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Biomedical subjects

U Haller

Publications and source records attributed to U Haller.

At least 37 records · Page 2Linked to original sources
PubMed2002

Photodynamic therapy of DNA mismatch repair-deficient and -proficient tumour cells.

Loss of DNA mismatch repair is a common finding in hereditary nonpolyposis colon cancer as well as in many types of sporadic human tumours. DNA mismatch repair-deficient cells have been reported to be resistant to many chemotherapeutic agents and to radiotherapy, and to have the potential of rapidly acquiring additional mutations leading to tumour progression. Photodynamic therapy is a new treatment modality using light to activate a photosensitiser that preferentially localises in tumour cells. An oxygen dependent photochemical reaction ensues, resulting in selective tumour necrosis. The effect of loss of DNA mismatch repair activity on the sensitivity to photodynamic therapy was tested using pairs of cell lines proficient or deficient in mismatch repair due to loss of either MLH1 or MSH2 protein function. Cells were incubated with the photosensitiser 5,10,15,20-meta-tetra(hydroxyphenyl)chlorin and exposed to laser light at 652 nm with various optical doses ranging from 0-1 J cm(-2). Cell survival was assessed using the clonogenic assay. Loss of MLH1 or MSH2 function was not associated with resistance to photodynamic therapy. MCF-7 cells repeatedly treated with photodynamic therapy expressed parental levels of MLH1, MSH2, MSH6, and PMS2. DNA mismatch repair-deficient and -proficient cells showed similar subcellular distributions of meta-tetra(hydroxyphenyl)chlorin as analysed by laser scanning and fluorescence microscopy. Therefore, repeated exposure of tumour cells to photodynamic therapy does not seem to result in loss of DNA mismatch repair, and loss of mismatch repair, in turn, does not seem to contribute to resistance to photodynamic therapy. Our results suggest recommending photodynamic therapy as a strategy for circumventing resistance due to loss of DNA mismatch repair.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Impact of the reduction of anaesthesia turnover time on operating room efficiency.

BACKGROUND AND OBJECTIVE: We investigated whether an increase in anaesthesia staffing to permit induction of anaesthesia before the previous case had ended ('overlapping') would increase overall efficiency in the operating room. Hitherto, the average duration of operating sessions was too long, thus impeding the timely commencement of physicians' ward duties. METHODS: The investigation was designed as a prospective, non-randomized, interrupted time-series analysis divided into three phases: (a) a baseline of 3.5 months, (b) a 2.5 month intervention phase, in which anaesthesia staffing was increased by one attending physician and one nurse, and (c) a further 2 months under baseline conditions. Data focussed on process management were collected from operating room staff, anaesthesia personnel and surgeons using a structured questionnaire collected daily during the entire study. RESULTS: Turnover time between consecutive operations decreased from 65 to 52 min per operation (95% CI: 9; 17; P = 0.0001). Operating room occupancy increased from 4:28 to 5:27 h day-1 (95% CI: 50; 68; P = 0.005). The surgeons began their work on the ward 35 min (95% CI: 30; 40) later than before the intervention and their overtime increased from 22:36 to 139:50 h. CONCLUSIONS: The time between surgical operations decreased significantly. Increased operating room efficiency owing to overlapping induction of anaesthesia allows more intense scheduling of operations. Thus, physicians and nurses can be released to spend more time with their patients in the ward. Improving the efficiency of the operating room alone is insufficient to improve human resource management at all levels of a surgical clinic.

Anesthesiology↗
PubMed2002

[Cesarean section on demand or elective. Cesarean section: request for rethinking].

Nowadays, the mortality and morbidity of caesarean section, particularly elective caesarean section, are hardly different from those of vaginal delivery. 'Section on request' is so extremely rare that it is of no importance and that these terms should not be used at all. A change in thinking is necessary because only real misgivings make the pregnant woman wish for this procedure. In this context, the increasing importance of autonomy and the right to self-determination of the woman lead to a fundamental shift in the relationship between doctor and patient. Long-term sequelae after vaginal delivery, e.g. injury to the pelvic floor with functional impairment and disturbances of sexual function, but also considerations about the safety of the child become more and more important for the pregnant woman and have to be taken seriously by the physician. Although there are no precise bases for assessment, a global comparison of costs between vaginal delivery and elective caesarean section with regard to the long-term sequelae will hardly show any true differences, and therefore the health insurances are not entitled to refuse the reimbursement of costs.

