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R Kimmig

Publications and source records attributed to R Kimmig.

At least 55 records · Page 3Linked to original sources
PubMed1998

Epidermal-growth-factor receptor correlates negatively with cell density in cervical squamous epithelium and is down-regulated in cancers of the human uterus.

The role of the epidermal-growth-factor receptor (EGFR) in cervical cancer is controversial, due to technical difficulties in localizing or in quantifying EGFR by homogenate assays or immunohistochemistry. Our autoradiographic approach, in combination with morphometry, allowed cell-type-specific quantification of EGFR, leading to the following observations: (i) In normal cervical epithelium, EGFR levels per cell were high in non-dividing squamous cells of the upper layers of normal epithelium, where a mitogenic function of these EGFRs can be excluded. (ii) In contrast to earlier findings in tissue homogenates, but consistent with our observation in normal cervical epithelium that cells of the proliferating strata (basal and parabasal cells) express intermediate and comparatively reduced levels of EGFR per cell, cervical cancers displayed a significant reduction both of specific EGF binding and of EGFR levels per cell as compared with normal epithelium. (iii) A significant negative correlation of cell density and EGFR number per cell was obtained. In normal cervical epithelium, cervical intra-epithelial neoplasia and invasive cervical cancer (p = 0.002). This negative correlation was most evident in normal epithelium, where large changes of cell density occur within one slide (p < 0.001). (iv) Specific EGF-binding was also significantly reduced in endometrial cancers when compared with normal endometrium. It is proposed that in uterine tissues low or intermediate levels of EGFR do not exclude their function as mediators of cell proliferation.

Autoradiography↗
PubMed1998

Group A streptococcal toxic shock syndrome with severe necrotizing fasciitis following hysterectomy--a case report.

In the last 10 years an increasing number of cases of group A streptococcal toxic shock syndrome have appeared in various clinical settings. The manifestation of this syndrome includes rapidly progressive multiorgan failure and soft-tissue necrosis. This report presents a case of streptococcal toxic shock syndrome caused by Streptococcus pyogenes with severe necrotizing fasciitis of the abdominal wall following hysterectomy. Aggressive surgical intervention with debridement of all necrotic tissue necessitated resection of the complete abdominal wall (skin, subcutaneous tissue, muscle and peritoneum). The abdominal wall defect was covered with free myocutaneous flaps and split-skin grafts. Optimal treatment, including adequate antibiotic therapy and radical surgical intervention, is an indispensable prerequisite of successful outcome.

Fasciitis, Necrotizing↗
PubMed1998

Flow cytometric detection and binding studies of human endometrial stromal cell epidermal growth factor receptor in monolayer culture: influence of progesterone.

Epidermal growth factor (EGF) has been shown to modulate endometrial differentiation in vivo and in vitro. Therefore, endometrial stromal cell EGF receptors were characterized in intact endometrial stromal cells, cultured in vitro. The methods used for characterization were flow cytometry, binding and displacement studies, and gel electrophoresis followed by autoradiography. In flow cytometry the histogram of labelled stromal cells was identical to Caski cells, which served as a positive control. EGF binding revealed the typical binding hierarchy for EGF receptors. The Scatchard analysis showed a curvilinear plot with a calculated dissociation constant of 0.36 nM for high affinity binding sites. In autoradiography a band of approximately 170 kDa was visualized corresponding to the known size of the EGF receptor. The intensity of this band was increased by pretreatment of stromal cells with 10 nM progesterone for 4 days. Furthermore, stimulation with progesterone led to an increase in specific EGF binding activity of stromal cells by 21% compared to control. These data indicate that intact stromal cells in monolayer culture maintain specific EGF receptors, which are up-regulated by progesterone.

Adult↗
PubMed1998

Parametrial invasion in cervical carcinoma: evaluation of detection at MR imaging with fat suppression.

