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- Benson, Tyler W, et al.
(author)
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Glycoprotein VI is Critical for the Detection and Progression of Abdominal Aortic Aneurysms.
- 2023
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In: bioRxiv : the preprint server for biology.
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Journal article (peer-reviewed)abstract
- UNLABELLED: A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (J) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist.KEY POINTS: Soluble glycoprotein VI, which is a platelet-derived blood biomarker, predicts a diagnosis of AAA, with high sensitivity and specificity in distinguishing patients with fast from slow-growing AAA.Blockade of glycoprotein VI in mice with established aneurysms reduces AAA progression and mortality, indicating therapeutic potential.
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| 3. |
- Cucchiara, BL, et al.
(author)
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Early impairment in consciousness predicts mortality after hemispheric ischemic stroke
- 2004
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In: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 32:1, s. 241-245
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Journal article (peer-reviewed)abstract
- Objective: Early predictors of poor outcome after acute ischemic stroke may be useful in selecting patients for potentially beneficial but high-risk interventions. Design. Cohort study of patients given placebo in a randomized clinical trial. Setting. Multicenter trial at 139 U.S. and 14 Canadian hospitals. Patients. A cohort of 564 placebo-treated patients with major anterior circulation ischemic stroke enrolled in the Clomethiazole in Acute Stroke Study-Ischemic Stroke (CLASS-I) trial. Patients did not have significant impairment in consciousness at baseline and were enrolled within 12 hrs of symptom onset. Interventions: Prospective data collection of a number of clinical variables including use of a 6-point level of consciousness scale (1 = awake, 6 = no reaction to pain) to measure patients' level of consciousness at enrollment and 12 additional times during the first 24 hrs after enrollment. The ability of level of consciousness score and additional clinical data to predict 30-day mortality was assessed. Measurements and Main Results., At 1 month, 114 of 564 patients (20%) had died. In univariate analysis, factors significantly associated with mortality included older age, white race, higher National Institutes of Health Stroke Scale score, higher serum glucose, atrial fibrillation, and any impairment in level of consciousness (p < .05). After controlling for these factors, increasing level of consciousness score at 3 hrs after enrollment and at all but one subsequent time point was significantly associated with increased mortality (odds ratio, 1.8 per point, 95% confidence interval, 1.2-2.6, p = .003 at 3-hr time point). Maximum level of consciousness score during the initial 24 hrs of monitoring also predicted mortality (odds ratio, 1.9 per point, 95% confidence interval, 1.4-2.5, p < .001). Conclusion: The development of a decreased level of consciousness within the initial hours after stroke onset, as evaluated by a simple six-point scale, is a powerful independent predictor of mortality after major anterior circulation ischemic stroke.
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| 4. |
- Cucchiara, B, et al.
(author)
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Lack of hemispheric dominance for consciousness in acute ischaemic stroke
- 2003
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In: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 74:7, s. 889-892
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Journal article (peer-reviewed)abstract
- Background: Previous reports have suggested left hemispheric dominance for maintaining consciousness, although there is controversy over this claim. Objective: To compare early impairment of level of consciousness between patients with right and left hemispheric stroke. Methods: Data from 564 patients with ischaemic stroke enrolled in the placebo arm of a trial of a putative neuroprotectant were analysed. All patients had major hemispheric stroke with cortical dysfunction, visual field deficit, and limb weakness, with symptom onset within 12 hours of enrolment. Patients were prospectively evaluated on a predefined scale (1-6, 1 = fully awake, higher scores representing greater impairment) to measure level of consciousness at multiple time points over the initial 24 hours after presentation. The National Institutes of Health (NIH) stroke scale score at presentation and infarct volume at 30 days were determined. Results: Some degree of impairment in level of consciousness was observed in 409 of the 564 patients (73%). Median maximum sedation score was 2 for both right and left hemispheric stroke (p = 0.91). Mean sedation score over 24 hours was 1.5 for both right and left stroke (p = 0.75). There was no difference between level of consciousness scores in right and left stroke at any individual time point during the 24 hour monitoring period. No association between side and impairment in level of consciousness was seen after adjustment for stroke severity and infarct volume. Conclusions: In contrast to previous reports, there was no evidence for hemispheric dominance for consciousness in the setting of a major hemispheric stroke.
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| 5. |
- Lydén, Anders
(author)
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Biologiska undersökningar i Iggesundsrecipienten 1978 och 1979.
- 1982
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Reports (other academic/artistic)abstract
- Växtplanktonbiomassa och primärproduktion undersöktes i pelagialen utanför en sulfatmassafabrik vid Bottenhavet under två sommarperioder. Produktionen var kraftigt reducerad i recipientens närområde, medan algbiomassan där inte entydigt skiljde sig från ett kontrollområde. Orsaken till den låga produktionen kan tillskrivas det färgade avloppsvattnets ljusreduktion. Möjligheten att algerna kan tillväxa heterotroft, och därmed utnyttja organiska ämnen i avloppsvattnet diskuteras.
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