Cesarean Section↗
PubMed2002

[Urinary and anal incontinence: a taboo subject].

The prevalence of urinary incontinence is estimated at about 6 % in the overall population and may be as high as 40 % in women after menopause. For many women with stress incontinence, the new vaginal tape operations appear to offer cure rates comparable to those achieved with conventional procedures, but with less invasiveness and a shorter hospital stay. Pelvic organ prolapse and stress incontinence are two separate conditions which frequently coincide. Correcting prolapse alone may not cure stress incontinence - and may even unmask latent incompetence of the urethral sphincter. Depending on which definition is used, the prevalence of anal incontinence is between 1 and 5 %. In women, injuries sustained at vaginal delivery appear to be the most important risk factor. The prevalence of combined urinary and anal incontinence may approach 5-10 %. All women we see as gynecologists and obstetricians should be asked about symptoms of incontinence, and women with symptoms should be evaluated specifically and offered appropriate measures to improve their quality of life.

Cross-Sectional Studies↗
PubMed2002

[Stereotaxic breast biopsy techniques have become the standard of care for mammographically suspicious lesions].

An optimal technique for the evaluation of nonpalpable, suspicious mammographic lesions should have a low technical failure rate, no false-negative results and should remove the lesion completely. Since most of these lesions are benign, the procedure should be carried out in an outpatient setting without general anesthesia. Cancer is missed in 2.6% of cases with excisional biopsy following needle localization. Furthermore, 50-83% of these patients undergo a second surgical intervention for definitive surgical treatment. In contrast, the rate of missed cancers is less than 0.7% following stereotaxic core or large-core biopsies. However, using these techniques, discordant results and histologic high-risk lesions need to be recognized and reexcized. The cost-effectiveness of stereotaxic vacuum-assisted core biopsy has been demonstrated. Stereotaxic breast biopsy techniques such as vacuum-assisted core biopsy and large-core biopsy for suspicious mammographic lesions have low false-negative rates and result in few histologic underestimations.

Biopsy↗
PubMed2002

[Breast diagnosis: new acquisitions and developments].

The development and refinement of breast diagnosis have increased the significance of breast ultrasound, have led to the establishment of mammographic classification criteria (BI-RADS) and to the standardisation of the terminology used for reporting the results and thus its codification. Targeted stereotactic biopsies (Mammotome and SiteSelect) have become established methods of pretreatment diagnosis.

Biopsy, Needle↗
PubMed2001

Resistance to topoisomerase poisons due to loss of DNA mismatch repair.

Sporadic breast carcinomas demonstrate microsatellite instability, reflecting the presence of DNA mismatch repair-deficient cells, in about one fourth of cases at the time of diagnosis. Loss of DNA mismatch repair has been reported to result in resistance not only to cisplatin and alkylating agents but also to the topoisomerase II poison doxorubicin, suggesting an association between DNA mismatch repair and topoisomerase II poison-induced cytotoxicity. Our study investigates the relationship between loss of MSH2 or MLH1 function and sensitivity to the topoisomerase I and II poisons, and to the taxanes, 2 classes of cytotoxic drugs commonly used in breast cancer. Two pairs of cell lines proficient and deficient in mismatch repair due to loss of either MSH2 or MLH1 function were used. Loss of either MSH2 or MLH1 function resulted in resistance to the topoisomerase II poisons doxorubicin, epirubicin and mitoxantrone, whereas only loss of MLH1 function was associated with low-level resistance to the topoisomerase I poisons camptothecin and topotecan. In contrast, there was no resistance to docetaxel and paclitaxel. Our data support the hypothesis that both MSH2 and MLH1 are involved in topoisomerase II poison-mediated cytotoxicity, whereas only MLH1 is involved in topoisomerase I poison-mediated cytotoxicity. Since our study shows that loss of DNA mismatch repair does not result in resistance to the taxanes, these drugs can be recommended for use in breast cancer deficient in mismatch repair.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Photodynamic diagnosis of breast tumours after oral application of aminolevulinic acid.

