Structural and functional abnormalities of the small intestine due to nutritional folic acid deficiency in infancy.

Structural abnormalities and disaccharidase deficiency were demonstrated in biopsies of duodenal mucosa from four infants who had symptoms of failure to thrive and chronic diarrhea associated with a megaloblastic anemia. Goat's milk was the main dietary constituent for each infant for six to eight months prior to presentation. The structural abnormalities consisted of villous blunting, crypt hypertrophy, megaloblastic changes in epithelial cells, and nuclear enlargement. All changes reverted to normal with the addition of folic acid to the diet. This study provides evidence that nutritional folic acid deficiency can cause structural and functional alterations of the small intestine in infants.

Intraepithelial lymphocyte counts in small intestinal biopsies from children with diarrhoea.

We have investigated small intestinal biopsies from children with coeliac disease, acute gastroenteritis, failure to thrive and giardiasis, to find out if a high intraepithelial lymphocyte count is a feature specific to coeliac disease, or whether it is always associated with partial or subtotal villous atrophy. The results indicate that the normal range for childrens' intraepithelial lymphocyte counts is similar to that for adults (around 6-40 lymphocytes per 100 epithelial cells); that counts are high in coeliac disease, but also in some children with giardiasis or with failure to thrive in whom the jejunal biopsy appears otherwise normal; and that intraepithelial lymphocyte counts are normal in acute gastroenteritis even when there is partial villous atrophy with increased lamina propria lymphoid cell infiltrate. Thus, this measurement of small intestinal lymphocyte infiltration may be of diagnostic value is differentiating the diarrhoea of food intolerance from infectious diarrhoeas in young children.

Gastrointestinal milk allergy in childhood: a rational approach.

Nine children with "unequivocal symptoms attributable to cow's milk allergy" were referred for assessment. Detailed gastrointestinal and immunoallergic investigations confirmed this diagnosis in only one case. In three of the children an abnormality of sucrose absorption was detected by disaccharidase assay. The results of this study indicate the need for cow's milk provocation under controlled conditions before the diagnosis of gastrointestinal cow's milk allergy can be made. A protocol for the assessment of children with suspected cow's milk allergy is proposed.

Sucrase-isomaltase deficiency. Absence of an inactive enzyme variant.

Deficiency of sucrase-isomaltase, an intestinal enzyme complex that is essential for digestion of nutritionally important carbohydrates, appears to be inherited as an autosomal recessive in 0.2 per cent of North Americans. The molecular basis of the deficiency has not been elucidated. To characterize the enzyme defect quantitatively, papain-solubilized intestinal biopsies were analyzed for total enzyme protein by radioimmunoassay and for enzyme activity by hydrolytic assay. Normal intestine had a close correlation between immunologically reactive enzyme and enzymic activity. In contrast, seven patients with sucrase-isomaltase deficiency were found to have complete absence of the enzyme protein by radioimmunoassay even though up to 10 times more intestinal protein was present than with normal tissue. This absence of an inactive enzyme variant can be explained by a major (no-sense) mutation of the structural gene or by a complete repression of the regulatory mechanism that controls structural gene function.

Reversible intestinal mucosal abnormality in acrodermatitis enteropathica.

In 3 cases of acrodermatitis enteropathica duodenal biopsy performed at the outset of treatment showed a similar abnormality of the intestinal mucosa. Further biopsies taken during treatment showed progressive improvement of the intestinal mucosa with subsequent complete restoration of the normal cellular and villous pattern. The initial treatment was with expressed human breast milk and oral di-iodohydroxyquinoline. The latter was continued alone and later replaced by zinc sulphate. Changes in the intestinal epithelial cells and inflammatory cell infiltration of the lamina propria still detectable on di-iodohydroxyquinoline therapy reverted to normal with oral zinc.

An epidemic of diarrhoea in human neonates involving a reovirus-like agent and 'enteropathogenic' serotypes of Escherichia coli.

During December 1974, an epidemic of diarrhoea occurred in the Royal Children's Hospital, Melbourne, in a ward caring for neonates with acute or chronic medical and surgical problems. Electron microscopy of diarrhoeal faeces revealed a reovirus-like particle ('duovirus' or 'rotavirus') known to cause acute enteritis in older children. This virus is considered to have been primarily involved in the aetiology of the epidemic. In addition, three 'enteropathogenic' serotypes of Escherichia coli were isolated from babies during the epidemic, but none produced enterotoxin when tested in ligated ileal loops of rabbits or in monolayers of Y1 adrenal cells. Further epidemics of neonatal diarrhoea must be studied using culture and electron microscopy of faeces to determine the relative importance of this virus and of E. coli in the aetiology of diarrhoea in this age-group.

