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Biomedical subjects

W Wolf

Publications and source records attributed to W Wolf.

At least 145 records · Page 8Linked to original sources

Metabolic and distribution studies with radiolabeled 5-fluorouracil.

5-Fluorouracil (5-FU) is an effective anti-tumor drug, which has been used both as a single agent and in combination with other chemotherapeutic agents for the treatment of tumors such as breast and colorectal carcinoma. We synthesized 5-FU with trace amounts of 18F-5-FU and administered the compounds intravenously to 6 cancer patients. The patients were scanned at 2 hr intervals for 12 hrs and their urine collected whenever possible. We also injected 5-FU with the tracer 18F-5-FU, at pharmacological doses, into non-tumored rats, and sampled their bile and blood for 95 mins post-injection. For comparison, 2-14C-5-FU was injected into non-tumored rats and their bile and blood sampled at the same intervals. Minute quantities of rat bile and serum were analyzed chromatographically by high-performance TLC. 5-FU and two of its metabolites (FBAL and FUPA) were identified and quantified by this technique. Both percentage and absolute amounts of 5-FU in the bile follow comparative kinetic patterns. While the liver and the urinary bladder were clearly observable in all 16 patients, the detectability of the gall-bladder was correlated to the inverse of the alkaline phosphatase level in the blood. This work suggests that the diversity of the 5-FU metabolism in cancer patients may allow the use of 18F-5-FU as a probe for understanding those individual variabilities in clinical situations.

Adenocarcinoma↗

Review of nuclear pharmacy practice in hospitals.

An operational profile for nuclear pharmacy practice is presented, and the technical and professional role of nuclear pharmacists is reviewed. Key aspects of nuclear pharmacy practice in hospitals discussed are the basic facilities and equipment for the preparation, quality control, and distribution of radioactive drug products. Standards for receiving, storing, and processing radioactive material are described. The elements of a radiopharmaceutical quality assurance program, including the working procedures, documentation systems, data analysis, and specific control tests, are presented. Details of dose preparation and administration and systems of inventory control for radioactive products are outlined.

Facility Design and Construction↗

Renal toxicity studies of protein-bound platinum(cis).

Incubation of dialyzed rat serum with cisplatin at a concentration of 908 ppm results in binding of platinum to the proteins and electrophoretic evidence of protein alterations. Intravenous administration of protein-bound platinum(cis), containing the same platinum content as an 8.5-mg/kg dose of cisplatin, fails to produce elevated serum BUN and creatinine levels as do equivalent doses of 'free' cisplatin in 0.9% saline. Light microscopy of the right side kidneys of rats receiving protein-bound platinum(cis) revealed no obvious pathology while the kidneys of rats receiving 'free' cisplatin showed consistent pathological alterations including hydropic degeneration and pyknotic nuclei. These observations suggest that a protein-bound form of platinum will be unlikely to contribute to the renal toxicity observed during cisplatin chemotherapy.

Animals↗

Haloperidol-induced reduction of nigral substance P-like immunoreactivity: a probe for the interactions between dopamine and substance P neuronal systems.

Protracted blockade of dopamine receptors by haloperidol has been shown to cause a reduction in nigral content of substance P-like immunoreactivity (SPLI). This pharmacological effect is used to study the mechanisms whereby the dopaminergic and substance P systems interact. Data presented in this paper suggest that 1) blockade of dopamine postsynaptic receptors alters nigral SPLI levels associated with the substance P striatal-nigral loop, 2) destruction of the nigral-striatal dopaminergic pathway results in changes in nigral content of SPLI similar to that induced by haloperidol, 3) several weeks after nigral-striatal lesions, compensatory mechanisms mediate a return of nigral SPLI content to control levels and 4) substance P striatal-nigral circuits continue to respond to dopaminergic input after kainic acid lesions in the anterior striatum, whereas properly placed mechanical striatal-nigral lesions appear to be effective in preventing this interaction. The data support a dynamic role for striatal-nigral substance P fibers in the extrapyramidal circuitry and suggest that his pathway must be accounted for when studying the interactions of transmitter systems within this locomotor center.

Animals↗

[Experiences with transluminal angioplasty in critical coronary artery stenosis (author's transl)].

