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E Savilahti

Publications and source records attributed to E Savilahti.

At least 19 recordsLinked to original sources
PubMed2007

Severe adverse reactions to Infliximab therapy are common in young children with inflammatory bowel disease.

UNLABELLED: Since 2000 we have introduced 141 Infliximab infusions to 23 children with severe inflammatory bowel disease. A total of seven severe adverse reactions occurred in 26% (6 of 23) of the children. Four reactions were acute (anaphylaxis n = 2; allergic reaction n = 2) and 3/4 of these children were younger than 10 years of age. Two children developed an abscess and one child had septicaemia and brain lesions related to progressive multifocal leucoencephalopathy. CONCLUSION: adverse reactions to Infliximab infusions are common. Young children seem to be prone to severe allergic reactions although they are on azathioprine and conventional glucocorticoid therapy.

Adolescent↗
PubMed2005

Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study.

AIMS/HYPOTHESIS: We aimed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood. METHODS: We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles. After exclusive breastfeeding, the infants underwent a double-blind, randomised pilot trial of either casein hydrolysate (Nutramigen; Mead Johnson) or conventional cow's milk-based formula until the age of 6-8 months. During a mean observation period of 4.7 years, autoantibodies to insulin, anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays, and islet cell antibodies (ICA) by immunofluorescence. RESULTS: The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility, enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established. The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group, suggesting the need for a larger well-powered study. After adjustment for duration of study formula feeding, life-table analysis showed a significant protection by the intervention from positivity for ICA (p=0.02) and at least one autoantibody (p=0.03). CONCLUSIONS/INTERPRETATION: The present study provides the first evidence ever in man, despite its limited power, that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy.

Autoantibodies↗
PubMed2005

Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial.

BACKGROUND: Probiotic bacteria are suggested to reduce symptoms of the atopic eczema/dermatitis syndrome (AEDS) in food-allergic infants. We aimed to investigate whether probiotic bacteria have any beneficial effect on AEDS. METHODS: Follow-up of severity of AEDS by the Severity Scoring of Atopic Dermatitis (SCORAD) index in 230 infants with suspected cow's milk allergy (CMA) receiving, in a randomized double-blinded manner, concomitant with elimination diet and skin treatment, Lactobacillus GG (LGG), a mixture of four probiotic strains, or placebo for 4 weeks. Four weeks after the treatment, CMA was diagnosed with a double-blind placebo-controlled (DBPC) milk challenge in 120 infants. RESULTS: In the whole group, mean SCORAD (at baseline 32.5) decreased by 65%, but with no differences between treatment groups immediately or 4 weeks after the treatment. No treatment differences were observed in infants with CMA either. In IgE-sensitized infants, however, the LGG group showed a greater reduction in SCORAD than did the placebo group, -26.1 vs-19.8 (P=0.036), from baseline to 4 weeks after the treatment. Exclusion of infants who had received antibiotics during the study reinforced the findings in the IgE-sensitized subgroup. CONCLUSION: Treatment with LGG may alleviate AEDS symptoms in IgE-sensitized infants but not in non-IgE-sensitized infants.

Bacteria↗
PubMed2004

Increased cell turnover, but no signs of increased T-cell infiltration or inflammatory cytokines in the duodenum of pediatric patients after allogeneic stem cell transplantation.

Intestinal immunopathology was studied after allogeneic stem cell transplantation (SCT) in a common clinical setup in 20 children with malignant (n=17) or nonmalignant diseases (n=3) receiving grafts from siblings (7) and unrelated donors (13). In all, 19 had total body irradiation. Duodenal biopsies at 6 and 12 weeks post transplant were evaluated by histology, immunohistochemistry, and ISEL for the detection of T-lymphocytes, inflammatory cytokines, proliferation, and apoptosis. The controls were 12 healthy children and three patients with proven intestinal graft-versus-host disease. An increased rate of apoptosis and proliferation with upregulated expression of HLA-DR antigen was detected up to 3 months post transplant in the SCT patients, even in those with a histologically normal small intestine. A low level of IFNgamma and TNFalpha was observed in the lamina propria. The initial low density of gammadelta-positive T cells had recovered to normal by the time of the second endoscopy at 12 weeks post transplant. We conclude that inflammatory activity and T cell infiltration detected by immunohistochemistry may not belong to the 'normal' recovery of the small intestine after SCT. Increased cell turnover in the intestinal crypts continues until 3 months after SCT, suggesting either an unexpectedly long-lasting effect of transplant-related toxicity or, preferably, an ongoing subclinical alloreactive process, also present in the patients without intestinal symptoms.

