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D Wallwiener

Publications and source records attributed to D Wallwiener.

At least 91 records · Page 5Linked to original sources
PubMed2000

Immunological properties of a single-chain fragment of the anti-idiotypic antibody ACA125.

Vaccination with anti-idiotypic antibodies has been described as a promising concept for treatment of several malignant diseases. The murine monoclonal anti-idiotypic antibody ACA125 imitates a specific epitope of the tumor-associated antigen CA125 expressed by 80% of ovarian carcinomas. In the first clinical trial it could be shown that mAb ACA125 is able to elicit anti-anti-idiotypic antibodies (Ab3) with anti-CA125 specificity in patients with advanced ovarian cancer. In order to improve the capabilities of anti-idiotype vaccines we generated a genetically engineered single-chain fragment (scFv) ACA125 composed of heavy- and light-chain variable regions connected by a flexible linker. The antigenicity of scFv ACA125 was demonstrated by immunizing rats i.p. with scFv or complete mAb in complete/incomplete Freund's adjuvants (CFA/IFA) or precipitated by aluminium hydroxide. Negative control groups included applications of irrelevant mouse IgG or adjuvants alone. Anti-anti-idiotypic antibodies (Ab3) directed against the mAb ACA125 as well as specific anti-CA125 antibodies (Ab1') could be detected in all animals treated with scFv in CFA/IFA. Nevertheless, antibody titers were lower than when the complete mAb ACA 125 was used. Suprisingly, an increase of specificity could not be observed in scFv-immunized animals, which had been expected because of the lack of heavy- and light-chain constant regions that could raise rather unspecific anti-isotypic and anti-allotypic rat anti-(mouse Ig) antibodies (RAMA). In contrast, the RAMA responses detected in these rats were even stronger than those following immunization with complete mAb ACA125. In conclusion, the anti-idiotypic scFv ACA125 alone cannot improve the immunogenic features of the corresponding mAb, but provides a useful tool for the further development of genetic vaccines.

Aluminum Hydroxide↗
PubMed2000

[Bipolar irrigation forceps. Initial experiences with a new device in high frequency surgery].

PROBLEM: During most surgeries, tissues are coagulated by a high-frequency current in order to stop the bleeding. Usually, bipolar forceps are used for this procedure. Until now it could not be avoided, however, that the biotissue would adhere to the forceps ends making hemostasis more difficult to achieve. Can this negative effect possibly be avoided? MATERIAL AND METHOD: A newly developed bipolar irrigation forceps spilling out a 0.9% sodium chloride solution during the coagulation process has been designed to avoid this disadvantage. The irrigation forceps has been tested and evaluated experimentally in surgery as well as clinically. RESULTS: The irrigation liquid selected is a 0.9% sodium chloride solution. Thermal imaging during biotissue coagulation has shown that the tissue heats up more and faster with flushed coagulation, and that the tip of the forceps heats up less than with unirrigated coagulation. In both experimental-surgical as well as in clinical tests it was possible to stop the biotissue sticking to the ends of the forceps. This effect was also confirmed histologically. CONCLUSION: Since other methods of avoiding the sticking effect during tissue coagulation by a high-frequency current have not been successful until now, the bipolar irrigation electrode is a promising new development. It helps the surgeon to work more efficiently and safely without having to adapt to big changes, and, at the same time, it reduces the risk of complications.

Animals↗
PubMed2000

Effect of oral contraceptives on the urinary excretion of biochemical markers indicating vasoactive action.

