Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:EPR detection of heme and nonheme iron-containing protein nitrosylation by nitric oxide during rejection of rat heart allograft. 137 34

Under FK 506-based immunosuppression, the entire cadaver small bowel except for a few proximal and distal centimeters was translated to 17 randomly matched patients, of whom two had antigraft cytotoxic antibodies (positive cross-match). Eight patients received the intestine only, eight had intestine in continuity with the liver, and one received a full multivisceral graft that included the liver, stomach, and pancreas. One liver-intestine recipient died after an intestinal anastomotic leak, sepsis, and graft-versus-host disease. The other 16 patients are alive after 1 to 23 months, in one case after chronic rejection, graft removal, and retransplantation. Twelve of the patients have been liberated from total parenteral nutrition, including all whose transplantation was 2 months or longer ago. The grafts have supported good nutrition, and in children, have allowed growth and weight gain. Management of these patients has been difficult and often complicated, but the end result has been satisfactory in most cases, justifying further clinical trials. The convalescence of the eight patients receiving intestine only has been faster and more trouble free than after liver-intestine or multivisceral transplantation, with no greater difficulty in the control of rejection.
 ...
PMID:Intestinal transplantation in composite visceral grafts or alone. 138 43

The intestine was one of the first organs to be successfully transplanted experimentally. Results in humans were disappointing until recently, partly due to the large quantity of lymphoid tissue present in the intestine, resulting in a vigorous rejection process which is difficult to control. Recent advances in experimental studies have improved our knowledge about mechanisms of rejection and graft-versus-host disease, and have allowed the development of new immunosuppressive therapies. At the present time, major obstacles remain in clinical intestinal transplantation (i.e. difficulty of preventing rejection despite massive immunosuppression, high rate of postoperative sepsis). However, the protective effect of a concomitant transplanted liver and the use of FK 506 have allowed a dramatic improvement in clinical results, justifying continuation of experimentation of intestinal transplantation in humans.
 ...
PMID:[Small intestine transplantation. Experimental and clinical results]. 750 99

Our experience with clinical intestinal transplantation under FK 506 immunosuppression showed that 50% of the recipients were able to be independent from TPN after transplantation, but 10% require partial TPN with functioning grafts, 10% needed total TPN after graft removal, and 30% of the recipients died postoperatively, mostly from sepsis due to severe graft rejection. For further improvement in patient survival and in the quality of life for patients after intestinal transplantation, it is mandatory to establish a new strategy for treatment and prevention of graft rejection and systemic infection.
 ...
PMID:Intestinal transplantation at the University of Pittsburgh. 751 36

The L-arginine:nitric oxide (NO) biosynthetic pathway has been proposed as an important mediator in host defense mechanisms and may therefore play a role in the acute allograft response. We have studied NO generation in liver allograft rejection and determined its value in immunological monitoring. Stable end products of this pathway have been determined serially in 50 primary liver recipients and compared with 2 known mediators and markers of acute allograft rejection (IL-2R positive lymphocytes and circulating TNF alpha). Plasma concentrations of acid-labile nitrosocompounds (NOx), which increased during acute allograft rejection (P < 0.0001), correlated with rejection severity and were reduced after administration of supplemental high dose glucocorticoids. Concentrations were significantly lower in nonrejection graft complications but were elevated during episodes of sepsis. Correlations between plasma NOx levels and circulating TNF-alpha (r = 0.451, P < 0.001) and IL-2R-positive lymphocytes in peripheral blood (r = 0.781, P < 0.001) were demonstrated. In a logistic analysis of these variables, plasma NOx was the most predictive parameter of an episode of acute cellular rejection. Nitric oxide generation in FK506-treated patients was lower compared with patients receiving a CsA-based immunosuppression regimen and was associated with a reduced frequency of acute rejection in the FK506 group. These data are consistent with a role for NO in the cellular alloantigen immune response and indicate that monitoring of plasma levels of NOx may be useful in the detection of acute allograft rejection.
 ...
PMID:Nitric oxide generation. A predictive parameter of acute allograft rejection. 752 65

Under FK506-based immunosuppression, 13 abdominal multivisceral transplantations were performed in 6 children and 7 adults. Of the 13 recipients, 7 (53.8%) are alive and well with functioning grafts after 9 to 31 months. Six recipients died: three from PTLD, one from rejection, one from sepsis, and one from respiratory failure. In addition to rejection, postoperative complications occurring in more than isolated cases included PTLD (n = 6), abdominal abscess formation (n = 5), pancreatitis (n = 3), and ampullary dysfunction (n = 2). In addition, infection by enteric microorganisms was common during the early postoperative period. Currently, all 7 survivors are on an oral diet and have normal liver function. Two recipients (one insulin-dependent) require antidiabetes treatment, in one case following distal pancreatectomy and in the other after two episodes of pancreatic rejection. Thus, abdominal multivisceral transplantation is a difficult but feasible operation that demands complex and prolonged posttransplantation management. It is not yet ready for application and awaits a better strategy of immune modulation.
 ...
PMID:Abdominal multivisceral transplantation. 753 Aug 73

