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Biomedical subjects

B Finley

Publications and source records attributed to B Finley.

At least 19 recordsLinked to original sources

The glucuronidation of morphine by dog liver microsomes: identification of morphine-6-O-glucuronide.

Canines are used extensively in the pharmaceutical industry for the preclinical screening of novel therapeutics, yet comparatively little is known about the phase 2 metabolism in this species. In humans, morphine is known to undergo extensive metabolism by glucuronidation, and the UDP-glucuronosyltransferase isoform, which catalyzes the formation of morphine-3-O-glucuronide and morphine-6-O-glucuronide is UGT2B7. This study was designed to investigate the glucuronidation of morphine using dog liver microsomes. Liver microsomes from beagle dogs catalyzed the glucuronidation of morphine-3(and 6)-O-glucuronide at rates 4 to 10 times that of rhesus monkey and human liver microsomes. The K(m) of morphine using beagle dog liver microsomes was approximately 270 microM, which is similar to that found for expressed human UGT2B7. The V(max) for morphine, using dog liver microsomes, was 27 nmol/min/mg of protein. Flunitrazepam inhibited the glucuronidation of morphine in dog liver microsomes, and the K(i) was 40 microM, which is similar to human UGT2B7 for other substrates. The effects of detergents were also investigated with dog liver microsomes, and Brij 35 and Brij 58 were found to be the best detergents to use for maximal activation of the dog liver morphine UGT. These studies suggest that dog has a UGT2B isoform similar to human UGT2B7.

Animals↗

Nutritional needs of the person with Alzheimer's disease: practical approaches to quality care.

Intellectual losses in Alzheimer's disease include ever-decreasing attention span, lack of judgment, compromised logic and reasoning skills, and lack of ability to plan and organize complex tasks. Patients have great difficulty staying focused on the task of eating. Extensive damage to the parietal, temporal, and occipital lobes causes altered processing of sensory input, resulting in distorted perceptions of the world around them. Many so-called "behaviors" are the direct result of clients' responses to their perceived environment. The ability to use utensils deteriorates because of both cognitive and motor losses. These patients commonly have slow, progressive weight loss over the span of their illness, despite high-energy diets. Altering the environment, staff approaches, and food items will make patients' lives easier and maintain good nutrition for as long as possible.

Alzheimer Disease↗

Interlaboratory validation of a new assay for DNA-protein crosslinks.

In 1992, a simple and sensitive assay for detecting DNA-protein crosslinks was developed [1]. In an effort to facilitate the greater use of the assay, a number of studies were conducted to evaluate its reliability and reproducibility. During this work, the assay was used to assess whether various metals and other compounds could induce crosslinks in cultured human lymphocytes (Epstein-Barr virus-transformed Burkitt's Lymphoma cell line). Potassium permanganate, mercury chloride, lead nitrate, magnesium perchlorate, aluminum chloride, and cadmium chloride did not induce DNA-protein crosslinks at either cytotoxic or non-cytotoxic levels. Copper sulfate, arsenic trioxide, and potassium chromate induced DNA-protein crosslinks only at cytotoxic concentrations. Acute lethality of the cells was assessed immediately after exposure to metals by trypan blue exclusion while long-term lethality was assessed by cell proliferation and trypan blue exclusion following an incubation period of 5 days after exposure to the metal compound. All metals exhibited more toxicity in the long-term lethality assay compared to the short-term assay. The cultured human lymphocytes treated with various doses of lead acetate, cadmium chloride, arsenic trioxide and copper sulfate, as well as cis-platinum and chromate, were sent to four different laboratories to compare the reliability and reproducibility of the DNA-protein crosslink assay. Depending on the chemical studied, there were quantitative differences in the results observed among the various laboratories using the assay. However, all laboratories generally showed that cis-platinum, chromate, arsenic trioxide and copper sulfate induced DNA-protein crosslinks at levels that produced acute cytotoxicity, whereas cadmium chloride and lead acetate did not.

Arsenic Poisoning↗

The benefits of probabilistic exposure assessment: three case studies involving contaminated air, water, and soil.

Probabilistic risk assessments are enjoying increasing popularity as a tool to characterize the health hazards associated with exposure to chemicals in the environment. Because probabilistic analyses provide much more information to the risk manager than standard "point" risk estimates, this approach has generally been heralded as one which could significantly improve the conduct of health risk assessments. The primary obstacles to replacing point estimates with probabilistic techniques include a general lack of familiarity with the approach and a lack of regulatory policy and guidance. This paper discusses some of the advantages and disadvantages of the point estimate vs. probabilistic approach. Three case studies are presented which contrast and compare the results of each. The first addresses the risks associated with household exposure to volatile chemicals in tapwater. The second evaluates airborne dioxin emissions which can enter the food-chain. The third illustrates how to derive health-based cleanup levels for dioxin in soil. It is shown that, based on the results of Monte Carlo analyses of probability density functions (PDFs), the point estimate approach required by most regulatory agencies will nearly always overpredict the risk for the 95th percentile person by a factor of up to 5. When the assessment requires consideration of 10 or more exposure variables, the point estimate approach will often predict risks representative of the 99.9th percentile person rather than the 50th or 95th percentile person. This paper recommends a number of data distributions for various exposure variables that we believe are now sufficiently well understood to be used with confidence in most exposure assessments. A list of exposure variables that may require additional research before adequate data distributions can be developed are also discussed.

