The Experts below are selected from a list of 249 Experts worldwide ranked by ideXlab platform
Ian S Fraser - One of the best experts on this subject based on the ideXlab platform.
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effective treatment of heavy menstrual bleeding with estradiol Valerate and dienogest a randomized controlled trial
Obstetrics & Gynecology, 2011Co-Authors: Jeffrey T Jensen, Susanne Parke, Uwe Mellinger, A Machlitt, Ian S FraserAbstract:OBJECTIVE: To estimate the efficacy of a fixed estrogen step-down and progestin step-up 28-day estradiol (E2) Valerate and dienogest oral contraceptive regimen in women with heavy menstrual bleeding prolonged menstrual bleeding or heavy and prolonged menstrual bleeding without organic pathology. METHODS: This double-blind placebo-controlled study randomized women aged 18 years or older with prolonged frequent or heavy menstrual bleeding objectively confirmed during a 90-day run-in phase to treatment with E2 Valerate and dienogest or placebo (2:1) for 196 days. Data from the last 90 days of treatment and the run-in phase were compared. The primary variable was the "complete response" rate (complete resolution of qualifying abnormal menstrual symptoms including a 50% or greater reduction in pretreatment menstrual blood loss volume in women with heavy menstrual bleeding). Secondary variables included objective changes in menstrual blood loss volume (alkaline hematin methodology) and iron metabolism parameters. Overall 180 women were needed to provide 90% power. RESULTS: There were no marked differences in the characteristics of E2 Valerate and dienogest (n=120) and placebo (n=70) recipients. The proportion of "complete responders" in the evaluable group was significantly higher in E2 Valerate and dienogest (35/80; 43.8%) compared with placebo (2/48 4.2% P<.001) recipients. The mean [standard deviation] reduction in menstrual blood loss with E2 Valerate and dienogest from the run-in phase to the efficacy phase was substantial (-353 mL [309 mL]; mean -64.2%; median -70.6%) and significantly greater than that in placebo recipients (-130 mL [338 mL]; mean -7.8%; median -18.7%; P<.001). Significant improvements in hemoglobin hematocrit and ferritin were seen with E2 Valerate and dienogest but not with placebo. CONCLUSION: Oral E2 Valerate and dienogest was highly effective compared with placebo in the treatment of women with heavy menstrual bleeding prolonged menstrual bleeding or heavy and prolonged menstrual bleeding without organic pathology. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov www.clinicaltrials.gov NCT00293059. LEVEL OF EVIDENCE: I.
Jeffrey S. Ledford - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and Characterization of Tin Valerate and Tin Oxide Thin Films
Langmuir, 1995Co-Authors: Kathryn G. Severin, Jeffrey S. LedfordAbstract:Tin Valerate films have been prepared by spincasting solutions produced from the hydrolysis of tin(II) methoxide or tin(IV) isopropoxide in alcohol and valeric acid. Tin oxide films were made from tin Valerate films using two methods : calcination at 400 °C in air and by room temperature hydrogen peroxide treatment. All tin Valerate and tin oxide films are transparent and exhibit uniform adhesion to quartz substrates. FTIR and XPS analyses indicate that the structure and composition ofValerate films prepared from either alkoxide are similar despite differences in precursor oxidation state and concentrations of acid and alcohol used for the syntheses. Tin Valerate films are comprised of an oxygen-tin polymer backbone coordinated with Valerate ligands. Both monodentate and bidentate carboxylates are present, the former apparently stabilized by hydrogen bonding with sorbed water. Quantitative XPS analysis indicates that Valerate/tin and hydroxy/tin ratios are 0.26 and 0.55, respectively. This level of film carboxylation is consistent with the extent of carboxylate formation in tin(IV) isopropoxide/valeric acid solutions. Hydrogen peroxide treatment of tin Valerate films removes organic ligands and increases the level of backbone oxygen. Hydrogen peroxide treatment or calcination results in the formation of amorphous tin(IV) oxide films.
