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F Koenig

Publications and source records attributed to F Koenig.

At least 19 recordsLinked to original sources

[The impact of ALA (5-aminolevulinic acid)-fluorescence detection on the prognosis of superficial bladder cancer].

PURPOSE: Throughout the past years, several studies have shown that fluorescence cystoscopy with ALA (5-aminolevulinic acid) improves the detection rate of superficial bladder tumors by approximately 20 % compared to standard white light cystoscopy. These results suggest a reduced rate of residual/recurrent tumors with the routine use of ALA fluorescence technique prior to bladder tumor resection. The present prospectively randomized study was performed to verify this hypothesis. MATERIALS AND METHODS: A total of 115 bladder tumor patients were randomized for initial resection under white light or ALA fluorescence. After 6 to 8 weeks, a second-look resection was performed in all patients guided by ALA fluorescence. Additional white light cystoscopies were performed after 3, 6 and 12 months. RESULTS: The second-look resection did not find a tumor in 31 of 51 (59 %) patients initially resected under white light guidance compared to 43 of 51 (84 %) patients in the fluorescence group. This difference was statistically significant (p = 0.005). At 12 months, a tumor was not found in 17 of 48 patients from the white light group vs. 25 of 47 patients from the fluorescence group (p = 0.03). Seven patients were lost to follow-up. CONCLUSIONS: By reducing otherwise inevitable re-operations, fluorescence cystoscopy decreases morbidity and lowers treatment costs.

Adult↗

Calcium release from sarcoplasmic reticulum is facilitated in human myotubes derived from carriers of the ryanodine receptor type 1 mutations Ile2182Phe and Gly2375Ala.

Malignant hyperthermia (MH) is caused by increased calcium release from sarcoplasmic reticulum, triggered by volatile anesthetics or depolarizing muscle relaxants. Numerous mutations associated with MH have been detected in the skeletal muscle type ryanodine receptor gene (RyR1), but so far facilitated calcium release has only been demonstrated for a few of them. This is a prerequisite for confirming the causative role of an RyR1 mutation for MH. Calcium release from sarcoplasmic reticulum induced by 4-chloro-m-cresol (4CmC), caffeine, and halothane was determined in human myotubes by calcium imaging. The RyR1 Ile2182Phe mutation and the RyR1 Gly2375Ala mutation have been identified in individuals susceptible to MH. In myotubes of individuals carrying the RyR1 Ile2182Phe or the RyR1 Gly2375Ala mutation, the EC(50) for caffeine and halothane was reduced; in the Ile2182Phe myotubes, the EC(50) for 4CmC was also reduced, all consistent with facilitated calcium release from the sarcoplasmic reticulum. From these data we conclude that both mutations are pathogenic for MH.

Adult↗

Child-Pugh versus MELD score in predicting survival in patients undergoing transjugular intrahepatic portosystemic shunt.

BACKGROUND: In patients undergoing transjugular intrahepatic portosystemic shunt (TIPS), prognostic scores may identify those with a poor prognosis or even those with a clear survival benefit. The Child-Pugh score (CPS) is well established but several drawbacks have led to development of the model of end stage liver disease (MELD). AIM: The aim of the study was to compare the predictive power of CPS and MELD, to validate the original MELD formula, and to assess the predictive value of the determinants used in the two prognostic scores outside of a study setting. PATIENTS: A total of 501 patients underwent elective TIPS placement and 475 patients fulfilled the inclusion criteria. METHODS: Data of all patients undergoing elective TIPS in one university hospital and four community hospitals in Vienna, Austria, between 1991 and 2001, were analysed retrospectively. The main statistical tests were Cox proportional hazards regression model, the log rank test, Kaplan-Meier analysis, and concordance c statistics. RESULTS: Median follow up was 5.2 years and median survival was 4.6 years. During follow up, 230 patients died, 75 within three months after TIPS placement. In stepwise proportional hazards analyses, independent predictors of death were creatinine level, bilirubin level, age, and refractory ascites. MELD was better in predicting survival in a stepwise Cox model but both scores were equally predictive in c statistics for one month, three month, and one year survival. Renal function was the strongest independent predictor of survival. CONCLUSIONS: Although MELD was the primary predictor of overall survival in multivariate analysis, c statistics showed that both scores can be used for patients undergoing TIPS with equal accuracy. For assessing prognosis in patients undergoing TIPS implantation, there seems little reason to replace the well established Child-Pugh score.

