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)

Cholestasis is a common finding after liver transplantation and usually signifies graft dysfunction. The most important factor in the evaluation of patients with cholestasis is an awareness of the disorders that commonly arise along a time continuum post-transplant. Therefore, the approach to cholestasis requires a systematic review of biochemical, histological, and radiographic data. This article considers the causes of cholestasis in liver transplant recipients, excluding those associated with biliary anastomotic stricturing. These causes include conditions as diverse as ischemia reperfusion injury, ABO blood group incompatibility, hepatic arterial thrombosis, cytomegalovirus infection, fibrosing cholestatic hepatitis secondary to hepatitis B and C viruses, recurrent primary sclerosing cholangitis, recurrent primary biliary cirrhosis, and chronic rejection. Also examined are management issues pertinent to these conditions and strategies used in preventing or diminishing the effects of cholestasis once established.
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PMID:Cholestatic diseases of liver transplantation. 1135 20

1. Livers from donors previously exposed to hepatitis B virus (HBV) can fail after transplantation as a result of severe HBV reactivation in the transplant recipient. 2. Antibody against hepatitis B core antigen (HBcAb) in the donor is a marker for risk for transmission of HBV and reactivation after liver transplantation. 3. Recipient HBcAb positivity and antibody to hepatitis B surface antigen (HBsAb) positivity are associated with less risk for HBV reactivation. Conversely, the absence of HBcAb and/or HBsAb in the transplant recipient, higher Child-Pugh score, and presence of HBV DNA in the donor liver may be risk factors for HBV reactivation in the transplant recipient. 4. Recipients of HBcAb-positive (HBcAb(+)) livers at high risk for HBV reactivation should be treated prophylactically with lamivudine alone or a combination of hepatitis B immunoglobulin (HBIg) and lamivudine. The value of monoprophylaxis with HBIg has not been established in this setting. 5. Until data from larger studies are available, for low-risk recipients of HBcAb(+) livers, no prophylaxis, with very close serological and virological monitoring, appears to be a potential alternative to lamivudine monoprophylaxis. 6. Recipients of HBcAb-negative livers should be investigated for HBV infection when an episode of allograft dysfunction is not readily explained by the usual causes (rejection, ischemia, or hepatitis C recurrence).
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PMID:Use of hepatitis B core antibody-positive donors for liver transplantation. 1236 4

Although tightly regulated programmed cell death (apoptosis) possesses great importance for tissue homeostasis, several pathologic processes are associated with organ failure due to adversely activated cell apoptosis. Transient increase in apoptosis has been shown to cause organ damage during fulminant hepatitis B, autoimmune diseases, ischemia-reperfusion injury, sepsis, or allograft rejection. A defined and temporary inhibition of cell apoptosis may therefore be of high clinical relevance. Activation of death receptors results in caspase-8 recruitment to the death-inducing signaling complex, which initiates the apoptotic process through cleavage of caspase-8 and downstream substrates. This initial step may be inhibited by the caspase-8 inhibitor FLIP (FLICE inhibitory protein). To specifically inhibit the initiation of death receptor-mediated apoptosis we constructed a fusion protein containing FLIP fused N-terminally to the human immunodeficiency virus TAT domain. This TAT domain allows the fusion protein to cross the cell membrane and thus makes the FLIP domain able to interfere with the death-inducing signaling complex inside of the cell. We observed that incubation of lymphocytic Jurkat or BJAB cells with TAT-FLIPS proteins significantly inhibits Fas-induced activation of procaspase-8 and downstream caspases, preventing cells from undergoing apoptosis. Systemic application of TAT-FLIPS prolongs survival and reduces multi-organ failure due to Fas-receptor-mediated lethal apoptosis in mice. Therefore, application of cellular FLIPS in the form of a TAT fusion protein may open a promising, easily applicable new tool for providing protection against transient, pathologically increased apoptosis in various diseases.
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PMID:Transduction of the TAT-FLIP fusion protein results in transient resistance to Fas-induced apoptosis in vivo. 1530 99

