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- Apelqvist, G, et al.
(författare)
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Dynamic and kinetic effects of chronic citalopram treatment in experimental hepatic encephalopathy
- 2000
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Ingår i: Clinical neuropharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0362-5664 .- 1537-162X. ; 23:6, s. 304-317
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Tidskriftsartikel (refereegranskat)abstract
- Chronic hepatic encephalopathy (HE) is a neuropsychiatric syndrome that arises in liver-impaired subjects. Patients with HE display various neuropsychiatric symptoms including affective disturbances and may therefore likely receive treatment with novel thymoleptics like citalopram (CIT). The simultaneous pharmacokinetic and pharmacodynamic outcome of the commonly used serotonin-selective thymoleptic drugs in liver-impaired subjects with pending chronic HE is far from understood today. We therefore investigated the effects of chronic, body-weight-adjusted (10 mg ╖ kg-1 ╖ day-1), treatment with CIT in rats with and without portacaval shunts (PCS). Open-field activity was monitored. The 5-HT, 5-HIAA, noradrenaline (NA), and dopamine (DA) output were assessed in the frontal neocortex. The racemic levels of CIT and its metabolites DCIT and DDCIT, including the S- and R-enantiomers, were determined in serum, brain parenchyma, and extracellular fluid. The rats with PCS showed higher (2-3-fold) levels of CIT than rats undergoing a sham treatment with CIT in all compartments investigated. The PCS rats also showed elevated levels of DCIT and DDCIT. No major differences in the S/R ratios between PCS rats and control rats could be detected. The CIT treatment resulted in neocortical output differences between PCS rats and control rats mainly within the 5-HT and DA systems but not within the NA system. For the 5-HT system, this change was further evidenced by outspoken elevation in 5-HT output after KCl-depolarizing challenges. Moreover, the CIT treatment to PCS rats was shown to "normalize" the metabolic turnover of 5-HT, measured as a profound lowering of a basal elevation in the 5-HIAA levels. The CIT treatment resulted in an increased or "normalized" behavioral activity in the PCS group. Therefore, a dose-equal chronic treatment with CIT in PCS rats produced pharmacokinetic and pharmacodynamic changes not observed in control rats. The results further support the contention of an altered 5-HT neurotransmission prevailing in the chronic HE condition. However, the tentatively beneficial behavioral response also seen following chronic CIT treatment to PCS rats in this study has to be viewed in relation to both the pharmacokinetic and pharmacodynamic changes observed.
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| 2. |
- Bergqvist, D, et al.
(författare)
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Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer.
- 2002
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 346:13, s. 975-980
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Tidskriftsartikel (refereegranskat)abstract
- Background: Abdominal surgery for cancer carries a high risk of venous thromboembolism, but the optimal duration of postoperative thromboprophylaxis is unknown. Methods: We conducted a double-blind, multicenter trial in which patients undergoing planned curative open surgery for abdominal or pelvic cancer received enoxaparin (40 mg subcutaneously) daily for 6 to 10 days and were then randomly assigned to receive either enoxaparin or placebo for another 21 days. Bilateral venography was performed between days 25 and 31, or sooner if symptoms of venous thromboembolism occurred. The primary end point with respect to efficacy was the incidence of venous thromboembolism between days 25 and 31. The primary safety end point was bleeding during the three-week period after randomization. The patients were followed for three months. Results: The intention-to-treat analysis of efficacy included 332 patients. The rates of venous thromboembolism at the end of the double-blind phase were 12.0 percent in the placebo group and 4.8 percent in the enoxaparin group (P=0.02). This difference persisted at three months (13.8 percent vs. 5.5 percent, P=0.01). Three patients in the enoxaparin group and six in the placebo group died within three months after surgery. There were no significant differences in the rates of bleeding or other complications during the double-blind or follow-up periods. Conclusions: Enoxaparin prophylaxis for four weeks after surgery for abdominal or pelvic cancer is safe and significantly reduces the incidence of venographically demonstrated thrombosis, as compared with enoxaparin prophylaxis for one week. (N Engl J Med 2002;346:975-80.) Copyright (C) 2002 Massachusetts Medical Society.
