Allergy to cow's milk proteins in mother's milk or in hydrolyzed cow's milk infant formulas as assessed by intestinal permeability measurements

An intestinal permeability test analyzing the differential urinary elimination of lactulose and mannitol orally ingested at the same dosage allowed us to establish a significant correlation between alterations of intestinal permeability and ingestion of reputedly hypoallergenic foods, breast milk, and hydrolyzed protein formulas in some infants with cow's milk allergy. In all, clinical disappearance of symptoms was observed after removal of milk from the mother's diet and/or elimination from the child's diet of any cow's-milk-based hypoallergenic formula.     

Increased intestinal sugar permeability after challenge in children with cow's milk allergy or intolerance

The diagnosis of cow's milk allergy or intolerance (CMAI) is based on clinical improvement on exclusion diet and relapse after challenge with milk. The aim of this work was to investigate the value of the cellobiose/mannitol (C/M) sugar permeability test, performed before and after cow's milk challenge, as a tool for the diagnosis of CMAI. Thirty-two patients underwent milk challenge at a median age of 13 months (range 3–84 months). A dual sugar (C/M) permeability test with an iso-osmolar solution was performed before and 24 h after challenge. Of the 10 patients who developed symptoms after challenge, nine showed increased postchallenge C/M ratio, whereas such an increase was observed in only one of the 22 nonrelapsed subjects. The postchallenge C/M ratio increase in relapsed subjects is to be attributed to both higher cellobiose and lower mannitol urinary excretion. These results suggest the use of the sugar permeability test, in addition to clinical observation, as an aid in the evaluation of provocation tests in infants with suspected CMAI.     

Concurrent cereal allergy in children with cow''s milk allergy manifested with atopic dermatitis

BACKGROUND: There is increasing consensus about the significance of food allergens in the pathogenesis of atopic dermatitis (AD) in infancy and childhood, with cow's milk and egg accounting for most of the reactions. Previous studies have indicated that multiple food sensitization, such as cereals, is very common in patients with cow's milk allergy (CMA). Evidence is lacking, however, as to its clinical relevance. OBJECTIVE: The purpose of this study was to determine the concurrent occurrence of cereal allergy among children with challenge-proven CMA who have residual symptoms, such as AD and/or gastrointestinal symptoms, during cow's milk elimination diet. Further, we sought to evaluate the utility of patch testing in prescreening foods other than cow's milk behind allergic symptoms in children. METHODS: The study population comprised 90 children, aged from 2.5 to 36 months (mean 1.1 years), with challenge-proven CMA. As a result of residual symptoms during meticulous cow's milk elimination diet (AD: n=80, and gastrointestinal: n=10), the children were put on a cereal elimination diet (oats, wheat, rye, and barley) and skin prick tests (SPT) and patch testing with cereals were performed. Open cereal challenge was performed to confirm cereal allergy. RESULTS: Cereal challenge was positive in 66 (73%) of the children with CMA. Of them, 17% reacted with immediate reactions and delayed-onset reactions were seen in 83% of the children. SPT was positive in 23%, patch test in 67%, and either SPT or patch test was positive in 73% of the children with cereal allergy. SPT gave the best positive predictive value, whereas SPT together with patch test gave the best negative predictive value. CONCLUSIONS: Residual symptoms, such as eczema or gastrointestinal symptoms in CMA children may be a sign of undetected allergy to other food antigens. SPT with cereals aids in diagnosing cereal allergy in small children, especially when used together with patch testing.     

Gastrointestinal permeability in children with cow's milk allergy: effect of milk challenge and sodium cromoglycate as assessed with polyethyleneglycols (PEG 400 and PEG 1000)

