Intestinal transplantation at the University of Pittsburgh: six-year experience.
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Biomedical subjects
Publications and source records attributed to S Todo.
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Graft failure and extrahepatic organ complications, which frequently develop after transplantation, may be related to inflammatory mediators stimulated by endotoxin (ET). The role of endotoxemia after liver transplantation is controversial and may depend upon differences in the ET assay method used in the various contradicting studies. While the standard Limulus amebocyte lysate (LAL) is reactive for ET and beta-glucan, a novel turbidimetric assay method enables separate determinations of ET and beta-glucan. Beagle dogs undergoing orthotopic liver transplantation were divided into two groups. In Group I (n = 6) the grafts were transplanted immediately and in Group II (n = 6) grafts were preserved for 48 h in University of Wisconsin (UW) solution. Animals received cyclosporine immunosuppression and were followed for 14 days. Daily measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were performed. Samples for ET and beta-glucan measurement were collected serially and processed using the turbidimetric assay method. While no graft failure was seen in Group I, three of six Group II animals died from graft failure within 1 day after transplantation. Preservation and reperfusion injury was much more severe in the Group II grafts than in Group I grafts. While endotoxemia could not be detected, postoperative beta-glucan levels (undetectable pretransplant) were seen in both groups. Beta-glucan levels were much higher in Group II grafts than in Group I grafts, and correlated with the severity of liver damage. In conclusion, this study shows that beta-glucan, instead of ET, appears during the early posttransplant period. We believe that posttransplant elevation of beta-glucan is related to liver damage, especially endothelial damage by preservation and reperfusion.
A 2-month-old infant who had undergone orthotopic liver transplantation at the age of 2 weeks for carbamoyl phosphate synthetase deficiency developed infection of the CNS due to Aspergillus fumigatus. The patient was successfully treated with administration of a combination of antifungal agents (including intraventricular amphotericin B), drainage of the parietal lobe abscess, and cessation of immunosuppression. An intraventricular catheter was used both to obtain ventricular fluid for microbiologic testing and to deliver amphotericin B during nearly 4 months of treatment. We review literature on aspergillosis in solid-organ transplant recipients, especially those in whom the disease involves the CNS, and discuss in particular clinical presentation, diagnosis, treatment, and outcome.
The incidence of hepatolithiasis is high throughout East Asia compared with the West, but the marked difference in the relative proportion of hepatolithiasis to all cholelithiasis cases exists even among countries of similar ethnic backgrounds. A retrospective study of cases was conducted in two areas in China with the aim of clarifying the presence of such regional difference in China itself. The relative proportion of hepatolithiasis was 21.2% in Shenyang, 9.2% in Beijing and 4.1% in Fukuoka, Japan. A significant difference in the location of stones was also found between Shenyang, Beijing and Fukuoka. Intra- and extrahepatic hepatolithiasis in all hepatolithiasis cases was 95% in Shenyang and 75% in Beijing. Involvement of both hepatic lobes was found in 73% in Shenyang and less than 60% in the other two, suggesting that hepatolithiasis of the old form or of an advanced stage still lingers in Shenyang. In conclusion, regional differences in the proportion and the type of hepatolithiasis exist in China itself, as well as in the Chinese population in Taiwan, Hong Kong and Singapore, as previously reported. The possible contribution of environmental factors to the occurrence of hepatolithiasis is again emphasized.
BACKGROUND: The purpose of the study was to quantify changes in the quality of life of small bowel recipients before and after transplantation and of home parenteral nutrition (HPN)-dependent patients before and after therapy. We examined quality of life across multiple areas of function including physical, social, and emotional indices. METHODS: The Quality of Life Instrument in the form of a self-administered questionnaire was completed voluntarily by the recipients of small intestinal transplants and by a cohort of HPN-dependent patients. RESULTS: Small intestinal transplant recipients reported significant improvement in the quality of their life and function. They also rated their quality of life and function during the pretransplant, TPN-dependent period to be worse than before the development of chronic intestinal failure. Similarly, HPN recipients reported significant worsening across most areas of quality of life when they compared their premorbid period to the HPN-dependent state. CONCLUSIONS: TPN dependence causes significant impairment in the quality of life in most areas of functioning. In contrast, small intestinal transplantation restores the quality of life among recipients with functioning grafts.
A 2-year-old girl with acute lymphoblastic leukemia (ALL) showing a t(4;11)(q21;q23) karyotype underwent allogeneic bone marrow transplantation (BMT) with the conditioning regimen of L-PAM (70 mg/m2/d for 3 days), busulfan (140 mg/m2/d for 2 days), and total body irradiation (12 Gy). On day 57, the patient developed pneumatosis cystoides intestinalis (PCI) when she received cyclosporin A and corticosteroids for graft-versus-host disease (GVHD). Because of the presence of massive abdominal free air and the suspicion of peritonitis, she underwent surgical intervention, which, however, revealed neither intestinal perforation nor peritoneal infection. She recovered from PCI in 10 days with nasogastric suction, fasting, and systemic broad-spectrum antibiotics. PCI with massive abdominal free air after BMT should be manageable by conservative therapy alone.
To investigate whether electrophysiologic changes can detect the early onset and progress of intestinal rejection, changes in in vitro electrophysiologic function, intestinal histopathology, and Na-K-ATPase activity were studied in dogs. Adult mongrel dogs of both sexes, weighing 18-24 kg, were used for auto and allo small bowel transplantation. The entire small bowels, except for short segments at the proximal and distal ends, were switched between a pair of dogs (allograft). Animals receiving intestinal autotransplantation were used as controls. Allograft recipients were sacrificed 3, 4, 5, 7, or 9 days after transplantation, and autograft recipients were sacrificed 3, 7, or 14 days after transplantation. Immunosuppression was not used. Electrophysiologic measurements were done with an Ussing chamber. Histological analysis was performed blindly using whole thickness sections. Na-K-ATPase activity in the mucosal tissue, which is said to regulate the potential difference, was also measured. Potential difference, resistance, and Na-K-ATPase activity of the allograft intestine decreased with time and were significantly lower 7 and 9 days after transplantation compared to host intestine, normal intestine, and graft intestine of controls (autograft). Potential difference, resistance, and Na-K-ATPase activity of the native intestinal tissue and the autografts did not decrease with time. Detection of histologically mild rejection of the intestine, which is important for appropriate immunosuppressive treatment in clinical cases, could not be achieved based on electrophysiology or Na-K-ATPase activity. Deterioration of electrophysiologic function during rejection correlated with the histological rejection process and Na-K-ATPase activity; however, electrophysiology may not be a reliable tool for monitoring grafts, since it cannot detect early intestinal rejection.