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Biomedical subjects

D Shea

Publications and source records attributed to D Shea.

At least 19 recordsLinked to original sources

Elimination rate constants of 46 polycyclic aromatic hydrocarbons in the unionid mussel, Elliptio complanata.

Elimination rate constants (k2), biological half-lives (t(1/2)), and the time required to reach 95% of steady-state (t95) are reported for 46 individual polycyclic aromatic hydrocarbons (PAHs) including both parent and alkyl homologues, for the freshwater unionid mussel, Elliptio complanata. Elimination rate constants generally follow first-order kinetics and range from 0.04/day (d) for perylene to 0.26/d for 2,6-dimethylnapthalene, half-lives range from 2.6 to 16.5 d, and t95 values range from 11.3 to 71.3 d. These values compare well with other k2, t(1/2), and t95 values reported in the literature for PAHs and other classes of hydrophobic organic contaminants. A linear regression of k2 versus log Kow demonstrates dependence of PAH elimination on hydrophobicity, as measured by an r2 value of 0.83, and produces the following regression equation: k2 = -0.06 (log Kow) + 0.44. This study provides evidence that mussels experiencing different forms of physiological stress (e.g., handling stress and fungal or bacterial growth) can exhibit large variation in toxicokinetic parameters. These results are particularly relevant to the extrapolation of laboratory results to field situations.

Animals↗

Species, tissue and gender-related organochlorine bioaccumulation in white-sided dolphins, pilot whales and their common prey in the northwest Atlantic.

Organochlorine concentrations were measured in white-sided dolphins, pilot whales, and their prey from the Gulf of Maine and used to identify species, tissue, and gender differences, and trophic transfer trends, in bioaccumulation. Polychlorinated biphenyl concentrations ([PCB]) in dolphin blubber (13 +/- 7.1 micrograms/g fresh wt.) were twice those in pilot whales, but pesticide concentrations (20 +/- 13 micrograms/g fresh) were similar between species. 4,4'-DDE, trans-non-achlor, Cl6(153) and Cl6(138) concentrations were highest. Skin tissues had more recalcitrant organochlorines than the internal organs. Male dolphins bioaccumulated higher concentrations of nonmetabolizable PCBs and hexachlorocyclohexane (HCH) isomers, whereas pilot whales had no gender-related differences in bioaccumulation. Pilot whales, mackerel, and herring had proportionately higher concentrations of DDTs, whereas [PCB] were higher in dolphins and squid. Although these odontocetes feed at the same trophic level and store a similar suite of contaminants, dolphins bioaccumulated higher and potentially hazardous 4,4'-DDE and PCB concentrations from food in their more geographically restricted range.

Animals↗

Cost analysis of telehomecare.

The demand for home health care has skyrocketed in recent years. The aging population and the push for more efficient delivery of hospital services have fueled this growing demand. However, health care financing reforms have constrained the industry's growth. Home health agencies struggle to deliver high-quality services while staying within the financial limitations imposed by reimbursement changes. Telehomecare is one way to provide cost-effective care in the current environment. Personal computers and video equipment can transmit data over ordinary telephone lines and allow home health providers to monitor patients and provide care at a much lower cost than earlier technologies that required wider bandwidth telephone lines and more complex equipment. But can telehomecare yield cost-savings for home health agencies? This article addresses the costs associated with a telehomecare intervention in a large, urban, home health agency. The purpose of the study was two-fold: (1) to test the effects of telehomecare on clinical outcomes, and (2) to estimate the financial costs associated with providing telehomecare services. Our results show that, while telehomecare imposes additional expenses for care delivery, it contributes substantial savings without compromising quality. Additionally, we found that the financial benefit increases exponentially as the duration of the patient care episode increases.

Aged↗

Separation of acidic solutes by nonaqueous capillary electrophoresis in acetonitrile-based media. Combined effects of deprotonation and heteroconjugation.

