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Biomedical subjects

R M Merion

Publications and source records attributed to R M Merion.

At least 19 recordsLinked to original sources
PubMed2003

Orthotopic liver transplantation from a donor with a history of schistosomiasis.

The shortage of liver donors and the increasing number of patients on the waiting list for liver transplantation have led to a widening of the definition of suitable liver donors. In this case report, we describe transplantation of a liver from a 20-year-old brain-dead donor with a past history of schistosomiasis. Careful evaluation for schistosomiasis-related hepatic complications using hepatic function tests, clinical assessment for manifestations of portal hypertension, as well as abdominal ultrasound, and liver biopsy were performed. At 7 months follow-up, the recipient is doing well with normal liver function. Liver transplantation from a donor with a history of schistosomiasis is acceptable in carefully screened cases.

Accidental Falls↗
PubMed2003

Successful surgical salvage of partial pancreatic allograft thrombosis.

BACKGROUND: Venous thrombosis remains an important cause of pancreatic graft loss. Nevertheless, reports are scarce of treatment alternatives to complete graft removal. We describe a case of surgical salvage of a partial pancreatic graft thrombosis. METHODS: We used descriptive retrospective analysis. RESULTS: A 36-year-old patient with juvenile-onset diabetes mellitus and previous living related renal transplant received a cadaveric pancreas transplant in the right iliac fossa with enteric exocrine drainage and standard vascular anastomosis. Two days after discharge from the hospital, he presented with severe right upper quadrant pain, nausea, vomiting, fever, and leukocytosis. He was taken to the operating room for exploration. The tail of the pancreas, which was kinked under the gallbladder, was necrotic and excised. The remainder of the pancreas looked normal. The patient recovered well from surgery and was discharged home 7 days later. CONCLUSIONS: Partial pancreatectomy is an acceptable surgical alternative for incomplete graft thrombosis.

Adult↗
PubMed2001

Hemophilia.

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Hemophilia A↗
PubMed2001

Randomized controlled trial of hand-assisted laparoscopic versus open surgical live donor nephrectomy.

BACKGROUND: Laparoscopic live donor nephrectomy for renal transplantation is being performed in increasing numbers with the goals of broadening organ supply while minimizing pain and duration of convalescence for donors. Relative advantages in terms of recovery provided by laparoscopy over standard open surgery have not been rigorously assessed. We hypothesized that laparoscopic as compared with open surgical live donor nephrectomy provides briefer, less intense, and more complete convalescence. METHODS: Of 105 volunteer, adult, potential living-renal donors interested in the laparoscopic approach, 70 were randomly assigned to undergo either hand-assisted laparoscopic or open surgical live donor nephrectomy at a single referral center. Objective data and subjective recovery information obtained with telephone interviews and validated questionnaires administered 2 weeks, 6 weeks, and 6-12 months postoperatively were compared between the 23 laparoscopic and 27 open surgical patients. RESULTS: There was 47% less analgesic use (P=0.004), 35% shorter hospital stay (P=0.0001), 33% more rapid return to nonstrenuous activity (P=0.006), 23% sooner return to work (P=0.037), and 73% less pain 6 weeks postoperatively (P=0.004) in the laparoscopy group. Laparoscopic patients experienced complete recovery sooner (P=0.032) and had fewer long-term residual effects (P=0.0015). CONCLUSIONS: Laparoscopic donor nephrectomy is associated with a briefer, less intense, and more complete convalescence compared with the open surgical approach.

Activities of Daily Living↗
PubMed2001

Excess risk of renal allograft loss associated with cigarette smoking.

