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Biomedical subjects

B Portmann

Publications and source records attributed to B Portmann.

At least 145 records · Page 8Linked to original sources
PubMed1987

Primary sclerosing cholangitis in childhood.

Thirteen children (8 female) with primary sclerosing cholangitis are described, in whom the diagnosis was confirmed by the presence of characteristic changes on endoscopic retrograde cholangiopancreatography. Nine had clinical features of chronic inflammatory bowel disease 1 mo to 5 yr before the onset of primary sclerosing cholangitis (6 patients) or appearing simultaneously with primary sclerosing cholangitis (3 patients). In 4 patients clinical evidence of chronic inflammatory bowel disease was absent but 1 of the 4 was found to have microscopic colitis in colonoscopic biopsy specimens. Biopsies were not performed in the remaining 3 patients. High immunoglobulin G concentrations and positive antinuclear or smooth muscle antibodies were present in all patients except 1 who had been given immunosuppressants. In 7 patients treated with immunosuppressants and followed up for 9 mo to 10 yr there was modest symptomatic improvement. This improvement was accompanied by a fall in transaminase levels in 6 of the patients and histologic improvement in 3 of 4 patients who had undergone biopsy. Greater use of endoscopic retrograde cholangiopancreatography in the last 6 yr led to the identification of 10 of these 13 cases, suggesting a higher incidence of primary sclerosing cholangitis in childhood than would appear from the literature.

Adolescent↗
PubMed1987

Immunoglobulin on the surface of isolated hepatocytes is associated with antibody-dependent cell-mediated cytotoxicity and liver damage.

Hepatocytes isolated from patients with chronic liver disease are often covered by immunoglobulin. The aim of the present study was to establish whether this surface immunoglobulin (SIg) mediates liver cell damage. Freshly isolated hepatocytes from percutaneous liver biopsy of 16 patients with chronic active hepatitis (CAH) (6 HBsAg positive), 3 with HBsAg-positive chronic lobular hepatitis (CLH), 5 with HBsAg-positive chronic persistent hepatitis (CPH) and 12 with minor histological abnormalities (MHA) (5 HBsAg positive) were divided into two aliquots. One was studied for the presence of membrane-bound immunoglobulin and the third component of complement by direct immunofluorescence and the other was incubated, in an allogeneic cytotoxic assay, with peripheral blood mononuclear cells prepared from healthy volunteers as a source of effectors for antibody-dependent cell-mediated cytotoxicity (ADCC). Liver biopsies were scored for portal and parenchymal inflammatory activity. The percentage of SIg positive hepatocytes was significantly higher in patients with CAH (median 52.5%) than in patients with CLH/CPH (20.5%) or in patients with MHA (1%). Percentages of SIg-positive liver cells were significantly correlated with total liver biopsy scores and with both portal or parenchymal scores considered independently. SIg were found to belong to the IgG class in all groups of patients. When hepatocytes were cultured with normal human lymphocytes, allogeneic cytotoxicity values were significantly higher in patients with CAH (median 34%) than in patients with CLH and CPH (18%) or in those with MHA (12%). Percentage cytotoxicity was positively correlated with total biopsy scores and with portal activity but not with parenchymal activity, suggesting that ADCC might play a damaging role mainly in the portal areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Hepatic sarcomas in adults: a review of 25 cases.

Twenty-five patients with an apparently primary sarcoma of the liver are reviewed. Presenting complaints were non-specific, but hepatomegaly and abnormal liver function tests were usual. Use of the contraceptive pill (four of 11 women) was identified as a possible risk factor; one patient had previously been exposed to vinyl chloride monomer. Detailed investigation showed that the primary tumour was extrahepatic in nine of the 25 patients. Distinguishing features of the 15 patients with confirmed primary hepatic sarcoma included a lower incidence of multiple hepatic lesions and a shorter time from first symptoms to diagnosis, but the most valuable discriminator was histology. Angiosarcomas and undifferentiated tumours were all of hepatic origin, epithelioid haemangioendotheliomas (EHAE) occurred as primary and secondary lesions and all other differentiated tumours arose outside the liver. The retroperitoneum was the most common site of an occult primary tumour and its careful examination therefore crucial: computed tomography scanning was found least fallible in this respect in the present series. Where resection (or transplantation), the best treatment, was not possible, results of therapy were disappointing, prognosis being considerably worse for patients with primary hepatic tumours. Patients with EHAE had a better overall prognosis regardless of primary site.

