| 1. |
- Bereczky-Veress, Biborka, et al.
(författare)
-
Host strain-dependent difference in susceptibility in a rat model of herpes simplex type 1 encephalitis.
- 2008
-
Ingår i: Journal of neurovirology. - : Springer Science and Business Media LLC. - 1538-2443 .- 1355-0284. ; 14:2, s. 102-18
-
Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex encephalitis (HSE) is characterized by severe focal brain inflammation leading to substantial loss of nervous tissue. The authors established a model of Herpes simplex virus type 1 (HSV)-1-induced acute encephalitis in the rat by injecting into the whiskers' area a virus strain isolated from a fatal human HSE case. The model might resemble natural propagation of HSV-1 in humans; spreading from the mouth and lips via the trigeminal nerve to trigeminal ganglia and subsequently entering the central nervous system (CNS). HSV-1 infected Dark Agouti (DA) rats developed a well-synchronized disease and died 5 days after inoculation. HSV-1 detection by quantitative polymerase chain reaction (qPCR), virus isolation and immunohistochemistry, magnetic resonance imaging, and histopathological examination verified dramatic encephalitis mainly in the brainstem, but also in the olfactory bulb and other segments of the brain of diseased rats. In contrast, Piebald Virol Glaxo (PVG) rats were completely resistant to disease, displaying a more rapid clearance of peripheral infection and no evidence of virus entering into neither the trigeminal ganglia nor the CNS. These results suggest a regulation of susceptibility to HSV-1-induced encephalitis at the level of peripheral infection and subsequent neuronal uptake/transport of the virus. This provides a basis for future positioning of genetic polymorphisms regulating HSE and for dissection of important pathogenetic mechanisms of this severe human disease.
|
|
| 2. |
- Alström, Ulrica, et al.
(författare)
-
Platelet inhibition assessed with VerifyNow, flow cytometry and PlateletMapping in patients undergoing heart surgery
- 2009
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 124:5, s. 572-577
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: A substantial number of patients with coronary artery disease undergo cardiac surgery within five days of discontinuing anti-platelet treatment with aspirin and clopidogrel. The aims of this study were to describe the degree of platelet inhibition in patients with dual anti-platelet treatment scheduled for coronary artery bypass graft (CABG) surgery and to investigate whether the measured platelet inhibition correlated to intra- and postoperative risk for bleeding and transfusion requirements. MATERIAL AND METHODS: Sixty patients were included. Platelet inhibition was analysed with flow cytometry including phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP-assay) and two bed-side analyzers, VerifyNow-System and PlateletMapping, a modified thrombelastograph. All 60 patients were analysed with VerifyNow and PlateletMapping, and 48 were analysed with flow cytometry and VASP-assay. RESULTS: There was a correlation between the ADP-receptor inhibition as measured by VASP-assay and VerifyNowP2Y(12) (r = -0.29, p<0.05), and between VASP-assay and the expression of P-selectin (r = 0.29, p<0.05) as measured by flow cytometry when platelets were stimulated with 5 microM ADP. VerifyNowP2Y(12) was the only measurement of platelet inhibition correlated to total blood loss (Spearman r = 0.29, p=0.03) and red blood cell transfusion (Spearman r = 0.43, p<0.01) requirements, although this might be confounded by aprotinin treatment. CONCLUSION: We found a modest agreement between the methods for preoperative platelet inhibition, though not for PlateletMapping-MA(ADP). There was a correlation between preoperative platelet inhibition measured by VerifyNowP2Y(12) and surgical blood loss or transfusion requirements. However, for the individual patient, preoperative use of VerifyNowP2Y(12) as an instrument to decide bleeding and transfusion risk does not seem helpful.
|
|
| 3. |
- Altman, Daniel, et al.
(författare)
-
Anticholinergic drug use for overactive bladder in Sweden: a nationwide pharmacoepidemiological study
- 2009
-
Ingår i: International Urogynecology Journal. - : Springer Science and Business Media LLC. - 1433-3023 .- 0937-3462. ; 20:11, s. 1285-1291
-
Tidskriftsartikel (refereegranskat)abstract
- Nationwide use and costs of anticholinergic drug for overactive bladder are unknown. We performed a nationwide study based on the Swedish Register on Prescribed Pharmaceuticals. From 2000 to 2007, there was a 68.8% increase in dispensed anticholinergic drugs in a population of 9 million. More than 93 million DDDs (calculated average maintenance dose per day) of anticholinergic drugs were dispensed corresponding to an overall DDD/TID (DDD per 1,000 inhabitants per day) of 3.5 per 1,000 persons per year. Approximately two thirds of anticholinergic drugs were prescribed to women, regardless of drug type. In 2007, the cost for anticholinergic drugs was 22 million a,not sign of which tolterodine comprised 70.8%. Solifenacin and darifenacin steadily increased their DDD/TIDs after market introduction. In this nationwide study, there was a 70% increased rate of expedited prescriptions of anticholinergic drugs for the treatment of overactive bladder in a relatively stable population.
|
|
| 4. |
- Askling, Johan, et al.