Photodynamic diagnosis is of increasing interest for diagnosis in oncology. It is based on a more intense incorporation of a fluorescent dye in tumours compared to normal tissue. As a feasibility study we investigated the effectiveness of oral application of 5-aminolevulinic acid for photodynamic diagnosis of human primary mammary tumours. The study included 16 patients with palpable breast tumours. Aminolevulinic acid was administered at a concentration of 40 mg kg(-1)bodyweight 150-420 min prior to tumourectomy. Intraoperatively blue light (405 nm) was applied to the operation site. Sections of the excised tumour and some lymph nodes were prepared and analysed with a fluorescent microscope. All primary mammary tumour tissues showed significantly higher fluorescence intensity than surrounding normal mammary tissue. Fluorescence of the mammary tumours could also be discriminated macroscopically and intraoperatively. Fluorescence intensity in nonmetastatic lymph node tissue was higher in 2 out of 3 patients than in primary tumour tissue. By photodynamic diagnosis using aminolevulinic acid we were able to reliably distinguish primary mammary tumours from normal mammary tissue microscopically and macroscopically in all our patients. We suggest that photodynamic diagnosis with aminolevulinic acid for breast tumours should be further investigated and developed for intraoperative use and may well be a simple tool for better intraoperative diagnosis and recognition of tumour margins. We hypothesize that lymph node metastasis of breast tumours will not be detectable by this method.

Administration, Oral↗
PubMed2001

Skin protection for photosensitized patients.

BACKGROUND AND OBJECTIVE: The goal of this study was to evaluate various creams for their capability to protect photosensitized skin from visible light. STUDY DESIGN/MATERIALS AND METHODS: Two cover creams and creams containing various combinations of Vaseline with TiO(2), ZnO, and Fe(2)O(3) were used to measure the reduced light transmission and the light absorption spectrum. In vitro and in vivo tests were performed to assess the protection from light by above mentioned compounds. RESULTS: The cover creams and the 50% TiO(2) cream showed similar efficacy in reducing light transmission, while the sunscreen was less efficient by a factor of 5. Cell protection by 25% TiO(2)+25% ZnO, TiO(2), or the cover creams was more efficient than protection by the sunscreen or other compounds. In vivo, the dark cover cream protected the skin by a factor of 3.4 better than the sunscreen. CONCLUSION: The dark cover cream has acceptable properties to protect photosensitized skin.

Absorption↗
PubMed2001

Photodynamic therapy of vulvar intraepithelial neoplasia III using topically applied 5-aminolevulinic acid.

OBJECTIVES: The aim of this study was twofold: first, to determine the feasibility of photodynamic therapy (PDT) of vulvar intraepithelial neoplasia III (VIN III) using topically applied 5-aminolevulinic acid (ALA) for photosensitization, and second, to compare PDT results with those of laser evaporation and local excision. METHODS: Fifteen patients with VIN III had 10 g of 10% ALA gel applied to the entire vulva. Two to three hours after drug application the vulva was irradiated with 120 J/cm(2) laser light at a wavelength of 635 nm. The procedure was performed without anesthesia in most patients. Thirty patients with VIN III treated by laser evaporation and 27 patients treated by surgical excision served as controls. RESULTS: Eight weeks following PDT, 11 of 15 patients were free of VIN III as determined by biopsy. Excellent tissue preservation was achieved and no ulcers or scarring occurred. Three recurrences were seen during follow-up, at 5, 6, and 7 months after PDT. Twelve months after treatment, analysis of disease-free survival revealed no statistically significant difference between patients treated with PDT and patients treated with conventional treatment modalities (P = 0.67) but the power of this analysis is low. In multivariate analysis, multifocal disease was the sole variable associated with a reduced disease-free survival. CONCLUSION: While PDT of VIN III seems to show efficacy similar to that of conventional treatment modalities it offers unique advantages: healing time is short, preservation of normal vulvar appearance is excellent, and PDT may be performed without anesthesia. Hence, PDT of VIN III deserves further investigation.

Administration, Topical↗
PubMed2001

[Ultrasound endometrium follow-up during tamoxifen treatment: Really not reliable or useful after all?].

