Effects of vitamin E on chronic and acute endothelial dysfunction in smokers.

OBJECTIVES: The aims of this study were to determine whether chronic or acute impairment of flow mediated vasodilation (FMD) in the brachial artery of smokers can be restored or preserved by the antioxidant vitamin E. BACKGROUND: Transient impairment of endothelial function after heavy cigarette smoking and chronic endothelial dysfunction in smokers result at least in part from increased oxidative stress. METHODS: We studied 22 healthy male smokers (mean +/- SD, 23 +/- 9 cigarettes per day) randomly assigned to receive either 600 IU vitamin E per day (n = 11, age 28 +/- 6 years) or placebo (n = 11, age 27 +/- 6 years) for four weeks and 11 age-matched healthy male nonsmokers. Flow mediated vasodilation and endothelium-independent, nitroglycerin-induced dilation were assessed in the brachial artery using high resolution ultrasound (7.5 MHz) at baseline and after therapy. Subjects stopped smoking 2 h before the ultrasound examinations. At the end of the treatment period, a third scan was obtained 20 min after smoking a cigarette (0.6 mg nicotine, 7 mg tar) to estimate transient impairment of FMD. RESULTS: Flow mediated vasodilation at baseline was abnormal in the vitamin E (5.3 +/- 3.8, p < 0.01) and in the placebo group (6.4 +/- 3.5, p < 0.05) compared with nonsmoking controls (11.6 +/- 4.7). Using a two-way repeated measures analysis of variance (ANOVA) to examine the effects of vitamin E on FMD, we found no effect for the grouping factor (p = 0.5834) in the ANOVA over time but a highly significant difference with respect to time (p = 0.0065). The interaction of the time factor and the grouping factor also proved to be significant (p = 0.0318). Flow mediated vasodilation values remained similar after treatment for four weeks in both groups but declined faster after smoking a cigarette in subjects taking placebo compared with those receiving vitamin E (p values from successive differences for the time/group factor: 0.0001/0.0017). The transient attenuation of FMD (calculated as the percent change in FMD) was related to the improvement of the antioxidant status, estimated as percent changes in thiobarbituric acid-reactive substances (r = -0.67, p = 0.0024). Nitroglycerin-induced dilation did not differ between study groups at baseline or after therapy. CONCLUSIONS: These results demonstrate that oral supplementation of vitamin E can attenuate transient impairment of endothelial function after heavy smoking due to an improvement of the oxidative status but cannot restore chronic endothelial dysfunction within four weeks in healthy male smokers.

Structural chromosomal abnormalities in gynecologic malignancies.

Surgical specimens taken from four patients with gynecologic malignancies were cultured, and metaphase chromosomes were prepared after staining with chromamycin-A, distamycin, and DAPI. Four specially selected karyotypes and their structural aberrations are discussed in this study and compared with those (also from carcinomas) previously described in the literature.

Serum 3 alpha-androstanediol-glucuronide is decreased in nonhirsute women with acne vulgaris.

OBJECTIVE: To determine if acne vulgaris in women has a different pattern of androgen activity than hirsutism at the pilosebaceous unit. DESIGN: Prospective clinical study. SETTING: Outpatient clinic for gynecological endocrinology at a university hospital. PATIENT(S): Twenty women suffering from mild or moderate acne vulgaris compared with 38 controls. MAIN OUTCOME MEASURE(S): Serum androgens DHEAS, androstendione, T, including 3 alpha-androstanediol-glucuronide (3 alpha-diolG), the metabolite of 5 alpha-reductase activity. RESULT(S): Serum 3 alpha-diolG was decreased in the acne groups depending on the grade of severity. No statistically significant differences were observed between the other androgens measured in acne patients and controls. CONCLUSION(S): In contrast to hirsutism, acne is influenced directly by T and not by its 5 alpha-reduced metabolites. In female acne patients, 5 alpha-reductase activity appears to be reduced, which is reflected in decreased serum levels of 3 alpha-diolG. Consequently, 5 alpha-reductase inhibitors are most likely not promising candidates for acne therapy; a postulation that, however, requires further clinical investigation.

Effect of hormone replacement therapy on growth hormone stimulation in women with premature ovarian failure.

OBJECTIVE: To assess the effect of oral hormone replacement therapy (HRT) on body weight, insulin-like growth factor I (IGF-I), and GH response to exogenous GHRH [corrected] in women with premature ovarian failure (POF) [corrected]. DESIGN: Controlled clinical study. SETTING: Outpatients studied in the department of endocrinology of the University Hospital in Vienna. PATIENT(S): Twenty-four women with POF (study group) and 24 volunteers with normal ovarian cycles (control group). INTERVENTION(S): Pituitary GHRH [corrected] stimulation was performed in all women at study entry and in patients with POF after 1, 6, and 12 months of standard oral HRT. Blood samples were collected from 15 minutes before to 120 minutes after GHRH administration [corrected]. Body weight also was evaluated. RESULT(S): No differences in baseline and stimulated serum GH were found either between POF women and controls or in POF women during HRT. Women with POF without HRT had significantly higher IGF-I levels; a reduction in circulating IGF-I levels occurred during HRT. Body weight remained stable. CONCLUSION(S): Our results show the following: [1] Women with POF have similar Gh secretion patterns as healthy age-matched women; [2] physiologic HRT has no impact on GHRH-induced [corrected] GH stimulation; and [3] HRT has no impact on body weight in women with POF.

