Intestinal immune activation in juvenile idiopathic arthritis and connective tissue disease.

OBJECTIVES: To examine the prevalence of immune activation in gastrointestinal (GI) mucosa in children with juvenile idiopathic arthritis (JIA) or connective tissue disease (CTD). STUDY DESIGN: We studied 27 children (15 girls, mean age 9.8+/-4.8 years) with JIA/CTD and GI symptoms, including nine with oligoarthritis, nine with polyarthritis, two with systemic arthritis, three with enthesitis-related arthritis, and four with various CTDs. The control group consists of 54 children (31 girls, mean age 11.3+/-6.3 years) with GI symptoms but shown to have no significant GI or rheumatoid disorder. The subjects were examined by gastroduodenoscopy (22 patients, 50 controls) and colonoscopy (23 patients, 16 controls). Intraepithelial CD3+, alpha/beta+, and gamma/delta+ lymphocytes were counted from duodenal and ileal biopsies. RESULTS: Five patients with JIA/CTD (19%) had ulcerative colitis. Lymphoid nodular hyperplasia (LNH) was more common in the patients [74% (20/27)] than in the controls [16% (8/50), p = 0.001], as well in the duodenal bulb [29% (7/24) vs. 10% (5/50)], terminal ileum [74% (14/19) vs. 38% (5/13)], and the colon [50% (11/22) vs. 14% (2/14)]. In the duodenum, CD3, alpha/beta+, and gamma/delta+ lymphocytes counts were higher in JIA/CTD (p<0.05). In the ileum, gamma/delta+ cell numbers had increased in JIA/CTD (p<0.05). Either LNH, increased gamma/delta+ count, or both were more common in JIA/CTD [89% (24/27)] than in the controls [13% (7/54), p<0.0001]. CONCLUSIONS: The majority of children suffering from JIA or CTD with GI symptoms show abnormalities consistent with activation of the intestinal immune system. The aetiology of this reaction remains unknown, but similar features are seen in delayed-type food allergy.

IgE cross reactivity between reindeer and bovine milk beta-lactoglobulins in cow's milk allergic patients.

BACKGROUND: Allergic reactions to cow's milk are common in small children. One of the main protein allergens found in cow's milk is beta-lactoglobulin (beta-Lg). Reindeer and bovine milk both contain related beta-Lg proteins, but the allergenicity of reindeer beta-Lg has not previously been studied. The purpose of this study was to analyze the immunological cross-reactivity of IgE antibodies from children with cow's milk allergy to reindeer and bovine beta-Lg. METHODS: Sera from 17 children and a serum pool of 4 patients with elevated cow's milk-specific IgE were investigated. Beta-Lg from bovine and reindeer milk was isolated in native form and an enzyme-linked immunosorbent inhibition assay was developed. Bovine beta-Lg was used as a capturing antigen and the inhibiting effects of reindeer and bovine beta-Lg on the IgE binding were measured. RESULTS: Cross-reactivity patterns of bovine milk beta-Lg specific IgE to reindeer beta-Lg varied among patients. In general, reindeer beta-Lg showed significantly lower inhibition (mean 43%) of IgE binding to the capturing antigen than did bovine beta-Lg (mean 89%). In some patients, even high concentrations of reindeer beta-Lg only partly eliminated the IgE binding to bovine beta-Lg. CONCLUSIONS: The partial cross-reactivity of human anti-bovine IgE with reindeer beta-Lg suggests that it lacks important bovine epitopes and those that are recognized are only weakly bound.

Serum concentrations of interferon-gamma and intercellular adhesion molecule-1 eight years after an early respiratory syncytial virus infection.

