Age at development of type 1 diabetes- and celiac disease-associated antibodies and clinical disease in genetically susceptible children observed from birth.

OBJECTIVE: To compare the ages and sequence in which antibodies associated with type 1 diabetes and celiac disease appear and overt diseases develop in children with an HLA-conferred susceptibility to both diseases. RESEARCH DESIGN AND METHODS: We observed 2,052 children carrying genetic risks for both type 1 diabetes and celiac disease from birth until the median age of 5.7 years and analyzed diabetes- and celiac disease-associated antibodies in serum samples collected at 3- to 12-month intervals. Diabetes was confirmed by World Health Organization criteria and celiac disease by duodenal biopsies. RESULTS: Altogether 342 children seroconverted to positivity for at least one diabetes-associated autoantibody and 88 to positivity for at least one celiac disease-associated antibody at the median ages of 3.0 and 1.5 years, respectively (P < 0.001). If only children with biochemically defined diabetes-associated autoantibodies against insulin, GAD, or IA-2A protein (n = 146) and children with tissue transglutaminase autoantibodies were compared (n = 86), the median seroconversion ages were 2.5 and 3.0 years (P = 0.011). Fifty-one children progressed to overt diabetes at 4.5 years and 44 children to celiac disease at 4.3 years (P = 0.257). Of the 19 children who developed both diabetes- and celiac disease-associated antibodies, 3 progressed to both diabetes and celiac disease. CONCLUSIONS: Children with HLA-conferred susceptibility to type 1 diabetes and celiac disease develop celiac disease-associated antibodies mostly at a younger age or the same age at which they develop diabetes-associated autoantibodies. Clinical diabetes and celiac disease are commonly diagnosed at the same median age.

Fate of five celiac disease-associated antibodies during normal diet in genetically at-risk children observed from birth in a natural history study.

OBJECTIVES: To explore the natural history of antibodies against tissue transglutaminase (TGA), endomysium (EMA), reticulin (ARA), and gliadin (AGA-IgG and AGA-IgA) in children carrying HLA-conferred risk for celiac disease (CD) and observed frequently from birth. METHODS: TGA was measured in serum samples obtained between years 2000 and 2003 from 1,320 children carrying genetic CD risk. If a sample was TGA positive, all five antibodies were analyzed in all banked and forthcoming samples from that child, and a duodenal biopsy was recommended. At the end of this observation, in August 2004, the age of the children was from 1 to 9.5 yr (mean 4.1 yr). RESULTS: Forty-nine children (3.7%) were TGA positive. In these children, AGA-IgG had emerged at the mean age (+/- SD, range) of 2.0 +/- 1.5, 0.5-6.6 yr, while TGA, EMA, and ARA all emerged concurrently somewhat later (TGA at 3.2 +/- 1.5, 1.0-7.0 yr, P < 0.001 when compared to AGA-IgG). Despite continuing gluten exposure, positive TGA, EMA, ARA, AGA-IgA, and AGA-IgG values were spontaneously lost in 49%, 45%, 43%, 41%, and 32% of the children, respectively. CD was diagnosed by biopsy in 20 of the 26 TGA-positive children who consented to a biopsy. CONCLUSIONS: Potential CD trigger(s) other than only gluten probably function before AGA-IgG emerges, i.e., > or =3 months earlier than the transglutaminase-associated antibodies appear. In a remarkable proportion of the children, antibodies disappear spontaneously suggesting that regulatory immune phenomena under favorable circumstances are able to extinguish incipient CD in genetically at-risk children even without exclusion of gluten from the diet.

Poor cognitive development and abdominal pain: Wilson's disease.

An 8-year-old boy was referred to our hospital because of learning disabilities. His general cognitive functions were below the level for age, and he was diagnosed with dysphasia. The boy was transferred to a special class for children with learning problems. Three months later he was again referred to us because of acute epigastric pain. The only abnormal laboratory finding was a slightly elevated level of alanine aminotransferase. Although the symptoms disappeared in a few days, the transaminase levels remained above normal for the next 6 months. Further diagnostic work-up revealed low serum ceruloplasmin concentration and high 24-h urinary copper excretion. The hepatic copper concentration in liver biopsy was high (2900 microg/g dry weight), confirming the diagnosis of Wilson's disease. Brain MRI showed slight changes in white matter. The patient's asymptomatic sister was also diagnosed with Wilson's disease. Both siblings started penicillamine therapy and a copper-restricted diet. The copper content of the household water was found to be above average and a new plumbing system was installed. After 1 year from the initiation of the therapy, the transaminase concentrations normalized and both siblings were free of symptoms. After 2 years of therapy the patient was able to return to normal school. Wilson's disease must be borne in mind, when children are evaluated because of poor school performance, especially if they complain of abdominal symptoms.

Natural history of transglutaminase autoantibodies and mucosal changes in children carrying HLA-conferred celiac disease susceptibility.

OBJECTIVE: The natural history of the appearance and fate of transglutaminase autoantibodies (TGAs) and mucosal changes in children carrying HLA-conferred celiac disease (CD) risk remains obscure. The aim of this study was to investigate the sequence of events leading to overt CD by retrospective analysis of TGA values in serum samples collected frequently from genetically susceptible children since birth or early childhood. MATERIAL AND METHODS: A total of 1101 at-risk children were recruited in the study. A duodenal biopsy was recommended to all TGA-positive children and performed if parental consent was obtained. RESULTS: During up to 8 years of follow-up, 35 of the cohort children developed TGAs, the youngest at age 1.3 years. After age 1.3 years the annual TGA seroconversion rate was constantly around 1% at least until age 6 years. However, 18 of the 35 TGA-positive children (51%) lost TGAs, without any dietary manipulation. A further 7 children were IgA deficient; of these children, 2 developed IgG antigliadin antibodies (IgG-AGA). Only 13 of the 21 children (62%) who had duodenal biopsies had villous atrophy. The time that passed since emergence of TGAs failed to predict the biopsy findings. Only one of the children with TGAs and both of the IgA-deficient children with IgG-AGA had noticeable abdominal symptoms. CONCLUSIONS: TGAs appear in children at a constant rate after 1 year of age until at least the age of 6 years. Over half of the children loose TGA without gluten exclusion, challenging TGA positivity-based CD prevalence estimates. In symptom-free children, a requirement of two consecutive TGA-positive samples taken >or=3 months apart before performing a duodenal biopsy might diminish the number of unnecessary intestinal biopsies.

Comparing patient and nurse perceptions of perioperative care quality.

This study compared surgical patients' (n = 874) and perioperative nurses' (n = 143) perceptions of the quality of perioperative nursing care. The data were collected with a structured questionnaire in five hospital operating departments in Finland. The questionnaire items were divided into five main categories (staff characteristics, nursing activities, preconditions, progress of nursing process and environment); some of these categories were further divided into subcategories. Overall, patients tended to give significantly higher (P <.001) ratings than nurses, but for some items the patients had more critical perceptions. The results provide important clues for improving the quality of patient care so that staff activities better serve the needs of patients.