Small intestinal intraepithelial lymphocyte levels in cow's milk protein intolerance.

The mean small intestinal intraepithelial lymphocyte count in seven children with untreated cow's milk protein intolerance (CMPI) on a milk-containing diet was significantly higher than 22 control children also having a milk-containing diet. Ten milk-intolerant children on a milk-free diet had a mean intraepithelial lymphocyte count which was significantly lower than the level in the 22 control children on a milk-containing diet. When these 10 children were challenged with cow's milk they relapsed clinically, and in every case the intraepithelial lymphocyte count rose, although it remained within normal limits. Nineteen children on milk-free diets who had recovered from CMPI had a mean lymphocyte count which was also significantly lower than controls on normal diets, suggesting that when milk is remo-ed from the diet the lymphocyte count is low regardless of whether the child is milk sensitive or not. The reaction of intraepithelial lymphocytes to milk in CMPI is markedly different from their response to gluten in coeliac disease.     

Immunochemical study of the malabsorption syndrome with cow's milk intolerance

The effect of cow's milk provocation on the immunoglobulins in the intestinal mucosa, intestinal juice, stool extracts, as well as on the levels of antibodies to cow's milk and beta-1C/A in serum, was studied in 18 infants with the malabsorption syndrome. The infants improved on breast milk and were therefore suspected to be intolerant to cow's milk and challenged with it.At the time of clinical relapse a marked and uniform increase in the numbers of IgA- and IgM-containing cells, 2.4 times as many on the average as before challenge, was observed in the jejunal mucosa of eight reacting patients at nine provocations with cow's milk. There was no abnormality in the immunoglobulin-containing cells before challenge or in biopsy specimens taken shortly after the resumption of the elimination diet (breast milk). The clinical reaction was preceded by a pronounced rise in the IgA and IgM contents of stool extracts, and a rise in the titre of haemagglutinating antibodies and serum IgA, changes which subsided rapidly after withdrawal of cow's milk. There was no evidence that the reaction was IgE-mediated or complement-consuming.In some of the 10 patients who tolerated cow's milk challenge clinically there was an increase in both IgA- and IgM-containing cells suggestive of a local immunological reaction although no clinical intolerance was provoked and other immunological signs were weak or absent. In other non-reacting patients no immunological reaction was noted. Therefore it is evident that cow's milk is the agent responsible for the strong local intestinal reaction coinciding with the clinical symptoms.     

Cell kinetics in the jejunal crypt epithelium in malabsorption syndrome with cow's milk protein intolerance and in coeliac disease of childhood.

Cell kinetics in the proximal jejunal epithelium were studied by the methods of Cairnie et al. and Wright et al. Seventeen children with untreated malabsorption syndrome and cow's milk protein intolerance (CMI) and 12 of these on a cow's milk free diet were compared with 47 children with untreated coeliac disease, with 15 of these on a gluten free diet, and with 15 controls. The total number of cells in the crypts of the patients with CMI was 1.8 times (P less than 0.001) and in patients with coeliac disease 2.4 times (P less than 0.001) that seen in the controls. During the elimination diet the total number of cells in the crypts returned to the level seen in the controls. The mitotic indices, both crude and corrected, were significantly higher (P less than 0.001) in untreated patients with CMI and those with coeliac disease than in the controls. During dietary treatment the indices fell, but not quite to the level of the controls. These small differences between the two groups may be due to the difference in the causative agents or to the different ages of the patients.     