Adult↗

[Clinical significance of macroscopic 5-aminolevulinic acid (ALA)-inducer fluorescence in transurethral resection of non-invasive bladder cancer].

Macroscopic fluorescence which is induced with aminolevulinic acid (ALA) allows visualizing of small flat tumors, carcinoma in situ, true neoplasm margins and dysplasias of the bladder. Following ALA instillation, cystoscopy was performed under both standard and blue light illumination. In a prospective randomized multicenter study, 102 patients underwent TUR of bladder tumor(s) either with white light or ALA-fluorescence. Significant reduction in the number of residual tumours was detected in 59% (p = 0.005) after 8 weeks, 3 months--in 58% (p = 0.002) and 6 months in 38% (p = 0.01) respectively.

Aminolevulinic Acid↗

Photosystem I from the unusual cyanobacterium Gloeobacter violaceus.

Photosystem I (PS I) from the primitive cyanobacterium Gloeobacter violaceus has been purified and characterised. Despite the fact that the isolated complexes have the same subunit composition as complexes from other cyanobacteria, the amplitude of flash-induced absorption difference spectra indicates a much bigger antenna size with about 150 chlorophylls per P700 as opposed to the usual 90. Image analysis of the PS I preparation from Gloeobacter reveals that the PS I particles exist both in a trimeric and in a monomeric form and that their size and shape closely resembles other cyanobacterial PS I particles. However, the complexes exhibit a higher molecular weight as could be shown by gel filtration. The preparation contains novel polypeptides not related to known Photosystem I subunits. The N-terminal sequence of one of those polypeptides has been determined and reveals no homology to known or hypothetical proteins. Immunoblotting shows a cross-reaction of three of the polypeptide bands with an antibody raised against the major LHC from the diatom Cyclotella cryptica. Electron microscopy reveals a novel T-shaped complex which has never been observed in any other cyanobacterial PS I preparation. 77 K spectra of purified PS I show an extreme blue-shift of the fluorescence emission, indicating an unusual organisation of the PS I antenna system in Gloeobacter.

Journal Article↗

Increased sensitivity to 4-chloro-m-cresol and caffeine in primary myotubes from malignant hyperthermia susceptible individuals carrying the ryanodine receptor 1 Thr2206Met (C6617T) mutation.

Malignant hyperthermia (MH) is an autosomal-dominant disorder of skeletal muscle, triggered by volatile anaesthetics and depolarizing muscle relaxants. The causative defect lies in the control of Ca(2+) release from the sarcoplasmic reticulum in skeletal muscle. Numerous mutations have been detected in the ryanodine receptor 1 (RyR1) gene, but so far an MH-causative role has only been confirmed for 16 human RyR1 mutations. In this report we show that myotubes derived from individuals carrying the RyR1 Thr2206Met (C6617T) mutation have an abnormal response of the intracellular calcium concentration to 4-chloro-m-cresol and to caffeine. Satellite cells were obtained from muscle biopsies of patients referred for diagnosing MH. The intracellular calcium concentration in response to 4-chloro-m-cresol and to caffeine was investigated by fluorescence calcium imaging. In myotubes the half-maximal activation concentration (EC(50)) for 4-chloro-m-cresol was reduced from 203 micro m (wild type) to 98 micro m (Thr2206Met), and for caffeine from 3.8 mm to 1.8 mm. From the reduction of EC(50) we conclude that the RyR1 Thr2206Met mutation is pathogenic for MH.

Amino Acid Substitution↗

Excretion of matrix metalloproteinases 2 and 9 in urine is associated with a high stage and grade of bladder carcinoma.

OBJECTIVES: To analyze the excretion of matrix metalloproteinases (MMPs) 2 and 9 in the urine of patients with bladder cancer according to the stage and grade of tumor and to evaluate their diagnostic clinical validity. In numerous carcinomas, increased expression of MMPs is associated with a higher grade of malignancy and poor prognosis. METHODS: The study population included 44 controls without evidence of malignancy, 14 patients with cystitis, and 43 patients with Stage Ta-T1, 18 patients with Stage T2, and 10 patients with Stage T3-T4 bladder cancer. MMP-2 and MMP-9 excretion in urine samples was measured with gelatin zymography and related to the urine creatinine concentration. The evaluation of data was performed by univariate statistical analysis, logistic regression analysis, and receiver operating characteristic analysis. RESULTS: The upper cutoff limit for MMP-2 and MMP-9 excretion was 277 microg/g creatinine and 648 microg/g creatinine, respectively. Levels of MMP-2 and MMP-9 correlated with each other and with tumor stage and grade. Elevated excretions were mainly observed in patients with invasive tumors (Stage T2-T4). In the receiver operating characteristic analysis, the areas under the curves for MMP-2 and MMP-9 were significantly higher in patients with muscle-invasive than in patients with noninvasive tumors. Related to the cutoff limits, the overall sensitivity to detect bladder cancer was 0.51 for MMP-2 and 0.31 for MMP-9. In logistic regression analysis, MMP-2 showed the best results. CONCLUSIONS: Urinary excretion of MMP-2 and MMP-9 is associated with a high stage and grade of bladder cancer, and they may serve as indicators of tumor progression and recurrence in the future.

