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The aim of the study was to delineate the most optimal preservation conditions for small bowel grafts. Established preservation solutions such as EuroCollins, University of Wisconsin, histidine-tryptophane-ketoglutarate-Brettschneider, phosphate-buffered sucrose (PBS 140), and 3 new solutions--extracellular fluid (ECF), lactobionate fructose, and a modified lactobionate fructose solution--were compared with saline to determine the most optimal solution for the intestine. Recipient survival, standard histology, and glutaminase activity were used to assess the degree of injury encountered after 12 hr of preservation followed by transplantation. To evaluate the various preservation conditions, ECF was used at pH 6.8 (original ECF). Grafts were preserved most optimally when a vascular washout after the cold storage period was omitted and when topical rewarming of the graft with 37 degrees C saline before reperfusion was performed. Graft survival was not significantly different after preservation with any solution tested (50-83%). Highest graft survival (83%) was achieved with lactobionate fructose and PBS140. Histologic evaluation 20 min after reperfusion revealed minor differences between most groups; a slight advantage was observed for PBS140-preserved grafts. Mucosal glutaminase activity of PBS140-preserved grafts was significantly higher 20 min after reperfusion compared with any other solution evaluated, indicating a superior graft function. These data indicate that different preservation conditions have a great impact on postoperative graft survival and that PBS140 might be preferable to any of the other preservation solutions tested.

The present study in Lewis rats was designed to assess the predictive value of the mucosal enzyme activities of glutaminase, maltase, and xanthine oxidase and of histology as parameters to delineate the degree of small bowel preservation injury. Small bowel grafts were flushed with saline or a modified phosphate-buffered sucrose (PBS) solution, stored at 8 degrees C for 1, 6, or 12 hr, and transplanted heterotopically. Tissue samples for determination of mucosal enzyme activities were taken after the cold storage period, 20 min after reperfusion and 2 and 7 days postoperatively. Biopsies for light microscopic evaluations were obtained at the same time points, but not after cold storage. Glutaminase activity was well maintained after cold storage, regardless of the duration of preservation. Enzyme activities measured 20 min after reperfusion decreased with increasing duration of preservation (saline: R2 = 32.8%; P < 0.01; PBS: R2 = 52.3%; P < or = 0.001) and with increasing histologic preservation injury. Glutaminase activities were predictive for survival of grafts preserved with the PBS solution (R2 = 49.6%; P < or = 0.001; sensitivity 92%; specificity 100%), while the activities of maltase and of xanthine oxidase failed to do so. The degree of histologic preservation injury seen in graft specimens obtained 20 min after reperfusion was a good predictor of graft survival with a sensitivity of 90% for saline-preserved grafts and 92% for PBS-preserved grafts and a specificity of 88 and 67%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A retrospective analysis of 462 consecutive orthotopic liver transplantations was undertaken to evaluate incidence, risk factors, clinical course, and outcome of fungal infections. Infections involving Aspergillus (6 cases), Candida (5 cases), Mucor (1 case), and Cryptococcus (1 case) were observed in 2.8% (13/462) of our patients. Twelve of the 13 episodes developed during the first 2 postoperative months. None of the potential risk factors for fungal infections described by other authors (i.e., age, rejection treatment, dialysis, mechanical ventilation, graft failure, long operation time, second transplant, serious non-fungal infection) correlated significantly with the episodes in our patients. However, in patients who exhibited three or more of these potential risk factors the incidence of fungal infections was elevated (P < 0.001). Six of seven exogenous infections (Aspergillus, Mucor) began before July 1991 when our department moved from Charlottenburg to Wedding, thus indicating that the incidence of these infections is highly influenced by exposure (P = 0.01). Exposure prophylaxis should therefore by meticulously followed, particularly when severely compromised patients are involved, in order to prevent exogenous infections (i.e., Aspergillus/Mucor). Infections involving such patients are combined with a very high mortality (57%). We observed Candida infection as a pathological overgrowth of physiological oropharynx flora into the esophagus and/or trachea in five patients. In each case treatment led to full recovery.

