Jan P. Blomhoff

Metronidazole in Crohn's disease. A double blind cross-over clinical trial.

Twenty-two patients with active Crohns disease treated with salazosulfapyridin or prednisone, were in addition given metronidazole 1.000 mg daily or placebo for two months each in a double-blind cross-over study. No statistically significant effect was observed on the overall clinical condition in the 20 patients who completed the trial, although haemoglobin rose and ESR fell significantly in the metronidazole periods. In the 6 patients with colonic involvement only an improvement was registered both in symptoms and laboratory values.

Serum cholesterol determination by gas-liquid chromatography

Abstract A gas-liquid chromatographic (GLC) method adapted from Schmit and Mater is described for the measurement of total and free cholesterol in serum. The method has been found to be simple, sensitive and precise. The results have been compared with the colorimetric method of Carr and Drekter for total cholesterol and the method of Sperry and Webb for free cholesterol. For total cholesterol lower values were obtained by the GLC method both in sera from patients without signs of liver disease and in sera with high total bilirubin. There was a tendency for somewhat higher values for free cholesterol by the GLC method than by the colorimetric method. This difference was not significant. The present study has demonstrated that the GLC method for total and free cholesterol determination is more specific than colorimetric methods. Gas-liquid chromatography should be given consideration as a reference method for the estimation of free cholesterol and total cholesterol.

Serum selenium levels in liver diseases

A possible pathogenetic role of selenium deficiency in alcoholic cirrhosis of the liver has previously been discussed. In the present study serum selenium was analyzed in 5 groups of liver diseases. The method used for selenium determination was electrothermal atomic absorption, after thermal stabilization of selenium compounds by addition of nickel nitrate. The selenium level of a reference group of healthy Norwegian adults (n = 40) was 1.53 +/- 0.25 mumol/l. The serum concentrations of selenium in patients suffering from alcoholic cirrhosis, chronic active hepatitis and chronic persistent hepatitis were lowered to 40-80 per cent of those of the reference group. In alcoholic cirrhosis and chronic active hepatitis the decreased serum selenium concentrations were significantly correlated to decreased levels of albumin and prealbumin.

Diagnosis of Liver Diseases by Laboratory Results and Discriminant Analysis Identification of Best Combinations of Laboratory Tests

Patients with different liver diseases were studied by discriminant analysis. Groups of patients classified mainly on the basis of liver biopsy findings showed functional differences which permitted a consistent reclassification by discriminant functions using laboratory results. Optimal combinations of laboratory tests for the separation of liver diseases were defined. Different combinations were found, dependent on the subsets of liver diseases studied.

Possible association between an abnormal low density lipoprotein and nephropathy in lecithin: CHolesterol acyltransferase deficiency

Abstract A brother and sister with familial lecithin:cholesterol acyltransferase (LCAT) deficiency living in the same area as two previously described Norwegian families are reported. All together 4 Scandinavian families with 8 living members having LCAT deficiency are now known. The brother of 55 years of age showed typical symptoms of the disease including kidney failure. His 60-year-old sister had always been healthy, and proteinuria had never been detected. Her kidney function was normal. This is the only patient with familial LCAT deficiency so far described without kidney disease. Plasma from the latter patient had normal serum triglyceride content on an ordinary diet. Ultracentrifugation and gel filtration on 2% agarose failed to show any large molecular weight low density lipoprotein (LDL) fraction as has hitherto been described in all other patients with this disease including her brother. She therefore represents a subgroup of familial LCAT deficiency. An association between occurrence of the large molecular weight plasma LDL and the kidney lesion in LCAT deficiency therefore seems a reasonable hypothesis.

Lecithin.cholesterol acyl-transferase and lipoprotein-X in liver disease

Abstract Determinations of serum lecithin : cholesterol acyl transferase (LCAT) and the “abnormal serum lipoprotein of cholestasis” (LP-X) have been carried out in 52 patients with different liver disorders and in 20 normal subjects. In acute hepatitis reduced LCAT activity was demonstrated in both LP-X positive and LP-X negative patients. In primary biliary cirrhosis and large bile duct obstruction the presence of LP-X was associated with reduced, normal or increased LCAT activity. Thus this study could reveal no specific LCAT/LP-X pattern in liver diseases, nor were we able to differentiate between intra- and extrahepatic cholestasis on the basis of these two tests. Possible relationships between LP-X and LCAT are discussed and mechanisms for the formation of LP-X in liver- and bile duct diseases are considered.

