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Biomedical subjects

A L Karvonen

Publications and source records attributed to A L Karvonen.

At least 19 recordsLinked to original sources
PubMed2002

The role of Herpes simplex and Helicobacter pylori infection in the etiology of persistent or recurrent gastric erosions: a follow-up study.

The etiology of chronic gastric erosions is unknown. We have evaluated the significance of Helicobacter pylori and herpes simplex virus (HSV) infections, the use of nonsteroidal antiinflammatory drugs (NSAIDs), alcohol, and smoking in a prospective long term follow-up study. A prospective series of 117 patients with gastric erosions and 117 controls were studied in 1974-1981, and invited for reendoscopy in 1996. At both visits, H. pylori infection was diagnosed by histology, serum HSV antibodies were measured, and the use of NSAIDs, alcohol, and smoking was evaluated by interview. Biopsies from erosions from the latter visit were studied for HSV by immunohistochemistry and polymerase chain reaction (PCR). In the follow-up visit, 16 of 42 patients had still gastric erosions while six of 47 controls had developed erosions. No HSV antigen or DNA could be detected in biopsy specimens. However, only high antibody titers (> or = 32) against HSV at the first visit predicted persistence of erosions (P = 0.000), while H. pylori infection, use of NSAIDs, alcohol, or smoking were not associated with chronic erosions. High HSV titers at the follow-up visit were also significantly associated with concurrent erosions in the patient group. In conclusion, the results suggest that a significant proportion of chronic gastric erosions are related to HSV infection.

Aged↗
PubMed2001

Genetic analysis in Finnish families with inflammatory bowel disease supports linkage to chromosome 3p21.

In inflammatory bowel diseases (IBD), certain chromosomal candidate loci have been repeatedly identified by independent studies in different populations. To investigate the contribution of the loci on chromosomes 1, 3, 7, 12, 14, and 16 to the susceptibility of IBD in Finnish population, where the predominant feature is the excess of ulcerative colitis (UC) families compared to Crohn's disease (CD) families, we carried out linkage analyses using 93 Finnish, multiply-affected IBD families. We observed nominal evidence for linkage to chromosome 3p21, consistent with earlier reports. The lod scores peaked at D3S2432, with a maximum two-point lod score of 1.68 (P=0.0027). In addition, we studied whether risk of IBD is associated with functional variants of two positional candidate genes; the chemokine receptor CCR5 gene on chromosome 3p21 and the interleukin-4 receptor alpha-subunit gene (IL4RA) on chromosome 16. We did not find any significant correlation between a 32-bp deletion variant of CCR5 or a single nucleotide change A1902G (Gln576Arg) of IL4RA, and IBD phenotypes, with the exception that in the UC group homozygosity for the G1902 allele of IL4RA was less frequent (0.019 vs 0.049, P=0.038). In conclusion, our study, carried out in a genetically homogenous population, suggests that chromosome 3 may contain a susceptibility gene for IBD.

Alleles↗
PubMed2001

Factors predicting interferon treatment response in patients with chronic hepatitis c: late viral clearance does not preclude a sustained response.

OBJECTIVES: Because of the suboptimal efficacy, cost, and adverse effects of interferon in chronic hepatitis C (HCV), predictors have been sought to detect patients with a good treatment response. Also, markers for determining a poor response early in the course of therapy, such as the lack of early viral clearance, have been proposed. METHODS: Ninety-seven patients with chronic hepatitis C were enrolled to receive leukocyte alpha-interferon according to a stepped-care management protocol. The final virological treatment response was evaluated in 74 patients after a 6-month post-treatment follow-up. The relationship between pretreatment and during-treatment variables and the long-term response was assessed. RESULTS: Non-1 viral genotype, higher pretreatment ALT levels, and lower gamma-glutamyl transferase (GGT)/ALT ratios and GGT as well as younger age were significantly associated with a sustained response; a trend was also detected for lower serum ferritin levels. Normalization of ALT by 3 months was also a significant predictor of a long-term response. Of the 27 patients carrying the HCV genotype 3a, seven (26%) were still HCV RNA positive at 6 months. Of these patients, however, five (19%) still achieved a sustained virological response after treatment for up to 12 months. CONCLUSIONS: In contrast to some previous reports, our results suggest that a late viral clearance after 6 months of interferon monotherapy may not preclude a favorable long-term response after a 12-month treatment, especially in patients carrying a non-1 HCV genotype. A low pretreatment GGT/ALT ratio is a predictor of a good treatment response.

