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Biomedical subjects

A N Langnas

Publications and source records attributed to A N Langnas.

At least 19 recordsLinked to original sources
PubMed2006

Inflammatory bowel disease after liver transplantation: risk factors for recurrence and de novo disease.

Inflammatory bowel disease (IBD) is associated with primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) and can recur or develop de novo after orthotopic liver transplantation (OLT). The aim of this study was to investigate the incidence and severity of IBD after liver transplantation and to perform a multivariate analysis for possible risk factors. In this retrospective study, 91 patients transplanted for PSC or AIH, without prior colectomy, were included. Sixty patients were transplanted for PSC, 31 for AIH. IBD activity before and after OLT and other possible risk factors were analysed in a multivariate model. Forty-nine patients (54%) had IBD before OLT. Forty patients (44%) had active IBD after transplantation: recurrence in 32 and de novo in 8. Cumulative risk for IBD after OLT was 15, 39 and 54% after 1, 5 and 10 years, respectively. In 59% of patients with IBD prior to OLT the disease was more active after transplantation. Risk factors for recurrent disease were: symptoms at time of OLT, short interval of IBD before OLT and use of tacrolimus. 5-aminosalicylates were protective. A cytomegalovirus positive donor/negative recipient combination increased the risk for de novo IBD.

Adult↗
PubMed2004

Functional liver recovery parallels autologous gut salvage in short bowel syndrome.

BACKGROUND/PURPOSE: Parenteral nutrition (PN) is life saving in short bowel syndrome. However, long-term parenteral nutrition is frequently complicated by a syndrome of progressive cholestatic liver disease that is considered to be irreversible beyond the early stages of cholestasis, particularly in the presence of any degree of fibrosis in the liver. The purpose of this study was to examine apparent improvement in PN-associated liver dysfunction in a cohort of children with short bowel syndrome. METHODS: A retrospective case-record review of all patients managed within a dedicated Intestinal Rehabilitation Program (IRP) identified 13 patients with short bowel who had PN-associated liver dysfunction, defined for this purpose as hyperbilirubinemia or an abnormal liver biopsy. RESULTS: At referral, 12 of the 13 patients were exclusively on PN, and one was on 50% PN. At current follow-up, 3 patients have achieved complete enteral autonomy from PN, and 7 patients have had smaller decrements in PN requirements. Specific operative procedures to improve intestinal function were undertaken in 11 patients; 4 patients also underwent cholecystectomies with biliary irrigation at the time of intestinal reconstruction. The median highest bilirubin level in these 13 patients was 10.7 mg% (range, 3.2 to 24.5 mg%). Liver biopsy results indicated that 5 patients were cirrhotic, 3 had bridging fibrosis, and 4 had severe cholestasis or lesser degrees of fibrosis. Of 10 survivors in this series, 9 patients currently have a serum bilirubin less than 1 mg% with a median bilirubin in the group of 0.6 mg% (range, 0.3 to 6.4 mg%). Twelve of the 13 patients in this series were initially referred for liver-small bowel transplantation. CONCLUSIONS: This preliminary experience suggests that PN-dependent patients with advanced liver dysfunction in the setting of the short bowel syndrome may, in some instances, experience functional and biochemical liver recovery. The latter appears to parallel autologous gut salvage in most cases. As a corollary, the authors believe that even advanced degrees of liver dysfunction should not preclude attempts at autologous gut salvage in very carefully selected patients. Such a policy of "aggressive conservatism" may help avoid the need for liver/intestinal transplantation in some patients who appear to be not responding to PN.

Adolescent↗
PubMed2003

The interaction defect of accessory molecules is responsible for the poor ex vivo response to human antigens of mouse T helper cells.

