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Spontaneous pathology of the gray short-tailed opossum (Monodelphis domestica).

The gray short-tailed opossum, Monodelphis domestica, is a newly established laboratory animal that is becoming increasingly important to biomedical research. Because little disease information is available for this species, we reviewed records for spontaneous gross and histologic lesions and microbiologic results in 150 M. domestica necropsies during an 11-year period. We identified 150 (91 female, 59 male) animals from 441 necropsy cases which were controls in experimental protocols or were members of the breeding colony. Initial statistical examinations indicated that the sample was representative of the living members of the breeding colony with respect to age, sex, and range of inbreeding. Causes of death and types of tumors were specifically evaluated. Females died earlier than males (22.6 +/- 13.0 months versus 30.9 +/- 11.9 months), but this difference was not associated readily with diet or inbreeding levels. The organ systems with the greatest lesion prevalences, in decreasing order, were the digestive, urogenital, cardiovascular, and respiratory systems. The most probable causes of all deaths were associated with the digestive system, followed by the cardiovascular and integumentary systems. The principal disease problems were rectal prolapse, congestive heart failure, and dermatitis. Neoplasia was found in 39 of the animals. The prevalence of neoplasia was greatest in the digestive system, followed by the endocrine, urogenital, integumentary, and hematopoietic systems. Pituitary adenoma was the most common neoplasm, followed by uterine leiomyoma and cutaneous lipoma. Specific microbially-induced diseases were not recognized, and endo- and ectoparasites were not found in colony-born M. domestica.

Animal Diseases↗

Bioassay of N-nitrosodiphenylamine for possible carcinogenicity.

A bioassay of N-nitrosodiphenylamine for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex were administered N-nitrosodiphenylamine at one of two doses, either 1,000 or 4,000 ppm, for 100 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of administration of the test chemical. Groups of 50 male mice were administered N-nitrosodiphenylamine at one of two doses, either 10,000 or 20,000 ppm, for 101 weeks. Groups of 50 female mice were administered the test chemical at one of two doses, initially 5,000 or 10,000 ppm, for 38 weeks. Because of excessive depression in the amount of mean body weight gained in the dosed groups, the doses for the females were then reduced to 1,000 and 4,000 ppm, respectively, and administration at the lowered doses was continued for 60 weeks. The time-weighted average doses for the female mice were either 2,315 or 5,741 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at the end of administration of the test chemical. Mean body weights of dosed rats and mice of each sex were lower than those of corresponding controls, and were dose related throughout the bioassay, except for those of female rats during the first part of the bioassay. Mortality was dose related in the female rats, but was not affected when the test chemical was administered to the male rats or the male or female mice. Survival at the end of the bioassay was 64% or greater in the dosed and control groups of rats and mice of each sex, and sufficient numbers of animals were at risk in all groups for the development of late-appearing tumors. Transitional-cell carcinomas of the urinary bladder occurred at incidences that were dose related (P</= 0.001) in both male and female rats, and in direct comparisons the incidences of these tumors in the high-dose groups of each sex were significantly higher (P</= 0.001) than those in the corresponding controls (males: controls 0/19; low-dose 0/46; high-dose 16/45; females: controls 0/18; low-dose 0/48; high-dose 40/49). The possible mechanism by which these tumors were induced, such as calculi formation in the bladder or nitrosation of amines present in feed to a carcinogenic nitrosoamine, is unknown. Fibromas of the integumentary system occurred in male rats at incidences that were dose related (P=0.003), although in direct comparisons the incidences of these tumors in the individual dosed groups were not significantly higher than those in the control group (controls 1/20, or 5%; low-dose 1/50, or 2%; high-dose 10/50, or 20%). The incidence of fibromas of the integumentary system in historical-control male F344 rats at this laboratory is 6/285, or 2%. These results suggest an association of the fibromas in the male rats with the administration of the test chemical. No tumors occurred in the mice of either sex at incidences that were significantly higher in the dosed groups than in the corresponding control groups. The only changes related to compound administration were chronic inflammatory lesions in the urinary bladders of dosed mice. It is concluded that under the conditions of this bioassay, N-nitrosodiphenylamine was carcinogenic for both sexes of F344 rats, including transitional-cell carcinomas of the urinary bladder, but was not carcinogenic for B6C3F1 mice of either sex.

