A biopsy-based quick test in the diagnosis of duodenal hypolactasia in upper gastrointestinal endoscopy.

BACKGROUND AND STUDY AIMS: The usefulness of a new quick test for endoscopic diagnosis of adult-type hypolactasia was tested in duodenal biopsies. In this test, an endoscopic biopsy from the postbulbar duodenum is incubated with lactose on a test plate, and a color reaction develops within 20 min as a result of hydrolyzed lactose (a positive result) in patients with normolactasia, whereas no reaction (a negative result) develops in patients with severe hypolactasia. PATIENTS AND METHODS: Two postbulbar duodenal biopsies were taken from 80 prospectively enrolled adult outpatients with dyspepsia. The biopsies were used for the Quick Lactase Test (Biohit PLC, Helsinki, Finland) and in biochemical disaccharidase (lactase, sucrase, and maltase) assays. In addition, the C/T (-13,910) genotype was determined from DNA extracted from gastric antral biopsies using polymerase chain reaction sequencing in genomic analysis of adult-type hypolactasia. RESULTS: Twenty-one of 22 patients (95 %; 95 % CI, 87 - 100 %) with biochemical lactase activity < 10 U/g protein, but none of the 58 patients with lactase activity of 10 U/g protein or more had a negative result in the Quick Lactase Test. Seven of the 80 patients (9 %; 95 % CI, 3 - 15 %) had a Quick Lactase Test result that indicated mild hypolactasia (a mild color reaction). All patients with celiac disease (n = 6) had a negative Quick Lactase Test result. Nine of 74 patients (six patients with celiac disease were excluded) had a CC (-13,910) genotype in genomic testing, indicating adult-type hypolactasia. All of them had negative test results with the Quick Lactase Test. Twenty-six patients had a TT genotype, indicating normolactasia, and none of these patients had a negative test result in the Quick Lactase Test. Six of 39 patients (15 %; 95 % CI, 4 - 27 %) with a CT genotype had a negative result in the Quick Lactase Test. CONCLUSIONS: The Quick Lactase Test effectively identifies patients with severe duodenal hypolactasia. In comparison with CC (adult-type hypolactasia) and TT individuals (normolactasia), the sensitivity and specificity of the Quick Lactase Test result was 100 %. In comparison with biochemical lactase assays, the sensitivity and specificity of a negative Quick Lactase Test for indicating hypolactasia (lactase activity < 10 U/g protein) were 95 % (95 % CI, 87 - 100 %) and 100 %, respectively.

Non-endoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicentre study.

BACKGROUND AND AIMS: Serum levels of gastrin-17 (S-G-17) and pepsinogen I (S-PGI) are biomarkers of gastric antral and corpus mucosa, respectively. In a prospective multicentre investigation, we determined whether these tests, together with the assay of Helicobacter pylori antibodies, are a non-endoscopic tool for the diagnosis of atrophic gastritis. MATERIALS AND METHODS: The series comprised 404 consecutive adult outpatients undergoing diagnostic upper-gastrointestinal endoscopy for various dyspeptic symptoms in five outpatient clinics. Gastric biopsies from the antrum and corpus (at least two biopsies from both sites) were available from all patients, and they were evaluated according to the guidelines of the updated Sydney system. S-PGI and S-G-17 were assayed with ELISA methods using monoclonal antibodies to pepsinogen I and amidated gastrin-17. In addition to the fasting level (S-G-17(fast)), a postprandial S-G-17 (S-G-17(prand)) level was measured 20 min after ingestion of a protein-rich drink. H. pylori antibodies were determined using a polyclonal EIA method. RESULTS: S-G-17(prand) (and S-G-17(fast)) and S-PGI levels decreased with increasing grade of atrophy of the antrum or corpus, respectively. S-G-17(prand) levels were significantly lower in patients with advanced (moderate or severe) atrophic antral H. pylori gastritis than in those with non-atrophic H. pylori gastritis. All patients with a resected antrum demonstrated S-G-17(prand) levels that were almost undetectable. Of the nine patients with an H. pylori-positive moderate or severe atrophic antral gastritis, six had S-G-17(prand) levels below 5 pmol/l. Similarly, S-PGI levels were significantly lower in patients with advanced corpus atrophy than in those without. Of the 45 patients with moderate or severe corpus atrophy in endoscopic biopsies, 35 patients had S-PGI levels < 25 microg/l. By using the cut-off levels for S-G-17(prand) and S-PGI with the best discrimination, the sensitivity and specificity of the blood test panel in delineation of patients with advanced atrophic gastritis (either in the antrum or the corpus, or both) were 83% and 95%, respectively. The predictive values of the positive and negative test results were 75% and 97%, respectively. In the diagnosis of atrophic gastritis, the application of S-G-17(fast) showed a slightly lower sensitivity and specificity than the application of S-G-17(prand) as a biomarker for antral atrophy. CONCLUSIONS: The diagnosis of atrophic gastritis obtained with the blood test panel of S-G-17, S-PGI and H. pylori antibodies is in good agreement with the endoscopic and biopsy findings. The panel is a tool for non-endoscopic diagnosis and screening of atrophic gastritis.