PURPOSE: To evaluate detection of parametrial invasion at magnetic resonance (MR) imaging with fat suppression. MATERIALS AND METHODS: In 35 patients with cancer of the cervix, MR imaging was performed with the following sequences: T2-weighted turbo spin echo (SE), turbo short inversion time inversion recovery (STIR), and unenhanced or gadolinium-enhanced T1-weighted SE with and without excitation-spoiling fat suppression. Images obtained with each sequence were evaluated for parametrial invasion by two blinded radiologists separately, who scored their level of diagnostic confidence from 0 to 10 (no confidence to high confidence). Then, all images were evaluated together and findings were correlated with histopathologic findings. RESULTS: No statistically significant differences were found between staging with T2-weighted turbo SE, turbo STIR, and T1-weighted fat-suppressed gadolinium-enhanced SE images. Staging with T1-weighted SE, T1-weighted gadolinium-enhanced SE, and T1-weighted fat-suppressed SE images was significantly worse (P < .05). Diagnostic confidence was lower (P < .001) with T1-weighted gadolinium-enhanced SE and T1-weighted fat-suppressed gadolinium-enhanced SE images (5.5 and 6.2 points, respectively) compared to staging with T2-weighted turbo SE and turbo STIR images (8.2 and 7.6 points, respectively). No statistically significant improvement in staging accuracy was found when all images were evaluated together. CONCLUSION: In MR diagnosis of parametrial invasion, the addition of fat-suppressed or gadolinium-enhanced MR images did not improve the accuracy with T2-weighted turbo SE images alone.

Cervix Uteri↗
PubMed1997

Quantitative determination of the epidermal growth factor receptor in cervical cancer and normal cervical epithelium by 2-color flow cytometry: evidence for down-regulation in cervical cancer.

Expression of epidermal growth factor receptor (EGFR) was quantified by 2-color flow cytometry in cervical cancer (n = 73) and normal cervical epithelium (n = 11). EGFR was determined using a murine monoclonal EGFR antibody, and number of bound antibodies was quantified adding calibration beads with defined antigenic binding sites. Tumor cells were identified by simultaneous DNA staining. Epithelium of normal cervical tissue was detected by labeling for cytokeratin. Results were compared with EGFR quantification by autoradiography on cryostat sections using a radioligand binding assay. A high degree of correlation was found between the 2 methods. In cervical carcinomas 14,600 binding sites/cell (median; range, 160-283,000 binding sites/cell) were detected, considerably less compared with normal cervical squamous epithelium, which was 30,700 binding sites/cell (median; range, 19,900-44,000 binding sites/cell). This finding clearly contrasts with other reports of enhanced EGFR expression in cervical cancer. The discrepancy may be explained by contamination of tissue homogenates used for radioligand or enzyme immunosorbent assays by non-epithelial tissue elements with low or absent EGFR expression. Interference with quantitative EGFR determination in epithelial cells may result in false low estimates of EGFR expression predominantly in normal cervical tissue. This should be avoided by identifying tumor and normal epithelial cells prior to analysis. In our study, 63% of cervical cancers expressed low levels of EGFR compared with normal cervical epithelium, and only 10% showed overexpression. There is evidence that cervical carcinomas overexpressing EGFR represent a small, but biologically distinct group of cervical cancers exhibiting enhanced aggressiveness associated with poor survival of the patients.

Antibodies, Monoclonal↗
PubMed1997

mRNA expression of ligands of the epidermal-growth-factor-receptor in the uterus.

