Neoplastic and life-span effects of chronic exposure to tritium. II. Rats exposed in utero.

A study was conducted to determine the effects on neoplasia incidence and life-span of exposure in utero to a major environmental radionuclide. Sprague-Dawley rats were continuously exposed to tritiated water (HTO) from conception through birth in doses of 0, 1, 10, 50, and 100 muCi HTO/ml body water. HTO administration was terminated at birth. Calculated cumulative doses during gestation were approximately 0, 6.6, 66, 330, and 660 rads of total body irradiation. Under these exposure conditions, the two highest doses resulted in sterile offspring. Animals surviving through 30 days postnatally were defined as the study population and observed until their deaths. Intrauterine exposures to doses up to 66 rads had no significant effects on either sex with respect to life-span, overall neoplasia incidence, incidence rate, or onset of mammary fibroadenomas. Females exposed to 330 or 660 rads were sterile and had lower incidence rates of mammary fibroadenomass than did controls; at 660 rads females had a lower incidence of overall neoplasia and reduced mean life-spans. Sterile male offspring had reduced mean longevity after irradiation at 660 rads. Regardless of dose group, females had significantly higher incidences of neoplasia and longer life-spans than males.

Neoplastic and life-span effects of chronic exposure to tritium. I. Effects on adult rats exposed during pregnancy.

Female Sprague-Dawley rats were continuously exposed to equilibrium levels of tritiated water (HTO) during pregnancy. The tritium activities were 1, 10, 50, and 100 muCi HTO/ml body water which provided cumulative, whole-body radiation doses of approximately 6.6, 66, 330, and 660 rads. Administration of the radioisotope was terminated at parturition. Throughout their life-spans and at autopsy, the dams showed an increased incidence of mammary fibroadenomas at exposure to 330 and 660 rads. Although the data for the incidence of malignant mammary neoplasms were consistent with a linear dose response, the small numbers of tumors preclude specific definition of the dose-response curve. Postexposure life-spans for dams chronically exposed to 66, 330, and 660 rads during pregnancy were reduced by 14, 24, and 22%, respectively. Accelerated aging was also demonstrated in these rats: The mean age for mammary fibroadenoma onset decreased with an increasing dose of radiation.

Developmental and behavioral changes in the rat during chronic exposure to lead.

Young male and female Sprague-Dawley rats were given drinking water containing 5 or 50 ppm Pb for 40 days prior to mating. Pregnant females were continued on these regimens throughout gestation and lactation. After weaning the offspring were similarly exposed through adulthood. Reflex development, body weights, and locomotor activity were measured in the offspring. Significant delays were noted in the development of the righting reflex at 5 and 50 ppm and in eye opening at 50 ppm. No difference was observed in development of the startle reflex at either dose. Mean body weights of treatment groups during this developmental period were not significantly different from controls. Locomotor activity was measured in adult males utilizing a residential maze. Both levels of lead produced a significant reduction in locomotor activity. When groups were treated with d-amphetamine (4.0 mg/kg subcutaneous), lead treatment caused a dose-related diminution in the amphetamine-induced hyperactivity. These results indicate that rats exposed to low levels of lead from conception until adulthood show a delay in nervous system development. As adults, these animals exhibit hypoactivity and decreased responsiveness to amphetamine.

The danger of applying group-level utilities in decision analyses of the treatment of localized prostate cancer in individual patients.

The optimal management strategy for men who have localized prostate cancer remains controversial. This study examines the extent to which suggested treatment based on the perspective of a group or society agrees with that derived from individual patients' preferences. A previously published decision analysis for localized prostate cancer was used to suggest the treatment that maximized quality-adjusted life expectancy. Two treatment recommendations were obtained for each patient: the first (group-level) was derived using the mean utilities of the cohort; the second (individual-level) used his own set of utilities. Group-level utilities misrepresented 25-48% of individuals' preferences depending on the grade of tumor modeled. The best kappa measure achieved between group and individual preferences was 0.11. The average quality-adjusted life years lost due to misrepresentation of preference was as high as 1.7 quality-adjusted life years. Use of aggregated utilities in a group-level decision analysis can ignore the substantial variability at the individual level. Caution is needed when applying a group-level recommendation to the treatment of localized prostate cancer in an individual patient.

A suggested limit for population exposure to radiofrequency radiation.