Basal calcitonin levels and the response to pentagastrin stimulation in patients after kidney transplantation or on chronic hemodialysis as indicators of medullary carcinoma.

Plasma concentrations of calcitonin (hCT) were determined in 150 patients with chronic renal failure on chronic hemodialysis therapy (CHD) and in 800 patients after successful kidney transplantation (KT). Basal hCT concentrations exceeded 10 pg/mL in 44 of 150 patients (29%) with CHD and in 48 of 800 (6%) in patients with KT. Among these patients with elevated basal hCT, pentagastrin-stimulated concentrations of hCT exceeded 100 pg/mL in 4 patients with CHD and in 7 with KT. Thyroidectomy was performed in 8 patients (5 with KT, 3 with CHD) revealing the presence of medullary thyroid carcinoma (MTC) (n = 2) or of C-cell hyperplasia (n = 6). Two patients with C-cell hyperplasia had the neoplastic form of this disorder. One patient with MTC and 1 with C-cell hyperplasia also presented a papillary microcarcinoma. Stimulated concentrations of hCT were only moderately elevated in the remaining 3 patients and follow-up rather than surgery was deemed appropriate due to their concomitant severe medical problems. In conclusion, basal concentrations of hCT higher than 10 pg/mL are more common in patients with CHD (29%) and after successful KT (6%) than previously described in patients with thyroid nodular disease (3%). In spite of various additional factors complicating the interpretation of elevated hCT in CHD, pentagastrin-stimulated values above 100 pg/mL must be considered to indicate the presence of C-cell hyperplasia and/or of medullary thyroid carcinoma. Although thyroidectomy would theoretically be the therapy of choice, the potential benefit of the operation must be seen in the context of the patient's general condition.

Altered growth hormone (GH) secretion in women gaining weight during hormone replacement therapy (HRT).

OBJECTIVES: The relationship between GH response to GHRH-stimulation and changes in body weight in pre- and postmenopausal women before as well as after 4 and 20-22 weeks of oral HRT was tested. METHODS: 18 postmenopausal women (FSH > 30 mU/ml) were compared to 18 premenopausal women suffering from post-pill amenorrhoea (FSH < 10 mU/ml). Both patient-groups reported an anamnestic increase in body weight during former use of sex hormones. In addition 18 postmenopausal women without anamnestic weight change were studied. RESULTS: A significant reduction in GH response to GHRH stimulation was observed during the first month of HRT in both groups gaining weight. However, the body mass index of the patients reverted to pretherapeutic levels after 5 months of HRT. In all patients, a small but statistically significant increase in IGF-1 levels was registered during HRT. These changes in GH stimulation testing and IGF-1 levels were accompanied by distinct changes in body weight. No alterations in GHRH response were observed in those patients whose body weight did not increase. CONCLUSIONS: Our results confirm that in predisposed women, HRT is associated with increments in body weight as well as with changes in the GH-IGF-1 axis.

[The clinical value of 3 alpha-androstanediol-glucuronide in hirsute women]. / Die klinische Wertigkeit von 3 alpha-Androstanediol-Glucuronid bei hirsuten Frauen.

Aim of this prospective diagnostic study was to determine the serum 3 alpha-androstanediol-glucuronide (AdiolG) level in hirsute women in order to assess the androgenic activity in peripheral tissue and to differentiate between hirsutism of peripheral origin and that of adrenal or ovarian origin. Diagnostic advantages might have been expected in patients with idiopathic hirsutism, in whom increased 5 alpha-reductase activity may be reflected by this parameter. Apart from serum AdiolG, we determined the established parameters testosterone, androstendione and dehydroepiandosterone sulfate in 63 hirsute premenopausal women and in 51 non-hirsute controls. AdiolG (P < 0.05), as well as the 3 established parameters (P < 0.001) were elevated in the hirsute women as compared with the controls; however, the subgroup of women with idiopathic hirsutism (n = 32) showed no elevation of serum AdiolG. Analysis of the combined hirsute and control groups showed that the correlation of AdiolG to the hirsutism score (r = 0.42) was markedly weaker than that of testosterone to the latter (r = 0.62). Moreover, no correlation was found between the body-mass index and AdiolG. Our data show that serum AdiolG is obviously not a specific marker for peripheral 5 alpha-reductase activity, but appears to reflect the adrenal and ovarian androgen precursors. Thus, determination of serum AdiolG is of no diagnostic benefit in the clinical assessment of hirsute women.

