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The occurrence of intestinal metaplasia with colonic-type sulphomucins: (abbreviated: s-IM or s-positive IM) in the gastric mucosa was studied in 125 patients with gastric carcinoma (GCA), 62 patients with pernicious anemia (PA), 301 and 183 first-degree relatives of GCA and PA patients, 406 outpatients and in 358 controls matched from a large population sample. The sulphomucins (s-mucins) were demonstrated histochemically in endoscopic biopsy specimens by using high iron diamine and Alcian blue (pH 1) methods. The prevalence of s-IM, especially the strongly s-positive IM, was significantly higher in GCA patients than in other series or controls of the same age group. Further, s-IM was significantly more common in PA patients and its prevalence higher in GCA relatives and outpatients than in other series or controls. The occurrence of s-IM was also age-dependent and dependent on the extent of IM. It was suggested that the occurrence of s-IM can be used as a sign of lesions that are more closely associated with GCA than IM is in general.

Plasma triglyceride turnover has been measured in 34 adult healthy human volunteers selected on the basis of normal serum cholesterol and triglyceride concentrations and a normal b.wt. The circulating triglyceride was labelled in vivo with tritiated glycerol and the disappearance of radioactivity was followed up to 24 h. The descending part of the slope was divided into exponential components with the aid of a computer and the one-exponential resolutions were used for analysis. The enzymatic nature of the triglyceride removal mechanism was confirmed. When it was assumed that all subjects have a common maximal removal velocity (Vmax) level, calculation of Km values indicated that the population under study is definitely composed at least of two and perhaps of three groups. The next analysis was therefore carried out without any presumptions and the conventional enzyme kinetic plots were drawn. These revealed that the two groups differ in regard to Vmax but not to Km. Two of the subjects did not fit into either of these groups. Group I with a higher Vmax had a significantly higher turnover rate than group II, which showed a rather uniform distribution of both turnover rate and concentration. The two groups had identical age, sex and b.wt. distribution. There was a definite difference in the triglyceride kinetics between males and females. Both had identical turnover rates, but females showed a lower Km and, correspondingly, a lower plasma concentration of triglyceride. The well known difference in plasma triglyceride concentration between men and fertile-aged women is thus accounted for by the more efficient removal system in the latter. It is concluded that the plasma triglyceride concentration in any individual and under any conditions is determined by three factors: (1) the turnover (synthesis) rate, (2) the maximal removal velocity (Vmax), and (3) the Michaelis constant (Km) of the removal enzyme(s). All of these may be influenced by factors like diet, hormones, metabolites and drugs, but obviously the first two are also genetically determined. It is suggested that any classification of hypertriglyceridemias should include an enzyme kinetic analysis, and this will be attempted in the studies in progress.

The long-term course of Helicobacter pylori gastritis is not well known because there are few follow-up studies available, and the follow-up time has been short.The progression of H. pylori infection and chronic gastritis was retrospectively examined in 102 patients followed up for 32 years. In all patients a blind suction biopsy from the corpus mucosa was taken in 1952, and an endoscopic re-examination with biopsy specimens from the antrum and corpus was performed in 1983.In the first examination 85 patients (83%) were H. pylori-positive as assessed from Giemsa-stained corpus mucosa specimens as compared with 70 H. pylori-positive patients (69%) at the end of the follow-up (1983). Two of the 17 patients who were initially H. pylori-negative became positive in 1983, implying an infection rate of 0.4% per patient-year. On the other hand, 17 of the 85 patients who were initially H. pylori-positive became negative in 1983, representing a disappearance rate of 0.6%. However, the stomach became completely normal in only eight cases, which represents a healing rate of 0.3% per patient-year. All patients with duodenal ulcer disease were H. pylori-positive at the first examination and remained so during the follow-up. In these patients chronic gastritis affected predominantly the antral mucosa, and corpus atrophy did not develop. Parietal cell antibodies appeared during the follow-up in six cases, and five of them were H. pylori-positive at the first examination. In most of these cases gastritis progressed into severe grades of corpus atrophy accompanied by the disappearance of H. pylori infection and normalization of the antral mucosa.New H. pylori infection and complete healing of infected mucosa may occur in adult life, but this is rare. Duodenal ulcer disease is associated with persistent H. pylori infection and absence of corpus atrophy. The appearance of parietal cell antibodies leads to progression of corpus atrophy and disappearance of H. pylori.

We describe here our observations on colonization of the gastric mucosa by Helicobacter pylori in a long-term follow-up of 25 patients with gastric ulcer (GU).All patients were followed-up endoscopically for more than 10 years (mean, 16 years) and endoscopically verified to have GU in the angular or corpus area of the stomach. None had received treatment with H2 blockers or omeprazole or had undergone any maintenance therapy or surgery. On the basis of the endoscopic findings on the activity of GU at follow-up endoscopies, the patients were divided into a group of subjects with 'low risk' of recurrence (15 patients who either had no (7 patients) or only a single recurrence (8 patients) at the first follow-up endoscopy but not thereafter) and into those with a 'high risk' of recurrence (10 patients who had at least 2 episodes of recurrence at follow-up endoscopies).A severe bilateral (antrum and corpus) colonization of the gastric mucosa by H. pylori at the first re-examination (1-6 years after the initial diagnosis of GU) was the most important characteristic feature in the patients with high risk of recurrence as compared with those with low risk. In the course of the follow-up, colonization of the corpus mucosa by H. pylori remained rather unchanged in both high- and low-risk subjects but decreased in grade in antrum particularly in those with low risk (no bacteria at the last endoscopy in 13 of 16 low-risk patients and in 2 of 8 high-risk patients). In both low- and high-risk groups corpus gastritis developed progressively into atrophic gastritis (11 of 25 patients had severe corpus atrophy at the last endoscopy). On the other hand, antral gastritis showed a tendency to heal (13 of 24 patients had normal or only slightly gastric antrum at the last endoscopy).The observations indicate that the H. pylori plays a role in and associates closely with the long-term course of angular or corpus GU disease and is related to the tendency of these ulcers to recur.

