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Biomedical subjects

H Hepp

Publications and source records attributed to H Hepp.

At least 19 recordsLinked to original sources

Prenatal diagnosis of congenital heart disease and neonatal outcome--a six years experience.

BACKGROUND: Prenatal diagnosis of congenital heart disease (CHD) is important for proper perinatal and neonatal management, as CHD occurs in approximately eight of 1000 live births. Antenatal detection of cardiac malformations is crucial as altered obstetric and neonatal management may be required and the neonate will benefit from delivery at a tertiary care center. METHODS: A retrospective comparison between pre- and postnatal diagnoses was accomplished. All fetal echocardiographic scans performed and CHD's detected postnatally between January 1994 and December 1999 by the department of obstetrics and gynecology and pediatric cardiology - Grosshadern, Munich University Hospital were reviewed. RESULTS: The incidence of CHD was 1.5% (116/ 7913). CHD was suspected by prenatal ultrasound in 57 fetuses. Postnatally, 116 congenital cardiac anomalies were diagnosed. Overall, the intrauterine detection rate was 38% (44/116). 72% (84) of the diagnosed anomalies were Septal Defects, 16% (19) disorders of the Atrioventricular Valves and 11% (13) Anomalies of the Great Vessels. In 10% (11) of fetuses chromosomal abnormalities were found. 8% (9) newborns suffered from congenital syndromes. In 55% (64) children were delivered preterm (<37 weeks of gestation). 5% (6) of the neonates required surgery within their first year of life. 28% (33) of children with CHD did not survive the first year of life. CONCLUSION: As the prenatal diagnosis is important for pre-, peri- and postnatal management, diagnostic accuracy is essential. Nevertheless, the accuracy of postnatal pediatric echo still exceeds that of the prenatal scan.

Adolescent↗

Drug interactions and cytotoxic effects of paclitaxel in combination with carboplatin, epirubicin, gemcitabine or vinorelbine in breast cancer cell lines and tumor samples.

The purpose of this study was to analyze the drug interactions of paclitaxel (PTX) with epirubicin (EPI), carboplatin (CBDCA), gemcitabine (GEM) and vinorelbine (VIN) in human breast cancer cells and compare the cytotoxic activity of each drug combination in primary breast cancer samples. These experiments were intended to identify the most active agents in combination with PTX, and to provide a preclinical rational for future clinical investigations in breast cancer. Multiple drug effect/combination index (CI) isobologram analysis was applied to combinations of PTX with either CBDCA, EPI, GEM or VIN in MCF-7, MDA-MB-231 and SK-BR-3 human breast cancer cell lines. Drug concentrations were limited to the ranges achievable in humans in vivo, and the drugs were applied simultaneously at fixed molar ratios for each drug combination. Interactions were assessed at multiple effect levels (IC10-IC90). Additionally, the cytotoxic activity of these combinations was assessed in tumor samples of 50 primary breast cancer patients, utilizing the ATP-tumorchemosensitivity assay (ATP-TCA). Drug interactions were shown to be strongly dose-related in the human breast cancer cell lines investigated. At clinically relevant concentrations, CBDCA/PTX demonstrated synergistic (MCF-7) or additive (MDA-MB-231, SK-BR-3) interactions, and EPI/PTX showed additive (SK-BR-3, MCF-7) and antagonistic (MDA-MB-231) interactions. GEM/PTX and VIN/PTX, however, demonstrated antagonism over multiple dose effect levels at clinically relevant drug concentrations in all three cell lines tested. At plasma peak concentrations, EPI/PTX, CBDCA/PTX, GEM/PTX and VIN/PTX achieved > or = 90% tumor growth inhibition in 93, 86, 63 and 50%, respectively, of primary breast cancer samples investigated with the ATP-TCA. Cumulative dose-response plots of primary breast cancer tumor cells responding in vitro with > or = 90% growth inhibition showed a strong dose dependence for both EPI/PTX and CBDCA/PTX. In conclusion, the current data indicate favorable drug interactions for CBDCA/PTX at clinically relevant drug concentrations in breast cancer cells, and demonstrate superior in vitro cytotoxicity of EPI/PTX and CBDCA/PTX compared to GEM/PTX and VIN/PTX in primary breast cancer cultures.

Antineoplastic Agents↗

[Gynäkologisch-geburtshilfliche Rundschau -revisited, future directed and practice oriented].