OBJECTIVE: In the present study the effect of two contraceptive pills, i.e. Neorlest, containing ethinylestradiol and norethisterone acetate, and Valette, containing ethinylestradiol and the new progestin dienogest, was investigated on the urinary excretion of vasoactive markers. As markers prostacyclin and its antagonist thromboxane, cGMP, serotonin, and the vasorelaxing mediators relaxin and urodilatin were measured. METHOD: 30 women received Neorlest and 33 women Valette in a randomized, open, parallel-group study design. Nocturnal urine was collected before treatment and during cyclic treatment after 6 and 11 weeks. RESULTS: For prostacyclin, the ratio of prostacyclin to thromboxane, relaxin and urodilatin significant increases compared to the pretreatment values were observed with Valette within 11 weeks treatment. For the markers cGMP and serotonin both contraceptive pills showed a tendency to an increase of the renal excretion after 11 weeks treatment. No significant differences between the two pills were observed, except in the case of the ratio of prostacyclin to thromboxane, which showed a significant, clear-cut enhancement with Valette. CONCLUSION: These results indicate that contraceptive pills may stimulate the production of vasodilative markers, an effect which can be attributed most likely to the oestrogenic component of the pill. The progestogenic component of the pill may elicit an impact on this oestrogen-induced vasodilation, which, however, seems to be minimized in the case of the new compound dienogest, a C-19 progestin with antiandrogenic properties.

Adult↗
PubMed2000

[Effectiveness and tolerance of depot leuprorelin acetate for preoperative endometrium flattening before endometrial ablation. German Leuprorelin Study Group].

OBJECTIVE: In order to assess the efficacy and tolerability of leuprorelin acetate depot in pre-operative flattening of the endometrium prior to hysteroscopic endometrial ablation, 94 patients from eight centres were included in the per protocol analysis. MATERIAL AND PATIENTS: The patients included were pre- or peri-menopausal, had completed their family planning and had intractable uterine bleeding. The primary target criterion was the reduction in maximum endometrial thickness after two injections of leuprorelin acetate depot with an interval of four weeks between injections. Surgery took place two weeks after the second injection. RESULTS: Sufficient pre-treatment was achieved in 91.5% of the patients with > 50% decrease and/or a type 1 endometrium according to sonographic and/or endometrial atrophy (Score 11) according to the central histological evaluation. The endometrium was flattened by a mean of 4.0 +/- 4.1 mm. In terms of clinical response, amenorrhoea, hypomenorrhoea or normal menstruation were achieved after endometrial ablation. Hence 91.5% of patients benefited from the overall treatment after six weeks and still 83% after six months. The trial medication was well tolerated overall. The most common side-effect described was hot flushes which could be attributed to the deliberate oestrogen withdrawal. CONCLUSION: In view of the good study results, hormone-suppressive pretreatment of the endometrium can be recommended prior to elective ablation. Surgery should take place during the oestrogen-suppressed phase.

Adult↗
PubMed2000

Inhibition of proliferation and differentiation by RU 486 in human endometrial stromal and epithelial cells in vitro.

The effects of progesterone and RU 486 on cellular proliferation and differentiation in long term cultures of mixed human endometrial cells were studied. The endometrial tissue was obtained from women with normal menstrual cycles who were undergoing hysterectomy for benign growths. Estradiol supplemented cultures were treated with progesterone and/or RU 486 for 27 days. Cell number was measured by crystal violet assay, and prolactin secretion was used as a marker of differentiation. Progesterone doubled the rate of proliferation, but the addition of RU 486 reduced it to baseline again. The gestagen increased prolactin secretion up to 30 times, while the addition of RU 486 suppressed it to baseline levels. When administered to cells that were pretreated with progesterone for 15 days RU 486 abolished the progesterone effects. RU 486 alone was without any effect. Our results indicate that (1) in vitro progesterone is essential for the initiation and maintenance of proliferation and differentiation of endometrial cells and (2) RU 486 acts as a pure progesterone antagonist in our culture model.

Cell Differentiation↗
PubMed2000

Fluvastatin combined with 17beta-estradiol: effect on the oxidation of human low density lipoprotein.

