Kenneth N. Gray

50-MeVd→Be neutrons: A comparison of normal tissue tolerance in animals with clinical observations in patients☆

The acute and late effects of 50 MeV neutrons were investigated by irradiating a variety of organ systems in large animals using dosage schedules similar to those that have been employed clinically. The RBEs for acute effects in pig skin and rhesus monkey oral mucosa were significantly less than the RBEs for late effects. This observation has also been noticed clinically. The RBEs for late effects in pig skin, rhesus monkey oral mucosa, and rhesus monkey kidney were consistent with values of 3.1 to 3.4 relative to approx.200 rad /sup 60/Co fractions and approx.2.2 to 2.6 relative to approx.400 rad /sup 60/Co fractions. The RBE for radiation myelitis was significantly greater (4.2 to 4.6 relative to approx.270 rad /sup 60/Co fractions). The tolerance doses for 50 MeV/sub d..-->..Be/ neutrons in large animals were approx.2200 rad/sub n..gamma..//6-1/2 weeks for skin contraction, approx.2100 rad/sub n..gamma..//6-1/2 weeks for oromucosal necrosis, approx.1300 rad/sub n..gamma..//4-1/2 weeks for radiation myelitis, and approx.960 rad/sub n..gamma..//4 weeks for radiation nephritis. These values correlate well with clinical observations at TAMVEC, since the majority of soft tissue complications in patients occurred following tissue doses in excess of 2100 rad/sub n..gamma../.

Postirradiation sarcomas in Sprague-Dawley rats.

A series of radiation-induced neoplasms occurred in Sprague-Dawley rats 4-8 months after irradiation of a single hind leg with 60Co gamma rays. The rats were exposed to fractionated cumulative doses that ranged from 0 to 106 Gy. Osteosarcomas, malignant fibrous histiocytomas and fibrosarcomas developed in the radiation fields of a number of the rats in the higher-dose groups. Tumors did not develop throughout an 8-month observation period in rats that received doses of only 0 or 46 Gy. The most common postirradiation sarcomas in humans are osteosarcoma, malignant fibrous histiocytoma and fibrosarcoma. The Sprague-Dawley rat may serve as a good animal model in studying the development of sarcoma in humans after regional radiotherapy.

A Comparison of the Effects of 50 MeVd→Be Neutron and Cobalt-60 Irradiation of the Kidneys of Rhesus Monkeys

Twenty rhesus monkeys had one kidney irradiated (after undergoing unilateral nephrectomies) with one of four doses: 960 or 1080 rads of 50 MeVd→Be neutrons, or 2350 or 2700 rads of 60Co. Whereas animals treated with the lower dose of neutrons or 60Co are alive with relatively normal renal function, those treated with the higher dose of neutrons died of radiation nephritis. Animals treated with the higher dose of 60Co developed radiation nephritis but survived. The physiological and histopathological changes of radiation nephritis secondary to neutron irradiation are not qualitatively different from those reported for radiation nephritis secondary to photon irradiation.

Radiation response of the monkey kidney following contralateral nephrectomy

PURPOSE The long-term functional and morphologic responses of the hypertrophied monkey kidney after unilateral nephrectomy to fractionated irradiation were assessed. METHODS AND MATERIALS The right kidney of 13 adult female rhesus monkeys was removed. Twelve weeks after unilateral nephrectomy (UN) the remaining kidney received fractionated doses of gamma-rays ranging from 35.2 Gy/16 fractions (F) up to 44 Gy/20 F. Glomerular filtration rate, effective renal plasma flow, blood urea nitrogen, serum creatinine, and hematocrit values were measured up to 107 weeks postirradiation (PI). The monkeys were killed and the remaining kidneys were removed 107 weeks PI or earlier when end-stage renal failure was exhibited. Glomeruli were scored for the presence/absence of several pathologic features including increased intercapillary eosinophilic material (ICE), ectatic capillaries, and thrombi. The relative proportion of renal cortex occupied by glomeruli, interstitium, normal tubules or abnormal tubules was determined using a Chalkley point grid. These quantal dose response data were analyzed using a logistic regression model. RESULTS Irradiation of the remaining kidney in UN monkeys resulted in a dose-dependent reduction in renal function and anemia. Glomerular dysfunction preceded tubular dysfunction. Animals receiving 44 Gy all manifested progressive clinical renal failure. Conversely, those receiving < or = 39.6 Gy showed stable, albeit impaired, renal function for the duration of the observation period of 107 weeks. Morphologically, the incidence of ICE, ectatic glomerular capillaries, thrombi, and periglomerular fibrosis was significantly dose-related (p < 0.005). A significant (p < 0.001) dose-related increase in the relative proportion of renal cortex occupied by abnormal tubules was indicative of tubular injury. A highly significant (p < 0.001) dose-dependent increase in the proportion of abnormal to normal tubules was also seen. CONCLUSION The pathogenesis of radiation nephropathy is difficult to fully understand because of the complex and dynamic interactions among all components of the nephron that make discrimination between primary radiation effects and secondary pathophysiological consequences very difficult. Notwithstanding, the current experiment shows that the functional and morphological expressions of radiation injury in the kidney are dose dependent. Renal failure occurs when both the glomeruli and tubules are dysfunctional. In monkeys following UN, a total dose of 44 Gy to the remaining kidney damages all components of the nephron and causes renal failure in less than 45 weeks. With lower doses, changes to the glomeruli predominate and the animals survive. Kidney doses of up to 39.6 Gy/18 fractions of 2.2 Gy are compatible with survival for at least 2 years in primates.