Six different ligands of the epidermal-growth-factor receptor (EGFR) have been identified in the past. In some cervical squamous-cell carcinomas, an increased amount of proteins binding to the EGFR has been reported. In order to identify the mRNA of EGFR ligands (EGFRL), which might be overexpressed in cervical and endometrial cancers, we performed semi-quantitative reverse-transcription/polymerase chain reactions (RT-PCR) for all 6 EGFRL in RNA extracts of normal and malignant tissue samples of the human uterus. PCR products from RNA extracts of 83 patients were quantitated relative to the housekeeping gene and internal standard pyruvate dehydrogenase by analyzing the PCR kinetics of product synthesis. In extracts of normal cervix, the level of mRNA expression of the EGFRL was significantly higher than in endometrium. No significant difference was detected between normal cervix and cervical carcinomas. However, both in cervical and in endometrial cancers, mRNA expression was non-parametrically distributed and in some cervical cancers overexpression of transforming growth factor alpha (TGF-alpha), amphiregulin or EGF was observed. In endometrial cancers, mRNA levels of all EGFRL were higher than in normal endometrium. This increase was significant (p < 0.005) for TGF-alpha and amphiregulin. Thus, TGF-alpha mRNA is overexpressed in approximately 10% of cervical cancers and in the majority of endometrial cancers. Since TGF-alpha anti-sense therapy might represent a future strategy in such cancers, we also determined the absolute level of TGF-alpha mRNA expression by quantitative PCR using a cloned standard.

Cloning, Molecular↗
PubMed1997

[Lymph node staging in cervix carcinomas: the results of high-resolution magnetic resonance tomography (MRT) with a phased-array body coil].

PURPOSE: To determine the diagnostic value of high resolution MR imaging with a circularly polarised (c.p.) body phased-array coil for the staging of pelvic lymph nodes in cervical carcinoma. MATERIAL AND METHODS: 42 patients with histologically proven carcinoma of the cervix were studied on a 1.5 T scanner by using a c.p. body phased-array coil. The imaging protocol included T2-weighted turbo-spin-echo (TSE) and T1-weighted spin-echo sequences pre and post i.v. application of Gd-DTPA; slice thickness was 5-7 mm and pixel size 0.53 mm2. Lymph nodes with a diameter of > or = 8 mm were considered to have metastatic involvement. MR imaging results were compared with histopathologic findings. RESULTS: MR imaging showed enlarged lymph nodes (> or = 8 mm) in 16 of 18 patients with histologic proof of lymph node metastases (sensitivity 89%). In 22 of 24 cases MR findings were true negative (specificity 92%). Diagnostic accuracy was 91%. CONCLUSION: High-resolution MR imaging with a c.p. body phased-array coil provides high sensitivity, specificity, and diagnostic accuracy for pelvic lymph node staging in cervical carcinoma.

Adult↗
PubMed1997

[Parametrial infiltration of cervix carcinoma: diagnostic value of contrast-enhanced fat-suppressed T1-weighted SE sequences at 1.5 tesla].

PURPOSE: To determine whether contrast-enhanced and fat-suppressed sequences contribute to the MR imaging diagnosis of parametrial invasion. METHODS: 21 patients with carcinoma of the cervix were prospectively examined with a phased-array coil and a 1.5T MR-scanner using the following sequences: transverse T2-weighted turbo spin echo (T2-TSE), T1-weighted spin echo (T1-SE) and fat suppressed T1-weighted SE sequences before and after Gd-DTPA. The sequences were evaluated separately for the presence of parametrial invasion. Image quality and diagnostic confidence were classified on a scale of 0-10 (nondiagnostic-excellent). Findings were compared to the results of the pathohistological examination. RESULTS: Sensitivity, specificity and diagnostic accuracy were highest for T2-TSE sequences (100%, 79% and 86%, respectively). Contrast-enhanced T1-SE sequences with fat-suppression (71%, 79%, and 76%) showed no improvement compared to T2-TSE. Unenhanced fat-suppressed T1-SE (100%, 30%, and 56%) and unenhanced T1-SE (100%, 7%, and 38%) as well as contrast-enhanced T1-SE (86%, 20%, and 47%) were significantly worse than T2-TSE. With similar image quality (p < 0.05) diagnostic confidence was higher on T2-TSE than on any of the other sequences (p < 0.001). CONCLUSION: Considering the cost-effectiveness of the examination, for the MR diagnosis of parametrial invasion the use of fat-suppressed contrast-enhanced sequences can be abandoned in favour of T2-weighted TSE sequences.

