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Biomedical subjects

U Steiner

Publications and source records attributed to U Steiner.

At least 19 recordsLinked to original sources

Electrically induced structure formation and pattern transfer

The wavelength of light represents a fundamental technological barrier to the production of increasingly smaller features on integrated circuits. New technologies that allow the replication of patterns on scales less than 100 nm need to be developed if increases in computing power are to continue at the present rate. Here we report a simple electrostatic technique that creates and replicates lateral structures in polymer films on a submicrometre length scale. Our method is based on the fact that dielectric media experience a force in an electric field gradient. Strong field gradients can produce forces that overcome the surface tension in thin liquid films, inducing an instability that features a characteristic hexagonal order. In our experiments, pattern formation takes place in polymer films at elevated temperatures, and is fixed by cooling the sample to room temperature. The application of a laterally varying electric field causes the instability to be focused in the direction of the highest electric field. This results in the replication of a topographically structured electrode. We report patterns with lateral dimensions of 140 nm, but the extension of the technique to pattern replication on scales smaller than 100 nm seems feasible.

Journal Article↗

Theophylline improves acute mountain sickness.

A randomized two-part study was conducted in order to determine the efficacy of theophylline in the treatment of acute mountain sickness during fast ascent to altitudes >2,500 m. Fourteen healthy male subjects participated in a randomized single-blind placebo-controlled crossover study carried out in a decompression chamber (simulated altitude 4,500 m). A second randomized single-blind, placebo-controlled study was conducted at a high-altitude research laboratory (3,454 m) and included 21 healthy male subjects. The study medication was either 375 mg oral slow-release theophylline (250 mg if <70 kg) or a matched placebo tablet taken twice daily. The acute mountain sickness score (AMSS) was assessed three times a day, beginning 18 h prior to altitude exposure and continuing for 18 h after altitude exposure. In addition, measurements of respiratory frequency, pulse rate, oxygen saturation and arterial blood gas levels were performed. Acute mountain sickness was significantly reduced by theophylline during the decompression chamber study (mean+/-SD 1.2+/-0.9) with placebo versus 3.6+/-0.8 with theophylline; p=0.03). During the high-altitude study, subjects with theophylline showed a significantly lower AMSS on arrival and after 18 h at altitude (0.6 versus 2.3, p=0.03). Oxygenation was improved in both parts of the study. In conclusion, oral slow-release theophylline improves acute mountain sickness.

Administration, Oral↗

Nanophase-separated polymer films as high-performance antireflection coatings

Optical surfaces coated with a thin layer to improve light transmission are ubiquitous in everyday optical applications as well as in industrial and scientific instruments. Discovered first in 1817 by Fraunhofer, the coating of lenses became standard practice in the 1930s. In spite of intensive research, broad-band antireflection coatings are still limited by the lack of materials with low refractive indices. A method based on the phase separation of a macromolecular liquid to generate nanoporous polymer films is demonstrated that creates surfaces with high optical transmission.

Journal Article↗

[Lymph node positive prostate carcinoma. A case for radiotherapy].

The role of radiotherapy of the pelvic lymphatic pathways in patients with node positive prostate cancer remains uncertain. Interpretation of the few prospective studies (RTOG 75-06 and 77-06) is hampered by severe flaws in the study design. Extension of the radiation to the paraaortal region shows no advantage over radiation of the pelvic lymphatics alone and is not warranted. Data on longterm side-effects are only available from older studies with outdated radiation techniques. According to more recent studies short term side effects are considerably higher with radiation of the pelvic lymphatics when compared with radiation of the prostate alone. In summary radiation of the lymphatic pathways in lymph node positive prostate cancer cannot currently be considered as standard treatment and should be carried out within clinical studies.

Clinical Trials as Topic↗

Quantitative detection of human complement factor H-related protein in transitional cell carcinoma of the urinary bladder.

OBJECTIVE: The purpose of this study was to assess a new quantitative urinary tumor marker for transitional cell carcinoma of the urinary bladder (TCC), human complement factor H-related protein (hCFHrp, BTA TRAK). METHODS: Urine samples of 298 individuals (76 healthy volunteers, 118 patients with benign urologic disorders, 104 patients with histologically proven bladder cancer) were examined for the presence of hCFHrp. Samples of all patients were obtained prior to therapy. RESULTS: In comparison to healthy volunteers, patients with TCC had significantly higher urinary levels of hCFHrp (117.60 vs. 2.05 U/ml; p < 0.001). HCFHrp levels were positively correlated with tumor grade and stage. Patients with invasive TCC had significantly higher levels of hCFHrp than patients with superficial TCC (p = 0.001). Marker levels in superficial bladder cancer at high risk of tumor progression (pT1G3) were significantly higher as compared to low and intermediate grade superficial cancers. Elevated levels of hCFHrp were also found in patients with benign urologic disorders (median: 72.65 vs. 117.60 U/ml in cancer patients). Using a cutoff of 17.1 U/ml, hCFHrp had a sensitivity of 72.1% and, due to a high rate of false-positive determinations in patients with benign urologic disorders, a total specificity of 50.5%. CONCLUSIONS: HCFHrp (BTA TRAK) is a sensitive test for detection of bladder cancer and for identification of patients at high risk. Due to a high rate of false-positive results in patients with benign urologic diseases, the test should not be used in an unselected population.

