Adequacy of endoscopic biopsy specimens for disaccharidase assays

Intestinal mucosa from 40 patients obtained by fiber-endoscopic biopsy was assayed for disaccharidases to determine suitability of this tissue for assay. The combined specimens from each patient provided 4.7–38.7 mg of tissue, adequate in all instances for duplicate determinations of protein, lactase, sucrase, and maltase. Tissue remained for assays of palatinase in 39 instances, trehalase and cellobiase in 37, and alkaline phosphatase in 22 cases. Twenty-four subjects had normal lactose tolerance tests and normal sucrase/lactase ratios. Thirteen patients with abnormal oral lactose tolerance tests were identified as having a primary low lactase activity on the basis of elevated sucrase/lactase ratios. This ratio was most helpful in making the diagnosis of a primary low lactase, since the mucosal specimens were not obtained from comparable areas. Tissue from three subjects with an abnormally low maltase was unsuitable for diagnosis. Endoscopic biopsy of mucosa appears to be satisfactory for disaccharidase assays in most instances.This work was supported by the Medical Research Service of the Veterans Administration.     

Disaccharidase levels in the small intestine in patients with diarrhoea following vagotomy and pyloroplasty

Diarrhoea is a common sequel to vagotomy and pyloroplasty but its cause is unknown. One of our patients who developed this complication had an abnormal lactose barium meal and responded well to a lactose-free diet. This led us to make a systematic study of disaccharidase activity in the small intestine in patients with diarrhoea following vagotomy and pyloroplasty.The small-intestinal disaccharidases have been estimated in jejunal biopsy specimens taken from 23 patients suffering from persistent diarrhoea, either continuous or episodic, after vagotomy and pyloroplasty. The disaccharidase values were normal in all but one of these patients. This patient showed hypolactasia but the sucrase and maltase levels were normal. The jejunal biopsy specimen taken from this patient showed a convoluted pattern under the dissecting microscope and severe partial villous atrophy under the light microscope. A repeat jejunal biopsy taken 20 cm beyond the duodeno-jejunal flexure showed similar appearances and also had a low level of lactase. However, two lactose tolerance tests and a lactose barium meal yielded normal results, suggesting that the low level of lactase in the upper jejunum was not a limiting factor in lactose absorption.The finding of one example of a low lactase level among 23 postvagotomy patients corresponds with what is being found in a study of normal subjects at present in progress.In effect, almost all patients with persistent diarrhoea after vagotomy and pyloroplasty have normal small-intestinal disaccharidase activity.     

The Effects of Iron Deficiency, Protein Deficiency and Worm Infestation upon Disaccharidase Activity in the Rat

The effect of iron deficiency anaemia, protein deficiency and worm infestation upon intestinal disaccharidase activity in the rat was assessed following the observation that these factors may have contributed to the premature onset of lactase deficiency in man. Adaptation of intestinal lactase occurred between eight and ten weeks of age in young rats fed a 10% lactose diet. Iron deficiency anaemia depressed jejunal and ileal lactase activity. Sucrase and maltase activities were not significantly affected by iron deficiency. Adaptation of intestinal lactase was prevented by both protein deficiency and combined iron/protein deficiency. Sucrase activity was not significantly depressed by either of these and in many instances activity was higher than the control group. Similar changes were noted with maltase. Worm infestation with Nippostrongylus brasi-liensis consistently depressed jejunal lactase and maltase activities, but had little effect on sucrase activity. It was concluded that intestinal lactase in particular was depressed by a number of environmental factors and adaptation of lactase thereby prevented.     

Ligation or external fistulation of the common bile duct in the rat. II. Intestinal disaccharidase activities.

72 h after ligation or external fistulation of the common duct the activities of maltase, sucrase and lactase in the homogenate of the small intestinal mucosa of the rat were determined. The experiments were performed in connexion with intestinal perfusion studies, and the disaccharidase activities were measured in unperfused intestinal segments as well as in intestinal loops which had previously been perfused with a sucrose-containing solution. After bile duct ligation, the sucrase and maltase activities in a previously perfused intestinal loop were not different from those in sham-operated animals, the lactase activity was diminished. In a nonperfused segment, the sucrase activity was greater, the maltase activity was unchanged, and the lactase activity was lower than in control animals. After bile duct fistulation, the sucrase, maltase and lactase activities in a perfused segment were lower than in sham-operated rats. In a nonperfused loop, the sucrase activity was greater, the maltase activity was unchanged, and the lactase activity was lower then in the corresponding control group. These data suggest that bile is a factor which influences the total mucosal disaccharidase activities, and, probably, the intracellular enzyme distribution.     