Adult↗
PubMed1997

Magnetic resonance imaging of the female pelvis. New circularly polarized body array coil versus standard body coil.

RATIONALE AND OBJECTIVES: The authors compare the value of a new circularly polarized body array coil (BAC) system with a standard body coil (BC) for high-resolution magnetic resonance imaging of the female pelvis. METHODS: Twenty patients with cervical cancer were examined with a BC and BAC. Imaging parameters were kept constant (sagittal T2-weighted turbo spin-echo: repetition time = 4000 mseconds; effective echo time = 99 mseconds; 160 x 160 mm field of view; 256 x 256 matrix; 0.63 x 0.63 mm pixel size; 4-mm slice thickness). Images were scored for lesion-to-organ delineation and overall image quality/ artifacts using a scale from 5 to 1 (excellent to poor). Signal-to-noise (S/N) ratios for different tissues (tumor, uterus, vagina, rectum, muscle, and fat) as well as contrast-to-noise (C/N) ratios between tumor and (1) uterus, (2) vagina, and (3) rectum were calculated. Magnetic resonance tumor staging was performed according to the International Federation of Gynecology and Obstetrics (FIGO) classification. RESULTS: Using the BAC, S/N and C/N ratios increased significantly compared with the BC (S/N: 2.7-3.4-fold increase for all organs evaluated, P < 0.001: C/N: tumor versus uterus 2.4-fold, P < 0.01; tumor versus vagina 6.1-fold, P < 0.001; tumor versus rectum 3.1-fold, P < 0.01). This resulted in an improved overall image quality (average ratings: BAC-4.3 points; BC-2.6 points; P < 0.001). Lesion-to-organ delineation (average ratings: BAC 4.3-4.1 points, BC 3.5-2.7 points for all organs evaluated; P < 0.001) was increased noticeably on BAC images. No significant difference was found for staging accuracy. CONCLUSIONS: Circularly polarized BAC provide superior S/N and C/N ratios and improve lesion conspicuity compared with standard BC.

Adult↗
PubMed1997

[Epidemiology and diagnosis of cervical intraepithelial neoplasia--is the present concept of screening and diagnosis still current?].

Infection with human papillomavirus (HPV) is the major factor in the genesis of cervical intraepithelial (CIN) and invasive neoplasia. However, screening is still based upon cytology and further diagnostic investigation relies on colposcopy with punch biopsy. In this review, recent studies are evaluated with regard to consequences for optimal screening and management strategies of CIN. In summary, exfoliative cytology is still widely considered as the method of choice for population screening. Primary HPV DNA screening proves equivalent or superior to cytology only in populations with a low prevalence of HPV infections. Preliminary data from serological HPV tests are less promising. Cytological diagnosis of HPV infection may be verified by HPV testing. Recognizing high oncogenic risk viruses in CIN 1 may help to reduce the control period from 24 to 12 months and may lead to immediate therapy for CIN 2 lesions. However, further prospective studies evaluating the cost-effectiveness of HPV DNA tests in German-speaking countries are necessary.

Biopsy↗
PubMed1996

[13-cis retinoic acid and interferon-alfa-2a as palliative therapy in pretreated, recurrent squamous epithelial carcinoma of the cervix uteri and vulva].

