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Inflammatory Activity (inflammatory + activity)
Selected AbstractsA pilot study of interferon alfa and ribavirin combination in liver transplant recipients with recurrent hepatitis CHEPATOLOGY, Issue 5 2002A. Obaid Shakil Although interferon alfa (IFN-,) and ribavirin are widely used in the treatment of hepatitis C, their role in the transplant recipient is unclear. We conducted a pilot study to determine the efficacy and safety of this therapy in transplant recipients with recurrent hepatitis C. Patients at least 6 months posttransplantation were treated with IFN-, 3 million units 3 times a week subcutaneously and ribavirin 800 mg daily by mouth for 48 weeks followed by ribavirin monotherapy for 24 weeks. The primary end point was sustained virologic response, and secondary end points included biochemical, virologic, and histologic responses at the end of combination treatment. Thirty-eight patients initiated therapy but 16 withdrew due to adverse effects, including 2 with myocardial infarction. Median age was 50 years; 74% were men, and 91% had genotype 1. The median interval between transplantation and enrollment was 23 months. On an intention-to-treat basis, 7 patients (18%) had a biochemical and 5 (13%) had a virologic response at the end of combination treatment. Inflammatory activity did not change, but fibrosis worsened in virologic nonresponders. Ribavirin maintenance caused a further decrease in serum alanine aminotransferase levels, but hepatitis C virus (HCV) RNA levels increased. Only 2 of the 38 patients (5%) had a sustained virologic response. Several patients required treatment with erythropoietin for anemia. In conclusion, IFN-, and ribavirin are effective in a small proportion of liver allograft recipients with recurrent hepatitis C. Adverse effects occur commonly, requiring dose reductions and treatment withdrawal. [source] MAGNIFYING COLONOSCOPY FOR THE DIAGNOSIS OF INFLAMMATORY CHANGES IN ULCERATIVE COLITISDIGESTIVE ENDOSCOPY, Issue 3 2006Satoshi Sugano Background:, Endoscopic observation is the most effective method for the evaluation of staging in ulcerative colitis (UC). However, in cases with very mild inflammatory activity, histopathological diagnosis may also be required. Unfortunately, biopsy-related accidents are not uncommon. As an alternative, we have used a magnifying colonoscope commonly used for tumor diagnosis to examine in detail the colon mucosa of UC patients in clinical remission, and then compared these findings relative to conventional endoscopy using histopathological diagnosis. Subjects and Methods:, Among UC cases examined by colonoscopy between April 2000 and April 2005, 27 cases without hematochezia for at least 1 month were enrolled in this study. Following observations of inflammatory changes using conventional colonoscopy, magnifying observation and biopsies at a total of 144 sites were evaluated. Using histopathological standards, acute-phase inflammation was indicated by the presence of neutrophil infiltration, whereas chronic-phase inflammation was indicated by infiltration of lymphocytes, plasma cells and eosinophils. Results:, Indicators of significant inflammation by conventional observation was erosion. Under magnification, inflammation appears as superficial defects in mucosa and small whitish spots. When the presence of infiltrating neutrophils was used as a positive histological marker for inflammation, there was no difference in the accuracy of diagnosis by conventional observation (95.1%) versus magnifying observation (97.2%). In contrast, when lymphocyte infiltration was used as a marker, the accuracy of diagnosis increased significantly (88.2%) using magnifying observation relative to conventional observation (61.1%). Conclusions:, Magnifying endoscopy can be used effectively in the evaluation of minute mucosal changes in cases of UC remission. [source] Low cholesterol along with inflammation predicts morbidity and mortality in hemodialysis patientsHEMODIALYSIS INTERNATIONAL, Issue 2 2009George TSIRPANLIS Abstract Low and not high cholesterol seems to predict high mortality in hemodialysis (HD) patients. The confirmation of this reverse epidemiology as well as its possible interconnection with the increased inflammatory activity observed in this population is being explored in the present study. A group of 136 HD patients was prospectively studied for 2 years, and cardiovascular disease (CVD) as well as all-cause mortality and morbidity were recorded. Baseline lipid profile, inflammatory status, and patients' characteristics were studied as potential survival and hospitalization predictors. During the 24-month follow-up, 21 deaths (52.4% due to CVD) and 38 hospitalizations (55.3% due to CVD) were recorded. In multivariate Cox regression analysis, decreased interleukin-10 (IL-10) and decreased total serum cholesterol (TChol) were the only independent predictors of CVD mortality while C-reactive protein and decreased TChol predicted all-cause mortality. Interleukin-10 at baseline was 11.29 ± 21.49 vs. 5.51 ± 4.57 pg/mL (P<0.018) and TChol 167.37 ± 47.84 vs.122.04 ± 26.48 mg/dL (P<0.000) in survivors vs. nonsurvivors from CVD, while C-reactive protein at baseline was 9.37 ± 11.54 vs. 23.15 ± 18.76 mg/L (P<0.000) and TChol 169.26 ± 46.42 vs. 133.26 ± 46.33 mg/dL (P<0.003) in survivors vs. nonsurvivors from any cause of death. Using the same method of statistical analysis, IL-6 