Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immune response to foreign or self antigens mediates liver damage during viral or autoimmune hepatitis. However, it now appears that also specific antigen-independent liver diseases, where liver damage has been attributed to occur from oxygen radical formation, seem to be mediated by cells of the innate and adaptive immune response. These liver disorders include alcoholic liver disease, non-alcoholic fatty liver disease or non-alcoholic steatohepatitis, and ischemia/reperfusion injury that impairs the function of liver grafts. Here it seems that breakdown of the gastrointestinal barrier might increase the concentration of bacterial toxins in the portal blood, which then activate cells of the innate immune system, e. g., Kupffer cells, but, depending on the nature of the toxin, probably also conventional T cells. Invariant NKT cells which specifically recognize glycolipid antigens were supposed to become activated during metabolic disorders related to obesity. However, both steatohepatitis as well as ischemia/reperfusion injury are associated with a Th1 cytokine response characterized by IFNgamma and TNFalpha elevation, that might reflect an NKT cell response on the one hand, but also conventional T lymphocytes, in particular CD4 (+) T cells, are critical for the pathophysiology of these disorders. In 1992 we described a model of T cell-dependent liver injury inducible by the T cell-mitogenic lectin concanavalin A. This model of immune-mediated liver injury was intensively used to study pathophysiological immune effector mechanisms as well as cytokine signaling important for hepatocellular apoptosis, inhibition of apoptosis and regeneration. Recently it became evident that the inflammatory response in this model is regulated by specific cytokine signals as well as by immune regulator cells. The immune-regulatory functions of the liver are of particular interest with respect to the scavenger function of this organ, being continuously exposed to foreign antigenic material from the gut which should be eliminated without causing chronic disease.
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PMID:Cellular and cytokine-mediated mechanisms of inflammation and its modulation in immune-mediated liver injury. 1723 22

Posttransplant de novo autoimmune hepatitis (d-AIH) is increasingly described as a long-term complication after pediatric liver transplantation (LT). d-AIH is characterized by graft dysfunction, the development of autoimmune antibodies and histologic evidence of hepatitis in liver transplant recipients without previous history of autoimmune liver disease. This study is a matched case-control, univariate analysis aimed at identifying risk factors for the development of d-AIH and evaluating response to treatment. From 1984 to 2003, 619 children received 788 LTs at a single center. Forty-one patients developed d-AIH and were matched with controls for year of LT, age at time of LT and diagnosis. The following variables were insignificant in the development of d-AIH: age, gender, race, initial diagnosis, ischemia time, graft type, Epstein-Barr virus and cytomegalovirus status, HLA typing and primary immunosuppression. Compared to controls, d-AIH patients were less likely to be on monotherapy immunosuppression or weaned off prednisone at the time of diagnosis. The d-AIH group relative to the controls had statistically significant greater numbers of rejection episodes. d-AIH was treated with prednisone and/or MMF in 39 of 41 patients and lead to significant improvements in liver function tests. Thirty-nine patients are alive at a mean of 4.0 years follow-up after diagnosis. Three have required retransplantation.
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PMID:Rejection and steroid dependence: unique risk factors in the development of pediatric posttransplant de novo autoimmune hepatitis. 1739 Nov 35

