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Biomedical subjects

A J Weiss

Publications and source records attributed to A J Weiss.

At least 37 records · Page 2Linked to original sources
PubMed1983

A hypothesis concerning the effect of changes in scheduling upon the cardiotoxicity of adriamycin.

Evidence is accumulating that the cardiotoxicity of adriamycin is a function of not only total dosage but of scheduling, with those schedules associated with low peak plasma levels of the drug being associated with significant decrease in cardiac toxicity. It is believed that adriamycin enters the cell by passive diffusion, and most cells studied, both normal and neoplastic, have an active excretory mechanism that pumps adriamycin out of the cell. If it is assumed that the myocardium has such a pump then it can be shown pharmacokinetically that those schedules associated with a low peak plasma level can, under certain circumstances, selectively protect the myocardium.

Doxorubicin↗
PubMed1982

Preoperative embolization of retroperitoneal hemangiopericytomas as an aid in their removal.

The first reported cases of preoperatively embolized hemangiopericytomas are presented. Both lesions presented in the retroperitoneum where most lesions are now considered to be malignant. In the past, the highly vascular nature of these tumors has made resection in these areas difficult. Since the angiographic picture of hemangiopericytomas is now thought to be specific, it became feasible to add preoperative embolization to the overall management of these cases. In the first case, the diagnosis had been established 15 years previously. When first seen at Thomas Jefferson University Hospital, extensive bone destruction of the sacrum and lumbar vertebrae were present. Preoperative Gelfoam embolization aided in the palliative debulking of the tumor at operation. With this experience, preoperative embolization became part of the management in the second case and aided in the complete surgical removal of the tumor. Radiation therapy in the dosage of 5000 rad was given postoperatively in this case and should also be part of the treatment plan for these lesions.

Adult↗
PubMed1981

Protection of mice against 7,12-dimethylbenz(a)anthracene-induced skin tumors by immunization with a fluorinated analog of the carcinogen.

5-Fluoro-12-methylbenzanthryl-7-acetic acid (5-FMBAAA) is an analog of the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) with little or no carcinogenic activity. CD-1 mice immunized with 5-FMBAAA conjugated to bovine serum albumin (BSA) developed serum antibodies capable of binding DMBA. As a means of testing whether this immunization protected against DMBA-induced tumors, a low-dose carcinogenesis model system was developed, entailing the repeated skin application of 25 ng DMBA in dodecane alternating with applications of the tumor promoter, phorbol myristate acetate. Mice immunized with the 5-FMBAAA:BSA conjugate and subsequently exposed to this low-dose regimen for 40 weeks developed significantly fewer skin tumors (0.23 papilloma/mouse) than did unimmunized mice, mice immunized with BSA, or mice immunized with an unconjugated mixture of BSA and 5-FMBAAA (0.47 to 0.54 papilloma/mouse). Immunization did not reduce tumor incidence in mice treated with phorbol myristate acetate alone. The results suggest that, when mice are exposed to a carcinogen at doses low enough to approach environmental levels, immunization against the carcinogen can provide specific protection.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1980

Analysis of procarbazine and metabolites by gas chromatography-mass spectrometry.

Twelve compounds representing procarbazine, seven metabolites, and an internal standard were analyzed by gas chromatography-mass spectrometry on a 3% OV-1 column. Procarbazine and four metabolites were derivatized with acetic anhydride. A sensitive, specific and quantitative assay was established by selected ion monitoring using a synthetic analogue of the drug as an internal standard. The limits of detection were approximately 1 ng/ml of plasma while the limits of quantitation were 10 ng/ml of plasma. Studies of the degradation of procarbazine . HCl in 0.05 M phosphate buffer (pH 7.4) were compared to in vivo studies. At 1 h after incubation of procarbazine . HCl in buffer, the azo and aldehyde metabolites were detected in the highest concentrations representing 27.2% and 20.3% of total drug and metabolites. In the in vivo studies, analyses of rat plasmas indicated that 1 h after an oral dose of procarbazine . HCl, the aldehyde metabolite represented 72% of the total drug and metabolites, and that relatively little of the azo metabolite was present.

Animals↗
PubMed1978

Yoshi 864 (1-propanol, 3,3'-iminodi-, dimethanesulfonate [ester], hydrochloride): a phase II study in solid tumors.

Two hundred and eight acceptable patients were treated with Yoshi 864 (2 mg/kg/day by iv push X 5 days repeated once every 6 weeks). Toxicity was minimal. There was an overall response rate of 11%. Cross resistance with other alkylating agents may not be present. Because of its lack of toxicity, Yoshi 864 should be further evaluated in chronic myelocytic leukemia, lymphomas, and carcinomas of the ovary and bladder where significant responses were seen. It should also be evaluated in combinations as a replacement for other alkylating agents which cause more nausea and vomiting.

Alkylating Agents↗
PubMed1977

Management of brachial plexus tumors.

Brachial plexus neoplasms are uncommon. When this diagnosis is suspected, the functional and anatomical integrity of the brachial plexus and cervical spinal cord must be carefully assessed. A thorough search for other signs of neurofibromatosis (von Recklinghausen's disease) must also be completed. The distinction between neurilemoma and neurofibroma is an important and useful one to know. Evaluation by a pathologist who is well versed in neural tumors is mandatory for appropriate treatment of these usually benign lesions. Surgical intervention, adequately prepared on the basis of the patient's age, the amount of neural impairment, and the extent and histology of the tumor requires a surgeon who is experienced in peripheral nerve surgery and in microdissection techniques. Long-term follow-up is necessary to monitor the growth of known tumors, the detection of malignant change, and the appearance of other stigmata of von Recklinghausen's disease.

