| 1. |
- Elgqvist, Jörgen, 1963, et al.
(författare)
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Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab')2.
- 2006
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 66:4, s. 1228-37
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To elucidate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice. This study: (i) estimated the minimum required activity (MRA), giving a reasonable high therapeutic efficacy; and (ii) calculated the specific energy to tumor cell nuclei and the metastatic cure probability (MCP) using various assumptions regarding monoclonal-antibody (mAb) distribution in measured tumors. The study was performed using the alpha-particle emitter Astatine-211 (211At) labeled to the mAb MX35 F(ab')2. METHODS AND MATERIALS: Animals were inoculated intraperitoneally with approximately 1 x 10(7) cells of the cell line NIH:OVCAR-3. Four weeks later animals were treated with 25, 50, 100, or 200 kBq 211At-MX35 F(ab')2 (n = 74). Another group of animals was treated with a nonspecific mAb: 100 kBq 211At-Rituximab F(ab')2 (n = 18). Eight weeks after treatment the animals were sacrificed and presence of macro- and microscopic tumors and ascites was determined. An MCP model was developed and compared with the experimentally determined tumor-free fraction (TFF). RESULTS: When treatment was given 4 weeks after cell inoculation, the TFFs were 25%, 22%, 50%, and 61% after treatment with 25, 50, 100, or 200 kBq (211)At-MX35 F(ab')2, respectively, the specific energy to irradiated cell nuclei varying between approximately 2 and approximately 400 Gy. CONCLUSION: As a significant increase in the therapeutic efficacy was observed between the activity levels of 50 and 100 kBq (TFF increase from 22% to 50%), the conclusion was that the MRA is approximately 100 kBq (211)At-MX35 F(ab')2. MCP was most consistent with the TFF when assuming a diffusion depth of 30 mum of the mAbs in the tumors.
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| 2. |
- Elgqvist, Jörgen, 1963, et al.
(författare)
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Alpha-radioimmunotherapy of intraperitoneally growing OVCAR-3 tumors of variable dimensions: Outcome related to measured tumor size and mean absorbed dose.
- 2006
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 47:8, s. 1342-50
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this work was to (a) investigate the efficacy of radioimmunotherapy using 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2 (nonspecific antibody) against differently advanced ovarian cancer in mice; (b) image the tumor growth on the peritoneum; and (c) calculate the specific energy and mean absorbed dose to tumors and critical organs. METHODS: Two experiments with 5-wk-old nude mice (n = 100 + 93), intraperitoneally inoculated with approximately 1 x 10(7) NIH:OVCAR-3 cells, were done. At either 1, 3, 4, 5, or 7 wk after inoculation animals were intraperitoneally treated with approximately 400 kBq 211At-MX35 F(ab')2 (n = 50 + 45), approximately 400 kBq 211At-Rituximab F(ab')2 (n = 25 + 24), or unlabeled Rituximab F(ab')2 (n = 25 + 24). At the time of treatment 29 animals were sacrificed and biopsies were taken for determination of tumor sizes using scanning electron microscopy (SEM). Eight weeks after each treatment the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. The specific energy and mean absorbed dose to tumors were calculated. The activity concentration was measured in critical organs and abdominal fluid. RESULTS: When given treatment 1, 3, 4, 5, or 7 wk after cell inoculation the tumor-free fraction (TFF) was 95%, 68%, 58%, 47%, 26%, and 100%, 80%, 20%, 20%, and 0% when treated with 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2, respectively. The SEM images revealed maximum tumor radius of approximately 30 mum 1 wk after cell inoculation, increasing to approximately 340 mum at 7 wk. Specific energy to cell nuclei varied between 0 and approximately 540 Gy, depending on assumptions regarding activity distribution and tumor size. The mean absorbed dose to thyroid, kidneys, and bone marrow was approximately 35, approximately 4, and approximately 0.3 Gy, respectively. CONCLUSION: Treatment with 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2 resulted in a TFF of 95%-100% when the tumor radius was < or =30 microm. The TFF was decreased (TFF < or = 20%) for 211At-Rituximab F(ab')2 when the tumor radius exceeded the range of the alpha-particles. The specific antibody gave for these tumor sizes a significantly better TFF, explained by a high mean absorbed dose (>22 Gy) from the activity bound to the tumor surface and probably some contribution from penetrating activity.
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| 3. |
- Elgqvist, Jörgen, 1963, et al.
