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| 2. |
- Erlinge, D., et al.
(författare)
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Bivalirudin versus Heparin Monotherapy in Myocardial Infarction
- 2017
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:12, s. 1132-1142
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Tidskriftsartikel (refereegranskat)abstract
- Background The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. Methods In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. Results A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). Conclusions Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).
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| 3. |
- Hart, Andrew McKay, et al.
(författare)
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Sensory neuroprotection, mitochondrial preservation, and therapeutic potential of N-acetyl-cysteine after nerve injury.
- 2004
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 125:1, s. 91-101
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Tidskriftsartikel (refereegranskat)abstract
- Neuronal death is a major factor in many neuropathologies, particularly traumatic, and yet no neuroprotective therapies are currently available clinically, although antioxidants and mitochondrial protection appear to be fruitful avenues of research. The simplest system involving neuronal death is that of the dorsal root ganglion after peripheral nerve trauma, where the loss of approximately 40% of primary sensory neurons is a major factor in the overwhelmingly poor clinical outcome of the several million nerve injuries that occur each year worldwide. N-acetyl-cysteine (NAC) is a glutathione substrate which is neuroprotective in a variety of in vitro models of neuronal death, and which may enhance mitochondrial protection. Using TdT uptake nick-end labelling (TUNEL), optical disection, and morphological studies, the effect of systemic NAC treatment upon L4 and 5 primary sensory neuronal death after sciatic nerve transection was investigated. NAC (150 mg/kg/day) almost totally eliminated the extensive neuronal loss found in controls both 2 weeks (no treatment 21% loss, NAC 3%, P=0.03) and 2 months after axotomy (no treatment 35% loss, NAC 3%, P=0.002). Glial cell death was reduced (mean number TUNEL positive cells 2 months after axotomy: no treatment 51/ganglion pair, NAC 16/ganglion pair), and mitochondrial architecture was preserved. The effects were less profound when a lower dose was examined (30 mg/kg/day), although significant neuroprotection still occurred. This provides evidence of the importance of mitochondrial dysregulation in axotomy-induced neuronal death in the peripheral nervous system, and suggests that NAC merits investigation in CNS trauma. NAC is already in widespread clinical use for applications outside the nervous system; it therefore has immediate clinical potential in the prevention of primary sensory neuronal death, and has therapeutic potential in other neuropathological systems.
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| 4. |
- Havton, Leif A, et al.
(författare)
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Correlation of median forearm conduction velocity with carpal tunnel syndrome severity.
- 2007
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457. ; 118:4, s. 781-5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Median nerve entrapment neuropathy at the wrist can be accompanied by slowed motor conduction within the forearm. Existing studies conflict regarding a correlation between the severity of the entrapment neuropathy in carpal tunnel syndrome (CTS) and slowing of median motor nerve conduction velocity (MNCV) in the forearm. Here, it was asked if there is a correlation between markers of CTS severity and median forearm MNCV, and if there is an explanation for the preceding conflicting results. METHODS: Median MNCV in the forearm was correlated with neurophysiologic markers of severity of a median neuropathy at the wrist in 91 hands from 64 patients with clinical and electrodiagnostic evidence of CTS. RESULTS: Median MNCV within the forearm segment was negatively correlated with the median nerve distal motor latency (r=-0.64, P<0.001, n=91) and positively correlated with the CMAP amplitude of the abductor pollicis brevis muscle (r=0.45, P<0.001, n=91). These correlations only occurred in patients with a prolonged median distal motor latency. Previous investigations that failed to find such correlations used variable or non-standardized methods or analyzed smaller numbers of patients. CONCLUSIONS: Slowing of median MNCV in the forearm is related to the severity of the entrapment of median motor fibers at the wrist. SIGNIFICANCE: Slowed forearm median MNCV can be a marker of motor nerve injury at the wrist.
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| 5. |
- Havton, Leif A, et al.
(författare)
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Plasticity of lumbosacral monosynaptic reflexes after a ventral root transection injury in the adult cat.
- 2004
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Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 155:1, s. 111-4
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Tidskriftsartikel (refereegranskat)abstract
- Injuries to spinal ventral roots may induce plastic changes in adjacent segmental reflex pathways. Earlier studies in the cat have demonstrated that a partial loss of target motoneurons, following a ventral root avulsion injury, induces a compensatory enhancement of monosynaptic reflexes in adjacent segments. Here, we studied electrophysiologically the effects of a primarily non-lethal motoneuron injury of lumbosacral ventral roots on monosynaptic reflexes in adjacent intact motoneurons in the adult cat. A unilateral L7 or a combined L7 and S1 ventral root transection was first performed. We next recorded bilaterally monosynaptic reflexes from the L6 and S1 ventral roots while stimulating the bilateral L6, L7 and S1 dorsal roots at 6 and 12 weeks postoperatively. We demonstrated a prominent strengthening of monosynaptic reflexes in the immediately adjacent spinal cord segments. The reflexes had almost doubled in size at 6 and 12 weeks postoperatively. Possible mechanisms and factors contributing to the reflex enhancement are discussed.
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| 6. |
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| 7. |
- Ma, Jianjun, et al.
(författare)
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Early nerve repair after injury to the postganglionic plexus : an experimental study of sensory and motor neuronal survival in adult rats.
