PubMed Health⌕ Search

Biomedical subjects

O Epstein

Publications and source records attributed to O Epstein.

At least 91 records · Page 5Linked to original sources
PubMed1981

Is Wilson's disease caused by a controller gene mutation resulting in perpetuation of the fetal mode of copper metabolism into childhood?

Wilson's disease is an inborn error of copper metabolism, characterised by raised liver-copper concentrations and low serum levels of copper and caeruloplasmin. The autosomal recessive mode of inheritance strongly suggests that mutation of a single gene causes the impairment of both caeruloplasmin synthesis and biliary copper excretion. The normal infant is born with the biochemical features of Wilson's disease (very high liver-copper levels and low serum copper and caeruloplasmin). Induction of normal copper metabolism after birth results in a fall in liver-copper concentrations and rise in serum caeruloplasmin. The repression of normal copper metabolism in the fetus and its induction after birth is probably regulated by a controller gene. It is suggested that mutation of a controller rather than a structural gene underlies the pathogenesis of Wilson's disease and that the disease results from failure to switch from the positive copper balance of the fetus to the normal copper balance of the child.

Carrier Proteins↗
PubMed1981

Prospective study of periostitis and finger clubbing in primary biliary cirrhosis and other forms of chronic liver disease.

The association of finger clubbing and periostitis has been reported in primary biliary cirrhosis and, more rarely, in other forms of chronic liver disease. The prevalence of periostitis and its relationship to finger clubbing is unknown. In this prospective study, we have determined the prevalence of periostitis and finger clubbing in 74 patients with primary biliary cirrhosis and 54 with other forms of chronic liver disease. Clubbing was present in 24% of patients with primary biliary cirrhosis, 29% with HBsAg negative chronic active hepatitis, and 23% in the group of miscellaneous liver diseases. Symmetrical periostitis affecting the tibiae and fibulae occurred in 35% of patients with primary biliary cirrhosis, 29% with chronic, active hepatitis and 40% of patients in the miscellaneous group. The distal radii and ulnae were affected in only eight patients (6%). In primary biliary cirrhosis, the presence of finger clubbing was strongly associated with periostitis (P less than 0.01), but this association was uncommon in other forms of chronic liver disease. In all forms of chronic liver disease periostitis commonly occurs in the absence of finger clubbing. Marked tenderness over the distal leg bones is a reliable sign of underlying periostitis, but this sign is present in only a third of affected patients. This study indicates that periostitis affecting the lower leg bones is common in patients with chronic liver disease, and its presence should be sought whether or not the patient has finger clubbing.

Adult↗
PubMed1981

Results of portal decompression in patients with primary biliary cirrhosis.

Twenty-five patients with primary biliary cirrhosis undergoing portal decompression have been followed up for a mean of 51 months. Five patients with decompensated cirrhosis died postoperatively. Overall five year survival of 66% is comparable with that for other forms of cirrhosis but none of the long-term survivors, including three patients with a precirrhotic stage of primary biliary cirrhosis at the time of surgery, developed significant portal-systemic encephalopathy. The results suggest that portal decompression may be the therapy of choice for patients with well-compensated primary biliary cirrhosis who suffer recurrent variceal haemorrhage.

Adult↗
PubMed1981

Is copper hepatotoxic in primary biliary cirrhosis?

In primary biliary cirrhosis (PBC) liver copper retention occurs as a complication of cholestasis. By analogy with Wilson's disease, it has been suggested that copper retention is hepatotoxic in PBC, and this has been the rationale for the use of D-penicillamine in this disease. The hypothesis that copper is hepatotoxic in PBC has not been tested and in this study we have evaluated the role of liver copper retention in the pathogenesis of PBC. Sixty-four patients with PBC have been studied. Fifty-four had increased liver copper concentrations. Liver cell synthetic function was well preserved. All the patients had normal prothrombin times, and only two had subnormal serum albumin concentrations. There was no correlation between liver copper concentrations and the degree of liver cell damage assessed biochemically (aspartate transaminase), and histologically. Electron microscopy was performed on liver biopsies from five patients with markedly increased liver copper concentrations. The liver cell ultrastructure was compatible with cholestasis. Liver cells contained electron dense lysosomes, which were shown to contain copper and sulphur by x-ray probe microanalysis. The characteristic organelle changes associated with copper toxicity in Wilson's disease were not observed. The biochemical, histological, and histochemical differences between PBC complicated by liver copper retention, and Wilson's disease, indicates that there are differences in the handling of copper in these disease. In this study we could find no evidence to suggest that copper plays an important role in the pathogenesis of liver dysfunction in PBC.

Copper↗
PubMed1981

Granulomas in primary biliary cirrhosis: a prognostic feature.