Air Pollutants↗

Recommended distributions for exposure factors frequently used in health risk assessment.

Although there has been nearly complete agreement in the scientific community that Monte Carlo techniques represent a significant improvement in the exposure assessment process, virtually all state and federal risk assessments still rely on the traditional point estimate approach. One of the rate-determining steps to a timely implementation of Monte Carlo techniques to regulatory decision making is the development of "standard" data distributions that are considered applicable to any setting. For many exposure variables, there is no need to wait any longer to adopt Monte Carlo techniques into regulatory policy since there is a wealth of data from which a robust distribution can be developed and ample evidence to indicate that the variable is not significantly influenced by site-specific conditions. In this paper, we propose several distributions that can be considered standard and customary for most settings. Age-specific distributions for soil ingestion rates, inhalation rates, body weights, skin surface area, tapwater and fish consumption, residential occupancy and occupational tenure, and soil-on-skin adherence were developed. For each distribution offered in this paper, we discuss the adequacy of the database, derivation of the distribution, and applicability of the distribution to various settings and conditions.

Adult↗

A study of chromium induced allergic contact dermatitis with 54 volunteers: implications for environmental risk assessment.

Over the past 60 years, dose-response patch test studies by various methods have been conducted in an attempt to identify the minimum elicitation threshold (MET) concentration of hexavalent chromium (Cr(VI)) that produces an allergic response in Cr(VI) sensitive subjects. These data are not adequate, however, to provide an accurate estimate of the MET because of the variability in the patch testing techniques and the variability in diagnostic criteria used. Furthermore, the data were not reported in terms of mass of allergen per surface area of skin (mg Cr/cm2-skin), which is necessary for conducting occupational or environmental health risk assessments. Thus the purpose of this study was to determine the MET (mg allergen/cm2) for Cr(VI) and trivalent chromium (Cr(III)) by patch testing techniques. A patch test method that delivers a controlled amount of allergen per surface area of skin was used. A group of 54 Cr(VI) sensitised volunteers were patch tested with serial dilutions of Cr(VI) and Cr(III) to determine the cumulative response rate at several concentrations. The results indicate that the 10% MET for Cr(VI) based on the cumulative response was 0.089 micrograms Cr(VI)/cm2-skin. Only one of the 54 volunteers may have responded to 33 micrograms Cr(III)/cm2-skin, otherwise Cr(III) was unable to produce allergic contact dermatitis in these highly sensitive volunteers. Two supplemental studies were also conducted to assess whether the surface area of the patch and the concentration of Cr(VI) in the patch (related to patch thickness) were likely to influence the results. The data from these studies were used to assess the risk of developing allergic contact dermatitis due to contact with Cr(VI) and Cr(III) in soil. The findings indicated that soil concentrations at least as high as 450 ppm Cr(VI) and 165,000 ppm Cr(III) should not pose an allergic contact dermatitis hazard for at least 99.99% of the people in the community who might be exposed.

Adult↗

Safe concentrations for dermal allergens in the environment.

Recent work studies have examined the relationship between allergen dose per unit of skin surface exposed and the elicitation of response for chromium. The use of such data to arrive at levels in environmental contactants is discussed with reference to soil contaminated with chromium.

Chromium↗

Application of pattern recognition techniques to evaluate polychlorinated dibenzo-p-dioxin and dibenzofuran distributions in surficial sediments from the lower Passaic River and Newark Bay.

Isomer-specific determinations of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) were performed in 19 surficial sediment samples collected from the lower Passaic River and Newark Bay, New Jersey. Total PCDD and PCDF concentrations ranged from 415 to 23,300 ng/kg (dry wt) and 37 to 8400 ng/kg, respectively. OCDD and OCDF were the predominant congeners in all samples, followed by the hepta-, hexa-, tetra-, and penta-chlorinated compounds. Forty-seven percent (9/19) of the sediment samples contained no detectable levels of 2, 3, 7, 8-TCDD. The concentrations of 2, 3, 7, 8-TCDD and 2, 3, 7, 8-TCDF ranged from nondetect to 510 ng/kg (geometric mean of 5 ng/kg) and from 2.8 to 480 ng/kg (geometric mean of 13 ng/kg), respectively. The composition of PCDD/Fs in sediments was evaluated using chemometric pattern recognition techniques. Principal components analysis and complete linkage:farthest neighbor cluster analysis revealed the presence of at least five distinctive fingerprint patterns in surficial sediments collected from different locations in the Newark Bay estuary. Differences among PCDD/F patterns were attributable to the relative presence or absence of 1, 2, 3, 4, 6, 7, 8-HpCDF and the hepta-, hexa-, and octa-chlorinated congeners. To determine whether the presence of PCDD/Fs in sediments could be associated with a single source, residues in sediments were compared to those found in three soil samples and one sump sediment sample from a former 2, 4, 5-T manufacturing plant. Significant compositional differences were observed between the two data sets. Fingerprint patterns in sediments were dominated by the higher PCDD/F chlorinated congeners and contained significantly lower levels of the tetra-chlorinated congeners, particularly 2, 3, 7, 8-TCDD, than soils from the former 2, 4, 5-T plant. These differences, as well as those observed among surficial sediments from different locations, indicate that there are clearly several different sources of 2, 3, 7, 8-TCDD and other PCDD/Fs to the estuary.

