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1.
Transplant Proc ; 47(9): 2722-6, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26680081

ABSTRACT

PURPOSE: Combined heart-liver transplantation is an increasingly accepted treatment for select patients with heart and liver disease. Despite growing optimism, heart-liver transplantation remains an infrequent operation. We report our institutional experience with heart-liver transplantation. METHODS: All combined heart-liver transplantations at Cedars-Sinai Medical Center from 1998-2014 were analyzed. Primary outcomes were patient and graft survival and secondary outcomes included rejection, infection, reoperation, length of stay, and readmission. RESULTS: There were 7 heart-liver transplants: 6 simultaneous (single donor) and 1 staged (2 donors). Median follow-up was 22.1 (IQR 13.2-48.4) months. Mean recipient age was 50.8 ± 19.5 years. Heart failure etiologies included familial amyloidosis, congenital heart disease, hypertrophic cardiomyopathy, systemic lupus erythematosus, and dilated cardiomyopathy. Preoperative left ventricular ejection fraction averaged 32.3 ± 12.9%. Five (71.4%) patients required preoperative inotropic support; 1 required mechanical circulatory support. The most common indications for liver transplant were amyloidosis and cardiac cirrhosis. Median Model for End-stage Liver Disease score was 10.0 (9.3-13.8). Six-month and 1-year actuarial survivals were 100% and 83.3%, with mean survival exceeding 4 years. No patient experienced cardiac allograft rejection, 1 experienced transient liver allograft rejection, and 1 developed progressive liver dysfunction resulting in death. Five developed postoperative infections and 3 (42.9%) required reoperation. Median ICU and hospital stays were 7.0 (7.0-11.5) and 17.0 (13.8-40.5) days. There were 4 (57.1%) readmissions. CONCLUSIONS: For carefully selected patients with coexisting heart and liver disease, combined heart and liver transplantation offers acceptable patient and graft survival.


Subject(s)
End Stage Liver Disease/surgery , Heart Failure/surgery , Heart Transplantation/methods , Liver Transplantation/methods , Adult , Aged , Combined Modality Therapy/methods , End Stage Liver Disease/complications , Female , Graft Survival , Heart Failure/complications , Heart Transplantation/statistics & numerical data , Humans , Length of Stay , Liver Transplantation/statistics & numerical data , Male , Middle Aged , Patient Readmission/statistics & numerical data , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Reoperation/statistics & numerical data , Survival Rate , Treatment Outcome
2.
Int J Cardiol ; 173(2): 284-9, 2014 May 01.
Article in English | MEDLINE | ID: mdl-24655549

ABSTRACT

OBJECTIVE: To estimate the echocardiography confirmed prevalence of rheumatic heart disease (RHD) in school children in Fiji. DESIGN: Cross-sectional observational study. SETTING: Ten primary schools in Fiji. PATIENTS: School children aged 5-14 years. INTERVENTIONS: Each child had an echocardiogram performed by an echocardiographic technician subsequently read by a paediatric cardiologist not involved with field screening, and auscultation performed by a paediatrician. MAIN OUTCOME MEASURES: Echocardiographic criteria for RHD diagnosis were based on those previously published by the National Institutes of Health (NIH) and World Health Organization (WHO), and data were also analyzed using the new World Heart Federation (WHF) criteria. Prevalence figures were calculated with binomial 95% confidence intervals. RESULTS: Using the modified NIH/WHO criteria the prevalence of definite RHD prevalence was 7.2 cases per 1000 (95% CI 3.7-12.5), and the prevalence of probable RHD 28.2 cases per 1000 (95% CI 20.8-37.3). By applying the WHF criteria the prevalence of definite and borderline RHD was 8.4 cases per 1000 (95% CI 4.6-14.1) and 10.8 cases per 1000 (95% CI 6.4-17.0) respectively. Definite RHD was more common in females (OR 5.1, 95% CI 1.1-48.3) and in children who attended school in a rural location (OR 2.3, 95% CI 0.6-13.50). Auscultation was poorly sensitive compared to echocardiography (30%). CONCLUSION: There is a high burden of undiagnosed RHD in Fiji. Auscultation is poorly sensitive when compared to echocardiography in the detection of asymptomatic RHD. The results of this study highlight the importance of the use of highly sensitive and specific diagnostic criteria for echocardiography diagnosis of RHD.


