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Biomedical subjects

M Friedrich

Publications and source records attributed to M Friedrich.

At least 127 records · Page 7Linked to original sources

Raltitrexed (Tomudex): an alternative drug for patients with colorectal cancer and 5-fluorouracil associated cardiotoxicity.

Two patients with proven 5-fluorouracil (5-FU)-associated cardiotoxicity were treated with the specific thymidylate synthase inhibitor raltitrexed safely, without evidence of cardiotoxicity. Raltitrexed might be an alternative for patients with advanced colorectal cancer and 5-FU-associated cardiotoxicity. 5-FU cardiotoxicity is not due to the antineoplastic mechanisms via thymidilate synthase.

Adenocarcinoma↗

Human ovarian cancer xenografts in nude mice: chemotherapy trials with paclitaxel, cisplatin, vinorelbine and titanocene dichloride.

The new cytostatics titanocene dichloride and vinorelbine were compared to cisplatin and paclitaxel using a human ovarian cancer xenografts model. Biopsy material from a native human ovarian carcinoma was expanded and transplanted into 96 nude mice. The animals were divided into six treatment groups: cisplatin 3 x 4 mg/kg, paclitaxel 5 x 26 mg/kg, vinorelbine 1 x 20 mg/kg, titanocene dichloride 3 x 30 mg/kg, titanocene dichloride 3 x 40 mg/kg and a control group treated with 0.9% saline. Each experiment was repeated with eight mice in each treatment group. Treatment groups were evaluated in terms of average daily increase in tumor volume and average daily body weight increase of nude mice based on slopes of least-square regressions performed on individual animals. The slope factors alpha and beta of the body weight (alpha) and tumor volume changes (beta) within each group during the course of an experiment were calculated. Both a statistically significant decrease (p<0.05) in the body weight of the experimental animals (cisplatin: alpha = -0.5163, vinorelbine: alpha = -0.6598, paclitaxel: alpha = -0.6746, titanocene dichloride 3 x 30 mg/kg: alpha = -0.6259, titanocene dichloride 3 x 40 mg/kg: alpha = -0.7758) and a significant reduction (p<0.05) of the increase in tumor volume (cisplatin: beta = 12.049, vinorelbine: beta = 0.504, paclitaxel: beta = -1.636, titanocene dichloride 3 x 30 mg/kg: beta = 6.212, titanocene dichloride 3 x 40 mg/kg: beta= -0.685) was shown in all treated groups compared to the control group (alpha = -0.1398; beta = 23.056). No significant weight changes were observed between the individually treated groups. A statistically significant reduction of the tumor growth occured under paclitaxel (beta = -1.636), vinorelbine (beta = 0.504) and titanocene dichloride medication 3 x 40 mg/kg (beta = -0.685), as compared to the group treated with cisplatin (beta = 12.049). We found titanocene dichloride to be as effective as paclitaxel and more effective than cisplatin. Vinorelbine seems to be a very effective antineoplastic agent exhibiting a significant higher cytostatic effect than cisplatin. Both titanocene dichloride and vinorelbine provide new therapeutic options in women with ovarian carcinoma not responding to standard chemotherapy.

Analysis of Variance↗

Intra- and infrahepatic agenesis of the inferior vena cava with azygos continuation accompanied by duplication of the postrenal segment.

Agenesis of one or more segments and duplication of the infrarenal segment are, individually, rare abdominal variants of the inferior vena cava (IVC). In this article, the authors report on a case in which these two anomalies occurred concurrently. Details of the embryology are presented insofar as they are necessary for an understanding of this IVC variant. Spiral computed tomography makes it possible to define the vascular morphology and to make a differentiation from lymphadenopathy. Cavography gives an overall picture of the vascular morphology.

Abnormalities, Multiple↗

Expression of 1,25-dihydroxy vitamin D3 receptor in breast carcinoma.

