| 1. |
- Bergquist, Annika, et al.
(författare)
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Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis
- 2008
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Ingår i: Clinical Gastroenterology and Hepatology. - New York : Elsevier. - 1542-3565 .- 1542-7714. ; 6:8, s. 939-943
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. Methods: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. Results: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6–84.4), 11.1 (3.3–37.8), and 2.3 (0.9–6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3–4.9) and for Crohn's disease 1.4 (0.8–2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9–18.9). Conclusions: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.
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| 2. |
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| 3. |
- Carlsson, G, et al.
(författare)
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Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia
- 2006
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Ingår i: Journal of Periodontology. - : Wiley. - 0022-3492 .- 1943-3670. ; 77:4, s. 744-751
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Tidskriftsartikel (refereegranskat)abstract
- Patients with Kostmann syndrome (severe congenital neutropenia [SCN]) typically normalize their absolute neutrophil count (ANC) upon granulocyte colony-stimulating factor (G-CSF) therapy. However, although they no longer experience life-threatening bacterial infections, they frequently still have recurrent gingivitis and even severe periodontitis, often starting in early childhood. METHODS: We studied the periodontal disease in the four surviving patients belonging to the family originally described by Kostmann. Their odontological records, x-rays, color photos, bacterial cultures, serum antibodies to oral bacteria, and histopathological examinations were reviewed. The data were also correlated to previous investigations on their antibacterial peptides and molecular biology. RESULTS: Three patients had periodontal disease, despite normal ANC and professional dental care, and had neutrophils deficient in antibacterial peptides. One of these patients also had a heterozygous mutation in the neutrophil elastase gene, had severe periodontal disease and overgrowth of the periodontal pathogen Actinobacillus actinomycetemcomitans in the dental flora, and 15 permanent teeth had been extracted by the age of 27. One bone marrow-transplanted patient had no periodontal disease. CONCLUSIONS: Normalized ANC levels are not sufficient to maintain normal oral health in SCN patients, and because neutrophils are important for first-line defense and innate immunity, the deficiency of the antibacterial peptide LL-37 probably explains their chronic periodontal disease. Professional dental care is still important for SCN patients, despite treatment with G-CSF and normal ANC levels. Whether antibacterial peptides play a role in the pathogenesis of periodontitis in other patients remains to be elucidated.
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| 4. |
- Hemmingsson, Eva-Stina, et al.
(författare)
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Antiviral treatment associated with reduced risk of clinical Alzheimer's disease : A nested case-control study
- 2021
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Ingår i: Alzheimer’s & Dementia. - : John Wiley & Sons. - 2352-8737. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In this nested case-control study, we investigated if antiviral treatment given prior to onset of Alzheimer's disease (AD) could influence incident AD.Methods: From a large population-based cohort study in northern Sweden, 262 individuals that later developed AD were compared to a non-AD matched control group with respect to prescriptions of herpes antiviral treatment. All included subjects were herpes simplex virus 1 (HSV1) carriers and the matching criteria were age, sex, apolipoprotein E genotype (ε4 allele carriership), and study sample start year.Results: Among those who developed AD, 6 prescriptions of antivirals were found, compared to 20 among matched controls. Adjusted for length of follow-up, a conditional logistic regression indicated a difference in the risk for AD development between groups (odds ratio for AD with an antiviral prescription 0.287, P = .018).Discussion: Antiviral treatment might possibly reduce the risk for later development of HSV1-associated AD.
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| 5. |
- Hindorf, Ulf, et al.
(författare)
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Characterisation and utility of thiopurine methyltransferase and thiopurine metabolite measurements in autoimmune hepatitis.
- 2010
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 52:1, s. 106-111
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Corticosteroids alone or in conjunction with azathioprine (AZA) is the standard treatment in autoimmune hepatitis (AiH). Individual variations in thiopurine (TP) metabolism may affect both drug efficacy and toxicity. Our aim was to investigate the utility of thiopurine methyltransferase (TPMT) as well as thioguanine nucleotide (TGN) and methylthioinosine monophosphate (meTIMP) metabolite measurements with regard to clinical outcome. METHODS: Two hundred thirty-eight patients with AiH were included in this cross-sectional study. TPMT status was assessed in all patients, while TGN and meTIMP were measured in patients with ongoing TP medication. Clinical outcome was evaluated by liver tests and the ability to withdraw steroids. RESULTS: TPMT genotyping (n=229) revealed 207 (90.4%) wild-type and 22 heterozygous patients. One hundred forty-three patients had ongoing TP therapy with AZA (n=134) or mercaptopurine (MP; n=9); response was judged as complete response (CR) in 113 patients and partial response (PR) in 30 patients. Both TP dose (1.64 vs 1.19mg/kg; p=0.012) and TPMT activity (14.3 vs 13.5; p=0.05) were higher in PR, resulting in similar TGN levels (PR: 121pmol/8x10(8) red blood cells [RBC]; CR: 113pmol/8x10(8) RBC; p=0.33) but higher meTIMP levels in PR (1350 vs 400pmol/8x10(8) RBC; p=0.004). Patients able to withdraw steroids or who were using 5mg prednisolone daily were treated with lower TP doses than patients on higher steroid doses (1.15 vs 1.18 vs 1.82mg/kg; p<0.001). CONCLUSIONS: TP metabolite measurements are of clinical value in AiH patients who do not respond to standard TP treatment and for the identification of a shifted metabolism, which may demand an alternative treatment strategy.