Androgen serum levels in women with premature ovarian failure compared to fertile and menopausal controls.

OBJECTIVE: The purpose of our study was to examine androgen serum levels and bone density in women with premature ovarian failure (POF) compared to healthy normal controls. STUDY DESIGN: Thirty-three women 19-35 years of age with idiopathic POF were compared to 33 well-matched women with normal ovarian function and 32 healthy postmenopausal (PMP) women concerning 17-hydroxyprogesterone (17-OHP), androstendione (A), testosterone (T), dehydroepiandrosterone-sulfate (DHEAS), insulin-like growth factor 1 (IGF-1), as well as bone density (BD). RESULTS: Women with POF showed statistically significantly lower concentrations of 17-OHP, A, T (p < 0.001) and a reduced bone density (p < 0.001) compared to fertile controls. No differences were found between POF and PMP women concerning estradiol (E2), T, A and 17-OHP. Regarding DHEAS, no statistically significant differences were found between women with POF and fertile controls whereas PMP women proved to have significantly lower DHEAS concentrations than fertile controls. Women with POF had the highest IGF-1 serum concentrations and PMP women the lowest. CONCLUSION: An important decrement of ovarian steroids and bone density was noticed in women with POF, while the time since menopause had no influence on androgen concentrations. The hormone concentrations in women with POF are similar to those observed in normal PMP women with the exception of DHEAS and IGF-1 levels.

[Gynecologic Doppler ultrasonography]. / Gynäkologische Dopplersonographie.

The resistance of the vessel of the ovarian artery changes during the cycle. At the time of ovulation the resistance of the vessel of the ovarian artery decreases under the influence of steroid production in the ovary. The resistance decreases and the blood flow increases. In our study we could show that women with a normal cycle have low pulsatility indices in the ovarian arteries when oestradiol is rising. In women with PCO-Syndrome the blood flow in the ovarian artery is very low in spite of the fact that the patients got hormonal treatment. On the day of follicular puncture in our IVF-group and also on the day before, the pulsatility-index of the ovarian artery was very high in patients with PCO-Syndrome and it was significantly lower in patients with normal cycle. The women with PCO-Syndrome had also low oestradiol levels in the plasma. In the group with PCO-Syndrome no woman became pregnant, women with high oestradiol levels and low PI of the ovarian artery at the time of follicular puncture became pregnant in 19%.

[Early diagnosis of tubal pregnancy with vaginal sonography]. / Frühdiagnose der Tubargravidität mit der Vaginosonographie.

In 19 patients, the transvaginal (TVU) and in 24 patients, the transabdominal (TAU) ultrasound approaches were compared in their ability to identify by visualization the adnexal mass of ectopic pregnancy. The direct visualization of ectopic pregnancy (EUP) was 25% in TAU and 94.7% in TVU approach (p 0.03). All women had a proven EUP in laparoscopy. TAU approach showed a significant inferiority (p 0.02) and TVU a significant superiority (p 0.08) in comparison to palpation. 83% out of 43 women had spotting. Unspecific signs for EUP, like retrouterine fluid, was seen in 20.9%. Striated endometrium was seen in 6.9%, in 37.2% the thickness of endometrium was less than 10 mm, in 55.8% more than 10 mm. A pseudogestationsac was detected in 6.9%, corpus luteum formation in 27.2%. With vaginosonography, organs can be seen at close range, and the specific signs of EUP, an extrauterine ring-formation surrounded by a dam-like structure of the tube, was identified in 94.7%.

[Simplified hamster ovum-sperm penetration test (HSPT) in routine sterility testing]. / Vereinfachter Hamsterei-Spermien-Penetrationstest (HSPT) in der Sterilitäts-routine.

In 67 patients, in most of whom the spermiogram did not, a priori, furnish definitive proof of fertility, the hamster egg human sperm penetration test was performed as part of a screening programme for infertility therapy conducted from February 1984 to February 1985. Evaluation of the test was facilitated by identification of the decondensed spermatozoon head in the penetrated hamster egg with a simple fluorescein staining instead of the usual aceto-lacmoid staining. The penetration rate (= percentage proportion of the hamster ova liberated from the zona pellucida which are penetrated within 3 hours following incubation with 1 million motile spermatozoa) was evaluated statistically in comparison to the fertility criteria of the spermiogram (motility, density, pathoforms), in order to verify the existence of possible fertility disturbances due to inability to penetrate despite the motility of the spermatozoa. In 42 patients the diagnosis of infertility was confirmed by a penetration rate of less than 10%. In 17 patients fertility was conformed according to HSPT (penetration rate of over 20%), while in 7 patients fertility was in the lower normal range. In the light of the authors' findings fertility confirmed by the HSPT is a precondition of referral for extracorporeal insemination. In the light of the authors' findings intrauterine insemination appears advisable for women whose fertility is in the lower normal range according to HSPT.

