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Biomedical subjects

U Haller

Publications and source records attributed to U Haller.

At least 73 records · Page 4Linked to original sources
PubMed1998

Enhanced photodynamic effects using fractionated laser light.

Photodynamic eradication of tumour cells depends on the presence of a photosensitizer and light delivery to the cells. The present study investigated the influence of fractionated light (on-off mode) on cell killing as documented by a colony-forming assay. Photosensitizers were m-THPC (ethanol soluble, Foscan) and m-THPC-MD (water soluble, both from Scotia Pharmaceuticals, Guildford, UK). Fractionated laser light at a wavelength of 652 nm with a light duration of 0.05 s was more effective than continuous illumination at the same power density for both photosensitizers. We propose that fractionated laser light is more toxic due to short phases of recovery during the dark intervals, probably resulting in more singlet oxygen under these conditions. By use of Foscan, for example, and fractionated laser light, a similar effect is expected for the treatment of solid tumours. In this case we expect improvements in photodynamic therapy (PDT) for patients by lowering the concentrations of photosensitizer and/or by reducing the applied light dose.

Antineoplastic Agents↗
PubMed1998

["Evidence-based medicine"--guidelines as a threat or necessity for physician and patient?].

Guidelines derived from 'evidence-based medicine' are supposed to provide assistance and information in order to improve diagnosis and therapy of individual patients and build up confidence in medical decisions. Guidelines possess no direct legal power. The doctor's freedom of decision must be warranted. Inadequate guidelines may have serious consequences: curtailment of therapeutic freedom, hampering of medical progress, deterioration of the relationship between doctors and their patients, risk of legal implementation and emergence of a defensive medicine.

Defensive Medicine↗
PubMed1998

[Our university clinics need research--so does our specialty!].

University research has to serve as a substrate for science and technology and should raise a qualified, critical but motivated younger generation of scientists. These need a basic research which is independent and not oriented towards any short-term goals. An open and easy collaboration without any interdependence is necessary between the university and industry. All this requires greater autonomy for the universities. in German-speaking countries, many people distrust progress. However, it is not a matter of 'progress at any price' but of a careful, pertinent analysis of the benefits and risks. Parsimony in science and research is dangerous and shortsighted. To invest in research means to invest in the future.

Curriculum↗
PubMed1998

m-THPC-mediated photodynamic therapy (PDT) does not induce resistance to chemotherapy, radiotherapy or PDT on human breast cancer cells in vitro.

Photodynamic therapy (PDT) uses laser light to activate a photosensitizer that has been absorbed preferentially by cancer cells after systemic administration. A phototoxic reaction ensues resulting in cell death and tissue necrosis. Some cells, however, may survive PDT. This study was performed to determine if surviving human breast cancer cells (MCF-7) can become resistant to PDT, chemotherapy or radiotherapy. The MCF-7 cells were cultured under standard conditions prior to being exposed to the photosensitizer, 5,10,15,20-meta-tetra(hydroxyphenyl)chlorin (m-THPC), for 24 h and then irradiated with laser light (652 nm). Surviving cells were allowed to regrow by allowing a 2 week interval between each additional PDT. After the third and final treatment, colony formation assays were used to evaluate the sensitivity of cultured cells to ionizing radiation and PDT and the ATP cell viability assay tested in vitro chemosensitivity. Flow cytometry was used to analyze the cell cycle. No alterations in the cell cycle were observed after three cycles of PDT with m-THPC. Similar responses to chemotherapy and ionizing radiation were seen in control and treatment groups. The m-THPC-sensitized PDT did not induce resistance to subsequent cycles of PDT, chemo- or radiotherapy. Photodynamic therapy with m-THPC may represent a novel adjunctive treatment of breast cancer that may be combined with surgery, chemotherapy or ionizing radiation.

Antineoplastic Agents↗
PubMed1997

In vitro effects and localisation of the photosensitizers m-THPC and m-THPC MD on carcinoma cells of the human breast (MCF-7) and Chinese hamster fibroblasts (V-79).

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is the combination of a photosensitizer with laser light to induce preferential destruction of malignant cells. In this study two new photosensitizers--5,10,15,20-meta-tetra(hydroxyphenyl) chlorin (m-THPC) and m-THPC MethoxyPEG2000 derivative (m-THPC MD)--were tested, both for their dark toxicity, i.e., cytotoxicity in the absence of light, and for their light-induced cytotoxicity in mammalian cell cultures. STUDY DESIGN/MATERIALS AND METHODS: Cell lines used were MCF-7 (human breast carcinoma) and V-79 (Chinese hamster lung fibroblast). After cultivation under standard conditions, cells were administered the photosensitizers and 24 hr later exposed to various energy levels of laser light at a wavelength of 652 nm. Cell survival was monitored using a clonogenic assay and was expressed as the surviving fraction of the untreated control. RESULTS: Up to an m-THPC concentration of 1 microgram/ml, no dark toxicity was observed; at higher concentrations a rapid fall in survival occurred. m-THPC MD showed no dark toxicity up to 100 micrograms/ml. In vitro m-THPC was approximately 10 times more cytotoxic than m-THPC MD. The MCF-7 and V-79 cell lines displayed similar responses to PDT. CONCLUSIONS: Both m-THPC and m-THPC MD are very efficient photosensitizers in vitro. Up to the therapeutic dose, neither exhibited dark toxicity. There is clinical relevance of the photosensitizers by a large therapeutic index.

