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Biomedical subjects

A Pfleiderer

Publications and source records attributed to A Pfleiderer.

At least 37 records · Page 2Linked to original sources
PubMed1994

Recurrent cytogenetic aberrations and loss of constitutional heterozygosity in ovarian carcinomas.

Cancer is regarded as the result of the accumulation of multiple genetic changes leading to either the activation of oncogenes and increased expression of mitogenic pathways or the inactivation of tumor suppressor genes. It was our interest to investigate malignant ovarian tumors with cytogenetic and molecular techniques to evaluate their consistent genetic alterations. Cytogenetic analysis was performed on 30 short-term cultured ovarian carcinomas. Fifteen tumors revealed clonal cytogenetic abnormalities, 10 of which had very complex karyotypes. The most consistent finding was a 19p+ marker chromosome which was present in half of the cytogenetically abnormal tumors with complex chromosome aberrations. Four tumors showed structural rearrangements resulting in loss of 11p13-pter material. Parallel DNA extracts from 18 tumor samples and corresponding normal white blood cells were analyzed by Southern blotting using 4 polymorphic probes spanning the region 11p15.1 to 11p15.5 and one polymorphic probe mapped to 19p13. Regarding the 11p probes, reduction to homozygosity in the tumor DNA was found in 9 of 17 informative cases. Loss of 19p alleles was found in 5 of 13 informative tumors. Our findings suggest that tumor suppressor genes located on the short arms of chromosomes 11 and 19 are involved in the development of human ovarian cancer.

Adult↗
PubMed1994

Therapeutic strategies in cervical pregnancy.

Cervical pregnancy is a rare condition associated with a high maternal morbidity rate. Standard recommendations for the management of this ectopic pregnancy are not available. This paper presents a case report and reviews the respective literature. In many cases hysterectomy was the ultimate solution. In order to avoid hysterectomy chemotherapy using methotrexate has been suggested. Local injections of prostaglandins or vasopressin have also been proposed. Based on data collected from the literature and our own experience it is concluded that the management of cervical pregnancy requires individualized therapeutic strategies to minimize the rate of hysterectomies.

Adult↗
PubMed1994

Color Doppler flow criteria of breast lesions.

Color Doppler technique has been available for several years. The sensitivity of the equipment has improved and allows for assessment of tumor vascularity. We investigated multiple parameters in 258 patients, with 176 benign and 82 malignant lesions to define characteristic flow criteria. Median (25-75% quartiles) and p-values are given for benign vs. malignant lesions. Number of tumor vessels: 2 (1-2) vs. 8 (5-14), p < 0.0001; mean peak systolic flow velocity: 11.1 cm/s (6.4-14.9) vs. 18.8 cm/s (13.7-25.1), p < 0.0001; maximum flow velocity: 12.5 cm/s (6.7-18) vs. 32.5 cm/s (22.5-47.3), p < 0.0001; sum of all systolic flow velocities: 18.9 cm/s (7-34.2) vs. 147 cm/s (71.3-266.7), p < 0.0001; minimum systolic flow velocity: 8.9 cm/s (5.4-12.1) vs. 9 cm/s (6.3-11.3), p > 0.05; average resistance index (RI): 0.68 (0.58-0.72) vs. 0.75 (0.67-0.81), p > 0.05; maximum RI: 0.71 (0.65-0.78) vs. 0.88 (0.78-0.99), p < 0.0001; minimum RI: 0.64 (0.57-0.68) vs. 0.64 (0.53-0.71), p > 0.05; average A/B ratio: 3.1 (2.7-3.7) vs. 4.3 (3.2-7.7), p < 0.0001; maximum A/B ratio: 3.4 (2.9-4.6) vs. 8.4 (4.5-9.9), p < 0.0001; minimum A/B ratio: 2.8 (2.3-3.2) vs. 2.9 (2.2-3.5), p > 0.05. The data analysis shows that flow resistance in malignancies is increased. This is in contrast to gynecological malignancies, where an increased diastolic flow indicates that flow resistance is decreased.

Adolescent↗
PubMed1994

[Color Doppler flow data of breast tumors].

