Clinics of coeliac disease in children in the 2000s.

OBJECTIVE: To describe the clinical picture of patients with coeliac disease (CD) and the change in its presentation over the past decades. STUDY DESIGN: Patients with CD were identified and clinical data collected from hospital records over a 6-year period (2000-2005). RESULTS: Altogether 197 patients aged 0.6-15.9 (mean 7.2) years were identified. They were found amongst the child population served by the hospital, the mean number of children at age 0.5-16 years was 268 000 during 2000-2005. The presenting symptom amongst the youngest patients (<3 years) was chronic diarrhoea (in 67%), and amongst older patients, abdominal pain. At the time of diagnosis, growth was severely retarded (height <2 SD for age) in 6.6%; mean height was -0.06 SD and weight + 1% for height. After diet treatment for a mean of 6 months, both height and weight increased significantly. Anaemia and iron deficiency were present in 25% and 43% of patients respectively. Intraepithelial T-cell receptor gamma/delta cells were pathologic in all 150 specimens studied. CONCLUSIONS: The presentation of CD depends on age. Even when we found six times more patients than during years 1976-1985 in the same hospital, published data on the prevalence of CD suggest that we found only a small minority of children with CD.

Infiltration of forkhead box P3-expressing cells in small intestinal mucosa in coeliac disease but not in type 1 diabetes.

Because the role of regulatory T cells in the intestinal inflammation is unknown in coeliac disease (CD) and type 1 diabetes (T1D), the expression of forkhead box P3 (FoxP3), CD25, transforming growth factor-beta, interferon (IFN)-gamma, interleukin (IL)-4, IL-8, IL-10, IL-15 and IL-18 was measured by quantitative reverse transcription-polymerase chain reaction in the small intestinal biopsies from paediatric patients with active or potential CD, T1D and control patients. The numbers of FoxP3- and CD25-expressing cells were studied with immunohistochemistry. Enhanced intestinal expressions of FoxP3, IL-10 and IFN-gamma mRNAs were found in active CD when compared with controls (P-values < 0.001, 0.004, <0.001). In potential CD, only the expression of IFN-gamma mRNA was increased. The numbers of FoxP3-expressing cells were higher in active and potential CD (P < 0.001, P = 0.05), and the ratio of FoxP3 mRNA to the number of FoxP3-positive cells was decreased in potential CD when compared with controls (P = 0.007). The ratio of IFN-gamma to FoxP3-specific mRNA was increased in active and potential CD (P = 0.001 and P = 0.002). Patients with T1D had no changes in regulatory T cell markers, but showed increased expression of IL-18 mRNA. The impaired up-regulation of FoxP3 transcripts despite the infiltration of FoxP3-positive cells in potential CD may contribute to the persistence of inflammation. The increased ratio of IFN-gamma to FoxP3 mRNA in active and potential CD suggests an imbalance between regulatory and effector mechanisms. The increased intestinal expression of IL-18 mRNA in patients with T1D adds evidence in favour of the hypothesis that T1D is associated with derangements in the gut immune system.

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.

cagA, vacA and iceA virulence genes of Helicobacter pylori isolates of children in Finland.

cagA, vacA s and m genotypes and iceA alleles were analyzed from Helicobacter pylori strains isolated from 17 Finnish children and 32 children of non-Finnish origin living in Finland. Twelve children in the latter group were eastern European and 15 were of African origin. Only three children of non-Finnish origin were born in Finland. The vacA sla subtype was more prevalent in the isolates from Finnish children than African children (76% vs. 7%, P<0.001); vacA s1b frequencies were 5% and 67%, respectively (P<0.001). The iceA1 allele was significantly more prevalent in African than Finnish isolates (93% vs. 35%, P< 0.01). Considerable variation was noted in the frequency of vacA s1 subtypes and iceA alleles in children originating from different geographic regions, but the geographic variation of s1 subtypes resembled that described in other reports.