Adolescent↗
PubMed1977

Experience with the use of adriamycin in combination with other anticancer agents using a weekly schedule, with particular reference to lack of cardiac toxicity.

Two hundred and seven patients have been treated using a weekly regimen of adriamycin in combination with various other anticancer agents. Thirty-six of these patients have received between 600 and 1000 mg/m2 of Adriamycin and 27 have received more than 1000 mg/m2 of the agents. While electrocardiographic abnormalities were relatively common in this group of patients, no patient developed evidence of a cardiomyopathy. Significant remission rates were seen with patients having malignant lymphomas, carcinoma of the breast, various soft tissue sarcomas, and carcinoma of the ovary. We now have data on 149 patients given Adriamycin weekly who have received over 600 mg/m2 of the drug. Sixty-four of these patients have received over 1000 mg/m2 of Adriamycin. Eight patients were suspected of having an Adriamycin-induced cardiomyopathy and this was believed to be likely in only four of these patients. One patient died of a cardiomyopathy apparently induced by Adriamycin. It is our opinion that Adriamycin can be given with only a slight risk of developing a severe cardiomyopathy, in doses greater than 600 mg/m2, either as a single agent or in combination with methotrexate, Cytoxan, vincristine, or 5-fluorouracil, if the Adriamycin is given weekly.

Adult↗
PubMed1976

Studies on adriamycin using a weekly regimen demonstrating its clinical effectiveness and lack of cardiac toxicity.

Adriamycin has been given to 442 patients using the weekly regimen as initially described by Bonadonna et al. Hematologic toxicity and clinical effectiveness have been similar to those described with regimens in which the drug is given every 3 weeks. Stomatitis is more frequent with the weekly regimen than with the usual triweekly regimen. The incidence of electrocardiographic changes and arrhythmias was similar to that reported in other studies. Nine patients received between 500 and 550 mg/m2, nine between 550 and 600 mg/m2, 28 between 600 and 1000 mg/m2, and 22 between 1000 and 2500 mg/m2. None of the patients developed definite evidence of cardiomyopathy although six showed some disturbance of myocardial function. In each of the six patients, factors other than adriamycin cardiotoxicity were believed to play a major role in the myocardial abnormality. The difference between the incidence of cardiomyopathy seen in this series and that previously reported is statistically significant. The reasons for the difference are not clear but are probably related to the schedule that was used.

Adult↗
PubMed1975

Streptozotocin therapy in 22 cancer patients.

Twenty-two cancer patients were treated with streptozotocin (SZN) in six weekly intravenous doses of 1.0-1.5 g/m2. The results of the initial courses of therapy include 3 complete and 2 partial responses, 11 patients with no change, 4 with progression, and 2 deaths due to tumor progression. Three additional deaths also due to tumor progression occurred in previously responding patients. All responses were in patients with pancreatic tumor. Toxicity consisted of transient proteinuria in 11/15 patients, transient azotemia in 11/18 patients, marked reduction of creatinine clearance in 1 patient, burning pain at site of injection, nausea, and vomiting in 20/22 patients, change of FBS from pretherapy to post-therapy of at least 10 mg/100 ml in 11/17 patients, significantly decreased platelet count in 1/22 patients, decreased Hgb in 2/22 patients, and duodenal ulcer in 2/22 patients. A reduced dosage schedule and combination with other drugs known to be effective in pancreatic tumors deserves further investigations.

Aged↗
PubMed1975

Phase I studies of porfiromycin (NSC--56410) in solid tumors.

Porfiromycin was given to a group of patients with a variety of solid tumors. Of 114 patients admitted to the study, 103 yielded evaluable data. The following dosage schedules were used to determine the toxicity of porfiromycin when given in multiple doses by intravenous injection: 0.2 mg/kg x 5 days, 0.3 mg/kg x 5 days, 0.35 mg/kg x 5 days, 0.4 mg/kg x 5 days, 0.24 mg/kg x 10 days and 0.6 mg/kg weekly. Toxic effects noted were mainly leukopenia, thrombocytopenia, and, when injected paravenously, local tissue necrosis. Biological effects were noted at all dosage levels and were more severe at the higher dosages. The data suggest that profiromycin administered intravenously at a dose of 0.35 mg/kg daily for 5 days results in moderate hermatological toxicity and clinical evaluation in a Phase II study at this dosage level is indicated.

Drug Evaluation↗
PubMed1975

A phase III study in lung carcinoma comparing hexamethyl-melamine (NSC 13875) to dibromodulcitol (NSC 104800) 1,2.

A phase III study was designed comparing the effectiveness of Hexamethyl-melamine (NSC 13875) to Dibromodulcitol (NSC 104800) in lung carcinoma. 250 of the 316 patients entered on the study were stratified into groups according to stage of disease and cell type. The results showsed Hexamethylmelamine to be more effective in patients with squamous cell carcinoma and slightly superior to Dibromodulcitol in patients with anaplastic/undifferentiated cell carcinoma, whereas Dibromodulcitol proved to be more effective in patients with adenocarcinoma.

Adenocarcinoma↗