Lecithin: Cholesterol acyltransferase and plasma proteins in liver disease☆

Abstract Lecithin: cholesterol acyltransferase (LCAT) activity has been measured by the method of Stokke and Norum and by the method of Glomset and Wright in plasma from 53 patients with various liver diseases. The results were compared with the concentration of plasma albumin, prealbumin and α-lipoprotein and with Normotest as well as plasma cholesterol. In most cases, the method of Stokke and Norum and the method of Glomset and Wright gave the same results. Therefore, substrate deficiency probably does not contribute much to low activities obtained by the method of Stokke and Norum in liver disease. The activity of LCAT was found to parallel the levels of plasma proteins. In acute hepatitis LCAT activity followed the proteins with short half-life. In chronic liver disease the LCAT activity was also correlated with plasma albumin. LCAT activity was normal in some patients with primary biliary cirrhosis who had subnormal levels of prealbumin, but normal or high levels of α-lipoprotein. The previously reported stimulating effect on LCAT activity with inactivated substrates from patients with primary biliary cirrhosis may be caused by high concentration of α-lipoprotein, either as substrate or as LCAT cofactor. In the total material the activity of LCAT was not correlated with the concentration of free cholesterol, but was correlated with the levels of cholesteryl esters.

Serum immunoglobulins and organ non-specific antibodies in diseases of the liver.

Serum immunoglobulins and C3 levels, auto-antibodies to smooth muscle (SMA), mitochondria (MA), and nuclei (ANA), rheumatoid factors (RF), HB-antigen and HB-antibody were studied in 9 groups of liver disease. Hypergammaglobulinaemia was a prominent feature in most groups, IgG being particularly raised in active chronic hepatitis, IgM in primary biliary cirrhosis, and IgA in alcoholic liver disease, respectively. IgE was often increased in alcoholic liver disease and was frequently low in hepatic tumours, whereas IgD showed no typical pattern in any liver disorder. SMA was most frequently found in active chronic hepatitis (68%), and MA in primary biliary cirrhosis (58%), while ANA was detected in 50% of the patients with active chronic hepatitis. However, a pronounced over-lap of tissue antibodies was observed among the various groups of liver disease, particularly in active chronic hepatitis and primary biliary cirrhosis. The concurrent presence of SMA and ANA was most frequent in active chronic hepatitis. It was not excluded that antibody titres might have provided better diagnostic discrimination, since titration of antibodies was not performed. Low C3 levels in active chronic hepatitis were correlated with low levels of other liver-synthetized proteins, and no evidence was found of increased consumption by immunologic reactions.

Immunohistochemical Characterization of Hepatic Tissue Lymphocyte Subpopulations in Liver Disease

Liver biopsies from 27 patients were studied by the indirect immunofluorescence and immunoperoxidase technique for relative distribution of B cells and T-cell subpopulations. T-cell subsets were defined for OKT4(+) (helper/inducer) and OKT8(+) (suppressor/cytotoxic) cells by using mouse hybridoma monoclonal antibodies. Patients with chronic active hepatitis and those with primary biliary cirrhosis showed marked relative increments in suppressor/cytotoxic OKT8(+) lymphocytes within hepatic lymphocytic infiltrates. Other patients with acute hepatitis or those with only reactive changes also showed a relative increment in OKT8(+) T lymphocytes within hepatic biopsy material. These findings suggest that tissue lymphocytic subpopulation increments in suppressor/cytotoxic T-cell subpopulations are commonly associated with hepatic lymphocytic infiltrates and may be related to disorders of immune regulation or expression in some of these disorders.

Familial Lecithin: Cholesterol Acyltransferase Deficiency: Report of a Third Norwegian Family with Two Afflicted Members

A brother and sister with familial LCAT deficiency are reported. They live in the same arca as the two previously described Norwegian families. The brother. 55 years of age, had typical signs and symptoms of the disease, including kidney failure, and has undergone kidney transplantation. His 60-year-old sister had always been healthy. Protein uria had never been detected, and her kidney function was normal. She is the only patient with familial LCAT deficiency so far described without detectable renal disease. Ultra-centrifugation and gel filtration on 2% agarose failed to show any large molecular weight low-density lipoprotein (LM-LDL) fraction as has hitherto been described in plasma of all other patients with this disease, including her brother. An association between occurrence of plasma LM-LDL and the kidney lesion in LCAT deficiency may therefore exist. The genetic studies indicate that the disease is caused by a mutation at a locus coding for the production of plasma LCAT. There is good evidence th...