| 11. |
- Glimelius, Bengt, et al.
(författare)
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A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer
- 2008
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 19:5, s. 909-914
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Tidskriftsartikel (refereegranskat)abstract
- Background: To compare irinotecan with the Nordic 5-fluorouracil (5-FU) and folinic acid (FA) bolus schedule [irinotecan 180 mg/m2 on day 1, 5-FU 500 mg/m2 and FA 60 mg/m2 on day 1 and 2 (FLIRI)] or the Lv5FU2 schedule [irinotecan 180 mg/m2 on day 1, FA 200 mg/m2, 5-FU bolus 400 mg/m2 and infused 5-FU 600 mg/m2 on day 1 and 2 (Lv5FU2-IRI)] due to uncertainties about how to administrate 5-FU with irinotecan. Patients and methods: Patients (n = 567) with metastatic colorectal cancer were randomly assigned to receive FLIRI or Lv5FU2-IRI. Primary end point was progression-free survival (PFS). Results: Patient characteristics were well balanced. PFS did not differ between groups (median 9 months, P = 0.22). Overall survival (OS) was also similar (median 19 months, P = 0.9). Fewer objective responses were seen in the FLIRI group (35% versus 49%, P = 0.001) but the metastatic resection rate did not differ (4% versus 6%, P = 0.3). Grade 3/4 neutropenia (11% versus 5%, P = 0.01) and grade 2 alopecia (18% versus 9%, P = 0.002) were more common in the FLIRI group. The 60-day mortality was 2.4% versus 2.1%. Conclusions: Irinotecan with the bolus Nordic schedule (FLIRI) is a convenient treatment with PFS and OS comparable to irinotecan with the Lv5FU2 schedule. Neutropenia and alopecia are more prevalent, but both regimens are equally well tolerated. © The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
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| 12. |
- Glimelius, Bengt, et al.
(författare)
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Adjuvant chemotherapy in colorectal cancer: a joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group
- 2005
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Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 904-12
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Tidskriftsartikel (refereegranskat)abstract
- Due to uncertainties regarding clinically meaningful gains from adjuvant chemotherapy after colorectal cancer surgery, several Nordic Groups in the early 1990s initiated randomised trials to prove or reject such gains. This report gives the joint analyses after a minimum 5-year follow-up. Between October 1991 and December 1997, 2 224 patients under 76 years of age with colorectal cancer stages II and III were randomised to surgery alone (n = 1 121) or adjuvant chemotherapy (n = 1 103) which varied between trials (5FU/levamisole for 12 months, n = 444; 5FU/leucovorin for 4-5 months according to either a modified Mayo Clinic schedule (n = 262) or the Nordic schedule (n = 397). Some centres also randomised patients treated with 5FU/leucovorin to+/-levamisole). A total of 812 patients had colon cancer stage II, 708 colon cancer stage III, 323 rectal cancer stage II and 368 rectal cancer stage III. All analyses were according to intention-to-treat. No statistically significant difference in overall survival, stratified for country or region, could be found in any group of patients according to stage or site. In colon cancer stage III, an absolute difference of 7% (p = 0.15), favouring chemotherapy, was seen. The present analyses corroborate a small but clinically meaningful survival gain from adjuvant chemotherapy in colon cancer stage III, but not in the other presentations.
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| 13. |
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| 14. |
- Hafstrom, I, et al.