Mouse T cells fail to respond to xenogeneic pig and human antigens using the direct antigen-presenting pathway. The poor response by mouse CD8 cells is because of multiple defects in the molecular interactions between mouse CD8 cells and xenogeneic antigen-presenting cells (APCs). Using human CD4/DR3+, mouse CD4-/major histocompatibility complex (MHC) class II - mice, we investigated the defects in molecular interaction responsible for the poor response to xenogeneic antigens by naïve mouse CD4+ cells. Mouse CD4 cells failed to respond to human leucocyte antigen (HLA)-DR3 expressed on mouse APCs but developed a strong response to alloantigens, indicating a defect in the interaction between mouse CD4 and HLA-DR3 molecules. Human CD4+/mouse CD4- mouse T cells respond poorly to human and pig APCs but not allogeneic APCs, indicating that accessory molecular interactions are deficient across highly separated species. Adding mouse interleukin-2 (IL-2) to the mixed lymphocyte reaction system did not improve the poor response to human or pig antigens by mouse or human CD4+/mouse CD4- mouse T cells. Therefore, multiple molecular interactions deficient between mouse CD4 cells and human or pig APCs may lead to the poor response to xenogeneic antigens by naïve mouse CD4 cells.

Animals↗
PubMed2002

Late graft loss and long-term outcome after isolated intestinal transplantation in children.

BACKGROUND/PURPOSE: The aim of this study was to determine causes of late graft loss and long-term outcome after isolated intestinal transplantation in children at a single center. METHODS: All children who underwent primary isolated intestinal transplantation at our center with a minimum follow-up of 1 year were the subject of this retrospective study. RESULTS: Twenty-eight children underwent primary isolated intestinal transplantation. Median graft survival was 705 days (range, 0 to 2,630 days) and median patient survival was 1,006 days (range, 0 to 2,630 days). There were 6 deaths and 15 graft losses (including the 6 nonsurvivors). Seven of the losses occurred 6 or more months after transplant. Of these, 2 losses occurred because of death of the recipients of sepsis; both recipients had functioning grafts. The 5 remaining late graft losses occurred because of acute rejection in 2 patients, chronic rejection in 2 (1 with concomitant acute rejection) and a diffuse stricturing process without the histologic hallmarks of chronic rejection in the fifth. All late survivors with intact grafts are off total parenteral nutrition (TPN). CONCLUSIONS: Late graft loss remains a concern in a small percentage of patients after isolated intestinal transplantation. Nutritional autonomy from TPN is possible in the majority of these children after transplantation.

Age Factors↗
PubMed2001

A new technique for combined liver/small intestinal transplantation.

The most common application of small bowel transplantation is for the patient with parenteral nutrition-induced liver failure. In this setting, the small intestine is transplanted simultaneously with the liver. We identified three technical problems that we believe contributed to complications in our first eight patients. First, pancreaticoduodenectomy was challenging in the infant donor. Second, the bowel graft was prone to volvulus around the skeletonized donor portal vein. Third, in the pediatric recipient, use of the donor bowel for Roux-en-Y biliary reconstruction was associated with biliary leaks in the early postoperative period. Our surgical technique of liver/small bowel (L/SB) transplantation has evolved since our early experience in 1990. Modifications in the L/SB operation, reported briefly in 1996 and 1997, have led to easier graft preparation and have reduced the incidence of technical complications.

Humans↗
PubMed2001

Lack of utility of intestinal fatty acid binding protein levels in predicting intestinal allograft rejection.

INTRODUCTION: The enterocyte-specific protein, intestinal fatty acid binding protein (I-FABP), is detectable in serum only after intestinal injury. Previous studies in animals suggest that I-FABP might be a useful marker of intestinal allograft rejection. MATERIALS AND METHODS: I-FABP was repetitively measured in nine intestinal transplant recipients and correlated with findings of surveillance endoscopy. RESULTS: Average interval between I-FABP determination and biopsy was 3.4 days (SD=4.2 days). Average number of rejection episodes per patient totalled 1.6+/-1.2. General linear modeling demonstrated no tendency for increases in serum FABP to precede histologic graft rejection (P=0.263). Restriction of the analysis to I-FABP determinations 1 day before or on the day of biopsy failed to affect these results. Minor increases in I-FABP were often associated with histologically normal grafts, whereas rejection often occurred when I-FABP was not detectable. DISCUSSION: Serum I-FABP levels do not predict clinical intestinal allograft rejection.

