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Biomedical subjects

D Krebs

Publications and source records attributed to D Krebs.

At least 127 records · Page 7Linked to original sources
PubMed1990

[A trial with immunotherapy of ovarian cancer by idiotype vaccination. Activation of the idiotype network in patients with advanced ovarian cancers by treatment with monoclonal antibody OC125].

Up to date, the positive effect of immunotherapy, using tumour-associated antigens or tumour cells of ovarian carcinomas, is still vague. Another and effective approach to overcome an experimentally induced tolerance, is the presentation of an definitive antigen in a different surrounding by the induction of the idiotypic network. Antibodies against a tumour-associated antigen are used to induce following antibodies, which are directed against the variable antigen-binding group, the so-called idiotype of the antibody-vaccine. Then, the induced antibodies carry a mirror image of the tumour-associated antigen and are therefore able to modulate the host's immune response against the tumour. For the induction of this system, we used the monoclonal antibody OC125 as a F(ab)2-fragment, which is directed against the tumour-associated antigen CA125 of epithelial ovarian carcinomas. 12 patients with advanced ovarian carcinomas received antibody fragments of the OC125 in the course of radioimmunodetections since 1985. Until April 1990 only these 5 patients, who developed the anti-idiotypic antibodies after the vaccination, are still alive. Our first results with the induction of the idiotypic network system for patients with advanced ovarian carcinomas indicate, that in spite of the same surgical and chemotherapeutical treatment, patients show a delayed clinical course after the induction of the idiotypic system. The transfer of the definitive tumour-associated antigen in an idiotypic antigen, seems to modulate the immunoresponse of the patients and in this way also the clinical course of a malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗
PubMed1990

[Chemosensitivity studies with soft agar culture systems in ovarian cancer].

Since 1982, chemosensitivity studies have been conducted in our laboratory with 181 tumour samples from 132 woman patients suffering from carcinoma of the ovaries, using the colony test and capillary assays. Colonisation rates were 67% and assay rates between 60 and 47%; in 36 cases the in vitro result was compared with the course of the disease observed in vivo. Whereas in 11 of 12 patients it was possible to correctly assess chemoresistance (in vitro growth inhibition less than or equal to 49%) pretherapeutically, chemosensitivity (growth inhibition greater than or equal to 50%) proved more difficult to confirm, 15 predictions being true and 9 false. To assess the prognostic significance of the test results, survival curves were calculated from the data of 33 patients. With a p-value of 0.49, the courses of disease of "in vitro resistant" and "in vitro sensitive" patients differed only slightly from one another. We can conclude from our experiments, that an important indication for performing the colony test in ovarian carcinoma should always be assumed in patients with a poor prognosis, e.g. in women having a large postoperative residual tumour. If, in such cases, the possibility of chemosensitivity testing via the colony test is considered, this examination may offer the chance of sparing the patient additional strain due to the side effects of a treatment with cytostatics if the latter is most likely to be of no significant use.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[Effect of sequential embryo transfer on pregnancy following in vitro fertilization].

In this study, the influence of sequential embryo transfers in an in-vitro fertilisation programme was examined. After in-vitro fertilisation, a maximum of 6 fertilised oocytes were cultured. In cases with more than 6 fertilised oocytes, the rest was cryopreserved in the pronucleus stage. At day 2 after an oocytes retrieval, three embryos with the best morphological appearance were replaced and the remaining embryos (1-3) were cultured for further 3 days. At day 5 after oocytes collection, second a embryo transfer was performed, if one of these embryos had reached the blastocyst stage. In a total of 106 patients, 40 pregnancies (38%) could be observed. No statistical difference in the pregnancy rate could be seen between the group with a second embryo transfer (n = 38; 42%) and the group without second transfer (n = 68; 35%). The incidence of multiple pregnancy was not statistically different between both group and no high-rank multiple pregnancy (greater than Triplete) were observed. Out of 300 cultured embryos, only 59 embryos (17%) reached the blastocyst stage. In the group, in which a second embryo transfer was performed, 22 patients received one blastocyst and 13 patients two blastocysts during the second transfer. The second transfer did not have a significant effect on the pregnancy rate in this series. The most important factor for the induction of pregnancy seems to be the quality of the embryos transferred on day 2 following oocyte retrieval.

Embryo Transfer↗
PubMed1990

Preliminary results on transvaginal tubal embryo stage transfer (TV-TEST) without ultrasound guidance.

