| 11. |
- Albertsson, Maria, et al.
(författare)
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Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer
- 2007
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 24:4, s. 407-412
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of these studies was to compare efficacy and toxicity of docetaxel alone with the combination of gemcitabine and docetaxel for treatment of metastatic esophageal carcinoma. PATIENTS AND METHODS: These studies enrolled patients with histopathologically verified squamous cell carcinoma or adenocarcinoma of the esophagus or cardia. Between March 1997 and June 1999, 52 patients were enrolled in the initial Phase II study (Study 1). They were scheduled for treatment with docetaxel 100 mg/m2 every third week as a 1-h infusion. The second Phase II study between September 2000 and March 2003 included 65 patients (Study II). They were given docetaxel 30 mg/m2, administered as a 30-min i.v. infusion weekly for four times, followed by 2 weeks of rest, and gemcitabine starting with a dose of 750 mg/m2 (if well-tolerated 1,000 mg/m2) on days 1 and 15, followed by 3 weeks of rest. A new cycle began on day 36. Patients were premedicated with betamethasone 8 mg p.o. on the evening before, and 8 mg i.v. 30-60 min before the docetaxel infusion. Response was confirmed by computed tomography and assessed at 12 and 24 weeks. Toxicity was assessed according to WHO scales. RESULTS: In study I, 38 out of the 52 enrolled patients were valuable. Two patients experienced complete remission (CR) (5%), 10 patients partial remission (PR) (26%), nine patients stable disease (SD) (24%), and 17 patients showed progressive disease (PD) (45%). Toxicity mainly involved leukopenia, which in some cases required hospitalization and treatment with antibiotics. In Study II, 46 out of the 65 enrolled patients (70%) were assessable. Out of these, three patients (7%) had CR, eight patients (17%) had PR, 10 patients (22%) had SD, and 25 (54%) PD. Overall response was 24% while an additional 22% showed stable disease. Toxicity mainly consisted of leucopenia and pain. CONCLUSION: Docetaxel as a single agent is active in esophageal cancer, both in treatment naive and in previously treated patients with recurrent disease. The overall response rate was 31%, with a good-safety profile. The addition of gemcitabine is well tolerated, but adds no efficacy. Weekly administration of docetaxel may be less effective. It demonstrates moderate efficacy and the doses used provide an acceptable safety profile.
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| 12. |
- Andersson, Ellen, et al.
(författare)
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GRACE: Geriatric patients tReated with Avastin in CRC multiple linEs
- 2017
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Ingår i: Clinical Practice. - : Future Medicine. - 2044-9038 .- 2044-9046. ; 14:3, s. 175-182
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Tidskriftsartikel (refereegranskat)abstract
- Continuous treatment with bevacizumab in elderly patients with mCRC: A phase IV prospective, open-label, single-arm trial to evaluate outcomes and safety with continuous bevacizumab treatment in combination with chemotherapy over disease progression.
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| 13. |
- Andersson, Maria L. E., et al.
