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R M Merion

Publications and source records attributed to R M Merion.

At least 37 records · Page 2Linked to original sources
PubMed1997

Mini-microabscess syndrome in liver transplant recipients.

Cytomegalovirus (CMV) is a significant cause of morbidity in immunosuppressed patients. It is characterized in the liver by parenchymal microabscesses, usually containing CMV-infected cells. However, not all hepatic microabscesses are due to CMV infection. In 1992, we described "mini" microabscess (MMA) syndrome, a distinct clinical syndrome that occurs in transplanted livers. This report analyzes the clinical and laboratory features of 57 cases of MMA syndrome occurring in 52 patients and compares these with 19 biopsy-proven cases of CMV infection. The diagnosis of MMA syndrome can only be made histologically. The microabscesses are smaller and more numerous than in CMV infection, and there are no viral inclusions present. CMV DNA could not be detected in liver biopsy specimens with MMAs by using "nested" polymerase chain reaction (PCR), indicating that MMA syndrome is not caused by CMV infection. The pattern of liver enzyme and bilirubin elevation is predominantly hepatocellular, with transaminase levels elevated, on average, six to eight times the upper limit of normal. The clinical features of MMA syndrome are that it predominantly affects female (40 of 52 patients) orthotopic liver transplant (OLT) recipients of all ages (range, 11 months to 66.9 years). MMA syndrome is unrelated to the indication for initial OLT and tends to occur later after transplantation than CMV infection (median, 91 days post-OLT vs. 32 days for CMV hepatitis). Although the etiology of MMA syndrome is not clear, it does not appear to adversely affect graft or patient survival.

Adolescent↗
PubMed1997

Prostaglandins in liver transplantation.

This review summarizes experimental studies and clinical experiences with prostaglandins in liver transplantation emphasizing two randomized, double blinded placebo controlled clinical trials of prostaglandin E1 (PGE1) involving nearly 300 liver transplant recipients. Resource utilization and pharmacoeconomic aspects are also discussed. In the randomized trials, PGE1 did not affect patient and graft survival. Acute cellular rejection and primary allograft non-function were not reduced by PGE1. Postoperative renal failure was significantly less frequent among PGE1 patients in both trials and in one study perioperative blood product utilization was significantly lower. PGE1 treated patients had reduced intensive care unit length of stay, shorter hospitalization, and significantly lower total health care charges. Despite its failure to show improvements in patient and graft survival, rejection, or primary non-function, PGE1 use in hepatic allograft recipients reduces morbidity and results in notable reduction in the cost of liver transplantation.

Alprostadil↗
PubMed1996

Gynecological and reproductive function after liver transplantation.

Women of reproductive age who underwent orthotopic liver transplantation were surveyed to determine timing and pattern of menstruation, sexual activity, contraception, and incidence of pregnancy and gynecological disorders. Eighty two female recipients of liver transplantation at the University of Michigan between August 1985 and January 1992 were surveyed about menstrual function and gynecological and obstetrical histories before and after transplantation. Additional information was retrieved from medical records regarding their liver disease and details of pregnancies and gynecological care. In the year before transplantation, 27 women (42%) reported regular menstrual cycles, 18 (28%) irregular and unpredictable bleeding, and 19 (30%) amenorrhea. After transplantation, 30 women (48%) experienced regular menses, 16 (26%) irregular bleeding, and 16 (26%) amenorrhea. In women less than 46 years old, 27 (53%) had regular menses before and after transplant. Most women with acute liver disease had regular periods before (82%) and after transplant (73%). A total of 95% of women under the age of 46 had return of menstrual bleeding within the first year after transplantation. Of these women 49% had normal liver function tests at the time of survey, 33% mildly abnormal, and 18% severely abnormal. Liver function was not correlated with menstrual patterns. A total of 72% of women were sexually active after transplantation. Of 24 women under age 46 who had not undergone sterilization or hysterectomy, six women conceived seven pregnancies. Seven women reported abnormal cervical cytology results after transplantation. Six underwent colposcopy and 4 required some form of destructive therapy for cervical dysplasia. In women with liver disease, menstrual patterns may change after orthotopic liver transplantation. This is more common in women with chronic liver disease than in those with acute liver disease. There was no correlation between liver function and menstrual regularity after transplant. Return to sexual activity can be expected and pregnancies are not rare in a population of young women after liver transplantation. Regular cervical cytology is critical due to a recognized increase in cervical neoplasia in immunocompromised patients.

Adolescent↗
PubMed1996

Intestinal intraepithelial lymphocytes: identification of an inhibitory subpopulation.

