Gastric emptying in patients with flatulent dyspepsia, with and without gallbladder disease

It has been suggested that the symptoms of flatulent dyspepsia are caused by a functional disturbance of the upper gastrointestinal tract. The aim of this study was to investigate delayed gastric emptying as the basis of symptoms in patients with and without gallbladder disease and after cholecystectomy. There were 13 dyspeptic patients with gallbladder disease, 12 with normal gallbladders, and 13 post-cholecystectomy patients. Gastric emptying was measured by means of a 99mTc-labelled scrambled egg meal and external scintillation counter. The rate of emptying in the symptomatic groups was compared with that in 24 asymptomatic normal control subjects and 12 non-dyspeptic patients with gallbladder disease. Delayed gastric emptying tended to occur in patients with gallbladder disease with and without dyspepsia and was not specifically associated with symptoms.     

Enzyme activities in jejunal biopsy samples from patients with adult coeliac disease with and without steatorrhoea

Highly sensitive techniques have been used for the assay of a range of marker enzymes including lactase, sucrase, alkaline phosphatase, leucyl-beta-naphthylamidase (brush border), and 5'-nucleotidase (basolateral membrane) in jejunal biopsy homogenates from patients with adult coeliac disease with and without steatorrhoea and from a control group. The absorption of D-xylose and vitamin B12 was compared in the two groups with coeliac disease. All enzymes assayed were equally depressed in both groups of coeliac disease as compared with the controls. The absorption of D-xylose and vitamin B12 were reduced in the patients with steatorrhoea compared with those without steatorrhoea. The findings suggest that lack of steatorrhoea in some patients with coeliac disease is due to better preservation of the ileal function rather than to a less severe jejunal mucosal injury.     

Immunoglobulins in jejunal mucosa and serum from patients with adult coeliac disease.

Immunoglobulin (Ig)-containing cells were quantitated immunohistochemically in biopsy specimens from the proximal jejunal mucosa. The numbers of IgA, IgM, and IgG immunocytes in a defined "mucosal tissue unit" were, on the average, raised 2.4, 4.6, and 6.5 times, respectively, when 13 adult patients with untreated coeliac disease (CD) were compared with 15 patients who had a histologically normal mucosa. The IgA-:IgM-:IgG-cell ratios averaged 66:28:6 in untreated CD and 79:18:2.6 in the controls. Similar quantitative data in 10 patients with treated CD were intermediate. IgD- and IgE-containing cells were rare in all patient groups. Most patients in a heterogeneous malabsorption group showed a jejunal Ig-containing cell population similar to that seen in CD, indicating that the local immunocyte pattern may not be specific for the latter disease. The only significant alteration in serum Ig levels related to CD was a raised concentration of IgA compared with normal. This was consistent with the increased amounts of extracellular IgA revealed in the mucosa. However, there was no indication of a defect in the transport of dimeric IgA and IgM through SC-producing cells, which in the CD mucosa were present in both crypt and surface epithelium.     

Cellular infiltrate of jejunal biopsies in adult coeliac disease in relation to gluten withdrawal

A comparison has been made of inflammatory cell counts in the lamina propria and epithelium of jejunal biopsies in 11 patients with adult coeliac disease with those found in 12 control subjects. In the coeliac patients, there were significant increases in the numbers of total cells, plasma cells, and intraepithelial lymphocytes, but a significant reduction in lamina propria lymphocytes. Following clinical improvement on a strict gluten-free diet, significant changes in cell counts occurred, but with the exception of lymphocytes in the lamina propria, the counts were still abnormal. Analysis of five patients in whom the biopsy improved to near normal morphology and of six in whom there was no such improvement showed that significant falls in plasma cells and rises in lymphocytes in the lamina propria could occur without improvement in other morphological appearances. These results seem relevant to the problem of diagnosing coeliac disease in patients who, on gluten withdrawal, show an unequivocal clinical response, but no gross morphological improvement in the jejunal biopsy. On the basis of the observed changes in cell counts, there seems little justification in questioning the diagnosis of coeliac disease in such patients.     