Patients with metastasising carcinoma of the uterine cervix or recurrent disease, in whom local treatment as surgery or radiotherapy has failed, are still an unsolved problem. Platinum-based multi-agent chemotherapies achieve overall response rates up to 60%, but side effects are serious and so far no survival benefit has been proven. Recent publications report on a synergistic effect of combination therapy using 13-cis-retinoic acid and interferon alpha-2 a in the treatment of squamous cell carcinoma of the cervix. In a pilot study we include 6 patients with locally recurrent or metastasising squamous cell carcinomas, five of the uterine cervix, one of the vulva. The systemic therapy consisted of-orally administered 13-cis-retinoic acid (80 mg q. d.) and subcutaneously injected interferon alpha-2 a (6 x 10(6) I.E. q. d.). All patients were primarily treated by surgical and/or radiation therapy. In each case chemotherapy had been either already performed or rejected by the patient. Median duration of treatment was 52 days, median survival time 107 days. Out of 6 patients 3 experienced progression of disease uninfluenced by therapy. One patient with multiple subcutaneous lymph node metastases showed mixed response for a short period of 3 weeks before progression and eventual death. One patient had no change or disease for 13 months with subsequent progression and eventual death after 22 months. One patient could not be evaluated for an allergic reaction after only 15 days of treatment. Other side effects were "flu-like symptoms", skin irritations, conjunctivitis sicca and chileitis, all WHO 1-2. Overall toxicity must be rated low compared to standard chemotherapy, but is not negligible. In our study the positive reports in literature concerning the treatment of primary advanced cervical cancer and recurrent advanced carcinoma of the skin could not be reproduced. This might be due to the small number of cases, which is a common problem in immunotherapeutic studies. Moreover, very unfavourable patient selection criteria in our study compared to primarily untreated patients may also have contributed to different response rates. However, in our opinion the tested regimen cannot be considered sufficiently effective in patients suffering from pretreated, recurrent squamous cell carcinoma of the cervix or vulva.

Administration, Oral↗
PubMed1996

[Results of long-term follow-up in treatment of endometriosis with the GnRH agonist leuprorelin acetate depot (Enantone-Gyn monthly depot)].

In a previous study 198 patients with histologically confirmed endometriosis underwent a "three-step" therapy, where surgical removal of endometriosis implants was followed by a 6 months treatment with 3.75 mg leuprorelinacetate depot as monthly subcutaneous injections and a second look laparoscopy with removal of residuals. In the following report long-term follow-up data generated in 112 of the above 198 patients on the post-treatment effect in respect to symptoms and pregnancy outcome in infertility are reported. For this purpose a special questionnaire was used. The follow-up period was up to 60 months with a median time of 33.5 months. Out of 112 patients 91 complained of infertility. 43 out of these 91 (47.3 %) became pregnant during the follow-up period, resulting in 55 pregnancies and 36 newborns. More than half of these patients conceived spontaneously, whereas in the rest stimulation programs became necessary. Recurrence of dysmenorrhoea, dyspareunia and pelvic pain was defined as recurrence of disease. During the follow-up period 70/112 (62.5 %) of the patients complained recurrence of symptoms with median first onset at 11 months. In two third symptoms were still less severe than at admission and classified as mild and moderate. The r-AFS score at first and second look laparoscopy did not differ in patients with and without recurrence of disease (p = 0.311 and 0.750). Only 28.6 % (20/70) of patients required an additional medical or surgical treatment. A subgroup of 51 patients could be evaluated in respect to quality of life and improvement of subjective conditions. Regain of quality of life and improvement of subjective conditions were reported in 54.9 % (28/51) and 52.9 % (27/51) respectively. The study results suggest that although the physiological effects of leuprorelin acetate treatment as suppression of ovarian function is rapidly reversible, the therapeutic effects linger, as evidenced by ongoing reduction of symptoms from baseline, leaving many patients asymptomatic or much improved longer than 1 year after treatment has ended. Besides long term relief and/or sustained reduction in symptom severity, the high pregnancy rate in infertility, as well as regain of quality of life and well being favour this therapeutic approach in endometriosis.

Adult↗
PubMed1995

Conservative treatment of endometrial cancer permitting subsequent triplet pregnancy.

