Erkki Savilahti
University of Helsinki, Pediatrics, Emeritus
Research Interests:
Small-intestinal adaptation to resection has been extensively studied in rats. The present study investigates morphology, crypt cell proliferation, and disaccharidase activities of the remaining small intestine and colon after 75%... more
Small-intestinal adaptation to resection has been extensively studied in rats. The present study investigates morphology, crypt cell proliferation, and disaccharidase activities of the remaining small intestine and colon after 75% proximal resection of porcine small intestine. Specimens were obtained from the proximal jejunum, middle and distal ileum, and proximal colon preoperatively (n = 5) and 14 weeks after small-bowel transection (n = 5) or resection (n = 5). Proliferation was analyzed immunohistochemically with the Ki-67 antigen MIB-1. Disaccharidase activities were determined in accordance with the method of Dahlqvist. In addition to macroscopic enlargement, resection markedly increased the villi and crypts of the remaining small bowel. Crypt cell proliferation decreased with advancing age after transection but remained at the preoperative level after resection. Specific, but not total, activities of maltase and sucrase in the mid-ileum decreased after resection. Small-intestinal adaptation in the pig involves macroscopic enlargement and a prompt increase in villus size, which is associated with high crypt cell proliferation.
Research Interests:
Research Interests:
A family is presented in which three of four siblings had truncus arteriosus and other anomalies compatible with the third and fourth pharyngeal pouch syndrome (DiGeorge syndrome). The syndrome is uncommon and most of the reported cases... more
A family is presented in which three of four siblings had truncus arteriosus and other anomalies compatible with the third and fourth pharyngeal pouch syndrome (DiGeorge syndrome). The syndrome is uncommon and most of the reported cases have been solitary. In this family an autosomal recessive inheritance is possible.
Research Interests:
Research Interests:
Research Interests:
These studies support the transport model depicted in Figure 3: Incorporation of J chains into dimeric IgA induces a configurational fit allowing complexing of IgA with SC available in the plasma membrane of serous secretory epithelial... more
These studies support the transport model depicted in Figure 3: Incorporation of J chains into dimeric IgA induces a configurational fit allowing complexing of IgA with SC available in the plasma membrane of serous secretory epithelial cells. This complexing on the surface of the cell stimulates pinocytosis, and the completed secretory IgA molecules are transported in cytoplasmic vesicles to the gland lumen. The same transport model can be applied for the external translocation of IgM.
Research Interests:
Research Interests:
Research Interests:
A slight to moderate increase in autoantibodies to transglutaminase 2 (TG2), but no morphological evidence of villous atrophy to confirm the diagnosis of celiac disease (CD) poses a challenge for clinicians. Our aim was to study the... more
A slight to moderate increase in autoantibodies to transglutaminase 2 (TG2), but no morphological evidence of villous atrophy to confirm the diagnosis of celiac disease (CD) poses a challenge for clinicians. Our aim was to study the matrix metalloproteinase (MMP) profile, proliferative and apoptotic characteristics of jejunal biopsies obtained from such pediatric patients in order to find markers predictive of early changes in extracellular matrix degrading enzymes in the development of CD. Twenty-eight children with positive screening tests (increase in transglutaminase and/or endomysium antibodies), but minor histological changes in the gut (Marsh grade 0-2), were studied and followed up for 2-3 years. In situ hybridizations for MMP-1, -3 and -12 were performed and sections were immunostained for MMP-19 and -26. Proliferating cells were identified by Ki-67 immunostaining and apoptotic cells using the TUNEL technique. MMP-12 was detected in macrophages in 16/28 samples and its expression was associated with increased autoantibodies for TG2 and densities of CD3 and gammadelta positive T-cells in the epithelium. The number of stromal MMP-26 positive cells was high in patients with high TG2 titers. Expression of MMP-12, MMP-1 and -3 clustered in children with type 1 diabetes (T1D) and the proportion of apoptotic mucosal cells was increased in patients with T1D compared to the others. When children with CD were compared to those who did not develop it, the numbers of IEL, cryptal Ki-67, CD-3, and MMP-12 positive cells were higher and showed the most significant differences. In pediatric patients, increased numbers of MMP-12 positive macrophages in lamina propria associate with high titers of antibodies to TG2 and proness to CD. A stage of mild inflammation may contribute to the upregulation of MMPs in the gut of patients with T1D.