AIM: To investigate whether an examination of the endometrium of women treated with tamoxifen (TAM) is useful or not. METHOD: 40 breast cancer patients who displayed a thickened endometrium of > 8 mm and/or vaginal bleeding were included in the study. They received daily TAM adjuvantly. Histologic clarification by hysteroscopy and D&C was recommended for patients with an endometrium of > 8 mm or vaginal bleeding. RESULTS: In our collective, the mean endometrial thickness was 13.7 +/- 5.6 mm (SD). 32 patients underwent a histological examination. Most had a benign lesion; in 2 cases we merely found a cystic atrophy (11 mm, 18 mm), 2 displayed atypical tissue (13 mm, 25 mm) and 2 an endometrial cancer (19 mm, 33 mm). All patients with atypical tissue or cancer had an endometrial thickness markedly above the norm, but 3 of them were not bleeding. No linear correlation between thickness of the endometrium and duration of TAM intake was found. CONCLUSION: To detect early premalignant or malignant changes of the endometrium, we recommend histological examination by hysteroscopy and dilatation and curettage when the endometrium is > 8 mm thick, even in the absence of symptoms. Therefore, these patients should have regular examinations by transvaginal ultrasound once or twice a year. Moreover, continuing regular screening of the endometrium for years after termination of tamoxifen-therapy is also to be recommended.

Adult↗
PubMed2001

[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↗
PubMed2000

Comparative genomic hybridization of fine needle aspirates from breast carcinomas.

Detailed knowledge of chromosomal aberrations in a specific tumor may facilitate the development of individually tailored chemotherapy, hormone or gene therapy. Unfortunately, karyotype analysis requires living cells and is complicated by the low number of good metaphase spreads obtained. Comparative genomic hybridization (CGH), however, is capable of detecting and mapping genome-wide amplifications and deletions using an equimolar mixture of normal and tumor cell DNA. We show here that even the few cells from a fine needle aspirate of a tumor are sufficient for a direct CGH assay, independent of DNA amplification. Ten primary breast cancers were analyzed by CGH. A fresh frozen fine needle aspirate and a formalin-fixed and paraffin-embedded section were used for each tumor. Metaphases from each CGH reaction were imaged, and a sum ratio profile was determined for every chromosome. The ratio profiles of DNA isolated from the 2 material sources were then compared. Fine needle aspirates and the paraffin-embedded material of a single tumor yielded the same fluorescence ratio profiles, albeit with slightly different confidence intervals. Different tumors showed a variety of aberrations. The most frequently observed changes were 1q+, 8q+, 14q-, 16p+, 16q-, 17p-, 17q+, 19q+, 20q+, 21q- and 22q-. The ability of CGH to assess chromosomal changes in breast cancer from fine needle aspirates could facilitate genetic evaluation of tumors prior to surgery.

Adult↗
PubMed2000

[Gynecology 1999].

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Abortifacient Agents, Steroidal↗
PubMed2000

Value of (18F)-FDG positron emission tomography, computed tomography, and magnetic resonance imaging in diagnosing primary and recurrent ovarian carcinoma.

The aim of this study was to compare prospectively the accuracy of whole-body positron emission tomography (PET), CT and MRI in diagnosing primary and recurrent ovarian cancer. Nineteen patients (age range 23-76 years) were recruited with suspicious ovarian lesions at presentation (n = 8) or follow-up for recurrence (n = 11). All patients were scheduled for laparotomy and histological confirmation. Whole-body PET with FDG, contrast-enhanced spiral CT of the abdomen, including the pelvis, and MRI of the entire abdomen were performed. Each imaging study was evaluated separately. Imaging findings were correlated with histopathological diagnosis. The sensitivity, specificity and accuracy for lesion characterization in patients with suspicious ovarian lesions (n = 7) were, respectively: 100, 67 and 86% for PET; 100, 67 and 86% for CT; and 100, 100 and 100% for MRI. For the diagnosis of recurrent disease (n = 10), PET had a sensitivity of 100%, specificity of 50% and accuracy of 90%. The PET technique was the only technique which correctly identified a single transverse colon metastasis. Results for CT were 40, 50 and 43%, and for MRI 86, 100 and 89%, respectively. No statistically significant difference was seen. Neither FDG PET nor CT nor MRI can replace surgery in the detection of microscopic peritoneal disease. No statistically significant difference was observed for the investigated imaging modalities with regard to lesion characterization or detection of recurrent disease; thus, the methods are permissible alternatives. The PET technique, however, has the drawback of less accurate spatial assignment of small lesions compared with CT and MRI.

Adult↗