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Biomedical subjects

C C Brown

Publications and source records attributed to C C Brown.

At least 163 records · Page 9Linked to original sources

Sex differences in drug evaluations.

Twenty normal, nonobese subjects (10 males and 10 female) were administered a battery of seven psychomotor tests as well as affect checklists and physiological measurements on 6 alternate days. Subjects performed the entire battery predrug and at 45,90, and 135 min postdrug. Fenfluramine, dextroamphetamine, two combined doses of the drugs, and a placebo were given in a double-blind, repeated measures design. Findings revealed significant sex-based differences in initial performance on five of the seven psychomotor tasks and in two physiological measures, with males performing at higher levels than females. Additionally, sex differences in postdrug changes were found in three psychomotor and two physiological measures, with females evidencing greater change scores than males.

Adult↗

Estimated median survival times of patients with colorectal cancer based on experience with 9,745 patients.

From the End Results Group file at the National Cancer Institute, 9,745 colorectal cancer patients diagnosed from 1965 through 1971 and classified as adenocarcinoma NOS were selected to evaluate the joint effect of various prognostic factors on MST. A technic was developed which enables a physician to estimate the MST for a patient with a given set of patient/disease characteristics. The results are also summarized in an appendix, allowing the physician to bypass the calculation and refer directly to the MST. These results will aid the physician in determining whether a patient is at sufficiently high risk to warrant adjuvant therapy. The survival experience of this broad historical group of patients with varying prognostic factors can also serve as a basis for comparison of results of studies on highly selected patients treated in various experimental ways.

Adenocarcinoma↗

Histopathological evaluation of the inhibition of rat bladder carcinogenesis by 13-cis-retinoic acid.

An objective system for histopathological and statistical evaluation of rat bladder lesions induced by the carcinogen, N-methyl-N-nitrosourea, is described. This system has been used to measure the inhibitory effects of 13-cis-retinoic acid on the development of bladder cancer in female Wistar/Lewis rats. 13-cis-Retinoic acid caused significant inhibition of development of both preneoplastic and neoplastic lesions in bladder epithelium.

Animals↗

Mathematical aspects of dose-response studies in carcinogenesis--the concept of thresholds.

Many of the previously proposed theories of carcinogenesis which relate the exposure level of a carcinogen to expected tumor response, are summarized and it is pointed out that these theories assume the existence of no threshold level. A modification of the one-hit carcinogenic model which would incorporate a threshold, is proposed along with a generalization to variable thresholds over the population at risk. The statistical problems of discriminating between threshold and non-threshold models from experimental bioassay data are discussed and an example is given.

Animals↗

From mouse to man--or how to get from the laboratory to Park Avenue and 59th Street.

Where does this all leave us? It leaves us able to develop rather good animal data at dose levels that do not really interest us. That is a first-class highway that takes us where we do not want to go. It leaves us unlikely to be able to develop good data at "realistic" doses. To extrapolate animal results to man exposed at these "realistic" doses today requires assuming a mathematical model of dose-response in the animal and conservative use of this model. Then we have to jump from one species to another in ignorance of the terrain of the landing site, i.e., the many species differences. However, we will have knowledge of some important species similarities and that makes the jump a lot less dangerous. With respect to costs and benefits we are just beginning to understand some of the implications of the arithmetic. We have begun to see that there are few, if any, good ways of totaling the costs or computing the benefits. Cost-benefit may be another blind alley. Tomorrow and the next day we must do the appropriate research on species differences in metabolism and in the mathematics of the modeling and extrapolation--as a minimum. The socially related issues, such as what is an acceptable risk, what are the costs, what are the benefits, must be discussed in the open, freely. This implies recognizing that someone's costs may be someone else's benefits. (Our medical costs are our physician's source of living.) The inputs to the cost-benefit algebra are not well worked out. Our ways of working must include the adversary approach as well as the pleasanter way of cooperation. And today, we must get to precautionary decisions for man's safety and health based on the road maps from animal data--inadequate as they are. We have gotten to the neighborhood of Park Avenue and 59th Street and we can probably one day get to a lot of other places.

Animals↗

Field dependence and self-actualization in alcoholics.

Field independence and self-actualization were significantly increased in alcoholic patients following a 6-week treatment program. There were no differences, however, between patients treated by drug-assisted individual therapy, individual therapy, or milieu therapy. Some causal factors are hypothesized, and implications for treatment are discussed.

Adult↗

An improved Mantel-Bryan procedure for "safety" testing of carcinogens.

A published method by Mantel and Bryan for calculating "safe" doses of carcinogens is updated by incorporating several improvements. These improvements include more effective procedures for taking into account any spontaneous tumor rate and for combining data at several dose levels. An added feature is that it permits the combining of data from several experiments by postulating that it is only the spontaneous rate that differs between experiments. The improved method is illustrated with data from five hypothetical experiments, using a risk level of 10-8, a conservative slope of one probit or normal deviate per tenfold dose increase, and a nominal assurance level of 99%. The hypothetical experiments were geared to bring out particular pointsas, for example, the applicability of the model in the absence of control data. A large variety of issues involved in the determination of "safe" doses are discussed, including questions of experiment design and extrapolitan between species. A statistical appendix is provided, laying the framework for the calculating procedure and detailing complications therein. The "safe" dose approach helps resolve certain dilemmas in questions relating to food additives. A "no-detectable-level" prescription for chemical residues may be dangerous to the public where detection techniques are insufficiently sensitive, but it can become far too restrictive as exquisitely sensitive detection techniquesare developed. Only levels in excess of the "safe" dose would require detection. Calculated values for the "safe" dose could be updated and increased as more clear evidence of safety becomes available.

Animals↗