Demyelinating encephalomyelopathy associated with lead poisoning in nonhuman primates.

Lead poisoning was diagnosed in four primates by the finding of toxic amounts of lead in tissues. Abnormalities in the brain and spinal cord were characterized by vascular lesions and demyelination. These findings suggest a new animal model for the study of demyelination and strengthen the supposition that lead may be a factor in some idiopathic demyelinating diseases.

Neoplasia in fast neutron-irradiated beagles.

One hundred fifty-one beagle dogs were irradiated with either photons or fast neutrons (15 MeV) to one of three dose-limiting normal tissues--spinal cord, lung, or brain. The radiation was given in four fractions per week for 5 weeks (spinal cord), 6 weeks (lung), or 7 weeks (brain) to total doses encompassing those given clinically for cancer management. To date, no nonirradiated dogs or photon-irradiated dogs have developed any neoplasms. Seven dogs receiving fast neutrons have developed 9 neoplasms within the irradiated field. Of the neutron-irradiated dogs at risk, the incidence of neoplasia was 15%. The latent period for radiation-induced cancers has varied from 1 to 4 1/2 years at this time in the study.

Morphologic effects of fast neutrons or photons on the canine kidney.

Thirty-nine adult male Beagles received either fast neutron or photon irradiation to the right thorax to determine the relative biological effectiveness of fast neutrons on normal pulmonary tissue. The right anterior abdomen, including the cranial half of the right kidney, was included in the field of irradiation. Twenty-four dogs (six/group) received fast neutrons with an average energy of 15 MeV to total doses of 1000, 1500, 2250, or 3375 cGy in four fractions per week for 6 weeks. Fifteen dogs received 3000, 4500, or 6750 cGy of photons (five/group) in an identical fractionation pattern. All 12 neutron irradiated dogs receiving 3375 and 2250 cGy and 1 of 6 receiving 1500 cGy, developed clinical and clinical pathologic signs of hepatic, pancreatic, and gastrointestinal disturbances, but no signs of renal injury were seen. These 13 dogs died or were euthanatized 47-367 days after irradiation. Only 1 of 5 dogs receiving 6750 cGy of photons developed similar signs and died 708 days post-irradiation. The remaining 11 neutron irradiated dogs and 14 photon irradiated dogs eventually died of other causes. All 39 dogs were necropsied and their kidneys were compared to each other and to control dogs. Radiation induced lesions included hemorrhages, necrosis and disappearance of tubular epithelia, glomerulosclerosis, atrophy and fibrosis. These lesions were associated with degenerative and occlusive vascular changes and were much more severe in the neutron irradiated dogs. The relative biologic effectiveness of fast neutrons for canine kidney assessed by gross and microscopic pathology is approximately 4.5 (6750/1500).

Pathologic effects of fractionated fast neutrons or photons on the pancreas, pylorus and duodenum of dogs.

Thirty-nine adult male Beagles received either fast neutron or photon irradiation to the right thorax to determine the relative biological effectiveness (RBE) of fast neutrons on normal pulmonary tissue. The right anterior abdomen was included in the field of radiation. Twenty-four dogs (six/group) received fast neutrons with an average energy of 15 MeV to total doses of 1000, 1500, 2250 or 3375 rad in four fractions per week for six weeks. Fifteen dogs received 3000, 4500 or 6750 rad of photons (five/group) in an identical fractionation pattern. All neutron irradiated dogs receiving 3375 and 2250 rad and one receiving 1500 rad developed clinical signs of pancreatic, hepatic and gastrointestinal disturbances. The liver enzymes of these dogs became elevated and they died or were euthanatized in extremis 47-367 days after irradiation. Only one 6750 rad photon dog developed similar signs and died 708 days post-irradiation. Five neutron and 10 photon exposed dogs died of other causes. Neutron-induced lesions in the stomach and duodenum included hemorrhages, erosions, ulcerations and fibrosis. Ulcers perforated the GI tract of five dogs. Pancreatic lesions included degranulation and necrosis of acinar cells, fibrosis ans atrophy. Islet cells were not obviously damaged. All lesions were associated with degenerative and occlusive vascular changes. The RBE of fast neutrons, assessed by clinical signs, gross and microscopic pathology, is approximately 3-4.5 for pancreas and about 4.5 for pylorus and duodenum.