Adult↗

The average dose-area product at intravenous urography in 205 adults.

The intravenous urography (IVU) is the most important and most frequently performed radiological examination in urology. This prospective study determined the dose-area product as a measurement of radiation dose in 205 adult patients undergoing IVU. Average dose-area product was 1017 cGy cm2. An average 3.7 radiographs were obtained per patient. Tomographic views were required in only 8.8% of cases. Radiation dose is dependent not only on the number and size of the obtained radiographs, but on the physical constitution of the patient. The dose-area products measured show a clear relationship to the body weight of the patient.

Adolescent↗

Expression of CD44V2 in transitional cell carcinoma of the urinary bladder and in urine.

CD44 is the principal cell surface receptor for hyaluronate. Variant forms of the receptor, produced by alternative splicing, have been found to be associated with tumor progression in a variety of cancers. Based on investigations at the RNA level, it has recently been proposed that expression of CD44 variant V2 was present in urothelial cancer but not in normal urothelium. Since a distinctive marker for urothelial cancer would be extremely useful, frozen sections of normal urothelium and urothelial cancer were examined for expression of standard CD44 and CD44V2. Frozen sections of specimens of 35 patients with transitional cell carcinoma of the bladder, 16 specimens of normal bladder and 5 ureters were examined. Immunohistochemical staining was performed using a polyclonal antibody to CD44V2 (PAB CD44V2), a monoclonal antibody to CD44V2 (MAB CD44V2) and a monoclonal antibody to CD44S (MAB CD44S). CD44V2 and CD44S were also measured in lysates of urine sediments from 21 patients by enzyme-linked immunoabsorbent assay (ELISA). All investigated transitional cell carcinomas expressed CD44V2. There was no differentiation between invasive and noninvasive carcinoma. CD44V2 was also expressed in normal urothelium. Standard CD44 was expressed by the transitional cell carcinoma, normal urothelium, musculature and interstitial tissue. The amount of CD44V2 and CD44S in lysates of urine sediments is not correlated to diagnosis. In contrast to investigations at the RNA level, CD44V2 on the protein level seems not to be a distinctive marker for urothelial cancer. Therefore, CD44V2 will not be a useful diagnostic marker for detection of transitional cell carcinoma.

Antibody Specificity↗

[Radiotherapy after radical prostatectomy: indications, results and side effects].

BACKGROUND: Radiation therapy following radical prostatectomy in locally progressed prostate carcinoma has become increasingly important in the last few years as both adjuvant therapy in patients with pT3-tumors with or without positive margins and treatment for a PSA increase in local recurrence of disease. The background for this is the knowledge gained by using PSA that up to 60% of the patients with histopathologically confirmed pT3/4 tumors or involvement of the lymph nodes are systemically and/or locally progressive after 3 to 5 years if only surgical or radiation therapy was performed. RESULTS: A number of studies, albeit exclusively retrospective, substantiated a significantly high local tumor control by radiotherapy after radical prostatectomy. This holds true for adjuvant therapy with a PSA in the "zero range" as well as with a PSA increase from the "zero range", whereby it must be taken into consideration that a certain percentage of treated patients with a PSA in the "zero-range" with or without positive margins actually do not need further therapy. Two retrospective studies demonstrated a significant better lengthening of "freedom from treatment failure" that is local and systemic progression of disease. Lengthening the survival time has, however, not yet been proven. With an increase in the PSA from the "zero range" after radical prostatectomy, there are indications that systemic metastatic spread already occurs with values higher than 2.5 to 4 ng/ml and the radiotherapy no longer has any curative intention. CONCLUSIONS: Adjuvant RT following radical prostatectomy gives better local control rates and probably better rates of "freedom from treatment failure" in patients with locally advanced prostate cancer with positive margins and probably in patients with negative margins. However, in retrospective studies no advantage in overall survival was shown.

Follow-Up Studies↗

Side effects of chemotherapy for advanced urothelial carcinoma with etoposide and ifosfamide.

OBJECTIVES: To date, chemotherapy for advanced urothelial carcinoma has been associated with only moderate therapeutic success and minimal extension of survival. This, coupled with the occurrence of serious side effects and the resulting reduced quality of life, underscores the need for new chemotherapeutic agents. A first study investigating combination therapy with etoposide and ifosfamide reported not only comparable therapeutic effectiveness but, due primarily to the elimination of the cisplatin component, a reduction in nephrotoxic side effects. In the present study, therefore, patients with advanced urothelial carcinoma and minor compromised renal function received combination chemotherapy with etoposide and ifosfamide. METHODS: Fourteen patients with advanced urothelial carcinoma underwent chemotherapy with a combination of etoposide and ifosfamide. On days 1-5, patients received 1,500 mg/m2 ifosfamide and 120 mg/m2 etoposide. The next corresponding cycle was started on day 22. RESULTS: A number of serious side effects were observed. These consisted predominantly of high-grade myelosuppression requiring therapy, as well as disturbances in the central nervous system and impairment of renal function. Due to severe side effects, chemotherapy had to be prematurely terminated in 8 of 14 patients (57%). The efficacy of therapy, however, was observed in patients completing the treatment regimen. CONCLUSIONS: The new combined chemotherapy with etoposide and ifosfamide shows efficacy in the treatment of advanced urothelial carcinoma. This, however, is overshadowed by the high rate of serious side effects leading to premature interruption of therapy.