Serum levels of amidated gastrin-17 and pepsinogen I in atrophic gastritis: an observational case-control study.

BACKGROUND: Helicobacter pylori infection is often diagnosed with non-endoscopic methods, such as serology or breath or antigen stool tests. These tests provide information on the presence or absence of the H. pylori gastritis only. We investigated whether atrophic gastritis can be diagnosed and typed non-endoscopically if the serum levels of pepsinogen I (S-PGI) and gastrin-17 (S-G-17) are assayed in connection with H. pylori testing. METHODS: The present investigation is an observational case-control study comprising 100 selected dyspeptic outpatients with (cases) or without (controls) advanced (moderate or severe) atrophic gastritis. Before the blood tests, all patients underwent a diagnostic gastroscopy with multiple biopsies. The series of cases includes 56 patients. Eight had an advanced antrum limited atrophic gastritis, 13 had resected antrum (in two of whom the corpus mucosa in the stump was atrophic), and 30 had corpus-limited atrophic gastritis. Four patients had an advanced atrophic gastritis in both the antrum and corpus (multifocal atrophic gastritis), and the whole stomach was removed in one patient. Twenty of the 44 controls had a non-atrophic H. pylori gastritis. Both the antrum and corpus were normal and healthy in 24 patients. The S-PGI and S-G-17 were determined with EIA methods using monoclonal antibodies to PGI and amidated G-17. Postprandial S-G-17 (S-G-17prand) was measured 20 min after a protein-rich drink. The H. pylori antibodies were assayed with a polyclonal EIA method. RESULTS: A low S-PGI (<25 microg/l; an empirical cut-off with best discrimination) was found in 31 of 37 patients (84%) with and in 3 of 63 patients (5%) without corpus atrophy in the biopsy specimens. A low S-G-17prand (<5 pmol/l) was found in all 8 patients with H. pylori-associated antral atrophy and in 11 of 14 patients (79%) with resected antrum but in 3 of 20 control patients (15%) with H. pylori-related non-atrophic gastritis. Median and mean values of both S-G-17prand and S-PGI decreased with increasing grade of antral and corpus atrophy, respectively. Among all patients with atrophic gastritis (multifocal atrophic gastritis, or atrophic gastritis limited to antrum or corpus) or resected stomach, 50 of 56 patients (89%; Cl 95%: 81%-97%) had a low S-PGI and/or a low S-G-17prand with positive H. pylori serology. Such low values werc found in 3 of the 44 control patients (7%; CI 95%: 0%-14%). CONCLUSIONS: Low serum levels of G-17prand and PGI are conceivable biomarkers of atrophic antral and corpus gastritis, respectively. A low S-G-17prand is a sign of the multifocal or antrum-limited atrophic gastritis in patients infected with H. pylori.

Fall in the prevalence of chronic gastritis over 15 years: analysis of outpatient series in Finland from 1977, 1985, and 1992.