The in vitro effect of a statin and an estrogen on oxidation of human LDL was investigated for the first time, comparing the monosubstances fluvastatin and 17beta-estradiol as well as the effect of the combination. Fluvastatin significantly delayed the onset of LDL oxidation (controls = 90 min) by 23 min at 1 microM, by 110 min and by 221 min at 5 and 10 microM, respectively. 17Beta-estradiol significantly impeded the onset by 70 min at 1 microM and by more than 300 min at 5 and 10 microM. The combination of 1 microM 17beta-estradiol with 1, 5 and 10 microM fluvastatin showed an additive antioxidative effect; the onset was delayed by 100 min, by 167 min and by more than 300 min, respectively. It can be concluded that treatment of postmenopausal women with fluvastatin and 17beta-estradiol may have not only beneficial effects on lipid disorders but may also elicit a direct potent anti-atherosclerotic action on the vasculature.

Copper↗
PubMed2000

Comparison of the effects of continuous combined and sequential combined medroxyprogesterone acetate-estradiol treatment on the proliferation of MCF-7 cells.

OBJECTIVE: The aim of the study was to examine the effects of two different, clinically relevant, hormone replacement therapy (HRT) regimen types, continuous combined and sequential combined, on breast cancer cells by means of an in vitro model. The study was carried out using the C21-progestin medroxyprogesterone acetate (MPA) in combination with estradiol, and with the proliferation of MCF-7, a human breast cancer cell-line, as end-point. METHODS: Proliferation of MCF-7 cells was measured by means of a crystal violet staining technique. Growth was triggered using a constant estradiol concentration of 10(-10) mol/l, while varying the MPA concentration from 10(-11) to 10(-6) mol/l. RESULTS: The continuous combined model of treatment led to the inhibition of estradiol-induced growth of MCF-7 with MPA concentrations of 10(-10) mol/l and upwards, compared with estradiol-alone-induced growth. The sequential combined model showed a greater inhibition at the higher MPA concentrations of 10(-8)-10(-6) mol/l, with reduced sensitivity to inhibition at the lower MPA concentrations tested, of 10(-11)-10(-9) mol/l. The different treatment types resulted in significantly different sensitivities of the MCF-7 cells to inhibition of estradiol-induced proliferation at the higher MPA concentrations of 10(-8)-10(-6) mol/l. CONCLUSIONS: The results demonstrate the importance of considering in vivo factors in an in vitro model with regard to improving the cell culture techniques used, to obtain a clearer picture of the possible mechanisms involved in the potential breast cancer risk with different HRT regimens.

Breast Neoplasms↗
PubMed2000

Hysteroscopic surgery--complications and their prevention.

During the last few years, diagnostic hysteroscopy has become a standard procedure in the diagnosis of abnormal uterine bleeding, sonographically suspicious endometrial reflex and fertility disorders. At the same time the hysteroscopic treatment of intrauterine pathology is becoming more common. Today, hysteroscopic resection of uterine myomas, dissection of uterine septa, and endometrial ablation are standard procedures. Using monopolar cutting devices and saline-free distension media, hysteroscopic surgery bears specific risks. The knowledge of these risks is important to avoid typical complications of operative hysteroscopy. This article gives an overview about the most common procedures of operative hysteroscopy and the combined risks. Criteria for a safe procedure are defined in order to increase the quality management of operative hysteroscopy.

Endometrium↗
PubMed2000

The 'HysteroTrainer'--an in vitro simulator for hysteroscopy and falloposcopy. Experimental and clinical background and technical realisation including the development of organ modules for electrothermal treatment.

Hysteroscopy and falloposcopy are routine procedures in gynecological endoscopy. Injuries to the cervix or uterine perforations due to blind manipulation or wrong use of instruments are the most common complications associated with these procedures. In vitro simulators have been shown to be valuable tools in the laparoscopic training of physicians. Therefore we developed a simulator for hysteroscopy offering realistic anatomical and physiological training conditions. Additionally, we examined different polymer substances as basic materials for organ modules that allow the realistic application of electric instruments, e.g. resector blades and rollerball.