Aged↗

Photodynamic effects of sulfonated aluminum chlorophthalocyanine in human urinary bladder carcinoma cells in vitro.

OBJECTIVES: Topically applied photosensitizers are particularly suited for use in the photodynamic therapy of urinary bladder tumors. The objective of the present study was to investigate the photodynamic effects of sulfonated aluminum chlorophthalocyanine on human bladder carcinoma cells. METHODS: The photodynamic efficiency and the morphologic changes induced by sulfonated aluminum chlorophthalocyanine on human bladder carcinoma cells and normal bladder wall cells were investigated in vitro using light microscopy and in order to determine the subcellular target organelles using electron microscopy. RESULTS: Examination of tumor cells with light microscopy after previous photodynamic therapy initially showed distension of the cells and, depending on the duration, a significant blistering of the cell membrane, leading, in some cases, to rupture of the cells. Electron microscopy revealed destruction of the mitochondria. No changes in other cell organelles or structures were observed. CONCLUSIONS: Sulfonated aluminum chlorophthalocyanine exhibits good photodynamic activity in bladder tumor cells with relative tumor selectivity. The primary cellular target of photodynamic therapy seems to be the mitochondria.

Aluminum↗

Assay for tyrosine hydroxylation activity of tyrosinase from betalain-forming plants and cell cultures.

In our studies on tyrosinase-catalyzed tyrosine hydroxylation, possibly involved in betalain biosynthesis, we have evaluated different assays for the detection and quantification of the enzymatic product Dopa with respect to sensitivity, simplicity, and suitability for automatization. A tyrosinase assay including reversed-phase high-performance liquid chromatography with isocratic elution and fluorescence detection has been developed (native fluorescence of Dopa; excitation at 281 nm, emission at 314 nm). This improved assay was sensitive (detection limit: 2 pmol Dopa) and showed a wide linear range of Dopa detection (10 pmol-20 nmol Dopa). The method proved to be suitable for high-performance liquid chromatography with an autosampler and has been applied for measuring tyrosinase activity of cell cultures and different tissues of Portulaca grandiflora.

Betalains↗

[Functional results and complications of the ileal neobladder in over 200 patients].

Between April 1986 and October 1992, a total of 229 patients with invasive bladder cancer underwent radical cystectomy and lower urinary tract reconstruction by means of the ileal neobladder. The perioperative mortality was 2.4%. Subsequently 10.5% of the patients suffered from early complications that led to relaparotomy and 3.8% of the patients had bowel occlusion. Significant late complications were urethro-ileal strictures (6.7%) and stenosis of the ureteral anastomosis (3.3%). Despite a very strict definition of continence, only 2 patients with a follow up of more than 2 years had an incontinence grade 3. Most (77%) of the patients in this collective were perfectly continent day and night, while 11.5% had only occasional spotting and wore pads to be on the safe side. In conclusion, the medium-term results are now available (average follow up 41 months) and show that the ileal neobladder is the treatment of choice for male patients after radical cystectomy for the treatment of invasive bladder cancer.

Adult↗

A glutathione S-transferase with glutathione-peroxidase activity from Arabidopsis thaliana. Molecular cloning and functional characterization.

A full-length cDNA clone for a novel glutathione S-transferase was isolated from Arabidopsis thaliana and characterized. The cDNA encodes a polypeptide of 218 amino acids with a calculated molecular mass of 24,363 Da. The sequence was most related to the theta class within the glutathione-S-transferase superfamily of enzymes. The protein encoded by the cDNA was functionally expressed and enzymically active in Escherichia coli; glutathione-S-transferase activity with the standard enzyme substrate 1-chloro-2,4-dinitrobenzene was demonstrated (apparent Km, 10 mM; apparent Km for glutathione, 0.08 mM). The enzyme is substrate specific and did not use several electrophilic reduced-glutathione acceptor molecules for conjugation. However, it efficiently catalyzed the conversion of 13-hydroperoxy-9,11,15-octadecatrienoic acid (Km, 0.67 mM) as well as 13-hydroperoxy-9,11-octadecadienoic acid (Km, 0.79 mM) to the corresponding hydroxy derivatives with concomitant formation of oxidized glutathione. The enzyme did not use H2O2 as substrate. Thus, the cloned A. thaliana enzyme functions as glutathione peroxidase and, in the plant cell, may be involved in the removal of reactive organic hydroperoxides, such as the products of lipid peroxidation. The enzyme is structurally and enzymatically, however, unrelated to the selenium-containing glutathione peroxidases. Enzymic and immunoblotting data suggest that the A. thaliana enzyme is soluble and constitutively expressed in vegetative rosettes, but is under developmental control during the transition to bolting and flowering.

Amino Acid Sequence↗