Biomedical subjects

D Wallwiener

Publications and source records attributed to D Wallwiener.

At least 19 recordsLinked to original sources

PubMed2003

Local and systemic tolerability of magnesium sulphate for tocolysis.

An open-label, randomised, parallel-group, study was conducted in three study centres in women with premature labor and indication for a single agent intravenous tocolysis therapy with magnesium sulphate. The aim of this study was to examine the local and general tolerability and side-effects of magnesium sulphate for tocolysis. Furthermore, we tested the tolerability of a ready-for-use magnesium solution. No measurements of efficacy were performed during this study. Initially, patients received a loading dose of 4.0 g magnesium sulphate administered over 30 min. Thereafter, a continuous intravenous infusion of 1-2 g magnesium sulphate per hour up to 21 days was given. Venous score (Maddox), vital signs, adverse events as well as general tolerability (assessed by investigator and patients) and blood parameters were assessed. We showed good local and systemic tolerability of high dose magnesium sulphate for tocolysis. Only seven patients (15%) were withdrawn from the study prematurely due to minor adverse events. Potential serious complications of MgSO(4) such as respiratory arrest or clinically relevant respiratory depression were not observed. The most frequently reported local adverse events were injection site pain, itching, erythema, swelling, induration and palpable venous cord. The most common systemic adverse events considered to be possibly related to the study drugs involved the nervous system (dizziness) followed by the digestive system (nausea, constipation). Systolic and diastolic blood pressure changed only slightly during the treatment. Respiratory rate and body temperature remained stable also. Toxic magnesium levels (>2.5 mmol/l) were not observed. The assessment of the clinical investigators with regard to tolerability was very good or good in 72.5% of the patients. The introduction of the ready-to-use solution has the advantage of eliminating the need to mix the solution prior to administration. This means a lower risk of overdose and contamination.

Adult↗

PubMed2003

Effects of tibolone on human breast cancer cells and human vascular coronary cells.

Tibolone is a synthetic progestin with estrogenic and progestogenic properties, used to alleviate menopausal syndromes and for osteoporosis prophylaxis in postmenopausal women. However, only little data are available on tibolone and breast cancer risk and on the effects of tibolone on the cardiovascular system. Therefore, in the present in vitro study, we investigated the effect of tibolone on the growth of the human breast cancer cell line, MCF-7, and on the direct effects of tibolone on the vasculature, i.e. human female coronary endothelial and smooth muscle cells. In the breast cancer cell experiments, tibolone was examined alone and in the presence of 0.1 nM estradiol in the concentration range from 0.001 microM to 1 microM. Tibolone lead to significant cell growth in the concentration range of 0.01 micro M to 1 microM and was not able to inhibit estradiol-induced proliferation at the concentrations of 0.01 microM and 0.1 microM. In the vascular endothelial cell culture experiments, tibolone was tested at the concentrations 0.1 microM, 1 microM and 10 microM. Tibolone reduced the synthesis of endothelin as well as the concentrations of E-selectin, PAI-1 and pro-MMP-1. The magnitude of the effects on these markers varied and was in the range of 11%-42%. Concerning smooth muscle cells, tibolone elicited no changes in the proliferation compared to control values. These data suggest that tibolone does have tumour cell-growth promoting effects in vitro. However, tibolone can positively influence the synthesis of markers in cell cultures of human female coronary artery, which modulate vascular tone and which play a decisive role in the various stages of atherosclerosis. Drawing a clinical consequence from our experiments would result in not recommending the use of tibolone in postmenopausal women at high risk for breast cancer development until long-term controlled clinical studies have been performed on the effect of tibolone administration and breast cancer risk. Experimental studies, such as the present one, are useful to explore mechanisms, but clearly cannot replace clinical studies.

Breast Neoplasms↗

PubMed2003

The laser diffractoscope - a new and fast system to analyse red blood cell flexibility with high accuracy.