BACKGROUND: Respiratory syncytial virus (RSV) infection may influence the development of recurrent wheezing and atopy, but the mechanisms are unclear. OBJECTIVE: The purpose was to evaluate serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), CD14, IgE, IL-5 and IFN-gamma in children 6-10 years after an RSV infection and their correlation with subsequent asthma and atopy. METHODS: Fifty-one subjects admitted to hospital for RSV infection during the first year of life and controls matched for birth date and sex underwent clinical examinations including lung function, skin prick and blood tests. RESULTS: The RSV subjects had significantly higher serum concentrations of IFN-gamma and sICAM-1 than the controls (for IFN-gamma 224.9 pg/mL (standard deviation (SD) 271.3) vs. 187.1 pg/mL (372.9), difference 37.8 pg/mL, 95% confidence interval (CI) -90.3 to 166.0, P = 0.05; for sICAM-1 170.2 ng/mL (SD 63) vs. 147.8 ng/mL (SD 57), difference 22.4 ng/mL, 95% CI -1.4 to 46.1, P = 0.04). The RSV subjects with asthma had significantly higher concentrations of IFN-gamma than the controls with asthma, and the RSV subjects with wheezing during the previous 12 months had significantly higher concentrations of both IFN-gamma and sICAM-1 than the controls with wheezing. CONCLUSIONS: Children hospitalized for RSV infection in infancy still differ in IFN-gamma and sICAM-1 production 6-10 years after the infection. The data suggest that the pathomechanism of asthma and wheezing after an early RSV infection may be different from that of children without an early RSV infection.

Gastrointestinal complaints and diagnosis in children: a population-based study.

AIM: To find out the extent to which children at 10-11 y of age suffer from various gastrointestinal complaints and how often a food-induced or other diagnostic disorder might be assessed behind them, we carried out a population-based survey of 404 children in a rural Finnish town. METHODS: A questionnaire filled in retrospectively by their parents was used to describe the frequency of various abdominal symptoms during the previous 2 y and to select the symptomatic subjects for closer clinical examination. In the clinical investigation of the children, an elimination challenge with milk protein and lactose intolerance tests, as well as endoscopic examinations in selected cases and blood tests, were performed. RESULTS: In all, 110 (27%) subjects reported some gastrointestinal (GI) complaints during the last 2 y; 64 (16%) meeting the Apley criteria for recurrent abdominal pain. A specific organic or functional disorder was found in 26 subjects (6%), two having no GI symptoms. Milk protein intolerance was the most common specific disorder diagnosed in nine subjects (2.2%), followed by lactose intolerance in eight (2%), coeliac disease in five (1.2%) and Helicobacter pylori infection in three (0.7%). An endoscopic examination performed on 17 subjects (4.2%) and a colonoscopy on three revealed significant findings in 11; lymphonodular changes being most common, occurring in five subjects. Subjects with milk protein-induced disorders showed significantly lower IgA-class antibodies to milk and its fractions than the non-symptomatic controls. Chronic diseases, short breastfeeding, GI problems and food intolerance during the first year of life were observed as significant risk factors in determining whether a subject belonged to the group experiencing any GI complaints. CONCLUSION: We conclude that in one in five of those with any, even mild, GI complaints we were able to assess a specific organic disease; milk-induced disorders being most common. A milk protein and/or lactose load test, completed in some cases with an endoscopic examination, would help in assessing a proper individual diagnosis.

Food habits in 10-11-year-old children with functional gastrointestinal disorders.