Abstract. Sixteen children with immediate-type cow's milk allergy were challenged with increasing amounts of cow's milk. Gastrointestinal permeability was investigated before and after challenge by the 6-hr urinary recovery of a mixture of different-sized polyethyleneglycols (PEG 400 and PEG 1000). The results were related to clinical symptoms in the individual patients. The majority of the children displayed changed permeability characteristics after the challenge, both with respect to the maximum uptake of a small test molecule (usually 370 dalton PEG) and/or a large molecule (1074 dalton PFG), and to size-dependent exclusion of probe molecules. When corrected for the dose of milk taken, the children showing the most severe immediate-type symptoms also displayed the greatest alteration of permeability. Treatment with sodium cromoglycate (SCG) before the challenge diminished the effect on the uptake of probe molecules, usually decreased the severity of elicited symptoms, allowing about a tenfold increase in the milk dose. Cow's milk challenge in healthy children caused only minor permeability changes, whereas challenge in the sensitized subjects significantly changed (increased or decreased) the recovery of a large test molecule. The difference between healthy and allergic subjects was most obvious when correcting for dose of milk ingested. We conclude that (i) oral challenge with cow's milk in allergic subjects affects the mucosal barrier, and (ii) peroral treatment with SCG moderates immediate hypersensitivity reactions with respect to both tolerated antigen dose and intestinal permeability properties.     

Prevalence of soy protein hypersensitivity in cow's milk protein-sensitive children in Korea

This study was aimed to evaluate the prevalence of soy protein hypersensitivity in cow's milk protein-sensitive children in Korea. A total of 1,363 patients with atopic dermatitis, urticaria, enterocolitis syndrome, bronchial asthma or allergic rhinitis were recruited. First, we estimated the prevalence of sensitization to soy in children sensitized to cow's milk. Specific IgE levels > 0.7 kU/L by CAP assay were considered positive. Next, the prevalence of soy allergy in cow's milk allergy (CMA) patients was investigated. Those children whose parents agreed to participate the open challenge test with soy had a convincing history of allergic reactions elicited by cow's milk and these symptoms were relieved by elimination. All of them had negative soy-specific IgE. Patients with positive soy-specific IgE accounted for 18.3% of 224 children sensitized to cow's milk protein. The prevalence of sensitization to soy decreased with age (36.8% in the first year of life, 16.4% in the second year, and 13.7% in the third year). Of 21 CMA patients, 42.9% (n=9) were determined to have soy allergy (mean age 10.3 months). Our results suggest that soy protein formula should be carefully used as a substitute for cow's milk in CMA patients, especially during infancy.     

Feeding mode, intestinal permeability, and neopterin excretion: a longitudinal study in infants of HIV-infected South African women

Exclusive breast feeding has been associated with a lower rate of mother-to-child HIV transmission than breast feeding plus other foods. To obtain further information on biologic outcomes of different feeding modes, we examined 272 infants of HIV-infected South African women at ages 1, 6, and 14 weeks. At each visit information about infant diet and morbidity was collected and infants underwent a lactulose/mannitol dual sugar intestinal permeability test. In a subset of infants, urinary neopterin excretion was measured as an indicator of immune system activation. Infants who had themselves become HIV-infected by 14 weeks had higher ( p <.01) intestinal permeability at 6 and 14 weeks and slightly (.05 < p <.1) higher neopterin excretion at all times than uninfected infants. At 1 week infants given no breast milk had higher ( p <.05) intestinal permeability than infants given breast milk exclusively or with other foods. Intestinal permeability in infants fed breast milk plus other foods was never increased relative to that of exclusively breastfed infants. Feeding mode had no effect on neopterin excretion. Thus, infant HIV infection induces changes in gut permeability and possibly immune system activation before clinical symptoms become apparent. The effects of feeding mode on infant intestinal permeability or urinary neopterin excretion do not explain a possible protective effect of exclusive breast feeding on mother-to-child transmission of HIV.     