IVF procedures have been increasingly used in male subfertility for both therapeutic and diagnostic purposes. As we assume a positive influence of the tubal milieu on the early embryonal development, any therapy should aim at intratubal embryo transfer. In this respect, only invasive techniques such as laparoscopy or laparotomy have been available hitherto (Asch et al., 1986; Balmaceda et al., 1988; Diedrich et al., 1989). Transvaginal intra-tubal embryo stage transfer (TV-TEST) was performed in 15 patients. After stimulation with clomiphene/HMG, HMG or GnRHA/HMG, patients with a follicle size of 18 mm were given 10000 IU HCG. Thirty six hours later, the transvaginal oocyte retrieval was performed without anaesthesia. Altogether, 109 oocytes were recovered. A fertilization rate of 30.3% yielded 33 embryos. Forty-eight hours after oocyte retrieval, the TV-TEST was performed without anaesthesia, in the course of which a maximum of three embryos in the 2- to 8-cell stage were transferred into one tube. Six of these patients are now pregnant.

Catheterization↗
PubMed1990

Significance of cumulus oophorus in in-vitro fertilization and oocyte viability and fertility.

Fertilization and cleavage rates of human cumulus-intact oocytes incubated in vitro for 36-48 h with normal spermatozoa tended to be higher than those which were cumulus-denuded (73 versus 68%; 68 versus 56%, respectively); however, the difference was not significant. Nor were these differences significant when using sperm samples of various qualities (normozoospermic samples: 75 versus 70% fertilized oocytes; asthenozoospermic: 66 versus 64%; oligozoospermic: 64 versus 56%; oligoasthenozoospermic: 35 versus 33%). The beneficial effect of the human cumulus oophorus on the binding of human spermatozoa to denuded hamster oocytes and on head decondensation of human spermatozoa observed after 2 h of incubation (9.3 versus 7.0 bound spermatozoa per oocyte, P less than 0.05; 0.5 versus 0.3 decondensed sperm heads per oocyte, P less than 0.02) disappeared after 6 h. A protective effect of the cumulus oophorus on hamster oocytes preincubated in medium containing 50% human preovulatory follicular fluid was observed in the sperm penetration assay (fertilization rate of cumulus-intact: cumulus-denuded oocytes, 26 versus 13%, P less than 0.05) and confirmed using fluorescein diacetate stain (cumulus-intact oocytes: 86 versus 100% vitality, non-significant; cumulus-denuded oocytes: 64 versus 100%, P less than 0.01). These data suggest the accelerating effect of the human cumulus oophorus on fertilization in its early stages. Furthermore, the cumulus plays an important part in protecting the oocyte against adverse environmental influences.

Animals↗
PubMed1990

Gas exchange in extracorporeal circuits for neonates: comparison of three different canulation systems during animal experiments.

During twenty animal experiments the effectiveness of the gas exchange during extracorporeal membrane oxygenation (ECMO) was evaluated. Arteriovenous, venovenous and venoarterial perfusion systems were compared. While PO2 saturation values were sufficient in all three groups the PO2 values were significant higher during arteriovenous perfusion (84.22 +/- 3.5 mmHg) compared to venovenous 71.99 +/- 7.3 mmHg) and venoarterial (65.11 +/- 4.5 mmHg) perfusion (p less than 0.001). PCO2 values correlated with the flow in the extracorporeal circuit in all three groups. The absolute values of PCO2 were significantly lowest during venoarterial perfusion (39.68 +/- 3.1 mmHg) compared to the venovenous (42.69 +/- 3.3 mmHg) and the arteriovenous mode (49.96 +/- 4.1 mmHg). These results indicate that perfusion circuits other than the original venoarterial ECMO could provide sufficient gas transfer for respiratory insufficient neonates while avoiding points of criticism of such systems.

Animals↗
PubMed1990

Effect of tamoxifen and high-dose medroxyprogesterone acetate (MPA) on cell-mediated immune functions in breast cancer patients.

