Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cecal perforation was diagnosed in a dog with a history of acute vomiting. The dog also had an adrenocortical adenoma. Intestinal perforation can be a serious complication of cortico-steroid treatment in the dog, but has not been attributable to hyperadrenocorticism. Fever and an inflammatory CBC were not observed, which could have been secondary to adrenal-dependent hyperadrenocorticism. The acute abdominal crisis associated with peritonitis required quick resolution in an attempt to save the dog, but also precluded any further diagnostic procedures for possible hyperadrenocorticism. The signs that suggested hyper-adrenocorticism in this dog included alopecia, lymphopenia, eosinopenia, high liver enzyme activities, hypercholesterolemia, and one large and one small adrenal gland. This latter finding presumably indicated negative feedback suppression and atrophy attributable to a functional adrenocortical adenoma.
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PMID:Cecal perforation and adrenocortical adenoma in a dog. 361 Jul 87

The differential white blood cell (WBC) count often reveals relative lymphopenia in Cushing's syndrome and may be a clue to the discovery of the ailment. However, the incidence of this finding has rarely been reported in the literature. We conducted a study on 40 patients with Cushing's syndrome due to adrenocortical adenoma to evaluate the diagnostic implications of relative lymphopenia. Total WBC count, differential WBC count, basal level of plasma cortisol, urinary excretion of free cortisol and thyroid function were evaluated preoperatively. We also investigated the differential WBC count in 40 patients with thyroid tumors matched for age and sex with the Cushing's syndrome patients. The proportion of lymphocytes among WBCs was also compared between the two groups. The proportion of lymphocytes among WBCs was significantly lower in the patients with Cushing's syndrome (19.4 +/- 10.8%) than in those with thyroid tumors (42.3 +/- 9.5%, mean +/- SD, p < 0.05). The incidence of relative lymphopenia was high (82.5%) as well as that of increased urinary excretion of free cortisol (85.3%) in Cushing's syndrome patients. The low T3 syndrome was frequently seen (73.9%), whereas the incidences of leukocytosis and an increased level of basal plasma cortisol were relatively low (42.5% and 47.5%, respectively). Relative lymphopenia provides useful information for diagnosing Cushing's syndrome since it has high sensitivity although it should be kept in mind that its specificity is low.
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PMID:[Relative lymphopenia in Cushing's syndrome]. 836 1

Urethane, a byproduct of fermentation found in alcoholic beverages, is carcinogenic in rodents and is classified by the International Agency for Research on Cancer as a possible human carcinogen. The United States Food and Drug Administration nominated urethane for study because of the widespread exposure of humans through the consumption of fermented foods and beverages and because of a lack of adequate dose-response data about the carcinogenicity of urethane with and without the coadministration of ethanol. Comparative studies of urethane in drinking water and in 5% ethanol were conducted to investigate possible effects of ethanol on urethane toxicity. Toxicokinetic studies of urethane in drinking water and in 5% ethanol and genetic toxicity studies of urethane in vivo and in vitro were also conducted. Groups of 10 male and 10 female F344/N rats and B6C3F1 mice, 6 weeks of age, received 0, 110, 330, 1,100, 3,300, or 10,000 ppm urethane in drinking water or in 5% ethanol for 13 weeks. Toxicokinetic evaluations were performed for urethane in the plasma of male mice after 13 weeks of administration in drinking water or 5% ethanol. The mutagenicity of urethane in Salmonella typhimurium strains TA97, TA98, TA100, TA1535, and TA1537 with and without S9 was tested at doses up to 16,666 micrograms/plate; urethane was also tested for induction of sister chromatid exchanges and chromosomal aberrations in cultured Chinese hamster ovary cells and sex-linked recessive lethal mutations and chromosomal reciprocal translocations in Drosophila melanogaster. The frequency of micronucleated erythrocytes induced in peripheral blood and bone marrow cells of mice by urethane in drinking water and in 5% ethanol was also evaluated. In rats that received urethane in drinking water, seven males and four females administered 10,000 ppm and one female administered 3,300 ppm died before the end of the study; body weight gains