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Biomedical subjects

D Krebs

Publications and source records attributed to D Krebs.

At least 145 records · Page 8Linked to original sources

[Comparison of a long-acting and short-acting GnRH analog in combination with gonadotropins in in vitro fertilization under various indications].

The occurrence of a premature luteinizing hormone (LH)-surge during gonadotropin stimulation for in-vitro fertilization leads to cancellation of the cycle. Moreover, insufficient follicular maturation is often caused by elevated basal gonadotropin levels. Therefore the gonadotropin releasing hormone (GnRH) agonist, D-TRP6-LHRH, was applied to patients exhibiting premature LH-surges, hyperandrogenemia or incipient premature menopause. 119 cycles were treated, using a long-acting versus a short-acting GnRH agonistic analogue. In protocol 1, patients received daily subcutaneous injections of 100-500 micrograms of a short-acting compound. In protocol 2, a long-acting bolus of 3.2 mg was given intramuscularly. Concomitant human gonadotropin (HMG) stimulation started in protocol 1 after clinical and biochemical evidence of pituitary suppression and in protocol 2 after a fixed suppression interval of 14 days. In protocol 1 higher estrogen levels were reached with more oocytes harvested. The pregnancy rate per transfer was increased from 3.5% to 18%, with most pregnancies occurring with protocol 2. The cancellation rate of 13.4% was mainly due to insufficient follicular development in patients, in whom premature menopause was suspected. Hyper-androgenemic patients with an elevated LH/FSH-ratio exhibited the best follicular recruitment with the highest pregnancy rate of 25% per transfer. Thus combined GnRH-agonist/gonadotropin stimulation offers a causal treatment for patients susceptible to premature LH-surges and for hyperandrogenemic patients.

Adult↗

[Intra-tubal embryo transfer. A new therapy in andrologic sterility].

The intratubal transfer of pronucleus or early cleavage stage embryos (2-8-cell stage) is a new method in the treatment of human infertility. Following transvaginal sonographic oocyte retrieval, in vitro fertilization is performed and the fertilized oocyte pronucleus-stage or embryos are transferred into the tube by laparoscopy. By comparison to GIFT (intratubal gamete transfer), 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 the embryonic development occurs in the physiological milieu of the oviduct. Up until the present, the new procedure was performed in 40 patients with male factor or unexplained infertility. In 11 cases (28%) a pregnancy could be achieved. One abortion, but no ectopic pregnancy was observed. No difference in the pregnancy rates could be observed between the transfer of pronucleus stage and the early cleavage stage embryos. This method combines the advantages of IVF and GIFT and offers a successful procedure for the treatment of infertility.

Adult↗

[Pregnancy and labor in acute intermittent porphyria].

We report on the pregnancy and delivery of a 33-year old nullipara suffering from acute intermittent porphyria. Despite high risk of mortality and exacerbation of the disease, no complications occurred, since basic therapeutic principles were followed.

Acute Disease↗

Establishment of pregnancy related to embryo transfer techniques after in-vitro fertilization.

The success rate of embryo transfers is not influenced by the choice of the catheter or the position of the patient during embryo transfer. The quality of embryos seems to be the crucial factor for the establishment of pregnancy and the transfer of more than one embryo (so-called multiple transfer) increases the pregnancy rate. Embryo transfer under general anaesthesia does not improve the pregnancy rate significantly. Intratubal embryo transfer in patients with normal Fallopian tubes seems to be promising, especially in cases of andrological infertility.

Embryo Transfer↗

Fertilization of human oocytes in capillary tubes with very small numbers of spermatozoa.

