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Biomedical subjects

K Diedrich

Publications and source records attributed to K Diedrich.

At least 73 records · Page 4Linked to original sources
PubMed2003

No influence of body weight on pregnancy rate in patients treated with cetrorelix according to the single- and multiple-dose protocols.

The question of whether adjustment to body weight is necessary in in-vitro fertilization (IVF) cycles using GnRH antagonists is currently under discussion. Therefore, a data analysis of five prospective studies using either the single- or the multiple-dose antagonist protocol with cetrorelix (Cetrotide) was performed. The influence of stimulation procedure, gonadotrophins and body weight on pregnancy rate was evaluated in a linear logit model. The effect of the stimulation procedure and body weight on the cumulus-oocyte complex (COC) and follicle number was explored in an ANOVA model. Cetrorelix plasma concentrations were tested for any correlation with body weight. Baseline and outcome parameters in different body weight groups (<50 kg, 50-59 kg, 60-69 kg, 70-79 kg, > or =80 kg) were assessed for human menopausal gonadotrophin and recombinant human FSH stimulation separately. Cetrorelix plasma concentrations were correlated with body weight, but no influence of the type of stimulation or body weight on pregnancy rate was found. Body weight did not influence cetrorelix plasma concentrations. In contrast, body weight significantly influenced the number of retrieved COC as well as the number of follicles on the day of human chorionic gonadotrophin administration. Body weight does not influence the outcome of treatment in cetrorelix cycles.

Body Weight↗
PubMed2003

Developments in drugs for ovarian stimulation.

Drugs for ovarian stimulation have been improved during the last decades. Initially gonadotrophins were extracted from human pituitary glands and urine; nowadays they are produced from transformed cell-lines. All three gonadotrophins--follicle stimulating hormone (FSH), luteinizing hormone (LH) and human chorionic gonadotrophin (hCG)--are now marketed as recombinant (r-) products. The near-100% pure FSH preparations might, in some situations, cause abnormally low LH levels and it is likely that the addition of LH may be beneficial in these situations. It is possible that r-LH will become available in sufficient dosages to replace hCG for ovulation induction and this may reduce the incidence of ovarian hyperstimulation syndrome due to its shorter half-life. In parallel to the development of gonadotrophin preparations, protocols for ovarian stimulation are now more comfortable for the patients, especially with the introduction of gonadotrophin receptor hormone (GnRH)-agonists in the early 1980s and, more recently, the introduction of GnRH-antagonists.

Chorionic Gonadotropin↗
PubMed2003

[Enhanced liposomal transfection through the application of sex steroids in gynecological cancer cells].

OBJECTIVE: Liposomal transfection in gene therapeutic application against gynecological malignoma does not reach satisfying efficacy. A desirable goal would be the specific intensification of transfection in these kind of cells. Steroids have successfully been used in other systems to increase liposomal transfection and hopefully there might be a specific impact of sexual steroids in cells from high sex steroid receptor expressing malignoma, like some mamma- and endometrium cancer. MATERIAL AND METHODS: The mamma carcinoma cell line T-47D was transfected with the transfection agent DOTAP and cyclodextrin solubilized steroids and cholesterol were co-applied. The efficiency of transfection was followed by luciferase activity resulting from the transfected reporter gene. RESULTS: Like cholesterol, which is already established as transfection co-agent, also the steroids progesterone, estrogen, testosterone and hydrocortisone provoked a clear increase in transfection efficiency shown in a dose dependent manner. CONCLUSIONS: These results indicate the usefulness of steroids as additives for liposomal transfection procedures in gene therapeutic application. As sexual steroid receptors migrate into the nucleus of a cell after binding its specific ligand a targeted enhancement of transfection is supposable in malignoma overexpressing steroid receptors. There is evidence that plasmid DNA can be co-transported with nuclear proteins into the nucleus.

Breast Neoplasms↗
PubMed2003

[Impact of the cellular estradiol response on the therapeutic inhibition of growth factor signaling].

