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Biomedical subjects

C C Brown

Publications and source records attributed to C C Brown.

At least 127 records · Page 7Linked to original sources
PubMed1986

Ontogeny of the opioid-mediated control of reproductive endocrinology in the male and female rat.

Endogenous opioids (EOP) appear to inhibit the release of luteinizing hormone-releasing hormone and, subsequently, luteinizing hormone (LH). These observations have led to the hypothesis that EOP-containing neuronal systems may be involved in the onset of puberty. To examine this possibility, rats were challenged with naloxone and morphine, as probes to decrease or exaggerate, respectively, the effects of EOP on luteinizing hormone releasing hormone/LH release at intervals from birth to adulthood. Morphine had no effect on serum LH up to 15 days of age in males, but thereafter was maximally effective. On the other hand, the onset of adult-appropriate responses to morphine occurred much later in females (30-35 days) and the depressions in LH were consistently less pronounced than in comparably aged males. Naloxone produced large increases in LH in 10- and 25-day-old females, but was ineffective at 15 or 20 days. After day 25, the response to naloxone declined gradually, but was still significantly greater than control values in adults. In contrast, naloxone failed to increase serum LH from 10 to 30 days after birth in males. Beginning at 30 to 35 days of age, however, a sudden onset in the sensitivity to naloxone occurred which increased exponentially until 60 days. At this time, serum LH levels were 5 times greater in naloxone-treated males than in controls, and were twice those found in similarly treated females. These age- and sex-related differences in response to the opiates were not related to pharmacokinetic variables and also could not be attributed to gross maturational alternations in the hypothalamic-pituitary-gonadal axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1986

Use of a toxoid vaccine to protect goats against intradermal challenge exposure to Corynebacterium pseudotuberculosis.

Two groups of male, 9-week-old goats (5 goats/group) were vaccinated subcutaneously with formalized exotoxin of Corynebacterium pseudotuberculosis, with Freund's incomplete adjuvant. Each goat was given 2 vaccinations, 2 weeks apart. At each vaccination, each group 1 goat was given 0.5 ml of toxoid, and each group 2 goat was given 1 ml of toxoid. Twenty days after the 2nd vaccination, vaccinated goats and 5 nonvaccinated 12-week-old goats (controls) were inoculated intradermally (challenge exposed) with live C pseudotuberculosis, monitored for 13 weeks, and euthanatized. At necropsy, 5 of the 10 vaccinated goats did not have C pseudotuberculosis lesions, 3 had abscesses limited to the inoculation site and draining lymph node, and 2 had disseminated bacterial lesions. Of the 5 nonvaccinated controls, 4 had disseminated abscesses and 1 had a single abscess in an internal node. Serologically, 9 of the 10 vaccinated goats developed positive (greater than or equal to 1:8) antibody titers against the exotoxin within 1 week after inoculation; the 10th goat seroconverted 2 weeks after inoculation, whereas control goats required 3 weeks to develop a positive antibody response. Therefore, early during an infection with C pseudotuberculosis, antibodies against the exotoxin may protect a goat against spread of the organism. All goats were injected intradermally before challenge exposure, 10 days after challenge exposure, and at 4, 8, and 12 weeks after challenge exposure with a skin-test reagent composed of fragmented bacterial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Serodiagnosis of inapparent caseous lymphadenitis in goats and sheep, using the synergistic hemolysis-inhibition test.

The synergistic hemolysis-inhibition (SHI) test, a serologic test for the detection of infection with Corynebacterium pseudotuberculosis, was applied to serum samples from 196 goats and 76 sheep, including animals both with and without C pseudotuberculosis abscesses. Fifty-one of 52 (98%) goats and 27 of 28 (96%) sheep with abscesses caused by C pseudotuberculosis had seropositive titers. Seropositivity continued on subsequent samplings, even after superficial lesions were completely healed. The SHI test may detect subclinically infected animals, as well as animals with clinically recognizable lesions. Of the animals without abscesses, 53 of 186 (28%) goats and 4 of 41 (10%) sheep were seropositive. Either the SHI test is lacking in specificity or these titers are a reflection of a past or a current infection without any grossly visible abscesses.

Animals↗
PubMed1986

Logistic regression methods for retrospective case-control studies using complex sampling procedures.