(författare)
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Early increase in serum-COMP is associated with joint damage progression over the first five years in patients with rheumatoid arthritis
- 2013
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Currently available biomarkers for the early tissue process leading to joint damage in rheumatoid arthritis are insufficient and lack prognostic accuracy, possibly a result of variable activity of the disease over time. This study represents a novel approach to detect an altered activity of the disease process detected as increasing serum-COMP levels over a short time and whether this would correlate with joint damage progression over the first 5 years of disease. Methods: In all, 349 patients from the Swedish BARFOT early RA study were examined. Serum-COMP was analysed by ELISA at diagnosis and after 3 months. Based on changes in serum-COMP levels, three subgroups of patients were defined: those with unchanged levels (change <= 20%) (N=142), decreasing levels (> 20%) (N=173) and increasing levels (> 20%) (N=34). Radiographs of hands and feet were obtained at inclusion, after 1, 2 and 5 years and scored according to Sharp van der Heijde (SHS). Radiographic progression was defined as increase in SHS by >= 5.8. Results: The group of patients with increasing COMP levels showed higher median change in total SHS and erosion scores at 1, 2 and 5 year follow-up compared with the groups with stable or decreasing COMP levels. Furthermore, the odds ratio of radiographic progression was 2.8 (95% CI 1.26-6.38) for patients with increasing COMP levels vs. patients with unchanged levels. The group of patients with increasing COMP levels had higher ESR at inclusion but there were no baseline differences between the groups for age, gender, disease duration, disease activity (DAS28), function (HAQ), CRP, nor presence of rheumatoid factor or anti-CCP. Importantly, neither did changes over the 3-month period in DAS28, HAQ, ESR nor CRP differ between the groups and these variables did not correlate to joint damage progression. Conclusion: Increasing serum-COMP levels between diagnosis and the subsequent 3 months in patients with early RA represents a novel indicator of an activated destructive process in the joint and is a promising tool to identify patients with significant joint damage progression during a 5-year period.
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| 14. |
- Ankarberg-Lindgren, Carina, 1963, et al.
(författare)
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Nocturnal application of transdermal estradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls.
- 2001
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X .- 1945-7197. ; 86:7, s. 3039-44
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Tidskriftsartikel (refereegranskat)abstract
- The objective of pubertal induction in children with hypogonadism is to mimic spontaneous puberty in terms of physical and psychological development. In a clinical observation study, we induced puberty in 15 girls with hyper- or hypogonadotropic hypogonadism using low doses of transdermal estradiol patches attached only during the night and compared the estradiol concentrations obtained with those in healthy girls. Pubertal induction was started between the ages of 12.3 and 18.1 yr. A transdermal matrix patch of 17beta-estradiol (25 microg/24 h; Evorel, Janssen Pharmaceuticals-Cilag) was cut into pieces corresponding to 3.1, 4.2, or 6.2 microg/24 h initially and attached to the buttock. After 4-14 months, the dose was increased gradually. Serum 17beta-estradiol concentrations were measured every 2 h by RIA (detection limit, 6.0 pmol/L; 1.6 pg/mL). The results show that it is possible to mimic the spontaneous levels as well as the diurnal pattern of serum 17beta-estradiol in early puberty, by cutting a transdermal 17beta-estradiol matrix patch and attaching a part of it, corresponding to 0.08-0.12 microg estradiol/kg BW, to the buttock nocturnally. In most of the girls, breast development occurred within 3-6 months of the start of treatment.
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| 15. |
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| 16. |
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| 17. |
- Barywani, Salim B., 1968, et al.
(författare)
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Acute coronary syndrome in octogenarians: association between percutaneous coronary intervention and long-term mortality
- 2015
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Ingår i: Clinical Interventions in Aging. - : Informa UK Limited. - 1178-1998. ; 10, s. 1547-1553
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Evidence of improved survival after use of percutaneous coronary intervention (PCI) in elderly patients with acute coronary syndrome (ACS) is limited. We assessed the association between PCI and long-term mortality in octogenarians with ACS. Methods and results: We followed 353 consecutive patients aged >= 80 years hospitalized with ACS during 2006-2007. Among them, 182 were treated with PCI, whereas 171 were not. PCI-treated patients were younger and more often male, and had less stroke and dependency in activities of daily living, but there were no significant differences in occurrence of diabetes mellitus, chronic obstructive pulmonary disease, hypertension, and uncured malignancies between the two groups. The association between PCI and all-cause mortality was assessed in the overall cohort and a 1: 1 matched cohort based on propensity score (PS). In overall cohort, 5-year all-cause mortality was 46.2% and 89.5% in the PCI and non-PCI groups, respectively. Cox regression analysis in overall cohort by adjustment for ten baseline variables showed statistically significant association between PCI and reduced long-term mortality (P < 0.001, hazard ratio 0.4, 95% confidence interval [CI] 0.2-0.5). In propensity-matched cohort, 5-year all-cause mortality was 54.9% and 83.1% in the PCI and non-PCI groups, respectively. Kaplan-Meier survival curves and log rank test showed significantly improved mean survival rates (P=0.001): 48 months (95% CI 41-54) for PCI-treated patients versus 35 months (95% CI 29-42) for non-PCI-treated patients. Furthermore, by performing Cox regression analysis, PCI was still associated with reduced long-term mortality (P=0.029, hazard ratio 0.5, 95% CI 0.3-0.9) after adjustment for PS and confounders: age, male sex, cognitive deterioration, uncured malignancies, left ventricular ejection fraction <45%, estimated glomerular filtration rate < 35 mL/min, ST-segment elevation myocardial infarction, mitral regurgitation, and medication at discharge with clopidogrel and statins. Conclusion: In octogenarians with ACS, PCI was associated with improved survival from all-cause death over 5 years of follow-up.