The recent development of high-quality colour Doppler instruments allows flow detection in small vessels below the resolution of B-mode imaging. Therefore, Doppler is now frequently used for flow detection in tumours. For breast examinations, CW Doppler has been in use for many years, which allows a sufficient definition of diagnostic criteria. Nevertheless, it is surprising that new studies using colour Doppler try to define different diagnostic criteria. To characterise the vascularity of breast lesions by colour Doppler we investigated 127 symptomatic patients. In 54 carcinomas the average flow velocity was 32 cm/s and 12.6 cm/s in 73 benign conditions (p > 0.0001). Total tumour vascularisation was characterised by a new parameter: the sum of all flow velocities in all tumour vessels. In carcinomas the mean total flow as 197.9 cm/s, and 52.7 cm/s in benign pathologies (p > 0.0001). Mean RI (resistance index) and PI (pulsatility index) were calculated to describe the flow profiles. The wide variation did not allow for a differentiation between benign and malignant lesions.

Arteries↗
PubMed1994

[The pubococcygeus patch--a method for correction of female stress incontinence in simultaneous prolapse].

The pubococcygeus patch procedure is introduced as a vaginal method for treatment of severe stress urinary incontinence of the female in combination with a marked descensus requiring vaginal surgery. It is based on physiological conceptions of urethral closure mechanisms. The primary success rate in 47 women with severe stress-urinary incontinence was 85% after 3-6 months, and 60% in women with hypotonic urethra (< 30 cm H2O). The complication rate was low. The material used for the patch was lyodura (n = 43) and gore-tex (n = 4), the latter showing a 50% repulsion rate.

Adult↗
PubMed1994

[Transvaginal color-coded Doppler ultrasound in ovarian tumors].

In 129 patients with ovarian tumours, a preoperative examination by transvaginal colour Doppler sonography (ATL UM9 HDI) was performed. 45 were malignant and 84 benign. 46 patients were premenopausal and 83 postmenopausal. All tumour vessels were analysed by spectrum analysis. The number of tumour vessels and the lowest resistance index (RImin) and pulsatility index (PImin) of all vessels were evaluated as diagnostic criteria of the neovascularisation. Up to 19 vessels were found in 115 (89%) tumours. In benign lesions, the number of vessels was significantly lower than in malignancies (median 3 versus 9, p < 0.0001). The RImin and PImin values between benign and malignant tumours were also significantly different, independent of the menopausal status. In postmenopausal patients, the median RImin in 42 benign tumours was 0.62 (0.26-1.0) and in 41 malignancies 0.40 (0.22-0.66). The median PImin was 0.98 (0.31-5.84) in benign tumours and 0.53 (0.25-1.22) in malignant tumours. However, due to the overlapping range between benign and malignant tumours, these parameters do not allow an accurate differentiation. With a cut off value for RImin = 0.5 and PImin = 0.7, the sensitivity is 85% or 82.5% respectively. The specificity for RImin and PImin is 77%, and the diagnostic accuracy is 84% and 80% respectively. The correlation coefficient between RImin and PImin is 0.99 in benign and malignant tumours and both indices are adequate. The calculation of the RI is more easily available and should be preferred as a diagnostic parameter.

Adolescent↗
PubMed1994

Transvaginal sonography of myometrial invasion depth in endometrial cancer.

The myometrial invasion depth of endometrial cancer is an important prognostic factor. The preoperative assessment is decisive for the appropriate surgical treatment. In 96 patients with endometrial cancer, the myometrial invasion depth (greater than 50% or less than 50%) was measured preoperatively using transvaginal sonography (TVS). The sonographic results were compared to the histopathological findings. A sensitivity of 93% was obtained for invasion depths greater than 50%. The predictive value of an invasion depth less than 50% was 93% as well. In 16% of the cases the invasion depth was overestimated while, in only 3% it was underestimated. The diagnostic accuracy was 81%. Forty-five patients were examined preceding a diagnostic dilatation and curettage and fifty-one were examined following a diagnostic dilatation and curettage. The diagnostic accuracy in both groups was equivalent. Using transvaginal sonography, the spread of cancer to the cervix was observed in five of the seven cases in which it was postoperatively confirmed. TVS is a valuable, non-invasive diagnostic method for patients with endometrial cancer. When the TVS data are combined with results from other preoperative tests, the prognostic information obtained provides a useful basis in choosing the appropriate therapy.