(författare)
-
Anti-TNF therapy in RA and risk of malignant lymphomas Relative risks and time-trends in the Swedish Biologics Register
- 2008
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 68:5, s. 648-653
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.Methods: Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67 743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n = 6604) were identified. A general population comparator (n = 471 024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.Results: Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26 981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365 026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3 355 849 person-years). RA patients starting anti-TNF therapy in 1998–2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.Conclusion: Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.
|
|
| 5. |
- Askling, Johan, et al.
(författare)
-
Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies : does the risk change with the time since start of treatment?
- 2009
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:11, s. 3180-3189
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To determine the short-term and medium-term risks of cancer in patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha) therapies that have proven effective in the treatment of chronic inflammatory conditions.METHODS:By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received.RESULTS:During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed.CONCLUSION:During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.
|
|
| 6. |
- Baecklund, Eva, et al.
(författare)
-
Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis
- 2006
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 54:3, s. 692-701
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Chronic inflammatory conditions such as rheumatoid arthritis (RA) have been associated with malignant lymphomas. This study was undertaken to investigate which patients are at highest risk, and whether antirheumatic treatment is hazardous or protective.METHODS:We performed a matched case-control study of 378 consecutive Swedish RA patients in whom malignant lymphoma occurred between 1964 and 1995 (from a population-based RA cohort of 74,651 RA patients), and 378 controls. Information on disease characteristics and treatment from onset of RA until lymphoma diagnosis was abstracted from medical records. Lymphoma specimens were reclassified and tested for Epstein-Barr virus (EBV). Relative risks (odds ratios [ORs]) for lymphomas (by subtype) associated with deciles of cumulative disease activity were assessed, as were ORs associated with drug treatments.RESULTS:The relative risks of lymphoma were only modestly elevated up to the seventh decile of cumulative disease activity. Thereafter, the relative risk increased dramatically (OR ninth decile 9.4 [95% confidence interval 3.1-28.0], OR tenth decile 61.6 [95% confidence interval 21.0-181.0]). Most lymphomas (48%) were of the diffuse large B cell type, but other lymphoma subtypes also displayed an association with cumulative disease activity. Standard nonbiologic treatments did not increase lymphoma risk. EBV was present in 12% of lymphomas.CONCLUSION:Risk of lymphoma is substantially increased in a subset of patients with RA, those with very severe disease. High inflammatory activity, rather than its treatment, is a major risk determinant.
|
|
| 7. |
- Baecklund, Eva, et al.
(författare)
-
Characteristics of diffuse large B cell lymphomas in rheumatoid arthritis
- 2006
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 54:12, s. 3774-3781
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, with a correlation between RA disease severity and lymphoma risk, most pronounced for diffuse large B cell lymphomas (DLBCLs), which also constitute the majority of RA-associated lymphomas. DLBCLs can be further subdivided into germinal center (GC)-like and non-GC-like subtypes, with different cellular origins and prognoses. This study was undertaken to investigate whether RA displays a specific association with any of the DLBCL subtypes.METHODS:We identified 139 patients with DLBCLs within a population-based case-control study of 378 RA patients with lymphoma. The DLBCLs were examined for CD10, Bcl-6, and interferon regulatory factor 4 expression patterns, subclassified into GC and non-GC subtypes, and then correlated with clinical parameters.RESULTS:We found a statistically significant predominance of the non-GC subtype (97 patients; 70% of all DLBCLs). These patients more often had an advanced stage of lymphoma at diagnosis and had a worse 5-year overall survival rate (16% versus 33%) compared with patients with the GC subtype. There was a strong association with RA disease activity in both subtypes, with >70% of the GC and non-GC cases occurring in RA patients with the highest overall disease activity scores.CONCLUSION: These findings suggest that severe RA is particularly associated with the non-GC subtype of DLBCL, and indicate a critical role of activated peripheral B cells as the cells of origin in these lymphomas.
|
|
| 8. |
- Bereczky, Sándor, et al.
