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Biomedical subjects

D Krebs

Publications and source records attributed to D Krebs.

At least 109 records · Page 6Linked to original sources

[Clinical use of photodynamic therapy in gynecologic tumor patients--antibody-targeted photodynamic laser therapy as a new oncologic treatment procedure].

The clinical report addresses the first application of a antibody-targeted photodynamic laser therapy with Phthalocyanines. Photodynamic therapy (PDT) has been proposed as a further treatment modality in oncology. The concept of PDT is based on the interaction between a dye which is accumulated in the target and laserlight. The phototoxic effect is achieved by the augmentation of oxygen radicals. The improvement of the selectivity and the reduction of side-effects is achieved by our concept of using an antibody-targeted phthalocyane induced PDT. The clinical application of the antibody-targeted Phthalocyanine was performed in 3 patients suffering from an advanced ovarian carcinoma (FIGO III). By means of an ultramicroscopical analysis a selective devitalisation of tumor cells was demonstrated. The perspective of PDT reaches far beyond the application for the ovarian carcinomas and relates to all tumor types, where the presence of tumor-associated antigens implicates a treatment in a similar way.

Combined Modality Therapy↗

Determination of tumor necrosis factor alpha (TNF alpha) and interleukin 2 (IL 2) in women with idiopathic recurrent miscarriage.

Some recurrent miscarriages may be due to a host versus graft reaction. Elevated Interleukin 2 (IL2) levels have been found during pregnancy and elevated TNF alpha levels during acute rejection crises of allotransplantats and so we determined IL2- and TNF alpha levels in women with recurrent miscarriages. Samples were taken for serum TNF alpha and IL2 radioimmunoassays (IRE Medgenix, Belgium) from 28 healthy non-pregnant women and in 49 women with at least 3 miscarriages between the 6th and 14th week of pregnancy, 38 women having their first or second miscarriage and 42 pregnant women with no complications. In women with recurrent miscarriage an increase in TNF alpha (P less than 0.05) and a decrease in IL2 serum levels (P less than 0.05) was found compared to women with normal pregnancies. These results support the concept that disturbances of immune tolerance of the fetus may account for some cases of recurrent miscarriage.

Abortion, Habitual↗

Photodynamic laser therapy of carcinomas--effects of five different photosensitizers in the colony-forming assay.

Photodynamic therapy (PDT) with laser radiation opens a new field in the treatment of malignancies. We evaluated the phototoxic effects of five different substances for photodynamic therapy in concentrations showing no systemic toxicity. We used gynecologic tumor cells and evaluated the photodynamic effects for cell growth in a colony-forming assay. For Indigocarmin we found a reduction in the colony-forming assay compared to the control group from 87% to 66% after irradiation at 50 mumol/l and 608 nm wavelength. "IR 132" showed a reduction in the colony-forming assay from 73% to 72% 50 mumol/l (590 nm). For the incubation of the HeLa cells with 50 mumol/l of "Sulfo-Phthalocyanin" we found a reduction of the colony-forming potential from 81% to 67% (595 nm). The most strikingly differences were found for the incubation and irradiation of Methylene Blue, showing a reduction from 77% to 16% caused by a toxic effect of the substance itself (5 mumol/l, 660 nm) and "Sulfo-Aluminium-Phthalocyanin" stained cells, which shows a reduction from 86% to 17% (50 mumol/l, 675 nm). We see the possibility of a photoactivation and cell devitalisation by "Sulfo-Aluminium-Phthalocyanin" and laser radiation. A future clinical trial would seem justified.

Cell Survival↗

Transvaginal intratubal embryo transfer: a new treatment of male infertility.

Intratubal embryo transfer is a new method in the treatment of human infertility. Following transvaginal sonographic oocyte retrieval, in-vitro fertilization (IVF) is performed and embryos are transferred into the Fallopian tube transvaginally. In comparison with gamete intra-Fallopian transfer (GIFT), fertilization under in vitro conditions offers the advantage that the success of the fertilization process can be examined. Therefore, this method can give important diagnostic information, especially in cases of poor sperm quality or unexplained infertility. After fertilization in vitro and transfer into the tube, embryonic development occurs in the physiological milieu of the oviduct. Transvaginal intratubal embryo transfer was performed in 95 patients with male factor infertility. In 29 cases (31%), a pregnancy was achieved. One abortion, but no ectopic pregnancy was observed. This method combines the advantages of IVF and GIFT and offers a successful procedure for the treatment of infertility.

Embryo Transfer↗

Animal experiments for the evaluation of laserspectroscopy in the fetus during labor.

Laserspectroscopy with near-infrared light is newly available for clinical application. The equipment consists of a near-infrared data collection unit (NIRDCU) and a personal computer. Emission of laser light at wavelengths of 775, 805, 845 and 904 nm is provided by the four laser diodes of the NIRDCU. By analyzing changes of optical density during laser radiation, information is obtained regarding the intracellular redox state and relative changes of blood volume. During measurement with the system on the fetal scalp during delivery we were able to get a first impression of the method's potential. While the application of the laser sensors is still cumbersome, signals providing information of the relative changes of hemoglobin concentration, relative changes of blood volume and cytochrome aa3 seems achievable. Laserspectrophotometric monitors may become safe, low cost and portable instruments for the non-invasive assessment of the biochemical and biophysical status in the fetus.