Sucrase deficiency in Greenland. Incidence and genetic aspects

The disaccharidase activities in small-intestinal surgical biopsy specimens from 97 Greenlanders were investigated. Five of the patients, or 5%, had sucrase deficiency. The diagnosis, sucrose malabsorption, was established by sucrose tolerance tests. In all parts of the world other than the arctic regions sucrase deficiency is a rare condition. The patients were divided into three separate groups in accordance with their sucrase activity. The middle group was considered to be heterozygote carriers of the sucrase-deficient gene. The number of people in the group corresponded to the theoretical number of heterozygotes in accordance with the Hardy-Weinberg equation, suggesting that sucrase deficiency is recessively inherited in a simple Mendelian fashion. Four of the five patients with sucrase deficiency had deficiency of lactase as well. The nutritional implications are discussed.     

Intestinal disaccharidase activities and activity ratios in a group of 60 adult German subjects

Lactase, maltase and sucrase activities were determined in samples of jejunal mucosa obtained by suction biopsy from 60 healthy adult German males. Primary adult hypolactasia ("lactase deficiency") was found in 8 subjects (13%). Maltase:lactase and sucrase:lactase activity ratios were significantly higher in post-weaning hypolactasia than in adult lactase persistence. Sources of variation in disaccharidase activities measured in biopsy tissue homogenates are discussed.     

Incidence and Clinical Significance of Lactose Malabsorption in Adult Coeliac Disease

Fifty-one adult patients with coeliac disease, verified by a proximal small-intestinal biopsy, were investigated. Before treatment with a gluten-free and low-lactose diet 52% showed a slight rise in blood glucose during the lactose tolerance test. Seventy-nine per cent of these patients had watery stools, and 88% had three or more bowel movements a day—statistically significantly different from the coeliac patients with a normal lactose tolerance test. After treatment 12% had a flat lactose tolerance curve. Half of them (6%) had specific lactase deficiency. This is approximately the incidence of lactose malabsorption in the general Danish population. The small-intestinal disaccharidases and alkaline phosphatase levels were severely depressed before treatment. After treatment the activities increased, but not to normal. We conclude that lactose malabsorption is a clinically important condition in many patients with untreated coeliac disease, giving rise to more frequent and more watery stools. In well-treated coeliac disease lactose malabsorption is not commoner than in the general population. The lactose activity in a proximal intestinal biopsy specimen was found to be an unreliable indicator of lactose malabsorption in coeliac disease.     

Incidence and clinical significance of lactose malabsorption in adult coeliac disease

Fifty-one adult patients with coeliac disease, verified by a proximal small-intestinal biopsy, were investigated. Before treatment with a gluten-free and low-lactose diet 52% showed a slight rise in blood glucose during the lactose tolerance test. Seventy-nine per cent of these patients had watery stools, and 88% had three or more bowel movements a day--statistically significantly different from the coeliac patients with a normal lactose tolerance test. After treatment 12% had a flat lactose tolerance curve. Half of them (6%) had specific lactase deficiency. This is approximately the incidence of lactose malabsorption in the general Danish population. The small-intestinal disaccharidases and alkaline phosphatase levels were severely depressed before treatment. After treatment the activities increased, but not to normal. We conclude that lactose malabsorption is a clinically important condition in many patients with untreated coeliac disease, giving rise to more frequent and more watery stools. In well-treated coeliac disease lactose malabsorption is not commoner than in the general population. The lactose activity in a proximal intestinal biopsy specimen was found to be an unreliable indicator of lactose malabsorption in coeliac disease.     

Influence of exocrine and endocrine pancreatic function on intestinal brush border enaymatic activities.

Digestive enzymatic activities (disaccharidases, alkaline phosphatase, peptide hydrolases) have been determined in the mucosa of 14 patients with chronic pancreatitis. All had an abnormal secretin-pancreozymin test. Four patients had insulin-dependent diabetes mellitus, four a pathological glucose tolerance test. Nine patients had steatorrhoea. Maltase, sucrase, and alkaline phosphatase activity was significantly elevated in patients with exocrine pancreatic insufficiency, whereas those of lactase, trehalase, and peptide hydrolase were normal. Patients with steatorrhoea had higher maltase and sucrase activity than those without steatorrhoea, whereas decreased glucose tolerance had no effect on brush border enzymatic activity. It is suggested thatdecreased exocrine rather than decreased endocrine pancreatic function is responsible for the increase in intestinal disaccharidase and alkaline phosphatase activity, possible by the influence of pacreatic enzymes on the turnover of brush border enzymes from the luminal side of the mucosal membranes or by direct hormonal stimulation though cholecystokinin.     

