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Biomedical subjects

J C Findlay

Publications and source records attributed to J C Findlay.

13 recordsLinked to original sources
PubMed1998

Exposure to 60 Hz magnetic fields and risk of lymphoma in PIM transgenic and TSG-p53 (p53 knockout) mice.

The results of a number of epidemiology studies suggest that exposure to power frequency (50 and 60 Hz) magnetic fields may be a risk factor for hematopoietic neoplasia. To generate experimental data to test this hypothesis, the influence of magnetic field exposure on lymphoma induction was determined in two strains of mice that are genetically predisposed to the disease. PIM mice, which carry the pim-1 oncogene, are highly sensitive to lymphoma induction by N-ethyl-N-nitrosourea (ENU); ENU-treated PIM mice were studied as a 'high incidence' lymphoma model. TSG-p53 (p53 knockout) mice, in which the p53 tumor suppressor gene has been deleted from the germ line, develop lymphoma as an age-related change; hemizygous TSG-p53 mice were studied as a 'low incidence' lymphoma model. Beginning 1 day after a single i.p. injection of 25 mg ENU/kg body wt, groups of 30 PIM mice/sex were exposed for 18.5 h/day to pure, linearly polarized, transient-free 60 Hz magnetic fields at field strengths of 0 (sham control), 0.02, 2.0 or 10.0 Gauss (G). An additional group of 30 PIM mice/sex was exposed intermittently (1 h on, 1 h off) to 10.0 G fields. Groups of 30 TSG-p53 mice/sex were exposed continuously to magnetic field strengths of 0 (sham control) or 10.0 G; TSG-p53 mice received no ENU. Studies were terminated after 23 weeks of magnetic field exposure. Lymphoma incidence in male PIM mice exposed continuously to 10.0 G magnetic fields was significantly reduced from that seen in sex-matched sham controls; survival, lymphoma incidence and lymphoma latency in other groups of PIM mice did not differ from sham controls. Survival and lymphoma incidence in all groups of TSG-p53 mice was 7% or less, regardless of magnetic field exposure regimen. These data do not support the hypothesis that exposure to magnetic fields is a significant risk factor for lymphoid neoplasia in mice with a genetic predisposition to the disease.

Animals↗
PubMed1997

Eight-week toxicity study of 60 Hz magnetic fields in F344 rats and B6C3F1 mice.

Toxicity studies were performed by exposing F344/N rats and B6C3F1 mice (10 animals per sex per species per group) to transient-free, linearly polarized 60 Hz magnetic fields for 8 weeks. Targeted magnetic fields strengths used were 0 gauss (G; sham control fields did not exceed 0.001 G), 0.02 G, 2 G, and 10 G. Exposure was whole-body and continuous for 18.5 hr per day, 7 days per week. An additional group of rats and mice was exposed intermittently (1 hr on/1 hr off) to 10 G fields for the same period of time. Endpoints evaluated included morbidity, mortality, gross pathology, histopathology, body/organ weights, clinical chemistry (rats only), and hematology (rats only). All mice and all male rats survived until the end of the study. One female rat (2-G exposure group) died during Week 7 of the study; the death was not attributed to magnetic field exposure. In both studies, the mean body weight gains of exposed animals were similar to those of the respective controls. There were no gross, histological, hematological, or biochemical lesions attributed to magnetic field exposure. Statistically significant increases in liver weight and liver to body weight ratio occurred in female rats of all exposure groups but only at the termination. These data suggest that, for the variables evaluated in these studies, an 8-week exposure to linear-polarized, transient-free 60 Hz magnetic fields at field intensities of up to 10 G is not associated with significant toxicity in F344/N rats and B6C3F1 mice. Furthermore, there was no toxicity observed in animals receiving intermittent (1 hr on/1 hr off) exposures to 10-G fields. A 2-year study in F344/N rats and B6C3F1 mice is nearing completion of the in-life phase without overt toxicity in any exposed group. It is premature, however, to make any prediction concerning the possible influence of exposure to 60 Hz magnetic fields on cancer rates.

Animals↗
PubMed1993

Familial adrenocorticotropin-independent Cushing's syndrome with bilateral macronodular adrenal hyperplasia.

