Experiments were performed to study the earliest changes and their sequence in the development of malignant tumors following implantation of 10 mg of nickel subsulfide (Ni3S2) into the right quadriceps muscle of seven male Fischer rats. Biopsies were performed when nodules reached one to three mm, and, later, when they were five to seven mm, and, finally, at sacrifice, to confirm the fully developed tumor pattern. Light microscopy of the earliest samples showed groups of cells clumped and scattered among degenerating muscle fibers. Mitoses were seen and inflammatory cells were not a feature. Electron microscopy showed individual degenerating muscle fibers, but also cells with characteristic features of myofibroblasts. In many cells osmium, dense fragments suggestive of crystalline material, were seen in the cytoplasm and nuclei. In the second set of biopsy material, myofibroblasts with well defined and dilated rough endoplasmic reticulum, intracellular membrane-bound collagen, and microfilaments with focal "dense bodies" were numerous. Mitoses were frequent. Immunohistochemistry showed strongly positive reaction to Vimentin and muscle-specific Actin in the tumor cells. In the fully developed tumors, the previously described typical storiform cell pattern with spindle and spheroidal cells with frequent mitoses was seen. Vimentin and muscle-specific Actin stains were strongly positive. The long latent period, the evidence of cell degeneration, necrosis, foreign material (probably of nickel composition), cell invasion, and subsequent rapid myofibroblast-type cell development, proliferating to malignant tumors highly suggestive of malignant fibrous histiocytoma, seem to suggest an epigenetic form of carcinogenicity of cytotoxic variety. Whether the tumor cells derive from transformed myofibrils or from activated pluripotential mesenchymal cells, or from both, remains in doubt.

Actins↗

PubMedDate not supplied

Damage in canine hearts following defibrillator shocks.

Experiments were performed to investigate possible differences in potential myocardial cell damage following the use of two clinically available difibrillators. One had a damped sine wave (DSW), and the other a truncated exponential waveform (TEW). The latter, therefore, had a lower peak current and voltage. After pilot studies to determine damage potential, an energy content of 10 Joules per kg was selected with three transthoracic shocks at 30 second intervals, delivered with paddles, by both defibrillators. Thirteen dogs were shocked with DSW (10 sacrificed at 24 hours and three at 72 hours). Eleven dogs were shocked with TEW (eight sacrificed at 24 hours and three at 72 hours). Three were used as untreated controls. Observations included ECG monitoring, technetium99m pyrophosphate (Tc-PyP) uptake, and gross and microscopic observations including electron microscopy. This report will concentrate on the morphologic changes. Eleven of 13 dogs shocked with DSW developed ventricular tachycardia, transient heart block, Tc-PyP uptake and myocardial cell death with acute necrosis, and aberrant contraction patterns associated with cell death. Progression of the lesions occurred from 24 to 72 hours. Only two (one at 24 hours and one at 72 hours) of the dogs shocked with TEW showed microscopic foci of necrosis. One was a chance finding (24 hours); the other was associated with an overlying "yellow streak". In neither case were arrhythmias or Tc-PyP uptake observed. The results indicate that in dogs at equivalent energy levels, TEW caused significantly less myocardial damage than DSW.

Animals↗

PubMedDate not supplied

The problems of environmental hazardous substances: an overview.

It was decided to present an overview of problems of environmental hazardous substances by selecting three areas of concern which represent different aspects of the overall subject. All three are topics of great interest at the present time. They provide examples of different causes of the hazards and different approaches to their resolution or containment. Aerial and water contamination by radon gas are a natural hazard only recently recognized. Radon can be contained, but it will require cooperative action and expenditure. Herbicides are a continuing problem demanding increased research activity to establish risk-benefit decisions. Pollution of estuaries and oceans require new development of models for establishing safe levels of some pollutants and prohibition of others.

Air Pollutants, Radioactive↗

PubMedDate not supplied

Effects in animals of chronic administration of spironolactone--a review.

Spironolactone, an aldosterone antagonist, has been found effective in the treatment of certain forms of hypertension, ascites, and edematous conditions. Since patients may receive daily doses of spironolactone for many years, it is important to determine the chronic effects on tissues. This study reviews the tissue changes in rats, dogs, and monkeys receiving spironolactone daily for up to two years. Dose levels were frequently in excess of 100 times the recommended human dose. The pituitary, adrenals, and kidneys of all animals showed no significant changes. Histologic changes were noted in rat livers, thyroid, and male internal genitalia. There were alterations in monkey testes and male mammary glands. This study found no evidence to suggest that spironolactone is tumorigenic or carcinogenic. Species differences in metabolism may account for the diversity of tissue observations.

Animals↗

PubMedDate not supplied

Sodium diethyldithiocarbamate administration in nickel-induced malignant tumors.

Studies were undertaken to ascertain the possible antitumorigenic effectiveness of sodium diethyldithiocarbamate (dithiocarb) on the development of tumors in rats following the muscular implantations of nickel subsulfide (Ni3S2). These tumors have histologic characteristics which suggest origin from striated muscle and have been classified as rhabdomyosarcoma. Most of the tumors metastasized. In two separate studies over a period of two years, a total of 100 four-month old Fischer rats received muscular implantations of Ni3S2. Of this total, 50 rats (25 males and 25 females) were treated with dithiocarb for a period of four to six weeks. Seventy-eight percent of the untreated rats developed sarcomas as compared to 32 percent of the treated rats. Analyses of the data revealed a striking difference in the sex responsiveness to dithiocarb. Of the 25 female rats with Ni3S2 implantations and treated with dithiocarb, only 12 percent developed sarcomas; of the male rats similarly treated, 52 percent developed sarcomas. The difference in sex response is statistically significant (p = 0.005). Therapeutic implications are suggested.

Animals↗

PubMedDate not supplied

Plastic embedding as a tool in surgical pathology diagnosis.

Plastic (polymer) embedding is recommended as the method of choice for studying small biopsies such as those obtained from liver, bone marrow, lung and by endoscopy from the gastro-intestinal tract. The method offers the opportunity to examine one to four micron thick sections and, therefore, to evaluate cytologic detail. Multiple levels can be obtained from such fragments, and the reasonably large blocks provide adequate section size for diagnostic purposes.

Acrylates↗