Adolescent↗
PubMed1987

Preferential activation of helper/inducer T lymphocytes in autoimmune chronic active hepatitis.

We found a significant increase of activated circulating T lymphocytes expressing interleukin 2 receptor (IL-2r) (mean +/- s.e.m. 11.0 +/- 1.1%) or DR antigen (5.0 +/- 0.49%) in patients with autoimmune chronic active hepatitis (CAH) starting in childhood when compared to healthy controls (0.14 +/- 0.09%, P less than 0.001 and 2.8 +/- 0.06%, P less than 0.01). Patients with liver disorders due to Wilson's disease (IL-2r 0.64 +/- 0.25%, DR 3.5 +/- 0.22%) or alpha-1-antitrypsin deficiency (IL-2r 0.1 +/- 0.06%, DR 2.8 +/- 0.35%) had levels similar to controls. Levels of both IL-2r and DR positive T lymphocytes were higher in patients with uncontrolled CAH (IL-2r 18.0 +/- 1.01%; DR 6.3 +/- 0.78%) than in patients with inactive disease (IL-2r 3.2 +/- 1.4%, P less than 0.001; DR 3.0 +/- 0.13%, P less than 0.01). In patients with active disease levels of IL-2r positive cells were higher than DR positive cells (P less than 0.001). Only 21% of activated T cells coexpressed the two markers of activation. Sixty-seven percent of IL-2r positive T lymphocytes were helper/inducer and 25% suppressor/cytotoxic, while 66% of the DR positive T cells were suppressor/cytotoxic and 31% helper/inducer. The finding that the highest levels of activated T lymphocytes are present in patients with uncontrolled CAH suggests that these cells are involved in its pathogenesis. The preferential increase of activated helper/inducer cells might explain the enhanced immune reactivity characteristic of autoimmune CAH.

Antibodies, Monoclonal↗
PubMed1986

Serum type III procollagen peptide as a non-invasive marker of liver damage during infancy and childhood in extrahepatic biliary atresia, idiopathic hepatitis of infancy and alpha 1 antitrypsin deficiency.

To evaluate the role of serum procollagen III peptide as a non-invasive marker of liver damage and prognosis in hepatobiliary disorders of infancy, we have measured its concentration at presentation and serially in 30 infants with extrahepatic biliary atresia, 22 with idiopathic hepatitis of infancy, 10 with alpha 1 antitrypsin deficiency and 105 age-matched controls. Raised procollagen III peptide concentrations occurred in 51% of patients at presentation and 59% at follow up but were not related to the type of liver disease or the severity of liver damage, as assessed either by standard biochemical tests of liver function, serum glycocholic acid, semiquantitative assessment of 11 histopathological features or hepatic prolyl hydroxylase activity. Serum procollagen III peptide concentrations also gave no guide to prognosis. Although the factors determining serum procollagen III peptide concentrations in hepatobiliary disorders of infancy are unknown at the present time, we suggest that changes in growth rate may be of major importance in determining the significance of serum procollagen III peptide concentrations in infants and children.

Biliary Atresia↗
PubMed1986

Fulminant hepatitis. An ultrastructural study.

Ultrastructural changes were observed in 23 consecutive patients who died from fulminant hepatic failure due to hepatitis B virus (4 cases), sporadic non-A, non-B (7), or paracetamol (acetaminophen) overdose (12) and in 3 patients with subacute hepatic necrosis of unknown cause. The findings are described in detail in 12 of these patients. Fatal fulminant hepatitis was characterised by massive confluent necrosis accompanied by collapse of reticulin framework and sudden drop-out of liver cells. No aetiological distinction could be made between different viral causes of fulminant hepatitis on the basis of ultrastructural pathology. Parenchymal changes in viral cases varied from reversible non-specific necrosis to irreversible changes where fragmentation of endoplasmic reticulum, mitochondria and nuclei had occurred. Differences in ultrastructural pathology between non-viral (paracetamol overdose-induced) and viral fulminant hepatitis were apparent. Modification of endoplasmic reticulum with enlarged attached polyribosomes, breakdown of plasma membrane, accumulation of cytoplasmic amorphous material and karyorrhexis and karyolysis of nuclei were the most prominent features in non-viral cases.