Cellular response to estradiol stimuli ist mediated by different signal transduction cascades. In addition to classical mechanisms like the activation of estrogen response elements, there is increasing interest in the so-called non- nuclear actions of estrogens. It has been shown, that the estradiol-induced activation of cytoplasmic kinases is an important alternative mechanism of the cellular estradiol response. Consequently, the question has been raised, whether estradiol-induced activation of growth factor signaling would be able to interfere with the action of antitumoral substances directed against receptor-tyrosine kinase signal transduction. Recent data demonstrated, that estradiol is able to diminish the effects of antitumoral drugs targeting the HER2 receptor in vitro. Novel insights into the non-nuclear estradiol response and its impact on the efficacy of antitumoral drugs observed in endometrial tumor cells are reviewed.

Antineoplastic Agents↗
PubMed2003

[Cumulus cell apoptosis as a predictor for oocyte quality in artificial reproduction technique].

OBJECTIVE: To be able to predict the success of ART reliable tests for determining the quality of the oocytes are necessary. Apart from a vague morphologic assessment via microscopy a direct analysis of the oocyte quality is not possible. Because of the very close relation between the oocyte and the cumulus cells the analysis of the cumulus cells might give sufficient information on the oocyte quality. In this study we correlate the apoptotic activity of cumulus cells to the outcome of fertilized oocytes after Intracytoplasmic Sperm Injection (ICSI). MATERIAL AND METHODS: 246 cumulus-oocyte-complexes from patients undergoing infertility treatment with the ICSI procedure were individually collected. The comet assay was used to determine the proportion of apoptotic cells within the cumulus population of each oocyte and correlated with oocyte fertilization and oocyte quality as well as with pregnancy outcome in 86 patients. RESULTS: We were able to show that high quality embryos correlate to a low rate of apoptotic cells in their corresponding cumuli. Differences regarding the pregnancy outcome were statistically not significant. CONCLUSIONS: Our results on cumulus cell apoptosis and embryo quality confirm other publications. To arrive at statistically proven criteria for the further development of single oocytes an increase in the number of analyzed patients is necessary.

Apoptosis↗
PubMed2003

[Retrospectively experiencing the menopause in Germany and in Papua New Guinea: a comparative report].

INTRODUCTION: The objective of this study was to examine the experience of menopause in postmenopausal women from Germany and in postmenopausal women from Papua New Guinea. METHODS: Experience of menopause were assessed by formation of symptom groups (e. g. hot flushes, cardiac or sleeping trouble, depression, touchiness, drop in performance, vaginal dryness, painful joints or muscles), following the Menopause Rating Scale (MRS). Apart from the translated English version a questionaire in Pidgin English was offered. Questions about positive and negative experience of menopause and the acceptance of hormonal replacement therapy were included. Statistical analysis was performed both descriptively and for the group analyses the Chi-squared-test and the Mann Whitney's U test. RESULTS: 40 postmenopausal German women and 41 postmenopausal women from Papua New Guinea were asked about their experience of menopause. The German women were 58.7 years old (range from 52 to 62) and had two children on average (range from 0 to 4). 87.7 % had experience of symptoms. In Papua New Guinea mean age was 55.2 years (range from 48 to 70), parity six (range from 2 to 12). 76.9 % had experience of symptoms. There were significant intercultural differences between the experience of depressive mood, general drop of performance, sexual experience and the vaginal dryness and we found no significant intercultural differences between the experiences of hot flushes, cardiac trouble, sleeping trouble, nervousness and urological symptoms. 50 % of the German women take hormonal replacement therapy and nobody of Papua New Guinea. CONCLUSION: The experience of menopause as seen in the developed countries does not exist in the developing countries. The perception about illness and well-being are formed by culturally produced patterns.

Attitude to Health↗
PubMed2003

[The use of oral antidiabetic drugs in the treatment of polycystic ovary syndrome].

The polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is a complex metabolic-endocrine disorder with severe long-term health consequences like type 2 diabetes. The increased risk for cardiovascular diseases in women with PCOS is due to diabetes, adipositas and dyslipidemia. Insulin resistance plays a key role in the pathophysiology of this syndrome. This makes the use of oral antidiabetic drugs most compelling. The majority of studies have shown amelioration of the typical symptoms like hyperandrogenism and cycle irregularities. Ovulation and pregnancy rates increased. Furthermore these drugs might be cardioprotective by improving insulin sensitivity and reduce the risk for type 2 diabetes. This article reviews the use of different oral antidiabetic drugs in the treatment of PCOS and their influence on fertility, the risk for type 2 diabetes and cardiovascular diseases.

Acarbose↗
PubMed2003

Interactions of insulin-like growth factors and estradiol in rat pituitary gonadotrophs.

Insulin-like growth factors are involved in the regulation of gonadotropin secretion. Insulin-like growth factor I (IGF-I) has an augmenting effect on gonodotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) release from female rat gonadotrophs that is facilitated by estradiol. To identify the underlying mechanisms, we investigated whether IGF-I influences total LH pool and the production of intracellular inositol phosphate. In another series of experiments we tested whether IGF-II and estradiol affect LH release of gonadotrophs. Pituitary cells were incubated with 100 pM IGF-I and/or 100 pM estradiol for 24 h. They were stimulated, partially in the presence of Wortmannin, an inhibitor of phosphoinositide 3-kinase, with 330 pM GnRH for 3 h. Subsequently, total LH pool (released and remaining hormone content in lysed cells) in cultures was measured. Intracellular inositol trisphosphate of alphaT3-1 cells, a gonadotrope cell line, treated with estradiol and IGF-I as described before and stimulated with 100 nM GnRH for 15 min was analyzed by ion exchange chromatography. To determine the interaction of IGF-II and estradiol on GnRH-stimulated LH secretion, cells were treated with increasing concentrations of IGF-II (0.05 pM-10 nM) and 100 pM estradiol. IGF-I significantly increased the accumulation of inositol trisphosphate in basal and GnRH-stimulated cells. IGF-I, estradiol, or their combinations did not change total LH pool, although they enhanced LH secretion. Wortmannin abolished the positive effects of IGF-I and estradiol on LH secretion. IGF-II alone increased basal, but not GnRH-induced LH secretion at low concentrations (0.05 pM). Additional estradiol treatment further increased basal, but not GnRH-induced LH secretion. In conclusion, our results suggest that increased LH secretion from female anterior pituitary cells after IGF treatment is due to the amplification of early signal transduction steps rather than changes in LH pool. The inositol trisphosphate signaling pathway is involved in the regulation of LH secretion from gonadotrophs treated with IGF-I. It is not likely that IGF-II plays an important role in the regulation of gonadotropin secretion.

Animals↗
PubMed2003

Ductal carcinoma in situ of the breast: diagnosis and management.

Currently, no precise morphologic or biologic prognostic factors reliably identify patients with ductal carcinoma in situ (DCIS) who are at high risk of disease progression. DCIS is a disease with an extremely favorable prognosis and a small likelihood of dying from breast cancer, regardless of what type of treatment is received. No retrospective or prospective study to date has demonstrated a significant difference in breast cancer specific mortality regardless of treatment. The similarities between DCIS and invasive cancer suggest that an important area for future research should be elucidating the processes that can either unleash or contain the invasive potential of DCIS cells. Thus, an understanding of the biology of DCIS can assist in the prevention, the assessment, and the diagnosis of invasive breast cancer.

Breast↗
PubMed2003

Actions of GnRH antagonists on IGF-II, IGF-binding protein-2 and pregnancy-associated plasma protein-A in human granulosa-lutein cells.