Familial Cushing's syndrome is rare, and when it occurs, it is usually associated with primary micronodular dysplasia. We report two cases, a mother and daughter, who each presented with clinical features of Cushing's syndrome at age 38 yr and were found to have ACTH-independent macronodular adrenal hyperplasia. In each case, bilateral adrenalectomy revealed the massively thickened adrenal cortex with nodules up to 1.3 cm in diameter and hyperplasia between nodules. Dynamic testing showed no suppression of free cortisol with high dose dexamethasone and no stimulation of 17-hydroxycorticosteroids with metyrapone. Two samples of serum obtained preoperatively from one patient that showed ACTH immunoreactivity of 4.6 and less than 2.2 pmol/L, respectively, each showed less than 2.2 pmol/L ACTH bioactivity. The lack of suppression with high dose dexamethasone, lack of stimulation with metyrapone, and low levels of ACTH immunoreactivity and bioactivity suggest that the bilateral hyperplasia was not dependent upon ACTH. These patients represent the first cases of ACTH-independent macronodular adrenal hyperplasia occurring in two generations of one family and illustrate the expanding clinical spectrum of Cushing's syndrome.

17-Hydroxycorticosteroids↗
PubMed1992

Cushing's syndrome with cranial and pulmonary lesions: necessity for tissue diagnosis.

This report describes two cases of Cushing's syndrome associated with radiologic abnormalities in the lung and brain. In both cases, the pathologic diagnosis of the intracranial lesion was unsuspected and prompted changes in management. These cases illustrate that the etiology of pulmonary and central nervous system mass lesions in patients with Cushing's syndrome may not be predicted on clinical grounds or by conventional radiologic methods. A tissue diagnosis is essential as a guide to appropriate management, and biopsies of such lesions are indicated.

Aged↗
PubMed1989

Treatment of primary hypogonadism in men by the transdermal administration of testosterone.

We tested the efficacy of a thin flexible testosterone-impregnated membrane applied to the scrotum for the long term treatment of male hypogonadism. Ten men with primary hypogonadism were treated for 3 months (2 men) or 13 months (8 men). Serum testosterone concentrations increased in all 10 men, to within the normal range in 8. Serum dihydrotestosterone concentrations increased to supranormal values in all of the men, decreased to the normal range in 6, indicating the biological effectiveness of the testosterone in those subjects. Two men whose serum LH concentrations did not fall to normal had small or distorted scrotal surfaces. Seven of the 8 men whose serum testosterone concentrations became normal said that their hypogonadal symptoms were corrected by this treatment. We conclude that the transdermal administration of testosterone is an effective means of treating the majority of hypogonadal men who have a normal scrotum.

Administration, Cutaneous↗
PubMed1987

Transdermal delivery of testosterone.

We administered testosterone transdermally to six hypogonadal men by applying a thin flexible polymeric membrane containing testosterone to the scrotum. Each man wore a placebo membrane and three doses (5, 10, and 15 mg) of testosterone-containing membranes for 22 h/day. Each dose was worn for 1 week, and one dose was worn a second week. Blood was sampled frequently for one 22 h period on the seventh day of each treatment period. After the application of a membrane, the serum testosterone concentration rose rapidly, reached a peak in 2-3 h, and decreased slowly to 60-80% of the peak value by 22 h. The mean (+/- SE) 22-h average testosterone concentration during the wearing period was dependent on the testosterone content of the membrane (placebo, 135 +/- 38 ng/dl; 5 mg, 348 +/- 66 ng/dl; 10 mg, 455 +/- 77 ng/dl; and 15 mg, 624 +/- 65 ng/dl; P less than 0.001, by analysis of variance). When the same dose was worn twice, the mean coefficient of variation was 13.9%. We conclude that the transdermal application of testosterone to hypogonadal men reproducibly raises their serum testosterone concentrations to within the normal range, and that it, therefore, warrants evaluation as a treatment for male hypogonadism.

Administration, Cutaneous↗
PubMed1980

Erythrocyte insulin binding in insulin-dependent diabetes mellitus: lack of relationship to duration and control of diabetes in children and adolescents.

Insulin binding was measured in the erythrocytes (RBCs) of four children and 12 adolescents with insulin-dependent diabetes mellitus in the basal (fasting, nonketotic) state. Children and adolescents with insulin-dependent diabetes mellitus showed normal binding of insulin to their RBCs when expressed as the total insulin bound over the physiologic range of insulin concentrations. The insulin receptor concentration and receptor binding affinity for insulin were also normal. These parameters of insulin binding were not correlated with either the duration of diabetes or the degree of diabetic control in the patients. Since insulin binding by erythrocytes has been shown to reflect binding by traditional target tissues (liver, fat), the data suggest that alterations in binding of insulin to cells in children and adolescents with insulin-dependent diabetes mellitus probably play little, if any, role in the response of these patients to exogenous insulin or in the control of their glucose metabolism in the basal state.