Journal Article↗

Clinical applications of scanning electron microscopy and X-ray microanalysis in dermatology.

Scanning electron microscopy is frequently applied to dermatological problems, as is evident from a review of the recent literature. In this tutorial, preparation methods and new techniques allowing experimental studies on the integumentary system are emphasized. Quantitative analysis in the electron microscope by use of energy-dispersive X-ray microanalysis ( EDX ) has become an important accessory technique. EDX can, for instance, be used to study problems involving physiological changes induced in skin by agents causing contact reactions. Recently, it has been shown that treatment with DNCB, chromate and nickel causes changes in elemental distribution in guinea-pig skin. In addition, elemental uptake in the integumentary system and in pathological inclusions in skin can be analyzed.

Animals↗

Bioassay of 5-nitro-o-anisidine for possible carcinogenicity.

A bioassay of 5-nitro-o-anisidine for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 5-Nitro-o-anisidine was administered in the feed at either of two concentrations, to groups of 50 male and 50 female animals of each species. The dietary concentrations used in the chronic bioassay for low and high dose rats were 0.4 and 0.8 percent, respectively. Dose A and B mice were fed dietary concentrations of 0.8 and 1.6 percent when initially placed on test, but after week 15 the concentration fed to dose B mice was reduced to 0.4 percent. After a 78-week period of chemical administration, observation of rats continued for up to an additional 28 weeks and observation of mice continued for up to an additional 19 weeks. For each species, 50 animals of each sex were placed on test as controls for the group receiving the higher concentration and 49 to 50 animals were of each sex were placed on test as controls for the group receiving the lower concentration. In both species, adequate numbers of animals in all groups survived long enough to be at risk from late-developing tumors. Feeding of 5-nitro-o-anisidine to rats was associated with increased incidences of tumors of the integumentary system. Basal-cell carcinomas, trichoepitheliomas, squamous-cell carcinomas and sebaceous adenocarcinomas each occurred in the skin of high dose male rats at statistically significant incidences. For both male and female rats, carcinomas (the combined incidence of sebaceous adenocarcinomas, ceruminous carcinomas and squamous-cell carcinomas) of the Zymbal's gland or the skin of the ear were significant in the high dose groups. In the clitoral gland of dosed female rats, the incidence of carcinomas and the incidence of adenomas were each significant. Among mice, the incidence of hepatocellular carcinoma was statistically significant for dose B females when compared to their appropriate controls. Under the conditions of this bioassay, dietary administration of 5-nitro-o-anisidine was carcinogenic in Fischer 344 rats, causing tumors of the integumentary system in males and females and of the clitoral gland in females. The compound was also carcinogenic to female B6C3F1 mice, causing hepatocellular carcinomas.

Journal Article↗

Bioassay of fenthion for possible carcinogenicity (CAS No. 55-38-9).

A bioassay of fenthion for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex and 50 mice of each sex were administered fenthion in the diet at one of two doses, either 10 or 20 ppm, for 103 weeks and then observed for 0 to 2 additional weeks. Matched controls consisted of groups of 25 untreated animals of each species and sex. All surviving animals were killed at 103 to 105 weeks. The mean body weights and the survival of the dosed animals were essentially unaffected by administration of the test chemical with the exception of the survival of the low-dose male mice, which was significantly lower than that of the corresponding matched control. Thus, most of the animals may have been able to tolerate higher doses. Sufficient numbers of animals in all groups of rats and mice were at risk for development of late-appearing tumors. In the male and female rats and the female mice, no tumors occurred at incidences that were significantly higher in dosed groups than in control groups. In the male mice, sarcomas, fibrosarcomas, or rhabdomyosarcomas of the integumentary system occurred at incidences that were dose related (P=0.043). In direct comparisons of the incidences of these tumors in the dosed groups with the incidence in the control group, the P values of 0.048 and 0.028 for the low- and high-dose groups, respectively, did not meet the Bonferroni criterion of P=0.025 for significance when multiple comparisons are made (controls 0/25, low-dose 7/49 or 14%, high-dose 8/48 or 17%). However, the incidence of sarcomas and fibrosarcomas in historical-control male B6C3F1 mice used in bioassays of other chemicals tested at this laboratory was 7/435 (1.6%), and no rhabdomyosarcomas occurred in the historical-control male mice. It is concluded that under the conditions of this bioassay, fenthion was not carcinogenic for male or female F344 rats or for female B6C3F1 mice. The increased incidence of sarcomas, fibrosarcomas, and especially rhabdomyosarcomas of the integumentary system in the male B6C3F1 mice suggested that the test chemical was carcinogenic in these animals.