Subject(s)
Echocardiography/statistics & numerical data , Mass Screening/statistics & numerical data , Rheumatic Heart Disease/diagnostic imaging , Rheumatic Heart Disease/epidemiology , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Developing Countries/statistics & numerical data , Female , Fiji/epidemiology , Heart Auscultation/statistics & numerical data , Humans , Male , Prevalence , Resource Allocation/statistics & numerical data , Schools , Sensitivity and Specificity , World Health Organization
3.
Vaccine ; 28(18): 3086-94, 2010 Apr 19.
Article in English | MEDLINE | ID: mdl-20199764

ABSTRACT

Fijian infants aged 6 weeks were stratified by ethnicity and randomized to receive 0, 1, 2, or 3 PCV-7 doses with or without the 23-valent pneumococcal polysaccharide vaccine (PPV-23) at 12 months. Strong booster effects for all 7 PCV-7 serotypes were elicited, and for 4/7 serotypes these responses were highest in the single PCV-7 group. There were fourfold rises in GMC for all non-PCV-7 serotypes. By 17 months the PPV-23 group still had significantly higher GMC (each p<0.001) for all serotypes. The PPV-23 was well tolerated and induced excellent responses for all serotypes which were greatest in the single PCV-7 group.


Subject(s)
Antibodies, Bacterial/blood , Immunization Schedule , Immunization, Secondary/methods , Pneumococcal Vaccines/adverse effects , Pneumococcal Vaccines/immunology , Child, Preschool , Heptavalent Pneumococcal Conjugate Vaccine , Humans , Immunoglobulin G/blood , Infant
4.
J Thromb Haemost ; 6(2): 297-302, 2008 02.
Article in English | MEDLINE | ID: mdl-18005235

ABSTRACT

BACKGROUND: Pulmonary embolism (PE) and intracardiac thrombosis (ICT) are rare but potentially lethal complications during orthotopic liver transplantation (OLT). METHODS: We aimed to review clinical and pathological correlates of PE and ICT in patients undergoing OLT. A systematic review of the literature was conducted using MEDLINE and ISI Web of Science. RESULTS: Seventy-four cases of intraoperative PE and/or ICT were identified; PE alone in 32 patients (43%) and a combination of PE and ICT in 42 patients (57%). Most frequent clinical symptoms included systemic hypotension and concomitant rising pulmonary artery pressure, often leading to complete circulatory collapse. PE and ICT occurred in every stage of the operation and were reported equally in patients with or without the use of venovenous bypass or antifibrinolytics. A large variety of putative risk factors have been suggested in the literature, including the use of pulmonary artery catheters or certain blood products. Nineteen patients underwent urgent thrombectomy or thrombolysis. Overall mortality was 68% (50/74) and 41 patients (82%) died intraoperatively. CONCLUSION: Mortality was significantly higher in patients with an isolated PE, compared to patients with a combination of PE and ICT (91% and 50%, respectively; P < 0.001). Intraoperative PE and ICT during OLT appear to have multiple etiologies and may occur unexpectedly at any time during the procedure.


Subject(s)
Heart Diseases/epidemiology , Intraoperative Complications/epidemiology , Liver Transplantation , Pulmonary Embolism/epidemiology , Thrombosis/epidemiology , Adolescent , Adult , Child , Child, Preschool , Combined Modality Therapy , Female , Heart Diseases/diagnosis , Heart Diseases/etiology , Heart Diseases/therapy , Hospital Mortality , Humans , Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/etiology , Hypotension/epidemiology , Hypotension/etiology , Infant , Infant, Newborn , Intraoperative Complications/diagnosis , Intraoperative Complications/etiology , Intraoperative Complications/therapy , Male , Middle Aged , Pulmonary Embolism/diagnosis , Pulmonary Embolism/etiology , Pulmonary Embolism/therapy , Risk Factors , Shock/epidemiology , Shock/etiology , Shock/therapy , Thrombelastography/statistics & numerical data , Thrombosis/diagnosis , Thrombosis/etiology , Thrombosis/therapy
5.
J Endocrinol Invest ; 30(4): 327-33, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17556871

