Successful use of biliary accessories in antegrade dilation of complex upper esophageal stricture due to chemoradiation and surgery.

Endoscopic management of complete or near complete upper esophageal strictures is challenging. Current methods such as retrograde esophageal access are high risk and may require additional abdominal surgery. A biliary cannulation technique with a 0.035 inch guidewire was utilized to obtain antegrade esophageal access in a patient with near complete high esophageal stricture due to chemo radiation and surgery for head and neck cancer. Biliary accessories including bougie and balloon dilators were used for the initial dilation of the esophageal stricture, followed by the traditional approach of stricture dilation using over-the-wire dilators. The procedure was successfully performed in a patient with near complete upper esophageal stricture due to chemo radiation and surgery for recurrent laryngeal cancer. The dysphagia of this patient was resolved following serial esophageal dilations and his esophageal stricture was wide open on the last upper endoscopy. Biliary accessories can be safely used for obtaining antegrade esophageal access and dilation of near complete upper esophageal strictures. This approach should be considered in patients with complex esophageal strictures, especially after chemo radiation or surgery for head and neck cancer and prior to seeking other more complex alternatives involving retrograde esophageal access.

Free estradiol in postmenopausal women with and without endometrial cancer.

To assess the role of biologically active estradiol in the development of endometrial cancer, 25 patients with endometrial tumors and a similar number of control subjects matched for age and body size were studied. No differences between the 2 groups were found for levels of total estradiol, sex hormone-binding globulin (SHBG), non-SHBG-bound estradiol, and absolute free estradiol. Body size correlated positively with levels of total, non-SHBG-bound, and absolute estradiol and negatively with SHBG levels. The obese postmenopausal women had higher total circulating levels and proportionally greater concentrations of free estradiol than nonobese subjects, suggesting a dual risk for the cellular action of circulating estradiol. These factors could contribute to the association of obesity and the occurrence of this tumor in susceptible women.

Total and free estrogens and androgens in postmenopausal women with hip fractures.

Hip fracture constitutes the most serious complication of postmenopausal osteoporosis. To examine the possible role of circulating estrogen or androgen levels in the development of this type of fracture, 25 patients with hip fractures after minimal trauma were compared to an equal number of controls, matched for age and years since menopause. All were from a retirement community, had intact ovaries, and had not taken estrogen replacement for longer than 3 months during their entire lifetime. Hip fracture patients were found to have a significantly lower (P = 0.031) mean (+/-SE) percent ideal weight (89.4 +/- 2.9%) than controls (100.0 +/- 2.5%). Sex hormone-binding globulin levels were significantly higher (P = 0.004) in patients (6.7 +/- 0.4 X 10-8 M) than in controls (4.9 +/- 0.3 X 10-8 M), resulting in lower concentrations of biologically available estradiol and testosterone. In a subgroup of 12 patients and controls matched for percent ideal weight, differences in sex hormone binding globulin and free testosterone and estradiol levels were no longer statistically significant; however, the difference in the percentage of free testosterone persisted. These data suggest that endogenous sex steroids in their unbound form may play a role in the pathogenesis of postmenopausal hip fractures. The differences in free hormone levels appeared to be influenced by the differences in mean body size of the 2 groups. This factor is known to have an important negative effect on the concentration of sex hormone-binding globulin.

Relationship of glutathione and glutathione-S-transferase to cisplatin sensitivity in human head and neck squamous carcinoma cell lines.

Factors controlling glutathione metabolism may govern sensitivity to chemotherapeutic agents such as cisplatin. Using a battery of cell lines derived from previously untreated head and neck squamous cell carcinomas, we examined cisplatin resistance relative to (a) glutathione-S-transferase (GST)-pi gene amplification and expression, (b) basal and inducible GST-total and GST-pi enzymatic activity, and (c) cellular levels of reduced glutathione (GSH). Using Southern blot analysis and northern blot hybridization, no relationship between GST-pi gene amplification, mRNA expression and drug resistance could be identified. Despite the capacity of cisplatin to induce GST enzyme activity, the response was variable and unrelated to cisplatin responsiveness. However, an inverse relationship between GSH levels and cisplatin sensitivity was identified. To further clarify these effects, cells were treated with S-allyl cysteine (SAC), a thioallyl derivative isolated from garlic (Allium sativum), which altered cellular GSH in a biphasic manner. Pretreatment with SAC to lower cellular GSH levels followed by exposure to cisplatin significantly enhanced the cytotoxic effects of cisplatin, while SAC alone had no effect on cell growth.

Long-standing virilism in a woman with hyperplasia and neoplasia of ovarian lipidic cells.

A woman with bilateral hyperplasia of ovarian hilar cells, stromal lipidic cells (hyperthecosis), and unilateral adenoma of Leydig cells is described. Her clinical course was characterized by long-standing virilism with a recent exacerbation suggesting growth of a tumor from the hyperplastic stromal lipidic cells. Evidence for this hypothesis included similar light and electron microscopic features of the hyperplastic and neoplastic cells and identical patterns of secretion of steroid hormones. Comparison of the in vivo steroid biosynthesis of the hyperplastic lipidic cells with that of testicular Leydig cells showed several similarities. These included 1) secretion of 5 and delta 4 steroids; 2) greater secretion of the delta 4 hormones, progesterone and 17-hydroxyprogesterone, than of the delta 5 steroids, pregnenolone and 17-hydroxypregnenolone; 3) prominent secretion of testosterone but not androstenedione; and 4) limited secretion of estrogens, with estradiol as the principal estrogen. These findings support prior microscopic evidence that ovarian lipidic cells and testicular Leydig cells represent cells of common function and, likely, common origin.

