| 1. |
- Nord, Maria, et al.
(författare)
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Levodopa Pharmacokinetics in Brain after Both Oral and Intravenous Levodopa in One Patient with Advanced Parkinson’s Disease
- 2017
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Ingår i: Advances in Parkinsons Disease. - : Scientific Research Publishing Inc. - 2169-9712 .- 2169-9720. ; 6:2, s. 52-66
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Tidskriftsartikel (refereegranskat)abstract
- Objective: One patient received oral levodopa during a study aiming for better understanding of the basal ganglia and of the mechanisms of deep brain stimulation of the subthalamic nucleus (STN DBS) with and without intravenous (IV) levodopa infusion in patients with Parkinson’s disease (PD). The results from oral and IV levodopa treatment are presented.Methods: Five patients with advanced PD were included in the original study. During planned STN DBS surgery microdialysis probes were implanted in the right putamen and in the right and left globus pallidus interna (Gpi). During the study, microdialysis was performed continuously and STN DBS, with and without IV levodopa infusion, was performed according to a specific protocol. After DBS surgery, but before STN DBS was started, one patient received oral levodopa/ benserazide and entacapone tablets out of protocol due to distressing parkinsonism.Results: The levodopa levels increased prompt in the central nervous system after the first PD medication intakes but declined after the last. Immediately the levodopa seemed to be metabolized to dopamine (DA) since the levels of DA correlated well with levodopa concentrations. Left STN DBS seemed to further increase DA levels in left Gpi while right STN DBS seemed to increase DA levels in the right putamen and right Gpi. There was no obvious effect on levodopa levels.Conclusions: The results indicate that PD patients still have capacity to metabolize levodopa to DA despite advanced disease with on-off symptoms and probably pronounced nigral degeneration. STN DBS seems to increase DA levels with a more pronounced effect on ipsilateral structures in striatum.
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| 2. |
- Nord, Maria, et al.
(författare)
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Is Levodopa Pharmacokinetics in Patients with Parkinson’s Disease Depending on Gastric Emptying?
- 2017
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Ingår i: Advances in Parkinsons Disease. - : Scientific Research Publishing. - 2169-9712 .- 2169-9720. ; 06:01
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Tidskriftsartikel (refereegranskat)abstract
- Levodopa uptake from the gastrointestinal tract in patients with Parkinson’s disease (PD) can be affected by delayed gastric emptying (GE). This might lead to fluctuating levodopa levels resulting in increased motor fluctuations. Continuous dopaminergic stimulation (CDS) improves motor fluctuations and could be a result of smoothening in levodopa uptake. In this study we wanted to study the levodopa pharmacokinetics peripherally in PD patients with motor fluctuations and investigate the relation between levodopa uptake and GE and the effect of CDS. PD patients with wearing off (group 1) and on-off syndrome (group 2) were included. Breath tests were performed to evaluate the half time (T1/2) of GE. Concomitantly 1 tablet of Madopark® was given and the levodopa concentrations in blood and subcutaneous (SC) tissue were analyzed for both groups. Group 2 was then given a 10-d continuous intravenous levodopa treatment and the tests were repeated. Higher levels of levodopa in group 1 compared to group 2 in blood (p = 0.014) were seen. The GE was delayed in both group 1 (p < 0.001) and group 2 (p < 0.05) compared to a reference group with healthy volunteers with T1/2 median values 105 and 78 min vs. 72 min. There was no difference in GE between the two PD groups (p = 0.220) or in group 2 before and after infusion period (p = 0.861). CDS resulted in lower levodopa levels in blood (p < 0.001) and SC tissue (p < 0.01). In conclusion, PD patients in early complication phase have a more favourable levodopa uptake than patients later in disease. We found delayed GE in PD patients with motor fluctuations but no obvious relation between GE and levodopa uptake or GE and PD stage. The effect of CDS indicates no effect of CDS on the mechanisms of GE but on the mechanisms of levodopa uptake.