Human oocytes can be fertilized with high rates of success under in-vitro conditions even if only low numbers of spermatozoa are used. A culture system has been developed in which fertilization is performed in haematocrit capillary tubes (length 75 mm; i.d. 0.8-0.9 mm). Oocytes were fertilized in 5-10 microliters of different sperm suspensions containing a total of 500, 1000, 2000 and 4000 spermatozoa per oocyte (0.1-0.4 x 10(6) spermatozoa/ml). Oocytes were obtained from 10 patients participating in an in-vitro fertilization programme; of these, 32 oocytes were fertilized in capillary tubes and 32 oocytes were cultured using standard methods (1 ml culture medium in tissue culture tubes; 0.1-0.2 x 10(6) spermatozoa/ml). The overall fertilization rate of oocytes cultured in tissue culture tubes was 78% (25/32) and the fertilization rates in capillary tubes using 4000, 2000, 1000 or 500 spermatozoa per oocyte were 71% (5/7), 86% (6/7), 60% (6/10) and 50% (4/8), respectively. The fertilization rate of mature oocytes was higher compared with immature oocytes when fertilization was performed in culture tubes (83 and 63%) or in capillary tubes (74 and 44%). Fertilization in capillary tubes using a 10 microliter of oocyte and spermatozoa suspension compared to 5 microliters seemed to provide better culture conditions, resulting in higher fertilization and cleavage rates. These preliminary results indicate that fertilization of human oocytes under in-vitro conditions can be achieved even with very low numbers of spermatozoa.

Female↗

Successful embryo transfer of cryopreserved and in-vitro fertilized rabbit oocytes.

In-vitro fertilization experiments with frozen/thawed rabbit oocytes were performed to develop an effective technique to be used for the in-vitro fertilization of cryopreserved human oocytes. Ovulatory oocytes, collected from the oviduct of virgin does 13 h after induction of ovulation by HCG injection, were cryopreserved slowly to -30 degrees C and plunged directly into liquid nitrogen. A mixture of 1.5 M 1,3-propanediol and 0.1 M sucrose was used as a cryoprotectant. After thawing, the oocytes were incubated with in-vitro capacitated sperm for 5 h in defined Brackett's medium. Fertilized ova were cultured for an additional 20 h until the 4-to-8-cell stage was reached. These embryos were transferred to pseudopregnant recipient rabbits which were 'asynchronous' in the sense that they had been given an injection of HCG 30, 24 and 18 h before starting to do the embryo transfer. A 32% survival rate of frozen/thawed oocytes was achieved. The fertilization rate was 74% (181/264) in this study. A total of 53 embryos was transferred to the oviducts of six recipients of three different asynchronicity and four young were born. The highest implantation rate (including resorptions) of 18% could be achieved in this investigation by using -6 h asynchronous recipients, while the overall implantation rate was 9.4%.

Animals↗

[Comparison of tumor-associated cellular and nonspecific humoral immune parameters in immunologic monitoring of breast cancer].

In 119 patients with breast cancer states pT1-4 N0-3 M0 the following parameters of tumor-associated cellular and unspecific humoral immunity were determined: (1) leukocyte-migration-inhibition test against preparations of the autologous and homologous tumor tissue; (2) determination of the immunosuppressive activity of the serum on the PHA-, Con A- and PWM-induced lymphocyte transformation; and (3) determination of the alpha-2 pregnancy-associated globulin (alpha-2-PAG) serum level. In both groups of lymph node negative and positive breast cancer patients, half of the patients showed a significant reaction in the LMI test in the form of a reduced or enhanced migration of the macrophages (enhancement). In lymph node negative breast cancer patients the immunosuppressive activity of the serum on the PHA- and CON A-induced lymphocyte reactivity was decreased, whereby we found a positive correlation between the immunosuppressive activity of the serum and the LMI reactivity against autologous tumor tissue. We found no differences in the alpha-2-PAG serum level between lymph node negative and positive breast cancer patients, but there were greatly increased alpha-2-PAG levels in LMI-reactive patients compared to those showing an enhancement in the LMI test. A tumor-associated cellular immunity could be shown in the LMI test in breast cancer patients, which can be correlated with other humoral immune parameters. Especially the demonstration of an immunological enhancement in the LMI test could possibly be used for the definition of high-risk groups.

Breast Neoplasms↗

[The effect of immunotherapy with thymopentin on the parameters of cellular immunity and the clinical course of gynecologic tumor patients].

In 25 patients with cervical, uterine and ovarian cancer with a depletion of T-helper cells and a lack of reactivity in the LMI-Test a course of immunotherapy with thymopentin (Timunox, Cilag Biotech) at a dosage of 100 mg/die for 2 weeks and subsequently 100 mg 3 x/week for 4 weeks was performed and a comparison was made with a control group of 59 patients receiving no immunotherapy. The following parameters of cell-mediated immunity were determined: (1) leucocyte-migration-inhibition-test (LMI-test) against the tumor and varidase, and (2) number of T-helper/inducer-, T-suppressor/cytotoxic-, total T-, and natural killer cells in the peripheral blood. After a course of immunotherapy no changes in the mean value of the percentage of the cell-subpopulations could be observed, but in a quarter of all patients a reaction in the LMI-test could be shown. In the control group, under chemotherapy, the percentage of T-helper-, T-suppressor- and total T-cells decreased strongly, whereas in the immunotherapy group the percentage of these populations remained unchanged. Under the restriction of a mean observation time of only 18 (5-32) months no differences concerning the survival time between both groups could be observed; only in advanced ovarian cancer patients could a slight positive effect of immunotherapy be shown. These results support the indication of a course of immunotherapy with thymopentin in combination with chemotherapy, especially in advanced cancer patients.

Adjuvants, Immunologic↗

Polychlorinated biphenyls: the occurrence of the main congeners in follicular and sperm fluids.

We have studied the presence of polychlorinated biphenyls in human body fluids associated with reproduction. Since the polychlorinated biphenyls represent a family of compounds, 3 of the main congeners of this family were selected for this study. The distribution of these 3 congeners was investigated in 37 specimens of follicular fluid and in 16 specimens of sperm fluid. Both fluids showed a similar, low contamination with total polychlorinated biphenyls (ca. 10 micrograms/kg on average), but it was evident that the follicular fluids preferentially accumulated the more highly chlorinated components. This finding must be taken into account when interpreting the concentration levels of the main congeners in relation to total pollution and the toxic potential of polychlorinated biphenyls.

Female↗

Laser spectrophotometry in the fetus.

Laser spectrophotometry with near-infrared light is newly available for clinical application. The equipment consists of a near-infrared datacollection unit (NIRDCU) and apersonal computer. Emission of laser light at wavelengths of 775, 805, 845 and 904 nm is provided by the four laserdiodes of the NIRDCU. By analyzing changes of optical density during laser radiation, information is achieved about the intracellular redoxstate and relative changes of blood volume. During measurement with the system on fetal head we were able to get a first impression of the methods potential. While the application of the laser sensors is still cumbersome, signals providing information of the relative changes of hemoglobine concentrations, relative changes of blood volume and cytochrome aa3 seem achievable. Laser spectrophotometric monitors may become save, low cost and portable instruments for the noninvasive assessment of the biochemical and biophysical status in the fetus.

Fetal Monitoring↗

Transvaginal sonography of the endometrium during ovum pickup in stimulated cycles for in vitro fertilization.

The endometrium of a series of 190 in vitro fertilization patients was investigated by transvaginal ultrasound. The endometrial pattern was related to the likelihood of implantation. No such relationship was found for the thickness of the endometrium. There was not a strong correlation between the endometrium and hormonal values. However, three endometrial patterns were detected after hormonal stimulation. The predominant pattern consisted of an outer hyperechogenic layer and an inner hypoechogenic layer. This pattern correlated in a positive fashion with subsequent implantation. It is concluded that the texture of the endometrium at the time of ovum pickup has a prognostic value for the likelihood of implantation to occur.

Embryo Implantation↗

Intraoperative, intraperitoneal chemotherapy in advanced gynecological malignancies. A report on the acceptability of a new therapeutic regimen.

Considering that in gynecologic carcinomas cells and cellular tumor parts can be left in the abdominal space leading to an increased growth of recurrences due to a change in the cell-kinetic situation, 19 patients with advanced gynecologic tumors were treated locally with 15 mg mitomycin or 30 mg (40 mg) mitoxantrone dissolved in 1000 mg saline before the operation was completed. The course of disease after intraoperative, intraperitoneal chemotherapy given in addition to the usual chemo- or radiotherapeutic regimen was as follows: in 14 patients assessed up to now, a NED state was achieved 4 times, while there was a partial remission in 2 cases and a SD situation in one. In two women there was progression. In the group with recurrent treatment (5 women), a further progressive course was observed in 4 patients. In one case there was a partial remission. With mitoxantrone serum levels between in 10-60 ng/ml, two subilium situations and postoperative nausea were noticed as side-effects. Among the changes noted in the chemical laboratory, there was one leukopenia grade IV and five grade III-leukopenias as well as various intermittent alterations of the liver values and electrocytes. One case of wound healing disturbances with prolapsed small intestine convolution in the wound area was observed in the tumor growth developing in the abdominal wall. The side-effects of the intraoperative and intraperitoneal therapy with cytostatics were generally acceptable. Given the observed courses of the disease, a continuation of the intraperitoneal therapy form aimed against postoperative residual and aggressively growing tumor cells would appear to be justifiable.

Combined Modality Therapy↗

Fertilization of human oocytes in capillary tubes using very low number of spermatozoa. A new treatment of severe oligozoospermia?

In this study a culture system was developed in which successful fertilization was performed in capillary tubes (75 x 0.9 mm) using very low numbers of spermatozoa. Oocytes were fertilized in 5-10 microliters medium containing 500-4,000 sperms (0.1-0.4 Mill. sperms/ml). In 10 IVF-patients with normozoospermia a total of 64 oocytes were cultured in capillaries and in tissue culture tubes (1 ml medium, 0.1 Mill. sperms/ml). The fertilization rate in tubes was 78% (25/32) and in capillaries using 4,000, 2,000, 1,000 and 500 sperms/oocyte: 71% (5/7), 86% (6/7), 60% (6/10) and 50% (4/8), respectively. The fertilization rate of mature oocytes was higher compared to immature oocytes (tubes: 83% vs 63%) capillaries: 74% vs 44%). Fertilization in capillaries using a volume of 10 microliters compared to 5 microliters seems to provide better culture conditions (fertilization rate: 75% vs 62.5%) cleavage rate: 91% vs 60%). The capillary technique may also provide a new treatment of severe oligozoospermia or in cases of poor sperm recovery after sperm preparation for IVF since in 3 patients with poor quality semen (total motile sperm/ejaculate: 0.2-1.4 Mill.) fertilization, cleavage and 1 pregnancy resulted. These preliminary results indicate the usefulness of capillary technique if standard IVF systems fail or before semen donation or sperm microinjection are anticipated.

Female↗

Continuous fetal intrapartum monitoring in supraventricular tachycardia by atraumatic measurement of transcutaneous carbon dioxide tension.

A case of premature beats and paroxysmal supraventricular tachycardia without resulting congestive heart failure was diagnosed in a fetus of 38 weeks of gestation by echocardiography. Transplacental antiarrhythmic therapy was initiated, but a complete cardioversion was not achieved. Due to these arrhythmias adequate fetal heart rate monitoring during labor was not possible. By using continuous transcutaneous measurement of fetal carbon dioxide tension the fetus was delivered spontaneously, having been adequately monitored in spite of the effect on the fetal heart rate of the arrhythmias.

Adult↗

Pregnancy following repair of a congenital atresia of the uterine cervix and upper vagina.

A case of congenital atresia of the uterine cervix combined with atresia of the upper vagina and without any other anomalies is reported. Direct anastomosis of cervix and vagina resulted in a restoration of reproductive function. The patient conceived 6 years afterward and delivered a healthy boy by cesarean section at 31 weeks of gestation. Therapeutic reconstructing options for this kind of genital tract malformation with respect to reproductive function are discussed.

Adolescent↗

[Immunocytochemical detection of the estrogen receptor and lectin binding sites in tumor cell colonies growing in vitro].

Since it became clear that tumor cell colonies growing in soft agar are closely related to embryonic tumor cells, it has been possible to examine, with the aid of immunohistochemical methods, the behavior of estrogen receptors (ER) and lectin binding sites on those tumor components which determine malignant growth. With this aim in mind, 14 breast cancers, four ovarian cancers, and one corpus cancer with ER concentrations known from DCC studies were cultured in a colony assay. Using immunohistochemical techniques it was possible, after preparing permanent cultures, to demonstrate the estrogen receptors and lectin binding sites on the tumor cell colonies cultured in vitro.

Breast↗