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Biomedical subjects

A Hasenburg

Publications and source records attributed to A Hasenburg.

At least 19 recordsLinked to original sources

[Diagnosis and treatment of malignant ovarian tumors 2005: recommendations of the Kommission Ovar of the AGO].

Recommendations for diagnosis and treatment of malignant ovarian tumors with regard to the most recent data were worked out in a consensus process and valued by level of evidence (LoE) and grade of recommendation (GoR) of the Canadian Task Force for Preventive Health Care by the members of the Kommission Ovar der Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) in June 2005. A short version of these guidelines is presented.

Aged↗

Specific induction of pp125 focal adhesion kinase in human breast cancer.

The pp125 focal adhesion kinase (FAK) is involved in integrin-mediated cell signalling and overexpressed in a variety of solid tumours. Focal adhesion kinase expression has been correlated to invasion and metastasis, but the data on breast cancer are inconclusive. We analysed FAK mRNA, protein levels and expression patterns in primary breast cancer and normal breast tissue. FAK expression on the functional protein level and mRNA was determined in 55 matched pairs of breast cancer and corresponding normal tissue by Western blot, immunohistochemistry and RT-PCR. Using a score ranging from 0 to +5 for Western blots, we determined in normal breast tissue a score of 1.51+/-0.84 (mean+/-standard deviation), which was strongly induced to 2.91 (+/-1.22) in breast cancers (P<0.001). Overall, 45 out of 55 tissue pairs (81.8%) showed this upregulation of FAK protein in tumours in comparison to normal tissue. Immunohistochemistry confirmed these findings with a significant higher score for tumours vs physiological tissue (1.0+/-0.63 vs 2.27+/-0.91; P=0.001). Interestingly, no overall significant difference in the mRNA levels (P=0.359) was observed. In conclusion, expression levels of the FAK protein are specifically upregulated in breast cancer in comparison to matched normal breast tissue supporting its pivotal role in neoplastic signal transduction and representing a potential marker for malignant transformation.

Biomarkers, Tumor↗

Three-dimensional ultrasound for the assessment of breast lesions.

OBJECTIVE: To evaluate the diagnostic accuracy of three-dimensional (3D) ultrasound in comparison with conventional two-dimensional (2D) ultrasound in the characterization of breast lesions. METHODS: The digitally stored 2D ultrasound images and the corresponding 3D scans of 100 breast lesions (57 malignant, 43 benign) that had been morphologically classified as solid tumors, were independently analyzed by six investigators. Ten 2D and 13 3D ultrasound characteristics were determined. Lesion characterization was classified on a four-point scale and a logistic regression model was used to analyze the data. A receiver-operating characteristics curve (ROC) analysis was performed to determine the diagnostic performance of 2D and 3D ultrasound, respectively. RESULTS: Ultrasound criteria showed major differences between 2D and 3D ultrasound. Logistic regression revealed the retraction phenomenon in the coronal plane of the 3D ultrasound scan to be a significant and independent factor for lesion characterization. The characteristics determined on the conventional planes of 3D ultrasound differed from those determined on the 2D ultrasound images. The diagnostic accuracy of 2D and 3D ultrasound in the ROC analysis was almost identical (area under the curve 0.846 and 0.851, respectively). CONCLUSIONS: Ultrasound features on 3D ultrasound differ significantly from those on 2D ultrasound. However, the diagnostic accuracy of both methods is almost identical. 3D ultrasound as an adjunct to conventional 2D ultrasound should be evaluated in larger trials to determine its clinical value in breast imaging.

Breast Neoplasms↗

Evaluation of patients after extraperitoneal lymph node dissection for cervical cancer.

