[The incidence of endemic sprue/celiac disease in Berlin (West). A prospective study with short discussion of a case]. / Inzidenz der einheimischen Sprue/Zöliakie in Berlin (West). Eine prospektive Untersuchung mit kurzer Falldiskussion.

This study was carried out between June 1986 and May 1988 in Berlin (West). In cooperation with 5 Pathological Departments, we prospectively recorded every bioptical diagnosis of total/subtotal villus atrophy (group S) or of partial villus atrophy (group SV). In addition, we registered anamnestic, clinical and laboratory findings from these patients. The diagnosis of coeliac disease was considered verified if the patient showed an unequivocal improvement of his clinical conditions and laboratory findings within three months on a gluten-free diet. In total, 42 patients were registered, among them were 29 with mucosal alterations typical for coeliac disease and 13 whose biopsies showed partial villus atrophy. The diagnosis of coeliac disease could be verified in 28 patients, among them one woman with intestinal lymphoma after longstanding untreated coeliac disease. A second patient with complete villus atrophy had intestinal lymphoma but without preceeding coeliac disease. Our findings show that the incidence of coeliac disease in Berlin is 1 out of 2113 newborn children. This figure is similar to the data reported from France, yet being clearly lower than those from Western Ireland, Switzerland and Sweden. Women are affected twice as often as men. 20 out of 28 patients were children under five years of age. The most common symptoms were meteorism/flatulence, recurrent diarrhea, loss of body weight, or inappropriate growth. 70% of the patients suffered from anaemia, the D-Xylose-test was pathological in 92% of the patients.

Identification of patients at high risk for colorectal carcinoma from biopsy studies of the apparently normal colorectal mucosa. A multivariate analysis.

A number of phenotypic abnormalities of the colorectal mucosa which appears normal have been described to be biomarkers of cancer development. To improve their sensitivity and specificity, we simultaneously determined 10 morphological and histochemical parameters in biopsies from the colonoscopically normal mucosa of the descending colon, sigmoid, and rectum. The results were analysed by multivariate statistical methods. We tested the discriminating power of proliferative, morphometric, enzyme and mucin histochemical parameters from 80 patients either at average risk (controls), with an increased risk for colorectal carcinoma (high-risk), or with a manifest carcinoma. The following parameters were investigated: number of mitotic figures per crypt, crypt length, apical, medial and basal crypt diameter, crypt surface, activity of succinate dehydrogenase (EC 1.3.99.1), activity of acid beta-galactosidase (EC 3.2.1.23), sulpho- and sialomucin contents. Univariate statistical analyses revealed that crypt length, crypt diameter and crypt surface were significantly increased in the high-risk group, the carcinoma carriers having intermediate values between average-risk and high-risk patients. In a two-group discriminant analysis, high-risk or carcinoma patients could be separated from average-risk patients with a sensitivity of 92.9% and a specificity of 100%. When the analysis was repeated for three groups (carcinoma carriers separated from high-risk patients), sensitivity and specificity were 100% for each group. We conclude that identification of patients at risk for colorectal carcinoma is possible from the normal-appearing left colonic and rectal mucosa by morphometric and cytochemical analysis of biopsies.

Adaptation of epithelial ion transport in the short bowel syndrome.

Ileal remnants 8 weeks after 70% proximal small intestinal resection were used as a model for the short bowel syndrome in man. For comparing active ion transport between control ileum and short bowel with the Ussing technique, the relative contribution of the subepithelial resistance has to be considered. Epithelial/subepithelial voltage divider ratios were determined in the Ussing chamber by positioning the tip of a microelectrode just below the epithelium. In control ileum, the ratio of total to epithelial voltage deflection was 1:0.56 +/- 0.03 (n = 48) and decreased to 1:0.42 +/- 0.01 (n = 67; p less than 0.001) under the short bowel condition. Thus, the factors by which a measured short-circuit current (Isc) underestimates the true electrogenic transport was 1.78 +/- 0.09 (n = 48) in control ileum and 2.36 +/- 0.08 (n = 67; p less than 0.001) in the short bowel. Glucose-dependent electrogenic Na absorption was defined using bathing media containing 48 mM 3-o-methyl-glucose as the decrease in Isc (delta Isc) after addition of 0.5 mM phlorizin. After correction for the respective contributions of the subepithelial resistance, delta Isc was -1.4 +/- 0.2 microEq.h-1.cm-2 (n = 13) in control ileum and -3.2 +/- 0.7 microEq.h-1.cm-2 (n = 11; p less than 0.01) in the short bowel. We conclude that the mucosa in the short bowel syndrome is characterized by an increase in glucose-dependent electrogenic Na absorption, probably as an adaptive response to the reduced overall absorptive area of the remaining intestine.