ABSTRACT

Hepatic carcinoid tumors are very uncommon; most are clinically non-functional and very few present with the symptoms of carcinoid syndrome. ACTH-producing carcinoid tumors most commonly originate in the lung or thymus and present insidiously with bronchospasm and/or chest mass. Occasionally, ectopic ACTH syndromes have been reported in association with pancreatic islet cell tumors, medullary thyroid cancer, pheochromocytoma, small-cell lung carcinoma, and rarely, ovarian and prostate tumors. We report here a patient with an ectopic ACTH-secreting primary hepatic carcinoid tumor who presented with cushingoid appearance, profound proximal muscle weakness, severe lower extremity edema, and markedly elevated urinary free cortisol. ACTH levels were in the low normal range. A solitary vascular hepatic lesion was found on magnetic resonance imaging, which was isodense with the surrounding liver on octreotide scan and photopenic on an 18-fluorodeoxyglucose (18FDG)-positron emission tomography (PET) scan. Following surgical resection of the hepatic tumor, histopathology confirmed an ACTH-secreting neuroendocrine tumor (NET), the patient had complete resolution of hypercortisolemic symptoms and remains in remission, now 4 yr after hepatic tumor resection. This case reports the first ACTH-secreting primary hepatic NET presenting as ectopic Cushing's syndrome. Interesting aspects of this case include the presence of a pituitary incidentaloma, the low normal ACTH, and photopenia on 18FDG-PET imaging.


Subject(s)
ACTH Syndrome, Ectopic/diagnosis , Carcinoid Tumor/diagnosis , Cushing Syndrome/diagnosis , Liver Neoplasms/diagnosis , ACTH Syndrome, Ectopic/etiology , Aged , Carcinoid Tumor/complications , Carcinoid Tumor/pathology , Diagnosis, Differential , Humans , Liver Neoplasms/complications , Liver Neoplasms/pathology , Male , Radiography, Abdominal
6.
Transplant Proc ; 39(1): 169-71, 2007.
Article in English | MEDLINE | ID: mdl-17275498

ABSTRACT

Endoscopic retrograde cholangiopancreatography (ERCP) is frequently employed in the management of postoperative biliary complications in the liver transplant patient. Bleeding after ERCP most commonly presents as gastrointestinal bleeding and often can be managed with repeat endoscopy. ERCP can also be complicated by retroperitoneal hematoma, which in rare cases can lead to hemodynamic compromise due to relentless hemorrhage or from secondary abdominal compartment syndrome. We describe the first reported case of post-ERCP retroperitoneal hematoma in a liver transplant recipient that led to abdominal compartment syndrome and shock liver. We will present the case, discuss management, and review the complications of ERCP in the liver transplant recipient. Close post-procedure monitoring, rapid detection, and low threshold for decompressive laparotomy are keys to the successful management of the liver transplant recipient experiencing expanding retroperitoneal hematoma after ERCP.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Compartment Syndromes/etiology , Hematoma/etiology , Liver Transplantation/physiology , Retroperitoneal Space , Carcinoma, Hepatocellular/surgery , Hematoma/complications , Hepatitis C/surgery , Humans , Liver Neoplasms/surgery , Male , Middle Aged
7.
Aliment Pharmacol Ther ; 19(9): 1033-9, 2004 May 01.
Article in English | MEDLINE | ID: mdl-15113371

ABSTRACT

BACKGROUND: Sirolimus is a potent immunosuppressive medication that acts by inhibiting T-cell proliferation. It has been used in kidney transplantation because of its lack of nephrotoxicity. It is now being investigated in liver transplantation, but there are concerns about safety and long-term side effects such as dyslipidaemia. Hypertriglyceridaemia is a common adverse event seen with sirolimus use, and often does not respond to dose reduction or anti-lipemic drugs. METHOD: We report six patients who have developed significant hyperlipidaemia while receiving sirolimus, in spite of therapeutic trough levels. CONCLUSION: All six patients showed either resolution or improvement in lipid levels with discontinuation of sirolimus.


Subject(s)
Hyperlipidemias/chemically induced , Immunosuppressive Agents/adverse effects , Kidney Transplantation , Sirolimus/adverse effects , Adult , Aged , Cyclosporine/therapeutic use , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Tacrolimus/therapeutic use
8.
Liver Transpl ; 7(12): 1023-33, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11753904