Chronic gastritis is a common disease which forms an important background to the pathogenesis of several gastric diseases. In most instances, gastritis seems to be a bacterial (microbial) disease. It begins as long-lasting, chronic inflammatory reaction directed against Helicobacter pylori (HP), or occasionally against other spiral bacteria, which colonize in the space between the surface epithelium and the mucous layer. Gastritis may, irrespectively of the HP-related or HP-independent origin, progress to an atrophy (chronic gastritis with atrophy) in the underlying mucosa. Prevalence of gastritis increases with increase in age, but great variations exist in the age-specific prevalence and in mean age of onset of the gastritis in different populations. A high rate and an early onset of the HP-related gastritis associates with low socio-economic status. Chronic gastritis, and the gastritis with atrophy in particular, may interfere with the function of the affected gastric mucosa, and may subsequently increase or decrease the risk of some gastric diseases, such as cancer and peptic ulcer. Both antral and corpus gastritis with coexistent severe atrophic changes have been shown to be associated with an increased risk of gastric cancer. In addition, gastritis seems to also play an important role in the pathogenesis of peptic ulcer. Virtually all patients with DU and GU have coexisting and preceding gastritis. The cumulative risk of ulcer has been estimated to be high in subjects with gastritis, but, in contrast, to be low in subjects who have normal gastric mucosa.

The possibilities to screen atrophic corpus gastritis with serum pepsinogen I (S-PGI) and serum gastrin (S-gastrin) concentrations have been studied in 774 subjects: 71 index subjects selected from a general population at random, 353 of their first-degree relatives, 276 first-degree relatives of patients with gastric cancer, 53 patients with pernicious anaemia, and 21 of their relatives. Discrimination function analysis was calculated from members of random and gastric carcinoma families. S-PGI less than 30 ng/ml had a high sensitivity for severe diffuse atrophic corpus gastritis (SDAG) alone (89.5%) and SDAG + severe patchy atrophic corpus gastritis (SPAG) (89.1%). Respective figures for specificity were 91.5% and 94.8%. The discriminatory power of S-PGI less than 30 ng/ml and S-PGI less than 25 ng/ml was of the same order. The sensitivity of low S-PGI decreased sharply in detection of slighter forms of atrophic corpus gastritis. The sensitivity of S-gastrin greater than 100 pmol/l to discriminate SDAG was 57.9% and SDAG+SPAG 58.7%. Respective figures for specificity were 90.2% and 92.2%. Diffuse and patchy atrophic changes behaved similarly regarding S-PGI and S-gastrin mean concentrations. Accordingly, the biopsy specimen with the severest atrophic changes indicates the degree of atrophy, which associates closely with the changes in S-PGI and S-gastrin. In conclusion, severe atrophic (diffuse or patchy) corpus gastritis may be screened from a general population with high sensitivity and specificity by low S-PGI less than 30 ng/ml, whereas an increased level of S-gastrin is too insensitive for this.

Of 1161 subjects consisting of 4 family samples (gastric carcinoma patient relatives, pernicious anaemia, duodenal ulcer and control families) 18 subjects representing 17 families had distinct atrophic changes in the gastric mucosa that were considered on the basis of risk calculations to carry an at least 7-fold risk to develop gastric carcinoma. Twelve of these 18 subjects could be used as probands and their 41 sibs were subjected to a closer statistical analysis. Sibs of probands having a very high relative risk of gastric carcinoma (18-fold or more) differed markedly from the general population. All sibs had some form of atrophic gastritis and there was a significantly higher than expected prevalence of subjects with severe corpus mucosal atrophy. It is concluded that sibs of subjects with severe atrophic changes may carry an increased risk of gastric malignancy.

To study the prevalence and course of chronic gastritis (CG), 142 adult subjects collected at random from an Estonian urban area were endoscopically and bioptically examined at a six-year interval. The histology of the antral and corpus mucosae was evaluated by grading gastritis without ("superficial gastritis"; SG) and with atrophy ("atrophic gastritis"; AG) into mild, moderate and severe categories. A total of 135 (95%) and 139 (98%) subjects showed CG in the 1st and 2nd examinations, respectively. The CG healed in one subjects (0.7%), and in 5 out of 7 subjects with normal stomach in the 1st examination the CG started during the follow-up. No change in the severity of CG was seen in 24% of subjects with gastritis in the 1st examination. The main trend of CG was a slow, "one-step progression" in severity of inflammation and appearance of atrophy and intestinal metaplasia. Inflammation progressed significantly, especially in the young age groups and in the antrum in particular. The prevalence of AG increased linearly with age in corpus (mean annual risk 1.25%). Parietal cell antibodies (PCA) were found in 2 subjects in the 1st examination, and a further 2 subjects developed these antibodies later. Three of four PCA-positive subjects belonged to a subgroup of 8 elderly subjects who had corpus AG at both examinations and who also showed normal or normalizing mucosa in the antrum. It is concluded that CG is a slowly progressive disease advancing with time and, once started, rarely healing spontaneously.

The mean pepsinogen I (PG I) level in a Finnish family sample was different in males and females and the difference was statistically significant. After exclusion of subjects with gastritis there remained 67 females and 68 males with morphologically completely normal antral and corpus mucosa. In females there was a significant increase of PG I with advancing age, the regression coefficient being 0.37 and statistically significant (p less than 0.01). In males no such increase was found, and individual cases revealed an almost random distribution with age. A similar increase with age has been noted in gastric acid output in females but not in males. Assuming that there is a linear relationship between PG I levels and the total chief cell mass, the PG I level would be determined by three main variables: thickness of the glandular layer, density of chief cells, and area occupied by chief cells. Of these variables the thickness and chief cell density showed neither in females nor in males any statistically significant increase with age, leaving the area as the variable which would account for the increase of PG I.

