Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gut transplantation is at a stage comparable to that of transplantation of the heart and liver in the late 1960s. The feasibility of this procedure has been demonstrated in large animals but has not been successful in clinical practice. Rejection, sepsis, and possible GVHD are the major obstacles. Ongoing clinical trials can be justified on the basis of the limited options that are available for patients with the short gut syndrome who develop complications while on TPN, the improved results in animals studies, the recent clinical success of pancreaticoduodenal transplantation, and the demonstrated ability to detect rejection and remove the intestinal graft without mortality (Table 1).
 ...
PMID:Intestinal transplantation: current status. 265 Mar 91

Multivisceral transplantation, combined liver-intestine transplantation, and isolated small bowel transplantation are very similar procedures that were first developed in the 1950s. If the viscera can be conceptualized as a cluster of grapes hanging from its arterial stems, the three procedures are characterized by virtually identical vascular anastomoses, with exclusion or inclusion of as many viscera (grapes) as necessary; however, these procedures languished for nearly four decades because of the imperfect immunosuppressive regimens of the 1960s, 1970s, and 1980s. Finally, after the development of FK506, pediatric patients may undergo intestinal transplantation with the hope for long-term survival. These procedures are reserved for TPN-dependent children with permanent intestinal insufficiency. Candidacy for transplantation is also predicated on development of potentially fatal TPN complications such as cholestasis, recurrent sepsis, or thrombosis of access sites. Since 1990, 32 pediatric patients have undergone intestinal transplantation at the University of Pittsburgh, with an overall survival of 65%. Immunosuppression has been accomplished with a combination of corticosteroids, FK506, and prostaglandin E1. Although GVHD has not been a major problem, most patients have experienced rejection episodes requiring intensification of immunosuppression with a steroid bolus, a steroid recycle, an increase in FK506 dosage, or addition of OKT3. CMV has caused little morbidity, but EBV-related PTLD has affected 20% of all patients. It has not been possible to discontinue immunosuppression in the face of PTLD without engendering severe small intestinal rejection. Other problems have included recurrent sepsis, intestinal dysmotility, and persistent food avoidance. Future therapeutic trends are likely to include the performance of combined bone marrow-visceral transplant to induce a chimeric tolerogenic state and to lessen the need for long-term immunosuppression.
 ...
PMID:Small bowel transplantation in infants and children. 769 29

Painful oral mucositis is a common complication after bone marrow transplantation (BMT). Glutamine is a nutrient for rapidly dividing cells and the major energy source for intestinal epithelium. This study tested whether an oral glutamine preparation could decrease the severity of oral mucositis in patients undergoing BMT. Glutamine or a placebo (glycine) were administered from admission until day +28 in 193 BMT patients in a randomized, double-blind, placebo-controlled study at a dose of 1.0 g amino acid/m2/dose swish and swallow four times a day. In autologous BMT patients (n = 87) glutamine was associated with significantly less mouth pain by self report and by opiate use (5.0+/-6.2 days of morphine for glutamine vs 10.3+/-9.8 days for placebo; P= 0.005). Matched sibling BMT patients had no effect by self report and an increased duration of opiate use (23.2+/-5.7 days for glutamine vs 16.3+/-8.3 days for placebo) (P = 0.002). However, day 28 survival of allogeneic patients was improved by glutamine. No significant differences in TPN use, rate of relapse or progression of malignancy, parenteral antibiotic use, acute or chronic GVHD, or days of hospitalization were observed in either autologous or allogeneic recipients. No toxicity of glutamine was observed. We conclude that oral glutamine can decrease the severity and duration of oropharyngeal mucositis in autologous BMT patients but not in allogeneic BMT patients, possibly due to interaction with methotrexate.
 ...
PMID:Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. 972 68

UDCA exerts its beneficial effect in liver diseases through a diverse, probably, complementary array of mechanisms. The clinical use and efficacy of UDCA in PBC have been evident. UDCA may also have a place in the management of PSC, ICP, cystic fibrosis, PFIC and GVHD involving the liver, although, more studies are needed to further determine its therapeutic potential in these diseases and in other hepatobiliary disorders such as liver allograft rejection, drug and TPN-induced cholestasis, NASH, and alcoholic liver disease.
 ...
PMID:Ursodeoxycholic acid 'mechanisms of action and clinical use in hepatobiliary disorders'. 1149 32

