Biomedical subjects
M Vuoristo
Publications and source records attributed to M Vuoristo.
[Hepatic failure, indicating a prompt liver transplantation].
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High-dose folic acid treatment for red-cell aplasia.
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A placebo-controlled trial of primary biliary cirrhosis treatment with colchicine and ursodeoxycholic acid.
BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) and colchicine have beneficial effects in primary biliary cirrhosis (PBC). The efficacy of colchicine and UDCA in PBC was compared in a 2-year placebo-controlled study (n = 90). METHODS: Clinical events, laboratory test results, and liver histology were recorded at the beginning and end of the trial. RESULTS: There were significantly fewer dropouts for hepatic reasons with UDCA than with placebo. Pruritus was reduced by both active drugs. Colchicine improved liver function test results only modestly, whereas UDCA significantly decreased the serum activities of aminotransferases, alkaline phosphatase, and gamma-glutamyltransferase compared with colchicine and placebo. Serum total bilirubin levels were decreased only by UDCA. Both colchicine and UDCA reduced serum cholesterol levels, and UDCA also reduced high-density lipoprotein cholesterol levels. Furthermore, UDCA reduced the serum levels of immunoglobulin (Ig) M and IgG, and colchicine reduced IgG levels compared with placebo. The elevated serum level of aminoterminal propeptide of type III procollagen remained unchanged by colchicine or UDCA, whereas the serum level of carboxyterminal propeptide of type I procollagen was significantly decreased by UDCA. UDCA significantly decreased ductular proliferation compared with colchicine or placebo. CONCLUSIONS: These data suggest that UDCA frequently is superior to colchicine and especially to placebo in the treatment of PBC.
Serum cholestanol, cholesterol precursors, and plant sterols during placebo-controlled treatment of primary biliary cirrhosis with ursodeoxycholic acid or colchicine.
A randomized placebo-controlled 2-year study was performed in 69 patients with primary biliary cirrhosis (PBC) on serum lipids during ursodeoxycholic acid (URSO) and colchicine treatments. In addition to serum bilirubin and alkaline phosphatase (AFOS), two variables considered to reflect liver function, serum lipoproteins, cholesterol precursors (squalene, delta 8-cholestenol, lathosterol and desmosterol), markers of cholesterol synthesis, cholestanol and plant sterols (campesterol and sitosterol), markers of liver function and cholesterol absorption, were studied before and during the treatments. Serum bilirubin was inconsistently improved by URSO, whereas improvement of AFOS values was better by URSO than colchicine, especially in patients with initially more advanced PBC. Serum total cholesterol was reduced by both drugs, very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) cholesterol by URSO. Cholesterol precursor sterols were increased by both URSO and colchicine mainly in patients with initially less severe PBC. On the other hand, the cholestanol values were markedly increased initially, and the values were related to bilirubin during the 2-year period, were further increased in the placebo group, and reduced in the URSO and colchicine groups, so that the improvement was highest in the URSO-treated patients with the severe form of PBC. The increase of the serum plant sterols, particularly that of sitosterol, was retarded by the two drugs so that the campesterol/sitosterol ratio, which was related to serum bilirubin, was increased especially in the cases with initially more advanced PBC.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolism of cholesterol and low- and high-density lipoproteins in primary biliary cirrhosis: cholesterol absorption and synthesis related to lipoprotein levels and their kinetics.