Gastric secretion and emptying after ordinary meals in duodenal ulcer.

We have studied the gastric response to an ordinary solid-liquid meal in 12 patients with active duodenal ulcer and 8 healthy volunteers. Our method employs gastric and duodenal markers to quantify acid, pepsin, and volume outputs in response to the meal, without manipulating intragastric pH. Intragastric volume, rate of gastric emptying, delivery of acid into the duodenum, and serum gastrin response were also measured simultaneously. On a separate day, peak acid output in response to betazole (1.5 mg per kg subcutaneously) was determined. Our results indicate an inappropriately prolonged gastric secretory response to meals in duodenal ulcer disease, without a concomitant increase in peak postprandial secretory rates or an increase in serum immunoreactive gastrin levels. Further, the stomach in duodenal ulcer disease did not "retain" the additional acid secreted in the later postprandial period, and abnormally high rates of acid delivery into the duodenum occurred. Our data are consistent with a dual defect in the duodenal mechanisms regulating both acid secretion and acid delivery into the duodenum.     

Identifying toxic fractions of wheat gluten and their effect on the jejunal mucosa in coeliac disease

THE TOXICITY OF THREE FRACTIONS (A, B, AND C) OBTAINED BY ULTRAFILTRATION OF A PEPTIC: tryptic digest of gluten has been assessed by serial feeding experiments in patients with treated coeliac disease.The first fraction (A), which contains amino acids and oligopeptides, produced no damage to the jejunal mucosa.The other two fractions (B and C) both caused mucosal damage.Fraction B, which contains the products of digestion of smaller molecular weight, consists of polypeptides which are concentrated in the region of 8000 molecular weight. It contains no gliadin (molecular weight 50 000) or gluten.Ultrastructural evidence of damage was visible six hours after challenge with fraction B and by 10 hours histological abnormalities were also present.Ultrastructural abnormalities occurred early in the epithelial cells and preceded changes in the basement membrane and capillaries.The disaccharidases showed a pronounced depression in all three subjects by 24 hours.The rapid onset of damage after challenge, coupled with the evidence of recovery as soon as 72 hours later, is more in keeping with a direct action on the surface epithelial cells rather than an immune mechanism.     

Immunoglobulins in the jejunal mucosa in adult coeliac disease and dermatitis herpetiformis after the reintroduction of dietary gluten.

Cells containing immunoglobulin (IgA, IgG, IgM) have been measured and the distribution of extracellular and epithelial cell immunoglobulin assessed in treated patients with adult coeliac disease (ACD) and dermatitis herpetiformis (DH) before and after gluten was reintroduced to the diet. Patients with ACD and DH frequently had IgM and IgG cells above the normal range even before re-exposure to gluten, although the range of IgA cells was normal. In both diseases IgA and IgM cells increased after gluten with a proportionally greater rise in the latter, so that numbers of IgM cells, but not of IgA, exceeded the control range in all but one patient. There were increased quantities of IgA and IgM extracellularly in the lamina propria and in epithelial cells after challenge with gluten. Third component of complement was also found in some biopsies after re-exposure to gluten. These findings support the suggestion that gluten induces a humoral immunological response within the small intestinal mucosa and that both IgA and IgM systems are involved.     

Reintroduction of gluten in adults and children with treated coeliac disease.

Twenty-eight patients, thought to have coeliac disease and on gluten free diets, were put on a normal diet to confirm their diagnoses. Nineteen had been diagnosed in adult life (ACD) and nine in childhood (CCD). Patients were assessed on jejunal, morphological, and symptomatic parameters. Eighteen patients with ACD relapsed within seven weeks. Nine patients with CCD relapsed at variable times but five took longer than seven weeks, the longest period beint 10 months. Seven patients had no symptoms despite morphological deterioration during challenge and one patient, with ACD, did not relapse and was HLA B8 negative. This patient with ACD had subtotal villous atrophy on two jejunal biopsies and later showed morphological improvement on a gluten free diet. There was no correlation between the relapse time and time spent on a gluten free diet.     