Recently, the clinical reality of intestinal, combined liver-intestinal, and multivisceral transplantation qualified the procedure by the American Health Care Financing Administration (HCFA) as the standard of care for patients with irreversible intestinal failure. The decision was supported by a decade of clinical experience with cumulative improvement in survival. Prior to tacrolimus, the worldwide experience was plagued with uncontrolled rejection, graft versus host disease (GVHD), and fatal infection. These undefeated barriers stemmed from the large gut lymphoid mass and heavy microbial load contained in the intestinal lumen with the absence of an effective immunosuppressive and antimicrobial therapy. With the emerge of small bowel and multivisceral transplantation in 1990, multiple factors, in addition to the clinical introduction of tacrolimus, have sustained and increased these efforts including evolution in surgical techniques and improvements in postoperative care. The most valuable achievement, however, has been the effective control of rejection and treatment of life threatening opportunistic infections. This chapter outlines the common current practice, surgical techniques and postoperative management of the three different types of intestinal transplantation. In addition, new strategies to overcome some of the current immunologic and biologic challenges are defined with the aim of raising the level of such a creative surgery to be a better therapy for TPN dependent patients.
 ...
PMID:The current status and future outlook of intestinal transplantation. 1237 Jun 57

This retrospective study comprehensively examined hepatic and gastrointestinal complications post-bone marrow transplant (BMT) in a heterogeneous group of 132 pediatric patients that underwent 142 transplants. Hyperbilirubinemia occurred in 28% of this population with clinically evident jaundice in 16%. Acute graft-versus-host disease (GVHD) occurred in 46% of the population, with liver involvement in 39% and intestinal involvement in 60% of those with acute GVHD. Veno-occlusive disease (VOD) occurred in 18% of the population. A greater increase in hepatic transaminases was noted in GVHD and VOD than nonspecific liver injury. Serum bilirubin may help to differentiate between VOD and hepatic GVHD. Biliary sludging occurred in 20% of patients and was associated with increased morbidity. Common post transplant gastrointestinal complications included mucositis in 90%, vomiting in 85% and abdominal pain in 71%. TPN support post transplant was required in 91%. Diarrhea occurred in 67% with the most common identified etiologies reported as GVHD (27%), viral (6%), Clostridium difficile (8%) infections and unknown (28%). Typhilitis developed in 3.5%. Melena or hematochezia occurred in 11 patients (8%). However, gastrointestinal bleeding was disproportionately represented in intensive care unit admissions (5/27) and 100 day mortality (5/21). Gastrointestinal and hepatic complications represent a major cause of morbidity and mortality in pediatric BMT recipients.
 ...
PMID:GI complications in pediatric patients post-BMT. 1590 80

Palifermin, a recombinant human keratinocyte growth factor, is commonly given to prevent mucositis following autologous transplantation. In the allogeneic hematopoietic stem cell transplant (allo-HSCT) setting, safety and efficacy data are limited. We conducted a retrospective study in 251 patients undergoing allo-HSCT, 154 of whom received peritransplant palifermin. In all patients, palifermin significantly decreased the mean number of days of total parenteral nutrition (TPN, 13 vs 16 days, P=0.006) and patient-controlled analgesia (PCA, 6 vs 10 days, P=0.023), as well as the length of initial hospital stay (LOS, 32 vs 37 days, P=0.014). However, the effect of palifermin was only significant in patients who received a TBI- but not BU-based chemotherapy conditioning regimen. In TBI recipients, palifermin decreased the mean number of days of TPN (13 vs 17 days, P<0.001) and PCA (7 vs 12 days, P=0.033), and the length of stay (32 vs 38 days, P=0.001). Palifermin did not affect GVHD, graft failure or relapse. Therefore, in the largest analysis with this patient population to date, we demonstrate that palifermin is safe in allo-HSCT patients, decreases TPN and PCA use and decreases LOS following TBI-based but not chemotherapy-based allo-HSCT.
 ...
PMID:Palifermin is efficacious in recipients of TBI-based but not chemotherapy-based allogeneic hematopoietic stem cell transplants. 2275 Sep 97