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Biomedical subjects

M A Friedman

Publications and source records attributed to M A Friedman.

At least 163 records · Page 9Linked to original sources
PubMed1978

Doxorubicin cardiotoxicity. Serial endomyocardial biopsies and systolic time intervals.

Doxorubicin, whose dose-limiting toxicity is cardiomyopathy, was given to four cancer patients. Endomyocardial biopsy specimens and test results of cardiac function were obtained before, during, and after treatment. The biopsy specimens were examined by light and electron microscopy and were graded blindly. Evidence of specific doxorubicin injury was found in 3/4 patients with as little as 180 mg/sq m of the drug and became progressively more severe with higher doses. All test results of cardiac function, including systolic time intervals, remained normal. These data suggest that a specific, progressive subclinical injury to the heart occurs with doxorubicin therapy, which cannot be reliably detected by routine tests. This potential risk must be taken into account with the use of doxorubicin, especially when combined with synergistic agents.

Adult↗
PubMed1978

A review of the bleomycin experience in the United States.

As bleomycin has up to now proved effective when used alone, the main thrust of current clinical investigations predominantly concerns its use in combination with other drugs. This has occurred along three broad patterns: 1) combination with vinca alkaloids which has been mainly in testicular carcinoma; 2) as part of multidrug regimens where bleomycin added for its lack of myelosuppression. This has occurred in the malignant lymphomas, lung cancer, and head and neck cancer; 3) in combination with radiotherapy which has taken place mostly in head and neck cervix cancer. To date, the combination of velban and bleomycin has had a major impact in improving the ability to induce complete remissions in advanced testicular carcinoma. Other drugs such as cis-platinum diaminedichloride and actinomycin D have been added and no definitive combination has been established. In the lymphomas the addition of bleomycin to the MOPP or CVP regimen has given higher complete response rates, but long-term survival data are still awaited.

Bleomycin↗
PubMed1978

The fluoropyrimidines: biochemical mechanisms and design of clinical trials.

Our understanding of the biochemical events of fluoropyrimidine-induced cytotoxicity remains incomplete. However, we have a good perception of the activation and degradation pathways of these agents. Additionally, from studies performed in vitro we are gaining a new appreciation of the interactions between methotrexate and the fluoropyrimidines. These studies suggest that the common clinical practice of simultaneously administering methotrexate and 5-fluorouracil may be disadvantageous. Several simple scheduling modifications of combination therapies with these two drugs could lead to improved clinical efficacy and deserve further investigation.

Antineoplastic Agents↗
PubMed1978

Potentiation of methylmercury toxicity by piperonyl butoxide.

Methylmercury (MeHg) is an extremely potent neurotoxin about 25% of which is degraded in vivo to inorganic mercury. Piperonyl butoxide (PB) is a widely used pesticidal synergist which inhibits many mammalian detoxification reactions. In a preliminary experiment with the high doses of PB and MeHg, PB induced a 12% decrease in mean survival time and a 20% decrease in mean latency time to neurotoxicity. The weight loss in PB-MeHg group was far greater than the control MeHg group. In a dose response experiment, mean survival times in rats fed 40 ppm MeHg-C1 were 5.75, 5.3, and 5.0 weeks at 0, 0.5, and 1% PB, respectively. By the ninth week 25% of rats fed 20 ppm MeHg-C1 showed neurotoxicity and 63% of the 0.5% PB fed showed neurotoxicity with some mortality. In experiments at 20 ppm MeHg-C1 both PB fed groups weighted considerably less than corresponding controls.

Animals↗
PubMed1978

Influence of acetaldehyde, dietary protein, carbon tetrachloride and butylatedhydroxytoluene on the toxicity of methylmercury in rats.

The influence of environmental or dietary factors on the toxicity of methylmercury (MeHg) was investigated due to possibilities that humans exposed to methylmercury may have been sensitized. Groups of 8 rats were exposed to 0, 20 or 40 ppm MeHg in a semisynthetic diet and fed 0.5% BHT, 5% protein (instead of 15%), or injected with 250 mg/kg CC14 or acetaldehyde. In control rats neurotoxicity occurred at 4 weeks and 9 weeks with 40 and 20 ppm MeHg, respectively. Mortality was observed at 6 weeks with 40 ppm and 1 rat died in week 9 with 20 ppm MeHg. Acetaldehyde injected rats died at week 4 and 6 when fed 40 or 20 ppm MeHg. Neurotoxicity was observed in week 3 and 5 in these groups, respectively. Treating rats with the low protein or BHT accelerated neurotoxicity and mortality by 1 week with 40 ppm MeHg. These agents had killed all test animals within 7 weeks at 20 ppm MeHg. Neither acetaldehyde nor BHT influenced 0 ppm MeHg controls while 5% protein induced precipitous weight loss. In the case of CC14, the rats lived longer in combination experiments than one would have expected from the individual treatments.

Acetaldehyde↗
PubMed1978

Malignant pleural effusions.

Recurrent malignant pleural effusion is a relatively common problem that often occurs many months before the terminal stages of a patient's malignant disease. Despite careful evaluation, it is often impossible to identify the exact physiologic cause of an effusion and difficult to identify a pragmatic course of therapy. Aggressive management including chest tube drainage, with or without instillation of inflammation-inducing drugs, and radiotherapy or surgery in selected cases is indicated for palliative treatment and probably for increased survival. In formulating a treatment plan, attention should be given to a variety of factors including pathogenic forces in the formation of malignant pleural effusion, tissue type of the metastatic malignancy, general clinical status of the patient, the presence of pleural loculations and adhesions, and the exclusion of other non-malignant causes of pleural effusion.

