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L Mieles

Publications and source records attributed to L Mieles.

At least 19 recordsLinked to original sources
PubMed2005

Successful conversion to rapamycin for calcineurin inhibitor-related neurotoxicity following liver transplantation.

INTRODUCTION: Neurotoxicity is a well-recognized side effect of calcineurin inhibitors. Rapamycin is considered to be significantly less neurotoxic than calcineurin inhibitors (CNIs). The aim of this study was to retrospectively analyze a group of post-liver transplant patients who had been converted to rapamycin because of CNI-related neurotoxicity. PATIENTS AND METHODS: Orthotopic liver transplantation (OLT) was performed in 56 consecutive patients between April 1, 2003, and August 15, 2004. Immunosuppression was administered with tacrolimus, mycophenolic acid, and corticosteroids. RESULTS: Seven patients were converted to rapamycin due to new-onset neurotoxicity or exacerbation of previous neurological symptoms secondary to CNI. None of the patients had toxic levels tacrolimus (>15 ng/mL) at the time of symptoms, which persisted despite reduction of CNI dose. The indications for conversion were: (1) peripheral neuropathy; (2) seizure; (3) metabolic encephalopathy; and (4) central pontine myelinolysis. All patients showed improvement or resolution of their neurological symptoms after conversion to rapamycin. Two patients died, the first due to a hypoxic event and the second due to central pontine myelinolysis with limited improvement and a family decision to withdraw care. There were no complications directly attributed to rapamycin. Specifically, there were no thrombotic events, wound complications, or biliary leaks. Three patients had a rejection episode that was successfully treated with pulse corticosteroids and low-dose tacrolimus (levels < 5 ng/mL). CONCLUSIONS: Rapamycin can be safely used in OLT recipients with severe neurological symptoms ascribed to or exacerbated by CNIs. Rapamycin monotherapy may be inadequate to control rejection early after transplantation. Rapamycin can be combined with low doses of CNI to prevent rejection.

Adrenal Cortex Hormones↗
PubMed2001

Reconstruction of double hepatic arterial and portal venous branches for right-lobe living donor liver transplantation.

Double hepatic arterial and portal venous branches are common anatomic variations of the isolated right hepatic lobe. Reconstruction of these vessels during transplantation can be challenging because of their small caliber, close proximity to other hilar structures, and abnormal alignment with the native vasculature. Practical techniques for the creation of these anastomoses would simplify the recipient surgery and might minimize the incidence of vascular complications. Alternative methods for management of these structures are summarized. The recipient's proper hepatic artery and its bifurcation are resected for use as an arterial Y-type graft. The donor arteries are individually anastomosed at the bifurcation of the recipient's hepatic artery at the back table. The free end of the Y graft is then replaced at the origin of the gastroduodenal artery using standard branch-patch technique. Reconstruction of a second donor portal branch is similarly facilitated by ex situ placement of a Y-type vascular conduit derived from the recipient's portal vein. Surgical management of these vessels and reconstruction of other hilar structures are noticeably less cumbersome. There have been no short-term vascular complications. The use of autologous vascular conduits with ex situ reconstruction facilitates management of double donor arterial and portal venous branches. The incidence of complications attributable to these methods is expected to be low.

Angiography↗
PubMed2001

Functional venous anatomy for right-lobe grafting and techniques to optimize outflow.

Right-lobe living donor liver transplantation has emerged as an alternative to cadaveric transplantation. An appreciation of the unique anatomy and behavior of the right lobe has emerged and has precipitated technical modifications. Living donors underwent right lobectomy, including preservation of significant inferior hepatic veins. The parenchyma was divided following a plane approximating the right border of the posterior two thirds of the midhepatic vein (MHV), but deviating anteriorly to include the distal one third of the MHV with the graft. Large venous tributaries from segment VIII were preserved. Anastomosis in the recipient was accomplished by means of complete cavoplasty. Significant inferior veins, tributaries to the MHV, and the distal portion of the MHV were reconstructed when technically possible. Forty-eight right-lobe resections and transplantations were performed in the manner described. There were no donor complications attributable to the technique. Forty-six of the 48 recipients are alive, and 44 of the 46 surviving patients have their original graft. Venous tributaries from segment VIII and/or the distal portion of the MHV were reconstructed in only 3 patients. Outflow obstruction was recognized intraoperatively in 2 patients; 1 patient had a caval web excised and the other patient required revision of the main anastomosis. Neither organ was lost. There were no other significant venous complications. The incidence of ascites was the same as that in recipients of whole organs. These methods of parenchymal transection and venous reconstruction resulted in a low rate of complications. The wide anastomosis and collateral pathways between the MHV and right hepatic vein seem to be more critical than reconstruction of tributaries from segment VIII or the distal MHV.