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Characterization of titanium and zirconium Valerate sol-gel films
Chemistry of Materials, 1994Co-Authors: Kathryn G. Severin, Jeffrey S. Ledford, Beatrice A. Torgerson, Kris A. BerglundAbstract:FTIR and XPS have been used to characterize titanium and zirconium Valerate thin films prepared using sol-gel techniques. Films were prepared by hydrolysis of titanium(IV) isopropoxide or zirconium(IV) n-propoxide in excess valeric acid at room temperature. Film solution chemistry, from precursors to cast films, was followed with FTIR. The structure and chemical composition of films spin cast from fresh and day-old solutions were determined. Results of these studies suggest that all films consist of a metal-oxygen polymer backbone coordinated with bidentate Valerate ligands. No evidence for the presence of alkoxide ligands has been found. A small amount of water is present in all cast films. While solution aging experiments indicate that the zirconium film structure does not change with solution reaction time, carboxylate ligand concentrations are higher in titanium films made from aged solutions. Titanium films made from aged solutions contain slightly less than 1.5 Valerate ligands/titanium atom. Zirconium films are more highly carboxylated with almost two Valerate groups per metal center. 57 refs., 6 figs., 1 tab.
Lesley J. Scott - One of the best experts on this subject based on the ideXlab platform.
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Estradiol Valerate/dienogest: in oral contraception.
Drugs, 2009Co-Authors: Sheridan M. Hoy, Lesley J. ScottAbstract:▴ Estradiol Valerate/dienogest is an oral contraceptive for women that combines the natural estrogen estradiol with the 19-nortestosterone derivative dienogest in a four-phasic formulation. ▴ Estradiol Valerate/dienogest demonstrated contraceptive efficacy in a large (n=1377), non-comparative, multicentre study in women aged 18–50 years, with 13 pregnancies over 1797.5 women-years of exposure generating an unadjusted Pearl Index (PI) of 0.73 (upper limit of 95% CI 1.24) [primary endpoint]. Six of the pregnancies were attributed to method failure, resulting in an adjusted PI, based on 1786.5 women-years of exposure, of 0.34 (upper limit of 95% CI 0.73). ▴ In a double-blind study in 798 women aged 18–50 years, estradiol Valerate/dienogest and ethinylestradiol/levonorgestrel demonstrated an acceptable bleeding pattern and level of cycle control, according to several co-primary endpoints. ▴ As reported in the UK manufacturer’s summary of product characteristics, the unadjusted PI for women aged 18–35 years or 18–50 years in a pooled analysis of clinical studies was 1.01 (upper limit of 95% CI 1.59) and 0.79 (upper limit of 95% CI 1.23). This pooled analysis of three studies excluded those pregnancies occurring within 14 days of the cessation of therapy. ▴ Estradiol Valerate/dienogest was generally well tolerated in this population, with the nature of adverse events generally similar across the studies and between estradiol Valerate/dienogest and ethinylestradiol/levonorgestrel.
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Estradiol Valerate/Dienogest
Drugs, 2009Co-Authors: Lesley J. ScottAbstract:▴ Estradiol Valerate/dienogest is an oral contraceptive for women that combines the natural estrogen estradiol with the 19-nortestosterone derivative dienogest in a four-phasic formulation. ▴ Estradiol Valerate/dienogest demonstrated contraceptive efficacy in a large (n=1377), non-comparative, multicentre study in women aged 18–50 years, with 13 pregnancies over 1797.5 women-years of exposure generating an unadjusted Pearl Index (PI) of 0.73 (upper limit of 95% CI 1.24) [primary endpoint]. Six of the pregnancies were attributed to method failure, resulting in an adjusted PI, based on 1786.5 women-years of exposure, of 0.34 (upper limit of 95% CI 0.73). ▴ In a double-blind study in 798 women aged 18–50 years, estradiol Valerate/dienogest and ethinylestradiol/levonorgestrel demonstrated an acceptable bleeding pattern and level of cycle control, according to several co-primary endpoints. ▴ As reported in the UK manufacturer’s summary of product characteristics, the unadjusted PI for women aged 18–35 years or 18–50 years in a pooled analysis of clinical studies was 1.01 (upper limit of 95% CI 1.59) and 0.79 (upper limit of 95% CI 1.23). This pooled analysis of three studies excluded those pregnancies occurring within 14 days of the cessation of therapy. ▴ Estradiol Valerate/dienogest was generally well tolerated in this population, with the nature of adverse events generally similar across the studies and between estradiol Valerate/dienogest and ethinylestradiol/levonorgestrel.