ABSTRACT

Cholangiocellular carcinoma (CCC) is a biliary malignancy that frequently presents in advanced unresectable stages. The role of liver transplantation (LT) as a surgical modality is unclear. The goal of this study is to evaluate outcomes of patients with CCC undergoing LT. A retrospective analysis of all patients undergoing LT was undertaken. Only those patients with the pathological diagnosis of CCC were included on the study. Patients were divided into two groups based on primary tumor location: extrahepatic (EH)-CCC and intrahepatic (IH)-CCC. The Kaplan-Meier method was used to calculate overall and recurrence-free survival. Log-rank analysis was used to determine the significance of prognostic variables. Twenty-five patients were identified: 9 patients with EH-CCC (5 patients, Klatskin-type; 2 patients, the middle third; and 2 patients, the distal third) and 16 patients with IH-CCC. Mean age was 47.1 +/- 10.6 years. There were 14 men and 11 women. Tumor stage was local (stages I and II; n = 9) or advanced (stages III and IV; n = 16). Overall and disease-free survival rates were 71% and 67% at 1 year and 35% and 32% at 3 years, respectively. Analysis of variables showed statistically significant improved outcomes (P < .05) for the absence of contiguous organ invasion at LT, small tumor size, and single tumor foci. This study indicates that early survival after LT for CCC is acceptable. Three-year disease-free survival is achieved in approximately 30% of patients. These outcomes can be improved by applying strict selection criteria based on prognostic variables identified in this study.


Subject(s)
Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/surgery , Cholangiocarcinoma/surgery , Liver Transplantation , Adult , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Chemotherapy, Adjuvant , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Female , Humans , Liver/pathology , Male , Middle Aged , Postoperative Care , Postoperative Complications , Retrospective Studies , Survival Analysis
9.
Liver Transpl ; 7(6): 513-7, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11443579

ABSTRACT

Donor shortage has led to the use of hepatitis B core antibody (anti-HBc)--positive (anti-HBc(+)) liver allografts for patients in need of relatively urgent orthotopic liver transplantation (OLT). Because anti-HBc(+) allografts transmit hepatitis B virus (HBV) infection at a high rate, effective prophylaxis is required. We assessed the effectiveness of lamivudine in preventing HBV transmission by anti-HBc(+) allografts. Between March 1996 and March 2000 at Cedars-Sinai Medical Center (Los Angeles, CA), 15 of 169 patients (8.9%) received liver allografts from anti-HBc(+) donors. Six patients were hepatitis B surface antigen (HBsAg)(+) (group 1), and 9 patients were HBsAg negative (HBsAg(-); group 2) before OLT. All patients were administered lamivudine, 100 or 150 mg/d, orally after OLT. Patients who were HBsAg(+) before OLT also were administered hepatitis B immunoglobulin (HBIG) prophylaxis. Hepatitis B serological tests were performed on all patients, and HBV DNA was determined in liver tissues in 10 patients. All 15 patients remained HBsAg(-) at their last follow-up 2 to 40 months (mean, 17 months) post-OLT. All patients in group 1 had antibody to HBsAg (anti-HBs) titers greater than 250 mIU/mL post-OLT (mean follow-up, 20 months; range, 7 to 40 months). Of the 2 patients in group 1 who underwent liver biopsy after OLT, 1 patient had detectable hepatic HBV DNA despite being anti-HBs(+) and HBsAg(-). Among the patients in group 2, none acquired anti-HBc or HBsAg. Hepatic HBV DNA was undetectable in the 7 patients in group 2 who underwent liver biopsy after OLT. Anti-HBc(+) allografts can be safely used in patients who undergo OLT for chronic hepatitis B and susceptible transplant recipients if prophylaxis with combination HBIG and lamivudine or lamividine alone is administered after OLT, respectively. However, more data are needed to determine the efficacy of lamivudine monotherapy in preventing transmission of HBV infection from anti-HBc(+) liver allografts to susceptible recipients.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B Antibodies/metabolism , Hepatitis B/prevention & control , Hepatitis B/transmission , Lamivudine/therapeutic use , Liver Transplantation/adverse effects , Adult , DNA, Viral/metabolism , Hepatitis B/virology , Hepatitis B Core Antigens , Hepatitis B Surface Antigens/metabolism , Humans , Middle Aged , Tissue Donors
10.
J Nucl Med ; 42(1): 110-6, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11197958

