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Biomedical subjects

A Scharl

Publications and source records attributed to A Scharl.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Influence on extratumoral organ activities of tumor-affinity samarium-153 preparations].

AIM: Possibilities to exercise an influence on the biodistribution of a tumor-affine 153Sm-preparation, samarium-153-nitrilotriacetate (NTA), were tested. METHODS: Animals experiments on tumor-bearing mice after additional application of EDTMP (ethylenediamine tetramethylene phosphonate) for the reduction of extratumorale liver-radioactivity and yttrium chloride for the reduction of unwanted underground radioactivity in bone were carried out. Furthermore, the combination of both measurements was tested. RESULTS: The biodistribution of 153Sm-NTA showed a rather low tumor-radioactivity of app. 0.72%/g. The additional EDTMP-application caused a dose-dependent decrease of the underground-radioactivity in liver especially if given 2 h in advance or simultaneously. The additional application of the stable yttrium salt reduced the bone radioactivity on simultaneous increase of liver- and spleen-radioactivity and practically unchanged tumor-radioactivity. The combined use of EDTMP together with the bone-affine metal salt led to a reduction of liver radioactivity on simultaneous reduction of bone radioactivity. CONCLUSIONS: The background radioactivity can be reduced on unchanged tumor-radioactivity by combined Na-EDTMP/YCl3-application. The present results do not allow a therapeutic exploitation because of the low tumor accumulation.

Animals↗
PubMed1997

[Blind prophylactic antibiotic administration in premature rupture of fetal membranes].

In a retrospective study based on patients treated at the Department of Gynecology and Obstetrics of the University of Cologne during 1984-1993, we tested whether antepartal prophylactic application of antibiotics in patients with premature rupture of membranes (PROM) decreases the frequency of maternal or fetal infections. With raising intervals between PROM and birth exceeding 24 hours, the frequency of maternal/fetal infections raised in the total study population (n = 940). The maternal infection rate increased from 4% to 11% and the frequency of fetal sepsis from 4% to 19% with a PROM to birth interval exceeding 24 hours. In the group of patients with prophylactic application of antibiotics the frequency of maternal or fetal infections was not lower than in the group without antibiotics. This holds true for the total study population as well as for subgroups with different gestational ages. In the total study population 12% of antibiotics-treated patients and 22% of their newborns had peripartal infections, whereas in the untreated population 3% of the mothers and 4% of the newborns showed signs of infection. The prophylactic application of antibiotics raises significantly the latency period in combination with or without tocolysis in PROM during 25. and 37. week of gestation.

Antibiotic Prophylaxis↗
PubMed1996

Qualitative [18F]FDG positron emission tomography in primary breast cancer: clinical relevance and practicability.

Positron emission tomography (PET) using fluorine-18 2-deoxy-2-fluoro-d-glucose (FDG) is of potential value for the diagnosis of malignant tumours. The aim of this study was to evaluate the use of FDG PET in patients with breast tumours, appraising its applicability in visualising primary carcinomas and regional metastases in a clinical setting. Results of FDG PET were compared with those of mammography, breast ultrasonography and histology in 30 patients with inconclusive breast findings. For PET, transmission and emission images were taken in one or two scan positions, depending on the available time and the clinical status of patients. PET showed focal FDG uptake with high contrast in 21 of 23 primary carcinomas. In one patient, only PET correctly visualized multifocal disease (three foci, O 0.4-1 cm). The accuracy of PET in the detection of primary breast cancer was 90%, and in the detection of involved axillary lymph nodes, 94%. All metastases (lymph nodes, lungs, bones, soft tissues) covered by the field of view and demonstrated by other methods (X-ray, computed tomography, magnetic resonance imaging, bone scan) showed FDG uptake. In three patients, only PET initiated further diagnostic procedures. The results indicate that FDG PET can provide a rapid diagnostic study (45-60 min) and allows accurate tumour staging of several organ systems for primary tumour and metastases with a single imaging study in a routine clinical setting.

Breast Neoplasms↗
PubMed1996

[Value of immunohistochemical determination of receptors, tissue proteases, tumor suppressor proteins and proliferation markers as prognostic indicators in primary breast carcinoma].