Adult↗

Fluorescence endoscopy with 5-aminolevulinic acid reduces early recurrence rate in superficial bladder cancer.

PURPOSE: Several investigators have demonstrated an approximately 20% higher tumor detection rate by 5-aminolevulinic acid (ALA) fluorescence endoscopy compared to standard white light cystoscopy, and suggested a reduction in tumor recurrences when fluorescence endoscopy was performed as standard procedure during transurethral resection. We test this hypothesis. MATERIALS AND METHODS: In a prospective randomized multicenter study 102 patients underwent transurethral resection of bladder tumor(s) either with white light or ALA fluorescence assisted endoscopy. A second look transurethral resection with ALA fluorescence endoscopy was performed 6 weeks after the initial operation. RESULTS: At second look transurethral resection tumor was detected in 20 of 51 patients (39%) in the white light group and in 8 of 51 (16%) in the ALA fluorescence endoscopy group. This difference was statistically significant (p = 0.005). CONCLUSIONS: ALA fluorescence endoscopy is an innocuous and inexpensive diagnostic procedure that significantly improves bladder tumor detection rates compared to standard white light endoscopy. In our controlled study ALA fluorescence endoscopy reduced the residual tumor detection rate at second look transurethral resection by 59%.

Adult↗

Urinary markers of malignancy.

Transitional cell carcinoma (TCC) is the second most common malignancy in the genitourinary tract. The majority of urothelial tumors are superficial when the patient first presents, but despite adequate resection of the primary lesion the recurrence rate is particularly high. In a small but significant group of patients the tumor is primary invasive or subsequently can progress and leads to death. Voided urine can be easily obtained and therefore diagnostic urine tests would be ideal for screening or follow up of TCC. Although many urinary markers have been described, none of them is used routinely in clinical practice. Promising tumor markers still need to be evaluated in multi-center clinical studies. Larger prospective trials are necessary in order to identify prognostic indicators that would help to predict disease progression or response to different treatment modalities (BCG, chemo-, radiotherapy, etc.). Hopefully, new diagnostic urine tests will allow to identify patients who will most benefit from early cystectomy with or without adjuvant treatment, bladder sparing protocols or systemic treatment. In this paper we have reviewed the literature and discuss, from the clinician's point of view, the current status of various diagnostic tests for urinary markers. [Lee SJ, Lee WE, Chang SG, Lee CH, Kim JI. A comparative study of telomerase, Lewis X, BTA, NMP22 and urinary cytology in bladder tumor. J Urol 1999;161(suppl):152.]

Antigens, Neoplasm↗

Laser-induced hyperthermia in rat prostate cancer: role of site of tumor implantation.

OBJECTIVES: To investigate the importance of the site of tumor implantation on the treatment response to laser-induced hyperthermia (LIH) of rat prostate cancer (PCa), because interventional manipulations of PCa have been reported to increase metastatic dissemination. METHODS: Seven to nine days after either subcutaneous or orthotopic implantation of MatLyLu cells, LIH (46.5 degrees C) was induced using pulsed irradiations of a neodymium:yttrium-aluminum-garnet laser. Both local control and distant metastases were evaluated. Plasma metalloproteinase 9 (MMP-9) was tested as a possible marker of PCa progression and LIH response. RESULTS: Twelve days after LIH treatment of subcutaneous tumors, the volumes were reduced by 64% after 8 minutes of irradiation, 73% after 10 minutes, 81% after 15 minutes, and 91.1% after 20 minutes. In the orthotopic model, the corresponding tumor reductions were 44% after 10 minutes, 61% after 20 minutes, and 65% after 30 minutes. Lung metastases were observed in only 1 animal with subcutaneous tumors. In contrast, 86% of the orthotopic tumor-bearing animals treated for 30 minutes had lung metastases compared with 23% of the untreated tumor-bearing rats. MMP-9 expression was detected in both orthotopic and subcutaneous tumor tissue and in the plasma of tumor-bearing rats. The prostate tissue of healthy rats and subcutaneous tumor-bearing rats was devoid of MMP-9. The plasma levels of MMP-9 showed a trend toward direct correlation with local tumor control but no correlation with the incidence of metastasis. CONCLUSIONS: These data emphasize the importance of the site of tumor implantation for evaluation of the efficacy of therapeutic interventions and may warrant further studies before widespread clinical application of LIH as monotherapy.