There are a number of possible designs for case-control studies. The simplest uses two separate simple random samples, but an actual study may use more complex sampling procedures. Typically, stratification is used to control for the effects of one or more risk factors in which we are interested. It has been shown (Anderson, 1972, Biometrika 59, 19-35; Prentice and Pyke, 1979, Biometrika 66, 403-411) that the unconditional logistic regression estimators apply under stratified sampling, so long as the logistic model includes a term for each stratum. We consider the case-control problem with stratified samples and assume a logistic model that does not include terms for strata, i.e., for fixed covariates the (prospective) probability of disease does not depend on stratum. We assume knowledge of the proportion sampled in each stratum as well as the total number in the stratum. We use this knowledge to obtain the maximum likelihood estimators for all parameters in the logistic model including those for variables completely associated with strata. The approach may also be applied to obtain estimators under probability sampling.

Clinical Trials as Topic↗
PubMed1985

Statistical aspects of the estimation of human risks.

The preceding paper has discussed the general problem of high dose to low dose extrapolation within a single animal species. The purpose of this extrapolation is to estimate the effects of low level exposure to toxic agents known to be associated with undesired effects at high dose levels. Mathematical models of dose response are necessary for this extrapolation process since the low dose effects, expected to be on the order of response rates of 10(-6, are too small to be accurately measured with limited study sample sizes. A number of mathematical dose-response models have been proposed for extrapolation purposes; we have shown how similar they can appear to one another in the range of observable response rates, yet how different they become at lower, unobservable response rates, the region of primary interest. This is the single, most important limitation of this extrapolation methodology. An estimate of risk at a particular low dose, or an estimate of the dose leading to a particular level of risk is highly dependent upon the mathematical form of the presumed dose response and differences of 3 - 4 orders of magnitude are not uncommon. Therefore, all these sources of uncertainty, dose-response model, pharmacokinetic behavior of the toxic agent, thresholds, heterogeneity, and patterns of exposure, lead to substantial uncertainties in estimates of risk based on high to low dose extrapolations.

2-Acetylaminofluorene↗
PubMed1985

Serologic response and lesions in goats experimentally infected with Corynebacterium pseudotuberculosis of caprine and equine origins.

Fifteen goat kids were experimentally inoculated with Corynebacterium pseudotuberculosis. Five were given a strain of caprine origin (nitrate-negative biotype) intradermally, 5 were given a strain of equine origin (nitrate-positive biotype) intradermally, and 5 were inoculated intranasally with the caprine-origin strain. Animals were monitored for 127 days. The goats given the inocula intradermally developed abscesses; those given caprine-origin strain had multiple lesions both peripherally and in visceral locations (primarily endothoracic abscesses), whereas those given the equine-origin strain had abscesses only at injection sites and draining nodes. The difference in extent of lesions could be due to biotypic bacterial differences or to the individual strains used. Intranasally inoculated goats did not develop abscesses and were essentially no different from controls. The cranial part of the respiratory tract may not be an important portal of entry for C pseudotuberculosis. Serum samples obtained monthly from all animals were subjected to the synergistic hemolysis-inhibition test, which measures antibodies to the exotoxin of C pseudotuberculosis. Animals with abscesses developed titers within 1 month of inoculation. Animals without abscesses remained seronegative. The synergistic hemolysis-inhibition test may be a reliable diagnostic assay for caseous lymphadenitis in goats.

Animals↗
PubMed1983

Hemorrhage in a cat caused by inhibition of factor XI (plasma thromboplastin antecedent).

A coagulation profile from a 5-year-old neutered male cat with severe epistaxis revealed an intrinsic coagulation defect characterized by prolonged activated partial thromboplastin time, with normal bleeding time, platelet count, and prothrombin time. Subsequent factor XI analyses, using bovine factor XI-deficient plasma, revealed factor XI deficiency. Hematologic and clinical studies on the cat failed to reveal an underlying disease process that might have resulted in acquired factor XI inhibition.

Animals↗
PubMed1983

Estimation of the increased risk of human infertility from alterations in semen characteristics.

Although many toxicants lower sperm counts in exposed men, there is no means of estimating the resulting increase in infertility. A mathematical model was developed to provide such estimates, using sperm counts (i.e., concentration) as an indicator of fertility potential. Continuous functions were fit to published distributions of sperm counts of men from fertile and infertile couples. A distribution of sperm counts for the overall population was constructed from these two functions. Equations were derived for calculating the infertility risk for a man with a given sperm count and the incidence of infertility in an exposed population. The increase in infertility was calculated for a proportional reduction of all sperm counts within a population and for a group of workers exposed to dibromochloropropane.

Female↗
PubMed1983

A new method for the analysis of cohort studies: implications of the multistage theory of carcinogenesis applied to occupational arsenic exposure.

