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Biomedical subjects

E A Pomfret

Publications and source records attributed to E A Pomfret.

At least 19 recordsLinked to original sources
PubMed2006

The Art and Science of Immunosuppression: the Fifth Annual American Society of Transplant Surgeon's State-of-the-Art Winter Symposium.

The 2005 American Society of Transplant Surgeons (ASTS) Winter Symposium entitled 'The Art and Science of Immunosuppression' explored ways to maximize existing immunosuppressive protocols and to develop new strategies incorporating novel agents and emerging diagnostic technologies to customize immunosuppression and reduce side effects. Several presentations evaluated steroid withdrawal or avoidance protocols reflecting the significant difficulties of bone loss, glucose control and growth retardation in children associated with long-term steroid use. Calcineurin-inhibitor related renal dysfunction of both native and transplanted kidneys was identified as significant, but no consensus was reached concerning effective prevention. Similarly, recurrence of Hepatitis C following liver transplantation was identified as problematic without identifying a preferred immunosuppressive regimen in this setting. Control of T-cell mediated rejection was found to be excellent, but recognition and treatment of non-T cell causes of allograft damage (i.e. B- or NK-cell mediated) was identified as an area of current interest. Immunosuppressive agents under development, such as those blocking co-stimulation or cytokine signals, and JAK-3 inhibitors were discussed. Finally, the available technologies for molecular and genetic diagnostics and the clinical correlation in the post-transplant setting were discussed.

Humans↗
PubMed2006

Improved survival after live donor adult liver transplantation (LDALT) using right lobe grafts: program experience and lessons learned.

We present our program experience with 85 live donor adult liver transplantation (LDALT) procedures using right lobe grafts with five simultaneous live donor kidney transplants using different donors performed over a 6-year period. After an "early" 2-year experience of 25 LDALT procedures, program improvements in donor and recipient selection, preoperative imaging, donor and recipient surgical technique and immunosuppressive management significantly reduced operative mortality (16% vs. 3.3%, p = 0.038) and improved patient and graft 1-year survival in recipients during our "later" experience with the next 60 cases (January 2001 and March 2005; patient survival: early 70.8% vs. later 92.7%, p = 0.028; graft survival: Early 64% vs. later 91.1%, p = 0.019, respectively). Overall patient and graft survival were 82% and 80%. There was a trend for less postoperative complications (major and minor) with program experience (early 88% vs. later 66.7%; p = 0.054) but overall morbidity remained at 73.8%. Biliary complications (cholangitis, disruption, leak or stricture) were not influenced by program experience (early 32% vs. later 38%). Liver volume adjusted to 100% of standard liver volume (SLV) within 1 month post-transplant. Despite a high rate of morbidity after LDALT, excellent patient and graft survival can be achieved with program experience.

Adolescent↗
PubMed2001

Live donor adult liver transplantation using right lobe grafts: donor evaluation and surgical outcome.

HYPOTHESIS: Live donor adult liver transplantation (LDALT) is a safe and efficacious treatment for patients with end-stage liver disease. DESIGN: Case-control study. SETTING: Hepatobiliary surgery and liver transplantation unit. PATIENTS: From December 10, 1998, through April 10, 2000, a single team performed 15 LDALT procedures with 2 simultaneous living donor kidney transplants. During this period, 66 potential donors were screened and evaluated. INTERVENTIONS: Potential donors were evaluated with 3-dimensional helical computed tomographic scan, including volume renderings for hepatic lobar volume, vascular anatomy, virtual resection planes, and morphologic features. Suitable donors undergo complete medical and psychiatric evaluation and preoperative arteriography. MAIN OUTCOME MEASURES: Donor demographics, evaluation data, operative data, hospital length of stay, and morbidity. RESULTS: A total of 38 men (58%) and 28 women (42%) were evaluated with 15 donors participating in LDALT. Two additional donors provided kidney grafts for simultaneous transplantation at the time of LDALT. Thirty-two donors (48%) were rejected for either donor or recipient reasons, and 10 patients (15%) elected not to participate after initial screening. Three-dimensional volume renderings by helical computed tomographic scan predicted right lobe liver volume within 92% of actual graft volume. Donor morbidity, including all complications, was 67% with no mortality. Residual liver regenerated to approximately 70% of initial volume within 1 week and 80% within 1 month after surgery. CONCLUSIONS: Donor evaluation is an important component of LDALT. Significant donor morbidity is encountered even with careful selection. To minimize donor morbidity, groups considering initiating living donor programs should have expertise in hepatic resection and vena cava preservation using the "piggyback" technique during liver transplantation.