ABSTRACT

UNLABELLED: The clinical usefulness of quantitative functional imaging techniques that use asialoglycoprotein receptor (ASGP-R) binding is based on the correlation between ASGP-R density and hepatic functional reserve. Portal-systemic shunting (PSS) is common in patients with cirrhosis and portal hypertension-the same group that is most frequently considered for such imaging. PSS occurs spontaneously through collateral vessels and from the creation of surgical shunts or placement of transjugular intrahepatic portal-systemic shunts (TIPS). Understanding the physiologic relationship between PSS and ASGP-R activity may aid in the interpretation of quantitative clinical imaging. This study was conducted to determine the relationship between PSS and ASGP-R density in the absence of parenchymal disease. METHODS: Sprague-Dawley rats with end-to-side portal-systemic shunts and sham-operated control rats were imaged with 99mTC-diethylenetriaminepentaacetic acid galactosyl-neoglycoalbumin. Pharmacokinetic modeling of the liver and heart time-activity data was used to measure ASGP-R concentration, as well as hepatic plasma volume and flow. RESULTS: The mean ASGP-R density (nmol/g of liver) was significantly decreased in the shunted rats. Blood ammonia was significantly elevated, whereas hepatic plasma flow, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase levels were unaltered. Liver histology was normal in both groups. CONCLUSION: A significant change in the ASGP-R density occurs with PSS in the absence of parenchymal disease. PSS appears to be an independent variable affecting ASGP-R activity. This could prove clinically important during interpretation of quantitative imaging from patients with varying degrees of PSS based on underlying disease or the presence of a surgical shunt or TIPS device.


Subject(s)
Asialoglycoproteins/metabolism , Liver/metabolism , Portal System/physiopathology , Portasystemic Shunt, Surgical , Receptors, Cell Surface/metabolism , Animals , Asialoglycoprotein Receptor , Liver/diagnostic imaging , Liver Circulation/physiology , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Rats , Rats, Sprague-Dawley , Technetium Tc 99m Aggregated Albumin/pharmacokinetics , Technetium Tc 99m Pentetate/pharmacokinetics
11.
Adv Intern Med ; 46: 155-76, 2001.
Article in English | MEDLINE | ID: mdl-11147252

ABSTRACT

Acute hepatic encephalopathy is a disorder linked between the 2 most complex organs of the body and is clearly an integral aspect of acute liver failure. Its presence defines fulminant hepatic failure and its progression reflects the prognosis. For the scientist, the pathophysiology of this syndrome is a fascinating and active area of research, bridging numerous independent disciplines in new and creative ways. For the clinician, acute hepatic encephalopathy invokes its due respect as a challenging aspect of the syndrome of fulminant liver failure.


Subject(s)
Hepatic Encephalopathy/diagnosis , Hepatic Encephalopathy/physiopathology , Acute Disease , Combined Modality Therapy , Female , Hepatic Encephalopathy/mortality , Hepatic Encephalopathy/therapy , Humans , Male , Prognosis , Risk Assessment , Severity of Illness Index , Survival Rate
12.
Ann Surg ; 232(3): 312-23, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10973381

ABSTRACT

OBJECTIVE: To determine the factors that influence patient survival after in vivo split liver transplantation (SLT). SUMMARY BACKGROUND DATA: Split liver transplantation is effective in expanding the donor pool, and its use reduces the number of deaths in patients awaiting orthotopic liver transplantation. Early SLTs were associated with poor outcomes, and acceptance of the technique has been slow. A better understanding of the factors that influence patient and graft survival would be useful in widening the application of SLT. METHODS: During a 3.5-year period, 55 right and 55 left lateral in vivo split grafts were transplanted in 102 pediatric and adult recipients. The authors' in vivo split technique has been previously described. Median follow-up was 14.5 months. Recipient, donor, and surgical variables were analyzed for their effect on patient survival after SLT. RESULTS: Overall survival rates of patients who received an SLT were not significantly different from those of patients who received whole organ transplants. Survival of left lateral segment recipients, at median follow-up time, was 76% versus 80% in patients receiving a trisegment. Fifty of 102 patients (49%) were high-risk urgent recipients (United Network for Organ Sharing [UNOS] status 1 and 2A) and 52 (51%) were nonurgent recipients (UNOS status 2B, 3). High-risk recipients had a survival rate significantly lower than that of nonurgent recipients. By univariate comparison, two variables-UNOS status and number of transplants per patient-were significantly associated with an increased risk of death. Preoperative recipient mechanical ventilation, preoperative prothrombin time, donor sodium level, donor length of hospital stay, and warm ischemia time approached significance. The type of graft (right vs. left) did not reduce the survival rate after transplantation. Multivariate logistic regression analysis identified UNOS status and length of donor hospital stay as independent predictors of survival. CONCLUSIONS: Patient survival of in vivo SLT is not significantly different from that of whole-organ orthotopic liver transplantation. The variables affecting outcome of in vivo SLT are similar to those in whole-organ transplantation. in vivo SLT should be widely applied to expand a severely depleted donor pool.