Adult↗
PubMed2001

Indications for pediatric intestinal transplantation: a position paper of the American Society of Transplantation.

Parenteral nutrition represents standard therapy for children with short bowel syndrome and other causes of intestinal failure. Most infants with short bowel syndrome eventually wean from parenteral nutrition, and most of those who do not wean tolerate parenteral nutrition for protracted periods. However, a subset of children with intestinal failure remaining dependent on parenteral nutrition will develop life-threatening complications arising from therapy. Intestinal transplantation (Tx) can now be recommended for this select group. Life-threatening complications warranting consideration of intestinal Tx include parenteral nutrition-associated liver disease, recurrent sepsis, and threatened loss of central venous access. Because a critical shortage of donor organs exists, waiting times for intestinal Tx are prolonged. Therefore, it is essential that children with life-threatening complications of intestinal failure and parenteral nutrition therapy be identified comparatively early, i.e. in time to receive suitable donor organs before they become critically ill. Children with liver dysfunction should be considered for isolated intestinal Tx before irreversible, advanced bridging fibrosis or cirrhosis supervenes, for which a combined liver and intestinal transplant is necessary. Irreversible liver disease is suggested by hyperbilirubinemia persisting beyond 3-4 months of age combined with features of portal hypertension such as splenomegaly, thrombocytopenia, or prominent superficial abdominal veins; esophageal varices, ascites, and impaired synthetic function are not always present. Death resulting from complications of liver failure is especially common during the wait for a combined liver and intestinal transplant, and survival following combined liver and intestinal Tx is probably lower than following an isolated intestinal transplant. The incidence of morbidity and mortality following intestinal Tx is greater than that following liver or kidney Tx, but long-term survival following intestinal Tx is now at least 50-60%. It is probable that outcomes shall improve in the future with continued refinements in operative technique and post-operative management, including immunosuppression.

Child↗
PubMed2000

Extracorporeal liver perfusion using human and pig livers for acute liver failure.

BACKGROUND: Patients with fulminant hepatic failure (FHF) often die awaiting liver transplantation. Extracorporeal liver perfusion (ECLP) has been proposed as a method of "bridging" such patients to transplantation. We report the largest experience to date of ECLP using human and porcine livers in patients with acute liver failure. METHODS: Patients with FHF unlikely to survive without liver transplantation were identified. ECLP was performed with human or porcine livers. Patients underwent continuous perfusion until liver transplantation or withdrawal of support. Two perfusion circuits were used: direct perfusion of patient blood through the extracorporeal liver and indirect perfusion with a plasma filter between the patient and the liver. FINDINGS: Fourteen patients were treated with 16 livers in 18 perfusion circuits. Nine patients were successfully "bridged" to transplantation. ECLP stabilized intracranial pressure (ICP) and cerebral perfusion pressure (CPP). Arterial ammonia levels fell from a median of 146 to 83 micromol/liter within 12 hr and this reduction was maintained at least 48 hr. Pig and human ECLP lowered ammonia levels equally. Serum bilirubin levels also fell from a median of 385 to 198 micromol/liter over the first 12 hr but the response was not sustained as well with porcine livers. There was no immunological benefit to using the the filtered perfusion circuit. INTERPRETATION: These data demonstrate that ECLP is safe and can provide metabolic support for comatose patients with fulminant hepatic failure for up to 5 days. While labor and resource intensive, this technology is available to centers caring for patients with acute liver failure and deserves wider evaluation and application.

Adolescent↗
PubMed2000

Characterization of an outbreak due to extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a pediatric intensive care unit transplant population.