Red blood cell (RBC) flexibility is one of the determining parameters of the microcirculation. As capillaries are smaller in diameter than RBC, RBC can only pass through by deformation. Reduced flexibility is associated with a reduced microcirculation. In obstetrics, pre-eclampsia and intrauterine growth retardation are regarded as diseases exhibiting a reduced microcirculation. With this new system it might be possible to achieve new data concerning the microcirculation in these diseases. The laser diffractoscope is based on laser light diffraction and computer-assisted image analysis. It offers the ability to determine the flexibility of RBC in whole blood with high accuracy between 0 and 30 Pa. Two hundred microlitres of whole blood are required, and the analysis is carried out in less than 5 min, with a standard deviation < or =1%. The laser diffractoscope is a new system which offers the ability to measure RBC deformability with high accuracy in a short time. Evaluation of reproducibility and validity, as well as comparison with data from other measuring systems, proves the excellence of the laser diffractoscope. An example of its application is shown by analysing the deformability of RBC in 10 uncomplicated pregnancies at term.

Erythrocyte Deformability↗

PubMed2003

Effect of tamoxifen and 2-methoxyestradiol alone and in combination on human breast cancer cell proliferation.

Endocrine therapy is widely accepted for the treatment of hormone receptor-positive breast cancer. However, in many cases eventually resistance will develop and tumor regrows. Combination therapy may be one way to resolve this problem. In the present study we investigated the effect of a combination of the widely used antiestrogen tamoxifen with the endogenous estradiol metabolite 2-methoxyestradiol (2-ME) on the proliferation of human estrogen receptor-positive and receptor-negative breast cancer cells. The receptor-positive cell line MCF-7 and the receptor-negative cell line BM were treated with 4-hydroxytamoxifen (4-OHTam) and 2-methoxyestradiol in the concentration range of 0.8-25 microM alone and equimolar combinations for 4 days. The proliferation of the cells was determined using the ATP-chemosensitivity test.4-Hydroxytamoxifen inhibited proliferation of MCF-7 and BM cells with IC(50) values of 31 and 10 microM, the corresponding figures for 2-methoxyestradiol were 52 and 8 microM. The combination showed IC(50) values of 6 microM and 4 microM. These results indicate that a combination of tamoxifen with 2-methoxyestradiol showed an additive inhibitory effect concerning the proliferation of estrogen receptor-positive and receptor-negative breast cancer cell lines. Thus a combination of these substances may allow ameliorating of adverse events of tamoxifen by reducing its concentrations and probably also drug resistance and should be tested in clinical trials.

2-Methoxyestradiol↗

PubMed2003

Statins can inhibit proliferation of human breast cancer cells in vitro.

The effect of five statins, i.e. atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin was investigated on the proliferation of the human breast cancer cell line MCF-7. All statins except of pravastatin were able to inhibit cell proliferation up to 90 % at a concentration of 50 micro M. Between the effective statins no significant difference was observed indicating a class-specific effect. These data suggest that statins may have clinical significance in the primary prevention of human breast cancer beyond their cholesterol-lowering effect. However, clinical proof must be awaited before drawing any further conclusions.

Breast Neoplasms↗

PubMed2003

The effect of progesterone and synthetic progestins on serum- and estradiol-stimulated proliferation of human breast cancer cells.