OBJECTIVE: To evaluate the role of food habits and nutrient intake in children with functional gastrointestinal disorders (FGIDs) considering their association with psychosocial factors. DESIGN: Cross-sectional. SETTING: A rural town in Mid-Western Finland. SUBJECTS: After excluding organic gastrointestinal (GI) disorders, a total of 49 children with FGID and 78 control children without GI symptoms from a cohort of 422 children were studied. METHODS: Food frequency questionnaire, GI-symptoms questionnaire and the Child Behaviour Check List (CBCL) filled in by parents together with their child, and 24-h dietary recall and anthropometric and haematological measurements. RESULTS: Compared to control children, fewer children with FGID had daily family dinner (77 vs 91%, P = 0.030) and they used less often vegetables (P = 0.023), fruits (P = 0.027) and berries (P = 0.011), but more often ice cream (P = 0.018) and soft drinks (P = 0.027) and had a higher sucrose intake (9 vs 7E%, P = 0.032) and lower lactose intake (27 vs 36 g, P = 0.001). Reported food-related symptoms were more common among FGID group (69 vs 11%), as well as restricted milk use (31 vs 0%). Children with FGID had higher total problem scores in CBCL (P=0.002), and the behavioural/emotional problems associated with occurrence of FGID (OR 1.04, 95% CI 1.07-1.076) as did the sugar intake (OR 1.1, 95% CI 1.004-1.215). CONCLUSIONS: This population-based study suggests that school-aged children with FGIDs have less-organized food habits and higher milk avoidance, and they display internalizing psychological characteristics. SPONSORSHIP: Juho Vainio Foundation, Finland; the Alma and K.A. Snellman Foundation, Oulu, and the Pediatric Research Foundation, Finland.

Enhanced local immune response in children with prolonged gastrointestinal symptoms.

AIM: Recently, we reported typical endoscopic findings and an increment in gammadelta+ T cells in the foregut among children with food-sensitive enteropathy other than coeliac disease. To find out the extend to which the upregulation of the local immune response might explain gastrointestinal (GI) complaints of the foregut, we sought to examine by the increment in gammadelta+ T cells a I-y consecutive series of children referred for recurrent GI complaints to a tertiary-level hospital. METHODS: A 1-y cohort of 102 children scheduled for gastroduodenoscopy were examined for mucosal histology and the densities of CD3+, alphabeta+ and alphabeta+ T-cell subsets from mid-duodenal specimens. The final diagnostic categories were used in analysing the data. RESULTS: Fifteen subjects showed villous atrophy and a high gammadelta+ T-cell density; the finding being compatible with coeliac disease (CD). At the other extreme, 20 subjects in whom diagnostic GI diseases were ruled out showed low densities and served as controls. The subjects reporting GI symptoms after an open food challenge with milk and/or cereals (n = 18) as well as children remitting with a milk- or cereal-eliminating diet but not responding to a challenge (n = 23) also expressed significantly higher densities of gammadelta+ T cells than the controls. In all, 45 of 102 children could be considered to have an elevated gamma6+ T-cell density as an indication of locally activated immune response. Lack of villous architecture and lymphonodular hyperplasia of the duodenal bulb as an endoscopic finding and atopic dermatitis but not the presence of DQ2 alleles showed a close association with these increased densities. CONCLUSION: Considering that an elevated incidence of gammadelta+ T cells is an indication of mucosal response against luminal antigens, up to half the children with prolonged GI symptoms have immune mediated disorder; CD and food allergy being the most obvious clinical entities.

Association of an early respiratory syncytial virus infection and atopic allergy.

BACKGROUND: Respiratory syncytial virus (RSV) causes postbronchiolitic wheezing but its role in allergic sensitization is controversial. The purpose of the study was to examine the effect of an early RSV infection on allergic sensitization. METHODS: Seventy-six subjects were examined 6-10 years after hospitalization for RSV infection during the first year of life. Fifty-one subjects (68%) attended clinical studies and 25 filled in a questionnaire. The study protocol included lung function, skin-prick and blood tests. The controls were matched for birth date and sex. RESULTS: Eight per cent of the subjects and 37% of the controls had at least one positive skin-prick test (SPT) (difference -35%, 95% CI -50 to -19%, P < 0.0001). Allergic rhinitis, atopic dermatitis and asthma occurred as often in both groups, but asthma had been diagnosed significantly earlier in the subjects than in the controls [mean age 3.0 years (SD 2.6) and 5.6 years (SD 3.0), difference 2.6 years, 95% CI 0.57-4.65, P = 0.014]. In a logistic regression analysis, RSV infection was associated with negative SPTs. CONCLUSIONS: An early RSV infection results in reduction of SPT positivity but not of occurrence of atopic diseases. This finding might explain why there is less atopic sensitization in countries with a greater probability of acquiring RSV infection at an early age.