Adolescent↗
PubMed2000

Leukocyte interferon-alpha in the treatment of chronic hepatitis C in Finland.

BACKGROUND: To evaluate the efficacy of leukocyte interferon in previously untreated patients with chronic hepatitis C, 97 patients were enrolled in a prospective study in Finland with a stepped-care management protocol. METHODS: The treatment was initiated with 3 million units of interferon-alpha subcutaneously three times a week. At 3 months, if the serum alanine aminotransferase was still abnormal, the dose was doubled. If serum hepatitis C virus (HCV) RNA had turned negative at 6 months, the treatment was stopped; if it was still positive, treatment was continued for up to 12 months. All patients were followed up after treatment for 6 months. Altogether, 74 patients completed the treatment and follow-up periods. RESULTS: Of all the originally enrolled patients 36% (35 of 97) achieved sustained virologic response, defined as HCV RNA negativity 6 months after the end of treatment. The commonest HCV genotype among these patients was 3a, and as many as 52% of such patients achieved sustained virologic response. Thirty-two per cent of the patients had HCV genotype 1a, 1b, or a mixture of these; a sustained response was achieved in only 6% of such patients but in 50% of patients with a non-1 genotype. Adverse effects caused treatment cessation for 10% of the patients and IFN dose reduction for 20%. CONCLUSIONS: Monotherapy with human leukocyte interferon resulted in sustained virologic response in 36% of patients with chronic hepatitis C. In those infected with a HCV genotype other than 1, the sustained virologic response rate was 50%.

Adult↗
PubMed1999

Low trehalase activity is associated with abdominal symptoms caused by edible mushrooms.

BACKGROUND: The purpose of the study was to evaluate whether maldigestion of trehalose causes abdominal symptoms and which available diagnostic method best distinguishes intolerant from tolerant subjects. METHODS: A 25-g oral trehalose load test was performed in 64 subjects. The 19 experiencing clear symptoms constituted the trehalose-intolerant subjects. Changes from base-line levels of blood glucose, breath hydrogen, and methane and symptoms were recorded after the test. Trehalase activity was determined in serum and on a duodenal biopsy specimen obtained by endoscopy. RESULTS: Intolerant subjects were best differentiated from tolerant subjects by changes in breath gases (hydrogen and methane) and duodenal trehalase to sucrase ratio. The change in breath gases correlated inversely with duodenal trehalase activity, duodenal trehalase to sucrase ratio, and plasma trehalase activity. The correlation between serum and duodenal trehalase activities was on the order of 0.6. Two subjects were found to have trehalase deficiency. CONCLUSIONS: It is obvious that trehalose maldigestion can cause symptoms similar to those of lactose maldigestion and intolerance. Three factors control the genesis of symptoms: 1) the activity of small-bowel trehalase: if it is low, trehalose is maldigested and more trehalose is passed into the colon; 2) the maldigested trehalose, which causes osmotic water flow into the colon, resulting in loose stools and diarrhea; and 3) most importantly, the microflora of the colon, from which symptoms will arise if there are bacteria capable of producing gases from maldigested trehalose. If colonic bacteria cannot produce gases, then distention of the abdomen and intestinal gas expulsion as eructations and flatus will not occur.

Abdominal Pain↗
PubMed1998

Small-bowel mucosal inflammation in reticulin or gliadin antibody-positive patients without villous atrophy.