Ideal role behaviours as seen by dentists and patients themselves and by their role partners: do they differ?

The aim of this study was to determine whether patients and dentists differ in their ideal role expectations concerning each others behaviour. This was done by further analysing a set of data containing responses to 124 five-class Likertian statements about ideal role expectations and questions about the background of the respondents with regard to different aspects of the dentist-patient relationship. The study groups consisted of a representative sample of lay people and all dentists in the Finnish Provinces Kuopio and North Karelia. To extract areas of ideal role expectations for both dentists and patients, orthogonal factor analyses were applied to the data. To evaluate the dissimilarity of the structure of the factor analyses, rotated factor matrices were used to conduct transformation analysis. Similarities between the ideal role expectations of dentists and patients were studied. When studied with transformation analysis, the ideal role expectations of dentists and patients were found to differ for both the ideal patient and the ideal dentist. However, dentists and patients shared expectations concerning one characteristic of the ideal dentist i.e. the importance of mutual communication, which was also considered the most important characteristic of the ideal dentist. For the characteristics of the ideal patient, the two groups shared the same expectations concerning the manageability of the patient. Previous research has compared dentist and patient expectations based only on single statements. No reports based on factor analysed data have been published, but transformation analysis was found to provide a useful tool for statistical evaluation of the dissimilarity of the factor structures.

Antiphospholipid antibodies in children.

Sera from children (n = 173) were tested for antiphospholipid antibodies (aPL) using an enzyme immunoassay detecting IgG anti-cardiolipin antibodies (GPL). Sera from adults (n = 100) were also tested. GPL were detected more frequently and at higher levels in children than in adults. Eighty-two per cent of the children and 27% of the adults tested positive (> or = 10 GPL Uml-1) for aPL (p < 0.001). Values of 45 GPLUml-1 or higher were detected in about 5% of the children, and 25 GPLUml-1 or higher in about 5% of the adults. Normal values should be adjusted accordingly.

Assessment of depression in chronic musculoskeletal pain patients.

OBJECTIVE: To analyze how the cognitive, affective, and somatic-vegetative symptoms of depression included in the modified Zung Self-Rating Depression Scale (ZSDS) relate to pain severity. SUBJECTS: Three groups of subjects were compared. The "no pain" group (n = 64) reported no musculoskeletal symptoms during the preceding year, the "low pain" group (n = 119) had a pain rating of < or = 4, and the "high pain" group (n = 137) had a rating of > or = 5 on a numerical pain rating scale (0-10). METHODS: Sum scores of the ZSDS and means of separate items in the three subgroups were compared. Factor analyses were performed to evaluate the structure of the ZSDS, and differences between subgroups on weighted factor scores were analyzed. RESULTS: The "high pain" group differed statistically significantly from both other groups on the sum score and on most of the items. Comparison of weighted factor scores in a three-factor solution revealed that in Factor I, "Psychic Energy," the "high pain" group differed from both other groups. In Factor II, "Despair," no differences between groups were found, while in Factor III, "Sleep problems," statistically significant differences were found between all subgroups; more severe pain was associated with more sleep problems, fatigue, and restlessness. CONCLUSION: ZSDS items describing symptoms which could be a consequence of the pain problem (e.g., sleep problems) are clearly related more to pain severity than other indicators of depression--e.g., feelings of hopelessness. A diagnosis of depression based on a sum score of an inventory which contains somatic-vegetative signs of depression may lead to an overestimation of depression in chronic musculoskeletal pain patients. in chronic musculoskeletal pain patients.

Antibodies against some bacterial antigens in children.