After a long period of 15 years, the SGGG recognized the Gynäkologisch-geburtshilfliche Rundschau once again as their official organ. Herewith a sign is given for a more intense cooperation with the Austrian Society for Gynecology and Obstetrics. Eventually, the possibility that the Bavarian Society of Gynecology and Obstetrics will also join might be achieved. In a time of rapid developments in the field of print media, publishers and editors are now facing new and upcoming challenges. The concept of our journal will be adapted to the modern requirements of our readership. Besides the traditional original papers, important with regard to the impact factor, other topics will be published, e.g., medicine and law, management and health care, and congress reports. As recently introduced, articles in German as well as in English are welcome.

Austria↗

Dose-dense and sequential strategies in adjuvant breast cancer therapy.

Several attempts have been made to improve the survival rates of breast cancer patients. The benefit of adjuvant chemotherapy was clearly shown, but the absolute difference of 2% to 11% in overall survival, depending on the patient group, is disappointingly small. In particular, high-risk patients, such as those with > or = 10 involved lymph nodes, extracapsular spread, or vascular invasion, still have an excessive risk of recurrence even after standard adjuvant chemotherapy. To increase the survival rates after adjuvant therapy, new chemotherapeutic agents and new strategies of application are currently being evaluated in clinical trials. Chemotherapy with cyclophosphamide (Cytoxan, Neosar), methotrexate, and fluorouracil (CMF) seems to be safe and effective in patients with breast cancer. In addition, in metastatic patients, dose-intensified chemotherapy is being investigated. The introduction of epirubicin (Ellence), an agent less cardiotoxic and equally active compared to doxorubicin, enabled the escalation of anthracyclines in adjuvant therapy without serious cardiotoxic effects. The combination of dose-intensified chemotherapy and sequential application in the treatment of breast cancer is reviewed.

Antineoplastic Agents↗

Association of urokinase-type plasminogen activator and its inhibitor with disease progression and prognosis in ovarian cancer.

PURPOSE: Urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor (PAI)-1, have been shown to be related to poor prognosis in a variety of malignant solid tumors. Studies on the prognostic relevance of uPA and PAI-1 in ovarian cancer, however, have been inconclusive. The current study tests the hypothesis that elevated expression of uPA and PAI-1 is associated with prognosis and disease progression. EXPERIMENTAL DESIGN: uPA and PAI-1 were prospectively measured by quantitative ELISA in tumor samples from 103 ovarian cancer patients (82 primary invasive epithelial carcinomas, 9 low malignant potential tumors, and 12 recurrent ovarian carcinomas). RESULTS: uPA but not PAI-1 levels were consistently associated with malignant progression, with levels increased from low malignant potential tumors to primary tumors (uPA, P = 0.04; PAI-1, P = 0.019), from early to advanced disease stages (uPA, P = 0.014; PAI-1, P = 0.23), and from primary to intra-abdominal metastatic tumors (uPA, P = 0.001; PAI-1, P = 0.16). High uPA and PAI-1 levels were associated with residual tumor volumes of >1 cm (P = 0.001 and P = 0.016, respectively). Among invasive International Federation of Gynecologists and Obstetrician stages I-IV tumors, elevated levels of uPA (>5.5 ng/mg) and PAI-I (>18.8 ng/ml) were associated with a shortened progression-free survival (uPA, P = 0.003; PAI-1, P = 0.039) and overall survival (uPA, P = 0.0002; PAI-1, P = 0.007). In multivariate analysis, uPA retained prognostic independence for progression-free survival (P = 0.037) and overall survival (P = 0.006). CONCLUSIONS: These data suggest that the uPA/PAI-1 axis may play an important role in the intra-abdominal spread and reimplantation of ovarian cancer cells. The prognostic relevance of uPA and PAI-1 supports their possible role in the malignant progression of ovarian cancer.

Adult↗

Her-2/neu and urokinase-type plasminogen activator and its inhibitor in breast cancer.

