Novel biomarkers of acute kidney toxicity.

Novel biomarkers of kidney toxicity are powerful tools not only with respect to their clinical applications but also because of their impact on drug development. These biomarkers can influence the assessment of efficacy of new drugs for kidney diseases as well as the risk management for new drugs. The science behind these novel biomarkers reflects the evolution over the past decade of genomic and proteomic platforms that have transformed the discovery and development of new biomarkers for preclinical and clinical applications in drug development. Several of these biomarkers are in use as transcriptomic biomarkers in animal models as well as translational proteomic biomarkers in animal models and in humans. Their ability to detect kidney damage earlier than is possible with currently accessible biomarkers is being given qualification through regulatory biomarker-qualification programs, which will help establish consensus for their widespread use.

Quantification of the refrigerants R22 and R134a in mixtures by means of different polymers and reflectometric interference spectroscopy.

The aim of this study was the quantification of vapors of the ozone-depleting refrigerant R22 in the presence of its most important substitute R134a, by the use of the reflectometric interference spectroscopy and polymers as sensitive layers. First, the sorption characteristic of different types of polymers exposed to the vapors of the two analytes was investigated. Then, binary mixtures of the two refrigerants were measured with an array set-up on the basis of six polymer sensors. The measurements were evaluated by the use of neural networks, whereby low limits of detection of 0.45 percentage volume (vol. %)for R22 and 1.45 vol. % for R134a could be established. Additionally, one polar polymer and one microporous polymer were selected for the measurements with a low-cost set-up. The quantification of R22 in the presence of R134a with this low-cost set-up was possible with a limit of detection of 0.44 vol. %, which would enable a fast and economical monitoring at recycling stations.

Quantification of butanol and ethanol in aqueous phases by reflectometric interference spectroscopy--different approaches to multivariate calibration.

This paper presents several methods for analysis of data from reflectometric interference spectroscopic measurements (RIfS) of water samples. The set-up consists of three sensors with different polymer layers. Mixtures of butanol and ethanol in water were measured from 0 to 12,000 ppm each. The data space was characterized by principal component analysis (PCA). Calibration and prediction were achieved by multivariate methods, e.g. multiple linear regression (MLR), partial least squares (PLS) with additional predictors, and quadratic partial least squares (Q-PLS), and by use of artificial neural networks. Artificial neural networks gave the best results of all the calibration methods used. Calibration and prediction of the concentration of the two analytes by artificial neural nets were robust and the set-up could be reduced to only two sensors without deterioration of the prediction.

High-dose MTX/5-FU and adriamycin for gastric cancer.

In a phase II trial we tried to evaluate the efficacy of a sequential combination of high-dose methotrexate (MTX) and 5-fluorouracil (5-FU) combined with Adriamycin (ADM). In a pilot study we had found high-dose MTX effective as a single agent in gastric cancer. MTX and 5-FU were combined sequentially because Cadman et al had shown synergism for this combination. The therapy protocol consisted of high-dose MTX, 1.5 g/m2 of body surface, and high-dose 5-FU, 1.5 g/m2. MTX was administered 1 hr prior to 5-FU. Both drugs were given as a bolus. Twenty-four hours after MTX administration, citrovorum factor rescue was started, 15 mg/m2, q.6h. X 12, orally. Forty-eight hours after MTX administration, serum concentration of the drug was measured by high performance liquid chromatography (HPLC). Fourteen days after MTX was given, ADM, 30 mg/m2, was injected as a bolus. This protocol was repeated every 28 days. Patients eligible for this treatment should have a creatinine clearance of greater than 60 ml/min. The study included 30 patients with metastasizing gastric cancer and performance status between 40% and 70%. The response rate was 63% (19 of 30 patients). Two of 30 patients had complete remissions, which are still maintained. The median survival for responders is not yet evaluable: 68% are living after 17+ mo. The median survival for nonresponders was only 5 mo. The difference in survival curves is significant at a level of p less than 0.05. Cytostatic treatment was well tolerated. Fifty percent of the patients could be treated on an outpatient basis. Total alopecia was observed in only 10% of the patients. Severe leukopenia, thrombocytopenia, and kidney disorders were not observed.

[Chemotherapy schedule for the management of metastasizing gastric cancer. Methotrexate, adriamycin and 5-fluorouracil]. / Chemotherapieprotokoll zur Behandlung des metastasierenden Magenkarzinoms. Methotrexat, Adriamycin und 5-Fluorouracil.

The possible effectiveness of methotrexate, 5-fluorouracil and adriamycin was tested in a phase I/II study of patients with metastasising gastric carcinoma. complete of partial remission occurred in 19 of 30 patients (approximately 63%). Two of 30 patients had complete remission. Median survival time of patients with remission cannot as yet be determined: about 68% are still alive after 17 months. Median survival time of patients with advanced tumour was only five months. The difference in survival curve is statistically significant (P less than 0.05). The study is continuing.