OBJECTIVE: We tested whether immunohistochemical detection of oestrogen and progesterone receptor (ER, PR), the oestrogen-dependent protein pS2, the growth hormone receptors p 185neu and EGF-R, the tumour suppressor protein p53, the tissue proteases Cathepsin D and Urokinase, and the proliferation marker PCNA are of prognostic relevance in breast cancer patients. METHODS: Expression of the proteins listed above was evaluated in formalin-fixed and paraffin-embedded sections of 311 primary breast cancer specimens using modified Avidin-Biotin-Complex methods. Results were correlated to clinical and morphological parameters (age, menopausal status, nodal status, tumour size, tumour grade), and clinical course of disease (complete follow-up in 301 women, median observation time 62 months) utilising univariate and multivariate statistical analyses. RESULTS: If univariate analyses and multivariate regression analyses according to the Cox-model were applied, only Cathepsin D correlated to an elevated risk for recurrence in nodally negative patients (n = 135). In nodally positive women (n = 161), increasing tumour size, tumour grade, lack of ER and PR, expression of p185neu, p53, and PCNA indicated a significantly increased relative risk. CONCLUSIONS: Immunohistochemistry allows the detection of parameters which may indicate prognosis in subgroup of breast cancer patients.

Adult↗
PubMed1996

[Detection of multi-focal breast carcinoma using 2[18F] fluoro-deoxy-D-glucose positron emission tomography (FDG-PET)].

The elevated rate of glycolysis in malignomas compared to normal tissues can be visualised by positron-emission-tomography (PET) using 2[18F]fluoro-deoxy-D-Glucose (FDG). Based on the case of a 38-year old woman with multifocal carcinoma of the right breast (pT1 c pN0 M0, G2) as a vehicle, we describe a FDG-PET procedure which is comparable to established methods of nuclear medicine (e.g. bone scan) with regard to patient's burden and time consumption and could be used on a routine basis. This technique allowed correct assessment of suspicious breast findings and visualised multifocal growth of a tumour which was judged to be a unifocal breast cancer by conventional methods of clinical examination, mammography and ultrasound.

Adult↗
PubMed1996

Prognostic value of cathepsin D in breast cancer: comparison of immunohistochemical and immunoradiometric detection methods.

AIM: To test whether immunoradiometric or immunohistochemical detection of lysosomal protease cathepsin D in breast cancer is more predictive of outcome. METHODS: Tumour tissues from 270 primary breast cancer patients were evaluated for the expression of cathepsin D using immunohistochemistry (IH; paraffin embedded tissues) and an immunoradiometric assay (IRMA; cytosol from frozen tissues). Immunohistochemical scores were based on immunoreaction in tumour cells and tumour associated macrophages. RESULTS: IRMA values (cut off 40 fmol/mg cell protein) correlated significantly with IH values. Recorded incidences of positive immunoreaction in tumour cells using two different cut off values were 52% and 35%, respectively. Macrophages stained positive in 31% of tissues. Combined evaluation of tumour cells and macrophages resulted in positivity rates of 59% and 48%, respectively. Node status was the only variable found to correlate with cathepsin D expression. IH results correlated significantly with clinical outcome (median observation time 68 months) in node negative patients (n = 120) but not in node positive patients (n = 145). Cathepsin D positivity as measured by IRMA was not related to clinical outcome in either group. On multivariate analysis in the node negative group, IH detection of cathepsin D appeared to be the only independent factor indicating prognosis. For node positive patients, tumour grade, size, and receptor status were of prognostic relevance. CONCLUSIONS: Because of the simple methodology and the minimal amount of tissue used for analysis, immunohistochemistry was preferred to immunoradiometry for cathepsin D measurement; it also provided more predictive data with respect to prognosis.

Aged↗
PubMed1995

ERBB2 gene amplification detected by fluorescent differential polymerase chain reaction in paraffin-embedded breast carcinoma tissues.