The prevalence of bacterial antibodies was determined in 173 children aged 0-15 years. The prevalence of IgG Borrelia burgdorferi antibodies in titres > 500 in children less than 8 years of age was 6% while none of the older children had these antibodies in titres > 400. IgG Helicobacter pylori antibodies were detected only in children older than 6 years of age, with a prevalence of 6.5%, as were IgA H. pylori antibodies, with a prevalence of 3.7%. The prevalence of high-titre IgG Campylobacter jejuni antibodies was 1.2%, that of IgA 1.8% and IgM 1.2%. The prevalence of high-titre (> 500 IU/ml) antistreptolysin O was 3%, that of antistaphylolysin-alpha (> or = 4 IU/ml) 2% and that of anti-teichoic acid antibodies (titre 2) 2%. Low-titre Yersinia antibodies were detected in 2%. High-titre Bordetella pertussis antibodies were detected in 6% of recently vaccinated children and in 8% of children in their first years of school. In the latter, high-titre antibodies were mainly of the IgM and IgA classes. Altogether 35 children tested positive for bacterial antibodies other than Bordetella pertussis antibodies. Clinical evaluation revealed a possible infection, suggested by the antibody, in 5 (3%) of the children. Two (vaccinated) children had evidence of whooping cough. Eight of the 35 children with high-titre bacterial antibodies (23%) also had elevated levels of autoantibodies (but not autoimmune diseases).

Randomised double blind trial of hypotonic oral rehydration solutions with and without citrate.

Hypotonic oral rehydration salts solutions (ORS) have been proved to be better than isotonic solutions with respect to water absorption. To establish whether a base precursor is essential in the composition of a hypotonic ORS with improved absorption properties, a randomised double blind clinical trial was conducted comparing two formulas of hypotonic ORS, each with an osmolality of 224 mmol/l, with or without citrate, in a group of 107 children admitted to hospital with acute diarrhoea. The two solutions were effective in the correction of dehydration and there was no difference between the treatments in the duration of diarrhoea. The patients receiving the hypotonic ORS with citrate consumed less of the solution, however, and their metabolic acidosis was corrected earlier. It is concluded that citrate is clinically advantageous in a hypotonic ORS, but a hypotonic formula without a base precursor is also effective.

Clodronate reduces plate osteopenia in the rabbit.

An osteosynthesis with a four-hole AO/ASIF-DCP plate was performed on the right tibia of 40 rabbits. Clodronate (50 mg/kg s.c.) was given once a week, resulting in a mean bone concentration of 509 micrograms/g in 2 hours. Plate fixation caused a decrease in mean net cross-sectional area of compact cortical bone of 17 percent at 9 weeks and 46 percent at 18 weeks. This resulted from bone resorption in bone under the plate, from pronounced cavitation in the plated bone (about 5 percent of cortical bone area at 9 weeks and 15 percent at 18 weeks), and from the fact that the medullary space was increased by 15 percent at 18 weeks. The total cross-sectional area of the diaphysis was increased by 31 percent at 9 weeks and by 17 percent at 18 weeks. Clodronate treatment reduced cortical porosity to about half of the mean values in the placebo group. Clodronate increased both the calcium content in the retained bone and the cross-sectional area of compact cortical bone, but induced only an insignificant increase in the area of periosteal new bone. Clodronate treatment seems not to be contraindicated in conjunction with rigid osteosynthesis, and may even slow down the osteopenic response occurring under the rigid plate.

Intestinal gamma/delta receptor-bearing T lymphocytes in celiac disease and inflammatory bowel diseases in children. Constant increase in celiac disease.

We studied the numbers of T-cell receptor alpha/beta- and gamma/delta-bearing lymphocytes in 27 jejunal specimens from 19 celiac patients, 27 rectal and colonic specimens from 14 ulcerative colitis patients and four patients with Crohn's disease, and 24 control specimens. MAb and a three-layer peroxidase staining method were used. Only low numbers of gamma/delta + cells were seen in normal jejunum and rectum of controls, as well as in the specimens of patients with inflammatory bowel diseases. In the lamina propria of celiac patients, the mean number of gamma/delta + cells was significantly higher than in the controls before treatment, during gluten-free diet, and after the gluten challenge. Within the jejunal epithelium, the number of gamma/delta + cells was elevated before and during gluten elimination and after the challenge test. The absolute number of intraepithelial gamma/delta + cells remained constant during gluten elimination and provocation. We infer that the constantly elevated population of gamma/delta + T cells in the epithelium of celiac patients may play an important role in the pathogenesis of celiac disease.

