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Biomedical subjects

E Elias

Publications and source records attributed to E Elias.

At least 109 records · Page 6Linked to original sources
PubMed1993

Detection of circulating intercellular adhesion molecule-1 after liver transplantation--evidence of local release within the liver during graft rejection.

The adhesion molecule ICAM-1 mediates leucocyte adhesion to target structures and other immune cells by binding with the leucocyte adhesion receptors LFA-1 and MAC-1. During rejection of human liver transplants there is increased expression of ICAM-1 on target structures such as bile ducts and venous endothelium and also on lymphocytes infiltrating the graft. Recent reports suggest that a soluble, functionally active form of ICAM-1 designated circulating ICAM-1 (cICAM-1) is released by activated lymphocytes and might be an important mechanism for modulating lymphocyte adhesion and the inflammatory process. We detected cICAM-1 in bile and serum after liver transplantation using an enzyme-linked immunosorbent assay. Serum cICAM-1 was elevated early in the course of acute rejection and appeared at the same time as the soluble interleukin-2 receptor, a marker of lymphocyte activation. Serum levels, however, were not specific for rejection since they were also elevated in infective complications. In contradistinction, biliary levels of cICAM-1 were only elevated in rejection and appeared to be due to local release/secretion within the liver. These data demonstrate that cICAM-1 is released within the liver during graft rejection, probably from activated lymphocytes, and support previous studies that suggested that factors in bile reflect immunological activity within the liver graft more closely than serum factors.

Bile↗
PubMed1993

Acute liver allograft rejection--is treatment always necessary?

A group of 195 consecutive adult patients who received a primary orthotopic liver allograft were reviewed retrospectively to analyze the incidence of rejection, the response to antirejection therapy, and the impact of acute rejection on the development of ductopenic rejection. The diagnosis of acute rejection (AR) was based on a combination of clinical and histological criteria, and 69.7% of the patients had at least one episode of acute rejection. Only 6.7% of the patients failed to respond to steroids and were treated with OKT3. Four (2.3%) patients developed acute vanishing bile duct syndrome (within 60 days) and 6 (3.5%) patients developed chronic rejection. Eight patients who spontaneously recovered from AR without additional immunosuppression are described in detail. In addition to histological damage, all developed significant hepatic dysfunction. Except for one patient who died from disseminated fungal infection, the 7 remaining patients are alive with excellent graft function 7 to 21 months posttransplant. While severe AR and recurrent AR should be treated without delay, some patients with mild-to-moderate rejection and hepatic dysfunction may resolve without additional immunosuppression.

Acute Disease↗
PubMed1993

Steroid withdrawal from long-term immunosuppression in liver allograft recipients.

Corticosteroids were withdrawn from the immunosuppressive regimen of 168/197 (85%) of liver transplant patients who survived for more than three months. In 14, steroids were restarted for reasons other than rejection. The remaining 154 patients were evaluated for the occurrence of rejection and graft loss. Risk factors for the development of rejection after steroid withdrawal were assessed. There were 13 episodes of rejection in 12 (7.8%) grafts; 7 (4.5%) experienced acute cellular rejection, and 6 (3.9%) developed chronic ductopenic rejection. All cases of acute rejection resolved with high-dose steroids. Graft and patient loss due to chronic rejection was 3 (1.9%) and 2 (1.3%), respectively. Chronic rejection resolved in 1 patient, 1 was successfully retransplanted, and in the other 2 the principal cause of death was recurrent tumor. None of the risk factors examined (primary indication for transplant, severity of previous acute rejection, use of OKT3, retransplantation, ABO blood group donor/recipient match, CMV infection, and CsA mono versus CsA and AZA double therapy) were associated with the development of chronic rejection poststeroid withdrawal. The prevalence of side effects, after steroid withdrawal, was low; 66% of patients never required antihypertensive medication; 14% experienced a significant septic episode, and only 4 died with sepsis as the major factor. There were no fungal sepsis and no new cases of diabetes. Withdrawal of corticosteroids after 3 months can be successfully achieved in the majority of liver allograft recipients and is associated with a low rate of rejection, graft loss, and complications attributable to immunosuppressive medication.

Adolescent↗
PubMed1993

Hepatitis C virus antibody positive blood donors.

In an analysis of 15 blood donors referred from the Blood Transfusion Service to the Queen Elizabeth Hospital, Birmingham, more than 50% of anti-hepatitis C virus (HCV) positive patients had a parenteral risk factor. Most were serum HCV-RNA positive, and all were liver HCV-RNA positive. Although no physical signs of liver disease were apparent, all anti-HCV positive donors had abnormal liver histology.

