Acute mesenteric infarction in elderly patients.

The clinical features, the treatment given, the factors governing treatment selection, and the result of such treatment were analyzed in all patients aged 65 years and over in whom a tissue diagnosis of acute mesenteric infarction was made at a major teaching hospital. Thirty-two such patients, of mean age 78.5 years, were identified during the 8-year study period. Expected clinical features of bowel infarction were commonly absent; for example, there was no abdominal pain and no abdominal tenderness in 29% and 26% of patients, respectively. A sizeable minority of patients (29%) were acutely confused at presentation. All patients not undergoing surgery died shortly after admission to hospital. For those 20 patients (63%) who underwent abdominal surgery, half were discharged alive from hospital. Whether or not the patient survived was associated with the ward to which they were originally admitted. Those admitted to a surgical ward tended to be younger and had a more typical clinical presentation than their counterparts admitted to a medical ward. In particular they were more likely to have abdominal pain and distention and less likely to be confused. Surgical intervention was undertaken more often and earlier in those admitted to surgical wards and this may have accounted for the better outcome. It should be emphasized that acute mesenteric ischemia is a potentially correctable surgical condition even in very elderly people. A realization that the presentation is often atypical should increase the likelihood of early recognition and lead to improved patient survival.

Synthesis of c-2, 3, 17 and 19-oxygenated androgens.

The synthesis of C19-androgens oxygenated at carbons 2, 3, 17 and 19 and of their deuterium or deuterium-tritium labeled analogs is described.

Biotransformation of progesterone to 14 alpha-hydroxypregna-1,4-diene-3,20-dione, a novel fungal metabolite, by Colletotrichum antirrhini.

The fermentation of progesterone by Colletotrichum antirrhini SC 2144 was examined. Instead of 15 alpha-hydroxyprogesterone, the reported product, this fungus converted progesterone to androst-4-ene-3,17-dione, androsta-1,4-diene-3,17-dione, 14 alpha-hydroxyandrosta-1,4-diene-3,17-dione, 11 alpha-hydroxypregn-4-ene-3,20-dione, 14 alpha-hydroxypregn-4-ene-3,20-dione, and a hitherto undescribed compound, 14 alpha-hydroxypregna-1,4-diene-3,20-dione.

Biological activities of 4-fluoro estrogen analogues.

As part of a study on the biological activity of gamma-emitting estradiol analogues, a series of fluorinated and/or brominated analogues of estradiol were synthesized. 4-Fluoro-1,3,5(10-estratrien-3,17 beta-diol (4-fluoro-estradiol) and 16 alpha-bromo-1,3,5(10)-estratrien-3,17 beta-diol (16 alpha-bromo-estradiol) had relative binding affinities (RBA) for the rabbit uterine cytosol receptor which were comparable to those of estradiol. However, while 4-fluoro-estradiol stimulated the increase in uterine weight of immature mice to the same amount as estradiol, 16 alpha-bromo-estradiol was less effective in this assay indicating that its metabolism is probably more rapid than that of estradiol. 16 beta-Bromo-1,3,5(10)-estratrien-3,17 beta-diol had a low RBA and was ineffective in stimulating uterine weight at the doses used. 4-Fluoro-16 alpha-bromo-estradiol had a lower RBA than either the 4-fluoro- or 16 alpha-bromo-estradiol and all the 4-fluoro-seleno-estrogens tested possessed low RBA's.

In vitro studies of the adrenal metabolism of halogenated side-chain analogues of cholesterol.

The cholesterol side-chain cleavage enzyme system of rat adrenal mitochondria and rat adrenocortical carcinoma cells was found to metabolize three halogenated side-chain cholesterol analogues to pregnenolone. The analogues were 26-bromocholesterol, 26-nor-25(RS)-bromocholesterol and 26-iodocholesterol. The addition of Ca2+ to rat adrenal mitochondria did not produce an increase in the rate of metabolism of the halogenated sterol to pregnenolone. The brominated sterols suppressed the de novo sterol biosynthesis of rat adrenocortical carcinoma cells. The experimental findings are supportive of the notion that a halogen atom at such a position in a sterol is analogous to a hydroxyl group but unlike a proton. ACTH, therefore, may not be a requirement for the uptake and utilization of such sterols. The halogenated sterols may have a use as probes in the study of sterol transfer into and within cells.