Helicobacter pylori is rarely found in gastric biopsy specimens from individuals with atrophic gastritis of the body mucosa. To determine if subjects with atrophic body gastritis have evidence of previous infection with H. pylori, immunoglobulin G antibody to H. pylori was measured by enzyme-linked immunosorbent assay in sera of 399 Finnish subjects. In 124 subjects, multiple biopsy specimens from body and antrum had been evaluated for the presence of H. pylori by Giemsa staining. Antibody correlated well with H. pylori staining except in the subgroup with atrophic body gastritis, in whom the prevalence of seropositivity (86%) was significantly greater than the prevalence of positive staining (33%) (P less than 0.001). Twenty-five subjects had positive antibody and negative staining. This group had a significantly higher prevalence of atrophic body gastritis (80%), lower maximal acid output, lower serum pepsinogen I levels, and higher serum gastrin concentrations than did seropositive subjects with H. pylori. These data suggest that most patients with atrophic body gastritis, despite having a low incidence of current overt infection, have been infected with H. pylori at some point in their lives.

The occurrence of different combinations of antral and corpus atrophic gastritis (AG) was studied in 127 sibs and 159 children of 73 gastric carcinoma patients. Seventy-three control probands, age- and sex-matched for the carcinoma probands, and their 379 first-degree relatives were used as controls. Sibs of gastric carcinoma patients revealed a significant enrichment of AG affecting simultaneously both antrum and corpus (combined AG), while no such enrichment could be demonstrated in children, who behaved on the whole similarly to the controls. In addition, sibs of gastric carcinoma patients showed a significant aggregation of combined AG also when compared with children of similar age. This suggests that genetic factors in addition to environmental ones participate in the accumulation of combined AG in sibs. The lack of phenotype AB in children excludes the possibility of dominant Mendelian inheritance, but leaves the possibility of a recessive autosomal or multigenetic inheritance. The enrichment of combined AG in sibs of gastric carcinoma patients could be one of the factors involved in the increased liability of close relatives of gastric carcinoma patients to contract gastric malignancy.

A series of 38 patients with high gastric ulcer (GU) was examined twice a seven-year interval. One-third of the patients had an active ulcer at the second examination. Chronic gastritis was evaluated, and the level of Helicobacter pylori (HP) colonisation assessed semiquantitatively. The results were compared with age and sex matched non-ulcer controls. The GU series differed from the controls in having a higher degree of HP colonisation in gastric mucosa. The relative risks (RR) in predicting high GU connected with high HP colonisation were significantly elevated, both in the antrum (RR = 6.0-4.8) and in the corpus (RR 5.0-4.4), and still higher when combined HP colonisation values were used (RR 9.5-7.1). The persistence of active ulcer (GU+) was associated with a very high level of HP colonisation, with absence of corpus atrophic gastritis at the first examination and with young patients. Half of the GU+ patients had the maximum grade of combined HP colonisation in both examinations. The study indicates that the presence of HP infection as well as the level of HP colonisation are of importance in both the development and chronicity of peptic GU disease.

A series of 143 subjects representing an Estonian urban population was examined for the occurrence and extent (absent, mild, moderate, severe) of Helicobacter pylori colonization in antral and body biopsy specimens (Giemsa staining). These data were correlated with the presence and grade of chronic gastritis (normal, mild, moderate, or severe superficial chronic gastritis; mild, moderate, or severe atrophic gastritis) in the antrum and the body. Gastritis of any grade was found in the antrum and/or the body in 140 (98%) subjects. The overall extent of H. pylori colonization in the whole series did not differ between the antrum and the body. Of 93 subjects with superficial gastritis, H. pylori was found in the antrum and/or the body in 87 (94%) cases. Of 47 subjects with atrophic gastritis in the antrum and/or the body. H. pylori was not found in 12 (25%). In subjects with gastritis the absence of H. pylori either in the antrum or in the body was relatively common (in 30 of 143 subjects). The grade of superficial gastritis showed a highly significantly positive correlation with the extent of H. pylori colonization in the antrum but not in the body. Correspondingly, the grade of atrophic gastritis in the antrum correlated negatively to the grade of colonization. The total absence of H. pylori was particularly associated with the absence of gastritis in the antrum. Conversely, severe body H. pylori colonization was found in subjects who had atrophic antral gastritis, and severe antral colonization in subjects who had at least moderate superficial antral gastritis and who showed a coexistent normal or slight superficial gastritis in the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon-14-labeled 5-hydroxytryptamine (5HT) was administered intraportally to normal and cirrhotic rats, and urine and bile were collected periodically for periods up to 6, and occasionally up to 10 hr. 14C-labeled 5HT metabolites were separated with the use of two-dimensional paper chromatography, and the radioactivity of nine metabolites of 5HT was measured. Cirrhotic rats excreted 14C metabolites into urine in less quantity than did normal rats. In addition, the biliary excretion of 14C-labeled 5HT metabolites was markedly depressed in cirrhotic rats. The preferential occurrence of glucuronide conjugates was demonstrated in both the urine and bile of cirrhotic animals. 14C-labeled 5-hydroxytryptophol conjugates decreased and relabeled 5HT conjugates increased in cirrhotic rats. In normal animals, at least one-third of the 14C-labeled 5HT metabolites excreted into the bile go through the enterohepatic circulation, and a significant proportion of these can be found again in bile after intrajejunal administration of prelabeled bile.