(författare)
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Remission achieved after 2 years treatment with low-dose prednisolone in addition to disease-modifying anti-rheumatic drugs in early rheumatoid arthritis is associated with reduced joint destruction still present after 4 years: an open 2-year continuation study
- 2009
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:4, s. 508-513
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate if remission induced by low-dose prednisolone during the first 2 years of rheumatoid arthritis (RA) in the BARFOT glucocorticoid (GC) study had a sustained effect on radiological damage for a total of 4 years.Methods:A total of 150 of 211 eligible patients with RA who had been randomised to the 7.5 mg prednisolone group (P) or no prednisolone group (NoP) in addition to the initial disease-modifying antirheumatic drugs were included. Radiographs of hands and feet were scored using the Sharp–van der Heijde scoring method. A patient was considered to be in remission if the 28-joint count disease activity score was <2.6.Results:Mean (SD) age was 53 (14) and 57 (12) years for the patients in the P and NoP groups, respectively. 64% were female, 64% rheumatoid factor positive, and disease duration at baseline was 6 months. At 2 years the proportion of patients in remission in the P and NoP groups was 55 vs 30%, p = 0.003. Longitudinal analysis showed that over the entire course of the disease, patients on prednisolone had a higher probability of being in remission. Patients in remission at 2 years, compared with those not in remission, had significantly lower total Sharp score, erosion score and joint space narrowing score at 2 and 4 years. The changes in bone mineral density during the 4 years did not differ between those in remission and those with active disease, and were similar in the two treatment groups.Conclusions:Prednisolone 7.5 mg daily in addition to disease-modifying anti-rheumatic drugs increases the rate of remission in patients with early RA, which has a beneficial and sustained effect on radiological damage.
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| 15. |
- Isaksson, B, et al.
(författare)
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Chronically administered islet amyloid polypeptide in rats serves as an adiposity inhibitor and regulates energy homeostasis
- 2005
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Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 5:1, s. 29-36
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Tidskriftsartikel (refereegranskat)abstract
- Aims/Hypothesis: Islet amyloid polypeptide ( IAPP) reduces food intake and body weight in laboratory animals. In addition, IAPP appears to regulate nutrient metabolism. In the present studies, we investigated the effect of chronic IAPP treatment on different aspects of energy homeostasis. Methods: IAPP was infused ( 25 pmol/kg/min) from subcutaneous osmotic pumps for 2 - 7 days. Rats in 2 saline-infused control groups were fed ad libitum (AF) or pair-fed (PF) against the IAPP-treated rats. Results: As expected, the IAPP infusion reduced food intake and body weight gain. In addition, the IAPP treatment decreased the epididymal fat pad ( vs. PF rats, p < 0.05) and lowered circulating levels of triglycerides (vs. PF rats, p < 0.05), free fatty acids ( vs. PF rats, p < 0.05), leptin ( vs. both AF and PF rats, p < 0.05) and insulin ( vs. AF rats, p < 0.05). In contrast, glucose and protein metabolism in the IAPP-treated rats was largely unchanged, as shown in results regarding serum glucose, glucose transport in skeletal muscle, blood urea nitrogen, and glycogen and protein content in the liver and in skeletal muscle. Conclusion/Interpretation: In summary, chronic IAPP exposure led to a changed lipid metabolism, which was characterized by decreased adiposity, hypolipidemia and hypoleptinemia, and to unchanged glucose and protein homeostasis. These results were similar to those seen in rodents during chronic exposure to another satiety/adiposity regulator, leptin. In conclusion, chronically administered IAPP plays a role as a satiety and adiposity signal in rats, and helps regulate energy homeostasis.
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| 16. |
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| 17. |
- Numata, Keiji, et al.
(författare)
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Branched poly(lactide) synthesized by enzymatic polymerization : effects of molecular branches and stereochernistry on enzymatic degradation and alkaline hydrolysis
- 2007
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 8:10, s. 3115-3125
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Tidskriftsartikel (refereegranskat)abstract
- In this article the effects of the number of molecular branches (chain ends) and the stereochemistry of poly(lactide)s (PLAs) on the enzymatic degradation and alkaline hydrolysis are studied. Various linear and branched PLAs were synthesized using lipase PS (Pseudomonas fluorescens)-catalyzed ring-opening polymerization (ROP) of lactide monomers having different stereochemistries (L-lactide, D-lactide, and D,L-lactide). Five different alcohols were used as initiators for the ROP, and the monomer-to-initiator molar feed ratio was varied from 10 to 100 and 1000 for each branch in the polymer architecture. The properties of branched PLAs that would affect the enzymatic and alkaline degradations, i.e., the glass transition temperature, the melting temperature, the melting enthalpy, and the advancing contact angle, were determined. The PLA films were degraded using proteinase K or 1.0 M NaOH solution, and the weight loss and changes in the number average molecular weight (M-n) of the polymer were studied during 12 h of degradation. The results suggest that an increase in the number of molecular branches of branched PLAs enhances its enzymatic degradability and alkali hydrolyzability. Moreover, the change in M-n of the branched poly(L-lactide) (PLLA) by alkaline hydrolysis indicated that the decrease in M-n was in the first place dependent on the number of molecular branches and thereafter on the length of the molecular branch of branched PLA. The branched PLLA, poly(D-lactide) (PDLA), and poly(D,L-lactide) (PDLLA) differed in weight loss and change in M-n of the PLA segment during the enzymatic degradation. It is suggested that the branched PDLLA was degraded preferentially by proteinase K.