BACKGROUND: We investigated whether individuals with positive coeliac disease antibodies but without small-bowel villous atrophy have mucosal inflammation implicating gluten-sensitivity. METHODS: Small-bowel mucosal morphology; CD3+, alphabeta+, and gammadelta+ T-cell receptor-bearing intraepithelial lymphocytes; and mucosal HLA-DR expression were studied in 96 IgA-class antireticulin or antigliadin antibody-positive adults suspected of having coeliac disease and in 27 control subjects. RESULTS: Villous atrophy compatible with coeliac disease was found in altogether 29 patients, in 18 of 21 (86%) patients with both antireticulin and antigliadin antibodies, in 9 of 15 (60%) patients with antireticulin antibodies only, and in 2 of 60 (3%) with antigliadin antibodies only. In 67 antibody-positive patients with normal villous architecture the densities of CD3+, alphabeta+, and gammadelta+ intraepithelial lymphocytes were significantly higher than in non-coeliac control subjects. Ten patients with initially increased densities of gammadelta+ T cells but normal villous structure underwent a follow-up biopsy after 4-18 months, which showed villous atrophy in five patients. CONCLUSIONS: IgA-class antireticulin or antigliadin antibody-positive patients with normal small-bowel mucosal morphology frequently have immunohistochemical markers of coeliac disease latency. Together with our follow-up data this implies that they may be gluten-sensitive.

Adolescent↗
PubMed1998

Antibodies to pyruvate dehydrogenase in primary biliary cirrhosis: correlation with histology.

Antimitochondrial antibodies to pyruvate dehydrogenase are the hallmark of primary biliary cirrhosis. Their pathogenic role has not been proven, although antibodies to pyruvate dehydrogenase are bound to biliary epithelium. The aim of this study was to characterize serum IgA antibodies to pyruvate dehydrogenase and to evaluate their response to different treatment regimens. We also compared the level of antibodies with severity of histological lesions and the data of biochemical liver tests. Serum samples were collected at baseline and after 24 months from 61 primary biliary cirrhosis patients, whereas 23 patients were treated with ursodeoxycholic acid, 20 with colchicine, and 18 with placebo. ELISA was used to detect antibodies to pyruvate dehydrogenase. IgA and IgG were separated with jacalin and protein-A, respectively. Capacity of immunoglobulins to inhibit enzymatic activity was detected by spectrophotometric observation of the rate of enzyme reaction. 49 (80.3%) of the 61 patients possessed IgA antibodies to pyruvate dehydrogenase. Significant decrease in IgA antibodies was observed only in the ursodeoxycholic acid group (p<0.05). 15 of 18 IgA preparations and all 24 IgG preparations of patients' sera were inhibitory towards pyruvate dehydrogenase (mean inhibitory percent +/-SD: 42+/-33.4% and 79+/-22.4%, respectively, at a protein concentration of 100 microg/ml). The level of serum antibodies to pyruvate dehydrogenase correlated with several histological parameters (fibrosis, inflammatory infiltrate), but not with biochemical parameters. Our data reveal that IgA antibodies to pyruvate dehydrogenase inhibit enzyme function. The correlation between antibodies to pyruvate dehydrogenase and histological parameters might suggest the pathogenic role of these antibodies.

Adult↗
PubMed1998

Serum ionized versus total magnesium in patients with intestinal or liver disease.

In serum, magnesium exists in three fractions: protein-bound, complex-bound and free ionized form. Only the free ionized fraction is biologically active. Until recently, only the measurement of serum total magnesium has been in clinical use. Now, commercially available instruments using new ion-selective electrodes for Mg++ have made possible the reliable measurement of serum ionized magnesium in clinical practice. For the measurement of serum ionized magnesium we used a magnesium-selective electrode installed in a six-channel electrolyte analyzer. We compared the use of ionized versus total magnesium measurement in 52 patients with intestinal disease, 54 with liver disease, and in 75 healthy control subjects. In the patients with alcoholic liver disease both serum ionized and total magnesium were lower, and in those with inflammatory bowel disease slightly higher than in control subjects. The correlation coefficient between serum ionized and total magnesium was r=0.87 (p<0.001) in the patients, and r=0.75 (p<0.001) in the controls. In the patient group the fraction of ionized magnesium in the total was negatively related to the serum albumin level (r=-0.41, p<0.001). Serum total magnesium was below the reference range in 30 out of 150 measurements, serum ionized magnesium in only 9 out of 150 measurements, respectively. Thus, 21 cases with low total but normal ionized magnesium (two thirds of hypomagnesemia according to serum total magnesium) were false positive. Total magnesium measurement may overestimate the incidence of hypomagnesemia when significant hypoalbuminemia is present. Measurement of serum ionized magnesium instead of total magnesium may therefore be of advantage in evaluating patients with hypoalbuminemia and when hypomagnesemia is expected.