Biopsy specimens from the antral and body mucosa of 183 patients with gastric polyps (adenoma, 4; hyperplastic polyp (HP), 52; foveolar hyperplasia (FH), 49; and inflammatory polyp (IP), 78 cases) have been examined. The prevalence of gastritis in the series was compared with that in 183 age- and sex-matched controls. The dynamics (progression) of gastritis was evaluated by means of an age-adjusted gastritic score. In the HP and FH groups the prevalence and progression of body gastritis were significantly higher and more rapid (p less than 0.001) while the prevalence of antral gastritis was lower (p less than 0.05) and its progression less rapid (p less than 0.001) than in controls. It is concluded that the pernicious anaemia type of gastritis (A-type gastritis) is closely related to gastric polyps of hyperplastic origin. The progression of this gastritis type seemed to increase in the order IP, FH, and HP. In addition, we observed an increase in the prevalence of intestinal metaplasia (p less than 0.001) and marked epithelial dysplasia (0.1 greater than p greater than 0.05; chi-square = 3.75) in stomachs with polyps as compared with in controls.

The epidemiology and dynamics of gastritis were studied in a representative sample of an urban population of Estonia. The sample consisted of 227 subjects 15-69 years old who were examined by direct-vision endoscopic biopsy, and the data were subjected to dynamic evaluation by stochastic principles. The prevalence of antral gastritis (64%) was similar to but that of body gastritis (62%) higher than that in other population samples studied by us. Correspondingly, the prevalence of atrophic antral and body gastritis was high: 38% and 37%, respectively. The prevalence of atrophic gastritis in the antrum and body increased significantly with age. On the other hand, no sex dependence of gastritis could be demonstrated. The prevalence of gastritis mainly affecting the body (32%) was significantly higher in the present than in the other Estonian sample (19%) studied by us. Complete loss of normal body glands was found in 14 subjects, and in 8 of these the antrum was normal or only slightly altered (type A gastritis). The prevalence of gastritis mainly affecting the body increased significantly with age, whereas that of gastritis mainly affecting the antrum decreased. Dynamic evaluation disclosed two basic dynamic patterns similar to those found in other population samples: the age-specific prevalences of gastritis increased with age according to the Poisson process, and gastritis started in the antrum at a younger age, but its progression was more rapid in the body mucosa. Dynamically, the chief finding of the sample was markedly more rapid progression of the body gastritis than in other samples, which explains the high prevalence of gastritis mainly affecting the body mucosa (type A gastritis) in the present series.

Chronic gastritis is classified in three groups, which have separate dynamical and biological behaviour. of these, type A gastritis affects mainly the gastric body mucosa, and type B gastritis mainly the antral mucosa whereas type AB gastritis («pangastritis») affects simultaneously both areas. Type A gastritis appears to be identical with the gastric lesion of overt pernicious anemia, and is significantly more often found in first-degree relatives of pernicious anemia patients than in matched controls from the general population. Dynamic and pedigree analyses of pernicious anemia families suggest that the rapid atrophy of normal fundal glands in type A gastritis is mainly caused by a single major factor («Factor A»), which is inherited by an autosomal dominant way. Severe atrophy of normal fundal glands leads to typical alterations of the gastric secretion, and is often associated with immunological phenomena. Type B gastritis shares the main characteristics of gastritis that starts in antrum and extends upwards along the lesser curvature. This type of gastritis is associated with normal or high secretion of hydrochloric acid and with normal or elevated level of serum pepsinogen group I. Type B gastritis is more common in duodenal ulcer families than in age- and sex-matched controls of a population sample. Dynamically this type of gastritis differs from the main behaviour of population samples in that in the body mucosa outside the lesser curvature the process is slowed up at the stage of superficial gastritis and virtually no atrophic changes appear with age. Type AB gastritis affects simultaneously both gastric body and antrum mucosa, but is in general more severe in antrum. Some dynamic data of our team suggest that this type of gastritis represents the main behaviour of the population at large. Also this type of gastritis aggregates in families, but nothing is known of its etiopathogenetic background.

The morphological state of gastric body mucosa was examined in 269 first-degree relatives of 64 index patients with gastric carcinoma and in 142 subjects selected at random. Gastric carcinoma was divided into three groups according to histological properties: carcinoma mucocellulare, carcinoma adenomatosum, and carcinoma anaplasticum. The state of gastric body mucosa was divided into five stages: normal, superficial gastritis, slight moderate, and severe atrophic gastritis. The results were subjected to the numerical analysis based on the stochastic theory. The term 'age-adjusted score' (AAS) employed therein defines the individual susceptiability to chronic gastritis. In terms of AAS, the material could be divided into 'high' and 'low' gastritis risk families. It appeared that the subjects belonging to carcinoma mucocellulare index patient families had a significantly higher susceptibility to chronic gastritis than the other relatives examined. These families were also significantly concentrated in the group of 'high risk' families. The heterogeneity of the relatives of gastric cancer patients as regards their gastritis risk should obviously be taken into account in future epidemiological studies. These findings constitute further justification of the genetic approach in studies concerning gastritis-gastric cancer relationship.

Lipoprotein-lipase activity (LPL) was measured in biopsies of adipose tissue and skeletal muscle of normal human subjects, and the results were related to concentrations of cholesterol and triglycerides in plasma lipoproteins. Adipose-tissue LPL activity was significantly higher in females than in males, whereas no sex difference was observed in skeletal-muscle LPL activity. A highly significant positive correlation was present between the plasma high density lipoprotein (HDL) cholesterol level and LPL activity in adipose tissue (r = +0.66, P less than 0.001) but not between HDL and skeletal-muscle LPL. The results suggest that the activity of LPL in adipose tissue and the rate of catabolism of triglyceride-rich lipoproteins might be one of the factors that determine the concentration of HDL in plasma and at least partly account for the known sex difference in plasma HDL level.