Correlation of kidney weight and volume and selected skeletal parameters to sex in the adult rhesus monkey (Macaca mulatta).

This report outlines a comparison of renal weight and volume and selected skeletal parameters to sex in 22 adult male and 156 adult female rhesus macaques. Means and standard deviations for kidney weight and volume, body weight, and radiographic measurements for both males and females are reported. Ninety‐five percent confidence intervals and P‐values for the mean differences between the sexes for these parameters were also compiled. Male monkeys were larger, but had kidneys of similar size to those of the females. Joint distributions of the radiographic measurements of the first lumbar vertebra and the skull showed that males were larger in both measurements. The distributions of these parameters were clearly separate in males and females, while joint distributions of kidney weight and volume for males and females overlapped almost completely. We found that, regardless of age, sex, weight, or skeletal size, all normal adult rhesus monkeys generally have similar‐sized kidneys.

Stenosing colonic adenocarcinoma in a female rhesus monkey.

Abstract: Laparoscopic surgery was performed on a 16 year‐old female rhesus monkey presenting with chronic lethargy and inappetence. The procedure revealed a “napkin‐ring” stricture located in the ascending large colon. Histologic evaluation of the colonic lesion exhibited large numbers of irregular acini lined by a single layer of well‐differentiated neoplastic epithelial cells. Based on the gross and histopathologic findings a diagnosis of adenocarcinoma of the proximal colon was made.

Visual laser ablation of the canine prostate with a diffusing fiber and an 805-nanometer diode laser

Although the popularity of visual laser ablation of the prostate (VLAP) as a treatment for symptomatic, benign prostatic hyperplasia (BPH) is increasing, the perceived advantages of VLAP over conventional transurethral electroresection of the prostate (TURP) is being debated because optimal technique and dosimetry for surgical lasers are still being refined. At this time, the 1.06 neodymium:yttrium‐aluminum‐garnet (Nd:YAG) laser and a laterally deflecting delivery system is the hardware combination most widely used for VLAP.

Laser ablation of normal porcine liver with the 805-nm diode laser and a diffuser fiber

The ability of the 1.06 Nd:YAG laser and the 805 nm diode laser to transurethrally and interstitially ablate prostate has been well documented by this lab and others. With the introduction of lower cost and physically smaller diode laser systems, and the potential for transcatheter and laparoscopic delivery of laser energy through diffuser fibers, laser ablation of tumors of the liver is feasible and could prove to be a cost effective treatment for this and other soft tissue applications. This study examined the acute pathologic effect of 805 nm diode laser radiation delivered via diffuser fibers on normal porcine liver. After preliminary dosimetry parameters were established in cadaveric canine liver, laparotomies were performed to expose the liver on domestic swine. Histopathological samples taken 3 hours after lasing revealed 4 distinct zones of tissue change. The outermost zone showed a 2 mm band of hemorrhage with disruption of hepatic cords adjacent to a zone of disruption of hepatic cords without hemorrhage. Working toward the fiber the next zone was intact with no visible changes. The innermost zone that was in contact with the fiber exhibited a very thin area of necrosis and char. The diameter of the outermost zone seemed to increase with increased wattage.