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- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- Modell, B., et al.
(författare)
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Epidemiology of haemoglobin disorders in Europe : An overview
- 2007
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 67:1, s. 39-69
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Forskningsöversikt (refereegranskat)abstract
- Objective. As a result of global population movements, haemoglobin disorders (thalassaemias and sickle cell disorders) are increasingly common in the formerly non-indigenous countries of Northern and Western Europe and in the indigenous countries of Southern Europe. This article presents an overview of the changing picture and a method for assessing service needs. Method. Data on country of birth or ethnic origin of residents are adjusted to obtain the estimated proportions of residents and births in non-indigenous groups at risk for haemoglobin disorders in European countries. The results are combined with prevalence data in each country of origin to obtain country prevalence estimates. Service indicators (annual tests or other interventions required to ensure equitable delivery of treatment and prevention) are then derived by country. Results. Haemoglobin disorders now occur at comparable frequency throughout Northern, Western and Southern Europe. Annually, there are more affected conceptions in Northern and Western than in Southern Europe, and sickle cell disorders are more common than thalassaemias. There is growing need for health policy-makers to support motivated professionals working to develop optimal patient care, carrier diagnosis, genetic counselling and access to prenatal diagnosis throughout the Region. Conclusion. There is a strong case for pan-European collaboration on haemoglobin disorders to share policies, standards and the instruments required to support them. These include methods for needs assessment, service standards, education and information strategies and materials, and methods for evaluating service delivery. © 2007 Taylor & Francis.
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- Pinay, Gilles, et al.
(författare)
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Patterns of denitrification rates in European alluvial soils under various hydrological regimes
- 2007
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Ingår i: Freshwater Biology. - 0046-5070 .- 1365-2427. - 0046-5070 ; 52:2, s. 252-266
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Tidskriftsartikel (refereegranskat)abstract
- 1. Denitrification in floodplain soils is one of the main biological processes emitting and reducing nitrous oxide, a greenhouse gas, and the main process responsible for the buffering capacity of riparian zones against diffuse nitrate pollution. 2. The aim of this study was to measure denitrification rates under a wide range of current climatic conditions and hydrological regimes in Europe (from latitude 64 degrees N to latitude 42 degrees N and from longitude 2 degrees W to longitude 25 degrees E), in order to determine the response patterns of this microbial process under different climatic and hydrological conditions, and to identify denitrification proxies robust enough to be used at the European scale. 3. Denitrification activity was significant in all the floodplain soils studied whatever the latitude. However, we found an increase in rates of an order of magnitude from high to mid latitudes. Maximum rates (above 30 g N m(-2) month(-1)) were measured in the maritime conditions of the Trent floodplain. These rates are similar to mineralisation rates measured in alluvial soils and of the same order of magnitude as the amount of N stored in herbaceous plants in alluvial soils. 4. We used Multivariate Adaptative Regression Splines to relate the response variable denitrification with five relevant predictors, namely soil moisture, temperature, silt plus clay, nitrate content and herbaceous plant biomass. 5. Soil moisture, temperature, and nitrate were the three main control variables of microbial denitrification in alluvial soils in decreasing order of importance. 6. The model developed for denitrification with interaction effects outperformed a pure additive model. Soil moisture was involved in all interactions, emphasising its importance in predicting denitrification. 7. These results are discussed in the context of scenarios for future change in European hydrological regimes.
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- Brokelman, Walter J A, et al.
(författare)
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Peritoneal transforming growth factor beta-1 expression during laparoscopic surgery: a clinical trial.
- 2007
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Ingår i: Surgical endoscopy. - : Springer Science and Business Media LLC. - 1432-2218 .- 0930-2794. ; 21:9, s. 1537-41
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transforming growth factor-beta 1 (TGF-beta1) is a growth factor involved in various biologic processes, including peritoneal wound healing and dissemination of malignancies. Laparoscopic surgery is evolving rapidly, and indications are increasing. The peritoneal TGF-beta1 expression during laparoscopic surgery is unknown. METHODS: For this study, 50 patients scheduled for laparoscopic cholecystectomy were randomized into five groups, then surgically treated with various pressures, light intensities, and dissection devices. Peritoneal biopsies were taken at the beginning and end of surgery. Tissue concentrations of total and active TGF-beta1 were measured using enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: There was no significant difference in either total or active TGF-beta1 concentration between peritoneal biopsies taken at the start of surgery and samples taken at the end of the procedure. Patients who underwent surgery with the ultrasonic scalpel had significant lower levels of both active (p < 0.005) and total (p < 0.01) TGF-beta1 at the end of surgery than patients treated with electrocautery. Patients who had surgery with a high light intensity had significantly lower levels of total TGF-beta1 levels (p < 0.005) with an unchanged active part than patients who had surgery with low light intensity. CONCLUSION: The choice of dissection device and the light intensity used in laparoscopic surgery affect peritoneal TGF-beta1 concentrations, indicating that peritoneal biology can be affected by laparoscopic surgery. Because TGF-beta1 is involved in various biologic processes in the peritoneal cavity, this observation may have important clinical consequences.
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- Kos, K., et al.