Variability in nutrient and food intakes among older middle-aged men. Implications for design of epidemiologic and validation studies using food recording.

The authors conducted a dietary methodology study in 1984 in Finnish men aged 55-69 years in order to validate two dietary assessment instruments being used in the US-Finland Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention Trial. Twelve 2-day food records collected from 162 men over a 6-month period, including every day of the week, served as the reference measure. This report focuses on three important questions for investigating diet and disease relations: 1) How many days are necessary to classify "usual" intake? 2) Is there loss as a result of using consecutive days? 3) Which days are necessary for assessment and classification of "usual" diet? A repeated-measures regression model was used to estimate the variance components and the effects of consecutive days, weekday (weekday vs. weekend), and season. Correlations between the averages of different numbers of days of food records and "true" usual intake were examined along with the resulting attenuations in relative risk. Results suggest that 7-14 days are required to adequately classify most individuals into categories of intake for most nutrients and some foods. There appears to be some loss of information from using consecutive days rather than days further apart. Weekday/weekend differences in mean intakes are slight, and the rank ordering of individuals appears to be preserved. A moderate seasonal effect is shown for classification of fruits, but only a slight one is seen for micronutrients and berries. Implications for the design of epidemiologic and validation studies are discussed.

Effect of diet and age on jejunal and circulating lymphocyte subsets in children with coeliac disease: persistence of CD4-8-intraepithelial T cells through treatment.

Monoclonal antibodies were used to determine the relative numbers of T lymphocyte subsets in 61 jejunal biopsies and in peripheral blood of 35 children with coeliac disease, and of 13 healthy controls. The T cell numbers in the lamina propria were unaffected by a change from gluten-free to gluten containing diet in the patients. The number of intraepithelial lymphocytes (where the CD8 cells predominated) were significantly raised in patients taking gluten. Ten to 20% of the patients' intraepithelial CD3 (mature T) cells expressed neither CD8 nor CD4 surface antigens. This CD4 8 T cell population persisted through gluten elimination and challenge. The circulating lymphocyte subsets showed little variation with the diet although there was a marked increase in the proportion (14.9%) of CD4 8 T cells in patients during gluten elimination. In the histologically normal jejunal mucosa from control subjects, the age of the subject showed a positive correlation with villus intraepithelial CD3+ and CD8+ cells, and crypt intraepithelial CD4+ cells. No clear cut effect of age was observed on lamina propria lymphocyte counts of the controls, or on the lymphocyte counts in jejunal mucosa of the coeliac patients. The observed CD3+4-8- lymphocytes may represent activated cells unable to present their surface antigens, or they may be gamma delta-receptor bearing T cells, which could have a significant role in the pathogenesis of coeliac disease.

HLA-DR expression, natural killer cells and IgE containing cells in the jejunal mucosa of coeliac children.

The expression of HLA-DR by surface and crypt epithelium and the numbers of cells of natural killer (NK) phenotype and of IgE containing cells were studied with monoclonal antisera using the peroxidase technique. We examined 48 jejunal biopsy specimens taken from 35 coeliac children before treatment (11), during gluten free diet (20) and after gluten challenge (17), and 13 control specimens. The luminal surface of the epithelial cells stained with HLA-DR antiserum in all specimens, but the cytoplasm of the surface epithelial cells took up the stain more frequently in the specimens from the controls (5/13) than those from the coeliacs (2/48) (p less than 0.01). In 21/28 specimens taken from coeliacs when on a gluten containing diet the crypt epithelium showed strong HLA-DR expression, while only 4/20 (p less than 0.01) specimens of coeliacs on a gluten free diet and 1/13 specimens of controls had similar staining. Among the intraepithelial lymphocytes no cells of NK phenotype were found in specimens from patients or controls. As compared with control specimens biopsy specimens from untreated coeliac patients showed smaller numbers of NK cells in the lamina propria. No difference was found in the numbers of IgE containing cells between the patients and controls. The strong expression of HLA-DR by the crypt epithelial cells in coeliac children on a normal diet suggest that these cells are involved in the presentation of the antigen.

