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Biomedical subjects

K M Walsh

Publications and source records attributed to K M Walsh.

At least 19 recordsLinked to original sources
PubMed1994

Spontaneous neoplasms in control Wistar rats.

Neoplastic data on 1370 control Wistar rats from 10 carcinogenicity bioassays done between 1980 and 1990 were reviewed. Mean percentage survival at 104 weeks was 58% for males and 59% for females. A total of 1857 neoplasms were diagnosed in 466 (68%) male and 582 (85%) female rats; 1390 were benign and 467 were malignant (12% with metastasis). Seventy-four percent of all neoplasms were in endocrine and reproductive systems. Most common neoplasms (affecting more than 7% of either sex) were pituitary adenoma (27.7% males; 55.0% females), mammary fibroadenoma (1.0% males; 25.3% females), mammary adenocarcinoma (1.0% males; 13.1% females), adrenal cortical adenoma (8.3% males; 9.3% females), and endometrial stromal polyp (9.6% females). Fourteen neoplasms affecting 2 to 6% of either sex included adrenal pheochromocytoma, thyroid C cell adenoma, thyroid follicular adenoma, pancreatic islet cell adenoma, lymphoma, histiocytic sarcoma, thymoma, hepatic adenoma, pancreatic acinar adenoma, mammary adenoma, dermal fibroma, astrocytoma, testicular interstitial cell tumor, and ovarian granulosa cell tumor. Remaining neoplasms were seen in less than 2% of animals.

Animals↗
PubMed1994

Comparative nephrotoxicity of a novel platinum compound, cisplatin, and carboplatin in male Wistar rats.

The nephrotoxicity of three platinum-containing antitumor agents was compared at doses that approximate the LD10 (cisplatin) or the LD50 (CI-973, carboplatin) doses. Male Wistar rats were administered single iv doses of 45 mg/kg CI-973, 6.5 mg/kg cisplatin, or 65 mg/kg carboplatin and observed for 4 days. Cisplatin treatment increased blood urea nitrogen (4x), creatinine (3x), glucose, and fractional electrolyte excretions, and decreased creatinine clearance by Day 4. These parameters were not significantly altered in CI-973- and carboplatin-treated animals. Cisplatin increased urinary excretion of LDH (six-fold), GGT (twofold), and NAG (twofold); CI-973 and carboplatin increased GGT excretion (approximately twofold). Cisplatin induced the following functional changes as a consequence of direct nephrotoxicity: decreases in GFR (84%), ERPF (97%), ERBF (96%), and ERTS (95%), and increases in FF (fivefold). Functional changes, attributed to prerenal effects of CI-973, included a decrease in ERPF (35%) and an increase in FF (48%). No changes were seen following carboplatin treatment. All cisplatin-treated rats had proximal tubular necrosis in the outer stripe of the outer medulla, extending multifocally into inner cortical medullary rays. No renal lesions were detected by light or electron microscopy in the control or CI-973- or carboplatin-treated rats. Cisplatin produced marked nephrotoxicity as determined by biochemical, functional, and histopathologic endpoints. CI-973 and carboplatin were significantly less nephrotoxic than cisplatin.

Animals↗
PubMed1993

Subacute and subchronic toxicology studies of CI-986, a novel anti-inflammatory compound.