Nonaqueous capillary electrophoresis (NACE) is a chemical separation technique that has grown in popularity over the past few years. In this report, we focus on the combination of heteroconjugation and deprotonation in the NACE separation of phenols using acetonitrile (ACN) as the buffer solvent. By preparing various dilute buffers consisting of carboxylic acids and tetrabutylammonium hydroxide in ACN, selectivity may be manipulated based on a solute's dissociation constant as well as its ability to form heterogeneous ions with the buffer components. ACN's low viscosity, coupled with its ability to allow for heteroconjugation, often leads to rapid and efficient separations that are not possible in aqueous media. In this report, equations are derived showing the dependence of mobility on various factors, including the pKa of the analyte, the pH and concentration of the buffer, and the analyte-buffer heteroconjugation constant (Kf). The validity of these equations is tested as several nitrophenols are separated at different pH values and concentrations. Using nonlinear regression, the Kf values for the heteroconjugate formation between the nitrophenols and several carboxylate anions are calculated. Also presented in this report are the NACE separations of the 19 chlorophenol congeners and the 11 priority pollutant phenols (used in US Environmental Protection Agency methods 604, 625/1625 and 8270B).

Acetonitriles↗

In vitro metabolism of polychlorinated biphenyl congeners by beluga whale (Delphinapterus leucas) and pilot whale (Globicephala melas) and relationship to cytochrome P450 expression.

We measured rates of oxidative metabolism of two tetrachlorobiphenyl (TCB) congeners by hepatic microsomes of two marine mammal species, beluga whale and pilot whale, as related to content of selected cytochrome P450 (CYP) forms. Beluga liver microsomes oxidized 3,3',4,4'-TCB at rates averaging 21 and 5 pmol/min per mg for males and females, respectively, while pilot whale samples oxidized this congener at 0.3 pmol/min per mg or less. However, rates of 3,3',4,4'-TCB metabolism correlated with immunodetected CYP1A1 protein content in liver microsomes of both species. The CYP1A inhibitor alpha-naphthoflavone inhibited 3,3',4,4'-TCB metabolism by 40% in beluga, supporting a role for a cetacean CYP1A as a catalyst of this activity. Major metabolites of 3,3',4,4'-TCB generated by beluga liver microsomes were 4-OH-3,3',4',5-TCB and 5-OH-3,3',4,4'-TCB (98% of total), similar to metabolites formed by other species CYP1A1, and suggesting a 4,5-epoxide-TCB intermediate. Liver microsomes of both species metabolized 2,2',5,5'-TCB at rates of 0.2-1.5 pmol/min per mg. Both species also expressed microsomal proteins cross-reactive with antibodies raised against some mammalian CYP2Bs (rabbit; dog), but not others (rat; scup). Whether CYP2B homologues occur and function in cetaceans is uncertain. This study demonstrates that PCBs are metabolized to aqueous-soluble products by cetacean liver enzymes, and that in beluga, rates of metabolism of 3,3',4,4'-TCB are substantially greater than those of 2,2',5,5'-TCB. These directly measured rates generally support the view that PCB metabolism plays a role in shaping the distribution patterns of PCB residues found in cetacean tissue.

Animals↗

Community-based long-term care for older persons with severe and persistent mental illness in an era of managed care.

The authors describe current needs and trends in the mental health care, including long-term care, of older persons with severe and persistent mental illness. The literature suggests that emerging models of managed long-term care hold promise for integrated services but do not currently address the specialized mental health needs of this patient group. The authors review issues in financing long-term mental health care, including controversies over fee-for-service and carve-out and carve-in arrangements. Without mechanisms to adequately finance services, adjust for risk, and measure outcomes, the authors conclude, managed care arrangements will be in conflict with the goal of high-quality care for older adults with severe and persistent mental illness. Proposed directions for future models of care for this group include integration of mental health and medical services, integration of specialized geropsychiatric services with developing community-based long-term care systems, blended financing under shared risk arrangements, and assurance of accountability and outcomes under managed care.

Adult↗

Medicare physician referral patterns.