Limited information exists regarding Klebsiella pneumoniae's production of an extended-spectrum beta-lactamase (KP-ESBL) in pediatric patients, particularly solid-organ transplant recipients. This study characterized the microbiological, epidemiological, and clinical features of a KP-ESBL outbreak in children receiving a liver transplant, an intestinal transplant, or both. All children found to have microbiologically confirmed K. pneumoniae during a 21-month period were reviewed. ESBL production was defined by double-disk diffusion, and 6 distinct pulsed-field gel electrophoresis patterns were identified. Fifty-six percent of the transplant patients we studied developed KP-ESBL, representing 87% of all microbiologically confirmed cases at our institution. As compared with 16 control transplant patients who were negative for KP-ESBL, the 20 transplant patients who acquired KP-ESBL were younger (aged < or = 5 years; 80.0% vs. 43.8%, P = .038) and experienced placement of > or = 3 central venous catheters before recovery of the first K. pneumoniae isolate (73.7% vs. 18.8%, P = .002). This study suggests that children who receive liver or intestinal transplants are at high risk for KP-ESBL acquisition.

Adolescent↗
PubMed2000

Disaccharidase activities and fat assimilation in pediatric patients after intestinal transplantation.

BACKGROUND: Intestinal transplantation has become an accepted therapy for short bowel syndrome and other types of intestinal failure. In order to assess digestive capabilities and feeding practices in a group of 22 pediatric patients after intestinal transplantation, we assessed mucosal disaccharidase activities and assimilation of total dietary lipid and vitamin E. Twelve of the patients had undergone contemporaneous liver transplantation. METHODS: Mucosal biopsies were assayed for disaccharidase activities between 15 and 412 days after transplantation in 7 of the 22 when all were receiving some enteral nutrition and were free of rejection. Coefficients of lipid absorption were determined in those patients receiving total enteral feeding (two-thirds polymeric/one-third elemental) between 43 and 1032 days after transplantation; oral vitamin E tolerance tests were done at about the same time. RESULTS: Activities of lactase, sucrase, maltase, and palatinase consistently exceeded reference ranges (P<0.05). Mean coefficient of lipid absorption equaled 86+/-12% and was not influenced by duration of time after transplantation. No patient required dietary lipid restriction. No significant absorption of vitamin E was demonstrated until 160 days after transplantation. Vitamin E absorption did correlate with length of time elapsed after surgery (r=0.64, P<0.0011). CONCLUSIONS: The results of this investigation show that, in the absence of histologic or clinical indications of allograft rejection, pediatric intestinal transplant recipients do not have primary disaccharidase deficiencies. Similarly, absorption of usual dietary lipid content is adequate once weaning from parenteral nutrition is complete. In contrast, early assimilation of vitamin E is poor. Vitamin E absorption subsequently improves, but the mechanism is obscure.

Child↗
PubMed2000

Effect of surrogate tolerogenesis on the vascular rejection of pig heart xenografts.

BACKGROUND: Organ xenografts are fulminantly rejected by antibody-mediated vascular rejection. Surrogate tolerogenesis (ST), the induction of tolerance within the donor, is effective with aorta xenografts. This preliminary study assesses the effect of ST on preformed antibodies and rejection of porcine heart xenografts. METHODS: Tolerance to the donor pig was induced by infusing recipient marrow into fetal pigs. Later, pig splenocytes were transfused and heterotopic pig hearts transplanted using chimeric or nonchimeric pigs. Anti-pig antibodies were assessed. RESULTS: With ST alone, xenografts developed cellular rejection at 4-6 days, whereas control grafts developed vascular rejection at 3-4 days (cellular vs. vascular, P<0.03). There was a reduction in preformed antibodies (P<0.03). ST combined with moderate cyclosporine prevented rejection at 9+ and 25 days in sensitized recipients compared with vascular rejection at 0.5-2 days for controls (P<0.07). CONCLUSIONS: ST seems to provide protection against vascular rejection. The cellular rejection seems sensitive to cyclosporine.

Animals↗