Apoptosis in different compartments of antrum and corpus mucosa in chronic Helicobacter pylori gastritis. An 18-year follow-up study.

BACKGROUND: The association of apoptosis was analysed in three different compartments (foveolar cells--FC, proliferating zone--PZ and glandular part--GP) of antrum and corpus mucosa specimens with development of atrophy and the extent of apoptosis as depending on grade of chronic inflammation, activity of gastritis and Helicobacter pylori colonization at two time points of an 18-year follow-up in an adult population from Saaremaa, Estonia, with a high prevalence of H. pylori infection were compared. METHODS: A total of 68 persons (31 men, 37 women; median age, 39 years in 1979) from a primary sample of 304 subjects, endoscoped in 1979 and reinvestigated by endoscopy and biopsy in 1997, were included in the study. The state of the gastric mucosa and the presence of H. pylori in the antrum and corpus mucosa were assessed in accordance with the Sydney system. The dynamics of apoptotic index (AI) between two time points in 1979 and 1997 was evaluated in antrum biopsies of 49 persons and in corpus biopsies of 64 persons. Apoptosis was measured using terminal deoxyuridine nucleotide nick end labelling (TUNEL) histochemistry. RESULTS: The antrum as well as the corpus of 2/68 persons were H. pylori negative at both time points. Atrophy developed in 9/68 persons in the antrum and in 23/68 in the corpus. In PZ and GP of the corpus mucosa as well as in GP of the antrum mucosa, AI decreased significantly during 18 years compared with initial values (P < 0.05), which was not associated with development of atrophy. In all compartments of the antrum and corpus mucosa, studied at the initial and end points of observation, AI did not reveal a difference in persons with and without development of atrophy (P > 0.05). In the samples of 1979 the highest independent effect on the value of AI in the FC compartment for the antrum was exerted by grade of activity of gastritis (P = 0.01) and in GP by degree of chronic inflammation (P = 0.03), while in the samples of 1997 the highest effect was exerted by grade of H. pylori colonization (P = 0.02 and 0.03 in FC and GP, respectively). For the corpus mucosa AI was most strongly affected also by grade of activity of gastritis in FC compartment (P = 0.02) and by degree of chronic inflammation in PZ (P = 0.04), but not by grade of H. pylori colonization. CONCLUSION: AI was not associated with development of atrophy, but was largely dependent on grade of activity of gastritis and degree of chronic inflammation; in the antrum mucosa AI depended also on grade of H. pylori colonization.

Seropositivity to Helicobacter pylori heat shock protein 60 is strongly associated with intensity of chronic inflammation, particularly in antrum mucosa: an extension of an 18-year follow-up study of chronic gastritis in Saaremaa, Estonia.

Helicobacter pylori is a cause of chronic gastritis and leads to development of atrophy in some cases. There is evidence that the heat shock protein 60 (HSP60) of H. pylori is involved in induction of chronic inflammation. Seroprevalence of IgG antibodies to H. pylori HSP60 in an adult cohort from Saaremaa, Estonia (68 persons, median age 57 years), with a high prevalence of antibodies to cell surface proteins of H. pylori (92%) and a well characterized dynamics of chronic gastritis in an 18-year follow-up study, was tested using purified H. pylori HSP60 at a concentration of 1 microg ml(-1) with ELISA. The state of the gastric mucosa and the presence of H. pylori in histological sections in the samples of 1979 and 1997 were assessed in accordance with the Sydney system. Seropositivity for H. pylori HSP60 was 65%. Immunological response to H. pylori HSP60 is associated with the morphological presence of H. pylori in the antrum and corpus (P=0.01) and is strongly correlated with the grade of chronic inflammation, particularly in the antrum mucosa (r=0.34; P=0.003; OR=5.97 (95% CI 1.21-29.3)), but is not associated with development of atrophy during 18 years of follow-up, or with the activity of gastritis. This finding supports the evidence that immunological response to H. pylori HSP60 may play a role in triggering of the inflammatory process in the gastric mucosa.