- 2003
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - 0284-4311 .- 1651-2073. ; 37:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- The optimal time for brachial plexus nerve repair is debatable. In this study we examined whether early re-establishment of neurotrophic support from the periphery might reduce neuronal loss. In 14 adult rats, the C7 spinal nerve was transsected. All sensory cells of the dorsal root ganglion and spinal motor neurons projecting into the C7 nerve were labelled retrogradely. The proximal and distal portions of the C7 nerve were then reanastomosed by either primary repair or by a vascularised or conventional ulnar nerve graft. At 16 weeks postoperatively, the nerve repair had significantly reduced the loss of both sensory and motor C7 neurons. Most striking was that a 30% motor neuronal loss in the control was almost eliminated by early nerve repair. In the grafted animals, half of the surviving neurons had regenerated through the graft, with no difference between vascularised and conventional nerve grafts. These results suggest that early surgical intervention may promote neuronal survival and regeneration after injuries to the brachial plexus.
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| 8. |
- Novikov, Lev N, et al.
(författare)
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A novel biodegradable implant for neuronal rescue and regeneration after spinal cord injury.
- 2002
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Ingår i: Biomaterials. - 0142-9612 .- 1878-5905. ; 23:16, s. 3369-76
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Tidskriftsartikel (refereegranskat)abstract
- After spinal cord injury, the severed neuronal pathways fail to regenerate spontaneously. This study describes a biodegradable implant using poly-beta-hydroxybutyrate (PHB) fibers as carrier scaffold for matrix components and cell lines supporting neuronal survival and regeneration after spinal cord injury. After cervical spinal cord injury in adult rats, a graft consisting of PHB fibers coated with alginate hydrogel + fibronectin was implanted in the lesion cavity. In control groups, PHB was omitted and only alginate hydrogel or fibronectin, or their combination, were used for grafting. In addition, comparisons were made with animals treated intrathecally after spinal cord injury with the neurotrophic factors BDNF or NT-3. The neurons of the rubrospinal tract served as experimental model. In untreated animals, 45% of the injured rubrospinal neurons were lost at 8 weeks postoperatively. Implantation of the PHB graft reduced this cell loss by 50%, a rescuing effect similar to that obtained after treatment with BDNF or NT-3. In the absence of PHB support, implants of only alginate hydrogel or fibronectin, or their combination, had no effect on neuronal survival. After addition of neonatal Schwann cells to the PHB graft, regenerating axons were seen to enter the graft from both ends and to extend along its entire length. These results show that implants using PHB as carrier scaffold and containing alginate hydrogel, fibronectin and Schwann cells can support neuronal survival and regeneration after spinal cord injury
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| 9. |
- Novikova, Liudmila N, et al.
(författare)
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Alginate hydrogel and matrigel as potential cell carriers for neurotransplantation.
- 2006
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Ingår i: Journal of Biomedical Materials Research part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 77:2, s. 242-252
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Tidskriftsartikel (refereegranskat)abstract
- Development of biosynthetic conduits carrying extracellular matrix molecules and cell lines expressing neurotrophic growth factors represents a novel and promising strategy for spinal cord and peripheral nerve repair. In the present in vitro study, the compatibility and growth-promoting effects of (i) alginate hydrogel, (ii) alginate hydrogel complemented with fibronectin, and (iii) matrigel were compared between olfactory ensheathing cells (OECs), Schwann cells (SCs), and bone marrow stromal cells (BMSCs). Neurite outgrowth from embryonic dorsal root ganglia (DRG) neurons was used to assess the efficacy of the hydrogels alone or in combination with cultured cells to promote axonal regeneration. The result showed that alginate hydrogel transformed OECs, SCs, and BMSCs into atypical cells with spherical shape and inhibited their metabolic activity. Combination of alginate hydrogel with fibronectin promoted only OECs proliferation. Alginate hydrogel also inhibited outgrowth of DRG neurites, although this effect was attenuated by addition of fibronectin, SCs, or BMSCs. In contrast, matrigel stimulated cell proliferation, preserved the typical morphological features of the cultured cells and induced massive sprouting of DRG neurites. Addition of cultured cells to matrigel did not further improve DRG neurite outgrowth. The present findings suggest that addition of extracellular matrix should be considered when engineering biosynthetic scaffolds on the basis of alginate hydrogels.
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| 10. |
- Novikova, Liudmila N, et al.
(författare)
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Biopolymers and biodegradable smart implants for tissue regeneration after spinal cord injury.
- 2003
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Ingår i: Current Opinion in Neurology. - 1350-7540 .- 1473-6551. ; 16:6, s. 711-5
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: This article reviews recent experimental advances in the development of biosynthetic implants for repair of spinal cord injury.RECENT FINDINGS: Various important advances in the development of biosynthetic conduits for spinal cord repair have recently been reported. It was found that implantation of freeze dried alginate sponge into completely transected spinal cord supports axonal regeneration across the lesion site. A poly(lactic-co-glycolic acid) scaffold seeded with neural stem cells has been developed that promotes axonal regeneration across the gap. It was found that polyethylene glycol can reseal damaged spinal cord axons and restore impulse conduction. Findings have been reported that poly-beta-hydroxybutyrate conduits in combination with alginate and fibronectin provide neuroprotection for axotomized descending neurones. It has been reported that conduits made of fibronectin mats or fibrin in combination with neurotrophic growth factors promote axonal growth into the grafts. Finally, magnetic resonance imaging after experimental spinal cord injury has been used to monitor regeneration in biosynthetic conduits in vivo over time.SUMMARY: Biosynthetic conduits carrying extracellular matrix molecules and different cell lines, and supplemented with neurotrophic growth factors have yielded encouraging results in the treatment of experimental spinal cord injury. These findings provide a basis for further development of techniques aimed at spinal cord repair in humans.
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