CI-986 (5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)- thione-2-hydroxy-N,N,N-trimethylethanaminium salt) is a novel anti-inflammatory compound classified as a dual inhibitor of cyclooxygenase and 5-lipoxygenase. Studies were undertaken to characterize the preclinical toxicology of the compound. CI-986 was administered to rats for 2 weeks (0, 50, 250, 750, and 1500 mg/kg) or 13 weeks (0, 20, 250, 500, and 1000 mg/kg), dogs for 2 weeks (0, 50, 150, and 500 mg/kg) or 13 weeks (0, 20, 100, and 200 mg/kg), and to monkeys for 2 weeks (0, 50, 250, and 1000 mg/kg). No drug-related deaths resulted. Mild clinical signs of toxicity were noted in rats given doses of 250 mg/kg and above. Drug-related emesis and diarrhea were absent at the low dose in the dog and monkey but increased in incidence and severity at higher doses. Severe clinical signs in monkeys (emesis and diarrhea) necessitated the lowering of the top dose to 500 mg/kg/day (administered b.i.d.) during the second week of the monkey study. Slight decreases (< 23%) in serum protein and/or albumin were noted in all studies at the higher doses. A dose-related increase in alkaline phosphatase was noted in both dog studies, with no other drug-related effect on clinical pathology parameters. A gastric ulcer occurred in one rat administered 500 mg/kg CI-986 for 13 weeks. Gastrointestinal ulcers were not noted at any other dose in rats or at any dose in dogs or monkeys. A dose-related eosinophilia of glandular stomach submucosa was noted in rats after 2 and 13 weeks of drug administration but not in dogs or monkeys. In the 2-week rat study, mean combined sex plasma drug concentrations monitored 2 hr after dose on Day 14 were 0.59, 1.10, 2.64, and 3.43 micrograms/ml for the 50, 250, 750, and 1,500 mg/kg dose groups, respectively. In the 2-week dog studies, maximum plasma drug concentrations on Day 10 or Day 11 were achieved within 2 hr of dose with mean combined sex Cmax values of 0.73, 2.05, and 2.62 micrograms/ml for the 50, 250, and 750 mg/kg groups, respectively. Hepatic microsomal induction characterized by increased microsomal protein, increased microsomal cytochrome P450 content, and increased p-nitroanisole O-demethylation activity was noted in dogs and monkeys but not rats. CI-986 was well tolerated in rats and dogs at the doses employed and in monkeys at doses up to 500 mg/kg (b.i.d.).(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1992

Stereological evaluation of altered hepatocellular foci in control Wistar rats.

Quantitative evaluation and stereological analysis of altered hepatocellular foci (AHF) were performed on hematoxylin and eosin-stained (H&E) liver sections from control Wistar rats from 9 2-yr carcinogenicity studies conducted between 1981 and 1991. Morphologic criteria previously described were used to classify AHF in H&E stained livers into basophilic, eosinophilic, clear, mixed, or vacuolated cell foci. Hepatocellular adenomas were seen in 1.6% of control rats and carcinomas were seen in 0.2%. AHF were diagnosed in 20% of control Wistar rats and were seen only in rats dying after 47 weeks. Basophilic foci were the most common AHF seen; incidences of tigroid and diffuse basophilic AHF were similar. Vacuolated foci were not identified in any rat. The mean number of AHF per cubic centimeter of liver was 101. The mean AHF volume varied from 0.002-0.048 mm3 and the mean volume fraction ranged from 0.005-0.026%. Compared to AHF in aged control Fischer 344 rats, AHF in control Wistar rats were fewer and smaller.

Animals↗
PubMed1991

Renal hyaline droplets in tumour-bearing female Wistar rats.

Renal hyaline droplets were defined by histochemical and ultrastructural methods in eight female Wistar rats in a carcinogenesis bioassay. All eight rats had neoplasms of varied type (five histiocytic sarcoma, one phaeochromocytoma, one rhabdomyosarcoma, one leiomyosarcoma). Renal hyaline droplets were not seen in female rats without tumours and, although in this study, rats with tumours did not all have hyaline droplets, the source of the protein is likely to be the neoplasm. Presence of hyaline droplets may be useful as a confirmatory criterion in tumour diagnosis.

Adrenal Gland Neoplasms↗
PubMed1991

Proliferative bone lesions in rats given anticancer compounds.

Proliferative endosteal lesions were observed in metaphysis and diaphysis of femur and sternebra of Wistar (CRL:[WI]BR) rats administered 3 chemically-distinct anticancer compounds with dissimilar mechanisms of action: trimetrexate glucuronate, an antifolate; pentostatin, an adenosine deaminase inhibitor; and CI-980, a mitotic inhibitor. Islands of woven bone, often circumscribed by conspicuous myelostromal proliferation, were seen on Days 8-28 in rats given trimetrexate glucuronate daily by gavage, and on Day 4 but not Day 29 in rats given a single intravenous dose of pentostatin. Intravenous administration of CI-980 for 1 or 5 days resulted in marrow necrosis, marked centripetal new bone formation, and myelostromal proliferation on Days 4 and 8, respectively. These lesions were not present at the termination of these latter studies (Days 29 and 35, respectively). In conclusion, anticancer compounds induced local bone marrow injury and the release of local inflammatory mediators which may have provided the stimulus for bone formation and myelostromal proliferation.