Adolescent↗
PubMed2004

Mothers of very low birth weight infants have less atopy than mothers of full-term infants.

BACKGROUND: Studies on the pregnancy outcome of asthmatic mothers have suggested an increased rate of preterm deliveries. In contrast, our earlier study suggests that mothers of very low birth weight (VLBW) (<1500 g) infants less frequently had atopy than did mothers of full-term infants. METHODS: We inquired about symptoms of atopy and doctor-diagnosed atopy in parents of 370 infants of VLBW (<1500 g) and 544 parents of full-term infants. Odds ratios for atopic symptoms and diagnosed atopy were calculated, and groups were compared with a trend test. RESULTS: Mothers of preterm infants of birth weight (BW) <1000 g significantly less often had physician-diagnosed allergic rhinitis (AR) (P=0.02). Among all the mothers, a trend test showed that maternal AR was significantly (P=0.03) higher in parallel with a higher infant BW. Fathers of infants with different BWs showed no differences in prevalence of atopic symptoms. CONCLUSION: We thus infer that maternal balance between T-helper type 1 (Th1) and Th2 cells, shifted towards Th2 in those with AR, may have a favourable effect on maintenance of pregnancy before gestational week 30.

Adult↗
PubMed2004

A genetic test which can be used to diagnose adult-type hypolactasia in children.

BACKGROUND/AIMS: Adult-type hypolactasia (primary lactose malabsorption) affects most of world's human population and limits the use of fresh milk due to lactose intolerance. The diagnosis of adult-type hypolactasia has been difficult to establish because of unsatisfactory diagnostic methods. C/T(-13910) single nucleotide polymorphism residing 13910 base pairs from the 5' end of the lactase gene has been shown to be associated with lactase persistence. The aim of the study was to assess the applicability of the C/T(-13910) variant as a diagnostic test for adult-type hypolactasia during childhood. METHODS: Intestinal biopsies were obtained from 329 children and adolescents of African, Finnish, and other White origins aged 0.1-20 years undergoing upper gastrointestinal endoscopy because of abdominal complaints. The biopsies were assayed for lactase, sucrase, and maltase activity and genotyped for the C/T(-13910) variant using polymerase chain reaction minisequencing. RESULTS: The frequency of the C/C(-13910) genotype defining lactase non-persistence was well in agreement in this study with published figures for the prevalences of adult-type hypolactasia in Africans and Whites. The C/C(-13910) genotype was associated with very low lactase activity (<10 U/g protein) in the majority of children tested at 8 years of age and in every child older than 12 years of age giving a specificity of 100% and sensitivity of 93% for the genetic test. The decline of lactase activity was somewhat earlier in African compared with Finnish children with C/C(-13910) genotype (p<0.03). CONCLUSIONS: Genetic test of C/T(-13910) polymorphism can be used as a first stage screening test for adult-type hypolactasia.

Adolescent↗
PubMed2004

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.

Abdominal Pain↗
PubMed2003

T-cell-mediated mucosal immunity is attenuated in experimental necrotizing enterocolitis.

In premature infants with necrotizing enterocolitis (NEC) the gastrointestinal mucosal barrier is immature, but little is known about the immune response of immature bowel. The aim of this study was to evaluate the intestinal mucosal immune response in experimental NEC. In general anaesthesia, NEC was induced in six newborn piglets by injection of bovine casein into terminal ileum. Six controls received an equal amount of saline. Four hours later, samples were taken from the macroscopically most affected part of the treated loop and from the macroscopically healthy untreated intestine. Monoclonal antibodies to porcine CD1, CD2, CD4, CD8, CD45 and IgM were used for immunohistochemical staining. Casein-treated bowel showed typical macro- and microscopic findings of NEC. No changes were found in the saline-treated bowel. In both groups the bowel outside the treatment sector was normal. In casein-treated animals, treated samples showed significant decrease in density of CD4+ cells when compared with saline-treated controls. Similar trend was found in CD2+ and CD8+ cells but without statistical significance. Macroscopically healthy proximal untreated samples showed significant decrease in densities of CD2+, CD4+ and CD8+ lymphocytes in casein-treated group when compared with control samples. In casein-treated animals the density of CD45+ cells in the non-injected bowel was also decreased, but this did not reach statistical significance. Densities of CD1+ and IgM+ cells did not differ between casein-treated and saline-treated groups. A significant T-cell decrease was found in the present NEC model. Surprisingly, this was most prominent in the macroscopically healthy bowel outside the casein injection segment. The reason for T-cell decrease remains unclear, but bovine casein is known to contain peptide fractions that can modulate immune function. These findings may have implications in the design of neonatal milk formulas.

