Dysfunction of the exocrine pancreas is observed in diabetes, but links between concurrent exocrine and endocrine pancreatic disease and contributing genetic factors are poorly characterized. We studied two families with diabetes and exocrine pancreatic dysfunction by genetic, physiological and in vitro functional studies. A genome-wide screen in Family 1 linked diabetes to chromosome 9q34 (maximal lod score 5.07). Using fecal elastase deficiency as a marker of exocrine pancreatic dysfunction refined the critical chromosomal region to 1.16 Mb (maximal lod score 11.6). Here, we identified a single-base deletion in the variable number of tandem repeats (VNTR)-containing exon 11 of the carboxyl ester lipase (CEL) gene, a major component of pancreatic juice and responsible for the duodenal hydrolysis of cholesterol esters. Screening subjects with maturity-onset diabetes of the young identified Family 2, with another single-base deletion in CEL and a similar phenotype with beta-cell failure and pancreatic exocrine disease. The in vitro catalytic activities of wild-type and mutant CEL protein were comparable. The mutant enzyme was, however, less stable and secreted at a lower rate. Furthermore, we found some evidence for an association between common insertions in the CEL VNTR and exocrine dysfunction in a group of 182 unrelated subjects with diabetes (odds ratio 4.2 (1.6, 11.5)). Our findings link diabetes to the disrupted function of a lipase in the pancreatic acinar cells.

Vitamin D production in human skin occurs only when incident UV radiation exceeds a certain threshold. From simulations of UV irradiances worldwide and throughout the year, we have studied the dependency of the extent and duration of cutaneous vitamin D production in terms of latitude, time, total ozone, clouds, aerosols, surface reflectivity and altitude. For clear atmospheric conditions, no cutaneous vitamin D production occurs at 51 degrees latitude and higher during some periods of the year. At 70 degrees latitude, vitamin D synthesis can be absent for 5 months. Clouds, aerosols and thick ozone events reduce the duration of vitamin D synthesis considerably, and can suppress vitamin D synthesis completely even at the equator. A web page allowing the computation of the duration of cutaneous vitamin D production worldwide throughout the year, for various atmospheric and surface conditions, is available on the Internet at http://zardoz.nilu.no/~olaeng/fastrt/VitD.html and http://zardoz.nilu.no/~olaeng/fastrt/VitD-ez.html. The computational methodology is outlined here.

Objective: To determine the vitamin D status of middle-aged women living in the Norwegian arctic and its relationship with vitamin D intake and exposure to ultraviolet (UV) radiation. Design: Cross-sectional study. Conclusions: Increased ingestion of marine food items that provide vitamin D should be promoted and further studies should be carried out to investigate vitamin D status in arctic populations in relation to both UV exposure and traditional food sources.

Olafsdottir E, Aksnes L, Fluge G, Berstad A. Faecal calprotectin levels in infants with infantile colic, healthy infants, children with in ammatory bowel disease, children with recurrent abdominal pain and healthy children. Acta Paediatr 2002; 91: 45-50. Stockholm. ISSN 0803-5253 This study investigated faecal calprotectin concentration, a measure of intestinal in ammation, in infants and children with abdominal pain. Faecal calprotectin was measured by an enzyme-linked immunosorbent assay kit in spot stool samples in 76 infants with typical infantile colic, 7 infants with transient lactose intolerance and 27 healthy infants. All infants were 2-10 wk of age. In addition, 19 children with recurrent abdominal pain (RAP; mean age 11.5 y), 17 with in ammatory bowel disease (IBD; mean age 11.1 y; 10 had Crohn's disease and 7 ulcerative colitis) and 24 healthy children (mean age 5.3 y) were studied. In infants with infantile colic the mean faecal calprotectin concentration was not different from that in healthy infants (278 § 105 vs 277 § 109 mg kg ¡1 , p = 0.97) or in infants with transient lactose intolerance (300.3 § 124 mg kg ¡ 1 , p = 0.60). The calprotectin level was similar in boys and girls and fell signi cantly with age (p = 0.04). Children with IBD had faecal calprotectin levels (293 § 218 mg kg ¡1 ) much higher than healthy children (40 § 28 mg kg ¡1 , p < 0.0001) and children with RAP without identi ed organic disease (18 § 24 mg kg ¡1 , p < 0.0001).Conclusion: Faecal calprotectin may differentiate between functional abdominal pain and IBD in school-aged children. In young infants high faecal calprotectin levels are normal.

Background/Aims: A food frequency questionnaire (FFQ) and a database for dietary supplements were developed for use in the Norwegian Mother and Child Cohort Study (MoBa). The aim of the present study was to investigate the relation between reported use and biomarkers in supplement and nonsupplement users and to validate self-reported intake of dietary supplements in mid pregnancy. Method: 120 women were recruited from MoBa, and 119 subjects completed the MoBa FFQ and a 4-day weighed food diary. Information on supplement use was collected by both methods. Venous blood specimens and 24-hour urine samples were obtained for measurement of dietary biomarkers. Results: Biomarker concentration/excretion and intake differed significantly between supplement and nonsupplement users for vitamin D, carotenoids, folate, the n–6/n–3 fatty acid ratio and iodine (p < 0.05 for all variables). Flavonoid excretion was higher in flavonoid-supplement users (p < 0.05). Significant correlations between total dietary intake (food and supplements) and biomarker concentration/excretion were found for vitamin D (r = 0.45, p < 0.001), folate (r = 0.26, p = 0.005), the n–6/n–3 fatty acid ratio (r = 0.36, p < 0.001) and iodine (r = 0.42, p < 0.001). Conclusion: The biochemical indicators examined in this study confirmed differences in self-reported micronutrient intake between supplement and nonsupplement users for vitamin D, beta-carotene, folate, n–3 fatty acids, flavonoids and iodine.

