Three-dimensional NMR microscopy of rat spleen and liver.

Three-dimensional microscopic NMR images of spleen and liver specimens from rats injected with dextran magnetite particles and from controls were obtained at 4.7 T, using a specially designed probe in conjunction with a 3D filtered back projection reconstruction algorithm. All of the images were reconstructed as 64(3) arrays with (25 microns) 3 isotropic voxels. With the aid of the MR contrast agent, the red pulp and marginal zone of the spleen and the portal triad of the liver could be distinguished from the surrounding tissue in T2-weighted images. For mature rat spleen, natural contrast in T2-weighted images was found to distinguish the same features. Histological examinations of the tissues with and without contrast agent were also performed using an optical microscope. Microscopic NMR images, despite their lower resolution, clearly revealed many features seen in the optical images.

A scientific basis for proposed quality assurance of a new screening method for tumor-like growths in the planarian, Dugesia dorotocephala.

Various abnormal growths appear on planarians, Dugesia dorotocephala, during and after exposure to polychlorinated biphenyls (PCBs) 28, 110, and 126; Aroclor 1254; cadmium sulfate; and L-buthionine-(R,S)-sulfoximine (BSO). Daily observations under magnification were used to describe the location, development, and morphology of three different types of tumor-like growths ("tumors"). "Post-head tumors" were found to be highly invasive, progressive, and lethal to the animal depending on concentrations and combinations of the compounds used. Survivors from post-head tumors exhibited aberrant morphogenesis, but developmental abnormalities were eventually shed. Post-head tumors occurred within 2 weeks of initial exposure, while "round tail tip tumors" appeared after 2-3 weeks. The rate of progression and invasiveness was greater for the round tail tip tumors. "Pigmented rose thorn tail tumors" occurred in low incidence (4-20%) and appeared to be harmless and noninvasive, requiring months to develop from the first appearance of pigmentation. The aggressive, proliferative, and invasive characteristics of post-head and round tail tip tumors are analogous to those of malignant tumors, while pigmented rose thorn tumors were benign. High dose of cadmium alone were sufficient to initiate the post-head and round tail tip tumors. PCBs potentiated the tumorigenicity of low cadmium doses and enhanced the very low spontaneous incidence of pigmented rose thorn tumors. PCBs also impaired motor activity, causing the graceful gliding locomotion to be replaced by a twisting serpentine movement accompanied by muscular dystrophy. In addition, high (50 micrograms) doses of PCB 110 depressed activity, while lower (5 micrograms) doses and 50 micrograms Aroclor 1254 induced restlessness and enhanced locomotion. These data provide the basis for quality assurance.

Cocarcinogenesis between cadmium and Aroclor 1254 in planarians is enhanced by inhibition of glutathione synthesis.

Asexual Dugesia dorotocephala planaria continuously exposed to 50 micrograms/beaker of Aroclor 1254 (A1254) and cadmium (Cd) developed tumors after 11 days of continuous exposure to 0.65 or 1.3 mg/liter Cd and after 23 days to 0.13 mg/liter Cd. The tumor rate at 14 days averaged 53% for the survivors in both 0.65 and 1.3 mg/liter Cd + A1254 and 40% at 0.13 mg/liter Cd + A1254. Other groups were either preexposed or coexposed to L-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of glutathione synthesis. In the presence of A1254 (50 micrograms/beaker), animals continuously exposed to BSO and 0.13 mg/liter Cd first developed tumors at 18 days, with a tumor yield equal to 41% of the survivors. Tumors developed by 6 days at 0.65 mg/liter Cd, with a yield equal to 75% of survivors. At 1.3 mg/liter Cd, BSO did not change the rate or frequency of planarian tumor production. Continuous BSO always produced high mortality over 20 days. In contrast, a 24-h preexposure to BSO caused little mortality. In these groups, tumor yields increased with cadmium concentration (0.13, 0.25, 0.65 mg/liter), and the large cocarcinogenic effect of A1254 was clearly evident. No tumors developed in animals exposed only to 50 micrograms/beaker of Aroclor 1254 or continuously only to 1 mM BSO.

Performance of a multi-sector ultrasound hyperthermia applicator and control system: in vivo studies.

A multi-element ultrasound hyperthermia system (Labthermics Technologies, Inc., Sonotherm 1000) was utilized to deliver energy to two relatively well-defined regions (3.8 X 3.8 cm) on the lateral aspect of the right rear leg of 22 dogs in 1, 2 and 3 weekly treatments to a target temperature of 42-43 degrees C, at a depth of 1 cm. The total treatment time was 30 min. One area heated on each dog was adjacent to the proximal femur and the other was 2-3 cm away from the distal aspect of the same bone. The system performed in an acceptably controlled manner and was able to deliver energy to a well-defined site. The mean temperature achieved, and rate of temperature rise in the heated regions, was independent of the region being treated. Little difference (0.12 degrees C) was noted between the mean temperatures of the heated regions, and the temperature bounds (42-43 degrees C) were exceeded by a small amount and for a relatively short period of time (out of range RMSE = 0.6 degrees C). Unheated regions showed much lower mean temperatures than did heated regions located 3.8 cm away, indicating that the energy was delivered in a well-defined manner. Superficial thermal injuries occurred in three of 22 dogs in the area heated 2-3 cm away from bone, and 11 of 22 dogs exhibited injuries in the tissue heated immediately adjacent to the femur.