Adolescent↗
PubMed2001

Life-threatening hypophosphatemia after right hepatic lobectomy for live donor adult liver transplantation.

Life-threatening hypophosphatemia (phosphorus < 1.0 mg/dL) has been reported only once after liver resection for tumor and was associated with a significant increase in postoperative complications. Hypophosphatemia is associated with reversible cardiac dysfunction, hypoventilation, and impaired immunity. The purpose of this study was to determine the incidence of hypophosphatemia after elective right hepatic lobectomy for live donor adult liver transplantation (LDALT), investigate the associated complication rate and surgical outcome of live liver donors, and determine the efficacy of prospective treatment with phosphate repletion as part of total parenteral nutrition (TPN). Evaluation of 30 donors who provided 30 right-lobe grafts between December 1998 and January 2000 was performed. Of the initial 18 live liver donors (group 1), 10 donors were treated with TPN that contained slightly more (35 +/- 8 mmol/d) than the recommended daily allowance (RDA) of phosphorus (30 mmol/d) starting on postoperative day 1. The last 12 donors (group 2) were prospectively studied and administered similar TPN with 2 times the RDA for phosphorus (60 mmol/d). All donors in group 1 developed hypophosphatemia that was either life threatening (phosphorus < 1.0 mg/dL) in 70% or severely depleted (phosphorus, 1.5 to 1.1 mg/dL) in 30%. With more aggressive phosphate repletion (group 2), only 8% developed life-threatening (phosphorus < 1.0 mg/dL) hypophosphatemia and 30% developed severe (phosphorus, 1.1 to 1.5 mg/dL) hypophosphatemia. Results suggest that hypophosphatemia is a universal event after LDALT and may have contributed to the observed complications in this study. Repletion of phosphorus at twice the RDA abrogates the incidence of hypophosphatemia and may reduce donor morbidity. Institutions performing LDALT should carefully monitor live liver donors for hypophosphatemia and correct abnormal phosphate levels. Additional studies are needed to determine whether more aggressive parenteral repletion can prevent postoperative hypophosphatemia and thus improve outcomes.

Adult↗
PubMed2001

Impact of multidetector CT on donor selection and surgical planning before living adult right lobe liver transplantation.

OBJECTIVE: This study was performed to document the impact of multidetector multiphase CT in facilitating patient selection and surgical planning in potential donors being evaluated for living adult right lobe liver transplantation. SUBJECTS AND METHODS: Forty consecutive potential donors were included in the study. There were 26 men and 14 women, (age range, 18-57 years; mean, 37 years) We performed CT using a multidetector scanner, after IV injection of 180 mL of contrast material at 5 mL/sec. Arterial phase images were acquired at 18 sec (collimation, 1.25 mm; table speed, 7.5) and portal phase images, at 60 sec (collimation, 2.5 mm; table speed, 15). Postprocessing was performed on a commercially available workstation. CT data included dual-energy assessment of liver parenchyma for fatty infiltration; depiction of arterial, portal venous, and hepatic venous anatomy and identification of important vascular variants; and determination of total and lobar liver volume. RESULTS: Of the 40 potential liver donors evaluated, 15 patients (37.5%) were excluded on the basis of CT findings, with most exclusions a result of portal vein anomalies (n = 8). Fatty infiltration resulted in four exclusions (10%), and small liver volume resulted in three exclusions (7.5%). CONCLUSION: Multidetector multiphase CT provided comprehensive parenchymal, vascular, and volumetric preoperative evaluation of potential donors undergoing living adult right lobe liver transplantation. This information had a major impact on patient selection because it was used to stratify patients. It allowed the surgeons to plan their surgical approach, and this planning may reduce postoperative complications.

Adolescent↗
PubMed2001

Accuracy of volumetric measurements after virtual right hepatectomy in potential donors undergoing living adult liver transplantation.