Aged↗
PubMed1994

Steroid receptors in carcinoma of the breast. Results of immunocytochemical and biochemical determination and their effects on short-term prognosis.

A group of 241 nonpretreated breast carcinomas was studied for estrogen receptor (ER) and progesterone receptor (PR) content by both immunocytochemistry (ICC) and biochemical analysis (dextran-coated charcoal [DCC]). While the tumors were judged to be ER positive in 67.6% and PR positive in 65.6% by ICC, DCC analysis showed positive results in 77.6% for both ER and PR. There was only a moderate correlation between the semiquantitative results of ER and PR ICC and the corresponding values for DCC receptor determination. Among tumors shown to be steroid receptor positive by ICC, a majority showed a wide spectrum of staining intensity, from negative to intensely positive (type C staining pattern, ER 87.7%, PR 73.4%). Less frequently, carcinomas showing uniform, intense staining of all epithelial tumor cells were observed (type A staining pattern, ER 11.7%, PR 18.4%). Finally, only very few tumors had both clearly negative and distinctly positive cells (type B staining pattern, ER 0.6%, PR 8.2%). On analyzing the relationship between the expression of steroid receptors (ICC and DCC) and the prognostic factors axillary node status, tumor size, tumor histology, grade and patient age, only a significant correlation between patient age and ER (ICC, r = .46; DCC, r = .43), a weakly significant negative correlation between node involvement and ER, and a weakly significant negative correlation between tumor grade and ER (ICC only) as well as between tumor grade and PR were found. Among all patients, the recurrence-free interval was significantly longer in patients with ER- or PR-positive carcinomas (ICC and DCC).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1993

Loss of constitutional heterozygosity on chromosome 11p in human ovarian cancer. Positive correlation with grade of differentiation.

BACKGROUND: There is increasing evidence suggesting that genes located on the short arm of chromosome 11 play an important role in the development of human ovarian cancer. Recent cytogenetic and molecular studies have demonstrated the loss of genetic material in this region. Loss of normal growth regulatory genes may allow for the expression of tumorigenicity or lead to tumor progression. METHODS: The authors used DNA recombinant techniques to examine the frequency of allelic losses at four loci spanning the chromosomal region 11p15.1-11p15.5 in 40 patients with malignant ovarian tumors. DNA extracts from normal leukocytes and 48 tumor samples were analyzed by Southern blotting using the polymorphic probes pEJ6.6 (HRAS1), phins310 (INS), p20.36 (PTH), and pEM36 (CALCA). RESULTS: Reduction to homozygosity in the tumor DNA was found in 47.5% of the informative cases (19 of 40). Comparing the results with clinical parameters, none of the well-differentiated tumors (6 of 40, Grade 1) and only one of the early stage tumors (6 of 40, International Federation of Gynecology and Obstetrics [FIGO] Stage I or II) showed alterations in this chromosome region. Statistical analysis revealed a strong correlation of rate of loss of constitutional heterozygosity (LOH) and grade of differentiation, in the sense of higher 11p allele losses occurring in poorly differentiated tumors. CONCLUSIONS: The authors concluded that the relatively high incidence of 11p allele losses marks an important step in ovarian cancer development. Furthermore, statistical analysis showed that loss of 11p alleles was strongly correlated with poorly differentiated ovarian cancer, indicating the location of genes involved in cellular functions associated with the development of more anaplastic tumors.

Adenocarcinoma↗
PubMed1993

Preoperative staging of breast cancer by palpation, mammography and high-resolution ultrasound.

In breast cancer preoperative determination of the tumor size is important for planning breast-conserving operations. In 100 patients with breast cancer, the preoperative tumor size was measured using clinical, mammographic and sonographic examinations and correlated with the results of a subsequent histological examination. Using a high-resolution real-time system, 98 tumors were visible. It was possible to detect not only early tumors under 1 cm in diameter, but also intraductal tumor components. This contributed greatly to the accuracy of the diagnosis. The sonographic measurement of tumor size demonstrated a correlation coefficient of 0.91 and was thus superior to mammography (0.79) and palpation (0.77). Measurement of the total tumor spread, including 39 multicentric lesions, showed an overestimation of 5% for the mammographic measurements and an overestimation of 4% for the sonographic measurements. Tumor extension was underestimated in 33% of the mammograms but in only 3% using ultrasound examination. The results, along with those of other studies, highlight the role of sonography in the diagnosis of breast cancer.