Animals↗
PubMed2003

A dual long-term effect of breastfeeding on atopy in relation to heredity in children at 4 years of age.

BACKGROUND: The long-term effect of early feeding on atopic sensitization is still unsolved. The aim of this study was to evaluate the long-term effect of breastfeeding on atopy in groups of 4-year-old children stratified by atopic heredity. METHODS: We collected four groups of 4-year-old children from a birth cohort: two groups with differing backgrounds of atopic heredity, all exclusively breast-fed for at least 3 months; and two groups with differing atopic heredity, but all fed with cow's milk-based formula during their first weeks. The data were collected with a questionnaire, skin prick testing, and measurement of serum total and allergen-specific IgE levels. RESULTS: Breastfeeding significantly decreased the risk of allergic rhino-conjunctivitis [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.18-0.95] and sensitization to furred pets, as measured by skin prick results, in children with atopic heredity, whereas in children without atopic heredity, breastfeeding was related to an increased risk of symptomatic atopy (OR 2.57, 95% CI 1.16-5.70), and high serum IgE values. A significant interaction was found between heredity and breastfeeding. CONCLUSIONS: The long-term effect of breastfeeding was dual: in children with atopic heredity, breastfeeding protected against atopy, whereas in children without atopic heredity, it increased the risk of atopy.

Animals↗
PubMed2003

Transcriptional regulation of the lactase-phlorizin hydrolase gene by polymorphisms associated with adult-type hypolactasia.

BACKGROUND AND AIMS: The mechanism of the developmental downregulation of the lactase-phlorizin hydrolase (LPH) gene underlying adult-type hypolactasia is unknown. We have determined the functional significance of the recently identified two single nucleotide polymorphisms (SNPs), C/T(-13910) and G/A(-22018), associated with adult-type hypolactasia by studying LPH mRNA levels in intestinal biopsy samples with different genotypes. METHODS: Intestinal biopsy samples were taken from 52 patients with abdominal complaints. Hypolactasia was diagnosed by determining lactase and sucrase activities and calculating their ratio (L/S ratio). The functional effect of the C/T(-13910) and G/A(-22018) genotype on expression of LPH mRNA was demonstrated in patients heterozygous for the C/T(-13910) and G/A(-22018) polymorphism and an informative expressed SNP located in the coding region of the LPH mRNA. Reverse transcription-polymerase chain reaction followed by solid phase minisequencing was used for accessing the relative expression levels of the LPH alleles using informative SNPs located in exons 1, 2, 6, 10, 13, or 17 as markers. RESULTS: Statistically significant differences between the three different genotypes CC(-13910) GG(-22018), CT(-13910) GA(-22018), and TT(-13910) AA(-22018) and their respective L/S ratios were observed. Relative quantitation of the expressed LPH alleles showed that the persistent allele represented 92 (6)% (mean (SEM), range 78-99%; n=14) of the expressed LPH mRNA. The patient with the homozygous persistent TT(-13910) AA(-22018), as well as hypolactasic patients with CC(-13910) GG(-22018), showed equal expression of both alleles (47 (1)%; n=7). CONCLUSIONS: Expression of LPH mRNA in the intestinal mucosa in individuals with T(-13910) A(-22018) alleles is several times higher than that found in individuals with C(-13910), G(-22018) alleles. These findings suggest that the two SNPs, C/T(-13910) and G/A(-22018), associated with adult-type hypolactasia, are associated with the transcriptional regulation of the LPH gene. The presence of the T(-13910) A(-22018) allele also shows significant elevation of the L/S ratio.

Adult↗
PubMed2002

Inflammatory cytokines in small intestinal mucosa of patients with potential coeliac disease.