Research Interests:
Pathology, Adolescent, Medicine, Antibodies, Humans, and 15 moreChild, Intestinal Mucosa, Celiac Disease, Female, Male, Infant, Jejunum, Clinical Sciences, Matrix Metalloproteinases, Type 2 Diabetes Mellitus, Tissue Transglutaminase, Transglutaminases, Case Control Studies, Child preschool, and Muscle fibers skeletal
In active coeliac disease, mucosal atrophy is associated with a marked decrease in intestinal disaccharidase enzyme activities. We investigated the value of duodenal mucosal disaccharidases to predict the severity of mucosal villous... more
In active coeliac disease, mucosal atrophy is associated with a marked decrease in intestinal disaccharidase enzyme activities. We investigated the value of duodenal mucosal disaccharidases to predict the severity of mucosal villous atrophy and its recovery in 50 patients with coeliac disease. Duodenal mucosal histology and disaccharidase activities were studied at least twice with a mean interval of 9 months. Histology of specimens from all patients was examined by the same pathologist blinded to the data on disaccharidase activities. Mucosal damage was scored into four groups as follows: Grade 0 = normal mucosa; grade I = slight villous atrophy, that is, cryptic component 30%-50%; grade 2 = moderate villous atrophy, that is, cryptic component 50%-90%; grade 3 = severe villous atrophy, that is, cryptic component >90%. The enzyme activities of the disaccharidases were determined as U/g protein. Duodenal mucosal disaccharidase activities were good predictors of the grade of mucosal villous atrophy. Positive predictive values for moderate or severe villous atrophy were 90% for maltase (maltase activity <150 U/g protein), 86% for sucrase (<40 U/g protein) and 71% for lactase (<20 U/g protein). Accordingly, negative predictive values, that is, none or only minimal villous atrophy (grades 0 or 1) with normal disaccharidase activities, were 71% for maltase, 70% for sucrase and 63% for lactase. The increase in duodenal disaccharidase activities correlated with recovery of the mucosa based on histology. Besides the histological examination, measurement of disaccharidase activities offers an additional tool to evaluate response to a gluten-free diet in patients with coeliac disease.
Research Interests:
Adult-type hypolactasia (lactase non-persistence) is a common cause of gastrointestinal symptoms. Several DNA sequence variants have been identified for the lactase-persistence/non-persistence (LP/LNP), the most common being the C to T... more
Adult-type hypolactasia (lactase non-persistence) is a common cause of gastrointestinal symptoms. Several DNA sequence variants have been identified for the lactase-persistence/non-persistence (LP/LNP), the most common being the C to T residing -13910 bp upstream of the lactase gene (LCT). We have analysed sequence variants of LP/LNP in subjects originating from Northern Russia. A total of 148 subjects with gastrointestinal complaints were genotyped covering about 400 bp around the -13910C/T variant using direct PCR-sequencing. All patients were interviewed about milk-related symptoms using the questionnaire. Disaccharidase activities were measured from intestinal biopsy specimens of the index person. The prevalence of the -13910C/C genotype among 148 patients was 28.4%. A G to A variant residing 13914 bp upstream from the LCT gene (-13914G>A) was identified in one participant carrying the -13910C/C genotype. In two biopsy specimens her lactase activity was above the generally accepted cut off level for adult-type hypolactasia, 10U/g protein. Three other family members also carried the -13914G>A genotype. Among eight family members five had the LNP genotype -13910C/C. A rare variant G to A residing 13914 bp upstream of the LCT gene was identified in a subject carrying the more frequent variant -13910C/C. The -13914G>A variant in heterozygous state was associated with increased lactase activity, suggesting that the increased lactase activity is most likely to be associated with the -13914G>A variant. Further studies need to be done to confirm the functional role of this variant.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
The clinical phenotype of Schimke immunoosseous dysplasia (SID) is characterized by growth retardation, renal failure, recurrent infections, cerebral infarcts, and skin pigmentation beginning in childhood. We report here on a 4-year-old... more
The clinical phenotype of Schimke immunoosseous dysplasia (SID) is characterized by growth retardation, renal failure, recurrent infections, cerebral infarcts, and skin pigmentation beginning in childhood. We report here on a 4-year-old male child who had all characteristic symptoms of SID, and, in addition, vomiting and prolonged diarrhea. The study results suggest that malabsorption, demonstrated as increased serum immunoglobulin A anti-gliadin antibody, steatorrhea and partial villous atrophy of the jejunal small bowel, is a previously unrecognized feature of SID.