and decreased soluble gp130 (sgp130),an antagonist of IL-6 action,were found to be the only independent prognostic factors for hospitalization due to CVD while decreased soluble gp130 remained the sole predictor of hospitalization due to any cause. In conclusion, reverse epidemiology regarding cholesterol is confirmed in the present study. Furthermore, inflammatory activity also predicts, independently of or in conjunction with low-cholesterol, CVD and all-cause morbidity and mortality in HD patients. [source] Transient elastography: Applications and limitationsHEPATOLOGY RESEARCH, Issue 11 2008Kentaro Yoshioka Transient elastgraphy with use of FibroScan is one of most accurate methods for assessment of liver fibrosis. FibroScan can be readily used with an operator with a short training. In many different studies, liver stiffness measured by transient elastgraphy correlates well with fibrosis stages, and cutoff values of liver stiffness for fibrosis staging are similar even among different diseases. However there is wide variation of stiffness values in the same fibrosis stage, and some overlap between the adjacent stages. In addition, inflammatory activity and size of nodule of cirrhosis affect the liver stiffness values. The reproducibility may be reduced by age, obesity, steatosis, narrow intercostal space and lower degrees of hepatic fibrosis in patients. Thus the estimation of fibrosis stages from liver stiffness should be cautiously done. To improve the accuracy of liver fibrosis staging, the combination of transient elastography with other noninvasive methods such as FibroTest should be required. [source] Symptomatic treatment of osteoarthritis: paracetamol or NSAIDs?INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2004Karel PAVELKA MD SUMMARY The clinical management of osteoarthritis (OA) is today symptomatic, its main goals being relief of pain and improvement of function. Therapy should be multimodal and composed of non-pharmacological, pharmacological and, if necessary, surgical procedures. Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) are evidence-based drugs for the symptomatic relief of OA. Newly published comparative studies have shown that NSAIDs are more effective than paracetamol , in contrast to studies from the early 1990s. Some studies have documented that more severe pain and the presence of inflammation can predict better response from NSAIDs than from paracetamol; on the other hand other studies have not confirmed this. Patient preference studies have shown that patients favour NSAIDs, but up to 40% consider paracetamol at least as effective as NSAIDs. With regard to efficacy, safety and cost, the majority of new guidelines recommend paracetamol as a first-choice analgesic for patients with OA of the knee or hip, and the use of NSAIDs only in cases of inadequate effect of paracetamol and especially in the presence of inflammation. There is much evidence that OA is a phasic disease and it may be that NSAIDs are useful during identifiable periods of inflammatory activity and can be avoided at other times. The concept of the short-term use of NSAIDs during flares and the use of a simple analgesic in the long term seems to be the best variant for the majority of patients with optimal benefit/risk and cost-effectiveness. [source] The CCR5,32 allele is associated with reduced liver inflammation in hepatitis C virus infectionINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2004O. Wald Summary CCR5,32 is a deletion mutation in the chemokine receptor CCR5. Liver inflammatory activity was found to be significantly reduced (P = 0.005) in Jewish Israeli patients infected with the hepatitis C virus (HCV) carrying the CCR5,32 allele. The CCR5,32 allele does not alter susceptibility to HCV infection; however, it may play a role in the progression and outcome of the disease. [source] Power Doppler assessment of overall disease activity in patients with rheumatoid arthritisJOURNAL OF CLINICAL ULTRASOUND, Issue 1 2006Adem Kiris MD Abstract Purpose. To examine synovial vascularity and flow patterns in hand and wrist joints,metacarpophalangeal (MCP) joints and ulnar stiloid (USTL) regions,of patients with rheumatoid arthritis (RA) using power Doppler sonography (PDUS) and spectral Doppler analysis and to assess the accuracy of PDUS in detecting overall disease activity in RA patients. Methods Two hundred forty MCP joints and 48 USTL regions in 24 RA patients were examined. Patients were categorized into 2 groups,active and inactive,according to the American College of Rheumatology remission criteria. Resistance indexes (RIs) were measured. Results Flow signals were detected in 50 MCP joints (in 13 patients) and 24 USTL regions (in 16 patients) and spectral analysis was performed in 46 MCP joints (12 patients) and 23 USTL regions (16 patients). The sensitivity and specificity of PDUS in detecting disease activity in RA were 92% and 40%, respectively. There was a negative correlation between flow signal number and RI, with higher scores of flow signals corresponding to lower RIs. Conclusion PDUS appears to be a reliable method for assessing inflammatory activity in rheumatoid synovium. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound34:5,11, 2006 [source] Chronic hepatitis B virus infection in Asian countriesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2000I Merican Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5,10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8,10% of males and 6,8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50,75% of those with HCC. In Taiwan, 75,80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of time. The outcome after anti-HBe seroconversion depends on the degree of pre-existing liver damage and any subsequent HBV reactivation. Without pre-existing cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with pre-existing cirrhosis, further complications may ensue. HBsAg-negative chronic hepatitis B is a phase of chronic HBV infection during which a mutation arises resulting in the inability of the virus to produce HBeAg. Such patients tend to have more severe liver disease and run a more rapidly progressive course. The annual probability of developing cirrhosis varies from 0.1 to 1.0% depending on the duration of HBV replication, the severity of disease and the presence of concomitant infections or drugs. The annual incidence of hepatic decompensation in HBV-related cirrhosis varies from 2 to 10% and in these patients the 5-year survival rate drops dramatically to 14,35%. The annual risk of developing HCC in patients with cirrhosis varies between 1 and 6%; the overall reported annual detection rate of HCC in surveillance studies, which included individuals with chronic hepatitis B and cirrhosis, is 0.8,4.1%. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. Prevention of HBV infection thorough vaccination is still, therefore, the best strategy for decreasing the incidence of hepatitis B-associated cirrhosis and HCC. [source] Autoimmune and inflammatory disorders and risk of malignant lymphomas , an updateJOURNAL OF INTERNAL MEDICINE, Issue 6 2008K. E. Smedby Abstract. As specific autoimmune disorders now constitute established risk factors for malignant lymphomas, we describe this association. We review reported risk levels, risk determinants, lymphoma subtypes and biological mechanisms in autoimmunity/inflammation, emphasizing on recent findings. Whilst numerous reports describe average lymphoma risks in large patient groups, there's a recent shift of focus to risk determinants and the role of inflammatory activity. Studies highlight associations with diffuse large B-cell lymphoma, apart from lymphoma development in target organs of inflammation. Future studies of high-risk patient subsets using detailed assessments of autoimmunity/inflammation and lymphoma may give important clues to lymphomagenesis. [source] Predictability of FTY720 efficacy in experimental autoimmune encephalomyelitis by in vivo macrophage tracking: Clinical implications for ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imagingJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2004Martin Rausch PhD Abstract Purpose To examine the efficacy of FTY720 as a new agent to reduce inflammatory activity in an animal model of multiple sclerosis (MS) by in vivo macrophage tracking. Material and Methods FTY720 was used for treatment of rats in a model of chronic relapsing experimental autoimmune encephalomyelitis (EAE) at an oral dose of 0.3 mg/kg/day. Magnetic resonance imaging (MRI) based on in vivo tracking of macrophages labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, immunohistological staining (IHC), and neurological readouts was used to study the burden of disease in treated and untreated animals. Results While untreated animals showed severe paralysis of the hind paws, intense accumulation of macrophages in brain tissue, and areas of blood-brain barrier (BBB) disruption, FTY720-treated animals displayed no signs of inflammatory activity or neurological impairment. These observations were made for both acute phase and first relapse. Conclusion Tracking of macrophages by MRI provides direct evidence of the immunomodulatory efficacy of FTY720 in the EAE model and correlates well with neurological symptoms and histology. J. Magn. Reson. Imaging 2004;20:16,24. © 2004 Wiley-Liss, Inc. [source] Progranulin: normal function and role in neurodegenerationJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Jason L. Eriksen Abstract Progranulin (PGRN) is a multifunctional protein that has attracted significant attention in the neuroscience community following the recent discovery of PGRN mutations in some cases of frontotemporal dementia. Most of the pathogenic mutations result in null alleles, and it is thought that frontotemporal dementia in these families results from PGRN haploinsufficiency. The neuropathology associated with PGRN mutations is characterized by the presence of tau-negative, ubiquitin-immunoreactive neuronal inclusions (frontotemporal lobar degeneration with ubiquitinated inclusions) that are also positive for the transactivation response DNA binding protein with Mr 43 kD. The clinical phenotype includes behavioral abnormalities, language disorders and parkinsonism but not motor neuron disease. There is significant clinical variation between families with different PGRN mutations and among members of individual families. The normal function of PGRN is complex, with the full-length form of the protein having trophic and anti-inflammatory activity, whereas proteolytic cleavage generates granulin peptides that promote inflammatory activity. In the periphery, PGRN functions in wound healing responses and modulates inflammatory events. In the CNS, PGRN is expressed by neurons and microglia; consequently, reduced levels of PGRN could affect both neuronal survival and CNS inflammatory