[Effect of ozone and ionizing radiation on an in vitro model--a pilot study of 4 gynecologic tumors]. / Zur Wirkung von Ozon und ionisierender Strahlung am In-vitro-Modell--eine Pilotstudie an vier gynäkologischen Tumoren.

In order to investigate the sensibility of cultured tumor cells to ozone and irradiation primary tissue cultures from one undifferentiated non-classified ovarian carcinoma, two solid adenocarcinomas of the ovary and one endometrial carcinoma were established. Cultivation was performed according to standard techniques involving the stem cell assay in soft agar as well as the monolayer technique in liquid nutrient media. The type of culture system did not influence the sensitivity of the culture cells to ozone and/or irradiation. Ozone treatment was performed with three different Ozone concentrations (0.03 ppm, 0.1 ppm, 0.3 ppm). Irradiation was done with 100 rd Ra226, Ir192 or Co60. A control experiment showed that the proliferative tendency of benign cells (skin fibroblasts) was not inhibited by the three ozone concentrations used in this study. Ra226 and even the combination of ozone and Radium did not influence the proliferative activity of these benign cells. Ir192 and Co60 were cytotoxic to benign as well as to carcinoma cells. Cultivated cells from endometrial carcinoma resisted to ozone treatment as well as to Ra226 (but they were destroyed by Ir119 and Co60). After pretreatment with ozone (0.1 ppm), Ra226 treatment of endometrial carcinoma cells induced a cytostatic effect implying that no cell divisions were observed after irradiation and the cells lysed within two weeks after irradiation. For the three ovarian carcinoma cell lines analysed in this study ozone treatment had a cytostatic effect even at the lowest concentration (0.03 ppm), with the two higher ozone concentrations a cytotoxic effect could be induced in ovarian carcinoma cells. Exclusive treatment with Ra226 induced a cytostatic effect, but it was cytotoxic after combination with ozone treatment of the lowest concentration (Ir192 and Co60 were cytotoxic in all cases). Our investigation confirmed the radiosensitizing effect of ozone treatment. Furthermore it was shown that exclusive ozone treatment even without combined irradiation displayed a selective cytotoxic action at the ovarian carcinoma cells.

IgE cross-reactivities against albumins in patients allergic to animals.

BACKGROUND: Type I allergic symptoms and severe asthma in particular are frequently caused by animal hair/dander proteins, among which albumins are possible cross-sensitizing allergenic components. METHODS: The significance and degree of IgE-cross-reactivities against various albumins were studied in a representative number (n = 200) of patients allergic to animals with hair/dander extracts, purified albumins from different animals, and a recombinant dog albumin fragment expressed in lysogenic Escherichia coli Y1089 and purified as a beta-galactosidase fusion protein. RESULTS: Despite a high degree of sequence homology among different albumins, a remarkable variability of IgE cross-reactivities was observed, indicating that some patients were sensitized preferentially against certain albumins. Most of the patients allergic to albumins, however, reacted to dog, cat, and horse albumin, which also bound a high percentage of albumin-specific IgE. CONCLUSION: The purified recombinant dog albumin fragment, representing 265 amino acids of the mature protein, bound IgE from all 15 patients allergic to albumin tested suggesting its potential usefulness for diagnosis and perhaps therapy.

Effects of estradiol valerate on growth hormone and prolactin response to growth hormone-releasing hormone stimulation in pre- and postmenopausal women.

We investigated the relationship between the growth hormone and prolactin response to stimulation of growth hormone-releasing hormone (GHRH) and changes in body weight in pre- and postmenopausal women before and after 4 and 20 weeks of oral hormone replacement therapy (HRT). Ten postmenopausal women (with levels of follicle-stimulating hormone (FSH) of > 30 mIU/ml) were compared to ten premenopausal women suffering from post-pill amenorrhea (FSH < 10 mIU/ml). Both patient groups reported anamnestic body weight increases in the course of the former use of sex hormones. Additionally, ten postmenopausal women without anamnestic weight changes were studied. A significant reduction in the growth hormone response to GHRH was observed during the first month of HRT in women gaining weight, which was restored to pre-therapeutic levels after 6 months of HRT. A small but statistically significant increase in insulin-like growth factor (IGF)-I levels occurred in the course of HRT in all patients studied. These changes in growth hormone stimulation testing and IGF-I levels were accompanied by distinct changes in body weight. No reduction in the GHRH response was observed in those patients who did not gain body weight. Although GHRH stimulation induces a significant rise of prolactin concentrations in all patients before therapy no influence on prolactin levels could be demonstrated during HRT.