Changes in circulating steroids with aging in postmenopausal women.

to examine the possible effects of aging on circulating steroid hormones in postmenopausal women, blood samples were drawn from 155 women, aged 34 to 83 years, with spontaneous ovarian failure. The C-21 steroids, pregnenolone and 17-hydroxypregnenolone; the delta 4 progestins, progesterone and 17-hydroxyprogesterone; and cortisol did not change with age and were similar in concentration to the levels measured during the follicular phase of premenopausal women. The delta 5 androgens, dehydropiandrosterone and dehydroepiandrosterone sulfate, declined significantly (P less than .001) with age, whereas no change was noted in the delta 4 androgens, androstenedione and testosterone. The levels of estradiol (E2) and estrone (E1) were strongly correlated with percent ideal weight but did not change with age. The authors conclude that 1) The production of progestins does not change with age in normal adult women, other than that resulting from the loss of secretion associated with ovarian corpus luteum function. 2) The decline of delta 5 androgens without corresponding changes in their precursors suggests an age-related change of adrenal 17,20 desmolase activity. 3) The levels of E2 and E1 reflect an effect of body size but not of age on peripheral aromatization of precursor androgens.

Endogenous cortisol and sex steroids in patients with osteoporotic spinal fractures.

Vertebral fractures due to osteoporosis commonly occur in postmenopausal women. Levels of cortisol and sex steroids in the circulation vary among older women. It has been suggested that this variation may contribute to the occurrence of osteoporotic fractures in some subjects but not others. To examine this, 30 patients with osteoporotic spinal fractures were compared to an equal number of controls matched to the patients for age and years since menopause. All subjects had intact ovaries and had not taken estrogen replacement therapy for more than 3 months during their entire lifetime. Spinal bone mineral density determined by dual photon absorptiometry was significantly lower (P less than .01) in the fraction group (0.75 +/- 0.03 g/cm2) than in the controls (1.0 +/- 0.03 g/cm2). No significant differences in body habitus or cortisol and sex steroid levels (both total and free) were found, with the exception of total estradiol levels, which were 16% higher in the fracture patients. This difference was presumably coincidental as there was no difference of free estradiol levels between groups. It is concluded that factors other than the differences of endogenous cortisol and sex steroid levels present in these postmenopausal women were responsible for the reduced bone mineral density of the spine observed in the fracture patients.

Sperm hyperactivation as quality control for sperm penetration assay.

The sperm penetration assay (SPA) is subject to considerable variation, and controls are needed to verify the accuracy of the results. It is proposed that sperm hyperactivation (HA) can serve as a quality control check for the SPA. The objective was to determine if there was an association between the SPA outcome and sperm HA measured at various times during the SPA procedure. The data showed a significant correlation between percent sperm HA and percent zona-free oocyte penetration by sperm preincubated for three hours prior to sperm-oocyte interaction (short preincubation). Some sperm hyperactivity was observed in liquefied raw semen samples, but this was insignificantly related to SPA results. Low correlation was observed between SPA results and sperm HA determined immediately after centrifuge washing of sperm. The results suggest that it is possible to utilize sperm HA measured immediately after the sperm-oocyte interaction period as a quality control check of SPA results.

Urinary pregnandiol-3-glucuronide and estrone conjugates to creatinine ratios in early pregnancies complicated by vaginal bleeding.

There is no simple and rapid test available to predict the outcome of an early pregnancy complicated by vaginal bleeding. In this prospective study, 15 women with normal pregnancies collected a weekly urine sample between 6 and 13 weeks' gestation. A single random urine sample was obtained from 15 women with bleeding who continued to carry their child and 50 women who proceeded to have a spontaneous abortion (SAB). Pregnandiol-3-glucuronide (PDG) was determined with the use of enzyme-multiplied immunoassay technique (EMIT) and estrone conjugates (E1C) were measured by radioimmunoassay (RIA). The ratios of these metabolites to creatinine (C) were calculated. PDG/C ratios in normal women rose gradually from 6 weeks on. All women with bleeding during a normal pregnancy had ratios in the normal range, but 94% of women with a SAB had ratios below the normal range. The E1C/C ratio remained unchanged from 6 to 11 weeks and then rose rapidly. Until 11 weeks, there was no clear separation between the E1C/C ratios of the women with a SAB and the women with bleeding who continued their pregnancies. The prognosis of threatened abortion can be made by a urinary PDG/C ratio but not by an E1C/C ratio. EMIT is simple and quick and uses technology present in many laboratories.

Atrial natriuretic peptide, plasma renin activity, and aldosterone in women on estrogen therapy and with premenstrual syndrome.

Estrogens are known to increase the renin-angiotensin-aldosterone system and to produce fluid retention, while atrial natriuretic peptide (ANP) induces an increase of the urinary output and tends to return the fluid balance to normal. The aim of this study was to test whether the levels of ANP were decreased during chronic estrogen and progestin administration, thereby possibly decreasing the amount of fluid excreted. The authors also studied women with premenstrual syndrome (PMS), because of the associated fluid retention often described with this syndrome. Levels of ANP, plasma renin activity (PRA), and aldosterone were determined in premenopausal women in the early follicular phase (EFP) and on low-dose oral contraceptives (OC), in postmenopausal patients with and without estrogen replacement therapy (ERT), and in women with PMS associated with fluid retention. The concentrations of ANP and PRA were enhanced in the women on OC, but those of aldosterone were unchanged. No differences were observed in the women on ERT or with PMS. It is concluded that the levels of PRA and ANP are affected by estrogen or progesterone therapy or the combination of the two and this response is dose dependent or additive. Furthermore, ANP and PRA do not seem to play a direct role in PMS.