The results from the Women's Health Initiative study on enhanced breast cancer risk in postmenopausal women using an estrogen/progestin combination clearly indicate the need for a comparison of different progestins with regard to cancer risk. To shed some light on this issue, we have investigated the influence of progesterone and various synthetic C19- and C21-progestins on cell proliferation of a human breast cancer cell line in vitro. Of special interested was the comparison of two different regimens commonly used in HRT, sequential and continuous combination with estradiol. We used the human breast cancer cell line MCF-7 as a model. Progesterone (P), chlormadinone acetate (CMA), dienogest (DNG), gestodene (GSD), 3-ketodesogestrel (KDG), levonorgestrel (LNG), medroxyprogesterone acetate (MPA), and norethisterone (NET) were investigated in the range of 0.01nm to 10 micro M alone and in combination with 10 nM estradiol. Cell proliferation was measured after 7 days using the ATP chemosensitivity test. Tested alone, CMA, DNG, GSD, KDG, MPA and NET significantly stimulated cell proliferation, but only at high dosages. Sequentially combined with estradiol, only CMA inhibited cell proliferation over the whole concentration range. Slight effects were found for DNG, GSD and KDG, whereas P and MPA only showed an effect at the highest concentration. NET had no significant effect on cell proliferation. Continuously combined, all progestins exhibited an inhibitory effect over the whole concentration range. The most prominent effects were found for P, CMA, GSD, and KDG. Only slight effects were found for DNG, MPA and NET. Our in vitro results indicate that the influence on breast cancer risk using HRT in postmenopausal women might depend on the type of progestin used as well as on the regimen applied. However, the net inhibitory in vitro effect of the progestins at clinically relevant dosages is rather minimal, and whether progestins in general can reduce breast cancer risk in long-term treatment remains uncertain. Further clinical trials are urgently needed to clarify this issue.

Analysis of Variance↗

PubMed2002

Wnt-7a is upregulated by norethisterone in human endometrial epithelial cells: a possible mechanism by which progestogens reduce the risk of estrogen-induced endometrial neoplasia.

Progestogens are added to oestrogen in hormone replacement therapy regimens to reduce the risk of endometrial cancer. We have performed in vitro studies analysing gene expression of isolated normal endometrial epithelia cells (NEE) treated with estradiol and the progestogen norethisterone acetate (NETA). We report here for the first time upregulation of the Wnt-7a gene by NETA in estrogen treated NEE. Wnt genes are a large family of developmental genes associated with cellular responses such as oncogenesis. We therefore suggest that upregulation of Wnt-7a may be associated with the antineoplastic effects of progestogens on the endometrium.

Cells, Cultured↗

PubMed2002

A multicenter survey of complications associated with 21,676 operative hysteroscopies.

OBJECTIVE: The following study analyses the hysteroscopic experience of multiple gynecologic centers throughout Germany in regard to the incidence of complications, the therapy of these complications and anesthesiological management during 21,676 hysteroscopic procedures. METHODS AND MATERIAL: Under the supervision of the German Society of Gynecology Endoscopy, 92 hysteroscopic centers were evaluated and the following information was collected: hysteroscopic experience in years, number of surgical hysteroscopies per year, total number of operative hysteroscopies, types of hysteroscopic procedures, intra- and post-operative complications. RESULTS AND CONCLUSION: The results of the study show that in most German centers, hysteroscopy is just being established. Nevertheless, the rate of complications such as perforation of the uterus, fluid-overload syndrome, infection and perioperative bleeding is small. This may be due to the high proportion of documented procedures performed by the more experienced centers.

Blood Loss, Surgical↗

PubMed2002

The role of neoadjuvant chemotherapy and interval laparotomy in advanced ovarian cancer.

Radical debulking surgery allows for optimal cytoreduction in less than 50% of patients with advanced ovarian cancer. In spite of highly efficient chemotherapeutic regimens, the prognosis of patients with residual tumor masses larger than 1 cm in diameter following staging laparotomy is very poor. This observation led to the initiation of numerous trials evaluating the feasibility and efficiency of the use of primary chemotherapy followed by interval laparotomy in women with advanced ovarian cancer. The available data is presented and discussed in this review.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Large-core needle biopsy for diagnosis and treatment of breast lesions.