Journal Article↗

Bioassay of 3-amino-9-ethylcarbazole hydrochloride for possible carcinogenicity.

A bioassay of 3-amino-9-ethylcarbazole (hydrochloride) for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice. Both the free amine and the hydrochloride salt were used. Groups of 50 rats of each sex and 50 mice of each sex were administered the test chemical at one of two doses, either 800 or 2,000 ppm for rats and either 800 or 1,200 ppm for mice, for 78 weeks. The rats were then observed for an additional 26-29 weeks, and the mice for an additional 16-17 weeks. Controls consisted of groups of 50 untreated rats of each sex and 50 untreated mice of each sex; separate controls were used for the groups of animals administered the different doses. All surviving rats were killed at 104-110 weeks; all surviving mice were killed at 94-97 weeks. Since the suppliers of the low-dose rats and mice differed from those of the corresponding low-dose controls, while the suppliers for the high-dose rats and mice were the same as those of the corresponding high-dose controls, comparisons of the high-dose groups with their corresponding controls were the most appropriate. Furthermore, since the low-dose animals did not receive the same regimen of administration of the test compound as that received by the high-dose animals, and since tests using the low-dose groups were not performed concurrently with those using the high-dose groups, analyses of the dose-related trends were not possible. Although the interpretation of results of the study was based primarily on comparisons of high-dose groups with their respective controls, the results obtained with the low-dose groups, regardless of the indicated complicating factors, supported the interpretation. Neoplasms of the liver were observed in significant incidences in rats and mice of both sexes. In male rats, hepatocellular carcinomas alone were significantly higher (P</=0.020) in both the low- and high-dose groups. When neoplastic nodules of the liver were combined with hepatocellular carcinomas, the combination occurred at significant incidences (P</= 0.012) in the low- and high-dose male rats and in the high-dose female rats (males: low-dose controls 0/36, low-dose 12/42; high-dose controls 1/48, high-dose 22/48; females: high-dose controls 0/50, high-dose 6/48). Hepatocellular carcinomas alone similarly occurred at significant incidences (P<0.001) in the low- and high-dose male and female mice (males: low-dose controls 7/48, low-dose 32/44; high-dose controls 6/44, high-dose 41/49; females: low-dose controls 1/47, low-dose 36/43; high-dose controls 1/45; high-dose 43/49). Papillomas or carcinomas of the integumentary system occurred at significant incidences (P</= 0.013) in both the low- and high-dose male rats (low-dose controls 0/36, low-dose 8/44; high-dose controls 0/48, high-dose 6/48); these tumors also occurred in low- and high-dose female rats, but not at incidences high enough to be statistically significant (low-dose control 0/39, low-dose 4/44; high-dose controls 0/50, high-dose 4/49). Carcinomas of the Zymbal's glands of the ear occurred at significant incidences (P</= 0.045) in the low- and high-dose male and female rats (males: low-dose controls 0/36, low-dose 5/44; high-dose controls 0/48, high-dose 7/48; females: low-dose controls 0/39, low-dose 10/44; high-dose controls 0/50, high-dose 12/49). These tumors were first observed as early as week 47 on study. Adenocarcinomas of the uterus or endometrium occurred at a significant incidence (P=0.002) only in the high-dose female rats (high-dose controls 1/50, high-dose 11/49); these tumors also occurred in the low-dose females, but not at an incidence high enough to be statistically significant (low-dose controls 4/38, low dose 11/43). It is concluded that under the conditions of this bioassay, 3-amino-9-ethylcarbazole (hydrochloride) was carcinogenic for the liver, inducing hepatocellular carcinomas in Fischer 344 rats and B6C3F1 mice of both sexes. Other tumors induced in the rats were carcinomas or papillomas of the integumentary system in males, carcinomas of the Zymbal's gland of the ear in males and females, and adenocarcinomas of the uterus.