Research Interests:
Research Interests:
The nutritional status of children with cow's milk allergy was followed during an elimination diet in 19 children (9 boys and 10 girls) beginning at the mean age of two years (range 0.6-4.1 years). The cow's milk allergy... more
The nutritional status of children with cow's milk allergy was followed during an elimination diet in 19 children (9 boys and 10 girls) beginning at the mean age of two years (range 0.6-4.1 years). The cow's milk allergy had been verified in hospital by a challenge test at a mean age of 0.9 years (range 0.2-1.9 years). Weight, height and laboratory indices to test protein, mineral and vitamin status were measured at three follow-up visits at three-month intervals. In addition to cow's milk allergy all these children had some other food allergies, and six of the 19 children were allergic to soy protein. Only two of the 19 children were given a soy-based formula. In the diets of the other children, cow's milk was replaced by increasing amounts of other foodstuffs and supplementary calcium. At the beginning of the study the relative heights of the children were slightly retarded (-0.6 SD) and remained unchanged during follow-up (-0.8 SD at the end of the study). The relative weights were found to be decreased during follow-up (p less than 0.05). There was a significant reduction in serum prealbumin values; eight of the 19 children showed abnormally low values. Low serum zinc values were seen in 12 children. Serum iron concentration was low in two children and two had high serum alkaline phosphatase values. Seven-day food recording indicated that dietary intake of energy was below the recommendation in some children, but protein intake was high. Some children had low intakes of riboflavin.(ABSTRACT TRUNCATED AT 250 WORDS)
Research Interests:
Research Interests:
Research Interests:
We measured IgG subclass levels by radial immunodiffusion with polyclonal antisera in 60 patients with IgA deficiency. The low IgA levels were measured by a sensitive and specific enzymoimmunometric method. None of the patients had... more
We measured IgG subclass levels by radial immunodiffusion with polyclonal antisera in 60 patients with IgA deficiency. The low IgA levels were measured by a sensitive and specific enzymoimmunometric method. None of the patients had complete deficiency of IgG2, but 4 patients had serum levels of IgG2 and 4 of IgG3 below the range for controls. Elevated levels of IgG1 were found in patients with juvenile rheumatoid arthritis and coeliac disease. None of the patients with coeliac disease or juvenile rheumatoid arthritis had low IgG2 or IgG3 levels. The levels of IgG4 were highly variable but patients with coeliac disease had particularly high values. The severity of IgA deficiency did not correlate with the level of serum IgG2.
Research Interests:
Immunology, Juvenile Idiopathic Arthritis, Rheumatoid Arthritis, Adolescent, Medicine, and 14 moreImmunopathology, Humans, Child, Celiac Disease, Female, Male, Adult, Respiratory Tract Infections, Coeliac Disease, immunoglobulin G, Nino, Radial Immunodiffusion Assay, Child preschool, and immunoglobulin M
Research Interests:
The change in activity of three disaccharidase enzymes (maltase, sucrase and lactase) was determined according to the method of Dahlqvist during acute rejection in non-immunosuppressed piglet small bowel grafts. In addition, two brush... more
The change in activity of three disaccharidase enzymes (maltase, sucrase and lactase) was determined according to the method of Dahlqvist during acute rejection in non-immunosuppressed piglet small bowel grafts. In addition, two brush border enzymes, lactase and aminopeptidase, were stained with monoclonal antibodies. Diminishing disaccharidase activity was an early event during rejection. Diminution began 2 days before distinct morphological changes were seen in the mucosal biopsies. Evaluation of disaccharidase activity can thus be used as a confirmatory method in detecting rejection. Reduction in immunohistological staining of lactase and aminopeptidase with monoclonal antibodies and changes in mucosal morphology were observed to progress simultaneously.