Hypertrophic gastritis in an infant with eczema and intolerance to cow's milk proteins (author's transl)

A 5-month-old infant presented with vomiting and severe hypoproteinemia from exsudation of proteins into the digestive tract, confirmed by isotopic tests. The association of hypertrophic edematous gastritis, interstitial jejunitis, and severe blood eosinophilia suggested the diagnosis of an exsudative eosinophil-type gastro-enteropathy. An allergy to cow's milk proteins was suspected because of the onset of the disorders at the time of weaning and the appearance of the eczema during the same period. Clinical, biological, and radiological recovery occurred after an exclusion diet and corticotherapy, and this persisted for 8 months, but the eczema remained. The authors describe a similar case (12) in an infant of 21 months with vomiting edema, and hypoproteinemia due to exsudation of proteins into the digestive tract. Radiological examination revealed the presence of hypertrophic gastritis. A relationship with Mentrier's disease had been suggested but not confirmed because of the rapid favourable outcome after a simple low protein diet.     

Prophylactic probiotics reduce cow's milk protein intolerance in neonates after small intestine surgery and antibiotic treatment presenting symptoms that mimics postoperative infection

BackgroundTo examine occurrence of cow's milk protein intolerance (CMPI) in newborns that underwent small intestine surgery and the clinical profiles of those newborns with postoperative CMPI, and to evaluate the preventive effects of probiotics on CMPI.MethodsWe retrospectively reviewed from 2000 to 2009, a total of 30 newborns required surgery on their small intestines. All of these patients had received antibiotics to prevent postoperative infection. Since 2005 we adopted a protocol of targeted probiotic therapy prophylaxis.ResultsEighteen patients received probiotic therapy, while twelve did not. One infant among those eighteen patients and eight patients among those twelve developed CMPI, a significantly lower rate for the group with probiotic therapy than that without it (p < 0.001). Patients with positive cultures for gram positive and gram negative organisms increased in number before and after surgery but then decreased after probiotics treatment. Poor weight gain, gastrointestinal symptoms, and rise in C reactive protein (CRP) levels were observed in all of those nine CMPI patients. Specific IgE antibodies were elevated in four of the nine subjects, and total IgE levels were elevated in seven of them. All CMPI patients had increased level of CRP without proven infections.ConclusionsCMPI was induced in newborns after surgery on their small intestines and antibiotics treatment with presentation of symptoms that mimic postoperative infection. Development of CMPI in this population possibly involves disruption of intestinal flora. Administration of probiotics can reduce the incidence of CMPI after small intestine surgery. The elevated CRP level may be useful in the diagnosis of CMPI.     

Intestinal blood loss as an aggravating factor of iron deficiency in infants aged 9 to 12 months fed whole cow's milk

GOALS: To verify the occurrence of occult intestinal blood loss and iron deficiency in infants aged 9 to 12 months. STUDY: A consecutive sample of 98 infants of the Pediatric Public Health Primary Care Unit in the town of Arapongas, Parana State, Brazil was involved in this cross-sectional study. Dietary history, hemoglobin, serum iron, transferrin saturation, ferritin, and an occult fecal blood loss investigation, by the immune chromatographic method specific for human hemoglobin were performed. RESULTS: Presence of occult intestinal blood occurred in 8/23 of the breast-fed (plus complementary feed) infants and in 30/64 of the infants who were fed with cow's milk (plus complementary feed) (P=0.449). The comparison of body iron indicators in accordance to positive or negative occult fecal blood, did not show any significant difference in the 23 breast-fed infants. Serum ferritin (median=4.2 ng/mL) was significantly lower (P=0.004) in infants who received whole cow's milk and had positive occult fecal blood, than in those infants who received whole cow's milk but were without occult fecal blood (median=12.1 ng/mL). CONCLUSIONS: In breast-fed infants with negative occult fecal blood, iron deficiency severity is not greater than in those with positive results. In infants fed whole cow's milk, occult fecal blood loss is an aggravating factor of iron deficiency.     

Lysinuric protein intolerance presenting deficiency of argininosuccinate synthetase.

A 35-yr-old woman, who suffered from relapsing coma with hyperammonemia for 17 yr, was diagnosed to have lysinuric protein intolerance (LPI). Increased urinary dibasic amino acids (lysine, arginine and ornithine) and impaired absorption of orally administered lysine and arginine proved the defects of renal tubular and intestinal transport of dibasic amino acids. These defects are the primary cause of impaired urea cycle metabolism in LPI. Further, the level of argininosuccinate synthetase (ASS), a urea cycle enzyme, was analyzed and it was found to be below the normal level. This is the second reported case of LPI presenting ASS deficiency.     