Adult↗
PubMed1998

Comparative histopathology of hepatic allografts and xenografts in the nonhuman primate.

Liver transplantation was performed in the following groups: Group 1, baboon-to-baboon allografting (n=8) (control group); Group 2, ABO-compatible vervet monkey-to-baboon xenografting (n=8); Group 3, ABO-incompatible vervet monkey-to-baboon xenografting (n=6); Group 4, pig-to-baboon xenografting (n=2); and Group 5, pig-to-rhesus monkey xenografting (n=6). Immunosuppressive therapy (cyclosporine, cyclophosphamide, and methylprednisolone) was begun 2-7 days before liver transplantation (LTx) and continued indefinitely after LTx. The liver grafts were biopsied pre-LTx and subsequently post-LTx at approximately 1 hr, 2-3 hr, 7-10 days, 20-30 days, 60 days, 120 days, and at euthanasia or spontaneous death. There were 19 successful LTxs with grafts functioning from one hour to 123 days. No pig liver (Groups 4 and 5) survived more than 5.5 hr, as there was an immediate severe vascular response after reperfusion, typical of hyperacute rejection (congestion and hemorrhage). Vascular rejection was not seen in allografts (Group 1), but early mild-to-moderate congestion and neutrophil infiltration were present in concordant xenografts (Groups 2 and 3), which were associated with moderate deposition of immunoglobulin, C3, and fibrinogen. Lymphoid cell infiltration, bile duct damage, and portal vein endothelialitis in the portal zones occurred later in both allografts (Group 1) and concordant xenografts (Groups 2 and 3), developing earlier in the presence of ABO-incompatibility (Group 3). In concordant xenografts it was usually followed by fibrosis.

Animals↗
PubMed1996

A high incidence of native portal vein thrombosis in veterans undergoing liver transplantation.

The incidence of native portal vein thrombosis (PVT) in liver transplant recipients has been reported to range from 2.1 to 13.8%. We have identified an inordinately high incidence of PVT in a consecutive series of U.S. veterans receiving liver transplants. Between October 1989 and February 1994, 88 consecutive U.S. veterans received 99 orthotopic liver transplants under primary Tacrolimus (Prograf, formerly FK506) based immunosuppression. A number of clinical features were examined in an effort to identify risk factors for PVT and outcome was compared to patients without PVT. Native PVT was present in 23/88 (26%) patients. All of these patients were male U.S. veterans with a mean age of 47 years. When compared to the 65 patients without PVT, we found no significant difference with respect to underlying liver disease, age, Childs-Pugh score (mean = 12), UNOS status as defined prior to April 1995 (95% UNOS 3 or 4), previous abdominal surgery, or liver volume. Median blood loss for patients with PVT (21 units of packed red blood cells) was greater than for those without PVT (14 units, P = 0.04). Portal thrombectomy was performed in 11 patients, 11 patients required mesoportal jump grafts, and 1 patient had an interposition graft. Standard veno-venous bypass was used in 10 patients with single bypass utilized for the remainder. Actuarial patient survival for all patients at 1, 2, and 4 years was 88, 85, and 79%, respectively. There was no significant difference in patients with or without PVT. Patients with PVT had poorer graft survival than patients without PVT (86% vs 65%, 1 year; 81% vs 65%, 2 years; 81% vs 61%, 4 years; P = 0.03); however, this was not related to technical problems with the portal venous inflow. PVT occurred in 26% of U.S. veterans undergoing liver transplantation. These patients had significantly higher operative blood loss and poorer graft survival. The high incidence of postnecrotic cirrhosis in a predominantly male group of patients with advanced disease, as is evident by the high mean Childs-Pugh score and UNOS status, perhaps accounts for our observations.

Female↗
PubMed1995

Secondary organ allografting after a primary "bridging" xenotransplant.