processes. In this review, we discuss current knowledge of the molecular genetics, neuropathology, clinical phenotype and functional aspects of PGRN in the context of neurodegenerative disease. [source] Immunological factors and their role in the genesis and development of endometriosis ARTICLE HAS BEEN RETRACTEDJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2006Charalambos Siristatidis Abstract The article presents an overview of immunological factors and their role in the genesis and development of endometriosis, with emphasis on inflammatory cytokines and growth and adhesion factors. Although retrograde menstruation is a common phenomenon among women of reproductive age, not all women with retrograde menstruation suffer the disease. Development of endometriosis seems to be a complex process, facilitated by several factors, including quantity and quality of endometrial cells in peritoneal fluid (PF), increased inflammatory activity in PF, increased endometrial,peritoneal adhesion and angiogenesis, reduced immune surveillance and clearance of endometrial cells, and increased production of autoantibodies against endometrial cells. Potential biomarkers like cytokines and autoantibodies, upregulated during development of endometriosis, seem useful in the development of a non-surgical diagnostic tool. In this review work, the immune role in endometriosis is examined through the role of immunological factors in the genesis and development of the disease. Furthermore, it could be concluded that, although endometriosis can be treated using hormonal suppression, there is a need today for non-hormonal drugs, probably to modulate immune function, in order to confront the disease and alleviate pain or infertility without inhibition of ovulation. [source] Increased plasma fibrin gel porosity in patients with Type I diabetes during continuous subcutaneous insulin infusionJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2003G. Jörneskog Summary.,Background:,Patients with Type 1 diabetes have a tighter plasma fibrin gel structure, to which impaired glycemic control might contribute. Improved glycemic control can be achieved with continuous subcutaneous insulin infusion (CSII). Objectives:,The aim of the present study was to investigate the effect of CSII on plasma fibrin gel properties and circulating markers of inflammatory activity in patients with Type 1 diabetes. Patients and methods:,Twenty-eight patients were investigated before and after 4,6 months' treatment with CSII. Fibrin gel structure formed in vitro from plasma samples was investigated by liquid permeation of hydrated fibrin gel networks. P-fibrinogen was analyzed by a syneresis method. Comparisons were made between patients with improved (> 0.5%) and unchanged (< 0.5%) glucosylated hemoglobin (HbA1c) during CSII. Results:,Eighteen patients showed improved and 10 patients unchanged HbA1c during CSII. P-fibrinogen, high sensitive C-reactive protein and serum amyloid A-antigen were not significantly changed, while fibrin gel permeability (Ks) and fiber mass,length ratio (µ) increased in both groups (P < 0.02). P-insulin and triglycerides decreased (P < 0.05) in both groups, while reductions of total cholesterol and intercellular adhesion molecule-1 were seen only in patients with improved HbA1c (P < 0.05). Absolute changes in Ks were inversely correlated to changes in plasma fibrinogen (r = 0.50; P < 0.01) and in LDL-cholesterol (r = 0.46; P < 0.05). Conclusions:,Treatment with CSII in patients with Type 1 diabetes is associated with increased plasma fibrin gel porosity. Slight attenuation of the inflammatory activity was also observed. The changes in fibrin gel porosity seem to be mainly mediated by changes in plasma fibrinogen and blood lipids, and are probably secondary to improved insulin sensitivity. [source] A Clinical Index for Disease Activity in Cats with Chronic EnteropathyJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2010A.E. Jergens Background: There is a need for a clinically useful, quantitative index for measurement of disease activity in cats with chronic enteropathy (CE). Objective: To develop a numerical activity index that is of practical value to clinicians treating CE in cats. Animals: Eighty-two cats with CE. Methods: Retrospective case review of 59 cats diagnosed with inflammatory bowel disease (IBD). Prospective validation study of 23 cats having either IBD or food-responsive enteropathy (FRE). Multivariate regression analysis was used to identify which combination of clinical and laboratory variables were best associated with intestinal inflammation of IBD. This combination of variables was expressed in a score that was used as an activity index for the prospective assessment of disease activity and of the effect of treatment in cats with IBD or FRE. Results: The combination of gastrointestinal signs, endoscopic abnormalities, serum total protein, serum alanine transaminase/alkaline phosphatase activity, and serum phosphorous concentration had the best correlation with histopathologic inflammation and comprise the feline chronic enteropathy activity index (FCEAI). Positive treatment responses in cats with CE were accompanied by significant (P < .05) reductions in FCEAI scores after treatment. Conclusions and Clinical Importance: The FCEAI is a simple numerical measure of inflammatory activity in cats with CE. The scoring index can be reliably used in the initial assessment of disease severity for