Characterization of stereomicroscopically identified preneoplastic lesions during dimethylhydrazine-induced colonic carcinogenesis.

Preneoplastic mucosal changes were studied at six different time-points during dimethylhydrazine (DMH)-induced colorectal carcinogenesis in the rat. After 40 weeks of treatment, seven of 10 animals were bearing a total of 11 colorectal adenocarcinomas. The crypt cell production rate in the normal mucosa of DMH-treated animals was greatly increased in the left colon and rectum and further rose with the duration of the experiment. Focal disturbances of the mucosal architecture could be detected as early as 4 weeks after the initiation of DMH-treatment using a stereomicroscope. Their incidence was greatest in the left colon and rectum and increased strongly with the duration of carcinogen exposure. Characterization of these mucosal alterations, by means of conventional histology, morphometry after microdissection, cell kinetics, mucin histochemistry and quantitative enzyme histochemistry performed with serial sections, revealed mild epithelial dysplasia, a considerable elongation and dilatation of the crypts and a marked increase of the crypt cell production, including a shift of the main proliferative compartment from the basal to the medial crypt segment as well as the occurrence of mitotic figures in the luminal epithelium. In affected crypts, the goblet cells completely lacked sulphomucins and exclusively contained sialomucins. The activities of the enzymes diaminopeptidase IV (brush-border), succinate dehydrogenase (mitochondria) and acid beta-galactosidase (lysosomes) were markedly reduced. We conclude that these early mucosal alterations are indeed preneoplastic lesions and indicate the existence of the adenoma-carcinoma sequence in this animal model.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in the lectin-binding pattern of PNA-agglutinin and UEA1 during the DMH-induced carcinogenesis in the normal appearing colonic mucosa of the rat.

The purpose of this study was the investigation of changes in the lectin-binding pattern prior to tumour formation in an experimental model. Female Wistar rats were treated with 1,2-dimethylhydrazine (DMH). After 4, 8, 16, 24, 32 and 40 weeks of treatment the lectin-binding-pattern of the colonic mucosa appearing morphologically normal was examined at the caecum, proximal colon, distal colon and rectum, using FITC-conjugated Peanut-agglutinin (PNA) and Ulex europaeus-agglutinin1 (UEA1). In contradistinction to what has been reported earlier by other authors, PNA did not indicate constant cancer-associated mucin changes. In addition, there was no difference in the UEA1-binding between the control animals and the DMH-treated rats. Thus, in the rat there is no specific PNA- and UEA1-binding pattern during tumour induction in the gut.

[Incidence of endemic sprue in Berlin (West). A retrospective study based on biopsy findings]. / Inzidenz der einheimischen Sprue in Berlin (West). Eine retrospektive Untersuchung anhand bioptischer Befunde.

The incidence of celiac disease in Berlin (West) during the years 1979-1984 has been studied retrospectively by investigating the records of the local Pathological Institutes, which examine small intestinal biopsies, for the occurrence of abnormal specimens typical of celiac disease (group 1) or consistent with the diagnosis of celiac disease (group 2). Group 1 exhibited a constant average incidence of 0.74 per 100,000 inhabitants per year, while group 2 showed a small increase between 1979 and 1984, averaging 1.03 per 100,000 inhabitants per year. Classified according to age the highest incidence was seen in the 0-5 year-olds, namely 8.04 in group 1 and 10.00 in group 2. For those children born and examined during the period of investigation the values ranged between 15.8 and 64.7 per 100,000 births. Girls, with an average frequency of 1:1919 births were more often affected than boys, who averaged 1:4219 births. These figures obtained in Berlin (West) indicate only the lower ranges of incidences and will have to be further supplemented by a prospective study.

Absorptive capacity of the transplanted small bowel.