PURPOSE: Large-core needle biopsy (LCNB) has become a more widely used technique in the evaluation of breast lesions. This study was undertaken to access the accuracy of percutaneous LCNB on breast lesions and the impact on further proceeding. METHODS: A retrospective review of imaging-guided LCNB of 159 breast lesions was done. 143 LCNB were taken with ultrasound guided automated spring gun biopsy and 16 stereotactic-guided with vacuum-assisted biopsy device. Histology and morphobiological parameters were compared with subsequent material from surgery. RESULTS: In 113 core biopsies (71%), an infiltrating breast cancer was diagnosed, 5 biopsies (3%) yielded in-situ/atypical lesions and a benign lesion was shown in 38 cases (24%). In 3 cases, insufficient/necrotic material was obtained. 108 patients underwent subsequent surgery. In 100/108 cases (93%), histology on LCNB and surgery was identical. LCNB was false negative in 5 core biopsies (5%). Immunhistochemical stains of hormone receptors, bcl-2, c-erbB-2, p53 and MIB-1 was comparable on LCNB and on surgical material. Based on the results of LCNB, 17/113 patients (15%) with infiltrating carcinoma were primarily treated with hormones or with neoadjuvant therapy. 32/38 patients (84%) with benign lesions were followed up by imaging control. CONCLUSIONS: In patients with benign lesions on imaging, open biopsies can be avoided by LCNB. In patients with biopsy proven carcinoma, therapy planning is improved. The addition of morphobiological parameters allows early individual treatment.

Adenocarcinoma, Mucinous↗

PubMed2002

Prenatal diagnosis and perinatal management of left coronary artery to right atrium fistula.

Serious complications due to coronary artery fistulae have been described. Most authors recommend early intervention at the time of diagnosis. We present a case of a fistula originating from a dilated left coronary artery and draining into the right atrium, which was diagnosed prenatally by color Doppler echocardiography. During pregnancy, the echocardiographic findings remained unchanged, and there were no signs of heart failure. After birth, the fistula was confirmed by angiography. Additionally, a persistent left superior vena cava draining into the coronary sinus and a very small ventricular septal defect were detected. The fistula was closed successfully by transcatheter coil embolization. At 17 months old the child was in good clinical condition. Prenatal diagnosis of coronary artery fistulae may be possible and may improve perinatal management and outcome.

Adult↗

PubMed2002

Clinically significant persistence and enlargement of an antenatally diagnosed isolated choroid plexus cyst.

Isolated choroid plexus cysts are usually diagnosed at the time of screening ultrasonography during the second trimester. While they raise the question of underlying chromosomal abnormalities, their clinical course is almost invariably benign with complete resolution often by the third trimester. We report the highly unusual case of a choroid plexus cyst diagnosed at 14 weeks of gestational age with subsequent further enlargement of the cyst, necessitating postpartum neurosurgical intervention.

Adult↗

PubMed2002

[CD80-modified tumor cell lines: implications for cell-based vaccinations in breast cancer patients].

A number of genetic alterations are required for malignant transformation. However, these mutations provide the source for tumor-associated antigens which can be recognized by cellular effectors of the immune system. Recent advances in tumor immunology - such as the improved understanding of antigen presentation as well as T cell activation - have opened new perspectives for cancer immunotherapy. The advantage of using tumor cell based vaccines is that these comprise the complete antigen pool of an individual tumor for activating polyclonal immune responses. However, the induction of antigen-specific immune responses is impaired by the fact that T cell activation is depending on additional nonspecific costimulatory signals provided by the antigen-presenting cell. The majority of solid human tumors does not express costimulatory molecules and is unable to deliver all signals required for T cell activation. In contrast, tumors often induce immunologic tolerance. Therefore, the introduction of genes encoding costimulatory molecules such as CD80 or cytokines is aimed at conferring the immunostimulatory potential of tumor cells. We have undertaken efforts at endowing a breast carcinoma cell line expressing at least seven known tumor associated antigens with immunostimulatory competence by CD80 gene transfer. In preclinical studies this cell line was demonstrated to induce specific immune responses. We designed a phase I/II trial to administer the CD80-modified cell line to patients with metastatic breast cancer to determine the toxicities of the vaccination protocol and nature of the vaccine-induced immune response.

Antigens, CD↗

PubMed2002

Reduced red blood cell deformability, an indicator for high fetal or maternal risk, is found in preeclampsia and IUGR.

