[Burnout, work disruptions, interpersonal and psychosomatic problems--degree-specific comparison of students at a German university]. / Burnout, Arbeitsstörungen, interpersonelle und psychosomatische Probleme--Abschlussspezifischer Vergleich von Studenten einer deutschen Hochschule.

In the context of the public debate on psychological strain among students, the prevalence of burnout, procrastination, test anxiety, other work disruptions, interpersonal problems and psychic symptoms were analyzed depending on academic degree. The data of 358 college students (of Leipzig University) were examined. The academic degree had only a marginal effect on burnout- and work disruptions-related variables. In terms of interpersonal problems and psychic symptoms, differences between students were identified, depending on the academic degree. Diploma students reported many complaints, whereas undergraduates aspiring for a State Examination, were comparatively less affected. Knowledge of the population-specific psychological load is useful in order to develop preventive and therapeutic measures.

Primary chemotherapy with doxorubicin and paclitaxel in patients with early breast cancer: final results of a multicenter phase II study.

PURPOSE: To assess the efficacy and safety of primary systemic treatment with doxorubicin and paclitaxel in patients with early breast cancer. PATIENTS AND METHODS: Forty patients with newly diagnosed, histologically confirmed breast cancer (T2, N0-1, M0) received primary chemotherapy with doxorubicin (60 mg/m2) and paclitaxel (200 mg/m2) in 3-week intervals for up to four courses. RESULTS: A total of 151 cycles were administered. The clinical response rate as assessed by sonographic measurement was 70%, and complete remissions of the primary tumor occurred in two patients. Eight patients (20%) had histologically confirmed complete responses. Predominant toxicity was myelosuppression with grade 3/4 neutropenia in 70% of patients. Non-hematological toxicity was generally moderate. Grade 4 non-hematological toxicities were not observed and grade 3 toxicity was reported with alopecia (98%) and stomatitis (10%). CONCLUSIONS: The combination of doxorubicin and paclitaxel is safe and highly active in patients with early breast cancer. The evaluated schedule is suitable for phase III studies.

The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR.

BACKGROUND: Abagovomab is a murine anti-idiotypic antibody against the antigen CA-125 which has been shown to elicit humoral and cellular immune responses against ovarian cancer (oc). PATIENTS AND METHODS: This phase I trial included 36 patients with recurrent oc comparing two subcutaneous (s.c.) vaccination schedules: nine (group L) versus six injections (group S), 18 patients in each group. Four injections of 2.0 mg abagovomab were administered every 2 weeks and then two or five additional doses monthly. Primary endpoint was drop-out rate due to toxicity, and the secondary endpoint was analysis of immunological response. RESULTS: Treatment was completed in eight (44%) and 16 (89%) patients in groups L and S, respectively. Premature termination occurred due to patient withdrawal or disease progression. No treatment-limiting toxicities occurred in either group. The most common toxicity related to the vaccine was grade 1/2 local injection site reaction. Induction of Ab3 was observed in all evaluable patients. There were no differences between the groups with regard to induction of human anti-mouse antibody (P = 0.1006). IFNgamma-expressing CA125-specific CD8+ T-cells were significantly more frequent in group L, while there was no significant difference between CD4+ T-cells in the two groups. CONCLUSIONS: Abagovomab s.c. vaccination is safe and well tolerated. The long vaccination schedule tended to be more effective with regard to AB3-induction and cellular cytotoxicity.

Neuroprotection with amifostine in the first-line treatment of advanced ovarian cancer with carboplatin/paclitaxel-based chemotherapy--a double-blind, placebo-controlled, randomized phase II study from the Arbeitsgemeinschaft Gynäkologische Onkologoie (AGO) Ovarian Cancer Study Group.

GOALS OF WORK: Neurotoxicity is a common side effect of platinum/taxane-based therapy of ovarian cancer. We performed a double-blind randomized placebo-controlled trial to evaluate the influence of the cytoprotectant amifostine on the neurotoxicity of first-line therapy of ovarian cancer with paclitaxel/carboplatin with or without epirubicin. PATIENTS AND METHODS: Of 72 patients randomized, 71 were treated with paclitaxel 175 mg/m2 and carboplatin AUC5 with or without epirubicin 60 mg/m2 (q21 x 6) and randomized for i.v. premedication with amifostine 740 mg/m2 or placebo. Assessment included a questionnaire, NCI-CTC, tendon reflex activity (TRA), two-point discrimination (2-PD), measurement of vibration perception threshold (VPT) and vibration disappearance threshold (VDT), and quality of life. RESULTS: The majority of neurotoxicity criteria showed a significant impairment during therapy in both treatment arms. A significant protective effect of amifostine was observed for 2-PD, TRA, VPT and VDT. Amifostine failed to improve the 'global health status quality of life' score significantly. Toxicities according to NCI-CTC showed improved sensory neuropathy (P = 0.0046) but a worsening in terms of nausea (P = 0.0005) and vomiting (P = 0.0083). No significant differences were observed for single sensory and motor symptoms, except for a better skilfulness in the amifostine group (P = 0.0404). CONCLUSION: Amifostine improved sensory neuropathy according to NCI-CTC and with regard to objective neurological assessment, but there were almost no differences in self-estimated specific sensory or motor symptoms. Disadvantages with regard to non-neurological toxicities and inconsistent results for quality of life demand further evaluation of neuroprotection with amifostine as well as alternative approaches to prevent platinum-taxane induced neurotoxicity.