Adolescent↗
PubMed1979

Effects of repeated exposures to peak concentrations of nitrogen dioxide and ozone on resistance to streptococcal pneumonia.

Exposures to various mixtures of nitrogen dioxide (NO2) and ozone (O3) reduced the resistance of mice to streptococcal pneumonia as evidenced by increased mortality rates and shortened survival time. Daily 3-h exposures (5 d/wk) for 2--6 mo to an air pollutant mixture consisting of 940 microgram/m3 (0.5 ppm) NO2 and 196 microgram/m3 (0.1 ppm) O3 were most effective in reducing the resistance to infection. The decrease in resistance to the infection occurred sooner than the mice continued to be exposed to the air pollutants instead of clean air for 14 d after the respiratory challenge with Streptococcus pyogenes aerosol. After 3 mo of exposure to the pollutant mixture, there was some decrease in the ability of mice to clear inhalated streptococci from their lungs. At the same time the total cell count in the fluid lavaged from the lungs of mice was markedly reduced, as were the viability and phagocytic activity of the alveolar macrophages. Exposure to the pollutants combined with challenge with Streptococcus aerosol resulted in marked morphological changes in lung tissues as seen by scanning electron microscopy.

Animals↗
PubMedDate not supplied

Chronic toxicity/oncogenicity evaluation of 60 Hz (power frequency) magnetic fields in F344/N rats.

A 2-yr whole-body exposure study was conducted to evaluate the chronic toxicity and possible oncogenicity of 60 Hz (power frequency) magnetic fields in rats. Groups of 100 male and 100 female F344/N rats were exposed continuously to pure, linearly polarized, transient-free 60 Hz magnetic fields at flux densities of 0 Gauss (G) (sham control), 20 milligauss (mG), 2 G, and 10 G; an additional group of 100 male and 100 female F344/N rats received intermittent (1 hr on/1 hr off) exposure to 10 G fields. Mortality patterns, body weight gains throughout the study, and the total incidence and number of malignant and benign tumors in all groups exposed to magnetic fields were similar to those found in sex-matched sham controls. Statistically significant increases in the combined incidence of C-cell adenomas and carcinomas of the thyroid were seen in male rats chronically exposed to 20 mG and 2 G magnetic fields. These increases were not seen in male rats exposed continuously or intermittently to 10 G fields or in female rats at any magnetic field exposure level. No increases in the incidence of neoplasms, which have been identified in epidemiology studies as possible targets of magnetic field action (leukemia, breast cancer, and brain cancer), were found in any group exposed to magnetic fields. There was a decrease in leukemia in male rats exposed to 10 G intermittent fields. The occurrence of C-cell tumors at the 2 lower field intensities in male rats is interpreted as equivocal evidence of carcinogenicity; data from female rats provides no evidence of carcinogenicity in that sex. These data, when considered as a whole, are interpreted as indicating that chronic exposure to pure linearly polarized 60 Hz magnetic fields has little or no effect on cancer development in the F344/N rat.

Adenoma↗
PubMedDate not supplied

Chronic toxicity/oncogenicity evaluation of 60 Hz (power frequency) magnetic fields in B6C3F1 mice.

A 2-yr whole-body exposure study was conducted to evaluate the chronic toxicity and possible oncogenicity of 60 Hz (power frequency) magnetic fields in mice. Groups of 100 male and 100 female B6C3F1 mice were exposed to pure, linearly polarized, transient-free 60 Hz magnetic fields at flux densities of 0 Gauss (G) (sham control), 20 milligauss (mG), 2 G, and 10 G; an additional group of 100 male and 100 female B6C3F1 mice received intermittent (1 hr on/1 hr off) exposure to 10 G fields. A small but statistically significant increase in mortality was observed in male mice exposed continuously to 10 G fields; mortality patterns in all other groups of mice exposed to magnetic fields were comparable to those found in sex-matched sham controls. Body weight gains and the total incidence and number of malignant and benign tumors were similar in all groups. Magnetic field exposure did not increase the incidence of neoplasia in any organ, including those sites (leukemia, breast cancer, and brain cancer) that have been identified in epidemiology studies as possible targets of magnetic field action. A statistically significant decrease in the incidence of malignant lymphoma was observed in female mice exposed continuously to 10 G fields, and statistically significant decreases in the incidence of lung tumors were seen in both sexes exposed continuously to 2 G fields. These data do not support the hypothesis that chronic exposure to pure, linearly polarized 60 Hz magnetic fields is a significant risk factor for neoplastic development in mice.

Adenoma↗