In this study the first results of percutaneous transluminal angioplasty (TAP) at the university hospital of Graz, Department of internal Medicine, are presented. Out of 19 attempts in 18 patients (one with two vessel-disease) 15 were angiographically successful (79%). In three cases the stenosis could not be passed, in one patient with previous non transmural anterior infarction the vessel was nearly occluded after the procedure. Serum CK-levels of this patient increased up to the fourfold on the following day; however, no clinical or electrocardiographic features or reinfarction occurred. In the majority of patients the dilatation of the obstruction was accompanied by a diminuation of the gradient across the stenosis and followed by a significant clinical improvement, increase in exercise tolerance (64% of cases) and the degree of 201Tl-redistribution as a sign of disappearance of exercise-induced myocardial ischemia was normalized in 6 of 8 patients (75%). No serious complications were noted in this group of patients.

Adult↗

Preparation and metabolism of a cisplatin/serum protein complex.

195mPt-cis-Dichlorodiammine platinum(II) (195mPt-cisplatin) binds in vitro essentially irreversibly to bovine serum albumin (BSA) and rat plasma proteins at a 195mPt-cisplatin/protein molar ratio of 1:1 or less. The binding to rat serum proteins shows no apparent specificity, with albumin retaining the greatest fraction of the label (40-55%). The binding is neither instantaneous nor linear with time. Upon intravenous administration to rats of a rat serum protein bound 195mPt-cisplatin, the label remains bound to the proteins while in the blood. The label is cleared from the blood faster than a relatively native 131I-labeled human serum albumin (HSA) and accumulates primarily in the liver. The blood disappearance and organ distribution of the rat serum protein bound 195mPt-cisplatin is consistent with a modified protein. Approx. 11% of the injected dose was excreted via the urine in 24 h in a form which has a different chromatographic mobility than free 195mPt-cisplatin. Since little intact protein is lost in the urine, the excreted label probably represents the product(s) of metabolism of the rat serum bound 195mPt-cisplatin. Due to the apparent irreversibility (both in vivo and in vitro) of the protein/195mPt-cisplatin complex, it is unlikely that the protein bound fraction of the administered 'free' drug will serve as a therapeutically useful 'drug resevoir'.

Animals↗

Clinical results in the management of patients with uterine sarcoma.

From 24 Patients which were treated for uterine sarcomas during 1970-1977, 10 patients had a leiomyosarcoma, 6 an endometrial stromal sarcoma, and 8 a mixed mesodermal sarcoma. Surgical treatment was performed in 15 cases, and in 13 cases was followed by postoperative radiation. Eight patients were treated primarily by combined radium and cobalt 60 radiation therapy. Seventeen of 24 patients under control died, 15 of these within on year after onset of therapy. Regarding the histological patterns of sarcomas, both mitotic activity and vascular invasion was without significance in subsequent outcome.

Female↗

[Use of mezlocillin in open heart surgery (author's transl)].

Concentrations of mezlocillin in serum and heart tissue were studied in 29 patients undergoing open heart surgery. The antibiotic agent was administered three times as a bolus injection of 2 grams each: after induction of anaesthesia, after initiation of extracorporeal bypass (ECC) and shortly after discontinuation of ECC. Serum levels were measured in 25 patients from samples drawn 30 minutes after the bolus injection and subsequently biologic assays were carried out by the agar diffusion method. The mean initial values during the three phases of surgery were 119.2, 170.6 and 236.0 micrograms/ml, respectively; at 60 minutes the values were 61.3, 100.8 and 101.9 micrograms/ml. Calculation of the exponential curve enabled a mathematical comparison of the half-life of the substance during the pre-ECC, ECC and post-ECC periods. The most rapid elimination was found to occur prior to initiation of ECC, the slowest during ECC, while in the post-ECC period the elimination was similar to, but somewhat slower than that of, the pre-ECC period. The concentration, measured in the tissue of eleven aortic valves, averaged 35.96 (range 8.4 to 63.4) micrograms/ml. The mean concentration found in papillary muscles of the left ventricle, resected at the time of mitral valve replacement in six patients, was 31.54% (range 17.7 to 58.33) micrograms/ml. Mean tissue concentration found in five resected mitral valves was 43.77 (range 27.33 to 71.5) micrograms/ml. The findings indicate that mezlocillin, administered as described, will reach serum and tissue concentrations at all periods of open heart surgery well above those of the minimum inhibitory concentration of most clinically relevant bacteria.

Cardiac Surgical Procedures↗

[Central disequilibrium in boxers (author's transl)].

In 20 boxers the vestibular examination was made with pendular test. In 75% central vestibular changes of the per-rotatary nystagmus reaction were observes. Only in 3 cases the electronystagmogram was unremarkable. In 4 cases the EEG was normal although the nystagmus reaction was pathologic indicating central disorders.

Adult↗