| 61. |
- Eriksson, Per, et al.
(författare)
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Improved outcome in Wegener's granulomatosis and microscopic polyangiitis? A retrospective analysis of 95 cases in two cohorts
- 2009
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 265:4, s. 496-506
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Tidskriftsartikel (refereegranskat)abstract
- Mortality rates for Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) have decreased after the introduction of cyclophosphamide. Standardized mortality ratio (SMR) expresses the overall mortality of patients compared with the general population. The aims of this study were to compare survival in an old and a recent cohort of patients with WG and MPA using SMR and to determine predictors for death in both groups combined. Survival analyses were performed by Kaplan-Meier survival curves, SMR and proportional hazards regression models. The nephrology and rheumatology clinics at Linkoping University Hospital, Sweden. All patients diagnosed with WG or MPA in the catchment area during 1978-2005 were divided into two cohorts; patients diagnosed before (n = 32, old cohort) and after (n = 63, recent cohort) December 31, 1996. The two cohorts differed regarding the proportion of WG (75% vs. 56%, P = 0.03) and a tendency for more pronounced kidney involvement in the old cohort: 266 mu mol L-1 (16% dialysis-dependent) vs. 192 mu mol L-1 (5% dialysis-dependent), but were comparable regarding disease severity. SMR at 1 and 5 years were 2.1 (95% CI: 0.43-6.09) and 1.6 (95% CI: 0.6-3.2) in the recent cohort and 5.2 (95% CI: 1.07-15.14) and 2.5 (95% CI: 0.93-5.52) in the old cohort. Five-year survival was 87% and 81%. Serum creatinine, age, end-stage renal disease, diagnosis before 1997 and first relapse were independent predictors for death. Patient survival in WG and MPA analysed with SMR may be better than previously believed. Severe renal disease and disease relapse were the major predictors of reduced survival.
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| 62. |
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| 63. |
- Hedblad, Bo, et al.
(författare)
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Rosiglitazone and carotid IMT progression rate in a mixed cohort of patients with type 2 diabetes and the insulin resistance syndrome: main results from the Rosiglitazone Atherosclerosis Study.
- 2007
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 261:3, s. 293-305
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Insulin resistance is associated with progression of atherosclerosis. We assessed the effect of 12 months of treatment with rosiglitazone (RSG) on the progression of carotid intima-media thickness (IMT) in people with type 2 diabetes mellitus (T2DM) or the insulin resistance syndrome (IRS). Design. Randomized, double-blind, placebo-controlled trial. Setting. Malmo University Hospital, Malmo, Sweden. Subjects. 555 subjects (200 with T2DM and 355 nondiabetics with IRS according to EGIR criteria), aged 35-80 years. 447 subjects (165 T2DM and 282 IRS) completed the study. Intervention. Participants were allocated to placebo or RSG 4 mg for 2 months and then 8 mg daily. Main outcome measure. Change in composite IMT [mean IMT in the common carotid artery (CCA) and maximal IMT in the bulb] was the primary and various other IMT measures were secondary outcome variables. Results. There was no effect of RSG treatment in the mixed population. In T2DM patients there was a reduced progression of the composite IMT (mean change: 0.041 vs. 0.070 mm, P = 0.07), and of the mean IMT CCA (mean change: -0.005 mm vs. 0.021 mm, P = 0.007). RSG treatment led to significant reductions of HOMA-IR, fasting plasma glucose, HbA1c, PAI-1 activity, fibrinogen, C-reactive protein and matrix metalloproteinase-9. Conclusions. In a mixed study population of patients with T2DM and IRS RSG treatment was not associated with a statistically significant reduction of carotid IMT progression rate. Separate analyses of these two patient groups indicated, however, a significant beneficial effect on CCA IMT in T2DM patients but no similar effect in subjects with IRS.