Cholesterol absorption, elimination, and synthesis, and low-density lipoprotein (LDL) and high density lipoprotein (HDL) kinetics were studied in patients with mild to severe primary biliary cirrhosis (PBC) (n = 16) to show how this cholestatic disease modified cholesterol and lipoprotein metabolism as compared with healthy controls (n = 50). Serum total and lipoprotein cholesterol and triglyceride levels were similar in the two groups, but in PBC, especially in severe forms, very low density lipoprotein (VLDL) was rich in apoprotein (apo) B and cholesterol and low in triglycerides, whereas LDL was rich in triglycerides and low in esterified cholesterol, and HDL was enriched by surface lipids, phospholipids, and free cholesterol. In severe PBC, the fractional catabolic rate (FCR) for LDL apo B was reduced. The transport rate (TR) for LDL apo B was unaffected and it tended to correlate with the LDL apo B and LDL cholesterol levels in PBC, whereas in the controls the LDL apo B concentration was regulated by both the FCR and TR, and LDL cholesterol was regulated only by FCR. FCR for apo A-I in HDL was unaltered in PBC, but TR for apo A-I was reduced in the severe cases. Cholesterol absorption efficiency was significantly reduced in PBC (14.5 +/- 3.0% in severe PBC and 34.0 +/- 2.5% in mild PBC vs. 47.4 +/- 1.4% in the controls, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Treatment of patients with metastatic melanoma with a one day regimen of dacarbazine, vincristine, bleomycin and lomustine plus interferon-alpha.
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A combination of subcutaneous recombinant interleukin-2 and recombinant interferon-alpha in the treatment of advanced renal cell carcinoma or melanoma.
In this phase II study, we have evaluated the efficacy and toxicity of low-dose subcutaneous (s.c.) recombinant interleukin-2 (IL-2) and recombinant interferon (IFN)-alpha in 16 patients with advanced renal cell carcinoma (RCC) and in 4 patients with advanced melanoma. The complete course on this protocol comprised 6 weeks of s.c. IL-2 plus IFN-alpha followed by a 2-week rest period. The treatment was moderately strenuous for patients, requiring frequent dose reductions; only eight cycles (30%) could be administered to 75-100% of the projected dose. Main side-effects were fever, fatigue, hypotension, liver toxicity, neurotoxicity and skin reactions. Among the evaluable 17 patients, two responses (one partial, one complete) were seen in patients with RCC. This regimen proved to be rather toxic and yielded a modest response rate of 15% in RCC, but initial findings concerning the duration of survival seem promising.
Absorption, metabolism, and serum concentrations of cholesterol in vegetarians: effects of cholesterol feeding.
Serum concentrations and metabolism of cholesterol were studied in vegetarians basally and during a dietary cholesterol load. Cholesterol absorption efficiency was normal and synthesis was slightly enhanced, even though serum cholesterol precursors were not increased. The serum concentrations of total and low-density-lipoprotein cholesterol were decreased proportionally to the reduced intake and absolute absorption of cholesterol. Fecal plant sterols were negatively correlated with the absorption efficiency of cholesterol and positively with fecal sterols and cholesterol synthesis, suggesting interference of high plant sterol intakes with cholesterol absorption. Cholesterol saturation and bile acid composition of the bile were not changed. The increased serum plant sterol-cholesterol ratios were positively related to the intake and negatively to the biliary secretion of plant sterols. Cholesterol feeding increased absolute cholesterol absorption and serum concentrations of total and low-density-lipoprotein cholesterol, did not change absorption efficiency or synthesis of cholesterol, but increased fecal cholestanol excretion.
[Treatment and prevention of chronic viral hepatitis].
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Metabolism of cholesterol and apolipoprotein B in celiac disease.
To test the association of cholesterol malabsorption with cholesterol and lipoprotein metabolism, we determined low-density lipoprotein (LDL) apolipoprotein (apo) B kinetics simultaneously with measurements of cholesterol absorption and synthesis in six patients with celiac disease (CD) before and during the gluten-free diet (GFD). The basal condition was characterized by low cholesterol absorption, enhanced cholesterol synthesis, and high removal and transport rate of LDL apo B. The GFD markedly improved cholesterol absorption and decreased intestinal influx of cholesterol, fecal neutral steroids, and cholesterol synthesis. Of plasma total and lipoprotein cholesterol levels, only plasma high-density lipoprotein (HDL) was enhanced by the GFD proportionately to cholesterol absorption. The plasma LDL apo B level remained unchanged because of simultaneous decreases in the fractional catabolic rate (FCR) and transport rate of LDL apo B. In fact, the more cholesterol absorption was improved by the GFD, the more the FCR and transport rate for LDL apo B were decreased, and their reductions were closely related to the decrease in cholesterol synthesis. The present results show that cholesterol absorption, cholesterol synthesis, hepatic B/E receptor activity, and LDL apo B transport rate are closely associated with each other and that their levels can change markedly with no detectable change in serum levels of LDL cholesterol or apo B.