were reduced at these concentrations. Two males and all females given 10,000 ppm urethane in 5% ethanol died during the study, and the body weight gains of males and females that received 3,300 ppm were lower than those of the controls. Relative right kidney, liver, and lung weights of males and females and relative right testis weights of males administered 1,100 ppm or greater were generally higher than those of the controls in each study. Leukopenia and lymphopenia were observed in rats receiving urethane in either drinking water or ethanol and occurred in males receiving 330 ppm or greater and females receiving 110 ppm or greater. Other differences in hematology and clinical chemistry variables were not considered to be biologically significant. Lymphoid depletion of the spleen, lymph nodes, and thymus was observed in male and female rats receiving 1,100, 3,300, or 10,000 ppm urethane in drinking water. Cellular depletion of the bone marrow occurred in males and females in the 10,000 ppm groups. Hepatocellular fatty changes and clear cell foci of alteration were noted in the liver of males and females that received 3,300 or 10,000 ppm. The incidences of nephropathy were significantly increased in female rats that received 1,100 ppm or greater; the severity of this lesion in exposed males and females was greater than that in the controls. Females that received 330 ppm or greater had higher incidences of cardiomyopathy than the controls; the severity of this lesion was greater in males in the 10,000 ppm group and females in the 3,300 and 10,000 ppm groups than in the controls. In rats that received urethane in 5% ethanol, lymphoid depletion occurred in males and females in the 3,300 and 10,000 ppm groups. Cellular depletion of the bone marrow was observed in males and females in the 10,000 ppm groups. Only males in the 10,000 ppm group had hepatocellular fatty change (8/10) and clear cell foci (1/10); the incidence and severity of nephropathy in males and females and cardiomyopathy in males were similar to those in rats administered urethane in drinking water; however, no cardiomyopathy was observed in females receiving urethane in ethanol. The estrous cycle length of females receiving urethane in ethanol appeared to be longer than that of females receiving urethane in drinking water. Because cycle length was longer in the 10,000 ppm groups than in the controls in both the drinking water and ethanol vehicle studies, this difference may represent an exacerbation of the toxicity of urethane. A longer estrous cycle may be a sign of reproductive impairment and correlates with a decrease in female fecundity. All mice administered 10,000 ppm urethane in either vehicle died. All mice that received 3,300 ppm urethane in drinking water died, while only one male and four females receiving 3,300 ppm urethane in 5% ethanol died. Body weight gains of males and females in all 1,100 ppm groups were less than those of the respective controls, but the weight gains of mice receiving 1,100 ppm urethane in 5% ethanol were greater than those of mice receiving urethane in drinking water. The mean body weights of the lower exposure groups were similar to those of the respective controls, and there were no other differences between the body weights of mice receiving urethane in drinking water and those receiving urethane in 5% ethanol. Fluid consumption, and therefore total urethane intake, appeared lower in mice receiving the 5% ethanol vehicle than in those receiving the water vehicle. The relative right kidney, liver, and lung weights of males and females administered urethane in drinking water or ethanol were generally greater than those of the controls. Clearance of urethane from the plasma of male mice was complete within 2 hours after urethane was administered in water, but urethane was not cleared 12 hours after administration in 5% ethanol. At the end of 13 weeks of urethane administration, the plasma urethane elimination half-life was 0.8 hours; the kinetics were similar for concentrations of 110, 330, and 1,100 ppm urethane in water and in ethanol. However, at each exposure level, the plasma urethane concentration was four times greater for urethane administered in 5% ethanol than for urethane administered in drinking water, indicating a possible inhibition of urethane metabolism by ethanol. Kinetic measurements for elimination by female mice could not be obtained from the data collected. In mice administered urethane in drinking water, lung inflammation occurred in males and females that received 1,100 ppm or greater. Alveolar epithelial hyperplasia occurred in the lungs of