Kathryn G. Severin - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and Characterization of Tin Valerate and Tin Oxide Thin Films
Langmuir, 1995Co-Authors: Kathryn G. Severin, Jeffrey S. LedfordAbstract:Tin Valerate films have been prepared by spincasting solutions produced from the hydrolysis of tin(II) methoxide or tin(IV) isopropoxide in alcohol and valeric acid. Tin oxide films were made from tin Valerate films using two methods : calcination at 400 °C in air and by room temperature hydrogen peroxide treatment. All tin Valerate and tin oxide films are transparent and exhibit uniform adhesion to quartz substrates. FTIR and XPS analyses indicate that the structure and composition ofValerate films prepared from either alkoxide are similar despite differences in precursor oxidation state and concentrations of acid and alcohol used for the syntheses. Tin Valerate films are comprised of an oxygen-tin polymer backbone coordinated with Valerate ligands. Both monodentate and bidentate carboxylates are present, the former apparently stabilized by hydrogen bonding with sorbed water. Quantitative XPS analysis indicates that Valerate/tin and hydroxy/tin ratios are 0.26 and 0.55, respectively. This level of film carboxylation is consistent with the extent of carboxylate formation in tin(IV) isopropoxide/valeric acid solutions. Hydrogen peroxide treatment of tin Valerate films removes organic ligands and increases the level of backbone oxygen. Hydrogen peroxide treatment or calcination results in the formation of amorphous tin(IV) oxide films.
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Characterization of titanium and zirconium Valerate sol-gel films
Chemistry of Materials, 1994Co-Authors: Kathryn G. Severin, Jeffrey S. Ledford, Beatrice A. Torgerson, Kris A. BerglundAbstract:FTIR and XPS have been used to characterize titanium and zirconium Valerate thin films prepared using sol-gel techniques. Films were prepared by hydrolysis of titanium(IV) isopropoxide or zirconium(IV) n-propoxide in excess valeric acid at room temperature. Film solution chemistry, from precursors to cast films, was followed with FTIR. The structure and chemical composition of films spin cast from fresh and day-old solutions were determined. Results of these studies suggest that all films consist of a metal-oxygen polymer backbone coordinated with bidentate Valerate ligands. No evidence for the presence of alkoxide ligands has been found. A small amount of water is present in all cast films. While solution aging experiments indicate that the zirconium film structure does not change with solution reaction time, carboxylate ligand concentrations are higher in titanium films made from aged solutions. Titanium films made from aged solutions contain slightly less than 1.5 Valerate ligands/titanium atom. Zirconium films are more highly carboxylated with almost two Valerate groups per metal center. 57 refs., 6 figs., 1 tab.
Howard I. Maibach - One of the best experts on this subject based on the ideXlab platform.
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Simultaneous Diffusion and Metabolism of Betamethasone 17-Valerate in the Living Skin Equivalent
Journal of pharmaceutical sciences, 1995Co-Authors: Klyoshi Kubota, John I. Ademola, Howard I. MaibachAbstract:Simultaneous diffusion and metabolism of betamethasone 17-Valerate was studied using betamethasone 17-Valerate, betamethasone 21-Valerate, and betamethasone as permeants. These corticosteroids were suspended in silicone adhesive and applied to an artificial living skin equivalent (LSE) for 72 h. When betamethasone was applied, no metabolites were detected in the receptor medium. Conversely, with betamethasone 21-Valerate application, only betamethasone but no betamethasone 21-Valerate was detected in the receptor medium indicating the metabolism of the latter by skin esterases. When tested with the theory for simultaneous diffusion and metabolism, the result is consistent with the enzyme rate constant in the LSE homogenate measured in a previous study. When betamethasone 17-Valerate was applied to the LSE, more than half of the total amount of corticosteroids detected in the receptor medium was unchanged, consistent with the previously reported chemical (as opposed to enzymatic) degradation half-life of about 8 h. This result also indicated that very little metabolism of betamethasone 17-Valerate occurred in the skin.