Unlike a number of other nations, the U.S. does not currently have guidelines for the exposure of the public to radiofrequency (RF) radiation. In order to determine whether the current data base was sufficient to support an interim determination of a limit for population exposure to RF radiation (0.5 MHz-100 GHz), a critical and comprehensive review of the available literature on the biological effects of RF radiation was recently completed. In the analysis of this data, a number of simplifying assumptions had to be employed; among them was the use of the specific absorption rate (SAR) as the mass-normalized, frequency-independent measure of RF energy input into biological systems. The biological effects reported in acceptable studies were assessed in terms of their associations with (1) core temperature increases, (2) SAR, (3) SAR as a percentage increase over resting metabolic rate, and (4) direct evidence for human effects. Based on information now available and analyzed from these four perspectives, a conservative SAR threshold value of approx. 0.4 W/kg is apparent. Since the unknowns and uncertainties are potentially significant, one might consider, from the standpoint of prudence, the further application of a safety factor of 10. Given the present state of knowledge, the resultant SAR limit of 0.04 W/kg is, in the author's opinion, unlikely to be associated with the adverse health effects in the general population. This SAR translates into a power density of approximately 200 mu W/cm2 in the human resonant frequency range of 30-300 MHz.

The urban health care clinic and its substance abuse population.

The effect of large numbers of patients with a history of substance abuse upon a health care system is rarely considered, nor is the health care system's response to such a clientele ever assessed. In this preliminary study, the collective effect of large numbers of substance abuse patients upon a clinic serving the urban poor and homeless is evaluated. The study examines the types of problems patients present to the clinic and the health care response, in terms of diagnoses and treatment plans, provided by the clinic. Using a random sample of 163 medical records, a retrospective analysis of reasons for visit, diagnoses and treatment plans was performed. Results indicated that patients with a history of substance abuse were more likely to present with chronic complaints and were not frequent return visitors to the clinic. No significant differences in either diagnoses or treatment plans for patients with a history of substance abuse were discovered. The implication of these results for health services provided to urban poor and homeless patients with histories of substance abuse was considered, as were reasons for the type of system response indicated by the results obtained.

Quantifying physician teaching productivity using clinical relative value units.

OBJECTIVE: To design and test a customizable system for calculating physician teaching productivity based on clinical relative value units (RVUs). SETTING/PARTICIPANTS: A 550-bed community teaching hospital with 11 part-time faculty general internists. DESIGN: Academic year 1997-98 educational activities were analyzed with an RVU-based system using teaching value multipliers (TVMs). The TVM is the ratio of the value of a unit of time spent teaching to the equivalent time spent in clinical practice. We assigned TVMs to teaching tasks based on their educational value and complexity. The RVUs of a teaching activity would be equal to its TVM multiplied by its duration and by the regional median clinical RVU production rate. MEASUREMENTS: The faculty members' total annual RVUs for teaching were calculated and compared with the RVUs they would have earned had they spent the same proportion of time in clinical practice. MAIN RESULTS: For the same proportion of time, the faculty physicians would have generated 29,806 RVUs through teaching or 27, 137 RVUs through clinical practice (Absolute difference = 2,669 RVUs; Relative excess = 9.8%). CONCLUSIONS: We describe an easily customizable method of quantifying physician teaching productivity in terms of clinical RVUs. This system allows equitable recognition of physician efforts in both the educational and clinical arenas.

Some aspects of brain neurochemistry after intrauterine exposure to tritium.

Rats were continuously exposed to tritiated water (0, 1, 10 and 100 muCi HTO/ml body water) from conception to birth. Calculated, cumulative whole-body doses to the embryo and foetus were approximately 0, 6-6, 66 and 660 rad. The levels of several enzymes and established or presumptive central nervous system neurotransmitters were examined postnatally in whole brains. These were norepinephrine (NE), dopamine (DA), acetylcholinesterase (AChE) and monoamine oxidase (MAO). Intrauterine exposures to doses as low as 66 rad produced measurable and persistent decreases in brain weight and increases in NE concentrations at 21 and 45 days postnatally. No differences from control values were seen in the rate of turnover of NE or the concentrations of DA, AChE or MAO at 45 days. Exposure in utero to 6-6 rad produced no detectable postnatal effects on the brain neurochemical parameters measured.