Acute cellular graft-vs.-host disease (GVHD) following liver transplantation has an incidence of 1 to 2% and a mortality rate of 85%. Our aim was to identify a patient population at high risk for developing GVHD using a large clinical database to study both recipient and donor factors. We compared our liver transplant patients who developed GVHD to those that did not for recipient and donor factors and combinations of factors. For 2003-2004 we had 205 first-time liver transplant patients surviving >30 days. From this group, 4 (1.9%) developed GVHD. Compared to the control group, there were no significant differences in recipient age, recipient gender, donor age, donor gender, total ischemia time, donor-recipient human leukocyte antigen (HLA) mismatch, or donor-recipient age difference. Percentages of liver disease etiologies among the patients who developed GVHD were as follows: 16% (1/6) autoimmune hepatitis (AIH) (P = 0.003), 5.6% (3/54) alcoholic liver disease (ALD) (P = 0.057), and 7.1% (3/42) hepatocellular carcinoma (HCC) (P = 0.026). The incidence of GVHD in patients with glucose intolerance (either Type I or Type II diabetes mellitus [DM]) was significant (P = 0.022). Focusing on patients only with high-risk factors for GVHD during the years 2003-2005, we had 19 such patients. Four of these high-risk patients developed GVHD. Three of these 4 patients had received a donor liver with steatosis of degree >or=mild compared to only 2 of the 15 high-risk patients who did not develop GVHD (P = 0.037). In conclusion, we have identified liver transplant patients with AIH or the combination of ALD, HCC, and glucose intolerance who receive a steatotic donor liver as being at high risk for developing GVHD.
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PMID:Recipient and donor factors influence the incidence of graft-vs.-host disease in liver transplant patients. 1739 49

The burgeoning field of regenerative medicine promises significant progress in the treatment of cardiac ischemia, liver disease, and spinal cord injury. Key to its success will be the ability to engineer tissue safely and reliably. Tissue functionality must be recapitulated in the laboratory and then integrated into surrounding tissue upon transfer to the patient. Scaffolding materials must be chosen such that the microenvironment surrounding the cells is a close analog of the native environment. In the early days of tissue engineering, these materials were largely borrowed from other fields, with much of the focus on biocompatibility and biodegradation. However, attention has shifted recently to cell-cell and cell-surface interactions, largely because of enabling technologies at the nanoscale and microscale. Studies on cellular behavior in response to various stimuli are now easily realized by using microfabrication techniques and devices (e.g., biomedical microelectromechanical systems). These experiments are reproducible and moderate in cost, and often can be accomplished at high throughput, providing the fundamental knowledge required to design biomaterials that closely mimic the biological system. It is our opinion that these novel materials and technologies will bring engineered tissues one step closer to practical application in the clinic. This review discusses their application to cardiac, liver, and nerve tissue engineering.
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PMID:Nanofabrication and microfabrication of functional materials for tissue engineering. 1751 44

Preservation of the middle hepatic vein (MHV) for a right split liver transplantation (SLT) in an adult recipient is still controversial. The aim of this study was to evaluate the graft and patient outcomes after liver transplantation (LT) using a right split graft, according to the type of venous drainage. From February 2000 to May 2006, 33 patients received 34 cadaveric right split liver grafts. According to the type of recipient pairs (adult/adult or adult/child), the right liver graft was deprived of the MHV or not. The first group (GI, n = 15) included grafts with only the right hepatic vein (RHV) outflow, the second (GII, n = 18) included grafts with both right and MHV outflows. The 2 groups were similar for patient demographics, initial liver disease, and donor characteristics. In GI and GII, graft-to-recipient-weight ratio (GRWR) was 1.2 +/- 0% and 1.6 +/- 0.3% (P < 0.05), and cold ischemia time was 10 hours 55 minutes +/- 2 hours 49 minutes and 10 hours 47 minutes +/- 3 hours 32 minutes, respectively (P = not significant). Postoperative death occurred in 1 patient in each group. Vascular complications included anastomotic strictures: 2 portal vein (PV), 1 hepatic artery (HA), and 1 RHV anastomotic strictures; all in GI. Biliary complications occurred in 20% and 22% of the patients, in GI and GII, respectively (P = not significant). There were no differences between both groups regarding postoperative outcome and blood tests at day 1-15 except for a significantly higher cholestasis in GI. At 1 and 3 yr, patient survival was 94% for both groups and graft survival was 93% for GI and 90% for GII (P = not significant). In conclusion, our results suggest that adult right SLT without the MHV is safe and associated with similar long-term results as compared with those of the right graft including the MHV, despite that early liver function recovered more slowly. Technical refinements in outflow drainage should be evaluated in selected cases.
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PMID:Does middle hepatic vein omission in a right split graft affect the outcome of liver transplantation? A comparative study of right split livers with and without the middle hepatic vein. 1753 13

