Biomedical subjects

J Spona

Publications and source records attributed to J Spona.

At least 19 recordsLinked to original sources

PubMed2006

Individual differences and repeatability of post-prandial changes of plasma-free amino acids in young horses.

Few data are available on post-prandial changes of plasma amino acids (AAs) in horses and on the repeatability and the individual variance on different sampling days. The objective of the present study was to measure pre- and post-prandial concentrations of plasma AA in 10 yearling horses. Blood samples were taken on days 1 and 40 of the study before feeding of hay, oats and soya meal and over an 8 h post-prandial period in 2-h intervals. The plasma AAs were measured by high-pressure liquid chromatography after ortho-phthalaldehyde derivatization. Mean fasting concentrations of the AAs were not significantly influenced by the individuum and sampling day. Repeatability of the fasting AA levels in the individual horses on two different sampling days was only found for histidine, 3-methylhistidine, methionine, tryptophan and taurine. While the absolute post-prandial AA concentrations differed between sampling days, the relative changes were comparable. All AA concentrations except 3-methylhistidine increased after feeding by 13% to more than 200% of their fasting values if the combined data of both days were analysed. Four hours after feeding the concentrations of arginine, asparagine, lysine, leucine, isoleucine and threonine, decreased more than 20%. Histidine, methionine, phenylalanine, valine, tryptophan, glutamine, glycine, tyrosine and taurine concentrations decreased by less than 20%. Concentrations of aspartic acid, glutamic acid, ornithine, serine and citrulline remained elevated. Most AA approached the fasting concentrations at 8 h, only glycine increased between 6 and 8 h after meal and 3-methyl-histidine concentrations were constant throughout the entire period. In conclusion, the pre-prandial plasma AA in horses appeared less influenced by individuum or sampling day than post-prandial plasma AA concentrations. Therefore, plasma AA concentrations should be interpreted only under well-defined conditions, especially regarding the feeding regimen.

Amino Acids↗

PubMed2001

Dose finding in a low-dose 21-day combined oral contraceptive containing gestodene.

An open label, non-comparative study was carried out in 22 women over a total of five cycles. After an untreated cycle, oral administration of 20 microg ethinyl estradiol (EE) with 50 microg gestodene (GST) (tablets taken daily for 21 days with a break of 7 days) was commenced, and three treatment cycles were followed by an untreated follow-up control cycle. The ability of this formulation to inhibit ovulation and suppress ovarian activity was assessed by using hormonal parameters and ultrasound. One ovulation occurred during treatment. Luteinized unruptured follicles were observed in three cases in the second treatment cycle and in one case during the third treatment cycle. Follicle-like structures larger than 13 mm associated with a serum estradiol level of more than 30 pg/mL were noted in 19% of the women in the first treatment cycle. The rate of active follicle-like structures was 43% in the second treatment cycle and 28% in the third treatment cycle. The results were compared with previously reported findings of a preparation containing 20 microg EE and 75 microg GST. With regard to ovarian grading and endogenous hormone secretion, considerably more residual ovarian activity, with all parameters examined, was found in the 20 microg EE and 50 microg GST preparation compared to the 20 microg EE and 75 microg GST preparation. It was concluded that the 20 microg EE and 50 microg GST preparation administered for 21 days does not meet the requirements of a combined oral contraceptive with respect to ovulation inhibition.

Adult↗

PubMed1999

Effect of age on the response of the hypothalamo-pituitary-ovarian axis to a combined oral contraceptive.

OBJECTIVE: To examine the effect of age on the response to treatment with a combined oral contraceptive. DESIGN: Prospective, controlled clinical study. SETTING: Reproductive medicine unit in a tertiary care university medical center. PATIENT(S): Twenty-six healthy female volunteers aged 21-45 years. INTERVENTION(S): After a control cycle, all the women were given a combined oral contraceptive containing 20 microg of ethinylestradiol with 75 microg of gestodene for three cycles. The women were examined through the posttreatment cycle. MAIN OUTCOME MEASURE(S): Pituitary and ovarian activity was assessed with ultrasound and measurement of ovarian steroids. RESULT(S): Follicular activity was observed in all treatment cycles, although ovulation was inhibited. Ovarian suppression was maximal in cycle 1. Mean endogenous E2 levels were lower during cycles 2 and 3 in the older group. Serum FSH levels were higher in the control cycle and on day 28 of the treatment cycles in the older group. Most women ovulated during the posttreatment cycle. CONCLUSION(S): Combined oral contraceptives did not inhibit all ovarian activity; maximal suppression was seen in cycle 1. Less follicular activity was observed in cycles 2 and 3 in the older group. Raised FSH levels with age reflect increasing ovarian resistance to follicular development.

