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- Narod, SA, et al.
(författare)
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Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers
- 2002
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105. ; 94:23, s. 1773-1779
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oral contraceptive use has been associated with an increase in the risk of breast cancer in young women. We examined whether this association is seen in women at high risk of breast cancer because they carry a mutation in one of two breast cancer susceptibility genes, BRCA1 and BRCA2. Methods: We performed a matched case-control study on 1311 pairs of women with known deleterious BRCA1 and/or BRCA2 mutations recruited from 52 centers in 11 countries. Women who had been diagnosed with breast cancer were matched to control subjects by year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of ovarian cancer. All study subjects completed a questionnaire about oral contraceptive use. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. All statistical tests were two-sided. Results: Among BRCA2 mutation carriers, ever use of oral contraceptives was not associated with an increased risk of breast cancer (OR = 0.94, 95% CI = 0.72 to 1.24). For BRCAI mutation carriers, ever use of oral contraceptives was associated With a modestly increased risk of breast cancer (OR = 1.20, 95 % CI = 1.02 to 1.40). However, compared with BRCA1 mutation carriers who never used oral contraceptives, those who used oral contraceptives for at least 5 years had an increased risk of breast cancer (OR = 1.33, 95% CI = 1.11 to 1.60), as did those who used oral contraceptives before age 30 (OR = 1.29, 95% CI = 1.09 to 1.52), those who were diagnosed with breast cancer before age 40 (OR = 1.38, 95% CI = 1.11 to 1.72), and those who first used oral contraceptives before 1975 (OR = 1.42, 95 % CI = 1.17 to 1.75). Conclusions: Among BRCA1 mutation carriers, women who first used oral contraceptives before 1975, who used them before age 30, or who used them for 5 or more years may have an increased risk of early-onset breast cancer. Oral contraceptives do not appear to be associated with risk of breast cancer in BRCA2 carriers, but data for BRCA2 carriers are limited.
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- Brioni, JD, et al.
(författare)
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Activation of dopamine D-4 receptors by ABT-724 induces penile erection in rats
- 2004
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences; 1999. - 0027-8424 .- 1091-6490. ; 101:17, s. 6758-6763
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Tidskriftsartikel (refereegranskat)abstract
- Apomorphine, a nonselective dopamine receptor agonist, facilitates penile erection and is effective in patients suffering from erectile dysfunction. The specific dopamine receptor subtype(s) responsible for its erectogenic effect is not known. Here we report that the dopamine D(4) receptor plays a role in the regulation of penile function. ABT-724 is a selective dopamine D(4) receptor agonist that activates human dopamine D(4) receptors with an EC(50) of 12.4 nM and 61% efficacy, with no effect on dopamine D(1), D(2), D(3), or D(5) receptors. ABT-724 dose-dependently facilitates penile erection when given s.c. to conscious rats, an effect that is blocked by haloperidol and clozapine but not by domperidone. A proerectile effect is observed after intracerebroventricular but not intrathecal administration, suggesting a supraspinal site of action. s.c. injections of ABT-724 increase intracavernosal pressure in awake freely moving rats. In the presence of sildenafil, a potentiation of the proerectile effect of ABT-724 is observed in conscious rats. The ability of ABT-724 to facilitate penile erection together with the favorable side-effect profile indicates that ABT-724 could be useful for the treatment of erectile dysfunction.
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- Johnell, K, et al.
(författare)
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Neighbourhood social participation and women's use of anxiolytic-hypnotic drugs: a multilevel analysis.
- 2004
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 1470-2738 .- 0143-005X. ; 58:1, s. 59-64
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Tidskriftsartikel (refereegranskat)abstract
- Study objectives: To identify and quantify a hypothesised collective effect of the neighbourhood on individual use of anxiolytic-hypnotic drugs (AHD). To analyse the general impact of neighbourhood social participation on use of AHD, adjusting for individual characteristics. Design: Cross sectional analysis performed by multilevel logistic regression with women at the first level and neighbourhoods at the second level. Setting: Malmö (250 000 inhabitants), Sweden. Participants:15 456 women aged 45 to 73, residing in 95 neighbourhoods in Malmö, who took part in the Malmö diet and cancer study (1991–1996). Main results: The prevalence of AHD use was 5.5% in the study sample. Overall, 1.7% of the total individual differences in the propensity for using AHD were explained by the neighbourhood level. This percentage, however, differed between different individuals. Low level of social participation in the neighbourhood was associated with higher probability of AHD use (OR = 3.10 (95% CI 1.51 to 6.41)), independently of individual age, low social participation, low educational level, and living alone. This association was reduced (OR = 2.01 (95% CI 0.97 to 4.14)) after the additional accounting for individual disability pension, low self rated health, stress, and medication for somatic disorders. Conclusions: The neighbourhood level of social participation seems to affect individual use of AHD, possibly through individual characteristics. However, neighbourhood boundaries play a minor part in understanding individual AHD use in the city of Malmö.
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- Lynch, Iseult, et al.
(författare)
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Effect of a polymeric additive on the pore-size distribution and shrinking process of a hydrogel network
- 2003
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Ingår i: Macromolecular Chemistry and Physics. - : Wiley. - 1521-3935 .- 1022-1352. ; 204:3, s. 443-450
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Tidskriftsartikel (refereegranskat)abstract
- A systematic comparison of the effect of architectural modifications to the network structure on the internal microstructure of N-isopropylacrylamide (NIPA) based hydrogels showed that the addition of a second component to the network significantly increased the proportion of macropores in the network. The second components considered were short poly(N-isopropylacrylamide)(PNIPAM) chains grafted to the network backbone, high-molecular-weight polyacrylamide (PAM) chains, or microsphere particles of PNIPAM. Structures are proposed for each of the modified gel networks taking into account the new structural information. Through combination of the pore size and network structure data reported here, and with the shrinking data obtained previously, shrinking mechanisms are proposed for each of the modified network structures. In all cases, the enhanced shrinking rates were directly caused by the presence of the second component, which acted as nuclei for shrinking (graft-PNIPAM and PNIPAM microspheres) or as water-release channels (PAM gel), and indirectly caused by the second components via their affect on the network microstructure.
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- Lynch, Iseult, et al.
(författare)
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Release of model compounds from "plum-pudding"-type gels composed of microgel particles randomly dispersed in a gel matrix
- 2004
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Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 108:30, s. 10893-10898
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Tidskriftsartikel (refereegranskat)abstract
- A novel gel structure called the "plum-pudding" gel was described by us previously. I The gel was composed of randomly dispersed microgel particles ("plums") in a conventional hydrogel network. Depending on the preparation conditions, the microgels can be incorporated into the gel as expanded networks or dense collapsed globules. Where the microgel particles exist as collapsed globules, they have the potential to act as reservoirs for hydrophobic solutes, from which the solutes are released very slowly. The release of two model hydrophobic compounds (pyrene and BODIPY) from "plum-pudding" gels composed of 50:50 BAM:NIPAM microgels embedded in NIPA gel films was investigated. The release of pyrene was found to follow Fickian diffusion, while the release of BODIPY was found to be slightly non-Fickian. Thus, we propose that by controlling the attractiveness of the microgel particles to the solutes to be released, a range of release profiles can be obtained from pure-Fickian to almost any conceivable time scale.
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