Analysis and clinical effects of gluten in coeliac disease.

The prolamin working group coordinates research on laboratory gluten analysis in food and on clinical evaluation of patient sensitivity to prolamins. As an observer organization to the Codex Alimentarius Commission, the group summarizes current data on analysis and effects of gluten in coeliac disease. All types of gliadin, the ethanol-soluble fraction of gluten, contain the coeliac-active factor. However, coeliac toxicity and immunogenicity (humoral and cellular) of various prolamins are not identical in coeliac patients. There are no conclusive data on the threshold of gluten sensitivity of coeliac patients. Information as to the long-term risk to coeliac patients exposed to small doses of gliadin is lacking. Therefore, every effort should be made to keep the diet of coeliac patients as gluten-free as possible. The prolamin group is currently evaluating a new enzyme-linked immunosorbent assay (ELISA) protocol for gluten analysis that could serve as a basis for further Codex regulations. The group recommends adherence to a single Codex limit for gluten-free foods. The current limit of 200 ppm gluten is questionable and requires reconsideration based on new information that will be available soon.     

Gastric emptying and small intestinal mucosal injury in rats.

A technique was developed to produce small intestinal mucosal injury in vivo by perfusing the mid-small intestine of rats with HCl, NaOH, FeSO4, and AgNO3. Three hours following injury, gastric emptying and small intestinal transit were measured by examining the gastrointestinal distribution of a non-absorbable radioisotope which had been placed in the stomach for 1 hour. There was a strong association between the villus injury produced by various concentrations of the injurious agents and the degree of gastric retention. Necrosis of villus tips, as produced by AgNO3, was sufficient to cause marked gastric retention. Injury to the small intestinal mucosa of one parabiotic rat did not produce gastric retention in the partner. It is concluded that injury to small intestinal villi is sufficient to induce gastric retention and that the effect is most likely nerve-mediated.     

Jejunal mucosal immunoglobulin-containing cells and jejunal fluid immunoglobulins in adult coeliac disease and dermatitis herpetiformis

Immunoglobulin-containing plasma cell densities in the jejunal mucosa and serum and jejunal fluid immunoglobulins have been measured in patients with adult coeliac disease and dermatitis herpetiformis with and without jejunal mucosal abnormality. Studies were performed in patients before and after treatment of the jejunal lesion.

Total immunofluorescent plasma cells were increased in untreated adult coeliac disease and dermatitis herpetiformis patients with jejunal lesions, but in general the normal predominance of IgA > IgM > IgG was found. There was no difference from controls in IgA-containing cells in the two conditions before or after treatment. The numbers of IgM-containing cells were significantly increased both before and after treatment in groups of patients with adult coeliac disease and dermatitis herpetiformis who had jejunal lesions. IgG-containing cells were significantly raised in only the before-treatment groups. Patients with dermatitis herpetiformis without jejunal lesions, even whilst on gluten-containing diets, had normal numbers of immunoglobulin-containing cells. IgA and IgM jejunal fluid immunoglobulins were significantly raised in dermatitis herpetiformis and adult coeliac disease.

It is concluded that patients with dermatitis herpetiformis with jejunal morphological abnormality have a comparable immunological disturbance of the jejunal mucosa to that found in adult coeliac disease.