Research Interests:
Research Interests:
Gastroenterology, Adolescent, Medicine, Inflammatory Bowel Disease, Humans, and 15 moreChild, Internal Medicine, Female, Male, Colonoscopy, Clinical Sciences, Glucocorticoid, Feces, Biological markers, Glucocorticoids, Inflammatory Bowel Diseases, Calprotectin, Child preschool, discontinuation, and Adrenal cortex hormones
Research Interests:
Research Interests:
Research Interests:
An improvement in screening for celiac disease has recently been described that uses human umbilical cord as a substitute for monkey esophagus to determine IgA endomysium antibodies in adults. As using monkey esophagus is ethically... more
An improvement in screening for celiac disease has recently been described that uses human umbilical cord as a substitute for monkey esophagus to determine IgA endomysium antibodies in adults. As using monkey esophagus is ethically questionable for large-scale screening, we studied whether substitution of umbilical cord would be suitable for pediatric patients as well. Serum from 53 children with untreated celiac disease, 22 in remission and 13 on challenge, were screened for antigliadin IgA, antigliadin IgG, and IgA reticulin antibodies, in addition to IgA endomysium antibodies tested both on monkey esophagus and on human umbilical cord. Controls included 20 patients with cow-milk-sensitive enteropathy, 23 with inflammatory bowel disease, and 23 with diabetes mellitus, and 48 patients who were biopsied to exclude celiac disease either because of positive gliadin antibody test or disturbed growth. Sensitivity (0.94) and specificity (1.0) were similar for umbilical cord and esophageal determinations in active celiac disease. Both substrates detected identical positive cases and neither gave false-positive results. In celiac patients on a gluten-free diet, endomysium antibodies with either substrate were positive in seven identical cases and negative in 15 of 22 cases. Correlations with reticulin antibodies were comparable with human umbilical cord and monkey esophagus (0.83 and 0.85, respectively; Spearman Correlation Section Pair-Wise deletion). Human umbilical cord is an excellent substitute for monkey esophagus to determine endomysium antibodies in celiac diagnosis in children and adolescents.
Research Interests:
Pediatric Gastroenterology, Adolescent, Medicine, Humans, Child, and 15 moreCeliac Disease, Gliadin, Animals, Infant, Jejunum, Adult, Esophagus, Reference Values, Myofibrils, Enzyme Linked Immunosorbent Assay, immunoglobulin G, Immunoglobulin A, Child preschool, Haplorhini, and Medical and Health Sciences
Regulatory T (Treg) cells together with intestinal microflora play a central role in controlling allergic inflammation. We examined the markers related to Treg cells, and bacterial signaling, such as Toll-like receptors (TLR)-2 and -4, in... more
Regulatory T (Treg) cells together with intestinal microflora play a central role in controlling allergic inflammation. We examined the markers related to Treg cells, and bacterial signaling, such as Toll-like receptors (TLR)-2 and -4, in the duodenal mucosa of patients with food allergy (FA). Small intestinal samples were collected from patients with FA on a normal or an elimination diet, from healthy controls and patients with untreated celiac disease. Single and double immunohistochemistry were used to enumerate the densities of Foxp3-positive cells and TLR2- and TLR4-positive cells in the mucosa and evaluate the colocalization of Foxp3 expression in CD4, CD25, and CTLA-4 cells. The mRNA expression of CD25, Foxp3, TLR2, and TLR4 was measured by reverse transcriptase-polymerase chain reaction. The densities of Foxp3 and TLR4 cells were significantly increased in patients with untreated FA compared with healthy controls (P = 0.003, P = 0.033), and the Foxp3 cells were higher in untreated than in treated allergic patients (P < 0.001). The immense majority of Foxp3 cells were CD4 (median 100%), CTLA-4 (100%), or CD25 (81%). The ratio of Foxp3 mRNA to Foxp3 cells was decreased in patients with FA and in patients with celiac disease compared with controls (P = 0.036, P = 0.035). Foxp3 cells are increased in the duodenum of patients with untreated FA, but these cells are not able to suppress the harmful immune response, indicated by the low expression of Foxp3 transcripts. The increase of TLR4 cells and their correlation with TCRgammadelta intraepithelial lymphocytes suggest a role for the innate immunity and intestinal microbiota in FA.