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| 3. |
- Nord, Maria
(författare)
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Levodopa pharmacokinetics -from stomach to brain : A study on patients with Parkinson’s disease
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and it is caused by a loss of dopamine (DA) producing neurons in the basal ganglia in the brain. The PD patient suffers from motor symptoms such as tremor, bradykinesia and rigidity and treatment with levodopa (LD), the precursor of DA, has positive effects on these symptoms. Several factors affect the availability of orally given LD. Gastric emptying (GE) is one factor and it has been shown to be delayed in PD patients resulting in impaired levodopa uptake. Different enzymes metabolize LD on its way from the gut to the brain resulting in less LD available in the brain and more side effects from the metabolites. By adding dopa decarboxylase inhibitors (carbidopa or benserazide) or COMT-inhibitors (e.g. entacapone) the bioavailability of LD increases significantly and more LD can pass the blood-brain-barrier and be converted to DA in the brain. It has been considered of importance to avoid high levodopa peaks in the brain because this seems to induce changes in postsynaptic dopaminergic neurons causing disabling motor complications in PD patients. More continuously given LD, e.g. duodenal or intravenous (IV) infusions, has been shown to improve these motor complications. Deep brain stimulation of the subthalamic nucleus (STN DBS) has also been proven to improve motor complications and to make it possible to reduce the LD dosage in PD patients.In this doctoral thesis the main purpose is to study the pharmacokinetics of LD in patients with PD and motor complications; in blood and subcutaneous tissue and study the effect of GE and PD stage on LD uptake and the effect of continuously given LD (CDS) on LD uptake and GE; in blood and cerebrospinal fluid (CSF) when adding the peripheral enzyme inhibitors entacapone and carbidopa to LD infusion IV; in brain during STN DBSand during oral or IV LD treatment.To conclude, LD uptake is more favorable in PD patients with less severe disease and GE is delayed in PD patients. No obvious relation between LD uptake and GE or between GE and PD stage is seen and CDS decreases the LD levels. Entacapone increases the maximal concentration of LD in blood and CSF. This is more evident with additional carbidopa and important to consider in avoiding high LD peaks in brain during PD treatment. LD in brain increases during both oral and IV LD treatment and the DA levels follows LD well indicating that PD patients still have capacity to metabolize LD to DA despite probable pronounced nigral degeneration. STN DBS seems to increase putaminal DA levels and together with IV LD treatment also increases LD in brain possibly explaining why it is possible to decrease LD medication after STN DBS surgery.
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| 4. |
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| 5. |
- Friberg, Hans, et al.
(författare)
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Internationell och nationell konsensus om bästa vård efter hävt hjärtstopp. Många patienter blir helt återställda.
- 2010
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 107:8, s. 2-514
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Forskningsöversikt (refereegranskat)abstract
- An international consensus report on postresuscitation care after cardiac arrest has recently been published. Its content and main messages are in line with the recommendations from The Swedish Resuscitation Council, which include: diagnosing and treating the underlying disease, offering good general intensive care, considering hypothermia treatment, standardising prognostication and follow-up.
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| 6. |
- Hommel, Ami, et al.
(författare)
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Influence of optimised treatment of people with hip fracture on time to operation, length of hospital stay, reoperations and mortality within 1 year
- 2008
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Ingår i: Injury. - : Elsevier. - 0020-1383 .- 1879-0267. ; 39:10, s. 1164-1174
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Tidskriftsartikel (refereegranskat)abstract
- Hip fractures are a major cause of hospital stay among the elderly, and result in increased disability and mortality. In this study from 1 April 2003 to 31 March 2004, the influence of optimised treatment of hip fracture on time to operation, length of hospital stay, reoperations and mortality within 1 year were investigated. Comparisons were made between the first 210 patients in the period and the last 210 patients, who followed the new clinical pathway introduced at the University Hospital in Lund, Sweden. Early surgery, within 24h, was not associated with reduced mortality, but was significantly associated with reduced length of stay (p<0.001). Significantly more cases of osteosynthesis for femoral neck fracture were reoperated compared with all other types of surgery (p<0.001) when reoperations with extraction of the hook pins in healed fractures were excluded. Mortality was significantly higher among men than women at 4 (p=0.025) and 12 (p=0.001) months after fracture and among medically fit patients with administrative delay to surgery compared with patients with no delay (p<0.001).
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| 7. |
- Israelsson, Johan, et al.