For quantificative determination of ERBB2 gene amplification in archival human carcinoma specimens we have developed a rapid, non-radioactive approach, which is based on the differential polymerase chain reaction (PCR) and fluorescent DNA technique. Sequences from the ERBB2 gene and from a single-copy reference gene were amplified simultaneously by PCR, in which one of each primer pair was fluorescently labelled. PCR products were separated by polyacrylamide gel electrophoresis in an automated DNA sequencer and directly quantified after laser activation and emission scanning using appropriate software. This fluorescent differential polymerase chain reaction (fd-PCR) method was used for quantificative determination of ERBB2 gene amplification in 195 formalin-fixed, paraffin-embedded breast carcinoma tissues. ERBB2 gene amplification was found in 52 (26%) of these tumors and correlated significantly with tumor size, absence of estrogen receptor (ER) and pS2 expression, but not with absence of progesterone receptor (PR) or presence of epidermal growth factor receptor (EGF-R) expression, lymph-node metastases or grading. In univariate analysis, ERBB2 gene amplification showed no significant correlation with clinical outcome, either in the whole population or in the subgroup defined by positive axillary lymph-node metastases. However, within the node-negative subgroup, patients with ERBB2 gene amplification had significantly decreased relapse-free survival and overall survival (p < 0.05). The fd-PCR assay is a valuable tool for determination of amplification of ERBB2 gene as well as further oncogenes. In this way, more detailed information about individual tumor biology may be acquired by a routine assay.

Analysis of Variance↗
PubMed1995

Comparisons of radioiodoestradiol blood-tissue exchange after intravenous or intraarterial injection.

PURPOSE: Our study determines and compares how the major organs of large animals handle exogenous halogenated bioactive sex steroids within the first minutes after their i.v. or i.a. injection. The rationale is that an understanding is needed of the acute physiological events because they affect decisions for how to optimize delivery of radiohalogenated sex steroid receptor ligands for purposes of medical imaging and modes of radiotherapy. METHODS AND MATERIALS: We used an indicator dilution technique that allows monitoring of blood-tissue exchange of radioactivity in a continuous manner in anesthetized surgically prepared swine. RESULTS: In swine, with by-passed liver circulation, the lungs allow the vast majority of [I-125]-16 alpha-iodo-17 beta-estradiol ([I-125]E) to be extracted from the blood perfusing the lung in the initial transit after i.v. injection in vivo. Similar outcome was observed for most major organs, including the CNS, intestines, spleen, peripheral appendages, and kidneys after i.a. injection of [I-125]E in vivo. However, within minutes the organs released the [I-125]E in its original chemical form back into the vascular system, with the exception of estrogen receptor (ER) rich tissues and the kidneys that retained the [I-125]E in its original form, although in the kidneys a nonpolar metabolite also accumulated. CONCLUSION: Our experiments confirm in a large animal model that radioiodoestradiol can be sequestered or concentrated in ER-rich sites. The liver and sex steroid receptor-rich organs modify considerably, by metabolism and sequestration, respectively, the acute distribution of bioactive steroids. Our data indicate potential for detection of ER in vivo in hormone-sensitive tumors, that is, in breast and endometrial cancers, and offer improved understanding of the recent studies in subjects with breast cancer that demonstrated that receptor imaging in vivo of steroid receptors with high-affinity radiolabeled ligands is possible in a clinical setting.

Animals↗
PubMed1995

P53 protein in 204 patients with primary breast carcinoma--immunohistochemical detection and clinical value as a prognostic factor.

In a retrospective study, 204 formalin-fixed and paraffin-embedded biopsies of primary breast carcinomas were tested immunohistochemically for the expression of p53 protein (PAb 1801). 38% of the carcinomas were positive with respect to p53. The expression of p53 correlated significantly with the loss of tumor differentiation (P = 0.013), but not with menopausal status, patients' age, tumor size, axillary lymph node involvement or hormone receptor status. The influence of p53 expression on prognosis was evaluated in 197 patients (T1-4 N0-2 M0, median observation time 72 months). Detection of p53 protein was associated with a significantly longer disease-free survival in node-positive women (P = 0.03). However, p53 protein did not prove to be a prognostic factor in node-negative patients. The results demonstrate the prognostic value of p53 expression in breast cancer which appears to be limited to patients with node-positive tumors.

Adult↗
PubMed1995

[Bilateral breast carcinoma after recurrent myxoid liposarcoma of the breast].

The case is presented of a 26-year-old woman with myxoid liposarcoma of the right breast who developed a relapse with anaplastic spindle-cell mesenchymal tumor 7 months after primary therapy. Additionally, 13 months later a bilateral adeno-carcinoma of differing histological grade occurred in the breasts. To the best of our knowledge, no comparable sarcoma-carcinoma sequence in the mammary gland has been reported. For this reason this case is discussed, with special emphasis on possible causative factors and the relationship to the Li-Fraumeni syndrome.

Adenocarcinoma↗
PubMed1995

[Immunohistochemical detection of pS2 protein in paraffin sections of breast carcinoma tissue. Comparison with results of an immunoradiometry assay].