Equipment and Supplies↗
PubMed2000

Localization in tissues and secretion of eotaxin by cells from normal endometrium and endometriosis.

Our laboratories have focused recently on the production and localization of eotaxin, a C-C-chemokine of 8.4 kDa, whose major biological activity is the chemoattraction of eosinophils. Given evidence of autoimmune activity in the endometriosis syndrome, we hypothesized that eosinophil chemoattractants might be expressed in endometriosis. In histological sections, we observed eotaxin protein localized mainly in epithelial cells, with only very faint immunostaining in the surrounding stromal cells. Prominent eotaxin accumulation was noted in the luminal epithelium of secretory endometrium. Eotaxin distribution in endometriosis was similar to that seen in eutopic endometrium but with higher levels of eotaxin staining in the glandular epithelium. Peritoneal fluid concentrations of eotaxin were significantly higher in women with moderate or severe endometriosis than in women with minimal or mild endometriosis or no disease. The treatment of isolated human endometriosis epithelial cells with estradiol, medroxyprogesterone acetate, tumor necrosis factor-alpha, and interferon-gamma stimulated measurable eotaxin secretion into the conditioned media. The results indicate that eotaxin is produced in epithelial cells of normal endometrium and endometriosis tissues, varies across the menstrual cycle, and is elevated in women with endometriosis. We postulate that eotaxin, interacting with other known cytokines and immune cells, contributes to an inflammatory reproductive tract environment, leading to endometrial or blastocyst dysfunction.

Adult↗
PubMed2000

Urinary excretion of vasoactive markers following estrogen replacement therapy in postmenopausal women.

OBJECTIVE: The effect of estradiol on the renal excretion of vasoactive substances was studied in postmenopausal women. The following markers surrogating an estrogenic effect on the cardiovascular system were measured: prostacyclin and thromboxane, cGMP, which reflects systemic nitric monoxide production, serotonin and relaxin. METHODS: The effect of estradiol was compared using two clinical forms of administration, transdermal and oral, in two groups of 20 postmenopausal women each. The treatment was carried out for two and four weeks, respectively. Nocturnal urine was collected over 8 hours before and after estradiol treatment. The quantity of markers excreted during the experiment was determined. RESULTS: Excretion of prostacyclin and thromboxane, calculated as prostacyclin/thromboxane ratio, was increased using both forms of administration. Both forms of treatment brought about only slight non-significant changes in renal cGMP excretion compared with values before treatment. The production of serotonin and relaxin was only increased using transdermal treatment. CONCLUSION: The resulting data show that estradiol replacement in postmenopausal women is able to increase renal excretion of various vasoactive substances implying a vasodilative effect of estrogen. This was seen, both in transdermal and oral administration, transdermal application having a more pronounced effect on the markers than oral administration.

Administration, Cutaneous↗
PubMed2000

Additive antioxidative effect of hormone replacement therapy combined with a statin.

In treating postmenopausal women both statins and estrogens have been shown to elicit favourable effects on lipids and lipoproteins. In addition direct beneficial effects of these substances on the vascular wall are discussed. However, progestin addition to estrogen replacement therapy, which is mandatory in women with an intact uterus. is thought to deteriorate at least partly estradiol-induced direct effects on the vasculature. Oxidation of LDL, which mainly takes place in the vessel wall, seems to be a crucial step in the development of atherosclerosis. Therefore, for the first time, the effect of a statin and an estrogen/progestin combination on the in vitro oxidation of human LDL was investigated comparing the monosubstances fluvastatin. 17beta-estradiol and norethisterone acetate (NETA) as well as the effect of the combination. LDL was isolated from human female serum and oxidation was initiated by copper(II)-chloride. The progression of LDL oxidation was monitored spectrometrically at 234 nm for 300 min. Fluvastatin significantly delayed the onset of LDL oxidation (controls = 85 min) by 21 min at 1 microM, by 99 min and by 210 min at 5 and 10 microM. respectively. 17beta-estradiol significantly reduced the onset by 73 min at 1 microM and by more than 300 min at 5 and 10 microM. NETA had no significant effect. The combination of I microM 17beta-estradiol and 1 microM fluvastatin with 1, 5 and 10 microM NETA showed an additive antioxidative effect of estradiol and fluvastatin and no deterioration by the addition of NETA even at high dosages. It can be concluded that treatment of postmenopausal women with fluvastatin and a combination of 17beta-estradiol with NETA may have not only beneficial effects on lipid disorders but may also elicit a direct potent antiatherosclerotic action on the vasculature.