Isoflavone content of the soy based supplements.

A large number of soy isoflavone products with indications of possible health effects are available on the market. Fifteen different soy based products were analyzed using high performance liquid chromatography (HPLC) with coulometric electrode array detector to determine the total amount of isoflavones in aglycones after the hydrolysis and identify the different forms of the isoflavone conjugates. The aim of the study was to evaluate how well the isoflavone content data supplied by the producers correspond to our analysis results. Only one product contained isoflavones measured in aglycones the same amount as was the value given by the producer. The total amount of the isoflavones in aglycones ranged from 0.121 to 201 mg/g. Measured amounts of isoflavones in aglycones after the hydrolysis were in general lower than the values in the product labels. Product data were often confusing and the concrete amount of isoflavones was difficult to find out.

Coping of parents with physically and/or intellectually disabled children.

OBJECTIVE: The aim was to clarify how families with physically and/or intellectually disabled children cope, what kind of coping strategies they use and how the families with good and poor coping capacities differ. METHODS: The parents of eight children (aged 8-10 years) with physical and/or intellectual disability were interviewed twice, and the data elicited in these interviews were analysed qualitatively using the grounded theory method. RESULTS: Information and acceptance, good family co-operation and social support were related to the coping strategies most frequently used. Half of the families seemed to have found successful ways of coping, whereas another half had major problems. There were five main domains in which the high- and low-coping families differed most from each other: (1) parents' initial experiences; (2) personal characteristics; (3) effects of the child's disability on family life; (4) acting in everyday life; and (5) social support. CONCLUSION: The findings can be utilized in developing supportive activities for families with disabled children. By recognizing the coping strategies used by the family, professionals and service providers can find the right ways to support their adaptation. As the role of physicians, nursing staff and other professionals in this process is very important, more attention should be attached to the collaboration between these groups, to enable them to view the situation from the perspective of the whole family.

Cow's milk protein-sensitive enteropathy at school age.

OBJECTIVES: Cow's milk protein-sensitive enteropathy (CMSE) may persist in children to school age. We sought to define the morphologic and immunohistochemical features of persistent CMSE. STUDY DESIGN: We studied 15 children with a definite diagnosis of CMSE on the basis of a blind challenge, 12 children with suspected cases of CMSE, 11 children with celiac disease, and 12 control children. RESULTS: Typical findings in children with CMSE were endoscopically visible lymphonodular hyperplasia of the duodenal bulb and lymphoid follicles without villous atrophy in biopsy samples. The patients with definite CMSE showed significantly increased densities of intraepithelial T cells skewed clearly to gammadelta(+) cells, compared with the control patients but fewer than in the patients with celiac disease. The study children showed no aberrant upregulation of HLA-DR expression in the duodenal mucosa, and the prevalence of HLA DQ2 antigen among them was equal to that in the control children. CONCLUSIONS: Our observations corroborated the claim that CMSE at school age is an identifiable clinical entity. Immunohistochemical findings suggest the abrogation of antigen tolerance locally on the gastrointestinal mucosa. A careful clinical assessment that includes a long elimination-challenge test supported by typical endoscopic and histologic findings form the basis for diagnosis.

Chronic stretching and running economy.

Research demonstrates an inverse relationship between the range of motion of selected joint movements (flexibility) and running economy. Since stretching exercises have been shown to increase joint range of motion, stretching exercises may be contraindicated for endurance running performance. Hence, this study investigated the influence of a 10-week program of stretching exercises on the oxygen costs of a 10 min sub-maximal (approx. 70% peak VO(2)) treadmill run. Thirty-two (16 female, 16 male) physically active, treadmill accommodated, college students participated in the study. All participants maintained their current activity level, with half the participants (8 female, 8 male) adding a 40 min, 3 days per week session of thigh and calf muscle stretching exercises. After 10 weeks, the stretching group (STR) exhibited a significant (P<0.05) increase (3.1+/-2.2 cm) in the sit-and-reach, while the non-stretching group (CON) experienced no significant (P>0.05) change (0.0+/-0.4 cm). However, neither the STR nor the CON exhibited a significant (P>0.05) change in the O(2) cost for the submaximal run. It is concluded, therefore, that a chronic stretching program does not necessarily negatively influence running economy.