From September 1988 to November 1992 318 liver transplants were performed at our hospital. Of these patients 68 had end-stage cirrhosis due to non-A, non-B, hepatitis, 44 of whom (64.7%) had hepatitis C virus RNA in the serum. Of this subgroup 35 patients (79.5%) were also anti-HCV positive. Postoperatively most recipients remained anti-HCV positive and after 1 year more than 90% had HCV RNA in the serum. About 40% developed a mild, chronic hepatitis and 50% were carriers of HCV without histopathological signs. Two patients suffered from a temporary severe acute hepatitis and one patient had a fulminant liver failure due to reinfection. In general, in liver recipients transplanted for end-stage HCV hepatitis there was a high incidence of reinfection with HCV. The clinical course, however, was less severe than in hepatitis B recurrence.

Bacterial and fungal infections are a major cause of morbidity and mortality after orthotopic liver transplantation. In the immunocompromised host, infections are thought to arise from the gut, which is almost always colonized with potential pathogens. Using oral selective bowel decontamination (SBD), potential pathogens can be eradicated from the gut and infections prevented. In this catamnestic study we have reviewed gastrointestinal colonization, bacterial and fungal infections, and bacterial resistance to standard antibiotics in our first 206 liver transplant patients while under SBD. With few exceptions, gram-negatives were eradicated from the gastrointestinal tract and secondary colonization was inhibited. In spite of unsatisfactory elimination of Candida, probably because nystatin doses were too low, Candida infections were rare (n = 4) and none was fatal. One and two-year survival rates were 93% and 92%, respectively. The bacterial and fungal infection rate was 27.8% with an infection-related mortality of 1.95%. Infections with aerobic gram-positive bacteria prevailed and only 11 gram-negative and 11 fungal infections occurred; among the latter, Aspergillus and Mucor were the most serious and responsible for three of the six deaths in this series. With regard to the development of resistance, we found an increasing number of enterococci and coagulase-negative staphylococci resistant to ciprofloxacin and imipenem, respectively, but unlikely as a consequence of SBD.

Lewis rat recipients of long-term, surviving, orthotopic Brown-Norway rat intestinal allografts, initially treated with cyclosporin A (CyA) or FK 506, were evaluated for their functional capacity and morphology over 1 year after the immunosuppressive therapy had been discontinued. Functional parameters such as nitrogen and fat balances, maltose absorption, blood chemistry, hematologic studies, and the weight gained by the allografted animals did not differ from those of syngeneically grafted or age-matched normal animals. Immunohistochemical studies showed that the lamina propria of the allografts was repopulated with recipient MHC class II+ mononuclear cells and that a normal distribution of T helper, T suppressor/killer, and IgA+ plasma cells had occurred. However, fibrous replacement of the mesenteric lymph nodes and Peyer's patches were detected in all, and an inflammatory obliterative arteriolopathy developed in the mesenteric vasculature of half of the allografted animals. No such findings were observed in recipients of syngeneic grafts. These results demonstrate that the limited use of potent immunosuppressive agents immediately after transplantation averts rejection and is followed by recipient-type mucosal lymphocytic repopulation. Simultaneously, a clinically not recognizable chronic rejection evolves. This suggests that the timely diagnosis of chronic rejection may not be possible with the use of standard tests of gut function and random mucosal biopsies alone.

During the last 16 years, 14 patients with a gallstone ileus were treated at our institution. In 11 cases we performed in addition to the enterolithotomy, a cholecystectomy and a resection of the fistula as one-stage repair. Despite the high average age (74.3 years) and the presence of various other serious morbidity in our patient population, we only observed a hospital mortality of 7.1%. Serious postoperative complications, such as sepsis and/or shock were not observed. Utilizing today's advanced anesthesia and proper intensive-care therapy, as well as early operative intervention and safe surgical technique, we believe that enterolithotomy with cholecystectomy and fistula resection as one-stage operation, should primarily be considered before performing enterolithotomy alone.

