Biomedical subjects

Simon P Horslen

Publications and source records attributed to Simon P Horslen.

7 recordsLinked to original sources

PubMed2006

Optimal management of the post-intestinal transplant patient.

The lack of controlled interventional studies limits the ability to assess optimal management of intestine transplant recipients. This report aims to examine factors that probably impact on the quality of patient care in the setting of intestine transplantation. The specific practice in the most experienced intestine transplant programs in the United States was surveyed with regard to immunosuppressive regimens, treatment of acute allograft rejection, feeding, and viral surveillance and treatment. The most striking finding was in the level of agreement between the centers, particularly with regard to use of tacrolimus for maintenance immunosuppression, methylprednisone boluses for treatment of acute rejection, early postoperative enteral feeding, and ganciclovir prophylaxis.

Antiviral Agents↗

PubMed2004

Hepatocyte transplantation.

Isolated hepatocyte transplantation has long been recognized as a potential treatment for life-threatening liver disease. The basis for proceeding with clinical trials has been established by the extensive laboratory work in animal models. Human hepatocyte transplantation has been applied in individual cases and very small, uncontrolled series. Data, although sparse, demonstrate the safety and feasibility of this approach and are supportive, if less than conclusive, of effectiveness. The experience of hepatocyte transplantation in the laboratory and clinical arenas is reviewed and discussion will examine what is believed to be the primary cause for the slow growth of this technology in the clinical setting, namely a severe shortage of usable primary human hepatocytes. The potential of isolated hepatocyte transplantation remains largely untapped and awaits alternate sources of cells for transplantation other than those from discarded human cadaveric livers.

Animals↗

PubMed2004

Portosystemic shunts in children: a 15-year experience.

BACKGROUND: The role of portosystemic shunt (PSS) in children with portal hypertension has changed because of acceptance of liver transplantation and endoscopic hemostasis. We report our experience with PSS, mainly the distal splenorenal shunt, to define its role in the management of variceal bleeding. STUDY DESIGN: From 1987 to 2002, 20 children with variceal bleeding after endoscopic therapy underwent PSS. Patient and database records were reviewed. RESULTS: There were 14 boys and 6 girls; mean age was 11 years (range 3 to 18 years). Seventeen distal splenorenal and three mesocaval venous interposition shunts were performed. There was no operative mortality, 19 patients were alive at a median followup of 31 months (range 4 to 168 months) without evidence of recurrent gastrointestinal bleeding. One patient underwent transplantation 2 years after PSS and 1 patient died of hepatic failure while awaiting transplantation. The cause of portal hypertension was portal vein thrombosis (n = 13), biliary atresia (n = 3), congenital hepatic fibrosis (n = 2), hepatitis C cirrhosis (n = 1), and Budd-Chiari syndrome (n = 1). Eighteen children were Child-Turcotte-Pugh class A and the remaining two were class B. One patient had two episodes of hematemesis after PSS. Two patients had worsening ascites. One patient had mild encephalopathy and one patient had shunt stenosis requiring angioplasty. CONCLUSIONS: PSS is a safe and durable therapy for pediatric patients with portal hypertension. Liver transplantation should be reserved for children with poor synthetic function associated with variceal bleeding. PSS may also serve as a bridge to transplantation in patients with preserved hepatic function. PSS, in particular the distal splenorenal shunt, has produced excellent results. This experience challenges the need for alternative forms of portal decompression.

Adolescent↗

PubMed2003

Donor immune reconstitution after liver-small bowel transplantation for multiple intestinal atresia with immunodeficiency.

The syndrome of multiple intestinal atresia with immunodeficiency is a rare, invariably fatal congenital disorder. At 16 months of age, a child with this syndrome underwent liver-small bowel transplantation from a 1-of-6 HLA-matched donor. He acquired full enteral tolerance and normal liver function and has never shown evidence of allograft rejection. After mild graft-versus-host disease developed, studies revealed that more than 99% of his CD3(+) lymphocytes and 50% of his CD19(+) lymphocytes were of donor origin, whereas granulocytes and monocytes remained of recipient origin. He synthesizes polyclonal immunoglobulin G (IgG), IgA, and IgM and has developed antibodies to cytomegalovirus (CMV) and parainfluenza 3. His T lymphocytes are predominately CD3(+)CD4(-)CD8(-) with T-cell receptor gammadelta heterodimers and CD3(+)CD4(-)CD8(+) with CD8alphaalpha homodimers, populations consistent with an intraepithelial lymphocyte phenotypic profile. We postulate that he has engrafted a donor intestine-derived immune system and is incapable of rejecting his engrafted organs.

Cytomegalovirus Infections↗

PubMed2003

Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder.

