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Biomedical subjects

U Vogt

Publications and source records attributed to U Vogt.

At least 19 recordsLinked to original sources
PubMed2006

Whole genome expression analysis for biologic rational pathway modeling: application in cancer prognosis and therapy prediction.

Using semi-quantitative microarray technology, almost every one of the approximately 30 000 human genes can be analyzed simultaneously with a low rate of false-positives, a high specificity, and a high quantification accuracy. This is supported by data from comparative studies of microarrays and reverse-transcription PCR for established cancer genes including those for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2/ERBB2), estrogen receptor (ESR1), progesterone receptor (PGR), urokinase-type plasminogen activator (PLAU), and plasminogen activator inhibitor-1 (SERPINE1). As such, semi-quantitative expression data provide an almost completely comprehensive background of biological knowledge that can be applied to cancer diagnostics. In clinical terms, expression profiling may be able to provide significant information regarding (i) the identification of high-risk patients requiring aggressive chemotherapy; (ii) the pathway control of therapy predictive parameters (e.g. ESR1 and HER2); (iii) the discovery of targets for biologically rational therapeutics (e.g. capecitabine and trastuzumab); (iv) additional support for decisions about switching therapy; (v) target discovery; and (vi) the prediction of the course of new therapies in clinical trials. In conclusion, whole genome expression analysis might be able to determine important genes related to cancer progression and adjuvant chemotherapy resistance, especially in the context of new approaches involving primary systemic chemotherapy. In this review, we will survey the current progress in whole genome expression analyses for cancer prognosis and prediction. Special emphasis is given to the approach of combining biostatistical analysis of expression data with knowledge of biochemical and genetic pathways.

Cluster Analysis↗
PubMed2006

Medical uses of cosmetic colored contact lenses.

PURPOSE: To explore the clinical issues surrounding the use of hand-painted contact lenses for medical indications and to assess patient satisfaction with the use of these lenses for an unsightly eye. METHODS: A questionnaire was sent to all patients visiting the contact lens department of Western Eye Hospital for a colored contact lens fitting during a 1-year period. The questionnaire related to patient satisfaction with the lenses and aspects of wear. RESULTS: Replies were received from 25 of a total of 33 patients. The average wearing time was 11.3 hours per day. Most (88%) patients wore lenses for cosmetic reasons, and 12% wore lenses for cosmetic and refractive purposes. Satisfaction was 76% regarding lens comfort and 88% regarding lens color. CONCLUSIONS: Provided lens care is satisfactory and the patient does not have unreasonable expectations, a tinted contact lens can be a useful device. In view of the cost implication, this is a valuable service provided by the hospital.

Adolescent↗
PubMed2005

Comparison of various types of stiffness as predictors of the load-bearing capacity of callus tissue.

The ability to predict load-bearing capacity during the consolidation phase in distraction osteogenesis by non-invasive means would represent a significant advance in the management of patients undergoing such treatment. Measurements of stiffness have been suggested as a promising tool for this purpose. Although the multidimensional characteristics of bone loading in compression, bending and torsion are apparent, most previous experiments have analysed only the relationship between maximum load-bearing capacity and a single type of stiffness. We have studied how compressive, bending and torsional stiffness are related to the torsional load-bearing capacity of healing callus using a common set of samples of bone regenerate from 26 sheep treated by tibial distraction osteogenesis. Our findings showed that measurements of torsional, bending and compressive stiffness were all suitable as predictors of the load-bearing capacity of healing callus. Measurements of torsional stiffness performed slightly better than those of compressive and bending stiffness.

Animals↗
PubMed2004

Contact lens prescribing in a specialist medical contact lens clinic based in an NHS hospital: an audit of changing practice.

PURPOSE: To describe the range of indications for contact lenses and the types of lenses being used in an NHS hospital-based specialist medical contact lens clinic and contrast this with information from 12 years ago. METHODS: A retrospective audit of 596 clinic attendances was performed in the contact lens clinic at the Western Eye Hospital between April 2002 and March 2003. The results were compared with a similar audit performed in 1991. We used the hospitals electronic records, and information on contact lens prescribing was obtained directly from the receipts generated by the contact lens department and the accounts department. RESULTS: We saw 392 patients with 88.5% of patients requiring 2 or less visits per year. The majority of referrals are for high myopia (28.6%) closely followed by aphakia (25.2%) and keratoconus (24.7%). This is in contrast to 1991 when 68% of referrals were for aphakia and twice as many myopes (17%) were seen as keratoconus patients (8%). A total of 560 lenses were prescribed with 68 different types of lens in use. The seven most commonly used lens types accounted for 61% of all lenses prescribed. CONCLUSIONS: Medical contact lens clinics provide a specialist service and also provide an important training resource for junior ophthalmologists. Safer cataract surgical techniques have had a significant impact on the case mix seen in our clinic, with the emphasis moving away from aphakic and myopic patients and toward the more challenging to fit eyes with keratoconus or postcorneal surgery.