Animals↗

[Complications of radiotherapy in patients with age-related macular degeneration (AMD). A study of 48 cases].

PURPOSE: This study describes the ocular complications after teletherapy indicated for patients with age-related macular degeneration (AMD). MATERIAL: and methods: The study concerned 48 patients suffering from an exudative form of age-related macular degeneration, non suitable for laser photocoagulation, and irradiated by high-energy electron beam therapy. RESULTS: With a mean follow-up time of 2 years, late effects were observed in 16 (33. 3%) patients: 9 (18.75%) radiation optic neuropathies, 9 radiation retinopathies (18.75%) and 2 neovascular glaucomas (4.1%). CONCLUSION: The frequent and serious complications observed led us to adapt the technique and dose of radiation therapy indicated in patients with age-related macular degeneration.

Aged↗

Near-infrared confocal laser scanning microscopy of bladder tissue in vivo.

OBJECTIVES: To assess the potential of a near-infrared confocal laser scanning microscope (CLSM) for imaging bladder tissue in vivo. METHODS: Confocal images of the exposed bladder of male Sprague-Dawley rats were obtained with a CLSM. To minimize tissue motion, the bladder was placed in light contact under an objective lens housing, and the top surface was lightly flattened with a coverslip. Images were obtained from the outer and inner layers of the bladder wall with a lateral resolution of 0.5 to 1 microm and an axial resolution (section thickness) of 3 to 5 microm. The confocal images were later correlated with routine histologic studies. RESULTS: The CLSM allows imaging of the urothelium, the superficial and deep portions of the lamina propria, the muscularis propria, and the serosa of the bladder wall in vivo. Urothelial cells, collagen bundles and fibers, muscle, and circulating blood cells in capillaries and larger blood vessels are easily visualized. The confocal images correlated well with the histologic studies. CONCLUSIONS: Confocal microscopy allows real-time, high-resolution, high-contrast imaging of cellular and structural morphologic features to a maximal depth of 300 microm within the bladder wall in vivo. Artifacts caused by tissue motion can be minimized with a bladder-objective lens contact housing.

Animals↗

Diagnosis of bladder carcinoma using protoporphyrin IX fluorescence induced by 5-aminolaevulinic acid.

OBJECTIVE: To report the results of a clinical study investigating the diagnosis of malignant and dysplastic bladder lesions by protoporphyrin IX (PPIX) fluorescence and to compare them with those from earlier studies. PATIENTS AND METHODS: The study included 55 patients with suspected bladder carcinoma (at initial diagnosis or at tumour follow-up visits); 130 bladder biopsies from 49 patients were classified by pathological analysis. All patients received an intravesical instillation of 50 mL of a 3% 5-aminolaevulinic acid (ALA) solution a mean of 135 min before cystoscopy, which was then performed under white and blue light. Malignant/dysplastic lesions showing red fluorescence under blue-light excitation were noted and the increase in detection rate calculated. RESULTS: There were 63 benign and 67 malignant/dysplastic areas biopsied; 10 malignant/dysplastic lesions (four transitional cell carcinoma, two carcinoma in situ, four dysplasia) were not detected during routine white-light cystoscopy but were identified under blue light. Fluorescence cystoscopy improved the overall diagnosis of malignant/dysplastic bladder lesions by 18% over standard white-light cystoscopy. The improvement was greater for dysplastic lesions and carcinoma in situ (50%). However, the improvement over standard cystoscopy was less than that found by other groups. CONCLUSION: The ALA-based fluorescence detection system significantly enhanced the diagnosis of malignant/dysplastic bladder lesions. However, determining the optimum drug exposure time requires further investigation using well-characterized instrumentation and study protocols, which would then allow comparison of the results from different groups.

Adult↗

Long term results of radiotherapy for subfoveal choroidal neovascularisation in age related macular degeneration.