BACKGROUND: Cigarette smoking contributes to a number of health-related problems, but its impact on renal transplant survival beyond accelerated patient death is unclear. METHODS: We performed a cohort study of 645 adult renal allograft recipients from 1985 to 1995 to evaluate the relationship between smoking and graft outcome. RESULTS: Twenty-four percent of recipients (156/645) were smokers at the time of transplant evaluation. Of these, 90% continued to smoke after transplantation. Pretransplant smoking was significantly associated with reduced overall graft and death-censored graft survival. Patients who were smokers at the time of pretransplant evaluation had kidney graft survival of 84%, 65%, and 48% at 1, 5, and 10 years, respectively, compared with graft survival in nonsmokers of 88%, 78%, and 62% (P=0.007). Pretransplant smoking adversely affected death-censored graft survival in recipients of cadaveric (P=0.02) and of living donor kidneys (P=0.02). Reduced graft survival in pretransplant smokers could not be accounted for by differences in rejection (64% vs. 61%, P=0.35). In a multivariate analysis, pretransplant smoking was associated with a relative risk of 2.3 for graft loss. Among patients with a smoking history before transplantation, death-censored graft survival was significantly higher for those who quit smoking before transplant evaluation. CONCLUSIONS: Cigarette smoking before kidney transplantation contributes significantly to allograft loss. The effect of smoking on graft outcome is not explained by increases in rejection or patient death. Smoking cessation before renal transplantation has beneficial effects on graft survival. These effects should be emphasized to patients with end-stage renal disease who are considering renal transplantation.

Adult↗
PubMed2001

Outcome of liver transplantation for hepatitis B: report of a single center's experience.

Results of liver transplantation (LT) for hepatitis B have improved significantly with the use of hepatitis B immune globulin (HBIG) and/or lamivudine. The aim of this study is to review the long-term outcome of patients who underwent LT for hepatitis B. Records of 41 patients who underwent LT for hepatitis B and survived 3 months or longer post-LT were reviewed. Twenty patients were administered no immunoprophylaxis or short-term intramuscular HBIG, whereas 21 patients were administered high-dose intravenous (IV) HBIG. Median post-LT follow-up in these 2 groups was 76 months (range, 4 to 155 months) and 25 months (range, 4 to 68 months), respectively. Hepatitis B recurred in 15 (75%) and 4 patients (19%) who underwent LT in the pre-HBIG and post-HBIG eras, respectively. Cumulative rates of recurrent hepatitis B at 1 and 3 years post-LT in these 2 groups were 66% and 77% and 20% and 20%, respectively (P <.001). Recurrent hepatitis B in the post-HBIG era correlated with antibody to hepatitis B surface antigen titer less than 100 IU/L. Nine patients with recurrent hepatitis B were administered lamivudine for 13 to 49 months (median, 28 months); 6 patients continued to have stable or improved liver disease, whereas 3 patients developed virological breakthrough with slow deterioration of liver disease. Long-term IV HBIG is effective in preventing recurrent hepatitis B. The risk for recurrent hepatitis B is negligible after the first year post-LT. Among patients with no virological breakthrough, lamivudine can stabilize or improve liver disease for up to 4 years in patients with recurrent hepatitis B post-LT.

Adult↗
PubMed2000

Peripheral vascular occlusive disease in renal transplant recipients: risk factors and impact on kidney allograft survival.

BACKGROUND: This study evaluated the relationship between renal transplantation and the evolution of lower extremity peripheral vascular occlusive disease (PVOD). METHODS: A total of 664 adult renal allograft recipients from 1985-1995 were retrospectively reviewed for atherosclerotic risk factors and peripheral vascular occlusive disease (PVOD). PVOD events were defined as bypass, major amputation, claudication, or percutaneous angioplasty. Follow-up ranged from 2-12 years. RESULTS: The cumulative 5- and 10-year incidences of lower extremity PVOD after renal transplantation were 4.2 and 5.9%. Eight of 14 patients (57%) with pretransplant PVOD had additional PVOD events versus de novo appearance of PVOD in 21/650 patients (3.2%; P<0.0001). In a proportional hazards model, age, preoperative PVOD, diabetes, and postoperative smoking were independent risk factors for the development of PVOD after transplantation. Recipients with lower extremity PVOD had significantly lower 10-year patient and graft survival. Increased graft failure was due to an excess of deaths with a functioning graft. A total of 34 major interventions were performed. One- and two-year limb salvage rates were 64.2 and 53.8%. CONCLUSIONS: Lower extremity PVOD after renal transplantation is associated with diminished patient survival, and affects kidney graft survival via disproportionate patient attrition. Age, preoperative PVOD, diabetes, and postoperative smoking are important risk factors. Transplantation does not appear to either accelerate or retard the progression of disease. An aggressive approach towards limb salvage in properly selected patients is justifiable.