Implications of the multistage theory of carcinogenesis for evaluating the effect of exposure to carcinogens in the workplace are described. This theory predicts different patterns of excess risk related to duration of exposure, age at initial exposure, and follow-up time since exposure stopped, depending upon which stage of the carcinogenic process is affected by the carcinogen, i.e., action at an early stage or a late stage. New statistical methodologies are proposed to examine these patterns and are applied to the lung cancer mortality experience from a cohort study of smelter workers exposed to arsenic. Under this multistage hypothesis, the results indicate that arsenic exerts a definite late stage effect though an additional effect at the initial stage cannot be ruled out. The possibilities of biased conclusions resulting from incomplete exposure histories and lack of smoking information are also discussed as well as implications of these results to experimental animal studies.

Arsenic↗
PubMed1983

Implications of the multistage theory of carcinogenesis applied to occupational arsenic exposure.

The multistage theory of carcinogenesis and its implications for evaluating the effect of exposure to carcinogens in the workplace are described. This theory predicts different relationships between excess carcinogenic risk and duration of exposure, age at initial exposure, and follow-up time since exposure stopped. These relationships are shown to depend on the stage of the carcinogenic process affected by the carcinogen, i.e., action at an early stage or a later stage. The patterns of excess lung cancer mortality were examined for a cohort of copper smelter workers exposed to atmospheric arsenic and other contaminants. Under this multistage hypothesis, the results indicate that arsenic appears to exert a definite effect on a late stage of the carcinogenic process, although an additional effect at the initial stage cannot be conclusively ruled out. Other factors, such as exposure to sulfur dioxide in the environment, calendar year at start of employment, and the potential bias resulting from incomplete exposure histories are also discussed as well as the implications of these results to experimental animal studies.

Adult↗
PubMed1983

The statistical comparison of relative survival rates.

A statistical procedure for comparing the survival of two or more groups of patients adjusted for normal mortality expectation, i.e. for calculating relative survival, is proposed. The method is shown to correspond to some commonly used procedures for comparing unadjusted survival; it provides an improvement over these procedures in many situations, even when the normal mortality expectations for the patient groups are the same. An example of its use is given.

Black People↗
PubMed1982

Additional power computations for designing comparative Poisson trials.

Published power computations for designing comparative Poisson trials are extended to the case of unequal populations sizes. The goal is to determine the required duration of a study for testing the one-sided alternative that the incidence rate of a rare disease in one population exceeds that in another population, based on an exact test conditional on the total number of events observed. Tables are provided for two designs: observing until a predetermined number of events have been observed, or observing for a predetermined length of time. The results may also be used to determine sample sizes for comparative binomial trials with very small binomial parameters when the numbers of patients in the two groups are not necessarily equal.

Epidemiologic Methods↗
PubMed1981

The validity of approximation methods for interval estimation of the odds ratio.

The validity of a confidence interval is determined by the probability that the random interval covers the true parameter value. A valid interval will have coverage probabilities at least as large as the confidence coefficient for all values of the parameter. The validity of three methods for constructing an approximate confidence interval on the odds ratio parameter for 2 X 2 tables is examined in the conditional hypergeometric sampling situation. Two examples are shown for which Cornfield's method is seen to be valid over a fairly wide range of true odds ratios, while the methods of Miettinen and Woolf are often found to be invalid. A number of other examples are studied with qualitatively similar results.

Epidemiologic Methods↗
PubMed1981

Optimal designs for the analysis of interactive effects of two carcinogens or other toxicants.

In this paper we consider the design of animal experiments conducted to test for interaction between two carcinogens or other toxicants. We examine 2 x 2 designs which contain an untreated control group, two groups treated with a single dose of each toxic agent alone, and one group treated with both agents together. Optimal rules for allocating animals to the experimental groups are derived on the basis of expected response rates for acute toxicity studies and these rules are then extended to long-term carcinogenesis studies by considering times-to-tumor under an assumption of proportional hazards. Unbalanced designs with more animals in the combination group than in the control group are shown to provide a gain in efficacy of about 20% over balanced designs.

Animals↗
PubMed1981

Exact significance levels for multiple binomial testing with application to carcinogenicity screens.

A simple experimental design consisting of one control group and one or more treatment groups is considered. Relevant research often focuses on the presence or absence of any of several characteristics in the treatment group(s). The statistical analysis frequently includes the comparison of the control group with each treatment group by the use of Fisher-Irwin exact tests for each of many 2 x 2 tables. The multiplicity of comparisons has given rise to concern that individual Fisher-Irwin tests could seriously overstate the experimental evidence in some situations. This paper provides a method for calculating the exact permutational probability of at least one significant Fisher-Irwin test when only one treatment group and one control group is used. For multiple-treatment-group designs, upper and lower bounds on the probability are provided. Emphasis is given throughout to carcinogenesis screening experiments and an example of such an experiment is provided.

Animals↗