Benzofurans↗

Serum transferrin receptor for the detection of iron deficiency in pregnancy.

Measurements of circulating transferrin receptor provide a sensitive quantitative index of tissue iron deficiency in otherwise healthy subjects. This investigation was undertaken to examine the diagnostic utility of this new iron index in pregnancy. A battery of iron-related measurements, including serum transferrin receptor concentrations, was performed on 176 women in third-trimester pregnancy who were attending a university prenatal clinic. The mean receptor concentration of 5.96 +/- 2.37 mg/L (+/- 1 SD) did not differ significantly from concentrations in nonpregnant individuals and the frequency distributions were likewise comparable. Elevations in serum receptor greater than 8.5 mg/L occurred only in women with depleted iron stores defined by serum ferritin concentrations. Abnormal concentrations were found in 11 of 13 women with overt iron-deficiency anemia. Our findings indicate that serum receptor concentrations are not influenced by pregnancy per se and are a sensitive index of iron deficiency. By combining serum receptor and serum ferritin measurements, the entire spectrum of iron status in pregnancy can be assessed.

Adolescent↗

The role of the psychiatric nurse in a community substance abuse prevention program.

There is an increasing awareness of the need for prevention of substance abuse related problems. The psychiatric nurse is especially equipped to strengthen the bonds among citizens and parents, health agencies and schools, law enforcement and hospitals to assist the community in the design and implementation of its own prevention program. The nurse is able to facilitate the community's own vested interests in a manner congruent with its needs. The nature and scope of nursing practice have traditionally included responses to health-conducive behavior. The nurse emphasizes self-determination and choice in health matters; therefore, substance abuse prevention efforts are likely to be incorporated by the community. The nurse provides the knowledge of addiction and abuse and assists the community in its health enhancement by using addiction and nursing theory, interpersonal process, research competencies, and teaching skills.

Adolescent↗

The use of a battered women's shelter as a clinical agency for student learning.

Family violence is prevalent and professional nurses need to be skilled in nursing its victims. The use of the Battered Women's Shelter is an outstanding clinical agency with high potential for student learning. Students gain recognition of their own and other's value system and the importance of allowing others the mastery of life. The process of psychiatric nursing can be discovered and practiced in the shelter agency.

Adult↗

Counseling the alcoholic client.

In all helper-helpee relationships, the experiencing of the uniqueness of each person is crucial. Each alcoholic is a person and alcohol dependence is but one plane of that person's being. Obtaining current information about alcoholism enables the professional nurse to deal with the disease in a systematic fashion. The personhood of each alcoholic must be met with creativity that focuses on the entire scope of potential as the conflict "I can't drink" changes to resolution, and increasing fullness of life becomes the issue.

Adult↗

Role of exposure databases in risk assessment.

Risk assessments have assumed an increasingly important role in the management of risks in this country. The determination of which pollutants or public health issues are to be regulated, the degree and extent of regulation, and the priority assigned to particular problems are all areas of risk assessment that influence the country's $100 billion annual investment in environmental protection. Recent trends in public policy have brought the practice of risk assessment under greater scrutiny. As policy makers increasingly insist that specific numerical risk levels (so-called bright lines) be incorporated into regulatory decisions, the stakes for good risk assessment practice, already high, are raised even further. Enhancing the scientific basis of risk assessments was a major goal of the Workshop on Exposure Databases. In this article, we present the Risk Assessment Work Group's evaluation of the use of exposurerelated databases in risk assessment and the group's recommendations for improvement. The work group's discussion focused on the availability, suitability, and quality of data that underly exposure assessments, a critical component of risk assessment. The work group established a framework for evaluation, based on exposure scenarios typically used in regulatory decisions. The scenarios included examples from Superfund, the Clean Air Act, the Toxic Substances Control Act, and other regulatory programs. These scenarios were used to illustrate current use of exposure data, to highlight gaps in existing data sources, and to discuss how improved exposure information can improve risk assessments. The work group concluded that many of the databases available are designed for purposes that do not meet exposure and risk assessment needs. Substantial gaps exist in measurements of actual human exposure and in the data necessary to model exposures, to characterize distributions of exposure, to identify high-risk groups, and to identify possible environmental inequities in exposure. The work group, on the basis of its findings, made both short-term and longer-term recommendations for improving the collection of exposure data in the future.

Animals↗