Primary chemotherapy with gemcitabine as prolonged infusion, non-pegylated liposomal doxorubicin and docetaxel in patients with early breast cancer: final results of a phase II trial.

BACKGROUND: Combinations of anthracyclines, taxanes and gemcitabine have shown high activity in breast cancer. This trial was designed to evaluate a modified combination regimen as primary chemotherapy. Non-pegylated liposomal doxorubicin (NPLD) was used instead of conventional doxorubicin to improve cardiac safety. Gemcitabine was given 72 h after NPLD and docetaxel as a prolonged infusion over 4 h in order to optimize synergistic effects and accumulation of active metabolites. PATIENTS AND METHODS: Forty-four patients with histologically confirmed stage II or III breast cancer were treated with NPLD (60 mg/m(2)) and docetaxel (75 mg/m(2)) on day 1 and gemcitabine as 4-h infusion (350 mg/m(2)) on day 4. Treatment was repeated every 3 weeks for a maximum of six cycles. All patients received prophylactically recombinant granulocyte colony-stimulating factor. Patients with axillary lymph node involvement after primary chemotherapy received adjuvant treatment with cyclophosphamide, methotrexate and fluorouracil. RESULTS: The clinical response rate was 80%, and complete remissions of the primary tumor occurred in 10 patients (25%). Breast conservation surgery was performed in 19 out of 20 patients (95%) with an initial tumor size of less than 3 cm and in 14 patients (70%) with a tumor size

[Iatrogenic androgenization]. / Iatrogene Androgenisierung.

Virilization in postmenopausal women is suspicious for androgen-secreting adrenal or ovarian tumors; however, iatrogenic androgenization needs to be additionally considered. Here we report on a 64-year-old patient who presented clinically with progressive signs of virilization. An adrenal source of androgen excess was excluded, and the patient strictly denied the use of any androgenic medication. Thus, elevated serum levels of testosterone were suspicious of ovarian hyperandrogenism. Shortly before planned surgical exploration, the clinical finding of an extensive vulvar lichen sclerosus pointed towards a possible long-term use of testosterone-containing cremes for symptomatic relief of this disease. Apparently, the patient did not consider the mere topical application of potent agents to be a medication. This case demonstrates that besides adrenal or ovarian sources of hyperandrogenism, iatrogenic androgenization has to be considered.

Breast MRI for monitoring response of primary breast cancer to neo-adjuvant chemotherapy.

The objective of the present study was to monitor response to preoperative chemotherapy with breast MRI in patients with large breast cancer. Fifty-eight women in whom core biopsy had confirmed the presence of breast carcinoma underwent breast MRI prior to beginning chemotherapy and before surgical excision. In 24 cases patients underwent one or two additional examinations during chemotherapy to monitor their progress. Breast MRI included both T2-weighted spin-echo sequences and T1-weighted gradient-echo sequences before and 1, 2, 3, and 8 min after bolus injection of gadolinium-DTPA. Tumor size and the dynamic contrast medium uptake patterns of the respective carcinomas were evaluated and compared with the final histology findings. Based on their MR tomographic findings (change in tumor size and intensity of contrast media uptake), patients were assigned to groups with non-response (NR), partial response (PR), and complete response (CR). Based on MR tomographic findings, there were 12 patients in the NR group, 34 in the PR group, and 12 in the CR group. In NR group contrast medium uptake tended to increase or show no more than minimal decrease. Diagnostic accuracy for assigning patients to the NR group was 83.3% and to the PR group 82.4%. In patients whose tumors showed only slight response to chemotherapy, breast MRI proved very reliable in determining the size of the lesions. In patients whose tumors displayed significant response and in the CR group, the size of the residual tumor was underestimated in 8 of 12 cases. In 66.7% of patients in the CR group histology revealed residual tumor masses in areas up to 5 cm in diameter. During chemotherapy, intensity of contrast medium uptake decreased in 88.2% of patients with PR and in all patients with CR. Reliable determination of response was possible within 6 weeks following the initiation of chemotherapy. Breast MRI is suitable as a monitoring method. The determination of residual tumor size is unreliable in carcinomas exhibiting significant response to chemotherapy which may lead to false-negative results. The method may be employed for monitoring response to chemotherapy after 6 weeks.