Research Interests:
Molecular Biology, Diet, Medicine, Gene expression, Food Allergy, and 15 moreToll like receptor signaling, Humans, Child, Intestinal Mucosa, Celiac Disease, Female, Male, Infant, Biological markers, Duodenum, Child preschool, TLR, reverse transcriptase polymerase chain reaction, Medical and Health Sciences, and food hypersensitivity
Research Interests:
A syndrome of chronic diarrhea, vomiting, and failure to thrive was described 35 years ago. The syndrome was caused by damage in the jejunum after ingestion of cow's milk. Symptoms appeared in young infants shortly after... more
A syndrome of chronic diarrhea, vomiting, and failure to thrive was described 35 years ago. The syndrome was caused by damage in the jejunum after ingestion of cow's milk. Symptoms appeared in young infants shortly after introduction of cow's milk formula. Patients had moderate steatorrhea, decreased absorption of D-xylose, and, often, iron-deficiency anemia and hypoproteinemia. They had strong IgA and IgG antibodies to cow's milk. IgE antibodies to cow's milk were negative, as a rule. Indicators of cell-mediated immune reaction to cow's milk proteins were often positive. Patients were tolerant to cow's milk by the age of 3 years. Malabsorption was due to damage to the jejunal mucosa: Varying villus atrophy was associated with inflammation in surface epithelium and lamina propria. The epithelial cell renewal rate increased. Surface epithelial cells decreased in height, with short, furry microvilli and large aggregates of lysozymes. The number of intraepithelial lymphocytes was markedly increased, but normalized during cow's milk elimination. Most of these lymphocytes had alpha/beta T-cell receptors, and many were cytotoxic. Some specimens had an increase in gamma/delta T-cell receptor-bearing cells. In the lamina propria, CD4+ cells predominated, and some of them were activated. IgA- and IgM-containing cells were markedly increased during cow's milk exposure, but IgE cells were not abnormal. The density of eosinophils was moderately increased. Secretion of interferon-gamma by cells isolated from patients' intestines was markedly increased. Morphologic and immunologic findings suggest that T-cell-mediated reaction to proteins in cow's milk is present in the small intestines of patients with this syndrome and causes this enteropathy.
Research Interests:
Medicine, Antibodies, Humans, Animals, Infant, and 4 moreJejunum, Milk, Child preschool, and Medical and Health Sciences
Research Interests:
Food allergy (FA) is a subgroup of adverse effects of food on the health of an individual, and it is defined as caused by altered immunologic mechanisms. The evidence of IgE mediation in acute FA is well established, its most common... more
Food allergy (FA) is a subgroup of adverse effects of food on the health of an individual, and it is defined as caused by altered immunologic mechanisms. The evidence of IgE mediation in acute FA is well established, its most common manifestations are erythematous and urticarial skin symptoms, but acute gastrointestinal symptoms often associate these and may occur alone. The gastrointestinal symptoms of delayed FA are chronic diarrhoea, more rarely vomiting, and the associating skin symptom is chronic eczema. Immune mechanisms causing delayed FA are not well defined—at least in the chronic enteropathy, T cells play a role. Most studies on the intestinal inflammation of FA have dealt with chronic, slow reactions to foods, but some describe patients with immediate, IgE-mediate reactions, too. Enteropathy associated with allergy to cows’ milk and causing chronic diarrhoea and malabsorption was desribed 40 years ago (1). This type of food allergy is associated with severe morphologic and inflammatory changes in the intestine. The morphologic findings in the jejunal biopsy specimens are like those in Celiac disease, though often less pronounced: There is a varying degree villous atrophy with crypt hyperplasia and inflammation both intraepithelially and in the lamina propria. The average number of cells in the crypts was 1.8 times the number in controls. The morphology of jejunal damage in soy-protein-induced enteropathy had characteristics similar to those described for cows’ milk induced enteropathy. We found that the epithelial cell renewal rate was much increased as the result of increased mitotic rate and larger crypt cell compartment. Both morphology and a monoclonal antibody associating most strongly with mitotic cells have been used to measure mitotic activity in the jejunal crypts. Both methods showed increased mitotic activity in the crypts, though of a moderate degree (1). In most cases, there was an increase in the number of intraepithelial lymphocytes; we found three times as many lymphocytes intraepithelially as seen in the normal intestine, a value that did not differ from that found in untreated Celiac disease. During cow milk challenge, the counts did not always rise as much (1). The density of eosinophils in the epithelium has been shown to be increased. The great majority of intraepithelial lymphocytes are CD3+ /ß T-cell receptor-bearing cells, and as in normal intestines, they were mostly suppressor/cytotoxic, CD8+ cells. The proportion of TIA1 positive cells among intraepithelial lymphocytes (UCHL1+ cells) in specimens from patients with malabsorption in cow’s milk allergy (CMA) was increased and decreased with the length of the elimination diet. TIA1 is a specific cytotoxic granuleassociated protein expressed only by T lymphocytes and natural killer cells. Thus, the proportion of cytotoxic cells in the epithelium of these patients was high; the same has been shown for specimens from patients with Celiac disease (1). In patients with severe enteropathy, several studies have shown a moderately increased densities of intraepithelial / TCR+ cells. The same was seen in schoolaged children with slow developing mild gastrointestinal symptoms in cows’ milk challenges (1,2). In the lamina propria the numbers of lymphocytes, plasma cells and eosinophils are increased. Early studies on immunoglobulins and complement in the intestines of patients with this syndrome showed a strong infiltration of IgA and IgM containing cells at the time of clinical reaction either to cow’s milk (CM) or soy, while the role of complement remains uncertain. The presence of increased numbers of IgE-positive cells is disputed (1). CD4+ T helper cells predominated in the lamina propria, as in normal intestines. Many CD4+ cells were also HLA-DR+, suggesting that they were activated. These cells diminished during CM elimination. The number of lymphocytes positive for homing receptor 4/ß7 was increased in the lamina propria of adults with slow food reactions; these patients also showed a higher numbers of ICAM-1+ cells in the lamina propria (3). Hauer et al., using enzyme-linked immunoabsorbant spot technique, showed an elevation in IFNand, to a lesser extent, IL-4 secretion in duodenal biopsies of 14 infants with cow milk sensitive enteropathy (4). Cells secreting IFNwere ten times as abundant as cells secreting IL-4, indicating a Th1 dominance. The numbers of cells secreting interleukin-5 and -10 were unchanged (4). In our recent Address correspondence and reprint requests to: Dr. E. Savilahti, Hospital for Children and Adolescents, Helsinki University Central Hospital, FIN-00029 Helsinki, Finland (e-mail: erkki.savilahti@hus.fi). Journal of Pediatric Gastroenterology and Nutrition 39:S742–S743 © June 2004 Lippincott Williams & Wilkins, Philadelphia
Research Interests:
Research Interests:
Genetics, Human Evolution, Medical Genetics, Molecular Evolution, Biology, and 15 moreMedicine, Biopsy, Biological Sciences, Humans, Genetic Testing, Newborn Infant, Introns, Genotype, Genetic variation, Founder Effect, Gene Expression Regulation, Medical, alleles, Medical and Health Sciences, and Blood Donor
Early feeding with cow's milk (CM) may increase the risk of cow's milk allergy (CMA). We sought to examine prospectively whether supplementary feeding of CM at the maternity hospital would increase the risk when compared... more
Early feeding with cow's milk (CM) may increase the risk of cow's milk allergy (CMA). We sought to examine prospectively whether supplementary feeding of CM at the maternity hospital would increase the risk when compared with feeding with pasteurized human milk or hydrolyzed formula. We studied 6209 unselected healthy, full-term infants, of whom 5385 (87%) required supplementary milk while in the hospital. The infants were randomly assigned to receive CM formula (1789 infants), pasteurized human milk (1859 infants), or whey hydrolysate formula (1737 infants). The comparison group (824 infants) was composed of infants who were exclusively breast-fed. The infants were followed for 18 to 34 months for symptoms suggestive of CMA. The primary endpoint was a challenge-proven adverse reaction to CM after a successful CM elimination diet. The cumulative incidence of CMA in the infants fed CM was 2.4% compared with 1.7% in the pasteurized human milk group (odds ratio [OR], 0.70; 95% confidence interval [CI], 0. 44-1.12) and 1.5% in the whey hydrolysate group (OR, 0.61; 95% CI, 0. 38-1.00). In the comparison group, CMA developed in 2.1% of the infants. Among the infants who required supplementary feeding at hospital, both exposure to CM while in the hospital (OR, 1.54; 95% CI, 1.04-2.30; P =.03) and obvious parental atopy (OR, 2.32; 95% CI, 1.53-3.52; P <.001) increased the risk of CMA. Our data indicate that feeding of CM at maternity hospitals increases the risk of CMA when compared with feeding of other supplements, but exclusive breast-feeding does not eliminate the risk.