OBJECTIVE: To study patterns of referral between primary and specialty care providers among Medicare beneficiaries and to identify correlates of the probability of referral. DATA SOURCES: The 1992 and 1993 Medicare Current Beneficiary Survey (MCBS), including associated claims data. MCBS data are linked to the Area Resource File (ARF) and the Physician Identification Master Record (PIMR). STUDY DESIGN: This is a retrospective design using cross-sectional descriptive and multivariate correlational analysis. Estimates are made for two years. Key variables include two alternative definitions of referrals, patient socio-demographic and health status, physician characteristics, and county-level descriptors. DATA COLLECTION: The MCBS is a panel survey of a stratified random sample of Medicare beneficiaries begun in 1991. The data are linked to Medicare claims records for survey respondents. The ARF is a health resources data set that contains more than 7,000 variables at the county level, including information on health facilities, health professions, services resources and utilization, and socioeconomic and environmental characteristics. The PIMR is a record of all physicians in the United States and describes their professional characteristics. PRINCIPAL FINDINGS: The overall rate of physician referrals in the MCBS, approximately 10 percent, is higher than that found in prior research, as is the level of self-referral to specialists at about 70 percent. Depending on the dependent variable definition, between 60 and 85 percent of all Medicare beneficiaries had at least one referral, and the average number of referrals per person per year was greater than two. Referrals show a multi-directional pattern rather than a simple pattern of primary to specialty care, with referrals between primary care physicians, referrals between specialists, and referrals from specialty to primary care being not uncommon. Strong predictors of referral include patient health and patient insurance coverage and income. Physician factors do not contribute much to explaining referrals. CONCLUSIONS: Medicare referral patterns are similar to those found in other studies. Patient factors appear to be a more important factor in explaining referrals than was estimated from prior research. Additional research is needed to explain the more complex dynamics of referral patterns.

Female↗

Altered metabolic elimination of testosterone and associated toxicity following exposure of Daphnia magna to nonylphenol polyethoxylate.

The ability of nonylphenol polyethoxylate (nonylphenyl polyethylene glycol, NPPG) to alter the metabolic elimination of testosterone and elicit reproductive toxicity to Daphnia magna was assessed. NPPG (5.0 mg/liter) inhibited the elimination of testosterone as glucose and sulfate conjugates, but had minimal effect on the rate of elimination of oxido-reduced and hydroxylated derivatives of the steroid hormone. This exposure concentration of NPPG also approximated the acute threshold-effect concentration and the chronic value for daphnids. Results demonstrated that NPPG qualitatively elicits similar effects on the metabolic elimination of testosterone by daphnids as previously characterized with its degradation product 4-nonylphenol. Unlike 4-nonylphenol, significant chronic toxicity of NPPG, due to effects on steroid elimination processes, was not evident. Results from the present study provide no indication that concentrations of nonylphenol polyethoxylates typically measured in the environment pose a risk of chronic toxicity to invertebrates.

Animals↗

An economic evaluation of energy-absorbing flooring to prevent hip fractures.

An economic evaluation of energy-absorbing flooring designed to prevent hip fractures revealed a payback period of 10 1/2 years if only direct costs avoided were evaluated and just over 11 months when direct and indirect costs were included. Cost-effectiveness ratios of less than $0 per hip fracture prevented and life year saved were also estimated.

Accidental Falls↗

Induction and post-transcriptional suppression of hepatic cytochrome P450 1A1 by 3,3',4,4'-tetrachlorobiphenyl.