Adult↗
PubMed1993

GSTM1 null polymorphism at the glutathione S-transferase M1 locus: phenotype and genotype studies in patients with primary biliary cirrhosis.

Studies were carried out to test the hypothesis that the GSTM1 null phenotype at the mu (mu) class glutathione S-transferase 1 locus is associated with an increased predisposition to primary biliary cirrhosis. Starch gel electrophoresis was used to compare the prevalence of GSTM1 null phenotype 0 in patients with end stage primary biliary cirrhosis and a group of controls without evidence of liver disease. The prevalence of GSTM1 null phenotype in the primary biliary cirrhosis and control groups was similar; 39% and 45% respectively. In the primary biliary cirrhosis group all subjects were of the common GSTM1 0, GSTM1 A, GSTM1 B or GSTM1 A, B phenotypes while in the controls, one subject showed an isoform with an anodal mobility compatible with it being a product of the putative GSTM1*3 allele. As the GSTM1 phenotype might be changed by the disease process, the polymerase chain reaction was used to amplify the exon 4-exon 5 region of GSTM1 and show that in 13 control subjects and 11 patients with primary biliary cirrhosis, GSTM1 positive and negative genotypes were associated with corresponding GSTM1 expressing and non-expressing phenotypes respectively. The control subject with GSTM1 3 phenotype showed a positive genotype.

Base Sequence↗
PubMed1993

11 beta-Hydroxysteroid dehydrogenase deficiency and glucocorticoid status in patients with alcoholic and non-alcoholic chronic liver disease.

11 beta-Hydroxysteroid dehydrogenase (11 beta HSD), found predominantly in liver and kidney, is responsible for the shuttling of active cortisol to cortisone. A defect in this shuttle mechanism, e.g. after liquorice ingestion, results in an increase in the ratio of urinary cortisol [tetrahydrocortisol (THF)] to cortisone [tetrahydrocortisone (THE)] metabolites. The plasma cortisol half-life is prolonged, but concentrations remain normal because of a concomitant fall in cortisol production. Alcohol-induced pseudo-Cushing's syndrome is an ill defined cause of Cushing's syndrome. Because many of the documented cases have abnormal liver function tests, we have investigated whether abnormal hepatic 11 beta HSD activity may play a role in the pathogenesis of the condition. Fourteen patients with alcoholic (ALD) and 14 patients with non-alcoholic (CLD) chronic liver disease had marked deficiency of 11 beta HSD [5 alpha-THF + THF/THE: ALD, 1.94 +/- 0.38 (+/- SEM); CLD, 1.82 +/- 0.20] compared to controls (0.94 +/- 0.04; P < 0.01 and 0.001, respectively). In the CLD group, the daily cortisol production rate (as assessed by summation of principal cortisol metabolites) was reduced appropriately [median, 3,510; range, 1,101-8,940 micrograms/24 h; controls, 5,492 (range, 3,818-14,996) micrograms/24 h; P < 0.001], and normal 0900 h plasma cortisol and urinary free cortisol levels were maintained. However, in the ALD group, there was no concomitant fall in the cortisol production rate (sum of cortisol metabolites, 5,043 micrograms/24 h; range, 520-27,344). As a consequence, 0900 h plasma cortisol in the ALD group was significantly elevated (633 +/- 52 nmol/L) compared to values in the CLD group (487 +/- 48 nmol/L; P < 0.05) and controls (432 +/- 27 nmol/L; P < 0.001). Our findings of glucocorticoid excess in patients with chronic ALD may indicate that alcohol-induced pseudo-Cushing's syndrome develops as a result of continuing normal cortisol secretion in the face of impaired cortisol metabolism. The latter is mediated by defective hepatic 11 beta HSD activity; the former by either abnormal glucocorticoid feedback or stimulation of cortisol secretion at the level of the hypothalamus/pituitary.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1993

Vanishing bile duct syndrome: a possible mechanism for intrahepatic cholestasis in Hodgkin's lymphoma.

A syndrome of idiopathic intrahepatic cholestasis occurs in some patients with Hodgkin's lymphoma. The underlying mechanism is poorly understood. In this paper we describe three patients with Hodgkin's lymphoma in whom severe intrahepatic cholestasis of unknown pathogenesis developed. In two cases jaundice was the presenting symptom; all three patients died with intractable liver damage. The three patients were initially thought to have idiopathic Hodgkin's-associated cholestasis, but subsequent review of histological material revealed advanced vanishing bile duct syndrome in addition to severe cholestasis. Ten liver specimens were obtained from 4 to 97 wk after the onset of jaundice (seven needle biopsies, one wedge biopsy, two postmortem livers). In seven liver specimens taken within 30 wk of the onset of jaundice, portal tracts characteristically had a "burned-out" appearance without secondary periportal changes related to chronic cholestasis. Three biopsy specimens obtained from one of the patients more than 1 yr after the onset of jaundice showed evidence of progressive periportal damage in the form of fibrous expansion, marginal ductular proliferation and copper-associated protein deposition. More than 80% of small portal tracts lacked recognizable bile ducts in the final liver specimens obtained from the three patients. These observations suggest that Hodgkin's lymphoma should be included in the list of diseases associated with loss of intrahepatic bile ducts. The possibility of a vanishing bile duct syndrome should be considered in the differential diagnosis of unexplained intrahepatic cholestasis in patients with Hodgkin's disease.