(författare)
-
Multiclonal asymptomatic Plasmodium falciparum infections predict a reduced risk of malaria disease in a Tanzanian population
- 2007
-
Ingår i: Microbes and infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 9:1, s. 103-110
-
Tidskriftsartikel (refereegranskat)abstract
- Protective immunity to malaria is acquired after repeated exposure to the polymorphic Plasmodium falciparum parasite. Whether the number of concurrent antigenically diverse clones in asymptomatic infections predicts the risk of subsequent clinical malaria needs further understanding. We assessed the diversity of P. falciparum infections by merozoite surface protein 2 genotyping in a longitudinal population based study in Tanzania. The number of clones was highest in children 6–10 years and in individuals with long time to previous anti-malarial treatment. Individual exposure, analysed by circumsporozoite protein antibody levels, was associated with parasite prevalence but not with the number of clones. The risk of subsequent clinical malaria in children free of acute disease or recent treatment was, compared to one clone, reduced in individuals with multiclonal infections or without detectable parasites, with the lowest hazard ratio 0.28 (95% confidence interval 0.10–0.78 Cox regression) for 2–3 clones. The number of clones was not associated with haemoglobin levels. A reduced risk of malaria in asymptomatic individuals with multiclonal persistent P. falciparum infections suggests that controlled maintenance of diverse infections is important for clinical protection in continuously exposed individuals, and needs to be considered in the design and evaluation of new malaria control strategies.
|
|
| 9. |
- Egesten, Arne, et al.
(författare)
-
Increased Prevalence of Multiple Sclerosis Among COPD Patients and Their First-Degree Relatives: A Population-based Study.
- 2008
-
Ingår i: Lung. - : Springer Science and Business Media LLC. - 1432-1750 .- 0341-2040. ; 186, s. 173-178
-
Tidskriftsartikel (refereegranskat)abstract
- In both chronic obstructive pulmonary disease (COPD) and multiple sclerosis (MS), combinations of environmental and genetic factors are likely to increase the vulnerability to acquire disease. This study was undertaken to investigate any possible comorbidity of COPD and MS, thus indicating common inflammatory vulnerability. Individuals with a diagnosis of COPD (including chronic bronchitis and emphysema) during 1987-2002, according to the Swedish Inpatient and Cause of Death Registers, were identified (180,239 individuals). Thereafter, controls and first-degree relatives of both cases and controls were identified. Finally, all individuals were compared with the Inpatient Register to identify individuals discharged with a diagnosis of MS. In the COPD cohort, there was a more than twofold increased risk of MS compared with controls (HR 2.51; 95% CI 2.13-2.98). The risk of MS was even more pronounced among individuals discharged with a diagnosis of COPD before 60 years of age (HR 6.37; 95% CI 3.58-9.68). There was also an increased risk of MS among mothers (HR 2.24; 95% CI 1.04-4.61) and siblings (HR 1.50; 95% CI 1.08-2.08) of COPD patients. This study indicates that COPD and MS have an inflammatory vulnerability in common, at least in a subgroup of patients. These diseases may share inflammatory pathways, including predisposing variants of genes.
|
|
| 10. |
- Ekbom, Anders, et al.
(författare)
-
Increased risk of both ulcerative colitis and Crohn's disease in a population suffering from COPD
- 2008
-
Ingår i: Lung. - : Springer Science and Business Media LLC. - 1432-1750 .- 0341-2040. ; 186:3, s. 167-172
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways. In the majority of cases, the inflammation is triggered by tobacco smoke. Smoking also affects the pathogenesis of inflammatory bowel disease (IBD), protecting against ulcerative colitis (UC) and promoting development of Crohn's disease (CD). The present study was undertaken to investigate occurrence of IBD among COPD patients, indicating common inflammatory pathways and shared vulnerability on a genetic basis. The study was designed as a population-based cohort study. All individuals discharged with a diagnosis of COPD from 1987 to 2002 were identified in the Swedish Inpatient Register (n = 180,239). Controls and first-degree relatives of both cases and controls were identified using the Multi-Generation Register. Finally, all individuals (n = 1,174,557) were compared with the Inpatient Register, identifying discharges with a diagnosis of UC or CD. Hazard ratios (HR) for IBD were determined by Cox proportional hazards regression analysis. COPD patients had a significantly higher risk of both UC (HR 1.83; 95% CI 1.61-2.09) and CD (HR 2.72; 95% CI 2.33-3.18). Among first-degree relatives of COPD patients, there was also an overall increased risk of CD (HR 1.25; 95% CI 1.09-1.43) but not of UC (HR 1.09; 95% CI 0.96-1.23). The kinship of first-degree relatives displayed an increased risk of both UC and CD among siblings (HR 1.49; 95% CI 1.15-1.91 and HR 1.46; 95% CI 1.12-1.89, respectively). The results suggest that COPD and IBD may have inflammatory pathways in common, including genetic variants of genes predisposing for disease.
|
|