We investigated immunohistochemically the expression of 1,25 dihydroxy vitamin D3 receptors (VDRs) in normal human breast tissue and in breast carcinomas. For the first time, a VDR immunoreactivity score (VDR-IRS) in breast tissue is presented. Mean VDR-IRS in breast carcinomas was 7.28 compared to 1.55 in normal breast tissue. Comparing staining patterns for VDR and Ki-67, no visual correlation was found, indicating that VDR upregulation in breast carcinomas is not exclusively controlled by the proliferative activity of these tumor cells. Our study adds to the body of evidence that breast tissue may be a sensitive target organ for therapeutically applied new vitamin D analogues that exert few calcemic side effects.

Breast↗

[Nephrolithiasis in "disk-variant" cross-over renal dystopia. Report of a case].

Renal dystopia is a frequent urogenital anomality. Renal dystopia encloses pelvic kidney or malascending kidney, but also rare anomalities like renal duplication or crossed renal dystopia. These allotopias are often diagnosed on routine examination of the urogenital system. We report a case with fused crossed renal dystopia on the left with atypical symptoms of nephrolithiasis and give a summery of the embryological origin.

Diagnosis, Differential↗

Ultrasonography of the endometrium and endometrial pathology under tamoxifen treatment.

PURPOSE: The estrogenic effects of tamoxifen on the endometrium and the vaginal epithelium are evaluated. METHOD: 211 postmenopausal women were examined (tamoxifen group: 176 estrogen-receptor positive breast cancer patients; control group I: 35 estrogen-receptor negative breast cancer patients; control group II: 50 women without breast cancer taking no hormones). We determined the endometrial thickness and the maturation index (MI). Person's chi-square-test and the t-test for independent samples were used. RESULTS: In the tamoxifen group, the mean endometrial thickness and the MI were significantly higher (p<0.0001) than in the control groups. No evidence of correlation in duration of tamoxifen intake and endometrial thickness was found (Pearson's correlation coefficient: 0.4773; p=0.0001). The maturation index significantly (p<0.0001) increased under tamoxifen therapy. There was no correlation in the maturation index and endometrial thickness (Pearson's correlation coefficient: 0.1649; p=0.169). The histological clarification (N=47; endometrial thickness greater than 8 mm) revealed 3 neoplasms, 9 endometrial polyps, 2 glandular-cystic hyperplasias and in 32 cases atrophic endometrium. CONCLUSION: An apparent increase of endometrial thickness and the maturation of the vaginal epithelium caused by the estrogenic effect of tamoxifen was demonstrated.

Aged↗

Primary tubal carcinoma: a retrospective analysis of four cases with a literature review.

With an incidence of 0.1% to 1.0% of all genital malignancies, primary tubal carcinoma is a rare malignant disease of the female genital tract. The prognosis is generally regarded as very poor. It is comparable with that of ovarian carcinoma. From 1980-1995, four patients were treated for primary tubal carcinoma at the Department of Gynecology and Obstetrics at the University of Homburg/Saar. FIGO stages IIa-IV were manifested as the primary stage. Surgery was performed as primary treatment in all patients. Both chemotherapy and percutaneous radiation were used as adjuvant postoperative therapy. The recurrence-free interval was 18-30 months. One patient died 21 months after primary diagnosis. The other free patients are in a period of follow-up observation of 16-96 months in an NC or CR status.

Adenocarcinoma↗

[Right-sided double inferior vena cava and common iliac vein: imaging with spiral computerized tomography].

Duplications of the inferior vena cava (IVC) are rare variants of the abdominal vessels and are normally located on both sides of the abdominal aorta. The rare case of a rightsided infrarenal duplication of the IVC with involvement of the common iliac vein is reported. Details of the embryology are presented for the understanding of this IVC variant. The spiral CT with multiplanar reconstructions makes it possible to define the vascular morphology and to differentiate it from lymphoma.

Adult↗

[Uterine leiomyosarcoma with subsequent pregnancy].