Inhibition of maximal voluntary isokinetic torque production following stretching is velocity-specific.

Recent research has shown that a regimen of stretching provides an acute inhibition of maximal force production by the stretched muscle group. To further characterize this phenomenon, the effect of an acute stretching regimen on maximal isokinetic knee-extension torque at 5 specific movement velocities (1.05, 1.57, 2.62, 3.67, and 4.71 rad x s(-1)) was examined in 10 men and 5 women (22-28 years). Each person's 5 baseline maximal isokinetic knee-extension torques (dominant leg) were measured on a Cybex NORM dynamometer. Following the baseline torque measurements, the participants stretched the dominant quadriceps for 15 minutes using 1 active and 3 passive stretching exercises. Once the stretching exercises were completed, the maximal torque measurements were repeated. Poststretch maximal torque at 1.05 rad x s(-1) was significantly reduced (p < 0.05) from 218 +/- 47 Nm (mean +/- SD) to 199 +/- 49 Nm (7.2% decrease). At 1.57 rad x s(-1), a similar decrease (p < 0.05) was also seen (204 +/- 48 Nm vs. 195 +/- 47 Nm; 4.5% decrease), but at the other velocities (2.62, 3.67, and 4.71 rad x s(-1)), poststretch maximal torque was unaltered (p > 0.05). It appears, therefore, that the deleterious impact of stretching activities on maximal torque production might be limited to movements performed at relatively slow velocities.

Muscle glycogen supercompensation is enhanced by prior creatine supplementation.

PURPOSE: Recently, it was shown that glycogen supercompensation tended (P = 0.06) to be greater if creatine and glycogen were loaded simultaneously. Because the authors suggested that creatine loading increased cell volumes and, therefore, enhanced glycogen supercompensation, we decided to determine whether an enhanced glycogen supercompensation could be realized if the glycogen loading protocol was preceded by a 5-d creatine load. METHODS: Twelve men (19-28 yr) performed two standard glycogen loading protocols interspersed with a standard creatine load of 20 g.d(-1) for 5 d. The vastus lateralis muscle was biopsied before and after each loading protocol. RESULTS: The initial glycogen loading protocol showed a significant 4% increase (P < 0.05) in muscle glycogen (Delta upward arrow 164 +/- 87 mmol.kg(-1) d.m.), and no change (P > 0.05) in total muscle creatine. Biopsies pre- and post-creatine loading showed significant increases in total muscle creatine levels in both the left leg (Delta upward arrow 41.1 +/- 31.1 mmol.kg(-1) d.m.) and the right leg (Delta upward arrow 36.6 +/- 19.8 mmol.kg(-1) d.m.), with no change in either leg's muscle glycogen content. After the final glycogen loading, a significant 53% increase in muscle glycogen (Delta upward arrow 241 +/- 150 mmol.kg-1 d.m.) was detected. Finally, the postcreatine load total glycogen content (694 +/- 156 mmol.kg(-1) d.m.) was significantly (P < 0.05) greater than the precreatine load total glycogen content (597 +/- 142 mmol.kg(-1) d.m.). CONCLUSION: It is suggested that a muscle's glycogen loading capacity is influenced by its initial levels of creatine and the accompanying alterations in cell volume.

Activation of paracrine TGF-beta1 signaling upon stimulation and degranulation of rat serosal mast cells: a novel function for chymase.