Small bowel transplantation (SBT) has been carried out in man in several cases without success, because immunologic problems were unsolved. In experimental SBT a 'two step' model was developed, which enables long term observation of immunologic phenomena. In this model the graft is in a heterotopic position to the recipient's own small bowel. After 35 days the recipient's own bowel is removed and replaced by the graft, now in orthotopic position and again in contact with luminal chymus. To investigate functional and morphological changes, which result from the procedure, the resorption of glucose and water was measured in syngeneic transplanted rats by an in vivo recirculation system and the mucosa was evaluated three dimensionally. The graft mucosa showed a significant reduction in villus height, crypt length and villus surface and a corresponding decrease in glucose and water absorption during heterotopic position. If the graft came into the orthotopic position, the mucosa did regenerate which was expressed by the significant longer crypts of the graft compared with those of the controls, although the graft's villus height and surface are still smaller. Glucose and water absorption increased and were higher in orthotopic transplanted animals, when absorption was expressed per unit intestinal length. The results indicate that in the 'two step' model of SBT the absorption of water and glucose is influenced to such an extent, that recovery is possible after three weeks, thus enabling orthotopic SBT. This almost complete recovery of the mucosa is further evidence of the regeneratory capacity of the small bowel, which enables clinical small bowel transplantation.

The intestinal monoxygenase enzyme system in DMH-induced rat colonic carcinogenesis.

Four enzymes of the microsomal mixed function oxidase system were studied in two different segments of each the small and large intestine and in the liver of untreated female Wistar rats. In order to test a possible induction of this enzyme system, due to the application of the colonic carcinogen N,N-dimethyl hydrazine, three of these enzymes were determined in the same intestinal segments, in the liver and, in addition, in the kidney after 4 and 8 weeks of DMH-treatment (weekly s.c. injections of 20 mg DMH/kg b.w.). In the untreated rats, the four enzymes under investigation revealed significantly higher specific activities in the liver and in the jejunum than in the ileum and colon. In the DMH-treated animals, liver AHH-activity was decreased after 4 and 8 weeks when compared with the EDTA-treated controls; so was the AHH in the jejunum and in the ileum after 8 weeks. Liver EOD was only decreased after 4 weeks and had normalized after 8 weeks, being diminished, however, in the jejunum at that time. UDP-GT-activity was not altered at all. No alterations of the investigated enzyme activities could be demonstrated either in the colonic segments or in the kidney. These findings indicate that a local induction of the mixed function oxidase system is not likely to be responsible for the organotropism of the DMH-induced colonic carcinogenesis.

Segmental variations in the surface architecture of the normal rat colonic mucosa.

A microdissection technique used previously in the small intestine has been adapted for the rat colon in order to determine morphometric data and to calculate surface parameters in various proximal and distal segments (caecum, ascending and descending colon, rectum) of normal colonic mucosa. From the caecum to the rectum there was a gradual significant decrease in the diameter of the middle portions of the crypts, in the number of crypts per unit area and the inner intestinal circumference, as well as in the total mucosal surface per mm intestinal length and the surface of all crypts per unit area. However, there was an increase in the surface of the lining epithelium between the crypts from the caecum to the rectum. These findings are of importance when interpreting alterations in colonic function in terms of segmental changes in the mucosal architecture.

Adaptative response of alpha- and beta-glucosidase kinetics along the villi of rat self-filling jejunal blind loops.

Four and 12 days after the construction of self-filling jejunal blind loops in the rat, the apparent Km- and Vmax-values of lactase/beta-glucosidase and neutral alpha-glucosidase were determined by in-situ quantitative enzyme histochemistry, and changes in the villus-crypt architecture of the mucosa were examined by microdissection. The results were compared with corresponding data from sham-operated controls. The kinetics data were obtained from the base and the transition zone between medium and apical villus third by the use of a microdensitometric technique. The apparent Vmax of lactase/beta-glucosidase is significantly smaller than in the control rats at both measuring sites of the villi and even decreases from day 4 to day 12. The apparent Vmax of neural alpha-glucosidase is not affected, and thus the same increase in enzyme activity along the villi as in the controls is observed. The apparent Km of this enzyme, however, is already significantly increased on day 4 at both villus positions in the blind loops. A pronounced increase in villus surface area is detected in the blind loops as a result of an increase in crypt cell proliferation. The results indicate that enzymatic adaptation in the self-filling blind loops of rat jejunum exhibits different patterns for brush border alpha- and beta-glucosidases and is at least in part accomplished independently of the pronounced mucosal transformation occurring in this experimental condition.