(författare)
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Fractionated radioimmunotherapy of intraperitoneally growing ovarian cancer in nude mice with 211At-MX35 F(ab')2: therapeutic efficacy and myelotoxicity
- 2006
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Ingår i: Nucl Med Biol. - : Elsevier BV. - 0969-8051. ; 33:8, s. 1065-72
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate the therapeutic efficacy and myelotoxicity during fractionated radioimmunotherapy of ovarian cancer in mice. The study was performed using the monoclonal antibody MX35 F(ab')(2) labeled with the alpha-particle emitter (211)At. METHODS: Animals were intraperitoneally inoculated with approximately 1x10(7) cells of the cell line NIH:OVCAR-3. Four weeks later, the mice were given the first treatment. Six groups of animals were intraperitoneally injected with approximately 800, 3x approximately 267, approximately 400, 3x approximately 133, approximately 50 or 3x approximately 17 kBq (211)At-MX35 F(ab')(2) (n=18 in each group). The second and third injections for Groups 2, 4 and 6 were given 4 and 8 days after the first injection, respectively. As controls, animals were treated with unlabeled MX35 F(ab')(2) (n=12). Eight weeks after the last injection, the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. Blood counts were determined for each mouse in Groups 1 and 2 before the first injection and 3, 7, 11, 15 and 23 days after the first injection. The calculation of the mean absorbed dose to the bone marrow was based on the ratio between the (211)At-activity concentration in bone and blood [i.e., the bone-to-blood ratio (BBLR)] as well as that between the (211)At-activity concentration in bone marrow and blood [i.e., the bone-marrow-to-blood ratio (BMBLR)] and the cumulated activity and absorbed fraction of the alpha-particles emitted by (211)At in the bone marrow. RESULTS: The tumor-free fractions of animals were 56% and 41% when treated with approximately 800 kBq and 3x approximately 267 kBq (211)At-MX35 F(ab')(2), respectively; 39% and 28% when treated with approximately 400 kBq and 3x approximately 133 kBq (211)At-MX35 F(ab')(2), respectively; and 17% and 22% when treated with approximately 50 kBq or 3x approximately 17 kBq (211)At-MX35 F(ab')(2), respectively. The nadir of the white blood cell (WBC) counts was decreased (from 46% to 19%, compared with the baseline WBC counts) and delayed (from Day 4 to Day 11 after the first injection) during the fractionated treatment compared with the single-dose treatment. The percentage of injected activity per gram (%IA/g) for blood, bone and bone marrow all peaked 6 h after injection at 13.80+/-1.34%IA/g, 4.00+/-0.69%IA/g and 8.28+/-1.38%IA/g, respectively. The BBLR and BMBLR were 0.20+/-0.04 and 0.58+/-0.01, respectively. The mean absorbed dose to bone marrow was approximately 0.4 Gy after intraperitoneally injecting approximately 800 kBq (211)At-MX35 F(ab')(2). CONCLUSION: No advantage was observed in the therapeutic efficacy of using a fractionated regimen compared with a single administration, with the same total amount of administered activity. Alleviation of the myelotoxicity was observed during the fractionated regimen in terms of decreased suppression and delayed nadir of the WBC counts. No thrombocytopenia was observed during either regimen.
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| 4. |
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| 5. |
- Jacobsson, Christian, et al.
(författare)
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Managing stress and feelings of mastery among Swedish comprehensive school teachers
- 2001
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Ingår i: Scandinavian Journal of Educational Research. ; 45:1, s. 37-53
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT The purpose of this study was to create guidelines for stress management intervention by investigating the relationship of 12 factors with stress reactions (emotional exhaustion and irritation) and feelings of mastery among Swedish comprehensive school teachers. Data were collected via a questionnaire distributed to 928 teachers in 27 schools. The response rate was 89%. Multiple regressions were conducted on colleague support, cooperation, coordination problems, goal clarity, learning orientation, manager support, negative feedback, positive feedback, pupil misbehaviour, teacher age, work control and perceived work demands, all as independent variables. Perceived work demands was treated as a dependent variable in an additional regression analysis. Teacher stress reactions were best predicted by perceived work demands, pupil misbehaviour and negative feedback. Feelings of mastery were best predicted by learning orientation, positive feedback and goal clarity. In the additional analysis perceived work demands was best predicted by pupil misbehaviour, coordination problems and (low) work control. Practical implications are discussed.
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| 6. |
- Jacobsson, Ingela, et al.
(författare)
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Spontaneously reported adverse reactions in association with complementary and alternative medicine substances in Sweden.