The effects of 860 MHz radiofrequency radiation on the induction or promotion of brain tumors and other neoplasms in rats.

Sprague-Dawley rats were irradiated with a continuous- wave (CW) or a pulsed-wave (P) radiofrequency (RF) for 6 h/day, 5 days/week from 2 up to 24 months of age. The RFs emanated from dipole antennas (1 W average output) 2.0 +/- 0.5 cm from the tip of each rat's nose. The RFs had an 860 MHz frequency, and the specific absorption rate was 1.0 W/ kg averaged over the brain. Fifteen groups of 60 rats (900 total) were formed from offspring of females injected i.v. with 0 (groups 1, 2, 9, 10, 13), 2.5 (groups 5, 6, 7, 8, 11, 12, 14) or 10 mg/kg (groups 3, 4, 15) ethylnitrosourea (ENU) to induce brain tumors. Groups 1, 3, 5 and 7 received the PRF, and groups 9 and 11 the CWRF; groups 2, 4, 6, 8, 10 and 12 were sham-irradiated, and groups 13-15 were cage controls. All rats but 2, totaling 898, were necropsied, and major tissues were studied histopathologically. There was no statistically significant evidence that the PRF or CWRF induced neoplasia in any tissues. Additionally, there was no significant evidence of promotion of cranial or spinal nerve or spinal cord tumors. The PRF or CWRF had no statistically significant effect on the number, volume, location, multiplicity, histological type, malignancy or fatality of brain tumors. There was a trend for the group that received a high dose of ENU and was exposed to the PRF to develop fatal brain tumors at a higher rate than its sham group; however, the result was not significant using the log-rank test (P = 0.14, 2-tailed). No statistically significant differences were related to the PRF or CWRF compared to controls in the low- or zero-dose groups regarding tumors of any kind.

Effects of collagenase and chymopapain on spinal nerves and intervertebral discs of cynomolgus monkeys.

In order to test the safety and efficacy of Nucleolysin, a collagenase for intradiscal chemotherapy, laminectomies were performed on the L2-3 intervertebral discs of four groups of three young adult Cynomolgus monkeys. One primate from each group was injected with half the recommended human dose of Nucleolysin, chymopapain, or the same volume of sterile water. The remaining half of the human dose of each drug or equal volume of sterile water was equally divided and placed upon the right L-3 and L-4 nerve roots at their vertebral foramina. The right L-4 nerve root was first compressed for 10 seconds with an aneurysm clip. These procedures were done to simulate inadvertent contact of enzyme with spinal nerves in patients undergoing chemonucleolysis. After 4 weeks of observation, the 12 primates were humanely killed and examined post mortem. The effects of both enzymes were limited to those tissues with which they came in direct contact. Complete digestion of the nucleus pulposus of all enzyme-injected intervertebral discs was observed. Variable portions of the anulus fibrosus (from 2.3% to 57.4%) were also dissolved. Direct contact of Nucleolysin with lumbar nerve roots caused minor perineural reaction and no more intraneural changes than seen in sterile water controls. Chymopapain induced mild to severe perineural skeletal muscle necrosis and fibrosis with perineural arterial lesions as well as a degenerative neuropathy which was more marked in the traumatized nerve. The results of this study suggest that Nucleolysin and chymopapain are approximately equally effective on intervertebral discs, and that Nucleolysin is less injurious to spinal nerve roots and perineural tissue at the doses used.

Pathologic findings in rats following inhalation of combustion products of polytetrafluoroethylene (PTFE).