OBJECTIVE: Red blood cell (RBC) deformability is one of the factors determining microcirculation. In preeclampsia (PE) and some cases of intrauterine growth restriction (IUGR), microcirculation appears to be reduced. The aim of the study is to examine whether there are differences in RBC deformability in uncomplicated pregnancy when compared to pregnancies complicated by PE and/or IUGR. MATERIAL AND METHODS: RBC deformability of 87 pregnant women with initially normal pregnancies was evaluated with the laser diffractoscope. RBC deformability was measured beginning in week 16 of gestation up to 5 days after delivery. Thirty-seven women had an uncomplicated pregnancy. In addition, RBC deformability of 10 nonpregnant women was measured on days 5 and 22 of their menstrual cycle. RBC deformability of women with preeclampsia (PE, N=15), intrauterine growth restriction (IUGR, N=17), or PE plus IUGR (N=17) was measured weekly, beginning with the onset of clinical symptoms, up to 5 days after delivery. RESULTS: In early uncomplicated pregnancies, RBC deformability does not differ from the nonpregnant state. At week 30 of gestation, there is a slight decrease in RBC deformability followed by a return back to the values of nonpregnant women after delivery. Women with PE and/or IUGR show reduced RBC deformability. This is most pronounced in cases with severe fetal or maternal complications. After delivery, RBC deformability also returns to nonpregnancy values within 5 days. CONCLUSION: Reduced RBC deformability may contribute to a reduced microcirculation in PE and IUGR. Increasing RBC deformability therapeutically in these cases could offer new options for the treatment of decreased uterine and fetal perfusion and their sequelae.

Adult↗

PubMed2002

Tibolone versus 17beta-estradiol/norethisterone: effects on the proliferation of human breast cancer cells.

Tibolone is a synthetic progestin with estrogenic and progestogenic properties, widely used for alleviation of menopausal syndromes and for osteoporosis prophylaxis in postmenopausal women. Since only little data are available on tibolone and breast cancer risk the present study investigates the effect of tibolone on the growth of the human breast cancer cell line, MCF-7. Tibolone is clinically comparable to an estradiol/norethisterone combination, therefore we included this hormone combination in our experiments. Tibolone was examined alone and in the presence of 0.1 nM estradiol in the concentration range from 0.001 microM to 1 microM. Norethisterone was studied using the same concentration range in combination with 0.1 nM estradiol. Tibolone led to significant cell growth in the concentration range of 0.01 to 1 microM and was able to significantly stimulate estradiol-induced proliferation at the concentrations 0.01 and 0.1 microM. In contrast, the estradiol/norethisterone combination elicited significant inhibition of cell growth at the concentrations 0.001 and 0.01 microM. These data suggest that tibolone does have tumor cell-growth promoting effects in vitro whereas the estradiol/norethisterone combination partially inhibits cell growth. Therefore no differences in risk profile are to be expected between conventional hormone substitution using estradiol and norethisterone acetate and tibolone. Drawing a clinical consequence from our experiments would result in not recommending the use of tibolone in postmenopausal women at high risk for breast cancer development until long-term controlled clinical studies have been performed on the effect of tibolone administration and breast cancer risk.

Antineoplastic Agents, Hormonal↗

PubMed2002

Comparison of the effects of 17alpha-ethinylestradiol and 17beta-estradiol on the proliferation of human breast cancer cells and human umbilical vein endothelial cells.