(författare)
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DPP-IV inhibition enhances the antilipolytic action of NPY in human adipose tissue : DPP-IV inhibition in human adipose tissue
- 2009
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Ingår i: Diabetes Obes Metab. - 1463-1326. ; 11:4, s. 285-92
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Dipeptidyl peptidase IV (DPP-IV) inactivates the incretin hormone glucagon-like peptide. It can also affect the orexigenic hormone neuropeptide Y (NPY(1-36)) which is truncated by DPP-IV to NPY(3-36), as a consequence NPY's affinity changes from receptor Y1, which mediates the antilipolytic function of NPY, to other NPY receptors. Little is known whether DPP-IV inhibitors for the treatment of type 2 diabetic (T2DM) patients could influence these pathways. AIMS: To investigate the in vitro effects of NPY with DPP-IV inhibition in isolated abdominal subcutaneous (AbdSc) adipocytes on fat metabolism, and assessment of NPY receptor and DPP-IV expression in adipose tissue (AT). METHODS: Ex vivo human AT was taken from women undergoing elective surgery (body mass index: 27.5 (mean +/- s.d.) +/- 5 kg/m2, age: 43.7 +/- 10 years, n = 36). Isolated AbdSc adipocytes were treated with human recombinant (rh)NPY (1-100 nM) with and without DPP-IV inhibitor (1 M); glycerol release and tissue distribution of DPP-IV, Y1 and Y5 messenger RNA (mRNA) were measured and compared between lean and obese subjects. RESULTS AND CONCLUSION: rhNPY reduced glycerol release, an effect that was further enhanced by co-incubation with a DPP-IV inhibitor [control: 224 (mean +/- s.e.) +/- 37 micromol/l; NPY, 100 nM: 161 +/- 27 micromol/l**; NPY 100 nM/DPP-IV inhibitor, 1 M: 127 +/- 14 micromol/l**; **p < 0.01, n = 14]. DPP-IV was expressed in AbdSc AT and omental AT with relative DPP-IV mRNA expression lower in AbdSc AT taken from obese [77 +/- 6 signal units (SU)] vs. lean subjects (186 +/- 29 SU*, n = 10). Y1 was predominantly expressed in fat and present in all fat depots but higher in obese subjects, particularly the AbdSc AT-depot (obese: 1944 +/- 111 SU vs. lean: 711 +/- 112 SU**, n = 10). NPY appears to be regulated by AT-derived DPP-IV. DPP-IV inhibitors augment the antilipolytic effect of NPY in AT. Further studies are required to show whether this explains the lack of weight loss in T2DM patients treated with DPP-IV inhibitors.
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- Moschella, P. S., et al.
(författare)
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Low-crested coastal defence structures as artificial habitats for marine life: Using ecological criteria in design
- 2005
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Ingår i: Coastal Engineering. - : Elsevier BV. - 0378-3839. ; 52:10-11, s. 1053-1071
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Tidskriftsartikel (refereegranskat)abstract
- Coastal defence structures to protect sedimentary coastlines from erosion and flooding are increasingly common throughout Europe. They will become more widespread over the next 10-30 years in response to rising and stormier seas and accelerating economic development of the coastal zone. Building coastal defences results in the loss and fragmentation of sedimentary habitats and their replacement by artificial rocky habitats that become colonised by algae and marine animals. The engineering design and construction of these structures have received considerable attention. However, the ecological consequences of coastal defences have been less extensively investigated. Furthermore, due to their rapid proliferation, there is a growing need to understand the role of these man-made habitats in the coastal ecosystems in order to implement impact minimisation and/or mitigation measures. As part of the DELOS project, targeted studies were carried out throughout Europe to assess the ecological similarity of low-crested coastal defence structures (LCS) to natural rocky shores and to investigate the influence of LCS design features on the colonising marine epibiota. LCSs can be considered as a relatively poor surrogate of natural rocky shores. Epibiotic communities were qualitatively similar to those on natural rocky shores as both habitats are regulated by the same physical and biological factors. However, there were quantitative differences in the diversity and abundance of epibiota on artificial structures. Typically, epibiotic assemblages were less diverse than rocky shore communities. Also, LCSs offered less structurally complex habitats for colonisation and in some locations experienced higher disturbance than natural shores. We propose several criteria that can be integrated into the design and construction of LCSs to minimise ecological impacts and allow targeted management of diversity and natural living resources. (c) 2005 Elsevier B.V. All rights reserved.
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- Wollmer, M Axel., et al.
(författare)
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Association study of cholesterol-related genes in Alzheimer's disease
- 2007
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Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 8:3, s. 179-188
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a genetically complex disorder, and several genes related to cholesterol metabolism have been reported to contribute to AD risk. To identify further AD susceptibility genes, we have screened genes that map to chromosomal regions with high logarithm of the odds scores for AD in full genome scans and are related to cholesterol metabolism. In a European screening sample of 115 sporadic AD patients and 191 healthy control subjects, we analyzed single nucleotide polymorphisms in 28 cholesterol-related genes for association with AD. The genes HMGCS2, FDPS, RAFTLIN, ACAD8, NPC2, and ABCG1 were associated with AD at a significance level of P ≤ 0.05 in this sample. Replication trials in five independent European samples detected associations of variants within HMGCS2, FDPS, NPC2, or ABCG1 with AD in some samples (P = 0.05 to P = 0.005). We did not identify a marker that was significantly associated with AD in the pooled sample (n = 2864). Stratification of this sample revealed an APOE-dependent association of HMGCS2 with AD (P = 0.004). We conclude that genetic variants investigated in this study may be associated with a moderate modification of the risk for AD in some samples.
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