| 1. |
- Kvaerner, A. S., et al.
(författare)
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The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants
- 2021
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Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.
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| 2. |
- Blomquist, H K, et al.
(författare)
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Glycerol kinase deficiency in two brothers with and without clinical manifestations.
- 1996
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Ingår i: Clinical genetics. - 0009-9163 .- 1399-0004. ; 50:5, s. 375-9
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Tidskriftsartikel (refereegranskat)abstract
- We report two brothers with glycerol kinase deficiency (GKD). The older brother had serious clinical symptoms, mental and growth retardation, abnormal skeleton, spontaneous fractures and premature loss of abnormal teeth. He and his mother had low serum phosphate levels. He had elevated serum and urine glycerol levels and GKD was found in cultured fibroblasts. Prenatal diagnosis was performed in the second pregnancy. Glycerol kinase activity was considered normal in a chorionic villus sample of the foetus. After birth, it was found that the boy had elevated serum and urine glycerol levels. Enzymatic analysis in cultured fibroblasts revealed that this boy also had GKD, in spite of having no expression of the disease. Chromosomal analyses in the parents and both boys were normal. Major rearrangements or deletions were not detected in molecular studies of DNA from the two brothers. The hybridisation pattern was normal and no allelic loss was observed.
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| 3. |
- Braekken, I H, et al.
(författare)
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Pelvic floor function is independently associated with pelvic organ prolapse.
- 2009
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Ingår i: BJOG : an international journal of obstetrics and gynaecology. - : Wiley. - 1471-0528 .- 1470-0328. ; 116:13, s. 1706-14
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the risk factors for pelvic organ prolapse (POP), including physical activity, clinically measured joint mobility and pelvic floor muscle (PFM) function.
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| 4. |
- Abrahamsson, Kate, 1959, et al.
(författare)
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Effect of short-term treatment with pivalic acid containing antibiotics on serum carnitine concentration--a risk irrespective of age.
- 1995
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Ingår i: Biochemical and molecular medicine. - : Elsevier BV. - 1077-3150. ; 55:1, s. 77-9
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with pivalic acid containing prodrugs has been shown to cause carnitine depletion by loss of pivaloyl carnitine in urine. A 7-day standard pivmecillinam treatment of adults lead to a marked decrease of the free serum carnitine concentration (44.6 to 12.9 mumol/liter), whereas no change was seen in those given norfloxacine (40.0 to 40.5 mumol/liter). In some patients irrespective of age the free serum carnitine concentration was decreased to levels (around 10 mumol/liter) at which an impaired ketone-body production may occur. Therefore, there is reason for cautious use of this type of drug irrespective of the age of the patients.
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| 5. |
- Abrahamsson, Kate, 1959, et al.
(författare)
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Impaired ketogenesis in carnitine depletion caused by short-term administration of pivalic acid prodrug.
- 1994
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Ingår i: Biochemical medicine and metabolic biology. - : Elsevier BV. - 0885-4505. ; 52:1, s. 18-21
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Tidskriftsartikel (refereegranskat)abstract
- Long-term treatment with pivalic acid prodrug results in impaired ketone-body production. Therefore, it was of interest to investigate whether short-term treatment had any influence on the fatty acid oxidation. In this study six healthy males were given 1200 mg per day of pivmecillinam for 12 days to induce carnitine deficiency. The concentration of free carnitine in serum was reduced from a mean of 42.8 mumol/liter (range, 31-48) to 11.6 mumol/liter (range, 7.0-24), but the muscle carnitine concentration was not reduced. A 36-h fasting test was performed before and after drug administration to study the effect on ketone-body production. After treatment, the two subjects with the lowest level of serum free carnitine at the end of the fasting period had impaired ketogenesis. This indicates a carnitine deficiency in the liver which was reflected in the free carnitine concentration for by mobilization of muscle carnitine. We conclude that there is a substantial risk to develop carnitine deficiency and impaired fatty acid oxidation in the liver during short-term treatment with drugs conjugated with pivalic acid.
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| 6. |
- Bost, Jeremy P., et al.
(författare)
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Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides
- 2022
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments to reach their cytosolic and nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds to increase functional delivery. So far, development of these compounds has been hindered by a lack of high-resolution methods that can correlate SSO trafficking with SSO activity. Here we present in-depth characterization of two novel endosomolytic compounds by using a combination of microscopic and functional assays with high spatiotemporal resolution. This system allows the visualization of SSO trafficking, evaluation of endosomal membrane rupture, and quantitates SSO functional activity on a protein level in the presence of endosomolytic compounds. We confirm that the leakage of SSO into the cytosol occurs in parallel with the physical engorgement of LAMP1-positive late endosomes and lysosomes. We conclude that the new compounds interfere with SSO trafficking to the LAMP1-positive endosomal compartments while inducing endosomal membrane rupture and concurrent ON escape into the cytosol. The efficacy of these compounds advocates their use as novel, potent, and quick-acting transfection reagents for antisense ONs.
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| 7. |
- Dahlberg, Leif, et al.
(författare)
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A randomized, multicentre, double-blind, parallel-group study to assess the adverse event-related discontinuation rate with celecoxib and diclofenac in elderly patients with osteoarthritis.
- 2009
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 38, s. 133-143
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the adverse event (AE)-related discontinuation rate with celecoxib vs. diclofenac when given to reduce joint pain associated with knee or hip osteoarthritis (OA) in elderly patients. Methods: This was a double-blind, randomized, multicentre, parallel-group, 1-year comparison of celecoxib 200 mg once daily and diclofenac 50 mg twice daily in 925 patients with OA aged >/= 60 years. Study visits were at baseline and at 4, 13, 26, 39, and 52 weeks. At each visit, the Patient's and Physician's Global Assessment of Arthritis (PaGAA, PhGAA), the Patient's Assessment of Arthritis Pain - Visual Analogue Scale (PAAP-VAS), and AEs were assessed. A concomitant health economic analysis was conducted throughout. Results: The rate of study discontinuation due to AEs, laboratory abnormalities, and deaths was 27% for celecoxib and 31% for diclofenac (p = 0.22). The results of the arthritis/pain efficacy assessments were similar for celecoxib and diclofenac. Significantly fewer patients in the celecoxib group than the diclofenac group experienced cardiovascular/renal AEs (70/458 vs. 95/458, p = 0.039) or hepatic AEs (10/458 vs. 39/458, p<0.0001). Medication costs were higher for celecoxib than diclofenac but mean total treatment cost was slightly higher in the diclofenac group. Conclusion: Treatment with celecoxib 200 mg once daily and diclofenac 50 mg twice daily resulted in similar rates of AE-related study discontinuation in elderly patients with OA. Celecoxib and diclofenac demonstrated comparable efficacy in relieving the signs and symptoms of OA. However, the proportion of patients with cardiorenal and hepatic AEs was significantly lower in the celecoxib group than the diclofenac group.
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