Animals↗
PubMed1997

Can simultaneous perineal sonography and urethrocystometry help explain urethral pressure variations?

OBJECTIVE: To correlate urodynamic with perineal sonographic findings in pressure variations. PATIENTS AND METHODS: In 15 women presenting with urethral pressure variations a urodynamic evaluation with water filling cystometry, urethral pressure at rest and during coughing and uroflowmetry were performed. During water filling cystometry, there were simultaneous perineal video-sonography and urethrocystometry. Video ultrasound images and urodynamic curves were simultaneously monitored on a computer screen. RESULTS: Simultaneous ultrasound and urodynamic evaluation in the 15 patients revealed movements in two areas leading to urethral pressure variations: activity of the pelvic floor muscles and of the urethral sphincter muscles. For the pelvic floor, we found either slow or fast contractions with, respectively, slow (15-30 cm H2O for 3-10 sec) or fast (30-130 cm H2O for 1-3 sec) urethral pressure changes. Urethral sphincter contractions were always fast, resulting in fast pressure changes of 30-170 cm H2O for 1-3 sec. CONCLUSION: Evaluation of simultaneous perineal sonography and urethrocystometry shows the association of urethral pressure variations and muscle activity. Urethral pressure variations are caused by the activity of urethral sphincter or pelvic floor muscles. With ultrasound the activity of the urethral sphincter muscle can directly be seen whereas pelvic floor muscle activity is indirectly visible. Pelvic floor muscle contractions are either fast or slow, whereas the urethral sphincter muscle contractions are always fast contractions.

Adolescent↗
PubMed1997

In vivo fluorescence detection of ovarian cancer in the NuTu-19 epithelial ovarian cancer animal model using 5-aminolevulinic acid (ALA).

The purpose of this study was to determine whether in vivo fluorescence detection of protoporphyrin IX (PpIX) could be used to identify intraperitoneal micrometastases of epithelial ovarian carcinoma after application of 5-aminolevulinic acid (ALA). ALA was applied intraperitoneal at different concentrations (25, 50, and 100 mg/kg) and iv (100 mg/kg) to immunocompetent Fischer 344 rats bearing a syngeneic epithelial ovarian carcinoma. At different time intervals after ALA administration (1.5, 3, and 6 hr) the peritoneal cavity was illuminated with ultraviolet (uv) light. In vivo fluorescence of PpIX initially was determined by direct visualization. Subsequently ex vivo measurements were made with a slow-scan, thermoelectrically cooled CCD camera. Red in vivo fluorescence was observed in ovarian micrometastases smaller than 0.5 mm in 100% of the ALA-administered animals independent of time interval, drug concentration, or route of administration. The intensity of the fluorescence was concentration dependent as strong fluorescence was consistently found only above 25 mg/kg ALA. Ex vivo tumor to peritoneum fluorescence yield peaked 3 hr after administration of a 100 mg/kg intraperitoneal dose. Direct visualization of in vivo fluorescence after ALA application may improve the detection of intraperitoneal ovarian cancer micrometastases.

Aminolevulinic Acid↗
PubMed1997

Premenopausal node-negative breast cancer: may adjuvant chemotherapy be indicated by the analysis of nuclear DNA dynamics?

The management of premenopausal node-negative breast cancer patients is discussed controversially. Accurate cellular as well as biochemical markers are essential for this cancer group to identify high risk patients needing adjuvant chemotherapy. In the present study, flow cytometric DNA analysis (DNA-ploidy status, DNA-index, S-phase fraction, S+(G2+M)-phase fraction) and clinico-pathological variables (clinical stage, tumor size, receptor status, age, histological type and grade) as prognostic factors were determined on paraffin-embedded tumors to predict overall survival (OS) and disease-free survival (DFS). Median observation time was 6.1 years (n = 57). S+(G2+M)-phase fraction was the only flow cytometric DNA predictor of overall survival in the univariate analysis (log-rank test): As compared to the patients with lower S+(G2+M)-phase fraction (< or = 9.3%), patients with S+(G2+M)-phase fraction greater than 9.3% had shorter survival (P = 0.039). Of all the clinico-pathological parameters analyzed (univariate analysis), the survival time was found to be longer when estrogen- and/or progesterone-receptor status was positive (overall survival: P = 0.039; disease-free survival: P = 0.017) and the histological grade was low (overall survival: I + II vs III: P = 0.024; I vs II vs III: P = 0.046). In the multivariate analysis, receptor status was the strongest predictor for overall and disease-free survival. These results suggest that S+(G2+M)-phase fraction in premenopausal node-negative breast cancer could be an additional valuable prognostic factor to classify high risk breast cancer patients needing adjuvant chemotherapy.