Subject(s)
Liver Transplantation/methods , Postoperative Complications/mortality , Adolescent , Adult , Aged , Cause of Death , Child , Child, Preschool , Female , Follow-Up Studies , Hospital Mortality , Humans , Infant , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Rate
13.
J Neurosci Methods ; 99(1-2): 1-7, 2000 Jun 30.
Article in English | MEDLINE | ID: mdl-10936637

ABSTRACT

The use of cultured brain slices has become an accepted technique for the ex vivo analysis of neural mechanisms, yet the viability of this preparation is not routinely measured. The tetrazolium dye 3-(4, 5-dimethlythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) is reduced by active mitochondria to an insoluble purple precipitate which accumulates within living cells and is easily visualized with bright field or phase contrast microscopy. In this study, the MTT assay was used to assess the viability of cultured brainstem, hippocampal and spinal cord slices (150-300 micrometer) from 0 to 22 day-old neonatal rats at post-explant time points ranging from 2 to 29 days. After 2 weeks, 180-300 micrometer cultured slices from 4-13 day old rats remained 90-100% viable. Those from 0-1 day old rats had similar viability but displayed peripheral tissue outgrowth. Slices from older 18-22 day rats were no longer viable after 10-14 days. After 4 weeks, the thicker (300 micrometer) slices of hippocampus and spinal cord retained 75-89% viability, in contrast to the 50-74% viability of the brainstem. Thinner brainstem and hippocampal slices (150-220 micrometer) slices were less than 50% viable at 4 weeks. Morphologic characteristics of the brain regions gradually degenerated over the 4-week culture period. Slice viability was markedly influenced by tissue thickness, donor age and brain region. Use of the MTT assay provides an inexpensive and expeditious means to assess a significant functional parameter of regional slice viability under variable conditions and enhances the feasibility of this preparation for functional studies, such as those concerned with genetic and protein expression within circumscribed areas of the brain.


Subject(s)
Brain/metabolism , Cell Survival/physiology , Organ Culture Techniques , Animals , Animals, Newborn , Brain/cytology , Brain Stem/cytology , Brain Stem/metabolism , Coloring Agents , Hippocampus/cytology , Hippocampus/metabolism , Mitochondria/metabolism , Rats , Spinal Cord/cytology , Spinal Cord/metabolism , Tetrazolium Salts , Thiazoles , Time Factors
14.
Semin Liver Dis ; 20 Suppl 1: 7-12, 2000.
Article in English | MEDLINE | ID: mdl-10895438

ABSTRACT

Hepatitis B is the sixth most common indication for liver transplantation in the United States, accounting for about 7% of all transplants among adults. Transplantation for hepatitis B is especially problematic because the virus is not eradicated and there is great potential for reinfection that can lead to graft failure or death. This risk is higher still in patients with active viral replication and chronic liver disease. Treatment with short-term hepatitis B immune globulin (HBIG) delays reinfection of the allograft, but only long-term treatment with HBIG has led to a decline in the reinfection rate. Combination therapy using HBIG with nucleoside analogues will likely become the standard of care to maintain stable serum titers of protective anti-HBs antibody and to prevent posttransplantation reinfection.


Subject(s)
Hepatitis B/surgery , Liver Transplantation , Adult , Female , Hepatitis B/prevention & control , Hepatitis B Vaccines , Humans , Immunization, Passive , Immunoglobulins/therapeutic use , Lamivudine/therapeutic use , Liver Transplantation/methods , Male , Reverse Transcriptase Inhibitors/therapeutic use , Risk Factors , Secondary Prevention , Survival Analysis
15.
Antioxid Redox Signal ; 2(2): 347-54, 2000.
Article in English | MEDLINE | ID: mdl-11229538

ABSTRACT

Peroxiredoxin (Prx)-I and -II belong to a new class of antioxidants. Here, we report that they are induced by ischemia/reperfusion (I/R) in transplanted livers. Hypothesizing that Prxs are induced to protect liver from oxidative damage, we transduced these human genes into murine NIH-3T3 cells. The overexpressed Prxs made the cells more resistant to t-butylhydroperoxide-induced apoptosis. These results indicate that Prx-I and Prx-II are induced by the transplantation process and can protect cells against oxidant damage in tissue culture. Thus, proper genetic manipulations of Prxs may be useful in increasing the success rate of organ transplantation.


