Objective To determine if constipation predominant IBS (IBS-C) is associated with changes in intestinal barrier and secretory function. Design 19 IBS-C patients and 18 healthy volunteers (all females) underwent saccharide excretion assay (0.1 g 13C mannitol and 1 g lactulose), measurements of duodenal and colonic mucosal barrier (transmucosal resistance (TMR), macromolecular and E. coli Bio-Particle translocation), mucosal secretion (basal and ACh evoked short circuit current, Isc), in vivo duodenal mucosal impedance, circulating endotoxins and colonic tight junction gene expression. Results There were no differences in the in vivo measurements of barrier function between IBS-C and healthy: cumulative excretion of 13C mannitol (0–2 hr mean (SEM); IBS-C: 12.1 (0.9) mg vs healthy: 13.2 (0.8) mg) and lactulose (8–24 hr; IBS-C: 0.9 (0.5) mg vs healthy: 0.5 (0.2) mg); duodenal impedance IBS-C: 729 (65) Ω vs healthy: 706 (43) Ω; plasma mean endotoxin activity level IBS-C: 0.36 (0.03) vs healthy: 0.35 (0.02); and in colonic mRNA expression of occludin, ZO 1–3, and claudins 1–12, 14–19. Ex vivo findings were consistent, with no group differences: duodenal TMR (IBS-C: 28.2 (1.9) Ω*cm2 vs healthy: 29.8 (1.9) Ω*cm2) and colonic TMR (IBS-C: 19.1 (1.1) Ω*cm2 vs healthy: 17.6 (1.7) Ω*cm2); FITC Dextran (4 kDa) and E. coli Bio- Particle flux. Colonic basal Isc was similar, however, duodenal basal Isc was lower in IBS-C (43.5 (4.5) µA*cm2) vs healthy (56.9 (4.9) µA*cm2), p=0.05. ACh evoked ΔIsc was similar. Conclusions Females with IBS-C have normal colonic barrier and secretory function. Basal duodenal secretion is decreased in IBS-C.
Background: Natriuretic peptide concentrations in adults require age- and sex-specific reference intervals for optimal interpretation. Females have higher natriuretic peptide concentrations, and hypotheses suggest that estrogen may be responsible. This study sought to determine the influence of hormone modulation on N-terminal probrain natriuretic peptide (NT-proBNP) by using a pediatric cohort. Children/adolescents typically have rapid hormone changes during puberty, making them an ideal group to study. Methods: We selected 759 specimens (303 male, 456 female; ages 2 months to 18 years, mean 13 years) obtained from the Mayo Clinic Pediatric Residual Specimen Bank. We measured NT-proBNP, sex hormone–binding globulin (SHBG), estradiol, and testosterone by immunoassays or LC-MS/MS and calculated free testosterone. We performed univariate and multivariate analyses to investigate the significance of NT-proBNP with each hormone. Results: Reference values demonstrated a sex difference and sequential age differences in females. Univariate modeling of the hormones with NT-proBNP revealed an independent inverse association of NT-proBNP with testosterone, a direct association with SHBG, and no significant association with estradiol. Multivariate modeling confirmed a strong association of testosterone and SHBG with NT-proBNP. Correlation of hormones with NT-proBNP retained greater significance than either age or sex. Conclusions: In pediatric patients, NT-proBNP is independently associated with both testosterone and SHBG hormone concentrations. Measurements of testosterone are inversely associated with NT-proBNP, and estrogens are marginally associated with NT-proBNP in males but not females, suggesting that androgens and not estrogens modulate sex differences notable in natriuretic peptides. Children and adolescents may require an objective assessment of hormones if optimal interpretation of natriuretic peptide concentrations is desired or the concentrations are confounded. .
Introduction Hemolysis, icterus, and lipemia (HIL) are common pre‐analytical variables in the clinical laboratory. Understanding their effects on coagulation laboratory results is essential. Methods HIL effects on the prothrombin time (PT), activated partial thromboplastin time (APTT), dilute Russell's viper venom time (DRVVT), thrombin time (TT), and protein C chromogenic activity (CFx) were evaluated on the ACL TOP 750 optical analyzer and STA‐R Evolution mechanical analyzer (PT and APTT only) by spiking normal donor, patient, and commercial control samples with varying concentrations of hemolysate, bilirubin, or a lipid emulsion. The relative difference or bias compared to the original results was determined. Results Hemolysis (H) indices up to 900 mg/dL did not affect the APTT, PT, DRVVT Confirm, TT, and CFx; however, H indices above approximately 200 mg/dL resulted in a false‐negative DRVVT screen and screen/confirm ratio in samples with a lupus anticoagulant. There was an artifactual prolongation of the PT and APTT when conjugated bilirubin was dissolved in aqueous solvents and not when it was dissolved in dimethyl sulfoxide. Icterus (I) indices up to 45 mg/dL did not result in significant (>15%) bias for all assays evaluated. The PT and APTT assays failed to produce a robust clot curve when the lipemia (L) index exceeded 6000 milliabsorbance units (mAbs), and the TT and DRVVT assays failed when the L index exceeded 3000 mAbs; the CFx assay was unaffected by lipemia. Conclusions Verification of the manufacturer's recommended interference thresholds is important since it may avoid inappropriate instrument flagging and/ or sample rejection.
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