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Biomedical subjects

R M Merion

Publications and source records attributed to R M Merion.

At least 37 records · Page 2Linked to original sources
PubMed2000

Valganciclovir results in improved oral absorption of ganciclovir in liver transplant recipients.

The pharmacokinetics of an orally administered valine ester of ganciclovir (GCV), valganciclovir (VGC), were studied. These were compared to the pharmacokinetics of oral and intravenous GCV. Twenty-eight liver transplant recipients received, in an open-label random order with a 3- to 7-day washout, each of the following: 1 g of oral GCV three times a day; 450 mg of VGC per os (p.o.) once a day (q.d.); 900 mg of VGC p.o. q.d.; and 5 mg of intravenous (i.v.) GCV per kg of body weight q.d., given over 1 h. GCV and VGC concentrations were measured in blood over 24 h. One-sided equivalence testing was performed to test for noninferiority of 450 mg of VGC relative to oral GCV (two-sided 90% confidence interval [CI] > 80%) and nonsuperiority of 900 mg of VGC relative to i.v. GCV (two-sided 90% CI < 125%). The exposure of 450 mg of VGC (20.56 microg. h/ml) was found to be noninferior to that of oral GCV (20.15 microg. h/ml; 90% CI for relative bioavailability of 95 to 109%), and the exposure of 900 mg of VGC (42.69 microg. h/ml) was found to be nonsuperior to that of i.v. GCV (47.61 microg. h/ml; 90% CI = 83 to 97%). Oral VGC delivers systemic GCV exposure equivalent to that of standard oral GCV (at 450 mg) or i.v. GCV (at 900 mg of VGC). VGC has promise for effective CMV prophylaxis or treatment with once-daily oral dosing in transplant recipients.

Antiviral Agents↗
PubMed2000

Prospective, case matched comparison of hand assisted laparoscopic and open surgical live donor nephrectomy.

PURPOSE: The technical difficulty of standard laparoscopic live donor nephrectomy has limited its application. Hand assistance, which takes advantage of the incision necessary for organ removal, facilitates laparoscopy without significant impact on patient recovery. We prospectively compared open surgical and hand assisted laparoscopic donor nephrectomy. MATERIALS AND METHODS: Our first 10 laparoscopic live donor nephrectomies were matched with 40 open donor nephrectomies by gender, age and body mass index. Data were obtained by pain scales, SF-12 survey instruments, questionnaires and chart abstraction. RESULTS: Operative time was longer for the laparoscopic approach (mean 95 versus 215 minutes). However, laparoscopic group patients had a shorter hospital stay compared to those undergoing open surgery (mean 2.9 versus 1.8 days), returned sooner to nonstrenuous activity (mean 19.0 versus 9.9 days) and reported less pain 6 weeks postoperatively (mean 2.3 versus 0.6) (p </=0.03 for all). There were no differences between groups in terms of donor complications, allograft function and ureteral complications. Mean hospital cost was 23% greater in the laparoscopic group (p = 0.005) but global cost, which accounted for estimated loss of income from work during the recovery period, was only 15% greater (p = 0.10). Mean operative time was significantly improved for our second compared to our first 5 laparoscopic group patients (177 versus 254 minutes). CONCLUSIONS: Laparoscopic live donor nephrectomy appears to be a safe and effective alternative to open donor nephrectomy. Indexes of patient recovery suggest patient morbidity similar to that reported following standard laparoscopic donor nephrectomy and significantly less than after open nephrectomy. Improvement in operative time in the first 10 cases suggests that hand assistance "shortens" the learning curve, which might encourage more surgeons to offer laparoscopic live donor nephrectomy.

Adult↗
PubMed1999

Renal transplantation at the University of Michigan 1964 to 1999.

The Michigan Kidney Transplant Program has existed for 35 years. Outcomes have improved dramatically as the one-year survival of cadaver kidney grafts increased from 25% to 85-90%. Patient deaths in the first year are now uncommon. Indications for renal transplantation have been extended to infants, the elderly, diabetics and to patients with other significant health problems who would not have been candidates in the past. Chronic administration of large doses of corticosteroids is no longer necessary and the associated morbidity is largely avoided. Improvements in immunosuppression, especially the introduction of cyclosporine, account for much of this progress. With success has come increasing demand. Unfortunately, the gap between the number of available donor kidneys and the number of patients listed for a cadaver transplant continues to increase rather than diminish. Greater acceptance of volunteer donation, as has occurred in our own program, will help to reduce this shortage. If the past forecasts the future, we can anticipate extraordinary advances during the next 35 years.