Adolescent↗
PubMed2004

Quantitative analysis of the in situ Fourier transform infrared absorption and emission spectrum of gas-phase SiO (Deltav = 1 and 2) produced in Si-N-O fiber growth.

The in situ Fourier transform infrared (FT-IR) spectrum of gasphase SiO produced in silicon oxynitride fiber growth has been quantitatively analyzed. Both absorption and emission FT-IR spectra at a spectral resolution of 0.5 cm(-1) were produced from the reaction zone at 1450 degrees C. The fundamental and hot bands were observed with vibrational levels up to v = 7. For the purposes of quantitative analysis the individual vibration-rotation integrated line strengths for the three main isotopes,( 28)SiO,( 29)SiO, and( 30)SiO, were calculated based on ab initio quantum chemical calculations of the electric dipole moment function and the transition moment. Vibrational anharmonicity and Hermann-Wallis correction factors were also incorporated. From the line strengths at specific temperatures and the known Dunham coefficients, the absorbance spectrum was simulated with best fits giving the averaged SiO concentration in the 400 mm reaction zone of 1.0 x 10(17) molecules/cm(3). Such quantitative measurements demonstrate the power of in situ infrared (IR) spectroscopy combined with quantum chemical calculations. The rapid determination of synthetic calibration datasets for chemometric analysis can thus lead to correlation of gas-phase species concentrations with fiber growth properties and subsequently to real-time process control.

Journal Article↗
PubMed2003

[Remission rate of mediastinal lymph nodes after multimodal therapy of lung cancer--is it a prognostic factor?].

OBJECTIVE: General acceptance in the oncologic community has been gained for combined modality treatment of non-small cell lung (NSCLC) cancer in locally advanced stage IIIA and IIIB disease. However, no optimal regimen has been established. This study (chemotherapy and radiochemotherapy followed by operation) assesses feasibility, response, resectability, and survival in patients with stage IIIA and IIIB lung cancer. Currently, only little data is available about the prognostic significance of tumor clearance of mediastinal nodes. Thus, an important aim of our study was to evaluate the prognostic significance of the extent of tumor reduction in mediastinal nodes by a neoadjuvant multimodality protocol. PATIENTS: In a phase II protocol, 26 patients underwent neoadjuvant radiochemotherapy. Subsequently, a radical lymphadenectomy was performed during surgery. The extent of tumor regression was determined according to the methodology initially described by Salzer-Kuntschik for osteosarcoma: Grade I: no vital tumor cells, grade II: some tumor cells, grade III: less than 10 % vital tumor cells, grade IV: 10-50 % vital tumor cells, grade V: more than 50 % vital tumor cells, grade VI: no effect of chemotherapy. RESULTS: Complete pathologic response was seen in 30.7 % of primary tumors, in 38.5 % of mediastinal lymph nodes, and in 23 % of corresponding specimens simultaneously. Median survival was 34.7 months for those patients with grade I, 12.6 months with grade II, and 8.9 months for patients showing a grade III/IV regression in mediastinal nodes. Response rate to neoadjuvant chemotherapy in mediastinal nodes proved to be the only statistically significant parameter for long-term survival: In cases with no vital tumor cells in the operation specimen, median survival was 34.7 months in comparison to those with vital cells showing a median survival of only 11.4 months (P = 0.01). CONCLUSION: Patients with locally advanced NSCLCs can enjoy long-term survival after multimodal therapy. However, the complications related to therapy are considerably. Especially, clearance of tumor cells from mediastinal lymph nodes is an important independent prognostic factor.

Adult↗
PubMed2003

[Impact of DNA image cytometry (ICM) parameter and established prognostic factors on disease free survival (DFS) and overall survival (OS) of node-negative breast cancer (NNBC) patients].