Leiomyosarcoma are malignant tumors showing smooth muscle differentiation, they are rare, representing only about 25 percent of all uterine sarcomas and mixed malignant tumors and slightly more than 1 percent of all corporeal malignant tumors. Usually they arise in postmenopausal women and are not known to be related to the known risk factors for endometrial carcinoma (nulliparity, obesity, diabetes mellitus, hypertension, etc.) or carcinosarcoma (prior radiation therapy). They may occur in uteri that also bear typical benign leiomyomas, but leiomyosarcoma rarely can be proven to have arisen in or from benign leiomyomas. We report on two premenopausal women with leiomyosarcoma--out of totally 31 cases in our clinic from 1975-1995 who got pregnant after surgical treatment preserving the uterus. The patients are alive without evidence of disease 3 and 6 years after surgical resection.

Abortion, Incomplete↗

Human tumour xenografts in nude mice: chemotherapy trials with titanocene dichloride in different dosages.

PURPOSE: In this study new cytostatic therapies with titanocene dichloride in different dosages for the treatment of ovarian cancer are analyzed on human tumour xenografts in nude mice. The aim was to compare the effects of different dosages of titanocene dichloride on the growth of human tumour xenografts and nude mice body weight. METHODS: Biopsy material from one human ovarian carcinoma was expanded and transplanted into 52 nude mice. The treatment protocol included one experiment that consisted of the following six treatment groups: titanocene dichloride 3 x 10 mg/kg, titanocene dichloride 3 x 20 mg/kg, titanocene dichloride 3 x 30 mg/kg, titanocene dichloride 1 x 30 mg/kg, titanocene dichloride 1 x 40 mg/kg and a control group treated with 0.9% saline. Treatment groups were evaluated in terms of average daily increase in tumour volume and average daily body weight increase on nude mice. The slope factors alpha and beta of the body weight and tumour volume changes were calculated. RESULTS: Titanocene dichloride in the dosage of 3 x 30 mg/kg and 3 x 20 mg/kg brought about a significant reduction in tumour volume (p < 0.05) compared to the control group and to the treatment group under medication with titanocene dichloride 1 x 30 mg/kg. There were no significant changes in the body weight of nude mice. CONCLUSION: We found titanocene dichloride to be effective in the reduction of tumour volume increase in nude mice. Titanocene dichloride could be an active chemotherapeutic drug in women with ovarian carcinoma not responding to standard therapies.

Animals↗

Effects of vinorelbine and titanocene dichloride on human tumour xenografts in nude mice.

PURPOSE: In this study, the new antineoplastic agents titanocene dichloride and vinorelbine are compared to cisplatin and paclitaxel using a human ovarian cancer xenograft model. METHODS: Biopsy material from one native human ovarian carcinoma was expanded and transplanted into 48 nude mice. The animals were divided into six treatment groups: cisplatin 3x4 mg/kg, paclitaxel 5x26 mg/kg, vinorelbine 1x20 mg/kg, titanocene dichloride 3x30 mg/kg, titanocene dichloride 3x40 mg/kg and a control group treated with 0.9% saline. Treatment groups were evaluated in terms of average daily increase in tumour volume and average daily body weight increase of the nude mice based on slopes of least square regressions performed on individual animals. The slope factors alpha and beta of the body weight (alpha) and tumour volume changes (beta) within each group were calculated. RESULTS: A statistically significant decrease (p<0.05) in body weight of the experimental animals was shown in groups treated with paclitaxel (alpha = -0.6878) and titanocene dichloride 3x40 mg/kg (alpha = -0.7194) compared to the control group which was treated with 0.9% saline (alpha = -0.2643). Significant body weight changes were not observed in the comparison of the remaining treated groups (cisplatin: alpha = -0.4552, vinorelbine: alpha = -0.5606, titanocene dichloride 3x30 mg/kg: alpha = -0.6173 to the control group. A significant reduction (p<0.05) of the increase tumour volume (vinorelbine: beta = 5.260, paclitaxel: beta = 0.478, titanocene dichloride 3x30 mg/kg: beta = 10.283, titanocene dichloride 3x40 mg/kg: beta = 5.768) was shown in treated groups except for cisplatin (beta = 18.722) compared to the tumour bearing control group (beta = 30.136). A statistically significant reduction of the increase in tumour volume occurred under paclitaxel medication compared to the group treated with cisplatin. CONCLUSION: We found titanocene dichloride to be effective as vinorelbine and more effective than cisplatin. Vinorelbine seems to be a very effective antineoplastic agent with a significantly higher cytostatic effect than cisplatin. Both titanocene dichloride and vinorelbine provide new therapeutic options in women with ovarian carcinoma not responding to standard chemotherapies.

