Charlotte M. Anderson

Association of pancreatic insufficiency and chronic neutropenia in childhood.

In childhood, pancreatic exocrine insufficiency is rarely encountered except as one of the features of cystic fibrosis, which is in contrast to the pattern of pancreatic disease in adults, where pancreatitis is common. However, paediatricians recognize that some children with symptoms of pancreatic insufficiency do not have the chronic chest infection and raised levels of electrolytes in the sweat characteristic of cystic fibrosis. Recently Bodian, Sheldon, and Lightwood (1964) have described congenital hypoplasia of the exocrine pancreas in 2 such children. Variable neutropenia and thrombocytopenic purpura occurred in both but did not receive special comment. In 1964 Shwachman, Diamond, Oski, and Khaw reported 5 similar patients, drawing particular attention to the association of haematological and pancreatic abnormalities. These reports stimulated us to review those of our patients whom we knew to have pancreatic exocrine insufficiency but not the other findings of cystic fibrosis, and those children with so-called idiopathic neutropenia. Two of us (C.M.A. and J.H.C.) had recognized as far back as 1946 one patient with both pancreatic insufficiency and chronic neutropenia, but had not pursued this association. A preliminary report of some of the findings in these patients has been published (Colebatch, Anderson, Simons, and Burke, 1965), but further patients have been encountered since that time. In all, 19 children have presented with, initially, at least one of these features, and 11 of them have now been shown to have both. Although the syndrome is rare, we consider it to be the major disorder of pancreatic exocrine function of children in whom cystic fibrosis has been excluded. Associated features are noteworthy in a number of the patients, particularly the radiological changes of metaphysial dysostosis. A familial incidence of the

Bacterial microflora of the upper gastrointestinal tract in infants with protracted diarrhoea

The aerobic and anaerobic bacterial microflora of the upper gastrointestinal tract in infants with protracted diarrhoea has been described and compared with a group of control infants without diarrhoea. The duodenal juice of patients with protracted diarrhoea was rarely sterile and was characterized by an increase in numbers and types of microorganisms and by the presence of coliforms, particularly Esch. coli. In individual patients the same serotypes of Esch. coli were found throughout the intestinal tract. The presence of Esch. coli in the upper small intestine may be as important to the aetiology of protracted diarrhoea as it is to acute diarrhoea.

Role of bile salts in fat malabsorption of premature infants

Eighteen premature infants were studied. 9 were fed with human milk and 9 with a modified cows milk. Subsequent to a 72-hour fat balance, a duodenal intubation was performed on the 14th day of life. Total bile acids were determined in serial duodenal aspirates before and after a milk feed. Bile acid excretion in the faeces during a 72-hour period was also measured. Infants fed with human milk absorbed fat better (mean fat absorption coefficient, 75%) than those receiving a cows milk formula (mean fat absorption coefficient, 60%). In both groups the bile acid concentrations after a meal were often less than that required for the formation of micellar solutions and solubilization of fat (i.e. <2 mmol/l.). With human milk, a reasonable fat absorption occurred even with bile acid levels below the critical micellar concentration. In the infants fed with the cows milk formula, impaired fat absorption was correlated with low bile acid levels. Infants on human milk excreted less bile acids in the stool (mean, 41·9 μmol/kg per 24 hr) than did infants fed with the cows milk formula (mean, 72·4 μmol/kg per 24 hr). In both groups the faecal loss of bile acids was increased compared with that in older infants and children.

Peptidase activity of biopsies of the duodenal mucosa of children with and without coeliac disease

Abstract Duodenal mucosal biopsy specimens from coeliac patients were compared with similar specimens from control patients and with segments of rat intestine in their ability to hydrolyse a number of peptides. It was found that the following peptides were all hydrolysed by coeliac duodenal mucosa at rates similar to those found with mucosa from control patients and with rat intestine: l -alanyl-glycyl-glycine, glycyl- l -leucine, l -leucyl-glycine, glycyl-glycine, glycyl- l -proline, l -prolyl-glycine and l -leucinamide.

The relationship of dietary lactose to refractory diarrhoea in infancy.

Refractory diarrhoea occurring in young babies subsided following exclusion of lactose from the diet. In most patients investigated, small bowel biopsy demonstrated abnormal histology and depression of lactase activity. However, the intestinal mucosa eventually returned to normal and the ingestion of lactose no longer produced symptoms. The clinical value of the observations leading to decreased morbidity in babies with persistent gastroenteritis and the simple management of these patients, without the need for special investigations, is discussed.

Coeliac disease. Some still controversial aspects.

When Dicke (1950) discovered the harmful effects of dietary wheat and rye flour in children with coeliac disease he opened the way for an effective empirical form of dietary treatment which has been widely accepted. But in spite of the apparently specific nature of the intolerance to wheat and rye flour or, to be more precise, the gluten contained in these flours, and the numerous studies directed towards elucidating this relation, the precise pathogenesis of the disorder remains unclear. This has allowed the persistence of a non-uniform approach to its definition, diagnosis, and management, and a number of points of controversy regarding these three aspects still remain.

PANCREOZYMIN ‐ SECRETIN TEST OF EXOCRINE PANCREATIC FUNCTION IN CYSTIC FIBROSIS AND THE SIGNIFICANCE OF THE RESULT FOR THE PATHOGENESIS OF THE DISEASE*

Pancreozymin‐secretin tests were performed on 10 children with cystic fibrosis of the pancreas, who did not show any clinical symptoms of exocrine pancreatic insufficiency. The results indicate that in this particular group of patients water and bicarbonate secretion from the pancreas is more severely affected by the disease than enzyme secretion. Thus these patients secrete a small amount of pancreatic juice with a very low bicarbonate content but an abnormally high concentration of enzymes.

SUGAR INTOLERANCE AS A CAUSE OF PROTRACTED DIARRHOEA FOLLOWING SURGERY OF THE GASTROINTESTINAL TRACT IN NEONATES

Osmotic diarrhoea, resulting from disturbed sugar digestion and absorption is shown to occur quite frequently following a variety of gastrointestinal surgical procedures in neonates. These include gastrostomy, small bowel anastomosis and colostomy. Suitable manipulation of the sugar content of the diet will mitigate the symptoms, thus averting fluid loss, decreasing morbidity and sometimes mortality.

Assessment of medium-chain triglyceride feeding in infants with cystic fibrosis.

Impaired growth is a major clinical feature of cystic fibrosis (CF), and correlates well with the degree of impairment of pulmonary function (Sproul and Huang, 1964), though other factors contribute to poor growth. Steatorrhoea occurs in most patients and is reduced, but rarely eliminated, by administration of pancreatic extracts with meals. Substitution of medium chain triglycerides (MCT) for the long-chain fats contained in a normal diet is beneficial to patients with pancreatic insufficiency (Greenberger, Ruppert, and Tzagournis, 1967; Burke and Anderson, 1967). This is because of differences between the absorption of MCT, which consists of fatty acids with chain lengths of C8-10, and that of long-chain fats (Isselbacher, 1966). Replacement of dietary longchain fats by MCT has been shown to reduce greatly steatorrhoea in patients with CF (Kuo and Huang, 1965; Burke and Anderson, 1967). Kuo and Huang (1965) also reported increased weight gain in 4 infants fed an MCT diet for 6 weeks and 10 children treated for longer periods. However, the results of more prolonged treatment in a larger number of infants with CF have not been reported. Recently a commercial preparation (Triglyde-Mead Johnson), which contains MCT, has become available. This has prompted us to assess the effect of such a diet on growth rates of infants with CF before the clinical course is complicated by established pulmonary and hepatic disease.

Cystic fibrosis and coeliac disease: Coexistence in two children

Two children, unrelated, in whom cystic fibrosis had been diagnosed at the ages of 14 weeks and 10 months, respectively, were found subsequently to suffer from coeliac disease as well. Both children are responding well to dietary gluten withdrawal and to conventional treatment for cystic fibrosis. It is suggested that cystic fibrosis may predispose to the development of coeliac disease. Therefore, jejunal biopsy may be a useful investigation in the occasional child with cystic fibrosis, who presents with unusual features, and who fails to thrive as well as expected.