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Biomedical subjects

C O Esquivel

Publications and source records attributed to C O Esquivel.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effects of pentoxifylline pretreatment on Kupffer cells in rat liver transplantation.

Previous research with pentoxifylline (PTX), a methylxanthine phosphodiesterase inhibitor, suggests that this drug may be capable of suppressing the activation of Kupffer cells and thereby help decrease liver injury after transplantation. To investigate this possibility, the current study sought to determine whether the release of O2- and tumor necrosis factor (TNF) from Kupffer cells in donor livers can be suppressed if the organs are exposed to PTX before preservation. In an in vitro experiment, rat livers were flushed with PTX (25 mg/kg body weight) in University of Washington (UW) solution or UW solution alone (control) and then and stored in UW solution for either 4 or 24 hours. Kupffer cells then were purified and their degree of activation determined by measuring O2- release and the production of TNF after lipopolysaccharide stimulation. In an in vivo experiment, a group of rats underwent orthotopic liver transplantation with grafts prepared in the same manner as in the in vitro study. TNF and aspartate transaminase (AST) were measured in blood samples taken 3 hours and 24 hours after transplantation. Compared with controls, the Kupffer cells from grafts pretreated with PTX produced significantly less O2- and TNF, and the recipients of PTX-pretreated grafts had lower levels of TNF and AST 3 hours after transplantation. The current data indicate that O2- and TNF production in liver grafts is suppressed by PTX pretreatment. Through its suppressive effect on Kupffer cells, PTX may help minimize preservation-reperfusion injury and improve graft survival.

Animals↗
PubMed1994

Neurological complications of liver transplantation in adult versus pediatric patients.

Neurological complications are important contributors to morbidity and mortality after liver transplantation. We reviewed 391 patients who underwent 427 consecutive orthotopic liver transplantations to analyze the clinical features of patients who experienced one or more neurological complication (74 patients [19%]) and to compare postoperative neurological problems in adults versus children. Neurological complications were more frequent in adults (64 of 273 patients [23%]) than children (10 of 118 patients [8%]) (P < 0.01). The most common neurological complication was encephalopathy (59%), which ranged widely in severity and occurred with similar frequency in adults and children. Other common neurological complications were seizures (12 patients), brachial plexus and peripheral nerve injuries (16 patients, 15 of whom were adults), stroke (5 patients), and central nervous system infections (5 patients). In 27 patients, drug toxicity was the primary cause of neurological complications, all of which reversed with dosage reduction or discontinuation of drug. Cyclosporine and FK506, primarily during intravenous administration for induction of immunosuppression, accounted for 25 of 27 drug-induced neurological complications, which included encephalopathy, seizures, severe tremor, and severe headache. Despite a higher rate of neurological complications in adults, those in children were more severe and associated with a higher mortality rate. When compared with liver transplant recipients without neurological complications, patients with neurological complications had a higher posttransplant mortality rate (14% vs. 5% for adults, and 50% vs. 7% for children). In conclusion, neurological complications after liver transplantation are more common in adults, more severe and associated with a higher mortality rate in children, and associated with a higher mortality rate in both children and adults when compared with transplant recipients without neurological complications.

Adult↗
PubMed1994

FK506 conversion therapy in pediatric liver transplantation.

The safety and efficacy of conversion to FK506 after failing immunosuppression with cyclosporine was prospectively evaluated in 31 pediatric liver transplant recipients between April 1991 and March 1993. The patients, who ranged in age from 40 days to 14 years, accounted for 28 primary transplantations and 3 retransplantations. The initial immunosuppression regimen consisted of cyclosporine in combination with prednisone. The indications for conversion were acute or chronic rejection refractory to OKT3, Minnesota antilymphocyte globulin, or steroids (13 patients); hypertension (8 patients); inability to reach a therapeutic level of cyclosporine (6 patients); hirsutism (3 patients); and growth retardation (1 patient). After an average follow-up of 10 months (range, 2 to 25 months), 27 (87%) of the patients are alive and have functioning grafts. Of the 13 patients who were converted for refractory rejection, 9 are alive. Six of these 9 patients experienced a complete biochemical reversal of the rejection process within 3 months of conversion; 2 had a partial response to conversion, and 1 patient failed but underwent successful retransplantation. Three of the 4 patients who died did so without showing any improvement. The remaining 18 patients who were converted for various other reasons are alive and have functioning grafts. Of the 8 patients who developed hypertension on cyclosporine and prednisone, 6 experienced a resolution of this problem within 3 months of conversion. Three of the 18 children who underwent rescue therapy for reasons other than refractory rejection experienced rejection episodes after conversion to FK506. Two of these 3 children achieved resolution with either steroid therapy or an increased dosage of FK506, while the third child developed chronic rejection. The side effects of FK506 were generally minor and resolved by lowering the dose. Lymphoproliferative disease developed in 2 patients (6%). The present study suggests that FK506 is a relatively safe and effective rescue therapy for pediatric liver transplant recipients who have failed immunosuppression with cyclosporine. Longer follow-up is needed to assess the effect of FK506 on growth.