3,3',4,4'-Tetrachlorobiphenyl (TCB) can induce and inhibit cytochrome P450 1A1 (CYP1A1) in vertebrates. TCB may also suppress CYP1A1 protein levels, but the mechanism is unknown. This study examined transcriptional and translational aspects of hepatic CYP1A1 regulation in the fish scup (Stenotomus chrysops) given single intraperitoneal injections of low (0.1 mg/kg) or high (5 mg/kg) doses of TCB, and sampled over 16 days. The low dose strongly induced hepatic CYP1A1 mRNA (25-fold), protein (12-fold), and activity [ethoxyresorufin O-deethylase (EROD)] (15-fold). The high dose also strongly induced CYP1A1 mRNA (29-fold), in a pattern like that at the low dose, but microsomal CYP1A1 protein content was induced only 4-fold and EROD rates were near control levels. Both TCB doses caused similar increases in microsomal cytochrome b5 content, and in rates of NADPH-cytochrome c (P450) reductase and UDP-glucuronosyltransferase (with p-nitrophenol). The contents of CYP forms other than CYP1A1 (putative CYP2B or CYP3A) were only weakly affected by TCB at either dose. The strong and largely specific post-transcriptional suppression of CYP1A1 content was associated with high concentrations of TCB measured in the liver. Incubation of scup hepatic microsomes with TCB plus NADPH led to a time-dependent inactivation of CYP1A1 that was distinct from catalytic inhibition, and appeared not to involve reactive metabolites of TCB. This in vitro result suggests that TCB may inactivate CYP1A1 in vivo, which could account for the apparent antagonistic effect of TCB on CYP1A1 induction.

Animals↗

Separation of polycyclic aromatic hydrocarbons by nonaqueous capillary electrophoresis using charge-transfer complexation with planar organic cations.

In this study, we examine the use of charge-transfer interactions between polycyclic aromatic hydrocarbons (PAHs) and planar organic cations in nonaqueous capillary electrophoresis. Since the separations are performed in a purely nonaqueous medium, this method also facilitates the analysis of solutes that have low solubilities in aqueous or mixed media. Presented in this study are the separations of PAHs as well as the quantitative structure-migration relationships that assisted in achieving a better understanding of the forces through which the PAH molecules interact with the acceptor cation. It was found that, in addition to charge-transfer interactions, electrostatic and dispersive forces play an important role in PAH-cation binding.

Cations↗

Separation of fungicides by micellar electrokinetic capillary chromatography.

Capillary electrophoresis with ultraviolet detection (CE/UV) of selected fungicides (carbendazim, metalaxyl, propiconazole, and vinclozolin) using different buffer compositions was investigated. Capillary zone electrophoresis (CZE) with 10 mM sodium phosphate (pH 7.0) was not useful in separating the four fungicides used in this study. However, the four fungicides were well resolved by employing micellar electrokinetic capillary chromatography (MEKC). Among the two surfactants tested in MEKC, bile salts provided better separation compared to sodium dodecyl sulfate (SDS). A buffer consisting of 10 mM sodium phosphate with 100 mM sodium cholate and 10% methanol (pH 7.0) gave best results; excellent separation of the four compounds was achieved in less than 15 min. The CE/UV method was validated by analyzing deionized and lake-water samples fortified with known concentrations for the four fungicides. Average recoveries of the fungicides in lake water of 4 micrograms/L level ranged from 42 to 87%.

Alanine↗

Analysis of brevetoxins by micellar electrokinetic capillary chromatography and laser-induced fluorescence detection.

Micellar electrokinetic capillary chromatography (MEKC) with laser-induced fluorescence (LIF) detection was used to measure four red tide brevetoxins at sub-attomole levels. The separation of four brevetoxins by MEKC was achieved with a sodium borate/sodium dodecyl sulfate buffer at pH 9.3 Brevetoxins with a terminal alcohol group were derivatized with an acyl azide coumarin to form stable, highly fluorescent products. Brevetoxins with a terminal aldehyde group were reduced to the alcohol with sodium borohydride prior to derivatization with the coumarin. Three derivatized brevetoxins (PbTx-3, PbTx- 5, and PbTx-9) were separated by MEKC and detected using He/Cd laser excitation at 354 nm and fluorescence emission at 410 nm. A fourth brevetoxin (PbTx-2) was converted to PbTx-3 prior to derivatization and was then determined by subtraction. Instrumental detection limits for all four toxins were approximately 0.10 fg or about 10(6)-fold more sensitive than existing liquid chromatographic methods. Brevetoxins were isolated from cell cultures and fish tissue using an alumina column/gel-permeation chromatography procedure. Method detection limits for the brevetoxins in fish tissue were approximately 4 pg/g. These method detection limits are at least 100-fold better than previous chromatographic and/or electrophoretic methods. The MEKC-LIF method reported here allows measurement of brevetoxins at the trace levels considered critical for understanding toxin metabolism and mode of action.

