The effect of cow's milk protein (CMP) challenge on the levels of alkaline phosphatase (ALP) in the upper jejunal mucosa and the serum were studied in 25 infants clinically suspected to have cow's milk allergy. Following CMP provocation 3 groups were identified. Group 1 consisted of 10 infants who had clinical and histological reaction to CMP challenge. All 10 infants had significant depletion in the levels of tissue and serum ALP. Group 2 consisted of 5 infants who had histological reaction but no clinical reaction. Tissue ALP was depressed in 3 but not in 2 following CMP challenge. Serum ALP were essentially unaltered in all 5. Group 3 consisted of 10 infants who clinically and histologically tolerated CMP challenge. Tissue and serum ALP were not depressed in any. Estimation of sucrase levels in the mucosa and xylose absorption before and after CMP challenge were also performed for comparison with changes of tissue and serum ALP levels. The clinical significance of the changes in serum ALP level is discussed.
Eleven infants who were suspected clinically of having cows' milk protein sensitive enteropathy were fed with a protein hydrolysate formula for six to eight weeks, after which they had jejunal and rectal biopsies taken before and 24 hours after challenge with cows' milk protein. When challenged six infants (group 1) developed clinical symptoms and five did not (group 2). In group 1 the lesions developed in both the jejunal mucosa (four infants at 24 hours and one at three days), and the rectal mucosa, and the injury was associated with depletion of alkaline phosphatase activity. Infants in group 2 were normal. It seems that rectal injury that develops as a direct consequence of oral challenge with the protein in reactive infants may be used as one of the measurements to confirm the diagnosis of cows' milk protein sensitive enteropathy. Moreover, ingestion of such food proteins may injure the distal colonic mucosa without affecting the proximal small gut in some infants.
Enterokinase has a critical role in initiating proteolytic digestion by hydrolysing the conversion of pancreatic trypsinogen into trypsin. The enzyme is synthesised by enterocytes of the proximal small intestine and initially incorporated into the brush border from where it is released into the intestinal lumen by the action of pancreatic secretions. The aim of the study was to analyse enterokinase activity in the duodenal mucosa of infants with diarrhoeal disease including cow's milk protein-sensitive enteropathy. Our observations show that the mean depletion of enterokinase was only 17% compared to 60-80% for other brush border enzymes like disaccharidases, peptidases and alkaline phosphatases in infants with diarrhoea. This suggests that enterokinase activity in the small bowel enteropathies may be dependent not only on the degree of mucosal damage specifically but also on the extent of damage to the goblet cell population where the enzyme is synthesised. Thus the enterokinase activity was reduced in acute and chronic diarrhoea with marked mucosal damage where significant reduction of goblet cell population was evident but the enzyme was relatively little affected when the mucosa was damaged mildly.
The clinical response and the histological changes in the mucosa of the small bowel in response to continued feeding with cows' milk protein were assessed over a period of 2-6 weeks in 24 infants who had shown histological changes without immediate clinical symptoms after challenge with a diet containing cows' milk protein. Twenty of the 24 infants (83%) thrived well on cows' milk protein. Jejunal biopsy specimens taken six to eight weeks after the initial biopsy showed histological improvement in all 20 infants compared with biopsy specimens taken soon after the challenge, which had shown mucosal damage. The mucosa had returned to normal in 12, was mildly abnormal in seven, and moderately abnormal in one. Corresponding improvements in the activities of mucosal enzymes were seen. In four of the 24 infants (17%) symptoms developed between three and six weeks. Histological examination of the jejunal biopsy specimens showed that mucosal damage had progressed in two, and remained the same in two; moreover, the disaccharidase activities remained depressed. The present study shows that most infants with enteropathy caused by sensitivity to cows' milk protein but without clinical symptoms develop tolerance to the protein and the mucosa returns to normal despite continued feeding with cows' milk protein.