Adult↗

PubMed1999

Effect of 21-day and 24-day oral contraceptive regimens containing gestodene (60 microg) and ethinyl estradiol (15 microg) on ovarian activity.

OBJECTIVE: To compare ovulation inhibition and ovarian activity with 21-day and 24-day regimens of a low-dose combined oral contraceptive (COC) containing 60 microg of gestodene and 15 microg of ethinyl estradiol. DESIGN: Interventional observational study. SETTING: Reproductive medicine unit. PATIENT(S): Fifty-eight healthy volunteers aged 18-35 years. INTERVENTION(S): Ovarian activity was monitored every other day with the use of ultrasound to measure the diameters of follicle-like structures and blood samples to measure serum concentrations of 17beta-E2 and progesterone. Subjects were observed for five cycles: pretreatment and posttreatment control cycles and three cycles in which the COC was administered for either 21 or 24 days of each cycle. MAIN OUTCOME MEASURE(S): Occurrence of ovulation and evidence of ovarian activity. RESULT(S): The study was completed by 27 (90%) of the 30 subjects who received the 24-day regimen and by 24 (79%) of the 28 subjects who received the 21-day regimen. Ovulation was inhibited in all cycles in the 24-day group and in 74 of 75 cycles in the 21-day group. Luteinized unruptured follicles were seen in no cycles with the 24-day regimen and in 6 (8%) of 75 cycles with the 21-day regimen. Mean ovarian follicular development and serum 17beta-E2 and progesterone levels were lower in the 24-day group. CONCLUSION(S): The 24-day regimen is an innovative strategy for maintaining effective ovulation inhibition at ultra-low doses of contraceptive steroids.

Adolescent↗

PubMed1998

Comparison of immunohistochemical and biochemical measurement of steroid receptors in primary breast cancer: evaluation of discordant findings.

Tumor samples of 240 patients with primary breast cancer were biochemically and immunohistochemically investigated for estrogen receptors (ER) and, in 130 of the samples, for progesterone-receptors (PgR) in order to examine reasons for discordant findings. The biochemical (DCCA) and immunohistochemical assays (ICA) yielded positivity in 71% for ER, and in 44% for PgR. Concordant ER-DCCA and ER-ICA results were obtained in 84%; two thirds of the discordant ER-findings manifested as DCCA-neg/ICA-pos. Concordance in the case of PgR amounted to 72%, and of the discordances 60% were DCCA-neg/ICA-pos. Significant association with postmenopausal status existed only for ER positivity in ICA (p = 0.01), whereas ER-DCCA, PgR-DCCA and PgR-ICA were all more or less independent of the menopausal status. The frequency of discordances was independent of menopausal status. Discordance for ER-assays increased significantly near the respective cut-off point; this was not unequivocally true for PgR-assays. The correlation of tumor types of sparse cellularity, as well as prominent stroma content ('scirrhous carcinoma') with increased frequency of the constellation DCCA-neg/ICA-pos was of borderline significance for PgR (p = 0.06), but not for ER. The percentage of discordant ER-findings, figuring as DCCA-neg/ICA-pos, was statistically significantly increased in locally advanced breast cancer (p = 0.03). Fibrocystic disease in peritumoral breast tissue had no impact on receptor-assay discordance. In any case, the models derived from theoretical thought, laboratory data and singular observations can only in part explain the discordance in steroid receptor values measured with different methods.