Adult↗
PubMed1997

[Cervical pregnancy. A gynecologic-obstetric emergency situation].

The cervical pregnancy is defined as the implantation of the blastocyst into the cervical canal. The characteristic clinical sign is a severe asymptomatic uterine bleeding in early pregnancy or during curettage. Prior to 1978, correct preoperative diagnosis was rare and in almost all cases a hysterectomy was performed. Today, transvaginal sonography allows early diagnosis, and conservative treatment (two-time treatment: first treatment with systemic or intraamniotic methotrexate, secondly with curettage or ligature of the uterine arteries) improves the prospects of fertility.

Abortion, Induced↗
PubMed1996

Accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in normal and neoplastic human endometrial epithelial cells.

The aim of this study was to evaluate 5-Aminolevulinic acid (ALA)-induced fluorescence of normal and neoplastic endometrial epithelial cells for diagnosis and photodynamic treatment. Fluorescence of ALA-induced PpIX in vitro was measured by flow cytometry in two different human endometrial adenocarcinoma cell lines and in normal cells cultivated from fresh endometrial tissue of three premenopausal patients. The cells were analysed after incubation with different concentrations of ALA during 3, 6, or 24 hours. Both tumor cell lines showed a statistically significant higher fluorescence of PpIX than normal epithelial cells after incubation with 1 mg ALA per ml medium during 24 hours. The well-differentiated cancer cells produced significantly more PpIX than the poorly differentiated cancer cells. Relative PpIX intensity of the two cancer cell lines correlated with cell proliferation rate as measured by the doubling times of the cells. Higher accumulation of Pp IX in neoplastic endometrium compared to normal endometrial epithelial cells may provide targeted biopsies and selective photodynamic destruction of neoplastic micro-lesions.

Adenocarcinoma↗
PubMed1996

[Analysis of indications and results of fractional curettage in a large gynecological cohort].

AIM: To determine whether the term "fractional D&C" is justified with respect to the uterine cervix and corpus fractions, and what indications and results are found when a large population at a university hospital is analyzed. METHODS: In this retrospective study covering a 3-year period at the Department of Gynecology, University Hospital of Zurich, indications and results of fractional D&C were obtained from hospital records stored in a data bank. The curettage results of hysterectomized women were compared with the histological findings of the hysterectomy specimens. RESULTS: 938 women (mean age 52 years) underwent fractional D&C. 38% had postmenopausal, 36% premenopausal and 13% perimenopausal abnormal bleeding. For 5% there was a sonographic finding without bleeding disorders, 4% had cervical polyps, 1% breast cancer, and 3% other diagnoses. In 13% of the cases the corpus curettage material could not be evaluated. For 43%, the corpus material appeared normal and in 5% a malignancy was found. In 74% of the cervical fractions nothing abnormal was detected, in 14% no conclusive evaluation of the material was possible, and in 3% the histological report showed a malignancy. In 20% of the cases the cervix curettage material was contaminated with material from the uterus cavum. CONCLUSIONS: For cases with cancer of the cervix, the sensitivity of fractional D&C was 80%, compared with a specificity of 66.7%. With a positive predictive value of 52.2%, the term "fractional D&C" is in many cases not justified. Our data and recent literature have prompted us to draw up new criteria for evaluation of abnormal vaginal bleeding, or a new set of indications for fractional D&C and hysteroscopy.

Adolescent↗
PubMed1996

Usefulness of ultrasound contrast medium in perineal sonography for visualization of bladder neck funneling--first observations.

OBJECTIVES: To assess the efficacy of ultrasound medium when imaging bladder neck anatomy with perineal ultrasound. METHODS: In 10 female patients with urinary stress or stress-urge incontinence, a new echogenic contrast medium (Echovist) was intravesically administered and perineal ultrasound performed. The examination was done with the women in the upright position both without and with ultrasound contrast medium at rest and during pressing, and the pictures of the bladder base, bladder neck, and urethra were compared. RESULTS: With the patient in the upright position, the ultrasound contrast medium enters the urethra during pressing and bladder neck funneling is identified more accurately than without contrast medium. With Echovist, bladder neck funneling was detected in 9 of the 10 cases but without it in only 4 cases. CONCLUSIONS: The use of ultrasound contrast medium results in a better visualization of the bladder neck anatomy. Bladder neck funneling and urinary leakage are seen more distinctly, and this improves the diagnostic reliability in female urinary stress incontinence. This pilot study supports the necessity for further investigations in the use of ultrasound contrast medium as a diagnostic improvement of perineal ultrasound.

