Scott W. Jordan

Teratogenesis and carcinogenesis in rat offspring after transplacental and transmammary exposure to diethylstilbestrol.

Abstract Transplacental and transmammary exposure of tat offspring to diethylstilbestrol (DES) was studied in regard to potential teratogenesis and carcinogenesis. Pregnant and/or lactating rats received DES in oil subcutaneously. In females so exposed, abnormal development of the urogenital sinus (hypospadias and urethrovaginal cloaca formation) occurred. In exposed male offspring, hypospadias, phallic hypoplasia, inhibition of growth and descent of testes, as well as abnormalities of Wolffian derivatives, were observed. In 20–40 per cent of DES-exposed female offspring, vaginal adenosis, endometrial squamous metaplasia, and genital malignancy were encountered. Two DES-exposed offspring had a vaginal squamous carcinoma, one had an endometrial adenocarcinoma, and one had an ovarian adenocarcinoma. Vaginal squamous carcinomas may have originated in foci of squamous metaplastic epithelium of vaginal adenosis. None of the control rats developed genital malignancy.

Cervical papillomavirus infection and cervical dysplasia in Hispanic, Native American, and non-Hispanic white women in New Mexico.

BACKGROUND Human papillomavirus infections of the cervix are found with varying frequencies in different populations worldwide, and have been associated with cervical cytologic abnormalities. METHODS We studied 1,603 randomly selected Hispanic, Native American, and non-Hispanic White women in New Mexico to determine the prevalence of cervical HPV infection in these ethnic groups, and its association with Pap smear abnormalities, using a new commercial dot-blot hybridization assay. RESULTS Nine percent of all women screened had evidence of cervical HPV infection (13.7% of non-Hispanic White women, 9.7% of Hispanics, and 6.6% of Native American women). Prevalence was higher in younger women ages 14-19 years than in older age groups. Over half of women with cervical HPV infection (n = 145) had normal Pap smears. The proportion of infected women increased among those with more advanced cytopathologic abnormalities; 5.6 percent with normal Pap smears had cervical HPV vs 66.7 percent with moderate-severe dysplasia. CONCLUSIONS Cervical HPV infection is common among New Mexico clinic attendees, varies in prevalence among the three major ethnic groups, and is strongly associated with cervical cytopathologic abnormalities.

Decreasing rates of cervical cancer among American Indians and Hispanics in New Mexico (United States)

Minority women in New Mexico (United States)—including American Indian and Hispanic women—have shown disproportionately high incidence rates of invasive cervical cancer during the 1960s and 1970s. Several public health programs in New Mexico were directed toward early detection of cervical cellular abnormalities, particularly targeting the states minority women. To evaluate the effectiveness of these programs, we examined the New Mexico Surveillance, Epidemiology, and End Results (SEER) data collected from 1969–92, and calculated average annual, age-specific, and age-adjusted incidence rates by ethnic group (American Indian, Hispanic, and non-Hispanic White) for five-year time intervals. We also calculated age-adjusted mortality rates for cervical cancer in the same ethnic groups using state vital records. Age-adjusted incidence rates for invasive cervical cancer show substantial temporal decreases, especially for minority women in the state. The age-adjusted incidence rate decreased by 66 percent, from 30.3 to 10.3 per 100,000 for American Indian women, and by 61 percent, from 26.1 to 10.2 per 100,000 for Hispanic women. A stage shift to earlier stages of cervical neoplasia occurred over the study period, with a substantially higher proportion of in situ compared with invasive cancers diagnosed in the most recent cf the most remote time period. The ratio of incidence rates of in situ to invasive cancers changed dramatically for both American Indian and Hispanic women. Cervical cancer mortality rates decreased steadily among Hispanic women from 1958 to 1992; the decrease among American Indian women was less stable and fluctuated due to small numbers. Ongoing targeted sceening programs should help to reduce cervical cancer incidence and mortality further in New Mexico.

Dependence of RBE on fraction size for negative pi-meson induced renal injury

Abstract A method is described for quantitation of murine late renal radiation response using histopathologic grading. Effective dose-50 percent (ED 50 ) is defined as the radiation dose at which 50% of animals showed renal tubular alterations of a specific histologic grade. The designated histologic grade was selected on the basis of its correlation with renal failure manifested by elevated blood urea nitrogen levels, weight loss and mortality of the experimental animals. Using this system, the ED 50 was determined for single, two, five, and fifteen (daily) fraction exposures with 300 kVp X rays and negative pi-meson (pion) beams generated at the Los Alamos Meson Physics Facility. The correlation between total radiation dose and the number of fractions was linear for both x ray and pion exposures when plotted on logarith mic coordinates, i.e. this relationship followed a power function. The relative biological effectiveness (RBE) for pions increased from 1.12 for a single dose of 1130 red, to 2.18 for 15 daily fractions of 145 rad. This latter fraction size approaches that being used in clinical trials, and provides an estimate of the RBE to be expected for kidney injury under conventional treatment protocols.