OBJECTIVE: Transplantation of isolated hepatocytes in animal models has been shown to correct inborn errors of metabolism. Based on these studies and our experience with hepatocyte transplantation in a child with Crigler-Najjar syndrome, isolated hepatocyte transplantation was performed to attempt metabolic reconstitution in a male infant with severe ornithine transcarbamylase (OTC) deficiency. METHODS: An infant with an antenatal diagnosis of OTC deficiency was managed intensively to prevent hyperammonemia. Isolated hepatocytes were obtained by collagenase perfusion of donated livers not used for transplantation. Hepatocytes were infused in batches over the first 4 weeks of life via an umbilical venous catheter positioned in the portal vein. Immunosuppression consisted of tacrolimus and corticosteroids. RESULTS: Over 4 billion viable hepatocytes were transplanted during the first 3.5 weeks of life. A period of metabolic stability was achieved between days 20 and 31 during which normal protein intake was tolerated while phenylbutyrate was weaned. During this time, plasma ammonia and glutamine remained within normal limits. Hyperammonemia reappeared abruptly on day 31 of life. Protein tolerance diminished to baseline; metabolic stability was subsequently reattained only following successful liver transplantation at 6 months of age. CONCLUSIONS: Isolated hepatocyte transplantation appeared to result in temporary relief of hyperammonemia and protein intolerance attributable to OTC deficiency. The metabolic stability achieved was lost after 11 days presumably because of rejection of the transplanted cells because of insufficient immunosuppression. Future attempts at isolated hepatocyte transplantation for inborn errors of metabolism in humans should include adequate immunosuppression and a liver biopsy as a means of proving hepatocyte engraftment and function.

Adult↗

PubMed2002

Isolated liver transplantation in infants with end-stage liver disease associated with short bowel syndrome.

OBJECTIVE: To evaluate experience with isolated orthotopic liver transplantation in children with liver failure associated with short bowel syndrome (SBS). SUMMARY BACKGROUND DATA: Infants who have liver failure as a result of SBS are frequently referred for consideration for combined liver and small bowel transplantation. In a few patients the liver disease develops despite a seemingly adequate bowel, which if given time and appropriate management has the potential for full enteral adaptation. There is a limited literature suggesting the utility of OLT without replacement of the native bowel. The advantages over combined liver and small bowel transplantation are clear: organ availability is greater, liver-reduction techniques are well established, lower immunosuppression is required, and there is greater experience in the care of children after orthotopic liver transplantation. METHODS: Eleven infants, considered to have a good prospect of eventual gut adaptation to full enteral nutrition if it were not for their advanced liver disease, underwent isolated orthotopic liver transplantation. Age range was 6.5 to 17.7 months. All patients had been dependent on parenteral feeding but had also shown significant enteral tolerance at some time before listing for transplantation. Advanced liver disease was apparent both clinically and on histologic examination. All were jaundiced and had low albumin levels, and most had coagulopathy. As a group the infants had growth retardation. Estimated remaining length of small bowel beyond the ligament of Treitz was in the range of 25 to more than 100 cm. Six infants retained their ileocecal valve. RESULTS: Thirteen liver transplants were performed in the 11 patients. A combination of whole livers (n = 6) and reduced-size grafts, of which three were from living-related donors, were used. Biliary anastomosis was duct-to-duct in eight instances and involved a short Roux limb in the others. Eight patients are alive with follow-up of 15 to 66 months. Three deaths have occurred after transplantation as a result of sepsis. Of eight surviving patients, only two continue to receive intravenous support and in both there is increasing enteral tolerance. Since transplantation, all surviving children have shown adequate growth with maintenance of pretransplant centiles. CONCLUSIONS: In selected infants with liver failure secondary to short bowel syndrome in whom complete enteral autonomy is anticipated, isolated liver transplantation can offer long-term survival.

Humans↗

PubMed2002

Omeprozole therapy in pediatric patients after liver and intestinal transplantation.

BACKGROUND: Proton pump inhibitors such as omeprazole are increasingly used to prevent stress-related gastric bleeding in critically ill patients. In this investigation, the acid-suppressive potency of omeprazole was assessed in one at-risk group, pediatric patients undergoing liver or intestinal transplantation, or both. METHODS: Twenty-two patients ranging in age from 0.9 to 108 months (23.8 +/- 6.5) underwent isolated liver (n = 10) or intestinal (11 with composite liver allografts) transplantation. Omeprazole was delivered in bicarbonate suspension through a nasogastric tube. Therapy was started after surgery at 0.5 mg/kg every 12 hours. Gastric pH monitoring was performed approximately 2 days later. RESULTS: For the entire group, mean gastric pH equaled 6.1 +/- 0.3, the same in recipients of isolated liver and intestinal allografts. Twelve of the 22 patients demonstrated a discontinuous omeprazole effect, that is, dissipation of acid reduction before the next dose. Five of the 12 patients with discontinuous omeprazole effect had mean gastric pH of less than 5 (3.9 +/- 0.4). In 4 of these 5, the omeprazole dosing interval was shortened to every 8 or every 6 hours, resulting in an increase in mean pH to 6.6 +/- 0.2 ( P < 0.01). In the remaining 10 of 22 patients, acid suppression was uninterrupted until the next dose. No patient experienced bleeding attributable to gastric erosion. CONCLUSION: Omeprazole suspended in sodium bicarbonate is an effective acid-suppressing agent in pediatric recipients of liver or intestinal transplant, or both. A dosage of 0.5 mg/kg every 12 hours is sufficient for most patients, but dosing every 6 to 8 hours is required to assure maximal acid suppression in all.

Anti-Ulcer Agents↗