Journal Article↗

NTP Toxicology and Carcinogenesis Studies of Isophorone (CAS No. 78-59-1) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Toxicology and carcinogenesis studies of isophorone (greater than 94% pure), a widely used solvent and chemical intermediate, were conducted by administering 0, 250, or 500 mg isophorone/kg body weight per day by gavage in corn oil to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex, 5 days per week for 103 weeks. Doses selected for the 2-year studies were based on the 16-day studies in which rats and mice of each sex received doses of 0-2,000 mg/kg per day and on 13-week studies in which rats and mice of each sex received doses ranging from 0 to 1,000 mg/kg per day by gavage in corn oil. No chemically related gross or histopathologic effects were observed in the 16-day or 13-week studies, but 1/5 high dose male rats, 4/5 high dose female rats, and all high dose male and female mice died during the 16-day studies. During the 13-week studies, 1/10 high dose female rats and 3/10 high dose female mice died. The high dose for the 2-year studies was set at 500 mg/kg per day for each sex of rats and mice, based mainly on the deaths in the 13-week studies. Throughout the 2-year study, the mean body weights of the high dose male rats averaged 5% lower than those of the vehicle controls. During the second year, the mean body weights of the female high dose rats averaged 8% lower than those of the vehicle controls, and the high dose female mice averaged 5% lower. The survival of high dose male rats was significantly lower than that of the vehicle controls after week 96 (final survival: vehicle control, 33/50; low dose, 33/50; high dose, 14/50). The survival of dosed female rats was poor (30/50; 23/50; 20/50), due in part to 20 gavage-related accidental deaths of dosed animals. The survival of male mice was also low (16/50; 16/50; 19/50), but there was a significant trend toward increased survival of dosed female mice relative to that of the vehicle controls (26/50; 35/50; 34/50). Dosed male rats showed a variety of proliferative lesions of the kidney (tubular cell hyperplasia: 0/50; 1/50; 4/50; tubular cell adenoma: 0/50; 0/50; 2/50; tubular cell adenocarcinoma: 0/50; 3/50; 1/50; epithelial hyperplasia of the renal pelvis: 0/50; 5/50; 5/50). Dosed male rats also exhibited increased mineralization of the medullary collecting ducts (1/50; 31/50; 20/50), and low dose male rats showed a more severe nephropathy than is commonly seen in aging F344/N rats. Carcinomas of the preputial gland were increased in high dose male rats (0/50; 5/50; 5/50). With the exception of a moderate increase in nephropathy (21/50; 39/50; 32/50), female rats did not show chemically related increased incidences of neoplastic or nonneoplastic lesions. In high dose male mice, isophorone exposure was associated with increased incidences of hepatocellular adenomas and carcinomas (18/48; 18/50; 29/50) and of mesenchymal tumors of the integumentary system (fibroma, fibrosarcoma, neurofibrosarcoma, or sarcoma: 6/48; 8/50; 14/50). An increased incidence of lymphomas or leukemias was noted in low dose male mice (8/48; 18/50; 5/50). Coagulative necrosis (3/48; 10/50; 11/50) and hepatocytomegaly (23/48; 39/50; 37/50) were observed more frequently in the livers of dosed male mice than in vehicle controls. No compound-related neoplastic or nonneoplastic lesions associated with isophorone exposure were seen in female mice. Isophorone was not mutagenic in strains TA100, TA1535, TA1537, or TA98 of Salmonella typhimurium in the presence or absence of Aroclor 1254-induced male Sprague-Dawley rat or male Syrian hamster liver S9. Isophorone was weakly mutagenic in the mouse L5178Y/TK+/- assay in the absence of S9; it was not tested in the presence of S9. Isophorone induced sister-chromatid exchanges in the absence of S9 in Chinese hamster ovary cells; it did not induce sister-chromatid exchanges in the presence of Aroclor 1254-induced male rat liver S9, and it did not induce chromosomal aberrations in Chinese hamster ovary cells in the presence or absence of S9. An audit of the experimental data was conducted for the 2-year toxicology and carcinogenesis studies of isophorcarcinogenesis studies of isophorone. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year gavage studies, there was some evidence of carcinogenicity of isophorone in male F344/N rats as shown by the occurrence of renal tubular cell adenomas and adenocarcinomas in animals given 250 or 500 mg/kg per day; carcinomas of the preputial gland were also observed at increased incidence in male rats given 500 mg/kg. There was no evidence of carcinogenicity in female F344/N rats given 250 or 500 mg/kg per day. For male B6C3F1 mice, there was equivocal evidence of carcinogenicity of isophorone as shown by an increased incidence of hepatocellular adenomas or carcinomas (combined) and of mesenchymal tumors in the integumentary system in animals given 500 mg/kg per day and by an increase in malignant lymphomas in animals given 250 mg/kg per day. There was no evidence of carcinogenicity of isophorone in female B6C3F1 mice given 250 or 500 mg/kg per day. Synonym: 3,5,5-trimethyl-2-cyclohexen-1-one