FRACTION SIZE, DOSE AND TIME DEPENDENCE OF X RAY INDUCED LATE RENAL INJURY

Histologic quantitation of renal radiation injury based on an intact mouse model correlates well with loss of renal mass, as measured by the ratio of right to left renal weight, radiation dose, and time after irradiation. Use of the radiation dose at which 50% of animals show renal tubular changes of a specified grade (ED50), allows comparison of 1, 5 and 15 fraction exposures. The X-ray dose necessary to effect significant injury (Grade 3 change) by six months after irradiation (ED50) was 11.6, 25.7, and 44.0 Gy for single, 5, and 15 fractions, respectively. Isoeffect plots of total radiation dose as a function of fraction number are linear on logarithmic coordinates, indicating that this relationship followed a power function. When plotted as inverse total dose versus dose per fraction, the six month post-irradiation data were linear, but the 12 month data were not. Lack of linearity is not in agreement with the multi-fraction isoeffect linear quadratic model.

Late effects of radiation on the mouse kidney

Abstract Renal histopathologic changes have been described in unilaterally nephrectomized mice following 1250–5000 rads of 250 or 300 KVP X-rays. Significant late renal morphologic alterations occurred beginning 5 months after irradiation which were correlated with elevated blood urea nitrogen (BUN), weight loss and spontaneous mortality. Renal tubular damage was considered to be the most significant finding, initially manifested by nuclear enlargement, followed by basement membrane thickening, and cellular atrophy or disappearance. Glomerulosclerotic changes were quite variable in degree, and were not considered to be as significant as tubular alterations. Vascular changes were found in arteries and arterioles of a few animals, and possibly represent a change secondary to parencymal cell loss. Dose-response relationships were definable at three time intervals after irradiation. The X-ray dose necessary to produce a given effec in 50% of animals was inversely related to the time elapsed after irradiation.

Carcinoma of the cervix in Southwestern American Indians: Results of a cytologic detection program

Age‐specific detection rates for newly diagnosed in situ and invasive uterine cervical carcinoma were determined in a nine‐year cytologic cancer detection program during which 34,700 Southwestern American Indian women and 46,200 medically indigent non‐Indian women were screened for cervical cancer. For patients less than 35 years of age, cervical carcinoma was found more frequently among Indians and Spanish‐American Caucasians than among other Caucasian women. At ages 60 and older, the Indian cervical cancer rate was much higher than that of non‐Indians. The detection rate for invasive cervical carcinoma among Indian patients is inversely related to the proportion screened at 30 years of age or older. Although at least 60% of Indian women 20 years old, and older, in the geographic area served by the detection program were screened for cervical cancer during the nine‐year period, only 27% of those 50 years or older were screened. The age‐related variation in screening percentage, in conjunction with the disproportionately large numbers of younger low‐risk women, serves to explain the finding of significant invasive cervical carcinoma in an extensively screened population.

Meningeal carcinomatosis from an ovarian primary: A clinicopathologic study

Meningeal carcinomatosis due to primary ovarian carcinoma is an uncommon metastasis that presents difficult problems in diagnosis and management of patients known to have this disease. There is evidence that extended survival due to advances in treatment of ovarian carcinoma has improved our ability to diagnose meningeal carcinomatosis of this tumor more often. Herein the first case of meningeal metastasis of primary ovarian cancer with cytologic and postmortem examination is discussed.

Late effects of unilateral radiation on the mouse kidney.

A system is described for quantitative assessment of renal radiation damage in intact animals. Mice received 1000, 2000, 3000, or 6000 rad of single-dose x irradiation to the right kidney. Animals were sacrificed 6 months after irradiation, the ratio of left to right renal weight and the ratio of left to right renal weight showed reasonably good correlation with radiation dose, the latter comparison appearing to be more sensitive, due to the amplification of effect resulting from left renal hypertrophy and right renal atrophy. Mice receiving 1000 rad showed no significant histologic abnormalities, but evidenced definite tubular epithelial atrophic changes after doses of 2000 rad or greater.

Modulation of cis-platinum renal toxicity by the radioprotective agent WR 2721

Abstract Pretreatment with the radioprotective thiol compound WR 2721 resulted in amelioration of renal histologic damage induced at 5 and 31 days in rats by a single exposure to cis -dichlorodiammineplatinum II ( cis -Pt), an anticancer agent. Renal histopathologic changes 5 days after exposure consisted of tubular epithelial necrosis at the corticomedullary junction, while after longer time intervals, nuclear hypertrophy, anisonucleosis, and diminished tubular diameters were evident. The degree of histologic change at 5 days was inversely correlated with the amount of WR 2721 administered. At 31 days after a single cis -Pt dose following pretreatment with 200 mg/kg WR 2721, the dose reduction factor (treated/control) was 1.5–1.6.