T helper cell type 1 (Th1) response to gluten has been implicated in the pathogenesis of coeliac disease (CD). To characterize immunological activation and mild inflammations leading to overt CD in potential coeliac patients, jejunal biopsies were obtained from family members of patients with CD or dermatitis herpetiformis (DH). Nine family members and one latent CD, eight CD patients and eight normal controls furnished jejunal biopsy specimens. Immunohistochemical staining of sections for interleukin-1alpha (IL-1alpha), IL-2, IL-4, interferon-gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), CD3, gammadelta-T cell receptor (gammadelta-TCR), and alphabeta-TCR was carried out with monoclonal antibodies. Further, expression of IL-4 and IFN-gamma messenger RNA was detected by radioactive in situ hybridization in these same samples. In lamina propria, CD patients and potential CD patients had higher densities of IL-2 (P = 0.028, P = 0.043), IL-4 (P = 0.021, P = 0.034) and IFN-gamma positive cells (P = 0.000, P = 0.009) than did controls. Moreover, CD patients showed a higher density of TNF-alpha positive cells (P = 0.012, P = 0.001) than the other two groups, and expression of IFN-gamma mRNA (P = 0.035) was higher in them than in the other two study groups. Additionally, higher densities of TNF-alpha and IFN-gamma positive cells occurred in potential CD patients with high gammadelta-TCR+ intraepithelial lymphocytes (IELs). Our findings support the hypothesis that lamina propria T cells and macrophages, through their secretion of cytokines, play a central role in the pathogenesis of coeliac disease. The inflammatory cytokines found in potential CD specimens strongly suggest that these inflammatory markers can be identified long before visible villous changes have occurred.

Adolescent↗
PubMed2002

Iodine and gliadin challenge on oral mucosa in dermatitis herpetiformis.

Oral lesions and mucosal inflammatory changes may appear in dermatitis herpetiformis (DH). We examined whether potassium iodine, known to initiate blisters in the DH skin, or wheat gliadin, responsible for T-cell-dependent intestinal damage, can induce visible or microscopic changes in oral mucosa. Six patients with active DH were challenged with crude gliadin and 50% potassium iodine applied in patch test chambers on buccal mucosa for 12 h. After reading, biopsies were taken from the challenged and non-challenged mucosa. No macroscopic or microscopic vesicles were seen. However, gliadin- but not iodine-challenged epithelium showed increased numbers of CD4+ lymphocytes in all 5 patients with representative specimens (p = 0.06). No marked changes were found in the numbers of CD8+ or TcR alpha/beta+ lymphocytes, and the numbers of TcR gamma/delta+ cells remained at a low level. The results show that oral mucosa is resistant to production of macroscopic or microscopic DH lesions. It is, however, capable of reacting to locally applied gliadin by a T-cell response consisting of CD4+ lymphocytes.

Adult↗
PubMed2002

Coeliac disease in children and adolescents with type 1 diabetes: a study of growth, glycaemic control, and experiences of families.

UNLABELLED: The aim of this study was to evaluate whether coeliac disease affects growth, glycaemic control, and general well-being of children and adolescents with type I diabetes. Eighteen subjects were found to have coeliac disease by a screening program. Gastrointestinal symptoms, changes in growth and the levels of glycated haemoglobin (GHbA1) were analysed, as well as subjective well-being before and after diagnosis of coeliac disease. Overt gastrointestinal symptoms and deterioration of growth prior to disclosure of coeliac disease were seen only in one patient who had both of these conditions. Retrospectively, most subjects reported mild gastrointestinal complaints, which resolved on a gluten-free diet. Introduction of a gluten-free diet did not have any positive effect on glycaemic control, but was associated with an increase in weight-for-height (from 4.3+/-18.1 to 8.2+/-15.4% deviation from population median, p = 0.02). This increase in weight-for-height was inversely correlated with changes in GHbA1 (r = -0.574, p = 0.02). CONCLUSION: Coeliac disease is rarely associated with signs of malabsorption in children and adolescents with type I diabetes. Introduction of a gluten-free diet may be associated with excess weight gain. We recommend intensified follow-up for these subjects.

Adolescent↗
PubMed2002

Is coeliac disease prevalent among adolescent psychiatric patients?

