1.
Ericsson, Peter, et al.
(författare)
ECL Cell Histamine Mobilization Studied byGastric Submucosal Microdialysis in Awake Rats:Methodological Considerations.
2003
Ingår i: Pharmacology and Toxicology. - : Wiley. - 1600-0773 .- 0901-9928. ; 93:2, s. 57-65
Tidskriftsartikel (refereegranskat) abstract
The ECL cells are endocrine/paracrine cells in the acid-producing part of the stomach. They secrete histamine in response to circulating gastrin. Gastric submucosal microdialysis has been used to study ECL-cell histamine mobilization in awake rats. In the present study we assess the usefulness and limitations of the technique. Microdialysis probes were implanted in the gastric submucosa. Histological analysis of the stomach wall around the probe revealed a moderate, local inflammatory reaction 1-2 days after implantation; the inflammation persisted for at least 10 days. Experiments were conducted 3 days after the implantation. The "true" submucosal histamine concentration was determined by perfusing at different rates (the zero flow method) or with different concentrations of histamine at a constant rate (the no-net-flux method): in fasted rats it was calculated to be 87±5 (means±S.E.M.) nmol/l and 76±9 nmol/l, respectively. The corresponding histamine concentrations in fed rats were 93±5 and 102±8 nmol/l, respectively. With a perfusion rate of 74 mul/hr the recovery of submucosal histamine was 49%, at 34 mul/hr the recovery increased to 83%. At a perfusion rate below 20 mul/hr the microdialysate histamine concentration was close to the actual concentration in the submucosa. The ECL-cell histamine mobilization was independent of the concentrations of Ca2+ in the perfusion medium (0-3.4 mmol/l Ca2+). In one experiment, histamine mobilization in response to gastrin (10 nmol/kg/hr subcutaneously) was monitored in rats pretreated with prednisolone (60 mg/kg) or indomethacin (15 mg/kg). The two antiinflammatory agents failed to affect the concentration of histamine in the microdialysate either before or during the gastrin challenge, which was in accord with the observation that the inflammatory reaction was modest and that inflammatory cells were relatively few around the probe and in the wall of the probe. In another experiment, rats were given aminoguanidine (10 mg/kg) or metoprine (10 mg/kg) 4 hr before the start of gastrin infusion (5 nmol/kg/hr intravenously). Metoprine (inhibitor of histamine N-methyl transferase) did not affect the microdialysate histamine concentration, while aminoguanidine (inhibitor of diamine oxidase) raised both basal and gastrin-stimulated histamine concentrations. We conclude that microdialysis can be used to monitor changes in the concentration of histamine in the submucosa of the stomach, and that the inflammatory reaction to the probe is moderate and does not affect the submucosal histamine mobilization.
2.
3.
Hellström, Lina, et al.
(författare)
Impact of the Lund Integrated Medicines Management (LIMM) model on medication appropriateness and drug-related hospital revisits.
2011
Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 67:7, s. 741-752
Tidskriftsartikel (refereegranskat) abstract
PurposeTo examine the impact of systematic medication reconciliations when admitted to hospital, and medication review while in hospital, on the number of inappropriate medications and unscheduled drug-related hospital revisits in elderly patients.MethodsA prospective, controlled study in 210 patients, aged 65 years or older, who were admitted to one of three internal medicine wards at a University Hospital in Sweden. Patients received either standard care or care according to the Lund Integrated Medicines Management (LIMM) model. A multi-professional team, including a clinical pharmacist, provided medication reconciliations on admission and medication reviews during the hospital stay for the LIMM group. Blinded reviewers evaluated the appropriateness of the prescribing (using the Medication Appropriateness Index) on admission and discharge, and assessed the probability that a drug-related problem was the reason for any patient readmitted to hospital or visiting the emergency department within three months of discharge (using WHO causality criteria).ResultsThere was a greater decrease in the number of inappropriate drugs in the intervention group than in the control group for both the intention-to-treat population (51% [95% CI 43-58%] versus 39% [95% CI 30-48%], p=0.0446) and the per-protocol population (60% [95% CI 51-67%] versus 44% [95% CI 34-52 %], p=0.0106). There were 6 revisits to hospital in the intervention group which were judged as ‘possibly, probably or certainly drug-related’, compared with 12 in the control group (p=0.0469).ConclusionIn this study, medication reconciliation and reviews provided by a clinical pharmacist in a multi-professional team significantly reduced the number of inappropriate drugs and unscheduled drug-related hospital revisits for elderly patients.
4.
Magnusson, Marie, et al.