We reviewed retrospectively the clinical records, autopsy protocols and central nervous system tissue sections of 50 patients who underwent orthotopic liver transplantation for end-stage liver disease between 12/83 and 8/93. The postoperative survival period ranged from hours (6), weeks (17), months (17), to years (10). All patients received immunosuppressive drugs from the immediate postoperative period to the time of their death (cyclosporine, steroids; occasionally azathioprine, OKT3, FK506). Nineteen patients had neurological manifestations (hepatic encephalopathy) prior to surgery. Post-transplant neurologic signs and symptoms included: hepatic encephalopathy/altered mental status (11), focal or generalized seizures (9) and stroke (2). In the majority of cases (37) the cause of death was septicemia and/or bleeding diathesis. The neuropathologic findings present in 36 patients could be classified into 3 distinct categories: metabolic disorders: hepatic/anoxic encephalopathy, central pontine myelinolysis (15); cerebrovascular disease: subarachnoid and/or intracerebral hemorrhage, bland or hemorrhagic infarction (23); and infection: bacterial meningitis/cerebritis, multifocal fungal microabscesses, presumptive viral meningitis/encephalomyelitis (10). In conclusion, 72% of 50 patients who came to autopsy after liver transplantation were found to have neuropathologic abnormalities; these abnormalities were predominantly infections and vascular diseases.
 ...
PMID:Neuropathology of liver transplantation. 760 96

The clinical course of 37 patients who underwent 46 liver transplantations for primary (n = 33) and secondary (n = 4) sclerosing cholangitis was reviewed. The median follow-up was 37 months. The patient and graft survivals for patients with primary sclerosing cholangitis at 1, 2, and 5 years were 96.9%, 91.6%, 87.9%, and 83.1%, 74.2%, 65.2%, respectively. In the patients with primary sclerosing cholangitis (PSC), prior surgery except for simple cholecystectomy was associated with significantly greater operative time and blood loss. No cholangiocarcinoma was identified at the time of transplantation. Human leukocyte antigen typing for PSC patients was heavily weighed toward B8 (58.8%) compared with control (11.8%). Sixty-two percent of patients with PSC also had inflammatory bowel disease. Moderate or severe rejection requiring OKT3, "rescue therapy" with FK506, or retransplantation was relatively higher in patients with inflammatory bowel disease (70%) versus patients without inflammatory bowel disease (36.4%) and a matched control group (37.5%). Progressive inflammatory bowel disease was seen in 6 of 19 patients, with 3 developing cancer and a dysplasia. Two patients in the entire group died of sepsis and 3 of colon cancer (2 recurrent and 1 primary). These data demonstrate that excellent survival results can be achieved in this group of patients. Rejection is frequent and often severe and steroid refractory. Colon cancer represents the most frequent cause of death in PSC patients after liver transplantation and demands constant attention.
 ...
PMID:Liver transplantation for sclerosing cholangitis. 763 12

Renal dysfunction often complicates the course of liver transplant recipients. Preoperative renal dysfunction, including hepatorenal syndrome (HRS) may be present. Assessment of renal function in the pretransplant patient with end-stage liver disease is fraught with pitfalls. Direct measurement of GFR by a method other than creatinine clearance is recommended wherever possible. Preoperative renal biopsy should also be considered in those patients with renal dysfunction in whom the diagnosis of HRS is not definite. With the routine use of veno venous bypass, renal perfusion is maintained and intraoperative events generally do not play a significant role in the development of postoperative dysfunction. Postoperatively immunosuppressive medications such as CsA or FK506 account for most of the renal dysfunction that is observed. Other factors such as graft dysfunction, sepsis, and nephrotoxic drugs may also participate in renal impairment. The exact mechanism of cyclosporine or FK506 nephrotoxicity remains unknown. In liver transplant recipients, no convincing therapeutic strategies exist to combat nephrotoxicity other than dose reduction of immunosuppressive therapy. Patients with HRS can be successfully treated by liver transplantation with recovery of renal function and with patient survival rates comparable to recipients without HRS, despite increased morbidity.
 ...
PMID:The kidney in liver transplantation. 769 Dec 5

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


1 2 3 4 Next >>