Pentagastrin-stimulated gastric acid output and the histology of the antral and body mucosa were examined in 72 computer-selected probands and their 365 relatives, altogether 437 cases. The frequencies of upper abdominal complaints, peptic ulcer and hiatal hernia, and blood group distribution were comparable with those of the population at large. Acid output, expressed as mmol/h, mmol/h/kg of total body weight (TBW), mmol/h/kg of lean body mass (LBM), and mmol/h/kg of fat-free body weight (FFB), correlated with the changes in the body mucosa but not with those in the antrum. Acid output was lower in females than in males when expressed as mmol/h or mmol/h TBW but not when expressed in terms of FFB, which better than LBM accounts for the variation in the gastric surface area and, in this manner, for that of the parietal cell mass. This suggests that the lower acid output in females is due to a smaller gastric surface area and correspondingly smaller parietal cell mass rather than to a lower reactivity of the cells to stimulation. Acid output decreased with increasing age in both sexes, and this was due to a concomitant increase in the incidence and severity of atrophic changes in the body mucosa. An age-related decrease in acid output was not seen in males with a normal body mucosa. In females with a normal body mucosa, however, output expressed in terms of FFB showed a significant increase with age. The reason for this increase is not clear. In males and females with superficial gastritis of the body mucosa acid output decreased with increasing age regardless of the formulation used.

Conflicting results are reported in the literature on the structure and function of gastric mucosa in patients with chronic renal failure (CRF). In the present endoscopic study of 68 CRF patients on conservative treatment (regular dialyses or transplantations had not yet been undertaken), we sought to clarify whether CRF leads to hypertrophic or hypotrophic phenomena in gastric mucosa, as interpreted by the presence and grade of gastritis and by the thickness of the gastric mucosa. We found that the mean progression of gastritis in both antrum and body was significantly slower than expected in CFR patients, and that the thickness of both antral and body mucosa was significantly lower in CFR patients than in non-CRF controls. Furthermore, although the thickness of the oxyntic body mucosa in CRF showed a positive correlation to serum gastrin (SeGa) levels and even though 12 of the patients showed high SeGa levels corresponding to those seen in the Zollinger-Ellison synbdrome (300-1500 ng/l), the thickness of the oxyntic body mucosa in CRF patients did not exceed that seen in control subjects with normal SeGa. We conclude that CRF exerts inhibitory effects on the gastric mucosa resulting in retardation in the progression of chronic gastritis and hypotrophy of the gastric mucous membrane.

The course of antrum and body gastritis was studied using an essentially linear multicompartmental model in pernicious anemia probands, their first-degree relatives, and controls consisting of a representative family sample of a large Finnish population. Our earlier dynamic approach showed that progression of body gastritis was virtually identical in a series followed up with biopsies and in cross-comparison analyses, indicating that cross-sectional data can be used for dynamic analyses at a population level. The collected data fitted a model which consisted of stepwise progression of body gastritis to severe atrophy, of corresponding progressive steps for antral gastritis, and of regression of the antral changes after the end-stage of the body process had been reached. In addition, acceleration of the progression of gastritis in older subjects had to be taken into account in the model construction. The main findings which characterized pernicious anemia probands and their close relatives were: (1) a rapid overall progression of body gastritis particularly after 50 years of age; (2) a very rapid progression of body atrophy in its final stages, which was unrelated to age; (3) the occurrence of juvenile severe body atrophy; and (4) the healing of antral gastritis which was most marked at the stage of superficial gastritis. These results may offer a dynamic explantation for the occurrence of severe body atrophy in association with a normal or slightly altered antral mucosa in pernicious anemia and the prepernicious anemia state.

The applicability of the stochastic theory was tested by comparing dynamic data obtained from a cross-sectional population sample with the progression of gastritis observed during a long-term follow-up study of subjects with originally normal body mucosa or superficial gastritis. A good fit of the follow-up data with the basic stochastic assumptions was observed, and the progression of gastritis during the follow-up study was similar to that obtained by the stochastic analysis of the cross-sectional data.

Plasma endogenous triglyceride transport kinetics were determined in 16 hyperthyroid and in 12 hypothyroid patients and the results compared with those of euthyroid control subjects. In addition, the removal of exogenous particulate fat (Intralipid; Vitrum, Sweden) from the circulation and the postheparin plasma lipolytic activity (PHLA) were studied in these patients for further characterization of the alterations of plasma triglyceride metabolism in thyroid disease. In thyrotoxicosis the average plasma triglyceride level was slightly but significantly increased above that of control subjects. This change was associated with augmented production of triglycerides whereas the mean fractional removal rate was not different from normal. There was a significant linear correlation between the concentration and turnover rate of plasma triglycerides in both hyperthyroid and euthyroid subjects but the concentration/turnover rate ratio was less in the former group suggesting that the efficiency of removal of triglycerides from the circulation was improved in thyroid hyperfunction. The elimination of intravenously administered particulate fat occurred more rapidly in untreated hyperthyroid patients than in euthyroid control subjects. The mean PHLA was also above normal in thyrotoxicosis. Upon adequate treatment of the hyperthyroid state the fasting plasma triglyceride concentration was further increased. Hypothyroid patients showed another pattern of alteration of triglyceride kinetics. The synthesis of plasma triglycerides was normal but the fractional removal of both endogenous and exogenous triglycerides was markedly reduced and this change seems to account for the hypertriglyceridemia associated with thyroid hypofunction. The plasma PHLA was also clearly decreased in the hypothyroid state. Plasma FFA and glycerol levels were increased in hyperthyroidism and plasma FFA was slightly decreased in hypothyroid patients, but these variables were not significantly correlated with any parameter of triglyceride metabolism. Endogenous triglyceride turnover rate was significantly correlated with serum protein-bound iodine (PBI) and T3 uptake in thyrotoxicosis but not in hypothyroidism. Removal of exogenous fat was not related to postheparin plasma lipolytic activity but the fractional endogenous triglyceride transport showed a highly significant relationship to this lipase activity in a mixed group of hyper- and hypothyroid patients. The results suggest that thyroid hormones control both production and removal of plasma triglycerides. Different mechanisms for these interactions are considered.