Defective tumour necrosis factor-alpha production in mother''s milk is related to cow''s milk allergy in suckling infants

BACKGROUND: The precise role of leucocytes in human milk is still unresolved. OBJECTIVE: To assist in clarifying the immune mechanisms involved in the development of CMA in suckling infants, we studied the role of immunoregulatory leucocytes and their mediators in human breast milk. METHODS: The study population consisted of 43 lactating mothers and their infants, aged 0.25-8.0 months, followed-up prospectively from birth. Of these mothers, 27 had an infant with challenge-proven cow's milk allergy manifested with either skin (n = 23), gastrointestinal (n = 2) or skin and gastrointestinal symptoms (n = 3). Sixteen mothers with a healthy infant served as controls. We evaluated the spontaneous and mitogen-induced tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) production of human milk leucocytes and isolated peripheral blood lymphocytes in vitro with a commercial ELISA kit. RESULTS: TNFalpha production of breast milk leucocytes was significantly lower in the mothers with a cow's milk-allergic infant, whereas IFNgamma production of these cells was comparable in the two groups. CONCLUSION: Our results suggest that in the breast milk of mothers having an infant with cow's milk allergy, the number and function of TNFalpha-producing cells is defective. This might lead to a disturbance in the development of oral tolerance and thereby to the development of CMA in suckling infants. These novel results may help in clarifying the etiopathogenesis of CMA.     

Cow's milk allergy in adults is rare but severe: both casein and whey proteins are involved

Background Studies on cow's milk allergy (CMA) in adults are scarce. Little is known about the clinical symptoms, eliciting doses (ED), and allergens involved.
Objective The aim of this study was to analyse the clinical symptoms, ED and allergen recognition in adult CMA patients, compared with cow's milk (CM)-sensitized, but tolerant controls.
Methods Adult CMA patients were evaluated by standardized questionnaires ( n =30), skin prick tests (SPTs) and specific IgE for CM allergens ( n =18), and a double-blind placebo-controlled food challenge (DBPCFC, n =10). A control group ( n =25) of CM-sensitized, but tolerant adults was included.
Results The majority of CMA patients (20/30, 67%) reported severe symptoms. In all patients participating in DBPCFC, CMA was confirmed. ED for subjective symptoms (0.3–300 mg CM protein) were significantly lower than that for objective symptoms (300–9000 mg CM protein). The severity of CMA by history and ED was not correlated with SPT or IgE. Patients had higher SPT reactivity than controls for CM, α-lactalbumin and β-lactoglobulin ( P =0.002, P =0.014 and P =0.004) but not for casein. Specific IgE to CM tended to be higher ( P =0.068) and IgE to casein was higher in patients than that in controls ( P =0.016). No difference was observed for IgE to α-lactalbumin and β-lactoglobulin.
Conclusion Adult CMA is severe in nature. ED are low, starting from 0.3 mg CM protein. Patients with CMA recognize the same major allergens (casein and whey proteins) as controls, but display a stronger SPT and IgE reactivity.     

MMP-2、MMP-9与溃疡性结肠炎患者肠黏膜通透性的相关性研究

目的：观察血浆基质金属蛋白酶MMP-2、MMP-9表达水平与溃疡性结肠炎(ulcerative colitis,UC)患者肠黏膜通透性的联系,探讨UC的发病机制,为诊断提供较为可靠的参考指标。方法：纳入50例UC患者和30例健康志愿者,分别采集研究对象的外周静脉血,应用酶联免疫吸附法(ELISA)检测血浆MMP-2、MMP-9的表达,高效液相色谱法检测口服乳果糖(L)和甘露醇(M)混合液6 h内尿液L、M的含量,并计算乳果糖/甘露醇比值(LMR)。结果：与健康对照组相比,UC组血浆MMP-2、MMP-9水平显著升高(t=13.843,P<0.001;t=14.165,P<0.001)。UC组血浆MMP-2、MMP-9表达与疾病病变严重程度、病变范围呈正相关;UC组患者尿LMR显著高于健康对照组(t=9.804, P<0.001),UC患者血浆MMP-2、MMP-9表达与肠黏膜通透性呈一定程度的相关性(r=0.832, P<0.001;r=0.847,P<0.001)。结论：UC患者血浆MMP-2、MMP-9表达升高,并能反映UC病变严重程度、病变范围,作用机制可能与肠黏膜通透性增高有关。     

The efficacy of amino acid-based formulas in relieving the symptoms of cow''s milk allergy: a systematic review