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| 64. |
- Iosif, Robert
(författare)
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Factors Regulating Neurogenesis in Intact and Pathological Brain: Role of TNF-alpha
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the last decade it has been clearly demonstrated that the adult brain contains neural stem cells (NSCs) localized mainly in two regions: the subgranular zone in the dentate gyrus and the subventricular zone (SVZ) lining the lateral ventricles. In the intact brain, these NSCs give rise to new dentate granule cells and olfactory bulb neurons, respectively. Following a brain damage such as stroke and an epileptic seizure, the generation of new neurons (neurogenesis) in the hippocampus and the SVZ in adult rats, mice and probably humans is increased. The molecular mechanisms regulating the different steps of insult-induced neurogenesis (cell proliferation, survival, migration, and differentiation) are poorly understood. To learn more about the molecular mechanisms regulating neurogenesis we examined which factors in the epileptic and stroke generated environment that affects the newly formed neurons. In this thesis we explored the role of a prostaglandin and a cytokine in the hippocampus and subventricular zone, both during physiological conditions and after an insult. In the first paper we induced status epilepticus (SE) in rats by electrical stimulation in the hippocampus. We then compared the two different seizure grades, partial status epilepticus (pSE) and generalized status epilepticus (gSE), in order to identify factors in the microenvironment which are differentially regulated by SE severity and may underlie differences in neurogenesis. We particularly addressed the question whether SE severity differentially affects the expression of prostaglandin E2 (PGE2), cyclooxygenase (COX-2), the enzyme catalyzing the first committed step in PGE2 synthesis, and the brain-derived neurotrophic factor (BDNF). In conclusion, the results from paper I showed clear differences between pSE and gSE rats in hippocampal PGE2 and BDNF levels 7 days after SE. We found no evidence that the high levels of PGE2 and BDNF, in rats exhibiting pSE, during the first days after SE are of major importance for the survival of new neurons during the first days after formation. In the second study, we developed a new SE model for mice based on continuous electrical stimulation in the hippocampus, as done previously in rats. We then investigated whether the cytokine, tumor necrosis factor alpha (TNF-α), could influence neurogenesis. TNF-α is a well-known proinflammatory factor and we speculated that the detrimental action of inflammation on insult-induced neurogenesis might be caused by TNF-α. It had also been shown that NSCs themselves express TNF-α, which raised the possibility of an autocrine action involved in neurogenesis. We used transgenic mice with various genetic manipulations of TNF-α signaling to determine the influences on neurogenesis under physiological conditions and following a brain insult. Taken together, the results from paper II demonstrate the involvement of TNF-R1 and TNF-R2 signaling in the regulation of adult hippocampal neurogenesis, and that signaling through the two different receptors have differential actions on neurogenesis. Our data indicate that TNF-α can modulate the formation of new neurons both under physiological and pathological conditions by acting on these two receptors with differential effects on proliferation and survival, with TNF-R1 as the key mediator of TNF-α signaling. In the final study we examined whether signaling through TNF-R1 could influence progenitor proliferation in another neurogenic area during physiological conditions and following a pathological condition such as stroke and SE. We used the same transgenic mice to study TNF-α and its effects on the formation of new neurons in the SVZ. We found that mice lacking TNF-R1 function responded to stroke with enhanced SVZ cell proliferation and thereby that TNF-R1 signaling mediates a suppressant effect on the proliferation of progenitor cells. Following stroke TNF-R1 acts as a negative regulator on the progenitor proliferation. In contrast, deletion of TNF-R1 did not influence basal cell proliferation in SVZ. Further, loss of TNF-R1 function had differential effects on SVZ cell proliferation following the two pathological conditions SE and stroke and we did not find any differences in cell proliferation after SE. Although both insults gave rise to increased cell proliferation in the SVZ, the dampening action of TNF-R1 on proliferation was revealed only after stroke. Taken together, the results from paper II and III suggest that suppression of TNF-R1 signaling might be a strategy to promote the proliferative response in the SGZ after SE and in the SVZ after stroke, to stimulate neurogenesis in the adult brain. However, it will be important to establish how such an approach will affect other steps of neurogenesis and the functional outcome after both SE and stroke. There could be a positive therapeutic potential of neurogenesis from endogenous stem cells after brain insults. However, we need to know much more about the regulation of neurogenesis in order to make this response more effective. The current thesis work aims at elucidating some of the mechanisms of neuronal self-repair, which could have implications for the development of stem cell-based approaches for the treatment of brain disorders.
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| 65. |
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| 66. |
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| 67. |
- Li, Cairu, et al.
(författare)
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Incidence of Ischemic Stroke in Relation to Asymptomatic Carotid Artery Atherosclerosis in Subjects with Normal Blood Pressure. A Prospective Cohort Study.
