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W Wolf

Publications and source records attributed to W Wolf.

At least 91 records · Page 5Linked to original sources
PubMed1990

A kinetic model for 99mTc-DMSA in the rat.

A pharmacokinetic model was developed for the renal imaging agent 99mTc-DMSA in anesthetized rats, which incorporated data from serial measurements of blood and urine simultaneously with dynamic images obtained over an 8-h period. Animals which received a 10 mg/kg dose of unlabeled DMSA immediately before 99mTc-DMSA injection had a significantly reduced kidney accumulation and greater urinary elimination of 99mTc than animals which received the radiopharmaceutical alone. The kidney clearance was also significantly lower in rats receiving unlabeled DMSA, but no significant difference was determined between the urine clearance estimates of the two animal groups. Because the increase in the amount eliminated in the urine was not coupled with a significant change in urine clearance, it would appear that unlabeled DMSA saturated the kidney uptake mechanism(s) of 99mTc-DMSA without modifying the urinary clearance process. This interpretation is consistent with the hypothesis that renal handling of 99mTc-DMSA is governed by both glomerular filtration and peritubular capillary uptake. The simultaneous acquisition of blood, urine and non invasive image data allows for a comprehensive and informative model of the physiological disposition of 99mTc-DMSA.

Animals↗
PubMed1990

Quantitative subcellular distribution of platinum in rat tissues following i.v. bolus and i.v. infusion of cisplatin.

An analysis of the subcellular localization of platinum was conducted in Sprague-Dawley (SD) rats following administration of an i.v. dose of 6 mg/kg cisplatin (bolus and infusion). Biodistribution studies were carried out in the liver and kidney of control animals, as well as in these same organs and in the tumor (Walker 256 adenocarcinoma) of SD rats. The results obtained illustrate that in addition to the platination of DNA in these tissues, significant amounts of Pt are also incorporated into the chromosomal protein (CP) and cytosolic fractions. The localization of Pt in the cytosolic fractions was highest in the kidney, followed by the tumor, and lowest in the liver when determined as the fractional percentage of the total amount of injected drug (%ID/g). The significance of such cytosolic and CP localization of Pt is not known at this time, but they may be involved in the cytotoxic effects of cisplatin, as this drug is cytotoxic to tumors and kidneys but not to the liver. The localization of cisplatin in the subcellular fractions of liver, kidney, and tumor showed a trend toward being higher after i.v. infusion than after i.v. bolus administration of the drug.

Animals↗
PubMed1990

Tumor trapping of 5-fluorouracil: in vivo 19F NMR spectroscopic pharmacokinetics in tumor-bearing humans and rabbits.

The pharmacokinetics of 5-fluorouracil (5FU) were studied in vivo in patients with discrete tumors and in rabbits bearing VX2 tumors by using 19F NMR spectroscopy. The human studies were conducted in a 1.5-T Magnetom magnetic resonance imager (Siemens), and the rabbit studies were conducted in a 4.7-T GE/Nicolet 33-cm bore magnet. Free 5FU was detected in the tumors of four of the six patients and in all VX2 tumors but not in normal rabbit tissues. No other metabolites were seen in these tumors, contrary to the extensive catabolism we had previously documented using 19F NMR spectroscopy in both human and animal livers. The tumor pool of free 5FU in those human tumors that trapped 5FU was determined to have a half-life of 0.4-2.1 hr, much longer than expected and significantly longer than the half-life of 5FU in blood (5-15 min), whereas the half-life of trapped 5FU in the VX2 tumors ranged from 1.05 to 1.22 hr. In this initial experience, patient response to chemotherapy may correlate with extent of trapping free 5FU in the human tumors. These studies document that NMR spectroscopy is clinically feasible in vivo, allows noninvasive pharmacokinetic analyses at a drug-target tissue in real time, and may produce therapeutically important information at the time of drug administration. Demonstration of the trapping of 5FU in tumors provides both a model for studying metabolic modulation in experimental tumors (in animals) and a method for testing modulation strategies clinically (in patients).

Adenocarcinoma↗
PubMed1990

Human tumor fluorouracil trapping: clinical correlations of in vivo 19F nuclear magnetic resonance spectroscopy pharmacokinetics.