The aim of this systematic review was to evaluate the efficacy of amino acid-based formulas (AAF) in patients with cow's milk allergy (CMA). Studies were identified using electronic databases and bibliography searches. Subjects eligible for inclusion were patients of any age with CMA or symptoms suggestive of it. Comparisons of interest were AAF vs. extensively hydrolysed formula (eHF), AAF vs. soy-based formula (SF) and AAF vs. cow's milk or cow's milk-based formula. Outcomes of interest were gastrointestinal (GI), dermatological, respiratory and behavioural symptoms as well as growth. A total of 20 studies [three head-to-head randomized controlled trials (RCTs), three cross-over challenge RCTs, seven clinical trials (CTs) and seven case reports (CRs)] were included in the review. In infants with confirmed or suspected CMA, the use of an AAF was shown to be safe and efficacious. Findings from RCT comparisons of AAF with eHF showed that both formulas are equally efficacious at relieving the symptoms of CMA in confirmed or suspected cases. However, infants in specific subgroups (e.g. non-IgE mediated food-induced gastro-enterocolitis-proctitis syndromes with failure to thrive, severe atopic eczema, or with symptoms during exclusive breastfeeding) were more likely overall to benefit from AAF, as intolerance to eHF may occur. In such cases, symptoms persisting despite eHF feeding usually remit on AAF, and catch-up growth may be seen. Meta-analysis of the findings was not possible due to lack of homogenous reporting of outcomes in the original trials. This systematic review shows clinical benefit from use of AAF in both symptoms and growth in infants and children with CMA who fail to tolerate eHF. Further studies are required to determine the relative medical or economic value of initial treatment with AAF in infants at high risk of eHF intolerance.     

Intestinal permeability to mannitol and lactulose in children with type 1 diabetes with the HLA-DQB1*02 allele

Food antigens and enteroviruses are possible triggers of type 1 diabetes. Because permeability of the intestinal epithelium may facilitate contact of these antigens with the mucosal immune system, we set out to study intestinal permeability in patients with type 1 diabetes. Children with type 1 diabetes (n = 26, mean age 12 years, mean duration of disease 4 years) and 24 healthy age-matched control children were given mannitol and lactulose orally, and their intestinal permeability was measured as a percentage of this dose recovered in urine. Patients with type 1 diabetes did not differ in their permeability to lactulose, nor was their lactulose/mannitol ratio any different from that of controls. However, patients with type 1 diabetes who had the HLA-DQB 1*02 allele and, therefore, a higher risk for celiac disease (CD) absorbed significantly more mannitol (mean + 95% CI): 17.7% (15.2-20.2) than did those negative for this allele: 12.3% (8.2-16.4), p = 0.04. Their lactulose permeability was also higher: 0.30 (0.16-0.44) and 0.09% (0-0.18), respectively, p = 0.02. Although the differences in permeability reach statistical significance, there was still much overlap between the two groups in terms of actual laboratory values. The higher permeability of patients with the HLA-DQB1*02 allele suggests that these patients may be more prone to develop abnormal immune responses to food antigens.     

Does 'sugar' permeability reflect macromolecular absorption? A comparison of the gastro-intestinal uptake of lactulose and beta-lactoglobulin in the neonatal guinea pig

Intestinal closure to cow's milk beta-lactoglobulin occurs within 6 days of birth in the guinea pig. Passive intestinal permeability to lactulose persists through the suckling period. The uptake of small water-soluble markers does not reflect macromolecular absorption, and has no place in the measurement of immunologic protein handling by the gut.     

Cell-surface expression of CD25, CD26, and CD30 by allergen-specific T cells is intrinsically different in cow's milk allergy

