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- Angelison, Leif, et al.
(author)
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Long-term outcome of infliximab treatment in chronic active ulcerative colitis : a Swedish multicentre study of 250 patients
- 2017
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In: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell Publishing Inc.. - 0269-2813 .- 1365-2036. ; 45:4, s. 519-532
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Journal article (peer-reviewed)abstract
- Background: Real-life long-term data on infliximab treatment in ulcerative colitis are limited.Aim: To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined.Methods: A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age ≥18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant.Results: Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy.Conclusions: Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy.
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- Likus, W., et al.
(author)
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Correlations between selected parameters of nasal cavity in neonates and young infants - computed tomography study
- 2016
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In: FOLIA MORPHOLOGICA. - : VIA MEDICA. - 0015-5659. ; 75:3, s. 334-340
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Journal article (peer-reviewed)abstract
- Background: Correlations between selected metric parameters of the nasal cavity and nasopharynx in children without atresia may be useful for anticipating probable dimensions of this region in living subjects, in terms of changes with age. Materials and methods: One hundred and eighty children, age range 0-3 years, were divided into five age groups, and measurements of 18 distances between structures of nasal cavity and nosopharynx were performed on computed tomography scans. Correlation coefficients and relations between parameters have been determined. Results: Our study confirmed the existence of statistically significant correlations between linear dimensions within nasal cavity in children. The analysis demonstrated that for the values of following indexes: nasal septum length/piriform aperture width, and maximum length of the nasal septum/posterior nares width no statistically significant differences have been noted between age groups of children. All correlations have been positive. No statistically significant differences have been noted between the maximum width of the vomer and osseous parameters measured, both in the anterior and posterior part of the nasal cavity, and nasal septum length. Conclusions: The size of posterior nares changed with age in children by a constant value. So far, no such an analysis has been carried out assessing potential correlations between linear dimensions for the entire nasal cavity, nasopharynx, length of the nasal septum in children, as well as proportions of individual linear dimensions of the anatomical structures analysed, in various age groups.
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- Appleby, R. N., et al.
(author)
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Effects of conventional and a novel colonic-release bile acid sequestrant, A3384, on fibroblast growth factor 19 and bile acid metabolism in healthy volunteers and patients with bile acid diarrhoea
- 2017
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In: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 5:3, s. 380-388
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Journal article (peer-reviewed)abstract
- Background: Primary bile acid diarrhoea (BAD) is associated with increased bile acid synthesis and low fibroblast growth factor 19 (FGF19). Bile acid sequestrants are used as therapy, but are poorly tolerated and may exacerbate FGF19 deficiency. Aim: The purpose of this study was to evaluate the pharmacological effects of conventional sequestrants and a colonic-release formulation preparation of colestyramine (A3384) on bile acid metabolism and bowel function in patients with BAD. Methods: Patients with seven-day (75)selenium-homocholic acid taurine (SeHCAT) scan retention <10% were randomised in a double-blind protocol to two weeks treatment with twice-daily A3384 250mg (n=6), 1g (n=7) or placebo (n=6). Thirteen patients were taking conventional sequestrants at the start of the study. Symptoms were recorded and serum FGF19 and 7 alpha-hydroxy-4-cholesten-3-one (C4) measured. Results: Median serum FGF19 on conventional sequestrant treatment was 28% lower than baseline values in BAD (p<0.05). C4 on conventional sequestrant treatment was 58% higher in BAD (p<0.001). No changes were seen on starting or withdrawing A3384. A3384 improved diarrhoeal symptoms, with a median reduction of 2.2 points on a 0-10 Likert scale compared to placebo, p<0.05. Conclusions: Serum FGF19 was suppressed and bile acid production up-regulated on conventional bile acid sequestrants, but not with A3384. This colonic-release formulation of colestyramine produced symptomatic benefit in patients with BAD.
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- Bajor, Antal, 1962, et al.
(author)
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Indirect evidence for increased mechanosensitivity of jejunal secretomotor neurones in patients with idiopathic bile acid malabsorption.
- 2009
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In: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 197:2, s. 129-37
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Journal article (peer-reviewed)abstract
- The interdigestive motor rhythm, the migrating motor complex (MMC), is accompanied by active secretion of chloride during periods of distally propagating maximal motor activity (MMC phase III). We studied the behaviour of this system in bile acid malabsorption (BAM), a relative common cause of chronic diarrhoea. We measured motor activity and transmucosal potential difference (PD, reflecting active chloride secretion), in the proximal jejunum in healthy controls (n = 18) and in a group of patients with BAM (n = 11). The phase III-generated voltage was related to the degree of BAM quantified by the (75)SeHCAT test.
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- O'Leary, Patrick C., et al.
(author)
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Peroxiredoxin-1 protects estrogen receptor alpha from oxidative stress-induced suppression and is a protein biomarker of favorable prognosis in breast cancer
- 2014
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 16:4, s. R79-
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Journal article (peer-reviewed)abstract
- Introduction: Peroxiredoxin-1 (PRDX1) is a multifunctional protein, acting as a hydrogen peroxide (H2O2) scavenger, molecular chaperone and immune modulator. Although differential PRDX1 expression has been described in many tumors, the potential role of PRDX1 in breast cancer remains highly ambiguous. Using a comprehensive antibody-based proteomics approach, we interrogated PRDX1 protein as a putative biomarker in estrogen receptor (ER)-positive breast cancer. Methods: An anti-PRDX1 antibody was validated in breast cancer cell lines using immunoblotting, immunohistochemistry and reverse phase protein array (RPPA) technology. PRDX1 protein expression was evaluated in two independent breast cancer cohorts, represented on a screening RPPA (n = 712) and a validation tissue microarray (n = 498). In vitro assays were performed exploring the functional contribution of PRDX1, with oxidative stress conditions mimicked via treatment with H2O2, peroxynitrite, or adenanthin, a PRDX1/2 inhibitor. Results: In ER-positive cases, high PRDX1 protein expression is a biomarker of improved prognosis across both cohorts. In the validation cohort, high PRDX1 expression was an independent predictor of improved relapse-free survival (hazard ratio (HR) = 0.62, 95% confidence interval (CI) = 0.40 to 0.96, P = 0.032), breast cancer-specific survival (HR = 0.44, 95% CI = 0.24 to 0.79, P = 0.006) and overall survival (HR = 0.61, 95% CI = 0.44 to 0.85, P = 0.004). RPPA screening of cancer signaling proteins showed that ER alpha protein was upregulated in PRDX1 high tumors. Exogenous H2O2 treatment decreased ER alpha protein levels in ER-positive cells. PRDX1 knockdown further sensitized cells to H2O2- and peroxynitrite-mediated effects, whilst PRDX1 overexpression protected against this response. Inhibition of PRDX1/2 antioxidant activity with adenanthin dramatically reduced ER alpha levels in breast cancer cells. Conclusions: PRDX1 is shown to be an independent predictor of improved outcomes in ER-positive breast cancer. Through its antioxidant function, PRDX1 may prevent oxidative stress-mediated ER alpha loss, thereby potentially contributing to maintenance of an ER-positive phenotype in mammary tumors. These results for the first time imply a close connection between biological activity of PRDX1 and regulation of estrogen-mediated signaling in breast cancer.
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