The synthesis of pS2 protein is induced through estrogen-dependent transcription of the pS2 gene. The presence of the pS2 protein in breast cancer is thought to be as valuable as receptor status, or even more so, in predicting the response to hormonal therapy. Furthermore, pS2 appears to be a prognostic factor for primary breast cancer. In 162 cases of primary breast cancer, pS2 was tested by immunohistochemical procedures on formalin-fixed and paraffin-embedded tissues. Staining was evaluated semi-quantitatively using an immunoreactive score (IRS). The concentrations of pS2 in tumor cytosol were determined using an immunoradiometric assay. Positive staining for pS2 (IRS > or = 2) was seen in 27% of the tumors. Comparison of immunohistochemical and biochemical detection (26% of tumors had pS2 cytosol concentrations above the cut-off value of 26 ng/mg cell protein) revealed an 81% concordance rate (r = 0.76; P < 0.0001). Univariate analysis showed no significant correlation of immunohistochemical pS2 detection and age or menopausal status of patients, tumor size, tumor grade or nodal status. However, the immunohistochemical pS2 status correlated significantly with the immunohistochemical detection of the estrogen (ER; P < 0.001) and progesterone receptor status (PR; P < 0.0001). pS2-positive tumors were ER-positive in 66% of cases and PR-positive in 73%; 89% of pS2-positive tumors were positive for ER and/or PR. The incidence of immunohistochemical pS2 detection was 41% in the group of steroid receptor positive carcinomas (ER- and/or PR-positive) in contrast to 7% in steroid receptor negative tumors (ER- and PR-negative).

Adult↗
PubMed1995

[Prognostic value of immunohistochemical determination of urokinase plasminogen activator in primary breast cancers].

There is ample evidence that the protease urokinase plasminogen activator (uPA) plays a role in invasion and spread of tumours. Several publications suggest its biochemical measurement in tumour cytosols to be of prognostic significance in breast carcinomas. Our study set out to determine whether the immunohistochemical detection of uPA in formalin-fixed, paraffin-embedded primary breast cancer tissues is of prognostic relevance. We tested 269 surgical specimens of primary ductal infiltrating carcinoma immunohistochemically using a modified avidin-biotin method. Some 57% of carcinoma specimens yielded specific positive staining in tumour cells. Detection of uPA correlated to tumour grade (P = 0.04), and to the detected level of the proliferation marker PCNA (P = 0.002), but not to patients' age or menopausal status, tumour size, nodal or steroid receptor status (P > 0.05). At median 68 months' follow-up, 34% of patients had experienced tumour relapse and 28% had died from cancer. Clinical course was correlated significantly to tumour size, tumour grade, nodal and steroid hormone receptor status (P < 0.05). Immunohistochemical detection of uPA, however, could not be demonstrated to be of any prognostic significance with regard to relapse-free or overall survival (P > 0.05) in the total study group or in the N0 (n = 120) and N + (n = 144) subgroups, regardless of whether univariate or multivariate analysis was applied.

Biomarkers, Tumor↗
PubMed1995

[Immunohistochemical detection of epidermal growth factor receptor (EGF-R) in paraffin sections of breast carcinoma tissue: correlation and clinical significance].

Analyses of the level of expression of the epidermal growth factor receptor (EGF-R) of breast cancer tumours may add independent information about the prognosis for individual patients. Furthermore, the use of monoclonal antibodies directed against EGF-R as therapeutic tools (e.g., Mab 425) requires a reliable evaluation of the individual EGF-R content. Various analytical methods have been published, including (1) biochemical detectonn of EGF-R by a radiolabelled physiological ligand, (125I)EGF, (2) enzymatic analyses of EGF-R content (IEMA), (3) immunological analyses of EGF-R content with a monoclonal antibody (ELISA), and (4) immunohistochemical EGF-R detection. Studies with immunohistochemical analyses of EGF-R overexpression in formalin-fixed, paraffin-embedded tumour samples are rare. In a retrospective study, we examined the clinical data from 142 patients and the EGF-R expression in their formalin-fixed, paraffin-embedded tumour samples. The average follow-up was 69 months. EGF-R expression was compared to oestrogen (ER) and progesterone (PgR) receptor expression, histological grade, tumour size, lymph node metastases and menopause. 52 of 142 tumours were EGF-R positive. EGF-R overexpression correlated with high tumour grade, large tumours and elevated numbers of lymph node metastases. There was no significant correlation between ER or PgR and EGF-R expression. Determination of EGF-R overexpression revealed no significant difference in disease-free interval (DFI) or overall survival (OS). In this study, the determination of EGF-R in formalin-fixed, paraffin-embedded tumour samples proved feasible. Unfortunately, this did not add any additional information concerning DFI or OS.