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| 18. |
- Rajkhowa, Ritimoni, et al.
(författare)
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Enzyme-catalyzed copolymerization of oxiranes with dicarboxylic acid anhydrides
- 2005
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Ingår i: Journal of Applied Polymer Science. - : Wiley. - 0021-8995 .- 1097-4628. ; 97:2, s. 697-704
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Tidskriftsartikel (refereegranskat)abstract
- Ring-opening copolymerizations of the oxiranes glycidyl phenyl ether (GPE) and diglycidyl ether of bisphenol A (DGEBA) with a dicarboxylic acid anhydride [methyl hexahydrophthalic anhydride, nadic anhydride, maleic anhydride (MA), or itaconic anhydride (IA)] were carried out with the lipases Candida cylindracea (CCL), Lipozyme TL-IM (LIM), and Novozyme 435 (N435) as catalysts. The CCL-catalyzed reaction of DGEBA with MA or IA (at a 1:2 molar ratio) at 80 degrees C resulted in only partial curing. We monitored the reactions by Fourier transform infrared spectroscopy and by following the changes in the intensities of carbonyl stretching frequencies of the anhydride and ester groups. The reactivity of the oxirane group in GPE was higher than that in DGEBA; this may have been due to the higher viscosity of DGEBA. The reactivities of the enzymes for the copolymerization of the oxiranes and dicarboxylic acid anhydride were in the order LIM > CCL > N435.
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| 19. |
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| 20. |
- Svensson, Björn, et al.
(författare)
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Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate - A two-year randomized trial
- 2005
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 52:11, s. 3360-3370
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To assess the efficacy of low-dose prednisolone on joint damage and disease activity in patients with early rheumatoid arthritis (RA). Methods. At the start of their initial treatment with a disease-modifying antirheumatic drug (DMARD), patients with early (duration <= 1 year) active RA were randomly assigned to receive either 7.5 mg/day prednisolone or no prednisolone for 2 years. Radiographs of the hands and feet were obtained at baseline and after 1 and 2 years and scored according to the Sharp score as modified by van der Heijde. Remission was defined as a Disease Activity Score in 28 joints of < 2.6. Bone mineral density was measured by dual x-ray absorptiometry at baseline and after 2 years. Results. Of the 250 patients included, 242 completed the study and 225 had radiographs available both at baseline and at 2 years. At 2 years, the median and interquartile range (IQR) change in total Sharp score was lower in the prednisolone group than in the no-prednisolone group (1.8 [IQR 0.5-6.0] versus 3.5 [IQR 0.5-10]; P = 0.019). In the prednisolone group, there were fewer newly eroded joints per patient after 2 years (median 0.5 [IQR 0-2] versus 1.25 [IQR 0-3.25]; P = 0.007). In the prednisolone group, 25.9% of patients had radiographic progression beyond the smallest detectable difference compared with 39.3% of patients in the no-prednisolone group (P = 0.033). At 2 years, 55.5% of patients in the prednisolone group had achieved disease remission, compared with 32.8% of patients in the no-prednisolone group (P = 0.0005). There were few adverse events that led to withdrawal. Bone loss during the 2-year study was similar in the 2 treatment groups. Conclusion. Prednisolone at 7.5 mg/day added to the initial DMARD retarded the progression of radiographic damage after 2 years in patients with early RA, provided a high remission rate, and was well tolerated. Therefore, the data support the use of low-dose prednisolone as an adjunct to DMARDs in early active RA.
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