George W. Casarett

The effects of gonadal irradiation in clinical radiation therapy: A review

Recent improvements in radiation therapy of some malignancies in lower abdominal sites are leading to prolongation of life in persons of child‐bearing age. These successes require an evaluation of the possible undersirable consequences of the unavoidable gonadal irradiation that occurs in these cases. A review of radiobiological data from experimental animal studies and retrospective clinical studies suggests that in most instances human gonadal exposures in both sexes are insufficient to cause permanent sterility, because the exposures are fractionated and the total gonadal dose is much less than 600 rads. As a consequence, return of fertility must be anticipated, and the worrisome questions of radiation‐induced genetic damage in subsequent pregnancies must be addressed. This review did not substantiate this fear, because no case reports could be found of malformed infants among the progency of previously irradiated parents. Some experimental studies suggest that radiation‐damaged spermatogonia are self‐destructive, but any evidence for this phenomenon in the ovary is nonexistent. We suggest that the difference between fact and theory here may be the mathematical result of the interplay of low probability for occurrences and the few patients who until now have survived long enough for study.

Microcirculation of tumors Part I: Anatomy, function, and necrosis*

Microangiographic and histologic studies have been made of two transplantable rat tumours in order to correlate the microcirculation to tumour necrosis. The relationship of the capillary network to tumour necrosis is re-examined and it is shown that necrosis is not due to the absence of capillaries in tumour cores. The need for more functional studies is emphasized.

Clinical radiation pathology as applied to curative radiotherapy

The value of radiation pathology in understanding the radiation effects in normal tissues and tumors is stressed in developing curative radiotherapy. A theory of cell radiosensitivity is presented based on cellular proliferation, differentiation and life span. From this base, concepts of tissue and organ radiosensitivity are developed utilizing the knowledge of tissue organization, cell kinetics and microcirculation. Through a series of paradigmatic charts and drawings an attempt is made to explain different clinical manifestations of radiation reactions on the basis of similar histopathologic changes. Possible future directions for radiation research to explore are outlined.

Development of the vascular system in the hamster malignant neurilemmoma

Abstract The development of the vasculature in the hamster malignant neurilemmoma was studied during growth in the transparent cheek pouch chamber. Prominent features in this process are: (1) Progressive dilatation, tortuosity and some bulbous formations in host venules in the immediate vicinity of the tumor implant. Occasional focal dilatation of some host arterioles. (2) Small focal erythrocytic extravasations. (3) Sprouting of host venous vessels in the perimeter of the implant and subsequent anastomosing of these sprouts and/or their branches to form loops directed toward the center of the implant. Continued sprouting, in effect, produces remodeling of the host venules. (4) Establishment of the tumor capillary net in 4–7 days. The bed assumes a dense net-like arrangement of short, profusely anastomosing, thin-walled endothelial tubes which conduct blood at a brisk rate. (5) Progressive increase in capillary caliber during tumor growth. (6) Prominent focal or general reduction in blood flow after about 10 days of growth. This appears related to the development of tissue growth pressure within the rigid cheek pouch chamber.

A one-solution stain for spermatozoa.

Fresh semen is allowed to liquefy 30–60 minutes and thin, even smears of it made on clean slides or cover glasses. The smears are fixed 3 minutes with an equal-parts mixture of alcohol and ether, then air dried. They are stained 5–7 minutes in an aqueous solution made by mixing 2 volumes of 5% aniline blue (water soluble), 1 volume of 5% eosin B and 1 volume of 1% phenol. Staining at 40–60°C. is recommended. After staining, the smears are washed with distilled water, air dried and mounted in balsam or synthetic resin. The method was used on over 2000 samples of dog semen and some human specimens. Good preservation and differentiation of cytological structures was obtained uniformly, but tests were not made with other species.

RADIATION HYPERTENSION AND NEPHROSCLEROSIS.