Research Interests:
Pediatrics, Immunology, Incidence Geometry, Medicine, Pregnancy, and 15 moreAllergy, Humans, Female, Animals, Milk, Newborn Infant, Odds ratio, Adverse Drug Reaction, Breast feeding, Human Milk, Confidence Interval, Cumulative Incidence, Infant Formula, Clinical Allergy and Immunology, and Infant nutritional physiological phenomena
The incidence of cystic fibrosis (CF) in Finland is one tenth that in other Caucasian populations. To study the genetics of CF in Finland, we used a combined molecular and genealogical approach. Out of the 20 Finnish families with a... more
The incidence of cystic fibrosis (CF) in Finland is one tenth that in other Caucasian populations. To study the genetics of CF in Finland, we used a combined molecular and genealogical approach. Out of the 20 Finnish families with a living CF patient, 19 were typed for eight closely linked restriction fragment length polymorphisms (RFLP) at the MET, D7S8, and D7S23 loci. The birthplaces of the parents and grandparents were traced using population registries. Allele and haplotype frequencies in Finland are similar to those of other European and North American populations, but are modified by sampling: two regional CF gene clusters, evidently the results of a founder effect, were identified. Generally, the gene was evenly distributed over the population, carrier frequency being estimated at approximately 1.3%. We conclude that CF in Finland is caused by the common Caucasian mutation(s), and that the low frequency of the gene can be explained by a negative sampling effect and genetic drift.
Research Interests:
Research Interests:
Research Interests:
OBJECTIVE To study the humoral immune response to bovine serum albumin (BSA) and ovalbumin (OA) in children with newly diagnosed insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS We examined serum samples from 505... more
OBJECTIVE To study the humoral immune response to bovine serum albumin (BSA) and ovalbumin (OA) in children with newly diagnosed insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS We examined serum samples from 505 children 0.8–14.9 years of age with newly diagnosed IDDM for antibodies to BSA and OA by enzyme-linked immunosorbent assay (ELISA). We also had two control groups: 85 unrelated control children (0.8–7.1 years of age) and 395 nondiabetic siblings (3.0–14.9 years of age). The specificity of antibodies detected in ELISA was confirmed by immunoblotting in a subset of sera with varying levels of antibodies. RESULTS Diabetic children <7 years of age had a significantly higher level of IgG (immunoglobulin) antibodies to BSA than did unrelated control children (P < 0.0001). The difference was greatest in the youngest group of children, 0.8–2.9 years of age. IgA antibodies to BSA were detected more frequently among diabetic than control children (P = 0.0...
Research Interests:
Immunology, Adolescent, Finland, Antibodies, Children, and 15 moreHumans, Child, Internal Medicine, Diabetes mellitus, Albumin, Infant, Antibody, Bovine Serum Albumin, Enzyme Linked Immunosorbent Assay, Diabetes Care, immunoglobulin G, Immunoblotting, Immunoglobulin A, Child preschool, and Medical and Health Sciences
Because subclinical coeliac disease may decrease fertility or complicate pregnancy, we screened women with recurrent miscarriage of unknown aetiology (n = 63), unexplained infertility (n = 47) and infertility with a known cause (n = 82),... more
Because subclinical coeliac disease may decrease fertility or complicate pregnancy, we screened women with recurrent miscarriage of unknown aetiology (n = 63), unexplained infertility (n = 47) and infertility with a known cause (n = 82), for anti-endomysium antibodies in serum to find undiagnosed coeliac disease. One woman (1-6%) with recurrent miscarriage, another woman (2.1%) with unexplained infertility and one woman (2.0%) in the control group (n = 51), were considered to have coeliac disease. We could not demonstrate a higher frequency of coeliac disease in women with infertility or recurrent miscarriage, but suggest that undiagnosed coeliac disease is common in women.
Research Interests:
Obstetrics, Infertility, Medicine, Pregnancy, Humans, and 15 moreCeliac Disease, Female, Etiology, Gynecology, Adult, Female Infertility, Coeliac Disease, Miscarriage, Autoantibodies, Recurrent Miscarriage, Subclinical Infection, Immunoglobulin A, mass Screening, Medical and Health Sciences, and Muscle fibers skeletal
We studied the significance of antibodies to bovine serum albumin (BSA) as a risk factor for insulin-dependent diabetes mellitus (IDDM) in a case-control setting. IgA and IgG antibodies to BSA and ovalbumin were measured from sera of 104... more
We studied the significance of antibodies to bovine serum albumin (BSA) as a risk factor for insulin-dependent diabetes mellitus (IDDM) in a case-control setting. IgA and IgG antibodies to BSA and ovalbumin were measured from sera of 104 patients with newly diagnosed IDDM and of 111 matched controls by enzyme-linked immunosorbent assay. Patients with diabetes had significantly higher levels of IgA antibodies to BSA (p = 0.003); IgG antibodies also tended to be higher (p = 0.08). Levels of IgA antibodies to ovalbumin were similar in the patients and controls, but IgG antibodies were higher in controls (p = 0.02). When antibodies to BSA, beta-lactoglobulin, whole cow&#39;s milk and islet cell antibodies were studied as risk determinants of IDDM in a multivariate, logistic regression analysis, IgA antibodies to beta-lactoglobulin and to cow&#39;s milk were independently associated with the risk (p = 0.037 and 0.048, respectively), while antibodies to BSA were not a significant risk factor. The results question the role of BSA as a cross-reacting antigen with pancreatic beta-cell surface proteins in the aetiology of IDDM.