Adult↗
PubMed1995

[Biokinetics of tumor-affinity yttrium preparations--2].

After demonstrating that the application form 87Y-NTA-EDTMP-Ca is superior to the so far used citrate form of yttrium especially regarding the tumour/liver and tumour/bone ratios, the relationships between the concentrations of the components in the 87Y-NTA-EDTMP-Ca mixture and the 87Y biokinetics were investigated in tumour-bearing mice. The increase of the EDTMP and Ca2+ concentrations by several orders of magnitude caused no significant changes of tumour radioactivity but a clear radioactivity decrease in the liver, spleen and bone, respectively. The increase of the NTA concentration led also to a radioactivity decrease in all organs and tissues investigated. A significant radioactivity reduction in the tumour could be observed only after administration of rather high NTA amounts. Considerations of the tumour/background ratios depending on different compositions of the injection mixture showed the possibility of optimizing radionuclide biodistribution.

Animals↗
PubMed1995

Presurgical visualization of primary breast carcinoma with PET emission and transmission imaging.

UNLABELLED: The aim of this study was to investigate a technique that visualizes findings from PET images in a context useful for surgery. METHODS: Simultaneously acquired PET emission and transmission scans were used. By applying a multipurpose imaging, registration and rendering tool (MPM), displays of orthogonal and volume-rendered views or any combination thereof were obtained. The PET emission and transmission scans were acquired under routine conditions. The final user-customized display (with a combination of orthogonal cuts and rendered views) was processed in 10 min or less on commercially available hardware. Distinct features of the body shape were clearly visible on the volume-rendered transmission views. Hot spots, e.g., in primary breast cancer, from the emission scans could be easily assessed in their localization relative to the body outline. CONCLUSION: Rendering of the main signatures in a single comprehensive display makes this method potentially valuable for simple presurgical workup and therapeutic management of breast cancer.

Breast Neoplasms↗
PubMed1995

[Biokinetics of tumor-affinity yttrium preparations--Part 1].

Differences of yttrium biokinetics after application to male tumor-bearing mice of 87Y-citrate were studied in comparison to a 87Y-NTA-EDTMP-Ca mixture after variation of both the manner of application (intraperitoneal vs. intratumoral) and the tumor type (mamma carcinoma vs. melanoma). The application of 87Y as NTA-EDTMP-Ca preparation led--in comparison to the citrate form applied so far--to a similar radionuclide tumor accumulation and distinctly lower extratumoral radioactivities in liver, spleen and skeleton with clearly more favorable tumor/background ratios. Melanomas showed a significantly higher radioactivity accumulation (factor 2-3) after injection of 87Y-NTA-EDTMP-Ca than mamma carcinomas. Intratumoral application led to high initial radioactivities in the tumors. Radioactivity concentrations which are comparable with those after intraperitoneal application were achieved within 4 h after intratumoral application. The application of the EDTMP-containing mixture promises in comparison to the traditional citrate form higher radiation doses in the tumor related to the whole-body radiation exposure. The consequences for a possible tumor therapy will be further investigated.

Animals↗
PubMed1994

A prospective study concerning psychological characteristics of patients with breast cancer.

In a prospective study we have investigated the question of predisposing and reactive personality traits in breast cancer patients. The design of the study incorporated a prebioptic collection of data by means of an interview and psychological test questionnaires (STAI, SVF, FPI, CIP-DS), as well as follow-up questioning after a one year interval. In comparison with operated women with benign biopsy findings no unequivocal indications of a personality type predisposed to cancer were found. Both patient groups showed a high preoperative potential for anxiety. The tendency to suppress emotions, trivialise and to display self-pity was particularly noticeable in patients with advanced tumours at the time of diagnosis. Even after the disease had run for one year, it was not possible to demonstrate a distinct characterisation of the breast cancer patients by psychological testing methods. An increased concern over health, an inclination towards resignation and social isolation and a diminished contentment with life marked the changes that could be measured by psychological tests in some of the women affected.

Adult↗