Journal Article↗

Congenital malformations in twins.

Among 1195 twins born in the Collaborative Perinatal Project, for whom information was available, 219 (18.33%) were found to have malformations, 179 (14.98%) single and 40 (3.35%) multiple. The frequency of malformations among twins was significantly higher than that among singletons from the same population, but the difference was entirely contributed by MZ twins. This holds true for both major and minor malformations. The frequency among Negro twins was higher than among white, and among male twins higher than among female. Twins had more malformations of the central nervous, musculoskeletal, ear, respiratory, cardiovascular, and alimentary systems and fewer malformations of the genitourinary and integumentary systems than singletons. In a significant number of cases when one twin of a pair had a malformation, the cotwin also had a malformation though not necessarily the same as that of the first twin.

Abnormalities, Multiple↗

Intranuclear coccidiosis in tortoises: nine cases.

Chelonian intranuclear coccidiosis has been reported once, in two radiated tortoises (Geochelone radiata), and is apparently rare. We describe intranuclear coccidiosis diagnosed histologically in two radiated tortoises, three Travancore tortoises (Indotestudo forstenii), two leopard tortoises (Geochelone pardalis), one bowsprit tortoise (Chersina angulata), and one impressed tortoise (Manouria impressa). Infection was systemic and involved alimentary, urogenital, respiratory, lymphoid, endocrine, and integumentary systems. Trophozoites, meronts, merozoites, macrogametocytes, microgametocytes, and nonsporulated oocysts were seen histologically or by electron microscopy. Intracytoplasmic and extracellular stages of parasite development also were identified histologically. Sequencing of a coccidial 18S rRNA consensus polymerase chain reaction (PCR) product revealed a novel sequence that provided phylogenetic information and may be useful for further diagnostic test design. Intranuclear coccidiosis was associated with variable degrees of inflammation in all cases, was considered the cause of death in six tortoises, and was a substantial contributing factor to the cause of death in two tortoises.

Animals↗

Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada disease is a chronic, granulomatous systemic autoimmune disease with manifestations in the ocular, central nervous, auditory, and integumentary systems. The target of attack seems to be antigens associated with melanocytes. Patients are usually of Asian, Middle Eastern, Asian Indian, Native American, or Hispanic ethnicity, and complain of neurologic symptoms quickly followed by decreased vision caused by a choroiditis, frequently with exudative retinal detachments. Corticosteroids are the mainstay of therapy, but other immunosuppressive therapy may be required. Complications, including cataract, glaucoma, choroidal neovascular membrane formation, and subretinal fibrosis, may limit final visual acuity.

Humans↗

The contribution of associated congenital anomalies in understanding Hirschsprung's disease.