Animals↗
PubMed1989

Hypopigmentation in dogs treated with an inhibitor of platelet aggregation.

Hypopigmentation was the principal manifestation of systemic toxicity when the experimental platelet aggregation inhibitor, PD-89454, was orally administered to Beagle dogs for 28 days. Pigmentation changes were present in skin of nose, lips and eyelids and mucosa of hard palate. Fontana-Masson stain demonstrated decreased melanin within melanocytes and keratinocytes. Melanocytes were globoid with inconspicuous dendritic processes and had small, incompletely pigmented melanosomes that were quantitatively reduced relative to controls. Toxic mechanism of action of PD-89454, structurally distinct from known depigmenting compounds, was not established but ultrastructural findings suggest an interference in melanosome formation and/or melanization.

Animals↗
PubMed1987

Epithelial odontogenic tumours in domestic animals.

Epithelial odontogenic tumours are uncommon, poorly understood and often difficult to diagnose, oral neoplasms. Dental organ pre-ameloblasts and basal lamina induce development of mesenchymal cells into odontoblasts, which produce dentin and induce pre-ameloblasts to mature into secretory ameloblasts. These reciprocal sequential inductive interactions between dental epithelium and mesenchyme form the basis for classifying epithelial odontogenic tumours. There are three tumours classified as non-inductive: ameloblastoma characterized by cords and islands of stellate reticulum with peripheral palisades of polarized columnar cells, adenomatoid ameloblastoma which has acini, rosettes and ducts of polarized columnar cells and stellate reticulum and calcifying epithelial odontogenic tumour which contains foci of Congo-red-positive material surrounded by pleomorphic polygonal epithelial cells. There are five tumours in which induction of mesenchymal tissue is evident: ameloblastic fibroma with characteristics of ameloblastoma plus proliferation of closely associated pulp-like mesenchyme; dentinoma consisting of masses of dentin, often with minimal cellular component; ameloblastic odontoma which contains palisaded epithelium and stellate reticulum as in ameloblastoma, as well as foci of dentin and/or enamel; complex odontoma which is a disorderly array of dentin, enamel, ameloblastic epithelium and odontoblasts; and compound odontoma containing denticles with well-organized tooth morphology. This paper reviews the embryogenesis of teeth and describes six types of epithelial odontogenic tumours in 13 animals. The literature concerning these tumours in nearly 250 animals is reviewed. The most commonly reported tumour is ameloblastoma and the species in which all types are most commonly reported is the dog.

Animals↗
PubMed1987

Declining prevalence of anemia in childhood in a middle-class setting: a pediatric success story?

To study trends of anemia among middle-class children, we collected 6,162 hematocrit measurements from the medical records of 2,432 children, ages 9 months through 6 years, as seen at a private pediatric clinic during the past 18 years. A decline in prevalence of anemia was observed during that period. The overall age-adjusted rate of anemia decreased from 6.2% in 1969 to 1973, 5.8% in 1974 to 1977, 3.8% in 1978 to 1981, and 2.7% in 1982 to 1986. The decline was also observed when trends were determined for three age groups using a single hematocrit measurement per child. The 1982 to 1986 prevalences of anemia for various age groups among this middle-class pediatric population were relatively low: 2.8% among 9- to 23-month-old children, 2.4% among 24- to 47-month-old children, and 2.7% among 48- to 83-month-old children. Most of these recent cases of anemia were mild--most were only slightly less than the hematocrit values used to define anemia--and most did not show strong evidence of iron deficiency based on elevated levels of erythrocyte protoporphyrin. We conclude that iron deficiency is now mild and uncommon in these middle-class children. This improved nutritional status with regard to iron is probably related to increased intake of iron among infants and young children during the past two decades. These findings suggest that the recommended screening schedule for iron deficiency with hemoglobin or hematocrit measurements may need to be reassessed for well-defined populations of low-risk children.

Acute Disease↗
PubMed1986

Tricholemmomas in three dogs.

Tricholemmomas characterized by lobules of PAS-positive epithelial cells with a peripheral palisade surrounded by an amorphous eosinophilic band, are described in 3 dogs. This is the second report of this uncommon hair follicle tumour in domestic animals.

Animals↗
PubMed1986

Familial nonspherocytic hemolytic anemia in poodles.