The main site of injury induced during small bowel preservation is perceived to be the basement membrane and the endothelium of the highly vascularized mucosa, an aspect evaluated here in further detail. The effects of preservation were studied using a specific basement membrane stain (laminin antibody), an endothelial cell stain (factor 8 antibody) and standard histology. In addition, mucosal glutaminase activity reflecting enterocyte integrity was measured as monitor of the extent of preservation injury. Using a rat model, small bowel grafts were harvested, the vascular bed and bowel lumen were flushed, and the grafts were stored (4 degrees C) for 1, 6, 9, and 12 hr and transplanted into syngeneic hosts. After cold storage prior to transplantation, full-thickness small bowel biopsies were obtained for the various tissue preparations. Histologic evaluation at the end of the preservation period revealed separation of the villous epithelium from the lamina propria that increased with extending preservation time. Tissue staining with the laminin antibody disclosed progressive changes with increasing preservation intervals. Staining with the factor 8 antibody demonstrated also progressive changes, but failed to reflect in a gradual fashion increasing endothelial cell injury. Histologic injury became more pronounced after transplantation and reperfusion, then showing destruction of epithelial cells; the extent of injury correlated with the duration of preservation. Glutaminase activity was maintained after cold storage, indicating that the enterocytes remained intact during this period, but when assayed after reperfusion, glutaminase decreased with increasing preservation intervals and increasing histologic mucosal damage. We conclude that cold ischemic injury involves primarily the endothelium and the basement membrane, which progresses to global mucosal impairment with reperfusion.

Objective: The current study was designed to determine which cytokines produced during an alloimmune response stimulate macrophage nitric oxide (.N = O) production at allograft sites., Summary Background Data: Previous work has demonstrated that rat sponge matrix allograft infiltrating cells produce more .N = O on stimulation with alloantigen than syngeneic graft-infiltrating cells. Addition of NG-monomethyl-L-arginine (NMA), an inhibitor of .N = O synthesis, promotes allospecific cytolytic T-lymphocyte effector function., Methods: Polyurethane sponges were implanted subcutaneously in recipient Lewis rats and injected with 10 x 10(6) ACl splenocytes. On various days after grafting, graft-infiltrating cells were harvested for in vitro study. Adherent macrophages from the graft infiltrating cell population were obtained by a 2- to 3-hour incubation to plastic dishes with subsequent washing to remove nonadherent cells., Results: Stimulation of unseparated graft-infiltrating cell populations with lipopolysaccharide or interferon-tau resulted in enhanced .N = O synthesis by allograft infiltrating cells compared with syngeneic graft-infiltrating cells, early after grafting. Macrophages recovered from an allograft site spontaneously produce more .N = O than macrophages recovered from syngeneic grafts (p < 0.001). Significantly enhanced levels of .N = O were produced by allograft macrophages compared with syngeneic graft macrophages on stimulation with lipopolysaccharide or interferon-tau (p < or = 0.025)., Conclusions: Nitric oxide appears to be produced in response to the local cytokines secreted by an ongoing rejection reaction. Nitric oxide serves under these circumstances to modulate the alloimmune response.

Treatment with monoclonal IL-2 receptor antibodies has been successfully used for immunosuppressive induction therapy following organ transplantation in the recent past. The present study was conducted to compare for the first time a cyclosporine-based quadruple immunosuppressive regimen including a monoclonal IL-2 receptor antibody or ATG as induction therapy after orthotopic liver transplantation. In two groups of 33 patients each, postoperative survival, graft biopsies, liver function enzymes, and the clinical courses after OLT were evaluated. Our results indicate that monoclonal IL-2 receptor antibody therapy as part of a quadruple immunosuppressive regimen is better tolerated and is at least as effective as ATG in prevention of allograft rejection following OLT. Furthermore, our data indicate that a slightly better liver function in general and a lower incidence of rejection reactions necessitating treatment could be observed in the group of patients treated with the monoclonal IL-2 receptor antibody. This study provides evidence that monoclonal IL-2 receptor antibody therapy may be a useful tool for the immunosuppressive induction therapy following clinical orthotopic liver transplantation.

Aim: To represent the current state of the art of orthotopic liver transplantation (OLT). The constantly expanding spectrum of indications are discussed in detail, and the specific risks of the individual indications considered. Major points discussed: On the basis of the authors' own results obtained at the Rudolf Virchow Hospital, University of Berlin, the current survival rates following orthotopic liver transplantation are shown. In addition to established indications for liver transplantation (primary biliary cirrhosis, primary sclerosing cholangitis, acute hepatic failure, various metabolic diseases, small hepatocellular carcinomas and a number of posthepatic cirrhoses) the indication and results of liver transplantation in HbsAg-positive and alcoholic cirrhosis are presented in detail. In contrast to reports in the Anglo-American literature, the incidence and severity of graft re-infections with the hepatitis virus was appreciably reduced through the use of anti-HBs hyperimmunoglobulin preparations in HBsAg-positive cirrhotics. The results obtained were comparable with those achieved for other indications.