OBJECTIVE: The presence of nodal metastases is an important prognostic factor in patients with cervical cancer. To adjust our therapy to the anatomic extent of the disease, we performed a surgical staging with extraperitoneal lymph node dissection (EPLND). The goal of our study was to evaluate the clinical outcome and side effects of the combined treatment approach of EPLND and either radical hysterectomy in case of early stage cervical cancer (FIGO Ia/b and IIa) and negative nodes, or pelvic radiotherapy/extended field radiotherapy with concomitant chemotherapy in case of positive nodes or advanced stage cervical cancer (FIGO IIb, III, and IVa). PATIENTS AND METHODS: Fifty-nine patients with primarily diagnosed invasive cervical cancer underwent EPLND. The value of this procedure as a diagnostic tool for evaluating the extent of disease was determined. Additionally, treatment-related complications and clinical outcomes were monitored. RESULTS: A total of 983 lymph nodes were removed during EPLND (mean 16.7). According to the results of EPLND, radical hysterectomy was abandoned due to histopathologically confirmed lymph node involvement by frozen section in 11 out of 36 patients with early stage cervical cancer (31%). The most common adverse effects directly related to surgery in general (EPLND or combined EPLND and radical hysterectomy) were lymph cysts in seven patients (12%). Only in the group of patients who received EPLND followed by radical hysterectomy, 2 out of 25 patients (8%) developed a severe ileus postoperatively (WHO Grade 3 toxicity). The treatment approach of combined EPLND followed by radio- and chemotherapy was without major complications (WHO Grade 3 or 4 toxicity). After a mean follow up of 28 months (range 6-60), 44 out of 58 patients (one patient lost to follow up) are without evidence of disease (76%), 2 patients have progressive disease (3%), and 12 patients died of their disease (21%). Using Kaplan-Meier analysis, the estimated 5-year overall survival rate for all patients is 64% (SD +/- 9%). Performing the Cox proportional regression analysis, in contrast to clinical FIGO staging (P = 0.24; ns), lymph node involvement was the only significant independent predictor for overall survival (P = 0.04). CONCLUSION: Our data support the approach of pretherapeutic surgical staging by performing EPLND as a diagnostic tool with a low complication rate. This allows an individualized treatment for cervical cancer patients.

Adult↗

Aggressive management of recurrent ovarian cancer--the challenge of individualizing cancer therapy illustrated by a case report.

BACKGROUND: In clinical practice, treatment recommendations and the patient's wishes often diverge, facing the physician with difficult choices. CASE REPORT: The clinical course of a 36-year-old patient with 'platinum-refractory' ovarian cancer is reported. The patient experienced a symptomatic relapse 7 months after debulking surgery and completion of platinum-based first-line chemotherapy. As she had given birth to a son 22 months before diagnosis, she fought with outmost determination against her disease. Her husband supported her, and both asked for maximal therapy, including intensive care treatment for recurrent respiratory tract infections and total parenteral nutrition (TPN). For the patient, it was of major importance to stay with her family and make sure that her son would be able to remember his mother. Problems related to TPN and progression of disease affected her individual perception of quality of life to a much lower extent than expected and perceived by her caretakers. All professional health care providers were more than once very reluctant to continue treatment and only after extensive counseling gave in to the demand of the patient for further treatment, considering the effort futile - only to be surprised by treatment response and recovery. After 3 years of palliation, the tumor was resistant to all cytotoxic regimens and the patient died 2 months after withdrawal of chemotherapy. CONCLUSION: This case report illustrates that also in the age of evidence-based medicine individualized treatment beyond proven strategies can offer patient benefit. Taking the child's development into account makes it impossible to determine the cost-benefit ratio.

Adult↗

European experience with a novel noninvasive sensor for intra-amniotic or extra-amniotic evaluation of fetal oxygen saturation.