- 2009
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Ingår i: Pharmacoepidemiology and drug safety. - : Wiley. - 1099-1557 .- 1053-8569.
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Although the safety information is limited, use of complementary and alternative medicine (CAM) products is not without risks. Spontaneous reporting systems may be used in the surveillance of these products. We describe the pattern of spontaneously reported CAM related adverse reactions submitted to the Swedish Medical Products Agency (MPA) and highlight areas of safety concern. METHODS: All adverse reactions spontaneously reported to MPA between 1987 and 2006, where at least one CAM substance was a suspected agent, were scrutinised. From each report information about the patient, adverse reaction/s, drug treatment/s, dosage, time relationship and outcome was retrieved. RESULTS: Among a total of 64 493 reports, 778 reports concerned 967 suspected adverse reactions related to 175 different CAM products. The main distribution of suspected adverse reactions was: urticaria (8.3%), exanthema (7.4%) and contact dermatitis (5.7%). The most reported CAM substances were purple coneflower (Echinacea purpurea) (8.1%), purple coneflower + siberian ginseng (Eleutherococcus senticosus) + malabar nut (Adhatoda vasica) (7.3%) and ginkgo leaf (Ginkgo biloba) (6.7%). In 221 reports, at least one reaction was categorised as serious, the most frequent being pulmonary embolism (1.7%), mixed liver reaction (2.8%), and anaphylactic reaction (2.0%). Eleven of the serious adverse reactions had a fatal outcome. CONCLUSIONS: CAM substances were associated with a variety of adverse reactions. Some of these have previously been unrecognised or poorly documented and suggest further investigations. By stimulating the reporting of adverse reactions of CAM products, the signal detection power of the spontaneous reporting system may increase further.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Jönsson, Anna K., et al.
(författare)
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Cerebral haemorrhage induced by warfarin - the influence of drug-drug interactions
- 2007
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Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 16:3, s. 309-315
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Östergötland, Sweden.Methods: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated.Results: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100 000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid.Conclusions: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Karlsson, Sofia A., et al.
(författare)
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The impact of a changed legislation on reporting of adverse drug reactions in Sweden, with focus on nurses' reporting
- 2015
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 71:5, s. 631-636
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In March 2007, a legislative amendment was issued in Sweden compelling nurses to report all suspected adverse drug reactions (ADRs) to the national pharmacovigilance system. The aims of this study were to describe the status of ADR reporting, before and after the implementation of the legislative changes, and to describe the general characteristics of suspected ADRs reported by nurses. Methods: The Swedish pharmacovigilance system during the study period constituted six regional centres responsible for the handling of all spontaneous ADR reports within their region. In this study, we identified all individual ADR reports from 2005 and 2010, analysed in depth the ADR reports from two regional centres and collated information about the reporter and the nature of the reported ADR. Results: From the two regional centres, a total of 898 and 1074 reports were submitted in 2005 and 2010 respectively. Nurses submitted 31% (275 reports) of the reports in 2005 and 24% (260 reports) in 2010. Nurses' reporting of serious ADRs was 3% (seven reports) in 2005 and 7% (17 reports) in 2010 with reporting of unlabelled ADRs at 4% (11 reports) in 2005 and 17% (45 reports) in 2010. Most of the serious and/or unlabelled reactions were related to vaccine administration (14 reports in 2005 and 36 reports in 2010). Conclusions: The overall ADR reporting by nurses did not appear to increase after the change in reporting legislation. The proportion of serious and/or unlabelled ADRs reported by nurses did however appear to increase during the same period. Taken together, our data suggests that further pro-active measures should be considered in order to involve nurses in the reporting of suspected ADRs.
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| 15. |
- Nydahl, Margaretha, 1953-, et al.
(författare)
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A simplified health information model increased the level of knowledge regarding "five a day" and food safety in a city district
- 2012
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Ingår i: British Food Journal. - United Kingdom : Emerald Group Publishing Limited. - 0007-070X .- 1758-4108. ; 114:7, s. 910-925
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Tidskriftsartikel (refereegranskat)abstract
- Purpose – The aim of this paper was to analyze the effect according to knowledge and behavior, respectively, through a simplified health information model launched in a selected city district.Design/methodology/approach – The intervention in this study encompasses information meetings where two educational computer programs highlighting the “five a day” concept, and food hygiene were showcased in conjunction with a group discussion. In total, 92 people living or working in a selected city district participated. The effect of the intervention was determined by means of inquiries (multiple-choice) that were carried out prior to, immediately following, and three weeks after the intervention.Findings – A statistically significant improvement in knowledge of the concepts “five a day”, cross-contamination, and recommended storage temperature (for smoked salmon and raw mince meat) was observed, however, no major change in behavior was reported.Practical implications – The knowledge improvement suggests that the education programs, in conjunction with discussions, are a useful information model for raising awareness about the notion of “five a day” and food safety. The results of the study make it clear that there are difficulties in getting people to change their behavior, let alone getting them to participate in health education offered locally.Originality/value – Intervention projects are a communication tool that may be used in order to increase knowledge and produce behavioral change. The project is working from the inside out, i.e. it examines the needs first and then develops solutions for them.