To evaluate the significance of granulomas in primary biliary cirrhosis, 295 liver biopsy specimens from 100 patients with primary biliary cirrhosis were reviewed. Granulomas were found in specimens from 54 patients and were less frequent as histologic stage increased. They often persisted in multiple specimens from individual patients. Granulomas did not correlate with clinical presentation or biochemical values, but were associated with better survival since of the 18 patients who died, only 2 showed granulomas on biopsy. To test this finding in patients at a uniform stage of progression, patients with late primary biliary cirrhosis were evaluated separately. Patients with and without granulomas were closely matched in clinical, laboratory, and histologic features. Although 23 of these 57 patients showed granulomas, they were present in only 1 of 14 patients who died. Thus, the presence of granulomas in primary biliary cirrhosis seems to be of prognostic significance, independent of previously reported prognostic indicators.

Adult↗
PubMed1980

Effects of cyclosporin A on suppressor and inducer T lymphocytes in primary biliary cirrhosis.

There is a significant decrease in the ratio of inducer (helper) to suppressor T lymphocytes in the peripheral blood of patients with primary biliary cirrhosis (PBC). These changes are not seen in other forms of cholestatic liver disease, but are similar to those described in chronic graft-versus-host disease. Cyclosporin A treatment increased the proportion of suppressor A lymphocytes and improved liver function in 6 patients with PBC. This indicates that cyclosporin A is an immunoregulatory drug. Unfortunately nephrotoxicity precluded long-term use.

Cyclosporins↗
PubMed1980

Primary biliary cirrhosis is a dry gland syndrome with features of chronic graft-versus-host disease.

Primary biliary cirrhosis (PBC) is part of a disease complex characterised by dry eyes, dry mouth, and both biliary and pancreatic hyposecretion: it is a "dry gland" syndrome resulting from damage to ductular epithelium. Additional extraglandular features include scleroderma-like skin lesions, pigmentation, Raynaud phenomenon and severe abnormalities of both humoral and cellular immunity. Identical ductular and extraductal features, including abnormalities of the immune system, are seen in chronic graft-versus-host disease after bone-marrow transplantation. It is suggested that in PBC the ductular lesions and severe disturbance of the immune system including macroglobulinaemia and immune complex formation occur as a result of an immune response to the histocompatibility (HC) complex antigens which are present in high density on ductular epithelial cells of the biliary tree. This response could be caused by altered antigenicity of epithelial cell HC antigens or by failure of the HLA-dependent T cell self-recognition system.

Antigen-Antibody Complex↗
PubMed1980

Hair copper in primary biliary cirrhosis.

Rats fed on a copper-enriched diet develop increased liver copper concentrations, which correlate well with hair copper content. It has been suggested that in man, hair copper analysis may be a useful noninvasive method for predicting liver copper concentrations. We have tested this hypothesis in 11 patients with primary biliary cirrhosis, a disease complicated by the accumulation of copper in the liver. Ten patients had increased liver copper concentrations, but only one had increased hair copper. In primary biliary cirrhosis, hair copper does not reflect liver copper content and is of no value as a biopsy material for copper analysis.

Ceruloplasmin↗
PubMed1980

Measurement of trypsin in duodenal juice by radioimmunoassay.

Trypsin in duodenal aspirate and pure pancreatic juice samples has been measured by both radioimmunoassay and enzymatic mathods. The radioimmunossay has been shown to be specific and to detect trypsin in the presence of aprotinin (Trasylol). In duodenal juice samples from control subjects and from patients with primary biliary cirrhosis a good correlation was obtained between both immunoreactive trypsin concentration and trypsin activity. The immunoreactive trypsinogen concentration in pure pancreatic juice also correlated well with activated trypsin activity. The mean immunoreactive trypsin concentration and the concentration of enzymatically inert immunoreactive trypsin in duodenal juice samples from patients with primary biliary cirrhosis were significantly lower than controls, suggesting pancreatic hyposecretion in this disease. After five duodenal juice samples had been stored for three months at -70 degrees C, immunoreactive trypsin concentration in samples stored without Trasylol were reduced by 12 . 0 +/- 4 . 2 (mean +/- SD) times the concentration of samples stored in Trasylol. Trypsin autodegradation continues even at -70 degrees C; Trasylol protects against this. Radioimmunoassay is a reliable method of trypsin estimation in duodenal juice and has advantages over conventional enzymatic analysis.

Adult↗
PubMed1980

Triethylene tetramine dihydrochloride toxicity in primary biliary cirrhosis.

Triethylene tetramine dihydrochloride (trien) is a copper chelating agent used as the alternative drug of choice in the treatment of Wilson's disease. Because of its apparent safety, we have used the drug in 4 patients with primary biliary cirrhosis in whom penicillamine had to be withdrawn because of serious side effects. Trien is an effective cupruretic drug in primary biliary cirrhosis, but its use is limited by the occurrence of side effects that occurred in all 4 patients. Three patients developed gastrointestinal side effects, and one of these patients developed a skin rash. The 4th patient developed acute rhabdomyolysis within 48 hr of receiving the first dose of the drug. One patient tolerated therapy for 20 wk, and, although her liver copper concentration did not show a marked fall, aspartate transaminase levels fell, and her IgM concentration fell to normal. Trien is an unsuitable copper chelating drug in primary biliary cirrhosis, although it remains the alternative drug of choice in Wilson's disease.