Cholesterol malabsorption in pancreatic insufficiency: effects of enzyme substitution.
Defective lipolysis, steatorrhea, and hypocholesterolemia characterize pancreatic insufficiency. Lipid metabolism in pancreatic insufficiency was studied by measuring serum lipoproteins, cholesterol absorption with double labels and serum plant sterols, and bile acid and cholesterol synthesis with fecal and dietary steroid analysis and cholesterol precursor sterols before and during exogenous pancreatic enzyme substitution. Baseline fecal fat, masses, bile acids and neutral steroids, and cholesterol synthesis were increased, whereas cholesterol absorption was markedly reduced. In fact, the present data suggest that sterol absorption may be disturbed more sensitively than fat absorption in pancreatic insufficiency. Enzyme substitution significantly reduced fecal fat, masses, bile acids and neutral steroids, and synthesis of cholesterol and improved cholesterol absorption in relation to serum cholesterol, although normal values were not obtained. Serum level of high-density lipoprotein cholesterol was significantly elevated by exogenous enzymes, whereas levels of cholesterol or triglycerides in other lipoproteins remained unchanged. Improved sterol absorption increased also serum levels of plant sterols and reduced levels of cholesterol precursors and cholesterol synthesis and precursor sterol-plant sterol ratios. Thus, reduced intestinal lipolysis with expanded oil phase appears to be a major reason for impaired cholesterol absorption, causing enhanced cholesterol and, consequently, bile acid synthesis and reduced serum cholesterol level. Exogenous enzyme substitution seems partly to correct these abnormalities, improvements of which can be monitored by the gas-liquid chromatographic determination of serum plant sterols or cholesterol precursor-plant sterol ratios.
The effective charge number and diffusion coefficient of cationic cytochrome c in aqueous solution.
The diffusion coefficient and the effective charge number of cytochrome c as a function of ionic strength, temperature and pH have been measured. The measurements were carried out using a method based on a convective diffusion process across a porous membrane. The effect of ionic strength was studied in an NaCl solution the concentration of which varied from 0.001 to 1.0 M. The temperature range studied was 10-50 degrees C, and the pH values studied were 4.0, 6.5 and 8.25. The diffusion coefficient is fairly constant as a function of ionic strength and pH, and Walden's rule is valid in the temperature range studied. The effective charge number is practically constant (ca. 2) in the concentration range studied, except in 0.001 M solution, where it is the same as the titrated value. The charge number decreases slightly in the temperature range 10-30 degrees C, but seems to drop suddenly to zero at ca. 40 degrees C. Measurements using heavy water (D2O) as a solvent instead of water did not give zero charge at 40 degrees C for cytochrome c.
Effects of selenium supplementation on blood and urine selenium levels and liver function in patients with primary biliary cirrhosis.
To study the mechanism of the reduced serum selenium concentration in patients with liver damage we administered 200 micrograms (2.53 mumol) selenium daily as selenium-rich yeast to 8 patients with primary biliary cirrhosis and 8 healthy controls over 16 weeks. Initially selenium concentrations in serum were 24% lower (P less than 0.001) in patients than controls. During supplementation serum selenium levels increased in both groups but the difference between them persisted. Throughout the study whole blood selenium levels and glutathione peroxidase activities were also somewhat lower (P = NS) in patients than controls. Selenium supplementation had no effect on whole blood glutathione peroxidase activities in either group. The basal 24 h urinary excretion of selenium was similar in both groups but was increased more by supplementation in patients than controls. Selenium administration did not influence the liver function of the patients. We conclude that impaired hepatic production of selenium-containing serum compounds is the most likely explanation for the reduced serum selenium concentration in patients with primary biliary cirrhosis.
