| 1. |
- Bath, Philip M W, et al.
(författare)
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Tinzaparin in acute ischaemic stroke (TAIST) : A randomised aspirin-controlled trial
- 2001
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 358:9283, s. 702-710
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-molecular-weight heparins and heparinoids are superior to unfractionated heparin in the prevention and treatment of venous thromboembolism, but their safety and efficacy in acute ischaemic stroke are inadequately defined. Methods: This randomised, double-blind, aspirin-controlled trial tested the safety and efficacy of treatment with high-dose tinzaparin (175 anti-Xa IU/kg daily, 487 patients), medium-dose tinzaparin (100 anti-Xa IU/kg daily, 508 patients), or aspirin (300 mg daily, 491 patients) started within 48 h of acute ischaemic stroke and given for up to 10 days. Primary intracerebral haemorrhage was excluded by computed tomography. Outcome was assessed, with treatment allocation concealed, by the modified Rankin scale at 6 months (independence [scores 0-2] vs dependence or death [scores 3-6]). Findings: Of 1486 randomised patients, two did not receive treatment and 46 were lost to follow-up. The proportions independent at 6 months were similar in the groups assigned high-dose tinzaparin (194/468 [41.5%]), medium-dose tinzaparin (206/486 [42.4%]), or aspirin (205/482 [42.5%]). There was no difference in effect in any predefined subgroup, including patients with presumed cardioembolic stroke. Other outcome measures were similar between the treatment groups (disability, case-fatality, and neurological deterioration rates). During the in-hospital treatment period no patient assigned high-dose tinzaparin developed a symptomatic deep-vein thrombosis compared with nine assigned aspirin. Conversely, seven patients assigned high-dose tinzaparin developed symptomatic intracerebral haemorrhage compared with one in the aspirin group. Interpretation: Treatment with tinzaparin, at high or medium dose, within 48 h of acute ischaemic stroke did not improve functional outcome compared with aspirin. Although high-dose tinzaparin was superior in preventing deep-vein thrombosis, it was associated with a higher rate of symptomatic intracranial haemorrhage.
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| 2. |
- Norrving, Bo, et al.
(författare)
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Cerebrovaskulära sjukdomar
- 2006
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Ingår i: Neurologi. - 9147053135 ; , s. 188-188
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 3. |
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| 4. |
- Sprigg, Nikola, et al.
(författare)
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elationship between outcome and baseline blood pressure and other haemodynamic measures in acute ischaemic stroke : Data from the TAIST trial
- 2006
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Ingår i: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352 .- 1473-5598. ; 24:7, s. 1413-1417
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A poor outcome after stroke is associated independently with high blood pressure during the acute phase, however, relationships with other haemodynamic measures [heart rate (HR), pulse pressure (PP), rate-pressure product (RPP)] remain less clear. METHODS: The Tinzaparin in Acute Ischaemic Stroke Trial is a randomised, controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1484 patients with acute ischaemic stroke. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR measurements taken immediately prior to randomization were averaged, and the mid-blood pressure (MBP), PP, mean arterial pressure (MAP), pulse pressure index, and RPP were calculated. The relationship between these haemodynamic measures and functional outcome (death or dependency, modified Rankin Scale > 2) and early recurrent stroke, were studied with adjustment for baseline prognostic factors and treatment group. Odds ratios (OR) and 95% confidence intervals (CI) refer to a change in haemodynamic measure by 10 points. RESULTS: A poor functional outcome was associated with SBP (adjusted OR, 1.11, 95% CI, 1.03-1.21), HR (adjusted OR, 1.15, 95% CI, 1.00-1.31), MBP (adjusted OR, 1.15, 95% CI, 1.03-1.29), PP (adjusted OR, 1.14, 95% CI, 1.02-1.26), MAP (adjusted OR, 1.15, 95% CI, 1.02-1.31) and RPP (adjusted OR, 1.01, 95% CI, 1.00-1.02). Early recurrent stroke was associated with SBP, DBP, MBP and MAP. CONCLUSIONS: A poor outcome is independently associated with elevations in blood pressure, HR and their derived haemodynamic variables, including PP and the RPP. Agents that modify these measures may improve functional outcome after stroke. © 2006 Lippincott Williams & Wilkins.
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| 5. |
- Dizdar (Dizdar Segrell), Nil, et al.