OBJECTIVE: The purpose of this study was to evaluate accuracy for determining the total and lobar liver volumes using a multidetector CT scanner in potential donors undergoing living adult right lobe liver transplantation. SUBJECTS AND METHODS: Fifty-two adult donors underwent CT using a multidetector scanner after IV injection of 180 mL of contrast material. For volumetric determination, portal venous phase images were acquired at 60 sec. Hand-tracing was used to isolate the entire liver, and a curved hepatectomy plane was then identified in a manner simulating the surgical incision. Two observers performed hand-tracing of the entire liver to calculate total liver volume, and of the right lobe to calculate expected graft volume. RESULTS: The mean volume of the entire liver, right lobe, and left lobe was 1807 mL, 990 mL, and 817 mL, respectively, for observer 1, and 1788 mL, 1007 mL, and 781 mL, respectively, for observer 2. There was significant agreement between the two observers in determining total and lobar liver volumes (r = 0.996, 0.977, and 0.965 for total, right lobe, and left lobe volumes, respectively; p< 0.0001). There was no statistically significant difference between the two observers in measuring total or lobar liver volumes (p< 0.0001). There was significant agreement between right lobe volume measured by each observer and graft weight obtained in 14 donors at surgery (r = 0.898 and 0.879, for observers 1 and 2, respectively; p <0.001). CONCLUSION: Total and lobar volume determinations after virtual right hemihepatectomy provides accurate and reproducible information that is critical in selecting potential living liver donors.

Adolescent↗
PubMed1999

Cavernous hemangioma of the liver: anatomic resection vs. enucleation.

HYPOTHESIS: Patient outcome and the development of major intra-abdominal postoperative complications following removal of cavernous hemangiomas of the liver are affected by methods of resection. DESIGN: Case-control study. SETTING: Hepatobiliary surgery and liver transplantation unit in a tertiary care referral medical center. PATIENTS: Between December 1, 1987, and December 1, 1997, 28 patients underwent the surgical removal of cavernous hemangioma either by hepatic resection or enucleation. Indications for the operation were pain, enlarging tumors, uncertain diagnosis, or rupture. MAIN OUTCOME MEASURES: The technique of tumor removal, hospital course, and the development of intra-abdominal complications. Independent factors influencing the development of complications were ascertained by multivariate analysis. RESULTS: Twenty-four female and 4 male patients (age, 47.5+/-12.4 [mean +/- SD] years) underwent either enucleation (n = 23) or liver resection (n = 5). Lesions ranged from 2 to 16 cm in their postresection diameter. No surgical (30-day) mortality was observed. Four major intra-abdominal complications were found: 1 episode of intraoperative bleeding requiring abdominal packing and 3 intra-abdominal fluid collections requiring percutaneous drainage. Enucleation was the only independent factor found by univariate and multivariate analyses to be associated with a reduction in the number of intra-abdominal complications (P = .04). CONCLUSIONS: Cavernous hemangiomas of the liver can be removed safely by either hepatic resection or enucleation. Enucleation is associated with fewer intra-abdominal complications and should be the technique of choice when tumor location and technical factors favor enucleation.

Case-Control Studies↗
PubMed1999

Distal splenorenal shunt: role, indications, and utility in the era of liver transplantation.

HYPOTHESIS: The distal splenorenal shunt (DSRS) continues to play an important role in the management of recurrent variceal bleeding with minimal negative impact on subsequent orthotopic liver transplantation (OLT). DESIGN: Case-control study. SETTING: Hepatobiliary surgery and liver transplantation unit in a tertiary referral medical center. PATIENTS: From August 1, 1985, through October 31, 1997, a single team of surgeons performed 81 DSRS procedures for recurrent variceal hemorrhage. Eleven patients undergoing OLT subsequent to DSRS were compared with a group of 274 patients undergoing OLT without any previous shunt during the same period. MAIN OUTCOME MEASURES: Operative time, use of blood products, length of hospital stay, perioperative complications, and survival rates. RESULTS: Operative (30-day) mortality for DSRS was 6% (n = 5). From follow-up information available for 74 patients, the 1- and 5-year survival rates were 86.4% (n = 64) and 74.3% (n = 55), respectively. Recurrent variceal bleeding and hepatic encephalopathy occurred in 5 (6.8%) and 11 patients (14.9%), respectively, after DSRS. In 9 patients, DSRS was used as salvage for failed transjugular intrahepatic portosystemic shunt. CONCLUSIONS: Distal splenorenal shunt is a safe, durable, and effective treatment for controlling recurrent variceal hemorrhage in patients with acceptable operative risk and good liver function. It does not compromise future liver transplantation and can considerably delay the time until transplantation is required. Given the early occlusion rate and need for constant surveillance, transjugular intrahepatic portosystemic shunting should be reserved for patients with Child C classification cirrhosis with chronic hemorrhage or intractable ascites or as an emergency procedure for patients with uncontrollable bleeding using endoscopic therapy.