Influence of D-galactosamine and alpha-naphthylisothiocyanate on the activities of some intestinal enzymes

The activities of lactase, sucrase, maltase and gamma-glutamyl transferase (gamma-GT) were determined in homogenates of rat jejunal mucosa 24 h after acute administrations of D-galactosamine (GALN) (1.855 mmol/kg; i.p. injection) and alpha-naphthyl-isocyanate (ANIT) (0.540 mmol/kg; given by gastric tube). The animals were fasted either 24 h or 72 h prior to sacrifice. In rats fasted only 24 h, GALN treatment resulted in a pronounced decrease in lactase and in a moderate elevation of sucrase and maltase. ANIT clearly reduced lactase and, to a lesser extent, sucrase, while it increased maltase. Seventy-two hour fasting has a modifying role. All disaccharidase activities tended to decrease, except for maltase in the ANIT treated group, where an increase was recorded. gamma-GT showed no significant changes after either GALN or ANIT treatment in rats fasted 24 h. However, the 72-hour food deprivation diminished it in ANIT intoxication. It is obvious that the intestinal enzymes are influenced by the hepatic damage produced by GALN and ANIT.     

Disaccharidase activity in the small intestine of susceptible and resistant mice after primary and challenge infections with Giardia muris.

The activities of four disaccharidases were examined in resistant (C57Bl/6) and susceptible (C3H/HeN) mice during the primary infection with Giardia muris and after challenge with either trophozoite extract or cysts. Significant decreases in lactase, sucrase, trehalase, and maltase activities in C57Bl/6 mice and lactase and sucrase activities in C3H/HeN mice in the anterior 25% of the small intestine were observed on day 10 after infection. The activities of maltase, sucrase, trehalase, and lactase in the jejunum of C3H/HeN mice were significantly reduced after challenge with trophozoite extract, when compared with the uninfected or infected, but not challenged animals. Decreases in enzyme activities of C3H/HeN mice were evident as early as 12 hours after challenge with the extract. The resistant C57Bl/6 mice showed little change in disaccharidase activity after challenge with trophozoite extract. On the other hand, challenge with cysts resulted in a few decreases in disaccharidase activities in both strains of mice: C57Bl/6 mice showed decreases in the duodenum, while disaccharidases of C3H/HeN mice had lower activity more posteriorly. Thus, challenge with parasite antigen results in a more severe disaccharidase deficiency in susceptible hosts when compared with resistant ones.     

Duodenal disaccharidase activities in the follow-up of villous atrophy in coeliac disease

BACKGROUND: In active coeliac disease, mucosal atrophy is associated with a marked decrease in intestinal disaccharidase enzyme activities. We investigated the value of duodenal mucosal disaccharidases to predict the severity of mucosal villous atrophy and its recovery in 50 patients with coeliac disease. METHODS: Duodenal mucosal histology and disaccharidase activities were studied at least twice with a mean interval of 9 months. Histology of specimens from all patients was examined by the same pathologist blinded to the data on disaccharidase activities. Mucosal damage was scored into four groups as follows: Grade 0 = normal mucosa; grade I = slight villous atrophy, that is, cryptic component 30%-50%; grade 2 = moderate villous atrophy, that is, cryptic component 50%-90%; grade 3 = severe villous atrophy, that is, cryptic component >90%. The enzyme activities of the disaccharidases were determined as U/g protein. RESULTS: Duodenal mucosal disaccharidase activities were good predictors of the grade of mucosal villous atrophy. Positive predictive values for moderate or severe villous atrophy were 90% for maltase (maltase activity <150 U/g protein), 86% for sucrase (<40 U/g protein) and 71% for lactase (<20 U/g protein). Accordingly, negative predictive values, that is, none or only minimal villous atrophy (grades 0 or 1) with normal disaccharidase activities, were 71% for maltase, 70% for sucrase and 63% for lactase. CONCLUSIONS: The increase in duodenal disaccharidase activities correlated with recovery of the mucosa based on histology. Besides the histological examination, measurement of disaccharidase activities offers an additional tool to evaluate response to a gluten-free diet in patients with coeliac disease.     