OBJECTIVE: DNA ICM allows measurement of nuclear DNA content and genotypical grading of malignancy. The aim of this study was to prove the prognostic value of DNA parameter in comparison to established prognostic factors for DFS and OS. PATIENTS AND METHODS: Cytological imprints of 177 unselected primary NNBC patients were subjected to ICM. ICM parameter 2cDI, 5cEE, 9cEE, DNA mean value, proliferation fraction (SG2M) and ploidy were investigated together with established parameter like pT-stages, histology, grading, hormone receptor status and patient age regarding DFS and OS. Univariate and multivariate analysis were performed. RESULTS: Univariate analysis revealed that except ploidy all ICM parameter and pT-stages, histology as well as grading were significant prognostic factors for DFS. However, only 2cDI and pT-stages were proved independent prognostic factors in multivariate analysis. Regarding OS 9cEE, histology and pT-stages were significant factors in univariate analysis. However, only 9cEE and pT-stages were found to be independent prognostic factors in multivariate analysis. CONCLUSIONS: DNA - ICM parameter 2cDI and 9cEE together with pT-stages were proved independent prognostic factors in NNBC patients.

Analysis of Variance↗
PubMed2002

p53 Gene status in relation to ex vivo chemosensitivity of non-small cell lung cancer.

PURPOSE: About 40% of non-small cell lung cancer (NSCLC) patients are candidates for systemic chemotherapy, despite the fact that at diagnosis most NSCLC are usually chemoresistant both in vivo and ex vivo. It is important to develop sufficient methods of prediction of the response to chemotherapy and to find molecular markers that may prognose this response. Therefore, a study on the relationship of p53gene status to the ex vivo chemosensitivity of primary human NSCLC was performed. METHODS: Three drug combinations (carboplatin/etoposide, cyclophosphamide/etoposide/epirubicin, and paclitaxel/carboplatin) were tested in a modified ATP cell viability assay. A group of 28 cases of primary human NSCLC was assessed. RESULTS: Ex vivo chemosensitivity testing showed that tumors with p53 mutations were significantly more resistant to the cyclophosphamide/etoposide/epirubicin regimen than with normal p53 gene ( P = 0.012). However, no correlation was observed for two other treatment regimens. CONCLUSION: Mutations in the p53gene can lead to enhanced chemoresistance, confirming the hypothesis that the p53 gene may serve as a marker of tumor response to treatment in NSCLC. However, the data also illustrate that some additional factors might contribute to drug resistance of the examined tumors.

Aged↗
PubMed2002

Characteristics and functional outcomes of 130 patients with keratoconus attending a specialist contact lens clinic.

AIMS: To evaluate the demographic profile, management and functional outcomes of patients with keratoconus attending the contact lens clinic of a tertiary ophthalmic referral centre over a one year period. METHODS: A retrospective cohort analysis was conducted by reviewing the computerised hospital records of 130 patients attending The Western Eye Hospital contact lens department over the period 1st Jan 1999 to 31st Dec 1999. Data on age, gender, referral pattern, visual acuity, contact lens fitting, degree of visual success, and some information on penetrating keratoplasty were obtained. RESULTS: 16.4% of all patients attending the Contact Lens clinic had keratoconus. The mean age at referral was 28.6 years and the mean age of keratoconus during the study period was 34.9 years. There was a predominance of male patients. Optometrists formed 72.2% of the referrals, and had prescribed some form of refractive correction in 70% of patients (two-thirds contact lenses) prior to hospital assessment. Of the 130 patients seen in the department during the study period, the post-referral management included bilateral contact lens fitting for 102 patients (78.5%), monocular contact lens fitting for 24 patients (18.5%) and no intervention in four patients (3%). The types of contact lenses used included PMMA lenses (2.7%), rigid gas permeable lenses (96.1%) of the spherical, elliptical and special cone lens designs, Keratosoft or Softperm lenses (0.8%) and scleral lenses (0.4%). Eleven eyes of eight patients had received penetrating keratoplasty (PK) prior to hospital assessment, of whom seven eyes needed post-surgical contact lens fitting. The main reasons for PK were contact lens intolerance (83%), frequent contact lens displacement (8.5%) and unsatisfactory visual acuity despite good contact lens fit (8.5%). Sixty-five per cent of patients were able to wear their contact lenses for more than 12 hours a day. With contact lens wear, 87% of patients had a visual acuity of 6/9 or better and 59% of eyes had improved visual acuity of 0.6 logMAR or more. CONCLUSION: Optometrists were the main source of referral for keratoconus patients to the Hospital Eye Service (HES). The mean age at referral was 28.6 years, with a predominance of male patients. Blurred vision formed the main presenting visual symptom on initial hospital assessment; subsequently, more than two-thirds of patients required bilateral contact lenses. Rigid gas permeable contact lenses remain the mainstay treatment for advanced keratoconus, with various designs enabling a large proportion of patients to attain improved visual acuity.