OBJECTIVE: We evaluated the feasibility of a new instrument for continuous fetal pulse oximetry during labor. The measuring sensor can be placed on the fetal back before or after rupture of membranes. METHODS: One hundred adult women who had completed 32 weeks of gestation and had an anticipated duration of labor greater than 30 minutes were included in the study. Patients with premature rupture of membranes for 24 hours or more, low placental localization, placenta previa or abruption, vaginal bleeding, acute infection, polyhydramnios, oligohydramnios, or uterine or congenital abnormalities were excluded. RESULTS: All sensors were placed successfully. The mean continuous recording time was 276 minutes. Peripheral oxygen saturation as measured by pulse oximeter values were obtained during a median of 64.05% of the recording time. No chorioamnionitis or endometritis was noted. CONCLUSION: The new sensor instrumentation was safe for mother and fetus and was well accepted by parents and physicians.

Adolescent↗

Adenovirus-mediated thymidine kinase gene therapy in combination with topotecan for patients with recurrent ovarian cancer: 2.5-year follow-up.

OBJECTIVE: Patients with recurrent ovarian cancer were treated intraperitoneally (ip) with a replication-deficient recombinant adenovirus (ADV) containing the herpes simplex virus thymidine kinase gene. Vector delivery was followed by intravenous administration of an antiherpetic prodrug and a topoisomerase I inhibitor. METHODS: Ten patients with stage IIIc epithelial ovarian cancer underwent secondary debulking to < or =0.5 cm residual tumor. Patients with normal ip flow received delivery of ip ADV. Two patients each were treated on dose level 1 (2 x 10(10) vector particles), dose level 2 (2 x 10(11)), and dose level 3 (2 x 10(12)); four patients were on dose level 4 (2 x 10(13)). Acyclovir and topotecan were started 24 h after vector delivery. Five patients underwent second-look surgery about 4 weeks after application of gene therapy (GT). RESULTS: At the time of the second-look surgery, two out of five patients were free of tumor. Four weeks after GT none of the peritoneal biopsies showed residual vector DNA. Patients pretreated with an average of three different chemotherapeutic drugs and two different chemotherapy regimens had a median overall survival (OS) of 18.5 months. Three patients are still alive 30, 30, and 31 months after GT. CONCLUSION: With the combination of secondary optimal debulking, GT, and topotecan, median OS was about one-third longer than in previously reported second-and third-line trials. Survival was comparable to that of patients of other studies with secondary cytoreductive surgery in combination with chemotherapy.

Acyclovir↗

Psychiatric disorders and associated factors in cancer: results of an interview study with patients in inpatient, rehabilitation and outpatient treatment.

An association between mental disorders, especially affective and anxiety disorders, and cancer has been reported in many studies. The present study investigated current (4-weeks-, 12-months-, and lifetime-prevalence rates of comorbid mental disorders in cancer patients. Through a cross-sectional design, 517 patients (75% female patients) from two acute inpatient care clinics, two rehabilitation clinics and nine specialised practices for oncology were examined with standardised scales for psychological burden and quality of life. Somatic parameters were assessed through standardised medical records. In the second-stage-examination, a sample of 200 patients was interviewed with standardised clinical interview (CIDI) in order to obtain DSM-IV diagnoses of mental disorders. Differences in the type of mental disorders were examined for gender, treatment setting, severity of cancer and physical impairment. Prevalence rates of mental disorders were 23.5% for the 4-weeks, 40% for the 12-months, and 56.5% for the lifetime periods. The current and 12-months rates of affective and anxiety disorders were approximately 25-33% higher than prevalence rates found in recent epidemiological studies of the general population. These higher rates were, however, mainly due to the preponderance of female patients with a higher risk for mental disorders compared with males. The most prevalent current disorders were affective (9.5%), and anxiety disorders (13%). Female gender was associated with an approximately 2-fold risk of mental disorders during the patient's lifespan. Current diagnosis of affective disorders in women was highly related to the cancer. Physical impairment was also associated with the frequency of current psychiatric disorders, especially affective and anxiety disorders. The frequency of mental disorders in cancer patients does not differ from results of recent international epidemiological studies of the normal population. The slightly higher rates of anxiety disorders are mainly due to phobias (simple, social and agoraphobia) without urgent need for treatment. A relatively large portion of patients, however, fulfil the criteria of minor depressive disorder which deserves clinical attention.