both IBD and FRE and as a measure of clinical response to treatment for these disorders. [source] Expression of hepatitis B virus X protein is closely correlated with the high periportal inflammatory activity of liver diseasesJOURNAL OF VIRAL HEPATITIS, Issue 5 2001Y. M. Jin Hepatitis B virus X (HBx) protein is a multifunctional protein that exerts dual activity on cell proliferation and death. Although HBx is thought to be a major determinant that leads to hepatocellular carcinoma, its pathophysiological role in humans remains to be established. Attempts have been made to evaluate the role of HBx in liver specimens derived from patients with chronic B viral hepatitis and hepatocellular carcinoma. Among 25 paired liver specimens of hepatocellular carcinoma and corresponding nontumour liver tissues, HBx mRNA was hardly detected and was significantly lower than other HBV transcripts. An immunohistochemical study demonstrated that expression of HBx protein was also lower than other HBV gene products. Interestingly, however, expression of HBx protein changed with the progression of chronic hepatitis. HBx was expressed in 5.0% of patients with chronic hepatitis without cirrhosis but increased to 44.8% in chronic hepatitis with cirrhosis. In contrast, only one (3.7%) of 27 hepatocellular carcinomas showed HBx positivity whereas 29.6% of surrounding nontumour tissues was still HBx-positive. These results suggest that HBx may play a major role at the promotion stage of carcinogenesis. Noticeably, HBx-positive cells were preferentially localized in the periportal region of chronic hepatitis or periphery of cirrhotic nodules where high necroinflammatory activity was accompanied. We found a positive correlation between HBx expression and periportal inflammatory activity (P < 0.001). Thus, HBx may potentiate cell destruction and regeneration of liver that provide an opportunity for the accumulation of genetic mutations, which contribute to multistep hepatocarcinogenesis. [source] Association among Fas expression in leucocytes, serum Fas and Fas-ligand concentrations and hepatic inflammation and fibrosis in chronic hepatitis CLIVER INTERNATIONAL, Issue 3 2010Anatol Panasiuk Abstract Background: Replication of the hepatitis C virus (HCV) in peripheral blood mononuclear cells (PBMC) may impair immune functions and establish persistent infection. The aim of this study was to assess the influence of HCV on PBMC and their susceptibility to apoptosis in relation to liver inflammation and fibrosis. Methods: Eighty-one patients with chronic hepatitis C (CHC) were enrolled in this study. Flow cytometry was used to determine the amount of T cells (CD4+, CD8+), B cells (CD19+), monocytes (CD14+) and natural killer cells (CD16+) in the peripheral blood and the expression of CD95+ (CD95/APO-1) in each subset. Serum concentrations of sFas and sFasL were assessed by the enzyme-linked immunosorbent assay method. Results: An increased expression of Fas was observed in CD4+ and CD8+ cells in CHC. There was a more prominent expression of Fas on CD4+ cells in HCV genotype 1b in contrast to 3a. Increased Fas expression on CD4+ cells was seen in advanced stages of liver disease. Fas expression on monocytes was lower in advanced stages of liver inflammation and fibrosis. Serum sFas concentration was higher in CHC compared with the control group. There was an association between sFasL concentration and inflammatory activity in the liver. Serum sFasL concentration correlated positively with the mean intensity of fluorescence of the Fas receptor in CD4+ and CD8+ cells, granulocytes and monocytes. Conclusion: These findings indicate that there is an increased susceptibility of PBMC to apoptosis, which can be attributed to the constant contact of leucocytes with the inflamed liver tissue, or from direct HCV influence. [source] Risk factors for recurrence of autoimmune hepatitis after liver transplantation,,LIVER TRANSPLANTATION, Issue 10 2009Aldo J. Montano-Loza Autoimmune hepatitis has been reported to recur after liver transplantation. The aim of our study was to evaluate the risk factors associated with recurrence of autoimmune hepatitis. Forty-six patients that underwent liver transplantation because of end-stage liver disease secondary to autoimmune hepatitis were studied. Recurrence of autoimmune hepatitis was diagnosed in 11 of the 46 (24%) patients, and the overall 5-year probability of recurrence was 18%. By univariate Cox analysis, the features before liver transplantation associated with a higher risk of recurrence were concomitant autoimmune disease [hazard ratio (HR), 3.74; 95% confidence interval (CI), 1.05,13.36; P = 0.04], high aspartate aminotransferase (HR, 1.09; 95% CI, 1.03,1.14; P = 0.002), high alanine aminotransferase (HR, 1.09; 95% CI, 1.03,1.20; P = 0.003), and high immunoglobulin G (IgG; HR, 1.25; 95% CI, 1.11,1.41; P = 0.0003). Moreover, patients with recurrence had a higher frequency of moderate to severe inflammatory activity (HR, 5.3; 95% CI, 1.55,18.79; P = 0.008) and plasma cell infiltration in the liver explant (HR, 5.8; 95% CI, 1.52,22.43; P = 0.01). In the multivariate Cox analysis, only the presence of moderate to severe inflammation (HR, 6.9; 95% CI, 1.76,26.96; P = 0.006) and high IgG levels before liver transplantation (HR, 7.5; 95% CI, 1.45,38.45; P = 0.02) were independently associated with the risk of autoimmune hepatitis recurrence. In conclusion, patients with concomitant autoimmune