Animals↗

Continuous intrapartum transcutaneous carbon dioxide measurements during fetal arrhythmia.

In nine cases of fetal arrhythmias without cardiac anomalies or congestive heart failure a vaginal delivery was attempted. Due to these arrhythmias adequate fetal heart rate monitoring during labor was not possible. All cases were continuously monitored during labor with the transcutaneous measurement of fetal carbon dioxide tension (tcpCO2). Seven patients could be delivered spontaneously. In one of these cases the newborn was acidotic at birth (pH less than 7.20 in the umbilical artery) which was correctly identified (tcpCO2 greater than 60 mmHg). All newborns were vigorous (Apgar score after 1 minute greater than 7). In cases with uninterpretable fetal heart rate patterns tcpCO2 monitoring of the fetus during labor is an alternative method of fetal surveillance, which identifies fetal distress and can prevent unnecessary operative deliveries.

Acid-Base Equilibrium↗

Endoscopic fetal surgery by excimer laser. An experimental study in premature lambs.

Fetal malformations are detected early in pregnancy by means of ultrasound challenging fetal therapy. While open fetal surgery has been preformed during preliminary clinical trials we evaluated fetoscopic therapy avoiding laparotomy and uterotomy. We used a laser fibre (900 mu) which was introduced into the uterus by an endoscope. During animal experiments in five fetal lambs with a gestational age of 120-122 days we used an excimer laser (Technolas, x) with a wave-length of 308 nm. Laser incisions were compared with the conventional cutting technique using a scapel. During histological evaluation the tissue effect was morphometricly analysed. The zone of devitalisation was characterized by pycnosis of the nuclei and in a change of cytoplasma volume. The excimer laser incisions using a frequency of 40 HZ had a mean zone of devitalisation of 50.3 +/- 4.5 mu. Using the excimer laser with a frequency of 10 HZ we found a tissue alteration of only 11.2 +/- 3.4 mu. The incisions by scapel showed a extended traumatisation with a mean tissue effect of 153.2 +/- 16.3 mu. From these results we conclude, that endoscopic surgery may be come a usefull additional tool for fetal therapy.

Animals↗

[Locoregional ascites therapy with cytostatic drugs and immune modulators in gynecologic neoplasms].

35 ovarian cancer patients with ascites have been treated intraperitoneally with mitomycin C or mitoxantrone or interferon beta or tumor necrosis factor (TNF). We observed nor or a little bit ascites in 87.5 per cent after TNF and in 66.5 per cent after mitoxantrone. In addition we applied a systemic monochemotherapy. After mitomycin C or interferon beta only in 40 per cent each an effect could be observed. TNF to day is the most effective substance for treating ascites with moderate toxicity.

Ascites↗

An approach to fetal surgery: endoscopic use of excimer laser.

Recent progress in the area of prenatal diagnosis by means of ultrasound forces the improvement of surgical techniques for intra-uterine fetal therapy. By the use of short, intense pulses of ultraviolet laser light (20-200 ns long) a photoablation of defined samples of biological tissue is performed with no substantial thermal side effects. The experimental set-up applied in this study included endoscopic operation on five fetal lambs. Macroscopically, a sharp edge in the incision area was observed at both prechosen laser frequencies of 10 and 40 Hz. The clinical application of pulsed ultraviolet laser systems with the characteristics of guided photoablation and atraumatic incisions avoiding thermal side-effects opens new perspectives for fetal surgery.

Animals↗

[Effect of tamoxifen on parameters of cell-mediated immunity in postmenopausal patients with breast carcinoma].

In 48 postmenopausal breast cancer patients receiving an adjuvant therapy with 30 mg tamoxifen for 22 months on an average the effect of hormonal therapy on different immunologic parameters was examined and compared with an age-matched control group of breast cancer patients without hormonal therapy. Before beginning and after the end of tamoxifen treatment the following examinations were performed: Leucocyte Migrations-Inhibition-Test (LMI-Test) against autologous and homologous tumor and recall antigens, determination of the serum levels of tumor necrosis factor alpha, interleukin 2 and interferon alpha, as well as a determination of lymphocyte subsets (total T-, T-helper-, T-Suppressor- and natural killer cells) in the peripheral blood. Compared to the control group under a tamoxifen therapy the percentage of patients with a migration inhibition in the LMI-test increased, whereas the percentage of patients with an enhancement decreased. There were no changes concerning the LMI-reactivity against recall antigens as well as concerning the serum levels of the different cytokine and the differentiation of T-cell subsets compared to the control group. But we found an increase of natural killer cells. It can be discussed if the clinical effect of a tamoxifen treatment is possibly due to its immunological effect on the nk cell activity.