(författare)
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Human pharmacokinetics of L-3,4-dihydroxyphenylalanine studied with microdialysis
- 1999
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Ingår i: Clinical Chemistry. - 0009-9147 .- 1530-8561. ; 45:10, s. 1813-1820
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intravenous and subcutaneous microdialysis was performedto compare the free concentrations and pharmacokinetics of L-3,4-dihyroxyphenylalanine(L-dopa) in blood and tissue in healthy subjects and in patientswith Parkinson disease.Methods: Nine healthy volunteers and 10 patients with Parkinson disease, stage 1.5–2 according to the Hoehn-Yahr rating scale, took part of the study. In the patient group subcutaneous microdialysis and ordinary blood sampling were performed, whereas in the control group intravenous microdialysis was also performed. Microdialysis samples were collected in fractions of 15 min. The first two fractions were collected for analysis of basal concentrations. A blood sample was also taken. The patients were then given one tablet of Madopar® (100 mg of L-dopa and 25 mg of benserazide),and the microdialysis was continued for another 210 min. Bloodsamples were obtained at 30-min intervals.Results: The serum samples gave a significantly higher meanarea under the curve (AUC; 491 ± 139 µmol ·min/L) than that for intravenous dialysates (235 ± 55.3µmol · min/L), suggesting a protein binding of50%. The L-dopa concentrations from the subcutaneous dialysatesmatched those from the intravenous dialysates, indicating rapiddistribution of L-dopa to the tissues.Conclusions: Parkinsonian patients in early stages of the disease have a pharmacokinetic pattern of free L-dopa similar to that of healthy subjects. Comparison of AUCs from microdialysis with ordinary serum analysis revealed data indicating significant protein binding. Microdialysis is a suitable and easily applied tool in pharmacokinetic studies.
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| 6. |
- Dizdar (Dizdar Segrell), Nil, et al.
(författare)
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L-dopa pharmacokinetics studied with microdialysis in patients with Parkinson's disease and a history of malignant melanoma
- 1999
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 100:4, s. 231-237
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The pharmacokinetics of free L-dopa in blood and tissue of five parkinsonian patients with malignant melanoma was studied with microdialysis. In one case the effect of L-dopa treatment on 5-S-cysteinyldopa and the melanoma was studied. Gastric emptying and its effects on free L-dopa in blood were also investigated in one of the patients.METHODS: Five patients were given 100 mg L-dopa with 25 mg benserazide. Blood and dialysates from the circulation and fatty tissue were collected for analysis. [13C]-Octanoic breath test was used for analyzing gastric half-emptying time.RESULTS: Four of the patients had similar pharmacokinetic patterns for L-dopa and a significant (P < 0.05) increase of serum 5-S-cysteinyldopa occurring 30 min after L-dopa intake. Delayed L-dopa peaks and slow gastric half-emptying time were found in 1 patient. A dose-dependent increase of 5-S-cysteinyldopa occurred but no melanoma metastases were seen during long-term L-dopa therapy.CONCLUSION: L-dopa therapy increases 5-S-cysteinyldopa levels but does not seem to cause progress of melanomas. Gastric emptying impacts L-dopa pharmacokinetics.
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| 7. |
- Dizdar (Dizdar Segrell), Nil
(författare)
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Microdialysis as a Tool in Studies of L-Dopa and Metabolites in Malignant Melanoma and Parkinson’s Disease
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A model with human melanoma xenografts transplanted to athymic mice has been adopted for in vivo studies of 5-S-cysteinyldopa (an intermediate pigment metabolite), glutathione, and cysteine. L-Dopa is an intermediate metabolite in pigment formation and is also important in the treatment of Parkinson's disease, and therefore 1 have also studied the pharmacokinetics of this compound.We were first to describe in vivo microdialysis in melanoma tissue and showed that dialysis membranes of cuprophane or polyamide are suitable for studies of interstitial 5-S-cysteinyldopa and selected thiols. Analytical procedures were also improved for quantitation of 5-S-cysteinyldopa, L-dopa, glutathione, cysteine, and N-acetylcysteine (NAC). In the melanoma xenografts the interstitial concentration of 5-S-cysteinyldopa reflected the high intracellular production of this intermediate metabolite. For in vivo manipulation of glutathione in the melanoma tissue we gave intraperitoneal injection of buthionine sulphoximine to the animals and thus reduced the glutathione concentrations substantially. We showed that restitution of glutathione in melanoma tissue occurs spontaneously and is not much improved by treatment with the cysteine deliverers NAC and L-2-oxothiazolidine-4-carboxylate (OTC). 5-S-Cysteinyldopa was not substantially affected by great variations in glutathione concentrations. Transport of NAC from intraperitoneal injection to melanoma tissue occurred rapidly and deacetylation to cysteine in vivo could be detected soon after NAC injection. In vivo formation of cysteine was slower from OTC than from NAC.Pharmacokinetic studies of L-dopa in human subjects indicated a slight to moderate protein binding. Plasma free L-dopa had similar elimination T½ as interstitial L-dopa, but in some cases the elimination of total L-dopa was slower. Difficulties in intestinal absorption of L-dopa were revealed by microdialysis in blood and subcutaneous tissue. Studies showed that this was due to delayed emptying of the stomach. L-Dopa intake increased 5-S-cysteinyldopa concentrations in blood within 30 min in patients with Parkinson's disease and a history of melanoma. No melanoma activation occurred during long-term treatment with L-dopa.Microdialysis is thus a safe and easily applied method for in vivo studies of both pigment metabolites from human melanoma tissue transplanted to nude mice and for pharmacokinetic studies of L-dopa.