Hirschsprung's disease (HSCR) is a complex congenital disorder which, from a molecular perspective, appears to result due to disruption of normal signalling during development of enteric nerve cells, resulting in aganglionosis of the distal bowel. Associated congenital anomalies occur in at least 5-32% (mean 21%) of patients and certain syndromic phenotypes have been linked to distinct genetic sites, indicating underlying genetic associations of the disease and probable gene-gene interaction in its pathogenesis. Clear-cut associations with HSCR include Down's syndrome, dominant sensorineural deafness, Waardenburg syndrome, neurofibromatosis, neuroblastoma, phaeochromocytoma, the MEN type IIB syndrome and other abnormalities. Individual anomalies vary from 2.97% to 8%, the most frequent being the gastrointestinal tract (GIT) (8.05%), the central nervous system (CNS) and sensorineural anomalies (6.79%) and the genito-urinary tract (6.05%). Other associated systems include the musculoskeletal (5.12%), cardiovascular systems (4.99%), craniofacial and eye abnormalities (3%) and less frequently the skin and integumentary system (ectodermal dysplasia) and syndromes related to cholesterol and fat metabolism. In addition to associations with neuroblastoma and tumours related to MEN2B, HSCR may also be associated with tumours of neural origin such as ganglioneuroma, ganglioneuroblastoma, retinoblastoma and tumours associated with neurofibromatosis and other autonomic nervous system disturbances. The contribution of the major susceptibility genes on chromosome 10 (RET) and chromosome 13 (EDNRB) is well established in the phenotypic expression of HSCR. Whereas major RET mutations may result in HSCR by haploinsufficiency in 20-25% of cases, the etiology of the majority of sporadic HSCR is not as clear, appearing to arise from the combined cumulative effects of susceptibility loci at critical genes controlling the mechanisms of cell proliferation, differentiation and maturation. In addition, potential "modifying" associations exist with chromosome 2, 9, 20, 21 and 22, and we explore the importance of certain flanking genes of critical areas in the final phenotypic expression of HSCR.

Animals↗

An update on the early management of traumatic paraplegia (nonoperative and operative management).

Both the spinal cord physician and the spinal surgeon must be fully cognizant of the alterations of functions in multiple systems of the body caused by a spinal cord injury. Complications can easily arise, particularly within the respiratory, urinary, and integumentary systems. Most are preventable if the medical and nursing staff are sufficiently knowledgeable to anticipate them and if the necessary equipment and facilities are available. Regionalization of care with early referral to a spinal cord injury center has become a cost-effective way to manage these patients. Only if their medical needs are met and complications are prevented will surgery, performed to allow early mobilization, really accomplish the desired result. This update reviews the current medical and surgical points of view concerning diagnosis, fracture classification, spinal stability, reduction and stabilization of the fracture deformity, and spinal canal decompression.

Contracture↗

Quantum mechanical structure-activity relationship analyses for skin sensitization.

Allergic contact dermatitis (ACD) results in inflammation of the skin due to sensitization of the immunologic system to a particular substance. The sensitization process is limited by the compound's ability to both permeate and react with proteins in the integumentary system. Currently, only in vivo animal tests such as the local lymph node assay (LLNA) are recognized by regulatory authorities for risk assessment of ACD. A quantitative structure-activity relationship has been developed to predict relative potency, which allows for the prediction of relative sensitization potentials. The experimental values used in this study include EC3 values (the concentration at which the stimulation index equals 3) from LLNA tests. The predictions in this model enable categorization of the compounds into three groups on the basis of risk of sensitization and enable screening of candidate molecules using rapid SAM1 semiempirical calculations prior to animal testing. The model may also be used to reduce the number of animals subjected to testing by providing estimated concentrations required for useful data of risk assessment. The effect of averaging available literature values on predictive ability is also investigated. The model includes halogenated compounds, aromatic compounds, alcohols, aldehydes, and ketones. The computational investigation resulted in a two-descriptor model that is consistent with the assumed mechanism for sensitization.

Hypersensitivity↗

The aging immune system and common infections in elderly patients.

The number of elderly persons in the United States has increased to 12.5% of the population, and diseases affecting this age group have also risen. Infections of the respiratory, urinary, and integumentary systems, commonly seen in elderly patients, are a leading cause of death. Changes in the immune system cannot be prevented; however, nursing interventions may reduce the incidence of infection. An understanding of the changes in the immune system and careful nursing assessments may help the nurse to detect infections in elderly patients earlier.

Aged↗

A trace metal (zinc and iron) study on low dose x-radiation response in rat skin.

There is no reliable bio-dosimeter regarding low dose radiation effects in mammalian systems. In this study, chronic low dose (< 1 cGy) whole body x-irradiated rat skin have shown altered trace metal (zinc and iron) content which clearly indicated the redistribution of these metals in the integumentary system. The decreased zinc to iron ratios suggested enhanced oxidative stress of the tissue. Changes in trace metal content in irradiated rat skin, as a biological response to low dose radiation, were non-linear. Moreover, the lowered zinc content of E2, E3, E4 and E5 dose groups suggested a different steady state, compared to the control. The Zn: Fe ratio decreased with increasing radiation dose.