- 2008
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Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 26:3, s. 297-303
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Tidskriftsartikel (refereegranskat)abstract
- Background:Approximately 10-20% of stroke cases have normal blood pressure (BP). The objective of this study was to explore whether the risk of ischemic stroke is related to the carotid intima-media thickness (CIMT) and atherosclerotic lesions in a cohort of subjects with normal BP. Methods:Common CIMT and the presence of carotid plaque were determined by B-mode ultrasound in 6,103 subjects, randomly recruited between 1991 and 1994 from the 'Malmo Diet and Cancer' study. Normal BP was defined as BP <140/90 mm Hg, without pharmacological treatment for hypertension. Carotid artery atherosclerosis (CAA) was defined as CIMT >/=0.81 mm or/and the presence of plaque (i.e. focal CIMT >1.2 mm). The incidence of ischemic stroke was followed over a mean period of 10.7 years. Results:A total of 2,228 subjects (791 men and 1,437 women) had normal BP. During the follow-up, 34 patients suffered a first-ever ischemic stroke (crude incidence: 1.51/1,000 person-years). The Prevalences of CAA in subjects with and without stroke were 68.6 and 39.0%, respectively. It was estimated that the subjects with CAA had a 3-fold higher risk of ischemic stroke (RR: 3.33, 1.37-8.14), independent of other cardiovascular risk factors. Each increase of 1 standard deviation (0.13 mm) in CIMT increased the stroke risk by 43% (RR: 1.43, 1.002-2.02). Several factors were found to have a notable relation with CAA, including age, male sex, smoking, diabetes, systolic BP, HbA1c (glycosylated hemoglobin) and cholesterol. Conclusions: CIMT and atherosclerotic lesions are independent clinical markers for ischemic stroke among normotensive individuals.
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| 68. |
- Londos, Elisabet, et al.
(författare)
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Effects of a goal-oriented rehabilitation program in mild cognitive impairment: A pilot study
- 2008
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Ingår i: American Journal of Alzheimers Disease & other Dementias. - : SAGE Publications. - 1938-2731 .- 1533-3175. ; 23:2, s. 177-183
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Tidskriftsartikel (refereegranskat)abstract
- Background: Memory disturbance, deficient concentration, and fatigue are symptoms seen in amnestic mild cognitive impairment (MCI) as well as in mild traumatic brain injury (TBI). The aim of this study was to assess if an established rehabilitation program commonly used in TBI can aid MCI patients to develop compensatory memory strategies that can improve their cognition, occupational performance, and quality of life (QoL). Methods: Fifteen patients with MCI participated in the program 2 days per week for 8 weeks. Cognitive function, occupational performance, and self-perceived QoL were assessed at baseline, at the end of the intervention, and at follow-up after 6 months. Results: Significant improvements were seen in cognitive processing speed, occupational performance, and in some of the QoL domains. Conclusion: As this goal-oriented rehabilitation program in MCI resulted in some improvements in cognition, occupational performance, and QoL, further randomized controlled studies are warranted.
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| 69. |
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| 70. |
- Nilsson, Jonas, 1970, et al.
(författare)
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Norwalk virus-like particles bind specifically to A, H and difucosylated Lewis but not to B histo-blood group active glycosphingolipids.
- 2009
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Ingår i: Glycoconjugate journal. - : Springer Science and Business Media LLC. - 1573-4986 .- 0282-0080.
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Tidskriftsartikel (refereegranskat)abstract
- Noroviruses and norovirus virus-like particles (VLPs) exhibit strain specific patterns in their binding to ABH and Lewis histo-blood group antigens. In this study we demonstrate for the first time specific binding of Norwalk virus VLPs to type 1 and type 2 chain glycosphingolipids (GSLs) carrying ABH and Lewis antigens. N-succinimidyl-3-tributylstannyl benzoate (ATE) was precursor labeled with (125)I and then conjugated to VLPs. The (125)I-VLPs were used in GSL thin-layer chromatogram binding assays and displayed binding to H type 1, Lewis b, A type 1, A Lewis b GSLs but no binding to B type 1 or B Lewis b GSLs. For the type 2 chain GSLs the Norwalk VLPs bound to H type 2, Lewis y, A type 2 and A Lewis y. In addition, the VLPs bound to several complex GSLs from blood group O and A, but not from blood group B red blood cells.
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