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| 8. |
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| 9. |
- Ekbom, Karl, et al.
(författare)
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Restless legs - vanligt sjukdomstillstånd som ofta missas. Möjligheter till framgångsrik behandling finns idag
- 2006
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Ingår i: Läkartidningen. - 0023-7205. ; 103:4, s. 207-211
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Tidskriftsartikel (refereegranskat)abstract
- Restless legs syndrome (RLS) is characterized by intense restlessness and unpleasant creeping sensations deep inside the lower legs. The symptoms appear when the limbs are at rest and are worst in the evening and at night. They force the patients to keep moving their legs, and sometimes to get out of bed and wander about. Periodic limb movements of the extremities (PLM) are common during sleep thus causing severe reduction in sleep efficiency. In many cases RLS may be an inherited disorder and there is a common association with iron deficiency anemia and chronic renal failure. The pathophysiology of RLS is multifactorial and incompletely understood. Results of dopaminergic treatment and recent data by advanced neuroimaging suggest that symptoms of RLS may be generated in the central nervous system, notably in substantia nigra, putamen and by rhythmically active nuclei in the thalamus, brainstem and cerebellum. RLS is a very common disorder but has not seldom been under-diagnosed and poorly treated for many years in general practice. At present there is a wide range of treatment options including levodopa, dopamine agonists, opioids, antiepileptic drugs and benzodiazepines.
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| 10. |
- Eriksson, Sven-Erik, 1949-, et al.
(författare)
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Survival and recurrent strokes in patients with different subtypes of stroke : A fourteen-year follow-up study
- 2001
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Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 12:3, s. 171-180
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Tidskriftsartikel (refereegranskat)abstract
- In this study, 339 patients (154 men, 185 women) with a median age of 74 years (range 23-97) admitted to the Stroke Unit, Department of Neurology in 1986, have been followed up for 14 years. The diagnoses were intra-cerebral hemorrhage (ICH, 30, 8.8%), cardioembolic cerebral infarction (CE, 71, 20.9%), lacunar infarction (LI, 47, 13.9%) and atherosclerotic cerebral infarction (ACI, 191, 56.3%). The cumulative probabilities of recurrent stroke rates at 1-, 5- and 10-year follow-ups were 13.5% (95% confidence interval, CI, 9.6-17.4), 38.7% (95% CI 32.6-44.8) and 53.9% (95% CI 46.7-61.1). According to Cox proportional hazard regression analysis, age, severity of stroke, previous stroke and systolic blood pressure are each of importance in predicting recurrent stroke. During the observation period, 290 patients (85.5%) died. The mortality rate of 24.5% during the first year was 4.5 times higher compared to the normal population of the same age and gender. Patients with LI had lower mortality rates compared to ICH by the log rank test (p =0.0275), to CE (p =0.000) and to ACI (p =0.049). Thirty-nine percent of all vascular deaths after the first year were caused by recurrent strokes. Fatal index/recurrent stroke occurred statistically more frequently in the CE group versus the non-CE one (p =0.005). Cox proportional hazard regression analysis indicated that age, severity of stroke, previous stroke, heart failure and fasting blood glucose exceeding 6 mmol/l or history of diabetes were each predictors of mortality. In conclusion, this study has shown the worse outcomes for all subtypes of stroke compared to the normal population and also clearly pointed out independent predictors of recurrent stroke or death at the time of diagnosis. Copyright
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