Anticholesteremic Agents↗
PubMed1999

Adjuvant high-dose therapy with peripheral blood stem cell support for patients with high-risk breast cancer.

We report on the efficacy and toxicity of a sequential high-dose therapy with peripheral blood stem cell (PBSC) support in 107 patients with high-risk stage II/III breast cancer. There were 90 patients with more than 9 tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7,500 mg/m(2)) and epirubicin (120 mg/m(2)) was given, and PBSC were harvested during granulocyte colony-stimulating factor (G-CSF)-supported leukocyte recovery following the second cycle. The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide (total dose 12,000 mg/m(2)), carboplatin (900 mg/m(2)) and epirubicin (180 mg/m(2)). Patients were autografted with a median number of 4.1 x 10(6) CD34+ cells/kg (range 1.9-26.5 x 10(6)), resulting in haematological reconstitution within approximately 2 weeks following high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-nine patients (27.1% of all patients) relapsed between 3 and 46 months following the last cycle of high-dose therapy (median 15 months). The probability of disease-free and overall survival at 3 years was 56% and 83%, respectively. A multivariate analysis showed that patients with stage II disease had a significantly better probability of disease-free survival (71%) in comparison with patients with stage III disease (30%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (62%) compared with patients with receptor-negative ones (40%). In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy including the addition of non-cross-resistant drugs or immunological approaches may be envisaged for patients with stage III disease and hormone receptor-negative tumours.

Adult↗
PubMed1999

Reduction of aseptic measures in gynecologic endoscopy: a comparative clinical trial.

OBJECTIVE: A prospective comparative clinical study was conducted on 200 patients to evaluate the consequences of minimizing the following standard hygienic measures in gynecologic laparoscopy: surgical scrub, patient draping, surgical gowns. STUDY DESIGN: A group of 100 patients treated according to maximum hygienic protocol was compared to a group of 100 patients undergoing laparoscopic procedures with only limited aseptic precautions. Clinical control parameters were perioperative temperature and white blood cell count up to the 4th postoperative day. Furthermore, patients and their gynecologists were interviewed 2-4 weeks after surgery to rule out any delayed manifestation of an infection. RESULTS: Perioperative infection was low in both groups. CONCLUSION: As we found no significant difference between the two collectives' control parameters, we conclude that a reduction in perioperative hygiene seems feasible for certain laparoscopic procedures. However, a larger collective should be studied in order to confirm this action.

Adult↗
PubMed1999

Stage III and oestrogen receptor negativity are associated with poor prognosis after adjuvant high-dose therapy in high-risk breast cancer.