disease, high aspartate aminotransferase, alanine aminotransferase, and IgG before the transplant, or moderate to severe inflammatory activity or plasma cell infiltration in the liver explant have a higher risk of recurrent disease. These findings suggest that recurrence of autoimmune hepatitis may reflect incomplete suppression of disease activity prior to liver transplantation. Liver Transpl 15:1254,1261, 2009. © 2009 AASLD. [source] Expression of cyclooxygenase-2 in chronic hepatitis B and the effects of anti-viral therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2002A. S. L. Cheng Backgound: Cyclooxygenase-2 may play a role in the development of hepatocellular carcinoma, but the relationship between cyclooxygenase-2 and chronic hepatitis B is unknown. Aim: To investigate the expression and cellular localization of cyclooxygenase-2 in chronic hepatitis B patients and the effects of anti-viral therapy. Methods: Using immunohistochemistry, in situ hybridization, Western blot and reverse transcription polymerase chain reaction, protein and messenger RNA expression and cellular localization of cyclooxygenase-2 in 35 chronic hepatitis B patients were assessed. Fourteen histologically normal and non-viral-infected livers were used as controls. The cyclooxygenase-2 immunoreactivities of paired liver biopsies from 12 patients receiving anti-viral therapy were compared. Results: Immunohistochemistry and in situ hybridization revealed that cyclooxygenase-2 expression was confined to hepatocytes. Patients with chronic hepatitis B had significantly higher cyclooxygenase-2 expression compared with controls. The cyclooxygenase-2 expression of hepatitis B e antigen-positive and -negative chronic hepatitis B patients was not significantly different, although the necro-inflammatory activity of the latter group was significantly lower. Over-expression of cyclooxygenase-2 in patients with chronic hepatitis B was further confirmed by Western blot and reverse transcription polymerase chain reaction. Twelve hepatitis B e antigen-positive chronic hepatitis B patients received anti-viral therapy: lamivudine in seven and interferon in five. Despite hepatitis B e antigen seroconversion, disappearance of hepatitis B virus DNA in serum, normalization of liver enzymes and a significant reduction in necro-inflammatory activity in all 12 patients, no significant change in cyclooxygenase-2 expression was found. Conclusions: Chronic hepatitis B is associated with elevated cyclooxygenase-2 levels in hepatocytes, and the over-expression of this enzyme does not reflect inflammatory activity. Up-regulation of cyclooxygenase-2 persists after successful anti-viral therapy. [source] Iron and inflammatory bowel diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2001B. Oldenburg Both anaemia of iron deficiency and anaemia of chronic disease are frequently encountered in inflammatory bowel disease. Anaemia of iron deficiency is mostly due to inadequate intake or loss of iron. Anaemia of chronic disease probably results from decreased erythropoiesis, secondary to increased levels of proinflammatory cytokines, reactive oxygen metabolites and nitric oxide. Assessment of the iron status in a condition associated with inflammation, such as inflammatory bowel disease, is difficult. The combination of serum transferrin receptor with ferritin concentrations, however, allows a reliable assessment of the iron deficit. The best treatment for anaemia of chronic disease is the cure of the underlying disease. Erythropoietin reportedly may increase haemoglobin levels in some of these patients. The anaemia of iron deficiency is usually treated with oral iron supplements. Iron supplementation may lead to an increased inflammatory activity through the generation of reactive oxygen species. To date, data from studies in animal models of inflammatory bowel disease support the theoretical disadvantage of iron supplementation in this respect. The results, however, cannot easily be extrapolated to the human situation, because the amount of supplemented iron in these experiments was much higher than the dose used in patients with iron deficiency. [source] Histological grading and staging in chronic hepatitis: Its practical correlationPATHOLOGY INTERNATIONAL, Issue 11 2002Miyuki Nakaji Although the histological features of various causes of chronic liver disease have been well described, usually the inflammatory activity of the disease is important after the cause has been established. Some patients have co-infection,or,concomitant,liver,disease,and on occasion it is difficult to decide the treatment. In order to clarify the histological differences, we investigated the inflammatory activity among autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC),,chronic,hepatitis C (CHC) and chronic hepatitis B (CHB) in a standardized way using the modified histological activity index (HAI). According to the modified HAI, inflammatory activity is divided into four categories; categories A/D explains portal/periportal inflammation and categories B/C explains lobular activity. The inflammatory score of AIH tended to be greater in all categories from the early stage of fibrosis, whereas scores of PBC were lower, except for portal inflammation. Chronic hepatitis C patients had portal or periportal inflammation, and their inflammatory scores were linked to the development of fibrosis. Chronic hepatitis B patients tended to have severe lobular injury, but