Adolescent↗
PubMed1994

Modification of rejection by polyethylene glycol in small bowel transplantation.

The use of polyethylene glycol (PEG) in preservation solutions has been associated with a decreased incidence of rejection in clinical and experimental organ transplantation. In this study, we examined the effect of PEG with different molecular configurations on rejection of small bowel allografts in the rat. Male ACI and LEW rats were used as donors and recipients, respectively. Orthotopic small bowel transplantation was performed using the following preservation solutions: lactated Ringer's solution (n = 7), University of Wisconsin solution (n = 7), University of Wisconsin solution without hydroxyethyl starch (sUW; n = 7), sUW with PEG20M (n = 9), sUW with PEG8000 (n = 6), and sUW with PEG20L (n = 7). No immunosuppression was given. In orthotopic small bowel transplantation, only groups with a high molecular weight PEG, PEG20M and PEG20L, demonstrated longer survival (P < 0.01 and P < 0.001, respectively) and delayed onset of unkempt appearance (P < 0.05 and P < 0.001, respectively). In heterotopic small bowel transplantation, sUW was compared with sUW with PEG20L. Rejection occurred later and its progression was slower in the sUW with PEG20L than in the sUW alone. Our observations suggest that the onset and progression of rejection after small bowel transplantation were influenced by the molecular weight and configuration of the PEG molecule. The mechanism is unclear, but high molecular weight PEG appears to reduce or change the immunogenicity of the small bowel allograft.

Animals↗
PubMed1994

Comparison of transjugular and surgical portosystemic shunts on the outcome of liver transplantation.

OBJECTIVE: To analyze the effect of previous transjugular intrahepatic portosystemic shunt (TIPS) vs surgical portosystemic shunt (SPS) on the outcome of orthotopic liver transplantation (OLT). DESIGN: A case series of 38 patients who underwent OLT: 25 with a previous TIPS and 13 with a previous SPS. SETTING: A liver transplant center and interventional radiology service in a private, tertiary referral medical center. PATIENTS: Eighteen men and seven women who had a TIPS before OLT were compared with nine men and four women who had an SPS before OLT. MAIN OUTCOME MEASURES: Operative transfusion requirements, operative time, length of hospital stay, postoperative liver chemistry studies, and graft and patient survival. RESULTS: Compared with patients who had an SPS, patients who had a TIPS had significantly less median transfusion requirements for packed red blood cells (5 vs 12 U), fresh-frozen plasma (0 vs 8 U), and thrombocytes (0 vs 1 U). The median operative time (9 vs 13 hours), length of intensive care unit stay (3 vs 5 days), and length of hospital stay (12 vs 24 days) were also significantly less in patients who had a TIPS. The 2-year actuarial patient survival rate was 92% in both groups. CONCLUSIONS: In patients undergoing OLT, TIPS is associated with reduced operative transfusion requirements, operative time, and length of intensive care unit and hospital stays compared with SPS. In the potential liver transplant candidate with refractory complications of portal hypertension, TIPS is preferred to SPS.

Adult↗
PubMed1994

Treatment of hepatic failure secondary to isoniazid hepatitis with liver transplantation.

Two patients with liver failure secondary to isoniazid hepatotoxicity were successfully treated with orthotopic liver transplantation. A 49-year-old man received isoniazid prophylaxis for a positive tuberculin test, and a 60-year-old woman was treated for active pulmonary tuberculosis with isoniazid, rifampin, and pyrazinamide. Both patients developed hepatic failure 4 and 1.5 months after initiation of antituberculous drug therapy, respectively. Liver transplantation was performed for progressive hepatic failure and was successful in both patients. The patient with active pulmonary tuberculosis was successfully treated with a modified antituberculous drug regimen while taking standard doses of immunosuppressive drugs after transplantation. In conclusion, liver transplantation is feasible and effective therapy for patients with isoniazid-induced hepatic failure, and active pulmonary tuberculosis may represent a relative rather than absolute contraindication to transplantation.