Adult↗

PubMed1997

Double-blind, randomized, placebo controlled study on the effects of the monophasic oral contraceptive containing 30 micrograms ethinyl estradiol and 2.00 mg dienogest on the hemostatic system.

Forty healthy female volunteers aged between 19 and 35 years (27.3 +/- 4.1 years) with normal menstrual cycles were included in a double-blind, randomized, placebo-controlled study to investigate the influence on the hemostatic system of an oral contraceptive containing 30 micrograms ethinyl estradiol in combination with 2.00 mg dienogest, which is a 19-norprogestin without a 17 alpha-ethinyl group. At baseline and during one treatment cycle, 12 hemostatic parameters were measured on cycle days 7, 14, and 21. The hemostatic parameters were categorized as either procoagulatory, anticoagulatory and profibrinolytic, or antifibrinolytic and indicative of fibrin turnover. Differences between placebo and 30 micrograms ethinyl estradiol and 2.00 mg dienogest of plasma levels of hemostatic parameters on cycle days 21 of the precycle and treatment cycle were chosen as target variables. Prothrombin fragment 1 + 2 (F 1 + 2) was chosen as the main target variable. Equivalence of F 1 + 2 between placebo and active treatment was noted. Among the procoagulatory factors, only factor VII activity was found to be increased over placebo in the active treatment group, but decreased in the placebo group. Protein C activity increased during the treatment with 30 micrograms ethinyl estradiol and 2.00 mg dienogest, and was higher than that of the placebo group in which this parameter decreased during the treatment cycle. There was a corresponding increase in fibrinolytic activity being reflected by higher plasminogen levels in the active treatment group in comparison with placebo. An increase was noted for the fibrinolytic parameter D-dimer. Apart from isolated measurements, the parameters remained in their respective normal ranges. The data combine to suggest that 30 micrograms ethinyl estradiol and 2.00 mg dienogest has a balanced effect on the hemostatic system stimulating both procoagulatory and fibrinolytic activity.

Adult↗

PubMed1997

Modulation of ovarian function by an oral contraceptive containing 30 micrograms ethinyl estradiol in combination with 2.00 mg dienogest.

Twenty-two healthy female volunteers with normal ovulatory cycles, aged between 20 and 34 years (27.3 +/- 4.1), were included in a single-center, noncomparative study to investigate the modulation of ovarian function by an oral contraceptive containing 30 micrograms ethinyl estradiol in combination with 2.00 mg dienogest. At baseline, during three treatment cycles and post-treatment, serum levels of luteinizing hormone, follicle-stimulating hormone, 17 beta-estradiol, and progesterone were assayed and ultrasonography was used to measure follicular size and the thickness of the endometrium. The primary efficacy variable was inhibition of ovulation as measured by ovarian activity grading. All volunteers ovulated during the pretreatment cycle. During treatment, none of the subjects had ovulatory cycles, although there was still some ovarian activity in several subjects. During the first treatment cycle, only 4% (1 subject) of cycles showed active follicle-like structures. The frequency of follicle-like structures increased to 33% and 35% during treatment cycles 2 and 3. The frequency of presumptive luteinized unruptured follicle-like structures was 5% (1 subject) and 15% (3 subjects) in treatment cycles 2 and 3. The serum hormone concentrations were effectively suppressed in comparison to baseline. The ovarian activity returned to baseline during the post-treatment period. One subject was excluded from further study because of a medical problem believed unrelated to use of the oral contraceptive. No serious adverse events were recorded during the course of the study. The results of the present investigation indicate that the modulatory effects on ovarian function of the monophasic oral-contraceptive containing 30 micrograms ethinyl estradiol combined with 2.00 mg dienogest lead to adequate suppression of ovarian activity and effective inhibition of ovulation.

Adult↗

PubMed1996

Shorter pill-free interval in combined oral contraceptives decreases follicular development.