Aged↗

[The effect of adjuvant combined chemo/immunotherapy on immunological parameters and clinical course in patients with breast carcinoma].

In 61 breast cancer patients the effect of an combined adjuvant chemo-/immunotherapy with thymopentin (Timunox, Cilag) on different parameters of cell-mediated immunity (Leucocyte Migration Inhibition Test, serum level of tumor necrosis factor alpha, IL 2, Interferon alpha and distribution of lymphocyte subsets in the peripheral blood) and the clinical course of disease was evaluated and compared to patients receiving only chemotherapy. In cancer patients additionally treated with thymopentin an increase of the interferon alpha serum level could be observed, whereas the other parameters examined did not change. In the control group the percentage of T helper cells decreased under chemotherapy (p less than 0.05). Due to the short time of observation of 49 months until now no significant changes concerning the disease free interval and the time of survival between both groups could be found. Possibly the additional administration of thymopentin in breast cancer patients at least leads to a reduction of the immunosuppressive side effects of an adjuvant chemotherapy.

Breast Neoplasms↗

Cellular sensitization against spermatic and seminal plasma antigens in women after intrauterine insemination.

Using an indirect lymphokine-assay, the leucocyte-migration-inhibition-test (LMI-test), the cellular sensitization of fertile and infertile patients before and after homologous and heterologous intrauterine insemination (IUI) was investigated. In this assay several preparations of spermatozoa ("washed"-, "swim-up"- and "pellet"-spermatozoa) in different concentrations (1, 5 and 10 x 10(6) sperms/ml culture medium) and seminal plasma were tested as antigen. In all investigated groups a cellular immune response against spermatic antigen was demonstrable and seemed to be dose dependent. In contrast to fertile women who reacted with an enhancement of the macrophage migration for low concentrations the same concentration of antigen induced an inhibition of macrophage migration in fertile patients. For high concentrations of spermatic antigens there was a difference in the intensity of cell-mediated immune response between fertile and infertile women. Since infertile patients demonstrated an increased level of cell-mediated immune response it is possible that infertility may be caused by this altered immunological reaction. This response changes after multiple IUI-treatment and that change might be caused by the high concentration of spermatic antigens as there was a difference in the intensity of cell-mediated immune response between fertile and infertile women. Since infertile patients demonstrated an increased level of cell-mediated immune response it is possible that infertility may be caused by this altered immunological reaction. This response changes after multiple IUI-treatment and that change might be caused by the high concentration of spermatozoa. The immunological response of infertile patients seems to be similar in those receiving husband and donor IUI.

Adult↗

From the scene to the crime: the effect of alcohol and social context on moral judgment.

Forty men and women were given Kohlberg's Moral Judgment Interview (MJI) while drinking in a natural setting and were asked a series of questions about whether they should and would drive impaired. In a second testing in an academic context, these subjects were given an alternate form of the MJI and were asked whether they drove on the previous occasion. Forty additional men and women completed the MJI in an academic context and responded to the impaired driving questions hypothetically. Results revealed that Ss scored lower on moral maturity in the the social drinking contexts than in the academic contexts, especially when highly intoxicated. Ss responding hypothetically attributed more moral integrity to themselves than to others, indicating they would not drive impaired. The self-righteousness of these attributions was apparent in the behavior of Ss who drove to the social drinking settings--all but 1 drove home, however impaired.

Adult↗

[Continuous transcutaneous PCO2 measurement and laser spectroscopy for fetal monitoring in 3d degree atrioventricular block].

Obstetrical management in case of foetal third-degree AV block has been to date mainly via primary abdominal section, the indication being partly the foetal condition and partly also unsatisfactory childbirth monitoring. The article describes a childbirth associated with AV block, monitoring being effected by continuous measurement of the transcutaneous partial carbon dioxide pressure (tcpCO2) and via laser spectroscopy. Prenatal diagnostics and indications for vaginal delivery are also described. Updated knowledge on the pathogenesis of foetal AV block is presented.

Adult↗

[Laser spectroscopy--a new procedure in fetal monitoring].

Monitors for laser spectroscopy are available as an additional tool for foetal surveillance. Using this technique, continuous and non-invasive registration of four biochemical parameters (HbO2, HbR, blood volume and cytochrome aa3) can be performed. The calculation is based on the optical density after irradiation of the biological sample with pulsed laser light in the near-infrared range (755, 805, 845, 904 nm). We evaluated the new technique in a clinical trial of 20 patients. The application of the laser sensor was performed, using a modified amnioscope. During prenatal tracings in cases with suspect CTG patterns, hypoxia was not verified. In cases without late decelerations a decrease of the cytochrome aa3 signal was observed in less than 1%. During intrapartual measurements, near-infrared signals were compared with the result of the PO2 measurement in foetal blood analysis. We found a significant correlation for HbO2 and cytochrome aa3 with a correlation coefficient of r = 0.96 respectively r = 0.94. We conclude, that laser spectroscopy will potentially be of benefit for foetal monitoring as it might provide a basis for differentiation between foetuses at risk and non-hazardous cases.

Cardiotocography↗