Nonspherocytic hemolytic anemia, characterized by marked reticulocytosis, hepatosplenomegaly, hemosiderosis of reticuloendothelial organs and bone marrow myelofibrosis, and osteosclerosis, was diagnosed in 5 related Poodles. The unremitting anemia was clinically evident by 1 year of age, and was fatal as early as 3 years of age. Despite intense diagnostic endeavors including RBC fragility studies, RBC enzyme assays, and hemoglobin electrophoresis, the cause of this nonspherocytic hemolytic anemia remains to be determined.

Anemia, Hemolytic, Congenital↗
PubMed1984

Lymphangiosarcoma in two cats.

Cutaneous tumours consisting of irregular empty anastomosing spaces lined by spindle cells were diagnosed as lymphangiosarcoma in two cats. The tumour cells exhibited the characteristic lining up along pre-existing collagen and muscle fibres. Because of the small number of cases of lymphangiosarcoma in cats, conclusions regarding biological behaviour or breed incidence are not made.

Animals↗
PubMed1984

Canine multilobular osteosarcoma of the skull with metastasis.

A 6-year-old crossbreed dog had recurring nodular masses on the dorsum of the head which were diagnosed as multilobular osteosarcoma. At necropsy, metastases were present throughout the lungs. Histological features of the masses included multiple islands of cartilage and bone separated by a dense fibrovascular stroma. These tumours are slow growing malignant neoplasms which may metastasize.

Animals↗
PubMed1984

Comparison of porcine and semisynthetic human insulins using euglycemic clamp-derived glucose-insulin dose-response curves in insulin-dependent diabetes.

In order to compare the biologic effectiveness of porcine and semisynthetic human insulins, a euglycemic clamp method was used in eight insulin-dependent diabetic subjects. Each subject was tested for each insulin on separate days. In order to derive glucose-insulin dose-response curves for both insulins, sequential but constant infusion rates of 0.2, 0.5, 1.0, and 2.0 mU/kg/min were performed. Plasma glucose levels attained during the euglycemic clamp were 96 +/- 3 mg/dL. At each insulin infusion rate, the steady-state glucose infusion rate required to maintain euglycemia was measured. At each increment of insulin infused, steady-state glucose infusion rates for porcine insulin were 1.12 +/- 0.22, 1.90 +/- 0.59, 4.28 +/- 0.61, and 9.37 +/- 0.66 mg/kg/min compared with 1.27 +/- 0.42, 2.38 +/- 0.20, 4.25 +/- 0.43, and 8.87 +/- 0.67 mg/kg/min for semisynthetic human insulin. By ANOVA, no significant difference was noted between the two insulins. Because insulin infusion rates may not result in predictable circulating free insulin levels in subjects who have circulating insulin antibodies, free insulin levels were determined. When steady-state glucose infusion rates were compared with free insulin levels achieved at the four insulin infusion rates, dose-response curves for both porcine and semisynthetic human insulins were virtually identical. These data suggest that semisynthetic human insulin has equivalent biologic effects on overall glucose metabolism compared with porcine insulin in insulin-dependent diabetes.

Adult↗
PubMed1984

Quercetin: a mutagen, not a carcinogen, in Fischer rats.

Purified quercetin, as well as diets containing quercetin at 0.1% and 0.2%, are mutagens to Salmonella typhimurium TA100. This mutagenicity is enhanced with the S9 metabolic activation system. The urine of Fischer rats fed the 0.2% quercetin diet also is mutagenic with the S9 activation system, but the feces of these animals exhibited enhanced mutagenicity only without activation. This may indicate different quercetin metabolites in urine and feces. Rats fed these diets for 64 wk showed no consistent tissue lesions, carcinogenicity, or reproductive changes. Male rats fed 0.2% quercetin showed lowered blood serum glutamic oxaloacetic transaminase and urea nitrogen levels, but these values do not reflect pathological changes.

Animals↗
PubMed1984

Feline basal cell tumors: a review of 124 cases.

Basal cell tumors from 124 cats of six breeds which represented 4.2% of feline neoplasms and 10.9% of feline cutaneous neoplasms are characterized. The mean age of cats affected was 9.6 years, and an increased risk was correlated positively with increasing age (rxy = +0.85). Males, females, and castrates were affected equally. Long-haired breeds were at higher risk (p less than 0.01) for development of basal cell tumors which had two major histologic types--solid and cystic. No site predilection was apparent.

Age Factors↗