[Interventional treatment of hemorrhages in advanced cervical carcinoma]. / Interventionelle Behandlungsmöglichkeiten von Blutungen bei fortgeschrittenen Karzinomen der Cervix uteri.

PURPOSE: Retrospective evaluation of percutaneous interventional treatment of locally advanced cervical carcinoma. MATERIALS AND METHODS: Since 1991, 13 patients with advanced tumor disease have been referred to our department for diagnosis and therapy of an acute blood loss. In all patients (age 40-88 years, mean 61 years) hemorrhage was detected by decrease in red blood cell count. In all cases patients suffered from locally advanced or recurrent disease after surgery and/or additional radio- or chemotherapy. Embolization was performed by transfemoral access using minicoils in most cases, liquid agents less often and a covered vascular stent in one patient. RESULTS: The site of the hemorrhage or the blood pooling of the tumor could be seen in all cases angiographically. Twenty-seven treatment cycles (2.1 per patient) were performed at intervals of 3 days to 6 months. The maximum time of follow-up and additional treatments if necessary was 1 year. In 9 of 13 patients (69%) the bleeding could be stopped immediately with a single treatment or initial treatment via both iliac arteries. One patient (7,7%) died during therapy because of an uncontrollable bleeding and consecutive decrease in red blood cells count. The remaining three patients (23%) showed slight persistent or recurrent bleeding, which could be managed interventionally until the following episode. There were two complications (15%) during therapy, representing a coil misplacement and a coil wash-out, which both could be managed interventionally. CONCLUSION: Hemorrhage following locally advanced or recurrent cervical carcinoma can be stopped interventionally in about 70% of cases. Even in partial success it is possible to manage the acute life-threatening situation. Follow-up examinations of up to 1 year justify this therapeutic concept.

Multiplex PCR screening detects small p53 deletions and insertions in human ovarian cancer cell lines.

Mutations at the p53 tumor suppressor gene locus are a frequent genetic alteration associated with human ovarian carcinoma. Little information exists regarding whether mutational events occur other than point mutations and large deletions, causing loss of heterozygosity. Small intragenic deletions and insertions in the p53 gene have been observed in various human neoplasias. We developed a multiplex polymerase chain reaction (MPCR) screening assay to amplify the complete p53 coding region from genomic DNA in a single step. Deletions and/or insertions were found in six out of 11 newly established ovarian carcinoma cell lines. MPCR detected deletions as small as 2 bp, as confirmed by nucleotide sequence analysis. Most of the observed alterations (6/7) were homozygous or hemizygous. Structural aberrations of the p53 gene possibly leading to loss of p53 cell cycle control may be a consequence of a slipped-mispairing mechanism in rapid DNA replication during repetitious ovulation and wound repair of ovarian epithelial cells. MPCR may be a valuable tool for screening for possible p53 deletion and insertion mutations not only in ovarian cancer but also in other malignancies.

Detection of integrated papillomavirus sequences by ligation-mediated PCR (DIPS-PCR) and molecular characterization in cervical cancer cells.

Human papillomavirus (HPV) genomes usually persist as episomal molecules in HPV associated preneoplastic lesions whereas they are frequently integrated into the host cell genome in HPV-related cancers cells. This suggests that malignant conversion of HPV-infected epithelia is linked to recombination of cellular and viral sequences. Due to technical limitations, precise sequence information on viral-cellular junctions were obtained only for few cell lines and primary lesions. In order to facilitate the molecular analysis of genomic HPV integration, we established a ligation-mediated PCR assay for the detection of integrated papillomavirus sequences (DIPS-PCR). DIPS-PCR was initially used to amplify genomic viral-cellular junctions from HPV-associated cervical cancer cell lines (C4-I, C4-II, SW756, and HeLa) and HPV-immortalized keratinocyte lines (HPKIA, HPKII). In addition to junctions already reported in public data bases, various new fusion fragments were identified. Subsequently, 22 different viral-cellular junctions were amplified from 17 cervical carcinomas and 1 vulval intraepithelial neoplasia (VIN III). Sequence analysis of each junction revealed that the viral E1 open reading frame (ORF) was fused to cellular sequences in 20 of 22 (91%) cases. Chromosomal integration loci mapped to chromosomes 1 (2n), 2 (3n), 7 (2n), 8 (3n), 10 (1n), 14 (5n), 16 (1n), 17 (2n), and mitochondrial DNA (1n), suggesting random distribution of chromosomal integration sites. Precise sequence information obtained by DIPS-PCR was further used to monitor the monoclonal origin of 4 cervical cancers, 1 case of recurrent premalignant lesions and 1 lymph node metastasis. Therefore, DIPS-PCR might allow efficient therapy control and prediction of relapse in patients with HPV-associated anogenital cancers.