males in the 330 and 1,100 ppm groups and females in the 1,100 ppm group; one male mouse in the 330 ppm group had an alveolar/bronchiolar adenoma (see the following summary table). Mice receiving urethane in 5% ethanol had lower incidences and severity of lung inflammation but generally greater incidences and severity of alveolar epithelial hyperplasia than mice receiving the same concentrations of urethane in drinking water. Alveolar/bronchiolar adenomas occurred in four males and one female administered urethane in ethanol. [table: see text] Nephropathy was observed in males and females that received urethane in either vehicle, and the lesions in female mice were more severe than those in male mice; ethanol did not appear to increase the incidence or severity of nephropathy. Cardiomyopathy occurred in males and females that received 1,100 or 3,300 ppm urethane in drinking water and in females that received 3,300 ppm urethane in ethanol. Lymphoid depletion occurred in mice that received 3,300 or 10,000 ppm urethane; 5% ethanol did not appear to enhance these effects. However, urethane in 5% ethanol induced ovarian atrophy; the incidence of this lesion was lower in females receiving urethane in drinking water. A concentration of 1,100 ppm urethane in either drinking water or ethanol effectively stopped estrous cycling. Urethane is clearly genotoxic in vitro and in vivo. In vitro, urethane induced mutations in Salmonella typhimurium strain TA1535 in the presence of liver S9 enzymes. Sister chromatid exchanges were induced in cultured Chinese hamster ovary (CHO) cells with and without S9. However, no induction of chromosomal aberrations was observed in CHO cells treated with urethane, with or without S9. In vivo, urethane induced sex-linked recessive lethal mutations and reciprocal translocations in germ cells of adult male Drosophila melanogaster fed urethane. Significantly increased frequencies of micronucleated erythrocytes were observed in peripheral blood obtained from male and female mice after 45 days of exposure and in bone marrow and peripheral blood obtained after 13 weeks of exposure to urethane in drinking water. There appeared to be no significant difference in the magnitude of the response in the peripheral blood micronucleus test between mice administered urethane in drinking water and mice administered urethane in 5% ethanol. In summary, concentrations of 1,100 ppm urethane or greater in drinking water caused lymphoid and bone marrow cell depletion and hepatocellular lesions and increased the severity of nephropathy and cardiomyopathy in male and female rats. The lethal effects of 10,000 ppm urethane were slightly exacerbated by 5% ethanol in female rats. Urethane administered in drinking water induced lung inflammation, alveolar and bronchiolar hyperplasia, alveolar/bronchiolar adenomas, nephropathy, cardiomyopathy, lymphoid and bone marrow cell depletion, seminiferous tubule degeneration, and ovarian atrophy and follicular degeneration in mice. In female mice, 5% ethanol appeared to exacerbate ovarian atrophy. Mice administered urethane in 5% ethanol consumed less fluid, and therefore less urethane, than mice receiving urethane in drinking water. Coadministration of urethane and ethanol inhibited the clearance of urethane from plasma. (ABSTRACT TRUNCATED)
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PMID:NTP technical report on toxicity studies of urethane in drinking water and urethane in 5% ethanol administered to F344/N rats and B6C3F1 mice. 1180 5

Twenty-six neoplasms of the adenohypophysis were classified either as chromophobe adenomas (20 dogs) or adenomas of the pars intermedia (6 dogs). In 62% of the dogs the neoplasms were functionally active (14 chromophobe adenomas, 2 adenomas of the pars intermedia) and associated with a syndrome of hyperadrenocorticism (Cushing's-like disease). The adrenal cortical hypertrophy and hyperplasia, muscular weakness and wasting, leukocytosis with a neutrophilia, eosinopenia and lymphopenia, deposition of fat in the liver, increased serum corticosteroid, and increased urinary 17-hydroxycorticosteroids all suggested the neoplasms were producing ACTH. Mineralization of the lungs and other tissues was consistently present in dogs with functional neoplasms. Adenomas of the pars intermedia appeared to arise from the lining epithelium of the residual hypophysial lumen covering the infundibular process. They were sharply demarcated from the compressed pars distalis.
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PMID:Neoplasms in the Adenohypophysis of Dogs: A Clinical and Pathologic Study. 2999 Nov 15