It remains uncertain whether xenotransplantation can sensitize the recipient to alloantigens, rendering subsequent allotransplantation unsuccessful. This is of considerable importance if a xenograft is to be used as a "bridge" to support the patient until a suitable allograft becomes available. When sera from 9 baboons that had received pig or African green monkey heart or liver xenografts were tested against a panel of lymphocytes from 5 or 6 potential donor baboons, positivity was seen in only 1 baboon (and then to only 2 of the potential 5 donors). In 4 baboons that had undergone previous xenotransplants (1 from this series of 9 baboons and 3 others), subsequent organ allografting was not followed by hyperacute, antibody-mediated, or accelerated cellular rejection. We conclude that organ xenotransplantation using discordant or concordant donor species does not prohibit subsequent allotransplantation.

Animals↗
PubMed1995

Auxiliary liver allografting and xenografting in the nonhuman primate.

Auxiliary liver transplantation has been performed in the baboon using allografts (n = 8) and concordant xenografts from donor African green monkeys (n = 8). The native portal vein was ligated in all cases and the native common bile duct was ligated in 5 cases. The immunosuppressive therapy used was identical in both the allografts and xenografts and consisted of triple drug therapy (cyclosporine, cyclophosphamide, and methylprednisolone), all at dosages consistent with clinical use. During the determination of the surgical technique to be applied, there were 5 early failures (3 allografts, 2 xenografts), and 2 deaths at 10 and 20 days from multiorgan failure and sepsis, respectively (xenografts). The remaining 9 baboons (5 allografts, 4 xenografts) were electively euthanized at 16-62 days (allografts) and 35-120 days (xenografts). Hyperacute rejection or antibody-mediated rejection was not seen in the grafted livers. Episodes of acute cellular rejection occurred in the majority of animals within the first 30 days and recurred in the longer-term survivors, but could be controlled by bolus therapy with intravenous methylprednisolone. Satisfactory donor liver function was confirmed using a number of tests, including scintigraphy in 3 cases. We conclude that auxiliary liver transplantation using a closely related donor species is feasible in baboons and might be extended to humans with terminal liver failure. A baboon-to-man auxiliary liver graft may serve as a "bridge" until either a human cadaver donor liver became available or native liver function recovers in patients with fulminant hepatic failure.

Animals↗
PubMed1994

High-dose acyclovir compared with short-course preemptive ganciclovir therapy to prevent cytomegalovirus disease in liver transplant recipients. A randomized trial.

OBJECTIVE: To assess the efficacy of high-dose oral acyclovir therapy compared with preemptive, short-course ganciclovir therapy (administered only if cytomegalovirus [CMV] shedding occurred) to prevent CMV disease in liver transplant recipients. DESIGN: A randomized controlled trial. SETTING: Liver transplant center at a university-affiliated Veterans Affairs Medical Center. PATIENTS: 47 consecutive patients having liver transplantation. INTERVENTION: Patients were stratified by their CMV antibody status and the CMV antibody status of the donor and were randomly assigned to one of two treatment groups. Surveillance cultures for CMV (buffy coat and urine) were done every 2 to 4 weeks for 24 weeks in all patients. One group received high-dose oral acyclovir (800 mg four times daily). The experimental group received no acyclovir, but if surveillance cultures were positive, ganciclovir (5 mg/kg intravenously twice daily) was administered for 7 days. MEASUREMENTS: Cytomegalovirus shedding and CMV disease were measured in the two groups. RESULTS: Cytomegalovirus shedding before the onset of CMV disease occurred in 25% (6 of 24) of patients in the acyclovir group compared with 22% (5 of 23) in the experimental group. Cytomegalovirus disease developed in 29% (7 of 24) of the acyclovir group and in 4% (1 of 23) of the experimental group (P < 0.05). No hematologic toxicity occurred with ganciclovir. CONCLUSION: Oral acyclovir is ineffective prophylaxis against CMV in liver transplant recipients. Preemptive, short-course ganciclovir therapy in patients with CMV shedding was well tolerated and provided effective prophylaxis against subsequent CMV disease; this protocol targets the patients at risk for CMV disease and minimizes toxicity and expense.

Acyclovir↗
PubMed1994

Decreased incidence of viral infections in liver transplant recipients. Possible effects of FK506?

Cytomegalovirus (CMV) is a major infectious complication of organ transplantation and its incidence is influenced by the type and intensity of immunosuppressive therapy employed. Using a new immunosuppressive agent FK506, CMV infection was observed in 30% and CMV disease in 15% of the 26 liver transplant recipients. Delayed onset of CMV disease was noted; the mean time to the occurrence of CMV disease being 137 days posttransplantation. No graft loss or mortality could be attributed to CMV infection. Mucocutaneous herpes simplex virus (HSV) infections were encountered in 19% of the patients, while no disease could be attributed to varicella zoster virus or Epstein-Barr virus (EBV). The contribution of FK506 to a decrease in viral morbidity and associated mortality bears further investigation.

Cytomegalovirus Infections↗
PubMed1994

Improved detection of spontaneous bacterial peritonitis with Bactec as compared with conventional culture methods. A prospective study.

Bacteriologic diagnosis of spontaneous bacterial peritonitis is difficult due to the low yield of isolating the bacteria from the ascitic fluid. We prospectively compared the conventional culture method with the nonradiometric Bactec culture system for the detection of bacteria in 20 episodes of spontaneous bacterial peritonitis. The ascitic fluid culture was positive by the conventional culture method in 25% and by Bactec in 79% of the episodes of spontaneous bacterial peritonitis (P = 0.004). Of culture-positive episodes, Gram-negative bacteria were detected by conventional cultures in 20% and by Bactec in 47%. Bactec culture system was significantly better than the conventional cultures for the detection of streptococci (viridans streptococci and Enterococcus fecalis), 33% versus 0 (P < 0.05). Conventional cultures did not detect bacteria that were not also detected by Bactec cultures. In conclusion, the Bactec nonradiometric culture method is superior to conventional cultures for the diagnosis of spontaneous bacterial peritonitis.

Ascitic Fluid↗
PubMed1994

Survival following organ transplantation in an Oklahoma institution, 1985-1993.

Since 1985, a total of 413 patients have undergone 439 solid organ transplants at the authors' institution. The current actuarial one-year survival rate of patients undergoing heart, kidney, lung, or liver transplantation at our center is 94%, 90%, 87%, and 91%, respectively. Five-year survival of heart and kidney recipients is 80% and 75%, respectively. In view of these excellent results and the excellent quality of life that successful organ transplants provide patients with end-stage organ failure, every possible effort should be made to increase organ donation.

Actuarial Analysis↗
PubMed1993

Invasive aspergillosis in liver transplant recipients: association with candidemia and consumption coagulopathy and failure of prophylaxis with low-dose amphotericin B.

Invasive aspergillosis developed in three (5%) of 55 adult liver transplant recipients at our institution. All three of our patients had concomitant candidemia and consumption coagulopathy, and invasive aspergillosis developed while they were receiving therapy with intravenous amphotericin B (0.5 mg/[kg.d]). The simultaneous occurrence of candidemia and invasive aspergillosis in liver transplant recipients may reflect a common defect in the host-defense mechanism against Candida and Aspergillus organisms (i.e., impaired phagocytic and mononuclear macrophage function) and liver disease per se. These three cases suggest that such low-dose intravenous amphotericin B will likely be ineffective if used as antifungal prophylaxis for invasive aspergillosis.

Adult↗
PubMed1993

Insulin requirements after liver transplantation and FK-506 immunosuppression.

Hyperglycemia and new-onset diabetes mellitus is a well-recognized complication of solid organ transplantation. With the advent of FK-506 as a new immunosuppressive drug used in orthotopic liver transplantation (OLT), much attention has been paid to its diabetogenic effects. Currently, there are no data on the long term effects of FK-506 in glucose metabolism after OLT. In the present study, we determined the need for outpatient insulin in 52 American veterans who received 58 liver transplants using primary immunosuppression with FK-506 and PRED, with a mean follow-up of 467 days (range 17-952 days). We also analyzed their plasma glucose and FK-506 levels as well as the doses of PRED and FK-506 that they received at various intervals post-OLT. There were 7/52 (13.6%) patients who required insulin for the first time after OLT. Of these, the number of patients on insulin at 3, 6, and 12 months post-OLT was 5/47 (10.6%), 6/44 (13.6%), and 1/26 (3.8%), with none requiring insulin de novo at 18, 24, and 30 months post-OLT. Three patients required insulin temporarily but subsequently became normoglycemic without additional therapy. The need for insulin was not related to the dose of FK-506 administered nor the plasma level. Patients who required outpatient insulin were receiving higher doses of PRED than those not requiring insulin. The need for insulin did not affect the long-term graft or patient survival. In conclusion, the need for insulin with FK-506 compares favorably to that of previous immunosuppressive regimens, and FK-506 may have a reversible diabetogenic effect that is not dose dependent.

Actuarial Analysis↗