New virus associated with diarrhoea in neonates.

Since December, 1974, there has been an increase in the incidence of acute diarrhoea in the neonatal nurseries of five Melbourne metropolitan hospitals. Four of these have had epidemics, and the incidence of endemic diarrhoeal disease has increased. Extracts of faeces from 148 patients from the five hospitals were examined by electron microscopy. "Duovirus" particles were detected in 82 of these extracts, including at least one from each hospital. No bacterial pathogens were isolated. It seems likely that "duovirus" is an important cause of sporadic and epidemic acute diarrhoeal disease in neonates. It is important to note that the absence of a recognized bacterial pathogen does not exclude an infective cause, especially when sugar intolerance is present. Appropriate measures to minimize the spread of infection must be employed.

A family study of coeliac disease.

Studies by Thompson, 1 Carter et al, 2 MacDonald et al. and McCrae 4 have all shown a high familial frequency of coeliac disease (CD). The diagnostic criteria differed in each study; in Thompson's patients the diagnosis was based on clinical or historical data alone; in Carter's study response to a gluten-free diet was required, while in MacDonald's and McCrae's studies the diagnostic criteria included the demonstration of the lesion of CD by small bowel biopsy. In MacDonald's study some asymptomatic cases were discovered and a few of these had normal fat balance results. No hereditary pattern emerged from these studies though MacDonald postulated a dominant gene with variable penetrance while McCrae suggested that susceptibility to CD is inhereited multifactorially and that enviromental factors other than dietary gluten are of aetiological importance. Hoffman et al. 5, on the other hand, have described discordance for CD in identical twins.

Immunofluorescence in duodenal mucosa of children with acute enteritis due to a new virus.

Electron microscopy od duodenal mucosa from children with acute non-bacterial enteritis has shown virus particles in epithelial cells. Indirect immunofluorescent techniques applied to the same tissue showed virus antigen localized in the cytoplasm of epithelial cells of the villi. Specific IgM antibody was present in sera from infected patients as early as two days after the onset of symptoms. Virus particles from different patients appeared to share a common antigen. The evidence presented supports our belief that this new virus was the cause of acute enteritis in the children studied.

Importance of a new virus in acute sporadic enteritis in children.

In a year-long survey of children admitted with acute enteritis to hospital in Melbourne, Australia, an aetiological agent was found in approximately 75% of patients. During most months of the year a newly described virus belonging to the family Reoviridae was detected by electron microscopy of faecal extracts from more than 50% of patients. Recovery of this virus reached a peak (73%) during the winter. All age-group up to five years of age were susceptible to infection, which was occasionally fatal. Duration of infection was brief, with a probable incubation period of less than two days. Infections acquired in hospital were not uncommon. The name of this new virus is not decided. The name "duovirus" is proposed rather than "rotavirus" as previously suggested. There is already convincing evidence that this new virus will prove to be the most important aetiological agent of sporadic acute enteritis in young children.

The toxicity of certain cereal proteins in coeliac disease.

Gliadins from wheat, rye, and oats, and from wheat glutenin were digested with pepsin, trypsin, and pancreatin and the products (PTC digests) chromatographed on sulphopropyl (SP) Sephadex. Fractions eluted near neutral pH from wheat, rye, and oats gliadin digests all had very similar amino acid composition, although the oats fraction was higher in sulphur-containing amino acids. The major amino acids present in all were glutamine/glutamic acid and proline. The amount of fraction eluted near neutral pH from oats gliadin digest was about 13% of that eluted from digests of wheat and rye gliadins. Moreover, the yield of gliadin from oatmeal was only 0.5% compared with 2.4% and 2.8% from rye and wheat flours respectively. The amount of fraction eluted from wheat glutenin digest was about 70% of that obtained from wheat and rye gliadin digests. The fractions eluted near neutral pH from all protein digests were defectively digested by remission coeliac mucosa, and D-xylose excretion tests with the fraction from the wheat gliadin digest (fraction 9) indicated that it is harmful to subjects with coeliac disease, whereas the other fractions of this digest gave no such evidence. The results of the present work indicate that counterpart fractions to fraction 9 obtained from wheat glutenin and rye and oats gliadins may also be important in the aetiology of coeliac disease.