     

Gastric emptying of oil from solid and liquid meals

Digestion of fat in pancreatic insufficiency (PI) is strongly affected by how rapidly fat enters the duodenum. We postulated that: (1) oil empties faster in PI than in normals and (2) in both, it empties in a load-dependent fashion. We used a gamma camera to test these ideas by comparing gastric emptying of iodine-123 iodinated oil in normal and pancreatic-insufficient subjects after 15 g of free oil were ingested in a small spaghetti meal and 60 g of oil were ingested in a large spaghetti meal and in a milk emulsion. Indium-113m marked gastric emptying of water in the milk. In both groups after all meals, oil emptied fastest initially, slowing later; and oil emptied three to four times faster when 60 g vs 15 g were ingested. There were no significant differences between the groups of subjects with respect to gastric emptying of the spaghetti meals, but the pancreatic-insufficient subjects emptied both oil and water faster from the milk emulsion than did the normal subjects. The slower emptying of oil in the normal subjects was associated with significantly more layering of oil to the top of the intragastric milk emulsion.     

Low gluten diet in the treatment of adult coeliac disease: effect on jejunal morphology and serum anti-gluten antibodies.

Treatment of patients with coeliac disease with a low gluten containing diet (LGD) remains controversial. We have studied jejunal morphology and antigluten (AG) antibody titres by ELISA in patients on a LGD of 2.5-5 g/day for three to 14 months (median six months) and compared results with patients on a strict gluten free diet (GFD) for six to 27 months (median 13 months). We found no significant difference in villous height or crypt depth (eight LGD v 10 GFD patients) or serum AG-IgA, -IgG, and IgM titres (13 LGD v 12 GFD patients). there was however, a significant increase (p less than 0.05) in intra-epithelial lymphocytes in those patients on a LGD. We conclude that adult coeliac patients can tolerate a LGD without gross morphological change and without initiating significant AG antibody responses.     

Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease.

The functional integrity of the small bowel is impaired in coeliac disease. Intestinal permeability, as measured by the sugar absorption test probably reflects this phenomenon. In the sugar absorption test a solution of lactulose and mannitol was given to the fasting patient and the lactulose/mannitol ratio measured in urine collected over a period of five hours. The sugar absorption test was performed in nine patients with coeliac disease with an abnormal jejunum on histological examination, 10 relatives of patients with coeliac disease with aspecific symptoms but no villous atrophy, six patients with aspecific gastrointestinal symptoms but no villous atrophy, and 22 healthy controls to determine whether functional integrity is different in these groups. The lactulose/mannitol ratio (mean (SEM) is significantly higher in both coeliac disease (0.243 (0.034), p < 0.0001)) and relatives of patients with coeliac disease (0.158 (0.040), p < 0.005)) v both healthy controls (0.043 (0.006)) and patients with aspecific gastrointestinal symptoms (0.040 (0.011)). The lactulose/mannitol ratio in relatives of coeliac disease patients was significantly lower than in the coeliac disease patient group (p = 0.04). The lactulose/mannitol ratio was the same in healthy controls and patients with aspecific gastrointestinal symptoms. It is concluded that the sugar absorption test is a sensitive test that distinguishes between patients with coeliac disease and healthy controls. The explanation for the increased permeability in relatives of patients with coeliac disease is uncertain. Increased intestinal permeability may be related to constitutional factors in people susceptible to coeliac disease and may detect latent coeliac disease. The sugar absorption test may therefore be helpful in family studies of coeliac disease.     

Protein synthesis by cultured jejunal mucosa from control subjects and patients with coeliac disease.

Jejunal biopsies from patients with coeliac disease and from controls were cultured in vitro for 24 hours with 14C-labelled leucine. The net rate of protein synthesis was found to be linear over 24 hours for mucosa from control subjects and patients with coeliac disease. Protein synthesis by mucosa from untreated coeliac patients was significantly greater than by control mucosa. Protein synthesis by treated gluten-sensitive coeliac mucosa was significantly less than that by untreated coeliac mucosa and did not differ from control mucosa. Protein synthesis by treated non-responsive coeliac mucosa was significantly less than untreated coeliac mucosa but greater than control mucosa. The differences in protein synthesis could not be accounted for by differences in the size of the enterocyte leucine pool. Analytical subcellular fractionation of cultured jejunal mucosa showed that most of the protein synthesised in vitro was found in the cytosol and endoplasmic reticulum-brush border fractions of the enterocyte.