Significant increase in antigastric autoantibodies in a long-term follow-up study of H. pylori gastritis.

In 30% of H. pylori-infected patients a certain type of antigastric autoantibodies, reacting against canalicular structures within human parietal cells, is detectable. Furthermore, it has been shown that these autoantibodies are correlated with atrophy of the mucosa in the corpus. The aim of this study was to analyse the prevalence of these anticanalicular autoantibodies (ACAB) and their significance for development of gastric mucosa atrophy in a 12-year follow-up period. Gastric biopsy specimens from 62 persons in Saaremaa Island, Estonia, were collected in 1997 and assessed independently by two pathologists in accordance with the updated Sydney system. The sera of these persons were immunohistochemically screened for ACAB and for classic parietal cell antibodies (PCA). In addition, for 37 of the 62 persons, gastric biopsies and sera collected 12 years earlier (1985) were investigated in an analogous manner. ACAB increased significantly, from 8 out of 37 in 1985 to 17 out of 37 in 1997 (P=0.004; McNemar test). In 1997 a significant correlation existed between the presence of ACAB and corpus mucosa atrophy (19 out of 30 versus 10 out of 32 without atrophy; P=0.01; odds ratio (OR)=3.8, 95% CI 1.4-10.6). However, no correlation was found between ACAB and development of atrophy in the period from 1985 to 1997. All 37 persons were PCA negative in 1985, whereas in 1997, 2 turned out to be PCA positive. ACAB increased significantly with duration of H. pylori gastritis. The correlation between ACAB and presence of gastric corpus atrophy was confirmed. However, it is possible that ACAB are the consequence of and not a causative factor in gastric mucosa atrophy, insofar as the association of ACAB with progression of corpus atrophy was not significant.

An 18-year follow-up study of chronic gastritis and Helicobacter pylori association of CagA positivity with development of atrophy and activity of gastritis.

BACKGROUND: We wanted to evaluate the course of chronic gastritis and its association with Helicobacter pylori and CagA seropositivity in an adult sample from Saaremaa (Estonia) during an 18-year follow-up. METHODS: Seventy persons (31 men, 39 women; median age, 57.5 years) from a primary sample of 304 subjects endoscoped in 1979 were reinvestigated by endoscopy and biopsy in 1997. The state of the gastric mucosa and the presence of H. pylori in histologic sections from the antrum and corpus were assessed both in 1979 and 1997 in 66 subjects in accordance with the Sydney system, and H. pylori status in all 70 subjects was determined with the enzyme-linked immunosorbent assay (ELISA). Anti-CagA IgGs were determined with the ELISA, using the recombinant fragment of CagA. RESULTS: During an 18-year follow-up 11% of the subjects developed atrophy in the antrum, whereas 35% developed it in the corpus. Development of atrophy in the corpus and the appearance of intestinal metaplasia in the antrum were associated with increased activity of gastritis both in the initial and last follow-up biopsies. Anti-CagA positivity was found in 71% of H. pylori-seropositive persons (94% of subjects). There was a significant association between CagA positivity and the activity of gastritis, the presence of atrophy or damage to surface epithelial cells in the antrum and in corpus mucosal biopsy specimens at the last follow-up endoscopy. CONCLUSION: The CagA-positive strains of H. pylori enhance the development of atrophic gastritis compared with CagA-negative strains.

A 12-year follow-up study of chronic gastritis and Helicobacter pylori in a population-based random sample.