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| 18. |
- Bergenfeldt, Magnus, et al.
(författare)
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Current state of adjuvant therapy in resected pancreatic adenocarcinoma
- 2006
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 45:2, s. 124-135
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Forskningsöversikt (refereegranskat)abstract
- Pancreatic carcinoma cannot generally be cured by surgery alone. This review summarizes the development of adjuvant therapy over the past two decades. Four randomized controlled trials compare long-term survival of different treatments. The small GITSG-study supports combined chemoradiation, but the EORTC-study found no significant effect. A Norwegian study of adjuvant chemotherapy found an increased median survival, but no effect beyond two years. The large ESPAC-1 study shows a benefit for 5-FU based chemotherapy, while chemoradiation had a negative effect. Thus, evidence favours adjuvant therapy, but 5-FU may not be the ultimate drug. Support for gemcitabine is given by preliminary data from a German randomized trial, and further American and European studies are upcoming. However, postoperative therapy is problematic, as 20-30% of resected patients never undergo treatment because of slow recovery or other reasons. Preoperative therapy has some theoretical advantages, and moreover, patients with rapidly progressive disease may be spared surgery. Randomized controlled trials are lacking, but published results compare well with postoperative, adjuvant therapy. The value of locally targeted therapy is difficult to assess. Reasonable results have been obtained with regional chemotherapy, whereas intraoperative radiotherapy does not seem to increase survival despite reducing reducing local recurrences.
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| 19. |
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| 20. |
- Berger, Karin, et al.
(författare)
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Mitochondrial ATP synthase--a possible target protein in the regulation of energy metabolism in vitro and in vivo
- 2002
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Ingår i: Nutritional neuroscience. - : Informa UK Limited. - 1028-415X .- 1476-8305. ; 5:3, s. 201-210
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Tidskriftsartikel (refereegranskat)abstract
- The increasing prevalence of obesity in the Western world has stimulated an intense search for mechanisms regulating food intake and energy balance. A number of appetite-regulating peptides have been identified, their receptors cloned and the intracellular events characterized. One possible energy-dissipating mechanism is the mitochondrial uncoupling of ATP-synthesis from respiratory chain oxidation through uncoupling proteins, whereby energy derived from food could be dissipated as heat, instead of stored as ATP. The exact role of the uncoupling proteins in energy balance is, however, uncertain. We show here that mitochondrial F1F0-ATP synthase itself is a target protein for an anorectic peptide, enterostatin, demonstrated both after affinity purification of rat brain membranes and through a direct physical interaction between enterostatin and purified F1-ATP synthase. In insulinoma cells (INS-1) enterostatin was found to target F1F0-ATP synthase, causing an inhibition of ATP production, an increased thermogenesis and increased oxygen consumption. The experiments suggest a role of mitochondrial F1F0-ATP synthase in the suppressed insulin secretion induced by enterostatin. It could be speculated that this targeting mechanism is involved in the decreased energy efficiency following enterostatin treatment in rat.
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