Animals↗

Institutional factors of nursing homes that predict the provision of mental health services.

This article explores the likelihood of the provision of mental health services in a nursing home as a function of the home's institutional factors. Data from the Institutional Population Component of the National Medical Expenditure Survey were used, and a modified model of equilibrium quality and price in a multivariate logistic framework is employed. The results indicate that meeting the demands for active mental health treatment, as mandated by the Nursing Home Reform Act of 1987, may be more difficult in those institutions that are part of a chain, are small, or contain Medicaid skilled nursing facility beds.

Health Services Research↗

Metabolism of the aryl hydrocarbon receptor agonist 3,3',4,4'-tetrachlorobiphenyl by the marine fish scup (Stenotomus chrysops) in vivo and in vitro.

The metabolism of the polychlorinated biphenyl congener 3,3',4,4'-tetrachlorobiphenyl (TCB) was examined in vitro and in vivo in the marine fish scup (Stenotomus chrysops). Untreated scup liver microsomes catalyzed metabolism of TCB with an estimated KM of 0.7 microM, at a rate < or = 0.13 pmol/min/mg. Metabolism was NADPH-dependent and inhibited by cytochrome c and CO, indicating cytochrome P450 (CYP) involvement. alpha-Naphthoflavone strongly inhibited microsomal TCB metabolism, and treatment of fish with CYP1A inducers increased the rates by approximately 2-fold, suggesting involvement of CYP1A. Scup were injected intraperitoneally with 0.1 or 5 mg TCB/kg and sampled on days 1-16 after treatment (after 3 days without food at each sampling). Concentrations of unmetabolized TCB in liver peaked on day 5 in low dose fish and on day 12 in high dose fish. In both groups the TCB content in the liver had declined 60% or more by day 16, suggesting depuration or redistribution from the liver. GC and MS revealed TCB and TCB metabolites in bile within 24 hr of treatment. The concentrations of TCB and metabolites in bile peaked at the same time that TCB concentrations peaked in the liver. The major metabolites were 5-hydroxy-3,3'4,4'-TCB (5-OH-TCB) and 4-hydroxy-3,3',5,4'-TCB (4-OH-TCB); 2-hydroxy-3,3',4,4'-TCB and 6-hydroxy-3,3',4,4'-TCB were minor metabolites. Animals given the high dose had much less 5-OH-TCB and much more parent TCB in bile than did fish given the low dose. Amounts of 4-OH-TCB in bile did not differ between doses. The reduced excretion of 5-OH-TCB coincided with a suppression of CYP1A in fish given the high dose, that did not occur in low dose fish, consistent with an involvement of CYP1A in TCB metabolism and particularly in formation of 5-OH-TCB. This study provides the first direct demonstration of 3,3',4,4'-TCB metabolism by fish. Data also indicate that these fish are able to eliminate TCB both as parent compound and as metabolites, despite a very slow rate of metabolism in vitro.

Animals↗

Localization of 102 exons to a 2.5 Mb region involved in Down syndrome.

Exon amplification has been applied to a 2.5 Mb region of chromosome 21 that has been associated with some features of Down syndrome (DS). Identification of the majority of genes from this region will facilitate the correlation of the over-expression of particular genes with specific phenotypes of DS. Over 100 gene fragments have been isolated from this 2.5 Mb segment. The exons have been characterized by sequence analysis, comparison with public databases and expansion to cDNA clones. Localization of the exons to chromosome 21 has been determined by hybridization to genomic Southern blots and to YAC and cosmid clones representing the region. This has resulted in a higher resolution physical map with a marker approximately every 25 kb. This integrated physical and transcript map will be valuable for fine mapping of DNA from individuals with partial aneuploidy of chromosome 21 as well as for assessing and ultimately generating a complete gene map of this segment of the genome.

Base Sequence↗