In 48 postmenopausal patients with non-disseminated breast cancer an adjuvant therapy with tamoxifen, and in 17 breast cancer patients with disseminated disease a therapy with high-dose medroxyprogesterone acetate (MPA) was performed and the results obtained were compared to a control group of 35 postmenopausal patients with non-disseminated disease receiving no further adjuvant treatment and 9 patients with disseminated disease, who were not treated by hormonal therapy or chemotherapy. Before therapy was started and at the end of therapy reactivity in the leukocyte migration inhibition test (LMI-Test) against autologous and homologous tumor tissue, serum levels of TNF alpha, IL-2 and IFN alpha, as well as the differentiation of different lymphocyte subsets in the peripheral blood, were determined. In patients undergoing adjuvant therapy with tamoxifen an increase of reactivity in the LMI test against tumor tissue (14.6% before and 22.9% after tamoxifen therapy) and increase of the percentage of NK cells (13.6% before and 19.8% after therapy) could be observed, whereas with TNF alpha, IL-2 and IFN alpha serum levels, as well as the differentiation of other lymphocyte subsets, no differences were found. In breast cancer patients with disseminated disease treated with high-dose MPA no changes of LMI reactivity and cytokine serum levels could be observed. We only found a decrease of T-helper cells from 38.4% before to 22.7% (p less than 0.05) at the end of therapy. These results indicate that tamoxifen has no severe suppressive side effects on different parameters of cell-mediated immunity and possibly leads to an increase in the number of NK cells. Contrary to this, high-dose MPA must be considered as a depletor of T-helper cells.

Aged↗
PubMed1990

[Laser spectroscopic assessment of induced hyperoxia--an animal experiment in lambs].

The noninvasive determination of biochemical parameters has become an important aspect of intensive care medicine. The newly developed monitors for laser reflectometry provide the possibility of spectroscopic monitoring. The equipment consists of a near-infrared data collection unit and a personal computer. The four laser diodes emit light at wavelengths of 775, 805, 845 and 904 nm. By analyzing the changes in optical density during laser irradiation of biological tissue, information is obtained about the relative changes in the concentration of hemoglobin and the blood volume. In animal experiments with ten fetal lambs we evaluated the reliability of near infrared laser spectroscopy. Fetal hyperoxia was achieved by means of an extracorporeal circuit with interposition of a membrane oxygenator (0.8 m2, Scimed). During the induced hyperoxia the laser spectroscopic tracings showed a rise in the HbO2 signal with a synchronous decrease in the HbR signal. Additionally, the spectroscopic pattern showed a characteristic initial rise in the intracerebral blood volume, which stabilized after 4 minutes. We found a significant correlation between the intermittently measured PO2 values of the arterial blood samples and the laser spectroscopic HbO2 and HbR signals (r = 0.87, and r = -0.82, respectively; p less than 0.001). Furthermore, hyperoxia was indicated by the laser system with a short lag time. We conclude that laser spectroscopy is a reliable method with a high potential for clinical routine use in intensive care, as it provides noninvasive continuous information at comparatively low costs using portable monitors.

Animals↗
PubMed1990

Investigations on cell-mediated immunity in patients with breast and ovarian carcinomas receiving a combination of chemotherapy and immunotherapy with thymopentin.

In 78 patients with breast and 37 patients with ovarian cancer the effect of combined chemo- and immunotherapy with thymopentin (Timunox, Cilag) on different parameters of cell-mediated immunity (leukocyte migration inhibition test, serum level of TNF-alpha, IL-1, interferon-alpha, distribution of lymphocyte subsets) and the clinical course of disease was evaluated and compared to patients receiving only chemotherapy. In cancer patients additionally treated with thymopentin an increase in reactivity in the LMI test and an increase of IFN-alpha serum levels could be observed, whereas serum levels of TNF-alpha and IL-2 and the distribution of T-helper, T-suppressor, total T and natural killer cells did not change. Concerning the clinical course of disease, no significant differences could be observed in patients with disseminated spread of disease, whereas in patients receiving combined chemo-immunotherapy in the course of an adjuvant treatment a benefit was found compared to those receiving only chemotherapy. Thus, it seems that the additional administration of thymopentin in breast and ovarian cancer patients under chemotherapy results in a reduction of immunosuppressive side effects of chemotherapy and a positive effect of the survival time in patients with limited spread of disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Accumulation of pollutants in the genital tract of sterility patients.

In order to assess the burden of environmental pollutants in the genital tract, 12 different chlorinated hydrocarbons were determined in 152 samples of follicular, seminal and cervical fluids from sterility patients in the in vitro fertilization programme at the Centre for Obstetrics and Gynaecology of the University of Bonn. The lowest concentrations were found in the follicular fluids of patients who eventually became pregnant by in vitro fertilization. Higher concentrations were found in patients with sterility of unknown origin. Concentrations in the cervical secretion were up to twenty times higher than those in the seminal or follicular fluids. The results show that considerable concentrations of chlorinated hydrocarbons may be present in parts of the reproductive system, and that these compounds accumulate in the reception zone for spermatozoa. Certain pollutants therefore probably contribute to infertility.