BACKGROUND: The study is a 12-year endoscopic follow-up investigation on the course of chronic gastritis and Helicobacter pylori infection in a sample of 81 Estonian people. METHODS: The series is a subset from a random sample of 227 subjects in whom a gastroduodenal endoscopy had been done. The grade of superficial gastritis (SG), atrophy, and colonization of the mucosa by H. pylori was evaluated in biopsy specimens from both antrum and corpus in accordance with the principles of the Sydney System. RESULTS: The healing rate of the H. pylori and gastritis was 0.3% (3 of 81); H. pylori colonization with gastritis developed in 5 of 81 during the follow-up. The mean prevalence of atrophic gastritis (AG) was three times more common in the corpus than in the antrum on the average. The formation of new cases of AG and the disappearance of AG were quite equal during the follow-up, and the overall changes in the grade of SG and atrophy were slow. The mean life span of corpus AG was nearly three times as long as that of antrum AG. In the antrum the grade of chronic inflammation correlated positively with the grade of H. pylori colonization. In cases of SG a low grade of colonization of H. pylori in the antral mucosa in connection with moderate inflammation predicted a reduction or even a healing of gastritis in the long term. CONCLUSIONS: New H. pylori infections with subsequent gastritis may occur in adulthood; a healing of gastritis occurs but is a quite rare event in the course of the 12-year follow-up. Further, in the present random sample of Estonian people atrophic corpus gastritis did not show an overall progression, in contrast to our earlier findings.

Clinical picture of hypolactasia and lactose intolerance.

Selective adult-type hypolactasia, the main cause of primary malabsorption of lactose, shows considerable variation in terms of its symptoms, which mainly depend on the amount of milk consumption. The article discusses congenital lactase deficiency and familial lactose intolerance. Links between hypolactasia and non-specific abdominal complaints, coronary heart disease and cataract are presented. The decrease in lactase activity in the brush border of jejunal mucosa, associated with diseases of the mucosa or any other condition which damages the enterocytes, is discussed as a cause of secondary hypolactasia. It is shown that adult-type primary hypolactasia and selective lactose malabsorption represent a major problem in the everyday work of general practitioners, particularly in populations where hypolactasia is common. Therefore, the examination and treatment of non-selected patients with vague abdominal complaints is important in primary health care. As the need for calcium in humans is largely met by the intake of milk, the consumption of milk has to be in amounts that are tolerable for the individual.

[The clinical significance of the histological classification of stomach cancer after Laurén]. / Klinicheskoe znachenie gistologicheskoi klassifikatsii raka zheludka po Laurén.

Clinical parameters were evaluated in 179 operated cases of gastric cancer. They proved significantly different for intestinal, diffuse and undifferentiated tumors according to Laurén. Patients with undifferentiated cancer of the stomach had the worst prognosis; they more often presented with stage IV disease and tumors larger than 6 cm. Three-year survival rate for that histology was significantly lower (26%) as compared to that for intestinal (51%) and diffuse types (40%).

Dyspeptic complaints, diet, gastric mucosa and Helicobacter pylori among an Estonian urban population.

A representative sample of an adult population, earlier examined by gastroscopic biopsy, was subjected to correlation and regression analyses to quantitate the influences of different factors on the development of three dyspeptic complaints. In this study a large part of the complaints were incriminated by the subjects to poor tolerance of certain foods and/or beverages. According to the results of formal analysis, the state of the corpus and antral mucosa and the presence of Helicobacter pylori play only an accompanying role in some regression models.

Chronic gastritis: progression of inflammation and atrophy in a six-year endoscopic follow-up of a random sample of 142 Estonian urban subjects.

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.

Grade of Helicobacter pylori colonisation in relation to gastritis: a six-year population-based follow-up study.

The prevalence and density of Helicobacter pylori (HP) colonisation was assessed twice, with an interval of six years from antral and corpus biopsies from a randomly collected Estonian urban population sample. Positive HP colonisation was found in either at 1st or 2nd or in both examinations in 85 out of 86 subjects in whom gastritis without atrophy (chronic inflammation without atrophic changes, SG) either developed or remained during the follow-up at the SG level. There was a clear intraindividual tendency to keep the grade of HP colonisation at an unchanged level during the follow-up: the hypothesis of random variation of HP colonisation during follow-up could be statistically rejected. Close to half of the subjects had at both examinations an identical grade of HP colonisation in the antral or corpus mucosa. Distinct changes in HP colonisation were observed in three instances: (1) the appearance of HP colonisation occurred concomitantly with appearance of gastritis; (2) the development of antrum atrophic gastritis (AG) occurred with concomitant diminution and eventual disappearance of HP in the antral side, and (3) normalization of antral mucosa occurred with persistence of corpus AG with concomitant disappearance of HP colonisation at both sites of the stomach mucosa. The grade of HP colonisation increased with increase in severity of SG and decreased with the progression of AG changes. In the antrum at the SG level a distinct increase was seen both in the grade of HP colonisation and in the severity of SG up to middle age, but in the corpus mucosa only HP colonisation but no SG progression was seen in the younger age-groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Grade of Helicobacter pylori colonisation, chronic gastritis and relative risks of contracting high gastric ulcers: a seven-year follow-up.