Adolescent↗
PubMed1997

Expression and therapeutic response related to apolipoprotein E polymorphism in primary biliary cirrhosis.

BACKGROUND/AIMS/METHODS: Apolipoprotein E polymorphism, affecting intestinal absorption and biliary secretion of bile acids, might also contribute to the variable course and response to drug treatment of primary biliary cirrhosis. To test this possibility, we studied the apo E gene frequency, and the expression and response to drug therapy in different apo E isoforms of 88 patients with primary biliary cirrhosis, randomized to ursodeoxycholic acid, colchicine or placebo treatments for 2 years. RESULTS: The frequency of the epsilon2 allele was 2.4 times higher (p<0.01) in the patients with primary biliary cirrhosis compared with the Finnish population. At entry the patients with the epsilon4 allele were significantly younger (p<0.01) than those with other epsilon alleles, while the severity of primary biliary cirrhosis was similar in the three apolipoprotein E phenotypes. Liver enzymes, acute hepatic inflammation, serum total and low density lipoprotein cholesterol were decreased by ursodeoxycholic acid only in the patients with the epsilon4 and homozygous epsilon3 alleles, but not in those with the epsilon2 allele. Improvements of liver enzyme tests by ursodeoxycholic acid were more marked in the patients with the epsilon4 than other epsilon alleles. CONCLUSIONS: The present data show that in primary biliary cirrhosis the epsilon2 allele is overrepresented, and suggest that the expression of primary biliary cirrhosis and response of the disease to ursodeoxycholic acid treatment are closely related to the apo E polymorphism.

Adult↗
PubMed1997

Long-term comparison of antireflux surgery versus conservative therapy for reflux esophagitis.

OBJECTIVE: The purpose of the study was to evaluate the long-term symptomatic and endoscopic outcome in gastroesophageal reflux disease with erosive esophagitis, comparing conservative with operative management. METHODS: The study comprised 105 of 120 patients consecutively referred for severe reflux symptoms to the gastroenterologic outpatient department of a teaching hospital, where erosive esophagitis was confirmed endoscopically. If conservative management (modified lifestyle and medication) failed to relieve symptoms and heal the esophagitis, antireflux surgery (Nissen fundoplication) was undertaken. Follow-up (median, 10.9 years) evaluation of all patients included comprehensive, standardized interviews; self-scoring of symptoms at the time of referral and currently; and observations at endoscopy. RESULTS: Nissen fundoplication was performed on 37 of the 105 patients. At follow-up of these 37 patients, (31) 84% had no or only occasional mild heartburn, (33) 89% were free from erosive esophagitis, and (2) 5% were taking H2 antagonists or omeprazole. The corresponding figures in the 68 patients with only conservative treatment were (36) 53%, (31) 45%, and (14) 21%. The mean change in symptom score between referral time and follow-up was 5.7 in the surgically treated group and 1.7 in the nonsurgically treated group. Fifteen new cases of Barrett's metaplasia were found at follow-up. CONCLUSIONS: In gastroesophageal reflux disease with erosive esophagitis, surgical treatment gave results subjectively and objectively superior to those from conservative management.

Adult↗
PubMed1997

Gastritis classified in accordance with the Sydney system in patients with primary Sjögren's syndrome.