(författare)
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Health status and psychological distress among in-hospital cardiac arrest survivors in relation to gender
- 2017
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Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 114, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To describe health status and psychological distress among in-hospital cardiac arrest (IHCA) survivors in relation to gender.METHODS: This national register study consists of data from follow-up registration of IHCA survivors 3-6 months post cardiac arrest (CA) in Sweden. A questionnaire was sent to the survivors, including measurements of health status (EQ-5D-5L) and psychological distress (HADS).RESULTS: Between 2013 and 2015, 594 IHCA survivors were included in the study. The median values for EQ-5D-5L index and EQ VAS among survivors were 0.78 (q1-q3=0.67-0.86) and 70 (q1-q3=50-80) respectively. The values were significantly lower (p<0.001) in women compared to men. In addition, women reported more problems than men in all dimensions of EQ-5D-5L, except self-care. A majority of the respondents reported no problems with anxiety (85.4%) and/or symptoms of depression (87.0%). Women reported significantly more problems with anxiety (p<0.001) and symptoms of depression (p<0.001) compared to men. Gender was significantly associated with poorer health status and more psychological distress. No interaction effects for gender and age were found.CONCLUSIONS: Although the majority of survivors reported acceptable health status and no psychological distress, a substantial proportion reported severe problems. Women reported worse health status and more psychological distress compared to men. Therefore, a higher proportion of women may be in need of support. Health care professionals should make efforts to identify health problems among survivors and offer individualised support when needed.
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| 8. |
- Johnsson, Per, et al.
(författare)
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Increased S100B in blood after cardiac surgery is a powerful predictor of late mortality
- 2003
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 75:1, s. 162-168
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundLong-term outcome in patients who suffered stroke after undergoing a cardiac operation has been investigated sparingly, but increased long-term mortality has been reported. S100B is a biochemical marker of brain cell ischemia and blood–brain barrier dysfunction. The aim of this investigation was to record the long-term mortality in consecutive patients undergoing cardiac operations and to explore whether increased concentrations of S100B in blood had a predictive value for mortality.MethodsProspectively collected clinical variables, including S100B, in 767 patients who survived more than 30 days after a cardiac operation, were analyzed with actuarial survival analysis and 678 patients were analyzed with Cox multiple regression analysis.ResultsForty-nine patients (6.4%) were dead at follow-up (range, 18 to 42 months); 11.5% (88 of 767 patients) had elevated S100B 2 days after operation (range, 38 to 42 hours). The probability for death at follow-up was 0.239 if the S100B level was more than 0.3 μg/L, and 0.041 if it was less than 0.3 μg/L. The clinical variables independently associated with mortality were preoperative renal failure, preoperative low left ventricular ejection fraction, emergency operation, severe postoperative central nervous system complication, and elevated S100B values, which turned out to be the most powerful predictor.ConclusionsEven slightly elevated S100B values in blood 2 days after cardiac operation imply a bad prognosis for outcome, and especially so in combination with any central nervous system complication.
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| 9. |
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| 10. |
- Romlin, Birgitta S, et al.
(författare)
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Perioperative monitoring of platelet function in paediatric cardiac surgery by thromboelastometry, or platelet aggregometry?
- 2016
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912 .- 1471-6771. ; 116:6, s. 822-828
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Tidskriftsartikel (refereegranskat)abstract
- Background Impaired platelet function increases the risk of bleeding complications in cardiac surgery. Reliable assessment of platelet function can improve treatment. We investigated whether thromboelastometry detects clinically significant preoperative, perioperative, and postoperative adenosine diphosphate (ADP)-dependent platelet dysfunction in paediatric cardiac surgery patients. Methods Fifty-seven children were included in a single-centre prospective observational study. Clot formation (modified rotational thromboelastometry with heparinase, HEPTEM) and platelet aggregation (multiple electrode aggregometry) were analysed at five time points before, during, and after surgery. The accuracy of thromboelastometric indices of platelet function [maximal clot firmness (MCF) and clot formation time (CFT)] to detect ADP-dependent platelet dysfunction (defined as ADP-induced aggregation ≤30 units) was calculated with receiver operating characteristics analysis, which also identified optimal cut-off levels. Positive and negative predictive values for the identified cut-off levels (CFT≥166 s; MCF≤43 mm) to detect platelet function were determined. Results The MCF and CFT were highly accurate in predicting platelet dysfunction during cardiopulmonary bypass [CPB; area under the aggregation curve 0.89 (95% confidence interval 0.80–0.97) and 0.86 (0.77–0.96), respectively] but not immediately after CPB [0.64 (0.48–0.79) and 0.67 (0.52–0.82), respectively] or on arrival at the intensive care unit [0.53 (0.37–0.69) and 0.60 (0.44–0.77), respectively]. The positive and negative predictive values were acceptable during CPB (87 and 67%, respectively, for MCF≤43 mm; 80 and 100% for CFT≥166 s) but markedly lower after surgery. Conclusion In paediatric cardiac surgery, thromboelastometry has acceptable ability to detect ADP-dependent platelet dysfunction during, but not after, CPB.
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