We previously reported that fluorouracil (5FU) accumulation and metabolism in human livers and tumors can be studied by in vivo nuclear magnetic resonance spectroscopy (NMRS). We have extended these observations by evaluating the pharmacokinetics of 5FU in the tumors of 11 patients with carcinoma of the breast, colon, endometrium, cervix, and kidney, using 19F-NMRS in a 1.5 Magnetom (Siemens Medical Systems, Cerrito, CA) magnetic resonance imaging unit (MRI). These NMRS measurements detected a long-lived tumor pool of 5FU in six of 11 tumors in our patients including carcinomas in the pelvis, breast, lung, and liver. The half-life (T1/2) of this tumor pool of "trapped" 5FU was 0.33 to 1.3 hours (20 to 78 minutes), much longer than the T1/2 of 5FU in blood (5 to 15 minutes). Neither the anabolites of 5FU (fluorinated nucleosides, nucleotides, 5FU-RNA, or 5FU-thymidylate synthase) nor the catabolites (eg, fluorobetaalanine [FBAL]) were detectable by 19F NMRS. Patient response to chemotherapy appeared to correlate with the extent of trapping of free 5FU in the human tumors: in the seven patients receiving 5FU, or 5FU or FUdR plus leucovorin, four of four patients whose tumors trapped 5FU responded to fluorinated pyrimidine chemotherapy, whereas three patients in whom there was a failure to detect tumor trapping were resistant to 5FU. We conclude that NMRS is clinically feasible, and enables investigators to study 5FU pharmacokinetics and metabolism in tumors in vivo. 19F-NMRS of 5FU allows for in vivo evaluation of 5FU metabolic modulation and might be able to guide therapeutic decisions.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

A new radiochemical method to determine the stability constants of metal chelates attached to a protein.

A new method was developed to determine the stability constants of bifunctional chelates of indium (In) coupled to a protein. This method utilizes the displacement reaction between an indium complex and ferric ion. By measuring the position equilibrium constant 'K' of this reaction and knowing the stability constant of the corresponding ferric chelate, the overall formation constant of the indium chelate can be determined. Human serum albumin (HSA) was conjugated with ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) using their cyclic dianhydrides. A new method was developed to couple triethylenetetraminehexaacetic acid (TTHA) with HSA using Woodward's Reagent K. The chelating agents coupled to HSA were complexed with indium-114m-(114mIn) labeled indium and purified by dialysis or microcentrifugation. The stability constants of these indium complexes were determined at physiologic pH using ferric chelate of nitrilotriacetic acid (Fe-NTA) as the source of ferric ion. No significant differences were found between the stability constants of the indium chelates conjugated to protein and those of unconjugated species.

Acetates↗
PubMed1990

[2-stage, bilateral femoral amputation in severe arteriosclerosis].

It is reported about 26 patients with lower extremity amputation above knee on both sides in two times because most hardest vascular insufficiency. Amputation is necessary, if all other treatment are unsuccessful or impossible. In these very difficult cases amputation was made on second leg to save life. Especially the problems of treatment after operation are explained.

Aged↗
PubMed1989

Collateral nerve sprouting and twitch forces of single motor units in conditions with partial denervation in man.

Single motor units (MUs) were studied in the first dorsal interosseus muscle of 7 patients with slight partial denervation and in 10 controls. MU action potentials were recorded using the macro-EMG technique and their size was taken to assess collateral nerve sprouting. Simultaneously, the muscle force was monitored to determine the voluntary recruitment thresholds of the MUs and spike-triggered-averaging was applied to measure their twitch forces. At comparable force recruitment thresholds, both macro-EMG potentials and twitch forces were increased in the patients. We conclude, that collateral nerve sprouting increases MU force and can compensate for MU loss.

Adult↗
PubMed1989

Compartmental biodistribution of a monoclonal antibody against human lung adenocarcinoma grown in athymic mice.

The biodistribution of the radioiodinated monoclonal antibody KS1/4 and of its F(ab) and F(ab')2 fragments were studied in tumor-bearing nude mice. Intravenous administration of the intact antibody resulted in the highest tumor retention and tumor/blood ratios. No metabolites or antigen-antibody conjugates were detectable, in serum, by HPLC analyses. Reasonable correlations were obtained between the estimated time-course of KS1/4 and experimental biodistribution data using an eight-compartment linear radiopharmacokinetic model, suggesting that such models may be useful in predicting the biodistribution and effective targeting of this monoclonal antibody.