We report on the efficacy and toxicity of a sequential high-dose therapy with peripheral blood stem cell (PBSC) support in 85 patients with high-risk stage II/III breast cancer. There were 71 patients with more than nine tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7.5 g m(-2)) and epirubicin (120 mg m(-2)) was given, and PBSC were harvested during G-CSF-supported leucocyte recovery following the second cycle. The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide (total dose, 12,000 mg m(-2)), carboplatin (900 mg m(-2)) and epirubicin (180 mg m(-2)). Patients were autografted with a median number of 3.7 x 10(6) CD34+ cells kg(-1) (range, 1.9-26.5 x 10(6)) resulting in haematological reconstitution within approximately 2 weeks following high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-one patients relapsed between 3 and 30 months following the last cycle of high-dose therapy (median, 11 months). The probability of disease-free and overall survival at 4 years were 60% and 83%, respectively. According to a multivariate analysis, patients with stage II disease had a significantly better probability of disease-free survival (74%) in comparison to patients with stage III disease (36%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (70%) compared to patients with receptor-negative ones (40%). Bone marrow samples collected from 52 patients after high-dose therapy were examined to evaluate the prognostic relevance of isolated tumour cells. The proportion of patients presenting with tumour cell-positive samples did not change in comparison to that observed before high-dose therapy (65% vs 71%), but a decrease in the incidence and concentration of tumour cells was observed over time after high-dose therapy. This finding was true for patients with relapse and for those in remission, which argues against a prognostic significance of isolated tumour cells in bone marrow. In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy, including the addition of non-cross resistant drugs or immunological approaches such as the use of antibodies against HER-2/NEU, may be envisaged for patients with stage III disease and hormone receptor-negative tumours.

Adult↗
PubMed1999

Vascular endothelial growth factor A (VEGF-A) mRNA expression levels decrease after menopause in normal breast tissue but not in breast cancer lesions.

We hypothesized that the regulation of microvascular functions and angiogenesis in breast tissue, a well known target of ovarian steroid action, is dependent on the hormonal exposure of the breast. Relative expression levels of VEGF-A (vascular endothelial growth factor A), a putative key regulator of angiogenesis in breast cancer, were analysed in the tumour and the adjacent non-neoplastic breast tissue of 19 breast cancer patients by quantitative reverse transcriptase polymerase chain reaction. In non-neoplastic breast specimens the expression levels of all detected VEGF-A-isoforms (189, 165, 121) were significantly higher in premenopausal compared to post-menopausal women (P = 0.02) and were inversely correlated with the patient's age (P = 0.006). In contrast, in cancerous tissues menopausal status had no influence on VEGF-A-expression levels. Benign and malignant tissues exhibited a similar expression pattern of VEGF-A-isoforms relative to each other. Thus, the regulation of the vasculature in normal breast tissue, as opposed to breast cancer tissue, appears to be hormonally dependent. Endogenous and therapeutically used hormonal steroids might, therefore, cause clinically relevant changes of the angiogenic phenotype of the human breast.

Adult↗
PubMed1999

Disparate actions of mifepristone (RU 486) on glands and stroma in the primate endometrium.

Besides being an antiprogestin, mifepristone (RU 486) was recently shown to antagonize oestrogen-dependent growth in the endometrium. To explore the molecular mechanisms for this phenomenon, we investigated whether or not the morphological effects of mifepristone are mediated by the progesterone receptor (PR) and whether mifepristone has disparate effects on the glandular epithelium and stroma. Six groups of hypogonadal, oestrogen-primed cynomolgus monkeys were treated for 2 weeks with: vehicle only (group I); mifepristone (group II); mifepristone plus progesterone at 0.2 mg/kg (group III), 1.0 mg/kg (group IV) or 5.0 mg/kg (group V); and progesterone only (5.0 mg/kg) (group VI). Histomorphological evaluation showed strikingly compacted stroma in the mifepristone-exposed endometria (group II), which was partially reversible by additional progesterone treatment (groups III-V). Glandular proliferation (pseudostratification, glandular mitoses) in mifepristone-treated monkeys was not significantly different from that in vehicle (oestradiol)-treated monkeys, but was inhibited by progesterone-only treatment. Cells containing vacuoles were scarce in the mifepristone-exposed endometrium, but detected frequently in progesterone-exposed endometria, indicating the strong antisecretory effect of mifepristone on glands. We conclude that oestrogen-dependent oedema in the stroma is antagonized by mifepristone. The reversal of this effect by progesterone suggests a PR-mediated mechanism. In glands, mifepristone is antiprogestogenic, but not antioestrogenic. Thus, stromal cells may be the target of antiprogestin-induced inhibition of oedema and endometrial growth.

Animals↗