Journal Article↗
PubMed1993

Gene structure and expression analysis of the epidermal growth factor receptor, transforming growth factor-alpha, myc, jun, and metallothionein in human ovarian carcinomas. Classification of malignant phenotypes.

This study reports the structure and expression rates of genes of the transforming growth factor-alpha (TGF-alpha) signal transduction pathway (TGF-alpha, epidermal growth factor receptor [EGF-R], jun, myc, and metallothionein [MT]) in 47 specimens of ovarian cancer and 21 nonmalignant tissues. The objective was to establish a direct correlation between the genetic activities and the malignant phenotype of the ovarian cancer. The Southern blot technique identified four samples with myc amplification and two with rearranged EGF-R genes. By using the S1 nuclease assay, the analysis of myc transcription showed a similar use of both promotors. Although the size of the investigated transcripts was unaltered, significant differences in the transcription rates were noticed in malignant tissue probes (using northern blot analysis and RNAase protection assay). The following results of messenger RNA analysis in ovarian cancer were observed: EGF-R, negative in 25%, low in 65%, and strongly positive in 10%; TGF-alpha, negative in 34%, low in 36%, and strongly positive in 30%; myc, negative in 8%, low in 64%, and strongly positive in 28%; jun, negative in 4%, low in 58%, and strong in 38%; and MT, low in 80% and strongly positive in 20%. In most nonmalignant tissues studied, no or only a low expression of TGF-alpha, EGF-R, and myc. was found. A comparison of these messenger RNA results with the clinical data from tumors showed four different subgroups of ovarian carcinomas. The results of chemotherapy were known in 32 cases. Tumors with negative or low expression rates of all investigated genes did not respond to chemotherapy; 13 of 18 tumors with high expression rates did respond. Additional signal transduction chains distinct from the TGF-alpha pathway, however, are likely to influence both the expression and activity of transcription factors and MT.

Adult↗
PubMed1993

Human papillomavirus DNA in distant metastases of cervical cancer.

Eighteen distant metastases from cervical cancer to the extrapelvic abdomen, extraabdominal lymph nodes, vulva, suburethral region, skin, and breast in 17 patients were analyzed by Southern blot hybridization under nonstringent and stringent conditions for the prevalence of human papillomavirus (HPV) type 11, 16, 18, 31, 33, and 35 DNA. Fourteen metastases in thirteen patients were HPV-positive. Thirteen tumors contained HPV-16 and one HPV-related sequences with varying copy number. In 9 of 11 cases, where the corresponding primary tumor could be studied, HPV positivity and type were identical. Two HPV-negative primary lesions had HPV-positive metastases; in three cases differences in restriction pattern or copy number were revealed. The HPV status showed no clear association with age of the patient, latency period between primary tumor and metastasis, histological findings, therapy, and clinical course of the disease after metastasis. The rather conserved presence of HPV DNA in distant metastases of cervical carcinoma underlines the importance of these viruses also for the maintenance of the malignant state.

Adult↗
PubMed1993

[The course of pregnancy in patients with malignancies].

There is a low incidence of pregnancy associated with malignancy. We performed a retrospective analysis of patients of 16 to 35 years of age with malignancies, who had given birth to children in Freiburg 1980-1989. 170 patients were included. 118 patients became pregnant before a malignancy was diagnosed. Malignancy was diagnosed during pregnancy in 24 patients, and 28 patients became pregnant after diagnosis of and therapy for neoplasm. The frequency of preterm delivery, growth retardation and performance of Caesarean section was markedly increased only in patients with concurrent pregnancy and malignancy. 59 children were born after their mother had been treated for a malignancy. Treatment was started during pregnancy in 19 cases. 40 children were born to mothers who became pregnant after treatment. Malformations and abnormalities with respect to the development of the children were observed in similar frequency in both groups and occurred more frequently compared to the group of children, who were born before the treatment of the mother. These results were supported by an analysis of 16 siblings. We conclude, that there is a demand for national and international registries for all pregnancies associated with malignancies. Long-time observation of the children born to mothers, who had been treated for malignancy are necessary.