Research Interests:
Endocrinology, Medicine, Humans, Child, Internal Medicine, and 15 moreDiabetes mellitus, Animals, Risk factors, Risk Factor, Antibody, Risk Factors, Bovine Serum Albumin, Type 2 Diabetes Mellitus, Enzyme Linked Immunosorbent Assay, immunoglobulin G, Milk proteins, Immunoglobulin A, immunoglobulin M, Ovalbumin , and Paediatrics and reproductive medicine
A total of 16 children with Shwachman&#39;s syndrome were studied over a period of 17 years. Eight cases were detected in autopsy at 6 to 15 months; all had died of cardiac failure due to myocardial lesions. The left ventricles showed... more
A total of 16 children with Shwachman&#39;s syndrome were studied over a period of 17 years. Eight cases were detected in autopsy at 6 to 15 months; all had died of cardiac failure due to myocardial lesions. The left ventricles showed necrosis of myofibres in large areas and the pancreas was atrophic and replaced by adipose tissue. The other eight patients included two siblings of deceased cases. Only one of these showed transient cardiac failure and no significant nutritional deficiencies were found. They had steatorrhoea due to failure of the exocrine pancreas and either constant (6 cases) or cyclic (2 cases) neutropenia. The steatorrhoea improved with age. Pyogenic infections, mainly otitis media were frequent during the first three years of life. Measurements of humoral and cell-mediated immunity were normal, but in addition to low numbers of neutrophils, the neutrophilic chemotaxis was depressed in all seven patients tested. Skin lesions, hepatic inflammation, and growth tended to improve with age. The family data of the patients is consistent with an autosomal recessive trait inheritance.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Adolescent, Children, Inflammatory Bowel Disease, Humans, Child, and 15 moreClinical Medicine, Female, Adolescents, Infant, Frequency, Clinical Sciences, C reactive protein, Biological markers, Granulomas, Crohns Disease, Glucocorticoids, Crohn Disease, Case Control Studies, Child preschool, and Fecal calprotectin
Dietary wheat gluten has been associated with the risk of diabetes in animal models of human insulin-dependent diabetes mellitus (IDDM). To evaluate the role of wheat gluten as a T cell antigen in human IDDM, we studied the cell-mediated... more
Dietary wheat gluten has been associated with the risk of diabetes in animal models of human insulin-dependent diabetes mellitus (IDDM). To evaluate the role of wheat gluten as a T cell antigen in human IDDM, we studied the cell-mediated immune response to wheat gluten in patients with IDDM and in control subjects. The cellular response to gluten was measured by the peripheral blood mononuclear cell (PBMC) proliferation test, and the results were expressed as a stimulation index (SI). We observed an enhanced cellular immune response to gluten (SI &gt; or = 3) in seven of 29 patients with newly diagnosed IDDM (24.1%), in six of 39 patients with a longer duration of IDDM (15.4%), and in two of 37 non-diabetic controls (5.4%). Reactivity of T cells to gluten was associated with IDDM at diagnosis (P = 0.03), whereas patients with longer duration of IDDM did not differ from controls (P = 0.16). Responses of T cells to gluten were low in general: the median SI (range) was 2.0 (1-8.6) in patients with newly diagnosed IDDM and 1.5 (1-5.8) in control subjects (P = 0.03). Cellular responsiveness to gluten was not associated with HLA-DQB1 risk alleles for IDDM in patients. Although T cell responses to gluten were slightly increased in newly diagnosed patients the responsiveness was rare, and thus our results do not support a major role of gluten in the pathogenesis of human IDDM.