Several treatment options exist for the management of Budd-Chiari syndrome (BCS), yet the relative role and timing of liver transplantation (LT) remain poorly defined. Small case series published to date have not been able to delineate the impact of comorbidities and thromboembolic complications of BCS on survival after LT. To better understand the outcomes after LT for BCS, we analyzed 510 liver transplants performed for this disease in the United States between 1987 and 2006. Risk factors predicting graft loss or patient death included increased recipient age, hyperbilirubinemia, elevated creatinine, life support or hospitalization at the time of transplantation, prior transplantation, prior abdominal surgery, increased donor age, and prolonged cold ischemic time (CIT). Prior transjugular intrahepatic portosystemic shunt (TIPS) was not associated with worse outcomes. Transplantation in the Model for End-Stage Liver Disease (MELD) era was associated with significantly lower risk of graft loss (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.30-0.86; P = 0.012) and death (HR, 0.52; 95% CI, 0.29-0.93; P = 0.027). Similarly, MELD era was associated with significantly lower risk of early graft loss (odds ratio [OR], 0.35; 95% CI, 0.16-0.79, P = 0.012) and early death (odds ratio, 0.37; 95% CI, 0.14-0.95; P = 0.040). However, patients with BCS transplanted in the MELD era were less likely to have life support, hospitalization, prior transplants, and prolonged cold ischemia times. In conclusion, outcomes of LT for BCS are excellent, with further improvements since 2002 associated with a selection shift imposed by MELD-based organ allocation.
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PMID:Twenty years of liver transplantation for Budd-Chiari syndrome: a national registry analysis. 1776 80

The use of marginal liver donors can affect the outcomes of liver transplantation in patients with hepatitis C virus (HCV) infection. There are no firm conclusions about which donor criteria are important for allocation of high-risk grafts to recipients with HCV cirrhosis. We performed 120 consecutive liver transplantations for HCV infection between 1995 and 2005. Marginal donor criteria were considered to be: age >70 years, macrovesicular steatosis >30%, moderate-to-severe liver preservation injury, high inotropic drug dose (dopamine >15 microg/kg/min; epinephrine, norepinephrine, or dobutamine at any doses), peak serum sodium >155 mEq/L, any hypotensive episode <60 mm Hg and >1 hour, cold ischemia time >12 hours, ICU hospitalization >4 days, bilirubin >2 mg/dL, AST and/or ALT >200 UI/dL. Graft survival with donors showing these marginal criteria was compared with optimal donors using Kaplan-Meier analysis and the log-rank test. Independent predictors of survival were computed with the Cox proportional hazards model. Fifty-six grafts (46%) were lost during follow-up irrespective of the Model for End-Stage Liver Disease (MELD) scores of the recipients in each category. Upon univariate analysis, grafts with moderate-to-severe steatosis (P = .012), those with severe liver preservation injury (P = .007) and prolonged cold ischemia time (P = .0001) showed a dismal prognosis at 1, 3, and 5 years. Upon multivariate analysis, fat content (P = .0076; OR = 4.2) and cold ischemia time >12 hours (P = .034; OR = 7.001) were independent predictors of graft survival. Among HCV recipients, marginal liver donors worked similar to those from "good" donors, except for those with fatty livers >30%, especially when combined with a prolonged cold ischemia time.
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PMID:Contribution of marginal donors to liver transplantation for hepatitis C virus infection. 1788 69