Rats given single x-ray doses to the whole body or whole-body with temporarily exteriorized kidneys shielded (300 R or 500 R) or to the temporarily exteriorized kidneys only (300 R, 500 R or 1000 R), together with their surgical and nonsurgical sham-irradiated control rats, were studied periodically for 17 months or longer postexposure for systolic blood pressure and renal histopathology. Increased systolic blood pressure, above the time-dependent increases in nonirradiated animals, was induced by all doses and modes of irradiation; the increases were dose-dependent and time-dependent, but independent of the mode of irradiation at given dose levels. Progressive arteriolonephrosclerosis, greater in degree at given times than that in nonirradiated animals, was induced by all doses and modes of irradiation in dose-dependent fashion. Nephrosclerosis progressed more rapidly in animals whose kidneys were irradiated, less rapidly in those whose kidneys were shielded during irradiation, and least rapidly in nonirradiated animals. The initiation of blood pressure increase by renal irradiation required little renal damage, and this was apparently limited to subtle degenerative and occlusive changes in fine vasculature, especially cortical arterioles. Much of the progressive nephrosclerotic process developed after the rise of blood pressure, apparently partly as a result of

Effects of Single Thoracic X-Ray Exposure in Rats

Pathophysiologic changes in female and male rats after exposures to single doses of thoracic x-irradiation of 0, 600, 1200, 2400, or 3600 rad, are reported and discussed. The dose of 3600 rad cause...

Coronary arteriosclerosis and arterosclerosis in fast neutron or photon irradiated dogs

Abstract Thirty-nine adult male beagles received either fast neutron or photon irradiation to the right thorax to obtain values for the relative biological effectiveness (RBE) of fast neutrons as assessed by quantitative parameters of lung function. Fast neutrons (15 MeV avg.) were delivered in 4 fx/wk for six weeks to total doses of 1000, 15010, 2250 or 3375 rad while the photon irradiated dogs received total doses of 3000, 4500 or 6750 rad in the same fractionation schedule. The right atrium and coronary groove of the heart were included in the irradiated field. Cholesterol levels (and triglyceride levels when obtainable) were measured prior to irradiation and every three months until death. Arteries were graded (0, negative to 5, severe) for endothelial proliferation, disruption and duplication of the elastic lamina, perivascular fibrosis and the presence of foamy macrophages. All dogs that survived 75 days post-irradiation developed arterial changes; two neutron irradiated dogs showed severe atherosclerotic plaque formation. Data suggest an RBE between 4 and 5.

EFFECT OF EPSILON-AMINO-N-CAPROIC ACID (EACA) ON RADIATION-INDUCED INCREASE IN CAPILLARY PERMEABILITY.

Effects of a single intravenous injection of EACA administered at various times before or after single localized x-ray exposure of rabbit skin on temporal patterns and degrees of initial and delayed radiation-induced capillary permeability, as indicated by leakage of dye into irradiated skin, were studied. Minimal x-ray exposure to induce visibly detectable leakage of dye within 3 hours was 450 R. Average time between irradiation and first sign of increased capillary permeability, and duration of this initial period were inversely dose-dependent. EACA, injected intravenously within an hour before to an hour after irradiation, decreased or abolished initial radiation-induced increase in capillary permeability.

Pathologic Findings in Canine Brain Irradiated with Fractionated Fast Neutrons or Photons

Thirty-seven adult male purebred beagles received total doses of 1333, 2000, 3000, or 4500 rad of fast neutrons (15 MeV av) in 4 fractions/week for 7 weeks to the entire brain. Nineteen dogs received 4000, 6000, or 9000 rad of photons (/sup 60/Co) in an identical fractionation pattern. Dogs receiving 4500, 3000, and 2000 rad of neutrons and 9000 rad of photons developed neurologic signs and died or were euthanatized when moribund followed irradiation. Cerebrospinal fluid contained excess protein and erythrocytes during and sometimes before the generally brief course. The onset of neurologic symptoms was usually followed by a moribund state in less than 48 h. The relative biological effectiveness (RBE) as measured by onset of neurologic symptoms and mortality was greater than 4.5. Gross changes included hemorrhage, edema, and malacia primarily in the white matter, especially the corona radiata, cerebellar white matter, corpus callosum, and corpus fornicis. One beagle developed a brain tumor and died 1207 days following 1333-rad neutron irradiation.