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| 16. |
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| 17. |
- Palm, Stig, 1964, et al.
(författare)
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Cell growth kinetics of the human cell line Colo-205 irradiated with photons and astatine-211 alpha-particles
- 2000
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Ingår i: Anticancer Res. - 0250-7005. ; 20:3A, s. 1807-12
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Tidskriftsartikel (refereegranskat)abstract
- Cell growth kinetics following Astatine-211 (211At, alpha-particle emitter) and photon irradiation were studied for the human colorectal cell line Colo-205. A growth assay using 96-well plates was chosen. The growth kinetics could be simulated by assuming certain fractions of cells with various proliferative capacities, i.e. from none up to 5 cell doublings, in addition to the defined survivors with remaining unlimited clonogenic capacity. No significant difference in cell growth characteristics was seen between 211At and photon irradiation. The cell doubling time, as calculated from the increment in optical density, was compared with the results from BrdU experiments in the early phases of growth (Tpot = 18.5 +/- 0.6 h for LDR (low dose rate) photon irradiated and 20.3 +/- 0.8 hours for sham-irradiated cells 40-45 hours post-irradiation) confirming the transient accelerated growth of irradiated cells. No statistically significant difference in growth was found between LDR, MDR (medium dose rate) and HDR (high dose rate) photon irradiation.
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| 18. |
- Palm, Stig, 1964, et al.
(författare)
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Effects of the alpha-particle emitter At-211 and low-dose-rate gamma-radiation on the human cell line Colo-205 as studied with a growth assay
- 1998
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Ingår i: Anticancer Res. - 0250-7005. ; 18:3A, s. 1671-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to investigate the biological effect of the alpha-particle-emitting isotope astatine-211 on the human cell line Colo-205 and to compare it with that of low-dose-rate gamma-radiation. MATERIALS AND METHODS: Plastic (PMMA) rotating phantoms were constructed, allowing precise dosimetry on a cellular level for both types of radiation. Growth assays using 96-well plates were used to estimate apparent cell survival for the two types of radiation. From this, the relative biological effect (RBE) could be estimated. RESULTS: Irradiation of the cells with 211At resulted in an RBE of 25.1 +/- 6.7 at 37% survival, and 17.3 +/- 2.5 at 10% survival, when compared with low-dose-rate gamma-irradiation. The absorbed dose at 37% survival, 0.12 Gy, corresponds to 2.2 traversals of alpha-particles through the cell nuclei. For cells irradiated with gamma-radiation (1 and 2 Gy), an apparent cell survival above unity was observed up to 50 hours post-irradiation, indicating a possible radiation hormesis effect. CONCLUSIONS: The RBE of 211At found in this growth-assay study was significantly higher than previously presented values. The difference might be due to the use of low-dose-rate gamma-radiation as reference. The RBE presented here could prove valuable when evaluating 211At-labelled compounds for radiotherapy.
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| 19. |
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| 21. |
- Palm, Stig, 1964, et al.
(författare)
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In vitro effects of free 211At,211At-albumin and 211At-monoclonal antibody compared to external photon irradiation on two human cancer cell lines
- 2000
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Ingår i: Anticancer Res. - 0250-7005. ; 20:2A, s. 1005-12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to perform various 211At irradiations of importance for the evaluation of 211At-radioimmunotherapy, and compare the effect with that of low linear energy transfer (LET) radiation. MATERIALS AND METHODS: All irradiations were performed on low-concentration single-cell suspensions. Growth assays using 96-well plates were used to estimate apparent cell survival. Centrifuge tube filters were used to estimate the cell uptake and binding of 211At. RESULTS: A relative biological effect (RBE) of 12 +/- 2 (Colo-205) and 5.3 +/- 0.7 (OVCAR-3) was found from 211At-albumin irradiations. There was a 174 +/- 28 times higher free 211At concentration in the cell fraction than in the surrounding medium. For 211At-MAb, an 8,000-30,000 times higher concentration in the cell fraction was achieved, compared to the medium. Corrected for the uptake, an average of 31 +/- 2 ([211At]-astatine) or 26 +/- 5 ([211At]-MAb) decays per cell were required for 37% survival of Colo-205 cells. An average of 19 +/- 3 decays ([211At]-astatine) were required per OVCAR-3 cell. CONCLUSIONS: Cell uptake and binding of 211At was unexpectedly high, possibly favouring its therapeutic use. The binding is probably to the cell surface. The RBE is 5.3 +/- 0.7 for OVCAR-3 and 12 +/- 2 for Colo-205 cells.