We reviewed the medical records of 62 patients with systemic small and medium-sized vessel vasculitides and gastrointestinal tract involvement followed at our institution between 1981 and 2002. This group included 46 men and 16 women (male:female ratio, 2.9), with a mean age of 48 +/- 18 years. Vasculitides were distributed as follows: 38 polyarteritis nodosa (21 related to hepatitis B virus), 11 Churg-Strauss syndrome, 6 Wegener granulomatosis, 4 microscopic polyangiitis, and 3 rheumatoid arthritis-associated vasculitis. Gastrointestinal manifestations were present at or occurred within 3 months of diagnosis in 50 (81%) patients and were mainly abdominal pain in 61 (97%), nausea or vomiting in 21 (34%), diarrhea in 17 (27%), hematochezia or melena in 10 (16%), and hematemesis in 4 (6%). Gastroduodenal ulcerations were detected endoscopically in 17 (27 %) patients, esophageal in 7 (11%), and colorectal in 6 (10%), but histologic signs of vasculitis were found in only 3 colon biopsies. Twenty-one (34%) patients had a surgical abdomen; 11 (18%) developed peritonitis, 9 (15%) had bowel perforations, 10 (16%) bowel ischemia/infarction, 4 (6%) intestinal occlusion, 6 (10%) acute appendicitis, 5 (8%) cholecystitis, and 3 (5%) acute pancreatitis. (Some patients had more than 1 condition.) Sixteen (26%) patients died.The respective 10-month and 5-year survival rates were 71% (95% confidence interval [CI], 52-90) and 56% (95% CI, 35-77) for the 21 surgical patients; and 94% (95% CI, 87-101) and 82% (95% CI, 70-94) for the 41 patients without surgical abdomen (p = 0.08). Peritonitis (hazard ratio [HR] = 4.3, p < 0.01), bowel perforations (HR = 5.7, p < 0.01), gastrointestinal ischemia or infarctions (HR = 4.1, p < 0.01), and intestinal occlusion (HR = 5.5, p < 0.01) were the only gastrointestinal manifestations significantly associated with increased mortality in multivariate analysis. For this subgroup of 15 patients, 6-month and 5-year survival rates were 60% (95% CI, 35-85) and 46% (95% CI, 19-73), respectively (p = 0.003). None of the other gastrointestinal or extraintestinal vasculitis-related symptoms, or angiographic abnormalities (seen in 67% of the 39 patients who underwent angiography), was predictive of surgical complications or poor outcome. However, prognosis has dramatically improved during the past 30 years, probably owing to better management of these more severely ill patients, with prompt surgical intervention when indicated, and the combined use of steroids and immunosuppressants.
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PMID:Presentation and outcome of gastrointestinal involvement in systemic necrotizing vasculitides: analysis of 62 patients with polyarteritis nodosa, microscopic polyangiitis, Wegener granulomatosis, Churg-Strauss syndrome, or rheumatoid arthritis-associated vasculitis. 1575 41

Chronic renal failure represents a major problem of public health. Incidence for patients arrived at the terminal stage of the disease is in France 126.4/million inhabitants and the cost of medical care reaches 2 % of the expenses of the National Health Insurance. The progression of the disease is divided into 5 stages that are defined by the level of creatinine clearance from the stage of renal diseases with a normal renal function (clearance>90 ml/min) to the terminal stage (clearance <15 ml/min). Prevalence of patients at this ultimate stage is around 50,000. Prevalence for the totality of patients with a renal disease is evaluated between 2 and 3 millions. Renal diseases must be screened because they are silent and because an early pre-dialysis nephrological care allows renal replacement therapy to be delayed and the number of cardiovascular accidents to be diminished. Screening must be performed in the high-risk populations, essentially patients with diabetes, hypertension, coronary ischemia, renal tract diseases and all subjects treated with drugs toxic for the kidneys. Screening in the total population seems inadequate because of a high cost to benefit ratio. Screening is based on testing for the presence of proteinuria, quantifying the number of formed elements and plasma creatinine determination, the latter allowing, together with age and weight, glomerular filtration rate to be evaluated according to Cockcroft's formula. Prevention of renal diseases in the whole population necessitates the same life style as that recommended for prevention of cardiac and metabolic diseases. In the high-risk populations, one must control glycemia, blood pressure and cholesterol plasma level. In patients that have been already screened, renal function decay has to be slowed down by blocking the renin angiotensin system with converting enzyme inhibitors, controlling plasma cholesterol with statins and diminishing dietary proteins. In the light of these various data, the National Academy of medicine recommends: 1 - in the field of public health, to extend to the whole country the registries containing data on patients with terminal chronic renal failure, to support the creation of medical networks for the screening of renal diseases, to vaccine the patients against hepatitis B, flue and pneumococcal infections and to verify whether a low birth weight is associated with a greater risk of renal diseases in adulthood; 2 - in the field of teaching and research, to stop the decrease in the number of nephrologists, to promote research in genetics, to evaluate the efficacy of antifibrosis drugs and the possible renal toxicity of all new drugs.
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PMID:[Prevention and screening of chronic renal failure]. 1591 71

Infection-related vasculitis constitutes the most common cause of secondary vasculitis. A great variety of microorganisms can induce directly or indirectly inflammatory vascular damage resulting in vascular occlusion, tissue ischemia, and necrosis. In the developed world hepatitis B and C-related vasculitis remain the most common clinical syndromes, while HIV-associated vasculitis remains a concern in developing countries.
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PMID:Infection-related vasculitis. 1604 31