did not have a relationship between the inflammatory score and their stage. To know the distribution of inflammation using the modified HAI scoring system may be helpful and convenient in evaluating patients with chronic inflammatory liver disease. [source] Transgenic disruption of glucocorticoid signaling in mature osteoblasts and osteocytes attenuates K/BxN mouse serum,induced arthritis in vivoARTHRITIS & RHEUMATISM, Issue 7 2009Frank Buttgereit Objective Endogenous glucocorticoids (GCs) modulate numerous biologic systems involved in the initiation and maintenance of arthritis. Bone cells play a critical role in the progression of arthritis, and some of the effects of GCs on inflammation may be mediated via these cells. The aim of this study was to investigate the impact of osteoblast-targeted disruption of GC signaling on joint inflammation, cartilage damage, and bone metabolism in the K/BxN mouse serum transfer model of autoimmune arthritis. Methods Intracellular GC signaling was disrupted in osteoblasts through transgenic overexpression of 11,-hydroxysteroid dehydrogenase type 2 under the control of a type I collagen promoter. Arthritis was induced in 5-week-old male transgenic mice and their wild-type (WT) littermates, and paw swelling was assessed daily until the mice were killed. The mice were examined by histology, histomorphometry, and microfocal computed tomography, and serum was analyzed for cytokines, adrenocorticotropic hormone, and corticosterone. Results Acute arthritis developed in both transgenic and WT mice treated with K/BxN mouse serum. However, the arthritis and local inflammatory activity were significantly attenuated in transgenic mice, as judged by clinical and histologic indices of inflammation and cartilage damage. Bone turnover and bone volume remained unchanged in arthritic transgenic mice, while WT mice exhibited stimulated bone resorption, suppressed osteoblast activity, and significantly reduced bone volume, compatible with the known effects of active inflammation on bone. Circulating levels of proinflammatory cytokines tended to be lower in arthritic transgenic mice than in control transgenic mice. Conclusion Disruption of GC signaling in osteoblasts significantly attenuates K/BxN mouse serum,induced autoimmune arthritis in mice. These data suggest that osteoblasts modulate the immune-mediated inflammatory response via a GC-dependent pathway. [source] Improvement of lipid profile is accompanied by atheroprotective alterations in high-density lipoprotein composition upon tumor necrosis factor blockade: A prospective cohort study in ankylosing spondylitisARTHRITIS & RHEUMATISM, Issue 5 2009I. C. van Eijk Objective Cardiovascular mortality is increased in ankylosing spondylitis (AS), and inflammation plays an important role. Inflammation deteriorates the lipid profile and alters high-density lipoprotein cholesterol (HDL-c) composition, reflected by increased concentrations of serum amyloid A (SAA) within the particle. Anti,tumor necrosis factor (anti-TNF) treatment may improve these parameters. We therefore undertook the present study to investigate the effects of etanercept on lipid profile and HDL composition in AS. Methods In 92 AS patients, lipid levels and their association with the inflammation markers C-reactive protein (CRP), erythrocyte sedimentation rate, and SAA were evaluated serially during 3 months of etanercept treatment. HDL composition and its relationship to inflammation markers was determined in a subgroup of patients, using surface-enhanced laser desorption/ionization time-of-flight analysis. Results With anti-TNF treatment, levels of all parameters of inflammation decreased significantly, whereas total cholesterol, HDL-c, and apolipoprotein A-I (Apo A-I) levels increased significantly. This resulted in a better total cholesterol:HDL-c ratio (from 3.9 to 3.7) (although the difference was not statistically significant), and an improved Apo B:Apo A-I ratio, which decreased by 7.5% over time (P = 0.008). In general, increases in levels of all lipid parameters were associated with reductions in inflammatory activity. In addition, SAA was present at high levels within HDL particles from AS patients with increased CRP levels and disappeared during treatment, in parallel with declining plasma levels of SAA. Conclusion Our results show for the first time that during anti-TNF therapy for AS, along with favorable changes in the lipid profile, HDL composition is actually altered whereby SAA disappears from the HDL particle, increasing its atheroprotective ability. These findings demonstrate the importance of understanding the role of functional characteristics of HDL-c in cardiovascular diseases related to chronic inflammatory conditions. [source] 1366: Take home messagesACTA OPHTHALMOLOGICA, Issue 2010B BODAGHI This basic level course addressed the pathophysiology of ocular inflammation, its classifications and the major subtypes of uveitis, highlighting some of the new developments in uveitis that have become available in the past years and have contributed to the improvement in the care of the patients. It put forward clinical knowledge in uveitis, diagnostic tools as well as therapeutic strategies that allow ophthalmologists to go further in the precision of the assessment and monitoring of intraocular inflammatory activity as well as in therapeutic intervention. [source] 3131: Endothelial involvement indicates disease activity in Herpes