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- Grahnquist, Lena
(författare)
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Regulation of ion transport in the gastrointestinal tract : aspects of early development
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ion transport in the gastrointestinal tract is vital for cellular homeostasis and to ensure growth during ontogeny. We have therefore investigated the regulation and maturation of sodium, potassium and hydrogen transport in the gastrointestinal tract. Net jejunal sodium absorption is significantly higher in young as compared to adult rats. During high salt intake, net sodium absorption decreases in young but not in adult rats. When dopamine production was inhibited we did not observe decreased sodium absorption in young rats on high salt diet. The reduced sodium absorption during high salt intake in young rats requires endogenous dopamine action. Net colonic potassium absorption in young rats is five times higher than in adult ones. The majority of colonic net potassium absorption occurs in the distal part of the colon. Using different approaches this study shows that apically located transporters which reabsorb potassium are upregulated in the infant rat while secreting basolateral transporters are upregulated in adult rats. Infant rat H+, K+- ATPase and ouabain-sensitive sodium independent ATPase were higher but Na+, K+-ATPase was lower than in the adult rat. Angiotensin II induces potassium secretion in rat distal colon. This effect is mediated through both receptors (AT1, and AT2) and by at least three different pathways (Na+, K+, 2CI cotransporter, the apical barium-sensitive potassium channels and the Na+, K+-ATPase). Rat gastric H+, K+-ATPase matures postnatally. The expression of H+, K+-ATPase increases from day 10. Gastric H+, K+-ATPase increased 2.5-fold when 10-day-old rats were treated with a single dose of glucocorticoids. A study of human gastric H+, K+-ATPase enzyme was performed on biopsies from neonates. The amount of H+, K-ATPase increases in relation to gestational and postnatal age. Boys have a significantly higher amount than girls. This is the first study on a large number of infants showing that gastric H+, K+-ATPase is present before term birth and that it increases during development. Conclusion: In summary, these studies of ion transport in the gastrointestinal tract show new mechanisms that ensure proper regulation of sodium, potassium and hydrogen transport during development. We have found that glucorticoids and dopamine have specific actions on ion transport during early development. In addition we have found that angiotensin II regulates colonic potassium transport in a complex manner.
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| 2. |
- Malmborg, Petter, et al.
(författare)
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Cesarean section and the risk of pediatric Crohn's disease
- 2012
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Ingår i: Inflammatory Bowel Diseases. - Oxon, United Kingdom : Blackwell Publishing. - 1078-0998 .- 1536-4844. ; 18:4, s. 703-708
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Tidskriftsartikel (refereegranskat)abstract
- Background: Crohn's disease (CD) could involve an inappropriate immune response against normal bowel flora. Disrupted or atypical patterns of microbial bowel colonization may impair development of homeostasis between gut flora and the immune system. Perinatal microbial exposures may be particularly important in stimulating intestinal immune recognition. As birth by cesarean section is thought to represent an atypical pattern of early bowel colonization, we examined its association with pediatric CD. Methods: Some 1536 patients diagnosed with pediatric CD and 15,439 controls matched by delivery unit, week of birth, sex, and born between 1973 and 2006 were identified through Swedish registers. The association of birth by cesarean section with pediatric CD was examined using conditional logistic regression, with stratification by sex and adjustment for parental socioeconomic index and maternal infections during pregnancy. Results: Birth by cesarean section is associated with a modestly increased risk for pediatric CD among boys (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.01-1.54) but not girls, (OR = 0.99, 95% CI 0.76-1.29) and elective cesarean section is associated with a modest increased risk for the entire population (OR = 1.36, 95% CI 1.02-1.80). Conclusions: This study does not suggest that the delivery procedure should be altered, but the findings may be of etiological significance in CD, indicating a potential role for perinatal exposures associated with delivery mode. Although the sex difference may have arisen by chance, the modestly increased CD risk for boys delivered by cesarean section is consistent with sex-specific differences in susceptibility to some exposures.
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| 3. |
- Malmborg, Petter, et al.
(författare)
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Presentation and progression of childhood-onset inflammatory bowel disease in northern Stockholm County
- 2015
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Ingår i: Inflammatory Bowel Diseases. - : Wolters Kluwer. - 1078-0998 .- 1536-4844. ; 21:5, s. 1098-1108
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Tidskriftsartikel (refereegranskat)abstract
- Background: Some studies have suggested that childhood-onset inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid progression to complications. Here, we report the presentation and progression of patients diagnosed with IBD during childhood in a population-based cohort from northern Stockholm County.Methods: Medical records for all 280 patients diagnosed in the period 1990-2007 with childhood-onset IBD in northern Stockholm County were followed until 2011 (median follow-up time, 8.8 yr). Disease phenotypes were classified according to the Paris pediatric IBD classification.Results: Among the 74 patients with ulcerative colitis, 72% presented with pancolitis. Among the 200 patients with Crohn's disease (CD), 75% presented with colitis. Complicated disease behavior was observed in 18% of patients with CD by end of follow-up. Extension of the disease territory was observed in 22% of patients with ulcerative colitis and 15% of patients with CD. The cumulative risk of intra-abdominal surgery after 10 years was 8% (95% confidence interval, 4%-20%) for ulcerative colitis and 22% (95% confidence interval, 15%-28%) for patients with CD. Nonmucosal healing at 1 year was associated with a complicated disease course in patients with CD (hazard ratio = 14.56; 95% confidence interval, 1.79-118.68; P = 0.01).Conclusions: Patients with childhood-onset IBD were characterized by extensive colitis that was relatively stable over time and associated with a relatively low risk of complications and abdominal surgery. Our findings confirm the more extensive disease location in pediatric IBD but did not identify the proposed dynamic and aggressive nature of the childhood-onset phenotype. The association of nonmucosal healing with a complicated disease course suggests that endoscopy should guide treatment intensity in childhood-onset CD.