Actuarial Analysis↗
PubMed1998

Partial T-cell activation and anergy induction by polyclonal antithymocyte globulin.

BACKGROUND: Polyclonal antithymocyte globulins have been assumed to deplete or sequester immunocompetent T cells. We investigated the hypothesis that anti-human thymocyte globulin (ATGAM)-mediated immunosuppression is delivered via nondepletive, immunologically specific actions as a consequence of simultaneous engagement of multiple T cell receptors. METHODS: Purified T cells obtained from healthy volunteers or renal transplant recipients receiving their first dose of ATGAM were evaluated for proliferative responses and cell-mediated lympholysis. ATGAM binding and receptor expression were determined by flow cytometry. Cytokines and ATGAM levels were measured by enzyme-linked immunosorbent assay. RESULTS: ATGAM-treated T cells showed significant dose-dependent inhibition of proliferation in vitro at concentrations comparable to those measured in patients. Effectors raised after ATGAM treatment failed to develop cytotoxicity. Supernatant interleukin (IL)-2 levels in ATGAM-treated cultures were significantly reduced (P<0.01 vs. control). IL-4 was not significantly altered. In vivo studies confirmed significant ATGAM-mediated inhibition of proliferative responses. Concanavalin A and OKT3-driven proliferation were reduced 30-60% by ATGAM. Flow cytometry showed that ATGAM recognized multiple cell surface receptors and resulted in markedly increased IL-2R and CD28 expression in the absence of proliferation, demonstrating partial T-cell activation. ATGAM synergized with phorbol myristate acetate to produce strong proliferation, which suggests that it provides a calcium-based signal resulting in anergy. CONCLUSIONS: ATGAM recognizes and cross-links multiple cell surface receptors and costimulator molecules on human T cells. Simultaneous engagement by ATGAM in the context of allogeneic or mitogenic stimulation leads to partial T-cell activation and anergy.

Antilymphocyte Serum↗
PubMed1998

Hand-assisted laparoscopic live donor nephrectomy.

Minimally invasive live donor nephrectomy has been described using both standard laparoscopic dissection and "gasless" endoscopically assisted techniques. We report another method, hand-assisted laparoscopic live donor nephrectomy, which uses an occlusive sleeve to maintain pneumoperitoneum. The procedure is performed under excellent laparoscopic visualization in a generous operative field, and is facilitated substantially by manual assistance, which takes advantage throughout the procedure of the incision that is necessary for intact organ removal. The results of our first procedure are encouraging.

Adult↗
PubMed1998

Prospective multivariate analysis of donor monoethylglycine xylidide (MEGX) testing in liver transplantation. Transplantation Society of Michigan Scientific Studies Committee.

Measurement of the metabolism of lidocaine to MEGX by the hepatic cytochrome P450 system has been proposed as a means to assess liver function and metabolic activity of cadaveric organ donors. This prospective study of 102 potential liver donors from the State of Michigan sought to determine the role of MEGX determinations alone and in conjunction with traditional measures of donor acceptability. High MEGX values (> 80 microg/L) did not correlate with the acceptability of donor livers, and had no significant association with early posttransplant graft function, as determined by SGOT, SGPT, alkaline phosphatase, bilirubin, prothrombin time, or bile production. However, livers procured from donors with high MEGX values had improved actuarial graft survival when compared to low MEGX donors at 30 d (95% vs. 84%) and at 1 yr (68% vs. 43%) (p < 0.04). Multivariate analysis demonstrated a significant independent association of both shorter cold ischemic time and high MEGX value with improved graft survival (p < 0.002). We conclude that the MEGX test offers limited incremental value in predicting early function of donor livers when used in conjunction with traditional criteria of clinical evaluation, laboratory tests, and histology. However, knowledge of the results of MEGX determinations may be of value in predicting graft survival after liver transplantation.

Adult↗
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↗