To investigate whether the occurrence of chronic gastritis (and Helicobacter pylori acquisition) has changed in Finland in the past 15 years, the prevalence rates of chronic gastritis in biopsy specimens in consecutive series of outpatients (aged 20 or more) who had undergone diagnostic upper gastrointestinal endoscopy in 1977 (702 patients), 1985 (1309 patients), or 1992 (1447 patients) were compared. The prevalences of gastritis in these series were also compared with that in a random sample (438 subjects) of people who underwent endoscopy in 1974-76. It seemed that the prevalence of gastritis was significantly lower in the outpatients in 1992 than in the random endoscopy sample in 1974-76. The reduction was most noticeable in young age groups (20-49 years) in which the decline was 38% (drop from 66% to 41%). In addition, it seemed that the prevalence of gastritis was very dissimilar in different birth cohorts. The prevalence was high (70-80%) in 1977, 1985, and 1992 in the cohorts born at the beginning of the century and lower (40-50%) in those born during later decades. The prevalence rates had remained unchanged in the same cohorts over the 15 years (from 1977 to 1992) suggesting that the people had mainly been infected with H pylori and contracted gastritis before the age of 20. In conclusion, gastritis is a cohort phenomenon and its prevalence has fallen in Finland in the last 15 years. This decrease is caused by a decline of the rate of H pylori acquisition in birth cohorts, particularly in childhood and adolescence (below age of 20).

Chronic gastritis and gastroduodenal ulcer: a case control study on risk of coexisting duodenal or gastric ulcer in patients with gastritis.

Chronic (atrophic) gastritis (AG) is common in active duodenal (DU) and gastric ulcer (GU) disease. In this case control study in consecutive prospective outpatients (571 cases and 1074 controls) who had undergone diagnostic upper gastrointestinal endoscopy and routine biopsies from both antral and body mucosa, we calculated the risk of coexisting active DU and/or GU in different gastritis of the antrum or body and according to grade (superficial gastritis, mild, moderate or severe atrophic gastritis). The risk of coexisting active gastroduodenal ulcer (ulcer in duodenum and/or stomach), as well as the risk of DU or GU, was dependent upon the presence and grade of gastritis in antrum and body mucosa. The risk of coexisting ulcer, as expressed as an age adjusted relative risk (RR) and calculated as odds ratio of gastritis in cases and controls, was significantly increased in the presence of superficial antral and body gastritis (RR = 8.5 (7.0-20.0) in men; RR = 5.8 (3.3-10.2) in women), as compared with the risk of ulcer in subjects with histologically normal mucosa (RR = 1). The risk of ulcer, and the risk of GU in particular, increased further with increasing severity of antral gastritis. In such patients with moderate or severe atrophic antral gastritis the RR of coexisting ulcer even exceeded 20 in men and 10 in women (RR = 25.6 (9.0-72.7) in men; RR = 11.7 (5.9-23.0) in women). On the other hand, the RR of ulcer, and the RR of DU in particular, was below 1 in the presence of atrophic gastritis in the gastric body, irrespective of the grade of gastritis in the antrum. We conclude that the type and grade of gastritis strongly predicts the risk of coexisting peptic ulcer, and that the risk of coexisting DU or GU increases with an increase in grade of AG of the antrum but decreases with an increase in grade of AG of the gastric body.

Chronic antral gastritis, Lewis(a+) phenotype, and male sex as factors in predicting coexisting duodenal ulcer.