The objective of the study was to determine the suppressive effect on ovarian activity of 20 micrograms ethinylestradiol plus 75 micrograms gestodene administered for 21 or 23 days. The study was designed as a double-blind, randomized, multicenter trial in 60 women. A pre-treatment cycle, three treatment cycles and a post-treatment period were monitored by ovarian ultrasound and by LH, FSH, 17 beta-estradiol and progesterone measurements every other day. No ovulation and no luteinized, unruptured follicle were observed. Suppression of ovarian activity was more pronounced by the 23-day regimen. 17 beta-Estradiol serum levels during the last six days of a cycle and during the first six days of the next cycle were significantly less (p < 0.05) in the 23-day regimen. The superiority of the 23-day regimen in comparison to the 21-day regimen with regard to the suppression of ovarian activity was shown in this study. The observed differences in the 17 beta-estradiol levels and follicular development between a 21-day and 23-day preparation combine to suggest that shortening the pill-free interval in combined oral contraceptives may increase the contraceptive safety margin in women on low-dose formulations.

Adult↗

PubMed1996

Inhibition of ovulation by an oral contraceptive containing 100 micrograms levonorgestrel in combination with 20 micrograms ethinylestradiol.

Twenty-four healthy female volunteers with normal ovulatory cycles, aged between 20 and 34 years (27.5 +/- 4.3), were included in a single-center, non-comparative study to investigate the effect on inhibition of ovulation of an oral contraceptive containing 20 micrograms ethinylestradiol in combination with 100 micrograms levonorgestrel. At baseline, during three treatment cycles and post-treatment, ultrasonography was used to examine the ovaries, to measure follicular size, and to measure the thickness of the endometrium. Serum levels of LH, FSH, estradiol, progesterone, total testosterone, free testosterone, SHBG, and CBG were also measured. Compared with treatment cycle 1, an increase in residual ovarian activity (follicle grades 4-5) was observed in cycles 2 and 3. Mean levels of LH, FSH, 17 beta-estradiol and progesterone remained suppressed during treatment. No escape ovulation was observed during the treatment phase of the study and there were no pregnancies. Ovulation was noted to return rapidly in the posttreatment cycle. Subjective and objective tolerance of the present regimen was noted to be good. Results indicate that the monophasic oral contraceptive containing 100 micrograms levonorgestrel combined with 20 micrograms ethinylestradiol effectively inhibits ovulation, providing adequate suppression of ovarian activity.

Adult↗

PubMed1995

HER-2 amplification but not butyrylcholinesterase multability reflects aggressiveness of European-originated ovarian tumors.

Tumorigenic roles were variably suggested for HER-2 and INT-2 oncogene amplifications and the "atypical" aspartate to glycine mutability in the butyrylcholinesterase (BCHE) gene in ovarian adenocarcinomas. To examine this notion we searched for correlations between these three phenomena and ovarian tumor classification and aggressiveness, using quantitative polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct PCR sequencing. Our findings revealed no alleles carrying the atypical BCHE mutability in 30 European-originated patients with ovarian tumors compared with 11% (2/18) such alleles in Israeli patients with malignant ovarian tumors. This apparently reflected population diversity rather than disease relationship. INT-2 amplification was observed in 14/94 (15%) of the European patients; however, there was no correlation between this phenomenon and clinicopathological indices in the corresponding patients. In contrast, in 94 tumor samples we found that 40% (38/94) of the cases had HER-2 amplification. Moreover, there was a highly significant correlation (P < 0.008) between the over fivefold HER-2 amplification and ovarian tumor severity. These findings demonstrate an informative value for HER-2 amplification tests in tumor DNA, but not for INT-2 amplification or BCHE mutability, for the assessment of treatment.

Base Sequence↗

PubMed1995

A prospective analysis of immunohistochemically determined hormone receptors and nuclear features as predictors of early recurrence in primary breast cancer.

The immunohistochemically determined receptor status, as well as first-generation risk factors (tumor size, lymph node status, histologic grading including subfactors, tumor histology, and biochemically determined receptor status) were prospectively analyzed in 288 cases of primary breast cancer for their impact on recurrence-free survival (RFS) and overall survival (OS) after a median observation period of 41 months. Immunohistochemically (ER-ICA) and biochemically determined estrogen receptors (ER-DCC), as well as tumor size, lymph node status, histologic grading, mitotic rate, and nuclear polymorphism, were of prognostic value for recurrence-free survival and/or overall survival. In multivariate analysis, lymph node status, tumor size, and mitotic rate proved to be independent prognosticators; ER-ICA showed significance in the univariate analysis which dropped, however, when multivariate analysis was applied. The prognostic power of histologic grading in our series seemed to depend mainly on the subfactors which relate to nuclear features.