PURPOSE: Recent studies suggest that HER-2/neu specifically promotes the invasive capacity of tumor cells by up-regulating secretion of the proteolytic enzyme, urokinase-type plasminogen activator (uPA), or its inhibitor, plasminogen activator inhibitor-1 (PAI-1), in colon and gastric cancer. It was the purpose of this study to: (a) evaluate the association between HER-2/neu and uPA and PAI-1 expression in a large primary breast cancer cohort; (b) perform the first multivariate analysis, including HER-2/neu, uPA, and PAI-1 in breast cancer; and (c) define the effect of HER-2/neu overexpression on uPA and PAI-1 expression in breast cancer cells. EXPERIMENTAL DESIGN: HER-2/neu, uPA, and PAI-1 were measured as continuous variables by ELISA in primary breast cancer tissue extracts from 587 patients with clinical follow-up and analyzed for correlations with clinical outcome. Furthermore, a full-length human HER-2/neu cDNA was introduced into five human breast cancer cell lines to define the effects of HER-2/neu overexpression on uPA and PAI-1 expression. In addition, we tested whether HER-2/neu antibodies could reverse any given alteration of uPA and PAI-1 levels. RESULTS: Our findings indicate a weak positive association between HER-2/neu and uPA (r = 0.147; P < 0.001) and no association between HER-2/neu and PAI-1 (r = 0.07; P = 0.085). HER-2/neu overexpression (> or =400 fmol/mg) and high levels of uPA/PAI-1 (> or =5.5 ng/mg and/or > or =14 ng/mg, respectively) were significantly associated with shorter disease-free survival (DFS; P < 0.001 and P = 0.003) and metastasis-free survival (MFS; P = 0.015 and P < 0.001). Multivariate analysis revealed prognostic independence between HER-2/neu and the uPA/PAI-1 axis for DFS and MFS. Both uPA and PAI-1 had no significant discriminatory effect among HER-2/neu-positive patients for DFS. The prognostic value of HER-2/neu overexpression for MFS, however, was significantly enhanced by elevated uPA expression (P = 0.053). Stable transfection of the HER-2/neu gene into multiple human breast cancer cell lines resulted in consistent down-regulation of uPA or PAI-1 expression. In addition, anti-HER-2/neu antibodies did not significantly affect uPA or PAI-1 expression in human cancer cell lines naturally overexpressing HER-2/neu. CONCLUSIONS: The present findings suggest that the invasive phenotype elicited by HER-2/neu overexpression in breast cancer is not a direct effect of uPA or PAI-1 expression. HER-2/neu and the uPA/PAI-1 axis have been shown to affect the invasive capacity of breast cancer independently. Determination of uPA can provide significant additional prognostic information for MFS in HER-2/neu-positive and -negative patients.

Adult↗

Correlation of drug response with the ATP tumorchemosensitivity assay in primary FIGO stage III ovarian cancer.

OBJECTIVE: Our purpose was to: (a) study the in vitro chemosensitivity of primary epithelial ovarian cancer to drug combinations with cisplatin (CDDP), carboplatin (CBDCA), paclitaxel (PTX), epirubicin (EPI), or cyclophosphamide (CTX) utilizing the ATP tumorchemosensitivity assay (ATP-TCA); (b) correlate the test results with clinical response in patients with FIGO stage III ovarian cancer; and (c) analyze the most useful parameters for interpretation of test results. METHODS: CBDCA/CTX, CBDCA/PTX, CDDP/PTX, and EPI/PTX were tested in 93 fresh human primary epithelial ovarian cancer specimens. Correlations of in vitro drug sensitivity/resistance and clinical response were performed in 38 patients with FIGO stage III disease utilizing Fisher's exact test and by comparison of progression-free (PFS) and overall survival (OS) between those testing as sensitive or resistant. A progression-free interval of more than 12 months following surgery was classified as clinical response. ATP-TCA results were analyzed using the median effective dose, area under the curve, or a defined sensitivity index. RESULTS: Evaluable test results were achieved in 83 of 93 patients (89%). EPI/PTX had the highest in vitro activity (P < 0.001). In the clinical correlation, 29 of 38 patients (76%) were classified as in vitro sensitive (sensitivity index [SI] <250) and 9 patients as in vitro resistant (SI >250). The SI was superior for interpretation of test results. Patients testing as chemosensitive had a significantly longer mean PFS (28.5 vs 12.6 months, P = 0.033) and OS (46.1 vs 17.6, P = 0.03) compared to those patients predicted to be resistant. The assay demonstrated a sensitivity, specificity, and positive and negative predictive value of 95, 44, 66, and 89%, respectively (Fisher's exact test, P = 0. 007). CONCLUSION: The observed in vitro efficacy of EPI/PTX in primary epithelial ovarian cancer specimens warrants further clinical evaluation. The high evaluability rate and the observed correlation with PFS and OS, within the limitations of a nonrandomized study, support the use of the ATP chemosensitivity assay in future prospective assay-directed trials.

Adenosine Triphosphate↗

[Does the increasing cesarean section rate reflect a shift in indications or a decline in quality?].

The cesarean section rate is continuously increasing at our department, from 13.8 to 17.2% between 1999 and 2000. The mother's wishes regarding the mode of delivery weigh increasingly on our obstetric decisions. Patient acceptance of elective cesarean section is high, and the increasing cesarean section rate is influenced by paramedical factors. Obstetrics appears to be developing into a mostly surgical discipline. The effect this has on quality (and costs) remains to be seen.

Cesarean Section↗

[Retrospective analysis of dose intensity of epirubicin in breast cancer].