Growth of a sterol auxotroph derived fromSaccharomyces cerevisiae on chemically synthesized derivatives of cholesterol possessing side-chain modifications.

A number of cholesterol derivatives were analyzed for their ability to satisfy bulk membrane and high-specificity sparking requirements of a yeast sterol auxotroph (RD5-R) (Rodriguez, R. J., Taylor, F. R., and Parks, L. W. [1982], Biochem. Biophys. Res. Commun. 106, 435-441). Substitution of hydrogen by bromine or iodine at C-26 or substitution of C26-methyl by bromine enabled the resulting sterol to satisfy bulk or sparking functions. The presence of a side-chain hydroxyl or keto group at C-25 on a 26-norcholesterol completely abolished the ability of cholesterol to satisfy either sterol requirement. Growth studies revealed that, while the oxygenated cholesterol derivatives were not growth-supportive of RD5-R, they were not growth-inhibitory.

The biologic activity of selenoestrogens.

For differential imaging of mammary tumors with estrogen receptors and without estrogen receptors we required gamma-emitting estrogen analogues. In this paper we report on the binding properties of 7 alpha-, 16 alpha-, and 17 alpha-methylselenoestrogens and 17 alpha-phenylselenoestrogens relative to the binding properties of estradiol. The selenium-containing estrogens retained the ability to displace [3H]estradiol from the estrogen receptor of rabbit uterine cytosol, although in most instances the displacement was small (3-7% compared to estradiol). The most active compounds were 16 alpha-phenylselenoestrone, 16 alpha-methylselenoestradiol, and 17 alpha-methylselenomethyl-estradiol which had relative binding of 23, 27, and 31%, respectively, compared with that of estradiol. 16 alpha-Methylselenoestradiol was able to translocate the estrogen cytosol receptor to the nucleus, in vitro, but was not able to increase the uterine weight when administered to mice in vivo.

Biologic activity of the iodoestrogens and their use in breast cancer.

Several iodinated estrogens, 6-iodoestra-1,3,5(10), 6-tetraene-3, 17 beta-diol (4) 16 beta-iodo-estradiol (3) were shown to displace 3H-estradiol (1b) from the uterine cytosol receptor by a competitive type of inhibition. The three compounds translocated the cytosol receptor to the nucleus in vitro and increased mouse uterine weight in vivo. In all tests the relative activities were 16 alpha-(2a) greater than 16 beta-(3a) greater than 6-(4a). When the compounds were made with [125I] the 16 alpha-[125I]-iodoestradiol (2b) bound with high affinity, Kd = 0.4 x 10(-10), to the 8S cytosol receptor. No high affinity binding could be demonstrated for the 6-[125I]-iodoestratetraene (4b). In in vivo experiments following the administration of 16 alpha-[125]-iodoestradiol (2b) to rats, high levels of radioactivity were found in the uterus, liver and thyroid but only in the liver and thyroid following administration of 6-[125I]-iodoestratetraene (4b). After administration of (2b) to rats with DMBA-induced mammary tumors, no tumor concentration of radioactivity could be detected by imaging. When (4b) was administered similarly, radioactivity could be detected in some of the tumors by imaging. The radioactivity was associated with non-specific 4S proteins.

Iodoestrogens, syntheses, and interaction with uterine receptors.

The rationale for undertaking the present study was to evaluate the utility of iodoestradiol analogs made highly radioactive with iodine isotopes in (a) the non-invasive differentiation of estrogen-dependent from estrogen-independent breast tumors, (b) spread of metastases containing estrogen receptors, and (c) potential application in therapeutic irradiation of target tissues. In the present paper, the model syntheses of a number of nonradioactive 127I-estrogen analogs are described. The analogs were tested for their ability to displace (compete with) [3H]estradiol from receptor sites. The most active compounds, 16beta-iodoestra-1,3,5(10)-triene-3,17 beta-diol (17) and 6-iodoestra-1,3,5(10),6-tetraene-3,17 beta-diol (10b), showed a relative binding affinity of 0.57 and 0.49, respectively.