BACKGROUND: The release of T(H)2 cytokines by food-specific T cells is thought to be important in the etiology of food allergy. It has been suggested that the activation state of food-specific T cells also plays a significant role, but this has not yet been studied at the single-cell level. OBJECTIVE: Differences in the expression of cell-surface markers by cow's milk protein (CMP)-specific T cells between infants with and without cow's milk allergy (CMA) were evaluated at the clonal level. In addition, expression after the spontaneous development of tolerance of cow's milk in infants with CMA was analyzed. METHODS: We established CMP-specific T-cell clones (TCCs) from blood of infants with CMA and atopic dermatitis, from atopic controls with atopic dermatitis but without CMA, and from nonatopic controls. In addition, we established TCCs from infants with CMA after they had spontaneously developed tolerance to cow's milk. Expression levels of CD25, CD26, and CD30 by each TCC were analyzed by use of flow cytometry. RESULTS: Cow's milk protein-specific T cells from infants with CMA expressed much higher levels of CD25 and CD30 than CMP-specific T cells from infants without CMA. Expression of CD26 was much lower than in normal controls. After development of tolerance for cow's milk, expression of CD25 and CD30 was decreased, whereas the expression of CD26 was increased to normal levels. CONCLUSION: Antigen-specific T cells from patients with food allergy display an increased expression of cell-surface markers of activation compared with cells of patients without food allergy. This suggests an intrinsically stronger food-specific T-cell response in food-allergic patients, and points to the key role of food-specific T cells in the pathogenesis of food allergy.     

IgE and IgG binding epitopes on alpha-lactalbumin and beta-lactoglobulin in cow's milk allergy.

BACKGROUND: Cow's milk is one of the most common causes of food allergy in the first years of life. We recently defined IgE and IgG binding epitopes for alpha(s1)-casein, a major cow's milk allergen, and found an association between recognition of certain epitopes and clinical symptoms of cow's milk allergy (CMA). Since alpha-lactalbumin (ALA) and beta-lactoglobulin (BLG) are suspected to be significant allergens in cow's milk, we sought to determine the structure of sequential epitopes recognized by IgE antibodies to these proteins. We further sought to assess the pattern of epitope recognition in association with the clinical outcome of CMA. METHODS: According to the known amino acid sequence of ALA and BLG, 57 and 77 overlapping decapeptides (offset by two amino acids), respectively, were synthesized on a cellulose derivatized membrane. Sera from 11 patients 4-18 years of age with persistent CMA (IgE to cow's milk >100 kU(A)/l) were used to identify IgE binding epitopes. In addition, 8 patients < 3 years of age and likely to outgrow their milk allergy (IgE to cow's milk < 30 kU(A)/l) were used to investigate the differences in epitope recognition between patients with 'persistent' and those with 'transient' CMA. Seven patients 4-18 years of age were used for assessing the IgG binding regions. RESULTS: In patients with persistent allergy, four IgE binding and three IgG binding regions were identified on ALA, and seven IgE and six IgG binding epitopes were detected on BLG. The younger patients that are likely to outgrow their allergy recognized only three of these IgE binding epitopes on BLG and none on ALA. CONCLUSIONS: The presence of IgE antibodies to multiple linear allergenic epitopes may be a marker of persistent CMA. The usefulness of IgE binding to distinct epitopes on whey proteins in defining the patients that would have a lifelong CMA needs to be investigated in further studies.     

Intestinal Permeability to Mannitol and Lactulose in Children with Type 1 Diabetes with the HLA-DQB1*02 Allele

Food antigens and enteroviruses are possible triggers of type 1 diabetes. Because permeability of the intestinal epithelium may facilitate contact of these antigens with the mucosal immune system, we set out to study intestinal permeability in patients with type 1 diabetes. Children with type 1 diabetes (n = 26, mean age 12 years, mean duration of disease 4 years) and 24 healthy age-matched control children were given mannitol and lactulose orally, and their intestinal permeability was measured as a percentage of this dose recovered in urine. Patients with type 1 diabetes did not differ in their permeability to lactulose, nor was their lactulose/mannitol ratio any different from that of controls. However, patients with type 1 diabetes who had the HLA-DQB1 &#72 02 allele and, therefore, a higher risk for celiac disease (CD) absorbed significantly more mannitol (mean+95% CI): 17.7% (15.2-20.2) than did those negative for this allele: 12.3% (8.2-16.4), p = 0.04. Their lactulose permeability was also higher: 0.30 (0.16-0.44) and 0.09% (0-0.18), respectively, p = 0.02. Although the differences in permeability reach statistical significance, there was still much overlap between the two groups in terms of actual laboratory values. The higher permeability of patients with the HLA-DQB1 &#72 02 allele suggests that these patients may be more prone to develop abnormal immune responses to food antigens.     