Acetaminophen↗
PubMed1986

Progressive neuronal degeneration of childhood with liver disease. A pathological study.

A clinicopathological study of 10 cases of progressive neuronal degeneration of childhood is reported. In the typical clinical course early developmental delay is followed by intractable epilepsy leading rapidly to death, in some cases in liver failure. Diagnostically useful investigations include characteristic EEG changes, evidence of progressive atrophy (particularly occipital) on CT scan, absent or reduced visual evoked responses, and biochemical evidence of abnormal liver function in many cases before commencement of anticonvulsant therapy. Siblings of 4 of the reported cases suffered a similar clinical disorder. Macroscopic appearances of the brain varied from virtual normality to severe atrophy. The cortical ribbon showed patchy lesions, but the calcarine cortex was characteristically involved, narrowed, granular and discoloured. Histological damage to the cerebral cortex was widespread but patchily accentuated. In milder lesions status spongiosus, astrocytosis and neuronal loss occurred only in the superficial cortex, in moderately affected areas deeper laminae were involved, and in the most severe lesions the entire cortex was reduced to a thin densely gliotic remnant. There was a pronounced tendency for the striate cortex to be the worst affected area. Of subcortical structures the thalamus, hippocampus and cerebellum were particularly severely involved. There was usually accompanying liver disease, particularly a subacute hepatitis comprising massive fatty degeneration, hepatocyte loss, bile duct proliferation and fibrous scarring, with or without cirrhosis. These pathological features are distinct from other combined degenerations of liver and brain and the cortical lesions differ significantly from the neuropathological sequelae of birth injury or severe epilepsy. Hepatic pathology is distinctive and does not appear to be related to drug therapy. It is concluded that these 10 cases of progressive neuronal degeneration of childhood with concomitant liver disease, together with a small number of previously reported cases, are a nosological entity which may result from an autosomal recessive inherited metabolic defect, the nature of which is at present obscure.

Brain Diseases↗
PubMed1986

Wash off liver cytology: a complementary diagnostic tool to liver biopsy.

Parenchymal and non-parenchymal cells were harvested by washing the liver tissue core and needle after percutaneous biopsy. The cytological material obtained was suitable for morphological analysis, including showing the presence of surface and cytoplasmic antigens using labelled antibody techniques. This technique provides a combined cytological and histological approach to the diagnosis of liver disease.

Antigens↗
PubMed1986

In vitro study of IgG production and concanavalin A induced suppressor cell function in acute and chronic hepatitis B virus infection.

To investigate the relationship between liver damage and immune regulation in hepatitis B virus (HBV) infection, 68 patients with HBsAg in serum and a spectrum of liver damage have been studied and compared with 25 controls. In HBsAg carriers, spontaneous IgG production was elevated only in those with chronic active hepatitis (P less than 0.05) whilst those with less severe inflammation had values comparable to normals. Concanavalin A (Con A) induced suppressor cell regulation of IgG producing cells was impaired in those with chronic active hepatitis (P less than 0.01) and those with chronic persistent hepatitis (P = 0.05) and there was a correlation in both groups of patients with the severity of portal tract inflammation (P less than 0.05). In contrast those with minimal liver damage had values in the normal range. Patients presenting with acute hepatitis B also had elevated spontaneous IgG production (P less than 0.01) and impaired Con A induced suppressor cell regulation of IgG production (P less than 0.01). Sequential study of three patients prior to the detection of HBsAg in serum and subsequently during and after acute hepatitis B showed that such abnormalities were transient and closely related to the onset of liver damage.

Adult↗
PubMed1985

Randomised controlled trial of azathioprine withdrawal in autoimmune chronic active hepatitis.