Adult male Fischer 344 rats received single 30-min exposures to the aerosolized products of polytetrafluoroethylene (PTFE) heated to 595 degrees C. The concentrations of thermal degradation products of PTFE were at the LC50 dose of 0.045 mg/l for most rats, but some rats received doses ranging from 0.005 to 5.025 mg/l. Serial measurements of cardiopulmonary function were obtained and will be published subsequently. Necropsies were performed at 0, 2, 12, 24 and 36 h post-exposure, and a few rats were killed between 2 and 17 days. Signs of respiratory impairment were followed by death in some rats. Pathologic findings included focal hemorrhages, edema and fibrin deposition in the lungs. With time focal interstitial thickenings developed due to hypertrophy and hyperplasia of alveolar cells, and macrophages accumulated in alveoli. Thrombosis of pulmonary capillaries was common. Disseminated intravascular coagulation (DIC) occurred in 53% of test rats; its incidence and severity were positively related to the degree of pulmonary damage. Renal infarcts were common due to DIC. No lesions were seen in kidneys or other tissue (except lung and thymus) unless they were affected with DIC. Thymic lymphocytes underwent necrosis in many test and some vehical (warm air) control rats, possibly due to stress. The finding of DIC in PTFE combustion product exposure has not been reported to our knowledge. The toxicity of the thermal degradation products of PTFE requires further study, especially relative to induction of DIC.

Horizontal nystagmus in methylmercury poisoned squirrel monkeys.

Chronic states of methylmercurialism were induced in squirrel monkey subjects. Principal neurological signs included ataxia, abnormal gait, incoordination and amaurosis. Although slight to moderate vacuolization occurred in supporting cell layers of the cristae and maculae, receptor cell function was essentially normal. Except for a lowered cold threshold, bithermal caloric-induced nystagmus was not significantly different from control values. Pre and postrotatory (Barany chair) tests revealed a reduction only in frequency related variables. The development of spontaneous and positional nystagmus (sometimes with eyes open) coupled with the behavioral signs and the evidence of normal receptor response suggested cerebellar dysfunction. Severe pathologic changes were present in the cerebral cortex, but no lesions were found in the cerebellar cortex. Substantial neuronal degeneration and gliosis, however, were observed in several subcortical nuclei, including cerebellar and vestibular nuclei.

The Pathologic Anatomy of Lead Poisoning in Dogs.

Thirty-two dogs diagnosed as having lead poisoning were studied postmortem. Enlarged, pale staining nuclei of renal proximal tubular cells and hepatocytes were present in all affected dogs and frequently contained acid-fast inclusions. Bone changes consisting of persistent, thick cartilaginous trabeculae rimmed with bone caused radiopaque bands in the metaphyses of eight immature dogs. Brain lesions were characterized by vascular damage. Distended arterioles and capillaries were lined with swollen or necrotic endothelium and were often surrounded by hemorrhage and edema. These changes were associated with laminar necrosis in the cerebral cortex. Proliferation of new capillaries and gliosis occurred in dogs with chronic encephalopathies. Other changes included hyperplasia of bone marrow, metarubricytes in blood vessels, necrosis of occasional striated muscle fibers, decreased numbers of sperm and ovarian follicles, and peripheral neuropathy.

Anatomy of the beagle in cross-section: head and neck.

The transverse anatomy of the head and neck of the Beagle was studied. Cross-sectional preparations were photographed and compared with computerized tomographic scans, freshly prepared dissection specimens, and with skeletal preparations. Anatomic structures were identified by these means with the aid of anatomy texts. A series of labeled photographs were provided as a basis for interpretation of computerized tomography scans.

Canine anatomy as assessed by computerized tomography.

Computerized tomographic studies of normal canine anatomy were obtained, using a whole body scanner. The regions of interest were head and neck, thorax, and abdomen and pelvis. Scans were compared with gross transverse sections from one euthanatized dog. Identification and labeling of anatomic structures were aided by reference to recognized texts of canine anatomy.

Tyzzer's disease in Syrian hamsters.

Tyzzer's disease was diagnosed in 18 Syrian hamsters. The clinical signs included sudden onset of diarrhea, dehydration, and lethargy; all affected hamsters died within 48 hours. Gross lesions consisted of multiple white nodules in the heart; dilated cecum and colon containing semiliquid feces, sometimes bearing necrotic plaques on the mucosa; and occasionally, a few small scattered white spots in the liver. Microscopic study of those lesions revealed areas of necrosis and mixed cellular inflammation. The causative agent, Bacillus piliformis, was demonstrated within myocardial fibers, hepatocytes, and colonic epithelial cells. Inoculation of chicken embryos and a clinically normal hamster with a homogenate of cecal wall prepared from affected hamsters resulted in reproduction of the agent and transmission of the disease.