A series of 31 infants, 28 with cow's milk protein sensitive enteropathy (CMPSE) and 3 controls, was studied for severity and extent of mucosal damage of the upper small bowel in relation to the development of clinical symptoms. Following challenge with the offending cow's milk, 18 infants (Group 1) developed severe mucosal changes at both the proximal and distal small bowel mucosa and all of these infants presented with clinical symptoms. The other 10 infants (Group 2) who did not develop clinical symptoms following the challenge had less severe damage to the distal small bowel mucosa as compared to the proximal region. The histological score of both the proximal and distal postchallenge biopsies were significantly lower in Group 2 as compared to Group 1 infants. The mucosal disaccharidase and alkaline phosphatase levels were depleted in both the proximal and distal biopsies following challenge but the depletion was greater in the proximal than the distal biopsies. It is suggested that the extent and severity of mucosal damage to the proximal duodenum and jejunum have a critical bearing on the development of clinical symptoms.
Some infants intolerant to cow's milk protein (CMP) are often also intolerant to other food proteins including soy protein (SP). The effect of CMP and SP in infants recovering from diarrhoeal disease was studied in 22 infants who were maintained on an hypo-allergenic formula for 4-6 weeks. The infants were then challenged successively, initially with SP, followed 24 h later with CMP and then rechallenged with SP 24 h after CMP provocation. Three groups were recognized on the basis of clinical symptoms and mucosal changes following SP challenge. Group 1 comprised four infants who developed clinical and histological reactions on SP challenge. The subsequent CMP challenge, 24 h after the initial SP challenge, resulted in clinical symptoms in three of the four infants, and they developed increased mucosal injury. Rechallenge with SP in the three infants caused development of severe clinical symptoms. Group 2 comprised 12 infants who developed histological reaction but had no clinical symptoms to initial SP challenge. The subsequent CMP challenge caused further progression in mucosal pathology in 11 of the 12 infants and six also had associated clinical symptoms. Rechallenge with SP in the latter six infants resulted in development of clinical symptoms in three and tolerance to SP in three infants. Group 3 comprised six infants who tolerated SP and CMP but one of these infants developed mild histological changes to CMP. The progression of mucosal injury following SP and CMP challenge was associated with a significant decrease in mucosal disaccharidases, alkaline phosphatase levels and presence of reducing sugar in the stools. The 1 h blood xylose level continued to decrease significantly following the pre-SP, post-SP, and post-CMP challenge. It appears that the small bowel mucosa of young infants recovering from diarrhoeal disease remains sensitive not only to CMP but also to SP. The feeding of these proteins in rapid successive sequence to infants with mucosal damage might result in further progression of the mucosal injury. Thus, the exclusion for a variable period of time of antigenic food proteins like CMP and SP from the diet of young infants recovering from diarrhoea might reduce the risk of inducing mucosal sensitivity to these proteins in susceptible infants.
The effect of soy protein on the small bowel mucosa of 18 infants with acute gastroenteritis was studied. The infants were maintained on a protein hydrolysate formula for 6-8 weeks, following which they were readmitted for soy protein challenge studies. Jejunal biopsy was performed before and 24 h after challenge. On the basis of the clinical and histological reaction to soy protein challenge, three groups were identified. Group 1 consisted of three infants who had clinical and histological reaction. There was associated depletion of mucosal enzymes, lactase, sucrase, malatase, alkaline phosphatase, and blood xylose levels. Group 2 consisted of seven infants who had histological reaction but no clinical symptoms. Two of these seven infants, however, developed clinical reaction when rechallenged with soy protein 2 and 90 days later. Following challenge, mucosal enzymes and blood xylose levels were depressed in five of the seven infants tested. Group 3 consisted of eight infants who did not have either a clinical or a histological reaction. The mucosal enzymes and blood xylose levels were not depressed in four infants tested. The present study shows that the small bowel mucosa of some young infants recovering from acute gastroenteritis remains sensitive to soy protein for a variable period of time. The feeding of soy protein to these infants may result in the persistence of mucosal damage and perpetuation of diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS)