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D Krebs

Publications and source records attributed to D Krebs.

At least 55 records · Page 3Linked to original sources
PubMed1997

Success of intracytoplasmic sperm injection in couples with male and/or female chromosome aberrations.

This paper reports on results of intracytoplasmic sperm injection (ICSI) in patients in whom constitutional or secondary chromosome aberrations were detected in the male and/or female partner. Out of 434 couples treated by ICSI (590 cycles), 16 couples (3.7%) were affected by constitutional chromosome aberrations and 96 (22.1%) by secondary chromosome aberrations. Constitutional chromosome aberrations were found in eight male and eight female patients. Couples with the aberration in the male showed significantly lower fertilization, implantation and pregnancy rates (P < 0.05). The occurrence of female constitutional chromosome aberrations led to lower fertilization rates but implantation and pregnancy rates were similar to a control group; however, a higher abortion rate was noted. In the group with secondary chromosome aberrations, 22 males and 59 females carried an abnormality and in 15 couples, both partners. Compared to the remaining (unaffected) 322 couples, fertilization and embryo transfer rates were reduced but implantation rates and pregnancy rates were not different. In all couples where an abortion occurred, mainly parental autosomal aberrations were involved (six out of eight). Our retrospective analysis shows that an unexpectedly high number of infertile couples in an ICSI programme are affected by chromosome aberrations, which in turn may explain the reduced fertilization rates observed in this subgroup of patients.

Abortion, Spontaneous↗
PubMed1997

Combined cytogenetic and Y chromosome microdeletion screening in males undergoing intracytoplasmic sperm injection.

We evaluated the frequency of chromosomal aberrations and microdeletions of the Y chromosome in a sample of 204 patients included in an intracytoplasmic sperm injection (ICSI) programme. The prevalence of Y chromosome deletions in males with severely or only moderately reduced sparm counts is mainly unknown, so that patients were chosen with sperm counts ranging from mild oligozoospermia to azoospermia. While six out of 158 (3.8%) patients showed constitutional chromosomal aberrations, only two out of 204 (0.98%) patients were diagnosed with a microdeletion of Yq11. One had a terminal deletion in subinterval 6 of Yq11.23 which included the DAZ gene and a corresponding sperm count < 0.1 x 10(6) spermatozoa/ml. The second patient had an isolated deletion of marker Y6PH54c, a more proximal site in subinterval 5 on Yq11.23, but repeatedly showed sperm counts of 3-8 x 10(8) spermatozoa/ml. Thus, of the 158 patients who underwent a combined cytogenetic and Y-microdeletion screening, eight patients (5.1%) showed chromosomal abnormalities, either at the cytogenatic (n = 6) or the molecular level (n = 2). In conclusion, although rare in number, microdeletions of the Y chromosome can also be observed in patients with moderately reduced sperm counts. A more proximal site of the deletion breakpoint does not necessarily imply a more severe impairment of spermatogenesis than a distal deletion site. In our sample, the overall frequency of constitutional chromosomal aberrations exceeded the incidence of microdeletions of the Y chromosome even in patients with idiopathic azoo- or severe oligozoospermia.

Chromosome Deletion↗
PubMed1997

Breast preservation versus mastectomy--recurrence and survival rates of primary breast cancer patients treated at the UFK Bonn.

The aim of this retrospective long-term analysis was to evaluate the approach of breast conservation in the light of the results obtained, on the basis of mastectomy, in patients with early breast carcinoma. Additionally, the effect of internal mammary and supraclavicular radiotherapy was analyzed. Therefore, local-regional recurrence (LRR) and survival rates were examined in 411 patients with T1 and T2 stages who had undergone either breast-preserving surgery with radiation or mastectomy. Individual risk factors such as nodal status, lymphangiosis carcinomatosa and age of the patients were evaluated, too. The rate of local-regional recurrence in patients who were treated by mastectomy and conservative surgery was 9.2% and 11.0%, respectively, with relapse happening earlier in the latter group (median of 16 vs. 24 months). Survival rates, however, were not different in the two groups. Tumour stage and nodal status had no influence on the local-regional recurrence rate in either group. In connection with lymphangiosis carcinomatosa, however, the rate increased to 14.5% (mastectomy) and 19.0% (breast-preserving surgery), respectively. Patients < or = 40 years had an even higher risk of LRR, with 20.6% when they underwent mastectomy and 30.8% following breast conservation. Internal mammary and supraclavicular radiotherapy had no positive effect on the survival rates, neither in the mastectomy nor in the breast conservation group. As a conclusion, in more than 60% of all T1 stages. and more than 50% of all T2 stages, the therapeutic concept of breast preservation seems to be justified.

Adult↗
PubMed1997

[Criteria for successful outcome of external fetal version from breech presentation to cephalic presentation].

The technique of external version of breech presentations has been proposed as a tool to reduce morbidity of fetus and mother. 79 cases of a 3 year period were evaluated aiming at identification of risk factors improving the success rate of the intervention. A total of 48% of attempts was successful. The most frustrating single factor was identified to be the oligohydramnion. Posterior implantation of the placenta improved the rate to 61%. The umbilical cord being localized by coloured Doppler had little influence even if positioned around the neck as neither success nor complications were predictable in this case. Maternal adipositas had a negative influence on the success rate. Perinatal morbidity war not increased in the group of external versions.

Breech Presentation↗
PubMed1996

Association of allelic losses on human chromosomal arms 11Q and 16Q in sporadic breast cancer.

Breast-carcinoma development presumably results from multiple mutational events in tumor-associated genes. Certain results indicate that some tumor-suppressor genes may combine their pathogenetic potential to synergistically promote tumor growth. In an effort to identify such mechanisms in breast tumors, a series of 77 (group I) paired blood tumor samples from patients with sporadic mammary carcinomas was analyzed for loss of heterozygosity with 15 polymorphic markers on the chromosomal arms 7q, 11q, 13q, 16q, 17p and 17q. A significant association was observed for the combination of allelic losses on chromosomes 11q and 16q. In order to confirm these findings, we studied a second independent series of 189 breast-tumor patients (group 2) with comparable histopathological tumor stages. Group 2 was examined for the same genetic alterations using the identical set of polymorphic markers. The data from this group confirmed the detected association of loss of heterozygosity on chromosomes 11q and 16q and indicate the cooperation of putative tumor-suppressor genes on the chromosomal arms 11q and 16q in a sub-set of breast carcinomas. The regions involved harbor the candidate genes ATM (mutated in ataxiatelangiectasia) on chromosome 11q23 and UVO (uvomorulin, cadherin E) and BBCI (breast basic conserved I) on chromosome 16q22-q24.

Alleles↗
PubMed1996

Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro.

Utilizing a microplate ATP bioluminescence assay, two human breast carcinoma cell lines, MCF-7 and MDA-MB-231, were tested against doxorubicin (DOX), cisplatin (DDP), and paclitaxel (Tx) alone and in combination with ascorbic acid (Vit C). In both cell lines, Vit C exhibited cytotoxic activity at high concentrations (i.e. 10(2)-10(3) microM). Both cell lines also were resistant to DOX. MCF-7 was found to be DDP-resistant, MDA-MB-231 was moderately sensitive to DDP. Both cell lines were strongly sensitive to Tx. Vit C both at non-cytotoxic (1 microM) and moderately cytotoxic concentrations (10(2) microM) improved the cytotoxicity of DOX, DDP, and Tx significantly. Combination effects between Vit C and DDP or Tx were partly synergistic and partly additive or subadditive whereas a consistent synergism was found between Vit C and DOX. The mechanisms by which Vit C potentiates the cytostatics studied are yet unclear and should be evaluated further.

Antineoplastic Agents↗
PubMed1996

Dissection of the basic subdomain of the c-Jun oncoprotein: a structural analysis of two peptide fragments by CD, Fourier-transform infrared and NMR.

In a previous paper, we reported on the structural properties of a 35-residue peptide corresponding to a modified basic subdomain (bSD) of the basic zipper protein c-Jun (residues 252-281) as determined by combined use of 1H-NMR, circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopies [Krebs, D., Dahmani, B., El Antri, S., Monnot, M., Convert, O,. Mauffret, O., Troalen, F. & Fermandjian, S. (1995) Eur. J. Biochem. 231, 370-380]. The fragments NP and CP (the N-terminal residues 1-19 and C-terminal residues 16-35 of bSD, respectively) proved to be particularly useful for the assignment of the 1H-NMR spectra of the full-length bSD, which has been achieved completely in aqueous solution and partially in trifluoroethanol. Here, we report on the structural properties of NP and CP in aqueous solution and under varying H2O/trifluoroethanol conditions, again using 1H-NMR, CD and FT-IR experiments. Both CD and FT-IR results established that the fragments are weakly structured in aqueous solution. Addition of trifluoroethanol to aqueous solutions of the peptides produced their stabilization into helix, following a profile sigmoidal for NP and nearly linear for CP. Quantitative NOEs, secondary Halpha chemical shifts, NH temperature coefficients and 3JalphaN coupling constants for the peptides in aqueous solutions provided indications for weak helix features (nascent helices) manifested within two sites (continuous dNN NOEs) in both NP and CP. For each peptide, an excellent agreement was observed between experiments and predictions with the AGADIR program for the location of these nascent helices in the sequences. Trifluoroethanol provoked both the alpha-helix stabilization within these sites and the alpha-helix propagation to adjacent amino acid residues. Finally, our results reflected the high flexibility and helix potential of the NP and CP fragments, these two properties seeming crucial for the accommodation of c-Jun to its specific DNA targets. The results demonstrated also the fragmentation's benefits in dissecting a protein or a complex peptide into smaller fragments and analyzing their structure individually.

Amino Acid Sequence↗
PubMed1996

Scintimammography with technetium-99m methoxyisobutylisonitrile: comparison with mammography and magnetic resonance imaging.

The aim of the study was to compare the diagnostic accuracy of scintimammography with technetium-99m methoxyisobutylisonitrile (MIBI; SMM) in the detection of primary breast cancer with that of mammography (MM) and magnetic resonance imaging (MRI). Fifty-six patients with suspected lesions detected by palpation or MM were included in the study. Within the 4 weeks preceding excisional biopsy, MM and MRI were performed in all patients. Between 5 and 10 min after the injection of 740 MBq 99mTc-MIBI, SMM in the prone position was performed. In the total group of 56 patients, 43 lesions were palpable, while 13 were non-palpable but were detected by MM. Breast cancer was confirmed by histopathology in 27 of the patients (22 palpable and 5 non-palpable carcinomas). The tumour size ranged from 6 to 80 mm in diameter. For non-palpable lesions, the sensitivity of SMM, MM and MRI was 60%, 60% and 100%, respectively, while the specificity was 75%, 25% and 50%, respectively. For palpable breast lesions, all methods showed high sensitivity (SMM 91%, MM 95%, MRI 91%) but SMM demonstrated significantly higher specificity (SMM 62%, MM 10%, MRI 15%). In two mammographically negative tumours (dense tissue), SMM showed a positive result. In comparison to MRI, one additional carcinoma could be diagnosed by SMM. It may be concluded that for palpable breast lesions, the diagnostic accuracy of SMM is superior to that of MM and MRI. Through the complementary use of SMM it is possible to increase the sensitivity for the detection of breast cancer and multicentric disease. In patients in whom the status of a palpable breast mass remains unclear, SMM may help to reduce the amount of unnecessary biopsies.

Biopsy↗
PubMed1996

Heterogeneity of in vitro chemosensitivity in perioperative breast cancer cells to mitoxantrone versus doxorubicin evaluated by a microplate ATP bioluminescence assay.

Apart from clinical trials, mitoxantrone (MX) is rarely used in breast cancer (BC) due to the anticipated anthracycline cross-resistance. We have examined this drug versus doxorubicin (DOX) using data obtained from in vitro microplate ATP tumor chemosensitivity assays (ATP-TCA) of BC cells which were derived from 55 chemotherapy-naive patients at time of primary surgery. Both drugs were tested at 6 different concentrations ranging from 6.25% to 200% peak plasma concentration in vivo (PPC). Differences between DOX and MX observed for mean IC50, IC90, and a sensitivity index (SI) were not statistically significant. In vitro response rates were 44% for DOX and 52% for MX. 34 of 52 eligible assays (65%) showed comparable activity of both drugs whereas a lack of cross-resistance was observed in the remaining 18 (35%) tumors as indicated by differences for SI. Cumulative concentration-response plots of tumors responding in vitro with a > or = 50 percent or > or = 90 percent tumor cell inhibition showed a strong dose-dependence for both DOX and MX at concentrations which normally can be achieved within clinical tumors (i.e. 6.25%-50% PPC). At higher concentrations, however, cytotoxicity of DOX and MX could not be improved by further in vitro dose escalation. Moreover, a substantial proportion of BC specimens (DOX: 48.1%; MX: 40.4%) did not experience a > or = 90 tumor cell inhibition at 200% PPC. In conclusion, in vitro results obtained by ATP-TCA indicate that there is no cross-resistance between MX and DOX in a substantial proportion of BC patients. This may be clinically useful and suggests that combinations including MX should be tested in patients clinically resistant to DOX containing regimens. Since both drugs produced sigmoidal concentration-response curves, dose escalation beyond a certain point may not produce increased sensitivity.

Adenosine Triphosphate↗
PubMed1996

-Chemosensitivity testing in gynecologic oncology. Experiences with an ATP bioluminescence assay-.

In the present study, our first experiences with the ATP Tumour Chemosensitivity Assay (ATP-TCA), a novel method for pretherapeutic drug testing, are reported. During one year, a total of 111 samples obtained from patients suffering from different gynaecological malignancies (ovary: 53, breast: 41, others: 17) were sent for chemosensitivity testing. The quality of 104 single cell suspensions was sufficient for further processing. Evaluability rates ranged from 71% (breast cancers and non-ovarian tumours) to 83% (ovarian cancers) with an average of 77%. Evaluability of recurrences was slightly better compared to primaries. A total of 18 different antineoplastic agents and 67 drug combinations was used for in vitro testing with an average of 12.4 drugs/combinations tested per each sample (ovary: 14.8, breast: 9.7, others: 10.2). In 70 of 111 cases, the ATP-TCA was followed by chemotherapy with 44 cases treated in respect of the assay results and 29 cases receiving an antineoplastic regime, which differed from the standard treatment protocol. Compared to untreated patients, recurrences were treated more frequently based on the ATP-TCA, with a majority receiving an alternative protocol as proposed by the assay. In ovarian carcinoma, chemosensitivity testing was of particular importance for the further therapy. 41 of 53 patients were treated by chemotherapy with 29 therapies basing on the results of the assay (alternative protocol: 17). The good correlation of the ATP-TCA and the individual clinical course of the patients was demonstrated by two case reports of recurrent ovarian carcinomas, one of them responding well to platinum-based combinations and the other presenting in vitro and in vivo platinum-resistance. In conclusion, our first experiences with the ATP-TCA were promising. Our results, however, warrant confirmation by studies with a sufficient number of cases and an extended observation period.

Adenosine Triphosphate↗
PubMed1996

[Ileus in late pregnancy--sequela of follicle puncture within the scope of in vitro fertilization?].

Complications in connection with the puncture in in-vitro fertilisation (IVF) occur normally relatively soon after the operation. This is a report on a patient in her 28th week of gestation, operated on by laparotomy for ileus. Retrospectively this acute event must be seen as a very rare late complication connected with the puncture. It must be stressed that patients should be informed about this eventually.

Abdomen, Acute↗
PubMed1996

The combination of two semen preparation techniques (glass wool filtration and swim-up) and their effect on the morphology of recovered spermatozoa and outcome of IVF-ET.

The aim of this prospective study was to relate sperm quality, especially sperm morphology, to the outcome of IVF results, when glass wool filtration (GWF) and swim-up were used in combination for the preparation of spermatozoa. A total of 60 ejaculates were analysed. GWF was compared with glass wool filtration/swim-up (GWF-SU) by using aliquots from the same semen samples to increase the precision of the comparison and to establish the cumulative effect of these two semen preparation methods on the morphology of the recovered spermatozoa. Sperm parameters were examined in native semen, in semen preparation samples after GWF and GWF-SU. The mean percentages for motility, morphology and velocity were improved significantly over those in fresh semen only when GWF-SU was used. GWF alone resulted only in a significantly higher recovery of motile spermatozoa. In semen preparation, 10% of spermatozoa with normal morphology appeared to be the cut-off point as there was a significantly higher recovery in fresh semen samples containing > 10% morphologically normal spermatozoa after GWF-SU. Outcome of IVF-ET following preparation with GWF-SU showed better results in comparison to the swim-up procedure alone, though this difference was not statistically significant. The cut-off point was also > 10% morphologically normal spermatozoa. Improvement in all aspects of IVF-ET occurred when native semen contained > 10% morphologically normal spermatozoa. It is concluded that GWF alone did not produce significantly better results but, in combination with swim-up, it resulted in significantly better sperm morphology and in an improved outcome of IVF-ET for fresh semen samples with > 10% morphologically normal spermatozoa.

Adult↗
PubMed1996

Cerebral tissue oxygenation during hypoxia and hyperoxia using artificial placentation in lamb.

Aiming at a better understanding of the pathophysiologic basis of perinatal encephalopathy, we evaluated patterns of tissue oxygenation during hypoxia and hyperoxia. We utilized both laserspectroscopy and invasive tissue-Po2 microneed measurements synchronously in five newborn lambs (141-143 days of gestation). The model of artificial placentation provided defined changes of the blood gases, using a extracorporeal circuit with interposition of membrane lung. During hyperoxia, the Po2 at the blood outlet port of the lung was raised to > 300 mmHg for five minutes. During hypoxia, Po2 was diminished as oxygen at the gas phasis was replaced by nitrogen. After the induction of hyperoxia, a rise of tissue-Po2 was observed. The synchronously recorded data of the laserspectroscopy showed adequately rising HbO2 values in concordance (r = 0.97, p < 0.001). As a constant finding we did not observe Cyt-aa3 changes during induced hyperoxia with tissue-Po2 values of < 40 mmHg. Furthermore, no changes in blood volume occurred in this case. A different pattern of the laserspectroscopic parameters was found when the tissue-Po2 rose above a value of > 40 mmHg and Cyt-aa3 rose after a lag-time occurred. During induced hypoxia an immediate fall of tissue-Po2 corresponding with a fall of HbO2 in the spectroscopic tracing occurred (r = 0.87, p < 0.001). A fall of the Cyt-aa3 level was seen with a lag-time when the tissue-Po2 had reached values of below 10 mmHg. In addition, a rise of blood volume was recorded in all cases of induced hypoxia. In conclusion, the results indicated that cellular redoxe state remains stable over a large range of oxygen partial pressure changes.

Animals↗
PubMed1996

Technetium-99m-MIBI scintimammography for suspicious breast lesions.