Animals↗

Correlation between immunoreactivity for transglutaminase K and for markers of proliferation and differentiation in normal breast tissue and breast carcinomas.

We investigated immunohistochemically localization and expression of transglutaminase K (TGK) in normal breast tissue (n = 10) and in breast carcinomas (n = 30). Transglutaminase K was compared with the staining patterns of cytokeratin 10, Ki-67, p53, estrogen and progesterone receptors in these tumors. Weak to strong membrane bound immunoreactivity to TGK was detected in 17 out of 30 breast carcinomas analyzed. TGK staining was heterogeneous with visual differences between individual tumour cells. Ninety percent of normal breast tissues revealed no immunoreactivity to TGK. Both intensity of TGK immunostaining and number of TGK-positive cells were upregulated in breast carcinomas as compared to normal breast tissue. Analyzing coexpression of TGK with cytokeratin 10, Ki-67, p53, ER and PR, no statistically significant correlation was found. Our findings indicate that: (I) TGK is upregulated in breast carcinomas as compared to normal breast tissue. (II) Upregulation of TGK in breast carcinoma is not exclusively induced by alterations of epithelial differentiation or proliferation, but by different, unknown mechanisms. (III) Upregulation of TGK in breast carcinomas may play an important role in the regulation of tumour cell invasive properties by modulating cell-matrix interactions or by facilitating the assembly of matrix and tissue remodeling.

Antibodies, Neoplasm↗

Leiomyosarcomas of the female genital tract: a clinical and histopathological study.

INTRODUCTION: Leiomyosarcomas are malignant tumours showing smooth muscle differentiation. They represent approximately 25% of all uterine sarcomas and slightly over 1% of all uterine malignancies. The purpose of the present retrospective review is to relate clinical and pathological findings of leiomyosarcomas of the female genital tract to prognosis. MATERIAL AND METHODS: During 1972-1992 eleven patients had diagnosed uterine leiomyosarcomas treated at the Department of Gynecology of the University of Saarland. The hospital records of all patients were reviewed and complete primary treatment had been performed at this center. RESULTS: The mean age was 46.92 years (SD: +/-13.85). Atypical uterine bleeding and pelvic discomfort were the most common presenting complaints (72.7%). The mean follow-up time was 59.60 months (20-96 months). Overall 2-year survival was 70% and overall 5-year survival 30%. The overall survival of patients in FIGO-stage I was 57.14%, in FIGO-stage II 100%, in FIGO-stage III 0% and in FIGO-stage IV 0%. CONCLUSION: The primary therapy should consist of an operation as radical as possible. Treatment with organ preserving seems to be reasonable if the patient desires children. Also, chemotherapy might provide a hopeful sign in the improvement of survival rates.

Adult↗

The influence of tamoxifen on the maturation index of vaginal epithelium.