B-cell epitopes as a screening instrument for persistent cow's milk allergy

BACKGROUND: Cow's milk is one of the most common causes of food allergy in the first years of life. We recently defined IgE-binding epitopes of all 6 major cow's milk proteins (alpha(s1)-, alpha(s2)-, beta-, and kappa-casein; alpha-lactalbumin; and beta-lactoglobulin) and had some evidence suggesting that IgE antibodies from patients with persistent cow's milk allergy (CMA) recognize different epitopes on cow's milk proteins than do those from patients who were likely to outgrow their allergy. OBJECTIVE: In this study we sought to assess whether recognition of IgE antibodies of certain epitopes of cow's milk proteins would clearly separate the patients with life-long CMA from those who will become clinically tolerant to cow's milk. METHODS: According to the known IgE-binding regions of cow's milk proteins, 25 decapeptides of alpha(s1)-casein, alpha(s2)-casein, kappa-casein, alpha-lactalbumin, and beta-lactoglobulin, comprising the core epitopes, were synthesized on a cellulose-derivatized membrane. Sera from 10 patients with persistent CMA and 10 patients who subsequently outgrew their milk allergy were used to investigate the differences in epitope recognition. RESULTS: Five IgE-binding epitopes (2 on alpha(s1)-casein, 1 on alpha(s2)-casein, and 2 on kappa-casein) were not recognized by any of the patients with transient CMA but showed binding by the majority of the patients with persistent allergy. The presence of IgE antibodies against at least 1 of 3 epitopes (amino acid [AA] 123-132 on alpha(s1)-casein, AA 171-180 on alpha(s2)-casein, and AA 155-164 on kappa-casein) identified all patients with persistent CMA. CONCLUSIONS: The presence of IgE antibodies to distinct allergenic epitopes of cow's milk proteins can be used as a marker of persistent CMA. Prospective studies are needed to investigate the usefulness of these informative epitopes in predicting life-long CMA in young children.     

Cow's milk protein sensitivity assessed by the mucosal patch technique is related to irritable bowel syndrome in patients with primary Sjögren's syndrome

Introduction Patients with primary Sjögren's syndrome (pSS) are reported to have a variety of gastrointestinal symptoms partly attributed to an overrepresentation of celiac disease. We have observed that irritable bowel syndrome (IBS)-like symptoms are frequent complaints in this patient group. Allergic manifestations to various drugs are also common in pSS. A role of food allergy in IBS has been proposed.
Objective This study is aimed at evaluating the mucosal response to rectal challenge with cow's milk protein (CM) in patients with pSS and relates possible CM reactivity to their intestinal symptoms.
Methods A rectal challenge with CM was performed in 21 patients with pSS and 18 healthy controls. Fifteen hours after challenge the mucosal production of nitric oxide (NO) and the release of myeloperoxidase (MPO) as signs of mucosal inflammatory reaction were measured using the mucosal patch technique.
Results Eight out of 21 patients with pSS had a definite increase of mucosal NO synthesis and the luminal release of MPO after rectal CM challenge. This sign of milk sensitivity was not linked to IgG/IgA antibodies to milk proteins. The symptoms for IBS according to Rome III criteria were fulfilled in 13 patients. All patients who were CM sensitive suffered from IBS. In a small open study, patients reactive to CM reported an improvement of intestinal symptoms on a CM-free diet.
Conclusion A rectal mucosal inflammatory response after CM challenge is seen in 38% of patients with pSS as a sign of CM sensitivity. IBS-like symptoms were common in pSS, linked to CM sensitivity.     