Adult↗
PubMed1993

Secretion of soluble chemotactic factors, including interleukin-6: a mechanism for the recruitment of CD8-positive T lymphocytes to human liver allografts during rejection.

In 35 patients receiving first liver transplants we assessed the chemotactic responsiveness of peripheral blood lymphocytes to bile, the subset composition of the responding population and the ability of peripheral blood lymphocytes to produce chemotactic factors. In 13 patients in whom acute rejection developed, lymphocyte chemotaxis in vitro was significantly greater in bile sampled 1 or 2 days after transplantation and before episodes of acute rejection than in bile sampled when rejection was clinically apparent or after steroid therapy during stable graft function. The chemotactic factors present showed preferential activity for CD8-positive T cells. Bile sampled during the same posttransplant periods from 11 patients who did not exhibit rejection showed significantly less chemotactic activity. In vitro cultured peripheral blood lymphocytes from patients in whom rejection developed produced lymphocyte chemotactic factors that induced a similar pattern of chemotactic responsiveness with preferential activity for CD8-positive T cells. Separate culture of purified CD4-positive and CD8-positive T cells obtained from patients in whom rejection developed showed that CD4-positive cells produced the factor(s). Analysis of the subset responses of normal peripheral blood lymphocytes to a variety of chemotactic cytokines showed interleukin-6 to have specificity similar to that observed with chemotactic bile, mixed peripheral blood lymphocyte culture supernatants and supernatants of CD4-positive T cells. Chemotactic activity was reduced by 45% to 90% in five chemotactic bile samples and three peripheral blood lymphocyte culture supernatants by treatment with affinity purified interleukin-6 monoclonal antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Biliary excretion of chenodeoxycholyllysylrhodamine in Wistar rats: a possible role of a bile acid as a carrier for drugs.

The effect on biliary excretion of rhodamine after its conjugation to give chenodeoxycholyl-lysyl-rhodamine (cheno-lys-R) was studied in male Wistar rats. Following its intravenous injection via the jugular vein of animals cheno-lys-R was efficiently excreted into bile with a peak biliary excretion of 31.6 +/- 1.2% dose 5 min-1 and a cumulative biliary excretion of 96.4 +/- 2.0% in 30 min of the total dose administered. Unlike cheno-lys-R, rhodamine had a poor biliary excretion of 1.0 +/- 0.1% dose 5 min-1 and a cumulative biliary excretion of 3.3 +/- 0.6% in 30 min. Cheno-lys-R had a short plasma half-life (t1/2 alpha) of 4.0 +/- 0.5 min, whereas free rhodamine had a longer half life (t1/2 alpha) of 82.1 +/- 1.4 min. The plasma clearances of cheno-lys-R and rhodamine were 41.2 +/- 6.5 and 9.0 +/- 1.2 ml/min per kg, respectively. The data indicate that the cationic fluorescent xenobiotic, rhodamine, when conjugated to the bile salt analogue, greatly increased the biliary excretion of rhodamine and that cheno-lys acted as a carrier for hepatic uptake of rhodamine. Thus, an appropriate bile salt derivative may be used to target a drug to the liver.

Animals↗
PubMed1992

Detection of circulating intercellular adhesion molecule-1 in chronic liver diseases.

The leucocyte adhesion molecule intercellular adhesion molecule-1 is induced on bile ducts in patients with primary biliary cirrhosis and primary sclerosing cholangitis and may be involved in targeting immune damage to these structures. It has recently been reported that, when activated, in vitro lymphocytes release a soluble form of intercellular adhesion molecule-1 that can also be detected in human serum. Because it is functionally active, this circulating intercellular adhesion molecule-1 might play a role in regulating inflammation by blocking adhesion. We used an enzyme-linked immunosorbent assay to detect circulating intercellular adhesion molecule-1 in the serum of patients with primary biliary cirrhosis and primary sclerosing cholangitis. Levels of circulating intercellular adhesion molecule-1 were markedly elevated in primary biliary cirrhosis and primary sclerosing cholangitis when compared with other chronic liver diseases. Circulating intercellular adhesion molecule-1 is probably derived from activated lymphocytes rather than from bile ducts because biliary epithelial cells from patients with primary biliary cirrhosis did not release circulating intercellular adhesion molecule-1 when stimulated to express the membrane-bound molecule in vitro. These studies are the first to demonstrate circulating intercellular adhesion molecule-1 in chronic inflammatory diseases that are characterized by strong tissue expression of intercellular adhesion molecule-1 and as such suggest a potential immunoregulatory role for circulating adhesion molecules. The very high levels detected in primary biliary cirrhosis and primary sclerosing cholangitis probably reflect lymphocyte activation, which is further evidence of immune pathogeneses for these diseases.