Adult↗
PubMed2000

Randomized, prospective trial of mycophenolate mofetil versus azathioprine for prevention of acute renal allograft rejection after simultaneous kidney-pancreas transplantation.

BACKGROUND: In simultaneous kidney-pancreas (SPK) transplantation, manifestations of renal allograft rejection typically become evident before those of pancreatic rejection. This study compared mycophenolate mofetil (MMF) and azathioprine (AZA) in prevention of renal rejection after primary SPK transplantation. METHODS: In an open-label, randomized, multicenter study, patients received MMF 1.5 g twice daily (n=74) or AZA 1-3 mg/kg daily (n=76) for 1 year after transplantation. The incidence of rejection was assessed at 6 months. Adverse events were tracked through 1 year. Survival data are reported through 2 years. RESULTS: At 6 months, efficacy results for MMF vs. AZA patients, respectively, were the following: rejection (27% vs. 39%); rejection or death (34% vs. 42%); rejection, graft loss, death, or premature withdrawal (i.e., treatment failure; 41% vs. 55%). Six-month efficacy trends favored MMF, and time to rejection or treatment failure was significantly longer when compared with AZA (P=0.049). One-year efficacy results for MMF vs. AZA patients, respectively, were the following: treatment of renal rejection (35% vs. 47%); renal allograft loss or death (9% vs. 12%); pancreas allograft loss or death (15% vs. 14%). Five MMF patients (7%) and four (5%) in the AZA group died. More MMF than AZA patients developed opportunistic infections (54% vs. 38%), but the pathogens did not differ. CONCLUSIONS: Trends for most efficacy parameters favored MMF over AZA, and time to renal allograft rejection or treatment failure was statistically significantly longer for MMF. The use of MMF in the treatment of SPK recipients is a useful advance.

Acute Disease↗
PubMed2000

Intravenous mycophenolate mofetil: safety, tolerability, and pharmacokinetics.

An intravenous (i.v.) formulation of mycophenolate mofetil (MMF; CellCept, Roche Pharmaceuticals, Inc., Palo Alto, CA) that will enable its administration to patients unable to tolerate oral medication is available. Two separate studies, an open-labeled pharmacokinetic (PK) study and a double-blind safety study, were performed. Within 24 h after transplant, 153 (safety study) and 45 (PK study) first or second renal transplant recipients were started on i.v. MMF 1 g Q12h or placebo (used in the safety study only, 2:1 MMF:placebo), given over 2 h via a dedicated peripheral venous catheter. In the safety study, per os (p.o.) MMF (1g Q12h) or placebo was administered, starting within 72 h after transplant, whereas in the PK study, p.o. MMF was started on the evening of day 5. Sequential blood samples obtained on study days 5 (i.v. MMF) and 6 (p.o. MMF) before and up to 12 h after the AM dose were analyzed for mycophenolic acid (MPA) and MPA glucuronide (MPAG) concentrations by high-performance liquid chromatography. The area under the concentration curve (AUC) was calculated using the linear trapezoidal rule. The MPA AUC(0-12) was higher for i.v. MMF than p.o. MMF (40.8 +/- 11.4 microg x h/ mL vs. 32.9 +/- 15, p < 0.001). There were no other significant PK differences for plasma MPA or MPAG. In the safety study (n = 98 i.v. MMF vs. n = 55 placebo), 11 patients (11%, i.v. MMF) and 4 patients (7%, placebo) discontinued their use of the drug because of an adverse event (AE). Overall, AEs were similar between i.v. MMF and placebo. Injection site phlebitis (4%) and thrombosis (4%) were observed only with i.v. MMF. MMF i.v. 1 g twice daily (b.i.d.) should provide efficacy at least equivalent to p.o. MMF without increased toxicity, and it provides an acceptable alternative dose form in the immediate period after transplant.

Administration, Oral↗
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↗