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Biomedical subjects

Walter Wolf

Publications and source records attributed to Walter Wolf.

6 recordsLinked to original sources

Noninvasive methods to study drug distribution.

Positron emission tomography (PET) and nuclear magnetic resonance spectroscopy (MRS) are two techniques that allow the noninvasive monitoring of drug distribution in living systems (humans, animals), and dynamic contrast-enhanced magnetic resonance imaging (dMRI) provides noninvasive physiological information relevant for drug distribution. PET yields series of cross-sectional images that can be used to monitor the absolute radioactivity concentrations in tissues pixel-by-pixel, but does not allow direct identification of each of the products present. MRS produces spectra showing changes in the concentration of both the parent drug and of the metabolites separately for a sensitive volume, but does not provide a simple means for measuring absolute concentrations. dMRI, which measures the changes in the rates of relaxation of water, proportional to the concentrations of the contrast agent (usually Gd-DTPA), readily allows the determination of functional changes in cross-sectional images down to a pixel-by-pixel level. All of these methods are of special interest to evaluate the amounts of drug that can reach the target tissue, penetrate it, remain present at such targets for a sufficient length of time, and how they are metabolized at the target site. Such information may be of particular interest in the study of solid malignant tumors and may become very relevant for determining better treatment strategies. This article presents examples of successful studies of tissue pharmacokinetics with MRS and dMRI. The following article is devoted to PET.

Animals↗

New food technologies and processes and their impact on nutrition.

An evaluation of new technologies already applied or still under investigation has shown that those procedures allow a mild treatment mostly of liquid food materials. If also Osmotic Processing, Ionising Irradiation, Carbon-Dioxide High-Pressure-Gas treatment, Ultra-Sound treatment and Gas-Plasma treatment are considered a large array of new processes is available for processing of food with minimum impact on compounds of nutritional relevance. Those processes must however be operated under very special conditions in order to comply with hygienic standards. Since all this processes require very sophisticated equipment it is too early at the moment to predict which one of the New Technologies will survive the fierce competition with the classic and well established processes and which do not fall under the Novel Food Regulation of the EU. It must be stated however that the pressure which did arise from the New Technologies has initiated many developments in the area of the classical technologies which had at the very end an impact also on the quality of products produced with those procedures.

Food Handling↗

Does leucovorin alter the intratumoral pharmacokinetics of 5-fluorouracil (5-FU)? A Southwest Oncology Group study.

PURPOSE AND DESIGN: We previously documented that there was an association between the intra-tumoral pharmacokinetics (TPK) of 5-FU and response to therapy with 5-FU and leucovorin (p < .0001). Since we have shown that other modulators of 5-FU, such as methotrexate, interferon and neutrexin alter its TPK, it was of interest to determine if the modulating effect of leucovorin would also alter the tumoral PK of 5-FU. In order to determine the effect of leucovorin on intratumoral 5-FU pharmacokinetics, 23 patients (21 evaluable) underwent 19F magnetic resonance spectroscopy (19F-MRS) twice. The first 19F-MRS was following 5-FU 600 mg/m2 alone, and the second 19F-MRS was following by leucovorin 500 mg/m2 and then 5-FU 600 mg/m2. RESULTS: A comparison of the intratumoral 5-FU pharmacokinetics indicated that there was no general effect of leucovorin on the intratumoral half-life of 5-FU. In only two of these 21 patients was the half-life of 5-FU altered, and in both cases it was decreased by more than 20%. Partial responses to 5-FU plus leucovorin therapy were seen only in patients with a long intratumoral half-life (trapping) of 5-FU (3 PR in 11 patients with T1/2 > or = 20 minutes, compared to 0 PR in 11 patients with T1/2 < 20 minutes). There was a statistically significant correlation between tumor response and the intratumoral T1/2 of 5-FU, consistent with our prior results in a larger number of patients. However, there was no statistically significant correlation of time-to-progression or survival with classification of the patients into trappers or non-trappers, probably due to the small sample size in this current study. CONCLUSION: The data reported here are compatible with the hypothesis that leucovorin enhancement of 5-fluorouracil antitumor responses is not mediated by the levels of 5-FU in tumors, but rather, is due to the modulation by leucovorin of cellular metabolic processes that follow the uptake of free 5-FU into the tumor cell. The MRS technique may be useful in selected instances for elucidating the possible metabolic interactions of drugs in vivo.

Adult↗

Value of intravascular ultrasound for endovascular stent-graft placement in aortic dissection and aneurysm.

BACKGROUND: Endovascular stent-graft placement is a new concept for the treatment of aortic dissection and aneurysm. Intravascular ultrasound (IVUS) with established diagnostic features may be instrumental in guiding endovascular procedures. METHODS: We performed IVUS and digital angiography before, during, and after implantation of 47 stent grafts in 40 patients with Stanford type B dissection (26 patients, 28 stent grafts), thoracic aneurysm (9 patients, 11 stent grafts), and abdominal aneurysm (5 patients, 8 stent grafts). RESULTS: IVUS could clearly identify the aortic anatomy and differentiate between true and false lumen in all cases of dissection. In four patients with type B dissection extending from the thoracic to the abdominal aorta the true lumen was exclusively identified by IVUS, and thus, essential for safe execution of the procedure. In another patient stent-graft placement in the aorta was optimized by covering a second entry detected by IVUS, but undetected by angiography. The site of stent implantation, the true and false lumen, as well as entry and reentry were always identified in both thoracic and abdominal aorta. In comparison with angiography, IVUS information led to additional balloon molding due to incomplete stent apposition in seven cases. CONCLUSIONS: As an adjunctive imaging modality IVUS is likely to improve stent-graft placement in aortic type B dissection, especially in patients with abdominal extension.

Adult↗