Adolescent↗

Coxsackievirus-adenovirus receptor expression in ovarian cancer cell lines is associated with increased adenovirus transduction efficiency and transgene expression.

The expression of coxsackievirus-adenovirus receptor (CAR) and the integrins alpha(v)beta3 and alpha(v)beta5 was analyzed quantitatively (flow cytometry) and qualitatively (immunocytochemistry) in five human ovarian cancer cell lines (PEO1, PEO4, PEO14, SKOV-3, and OVCAR-3) and three control cell lines (293, HeLa, and CHO-K1). The transduction efficiencies were evaluated by adv/rsv-beta-Gal transduction followed by X-gal staining. The effects of 17beta-estradiol on cell growth, CAR and integrins alpha(v)beta3/5 expression, adenovirus transduction efficiency, and cell-killing efficacy of adv/rsv-tk plus ganciclovir were determined. The levels of CAR, integrin alpha(v)beta3, and integrin alpha(v)beta5 showed great variation between the cell lines. Whereas the expression of CAR appeared to be essential for and positively correlated with adenovirus transduction efficiency, the integrins alpha(v)beta3 and alpha(v)beta5 were not absolutely necessary for adenovirus transduction even though their presence may facilitate transduction. In PEO4 and PEO1 cells, proliferation was stimulated by 17beta-estradiol in a dose-dependent manner. In PEO4 cells, and much less pronounced in PEO1 cells, this was accompanied by an increase in CAR expression. The stimulation of CAR expression was paralleled by an increased transduction efficiency resulting in an increased cell-killing efficacy. Our data suggest that the expression of CAR is one of the most important prerequisites for successful adenovirus-mediated gene therapy of ovarian cancer.

Adenoviridae↗

Thymidine kinase gene therapy with concomitant topotecan chemotherapy for recurrent ovarian cancer.

INTRODUCTION: Patients with recurrent ovarian cancer were treated with a replication-deficient recombinant adenovirus containing the herpes simplex virus thymidine kinase gene administered intraperitoneally (i.p.) followed by administration of an anti-herpetic prodrug and topotecan. MATERIALS AND METHODS: A total of 10 patients with stage IIIc epithelial ovarian cancer underwent secondary debulking to < or =0.5 cm residual tumor. Patients with normal i.p. flow received i.p. delivery of adenovirus. Two patients each were treated on dose level 1 (2 x 10(10) vector particles (VP)), dose level 2 (2 x 10(11) VP), and dose level 3 (2 x 10(12) VP); four patients were treated on dose level 4 (2 x 10(13) VP). Acyclovir and topotecan were started 24 hours after vector delivery. RESULTS: No patient treated at any dose level incurred unanticipated toxic effects, and all side effects resolved. The most common adverse event was myelosuppression: grade 3 or 4 thrombocytopenia with grade 2-4 anemia in three patients and grade 3 or 4 neutropenia in eight patients. Three patients developed thrombocytosis and three patients had a mild elevation of serum glutamic pyruvic transaminase/alanine aminotransferase. Temperature elevations that were not associated with detectable infection occurred in two patients. DISCUSSION: I.p. delivery of adenoviral vector with concomitant topotecan chemotherapy was well tolerated without significant lasting toxicities. Side effects were independent of the dose of adenoviral vector.

Acyclovir↗

[Comorbid psychiatric disorders in cancer patients in acute inpatient treatment and medical rehabilitation].