Subject(s)
Antioxidants/metabolism , Liver Transplantation , Peroxidases/metabolism , 3T3 Cells , Animals , Apoptosis , Dose-Response Relationship, Drug , Fibroblasts/metabolism , Flow Cytometry , Green Fluorescent Proteins , Humans , Immunoblotting , Liver/metabolism , Luminescent Proteins/metabolism , Mice , Oxidative Stress , Peroxidases/genetics , Peroxiredoxins , Plasmids/metabolism , Reperfusion Injury , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Transduction, Genetic
16.
Ann Surg ; 229(6): 824-31; discussion 831-3, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10363896

ABSTRACT

OBJECTIVE: To determine the outcome of orthotopic liver transplantation (OLT) for end-stage liver disease caused by hepatitis C virus (HCV). SUMMARY BACKGROUND DATA: HCV has become the leading cause of cirrhosis and hepatic failure leading to OLT. Recurrent HCV after OLT is associated with significant complications and may lead to graft loss that requires retransplantation (re-OLT). The authors studied the outcome of transplantation for HCV, the effect of primary immunotherapy, and causes of retransplantation. METHODS: The authors conducted a retrospective review of their experience during an 8-year period (1990-1997), during which 374 patients underwent transplants for HCV (298 [79.6%] received one OLT; 76 [20.4%] required re-OLT). Median follow-up was 2 years (range 0 to 8.3). Immunosuppression was based on cyclosporine in 190 patients and tacrolimus in 132 patients. In a third group of patients, therapy was switched from cyclosporine to tacrolimus or from tacrolimus to cyclosporine (cyclosporine/tacrolimus group). RESULTS: Overall, 1-, 2-, and 5-year actuarial patient survival rates were 86%, 82%, and 76%, respectively. The 2-year patient survival rate was 81 % in the cyclosporine group, 85% in the tacrolimus group, and 82% in the cyclosporine/tacrolimus group. In patients receiving one OLT, overall 1-, 2-, and 5-year patient survival rates were 85%, 81%, and 75%, respectively. The 2-year patient survival rate was 79% in the cyclosporine group, 84% in the tacrolimus group, and 80% in the cyclosporine/tacrolimus group. The overall graft survival rates were 70%, 65%, and 60% at 1, 2, and 5 years, respectively. The graft survival rate at 2 years was similar under cyclosporine (68.5%), tacrolimus (64%), or cyclosporine/tacrolimus (60%) therapy. Re-OLT was required in 42 (11.2%) patients for graft dysfunction in the initial 30 days after OLT. Other causes for re-OLT included hepatic artery thrombosis in 10 (2.6%), chronic rejection in 8 (2.1%), and recurrent HCV in 13 (3.4%) patients. The overall survival rates after re-OLT were 63% and 58% at 1 and 2 years. The 1-year survival rate after re-OLT was 61 % for graft dysfunction, 50% for chronic rejection, 60% for hepatic artery thrombosis, and 60% for recurrent HCV. At re-OLT, 85.3% of the patients were critically ill (United Network for Organ Sharing [UNOS] status 1); only 14.7% of the patients were UNOS status 2 and 3. In re-OLT for chronic rejection and recurrent HCV, the 1-year survival rate of UNOS 1 patients was 38.4%, compared with 87.5% for UNOS 2 and 3 patients. In patients requiring re-OLT, there was no difference in the 1-year patient survival rate after re-OLT when cyclosporine (60%), tacrolimus (63%), or cyclosporine/tacrolimus (56%) was used for primary therapy. With cyclosporine, three patients (1.5%) required re-OLT for chronic rejection versus one patient (0.7%) with tacrolimus. Re-OLT for recurrent HCV was required in four (3%) and seven (3.6%) patients with tacrolimus and cyclosporine therapy, respectively. CONCLUSIONS: Orthotopic liver transplantation for HCV is performed with excellent results. There are no distinct advantages to the use of cyclosporine versus tacrolimus immunosuppression when patient and graft survival are considered. Re-OLT is an important option in the treatment of recurrent HCV and should be performed early in the course of recurrent disease. Survival after re-OLT is not distinctively affected by cyclosporine or tacrolimus primary immunotherapy. The incidence of re-OLT for recurrent HCV or chronic rejection is low after either tacrolimus or cyclosporine therapy.