Gluten challenge in children with dermatitis herpetiformis: a clinical, morphological and immunohistological study.

Twenty one children with dermatitis herpetiformis were studied in an attempt to evaluate the response in the skin, in jejunal morphology, and in jejunal immunoglobulin containing cell counts to gluten elimination and subsequent gluten challenge. In all of the 15 patients whose jejunal biopsy was studied after the eventual gluten challenge the jejunal lesion had returned in 2.4 to 28 months. The numbers of IgA- and IgM-containing cells were similarly raised in primary and postchallenge biopsies. In the 13 patients whose skin improved during a gluten free diet and who were challenged with gluten the rash worsened and the dapsone/sulphapyridine requirement increased. The jejunal deterioration was equally marked in the six patients whose gluten challenge was stopped because of an intractable rash as it was in those who completed the preplanned challenge. The specimens of the former, however, had significantly more IgA-containing cells than specimens of the latter. The number of intraepithelial lymphocytes clearly reflected the degree of intestinal damage. IgA-containing cells proved to be the most sensitive indicator of an immune reaction taking place in the gut of these patients. Even in the two children with initially normal or nearly normal jejunal mucosa, the IgA cell counts in the jejunal lamina propria were markedly raised.

HLA antigens, jejunal morphology and associated diseases in children with dermatitis herpetiformis.

Forty-five Hungarian and Finnish children from 1.5 to 15 years with dermatitis herpetiformis were studied for HLA antigens, jejunal morphology on gluten-containing diet and associated diseases in the patients and their relatives. A strong association with HLA-B8 was found in patients of both nationalities, the relative risks were 12.8 and 9.6, respectively. The Hungarian patients were also typed for HLA-DR locus, and an association with DR3 but not with DR7 was observed. Patients with subtotal villous atrophy had slightly more often HLA-B8 and DR3 than those with milder intestinal lesions. Atopic eczema occurred in 20% of the patients and family history of atopy seemed to have an inverse correlation with HLA-B8 and DR3.

Late mucosal relapse in a boy with coeliac disease and cow's milk allergy.

A case of coeliac disease where exceptionally long gluten challenge was needed to produce mucosal relapse is presented. An initial diagnosis of intestinal cow's milk allergy with total villous atrophy was made at the age of 3.5 months. The lesion healed after the child was put on a diet free of cow's milk and gluten. After 4.3 years on a normal diet his jejunal structure was still normal but at the age of 10.9 years, after 8.7 years of gluten ingestion, total villous atrophy was again observed. On a gluten-free diet the small intestinal structure is completely normal at the age of 17.1 years.

Fibrosarcoma in a girl with celiac disease and IgA deficiency.

A case of abdominal wall fibrosarcoma in a 17-year-old girl with celiac disease and IgA deficiency is described. Celiac disease was putatively diagnosed with intestinal biopsy at the age of 15 years when she came for hospital investigations because of IgA deficiency and recurrent respiratory infections. The tumor occurred at the age of 17 years during the gluten challenge performed for final diagnosis of celiac disease. Surgical excision, irradiation, and chemotherapy were initially successful. After 7 months, however, the tumor recurred. Reoperation and a new course of irradiation therapy coinciding with the reinstitution of a gluten-free diet proved to be effective in tumor eradication. Nine years after the cessation of cancer treatment she is well and has two healthy children.