OBJECTIVE: Recently, GnRH antagonists (GnRHants) have been introduced for the prevention of premature LH surges during controlled ovarian hyperstimulation (COH). Here we investigated whether the GnRHants cetrorelix and ganirelix exert effects on the human ovarian IGF system. Since controversy exists on the action of GnRH agonists in the human ovary, we also tested the effect of triptorelin on IGF-II, IGF-binding protein-2 (IGFBP-2) and pregnancy-associated plasma protein-A (PAPP-A) in cultured human granulosa-lutein cells. DESIGN: In vitro cell culture study in a research laboratory of a university hospital. PATIENTS: Cells were obtained from patients treated with different protocols of COH. In addition to gonadotropins they received triptorelin or cetrorelix. Cells were treated with triptorelin, cetrorelix or ganirelix, 1 nmol/l each, for 48 h. IGF-II, IGFBP-2 and PAPP-A were measured by RIA and enzyme immunoassay respectively. RESULTS: GnRHants and triptorelin did not affect IGF-II, IGFBP-2 or PAPP-A. CONCLUSIONS: We conclude that GnRHants do not exert any significant effects on the IGF system of granulosa-lutein cells and therefore their introduction into protocols of COH is unlikely to impair ovarian function.

Cells, Cultured↗
PubMed2002

Preparation of cycles for cryopreservation transfers using estradiol patches and Crinone 8% vaginal gel is effective and does not need any monitoring.

Supernumary pronucleated stage oocytes (PN) can be cryopreserved and later transferred in spontaneous, stimulated or artificial cycles. In this study, we re-evaluated 342 artificial cycles with a transdermal estradiol release system (Estraderm TTS 100) in combination with a vaginal progesterone delivery system (Crinone 8%). Endometrial thickness and serum estradiol on day 14 were correlated with clinical and ongoing pregnancy rates. Endometrial thickness between 7 and 15 mm did not relate to significantly different pregnancy rates. The estradiol serum level did not predict success. In conclusion, this method of endometrial preparation is comfortable for patients and monitoring is unnecessary.

Administration, Cutaneous↗
PubMed2002

Luteal phase support using either Crinone 8% or Utrogest: results of a prospective, randomized study.

The Crinone 8% preparation makes it possible to administer natural progesterone (90 mg) vaginally once daily for luteal phase support (LPS). Until now, no prospective, randomized studies have directly compared this new preparation with widely used Utrogest capsules, which were originally designed for oral administration but are used routinely as a vaginal preparation. A prospective, randomized study investigated 126 patients undergoing cycles of in vitro fertilization (IVF) and IVF/intracytoplasmic sperm injection (ICSI). Patients received either Crinone 8% (n = 73) vaginally once daily or two Utrogest capsules (n=53) vaginally three times daily (600 mg). Clinical pregnancy rates were comparable (28.8 versus 18.9%), as were clinical abortion rates until 12 weeks of gestation (14.3 versus 10.0%) and clinical ongoing pregnancy rates (24.7 versus 17.0%) in the Crinone 8% and Utrogest groups, respectively. Forty-seven non-pregnant patients were randomly selected to answer questions regarding comfort during LPS. Crinone 8% had a clear advantage over Utrogest as it resulted in less vaginal discharge (P < 0.01) and fewer application difficulties (P<0.05). Twenty patients familiar with the alternative preparation from a previous cycle also noted that Crinone 8% was easier to apply (P < 0.01) and less time consuming (P < 0.05) to use than Utrogest.

Abortion, Spontaneous↗
PubMed2002

Plasma and follicular fluid concentrations of LHRH antagonist cetrorelix (Cetrotide) in controlled ovarian stimulation for IVF.

Cetrorelix was administered in differing daily dosages for controlled ovarian stimulation. The dosage levels were 3 mg (9 cycles), 1 mg (19 cycles), 0.5 mg (43 cycles), 0.25 mg (46 cycles) and 0.1 mg (7 cycles). In the 3 mg, 1 mg and 0.5 mg group the respective median plasma concentrations of cetrorelix on the day of oocyte pick-up (OPU) were 2.10 ng/ml, 1.42 ng/ml and 0.88 ng/ml and 1.03 ng/ml, 0.46 ng/ml and 0.49 ng/ml on the day of embryo transfer (ET). In the 0.25 mg and 0.1 mg groups plasma cetrorelix levels were below the limit of quantification. The cetrorelix concentrations in follicular fluid (FF) in the 0.25 mg group were detectable in only 14 out of 44 samples, while in the 0.1 mg group no detectable concentrations could be obtained. We also examined 80 cycles after single doses of 5 mg (7 cycles), 3 mg (42 cycles), and 2 mg (31 cycles) cetrorelix. On the day of OPU the respective median plasma concentrations of cetrorelix were 0.57 ng/ml, 0.62 ng/ml, and 0.56 ng/ml, and 0.61 ng/ml and 0.28 ng/ml on the day of ET in the 5 mg and 3 mg groups. In the 2 mg group, the plasma concentrations fell to below limits of quantification in 8/9 samples on the day of ET. In 26 out of 27 FF samples cetrorelix was detectable in the 3 mg single dose group (median level: 0.69 ng/ml).