Disaccharidase deficiency in infants with cow's milk protein intolerance. Response to treatment

7 infants, aged 5 weeks to 11 months, with clinically documented intolerance to cow's milk protein, chronic diarrhea, and failure to thrive, underwent small intestinal (peroal, suction) biopsy before and after withdrawal of milk proteins. Mucosal specimens were examined by light microscopy and assayed for disaccharidase activities. In all patients, moderate to severe mucosal changes were presented, associated with marked inflammation of lamina propria and damages to the brushborder. Disaccharidase activities (lactase, sucrase, maltase and palatinase) were markedly depressed in all. Follow-up biopsies were obtained in 6 infants, after 3-5 months on a milk-protein-free diet. At the time of the second biopsy, the disaccharidase activities had risen significantly and histologic improvement had occurred in each instance. In infancy, intestinal mucosal lesions due to intolerance to cow's milk protein are histologically indistinguishable from those seen in gluten-sensitive enteropathy and are associated with marked secondary disaccharidase deficiencies. Following therapy, the activity of the disaccharidases become normal or near normal prior to the complete morphologic recovery of the small intestinal mucosa.     

The influence of age on intestinal dipeptidyl peptidase IV (DPP IV/CD26), disaccharidases, and alkaline phosphatase enzyme activity in C57BL/6 mice

The objective of this study was to determine and describe the age-related changes in intestinal brush border membrane enzyme activities that occur in C57Bl/6 mice. Specifically, jejunal, duodenal, and ileal dipeptidyl peptidase IV/CD26, disaccharidase (lactase, sucrase, and maltase), and alkaline phosphatase activities were determined. A significant correlation between analyzed intestinal brush border membrane enzyme activities and animal age was found. Our study revealed that intestinal dipeptidyl peptidase IV/CD26, lactase, sucrase, maltase, and alkaline phosphatase activities decline significantly with age (p < .05). Nevertheless, the horizontal (duodenum to ileum) enzyme activity patterns are not affected by age.     

Duodenal Disaccharidase Activities in the Follow-up of Villous Atrophy in Coeliac Disease

Background: In active coeliac disease, mucosal atrophy is associated with a marked decrease in intestinal disaccharidase enzyme activities. We investigated the value of duodenal mucosal disaccharidases to predict the severity of mucosal villous atrophy and its recovery in 50 patients with coeliac disease. Methods: Duodenal mucosal histology and disaccharidase activities were studied at least twice with a mean interval of 9 months. Histology of specimens from all patients was examined by the same pathologist blinded to the data on disaccharidase activities. Mucosal damage was scored into four groups as follows: Grade 0 = normal mucosa; grade 1 = slight villous atrophy, that is, cryptic component 30%- 50%; grade 2 = moderate villous atrophy, that is, cryptic component 50%-90%; grade 3 = severe villous atrophy, that is, cryptic component &gt;90%. The enzyme activities of the disaccharidases were determined as U/g protein. Results: Duodenal mucosal disaccharidase activities were good predictors of the grade of mucosal villous atrophy. Positive predictive values for moderate or severe villous atrophy were 90% for maltase (maltase activity &lt;150 U/g protein), 86% for sucrase (&lt;40 U/g protein) and 71% for lactase (&lt;20 U/g protein). Accordingly, negative predictive values, that is, none or only minimal villous atrophy (grades 0 or 1) with normal disaccharidase activities, were 71% for maltase, 70% for sucrase and 63% for lactase. Conclusions: The increase in duodenal disaccharidase activities correlated with recovery of the mucosa based on histology. Besides the histological examination, measurement of disaccharidase activities offers an additional tool to evaluate response to a gluten-free diet in patients with coeliac disease.     

Examination of small bowel enzymes in chronic diarrhea

BACKGROUND: In Indonesia, the proportion of daily carbohydrate intake is approximately 60-80%. A number of small bowel disorders can result in the impairment of absorption and enzyme deficiency. Chronic diarrhea is common in Indonesia. METHODS: Thirty-four functional dyspeptic patients with an endoscopically normal small bowel as a control group, and 17 chronic diarrhea patients from the Division of Gastroenterology, University of Indonesia/Cipto Mangunkusumo Hospital were included in this study. All patients underwent a gastroduodenojejunoscopy and an ileocolonoscopy examination. Biopsies were taken from the jejunum (two specimens) and the biopsy specimens were examined for enzyme analysis (lactase, maltase, sucrase). The data were analyzed by using the Kruskal-Wallis or anova. RESULTS: The lactase level of the chronic diarrhea group was significantly lower compared with that of the control group (1.941 +/- 1.621 vs 2.502 +/- 2.098 micro mol/min mg protein; P < 0.001). The maltase level of the chronic diarrhea group was significantly lower compared with that of the control group (280.942 +/- 148.173 vs 371.920 +/- 250.177 micro mol/min mg protein; P < 0.001). The sucrase level of the chronic diarrhea group was significantly lower compared with that of the control group (48.474 +/- 28.553 vs 66.727 +/- 49.685 micro mol/min mg protein; P < 0.001). CONCLUSION: The enzyme activity concentrations (lactase, maltase, sucrase) were much lower in chronic diarrhea cases compared with the controls.     