As a source of transforming growth factor beta1 (TGF-beta1), mast cells have been implicated as potential effector cells in many pathological processes. However, the mechanisms by which mast cells express, secrete, and activate TGF-beta1 have remained vague. We show here by means of RT-PCR, immunoblotting, and immunocytochemistry that isolated rat peritoneal mast cells synthesize and store large latent TGF-beta1 in their chymase 1-containing secretory granules. Mast cell stimulation and degranulation results in rapid secretion of the latent TGF-beta1, which is converted by chymase 1 into an active form recognized by the type II TGF-beta serine/threonine kinase receptor (TbetaRII). Thus, mast cells secrete active TGF-beta1 by a unique secretory mechanism in which latent TGF-beta1 and the activating enzyme chymase 1 are coreleased. The activation of latent TGF-beta1 specifically by chymase was verified using recombinant human latent TGF-beta1 and recombinant human chymase. In isolated TbetaRI- and TbetaRII-expressing peritoneal macrophages, the activated TGF-beta1 induces the expression of the plasminogen activator inhibitor 1 (PAI-1), whereas in the mast cells, the levels of TbetaRI, TbetaRII, and PAI-1 expression were below detection. Selective stimulation of mast cells in vivo in the rat peritoneal cavity leads to rapid overexpression of TGF-beta1 in peritoneal mast cells and of TbetaRs in peritoneal macrophages. These data strongly suggest that mast cells can act as potent paracrine effector cells both by secreting active TGF-beta1 and by enhancing its response in target cells.

Residual intestinal disease after milk allergy in infancy.

BACKGROUND: The subsidence of cow's milk allergy (CMA) has been a subject of controversy. In this study the authors examined whether children with this condition in infancy developed full tolerance or whether they continue to have vague gastrointestinal (GI) symptoms relating to the consumption of milk or dairy products and/or signs of mucosal lesion in the GI tract. METHODS: The authors reexamined 56 10-year-old subjects who manifested CMA before 1 year of age, and compared the results with a group of 204 randomly selected age-matched school children. Fifty-three and 90 subjects respectively attended a reexamination and were evaluated for growth, lactose tolerance, and immunoglobulin A (IgA)- and IgG-class antibodies to whole cow's milk. The subjects reporting milk-related GI symptoms were encouraged to do a 4-week blind elimination-challenge test with 1 week of low-lactose milk flour. Sixteen of the 25 children were able to complete the trial. RESULTS: Approximately half the study subjects (45%) reported milk-related GI symptoms, whereas the respective figure among the control subjects was 10%. Three of six study subjects and seven of 10 control subjects, although completing the challenge, responded with intestinal symptoms. The growth of the former CMA subjects was retarded compared with the control subjects, and the difference in height was most striking in those subjects still reporting milk-related GI symptoms. However, all subjects had normal hemoglobin and whole-blood folic acid levels. The CMA subjects had significantly (P = 0.014) lower concentrations of milk antibodies compared with the control subjects. Lactose malabsorption, defined as high counts in a hydrogen breath test and related clinical symptoms, was found in eight CMA subjects (14%) and six control subjects (3%). CONCLUSIONS: In a certain proportion of subjects with CMA in infancy, GI intolerance seems to persist even after small-dose tolerance has been achieved. The intestinal symptoms and the increased prevalence of lactose intolerance may be caused by a disturbance of the surface epithelial cells--a state to which the authors refer as residual intestinal disease.

Mucosal pathology of the foregut associated with food allergy and recurrent abdominal pains in children.