Adult↗
PubMed2002

Comparison of ductus venosus blood flow waveform indices of 607 singletons with 133 multiples at 10-14 weeks gestation. An evaluation in uncomplicated pregnancies.

Abnormal flow profiles in the ductus venosus during early pregnancy may aid in diagnosing chromosomopathies, malformations, congenital heart disease, and twin-twin transfusion syndrome in monochorionic twins. Whereas reference values of ductus venosus flow velocities and waveform indices for the late first and early second trimester have been reported in singletons, similar reference values for multiple pregnancies have not been established in this age group. Therefore, the aim of the present ultrasound study in 119 multichorionic and 14 monochorionic multiples in human fetuses between 10-14 weeks of gestation was to establish reference values for ductus venosus flow waveform indices for multiple pregnancies. Data in multiples were compared with those of 607 singletons. Analysis of the ductus venosus (DV) flow velocity waveforms consisted of the calculation of the pulsatility index (PIV) and peak velocity index (PVIV) for veins. Comparing the data of singletons and multichorionic multiples, no statistically significant differences were observed between the two groups in any of the assessed Doppler parameters. The DV Doppler parameters of the 14 monochorionic twins that were analysed separately in order to avoid any potential bias from preclinical twin-twin transfusion syndrome were also found within the normal ranges. In the study population fetal heart rate did neither significantly correlate with PIV nor with PVIV. PIV and PVIV decreased from 10 to 14 weeks gestation. A 2.9% rate of absent or reverse flow during atrial contraction in normal fetuses at 10-14 weeks gestation was found and needs to be taken into consideration when this pattern is defined abnormal in screening tests for fetal chromosomopathies or congenital heart disease.

Blood Flow Velocity↗
PubMed2002

Laparoscopic management of ovarian dermoid cysts. A series of 83 cases.

We did a retrospective survey of 83 patients who had laparoscopic removal of a benign dermoid cyst in our hospital since 1994. Preoperative transvaginal sonography led to the correct diagnosis in 57 cases (69%). In 59 cases cystectomy with ovarian conservation was performed; spillage of cyst contents occurred in 39 cases (66%). Salpingo-oophorectomy was performed in 24 patients with spillage in 8 cases (24%). The mean tumor size (n=83) was 4.5+/-1.6 cm and 4.9+/-2.8 cm for unspilled and spilled cysts, respectively. The tumor was placed in an endobag in 62 cases. No intra- or postoperative complications occurred. No case of chemical peritonitis was noted.

Adult↗
PubMed2002

Gonadotrophin-releasing hormone (GnRH) and GnRH agonists: mechanisms of action.

The hypothalamic decapeptide gonadotrophin-releasing hormone (GnRH) binds to specific receptors on pituitary gonadotrophs. These receptors belong to the family of G protein-coupled receptors. Their activation leads to phosphoinositide breakdown with generation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and diacylglycerol. These second messengers initiate Ca2+ release from intracellular stores and activation of protein kinase C, both of which are important for gonadotrophin secretion and synthesis. Prolonged activation of GnRH receptors by GnRH leads to desensitization and consequently to suppressed gonadotrophin secretion. This is the primary mechanism of action of agonistic GnRH analogues. By contrast, GnRH antagonists compete with GnRH for receptors on gonadotroph cell membranes, inhibit GnRH-induced signal transduction and consequently gonadotrophin secretion. These compounds are free of agonistic actions, which might be beneficial in certain clinical applications.

Female↗