Endoplasmic reticulum stress, initiated by protein overload or malfolding, activates a complex network of interacting and parallel responses that dampen the stress. However, when the protective response is insufficient, a set of responses leads to apoptosis. Coupled with the latter are promotion of lipid synthesis and proinflammatory responses. Evidence has been mounting for an important role of the endoplasmic reticulum (ER) stress response in the pathogenesis of chronic viral hepatitis, insulin resistance and nonalcoholic fatty liver disease, ischemia-reperfusion injury, genetic disorders of protein malfolding, and alcoholic liver disease. In the latter, a key candidate for inducing ER stress is hyperhomocysteinemia. Betaine treatment promotes removal of homocysteine and prevents ER stress, fatty liver, and apoptosis in a mouse model of alcohol-induced liver disease. With increasing interest in the potential role of ER stress in liver disease, greater understanding of pathophysiology, prevention, and treatment of liver disease is anticipated.
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PMID:Endoplasmic reticulum stress and liver injury. 1797 73

Previous studies have shown that donor hypernatremia and possibly recipient hyponatremia negatively impact graft function after orthotopic liver transplant (OLT). The purpose of this retrospective investigation was to determine whether measured differences in serum sodium values between cadaveric donors and OLT recipients (DeltaNa(+)) influence immediate postoperative allograft function and short-term patient outcomes. Two hundred and fifty patients that underwent OLT from January 2001 to December 2005 were included in this study. The DeltaNa(+) for each donor recipient pair was correlated with standard postoperative liver function tests as well as recipient length of intensive care unit stay (LOICUS), length of hospital stay (LOHS) and recipient survival. The relationship between donor hypernatremia (serum sodium >or= 155 mEq/mL), recipient hyponatremia (serum sodium level <or= 130 mEq/mL), and postoperative outcomes were analyzed as well. Adjustments were made for baseline potential confounders, including model for end-stage liver disease (MELD) score, preservation solution used (HTK vs. UW), recipient and donor demographics and cold ischemia time (CIT). DeltaNa(+) as well as donor hypernatremia and recipient hyponatremia were not found to be associated with immediate postoperative allograft function, intraoperative blood product usage, LOICUS, LOHS or short-term patient survival. However, both the preoperative MELD score and HTK preservation solution used were significantly associated with several patient outcomes. A higher MELD score was associated with both increased red blood cell (RBC) (P < 0.001) and fresh frozen plasma (FFP) usage (P = 0.002), elevated postoperative total bilirubin levels (P < 0.001), increased LOHS (P = 0.04), and a higher 30-day post transplant mortality (P = 0.02). The use of HTK preservation solution was associated with higher mean postoperative aspartate aminotransferase levels (P = 0.02) and decreased mean RBC (P < 0.001) and FFP usage (P = 0.009) compared to UW preservation solution use.
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PMID:Association between donor-recipient serum sodium differences and orthotopic liver transplant graft function. 1816 40

Biliary complications remain a significant problem following liver transplantation in the Model for End-Stage Liver Disease (MELD) era. We hypothesized that donor, recipient, and technical variables may differentially affect anastomotic biliary complications in MELD era liver transplants. We reviewed 256 deceased donor liver transplants after the institution of MELD at our center and evaluated these variables' association with anastomotic biliary complications. The bile leak rate was 18%, and the stricture rate was 23%. Univariate analysis revealed that recipient age, MELD, donor age, and warm ischemia were risk factors for leak, whereas a Roux limb or stent was protective. A bile leak was a risk factor for anastomotic stricture, whereas use of histidine tryptophan ketoglutarate (HTK) versus University of Wisconsin (UW) solution was protective. Additionally, use of a transcystic tube/stent was also protective. Multivariate analysis showed that warm ischemia was the only independent risk factor for a leak, whereas development of a leak was the only independent risk factor for a stricture. HTK versus UW use and transcystic tube/stent use were the only independent protective factors against stricture. Use of an internal stent trended in the multivariate analysis toward being protective against leaks and strictures, but this was not quite statistically significant. This represents one of the first MELD era studies of deceased donor liver transplants evaluating factors affecting the incidence of anastomotic bile leaks and strictures. Donor, recipient, and technical factors appear to differentially affect the incidence of anastomotic biliary complications, with warm ischemia, use of HTK, and use of a stent emerging as the most important variables.
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PMID:Biliary complications following liver transplantation in the model for end-stage liver disease era: effect of donor, recipient, and technical factors. 1816 43


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