Adult↗
PubMed1998

Effect of orthotopic liver transplantation on the progression of familial amyloidotic polyneuropathy.

BACKGROUND: Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disease associated with a mutant form of the protein transthyretin (TTR). It is characterized clinically by the systemic deposition of amyloid fibrils resulting in organ dysfunction and, ultimately, death. The majority of TTR is produced in the liver, and transplantation of the liver has been shown to ameliorate this source of mutant TTR, arresting the progression of this fatal disease. METHODS: Thirteen patients with FAP have undergone successful liver transplant surgery at our center since 1992. The impact of liver transplantation on amyloid-related polyneuropathy, cardiovascular, and gastrointestinal dysfunction is reported in this study. Three patients who died before cardiovascular and neurological follow-up are excluded from the analysis. RESULTS: Ten of 13 patients (77%) remain alive an average of 49 months (range, 17-64 months) after transplantation. Three patients suffered sudden death, with autopsy documentation of amyloid deposits involving the conduction system of the heart. Liver transplantation was performed more quickly, required less blood, and a shorter postoperative hospital stay in these patients, compared with patients with cirrhosis. Neurological and nutritional symptoms improved in the majority of affected patients. Those patients with echocardiographic evidence of ventricular wall and valve thickening before transplantation progressed postoperatively despite neurologic improvement. CONCLUSIONS: Liver transplantation offers the only cure for the genetic defect causing FAP and appears to result in subjective and objective improvement in neurological dysfunction. Patients with preexisting cardiovascular abnormalities progress despite transplantation; therefore, consideration for combined heart-liver transplantation may be warranted in this subset of patients.

Adult↗
PubMed1993

Blunt chest trauma.

Chest trauma remains the major initiating cause of respiratory failure in the trauma patient. The degree of injury can be substantially modified with appropriate early preventive and treatment measures. The lung injury itself can be divided into early and late phases. The early phase is primarily the result of mechanical forces transmitted to the chest. Initial management should focus not just on the lung; there should also be a search for commonly present, associated, nonpulmonary injuries. Optimizing early restoration of perfusion is also crucial in the multiple trauma patient, instead of too "wet" or too "dry." The most complex phase is the late phase resulting from the host inflammatory response to injury, both local and systemic. Stress modification and control of inflammation are the keys to controlling this aspect of the disease process.

Biomechanical Phenomena↗
PubMed1991

Effects of choline deficiency and methotrexate treatment upon liver folate content and distribution.

We examined the effects of feeding rats a choline deficient diet, of treating rats with low doses of methotrexate (MTX, 0.1 mg/kg, daily), and of combined choline deficiency and MTX treatment upon the content and distribution of folates in liver. We used a newly devised technique for analysis of folates which utilized affinity chromatography followed by high pressure liquid chromatography. Compared to control rats, total hepatic folate content decreased by 31% in the choline deficient rats, by 48% in the MTX treated rats, and by 60% in rats which were both choline deficient and treated with MTX. In extracts of livers from control rats, folates were present predominantly as penta (35%) and hexaglutamyl (52%) derivatives. The pteridine ring structure distribution of these folates was as follows: 48% 5-methyltetrahydrofolate, 14% formylated tetrahydrofolate, and 39% tetrahydrofolate. In choline deficient animals, there was a decrease in the relative concentration of pentaglutamyl folates and an increase in the relative concentration of heptaglutamyl folates. In livers from MTX treated animals, MTX-polyglutamates with 2-5 glutamate residues accumulated. The consequences of MTX treatment were: a) an elongation of the glutamate chains of the folates as the proportion of hepta- and octaglutamyl derivatives was increased relative to penta- and hexaglutamyl folates; b) the occurrence of unreduced folic acid; c) a decrease in the relative concentration of 5-methyltetrahydrofolate and an increase in the relative concentration of formylated tetrahydrofolate, and d) no change in the relative concentrations of tetrahydrofolate. In livers from animals that were both choline deficient and treated with MTX, the tetrahydrofolate concentrations were 50% of control while formylated tetrahydrofolate concentrations increased 3-fold. These data are discussed from the standpoint of the current understanding of mechanisms that regulate the elongation of the glutamic acid chains of folates and those that regulate folate dependent synthesis and utilization of one carbon unit.