Iron deficiency anemia and hypoproteinemia induced by fresh cow's milk]

We reported two patients who developed severe iron deficiency anemia and hypoproteinemia which were induced by excessive drinking cow's milk. Case 1, a 23-month-old girl, had started drinking 800-1,000ml of cow's milk everyday since the age of 9 months. She developed generalized edema at the age of 23 months and visited Saga Medical School for Treatment. Case 2, a 14-month-old girl began to drink cow's milk at the age of 6 months. She drank 1,500ml cow's milk every day at the age of 14 months. She was, referred to our hospital by her physician because of severe anemia. Hypoproteinemia and severe iron deficiency anemia in both of these patients were improved by oral iron intake and prohibiting of cow's milk. Although many children at their age usually drink more than 500ml cow's milk every day, manifestations of symptoms such as iron deficiency anemia and hypoproteinemia do not occur frequently. Thus some investigations suggest that genetic defects as well as other factors related to this disease may be important factors.     

Treatment of severe cow's milk protein allergy using Neocate

A hydrolysate of proteins is considered to be adapted to treatment of allergy to cow's milk proteins when it is tolerated by 90% of allergic children. This suggestion implies that 10% of the children who are allergic to cow's milk proteins do not tolerate the preparations based on hydrolysates of proteins and presupposes the case of intolerance or allergy henceforth widely reported. The diagnosis must mention before the existence or the persistence in an infant fed with a hydrolysate of proteins of non-specific clinical signs often attached to more frequent pathologies, such as gastro-oesophageal reflux or colic. Substitution of a hydrolysate by another is one alternative, but the level of residual peptides of protein hydrolysates explains only the cases of severe allergy, the child may show reactions to these residual epitopes. The alternative is use of a formulation based on amino-acids, which allows diagnosis by an elimination-provocation test of protein hydrolysate. An elementary formulation based on amino-acids may permit to await the period of acquisition of tolerance.     

Significance of cow's milk protein antibodies as risk factor for childhood IDDM: interactions with dietary cow's milk intake and HLA-DQB1 genotype

Summary Dietary factors are suspected to play an aetiological role in the development of insulin-dependent diabetes mellitus (IDDM). We analysed cow's milk formula, betalactoglobulin, and bovine serum albumin antibodies by an enzyme-linked immunoassay in unselected children with newly diagnosed IDDM and in their non-diabetic siblings and enquired about infant feeding practices by questionnaire. Among 410 diabetic sibling pairs matched for age and sex, by logistic regression analysis – including overall duration of breast-feeding, age at introduction of dairy products, recent consumption of cow's milk and HLA-DQB1 genotype (“high/moderate” vs “low/decreased” risk of IDDM) – bovine serum albumin IgG antibody levels (OR 2.12, 95 %CI 1.25–3.57) and genetic risk (OR 3.81, 95 %CI 2.43–5.17) were positively associated with IDDM; cow's milk formula IgM antibodies were inversely associated with the risk of IDDM (OR 0.50, 95 %CI 0.29–0.87). Of the diabetic sibling pairs, 42 were identical for HLA-DQB1 alleles associated with IDDM risk or protection (DQB1^*0201, *0301, ^*0302 and *0602/03). In these 42 pairs, children with IDDM had higher median levels of bovine serum albumin IgG, of betalactoglobulin IgG, and of cow's milk formula IgG and IgA antibodies than the non-diabetic siblings (p < 0.05). In conclusion, children with IDDM have higher levels of cow's milk protein antibodies than their HLA-DQB1-matched sibling controls, and these high levels of antibodies are independent risk markers for IDDM. [Diabetologia (1998) 41: 72–78] Received: 13 June 1997 and in revised form: 26 August 1997     