Acute and short-term toxicoses associated with the administration of doxorubicin to dogs with malignant tumors.

One hundred eighty-five dogs with histologically confirmed, measurable malignant tumors were used in a study to determine the toxicity of the anthracycline antitumor antibiotic, doxorubicin, which was administered once or twice (at a 21-day interval) at the rate of 30 mg/m2 of body surface area, iv. During this study, 7 dogs died as a direct result of doxorubicin-induced toxicosis and 16 died as a direct result of the malignant neoplastic disease. Each dog was evaluated for signs of toxicosis for 3 weeks after the last dose was administered (15 dogs received 1 dose, 170 dogs received 2 doses) or until the dog died, whichever came first. The most common signs of toxicosis were vomiting, diarrhea, colitis, anorexia, and pruritus. The probability of doxorubicin-induced toxicosis decreased significantly (P less than 0.0001) in inverse relationship to body weight. Dogs with signs of toxicosis during the 21-day interval from administration of the first dose of doxorubicin were 17.2 times (P less than 0.01; 95% confidence interval; 5.5, 54.2) more likely to develop signs of toxicosis during the 21-day interval from the second dose of doxorubicin. The performance status of each dog was evaluated using a modified Karnofsky performance scheme; the only time the performance status was adversely affected to a significant extent by doxorubicin-induced toxicosis was during the 21-day period, starting with the second dose (P less than 0.0001).

Phase II evaluation of doxorubicin for treatment of various canine neoplasms.

One hundred eighty-five dogs with histologically confirmed, measurable malignant tumors were used in a prospective study to determine the response to 2 doses of the anthracycline antitumor antibiotic, doxorubicin. Eighty-three dogs had been refractory to one or more previous treatment modalities (surgery, n = 54; chemotherapy, n = 22; radiation, n = 10; hyperthermia, n = 1; biological response modifier, n = 1). The extent of neoplastic disease was determined immediately prior to and 3 weeks after 2 doses of doxorubicin were administered (30 mg/m2 of body surface area, iv) 21 days apart. Eighty-four percent (n = 157) of the dogs received 2 doses of doxorubicin and were evaluated. Of the 28 dogs ruled ineligible, 4 had serious side effects to the first dose of doxorubicin, and 24 others acquired complications resulting from their malignant tumors. A partial or complete remission was obtained in 41% (64/157) of all evaluable dogs: 26% (11/43) of the dogs with carcinoma, 67% (42/63) of the dogs with lymphoma, and 22% (11/51) of the dogs with sarcoma. Tumors in which there was at least a 50% volume reduction (partial or complete remission) included malignant lymphoma (42/63), fibrosarcoma (1/14), solid follicular thyroid carcinoma (3/13), mammary adenocarcinoma (2/8), hemangiosarcoma (2/8), osteosarcoma (1/6), circumanal carcinoma (3/5), synovial cell sarcoma (2/3), undifferentiated sarcoma (2/3), nasal adenocarcinoma (1/2), liposarcoma (1/2), infiltrating lipoma (1/1), malignant melanoma (1/1), sclerosing mesothelioma (1/1), and neurofibrosarcoma (1/2).(ABSTRACT TRUNCATED AT 250 WORDS)

Use of radionuclide imaging to identify malignant mammary tumor bone metastases in dogs.

Radionuclide imaging techniques were used to indicate the location and incidence of bone metastases in 30 dogs with malignant mammary tumors. The method was successful in distinguishing mammary tumor metastases in the sternum of one dog.

The early detection of host immune response to spontaneous mouse mammary tumors by leukocyte adherence inhibition.

Longitudinal testing of C3H/HeJ female mice was carried out over a 52-week period with the leukocyte adherence inhibition (LAI) assay using solubilized tumor antigen prepared by 3 M KCl extraction. During this period, 75% of the mice developed histologically confirmed mammary adenocarcinomas. Of those mice 93% had a statistically significant (P less than 0.01) LAI response to soluble mammary tumor antigen prior to first detection of tumors by palpation. Five percent of the test group developed statistically significant LAI responses without development of detectable mammary tumors within a 34-week observation period. The first significant LAI reactivity of individual mice preceded the first detection of tumors by an average of more than 17 weeks.

A 280-day tolerance-efficacy study with mibolerone for suppression of estrus in the cat.

Mibolerone, a synthetic anabolic steroid, prevented estrus in domesticated cats when orally given a daily dose of 50 microng over a 180-day period. Doses of 20 microng daily and 50 microng given once a week failed to prevent estrus. Treatment with the 50-microng dose each day for 6 months had no apparent effects on subsequent estrus, mating, queening, or litter size. Kittens born to queens which had been treated did not have obvious developmental defects. Systemic metabolic changes produced by treatment were detected only in thyroid function, as revealed in dose- and time-related changes in serum cholesterol concentrations, thyroid gland weights, and thyroid histology. Clinical evidence of thyroid dysfunction was not apparent during the 6 months of treatment. Clinical and microscopic evidence of slight masculinization was apparent in cats after 3 months of treatment with 20 or 50 microng per day. Masculinizing changes consisted of thickening of the cervical dermis and clitoral hypertrophy. Behavioral changes were not observed. The apparent mechanism of action of mibolerone in the cat is the suppression of the release of pituitary luteinizing hormone.

Megestrol acetate for estrus postponement in the bitch.

Megestrol acetate was given orally to 389 bitches in early proestrus, at a dosage of 2.2 mg/kg (1 mg/lb) per day for 8 days. Estrus was suppressed in 357 (92%) of the bitches. Additionally, 119 bitches in anestrus were given the drug at the rate of 0.55 mg/kg (0.25 mg/lb) per day for 32 days. Estrus was suppressed in 115 (98%) of these bitches. Adverse effects were minimal. Pyometra developed in 3 (0.8%) of the 389 bitches treated in early proestrus. The drug also was given to 19 bitches at the rate of 0.55 mg/kg/day for 32 days, regardless of the stage ofting at the 1st posttreatment estrus and 4 after mating at the 2nd posttreatment estrus. Litter size, success in rearing pups, and sex ratios were not significantly different from these factors in 53 litters from untreated bitches.

PIP: The postponement of estrus by megestrol acetate (MA) was evaluated in 389 female dogs. MA was administered for 8 days in a daily dose of 2.2 mg/kg body weight, beginning in early proestrus. Estrus was suppressed in 357 of these animals (92%). An additional 119 bitches in anestrus received MA in a daily dose of .55 mg/kg body weight for 32 days. Estrus was suppressed in 115 of these animals (97%). Pyometra was observed in 3 of 389 animals (.8%); other adverse affects were minimal. 19 animals received MA in a daily dose of .55 mg/kg body weight for 32 days, regardless of the stage of the estrous cycle. 15 of these bitches whelped normal litters after the 1st posttreatment estrus, and 4 after mating at the 2nd posttreatment estrus. Litter characteristics were similar to those observed in controls.

Pathological changes in virus enteritis of mink.

The lesions which characterize viral enteritis of mink (VEM) were studied in twenty-six, ten-week-old mink which had been infected by force feeding a tissue suspension containing a Wisconsin strain of mink enteritis virus. The pathogenesis of the lesions was reconstructed from gross and histopathological changes observed in animals which were selected randomly from the group each day for necropsy during the course of the disease. Alterations were observed in the tissues of all mink examined from post-inoculation day (PID) 4 through 13. The principal macroscopic lesions which consisted of fibrinous enteritis, enlargement and hemorrhage of the spleen and edema of mesenteric and hepatic lymph nodes were most conspicuous on PID 7 and 8. Histopathological changes including necrosis and desquamation of intestinal epithelium, depletion of mature lymphocytes in lymph nodes, thymus and spleen and loss of partly differentiated myeloid and erythroid cells from spleen and bone marrow also reached full development on PID 7 and 8. However, nuclear inclusion bodies which were presumed to be a product of the causative agent and, therefore, of diagnostic significance were most prevalent on PID 3, 4 and 5. The inclusions were observed in mucosal epithelial cells of the intestine, parenchymal cells of the liver and in lymphocyte precursor cells of the spleen, intestinal lymph nodules and masenteric and hepatic lymph nodes.

Some clinical and hematological features of virus enteritis of mink.

Twenty-six, ten-week-old mink were infected by force feeding by pipette 2 ml of a tissue suspension containing a Wisconsin strain of mink enteritis virus. Four days later, diarrhea and partial or complete loss of appetite developed simultaneously in all of the animals. Squinting and occasional vomiting were also observed. By the sixth day after inoculation, all of the mink were anorectic and weak. Anorexia persisted for 48 to 96 hours. Diarrhea and vomiting continued until the eighth to ninth day after exposure. For the first two days after the appearance of diarrhea, the feces contained large quantities of mucus and intestinal casts were seen frequently in the droppings. Thereafter, the feces consisted mostly of yellowish green, watery fluid and contained no casts. Some of the animals died on the eighth day after infection. Those which survived were severely dehydrated and debilitated, but resumed eating and achieved complete clinical recovery within the next five to six days.Leukopenia, i.e., total leukocyte count of less than 5,000 cells per mm(3) of blood, was found in seven of nine mink examined during the height of the disease. Leukopenic animals were deficient in both lymphocytes and neutrophils.