Adult↗

PubMed1994

A comparison of the effects of two monophasic low dose oral contraceptives on the inhibition of ovulation.

Fifty-three women were randomly allocated to one of two combined low-dose monophasic oral contraceptives (20 micrograms ethinyl estradiol with 75 micrograms gestodene or 20 micrograms ethinyl estradiol with 150 micrograms desogestrel). The ability of these formulations to inhibit ovulation was compared using hormonal parameters and ovarian ultrasound. The effects on three treated cycles were compared with pre- and post-treatment cycles. No ovulations occurred in either group during therapy. Twenty-one percent of women were observed to show some follicle-like structures accompanied by raised serum estradiol in at least one treatment cycle. No significant differences between the two preparations were demonstrated on residual ovarian function. The secretion of estradiol and progesterone was significantly reduced throughout all three treatment cycles. Mean LH and FSH concentrations were comparable with both treatments. A secondary analysis of cycle control and tolerance was undertaken. Significantly less bleeding was seen in the gestodene group during cycle 2 (p = 0.02). There were no differences between the two treatments with respect to the other cycle control parameters. Approximately half the women recorded intracyclic bleeding during the first treatment cycle. This improved during cycles 2 and 3. Both formulations were tolerated well.

Adolescent↗

PubMed1994

Cystic fibrosis screening in neonates--measurement of immunoreactive trypsin and direct genotype analysis for delta F508 mutation.

This study investigated the clinical usefulness of screening for cystic fibrosis (CF) in 19,992 newborns, over 39 months, in an Austrian population. Immunoreactive serum trypsin (IRT) determination was followed by sweat chloride analysis (sweat test) to establish diagnosis. In a retrospective analysis covering 6 months of the study period, individuals who were considered to be at risk after IRT estimation (n = 22) were analysed for delta F508 mutation, using a new method of DNA extraction from the initial dried blood specimens. A total of 119 infants (0.6%) had values greater than 750 ng trypsin/ml whole blood. In 88 babies sweat tests were performed, leading to the diagnosis of CF in 11 cases. One patient was not initially identified by screening but was later discovered due to his clinical status. Three infants were noted to carry the delta F508 mutation (1 homozygous, 2 heterozygous). Two of these babies already had CF. The second heterozygote was a carrier. A highly efficient three tier screening strategy is presented in which IRT estimation, determination of delta F508 status and sweat chloride testing could lead to a high sensitivity analysis of this population.

Cystic Fibrosis↗

PubMed1994

Clinical therapy and HER-2 oncogene amplification in breast cancer: chemo- vs radiotherapy.

One hundred and five breast cancer patients with stage T3/4, N+/-, Mo were treated at random either with a pre- and postoperative chemotherapy (A) (5-drug-combination + tamoxifen) or with a pre- and postoperative radiotherapy (B). Paraffin embedded tissue samples were prepared from tumor material taken by biopsy prior to therapy as well as at surgery from patients of both groups to estimate the HER-2 oncogene copy numbers before and after treatment. In 53 and 50% of the pretherapeutic samples the HER-2 gene was amplified in groups A and B, respectively. In the post-therapeutic group 60% of the chemotherapy and 48% of the radiotherapy patients, respectively, had low or high HER-2 oncogene copy numbers. In addition, HER-2 amplification before and after therapy was estimated in 28 patients. An increase of oncogene copy numbers could be detected in 21% of the chemotherapy patients, and a decrease was noted in 11%. No radiotherapy patient showed a rise, but 11% a loss of copy numbers. Although amplification of HER-2 oncogene was not found to be associated with overall survival as it was in many studies before, it could still be a predictor of clinical outcome and the cause of mammary carcinomas developing into stage T3/4.