SummaryThe serum ceruloplasmin content was studied in 58 healthy persons, 31 patients with rheumatoid arthritis, 13 with ankylosing spondylitis, 70 with uncomplicated psoriasis, 27 with psoriasis complicated by arthritis, 11 with sarcoidosis and affected joints, and 10 with sarcoidosis and unaffected joints.Serum ceruloplasmin was significantly elevated in patients with rheumatoid arthritis and ankylosing spondylitis. The ceruloplasmin concentration was normal in patients suffering from uncomplicated psoriasis and in patients with joint involvement without roentgenologic evidence of arthritis. Patients with psoriasis and roentgenologically confirmed arthritis had a significantly elevated mean serum ceruloplasmin concentration. Patients with sarcoidosis showed a tendency towards high ceruloplasmin values if the joints were affected. This was not so clear, however, as in psoriatic arthritis.

The kinetic behaviour of extracellular myoglobin was studied by means of [ 131 I]myoglobin in four healthy persons. Less than 3% of the injected myoglobin was found in the urine, the rest being most probably catabolized by the kidney. The degradation rate was rather rapid. The time in which all myoglobin in the i.v. compartment was catabolized varied from 49 to 224 min. The extravascular compartment was rather large indicating a relatively high concentration of myoglobin in lymphatic and extracellular spaces. The intravascular space contained from 4 to 13.4% of the extracellularly circulating myoglobin.

The effect of oral contraceptives on the concentration, production rate, and removal efficiency of plasma triglycerides was studied in premenopausal women using an endogenous labeling of triglycerides with tritiated glycerol. Thirteen subjects were studied while receiving the drug and seventeen normal healthy females served as controls. In some instances the study was made both before and during the drug or repeated after discontinuation of the treatment. The elimination of triglycerides from the circulation was characterized using the Michaelis constant, Km, which gives the plasma concentration at half-maximal removal velocity. The control group showed a polymorphism of plasma triglyceride kinetics being composed of three subgroups which had different maximal turnover rates. Treatment with oral contraceptives was associated with highly significant increases of concentration, rate of production, and efficiency of removal of plasma triglycerides whereas the maximal turnover rate was apparently unaffected. Thus, the increase of plasma triglyceride concentration (average 1.5-fold) observed in women receiving oral contraceptives is accounted for by a much enhanced influx (average 1.9-fold). The influence of the latter is partly compensated by a simulataneous acceleration of triglyceride efflux, however. The effects are produced already by one cycle of treatment but almost no reversion of the changes can be observed at 1 mo after discontinuation of the drug. The triglyceride concentration and production rate were significantly correlated to the duration of intake of contraceptive preparations while the removal efficiency was not.

The kinetics of plasma endogenous triglyceride transport were assessed in nine hyperglyceridaemic patients before and after treatment with an effective hypolipidaemic compound of the clofibrate group, phenolic ether Su-13437. The triglyceride turnover was measured by endogenous 3H-glycerol labelling technique and the results were compared to those obtained earlier in selected normal subjects. In the untreated stage the plasma triglyceride transport (production) rate was above the normal range in seven of the nine patients but it did not correlate with the triglyceride concentration. On the other hand, the logarithm of the concentration showed a significant inverse correlation with the fractional transport rate. During administration of the drug both the plasma triglyceride concentration and production rate fell in all subjects, the mean decreases being 52 and 35%, respectively. The response of the fractional transport rate to treatment was very variable and although the mean increase of 26% was significant the change did not correspond to the decrease in the triglyceride concentration. On the basis of these observations it is suggested that the primary defect in most cases of type IV endogenous hyperglyceridaemia is an increased inflow transport of plasma triglycerides but the actual plasma triglyceride level is ultimately determined by the inherent type of transport kinetics. The compound Su-13437 is an effective triglyceride-concentration-lowering agent which acts mainly by decreasing the production of plasma triglycerides.

The kinetic parameters of plasma triglyceride metabolism were determined in 14 adult subjects with the nephrotic syndrome by endogenous labelling of circulating triglyceride with tritiated glycerol. The triglyceride production (turnover) rate and the apparent Km of removal were calculated from the slope of the radioactivity disappearance curve and compared to a normal control material studied previously. Plotting of the individual data in a log scale of triglyceride concentration versus turnover with the normal area and saturation curves in the background allowed a detailed characterization of the nature of kinetic alterations occurring in disease. It was found that in the majority of cases with the nephrotic syndrome the plasma triglyceride concentration and rate of influx are slightly above normal. However, the apparent Km of removal was significantly increased suggesting that efflux may also be somewhat impaired. In four cases the plasma triglyceride was produced at a rate which exceeded the value predicted by the normal saturation curves and it is believed that an uncontrolled overproduction of plasma triglyceride was present in these cases.—Complete remission of disease in one case brought both triglyceride concentration and turnover rate rapidly to normal values. An eight-hour infusion of human serum albumin in another patient promptly caused a return of high triglyceride turnover to normal.— The primary change behind the nephrotic hypertriglyceridaemia seems to be a controlled increase of plasma triglyceride synthesis. In some cases, however, this overproduction occurs in an uncontrolled fashion and in a number of patients decrease of removal efficiency contributes to the development of hyperglyceridaemia. All of these changes can be explained on the basis of an increased FFA/albumin molar ratio in plasma giving rise to the elevation of unbound FFA fraction.