Helicobacter pylori and duodenal ulcer. A study of duodenal ulcer patients and their first-degree relatives.
Out of 59 duodenal ulcer (DU) probands and their 199 first-degree relatives Giemsa-staining for the determination of Helicobacter pylori (HP) was performed in 51 probands and 155 relatives. Controls were matched by age and sex from a family sample representing the same geographical area. In all, 155 controls were found for the probands and relatives. The occurrence and score of HP density showed an excellent correlation with morphology of the mucosa, signs of acute inflammation and presence of gastric metaplasia in the duodenal bulb. The prevalence of HP was 94% in DU probands and significantly higher than in their relatives and controls. In sibs of DU probands the prevalence of HP (64%) was also significantly higher than in controls (51%) obviously due to the presence of a subgroup of sibs with signs of active or past duodenal ulcer disease, which show higher than expected prevalence of HP, and of acid hypersecretion and high levels of serum pepsinogen I (PG I). Peak acid output (PAO), serum pepsinogen I and II and fasting serum gastrin levels were in relatives without atrophy higher in HP positive than negative cases but significant differences were present only with regard to the pepsinogens. The occurrence of HP positivity as well as of high PAO and pepsinogen levels might be considered risk factors of DU disease in close relatives of DU probands. On the other hand, the significance of HP positivity as cause of abdominal complaints is doubtful, in view of the complete lack of correlation between HP and morphology and complaints in the present study.
Functional characteristics of duodenal ulcer patients and their first-degree relatives.
The behaviour of acid secretion, serum pepsinogen I and II (PG I and PG II) and morphology of the gastric mucosa were analyzed in 59 duodenal ulcer probands (DU probands), their 199 first-degree relatives and 228 control subjects. DU probands had as a rule antral gastritis with normal or slightly altered corpus mucosa, and higher mean peak acid output (PAO), PG I and II levels than their relatives and controls. Sibs of DU probands differed from their controls mainly with regard to morphology which showed features characteristic of DU probands, i.e. antral gastritis with normal or slightly altered corpus mucosa. Moreover, high PAO levels were found highly significantly more often in sibs of DU probands (13%) than in controls (6%). Likewise, the prevalence of endoscopic signs of active or past duodenal ulcer were present in sibs highly significantly more often than in controls and they accumulated in the subgroup of sibs with high PAO or PG I levels. It seems probable that the occurrence of high PAO and PG I levels in sibs of DU probands can be considered as signs of increased liability to duodenal ulcer. PAO and PG I were as expected significantly higher in male than in female probands, relatives and controls. Exclusion of cases of corpus gastritis decreased the levels but the sex difference persisted. PAO, PG I and II revealed a significant increase of the levels in middle age followed in older age in case of PAO and PG I by a significant decrease. The decrease was abolished when the cases of corpus gastritis were excluded suggesting an effect of gastritis. However, the earlier increase of the levels remained virtually unaffected although there was a uniform decrease of the mean values. This suggests the participation of factors unrelated to gastritis. The nature of the factors remains unknown, but literature data and data derived from our recent study suggest involvement of anatomical factors such as an increase in the size of acid and PG I secreting area.
Low prevalence of hepatitis C antibodies in chronic liver disease in Finland.
High prevalence of hepatitis C antibodies (anti-HCV) have been found in the Middle- and Southern European countries in connection with chronic liver diseases. In a study of Finnish chronic liver disease patients no anti-HCV antibodies were found in 22 autoimmune chronic active hepatitis, in 5 chronic persistent hepatitis and in 38 alcoholic liver disease patients. 2/30 primary biliary cirrhosis patients were anti-HCV positive. As a comparison 3/9 patients with acute community acquired non-A non-B hepatitis and 28/48 i.v. drug addicts had anti-HCV antibodies. The results indicate that HCV infections in Finnish chronic hepatitis patients are rare.
[Interferon is useful in the treatment of chronic hepatitis B].
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