Animals↗
PubMed1990

Effects of choline deficiency and methotrexate treatment upon rat liver.

Choline deficiency and treatment with methotrexate (MTX) both are associated with fatty infiltration of the liver. Choline, methionine, and folate metabolism are interrelated and converge at the regeneration of methionine from homocysteine. MTX perturbs folate metabolism, and it is possible that it also influences choline metabolism. We fed rats a choline deficient diet for 2 weeks and/or treated them with methotrexate (MTX; 0.1 mg/kg daily). Choline deficiency lowered hepatic concentrations of choline (to 43% control), phosphocholine (PCho; to 18% control), glycerophosphocholine (GroPCho; to 46% control), betaine (to 30% control), phosphatidylcholine (PtdCho; to 62% control), methionine (to 80% control), and S-adenosylmethionine (AdoMet; to 57% control), while S-adenosylhomocysteine (AdoHcy) and triacylglycerol concentrations increased (to 126% and 319% control, respectively). MTX treatment alone lowered hepatic concentrations of PCho (to 48% control), GroPCho (to 69% control), betaine (to 55% control), and AdoMet (to 75% control). The addition of MTX treatment to choline deficiency resulted in a larger decrease in AdoMet concentrations (to 75% control) and larger increases in AdoHcy and triacylglycerol concentrations (to 150% and 500% control, respectively) than was observed in choline deficiency alone. Livers from MTX-treated animals used radiolabeled choline to make the same metabolites as did livers from controls (most of the label was converted to PCho and betaine). In choline deficient animals, most of the labeled choline was converted to PtdCho. Therefore, MTX depleted hepatic PCho, GroPCho, and betaine by a mechanism that was different from that of choline deficiency. MTX increased the extent of fatty infiltration of the liver in choline deficient rats, and choline deficiency and MTX treatment damaged hepatocytes as measured by leakage of alanine aminotransferase activity. Our data are consistent with the hypothesis that the fatty infiltration of the liver associated with MTX treatment occurs because of a disturbance in choline metabolism.

Journal Article↗
PubMed1989

Effect of choline deficiency on S-adenosylmethionine and methionine concentrations in rat liver.

Choline and C1 metabolism pathways intersect at the formation of methionine from homocysteine. Hepatic S-adenosylmethionine (AdoMet) concentrations are decreased in animals ingesting diets deficient in choline, and it has been suggested that this occurs because the availability of methionine limits AdoMet synthesis. If the above hypothesis is correct, changes in hepatic AdoMet concentrations should relate in some consistent manner to changes in hepatic methionine concentrations. Rats were fed on a choline-deficient or control diet for 1-42 days. Hepatic choline concentrations in control animals were 105 nmol/g, and decreased to 50% of control after the first 7 days on the choline-deficient diet. Hepatic methionine concentrations decreased by less than 20%, with most of this decrease occurring between days 3 and 7 of choline deficiency. Hepatic AdoMet concentrations decreased by 25% during the first week, and continued to decrease (in total, by over 60%) during each subsequent week during which animals consumed a choline-deficient diet. Hepatic S-adenosylhomocysteine (AdoHcy) concentrations increased by 50% when animals consumed a choline-deficient diet. AdoHcy is formed when AdoMet is utilized as a methyl donor. In summary, choline deficiency can deplete hepatic stores of AdoMet under dietary conditions that only minimally decrease the availability of methionine within liver. Thus decreased availability of methionine may not have been the only mechanism whereby choline deficiency lowers hepatic AdoMet concentrations. We suggest that increased utilization of AdoMet might also have occurred.

Animals↗