OBJECTIVE: Little is known about the direct comparison between 17alpha-ethinylestradiol (EE2) and 17beta-estradiol (E2) on pre-existing breast cancer cells and on their angiogenetic effects. In this study we investigated the effect of both estrogens on the proliferation of MCF-7 cells, a human breast cancer cell model, and on human umbilical vascular endothelial cells (HUVECs). METHODS: The steroids were tested in the concentration range of 10(-10) to 10(-5) M. The proliferation of MCF-7 and HUVEC cells was measured after five and six days by the crystal violet staining technique. RESULTS: In the concentration range from 10(-10) to 10(-5) M both estrogens showed a proliferative effect in the MCF-7 cells, E2 having a gradually declining effect on proliferation with increasing concentration while EE2 showed a constant proliferative effect over a large concentration range. At the highest concentration tested E2 had no effect on proliferation while EE2 even inhibited growth. In the HUVEC cells both estrogens showed a slightly significant stimulatory effect at the lowest concentration, and no significant effect at the remaining concentrations. EE2 again inhibited cell growth at the highest concentration. CONCLUSIONS: At the serum concentrations seen in hormone replacement therapy, EE2 appears to have less proliferative effect on breast cancer cells compared with E2, while both estrogens appear to have similar effects on endothelial cells.

Breast↗

PubMed2001

Clinical relevance of genomic aberrations in homogeneously treated high-risk stage II/III breast cancer patients.

Little is known about the prognostic impact of chromosome aberrations in breast cancer. The aim of our study was to determine whether genomic aberrations of prognostic relevance can be identified in the context of a clinical study using molecular cytogenetics. Paraffin-embedded tumor samples of 44 patients with high-risk stage II/III breast cancer were analyzed by comparative genomic hybridization. All patients received identical therapy including dose-escalated chemotherapy followed by peripheral blood stem cell transplantation. The most frequent chromosomal aberrations were gains on chromosome arms 17q (24 cases), 1q (21 cases), 8q (17 cases), 20q (13 cases), 6p (9 cases) as well as losses on chromosome arms 13q (25 cases), 11q (20 cases), 5q (11 cases), 6q (11 cases), 9p (10 cases), 18q (10 cases), 8p (9 cases) and 16q (9 cases). In univariate analysis, the correlation with the clinical outcome revealed a higher risk for patients with tumors exhibiting 13q losses and a reduced risk for tumors exhibiting 16q losses (p = 0.020), 6q losses (p = 0.041) and estrogen-receptor positivity (0.051). In multivariate analysis using the Cox model, only the loss of 16q exhibited borderline significance (p = 0.065). These data show that comparative genomic hybridization can be performed in the context of a clinical trial. In our subgroup of high-risk breast cancer patients, chromosomal aberrations were valuable prognostic parameters.

Adult↗

PubMed2001

Effect on biochemical vasoactive markers during postmenopausal hormone replacement therapy: estradiol versus estradiol/dienogest.

OBJECTIVES: Aim was to compare the effects of estradiol-only therapy with combined estradiol/progestin treatment on the excretion of vasoactive mediators surrogating on possible effects in the vascular system. The progestin used was dienogest, a new C19-progestin with antiandrogenic properties. METHODS: Prospective, randomized trial, 25 healthy postmenopausal women treated for 3 months with estradiol valerate (2 mg/day) and 27 women with estradiol valerate (2 mg/day) continuously combined with dienogest (2 mg/day). Assessment of the following markers or their stable metabolites in nocturnal urine: cGMP, serotonin, prostacyclin and thromboxane, and urodilatin. RESULTS: Estradiol alone increased the excretion of cGMP and serotonin significantly suggesting vasodilating effects. The prostacyclin/thromboxane ratio known to be crucial for the relation of vasorelaxation to vasoconstriction significantly increased. No significant changes were found for urodilatin, which is known to elicit different effects in the cardiovascular and renal system, respectively. Combined estradiol/dienogest therapy also led to significant increases in cGMP and serotonin excretion suggesting that progestin addition for three months does not affect these markers. However, in contrast to estrogen-only treatment, there was no significant increase for the prostacyclin/thromboxane ratio, which can be explained by antagonistic action of the progestin. The excretion of urodilatin was increased significantly, which might be due to counterbalancing progestin effects in the renal vascular system. CONCLUSIONS: The changes in vasoactive markers suggest an estrogen effect that is vasorelaxant. Since there were no significant differences between the two groups, possible vascular effects of the progestin dienogest, for the first time evaluated, might not be of clinical relevance, at least not in women without cardiovascular diseases.

Administration, Oral↗