Browsing by Subject "SURROGATE MARKERS"

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  • Koivusalo, Antti; Mutanen, Annika; Nissinen, Markku; Gylling, Helena; Pakarinen, Mikko (2019)
    Objectives: We elucidated pathophysiology of pediatric gallstone disease by assessing liver expression of bile transporters in relation to bile acids and surrogates of cholesterol absorption and synthesis in serum and gallstones. Methods: RNA expression of canalicular bile transporters in liver biopsies from 32 pediatric gallstone patients and from 6 liver donors (controls) was measured by qRT-PCR (quantitative real-time reverse transcription polymerase chain reaction). Concentrations of cholesterol and precursors, plant sterols and bile acids in gallstones, and in serum of the patients and 82 healthy children were measured. Primary outcomes were the difference in RNA expressions and serum sterol profiles between patients and controls. Results: Cholesterol stones (CS; n = 15) contained cholesterol >42% and pigment stones (PS; n = 17)
  • Nissinen, Markku J.; Pitkänen, Niina; Simonen, Piia; Gylling, Helena; Viikari, Jorma; Raitakari, Olli; Lehtimäki, Terho; Juonala, Markus; Pakarinen, Mikko P. (2018)
    Background & aims: Gallstone disease is related to hypersecretion of cholesterol in bile, and low serum phytosterol levels. We examined how genetic polymorphisms of sterol transporters affect childhood cholesterol metabolism trait predicting adult gallstone disease. Patients and methods: In retrospective controlled study, we determined D19H polymorphism of ABCG8 gene, genetic variation at Niemann-Pick C1-like 1 (NPC1L1) gene locus (rs41279633, rs17655652, rs2072183, rs217434 and rs2073548), and serum cholesterol, noncholesterol sterols and lipids in children affected by gallstones decades later (n = 66) and controls (n = 126). Results: In childhood, phytosterols were lower (9.7%-23.4%) in carriers of risk allele 19H compared to 19D homozygotes. Lowest campesterol/cholesterol tertile consisted of 1.9-times more future gallstone subjects, and 3.7-times more 19H carriers than highest one. Campesterol/cholesterol-ratio was highest in 19D homozygote controls, but similar to 11% lower in gallstone 19D homozygotes and similar to 25% lower among gallstone and control carriers of 19H. Gallstone subjects with alleles CC of rs41279633 and TT of rs217434 of NPC1L1 had similar to 18% lower campesterol/cholesterol-ratio compared to mutation carriers. Conclusions: Risk trait of cholesterol metabolism (low phytosterols) in childhood favouring cholesterol gallstone disease later in adulthood is influenced by risk variant 19H of ABCG8 and obviously also other factors. NPC1L1 variants have minor influence on noncholesterol sterols. (c) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
  • Puolanne, Anna-Maija; Kolho, Kaija-Leena; Alfthan, Henrik; Ristimäki, Ari; Mustonen, Harri; Färkkilä, Martti (2017)
    Fecal calprotectin is a reliable surrogate marker for inflammatory activity in inflammatory bowel disease (IBD). For the noninvasive monitoring of the activity of colonic inflammation, we validated a symptom index suitable for ulcerative colitis and colonic Crohn's disease. By combining the symptom index with a rapid semi-quantitative calprotectin test, we constructed a new activity index based on the highest AUCs, using histological remission as a reference. We also evaluated the correlation of the patient-reported influence of the IBD in the daily life, measured by a VAS, with the inflammation activity. The disease activity of 72 patients with IBD of the colon was determined by endoscopic activity scores (SES-CD/UCEIS). The patients provided stool samples for determination of calprotectin and filled in a questionnaire about their symptoms during the last week. The results of the symptom index demonstrated a statistically significant correlation with the rapid calprotectin test, histological inflammation activity, and the VAS. No correlations were found between the VAS and calprotectin or the histological inflammation activity. The sensitivity of the combination index to detect active inflammation was slightly superior to fecal calprotectin alone. The new symptom index and the combination index are simple, noninvasive means for distinguishing remission from active inflammation in colonic IBD. With the VAS, we can pick up patients who need psychosocial support because of the disease burden, even if their IBD is in remission.
  • Koivusalo, Antti; Pakarinen, Mikko; Gylling, Helena; Nissinen, Markku J. (2015)
    Background: Cholesterol metabolism may be involved in pediatric gallstone disease. We aimed to reveal cholesterol metabolites and phytosterols and their relation to stone composition of sterols in children having black pigment and cholesterol stones. Methods: We performed retrospective controlled clinical study, in which we examined parameters of cholesterol metabolism and liver function values in serum (n = 28) and gallstones (n = 46) of consecutively cholecystectomized children. Serum values of age-, body mass index-and sex-matched children (n = 82) and adult gallstones (n = 187) served as controls. Results: Surrogate markers of cholesterol synthesis in serum (squalene/cholesterol, cholestenol/cholesterol and lathosterol/cholesterol) were 26-52 % higher in both stone subclasses compared to controls (p <0.05 for all). Respectively, cholestanol/cholesterol and plant sterols campesterol/cholesterol and sitosterol/cholesterol (cholesterol absorption markers) had decreasing order in serum: black pigment stone group > controls > cholesterol stone group (p <0.05 for all). In black pigment stone group, stone cholestanol/cholesterol was associated with serum bile acids (r = 0.620, p = 0.018). In cholesterol stone group, surrogate markers of cholesterol synthesis in serum (e.g., lathosterol/cholesterol) inversely reflected those of absorption (r-range -0.633--0.706, p-range 0.036-0.015). In cholesterol stone group, serum and stone lathosterol/cholesterol and cholestanol/cholesterol were positively interrelated (r-range 0.727-0.847, p <0.05 for both). Conclusions: Gallstone subclasses shared enhanced cholesterol synthesis. Cholesterol stone children were low cholesterol absorbers with intact homeostasis of cholesterol metabolism. Black pigment stone group was characterized by deteriorated cholesterol metabolism, and accumulation of cholestanol, campesterol and sitosterol in serum and stones suggesting their participation in pathogenesis.
  • Af Björkesten, C. -G.; Jussila, A.; Kemppainen, H.; Hallinen, T.; Soini, E.; Mankinen, P.; Valgardsson, S.; Veckman, V.; Nissinen, R.; Naessens, D.; Molander, P. (2019)
    Background and Aims: A retrospective non-interventional, multi-centre patient chart review study was conducted to investigate the association of faecal calprotectin (FC) 1 year (+/- 2 months) after biological therapy initiation with composite event-free survival (CEFS) consisting of surgical procedures, corticosteroid initiation, treatment failure or dose increase in patients with Crohn's disease (CD). In addition, the correlations of FC and other tests of disease activity were assessed. Materials and methods: Data on Finnish CD patients initiating a biological therapy between 2010 and 2016, were collected. The association of FC and CEFS was analysed with Kaplan-Meier and Cox proportional hazard modelling. The correlations were tested with Pearson's test. Results: Biological therapy was initiated in 186 patients, of which 87 (46.8%) had FC results available at 1 year and 80 had follow-up exceeding 14 months. The characteristics of patients with and without FC results were similar. Patients with elevated FC (>250 mu g/g) had a significantly increased risk of experiencing composite event (HR 3.4, 95% CI: 1.3-8.9; p = .013) when compared to patients with normal FC (FC