simplex virus keratitisACTA OPHTHALMOLOGICA, Issue 2010T HILLENAAR Purpose Corneal endotheliitis is a potentially sight-threatening clinical manifestation of herpes simplex virus (HSV) keratitis. Early detection and consequent treatment may prevent development of endothelial decompensation. The goal of this previously published study was to describe the morphological features, frequency, and clinical consequences of endothelial involvement in HSV keratitis as seen by in vivo confocal microscopy (IVCM). Methods We examined both eyes of 250 patients with HSV keratitis by slit-lamp and IVCM. All examinations were assessed for endothelial deviations characteristic of endotheliitis. To determine the specificity, we reviewed our IVCM database for morphologically comparable alterations. This database included 200 healthy volunteers and 1400 patients with various corneal pathologies. The endothelial cell density (ECD) change between the first and last visits of patients with HSV keratitis was evaluated. Results Endotheliitis-specific deviations were detected in 107 of 250 patients with HSV keratitis (43%). Pseudoguttata, enlarged intercellular gaps, infiltration of inflammatory cells into the endothelial layer, loss of defined cell boundaries, spot-like holes, and endothelial denudation disappeared within 3 weeks with appropriate antiviral and anti-inflammatory treatment. Alterations were non-specific for HSV keratitis. Similar alterations were detected in adenoviral, fungal, bacterial, and acanthamoeba keratitis. The HSV affected eyes with endothelial involvement showed a mean ECD decrease of 10.3% per year. Conclusion Endothelial involvement indicates inflammatory activity in HSV keratitis and is associated with irreversible endothelial cell loss. IVCM allows early detection and follow up of endotheliitis-specific alterations. [source] Optimised monitoring of inflammation suppressive therapy (IST) in uveitisACTA OPHTHALMOLOGICA, Issue 2009CP HERBORT Purpose The array of inflammation suppressive therapies (IST) has increased trumendously in the last two decades including the availability of biological molecules with potent immunomodulatary activities as well as new immunosuppressive agents. In parallel measuring methods for intraocular inflammation have become available allowing much more acurate monitoring of the evolution of inflammation and its response to therapy. In addition to the traditionally used fluorescein angiography (FA), laser flare photometrry (LFP), indocyanine green angiography ICGA) and optical coherence tomography (OCT) are among the new investigational methods that have become available, each of them allowing us to establish inflammatory activity with increased precision and to explore compartments previously poorly accessible. Methods The advantages of each method will be put forward. Illustrative cases will be taken as examples to show the degree of precision obtained by combining the different methods presently at our disposal for the follow-up and monitoring of inflammation suppressive treatment. Results These cases will show that the presently available tools for optimal monitoring of intraocular inflammation allow the clinician to be better aware of the level of inflammatory activity and to better adapt his treatment. Conclusion Not only he availability of potent new therapies but also the possibility to follow more precisely intraocular inflammation with new precise devices has certainly changed the outcome of uveitis cases in recent years. [source] Leptin, soluble interleukin-6 receptor, C-reactive protein and soluble vascular cell adhesion molecule-1 levels in human coronary atherosclerotic plaqueCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2006M. Karaduman Summary The aim of the present study was to explore the relationship between tissue levels of leptin, soluble interleukin-6 receptor (sIL-6R), high-sensitive-C-reactive protein (hs-CRP) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in atherosclerotic plaques, and traditional risk factors. Coronary artery specimens were obtained from 35 consecutive patients (26 men and nine women) who underwent coronary artery bypass grafting procedure. The mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in patients with diabetes mellitus than without diabetes mellitus. When patients were classified according to the smoking status, the mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in current smokers than both former smokers and non-smokers. In addition, the mean tissue levels of leptin and sIL-6R were significantly higher in former smokers than non-smokers. There was a positive association between leptin and hs-CRP, sIL-6R and plasma glucose in all patients. Plasma HDL levels were associated negatively with atherosclerotic tissue levels of leptin. Tissue levels of sIL-6R were associated significantly in a positive manner with leptin, hs-CRP and plasma glucose, while tissue levels of hs-CRP were associated with both leptin and sIL-6R. In conclusion, it is attractive to speculate that hs-CRP, sIL-6R and leptin could act synergistically in course of local inflammatory activity and those molecules may not be just markers of inflammation and cardiovascular risk but are also likely to play a pathogenic role in atheromatous plaque. In addition, atherosclerotic tissue levels of CRP, sIL-6R and leptin were significantly higher in current smokers and patients with diabetes. [source] | ||||||||||||||||||||||||||||