Adenocarcinoma↗
PubMed1989

American Indian youth and drugs, 1976-87: a continuing problem.

Continuing surveillance of drug use among American Indian adolescents living on reservations shows them to have rates of use higher than those of their non-Indian counterparts. Marijuana use is particularly high among Indian students. By the 7th grade a significant number of Indian youth have tried drugs, particularly marijuana and alcohol, and there are few significant differences by gender. Based on observed patterns of use, intervention strategies need to begin in the elementary school years and target both males and females equally.

Adolescent↗
PubMed1989

The impact of paired motor unit discharges on tremor.

We studied paired discharges (PDs) of single motor units (MUs) of the first dorsal interosseus muscle in parkinsonian and essential tremor. The number of PDs increased with increasing tremor strength and the duration of their intervals shortened. The amplitudes of the single tremor beats showed a significant negative correlation to the duration of the intervals of the preceding PDs. It is concluded that PDs play an important role as tremor amplifiers. The basic mechanism is probably the more than linear summation of two twitch contractions with short interval which is known from animal experiments.

Adult↗
PubMed1988

[Double discharges of motor units and tremor strength].

The relationship between the double-discharges (DDs) of single motor units (MUs) and the tremor strength was studied in 7 patients with parkinsonism and 3 with essential tremor. The potentials of single MUs and the force of the first dorsal interosseus muscle were recorded during slight isometric contractions. The rate of DDs and their interval duration were correlated with the global tremor strength and the amplitudes of the single tremor beats. With increasing tremor strength, the rate of DDs increased and the duration of their intervals decreased. It is concluded that DDs act as tremor amplifiers. This effect is probably accounted for by a more than linear summation of two consecutive MU contractions with short interval which is known from animal experiments.

Adult↗
PubMed1988

Aortic arch thrombosis in the neonate.

Thrombotic occlusion of the aortic arch in the neonate is a rare lesion for which successful operative repair with survival beyond the immediate postoperative period has not been previously reported. We report a case in which surgical repair of this lesion with survival was achieved and discuss the diagnostic and technical aspects of management of aortic arch thrombosis in the neonate.

Aorta, Thoracic↗
PubMed1987

Influence of saccades on manual reactions--a reaction time and VEP study.

Experiments were performed to investigate the retardation of motor reactions, triggered immediately after saccadic eye movements, by comparing VEP latencies and manual reaction times. As visual stimuli grating patterns of different spatial frequencies were used. They were presented during continuous fixation ("resting eye" condition) as well as shortly after a saccade ("saccadic" condition) with different onset delays (25, 50, 100, 150 msec), in order to determine the influence of saccades on VEP latencies and on manual reaction times. Compared with the reaction times in the "resting eye" condition, the postsaccadic reaction times were much prolonged whereas the respective VEP latencies are almost unchanged. Thus an inhibitory interaction of different motor responses (i.e. saccadic eye movements and manual reactions in this study) at higher levels of the afferent system or at the motor control site is postulated. This result has been confirmed for stimuli of different spatial frequencies.

Evoked Potentials, Visual↗
PubMed1987

Fluorine-19 NMR spectroscopic studies of the metabolism of 5-fluorouracil in the liver of patients undergoing chemotherapy.

Fluorine-19 nuclear magnetic resonance allows direct observation of fluorinated drugs and their metabolites in the human body without background signal from the tissue. A well-known fluorinated chemotherapeutic drug, 5-fluorouracil, and its metabolites were observed noninvasively in the liver of three patients undergoing cancer chemotherapy. Spectra were obtained at 1.5 T with a surface coil centered over the right lobe of the patient's liver. Administration of 1.5 gm of 5-fluorouracil was done after positioning in the magnet. Serial spectra, collected over a 2-h period, revealed both the nature of the metabolites present in the liver, and the time course of each patient's metabolism. These observations represent the first noninvasive NMR study of drugs in human patients and show the feasibility of using in vivo F-19 NMR spectroscopy for human studies of fluorinated compounds.

Female↗