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| 7. |
- Humble, Mats, 1952-, et al.
(författare)
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Reactivity of serotonin in whole blood : relationship with drug response in obsessive-compulsive disorder
- 2001
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Ingår i: Biological Psychiatry. - New York, USA : Elsevier. - 0006-3223 .- 1873-2402. ; 49:4, s. 360-368
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obsessive-compulsive disorder responds almost only to potent serotonin reuptake inhibitors. Previous studies have suggested a relation between serotonergic function and clinical outcome in serotonin reuptake inhibitor treatment of obsessive-compulsive disorder.Methods: In a randomized, double-blind trial, comparing clomipramine, paroxetine, and a placebo in obsessive-compulsive disorder, serotonin levels in whole blood (WB-5-HT) were measured at baseline, after 1 week, and after 4 weeks of treatment and related to clinical outcome in 36 patients.Results: In patients treated with serotonin reuptake inhibitors there was a pronounced decrease of WB-5-HT, variable after 1 week and uniformly maximal after 4 weeks. The decrease of WB-5-HT after 1 week of serotonin reuptake inhibitor treatment correlated negatively with clinical outcome after 12 weeks (r = -.61, p =.0006); hence, patients with slower WB-5-HT reactivity eventually responded better to treatment. Baseline WB-5-HT, but not WB-5-HT reactivity, was related to season. Depression, autistic traits, and previous serotonin reuptake inhibitor treatment predicted nonresponse.Conclusions: A fast decrease of WB-5-HT was associated with poor clinical outcome. This may be related to faster serotonin efflux from platelets, which has previously been linked to autism. Further studies are necessary to identify the underlying mechanism and discern whether serotonin reuptake inhibitor-induced WB-5-HT decrease is clinically useful.
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| 8. |
- Lindberg, F, et al.
(författare)
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Coagulation activation after laparoscopic cholecystectomy in spite of thromboembolism prophylaxis.
- 2000
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Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 14:9, s. 858-61
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to determine whether laparoscopic cholecystectomy (LC), in spite of its minimally invasive nature, causes coagulation activation.METHODS: Sixty-four patients undergoing LC were included prospectively. All received either dextran or low-molecular-weight heparin (LMWH). Blood samples taken the morning of the operation and the following morning were analyzed for TAT, FM, fragment 1+2, tPA, PAI-1, vWf, D-dimer, Hb, hematocrit, and APC resistance.RESULTS: Significant increases in TAT, FM, fragment 1+2, and D-dimer were seen, whereas APC resistance, Hb, and hematocrit decreased significantly. Dextran led to a decrease in vWf and no change in tPA, whereas LMWH led to an increase in both these parameters.CONCLUSIONS: Laparoscopic cholecystectomy causes coagulation activation. There are differences in the response between patients receiving dextran and LMWH as thromboembolism prophylaxis. Since most patients are discharged the day after the operation, there could be practical as well as theoretical advantages to using dextran.
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| 10. |
- Lindberg, F, et al.
(författare)
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Renal hemodynamics during carbon dioxide pneumoperitoneum : an experimental study in pigs.
- 2003
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Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 17:3, s. 480-4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Laparoscopic living donor nephrectomy is increasingly being performed, although the effects of carbon dioxide pneumoperitoneum (CO2 PP) on renal function and hemodynamics and the levels of vasopressin are not well studied.METHODS: Renal blood flow, renal venous pressure, urine output, and vasopressin concentrations in renal venous blood were measured in pigs subjected to 12 mmHg of CO2 PP for 150 min.RESULTS: Renal blood flow was decreased at induction of PP and increased during the first 30 min after exsufflation. Renal venous pressure was increased during PP. There was indirect evidence of a decrease in urine output during PP. No changes in renal venous vasopressin concentrations were seen.CONCLUSION: A CO2 PP of 12 mmHg causes changes in renal hemodynamics and urine output. No changes in vasopressin levels were seen in this pig model, suggesting that other explanations for the observed changes must be sought.
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