(författare)
A placebo-controlled study of retinal blood flow changes by pentoxifylline and metabolites in humans
2006
Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 61:2, s. 138-147
Tidskriftsartikel (refereegranskat) abstract
AIM: To investigate the possible effects of pentoxifylline metabolites on retinal blood flow in humans. METHODS: A randomized, placebo-controlled, four-period cross-over study that was observer blinded and partly blinded for the eight participants. On one occasion a placebo was given as an intravenous (i.v.) infusion over 100 min. On the other three occasions pentoxifylline was administered as i.v. infusions over 100 min at a rate of 3 mg min(-1). Before two of the pentoxifylline infusions the subjects were pretreated with either ciprofloxacin or rifampicin. Retinal blood flow was measured by scanning laser doppler flowmetry (SLDF) in a selected area of the central temporal retina before, during and until 5 h after the end of infusion. Blood samples for concentration analyses of pentoxifyllin, R-M1, S-M1, M4 and M5 were taken serially and areas under the curves (AUCs) were calculated. Linear mixed models were used for the statistical analyses. RESULTS: Mean AUCs (ng h ml(-1)) were significantly increased for pentoxifylline (1964 vs. 1453) and S-M1 (5804 vs. 4227), but not R-M1 when pentoxifylline was co-administered with ciprofloxacin. The mean AUC for M5 was significantly reduced when subjects were pretreated with rifampicin (2041 vs. 3080). Pentoxifylline with and without pretreatment with rifampicin significantly increased retinal blood flow assessed as mean flow, pulsation (i.e. 1-systole/diastole), and diastolic flow (but not during systole), compared with placebo. The increases over placebo were more pronounced on diastolic flow, 9.7% (95% confidence interval 4.2, 15.5) than on mean flow, 4.6% (1.1, 8.3) after pentoxifylline administration. With pentoxifylline after rifampicin pretreatment the corresponding differences were 11.7% (5.8, 17.9) and 5.1% (1.4, 7.8) over placebo, respectively. After co-administration of pentoxifylline and ciprofloxacin we saw only a nonsignificant trend towards increased flow during diastole, but a significant decrease in pulsation. When AUCs for pentoxifylline and its metabolites were used as regressor variables to retinal mean flow we found that pentoxifylline, R-M1 and M5 had coefficients with a positive sign indicating that they enhanced the retinal blood flow. In contrast, S-M1 and M4 had coefficients with negative sign and thus appeared to decrease the blood flow in subjects treated with pentoxifylline. CONCLUSION: The R-M1 and M5 metabolites of pentoxifylline contributed significantly to the effects of pentoxifylline on retinal blood flow.
5.
Bondesson, Åsa ÅB, et al.
(författare)
A structured questionnaire to assess patient compliance and beliefs about medicines taking into account the ordered categorical structure of data
2009
Ingår i: Journal of Evaluation In Clinical Practice. - : Wiley. - 1356-1294 .- 1365-2753. ; 15:4, s. 713-723
Tidskriftsartikel (refereegranskat) abstract
RATIONALE, AIMS AND OBJECTIVE: The objectives were to describe and evaluate the structured medication questionnaire and to improve data handling of results from the Morisky four-item scale for patient compliance and Beliefs about Medicines Questionnaire-specific (BMQ-specific). METHODS: A questionnaire was developed with the purpose of being used when identifying medication errors and assessing patient compliance to and beliefs about medicines. RESULTS: A majority of the respondents (62%; CI 45-77%) had at least one medication error. Assuming that all items are equally important in the Morisky four-item scale we presented four alternative ways to create a unidimensional global scale. A two-dimensional global scale was also constructed. The results from the BMQ-specific were presented in different ways, all taking into account that the scale has ordered verbal categories: at the level addressing each specific question, at the sub-scales 'concern' and 'necessity' level and at the global level. CONCLUSIONS: The structured medication questionnaire can be used in daily practice as a tool to identify drug-related problems. The choice of how to use and present data from those scales in research depends on patient characteristics and how discriminating one would like the scales to be.
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8.
Bergkvist, Anna, et al.
(författare)
Improved quality in the hospital discharge summary reduces medication errors-LIMM: Landskrona Integrated Medicines Management.