OBJECTIVE: In breast cancer the efficacy of epirubicin-based chemotherapy is possibly related to the actual dose intensity applied. We retrospectively determined the administered dose intensity and the relative toxicity and efficacy of an epirubicin-containing regimen in patients with primary or metastatic breast cancer. PATIENTS AND METHODS: Fluorouracil, epirubicin, and cyclophosphamide (FEC) were either given at a standard dose of 500/50/500 mg/m2 (FE50C) or at an intensified dose of 500/75/500 mg/m2 (FE75C) every 3 weeks. Of the 66 patients treated, 63 were evaluable; 43 had metastatic breast cancer, and 20 patients with an increased risk of relapse received FEC as an adjuvant treatment. RESULTS: Dose intensity and absolute dose of adjuvant treatment were 81 and 70% for FE50C and 96 and 88% for FE75C. In metastatic breast cancer, the dose intensity for FE50C was 94% and for FE75C 92%. In a retrospective comparison, the 4-year overall survival following adjuvant FE50C and FE75C was 40 and 48%, respectively (p = 0.47). The dose intensification led to a higher response rate of 34 vs. 44%. There were no significant differences in response duration and survival time. The toxicity profiles were comparable between FE50C and FE75C. CONCLUSIONS: In general, the doses applied were lower than initially planned. Higher doses of epirubicin did not result in a significant increase of toxicity. Despite the limitations of a retrospective analysis, our observations support the importance of adherence to the planned dose intensity as a prerequisite for optimal treatment of patients suffering from breast cancer. As our results could be related to selection bias, dose-intensified anthracycline-containing regimens should be further evaluated in prospective trials.

Adult↗

[Effects of tubal sterilization].

OBJECTIVE: Besides manifestations of hormonal deficits, psychological problems are also known as possible negative effects of tubal sterilization (here termed "operative contraception"--OC). It is generally assumed that the age at time of operation and the number of children play a crucial role in enabling the patient to come to terms with surgical contraception. We investigated whether these patients were satisfied and the frequency of a desire for refertilization as well as further factors possibly affecting our patients. PATIENTS AND METHODS: A standardized questionnaire was sent to 274 women in whom surgical contraception was performed from 1984 to 1990 in our hospital. Besides physical symptoms, the questions mainly inquired as to satisfaction, degree of regret and desire for refertilization. RESULTS: 5.4% of women were not satisfied with the operation. 13.7% of the patients regretted the operative contraception and 6.5% wished to have refertilization. The negative appraisal did not correlate with the number of children and age at the time of operative contraception. Altogether, satisfaction was very much greater in patients who had completed family planning than in patients who had received operative contraception for medical reasons. Appraisal of operative contraception was especially negative in women in whom the operation had been performed on the occasion of a cesarean section. CONCLUSION: Our follow-up investigation confirmed that operative contraception was experienced as being very liberating by most women and was accordingly appraised positively on the whole. The number of children and age only played a subordinate role in how patients came to terms with their situation. For a positive experience of operative contraception, the time of the operation appears to be of major importance. In particular, "favorable opportunities" on the occasion of cesarean section and the if anything doubtful need for this measure in the condition after prior cesarean sections must be avoided, since in these cases a free decision in favor of operative contraception, which the woman concerned feels to be autonomous, is not possible.

Adolescent↗

[LEEP versus cold knife conization for treatment of cervical intraepithelial neoplasias].

OBJECTIVE: This study was performed to evaluate the effectiveness and side effects of loop electrosurgical excision procedure (LEEP) in comparison to cold knife conization for the treatment of cervical intraepithelial neoplasia (CIN). MATERIAL AND METHODS: Between January 1996 and July 1998, 177 patients underwent conization. In a matched-pair setting, 50 cases with LEEP were compared with 100 classical conization cases. LEEP was performed with ectocervical and endocervical excision. RESULTS: Perioperative complications were less in the LEEP group (6% vs. 11%). The mean volume of LEEP specimens (1.6 cm3) was significantly smaller than the volume of cone specimens (2.6 cm3). Thermal artifacts were negligible. There were no significant differences in the proportion of margin involvement (20% vs. 19%) and residual/recurrent CIN. The endocervical excision contained dysplastic tissue in 38% of the cases; more important, a positive endocervical excision was found in 14/21 CIN 3 cases (67%). The success rate, was similar in both groups (96% vs. 97%). Hospitalization time was less for the LEEP group. CONCLUSIONS: LEEP conization is a safe and cost effective procedure with a lower complication rate providing a significantly smaller specimen compared to cold knife conization. Therefore, LEEP conization may substitute cold knife conization. However, we do recommend to perform LEEP conization with an endocervical excision to reduce residual CIN.