Antineoplastic Agents↗
PubMed1978

Effects of chronic administration of delta8- and delta9-tetrahydro-cannabinol on hepatic tyrosine aminotransferase activity in mice.

The effects of delta8-THC and delta9-THC administered twice weekly for 8 and 12 weeks at doses of 3, 10, and 30 mg/kg on murine hepatic tyrosine aminotransferase activity are described. These data suggest that treatment with relatively low doses of cannabinoids over long periods of time appear to produce some type of biochemical "tolerance," resulting in a diminished response, in contrast to previously reported data utilizing high doses of delta8-THC and delta9-THC over short experimental time periods.

Animals↗
PubMed1978

Inhibition of mitochondrial DNA synthesis by aflatoxin B1 and dimethylnitrosamine.

The acute and subchronic effects of aflatoxin B1 and dimethylnitrosamine (DMN) on in vitro incorporation of thymidine-3H into DNA (mt-DNA) from mouse liver mitochondria were studied after single injection or after one month or three months of weekly injection. Both carcinogens induced 50% decreases in mt-DNA synthesis acutely, with a 50% decrease in synthesis of high molecular weight mt-DNA. Subchronic administration of aflatoxin B1 inhibited mt-DNA synthesis by 54% with elution profiles similar to the controls. DMN showed only a 29% inhibition of mt-DNA synthesis at one month increasing to 55% at three months.

Aflatoxins↗
PubMed1977

Pathologic analysis of mink mortality in New England mink.

The underlying cause of death of a group of New England mink, which died in 1969 to 1970 was explored. PCB and chlorinated hydrocarbon pesticide levels were measured. Aroclor 1254 levels in these mink were elevated 73 fold over levels in healthy mink in 1974. DDT levels were elevated 5 times and DDE 3 times over those control animals. Gross pathology revealed desions of the lungs, liver and kidneys. There lesions were confirmed microscopically. The lungs of the New England mink showed inflammation and congestion. Areas of inflammation were also present in the liver. Massive areas of necrosis were seen in the kidneys, both in the medullary and cortical areas. Kidney involvement was greater than any other organ. P.A.S. positive material was seen in each of these organs with the kidneys showing largest amounts of this material. Since the New England mink did not show lesions of the G.I. tract, did not exhibit fatty degeneration of the liver, which PCB toxicity is known to induce in mink and because they showed areas of congestion, inflammation and positive P.A.S. material, PCB's were not considered the toxic agent. However, fungus or bacterial infection might be the causative agent.

Adipose Tissue↗
PubMed1977

Induction of micronuclei in mouse and hamster bone-marrow by chemical carcinogens.

Four carcinogens, dimethylnitrosamine (DMN), acetylaminofluorene (AAF), aflatoxin B1 (AFB1), and 3-methylcholanthrene (3-MC) were tested acutely and chronically in the micronucleus test in both mice and hamsters. In acute studies using mice, all compounds increased the relative frequency of micronuclei when compared to controls. There was a dose response which tended to tail off as bone-marrow suppression was observed. The order of activity appears to be DMN greater than AFB1 greater than or equal to 3-MC greater than AAF. In acute hamster studies, AFB1 was inactive at the highest dose tested (3 mg/kg). In the case of hamsters, all other compounds increased the incidence of micronuclei with DMN greater than 3-MC greater than AAF. Subacute studies with hamsters revealed that 3-MC was active at 1 week but not 8 weeks while DMN was active at both 1 and 8 weeks. AAF was active at 8 and 12 weeks and AFB1 was active at 12 weeks but not 8 weeks. The authors conclude that this test does not appear useful in chronic protocols and probably more reflects carcinogenicity of the test compounds than acute toxicity. Nevertheless, acute studies demonstrate that this test procedure is of value in the characterization of a compound's relative mutagenic potential.

2-Acetylaminofluorene↗
PubMed1977

Carcinogen activation by human liver enzymes in the Ames mutagenicity test.

Liver post-mitochondrial supernatants derived from 10 individuals were used as the source of metabolic activation for carcinogens in the Ames quantitative mutagenicity test using Salmonella typhimurium TA 100. The liver samples were obtained from brain-dead donors and autopsy cases. The ability of human enzymes to activate aromatic amines ranged from the undetectable to highly active for 2-acetylaminofluorene. None of the samples exhibited any ability to activate benzidine. A generally low activity was observed in the capability of human enzymes to activate the polynuclear aromatic hydrocarbons, 3-methylcholanthrene and benzo(a)pyrene. Most samples were positive for activating 4-nitrobiphenyl. However, the highest mutagenic activity in the presence of human enzymes was consistently observed for aflatoxin B1 and sterigmatocystin. These results indicated that (a) human enzyme systems, like rodent systems, are more effective in inducing mutagenic activity from mycotoxins than aromatic amines and polynuclear aromatic hydrocarbons, and (b) samples derived from different individuals exhibited considerable variation in the ability to activate carcinogens belonging to a same class of compound.

Adult↗
PubMed1977

Acute lethality of D- and L-ethionine in Swiss mice.

The acute, 7-day LD50 in Swiss mice of D-ethionine administered intraperitoneally, was determined as 185 mg/kg with 95% confidence limits of 163 and 210 mg/kg. L-ethionine, the stereoisomer, which is more potent in inhibiting liver RNA synthesis, was not lethal at 2500 mg/kg. This acute toxicity of D-ethionine was suppressed by L-methionine and adenine. Blood accumulation in the thoracic cavity and pericardium was the probable cause of death.

Adenine↗