ABSTRACT
BACKGROUND AND AIMS: Measurement of 7 alpha-hydroxy-4-cholesten-3-one (C4) in serum is a semiquantitative test for bile acid malabsorption (BAM). We have previously established pediatric normal values for C4 with an upper limit of normal of 66.5 ng/mL, independent of age and sex. Here we performed the C4 test in 58 pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: C4 was measured using high performance liquid chromatography (HPLC) in fasting serum samples of 44 patients with CD (range 7-19 years) and 14 with UC (4-18 years). Disease activity was assessed by the pediatric CD and UC activity indices (PCDAI and PUCAI, respectively) plus serum (CRP, ESR) and fecal inflammatory markers (calprotectin). RESULTS: C4 concentrations were increased in 10 CD (23%) (range: 70.8-269.3 ng/mL) but only one UC patient (72.9 ng/mL). CD patients with diarrhea (n=12) had higher C4-values compared to those without (76.9 vs. 30.4 ng/mL; p=0.0043). Ileal resection in CD patients (n=10) was associated with increased C4 concentrations (81.2 vs. 24.3 ng/mL, p=0.0004). No correlation was found between C4 values and inflammatory markers. Six of 7 CD patients with persistent diarrhea but quiescent disease (PCDAI ≤12.5) had C4 values indicating BAM. CONCLUSION: Elevated C4 concentrations indicating BAM are common in children with CD. They are associated with ileal resection and non-bloody diarrhea in the absence of active disease or elevated inflammatory markers. The C4-test identifies a subgroup of CD patients with persistent diarrhea in spite of clinical remission which may benefit from bile acid binding therapy.
Subject(s)
Bile Acids and Salts/metabolism , Cholestenones/metabolism , Inflammatory Bowel Diseases/metabolism , Intestinal Mucosa/metabolism , Adolescent , Biomarkers/metabolism , Child , Child, Preschool , Chromatography, High Pressure Liquid , Feces/chemistry , Female , Humans , Inflammatory Bowel Diseases/diagnosis , Intestines/pathology , Leukocyte L1 Antigen Complex/metabolism , Male , Reproducibility of Results , Severity of Illness Index , Young AdultABSTRACT
Both cerebrovascular disease (CVD) and depression are common conditions in the elderly, and there is emerging evidence of a bi-directional relationship: 1) depression can cause CVD and stroke, transient ischemic attack; and 2) subcortical CVD are associated with increased risk for depression. The frequency of poststroke depression is highest during the first month after the stroke, but remains high even after several years. Depression is associated with poorer functional prognosis and higher mortality after stroke. There is good evidence that severity of functional impairment, high neuroticism, low social support as well as genetic factors are associated with an increased risk for post-stroke depression. Deep white matter lesions are the most consistent imaging correlate of depression. Potential mechanisms mediating the association between depression and CVD are neuroinflammation and HPA-axis activation, fronto-subcortical circuit lesions, and serotonergic dysfunction. Antidepressants have demonstrated effect on poststroke depression in meta-analyses, and such drugs as well as vitamin B can reduce the incidence of depression in stroke survivors. In addition, serotonergic drugs may strengthen poststroke motor and cognitive recovery, potentially through restorative mechanisms. Psychotherapeutic strategies such as problem-solving therapy seem to be effective. There is emerging evidence that treatment of cardiovascular disease and risk-factors can reduce the risk for late-life depression, but more studies are needed to test this hypothesis.