Chemical and Drug Induced Liver Injury↗
PubMed1994

Pretransplant chemotherapy in pediatric hepatocellular carcinoma.

The prognosis for pediatric patients with hepatocellular carcinoma is poor, except for fewer than half the patients, who can be rendered disease-free with conventional liver resection. Multicentric, bilobar liver cancer remains unresectable, even after radiation and chemotherapy. Liver transplantation alone for primary hepatic cancer has had limited success. Chemotherapy has been reserved for use after transplantation, with little demonstrable benefit. A pilot program of pretransplant chemotherapy was undertaken. Four adolescent patients with unresectable, multicentric, bilobar hepatocellular carcinoma were staged noninvasively, underwent chemotherapy followed by a final staging laparotomy, and then had liver transplantation. Three of the four patients survived and have no evidence of recurrence 84, 67, and 47 months after diagnosis and 76, 65, and 44 months after transplantation. Pretransplant chemotherapy has four potential advantages: (1) minimized risk of posttransplant opportunistic infections, (2) less tumor bulk at the time of transplantation, (3) fewer local recurrences, and (4) a lower rate of metastasis.

Adolescent↗
PubMed1994

Hepatocellular carcinoma and liver cell dysplasia in children with chronic liver disease.

The histology of 72 livers from 72 children who underwent liver transplantation was reviewed. Nine children (12.5%) had hepatocellular carcinoma (HCC) and/or liver cell dysplasia (LCD) in their native livers. Ages at the time of transplantation ranged from 2 months to 11 years. Primary liver diseases included tyrosinemia (3), biliary atresia (2), chronic active hepatitis B (1), chronic active non-A non-B non-C hepatitis (1), idiopathic neonatal hepatitis (1), and neonatal iron storage disease (1). Explanted livers showed large multifocal HCC in two cases, incidental HCC in three, and dysplastic nodules in four. LCD also was present in three cases in conjunction with HCC. All patients had cirrhosis. Alpha-fetoprotein was measured in six children and was elevated in all six (range, 300 to 1,770,000 ng/mL; normal, 0 to 15 ng/mL). Abdominal computed tomography, ultrasonography, and/or magnetic resonance imaging showed large masses in two cases, but did not detect the tumors of less than 2 cm or the dysplastic nodules in the other seven children. After a follow-up period of 2 months to 3 years (mean, 19.8 +/- 12.1 months), eight children are alive and have no evidence of recurrence. The patient with neonatal iron storage disease died 2 months after transplantation, without evidence of tumor recurrence. The authors conclude that children with end-stage liver disease of diverse causes referred for liver transplantation may have LCD and/or HCC. Serial determination of alpha-fetoprotein and images studies may detect early lesions curable by liver transplantation.

Carcinoma, Hepatocellular↗
PubMed1994

Pulmonary varices presenting as a solitary lung mass in a patient with end-stage liver disease.

A man undergoing evaluation for liver transplantation was found to have an asymptomatic chest mass, which further evaluation revealed to be pulmonary varices. The left hilar lesion was discovered on a screening chest x-ray film and confirmed by a computed tomographic scan of the thoracic cavity. Bronchoscopy was nondiagnostic, and a thoracotomy was required to diagnose the vascular lesion and exclude carcinoma. The pathophysiology of this pulmonary venous anomaly appeared to be related to portal hypertension, since esophagogastric and colonic varices also were present and the pulmonary varices resolved after liver transplantation. This is the first reported case of pulmonary varices caused by portal hypertension.

Diagnosis, Differential↗
PubMed1994

Liver transplantation at California Pacific Medical Center, San Francisco, California.

A number of modifications in patient selection, operative technique, and immunosuppressive management have greatly contributed to the success of the liver transplant program at CPMC. Graft rejection and the timely detection of EBV infection are ongoing problems in hepatic transplantation that are foci of active research in our field. To address these issues, our group is investigating the activity of cytokines and adhesion molecules using sophisticated molecular techniques, and we are developing a sensitive assay for EBV markers in blood. These and other projects currently in progress will continue when we move our liver transplant program to Stanford University Medical Center in January 1995.

Actuarial Analysis↗