2009
Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 1432-1041 .- 0031-6970. ; 65, s. 1037-1046
Tidskriftsartikel (refereegranskat) abstract
PURPOSE: We have developed a model for integrated medicines management, including tools and activities for medication reconciliation and medication review. In this study, we focus on improving the quality of the discharge summary including the medication report to reduce medication errors in the transition from hospital to primary and community care. METHODS: This study is a longitudinal study with an intervention group and a control group. The intervention group comprised 52 patients, who were included from 1 March 2006 until 31 December 2006, with a break during summer. Inclusion in the control group was performed in the same wards during the period 1 September 2005 until 20 December 2005, and 63 patients were included in the control group. In order to improve the quality of the medication report, clinical pharmacists reviewed and gave feedback to the physician on the discharge summary before patient discharge, using a structured checklist. Medication errors were then identified by comparing the medication list in the discharge summary with the first medication list used in the community health care after the patient had returned home. RESULTS: By improving the quality of the discharge summary, patients had on average 45% fewer medication errors per patient (P = 0.012). The proportion of patients without medication errors was 63.5% in the control group and 73.1% in the intervention group. However, this increase was not significant (P = 0.319). Patients who used a specific medication dispensing system (ApoDos) had a 5.9-fold higher risk of suffering from medication errors than those without this medication dispensing system (P < 0.001). CONCLUSION: Review and feedback on errors in the discharge summary, including the medication report and a correct medication list, reduced medication errors during the transfer of information from hospital to primary and community care.
9.
Bergman, ASF, et al.
(författare)
Diltiazem infusion for renal protection in cardiac surgical patients with preexisting renal dysfunction
2002
Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1532-8422 .- 1053-0770. ; 16:3, s. 294-299
Tidskriftsartikel (refereegranskat) abstract
Objective: To evaluate if the calcium channel blocker diltiazem protects postoperatively renal function in cardiac surgical patients with preexisting mild-to-moderate renal dysfunction. Design: Prospective, randomized, placebo-controlled, double-blind, clinical study. Setting: Cardiothoracic anesthesia department at a university hospital. Participants: Adult patients undergoing elective cardiac surgery using cardiopulmonary bypass, with a preoperatively elevated serum creatinine level (n = 24). Interventions: Randomized infusions of diltiazem (bolus 0.25 mg/kg followed by a continuous infusion of 1.7 pg/kg/min) (DTZ, n = 12) or placebo (C, n = 12) were started 30 minutes before induction of anesthesia and continued for 24 hours. Measurements and Main Results: Median plasma concentrations of diltiazem (DTZ group) were 79 mug/L before cardiopulmonary bypass, 67 mug/L at the end of cardiopulmonary bypass, and 164 mug/L at 24 hours postoperatively. Serum creatinine levels; on postoperative days 1, 3, and 5; and 3 weeks postoperatively were similar between groups. lohexol clearance did not differ between the groups on day 5 but was higher in the DTZ group than in the placebo group 3 weeks after surgery (median, 51 v 40 mL/min/1.73 m(2); p < 0.05). Urinary N-acetyl-β-glucosamidase concentrations were similar between the groups during the study but were increased from baseline on days 2 and 4 and 3 weeks postoperatively. Conclusion: Diltiazem can be safely used in patients who have mild-to-moderate renal dysfunction and undergo cardiac surgery using cardiopulmonary bypass. Within the limits of this study, the data suggest that addition of prophylactic diltiazem may prevent further glomerular damage resulting from cardiopulmonary bypass and may improve glomerular function 3 weeks after cardiac surgery.
10.
Callréus, Torbjörn, et al.
(författare)
The influence of lithium on the antidiuretic effect of desmopressin.
2002
Ingår i: Journal of Pharmacy and Pharmacology. - 0022-3573. ; 54:9, s. 1279-1285
Tidskriftsartikel (refereegranskat) abstract
The objective of this study was to investigate the graded influence from lithium on the antidiuretic effects of desmopressin. Eight healthy male subjects participated in this open, randomised cross-over study with two periods comprising 6 days each. For each subject, one of the study days (6th day) was preceded by a period of lithium treatment. On the study days the subjects were orally water loaded to achieve a state of overhydration with a high urine flow rate. When a steady-state diuresis was achieved after approximately 2 h, 0.396 microg of desmopressin was administered intravenously as a bolus injection. An indirect-response model, where desmopressin was assumed to inhibit the elimination of response, was fitted to the urine osmolarity data. The effects of the independent variables, Uflow(baseline) (baseline urine flow rate), R0 (baseline osmolarity) and serum lithium concentration, on IC50 (concentration producing 50% of the maximum inhibition) could be expressed by multiple linear regression. In conclusion, we found that an indirect-response model can be a useful tool in investigating and describing the pharmacodynamic interaction between drugs, in this particular case, between lithium and desmopressin.