Adolescent↗
PubMed1993

[Effect of pregnancy on the incidence and course of malignant diseases].

Fortunately, coincidence of pregnancy associated with malignant neoplasm is rare. As reported in the literature, incidence is 1.5-10: 10,000 pregnancies. The study presented reports data on the incidence and outcome of 16-35 years old female patients suffering from malignant neoplasms. Patients, who were treated in Freiburg 1980-1989, were considered for evaluation. We analysed the impact of pregnancy on the outcome of these patients by stratifying patients for the time of diagnosis (before, during, or after a pregnancy). 247 patients were included. 118 patients developed a neoplasia after a successful pregnancy. In 24 patients, neoplasia was diagnosed during pregnancy, and 28 patients became pregnant after diagnosis and therapy for a malignancy. Further 77 patients without pregnancy, but in whom neoplasia diagnosed at the age of 16-35 years were included. Cancer of the cervix uteri, breast cancer, ovarian cancer, and malignant lymphomas were the most frequent neoplasias diagnosed in young women. In an analysis stratified for stage of disease, we found no significant difference between 3- and 5-years survival of patients with pregnancies before, during, or after diagnosis and treatment of neoplasia. Due to the inhomogeneity of the subgroups analysed, the question, whether pregnancy has any impact on the outcome of neoplasm could not be conclusively answered. The necessity for the establishment of national and international registries collecting sufficient data about incidence and outcome of patients with pregnancies associated with malignant neoplasms is emphasised.

Adolescent↗
PubMed1993

[Improving diagnosis of blood supply of breast tumors by echo-contrast media].

Doppler blood flow measurements allow differentiation of malignant lesions, that are characterised by an abnormal vascularity. The accuracy of this method is limited due to the physiological flow variation in normal breast parenchyma and in tumours. Magnetic resonance imaging in combination with contrast agents can also be used for flow assessment by measurement of the dynamic contrast enhancement. Recently, a new echo contrast agent (Levovist) has been developed, which survives pulmonary transit and increases the Doppler signal intensity after intravenous injection. Fourteen malignancies with low vascularity were selected for the study. Twenty-two seconds after injection of contrast agent, the Doppler signal intensity increased dramatically. This demonstrates, that echo contrast agents might improve the diagnosis of breast lesions in case of non-conclusive Doppler findings.

Blood Flow Velocity↗
PubMed1993

Therapy of ovarian malignant germ cell tumors and granulosa tumors.

High-dose cisplatin-based chemotherapy is highly effective in all cases of germ cell tumors, including dysgerminoma. The complete remission and cure rates are between 80 and 90% of all cases. In young women, fertility-preserving surgery can be recommended. This is true for stage III cases as well because removal of the second ovary and the uterus does not change the prognosis. For granulosa cell tumors, however, meticulous surgery is the primary therapy. Operation should include careful pelvic and para-aortic lymph-adenectomy. Better knowledge of disease spread, improved surgical staging, the use of alphafetoprotein and human chorionic gonadotropin immunoassays to monitor therapy, and the ability of chemotherapy to treat advanced and recurrent cases successfully have changed the recommendations for therapy of germ cell and granulosa cell tumors.

Cisplatin↗
PubMed1993

Doppler measurement of breast vascularity in women under pharmacologic treatment of benign breast disease.

Breast vascularization was measured with an 8-MHz continuous wave Doppler pencil probe. Flow values were low in asymptomatic women and high in patients with severe pain or dysplastic changes. Mild treatment with a plant extract produced only a small decrease in breast vascularization. Treatment with norethisterone acetate showed a dose-dependent decrease in blood flow. A good response was seen with a dosage of 5 mg/d, and a dramatic decrease was seen when 10 mg/d was taken. These results showed a good correlation with the patients' symptoms.

Adult↗