusion and control groups, respectively. In conclusion, islet rest by insulin infusion for 7 postoperative days did not improve subsequent pancreas transplant endocrine function.

Animals↗