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| 7. |
- Lindgren, Stefan, et al.
(författare)
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Transitions between variant forms of primary biliary cirrhosis during long-term follow-up
- 2009
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Ingår i: EUROPEAN JOURNAL OF INTERNAL MEDICINE. - : Elsevier BV. - 0953-6205 .- 1879-0828. ; 20:4, s. 398-402
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Tidskriftsartikel (refereegranskat)abstract
- Background: Conditions exhibiting features of two different autoimmune liver diseases are designated overlap syndromes. Variant forms display some, but not all, characteristics of a distinct autoimmune liver disease. We describe transitions over time between variant forms of PBC, i.e. AMA-negative PBC, autoimmune hepatitis (AIH)-PBC overlap and autoimmune cholangitis (AIC) in a large cohort of PBC patients in Sweden. Methods: We retrieved all patients with variant forms of PBC in six university hospitals in Sweden, covering 60% of the Swedish population. The diagnosis of PBC and its variants was based on laboratory findings and compatible histological features. The revised autoimmune hepatitis scoring system proposed by the International Autoimmune Hepatitis Group was used to establish the diagnosis of AIH. Results: In a population of 800 patients with PBC, we identified 35 (5%) variant forms; 25 patients with AIH-PBC overlap, 8 with AIC and 2 with AMA-negative PBC at the time of our study. The initial diagnoses were PBC (3 patients), AIH (3), AIH-PBC overlap (16), AIC (8) and AMA-negative PBC with (1) or without (4) concomitant AIH. The median follow-up was 125 (41-360) months. Immunosuppression and ursodeoxycholic acid induced a complete or good regression of increased aminotransferases in about half of the patients who were given one or both of these treatments. Conclusions: Variant forms of PBC are seen in approximately 5% of PBC patients in Sweden. Transition between different forms may occur, emphasizing the value of repeat biopsies, but established overlapping AIH-PBC seems to be stable over time.
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| 8. |
- Lövheim, Hugo, 1981-, et al.
(författare)
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Herpes Simplex Virus, APOE ɛ4, and Cognitive Decline in Old Age : Results from the Betula Cohort Study
- 2019
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 67:1, s. 211-220
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Tidskriftsartikel (refereegranskat)abstract
- Background: Herpes simplex virus (HSV) has been suggested to play a role in Alzheimer’s disease (AD) development.Objective: The aim of the present study was to investigate the early AD-related symptom episodic memory decline in relation to HSV and carriage of allele 4 of the apolipoprotein E gene (APOE ɛ4) in a large population-based cohort with a long follow-up time.Methods: The study included 3,413 persons, with longitudinal data available for 1,293 persons with a mean follow-up time of 11.6 years. The associations between HSV carriage, APOE ɛ4 carriage, and episodic memory was investigated at baseline, as well as in longitudinal analyses where individuals with and without HSV antibodies (HSV1/2 non-specific) were matched and episodic memory decline compared.Results: Cross-sectional analyses revealed an age-dependent association of HSV carriage with lower episodic memory function, particularly among APOE ɛ4 carriers (p = 0.008). Longitudinal analyses showed an increased risk of episodic memory decline in HSV carriers (≥65 years: p < 0.001, all ages: non-significant), and a significant interaction between HSV and APOE ɛ4 for episodic memory decline (p < 0.001).Conclusion: In this large population-based cohort study, both cross-sectional and longitudinal results support an association between HSV carriage and declining episodic memory function, especially among APOE ɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.
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| 9. |
- Moe-Nilssen, Rolf, et al.
(författare)
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Criteria for evaluation of measurement properties of clinical balance measures for use in fall prevention studies
- 2007
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Ingår i: Journal of Evaluation In Clinical Practice. - : Blackwell Publishing. - 1356-1294 .- 1365-2753. ; 14:2, s. 236-240
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Tidskriftsartikel (refereegranskat)abstract
- Work Package 3 of the Prevention of Falls Network Europe has evaluated measurement properties of clinical balance measures to be used to: (1) select participants for interventions with the goal to prevent falls in older people, and (2) assess the results of such intervention on balance function.Inclusion in a fall prevention study may be based on measures identifying subjects who have impaired balance or increased risk of future falls. We propose that an appropriate statistical method to analyse discriminative ability of a balance measure is discriminant analysis or logistic regression analysis. The optimal cut‐off score is best determined by plotting a receiver‐operating‐characteristic curve for different cut‐off values. The evaluation of predictors for risk of future falls should be based on a study design with a prospective data collection of falls.Sensitivity to change is a measurement property needed to evaluate the outcome of an intervention. The standardized response mean is frequently encountered in the literature and is recommended as a statistical measure of sensitivity to change in the context of an intervention study.Adequate reliability is a prerequisite for consistent measurement. Relative reliability may be reported as an intraclass correlation coefficient and absolute reliability as the within‐subject standard deviation (sw), also called standard error of measurement. When measurement error is proportional to the score, calculation of a coefficient of variation can be considered.In a second paper, the authors will evaluate clinical balance measures for use in fall prevention studies based upon criteria recommended in this report.
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| 10. |
- Mullins, N., et al.
(författare)
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Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
- 2021
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53, s. 817-829
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
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