UNLABELLED: Coeliac disease (CD) occasionally presents solely with neuropsychiatric symptoms and may predispose to mental and behavioural disorders. This study screened new adolescent psychiatric outpatients (n = 140) in the Department of Adolescent Psychiatry of the Hospital for Children and Adolescents, Helsinki, using immunoglobulin A antibody to tissue transglutaminase. The prevalence rate of CD was found to be 1 in 140. CONCLUSION: The results do not suggest that undetected CD is markedly overrepresented among adolescent psychiatric outpatients.

Adolescent↗
PubMed2001

Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial.

OBJECTIVE: To examine whether long term consumption of a probiotic milk could reduce gastrointestinal and respiratory infections in children in day care centres. DESIGN: Randomised, double blind, placebo controlled study over seven months. SETTING: 18 day care centres in Helsinki, Finland. PARTICIPANTS: 571 healthy children aged 1-6 years: 282 (mean (SD) age 4.6 (1.5) years) in the intervention group and 289 (mean (SD) age 4.4 (1.5) years) in the control group. INTERVENTION: Milk with or without Lactobacillus GG. Average daily consumption of milk in both groups was 260 ml. MAIN OUTCOME MEASURES: Number of days with respiratory and gastrointestinal symptoms, absences from day care because of illness, respiratory tract infections diagnosed by a doctor, and course of antibiotics. RESULTS: Children in the Lactobacillus group had fewer days of absence from day care because of illness (4.9 (95% confidence interval 4.4 to 5.5) v 5.8 (5.3 to 6.4) days, 16% difference, P=0.03; age adjusted 5.1 (4.6 to 5.6) v 5.7 (5.2 to 6.3) days, 11% difference, P=0.09). There was also a relative reduction of 17% in the number of children suffering from respiratory infections with complications and lower respiratory tract infections (unadjusted absolute % reduction -8.6 (-17.2 to -0.1), P=0.05; age adjusted odds ratio 0.75 (0.52 to 1.09), P=0.13) and a 19% relative reduction in antibiotic treatments for respiratory infection (unadjusted absolute % reduction -9.6 (-18.2 to -1.0), P=0.03; adjusted odds ratio 0.72 (0.50 to 1.03), P=0.08) in the Lactobacillus group. CONCLUSIONS: Lactobacillus GG may reduce respiratory infections and their severity among children in day care. The effects of the probiotic Lactobacillus GG were modest but consistently in the same direction.

Absenteeism↗
PubMed2001

Increased expression of intercellular adhesion molecule-1 and mucosal adhesion molecule alpha4beta7 integrin in small intestinal mucosa of adult patients with food allergy.

The mechanisms of adverse reactions to foods in the gastrointestinal tract are poorly understood. Previous studies of other atopic diseases and animal models suggest that adhesion molecules and mucosal lymphocytes may be implicated in the pathogenesis of food allergy (FA). The aim of our study was to investigate the expression of adhesion molecules and mucosal lymphocytes in duodena of patients with food allergies and of controls. Ten patients with FA to cereals (wheat, oats, and rye) or cow's milk and 9 control patients were included in the study. Quantitative analysis and immunohistochemical stainings for two pairs of adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1), alpha4beta7 integrin, and mucosal addressin cell adhesion molecule (MAdCAM-1) and lymphocyte markers on endoscopic duodenal biopsy specimens were performed. The villous structure and density of LFA-1-positive cells were normal in every biopsy specimen, but the patients had significantly more alpha4beta7+ cells in the intraepithelial space (P = 0.01). The expression of ICAM-1 in the lamina propria of patients with FA was also substantially increased (P = 0.003); however, staining with MAdCAM showed no intergroup difference. Moreover, we found significantly increased CD4+ and HLA-DR+ cells in the lamina propria of patients, in comparison to the controls, P = 0.05 and P = 0.04, respectively. The densities of CD3, CD8, HLA-DP, T cell receptor alphabeta+ and gammadelta+ cells and IgA-, IgA1-, and IgA2-containing cells did not differ in the two groups studied. Our results suggest that the increased expression of ICAM-1 and alpha4beta7 integrin may play an important role in the pathogenesis of food hypersensitivity and with the elevation of CD4- and HLA-DR-positive cells reflect a stage of inflammation in the structurally normal intestines.

Adolescent↗