UNLABELLED: The intestinal intraepithelial lymphocytes (iIEL) may play a critical role in preventing overwhelming sensitization to foreign luminal antigens. The purpose of this experiment was to identify the subpopulation of the iIEL responsible for this inhibitory action. One-way mixed lymphocyte cultures (MLC) were performed with rat splenocytes [Brown Norway (BN) as responder; irradiated Lewis as stimulator]. BN iIEL (comprising 5% of cells per well) were added to assess inhibitory function. In the control group, irradiated BN splenocytes were added to maintain identical cell numbers. Proliferation assays were expressed as mean counts per minute (CPM) +/- SD. Subpopulations of the iIEL were created by biomagnetically extracting iIELs labeled with monoclonal antibodies. The addition of iIELs to the MLC resulted in a 59% reduction in proliferation (P < 0.05). When the CD45+ population was removed from the iIEL this inhibitory activity was lost. Removal of the CD8+ population, but not the CD4+ population, also caused a loss of inhibitory activity. Separate analysis of either CD8(alpha)(alpha)+ or CD8(alpha)(beta)+ subpopulations identified the CD8(alpha)(alpha)+ population as having the majority of the inhibitory effect. IN CONCLUSION: 1) The iIEL has an inhibitory action on proliferation. 2) The involved population is of lymphoid origin, as a loss of CD45+ cells resulted in a loss of inhibition. 3) Loss of CD8+ iIEL cells resulted in a loss of inhibition demonstrating that these cells are responsible for this action. This inhibitory activity appears to be restricted to the CD8(alpha)(alpha)+ subpopulation.

Animals↗
PubMed1996

Histologic progression of recurrent hepatitis C in liver transplant allografts.

The incidence and severity of recurrent hepatitis C virus (HCV) infection in liver transplant recipients vary widely, and the long-term sequelae of recurrent infection are not known. To better define the biology of recurrent HCV in liver transplant patients, we reviewed the histology of recurrent HCV in serial biopsies of 19 patients with pretransplant polymerase chain reaction (PCR) evidence of HCV infection. All posttransplant (post-TX) biopsies (n = 81) were reviewed, and RNA was extracted from at least one paraffin-embedded biopsy from each patient. RNA was analyzed for HCV by nested, reverse transcription-PCR (RT-PCR) using primers for the 5' non-coding region of HCV as well as for albumin (as an internal control). All post-TX biopsies tested (12-1,677 days post-TX) were positive for HCV RNA by RT-PCR, while normal control biopsies were negative. Fifteen of 19 patients developed recurrent chronic hepatitis typical of HCV. Many of these patients showed a progression from early biopsies with acute lobular hepatitis to later biopsies with chronic hepatitis with portal lymphoid aggregates. An acute lobular hepatitis typified by sinusoidal lymphocytosis, acidophil bodies, and lobular disarray was seen an average of 135 days post-TX, with a range of 39-279 days. The time post-TX between this and earlier non-hepatitis biopsies was significantly different (p < 0.0004, Student's t test). Chronic hepatitis with portal lymphoid aggregates was seen an average of 356 days post-TX, with a range of 89-1,365 days. The time post-TX was significantly longer than for acute lobular hepatitis (p < 0.03, Student's t test). Fifty-three percent of HCV TX patients progressed from acute lobular hepatitis to chronic hepatitis with lymphoid aggregates within 1 year of TX, and 79% showed these changes within 4 years. Six patients had progressive fibrosis; one die of liver failure and two became cirrhotic. Recurrent HCV appears to progress from an acute lobular hepatitis to chronic hepatitis with lymphoid aggregates in the majority of patients. Significant scarring occurred in 32% of patients and 16% developed end-stage liver disease from recurrent HCV. These later findings suggest that the long-term course of recurrent HCV in liver allografts may not be as indolent as first thought.

Base Sequence↗
PubMed1996

Urethral disruption with urinary extravasation: a delayed complication of pancreatic transplantation.

PURPOSE: To describe the radiographic features and potential causes of urethral disruption in pancreas transplant recipients. MATERIALS AND METHODS: Eight episodes of urinary extravasation were depicted with retrograde urethrography in five male patients who had undergone pancreatic transplantation. The patients' medical records were reviewed to determine a cause of the extravasations. RESULTS: Four extravasations occurred at the proximal (deep) bulbar urethra, three at the bulbomembranous junction of the urethra, and one at the distal bulbar urethra. Four of eight cases of extravasation were preceded by recent cystoscopy or placement of a Foley catheter; one case was preceded by possible urethral injury due to a fall. CONCLUSION: Urethral disruption occurs as a complication of pancreatic transplantation. It has so far been seen only in male patients and occurs at the bulbar urethra or bulbomembranous junction. If the treating physician is unaware of this condition, diagnosis and institution of appropriate therapy may be delayed. Recent prior urinary tract instrumentation or trauma may be predisposing factors in urinary extravasation.

Anastomosis, Surgical↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