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.

The occurrence and extent of Helicobacter pylori colonization and antral and body gastritis profiles in an Estonian population sample.

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)

Helicobacter (Campylobacter) pylori infestation and the development and progression of chronic gastritis: results of long-term follow-up examinations of a random sample.

One hundred and thirty-nine subjects representing a randomly selected sample of an Estonian urban population examined endoscopically, bioptically and bacteriologically in 1979 was re-examined in 1985. In the antrum the development of superficial gastritis was clearly associated with the appearance or persistence of Helicobacter pylori (HP) infestation. The further progression of superficial gastritis could less clearly be related to HP infestation, although regression and progression of antral superficial gastritis was significantly associated with the disappearance or presence of the bacteria. The progression of atrophic antral gastritis as well as the development and progression of all body gastritis seemed unrelated to the HP infestation. It is concluded, that HP infestation is in some way involved in the appearance of the first stages of chronic gastritis, but is less related or unrelated to its further progression, which is probably determined mainly by factors other than HP.

The effect of vagotomy and antrectomy on serum pepsinogens I and II.

Ninety-seven consecutive patients with gastric surgery for peptic ulcer were studied; 86 had duodenal ulcer (DU), and 11 gastric ulcer (GU). DU patients were surgically treated by proximal vagotomy, proximal vagotomy and pyloroplasty, truncal vagotomy and pyloroplasty, or truncal vagotomy and antrectomy. All GU patients were operated on by the Billroth I method. Serum pepsinogen I(S-PG I), serum pepsinogen II (S-PG II), basal acid output (BAO), and maximal acid output (MAO) were determined before and 3 months and 1 year after the operation. The mean preoperative S-PG I concentration in DU patients (154 +/- 7 micrograms/l; mean +/- SE) was significantly higher than that (97 +/- 9 micrograms/l) in GU patients (p less than 0.001). A significant decrease in the mean S-PG I concentration in DU patients was seen 3 months (92 +/- 6 micrograms/l) and 1 year (66 +/- 4 micrograms/l) after the operation (p less than 0.001). This change did not depend on the type of vagotomy. However, this decrease was not seen in all individual patients as it was in BAO values. Moreover, the mean BAO decrease was much greater at 3 months (7% of the preoperative value) and 1 year (23%) after the operation than the respective decrease in S-PG I concentration. There was also no correlation between S-PG I and acid output (BAO and MAO) before and after the operation. In GU patients the decrease in mean S-PG I value after the Billroth I operation was smaller than in DU patients after vagotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of serum gastrin in different forms of gastritis among Estonian population.

Gastrin level was measured in frozen serum samples of 215 adult Estonians, who took part in a representative population study in 1979, and were followed-up in 1985. Gastric morphology was verified by multiple biopsy specimens from the fundal and antral parts of the stomach, obtained at direct-vision gastroscopy. Certain combinations of antral-body mucosa were revealed which have, and which do not have a significant influence on the fasting gastrin levels. Low values might be observed in subjects having severe atrophic gastritis simultaneously in fundal as well as in antral area. However, in others low concentration of gastrin was seen without any (or without severe) changes of the mucosa. Therefore different factors as duodenal gastrin-producing cells, several molecular forms of gastrin, age of the person seems to contribute to the total serum gastrin level besides the gastric mucosa. High values of gastrin are characteristic to normal antral mucosa accompanied by moderate or severe fundal gastritis.