Contrast Media↗
PubMed1996

Axillary lymphadenectomy--just how radical should it be?

UNLABELLED: To determine whether local axillary recurrences correlate with the number of lymph nodes extirpated, 779 cases of breast cancer were analysed in retrospect. RESULTS: The number of lymph nodes extirpated varied between 1 and 42 per axilla. The axillary recurrence rate of 5.5% showed a minimal correlation between the frequency of these recurrences and the number of lymph nodes removed. There is an equally insignificant correlation between the percentage of positive histological findings and the number of lymph nodes extirpated: The trend analysis shows that with fewer than five lymph nodes extirpated, 40% of positive histological findings can be expected, whereas with over 20 lymph nodes extirpated the percentage is 45%. CONCLUSION: The number of lymph nodes extirpated is an unsuitable indicator as to how radical axillary clearance is. Surgeons should rely on anatomical boundaries rather than focusing on the number of lymph nodes removed.

Adult↗
PubMed1996

Perineal ultrasound: determination of reliable examination procedures.

This is a report on the fundamentals of perineal ultrasound examination for female incontinence. The measurement method described here enabled us to determine the position of the bladder neck, the size of the retrovesical angle beta and the occurrence of funnelling. In four different investigations, each involving at least 30 patients, we investigated the influence of examination position, bladder filling volume and pressure of the ultrasound probe against the perineum on these measurements and analyzed the difference between coughing and the Valsalva maneuver. The results showed that when the patient is standing, the bladder neck is lower than when the patient is supine. We also observed that excessive pressure on the ultrasound probe displaces the bladder neck cranially and can squeeze the urethra. Increasing the bladder filling volume does not affect the measurement values, but funnelling can be seen better with higher bladder volumes. The best overall image quality was obtained at 300 ml. A comparison between coughing and the Valsalva maneuver showed that during coughing, the bladder neck descends less and remains closer to the symphysis than with the Valsalva maneuver.

Cough↗
PubMed1996

[Comparison of gynecologic and perineal ultrasound examination of women with stress incontinence].

UNLABELLED: A COMPARISON AIM: To determine how well results of gynecological and perineal sonographic examinations of the urethrovesical junction correlate. METHOD: 186 women with urodynamically verified stress incontinence underwent a perineal ultrasound and then a gynecologic examination. Standardised procedures were used for both. The findings of the gynecological examination were compared with measurement values and morphological findings from perineal ultrasound. RESULTS: There was agreement on the cystocele grade in 69% of the cases. The position of the bladder neck as assessed by the ultrasound image revealed typical measurement values for this disorder. The expected bladder neck funneling was detected in 49% of these women. CONCLUSION: In stress-incontinent women there is good correlation between the findings of the gynecological and perineal sonographic examinations. Bladder neck funneling-a morphological sign of stress incontinence-can be detected with perineal ultrasound in nearly one-half of the cases.

Adult↗
PubMed1996

[Benzoporphyrin derivative mono acid for photodynamic therapy of the endometrium].

The aim was to study the impact of photodynamic therapy (PDT) on the endometrium after local intrauterine application of photosensitiser (Ps) and laser light without sensitising the skin. To our knowledge Benzoporphyrin Derivative Mono Acid (BPD) was used for the first time for this purpose in the rat model. The advantage of using BPD is the fact that light of 690 nm (maximum absorption) penetrates deeper into tissue and shows less absorption by haemoglobin. Low-light level tissue fluorescence imaging revealed a distinct positive endometrium-to-myometrium ratio within the first 12 hours. Relative fluorescence was highest in the endometrial glands and lowest in the myometrium. After 12 hours the intensity of fluorescence levelled off in all compartments and values of the glands approached close to those of the other layers. REPRODUCTIVE PERFORMANCE AFTER PDT: There was a significant difference in nidations (p < 0.03) in the treated left uterine horn as compared to the untreated right horn and the control animals (light/no drug and drug/no light). HISTOLOGICAL CHANGES: Following PDT a marked atrophy of the endometrial layer was observed in most animals leaving just a single cell epithelial layer covering the myometrium. SKIN PHOTOSENSITIVITY: None of the animals showed any alterations in the light treated skin area at any time. These promising results show that PDT of the endometrium is possible after topical application of the photosensitising drug and the laser light without provoking skin sensitivity.

Animals↗