We have recently demonstrated in the rat species that sponge matrix allograft infiltrating cells spontaneously produce nitric oxide (.N = 0) and this .N = 0 production precedes the development of CTL. Compared with our experience in the mouse species, the CTL activity recovered from rat sponge grafts is of shorter duration and less intense. Assessment of the spontaneous .N = 0 production by mouse allograft infiltrating cells reveals a more delayed time course of production, paralleling the recovery of CTL activity from the graft. The in vitro spontaneous .N = 0 production by mouse allograft-infiltrating cells was greater than the production by syngeneic graft-infiltrating cells on all days tested. Exposure of allogeneic but not syngeneic graft infiltrating cells to the sensitizing alloantigen in vitro resulted in enhanced .N = 0 synthesis. In contrast, LPS stimulated .N = 0 production by both syngeneic and allogeneic graft cells on all days postgrafting. Culture of day-14 allograft infiltrating cells with alloantigen in the absence of NG-monomethyl-L-arginine (NMA), the competitive inhibitor of .N = 0 synthesis, resulted in elevated supernatant NO2- levels and decreased 3H-TdR uptake and CTL activity compared with cultures carried out in the presence of NMA. The supernatant NO2- levels, as well as the CTL activity and 3H-TdR incorporation of the cultured cells, was dependent on the concentration of NMA present, and these effects could be reversed by excess L-arginine. Thus, the species difference in .N = 0 synthesis (rat > mouse), observed by others, is evident in the sponge allograft model and may explain why CTL activity recovered from rat allografts is of shorter duration and less intense than that from the mouse allografts.

As acute rejection episodes are most frequently prevented or controlled in clinical organ transplantation, chronic rejection processes have become the major reason for late dysfunction and eventual loss of the allograft. The recent reports on successful clinical intestinal transplantation prompted us to investigate chronic rejection processes that may arise after the initial control of acute rejection. Using the strongly histoincompatible ACI-->LEW rat strain combination and serial graft biopsies after limited initial immunosuppressive therapy with cyclosporine, we defined the clinical and pathomorphologic course of chronic rejection of orthotopic small bowel allografts. Differing from acute rejection, the bowel wall (especially the mucosa and submucosa) was not the primary target of chronic rejection. We observed progressive destruction of the Peyer's patches and the mesenteric lymph nodes of the graft--a process which began during the 4-week course of CsA--and infiltration and destruction of graft mesenteric vessels. Testing the immunosuppressive drugs FK506 and CsA for their efficacy to ameliorate ongoing chronic rejection, we found that a short course (5 days) of FK506 was more effective than a second 4-week course of CsA. However, while allograft function recovered sufficiently to allow a temporary improvement of the recipient's global nutritional state, pathomorphologic graft changes failed to reverse substantially. Eventually all grafts failed due to progressive chronic rejection.

Acute rejection episodes often complicate clinical small bowel transplantation, which prompted us to investigate whether such episodes can be reversed and the intestinal graft salvaged. Inbred Lewis rats that received fully allogeneic Brown-Norway small bowel allografts were treated with cyclosporin A (10 mg/kg) for 5 days, and the drug was then discontinued. Clinical and histologic signs of acute rejection developed, and the animals were subsequently treated with FK 506 (2 mg/kg) on days 14, 16, and 18. Survival was significantly prolonged (201.7 +/- 46.8 days) when compared with animals that were not administered FK 506 (16.5 +/- 0.8 days) or allograft recipients that received no immunosuppressive therapy (10.8 +/- 0.7 days). The histologic changes and functional impairment due to rejection that were observed prior to the start of the FK 506-therapy were reversed. However, biopsy specimens of all animals exhibited features of chronic rejection. This study provides evidence that acute rejection of intestinal allografts can be successfully treated with a short course of FK 506.