To assess the value of azathioprine in the maintenance therapy of autoimmune chronic active hepatitis a controlled trial of azathioprine withdrawal was carried out in 50 patients who had been maintained in remission on a combination of azathioprine and prednisolone. The patients were randomly allocated to remain on combination therapy (23) or to discontinue azathioprine (27). These 2 groups were comparable at the start of the study. Over a follow-up period of up to 3 years, biochemical and histological relapse occurred in 8 patients in the azathioprine-withdrawal group but in only 1 patient in the combination-therapy group. Cumulative probability of relapse was 32% among the patients in the withdrawal group, compared with 6.0% for those in the combination group.

Adult↗
PubMed1985

Sequential and diagnostic features in primary biliary cirrhosis based on serial histologic study in 209 patients.

Four forms of piecemeal necrosis--biliary, lymphocytic, ductular, and fibrotic--were identified in 605 liver biopsy specimens from 209 patients with primary biliary cirrhosis. Whereas lymphocytic piecemeal necrosis, often associated with lobular hepatitis, was most common in stages 2 and 3 of the classical histologic staging, biliary piecemeal necrosis was frequent in all stages, except stage 1, and the fibrotic form appeared to be a late, mainly cirrhotic feature. In 77% of patients cholestatic features predominated, whereas hepatitic changes producing some histologic overlap with chronic active hepatitis occurred in the remaining patients. These patterns tended to be maintained throughout the course of the disease. Large hypocellular scars found in 36% and 59% of stage 3 and 4 specimens, respectively, appeared to be a characteristic feature of biliary disease. The prevalence of classical features was assessed. The analysis of sequential biopsy specimens from those patients who died showed that cirrhotic transformation, increasing cholestasis (in particular with prominent hyaline inclusions), abundance of coarse collagen bundles, and "halo" formation at the margins of the fibrous septa were associated with a poor prognosis. We were unable to show that the presence of granulomas is associated with a more favorable course of the disease.

Adult↗
PubMed1985

Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis. Final results of an international trial.

The effect of azathioprine on survival of patients with primary biliary cirrhosis was studied prospectively in a multinational, double-blind, randomized clinical trial including 248 patients of whom 127 received azathioprine and 121 placebo. There were 57 deaths in the azathioprine group and 62 in the placebo group. The actual survival was slightly longer during azathioprine than during placebo treatment. Using Cox multiple regression analysis and adjusting for slight imbalance between the two treatment groups, the therapeutic effect of azathioprine was statistically significant (p = 0.01), with azathioprine reducing the risk of dying to 59% of that observed during placebo treatment (95% confidence interval 40%-90%) or improving survival time by 20 mo in the average patient. Furthermore, azathioprine slowed down progressing incapacitation. Side effects of azathioprine were relatively few. The analysis revealed that the following five variables independently implied poor prognosis: high serum bilirubin, old age, cirrhosis, low serum albumin, and central cholestasis. These factors were combined to a "prognostic index" for prediction of outcome in new patients. The index was validated on independent patient data. On the basis of these results we recommend azathioprine as a routine treatment of primary biliary cirrhosis.

Actuarial Analysis↗
PubMed1985

Effects of ethanol ingestion on the hepatotoxicity and metabolism of paracetamol in mice.

The influence of ethanol on paracetamol-induced liver damage was studied in mice and related to changes in microsomal monooxygenases and plasma paracetamol metabolites in the same group of animals. Paracetamol (400 mg/kg body wt, p.o.) was administered alone or simultaneously with ethanol (3 g/kg, p.o.) to mice fed either a chow diet or pretreated for 4 weeks with a liquid diet containing ethanol (20% of energy). Acute ethanol administration protected against paracetamol hepatotoxicity, but this protection was complete only in mice not fed ethanol previously. Acute ethanol administration also appeared to reduce paracetamol monooxygenation in vivo, but ethanol (50 mM) added to microsomal incubations in vitro had no significant effect on paracetamol activation and covalent binding. The chronic ingestion of ethanol in the diet increased paracetamol-related liver damage, but there appeared to be no induction of paracetamol monooxygenation in these animals. We are unable to confirm current concepts that the potentiation of paracetamol hepatotoxicity by chronic ethanol ingestion and its reduction by acute ethanol administration result solely from contrasting effects of ethanol on cytochrome P-450, and alternative explanations are proposed.