The role of the kidneys and the liver in the catabolism of Bence Jones protein was investigated by studying the kinetics of [131]Bence Jones protein in normal subjects and in patients with hepatic and renal insufficiency. Bence Jones protein was isolated from urine of a myeloma patient who had earlier suffered from polycythemia vera. After radioiodination, [131]Bence Jones protein was infused to recipients, and both the protein-bound 131I and free 131I were determined serially from serum and urine. The kinetic analysis was carried out with an analogy computer. Results showed that the Bence Jones protein half-time was normally only about 4 h. The rapid disappearance of the protein from the circulation was mainly due to extensive catabolism because only 3 to 4% of the total removal was caused by proteinuria. The half-time of Bence Jones protein was longer in patients with renal insufficiency, ranging from 8 to 32 h. 30 to 50% of the urinary radioactivity was present in protein-bound form, indicating that the endogenous catabolism of Bence Jones protein is markedly reduced in uremia. Furthermore, gel filtration of the urine of the uremic myeloma patient suggested that a part of the bound radioactivity was in peptide form. That the liver apparently plays a minor role in the catabolism of Bence Jones protein was shown by finding that the half-time of [131]Bence Jones protein was within normal range in two patients with moderate liver damage. One patient with severe liver insufficiency and with signs of renal tubular dysfunction had, however, a markedly reduced Bence Jones protein catabolism.

In a series of healthy normolipaemic, adult subjects, plasma triglyceride turnover, heparin-releasable lipoprotein lipase (LPL), and plasma HDL choelesterol were determined. Strong correlations were found to exist between the fractional removal rate of plasma triglycerides (FTR) or LPL as one variable and HDL cholesterol as the other, whereas the triglyceride turnover rate (TR) did not correlate with HDL cholesterol. It is concluded that lipoprotein lipase action is largely reponsible for the formation of HDL cholesterol in the blood stream.

The interrelations among fasting serum gastrin, serum creatinine, gastric acid secretion variables, and G-cell densities were analyzed in 47 patients with chronic renal failure (CRF). The patients also underwent gastroscopy and radiologic upper gastrointestinal barium examination. It is suggested that the hypergastrinemia seen in CRF is related to several factors: gastric acidity, grade of renal failure, G-cell density, and basal gastrin secretion rate. With regard to serum gastrin two different populations can be found, the cutting-off point being 300 ng/l. Although the group with high gastrin levels included significantly more patients with gastric body atrophy than the other group (4 of 11 versus of 1 of 36), most of them had no atrophy, which indicates that (an)other mechanism(s) is responsible for the hypergastrinemia. In the relation between serum gastrin and gastric acidity also, two differently behaving subgroups emerged. In the first, strong acidity change corresponded to minor gastrin change, whereas in the other, minor acidity change corresponded to marked gastrin change. The correlation coefficients between gastrin and acidity were high within both subgroups. During regular dialysis patients preserve the characteristics delineated from non-dialyzed values. Patients with signs of duodenal ulcer disease had high maximal acid output and low serum gastrin. Otherwise no associations were found between GI findings and the variables studied.

In males with a normal gastric mucosa the acid secretion expressed in terms of fat-free body weight (FFB) shows a random distribution with age, whereas in females there is a significant increase. To explain this sex-related discrepancy, we examined maximal pentagastrin-stimulated gastric acid output (AO) and the parietal cell density (P) and thickness (T) in 50 males and 50 females with a normal antral and body mucosa randomly collected from a representative Finnish population sample. Two alternatives were considered: 1) the parietal cell reactivity remains constant, and the age variation in females is due to an increase in the total parietal cell mass, 2) the age variation in females is due to an increase in the reactivity of parietal cells, the total parietal cell mass (P X T X body area (A)) remaining constant. Starting from the first alternative, P and T were measured and showed no correlation with age in males and a decrease in females. The variable A is, according to the formula, expressed by the ratio AO/P X T, and this ratio shows an expected significant correlation with AO in both males and females. However, the variable A showed a significant increase with age in females but not in males. In view of the results of Cox that A should not vary with age, the present results suggest that the ratio AO/P X T in females must include, in addition to body area, other variables, such as the reactivity of parietal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphological changes in the remnant mucosa 2–20 years after operation for duodenal ulcer (DU) were analyzed in 124 male subjects by means of stochastic mathematics. Fifty non-operated male DU patients and 168 age-matched males from a population sample served as controls. Substantially no progression of gastritis was found in the DU patients. In contrast, the operative intervention caused a rapid initial progression of gastritis, continuing after 2 years approximately at the same speed as in the population at large.

The occurrence of chronic gastritis and intestinal metaplasia (IM) was studied in 257 patients with gastric carcinoma (GC). In all cases biopsies were available from the benign mucosal area adjacent to the tumor, and in 139 patients from the antrum and/or body mucosa outside the tumor. The results were compared with endoscopically and bioptically examined noncancer controls representing a large Finnish population sample. For every GC patient, a control subject was matched by age and sex. In addition, a mean age-adjusted score (AAS) of chronic gastritis, which expresses the progression of gastritis in GC patients as compared with that in the general population, was calculated for GC patients. The prevalences of chronic and atrophic gastritis in the antrum and body mucosa were similar in GC patients and controls when carcinoma cases were not more specifically classified according to histologic type or location of tumors. On the other hand, the location of the tumor showed a significant relation to gastritis: the progression of gastritis was more rapid (high mean AAS value) and the prevalence of atrophic gastritis was higher in the tumor-affected area (i.e., in the antrum in patients with antral [distal] tumors; in the body in patients with body [proximal] tumors), than in the general population, but were similar in the tumor-free area in both GC patients and controls. In the intestinal type of GC (IGC), the prevalence of chronic gastritis was higher and its progression was more rapid than in controls. In the diffuse type of GC (DGC), these correlations were less distinct. In GC patients, the IM adjacent to and outside the tumor area was significantly more common and extensive than in the corresponding area of controls, and a significant positive correlation was present between the location of the tumor and the distribution of IM. Like gastritis, the IM showed a closer relationship to IGC than to DGC. In all cases of GC and particularly of IGC, the antral mucosa tended to be more severely affected by gastritis and IM than the body mucosa, i.e., the prevailing type of gastritis found in this GC series was that morphologically corresponding to the so-called B-type of chronic gastritis.