Adolescent↗
PubMed2001

Evaluation of the energetic position of the lowest excited singlet state of beta-carotene by NEXAFS and photoemission spectroscopy.

In carotenoids the lowest energetic optical transition belonging to the pi-electron system is forbidden by symmetry, therefore the energetic position of the S(1) (2(1)A(g)) level can hardly be assessed by optical spectroscopy. We introduce a novel experimental approach: For molecules with pi-electron systems the transition C1s-->2p(pi*) from inner-atomic to the lowest unoccupied molecular orbital (LUMO) appears in X-ray absorption near edge spectra (NEXAFS) as an intense, sharp peak a few eV below the carbon K-edge. Whereas the peak position reflects the energy of the first excited singlet state in relation to the ionization potential of the molecule, intensity and width of the transition depend on hybridization and bonding partners of the selected atom. Complementary information can be obtained from ultraviolet photoelectron spectroscopy (UPS): At the low binding energy site of the spectrum a peak related to the highest occupied molecular orbital (HOMO) appears. We have measured NEXAFS and UPS of beta-carotene. Based on these measurements and quantum chemical calculations the HOMO and LUMO energies can be derived.

Electron Probe Microanalysis↗
PubMed2001

Loss of expression of HDAC-recruiting methyl-CpG-binding domain proteins in human cancer.

Dysregulation of CpG-methylation is a common feature of many human cancers and tumour suppressor genes can be silenced by hypermethylation. Recently, 2 methyl-CpG-binding domain proteins have been linked to gene inactivation by their ability to recruit co-repressors and HDAC-activity to methylated gene promoters. Here, we have analysed mRNA expression of these genes, MeCP2 and MBD2, in a wide variety of primary human tumours. In solid tumours, expression levels of MBD2 (57/71) and MeCP2 (64/71) were significantly reduced in the majority of primary tumours as detected by quantitative real-time RT-PCR. Western blot analyses of MeCP2 in matched tumour-normal samples of patients with non-small-cell lung cancer (NSCLC) indicated reduced protein in a significant percentage of patients. In acute myelogenous leukaemia (n = 26), expression levels were only slightly reduced and did not differ between samples analysed at diagnosis or at the time of relapse. In early-stage NSCLC (n = 70) expression of MeCP2 and MBD2 was significantly lower in squamous cell carcinoma than in adenocarcinoma or large cell carcinoma (P = 0.03 and P = 0.01). To further elucidate the mechanisms of gene regulation, we analysed MeCP2 and MBD2 regulation during haematopoietic differentiation. No significant changes in MeCP2 or MBD2 expression were found when NB4 cells were differentiated toward granulocytes suggesting that neither differentiation nor cell cycle status were relevant for the reduced expression of these genes in human cancer. In conclusion, the significant loss of MeCP2 and MBD2 expression in human cancers suggests a potential role of this phenomenon in the development of solid human tumours.

Cell Differentiation↗
PubMed2001

Absolute extreme ultraviolet yield from femtosecond-laser-excited Xe clusters.

Large Xe clusters (10(5)-10(6) atoms per cluster) have been irradiated with ultrashort (50 fs) and high-intensity ( approximately 2 x 10(18) W/cm(2)) pulses from a Ti:sapphire multi-TW laser at 800 nm wavelength. Scaling and absolute yield measurements of extreme ultraviolet (EUV) emission in a wavelength range between 7 and 15 nm in combination with cluster target characterization have been used for yield optimization. Maximum emission as a function of the backing pressure and a spatial emission anisotropy covering a factor of two at optimized yields is discussed with a simple model of the source geometry and EUV-radiation absorption. Circularly polarized laser light instead of linear polarization results in a factor of 2.5 higher emission in the 11 to 15 nm wavelength range. This indicates the initial influence of optical-field ionization for the interaction parameter range used and contrasts to collisional heating that seems to influence preferentially higher ionization. Absolute emission efficiency at 13.4 nm of up to 0.5% in 2pi sr and 2.2% bandwidth has been obtained.

Anisotropy↗
PubMed2001

Binding of IRE-BP to its cognate RNA sequence: SFM studies on a universal RNA backbone for the analysis of RNA-protein interaction.