An association between mental disorders, especially affective and anxiety disorders, and cancer has been reported in many clinical studies with inpatients. However, no data exist about the prevalence of mental disorders in patients undergoing acute care or rehabilitation treatment for cancer in Germany. The present study investigated 4-week, 6-month and lifetime prevalence rates of comorbid mental disorders in cancer. 256 patients from 2 rehabilitation clinics and 2 acute care hospitals were examined with standardized screening scales for psychological burden (GHQ-12, HADS) and quality of life (SF-36). Somatic parameters and interventions were assessed through standardized medical records from the attending oncologists. In the second-stage examination a subsample of 120 patients were interviewed with standardized clinical interview (CIDI) in order to obtain DSM-IV diagnoses of mental disorders. 44% (acute care) and 49% (rehabilitation) of the patients have high GHQ scores (cut-off > 4). Furthermore, more than 20% of the cancer patients have elevated scores on the HADS subscales depression and anxiety (cut-off > or = 11). Prevalence rates of mental disorders in the rehabilitation sample are 34% for the 4-week (vs. 24% in the acute care sample), 45% for the 6-month period (vs. 38%), and 79% for lifetime (vs. 49% in the acute care sample). The most frequent current disorders are affective (13% rehabilitation vs. 11% acute care) and anxiety disorders (17% in both samples). The rates of affective and anxiety disorders are much higher than the frequency of these disorders in recent epidemiological studies of the normal population in Germany. The high psychosocial burden expressed by the patients and the frequency of depressive and anxiety disorders emphasize the importance of (1) effective diagnostic strategies to recognize mental disorders, and (2) specialized psychosocial services in oncology, which provide psychological support and effective interventions for cancer patients in acute care and rehabilitation.

Adult↗

Comparison of long-term survival of cytomegalovirus promotre versus Rous Sarcoma virus promoter-driven thymidine kinase gene therapy in nude mice bearing human ovarian cancer.

The cytomegalovirus (CMV) promoter is considered one of the strongest positive regulators leading to expression of higher levels of the thymidine kinase (TK) enzyme than the Rous Sarcoma virus (RSV) promoter in vitro and in vivo. Cell killing efficacy of adenovirus-mediated CMV promoter-driven herpes simplex virus (HSV) TK gene therapy has been found to be 2 to 10 times more effective than RSV driven HSV-TK gene therapy in vitro. In this study the impact of CMV- versus RSV-driven HSV-TK gene therapy on long-term survival of nude mice bearing human ovarian cancer has been evaluated using a prospective randomized experimental design. The experiment was designed to show significance of survival differences from a 50% increase of survived days at a p-value of 0.05 with a power of 80%. All treatment groups showed an increase in median survival compared with control groups. Treatment benefit was ADV/CMV-TK vector dose dependent. At a given viral dose, no significant prolongation of survival was observed comparing CMV- and RSV-driven ADV-TK indicating that simply increasing cell killing efficacy in vitro above a minimal threshold level using a stronger promoter may not lead to prolongation of survival in the HSV-TK/GCV system.

Adenoviridae↗

[Use of alternative medicine in oncology patients].

BACKGROUND AND OBJECTIVE: Up to 60% of all oncological patients use methods of alternative medicine in the course of their illness. In earlier blinded studies demographic characteristics and the patients' motives of using alternative medicine had been recorded, but a correlation with individual illnesses had not been possible. PATIENTS AND METHODS: 142 patients of a oncological outpatient clinic gave their experience with alternative medicine in interviews and non-blinded questionnaires, 103 of them (72.5%; 46 men and 57 women; median age 58 years, range 18-91 years) returning questionnaires that could be evaluated. RESULTS: 46 patients stated that they had used alternative medicine. There was no difference between users and non-users regarding sex; age, profession, education, family status or religion. 58% of all patients with advanced disease used alternative medicine, compared with only 31% with partial remission or stable disease and 41% in complete remission (P = 0.042). Vitamins and mistletoe preparations were the most commonly used substances (50 and 45%, respectively). The predominant purpose was to stimulate the immune system (77%) and strengthen general physical capacity (64.5%). As main stimulus for using alternative medicine the patients came from their family doctor (56%), followed by family and friends (41%). Alternative medicine was used largely as complementary and not an alternative to conventional medicine. Health insurance met all or some of the costs of alternative treatment in 59% of patients. CONCLUSION: A large number of patients treated with conventional oncological regimens also use alternative medicine, most of them because of a polypragmatic attitude to tumor treatment. Family doctors and health insurance companies are playing a more important role than had hitherto been assumed in spreading the use of treatment options without providing scientifically based evidence of their efficacy.