PURPOSE: The estrogenic effect of tamoxifen on vaginal epithelium in postmenopausal women with breast cancer was evaluated over a period of more than 48 months. METHODS: The tamoxifen group consisted of 118 postmenopausal patients, control group I of 30 postmenopausal women with breast cancer receiving no tamoxifen or hormonal replacement therapy and control group II of 40 postmenopausal women without breast cancer taking no hormones. We determined the maturation index of the vaginal epithelium. Pearson's chi-square-test and t-test for independent samples were used in the statistical analysis. RESULTS: The maturation index increased under tamoxifen therapy within the first 24 months from 0.4026 before taking tamoxifen (n = 64) to 0.6066 (n = 162, p < 0.0001) and in the following 24 months to 0.6325 (n = 122, p < 0.0001). Under tamoxifen intake of more than 48 months, an additional small increase of the maturation index to 0.6735 (n = 42, p < 0.0001) could be noticed. The maturation index in the tamoxifen group was statistically significantly higher (p < 0.0001) than in the control groups (control group I: 0.3975, p < 0.0001; control group II: 0.4102, p < 0.0001). CONCLUSION: An apparent increase in the maturation of the vaginal epithelium caused by the estrogenic effect of tamoxifen could be demonstrated.

Aged↗

Influence of monomethylfumarate on monocytic cytokine formation--explanation for adverse and therapeutic effects in psoriasis?

Although the effectiveness of systemic antipsoriatic treatment with fumaric acid esters has been proven, their mode of action is still not understood. Recent results indicate their potency in inducing cytokine production in stimulated T cells. Since monocytes and their cytokines are also considered to be of pathogenic importance in psoriasis, we investigated the effect of monomethylfumarate (MMF) on proinflammatory (TNF-alpha, IL-12) and antiinflammatory (IL-10, IL-1RA) cytokine production by peripheral blood mononuclear cells (PBMC) and separated monocytes. In 24-h PBMC cultures from both psoriatic patients (n = 6-13) and healthy volunteers (n = 7-9), MMF at 100 microM induced secretion of TNF-alpha, IL-10, and IL-1RA. Kinetics of IL-10 protein and mRNA expression indicated de novo production. Moreover, MMF significantly augmented endotoxin-induced synthesis of TNF-alpha, IL-10 and IL-1RA. In contrast, no influence on IL-12 secretion was found. Similar effects of MMF in purified monocytes indicated these cells to be responsible for aberrant cytokine formation. Furthermore, enhanced expression of costimulatory molecules after MMF stimulation confirmed monocyte activation. Multiple restimulation with fumaric acid esters in vitro, however, and immunomonitoring in a patient during Fumaderm initial therapy suggested that initial monocyte activation is followed by subsequent deactivation associated with an antiinflammatory response. Our results may explain the well-known effects of therapy with fumaric acid esters. Thus, initial treatment is often accompanied by adverse effects which may be caused by MMF-induced TNF-alpha formation. The change in the IL-10/IL-12 balance as a result of elective induction of IL-10, however, may have antipsoriatic activity by diminishing type-1/proinflammatory cytokine over-expression and the antigen-presenting capacity of monocytes/macrophages, and by upregulation of IL-1RA.

Cells, Cultured↗

An episodic change of rDNA nucleotide substitution rate has occurred during the emergence of the insect order Diptera.

We have studied the potential reasons for a conspicuous deviation of substitution rates in Dipteran ribosomal genes. Systematic pairwise relative-rate tests reveal that a significant increase in substitution rate is characteristic for Diptera, but not for the other insects analyzed. Estimation of sequence change in specific lineages reveals that most of these substitutions took place during the evolution of the Dipteran stem lineage. When related to the paleontologically documented periods of absolute time, the substitution rate in the stem lineage of the Diptera underwent an at least 20-fold increase compared to other insect groups and subsequently dropped by a factor of 10 before the diversification of the major Dipteran subgroups. Systematic comparisons of nucleotide composition show that this episodic change in substitution rate was accompanied by a significant increase in A+T content of Dipteran rDNA. Our data suggest that the episodic evolution of the Dipteran rDNA has most probably been caused by a change of directional mutation pressure which must have occurred during the evolution of the stem lineage of the Diptera.

Animals↗