We have used an RNA consisting of the potato spindle tuber viroid (PSTVd) and 240 bp of double-stranded RNA derived from the GUS gene as a backbone for scanning force microscope (SFM) studies on RNA binding proteins. The in vitro transcribed RNA forms a rod-like structure of apparent 130 nm in length with a completely base paired central part flanked by the incompletely paired viroid helix with bulges on both sides. The termini of the molecule consist of loops such that no blunt or staggered RNA ends are exposed. Suitable, asymmetrical restriction sites in the construct allow for the insertion of sequences of interest, e. g. protein binding sites. We have inserted the IRE (iron responsive element) sequence into the construct and have used in vitro transcripts to study binding of IRE-BP. Relative binding frequencies show that 70% of the protein binds to the expected site in the molecule while only a slightly enhanced binding is observed at the termini. In the GUS-PSTVd-IRE backbone, the orientation of the molecule is easily determined by IRE-BP binding. It thus provides a versatile tool to study specific as well as preferential interaction of other proteins with sequences or structures inserted into a different part of the molecule.

Image Processing, Computer-Assisted↗
PubMed2000

c-myc oncogene gene dosage, serum CEA and CA-15.3 antigen levels, and cellular DNA values in relation to ex vivo chemosensitivity of primary human breast cancer.

A pilot study on relationships of selected molecular factors (c-myc oncogene average gene copy numbers (AGCN); serum CEA and CA 15.3 antigen levels; tumor cells' DNA values), to the ex vivo chemosensitivity of primary female human breast cancer in a modified adenosine triphosphate cell viability chemosensitivity assay (ATP-CVA), was performed. Four drug combinations were tested. A group of 75 cases of female primary breast cancer was assessed. Numerous correlations were found among molecular factors tested but none, with the exception of tumor grading, of these reflected ex vivo chemosensitivity of tumors tested. The results suggest that the parameters tested may not be important factors related to adjuvant chemoresponsiveness of primary human breast cancer to tested drug combinations.

Antineoplastic Agents↗
PubMed2000

Relationship of c-myc and erbB oncogene family gene aberrations and other selected factors to ex vivo chemosensitivity of ovarian cancer in the modified ATP-chemosensitivity assay.

A pilot study on relationships of selected molecular factors [erbB-1, erbB-2, erbB-3, and c-myc oncogene average gene copy numbers (AGCN); steroid receptors and pS2 gene expression; tumor cells' DNA values] to the ex vivo chemosensitivity of ovarian cancer in a modified adenosine triphosphate cell viability chemosensitivity assay (ATP-CVA), was performed. Despite the relatively small number of patients, numerous correlations among the factors tested were found. Nevertheless, only c-myc gene dosage positively affected ex vivo chemosensitivity of tumors tested.

Adenosine Triphosphate↗
PubMed1999

[Clinical importance of histology, grading and ploidies in primary breast cancer].

OBJECTIVE: In order to characterise carcinoma of the breast the determination of ploidy can be used in addition to established prognostic factors such as histology and grading. The aim of the investigation was to establish the association between histology, grading and ploidy and to indicate the prognostic and predictive value of these parameters in relation to disease free survival (DFS) and overall survival (OS). MATERIAL AND METHODS: 125 consecutive cases of primary breast carcinoma occurring between the years 1992-1995 were surveyed. The median follow up time lasted 45 months. Correlation analyses were carried out using the Chi-square test, Kaplan-Meier (univariate) and Cox (multivariate) methods. RESULTS: Histology and grading showed no correlation to ploidy but seems to be of importance for DFS in node-negative breast carcinoma. Ploidy did not influence neither DFS nor OS. Ductal histology appeared to be a useful factor in predicting the response of cases treated with an anti-oestrogen (Tamoxifen) since in this group a higher relapse rate of 25% occurred. CONCLUSIONS: Ploidy appears not to be of clinical importance.

Breast Neoplasms↗
PubMed1999

Lack of squamous cell lung carcinoma in vitro chemosensitivity to various drug regimens in the adenosine triphosphate cell viability chemosensitivity assay.

A pilot study on squamous cell lung carcinoma (LC) chemosensitivity in adenosine triphosphate cell viability chemosensitivity assay (ATP-CVA) was performed. Besides the histological investigation, a modified ATP-CVA was used for the analysis of cancer cell chemosensitivity to four drug regimens, including topotecan, a promising agent for non-small-cell lung cancer (NSCLC) chemotherapy. Results of in vitro chemosensitivity testing showed chemoresistance or only weak response in the predominant amount of tumors.

Aged↗