UNLABELLED: The aim of this study was to evaluate the diagnostic accuracy of scintimammography with 99mTc-MIBI in patients with suspected primary breast cancer as monitored by SPECT or planar imaging. METHODS: Patients with a suspect lesion detected by palpation or mammography were entered in the study. Excisional biopsy was performed on all patients and a mammography was performed within three weeks prior to scintigraphy. All patients received intravenously 740 MBq 99mTc-MIBI in the arm, contralateral to the suspicious breast, and were subsequently examined in a prone position. At 5-10 min postinjection, planar images were obtained in both the lateral and anterior views with an acquisition time of 10 min. After planar imaging, SPECT imaging was performed using a two-head high-resolution gamma camera. RESULTS: In the total patient group of 54 patients, 40 lesions were palpable and 14 were nonpalpable but were detected by mammography. Breast cancer was confirmed in 24 of the patients and 20 of the palpable masses were found to be carcinomas. The tumor size ranged from 6 to 90 mm in diameter. In scintigraphic studies, the overall sensitivity was 88% for planar imaging and 83% for SPECT. Specificity was 83% and 80%, respectively. Sensitivity for palpable lesions was 100%. The smallest detectable tumor measured was 9 mm in diameter and could only be visualized in the planar scintigram. CONCLUSION: Scintigraphy with 99mTc-MIBI is extremely sensitive for the detection of primary breast cancer in patients with a palpable mass. SPECT, however, did not improve the diagnostic accuracy over planar scintimammography.

Adenocarcinoma↗
PubMed1996

[Comparison of the cytostatic effect of epirubicin and mitoxantrone on native breast carcinoma cells using the ATP tumor chemosensitivity assay].

This trial was conducted to compare the cytotoxic efficacy of epirubicin (EPI) and mitoxantrone (MX) in clinical tumor samples derived from 34 chemotherapy-native women suffering from breast cancer by utilizing an in vitro ATP tumor chemosensitivity assay (ATP-TCA). An assay evaluability rate of 32/34 (94 %) was achieved. There was no significant difference between EPI and MX when regarding the mean IC90 and IC50 values corresponding to nearly identical overall in vitro response rates observed for both drugs (EPI: 62.5 %; MX 59.4 %). Individual IC90 values showed a weak correlation which was lacking for IC50. Accordingly, a lack of cross-resistance was found in 11/32 tumors (34 %) with 6 tumors showing sensitivity to EPI and resistance to MX and 5 tumors showing resistance to EPI and sensitivity to MX. At lower drug concentrations, a steep slope of the cumulative dose response curves for IC50 could be observed for both cytostatics with an apparent shift to higher concentrations at the IC90 level. For both drugs, a loss of linearity of the IC90 and IC50 dose-response curves was found at maximum concentrations. In conclusion, our results demonstrated an overall equality of EPI and MX in previously untreated breast cancers which already has been found clinically in metastatic disease. Nevertheless, we were able to show that approximately one third of chemotherapy-naive breast carcinomas are not cross-resistant to both EPI and MX. These findings could have implications on planning adjuvant chemotherapy for an individual breast cancer patient.

Adult↗
PubMed1996

[Does interferon-alpha enhance the effect of tamoxifen-medroxyprogesterone acetate and hydroxyflutamide on in vitro tumor cells?].

In our laboratory the influence of tamoxifen, medroxyprogesterone acetate (MPA) and hydroxyflutamid with and without interferon alpha (IFN) was tested on the proliferative capacity of two breast and one ovarian cancer cell line and three ovarian cancer tissues in the colony assay described by Hamburger and Salmon. The following results were seen: 1. Testing the four drugs alone in 6 different cell cultures, in vitro growth inhibition of more than 30% was seen 3 respectively 4 times. Growth inhibition of more than 50% could be shown only in particular cases. The higher dose of an active substance led up to three times more in comparison to the set growth restraint than the smaller dose. A reaction depending on the concentration was seen. 2. The combination of IFN and tamoxifen could not really increase the antiproliferative capacity of each substance alone. Nevertheless we were able to show a significant augmentation of the cell-growth inhibiting effect of MPA or hydroxyflutamid when it was given together with IFN: the increased antitumor activity was evident if cells were tested which showed progesterone-(PR) or androgenereceptors (AR). The results indicate that positive interactions of IFN and MPA or IFN and hydroxyflutamid are possible. Although an augmentation of the activity of tamoxyfen by IFN was not found it should be stressed that the schedule of treatment seems to be clearly critical.

Androgen Antagonists↗