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Metabolism and degradation of betamethasone 17-Valerate in homogenized living skin equivalent.
Dermatology (Basel Switzerland), 1994Co-Authors: Kiyoshi Kubota, John I. Ademola, Howard I. MaibachAbstract:The metabolism of betamethasone 17-Valerate was estimated using an artificial living skin equivalent (LSE). Betamethasone 17-Valerate, betamethasone 21-Valerate and betamethasone were measured by a normal-phase high-performance liquid chromatographic (HPLC) method. Betamethasone 17-Valerate was added to the culture medium with or without LSE homogenate. Degradation profiles (%) of betamethasone 17-Valerate remaining in the culture medium with skin homogenate did not differ from those without homogenate. However, the conversion of betamethasone 21-Valerate to betamethasone was accelerated by skin homogenate, indicating that LSE has a sufficient level of esterase.
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Plasma concentrations of betamethasone after topical application of betamethasone 17-Valerate: comparison with oral administration.
British journal of clinical pharmacology, 1994Co-Authors: Kiyoshi Kubota, G. Huttinot, P. H. Andersen, Howard I. MaibachAbstract:Plasma concentrations of betamethasone were measured by r.i.a. after oral administration of 0.6 mg betamethasone and topical application of betamethasone 17-Valerate in the same five healthy subjects. Betamethasone 17-Valerate was prepared as a suspension in medical grade pressure sensitive adhesive and applied to a 100 cm2 area on the back for 28 h. Mean maximum plasma concentrations were 5.0 and 0.24 ng ml-1 and mean AUC values were 75.4 and 7.74 ng ml-1 h after oral and topical administrations, respectively. The mean plasma elimination half-life of betamethasone after the removal of topical betamethasone 17-Valerate was 16.6 h which was twice that after oral administration, 8.1 h. Betamethasone 17-Valerate may require application to the skin more than twice daily.
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In Vitro Percutaneous Permeation of Betamethasone and Betamethasone 17-Valerate
Journal of pharmaceutical sciences, 1993Co-Authors: Kiyoshi Kubota, Howard I. MaibachAbstract:The percutaneous permeation and sorption isotherm (equilibrium) profiles of betamethasone and betamethasone 17-Valerate were estimated in an in vitro study with excised human skin. Corticosteroids were measured by HPLC. The stratum corneum (dry weight)/water partition coefficient of betamethasone 17-Valerate was 20 times greater than that of betamethasone. Nevertheless, when aqueous saturation was maintained in the donor solution, the mean steady-state flux of betamethasone 17-Valerate through split-thickness skin was 57.6 ng/cm2/h, whereas that of betamethasone was 15.2 ng/cm2/h. This was presumably because the aqueous saturation concentration of betamethasone (60 micrograms/mL) was 11 times greater than that of betamethasone 17-Valerate (5.4 micrograms/mL), so that the calculated saturation concentrations of the two corticosteroids in stratum corneum were within a factor of 2. However, the drug amounts or concentrations of the more lipophilic corticosteroid (betamethasone 17-Valerate) attained in viable layers (viable epidermis and dermis) at steady state were predicted to be greater than those of the less lipophilic corticosteroid (betamethasone) when the results in the permeation and equilibrium studies were interpreted by a mathematical model. The drug distribution pattern predicted (i.e., that a more lipophilic corticosteroid preferentially partitions into viable layers) was reasonable when compared with that observed in the permeation study. The mean drug amount of betamethasone 17-Valerate in dermis was four times greater than that of betamethasone, whereas the drug amounts of both corticosteroids in epidermis were similar to each other.
