Vertical mammaplasty: Postoperative changes, complications and patient evaluation.

The aim of the present study was to investigate postoperative changes after vertical mammaplasty. Between 2002 and 2005, 72 consecutive patients aged 15 to 69 years with an average weight of 72 kg underwent bilateral vertical mammaplasty. Forty-two patients attended the regular follow-up one week, four weeks, three months, six months and one year after the operation. Nipple diameter, notch-to-nipple distance, scar length and the number of skin folds along the vertical scar were evaluated. Complications were recorded during the entire follow-up period. A questionnaire was used to document patient satisfaction 12 months after the operation. The main changes took place during the first three months after surgery. Nipple diameter showed an average increase of 28% after surgery, and the notch-to-nipple distance increased by an average of 17% over the intraoperative value. The average increase of the scar length after one year was 22%. The rate of complications was low, and patient satisfaction was high.

Studies on modified estrogens: towards the synthesis of novel 14,15-cyclopropa[a]estra-1,3,5(10),8-tetraenes.

To improve the ratio of non-hormonal to hormonal activity, estrogens 3 and 4 were modified at various molecule positions. Isomerization of the 14 alpha,15 alpha-methylene bridge, controlled 3-methoxy group cleavage with respect to the 14 alpha,15 alpha-methylene bridge stereochemistry, reduction of the 8-double bond, and substitution of the oxyfunctionality at C-17 by a methylene and a difluoromethylene moiety were in the focus. As a result of in vivo and in vitro tests, compounds 27 and 29 were selected as potential follow-up candidates of lead 3.

17Beta-hydroxy-11alpha-(3'-sulfanylpropyl)oxy-estra-1,3,5(10)- trien-3-yl sulfamate--a novel hapten structure: toward the development of a specific enzyme immunoassay (EIA) for estra-1,3,5(10)-triene-3-yl sulfamates.

The title compound 17 has been synthesized for the use as hapten in the development of a competitive enzyme immunoassay for estrogen sulfamates. The synthesis started from estradiol diacetate 2. Oxyfunctionalization at C-11 to give 11alpha-hydroxy steroid 8 was accomplished by hydroboration/alkaline hydrogen peroxide oxidation of the 9(11)-dehydro derivative 7, which was obtained from compound 2 via 9-hydroxylation with dimethyldioxirane. After transformation of compound 8 into the allyl ether 9, the side chain was thio-functionalized at the omega-position affording the thioate 11 in two steps. Selective silylether deprotection at position 3 followed by sulfamoylation gave the sulfamate 19, which in turn was demasked at position 17 and treated with sodium borohydride/aluminum chloride to liberate the side chain thiol. Alternatively, title compound 17 was synthesized via the disulfides 13-16. For the preparation of the immunogen the title compound 17 was coupled to bovine gamma globulin in a two-step procedure using an amine and thiol specific bifunctional crosslinker. The immunization of rabbits resulted in the formation of antibodies which clearly discriminated the sulfamoylated estrogens from the non-esterified estrogens. The use of a biotinylated hapten derivative as a tracer in combination with a streptavidin-peroxidase-tetramethylbenzidine based detection system allowed the measurement of estradiol 3-sulfamate (1) in the range of about 1 to 1000 pg/well.

Synthesis of estrogen sulfamates: compounds with a novel endocrinological profile.

Estrogen sulfamates are promising hormones by oral administration. Therefore, generally applicable and convenient methods for the multigram synthesis of these derivatives are desirable. Numerous estra-1,3,5(10)-trienes derived from estrone, estradiol. 14 alpha,15 alpha-methylenestradiol, ethinylestradiol, and estriol have been esterified with sulfamoyl chloride and N-methylsulfamoyl chloride by a novel approach involving the use of 2,6-di-tert-butylpyridines as bases and chemoselective hydroxy group protections. These pathways circumvent the nonselective formation of esters and side reactions by in situ generated azasulfenes. For toxicological and clinical studies a new synthesis of estrone sulfamate on a 100-g scale was developed using dimethylformamide as the solvent and base.