Chronic antral gastritis, Lewis(a+) phenotype (Le(a+)), and male sex are common in patients with peptic ulcer. To approximate the relative risks (RR) and possible interactions of these factors in predicting coexisting active duodenal (DU) or gastric ulcer (GU), a consecutive endoscopic series of 140 ulcer patients and 215 non-ulcer controls was examined. The Lea phenotype (Le(a+) versus Le(a-)) was determined immunohistochemically as binding of Le(a)+-specific monoclonal antibody to surface epithelial secretory mucosubstances in gastric biopsy specimens. The presence versus absence of the gastritis was determined histologically from antral specimens. The RRs of the factors in the prediction of ulcer were approximated as age-adjusted RRs when the risk of ulcer in the absence of the factors--that is, in the absence of gastritis, in female sex and in Le(a-) phenotype--was applied as a base line (RR = 1). A case-control design, logistic linear modelling, and the maximal likelihood method were used in estimation of the risks. The RR of coexisting distal ulcer (DU or pyloric or prepyloric GU) was increased in the presence of gastritis (RR = 10.2), in male sex (RR = 3.0), and in Le(a+) phenotype (RR = 1.8). The RR of proximal ulcer (angular or corpus GU) was increased in the presence of gastritis (RR = 35) but decreased in the presence of male sex (RR = 0.5) and Le(a+) phenotype (RR = 0.7). As predictors of both distal and proximal ulcer, gastritis, sex, and Le(a) phenotype were independent of each other; that is, their joint value in prediction of ulcer is a multiplicand of the marginal risks. Thus, a 50-fold difference in the joint RR could be approximated between the extreme risk groups for distal ulcer--that is, between Le(a+) males with gastritis and Le(-a) females with normal antrum. In a consecutive series of outpatient endoscopies, 45% of females and 8% of males could be categorized to these extreme 'low'- and 'high'-risk groups, respectively. We conclude that sex, Le(a) phenotype, and gastritis are factors that, at least in ordinary outpatient endoscopy material, divide subjects to subgroups with very different risks and probabilities for having coexisting peptic ulcer.

Changes in the life expectancy of patients with severe haemophilia A in Finland in 1930-79.

Important advances have been made in the treatment of haemophilia during the past 30 years. We have analysed the data of all the known 163 patients with severe haemophilia A living in Finland in 1930-79 in order to study changes in the prognosis of severe haemophilia A. During the period of 50 years the mean age at death of the patients has increased from 7.8 years in 1930-39 to 25.5 years in 1970-79 and the annual death rate has markedly decreased in all age groups. The decline has been greatest in patients under 10 years of age. In this age group the annual death rate decreased from over 50 per thousand in 1930-39 and 1940-49 to 4.8 per thousand in 1970-79. The prognosis of patients with inhibitors has remained poor, however. Five of the six deaths during the last decade occurred in patients with inhibitors. The overall annual death rate of patients without inhibitors was only 1.2 per thousand in 1970-79, suggesting that at the present time the life expectancy of patients who do not develop inhibitors does not markedly differ from that of the general male population.

Joint involvement in patients with severe haemophilia A in 1957-59 and 1978-79.

Clinical findings of joint involvement in patients with severe haemophilia A were compared between two surveys made in 1957-59 and 1978-79. Permanent joint changes wee seen in 50 (81%) of 62 patients in 1957-59 and in 70 (86%) of 81 patients in 1978-79. The incidence of permanent changes was the same in the two surveys in all 10-year age groups, but the degree of involvement was less severe in the two youngest age groups in 1978-79. It is concluded that effective replacement therapy can delay but not prevent completely the development of progressive arthropathy in patients with severe haemophilia A.

Background and practical aspects of hepatitis B surface antigen carrier state.

The prevalence of hepatitis B surface antigen (HBSAg) carriers in the Europe and North America 0.1 - 0.2%, but can exceed a few per cent in South-East Asia and Africa. The HBSAg carrier state is considered to be connected with sociaohygienic conditions but it is evident that genetic factors also contribute the chronic carrier state. Practical measures concerning the treatment and management of HBSAg carriers are discussed.

Red cell glucose-6-phosphate dehydrogenase deficiency in Finland. Characterization of a new variant with severe enzyme deficiency.

Severe red cell glucose-6-phosphate dehydrogenase (G-6-PD) deficiency has been found in an 'aboriginal' Finnish family. 2 male and 9 female carriers of the variant G-6-PD were studied. The genetic pattern is consistent with x-linked recessive inheritance and the defect is associated with drug (primaquine) induced haemolysis. This was demonstrated by enzyme deficient red cell (51Cr-labelled) survival studies on a normal volunteer recipient. In addition, one of the hemizygotes studied had a slight chronic nonspherocytic haemolytic disorder. The partially purified enzyme had many of the characteristics of G-6-PD Mediterranean. The occurrence of this G-6-PD Mediterranean type variant in the Finnish population, which differs greatly from Mediterranean ethnic groups, as well as the association of slight chronic haemolysis with severe G-6-PD deficiency is discussed.