Biomedical subjects

Christine A O'Mahony

Publications and source records attributed to Christine A O'Mahony.

8 recordsLinked to original sources

PubMed2007

A pooled analysis of posttransplant survival following combined heart-liver transplantation.

Because no single center has accumulated a large experience with this complex operation, the effectiveness of combined orthotopic heart transplantation (OHT) and orthotopic liver transplantation (OLT) in achieving long-term survival has been unknown. Cases of OHT-OLT were pooled from a U.S. transplant recipient registry and from previously published literature. Aggregate data from these sources was used for survival analysis. Thirty-six patients having undergone OHT-OLT were listed in the national registry; the one- and five-year patient survival rates of these patients were 88% and 78%, respectively. Many patients remain alive at 8+ years after transplantation. An analysis of the pooled results of previously-published cases estimated a one-year patient survival rate of 84%. In selected disease processes, OHT-OLT can correct underlying metabolic deficiencies. While rarely indicated, OHT-OLT is a successful treatment for patients with end-stage heart and liver disease, with survival comparable to that seen after isolated orthotopic heart or orthotopic liver transplantation.

Adolescent↗

PubMed2006

The natural history of hepatitis C virus in pediatric liver transplant recipients.

Although rare in the pediatric population, the natural history of hepatitis C virus (HCV) recurrence in pediatric patients undergoing orthotopic liver transplantation (OLT) for end-stage liver disease secondary to HCV has not been well described. We performed an analysis of all 67 pediatric patients (< 17 years old) who have undergone OLT for HCV in the United States between 1/1988 and 6/2005. The 67 pediatric patients received a total of 83 OLTs for HCV. Following initial OLTs performed for HCV, the patient and allograft survival rates were 71.6% and 55.0%, respectively, at 5 years. Following retransplantation these rates decreased to 55.0% and 33.8%, respectively, following retransplantation. Recipients were listed for retransplantation after 31.3% of all OLTs, and overall recipients were retransplanted after 19.3% of OLTs. The overwhelming majority of retransplants were performed for HCV recurrence. A mean of 1.2 OLTs were performed per patient for HCV. The median time between OLTs for HCV was 290 days. In conclusion, the risk of HCV recurrence in pediatric OLT recipients is high and is associated with a high rate of retransplantation. Still, OLT represents the only treatment option that may achieve long-term survival in pediatric patients with end-stage liver disease secondary to HCV that is recalcitrant to medical management.

Adolescent↗

PubMed2006

Resolution of medically resistant hypothyroidism after liver transplantation for hepatic hemangioendothelioma.

Hepatic hemangioendothelioma (HHE) is a rare vascular tumor in neonates and may cause high-output cardiac failure and coagulopathy, and rarely has been associated with hypothyroidism. Hepatic hemangioendothelioma treatment options consist of corticosteroids, alpha-interferon, surgical resection, and liver transplantation. Herein, we report the case of a 6-week-old female neonate that presented with an HHE that involved all segments of the liver, resulting in respiratory failure and severe hypothyroidism that was recalcitrant to exogenous L-thyroxine therapy. After failure of medical and supportive therapy for the HHE, the patient underwent a cadaveric orthotopic liver transplantation that resulted in successful treatment of the severe hypothyroidism, respiratory failure, and cardiac symptoms. The patient is currently 1-year posttransplantation and disease free with normal thyroid function.

Female↗

PubMed2006

Etiopathogenesis of primary sclerosing cholangitis.

The etiopathogenesis of primary sclerosing cholangitis (PSC) remains undefined. Immunopathogenetic mechanisms appear to be involved, based on human leukocyte antigen complex susceptibility associations, existence of multiple autoantibodies, and presence of inflammatory bowel disease in > 75% of patients. PSC may represent an autoimmune disease with atypical features or an immune-mediated inflammatory disease, similar to inflammatory bowel disease itself. Immunogenetic susceptibility is closely linked to ligands for innate immune cells and capacity for sustained production of proinflammatory cytokines. Immunopathogenesis involves a multistep process initiated by the activation of cholangiocyte by bacterial pathogen-associated molecular patterns (stimuli of innate immunity) and proinflammatory cytokines in conjunction with aberrant expression of gut-specific chemokines and endothelial cell adhesion molecules in the liver. After recruitment of gut-primed memory T cells into the portal tracts and peribiliary space, additional mechanisms produce focal, fibrous, obliterative lesions. Progressive periductal fibrosis, chronic inflammation, and ischemic atrophy of biliary epithelia result in ductopenia, cholestasis, and obstructive strictures, culminating in secondary biliary cirrhosis.

Autoantibodies↗

PubMed2006

Evaluation and management of patients with propionic acidemia undergoing liver transplantation: a comprehensive review.

Propionic acidemia is a rare metabolic disorder that often results in episodic hyperammonemia, basal ganglia infarction, mental retardation, and cardiomyopathy. OLT has been used as a treatment for propionic acidemia, but its benefit in patients with this disease is unclear. The current study was undertaken to clarify the role of OLT in the management of this disease. The medical literature, a national registry of US OLT recipients, and a single institution liver transplant experience were reviewed for cases of OLT for propionic acidemia. Accumulated cases demonstrate that OLT has resulted in clear evidence of clinical improvement in several patients, often obviating the need for dietary restriction or other forms of medical management. OLT appears to halt the decline in neurocognitive function often associated with propionic acidemia. In total, 12 patients with propionic acidemia have undergone a total of 14 OLTs. A quantitative analysis of outcomes shows an overall patient survival rate of 72.2% at one year after OLT. In conclusion, OLT should be considered a treatment option for patients with propionic acidemia who continue to experience episodes of hyperammonemia in spite of maximal medical therapy. Early OLT may limit the development of mental retardation and/or cardiomyopathy.