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| 22. |
- Palm, Stig, 1964, et al.
(författare)
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Single-cell irradiation from [211At] astatine-labeled C215 monoclonal antibody: improved estimates of radiosensitivity from measurements on cellular uptake and retention
- 2003
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Ingår i: Anticancer Res. - 0250-7005. ; 23:2B, s. 1219-21
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Tidskriftsartikel (refereegranskat)abstract
- New data on the biological effect of 211At-C215 monoclonal antibody in a slowly rotating, widely dispersed single-cell suspension of the human cancer cell line Colo-205 is presented. Cell growth curves of each experiment were used to calculate an apparent cell survival after irradiation. Uptake measurements provided the data needed to calculate the average number of 211At decays per cell in the cell suspension. The results from each experiment were then fit to a mono-exponential function. From the exponential fit, an average of 35 +/- 2 (SD) astatine-211 decays per cell are required for 37% apparent cell survival (D0).
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| 23. |
- Palm, Stig, 1964, et al.
(författare)
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Therapeutic efficacy of astatine-211-labeled trastuzumab on radioresistant SKOV-3 tumors in nude mice.
- 2007
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 0360-3016. ; 69:2, s. 572-9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the potential use of astatine-211 (211At)-labeled trastuzumab for the treatment of HER-2-positive, radioresistant ovarian carcinoma. METHODS AND MATERIALS: Four-week-old nude mice were inoculated intraperitoneally with 5 . 10(6) SKOV-3 cells in 0.4 mL saline on Day 0. The endpoint was the total tumor weight in each mouse on Day 63. Three experiments were performed in which the response to single-dose and fractionated treatment with unlabeled and 211At-labeled antibody was evaluated. RESULTS: Experiment 1 showed, for the same total amount of trastuzumab, a dose-response relationship between 211At activity (0-400 kBq on Day 7) and therapeutic efficacy (p = 0.001). The effect of varying the amount of unlabeled trastuzumab was studied in Experiment 2. All mice, except for the controls, received 400 kBq 211At-trastuzumab, and different groups received 5, 50, or 500 microg trastuzumab on Day 7. The increase from 5 to 50 microg trastuzumab reduced the tumors by 78% in weight. No tumors were present in mice given 500 microg trastuzumab. In Experiment 3, the effect of a fractionated treatment regimen was studied. Mice that received 100 kBq 211At-trastuzumab on Days 7 and 8 had a 42% smaller tumor burden than did controls. Groups of mice injected with 200 + 100 kBq on Days 7 and 21 and mice injected with 100 kBq on Days 7, 8, and 21 both had 24% less tumor weight than the corresponding controls. CONCLUSION: The combination of 500 microg trastuzumab and 400 kBq 211At-trastuzumab had the greatest effect, with complete eradication of the tumors in this nude mouse model.
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| 24. |
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| 25. |
- Wijk, Helle, 1958, et al.
(författare)
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Verksamhetsförlagd utbildning på avancerad nivå : ny utmaning för specialistutbildningar för sjuksköterskor
- 2009
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Ingår i: Vård i Norden. - København : Sjuksköterskornas samarbete i Norden. - 0107-4083 .- 1890-4238. ; 29:94, s. 41-43
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this article is to discuss challenges in the development of Specialist Nursing Educations as a result of the 2007 Swedish Higher EducationReform: the implementation of the so-called Bologna process. Certain challenges follow this reform, particularly since the specialist nursingprogrammes will be part of the second cycle of the higher education system, and it will be possible to combine the professional degree witha masters degree (one year). Possible strategies in four areas related to the Specialist Nursing Education are discussed: integration of researchbasedknowledge, experienced-based knowledge, improvement knowledge, and strategies for collaboration between university institutions andclinics. Specific didactical issues are raised.
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