Adult↗
PubMed1979

Reduction of immune complexes and immunoglobulins induced by D-penicillamine in primary biliary cirrhosis.

Penicillamine has an effect on immune complexes and immunoglobulins both in vivo and in vitro. We therefore studied the effect of penicillamine on immune complexes and immunoglobulins in primary biliary cirrhosis. Twenty-eight patients were randomly allocated into a treatment group receiving 600 to 900 mg of penicillamine, or a control group, and followed for a maximum of 24 months. After 12 and 24 months, serum immune complexes had fallen significantly in treated patients as compared to controls (P less than 0.05, P less than 0.01). Treatment reduced IgA, IgG and IgM concentrations, with IgM being significantly different from controls at six, 12 and 24 months (P less than 0.01). Over 24 months, serum aspartate transaminase levels fell in treated patients but rose in controls (P less than 0.01). Bilirubin concentrations increased at a slower rate in treated patients. Penicillamine may favorably influence the course of primary biliary cirrhosis by its immunologic action in addition to its copper-chelating action.

Antigen-Antibody Complex↗
PubMed1979

Hypertrophic hepatic osteoarthropathy. Clinical, roentgenologic, biochemical, hormonal and cardiorespiratory studies, and review of the literature.

Twenty patients with biopsy proved liver disease, and roentgenologic features of hypertrophic osteoarthropathy have been studied, and the literature has been reviewed. The syndrome is a rare association of many chronic liver diseases, including primary biliary cirrhosis, bile duct carcinoma, benign bile duct stricture, chronic active hepatitis, posthepatitic cirrhosis and alcoholic cirrhosis. Patients may be asymptomatic, although bone pain, arthralgia or arthritis may be presenting symptoms. Ninety per cent of the patients are clinical jaundiced at the time of diagnosis, and 95 per cent have digital clubbing. The distal tibia and fibula are the first bones to become involved, although wrist, foot bones, femurs, hand bones and humeri may be affected in order of frequency. There is no correlation between the presence of esophageal varices or surgical portacaval shunts and the extent of the syndrome, neither is there a correlation with the degree of liver function impairment. Serum calcium and phosphate levels are normal, as is urinary hydroxyproline and estrogen excretion. There was no evidence to implicate elevated levels of growth hormone or overdosage of vitamin A. Although the majority of patients tested had mild arterial hypoxemia, increased cardiac output and evidence of right to left shunting, these were also present in disease-matched control subjects without osteoarthropathy. For screening purposes, patients with chronic liver disease and clubbing should have roentgenologic studies of the lower tibias and fibulas, to select those patients suitable for a more extensive skeletal survey.

Adult↗
PubMed1979

Effect of oral 1,25 dihydroxycholecalciferol on calcium and phosphate malabsorption in primary biliary cirrhosis.

Changes in calcium and phosphate absorption in response to treatment with small doses of oral 1,25 (OH)2D3 were studied in 10 patients with primary biliary cirrhosis by means of a combined radio-isotope technique. There was a marked improvement in the fractional rates of absorption of calcium (P less than 0.01) and phosphate (0.05 P less than 0.1) after treatment. This implies than there is no end organ unresponsiveness to the action of active Vitamin D metabolites at the intestinal level in primary biliary cirrhosis.

Administration, Oral↗
PubMed1979

Hematin and propranolol in acute intermittent porphyria. Full recovery from quadriplegic coma and respiratory failure.

The authors present a case of acute intermittent porphyria (AIP) in an almost fatal relapse with quadriplegia, bulbar paralysis and coma. Intravenous hematin produced an immediate arousal from coma and allowed a gradual resumption of bulbar and autonomic functions. Persistent tachycardia and hypertension necessitated huge doses of intravenous propranolol. Both hematin and propranolol administrations were followed by a remarkable decrease in urinary amino-levulinic acid and porphobilinogen excretion. Nevertheless, after the acute stage, the patient was left with a severe generalized muscle wasting. After 7 months of intensive physical therapy, complete recovery of all neuromuscular functions was achieved. The modern aspects of the management of AIP are presented; the efficacy and the limits of hematin and propranolol therapy are discussed.

Acute Disease↗
PubMed1978

Secretion of intrinsic factor and hydrochloric acid after 12 weeks' treatment with cimetidine.

A sample of 16 patients had pentagastrin stimulation studies performed before starting a 12 week course of cimetidine, and again 12 hours after completing the course. Basal and pentagastrin stimulated intrinsic factor secretion was assayed in 13 patients. There was no significant difference in the pattern of secretion after 12 weeks' treatment with cimetidine. The basal and peak acid outputs of all 16 patients were measured. No significant difference was found in the pattern of acid secretion after treatment. It appears that parietal cell secretory function is restored to normal within 12 hours of discontinuing a prolonged course of cimetidine.

Cimetidine↗