Animals↗

Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis.

Responses to the genotoxic effect of bleomycin in lymphocytes of blood cultures, expressed as the average number of chromatid breaks per cell (b/c), varied from less than 0.20 to more than 2.00 in 335 normal individuals. More than 11% of the subjects tested showed a b/c rate above 1.00 and more than 22% showed a b/c rate above 0.80. These individuals are considered sensitive to this radiomimetic drug. The distributional profile of bleomycin responses of the control individuals appears to be representative of the normal human population. In patients with cancers of the colon (83), upper aerodigestive tract (head/neck) (77), and lung (71), the frequencies of subjects in the hypersensitive class were found to be between 40 and 50%, and the response profiles were distinctly different from those of the control population. On the other hand, in a group of elderly cigarette smokers, who exhibited no symptoms of lung cancer, the bleomycin sensitivity profile was significantly skewed toward the more resistant stratum, with only one hypersensitive case among 56 individuals tested (1.78%). The sensitivity profile of patients with breast cancer (82) was similar to that of the control population. Our data suggest that: (1) mutagen sensitivity may play an important role in carcinogenesis of organs and tissues that have direct contact with the external environment (respiratory, digestive, and integumentary systems); (2) it appears to have no significant influence on carcinogenesis of tissues that are not directly exposed to the environment (e.g., breast, brain); and (3) it also has little impact on carcinogenesis in individuals with a hereditary predisposition to cancer (e.g., retinoblastoma, Gardner's syndrome). Development of more effective and precise test systems for carcinogen sensitivity is highly desirable for identification of persons at risk.

Adult↗

Spontaneous neoplasms in control Wistar rats: a comparison of reviews.

Spontaneous neoplasms in 930 control Wistar rats from five carcinogenicity bioassays conducted between 1990 and 1995 were reviewed and compared with review findings in studies between 1980 and 1990. Mean survival at 104 weeks was 55% for males and 60% for females, similar to that of the previous review. A total of 1599 neoplasms was diagnosed in 361 (78%) male and 415 (89%) female rats; 1293 (81%) of these were benign and 306 (19%) were malignant (11% with metastases). Sixty-eight percent of all neoplasms were in endocrine and integumentary systems, similar to 74% seen in the previous review. Most common neoplasms (affecting > 7% of either sex) were pituitary adenoma (34% of males, 50% of females), benign adrenal pheochromocytoma (10% of males, 1% of females), thyroid C cell adenoma (6% of males, 8% of females), mammary fibroadenoma (3% of males, 36% of females), keratoacanthoma (11% of males, 0.6% of females), testicular interstitial cell tumor (11% of males), uterine stromal polyp (16% of females), pancreatic acinar cell adenoma (13% of males, 0.6% of females), and benign thymoma (3% of males, 8% of females). Seventeen neoplasms affecting 2 to 6.9% of either sex included adrenal cortical adenoma, thyroid follicular adenoma, pancreatic islet cell adenoma, pituitary carcinoma, mammary adenoma, mammary adenocarcinoma, fibroma, fibrosarcoma, dermal papilloma, uterine schwannoma, uterine granular cell tumor, pancreatic acinar cell carcinoma, hepatocellular adenoma, lymphoma, granular cell meningioma, renal mesenchymal tumor, and hemangiosarcoma. Remaining neoplasms occurred in fewer than 2% of animals. Mean tumor incidence did not differ significantly between our two reviews. Ratios of benign to malignant neoplasms were similar in both reviews and percentages of survival at 104 weeks were similar. Between the two reviews, greater than threefold increase in frequency of some neoplasms occurred only in males and included keratoacanthomas, pancreatic acinar cell adenomas/carcinomas, and astrocytomas. Frequencies of remaining neoplasms were within twofold or within 10% of previous frequencies. Some neoplasms diagnosed in this review but not in the previous review included cardiac schwannoma, pilomatrixoma, parathyroid adenoma, and prostatic adenoma but incidence was approximately 1% for any one tumor. Based on these reviews, Wistar rats appear to have a predilection to pituitary neoplasms and mammary fibroadenomas (females).

Animals↗