Differences in antigen-specific T-cell responses between infants with atopic dermatitis with and without cow's milk allergy: relevance of TH2 cytokines

BACKGROUND: Cow's milk is the most important food antigen in infancy and may lead to acute cutaneous symptoms and atopic dermatitis (AD). The role of circulating allergen-specific T cells in the pathogenesis of food-allergic skin symptoms is still under investigation. OBJECTIVE: This study was designed to analyze the cow's milk protein (CMP)-specific T-cell response at the clonal level in infants with AD and cow's milk allergy (CMA) in comparison with infants with AD without CMA. METHODS: We used an antigen-specific culturing system with autologous B cells as antigen-presenting cells to establish CMP-specific T-cell clones derived from PBMCs in infants with AD. T-cell reactivity, measured by using a lymphocyte stimulation test, and cytokine production, measured by using ELISA, was compared between infants with AD with and without CMA. RESULTS: Both infants with and without allergy to cow's milk had a CMP-specific T helper cell response directed against the major proteins in milk. Analysis of antigen-specific cytokine production showed that this response was T(H)2 skewed in infants with CMA, with production of high levels of IL-4, IL-5, and IL-13. In contrast, infants without CMA had a T(H)1-skewed response, with high levels of IFN-gamma and low levels of IL-4, IL-5, and IL-13. CONCLUSION: These data confirm for the first time at the clonal level that food allergy in infants with AD is associated with production of T(H)2 cytokines by circulating antigen-specific CD4(+) T cells, whereas tolerance to food antigens is associated with low levels of these cytokines. This suggests a key role for the T helper cell-derived T(H)2 cytokines in food allergy-related skin symptoms.     

Increase in human intestinal permeability following ingestion of hypertonic solutions.

1. A simple oral loading technique involving the ingestion of solutions containing lactulose is described. Timed urinary excretion of lactulose, which is non-metabolizable, is used as an indicator of intestinal permeability, and measured by quantitative paper chromatography. 2. This technique has been used to investigate the intestinal permeability of apparently healthy adults following the ingestion of solutions made hypertonic by the addition of the solutes sucrose, glucose, mannitol, glycerol, urea and sodium chloride. 3. These experiments show that intestinal permeability to lactulose increases as the solute concentration in the ingested solution is increased. Susceptibility to this effect, though consistent for each individual, shows considerable variation between subjects. 4. Factors thought to be pernitent to the enhancement of intestinal permeability by hypertonic solutions, and some possible implications of this, are discussed.     

Incremental prognostic factors associated with cow's milk allergy outcomes in infant and child referrals: the Milan Cow's Milk Allergy Cohort study

BACKGROUND: The prognosis for many children with cow's milk allergy (CMA) is remission within 3 years, and the clinical parameters that predict duration of disease have not been measured incrementally. OBJECTIVE: To prospectively determine prognostic predictors of tolerance in a random cohort of referrals using CMA workup outcomes as covariates and tolerance as the status variable in a duration model of CMA. METHODS: The 2001-2006 Milan Cow's Milk Allergy Cohort (MiCMAC) enrolled children referrals using double-blind, placebo-controlled food challenges (DBPCFCs) as study end points (confirmation of CMA; onset of tolerance). The Cox regression model was used to analyze all clinical factors that contributed to tolerance. Covariates analyzed were skin, gastrointestinal, and respiratory symptoms; history and demographics at presentation; age at diagnosis and DBPCFC outcomes; sensitization (skin and serum) by cow's milk protein fractions; sensitization to other food and inhalant allergens; total IgE levels; specific IgE concentrations for cow's milk protein fractions, other ingestants, and aeroallergens; and threshold doses at DBPCFC. Sensitization and DBPCFC were performed at 6-month intervals. RESULTS: A total of 112 infants were enrolled (mean [SD] age, 13.85 [9.84] months), and 59 achieved tolerance (mean [SD] age when tolerance was achieved, 27.58 [11.81] months). On univariate analysis, asthma and/or rhinitis at presentation was an independent predictor of persistence (hazard ratio [HR], 2.19; 95% confidence interval [CI], 1.26-3.82). On multivariate analysis, predictors of persistence were a fresh milk wheal diameter increment of 1 mm (HR, 1.18; 95% CI, 1.07-1.31) and a positive skin prick test result with soy (HR, 6.99; 95% CI, 1.56-31.25). CONCLUSIONS: This is the first study, to our knowledge, to identify incremental biological predictors of delayed tolerance to cow's milk in children that should be integrated into DBPCFC schedules for CMA in infants.