Polyarteritis nodosa (PAN), the prototype of systemic vasculitis, is a rare condition characterized by necrotizing inflammation of medium-sized or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules. Signs and symptoms of this disease are primarily attributable to diffuse vascular inflammation and ischemia of affected organs. Virtually any organ with the exception of the lungs may be affected, with peripheral neuropathy and symptoms from osteoarticular, renal artery, and gastrointestinal tract involvement being the most frequent clinical manifestations. A clear distinction between limited versus systemic disease and idiopathic versus hepatitis B related PAN should be done because there are differences in the implicated pathogenetic mechanisms, their treatment, and prognosis. Currently, corticosteroids plus cyclophosphamide is the standard of care for idiopathic PAN, in particular for patients with adverse prognostic factors (more severe disease), in whom this combination prolonged survival. In contrast for hepatitis B related PAN treatment consists of schemes that include plasmapheresis and antiviral agents.
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PMID:Polyarteritis nodosa revisited. 1604 32

The liver is continuously exposed to a large antigenic load that includes pathogens, toxins, tumor cells and dietary antigens. Amongst the hepatitis viruses, only hepatitis B virus (HBV) and hepatitis C virus (HCV) cause chronic hepatitis, which can progress to cirrhosis and hepatocellular carcinoma. Of the different antiviral defense systems employed by the tissue, apoptosis significantly contributes to the prevention of viral replication, dissemination, and persistence. Loss of tolerance to the liver autoantigens may result in autoimmune hepatitis (AIH). This review outlines the recent findings that highlight the role and mechanisms of apoptotic processes in the course of liver diseases. Among factors that contribute to liver pathology, we discuss the role of tumor necrosis factor (TNF)-alpha, HBx, ds-PKR, TRAIL, FasL, and IL-1alpha. Since TNF and FasL-induced hepatocyte apoptosis is implicated in a wide range of liver diseases, including viral hepatitis, alcoholic hepatitis, ischemia/reperfusion liver injury, and fulminant hepatic failure, these items will be discussed in greater detail in this review. We also highlight some recent discoveries that pave the way for the development of new therapeutic strategies by protecting hepatocytes (for example by employing Bcl-2, Bcl-XL or A1/Bfl-1, IAPs, or synthetic caspase inhibitors), or by the induction of apoptosis in stellate cells. The assessment of the severity of liver disease, as well as monitoring of patients with chronic liver disease, remains a major challenge in clinical hepatology practice. Therefore, a separate chapter is devoted to a novel cytochrome c-based method useful for the diagnosis and monitoring of fulminant hepatitis.
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PMID:Apoptosis in liver diseases--detection and therapeutic applications. 1625 9

Polyarteritis nodosa (PAN) related to hepatitis B is an uncommon vasculitis that is sometimes associated with the rapid progression of distal ischemia. A few recent reports have proposed the use of antiviral therapy. However, there is not yet a consensus for the standard treatment of this disease entity and none of these treatments have been focused on fast symptomatic improvement. We describe here a 39-year-old female patient with PAN related to hepatitis B infection who completely recovered from the acutely progressing ischemic manifestations of her distal extremities with the use of alprostadil infusion (prostaglandin E1). The reactivation of her hepatitis B infection after glucocorticoid and cyclophosphamide therapy was successfully managed by the antiviral lamuvudine therapy. Most importantly, the vasodilator together with the conventional therapy may be desirable in the early stages of the disease before irreversible ischemic tissue damage can occur.
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PMID:Rapid improvement of distal vasculitis in PAN related to hepatitis B with alprostadil infusion: a case report. 1643 20

Adult living donor liver transplantation (ALDLT) is an accepted procedure to overcome the organ shortage. The advantages of ALDLT must be balanced against the first concern of donor safety. We analyzed the results of our early experience among a series of eight ALDLT performed between April 2001 and October 2003. All patients were listed as United Network for Organ Sharing UNOS status 2b and 3. Transplant recipients consisted of four men and four women. The living donors included four sons, three daughters, and one son-in-law (ages 20 to 45 years). One donor was anti-HBc-positive and negative for hepatitis B virus-DNA by polymerase chain reaction analysis in serum and in liver tissue. GR/WR >0.8 and fatty liver <10% were considered suitable for the hepatectomy. Residual left lobe volume was at least 33%. No exogenous blood and blood products were transfused into the donors and a cell-saver device was used in all donors (blood loss 490 +/- 160 mL). All procedures were right lobe hepatectomy; in one case the middle hepatic vein was withdrawn with the right graft. The mean ischemia time was 1.5 +/- 0.5 hours. All donors survived the procedure. Median hospital stay was 8.5 +/- 2.1 days in all donors but one who had a long stay because of drug-related hepatitis. One graft was lost and one donor aborted because of preoperative overestimated volumetry. Complications were experienced by two donors (25%). Five recipients (62.5%) experienced major complications; one patient underwent retransplantation because of donor graft loss. Two biliary and two vascular complications (33.3%) occurred in three patients. No perioperative death occurred. Two patients died at 9 and 10 months after transplant because of heart and respiratory failure in the first case and tumor recurrence in the second. One-year actuarial survival is 75%. ALDLT using right lobe has gained acceptance to overcome the organ shortage. Donor selection criteria must be stringent with respect to residual donor hepatic volume, steatosis, and liver function.
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PMID:Living donor liver transplantation: early single-center experience. 1675 77


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