Adult↗

Photodynamic therapy in women with cervical intraepithelial neoplasia using topically applied 5-aminolevulinic acid.

Photodynamic therapy (PDT) is a novel treatment modality that produces local tissue necrosis with laser light after prior administration of a photosensitizing agent. We performed a study of topically applied 5-aminolevulinic acid (5-ALA) in the photodynamic treatment of women with high-grade cervical intraepithelial neoplasia (CIN) using fixed 5-ALA doses and application protocols derived from previous in vitro and in vivo results. Three to 5 hr prior to PDT, 10 ml of a 20% solution of 5-ALA was topically applied using a cervical cap. PDT was performed with irradiation of 100 J/cm2 at an irradiance of 100-150 mW/cm2 with an argon-ion-pumped dye laser at 635 nm. For the endocervix, a specifically designed cylindrical applicator was used. Ten treatment cycles of PDT using 5-ALA were performed in 7 patients with high-grade CIN. Non-thermal laser treatment with 100-150 mW/cm2 was well tolerated. Local toxicity was minor as several patients reported burning sensations and vaginal discharge, but no necrosis, sloughing or scarring occurred. After 3 months, a significant reduction in the size of the ectocervical CIN lesions was noted in only 3 patients, who underwent a second PDT cycle. However, no significant improvement in CIN lesions was noted since cold knife conization revealed persistent CIN in all 7 cases. Therefore, PDT after topical application of 5-ALA using an irradiation of 100 J/cm2 produces only minimal side effects. However, it does not appear to be effective in treating CIN.

Administration, Topical↗

[Secondary debulking after dose-intensified chemotherapy of ovarian carcinoma].

Only 20-40% of patients with advanced ovarian cancer have no residual disease after primary cytoreductive surgery. For patients with residual tumor and good response to chemotherapy new therapeutic procedures have to be discussed. In our study the role of secondary debulking surgery, especially after G-CSF supplied dose intensification was evaluated. Between January 1986 and December 1995, 506 patients with primary ovarian cancer were treated at our institution. 117 patients with residual tumor after primary surgery had secondary debulking after four to six cycles of platinum based chemotherapy, 26 of them had G-CSF supplemented dose intensification by shortened therapy intervals. After secondary debulking 43% had no residual disease, 37% had residual tumor less than 2 cm and 20% more than 2 cm. Mean survival in patients without residual disease was 47 months and significantly longer than in patients without secondary debulking with only 35 months. In 25 to 26 patients with dose intensification chemotherapy cycles could be applied regularly, the results were in the expected range. Secondary debulking surgery can prolong survival in those patients without residual tumor after secondary surgery. Dose intensification is possible without remarkable side effects. In our study the percentage of patients without residual tumor could not be increased by dose intensification.

Adult↗

[How much preoperative information? - How can it be documented?].

Preoperative information for patients and documentation of this information are becoming increasingly significant. Opinions diverge especially on how to document the information provided, the information protocol being only an ancillary element. The patient must be in a position to make an informed decision without suffering any prejudice. Information protocols relating to treatment, that is to the operation, aim at ensuring the quality of the treatment and at documenting the information provided. A scheme of the operation is an important element of this information. Twenty-one presurgical information protocols have been tested in a pilot phase and are still being evaluated by a patients' association. Information and documentation concepts need to be set up by professional societies before insurance companies and governmental offices start getting involved.

Documentation↗

Treosulfan as an effective second-line therapy in ovarian cancer.

Despite radical surgery and aggressive platinum-containing primary chemotherapy, the outcome of patients with advanced ovarian cancer remains extremely poor; most of them suffer from recurrent or progressive disease. These patients should be treated with an effective second-line therapy showing only few toxic side effects so as not to affect quality of life. From July 1992 to August 1996, 88 patients with recurrent or progressive ovarian cancer have been treated with treosulfan, an alkylating agent, in our department. All of them could be evaluated for toxicity and 80 for response. There were 2 complete and 13 partial responses, giving an objective response rate of 19%. Among responding patients, median survival time was 41 months. Thirty-four percent of the patients had stable disease with median survival of 18 months. Thirty-eight (47%) nonresponding patients showed a survival time of only 5 months. In 48 women with progressive disease within 12 months after primary therapy, a response rate of 19% and stable disease in 31% could be achieved. Toxic side effects were rare and moderate in intensity. Life-threatening myelosuppression, emesis resistant to therapy, and alopecia were not observed. It can be concluded that tresosulfan is an effective drug in second-line therapy for patients with recurrent or progressive ovarian cancer without affecting quality of life.

Adult↗