Bilirubin↗
PubMed1992

Long-term immunosuppression after liver transplantation: are steroids necessary?

Steroid therapy was withdrawn in 85% of 152 orthotopic liver transplant recipients with grafts surviving for more than 3 months, and 87% of these remained steroid-free. Steroid therapy was restarted in 8% for reasons other than rejection. The most common was conversion of immunosuppression because of cyclosporine nephrotoxicity. The incidence of rejection after steroid withdrawal was low: 3.8% for chronic rejection (CR) and 4.5% for acute rejection. Only 3 grafts (1.9%) were lost because of CR. No risk factors have been identified for the development of CR after steroid withdrawal, but a protective role for azathioprine has been suggested.

Adolescent↗
PubMed1992

Liver disease in a district hospital remote from a transplant centre: a study of admissions and deaths.

The profile of liver disease admissions and associated deaths in a district general hospital was studied to determine whether patients with end stage liver disease are appropriately referred for consideration of liver transplantation. Admission details were provided by the Office of Population Censuses and Surveys (OPCS) and their accuracy was assessed by case note analysis. According to OPCS, 77 patients with liver disease were admitted on 113 occasions between 1 January 1987 and 31 December 1989. The case notes of 74 (96%) were retrieved and examined. Only 64 (86%) had primary liver disease. Twenty four (31%) died of liver failure. Alcohol was the aetiological agent in two thirds. According to accepted criteria, 11 patients were suitable for liver transplant assessment but only three had been referred to a transplant centre. Of the remaining eight, five died during the study period. Two of the three patients referred died without transplantation; one underwent transplant and survived. There is discrepancy between OPCS data and true disease aetiologies, with approximately 40% under reporting of alcoholic liver disease. If this population is representative of the situation nationally, substantial numbers of patients with end stage liver disease might benefit from liver transplantation, but are not referred to a centre.

England↗
PubMed1992

Sclerosing cholangitis associated with multifocal fibrosis: a case report.

The association of sclerosing cholangitis, retroperitoneal fibrosis, and Riedel's thyroiditis has been reported twice before, and on both occasions the authors successfully used steroids to control the fibrotic process. A further case of fibrosis with this triad of organ involvement in which a combination of surgery and steroid treatment has arrested disease progression is described. This suggests an inappropriate immune response in this type of fibrotic overlap syndrome.

Cholangitis, Sclerosing↗
PubMed1992

Is the intercellular adhesion molecule-1/leukocyte function associated antigen 1 pathway of leukocyte adhesion involved in the tissue damage of alcoholic hepatitis?

Alcoholic hepatitis is characterised histologically by an intense inflammatory cell infiltrate made up predominantly of neutrophils but including other cell types, particularly lymphocytes. Leukocyte cytotoxicity requires cell adhesion, which is mediated via receptors on the leukocyte surface including leukocyte function associated antigen-1 (LFA-1) which binds to the ligand intercellular adhesion molecule-1 (ICAM-1) on the target cell. The distribution of ICAM-1 and LFA-1 expression in liver biopsy specimens from patients with alcoholic liver disease was examined to ascertain whether this pathway of leukocyte adhesion is involved in the tissue damage of alcoholic hepatitis. Specimens were stained for ICAM-1 and LFA-1 by a three step immunoalkaline-phosphatase method using monoclonal antibodies against ICAM-1 and LFA-1. LFA-1 staining on portal tract inflammatory cells and parenchymal inflammatory cells and ICAM-1 staining on liver components were examined. ICAM-1 expression on hepatocytes was significantly greater in alcoholic hepatitis compared with fatty liver (p less than 0.001) and normal controls (p less than 0.01). ICAM-1 expression correlated with the histological degree of hepatocellular damage (tau = 0.79; p = 0.0005) and parenchymal inflammation (tau = 0.65; p less than 0.001, and with LFA-1 expression on parenchymal leukocytes (tau = 0.63; p = 0.01). The ICAM-1/LFA-1 pathway may therefore be involved in leukocyte mediated tissue damage during alcoholic hepatitis.

Antibodies, Monoclonal↗