Adult↗

PubMed2005

Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipients.

Epstein-Barr virus (EBV) is a common viral infection in pediatric liver transplant patients and can lead to development of post-transplant lymphoproliferative disorder (PTLD). Differing studies have used immunosuppression reduction, antiviral medications or i.v. CMV-immunogloublin for EBV prevention and treatment. The purpose of this study was to determine whether implementation of a protocol for frequent EBV monitoring and EBV viral load-driven immunosuppression reduction could decrease the incidence of PTLD in our patient population. All data were prospectively collected between 2001 and 2004 at a single institution. Seventy-three patients were entered into the study. Patients were divided into a historical control group (pre-2001, 30 patients) and a treatment group (post-2001, 43 patients). Approximately 1271 blood samples of 73 patients were collected between 2001 and 2004. Eleven out of 43 patients received immunosuppression tapering due to high EBV viral loads (>4000 copies/microg DNA). One patient developed allograft rejection after immunosuppression modulation. Prior to 2001, the incidence of PTLD at our institution was 16%. After instituting a protocol for EBV monitoring, the incidence of PTLD decreased to 2% (p-value<0.05). These findings illustrate that frequent EBV viral load monitoring and preemptive immunosuppression modulation have an integral role in preventing PTLD in the pediatric liver transplant population.

Adolescent↗

PubMed2003

Intestinal transformation results in transforming growth factor-beta-dependent alteration in tumor cell-cell matrix interactions.

BACKGROUND: An alteration in the expression of and response to transforming growth factor-beta 1 (TGF-beta 1) appears to be an important event during colorectal carcinogenesis. However, the precise role of TGF-beta 1 in colorectal carcinogenesis is not clear. We have previously described in detail the changes in cell proliferation and differentiation caused by chronic exposure to TGF-beta 1. In this study we sought to better characterize the changes in tumor cell-cell matrix interactions seen during TGF-beta 1-mediated intestinal transformation. METHODS: Rat intestinal epithelial cells (RIE) and RIE cells transformed by chronic exposure to TGF-beta 1 (RIE-Tr) were treated with TGF-beta 1 and production of components of the plasmin/plasminogen system measured by ELISA and Western blotting. TGF-beta 1 effects on invasion and adhesion were determined in vitro. The role of urokinase on TGF-beta 1-mediated invasion and adhesion were determined using immunoneutralization. The role of COX-2 was determined using a specific COS-2 inhibitor. RESULTS: TGF-beta 1 had no effect on RIE-1 adhesion to collagen types I and IV, fibronectin, and laminin, or invasion through collagen types I and IV. However, 5 ng/mL TGF-beta 1 significantly increased the invasiveness and decreased the adhesiveness of RIE-Tr. This effect of TGF-beta 1 on RIE-Tr was associated with a significant increase in plasmin activity secondary to increased expression of uPA. TGF-beta 1 had no effect on either uPA receptor or PAI-1 in this system. Antibodies to uPA completely blocked the TGF-beta 1-mediated invasiveness of the RIE-Tr cells and returned their adhesiveness to basement membrane proteins to baseline. Addition of the selective Cox-2 inhibitor SC-58125 resulted in a dose-dependent decrease in TGF-beta 1-mediated invasion and uPA expression. CONCLUSION: This study provides additional evidence for TGF-beta 1 as a tumor promoter during intestinal carcinogenesis and a possible new mechanism for Cox-2-related colon carcinogenesis.

Animals↗

PubMedDate not supplied

Isolated orthotopic liver transplantation for parenteral nutrition-associated liver injury.

BACKGROUND: Mild liver dysfunction is common after prolonged use of parenteral nutrition (PN), but end-stage liver failure occurs only rarely. Few treatment options other than combined liver-intestine transplantation exist for patients with liver failure associated with PN use, however. Herein, we report the results of a cohort of patients undergoing isolated orthotopic liver transplantation (OLT) for PN-associated liver injury. METHODS: A retrospective cohort study of 80 patients (73 pediatric patients and 7 adults) who have undergone isolated OLT for PN-associated liver injury as the primary indication for transplantation was performed. RESULTS: At the time of OLT, the mean total serum bilirubin was 19.5 mg/dL and the mean serum albumin level was 2.9 mg/dL. Severe hepatic encephalopathy was seen in 5%, spontaneous bacterial peritonitis was seen in 6.3%, and respiratory failure requiring mechanical ventilation was seen in 14% of patients at the time of OLT. Overall 1- and 5-year survival rates were 72% and 52%, respectively, with infection being the most common cause of death after OLT. Retransplantation was required in 25% of patients, and the 5-year posttransplant patient survival rate only reached 35% in these cases. CONCLUSIONS: Patients with end-stage liver disease associated with PN administration often have very severe liver disease, multiple comorbidities, and poor prognosis by the time they are listed for OLT. Nonetheless, isolated OLT is associated with good long-term survival and should be considered for selected patients with combined intestine-liver failure.

Adult↗