BACKGROUND/AIMS: Radiotherapy has been proposed as an alternative treatment for patients with subfoveal choroidal neovascularisation (CNV) that is untreatable according to macular photocoagulation study guidelines. This prospective study was designed to evaluate whether radiotherapy may affect the functional and anatomical outcome in a large cohort of patients affected by subfoveal CNV, with a follow up period up to 24 months. METHODS: 212 patients (231 eyes) with newly diagnosed subfoveal CNV not amenable to laser therapy were included in this study. Two radiotherapy methods, the lateral beam technique (6 MV, 20 Gy in five fractions) and lateral arc therapy (25 MV, 16 to 20 Gy, in four or five fractions), were used. Comparisons of best corrected visual acuity (VA), fluorescein (FA) and indocyanine green (ICG) angiography, at inclusion and 6, 12, 18, and 24 months after radiotherapy were performed using univariate analysis. RESULTS: A VA improvement of two or more lines was observed in 34% at 12 months, 31% at 18 months, and 32% of the eyes at 24 months. Paired comparisons of CNV areas in FA and ICG showed no significant change between baseline and each visit. However, 12 and 18 months after treatment, 47% of the eyes showed a decrease of 10% or more in CNV size both in ICG and FA. Radiation side effects included radiation retinopathy (eight eyes), optic neuropathy (four eyes), choroidal vasculopathy (five eyes), and branch retinal vein occlusion (three eyes). CONCLUSION: Compared with the natural course of subfoveal CNV, the results of this prospective study suggest that radiotherapy could stabilise visual and anatomical outcome in selected cases.

Aged↗

[Metalloproteinases (MMP-1, MMP-3) and their inhibitors (TIMP) in blood plasma of patients with prostate carcinoma].

Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are involved in important processes of tumor invasion and metastasis. In the study presented, matrix metalloproteinase 1 (MMP1) and 3 (MMP3), the tissue inhibitor of metalloproteinase 1 (TIMP1) and the complex MMP1/TIMP1 were measured by ELISA tests specific for these proteins in blood plasma. These components have been investigated in prostate cancer patients (PCa) with metastases (n = 18; T2, 3, 4 pN1, 2M1), prostate cancer patients without metastases (n = 29; T2, 3 pNOMO), patients with benign prostate hyperplasia (BPH; n = 29) and in healthy men (n = 35). Mean values of MMP1 and of the complex MMP1/TIMP1 were not different among the four groups. The mean values of MMP3 and especially TIMP1 were significantly higher in prostate cancer patients with metastases compared with controls, BPH patients and prostate cancer patients without metastases. Ten of these 18 patients had TIMP1 levels higher than the upper reference limit. TIMP1 concentrations correlate to the tumor stage but not to the tumor grade. These results indicate, that TIMP1 could be an potential marker for metastases in prostate cancer patients.

Aged↗

Autofluorescence guided biopsy for the early diagnosis of bladder carcinoma.

PURPOSE: We validate the usefulness of laser-induced autofluorescence for the detection of bladder carcinoma. MATERIALS AND METHODS: We obtained and analyzed fluorescence spectra from 75 patients in whom bladder cancer was suspected. Tissue fluorescence was excited by a nitrogen laser using a quartz optical fiber placed in gentle contact with the area of interest. The laser-induced autofluorescence spectrum was recorded using an intensified optical multichannel analyzer system. Spectra were corrected for the spectral response of the optical system, and the ratios of laser-induced autofluorescence intensities (I) at 385 and 455 nm. (I385/I455) were determined. We had previously established this ratio as a diagnostic algorithm. We included only suspicious bladder lesions (erythematous, edematous, raised and so forth) that were difficult to diagnose by cystoscopy as well as areas from which random biopsies were obtained. The fluorescence ratio algorithm was applied to 130 bladder areas. RESULTS: Of the 130 biopsies obtained during routine cystoscopy 107 (82%) were nonmalignant by histological classification. In contrast, because laser-induced autofluorescence effectively guides biopsies towards malignant lesions, only 30 biopsies (72% fewer) would have been obtained from nonmalignant tissue if the fluorescence ratio that identifies 95% of malignant lesions (95th percentile) had been selected as the decision criterion during standard cystoscopy. CONCLUSIONS: By guiding the surgeon to suspicious lesions that are most likely to be malignant, laser-induced autofluorescence substantially decreases the number of biopsies obtained from nonmalignant tissue during cystoscopy to diagnose bladder carcinoma.

Aged↗