Carnitine deficiency and L-carnitine supplementation in lysinuric protein intolerance

The aim of the study was to investigate the prevalence and mechanisms of development of carnitine deficiency in patients with lysinuric protein intolerance (LPI). In our cohort of 37 Finnish patients with LPI, 8 (8-52 years of age) have been diagnosed with hypocarnitinemia. Their free and total serum carnitine levels, acyl carnitine profiles, renal function, diet, and medication were compared with the data from 8 age- and sex-matched patients with LPI not treated with carnitine supplementation. In patients with LPI, hypocarnitinemia was strongly associated with female sex, renal insufficiency, and the use of ammonia-scavenging drugs. Of the 8 hypocarnitinemic patients, 3 complained of muscle weakness, and their symptoms disappeared during carnitine supplementation. Oral lysine supplementation did not correct hypocarnitinemia in our patients. The patients with LPI are at considerable risk for carnitine deficiency. Supplementation of hypocarnitinemic LPI patients with oral L-carnitine improved serum total carnitine values, but the ratio of free and total carnitine remained subnormal in all supplemented patients except one. Furthermore, decreased ratio of free and total serum carnitine was common even in LPI patients with normal total serum carnitine concentration.     

An in vitro test for cows' milk protein intolerance?

The clinical features and results of standard laboratory investigations have been studied in children with cows' milk protein intolerance and the results compared with an in vitro test, examining the degranulation of peripheral blood basophils to cows' milk antigen. Of 67 children investigated, 26 had probable intolerance to cows' milk, and maximal basophil degranulation responses in these children were significantly increased (p less than 0.01). The most striking differences were those observed between children with definite cows' milk protein intolerance and control individuals (p less than 0.002). Of 14 children with definite cows' milk intolerance clinically, only 4 had negative responses. The basophil degranulation test may be a valuable, simple and inexpensive investigation in the diagnosis of cows' milk protein intolerance and perhaps also in other conditions in which food sensitivity plays a part.     

Hidden presence of cow's milk proteins in foods.

Cow's milk is one of the first foreign proteins ingested by infants and is one of the most common and potent food allergens. The presence of cow's milk is widespread due also to its unlabelled inclusion as an ingredient, or to errors in cooking, processing and preparation, and in restaurant food. As several foods may contain cow's milk in a hidden form, foods for allergic babies should be prepared at home or with food items with all their ingredients listed on the label. Parents should be provided with appropriate material and instructed how to detect potential sources of hidden cow's milk by judiciously reading food labels to avoid possible untoward reactions. A study on products with potential hidden forms of cow's milk or its proteins is reported herein.     

In vitro diagnosis of cow's milk protein sensitive enteropathy by organ culture method.

The criteria that are used at present to diagnose cow's milk protein sensitive enteropathy (CMPSE) are based on an in vivo milk challenge which can be hazardous and life threatening. We have used an organ culture model to determine the usefulness of this technique in establishing the diagnosis of CMPSE on the basis of a single biopsy with in vitro milk challenge. Fourteen infants with diarrhoea clinically suspected to have CMPSE were studied prospectively. On the basis of milk challenge studies seven infants had CMPSE. They had clinical reaction to cow's milk with associated histological changes and depression of alkaline phosphatase levels in the jejunal mucosa. In all seven cases parallel changes in alkaline phosphatase levels were noted in the organ culture specimens of initial biopsy subjected to in vitro challenge. The seven control infants tolerated cow's milk and did not have histological changes. The alkaline phosphatase levels were moderately increased in the jejunal mucosa in five of the seven infants. The alkaline phosphatase levels in the organ culture specimens of initial biopsy were increased after in vitro challenge in all seven infants. This study suggests that organ culture methods may be useful in the vitro diagnosis of CMPSE, and also obviate the need for in vivo oral milk challenges and repeated biopsies.