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Biomedical subjects

J T Harries

Publications and source records attributed to J T Harries.

At least 19 recordsLinked to original sources

Specific autoantibodies to gut epithelium in two infants with severe protracted diarrhoea.

Two male infants with severe protracted diarrhoea presenting at 4 months (patient 1) and 10 weeks (patient 2) of age are reported. In both patients jejunal biopsy showed subtotal villous atrophy. Both had specific complement-fixing autoantibodies reacting by immunofluorescence with human duodenal, jejunal, and colonic epithelium. Patient 1 also had hypothyroidism and type 1 diabetes mellitus with thyroid and islet cell autoantibodies. His gut antibodies were of IgG class, reached a titre of 1:512, and remained positive throughout his illness. He died at 16 months of age. Patient 2 had gut antibodies of IgM class, which reached a titre of 1:128 and disappeared at the time of spontaneous recovery of the diarrhoea. The findings suggest that an autoimmune process was the basis for the enteropathy in these patients. We recommend that autoantibody tests should be performed in infants with unexplained protracted diarrhoea.

Antibody Specificity

The effects of magnesium on ion transport in short-circuited rabbit terminal ileum.

The effects of MgCl2 on the electrical characteristics and sodium and chloride transport in short-circuited rabbit terminal ileum in vitro were studied. Increasing the magnesium concentration from a basal concentration of 1.1 mmol/l to either 2.5 or 10.3 mmol/l (mucosal or serosal addition) resulted in increases in the unidirectional flux of chloride from serosa to mucosa (JCl sm), short-circuit current (SCC) and transmucosal potential difference (p.d.). Increasing the magnesium concentration from a low basal concentration (0.3 mmol/l) to 10.3 mmol/l (mucosal or serosal addition) abolished net sodium absorption and converted net chloride absorption into net secretion, as a result of a decrease in the unidirectional flux of sodium from mucosa to serosa (JNa ms), and increases in the unidirectional fluxes of sodium and chloride from serosa to mucosa (JNa sm and JCl sm). Increases in SCC and p.d. occurred after mucosal, but not serosal, addition of magnesium. Incubation of stripped ileal mucosa with MgCl2 (10.3 mmol/l) did not result in increased mucosal concentrations of cAMP or cGMP. These data suggest that at least part of the cathartic effect of magnesium salts is likely to result from marked changes in ileal ion transport and provide a rational explanation for the watery diarrhoea commonly seen after the oral administration of magnesium salts to hypomagnesaemic patients.

Animals

Food allergy: the major cause of infantile colitis.

Forty six children presented with colitis between 1977 and 1981, and all 8 of those below the age of 2 years had food allergic colitis which resolved completely after exclusion of certain foods. In most of the 8 the onset was soon after starting foods other than breast milk. The most common offending food was cows' milk protein, but soya (3 cases) and beef (1 case) were also implicated. A history of allergy in the child or family was common as were blood eosinophilia, high concentrations of serum IgE, and positive IgE antibodies. Colonoscopic appearances were distinctive and biopsies showed a noticeable increase in eosinophils and IgE-containing cells in the lamina propria. We suggest that food allergy is the major cause of colitis in infancy and that an exclusion diet is the treatment of choice.

Adolescent

Loperamide in severe protracted diarrhoea.

Six infants with severe life-threatening protracted diarrhoea were treated with loperamide. Steady-state perfusion studies of the jejunum showed that in 2 of them the small intestine was in a net secretory state with respect to water, and in the others this was inferred from the fact that the diarrhoea persisted despite nothing by mouth. Loperamide resulted in a prompt and impressive improvement in the condition of each infant. We conclude that this drug has an important role in the management of protracted diarrhoeal states in some infants who are unresponsive to current treatments, and that its effect is related to its antisecretory action.

Child, Preschool

Obstructive jaundice secondary to chronic midgut volvulus.

A case of progressive extrahepatic biliary obstruction due to chronic midgut volvulus secondary to malrotation in a 5-month-old girl is presented. The obstruction to the bile duct was relieved after correction of the malrotation and division of the obstructing bands.

Cholestasis, Extrahepatic

Disordered small intestinal motility: a rational basis for toddlers' diarrhoea.

Toddler diarrhoea is the commonest cause of chronic diarrhoea without failure to thrive in childhood, but its pathogenesis remains obscure. We have studied upper small intestinal motility in three groups of children (control group 1 - children with no intestinal pathology undergoing duodenal intubation, n = 6; control group 2 - children with gastrointestinal pathology other than toddler diarrhoea, n = 11; control group 3 - children with toddler diarrhoea, n = 8). We studied fasting motor patterns and the response of the migrating motor complex to intravenous cholecystokinin and an intraduodenal bolus of 5% dextrose. The characteristics of the migrating motor complex in the three groups did not differ but their response to dextrose did. Intraduodenal dextrose disrupted the migrating motor complex in four out of four children in group 1; seven out of nine children in group 2; and nil of eight children with toddler diarrhoea in group 3. We suggest that this failure of intestinal motor response may play a major role in the pathogenesis of the diarrhoea in this condition.

Child

A pathophysiological study of the intestinal manifestations of a vasoactive intestinal peptide, calcitonin, and catecholamine-secreting tumour.

A three year old girl with severe watery diarrhoea and a vasoactive intestinal peptide, calcitonin, and catecholamine-secreting supra-renal ganglioneuroblastoma is reported. Steady-state perfusion studies showed the jejunum to be in a net secretory state with respect to water, sodium, and chloride at low concentrations (2 mmol/l) of glucose whereas higher concentrations (56 mmol/l) reversed secretion to absorption; transmural rectal potential difference was increased (lumen negative); Na+ absorption by the rectum was impaired and secretion of potassium and bicarbonate excessive. Motility studies showed prolonged, slowly propagated migrating motor complexes with abnormal runs of non-propagated contractions in the fasting state. During perfusion with glucose, no postprandial activity occurred. These results suggest that diarrhoea results from small intestinal secretion with impaired colonic function and that tumour products may have a direct effect on intestinal motility.

Adrenal Gland Neoplasms

Increased adhesion of Escherichia coli to mucosal cells from infants with protracted diarrhoea: a possible factor in the pathogenesis of bacterial overgrowth and diarrhoea.

Mucosal adhesion of bacteria has been studied in eight infants with protracted diarrhoea and malnutrition, using a buccal epithelial cell technique. A known non-adhesive strain of Escherichia coli (O1:K1:H7) adhered to a significantly greater (p less than 0.001) proportion of buccal epithelial cells from patients with protracted diarrhoea, compared with children with acute diarrhoea, healthy infants, and healthy adults. Also, Enterobacteria isolated from the jejunum or stools of patients with protracted diarrhoea adhered to far greater numbers of their own buccal epithelial cells compared with healthy adults. These results suggest that bacterial adhesion may play an important role in the pathogenesis of protracted diarrhoea.

Adhesiveness

Small intestinal absorption of amino acids and a dipeptide in pancreatic insufficiency.

In this study a perfusion technique has been used to investigate in vivo jejunal absorption and transmural potential difference evoked by the neutral amino acids phenylalanine (56 or 20 mmol/l) and glycine (20 mmol/l), the dibasic amino acid lysine (56 or 5 mmol/l), and a dipeptide glycyl-l-phenylalanine (20 mmol/l) in 11 children with pancreatic insufficiency due to cystic fibrosis and in three children with other causes of exocrine pancreatic insufficiency. Net absorption and potential difference evoked by phenylalanine in both cystic fibrosis and pancreatic insufficiency, and net absorption of glycine in cystic fibrosis were significantly reduced; but the absorption of lysine and glycyl-l-phenylalanine was normal. Absorption of the constituent amino acids from the dipeptide was normal or increased in cystic fibrosis. Thus, these studies show a defect in active absorption of neutral amino acids in cystic fibrosis with pancreatic insufficiency and exocrine pancreatic insufficiency. We speculate that pancreatic factors participate in neutral amino acid absorption.

Amino Acids

The effect of zinc therapy on lysosomal inclusion bodies in intestinal epithelial cells in acrodermatitis enteropathica.

Two patients with acrodermatitis enteropathica had abnormal lysosomal inclusion bodies in the intestinal epithelial cells while in relapse but fewer smaller ones after zinc therapy. The third patient with acrodermatitis enteropathica in remission on zinc therapy had no inclusion bodies. The smaller inclusion bodies were similar to those found in coeliac disease.

Acrodermatitis

Mechanisms of action of loperamide.

The beneficial effect of loperamide in some children with severe protracted diarrhoea which persisted when nil by mouth, made us suspect that loperamide may have an antisecretory action. Using a steady-state perfusion technique in rat jejunum we showed that loperamide inhibits cholera toxin induced secretion of water, sodium and chloride (p less than 0.001). This antisecretory action was blocked by naloxone and not mediated via an effect on tissue cyclic AMP level or adenylate cyclase activity. More recently we have studied the effect of loperamide on secretion of water in the rat jejunum induced by other agents with differing mechanisms of action. The first set of observations suggest that loperamide's antisecretory effect is mediated via opiate receptors either distal to, or separate from the adenylate cyclase/cyclic AMP pathway. Our more recent studies support the notion that loperamide has an effect on specific transport systems rather than non-specific passive diffusional processes.

Animals