[Helicobacter pylori and chronic gastritis in the gastric biopsy material in a group of randomly selected adult inhabitants of Estonia]. / Helicobacter pylori i khronicheskii gastrit v gastrobiopsiinom materiale v gruppe sluchainoi vyborki vzroslykh zhitelei Estonii.

The occurrence of Helicobacter pylori (HP) was examined in 227 subjects randomly selected among the Estonian population of town Kuressaare. HP was present in 166 subjects (73%). In cases of normal mucosa both in antrum and body HP was lacking. If normal gastric body mucosa was associated with antral gastritis HP was found in both regions. More often the contamination of antral and body mucosa with HP occurred in case of superficial gastritis. In subjects with atrophic gastritis the occurrence of HP decreased. The frequency of HP was high (58%) already in the age group of 15-19 years and increased to 83% at the age of 20-29 years. In subjects over 60 years it decreased due to the development of atrophic gastritis.

Relation of parietal cell and thyroid antibodies to the state of gastric mucosa and basal serum gastrin levels during a 6-year follow up.

Two groups of volunteers (199 in total, 149 of whom were a random sample of an urban population) were examined twice, with a 6-year interval, for the occurrence of parietal cell antibody (PCA) and thyroid microsomal antibodies (TMA). The antibody findings were compared with the antral and fundal gastric mucosal state, and with the fasting serum gastrin-17 level. During the study period, two new PCA and four new TMA cases appeared. There were no significant changes in the state of gastric antral/fundal mucosa in relation to PCA and/or TMA persistence or appearance, as compared with the gastric mucosa changes in the whole random population sample. However, a good correlation was observed between PCA and basal serum gastrin elevation.

Development and progression of chronic gastritis in the antrum and body mucosa: results of long-term follow-up examinations.

A bioptical follow-up over 6 years of the status of the antral and body mucosa has been carried out in 81 subjects who formed a part of a random sample of an Estonian rural population. Gastritis in the body mucosa showed an expected progression. In the antral mucosa, on the other hand, progression was seen only in younger subjects, while in those over 50 years of age antral gastritis displayed a distinct slowing and even retardation of the gastritic process.

Serum pepsinogen I and the state of gastric mucosa in an Estonian population sample.

Seventy-seven adult subjects from a rural population were examined by gastroscopic biopsy and serum pepsinogen I (PG I) determination. A new radioimmunoassay method for PG I determination, based on enzymatic iodination and the double antibody solid-phase technique, was used. A highly significant correlation (r = 0.488, p less than 0.001) between the state of the fundal mucosa and the PG I level was observed. In persons with severe or moderate forms of atrophic fundal gastritis the PG I values were notably lower than those of the other groups. Good differentiation of persons with normal fundal mucosa and with severe fundal gastritis was obtained. In subjects with a normal fundal mucosa the PG I values were significantly higher in men (130 +/- 48 micrograms/l) than in women (87 +/- 17 micrograms/l). A decline in serum PG I level with age was observed. In patchy gastritis the PG I value is helpful in assessing the state of the fundal mucosa.

The relationship of parietal cell, gastrin cell, and thyroid autoantibodies to the state of the gastric mucosa in a population sample.

The occurrence of tissue autoantibodies in relationship to fundal and antral gastritis was examined in an Estonian rural population sample, consisting of 227 persons 15 to 69 years of age. The state of the gastric mucosa was verified with multiple biopsy specimens obtained at direct-vision gastroscopy. Isolated fundal gastritis was characterized as the presence of parietal cell (PCA) and/or thyroid antibodies. PCA was seen only in persons with normal antral mucosa. On the other hand, gastrin cell antibodies (GCA) showed no correlation to the extent of antral gastritis, being seen in normal antrum or in superficial or slight atrophic gastritis but not in moderate or severe gastritis. The findings of our present study thus strengthen the view that the occurrence of PCA is mainly limited to isolated fundal gastritis and excludes the occurrence of antral gastritis. On the other hand, an association of GCA and antral gastritis could not be established.