UNLABELLED: To determine whether children with recurrent abdominal pain (RAP) include an excess of children with food allergy (FA), this study examined a consecutive series of 84 children (43M, 41F, mean age 7.9 y, range 1.6-15 y) referred during 1 y to 2 university hospitals. In addition to a clinical examination, the patients underwent gastroduodenoscopy with three biopsy specimens, skin-prick and patch tests, and comprehensive laboratory tests for atopic allergy. Based on an open elimination-challenge test, a total of 28 (33%) subjects were diagnosed for FA. In the whole material, specific endoscopic abnormalities were found in 38 (45%) subjects: oesophagitis in 17, gastric erosions in 8, lymphonodular duodenitis in 12 and erosive duodenitis in 5. FA showed a close relationship with duodenal lesions, but no significant association with oesophagitis and gastritis. The histological findings were mild, although some alterations could be observed in up to 66 (79%) subjects, equally often in patients with and without FA. None showed villous atrophy or severe infiltration of eosinophilic or mononuclear cells. Slightly increased densities of eosinophilic cells were significantly associated with endoscopic findings, especially oesophagitis. At least one positive skin-prick test with food allergens was found in 11 subjects and a positive patch test in 21 subjects, but neither showed an association with the endoscopic or histological findings, or even with clinical FA. CONCLUSION: Since the children with FA showed significantly more often concomitant mucosal pathology of the foregut than those without FA, FA may be considered one of the major factors underlying RAP. The report suggests the trial of an elimination diet in cases with RAP if lymphonodular hyperplasia or duodenitis is seen on gastroduodenoscopy.

TIA1 and mast cell tryptase in food allergy of children: increase of intraepithelial lymphocytes expressing TIA1 associates with allergy.

BACKGROUND: Variability of symptoms and signs make the diagnosis of children's food allergy (FA) difficult. In addition, mechanisms and antigens involved vary with age. In young infants, cow's milk protein allergy is associated with an increase of cytotoxic intraepithelial lymphocytes (IELs) expressing T-cell-restricted intracellular antigen (TIA1). In the current study, the significance of TIA1 in FA in older children of mainly preschool and school age was analyzed and the findings correlated the with a detailed clinical, endoscopic, and histopathologic analysis. METHODS: The subjects of this study were 66 children (mean age, 7.9 years; range, 1-15), including 27 with untreated and 15 with treated FA, and 24 control subjects. The morphology of duodenal and antral biopsy specimens was evaluated, and the proportion of TIA1-positive IELs was counted from immunostained sections. Quantification of mast cells with immunostaining for mast cell tryptase (MCT) was completed, with the estimation of diffuse extracellular staining considered to indicate degranulation. RESULTS: Patients with untreated FA showed an increase in the total number of TIA1-positive cells and IELs and of the TIA1/IEL ratio. The number of mast cells in duodenal mucosa was decreased in children with FA, but no association with degranulation was observed. Endoscopic abnormalities were common in FA, but conventional histopathology showed no informative differences. CONCLUSIONS: The significant increase of TIA1-positive IELs in duodenal tissue specimens is associated with FA. The cytotoxicity of T lymphocytes seems to play a role in the pathogenesis of gastrointestinal FA. Activation and mechanisms of action should be studied further.

Ethanol infusion increases ANP and p21 gene expression in isolated perfused rat heart.

Whether alcohol-induced heart failure is caused by a direct toxic effect of ethanol, metabolites, or whether it is a secondary result of neurohumoral, hormonal, or nutritional factors is not clear. To address this question a Langendorff retrograde coronary perfusion model of rat heart was used to study the effect of 0.5% (v/v) ethanol (n = 7) and 0.5 mM acetaldehyde (n = 9) on left ventricular expression of ANP, BNP, p53, p21, TNF-alpha,bax, bcl-2 as well as on DNA-fragmentation. Ethanol infusion of 150 min duration significantly induced both ANP and p21 mRNA expression of ventricular myocardium compared with hearts infused with vehicle (n = 8). Acetaldehyde did not exert any significant effects on any of the parameters studied, although the mean expression of TNF-alpha tended to be lower in the acetaldehyde-treated hearts than in control hearts. No evidence of increased DNA-fragmentation was found in ethanol or acetaldehyde treated groups. We conclude that ethanol per se is capable of inducing genes associated with hypertrophy and impaired function of the heart whereas a significant apoptosis is not involved in the initial phase of alcohol-induced cardiac injury.