A 54-year-old male patient with end-stage liver failure from Budd-Chiari syndrome due to paroxysmal nocturnal hemoglobinuria (PNH) underwent liver transplantation (OLT) in 1989. Retransplantation became necessary 1 year later when thrombotic occlusion of the portal vein and common hepatic artery led to graft loss after withdrawal of anticoagulation therapy because of several gastrointestinal bleeding episodes. The patient is now alive 3 years after the first OLT. To the best of our knowledge and according to the literature, this is, to date, the longest that any PNH patient has survived after liver transplantation. Although the course of this patient was complicated in a way similar to that reported for other cases in the literature, patients with PNH should not, in principle, be excluded from liver transplantation. Lifelong anticoagulation with coumarin and the use of steroids together with cyclosporin reduce the risk of recurrent thrombosis and PNH crises.

The immunological status of Lewis (LEW) recipients of indefinitely surviving (greater than 400 days) orthotopic Brown-Norway (BN) small bowel allografts was investigated 1 to 1 1/2 years after cessation of immunosuppressive therapy with either cyclosporine or FK506 and compared with recipients of syngeneic grafts. A normal proliferative response (as measured by a mixed lymphocyte culture) of recipient peripheral lymph node lymphocytes in response to the donor-specific (BN) and the third-party (ACI) antigen, was observed in all experimental groups. Cytolytic T cell generation (as measured by a standard 51Cr-release cytotoxicity assay) in response to the donor-specific (BN) and the third-party (ACI) antigen was observed also in all groups. A FACS analysis of allograft-recipient splenocytes showed no evidence for systemic lymphoid chimerism. BN or ACI skin grafts transplanted onto recipients of allogeneic and syngeneic small bowel grafts were rejected completely in 12-17 days, while the intestinal grafts remained functional. Immunohistologic evaluation of the allografts, using anti-BN class I and anti-Lewis class II monoclonal antibodies showed anti-BN staining on the epithelial and endothelial structures, whereas the mononuclear cells in the lamina propria stained positively with the anti-LEW monoclonal antibody. However, lymphoid depletion and scarring of Peyer's patches and mesenteric lymph nodes as well as focal obliterative mesenteric arteriopathy, indicative of an indolent chronic rejection, were observed. These data demonstrate that recipients of indefinitely surviving small bowel allografts remain immune competent and do not retain the intestinal graft on the basis of specific hyporesponsiveness to the donor antigens.

Background: Our previous observation that nitric oxide (NO) is synthesized during antigen-specific immune reactions in vitro led us to investigate whether NO is produced during the in vivo immune response to a vascularized organ allograft., Methods: Orthotopic small-bowel transplantation in the rat was performed by standard microsurgical techniques in the LBNF1 to Lewis (rejection alone), Lewis to LBNF1 (graft-versus-host disease [GVHD] alone), and a syngeneic strain combination with and without immunosuppressive therapy with FK 506. The recipient serum NO2-/NO3- levels (stable end products of NO metabolism) were measured and erythrocytes were evaluated for the presence of nitrosylferrohemoglobin (specific for NO bound to hemoglobin)., Results: Animals that acutely rejected small-bowel allografts or suffered from acute GVHD showed significantly elevated serum NO2-/NO3- levels on days 6 and 9, and nitrosylferrohemoglobin electron paramagnetic resonance signals of different intensity were detected on days 3, 6, and 9. FK 506-treated allograft recipients and recipients of syngeneic grafts showed normal serum NO2-/NO3- levels and lacked nitrosylferrohemoglobin signals at all time points., Conclusions: This study indicates that NO is produced early during the course of small-bowel allograft rejection and GVHD and might therefore serve as a simple marker to detect such immune reactions.

The paramagnetic molecule nitric oxide (NO), produced from L-arginine by a specific enzyme (NO synthase), has been shown to be involved in a surprising variety of mammalian cellular responses, including the regulation of T cell immunity to alloantigens in vitro. In cytotoxic activated macrophages, NO production results in a characteristic pattern of alteration of iron-containing enzyme function that is mimicked by exposure to NO. Electron paramagnetic resonance (EPR) studies have shown the formation of iron-nitrosyl species during macrophage activation and also during sepsis, indicating that alteration of iron-containing protein function may be the result of the well-documented tendency of NO to bind to metal ions. We have recently shown that the NO synthesis induced during alloantigenic activation of rat splenocytes inhibits lymphocyte proliferation and cytotoxic T-lymphocyte generation. This report demonstrates that iron-nitrosyl EPR signals similar to those observed in macrophages and during sepsis are present in the blood and in the grafted tissue of rats during the rejection of allogeneic (but not syngeneic) heart grafts. These signals are found in the blood and at the site of allograft rejection, but are not found in other tissues (such as spleen and lung), and are obliterated by administration of the immunosuppressant FK506. These results directly demonstrate the formation of iron-nitrosyl complexes during vascularized allograft rejection and suggest that consequent destruction of iron-containing protein function plays an important role in the rejection response.