Adult↗

Phase II study of i.v. CI-980 in patients with advanced platinum refractory epithelial ovarian carcinoma.

CI-980 is a synthetic mitotic inhibitor that binds to tubulin at the colchicine site, inhibiting the polymerization of microtubules and arresting cellular division in metaphase. Myelosuppression and neurotoxicity were dose-limiting in phase I studies. Sixteen patients with stage III and IV platinum-refractory ovarian cancer received 4.5 mg/m2/day of CI-980 as a continuous i.v. infusion for 72 h, repeated every 3 weeks. Eleven patients had progression and four patients had stable disease. One patient (6%; 95% CI 0-25%) achieved a partial response after 9 months of treatment which lasted for 27 months. The overall median survival was 7 months. Grade 4 granulocytopenia occurred in five patients, with two episodes of neutropenic fever. Neurological toxicity was mild with 12 episodes of transient subclinical recent memory loss documented in four patients by specialized neuropsychological evaluations. One patient each had hallucinations and mild truncal ataxia, and four patients had mild, reversible neurosensory toxicity. One episode of severe hypoxemia and dyspnea occurred in a patient with chronic obstructive pulmonary disease. CI-980 has minimal activity and is tolerable in a population of heavily pretreated patients with platinum refractory ovarian cancer.

Adult↗

External four channel tocography in preterm labor. First results.

In order to known more about preterm labor the objective of our investigation was to look for a correlation between the spatial and temporal pattern of uterine contractions and the duration of pregnancy. 50 patients with preterm labor between 21 and 35 weeks of gestation underwent repeated measurements using four-channel tocography in which the pressure of contractions was registered simultaneously on the left and right sides at the fundus and the lower segment of the uterus. Half of all recorded signals were locally restricted (typical labor pattern in only one or two registration tracks). The following two phenomena were significantly associated with a shorter duration of pregnancy: 1. the reproducibility of a center of dominance (defined as the locus of registration with the highest sum of amplitudes), and 2. a predominant origin of labor in the right fundal region of the uterus. Four-channel tocography indicates whether preterm labor is likely to lead to preterm delivery. It may therefore help the obstetrician in deciding whether to use tocolytic therapy.

Adolescent↗

[Methemoglobinemia in the newborn infant--caused by prilocaine?-- A case report].

The occurrence of postpartum cyanosis is primarily linked to pulmonary or cardiac causes. However, under differential diagnoses, methaemoglobinaemia should also be taken into consideration the causes of which may have toxical or hereditary origins. Diagnosis can be made by photospectrometical analysis of the methaemoglobin level in blood. Pathogenetical evidence is obtained by way of reduction method with methylen blue. This method will lead to consistently reliable results only, if the methaemoglobinaemia is of toxic nature. An example of toxically induced neonatal methaemoglobinaemia, which with great probability was caused by pudendus anaesthesia with Prilocain, is discussed in this case report.

Adult↗

External four-channel tocography during delivery.

OBJECTIVE: A four-channel tocographic technique was developed in order to improve present knowledge of spatial uterine motility. METHOD: Fifty-four women were monitored during labor. Four pressure transducers were attached in a square around the umbilicus. RESULTS: The origin of uterine contractions was generally determined to be in the upper right segment of the uterus. The rate of operative deliveries was decreased in the case of predominant upper right origin of labor. Most of the contractions with clear propagation patterns originated on the upper right side, continued to the left and then spread to the lower right part of the uterus. The highest relative intensity was also measured on the upper right side. CONCLUSION: Predominant upper right origin of labor may be important for unassisted or spontaneous delivery.

Adult↗