Adult↗

PubMed1994

Prolactin: a possible mediator of graft-versus-host disease following allogeneic bone marrow transplantation in humans.

We have evaluated post-transplant serum levels of prolactin with respect to source of donated bone marrow (BM) and to the occurrence of either acute and/or chronic graft-versus-host disease (GVHD). Forty adult patients underwent allogeneic (n = 35), autologous (n = 4) or syngeneic (n = 1) bone marrow transplantation for haematologic malignancy (n = 32) or aplastic anaemia (n = 8), respectively. Serum prolactin levels measured within 100 days post-transplant were related to patients' sex but otherwise proved unrelated to the occurrence or severity of GVHD and to the source of the BM graft (allogeneic, autologous, syngeneic). Beyond day 100 post-graft, however, serum prolactin levels proved significantly elevated in allogeneic recipients exhibiting chronic GVHD (p = 0.0004) and were unrelated to the patients' sex. In this group of patients, serum prolactin levels were not related to serum cyclosporin levels. In allogeneic recipients exhibiting no GVHD, serum prolactin levels were positively correlated with serum cyclosporin levels (p < 0.05). These data show that serum prolactin levels are significantly elevated beyond day 100 post-graft in recipients exhibiting chronic GVHD. Prolactin, a hormone recently shown also to be released by mononuclear leucocytes and to be involved in lymphocyte activation plays a hitherto unrecognized role in the pathogenesis of GVHD in humans.

Adolescent↗

PubMed1993

Inhibition of ovulation by a triphasic gestodene-containing oral contraceptive.

The minimal effective dose of gestodene for inhibition of ovulation was studied in 30 female volunteers. Daily doses of 10 micrograms to 50 micrograms gestodene were given orally for 21 days. A control cycle prior to treatment and a treatment cycle were monitored for LH, FSH, estradiol, progesterone and cervical score. At a daily dose of 40 micrograms of gestodene, 6/7 volunteers exhibited inhibition of ovulation and 1/7 had a cycle with luteal insufficiency. Ovulation was inhibited in all volunteers on 50 micrograms gestodene, suggesting that the minimum dose required to inhibit ovulation was 40 micrograms gestodene. Cervical score was blunted even at 10 micrograms gestodene. Similarly, 20 volunteers were treated with coated tablets containing ethinylestradiol/gestodene at 30/50 micrograms for 6 days, 40/70 micrograms for 5 days and 30/100 micrograms for 10 days. This triphasic gestodene-containing preparation inhibited ovulation in all 20 females. In one cycle in which follicle development was observed only 43 pg estradiol/ml was secreted. Data from this investigation suggest that this triphasic gestodene-containing OC has a high contraceptive efficacy.

Adult↗

PubMed1993

Ovulation inhibition with a combined oral contraceptive containing 1 mg micronized 17 beta-estradiol.

OBJECTIVE: To evaluate ovarian function by ultrasonography and endocrine measurements. DESIGN: Prospective, open study. SETTING: Outpatient clinic of the First Department of Gynaecology and Obstetrics, University of Vienna, Austria. PARTICIPANTS: Twenty healthy women with regular cycles and established ovulation by ultrasonography. INTERVENTION: Treatment with a combination of 1 mg micronized E2 with 150 micrograms desogestrel daily for 21 days, followed by 7 pill-free days. MAIN OUTCOME MEASURES: Transvaginal ultrasonography and estimation of E2 and P at least twice a week for two consecutive cycles, followed by one after treatment cycle. RESULTS: Ovulation inhibition was apparent in all cases and no functional ovarian cysts were observed during treatment. On a few occasions a persistent follicle was noted, but in the majority of cases there was total absence of follicular activity. The bleeding pattern showed a tendency toward prolonged and more heavy bleeding when compared with the before treatment situation. Return of ovulation was prompt in all women but one. CONCLUSIONS: Ultrasonographic observations, accompanied by P and E2 measurements, allow us to conclude that the combination of 1 mg E2 with 150 micrograms desogestrel provides complete ovulation inhibition. However, the bleeding pattern does not show an acceptable profile.

Adult↗

PubMed1993

Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.

In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.

Animals↗