The Influence of Age on Intestinal Dipeptidyl Peptidase IV (DPP IV/CD26), Disaccharidases,and Alkaline Phosphatase Enzyme Activity in C57BL/6 Mice

The objective of this study was to determine and describe the age-related changes in intestinal brush border membrane enzyme activities that occur in C57Bl/6 mice. Specifically, jejunal, duodenal, and ileal dipeptidyl peptidase IV/CD26, disaccharidase (lactase, sucrase, and maltase), and alkaline phosphatase activities were determined. A significant correlation between analyzed intestinal brush border membrane enzyme activities and animal age was found. Our study revealed that intestinal dipeptidyl peptidase IV/CD26, lactase, sucrase, maltase, and alkaline phosphatase activities decline significantly with age (p < .05). Nevertheless, the horizontal (duodenum to ileum) enzyme activity patterns are not affected by age.     

Reinvestigation of lactose intolerant children: lack of correlation between continuing lactose intolerance and small intestinal morphology, disaccharidase activity, and lactose tolerance tests.

Thirty children on a lactose-free diet aged from 2-38 months who had previously been diagnosed as having secondary lactose intolerance were reinvestigated on 32 occasions by an oral lactose tolerance test, small intestinal biopsy, and measurement of disaccharidase activity in order to detect the presence of continuing lactose intolerance before reintroduction of milk. No correlation was found between continuing lactose intolerance, as diagnosed by the development of watery stools containing excess reducing substances after an oral load of lactose, and maximum blood glucose rise during a lactose tolerance test, lactase levels, and small intestinal morphology.     

The prevalence and severity of intestinal disaccharidase deficiency in human immunodeficiency virus-infected subjects

BACKGROUND: Gastrointestinal symptoms are distressing features of human immunodeficiency virus (HIV) infection, and management is often empirical, including withdrawal of dietary lactose. We assessed the prevalence and severity of intestinal disaccharidase deficiency in vitro and in vivo. METHODS: Fifty-four HIV-seropositive patients (19 HIV well +/- mild diarrhoea, 7 acquired immunodeficiency syndrome (AIDS) well, and 28 AIDS with diarrhoea) were studied with a combined non-invasive absorption-permeability-disaccharidase test that enables quantitative assessment of the rate of intestinal hydrolysis of lactose, sucrose, and palatinose. Thirty patients had jejunal biopsy specimens suitable for histomorphometric assessment, and 36 had in vitro disaccharidase activity measurement. RESULTS: Patients with HIV (with mild diarrhoea) and AIDS (with and without severe diarrhoea) had frequent but mild histomorphometric changes in jejunal specimens. This was associated with frequent (21%-100%) and often severe in vitro jejunal disaccharidase deficiency. In vivo hydrolysis of lactose, sucrose, and palatinose was impaired in 25%-75% of patients, apart from HIV well patients, who were normal. The prevalence of the in vivo lactase and sucrase deficiency was significantly (P < 0.006) lower than in vitro and severe in about 30%. CONCLUSIONS: Intestinal disaccharidase deficiency is common both in vitro and in vivo in HIV-seropositive patients but sufficiently severe to consider lactose withdrawal only in about a quarter of the patients with AIDS and diarrhoea.     

Lactose malabsorption in adult patients at the Hospital das Clínicas de Ribeir?o Preto

A standard oral lactose tolerance test (LTT) was performed in 32 white and 18 non-white hospitalized Brazilian adults. A flat LTT was found in 22 (68,75%) white and in 17 (97,45%) non-white patients indicating a 78% overall rate of lactose malabsorption, Both lactose absorbers and malabsorbers showed a modal milk ingestion of less than a 1 glass/day. Symptoms related to milk consumption or lactose administration were more common among lactose malabsorbers. Estimations of disaccharidase activity in intestinal mucosa specimens obtained by peroral biopsy in 28 patients confirmed a high prevalence of lactose deficiency, and disclosed only one false result, in the patient with a flat LTT and high intestinal lactase levels.