BACKGROUND: According to some earlier reports, chronic atrophic gastritis is a common finding in Sjögren's syndrome. However, the findings are controversial. The aim of this study was to investigate the occurrence of gastritis classified in accordance with the Sydney System in patients with primary Sjögren's syndrome. METHODS: Thirty-two consecutive patients (27 women, 5 men) with primary Sjögren's syndrome, and 64 age- and sex-matched control subjects with dyspepsia underwent gastroscopic examination. Mucosal biopsy specimens were taken from the gastric antrum and corpus. RESULTS: Eight (25%) patients with Sjögren's syndrome and three (4.1%) control subjects had atrophic antral gastritis (P = 0.01). Atrophic corpus gastritis was more frequently found in control subjects, but the difference was not statistically significant. None of the subjects had severe (grade 3) atrophy. Gastric inflammation, in either the corpus or antrum, was found in 85% of patients with Sjögren's syndrome and in 61% of control subjects (P = 0.02). Helicobacter pylori was present in 31% of Sjögren's syndrome patients and in 39% of controls (NS). CONCLUSIONS: In patients with primary Sjögren's syndrome mild atrophic changes in the antrum were common, but severe mucosal atrophy was rare. Compared with control subjects, gastric inflammation was seen more often in patients with Sjögren's syndrome.

Adult↗
PubMed1996

Ursodeoxycholic acid treatment lowers the serum level of antibodies against pyruvate dehydrogenase and influences their inhibitory capacity for the enzyme complex in patients with primary biliary cirrhosis.

A two-year randomized, double-blind, placebo-controlled clinical trial used paired serum samples from 122 patients with primary biliary cirrhosis to compare the effect of ursodeoxycholic acid and colchicine on their immune parameters. IgG antibodies to pyruvate dehydrogenase, the major autoantigen in primary biliary cirrhosis, were determined by enzyme-linked immunosorbent assay and immunoblot; enzyme inhibition assay against pyruvate dehydrogenase was used to test the changes of the functional reactivity of the serum autoantibodies. Treatment with ursodeoxycholic acid decreased both the level of IgG antibodies to pyruvate dehydrogenase (P < 0.01) and the inihibitory titer of the sera for pyruvate dehydrogenase (P < 0.01). Treatment with colchicine or placebo showed no statistically significant changes in either the antibody levels or the inhibitory titers. Ursodeoxycholic acid thus alters the immune parameters of patients with primary biliary cirrhosis. The mechanism of these changes needs further investigation.

Antibodies↗
PubMed1995

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.

Alanine Transaminase↗
PubMed1995

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)

Alkaline Phosphatase↗
PubMed1995

Olsalazine versus sulphasalazine for relapse prevention in ulcerative colitis: a multicenter study.

OBJECTIVE: To compare the relapse-preventing effect and the frequency of adverse events of olsalazine and sulphasalazine in sulphasalazine-tolerant patients with ulcerative colitis. METHODS: Patients in remission, with at least two episodes of active disease during the last 5 yr, were randomized to 2 g of sulphasalazine or 1 g of olsalazine daily and were followed for 6-18 months. Relapse rates in the two groups were compared using frequency and life-table analysis. Sixty-nine patients with proctitis, 140 with left-sided colitis, and 113 with subtotal or total colitis were evaluated. RESULTS: In the intention-to-treat analysis, the failure rate (relapses plus withdrawals) was 54.7% in the olsalazine and 47.2% in the sulphasalazine group. In the per-protocol analysis excluding withdrawals, 44.7% relapsed in the olsalazine and 39.3% in the sulphasalazine group. Remission curves did not differ significantly, although at all time intervals the frequency of remission was slightly higher in the sulphasalazine group (p = 0.19 in the intention-to-treat analysis and p = 0.42 in the per-protocol analysis estimated by the log-rank test). Twelve patients (of whom five had diarrhea) in the olsalazine group versus eight patients in the sulphasalazine group discontinued the study because of side effects. CONCLUSION: The relapse-preventing effect of olsalazine and sulphasalazine in sulphasalazine-tolerant patients did not differ. Furthermore, the tolerability of olsalazine, particularly concerning diarrhea, appears to be better than previously reported.

Adult↗