Disposition of [14C] bumetanide administered intravenously to four healthy volunteers could be described by a triexponential equation. The mean half-lives associated with each exponent were 5.9 min, 46 min, and 3.1 hr, respectively. The largest fraction of dose was eliminated during the second phase; only 17% was eliminated during the last phase. The total plasma clearance averaged 228 ml/min, with renal clearance about one-half of this value. The recovery of unchanged bumetanide in urine over 2 days was 47% of the dose, while the total recovery of radioactivity in urine averaged 82% of dose. In plasma 93% of bumetanide was bound to proteins. Thus bumetanide is rapidly eliminated by both renal and nonrenal mechanisms. The elimination kinetics resembled those described for furosemide.

Relative risk (RR) and cumulative risk of gastric cancer (GCA) were calculated for different grades of atrophic gastritis (AG) of the antrum and body. Cross-sectional data on the occurrence of AG in a representative population sample (371 subjects), and Finnish Cancer Registry data on GCA were used in the calculations. The RR was increased significantly in severe AG of the antrum and the body (18.1 and 4.6 times, respectively), but not significantly in the less severe grades of AG. As a risk factor, severe antral and body gastritis were independent of each other. The cumulative risk, i.e., the probability of contracting GCA within the following 10 years in age groups 50-54 . . . 70-74 years was calculated to vary from 2.3% to 9.3% and from 8.7% to 31.9% in severe antral AG and from 0.9% to 4.5% and from 3.6% to 16.6% in severe body AG in males and females, respectively.

Commercially available television-computer equipment was used in the counting of silver grains in autoradiograms. The counting was made very rapidly and easily. The counts were compared with the counts made visually. With some limitations both counts showed excellent agreement. The accuracy of the method used is discussed.

The turnover kinetics of ceruloplasmin was studied by means of I131-labeled human ceruloplasmin in 2 patients suffering from Wilson's disease and in 8 control subjects. A complete kinetic analysis was made of the patients during penicillamine treatment and was repeated after withdrawal of the drug. There was no significant difference in the distribution of ceruloplasmin in the intravascular and extravascular compartments between the patients and the control subjects. Penicillamine had no effect on the distribution of ceruloplasmin. The fractional catabolic rate of ceruloplasmin without treatment was normal, whereas a clear acceleration of the catabolism during the treatment was seen. The daily turnover was strongly depressed and showed a slight tendency towards acceleration during the treatment.

The metabolism of glycerol was studied by intravenous and oral glycerol tolerance test (single dose of 5 g orally and 2.4 g intravenously) in 15 healthy and 17 diabetic subjects.- The intestinal absorption of glycerol was rapid, the maximum serum level of glycerol occurring 15 minutes after the intake. In diabetic subjects the increment of serum glycerol was significantly smaller than in control cases. However, three patients with hyperlipemia and diabetes formed a striking exception in having abnormally high peak glycerol levels. The plasma FFA level was not altered by oral glycerol. Blood glucose remained unchanged in the controls, but rose on an average 13 mg/100 ml in insulin-requiring diabetics. The intravenous glycerol disappearance curves were analysed by an electronic computer. With a few exceptions the result was compatible with a one-compartment kinetic model. The fractional disappearance rate of glycerol from this pool was significantly smaller in diabetics (0.041 min−1) than in control subjects (0.059 min−1). However, the total disappearance rate was twice as high in the diabetic as in the control group (mean values 3.85 and 1.73 μmolesper minute per kilogram, respectively).

The state of the gastric body mucosa was examined bioptically in randomly selected 16-65-year-old subjects of a Finnish rural community, Pornainen. The series were representative of the whole population as regards sex, age, and occupational distribution.Gastritis was found in 53 per cent of the series, with no difference between the sexes, being superficial in 25 per cent and atrophic in 28 per cent. The prevalence rate of gastritis increased significantly with age, 1.40±0.10 (SD) yearly per cent of the total group of corresponding age. This increase was mainly due to the increase of atrophic gastritis, whereas the prevalence of superficial gastritis remained nearly constant. The results suggest a poor healing tendency of gastritis in general and of atrophic gastritis in particular. The yearly increase in the prevalence rate of atrophic gastritis at all ages examined, was computed to 1.25±0.19 (SD) per cent of the total group of corresponding age.The age-specific prevalence rates of gastritis have not an ...

The distribution and turn-over kinetics of ceruloplasmin were studied by means of 131I-labelled human ceruloplasmin in 7 patients suffering from active rheumatoid arthritis and in 13 control subjects. Total mass and absolute intravascular mass showed a tendency towards higher values in the patients, though some overlapping was seen. No difference was seen in the distribution of ceruloplasmin in the intravascular and extravascular compartments in the patients and the control subjects. The fractional catabolic rate (per cent of intravascular pool per day) was on an average on the same level in the patients and the controls. The daily turnover was significantly accelerated in patients with rheumatoid arthritis.

The highest specific activities 30 min. after intraportal administration of 14 C-5HT were observed in the intestine, liver, kidney and spleen of normal rats. In cirrhotic rats significantly lower activities were found in these organs, with the exception of the kidney. Platelet-poor plasma contained high radioactivity consisting of over 95% of the metabolites of 14 C-5HT. The similarity of the plasma and urinary metabolite patterns suggests that the kidney has no essential role in the metabolization of 5HT. It seems obvious that a great part of the 5HT liberated from intestinal storagesis rapidly inactivated by its metabolism. This inactivation process is accelerated in cirrhotic rats.