The oxidative metabolism of L-arginine to its bioactive product, nitric oxide (.N = O) has been shown to inhibit rat splenocyte mixed lymphocyte reactions. To determine if alloantigen-induced .N = O production might be operative in vivo, cells that had infiltrated a rat sponge matrix allograft were tested for de novo .N = O production as well as .N = O production upon restimulation with the sensitizing alloantigen. When graft-infiltrating cells were placed in culture, a peak in de novo .N = O production was observed by day 6 graft-infiltrating cells, the time when donor-specific CTL activity by the graft-infiltrating cells was first observed. Upon restimulation with alloantigen, allograft-infiltrating cells produced greatly increased levels of .N = O, and this production was associated with inhibition of lymphocyte cytolytic function. The addition of NG-monomethyl-L-arginine (NMA), the competitive inhibitor of oxidative L-arginine metabolism, inhibited .N = O production and promoted allospecific CTL development. Both observed effects of NMA were reversed by addition of excess L-arginine. Cytokine(s) able to induce proliferation of the IL-2-dependent T cell line CTLL-2 could be detected in alloantigen-stimulated cultures in both the presence and absence of NMA. However, proliferation of the graft-infiltrating cells in response to these cytokines was observed only in the presence of NMA. The immunosuppressive macrolide FK506 was a potent inhibitor of .N = O production in these cultures, presumably acting by inhibiting the production of those cytokines that induce the oxidative L-arginine pathway.

Activated macrophages are known to oxidatively metabolize L-arginine to nitric oxide and citrulline. We have recently shown that nitric oxide is a potent inhibitory molecule in the in vitro rat mixed-splenocyte culture, resulting in inhibition of proliferation and cytolytic T-cell induction. We undertook this study using the sponge matrix allograft model in the rat to determine whether nitric oxide plays a role in an in vivo allograft response. Our experiments showed that on day 6 after grafting, when cytolytic activity of allograft-infiltrating cells is first detected, allogeneic graft fluid contains higher levels of NO2-/NO3- (the stable endproducts of nitric oxide metabolism) than syngeneic graft fluid. Furthermore, evaluation of the supernatants of cultured graft-infiltrating cells revealed that allogeneic graft-infiltrating cells spontaneously produce higher amounts of nitric oxide than syngeneic graft-infiltrating cells. The nitric oxide production was inhibited in the presence of NG-monomethyl-L-arginine (NMA), the competitive inhibitor of nitric oxide production. Most of the nitric oxide production was observed in the adherent macrophage fraction of the allograft-infiltrating cells. When allograft-infiltrating cells were cultured in the presence of NMA, donor-specific cytolytic activity was observed, whereas allograft-infiltrating cells cultured in the absence of NMA showed no cytolytic activity. These data show that nitric oxide production may play an important regulatory role in the allograft response.

This study was undertaken to determine whether refeeding through the native small intestine or through a small bowel transplant would reverse hepatic steatosis induced by total parenteral nutrition (TPN), and of what influence a coexisting short-gut syndrome is. Three short-gut syndromes of different severity were established in Lewis rats (short-gut I, mild; short-gut II, moderate; short-gut III, severe). TPN was administered for 10 days and the animals were refed for 20 days. A liver biopsy after the TPN period confirmed a mild to moderate fatty infiltration of the liver in all groups. After the refeeding period a second liver biopsy was obtained and no evidence of hepatic steatosis was observed in Groups 1, 2, 3, and 4 (normal Lewis rat, short-gut I, II, and III). The animals in group 5 (short-gut I) received a syngeneic small bowel transplant after discontinuation of TPN. After the refeeding period the liver biopsies showed no evidence of fatty infiltration. The intestinal graft also reversed the nutritional deficiencies which were observed in the animals with short-gut and showed normal body weight gain and nitrogen and fat uptake in comparison to the normal animals (Group 1). These data show that a small bowel graft is capable of reversing the deleterious sequelae of short-gut syndrome as well as the TPN-related hepatic steatosis.