Eating difficulties in the pediatric small bowel recipient: the role of the nutritional management team.
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Biomedical subjects
Publications and source records attributed to A Tzakis.
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Our procedure for donor harvesting and preserving intestinal grafts has matured. In 27 consecutive cases, a protocol was established whose essentials consist of (a) selecting hemodynamically stable donors, (b) antibiotic pretreatment of the donor, and (c) short warm ischemic times (< 40 minutes). Assessment of graft quality can be achieved by daily inspection of stomas, inspection for diarrhea > 2.5 1/day in adults or > 300 ml in children, and weekly protocol or clinically directed endoscopic biopsies. Edema and microscopic separation of the mucosal surface and sloughing are routinely found during the first few post-engraftment days, but the crypt cells remain and regenerate a normal mucosa within a week. Recovery of a normal mucosal surface took place in all cases.
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Our ability to control both the cellular and humoral components of xenograft rejection in laboratory experiments, together with an organ shortage that has placed limits on clinical transplantation services, prompted us to undertake a liver transplantation from a baboon to a 35-year-old man with B virus-associated chronic active hepatitis and human immunodeficiency virus infection. Liver replacement was performed according to conventional surgical techniques. Immunosuppression was with the FK 506-prednisone-prostaglandin regimen used routinely for hepatic allotransplantation, to which a daily non-myelotoxic dose of cyclophosphamide was added. During 70 days of survival, there was little evidence of hepatic rejection by biochemical monitoring or histopathological examination. Products of hepatic synthesis, including clotting factors, became those of the baboon liver with no obvious adverse effects. Death followed a cerebral and subarachnoid haemorrhage that was caused by an angioinvasive aspergillus infection. However, the underlying cause of death was widespread biliary sludge that formed in the biliary tree despite a seemingly satisfactory choledochojejunostomy. During life and in necropsy samples, there was evidence of the chimerism that we believe is integral to the acceptance of both xenografts and allografts. Our experience has shown the feasibility of controlling the rejection of the baboon liver xenograft in a human recipient. The biliary stasis that was the beginning of lethal infectious complications may be correctable by modifications of surgical technique. In further trials, the error of over-immunosuppression should be avoidable.
Over a period of 33 years, it has become possible to successfully transplant individual intra-abdominal viscera or combinations of these organs. The consequences have been, first, new information about the metabolic interrelations that the visceral organs have in disease or health; second, the addition of several procedures to the treatment armamentarium of gastrointestinal diseases; and third, a more profound understanding of the means by which all whole organ grafts are accepted.
Liver biopsy is a frequently utilized diagnostic tool at a liver transplant center. It is occasionally utilized prior to OLTx to determine whether or not a potential recipient either has tumor or a disease process that has some chance of spontaneous recovery without OLTx. Following OLTx, it is often utilized to determine the need to alter a recipient's immunosuppression regimen or gauge the response to a recent change in immunosuppression. At the University of Pittsburgh Medical Center, adult liver transplant patients have been biopsied using 3 different techniques based upon the physician's (Tru-cut needle) or surgeon's (suction needle) personal choice and whether or not it has been the intent of the biopsy to obtain tissue from a focal lesion within a liver. In the latter cases, ultrasound guidance and an automated biopsy needle are used. In the former, either a suction-type needle (Jamshidi) or a cutting needle (Tru-cut) has been used. During the period between January 1, 1989, and December 31, 1991, a total of 12,750 liver biopsies have been done on patients admitted to the adult transplant service at this institution. Of these, 8500 were performed with a suction needle, 4195 were performed using a cutting needle, and 55 were performed under ultrasound guidance using an automated cutting needle. A total of 26 major complications occurred--19 with the suction needle (0.22%); 6 with the cutting needle (0.14%), and 2 using ultrasound guidance and an automatic cutting needle (3.6%). Nine of these 26 complications required surgical intervention consisting of a thoracotomy or laparotomy; 4 required the insertion of a chest tube and two required hepatic artery embolization. Based upon these data obtained at a large transplant center, it can be concluded that, in general: (1) a liver biopsy can be done safely in liver transplant recipients; (2) an overall low rate of major complications occurs varying from 0.1 to 3.6% depending upon the type of needle and other circumstances relating to the biopsy procedure; (3) complications, when they occur, are morbid and often necessitate either additional surgical or interventional radiologic procedures.
Evidence of recent parvovirus virus infection (as determined by the presence of a positive IgM antibody titer) without other identified causes of anemia was found in 5 of 26 pediatric solid-organ transplant recipients evaluated for moderate-to-severe anemia between June 1990 and July 1991. Anemia tended to be chronic (median duration of anemia at the time of diagnosis was 12 weeks) and was associated with normal red blood cell indices in the absence of reticulocytes. The median age of the children at the time of presentation with anemia due to parvovirus was 1.8 years at a median time of 8 months after transplantation. Four of the 5 children were treated with i.v. immunoglobulin because of persistence of anemia requiring blood transfusions. A response characterized by an increase in reticulocyte count and normalization of hemoglobin was seen in each of these patients 2-4 weeks after treatment. The remaining patient experienced a spontaneous recovery from her anemia. Parvovirus infection should be included in the differential diagnosis of solid-organ transplant recipients presenting with severe anemia associated with low or absent reticulocytes.
Pediatric liver transplantation has advanced remarkably over the past three decades. One-year survival has progressively increased to nearly 90% in patients transplanted for most forms of liver disease. Parallel advances in organ procurement, operative technique, immunosuppression, and infection control are responsible for improved patient survival. Among the most important advances are use of the University of Wisconsin (UW) organ preservation solution, the employment of venovenous bypass and/or "piggyback" operative technique, the development of cyclosporine A (CyA) and FK506, and the emergence of acyclovir, ganciclovir, foscarnet, and alpha interferon to combat life-threatening viral infections. The current organ shortage is being addressed by "cutdown" liver transplantation, "split liver" transplantation, and living-related donations. The next decade is likely to see advances in multi-visceral transplantation, induction of chimerism by simultaneous bone marrow-solid organ transplantation, and performance of cross-species xenografting.
Seven patients with steroid-resistant nephrotic syndrome were treated with FK 506 monotherapy. Four patients were children with focal sclerosing glomerulonephritis (FSGS). Three of these had evidence for chronic progressive renal disease consisting of interstitial fibrosis and tubular atrophy on pretreatment renal biopsies. Two patients had also failed cyclosporin A (CsA), two cyclophosphamide, and one chlorambucil prior to treatment with FK 506. Three patients were adults with mesangial proliferative, membranoproliferative, and membranous glomerulonephritis. Three patterns of response were noted: (1) a reduction in proteinuria to normal levels; (2) partial response (50% reduction) or; (3) no improvement. All patients except one experienced at least a 50% reduction in protein excretion at some time during FK 506 therapy. Two of the children and one adult reduced protein excretion to essentially normal values. One patient had no sustained reduction in protein excretion and is considered to be a treatment failure, although her protein excretion was approximately 50% of pretreatment values intermittently. The drug was generally well tolerated. The most common side-effect was nephrotoxicity, which was reversible. These encouraging results suggest that FK 506 monotherapy may be effective in controlling the proteinuria of some patients with steroid-resistant nephrotic syndrome. The use of this drug may extend our understanding of the role of T lymphocytes and cytokines in the pathogenesis of glomerulonephritis. Further study of this agent in a larger population of patients is warranted.
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