We report on a 28-year-old woman who received conservative treatment of endometrial carcinoma by curettage and progestins. After regression of endometrial lesions the patient's infertility was treated by gamete intrafallopian transfer (GIFT). Intact triplet pregnancy was diagnosed 3 weeks later. The patient was delivered of three infants by caesarean section following premature rupture of membranes at 30 weeks of gestation. Subsequent standard treatment of endometrial cancer by abdominal hysterectomy and bilateral salpingo-oophorectomy after 4 weeks revealed no clinical or histological evidence of persistent carcinoma. One year after surgery the patient remained without evidence of disease. We believe that individualized cancer therapy may be safely performed in carefully selected cases.

Adult↗
PubMed1995

DNA cell-cycle analysis of cervical cancer by flow cytometry using simultaneous cytokeratin labelling for identification of tumour cells.

DNA ploidy and cell-cycle distribution were determined by flow cytometry in fresh tumour tissue of 53 cervical carcinomas. Epithelial cells were labelled by a fluorescein-isothiocyanate-conjugated cytokeratin antibody (CK6, CK18) to study the influence of contaminating stromal and inflammatory cells on results of cell-cycle analysis of tumour cells. Without identification of cytokeratin-positive cells 30/53 (57%) tumours were found to be DNA-aneuploid compared to 43/53 (81%) after gating for cytokeratin. Only 7 of 15 DNA-multiploid tumours could be detected without cytokeratin staining. In addition, cytokeratin-negative cells, which are found in all tumours, can be used as an internal standard for the calculation of ploidy and for quality control (coefficient of variation, linearity) of each individual sample. Cell-cycle analysis revealed significantly higher S-phase and G2M-phase fractions in cytokeratin-gated compared to ungated samples (13.1% versus 10.0% and 8.0% versus 5.4%; P < 0.001). This difference was more pronounced in DNA-diploid than DNA-aneuploid tumours. In conclusion, about 30% of DNA-aneuploid tumours could only be detected after cytokeratin labelling of epithelial cells. Owing to the identification of cytokeratin-positive cells the influence of non-tumoural cell elements on cell-cycle analysis was reduced markedly. Therefore, in cervical cancer, cytokeratin labelling can optimize both the determination of DNA ploidy and cell-cycle analysis.

Cell Cycle↗
PubMed1995

[Hormonal replacement therapy and oral contraception. Risk of induction or reactivation of gynecologic malignancies].

The administration of oral contraceptives does not enhance the incidence of gynecologic malignancies. Only few subgroups of patients seem to have a slightly elevated relative risk of breast cancer. On the other hand, the incidence of endometrial and ovarian cancer is markedly reduced. This is also true for correct hormonal replacement therapy. In addition, no elevation of breast cancer risk has been evidenced for low-estrogen administration. In most cases, hormonal replacement therapy may also be performed safely following successful treatment of gynecologic cancers.

Contraceptives, Oral, Hormonal↗
PubMed1995

[Immunohistologic tumor cell detection in lymph nodes in node negative breast cancer: correlation with "established" and "recent" prognostic factors].

OBJECTIVES: The prognostic value of immunohistochemically detected micrometastases in lymph nodes as well as its association with newer prognostic factors is discussed controversially. PATIENTS AND METHODS: Using a monoclonal pancytoceratine antibody 1807 axillary lymph nodes of 122 pT1-2N0M0-patients were examined. Histological findings, established and newer prognostic factors were investigated additionally. The mean follow up time was 50 months. RESULTS: The detection of micrometastases in 16 of 122 (13.1%) patients were related with a prognostic disadvantage for recurrence free survival (p = .03). Tumour size, grading, vessel invasion and S-phase, but not the detection of micrometastases, were confirmed as independent prognostic factors in nodal negative patients by Cox-regression. CONCLUSION: Immunohistochemically detected micrometastases in axillary lymph nodes are of prognostic and therapeutic value but they are not independent prognostic factors.

Biomarkers, Tumor↗