Subject(s)
Cyclosporine/therapeutic use , Hepatitis C/surgery , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Liver Transplantation , Adult , Follow-Up Studies , Graft Survival , Hepatitis C/mortality , Humans , Liver Transplantation/mortality , Reoperation , Retrospective Studies , Survival Rate , Time Factors , Treatment Outcome
17.
Transplantation ; 67(5): 767-70, 1999 Mar 15.
Article in English | MEDLINE | ID: mdl-10096539

ABSTRACT

During orthotopic liver transplantation (OLT) for fulminant hepatic failure (FHF), some patients develop cerebral injury secondary to intracranial hypertension. We monitored intracranial pressure (ICP) and cerebral perfusion pressure (CPP) before and during OLT in 12 FHF patients undergoing transplantation. All four patients who had normal ICP preoperatively maintained normal ICP/CPP throughout OLT. During OLT, four of the eight patients with pretransplant intracranial hypertension had six episodes of ICP increase. These episodes of intracranial hypertension occurred during failing liver dissection (n=3) and graft reperfusion (n=3). At the end of the anhepatic phase, the ICP was lower than the preoperative ICP in all patients, and was below 15 mmHg in all but one patient. These data suggest that in FHF patients who develop intracranial hypertension before OLT, dissection of the native liver and graft reperfusion are associated with a risk of brain injury resulting from intracranial hypertension and cerebral hypoperfusion.


Subject(s)
Hepatic Encephalopathy/therapy , Intracranial Hypertension/etiology , Liver Transplantation/adverse effects , Adult , Brain Edema/etiology , Child , Female , Humans , Male , Middle Aged
18.
Liver Transpl Surg ; 4(6): 506-9, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9791162

ABSTRACT

Hypothermia during orthotopic liver transplantation (OLT) is common despite measures to prevent this complication. We retrospectively analyzed two groups of patients; those managed with (n = 113) or without (n = 109) a heat exchanger (HE) incorporated in the venovenous bypass (VVB) circuit to test the hypothesis that normothermia before liver reperfusion minimizes hypotension during reperfusion and decreases neohepatic transfusion requirements. Use of the HE resulted in significantly warmer patients during reperfusion and at the end of surgery (P < .001). An increase in neohepatic transfusion requirement was observed in patients with HE use: packed red blood cells, 4 +/- 4 versus 3 +/- 3 units; fresh-frozen plasma, 5 +/- 5 versus 4 +/- 4 units; platelets, 8 +/- 8 versus 6 +/- 7 units; and cryoprecipitate, 5 +/- 7 versus 3 +/- 5 units. There was no difference between the two groups in the untoward hemodynamic events during reperfusion of the liver (P = .31). We conclude that during OLT, the use of an HE in a nonheparinized VVB circuit helps maintain normothermia. Our limited experience suggests that its use is safe but does not improve hemodynamic stability during reperfusion or decrease blood loss during the neohepatic period.


Subject(s)
Heating/methods , Hypothermia/prevention & control , Intraoperative Complications/prevention & control , Liver Transplantation , Chi-Square Distribution , Female , Heating/instrumentation , Hemodynamics , Humans , Kidney Transplantation , Male , Retrospective Studies , Treatment Outcome
19.
Am Surg ; 64(10): 926-9, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9764693

ABSTRACT

The outcome of surgical intensive care unit (SICU) care after nonemergent orthotopic liver transplantation (OLTX) was evaluated in 168 consecutive patients over a 6-year period (1/90-12/95). Prospective data collected included age, first and last SICU day Simplified Acute Physiology Score and Quantitative Therapeutic Intervention System Score, SICU length of stay (LOS), and mortality. The patient population was 61 per cent male and 39 per cent female, with ages ranging from 20 to 75 years. A total of four patients died in the SICU, for a mortality of 2.4 per cent. Over the study period, SICU LOS decreased by 21 per cent, from 3.9 +/- 0.7 to 3.1 +/- 0.3 days (P < 0.05). Although no difference in admission severity of illness was observed over the study period, there was an increase in the intensity of intervention performed on admission to the SICU. Over the study period, there was no difference in severity of illness or intensity of intervention upon discharge to floor care. The decreased SICU LOS did not adversely affect patient mortality or severity of illness upon SICU discharge during the 6-year period. With intensified SICU intervention, nonemergent orthotopic liver transplantation patients can have a shorter SICU LOS without adverse effects on outcome.


Subject(s)
Critical Care/methods , Liver Transplantation , Postoperative Care/methods , Postoperative Complications/therapy , Adult , Aged , Female , Hospital Mortality , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Postoperative Complications/mortality , Severity of Illness Index , Survival Rate , Treatment Outcome
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