Olafsdottir E, Aksnes L, Fluge G, Berstad A. Faecal calprotectin levels in infants with infantile colic, healthy infants, children with in ammatory bowel disease, children with recurrent abdominal pain and healthy children. Acta Paediatr 2002; 91: 45-50. Stockholm. ISSN 0803-5253 This study investigated faecal calprotectin concentration, a measure of intestinal in ammation, in infants and children with abdominal pain. Faecal calprotectin was measured by an enzyme-linked immunosorbent assay kit in spot stool samples in 76 infants with typical infantile colic, 7 infants with transient lactose intolerance and 27 healthy infants. All infants were 2-10 wk of age. In addition, 19 children with recurrent abdominal pain (RAP; mean age 11.5 y), 17 with in ammatory bowel disease (IBD; mean age 11.1 y; 10 had Crohn's disease and 7 ulcerative colitis) and 24 healthy children (mean age 5.3 y) were studied. In infants with infantile colic the mean faecal calprotectin concentration was not different from that in healthy infants (278 § 105 vs 277 § 109 mg kg ¡1 , p = 0.97) or in infants with transient lactose intolerance (300.3 § 124 mg kg ¡ 1 , p = 0.60). The calprotectin level was similar in boys and girls and fell signi cantly with age (p = 0.04). Children with IBD had faecal calprotectin levels (293 § 218 mg kg ¡1 ) much higher than healthy children (40 § 28 mg kg ¡1 , p < 0.0001) and children with RAP without identi ed organic disease (18 § 24 mg kg ¡1 , p < 0.0001). Conclusion:Faecal calprotectin may differentiate between functional abdominal pain and IBD in school-aged children. In young infants high faecal calprotectin levels are normal.

Asthma-like symptoms and airway hyper-responsiveness (AHR) are frequently reported in children subsequent to premature birth and bronchopulmonary dysplasia (BPD). There is limited knowledge on the mechanisms underlying these respiratory manifestations. Generally, childhood asthma and AHR is described within a context of inheritance, allergy and eosinophilic airway inflammation, and often in relation to cigarette exposures. We investigated these factors in relation to current asthma and AHR in a population-based cohort of 81 young people, born with gestational age < or = 28 wk or birth weight < or = 1000 g, and in a matched term-born control population. In the pre-term population, asthma and AHR were additionally studied in relation to neonatal respiratory morbidity. At follow up, more pre-term than control subjects had asthma. Forced expiratory volume in first second (FEV1) was reduced, AHR was substantially increased, and the level of the urinary leukotriene metabolite E4 (U-LTE4) was increased in the pre-term population compared to the term-born. In control subjects, asthma and AHR was associated with a pattern consistent with inheritance, allergy, airway inflammation, and cigarette exposures. In the pre-terms, asthma and AHR was either unrelated or less related to these factors. Instead, AHR was strongly related to a neonatal history of BPD and prolonged requirement for oxygen treatment. In conclusion, asthma and AHR subsequent to extremely premature birth differed from typical childhood asthma with respect to important features, and AHR was best explained by neonatal variables. These respiratory manifestations thus seem to represent a separate clinical entity.

BackgroundCalprotectin is a calcium and zinc binding protein, abundant in neutrophils and is extremely stable in faeces. Faecal calprotectin is used as a non-specific marker for gastrointestinal inflammation. It has a good diagnostic precision to distinguish between irritable bowel syndrome and inflammatory bowel disease. Studies have established normal concentrations in healthy children; all these studies have been performed in high-income countries. The objective of this study was to determine the concentration of faecal calprotectin in apparently healthy children aged 0-12 years in urban Kampala, Uganda.MethodWe tested 302 apparently healthy children aged, age 0-12 years (162 female, 140 male) in urban Kampala, Uganda. The children were recruited consecutively by door-to-door visits. Faecal calprotectin was analyzed using a quantitative enzyme-linked immunosorbent assay. Faeces were also tested for Helicobacter pylori (H. pylori) antigen, for growth of enteropathogens and microscopy was performed to assess protozoa and helminths. A short standardized interview with socio-demographic information and medical history was obtained to assess health status of the children.ResultsIn the different age groups the median faecal calprotectin concentrations were 249 mg/kg in 0 < 1 year (n = 54), 75 mg/kg in 1 < 4 years (n = 89) and 28 mg/kg in 4 < 12 years (n = 159). There was no significant difference in faecal calprotectin concentrations and education of female caretaker, wealth index, gender, habits of using mosquito nets, being colonized with H. pylori or having other pathogens in the stool.ConclusionConcentrations of faecal calprotectin among healthy children, living in urban Ugandan, a low-income country, are comparable to those in healthy children living in high-income countries. In children older than 4 years, the faecal calprotectin concentration is low. In healthy infants faecal calprotectin is high. The suggested cut-off concentrations in the literature can be used in apparently healthy Ugandan children. This finding also shows that healthy children living under poor circumstances do not have a constant inflammation in the gut. We see an opportunity to use this relatively inexpensive test for further understanding and investigations of gut inflammation in children living in low-income countries.