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| 4. |
- Mårild, Karl, et al.
(författare)
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Down syndrome is associated with elevated risk of celiac disease : a nationwide case-control study
- 2013
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Ingår i: The Journal of Pediatrics. - : Elsevier BV. - 0022-3476 .- 1097-6833. ; 163:1, s. 237-242
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To provide risk estimates for celiac disease (CD) in Down syndrome (DS) compared with the general population.Study design: In this nationwide Swedish case-control study, we examined the risk of CD in individuals with DS born between 1973 and 2008. Study participants consisted of 2 populations: 11 749 patients with biopsy-verified CD (villous atrophy [VA], equivalent to Marsh grade III) who were identified through histopathology reports from the 28 pathology departments in Sweden and 53 887 population-based controls matched for sex, age, calendar year of birth, and county of residence. We used prospectively recorded data from Swedish health registers to identify individuals with DS. ORs were calculated using conditional logistic regression.Results: Of the 11 749 individuals with CD, 165 had a diagnosis of DS (1.4%) compared with 55/53 887 controls (0.1%). This corresponded to an OR of 6.15 (95% CI = 5.09-7.43) for subsequent CD in individuals with DS compared with the general population. The association between DS and CD was not affected by maternal age at delivery, infant sex, or presence of type 1 diabetes mellitus in the child.Conclusions: We found a sixfold increased risk of CD in individuals with DS. This study adds precision to the previously reported association between DS and CD.
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| 5. |
- Mårild, Karl, et al.
(författare)
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Highly increased risk of celiac disease in individuals with Down syndrome : a nationwide case-control study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background & Aims: Several studies have indicated a high prevalence of celiac disease (CD) in individuals with Down syndrome (DS), but data from population based studies are lacking.Methods: In this nationwide Swedish case-control study we examined the risk of CD in individuals with DS born between 1973 and 2008. Study participants consisted of two populations: 11,749 patients with biopsy-verified CD (villous atrophy [VA], equivalent to Marsh III) who were identified through histopathology reports from the 28 pathology departments in Sweden and 53,887 population-based controls matched for sex, age, calendar year of birth and county of residence. We used prospectively recorded data from Swedish health registers to identify individuals with DS. Odds ratios (ORs) were calculated using conditional logistic regression.Results: Of the 11,749 individuals with CD, 165 had a diagnosis of DS (1.4%) as compared with 55/53,887 controls (0.1%), corresponding to an OR of 6.15 (95% confidence interval [CI] = 5.09-7.43). The association between DS and CD was not affected by maternal age at delivery, infant sex, or presence of type 1 diabetes mellitus in the child.Conclusions: We found a six-fold increased risk of CD in individuals with DS. This study adds precision to the previously reported association between DS and CD and suggests that patients with DS should undergo screening for CD.
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| 6. |
- Olen, Ola, et al.
(författare)
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Antibodies Against Deamidated Gliadin Peptides and Tissue Transglutaminase for Diagnosis of Pediatric Celiac Disease - Diagnostic Performance and Cost in Clinical Practice.
- 2012
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Ingår i: Journal of pediatric gastroenterology and nutrition. - 1536-4801. ; 55:6, s. 695-700
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:: To evaluate diagnostic performance and actual costs in clinical practice of IgG/IgA deamidated gliadin peptide antibodies (DGP) as a complement to IgA antibodies against tissue transglutaminase (tTG) for the diagnosis of pediatric celiac disease (CD). PATIENTS AND METHODS:: All consecutive patients <18 years tested for tTG and/or DGP and who underwent duodenal biopsy because of suspected CD in Stockholm and Gothenburg, Sweden, 2008-2010 were included. Medical records were reviewed. RESULTS:: Of 537 children who underwent duodenal biopsy, 278(52%) had CD. 71(13%) were <2 years and 13(4%) had IgA deficiency. Sensitivity and specificity for tTG was 94% and 86% respectively. Corresponding values for DGP was 91% and 26%. Positive predictive values (PPV) were 88% for tTG and 51% for DGP. There were 148 children who were tTG negative and DGP positive, of which only 5%(8/148) had villous atrophy. Among children <2 years with normal IgA, PPV was 96%(25/26) for tTG and 48%(24/50) for DGP. In 13 IgA deficient children 9 were DGP positive of which 4 had CD (PPV 44%). 8/278 cases of CD would possibly have been missed without DGP. The cost of adding DGP and consequently more biopsies to be able to detect 8 extra cases of CD was &OV0556;399,520 or &OV0556;49,940 per case. CONCLUSION:: For diagnosing CD, tTG is superior to DGP, even in children <2 years. Combining tTG and DGP does not provide a better trade off between number of missed cases of CD, number of unnecessary duodenal biopsies and cost than tTG alone.
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