Acetaminophen↗
PubMed1985

Different mechanisms responsible for in vitro cell-mediated cytotoxicity to autologous hepatocytes in children with autoimmune and HBsAg-positive chronic liver disease.

To investigate mechanisms of hepatocyte injury, lymphocytes from 41 children with chronic liver disease were incubated with autologous liver cells in a microcytotoxicity assay. Cytotoxicity was significantly increased in 18 of 25 patients with chronic hepatitis B virus (HBV) infection, in five of nine with "autoimmune" chronic active hepatitis (CAH), and in only one of seven with histologically inactive liver disorders. There was a good correlation between cytotoxicity and biochemical and histologic markers of disease activity in children with autoimmune CAH, whereas in HBsAg-positive disease a positive correlation was found only with serum alanine aminotransferase (SGPT). Children with autoimmune CAH receiving steroid treatment had normal cytotoxicity, whereas increased values were found in two of three HBsAg-positive patients receiving prednisolone. Fractionation studies revealed that non-T cells were cytotoxic in both autoimmune and HBcAg-positive chronic liver disease. T cell cytotoxicity was exclusively found in children with chronic HBV infection, particularly with HBc antigenemia. Blocking experiments showed that T-lymphocytes from HBsAg-positive children reacted with HBV core antigen on the hepatocyte surface. Non-T cells were directed against hepatocyte membrane antigens in both HBsAg-positive and HbsAg-negative children. These results suggest that different immune mechanisms of liver damage are involved in autoimmune and HBsAg-positive chronic liver disease.

Adolescent↗
PubMed1985

Variation in serum type III procollagen peptide with age in healthy subjects and its comparative value in the assessment of disease activity in children and adults with chronic active hepatitis.

To determine the comparative value of serum Type III procollagen peptide (PIIIP) in paediatric and adult liver disease we have measured PIIIP in 201 healthy subjects (aged 1 day-77 years) and twenty-one children and five adults with chronic active hepatitis (CAH). Healthy children had significantly higher PIIIP levels than adults (P less than 0.001), with highest values of 298 +/- 88 ng ml-1 (s.d.) in the neonatal period. PIIIP fell to 30.9 +/- 7.0 by 1 year, 19.1 +/- 4.5 by 3 years and rose significantly (P less than 0.01) at puberty. Adult levels (8.3 +/- 3.2) occurred by 16 years of age. Serum PIIIP levels were significantly elevated (P less than 0.001) in adults when they had biochemical and histological evidence of active liver disease but were consistently within the normal range for age in 70% of children with similar hepatic pathology. The minor elevations in PIIIP in the other children were unrelated to clinical, biochemical or histological evidence of active liver disease. While raised PIIIP may be a non-invasive marker of liver disease activity in adults, its value in childrens' disorders appears to be limited by the high levels of PIIIP which occur during growth.

Adolescent↗
PubMed1985

Double blind controlled trial of d-penicillamine in patients with primary biliary cirrhosis.

One hundred and eighty nine patients with primary biliary cirrhosis were entered into a double blind, placebo controlled randomised trial starting in January 1978 to assess the therapeutic value of d-penicillamine 1200 mg daily. Eighteen of the 98 patients receiving d-penicillamine and 22 of the 91 placebo treated patients died during the study. Thirty six per cent of those on d-penicillamine and 8% of those on placebo were withdrawn from the study. No difference in overall survival was noted between the two groups of patients whether the results were analysed for the entire period of observation or only during the period in which the patients were receiving therapy. The mortality rate of those receiving d-penicillamine in histological stage I to II, however, was one third of that of the placebo group although this difference did not reach statistical significance. Using the occurrence rate ratio as the statistical method of analysis, no effect of d-penicillamine was noted on any clinical, biochemical or histological features examined, except the serum alanine aminotransferase activity which was greater in those on active treatment. In this trial we have been unable to establish any therapeutic benefit from the drug.

Clinical Trials as Topic↗