Cervix Uteri↗
PubMed1990

Evidence for interaction of human anti-idiotypic antibodies with CA 125 determination in a patient after radioimmunodetection.

Very high concentrations of CA 125 have been found in some ovarian cancer patients after repeated radioimmunodetection with anti-CA 125 antibodies [OC125-F(ab')2]. In one patient we measured a CA 125 concentration of 135,000 kilo-arb. units/L, using an enzyme immunoassay involving OC125 antibodies. With an immunoradiometric assay involving use of two new anti-CA 125 antibodies (B43.13 and B27.1), the CA 125 concentration was 34 kilo-arb. units/L, indicating a discrepancy. The component responsible for the high result in the enzyme immunoassay could be purified by immunoaffinity chromatography on Protein A-Sepharose. Furthermore this component bound to anti-human IgG-Sepharose in the same manner as did the serum IgG fraction. Adsorption of human anti-mouse antibodies present in the serum did not decrease the CA-125-like material. Binding of whole OC125 antibodies to the purified CA-125-like material was inhibited completely in the presence of CA 125 antigen. We infer that the false-positive CA 125 activity is ascribable to a human IgG directed against an idiotope of the OC125 antibody, which was induced by repeated application of OC125 antibodies. To avoid falsely positive results in patients receiving OC125 antibodies, CA 125 should be measured by an assay in which other antibodies are used.

Aged↗
PubMed1989

Differences in membrane properties between unfertilised and fertilised single rabbit oocytes demonstrated by electro-rotation. Comparison with cells from early embryos.

The apparent membrane capacity of tubular rabbit oocytes increases from 1.7-2.0 microF/cm2 before fertilisation to 3.7-4.0 microF/cm2 after fertilisation. The membrane conductivity measured on single cells was also increased by fertilisation from less than 1 mS/cm2 to 14 mS/cm2. Cells obtained from 2-, 4- or 8-cell embryos exhibited intermediate values of membrane capacity (2.3-2.8 microF/cm2) and conductivity (5-22 mS/cm2). The values quoted are those effective between 1 and 10 kHz, the frequency of the rotating field used. The large apparent capacities are probably due to the presence of structures such as microvilli which cause the actual membrane area to exceed the smooth sphere area. It must be assumed that these structures change in form or number on fertilisation, and that they persist in embryos, at least up to the 8-cell stage. No difference was apparent between cells fertilised in vitro or in vivo. Comparison of the above zona-free data with measurements on zona-complete oocytes indicate how fertilised and unfertilised rabbit eggs may be distinguished from one another, even in the presence of the zona pellucida.

Animals↗
PubMed1989

Immunoscintigraphy using CA 125 antibodies in the management of ovarian cancer.

Radioimmundetection (RID) using anti-CA 125 antibodies proved to be a valuable tool in the follow-up of metastasizing ovarian cancer. Sensitivity, specificity, and accuracy were high. RID had no clinical side effects. But some patients formed antibodies which interfered a) with the evaluation of the scintigram and b) with further measurement of CA 125 levels. We found 2 cm diameter metastases that were not detected by computed tomography. However, the heterogeneity of tumor metastases limits the sensitivity of this method. CA 125 serum levels, immunohistochemistry, and immunoscintigraphy did not always correlate. Monitoring serum levels of CA 125 was most valuable in clinical management of tumor spread and in the optimal use of RID.

Antibodies, Monoclonal↗
PubMed1989

[Severe EPH gestoses and pre-eclampsia in relation to hemolysis, increased liver enzymes and decreased thrombocytes--a report of experiences in emergency obstetric situations].

An increasing number of patients with hemolysis, elevated liver enzymes, and low platelet count (HELLP) have been noted in recent years. We report 11 patients at the Department of Obstetrics (University of Bonn), who were admitted during the past 3 years at between the 24th and 37th week of gestation, showing the typical symptoms of the HELLP syndrome with epigastrical pain and characteristic changes in the blood serum, partly associated with severe EPH gestosis or preeclampsia. No predisposition was found in the medical or pregnancy history. The aggravation of symptoms in combination with insufficient progress of delivery made cesaerian section necessary. In spite of intensive-care measures, two mothers and three newborns died. We present a proposal for obstetrical diagnosis and management.

Alanine Transaminase↗