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Biomedical subjects

D G Smith

Publications and source records attributed to D G Smith.

At least 73 records · Page 4Linked to original sources
PubMed2000

Efficacy of selamectin against experimentally induced and naturally acquired ascarid (Toxocara canis and Toxascaris leonina) infections in dogs.

The efficacy of selamectin against adult ascarids was evaluated in eight controlled and masked studies in dogs. Three laboratory studies evaluated selamectin against experimentally induced infections of Toxocara canis; three laboratory studies evaluated selamectin against naturally acquired infections of T. canis; one laboratory study evaluated selamectin against naturally acquired infections of both T. canis and Toxascaris leonina; one field study evaluated selamectin against naturally acquired infections of ascarids (T. canis and/or T. leonina) in dogs presented as veterinary patients. Selamectin was administered topically to the skin of dogs in unit doses designed to deliver a minimum of 6mgkg(-1) (range, 6-12mgkg(-1)). In all studies, dogs were allocated randomly to treatment assignments (selamectin or vehicle control in laboratory studies: selamectin or reference product in the field study) on the basis of pretreatment fecal egg counts. For induced infections, there were significant reductions in geometric mean numbers of adult T. canis after a single application of selamectin (93.9-98.1%, P=0.0001), after two monthly applications (> or =88.3%, P< or =0.0001), and after three monthly applications (100%, P< or =0.0002). In the natural infection laboratory studies, when selamectin was administered twice at an interval of 30 days, the percentage reductions in geometric mean numbers of adult T. canis at necropsy were 84.6, 91.3, and 97.9%, and when selamectin was administered on days 0, 14, and 30, the percentage reductions were 91.1 and 97.6%. Geometric mean fecal T. canis egg counts were reduced by > or =92.9% (P< or =0.0067) at the end of the studies. In the field study, geometric mean fecal ascarid egg counts were reduced by 89.5 and 95. 5% (P=0.0001) for 14 and 30 days, respectively, after a single treatment with selamectin, and by 94.0% (P=0.0001) 30 days after the second treatment with selamectin. These reductions compared favorably with the egg count reductions from dogs treated with a reference product containing praziquantel, pyrantel embonate, and febantel. There were no adverse drug experiences or treatment-related mortalities during any of the studies. Selamectin, when administered topically in a unit dose providing a minimum dosage of 6mgkg(-1), was safe and effective against adult T. canis and T. leonina and in reducing the fecal excretion of T. canis eggs in dogs.

Animals↗
PubMed2000

Implications of the distribution of Albumin Naskapi and Albumin Mexico for new world prehistory.

The known distributions of two mutational variants of the albumin gene that are restricted to Mexico and/or North America, Albumin Mexico (AL*Mexico) and Albumin Naskapi (AL*Naskapi), were expanded by the electrophoretic analysis of sera collected from more than 3, 500 Native Americans representing several dozen tribal groups. With a few exceptions that could be due to recent, isolated cases of admixture, AL*Naskapi is limited to groups that speak Athapaskan and Algonquian, two widely distributed language families not thought to be related, and to several linguistically unrelated groups geographically proximate to its probable ancestral homeland. Similarly, AL*Mexico is limited to groups that speak Yuman or Uto-Aztecan, two language groups in the American Southwest and Baja California not thought to be closely related to each other, and to several linguistically unrelated groups throughout Mexico. The simultaneous consideration of genetic, historical, linguistic, and archaeological evidence suggests that AL*Naskapi probably originated on the northwestern coast of North America, perhaps in some group ancestral to both Athapaskans and Algonquians, and then spread by migration and admixture to contiguous unrelated, or distantly related, tribal groups. AL*Mexico probably originated in Mexico before 3,000 years BP then spread northward along the Tepiman corridor together with cultural influences to several unrelated groups that participated in the Hohokam culture.

Albumins↗
PubMed2000

Additional highly polymorphic microsatellite (STR) loci for estimating kinship in rhesus macaques (Macaca mulatta).

Thirty-four short tandem repeat (STR) loci, not previously studied in rhesus macaques, were amplified by PCR. About one third of these were found to clearly and reliably amplify and exhibit high levels of genetic heterogeneity even in relatively inbred populations. These loci, together with 11 loci previously studied, were sufficiently informative to discretely differentiate between related and unrelated pairs and, in most cases, between parent/offspring and other relative pairs. An even greater number of hypervariable STR loci might be required to distinguish between half-sib and full-sib pairs in most rhesus populations.

Alleles↗
PubMed2000

California ground squirrel (Spermophilus beecheyi) blood sera inhibits crotalid venom proteolytic activity.

Some California ground squirrels (Spermophilus beecheyi) show limited necrosis following envenomation by northern Pacific rattlesnakes (Crotalus viridis oreganus). This study demonstrates that S. beecheyi blood sera inhibits venom proteases. Sera from rattlesnake-abundant habitats inhibited C. v. oreganus venom more effectively than venom from two allopatric rattlesnake species, C. v. viridis and C. atrox, suggesting evolutionary specialization. The pattern of inhibition among squirrel populations corresponds best with history of rattlesnake predation, in contrast to current rattlesnake density.

Animals↗
PubMed2000

Does patient-centered care pay off?

BACKGROUND: Hospitals have adopted patient-centered practices that focus on patients' needs, values, and preferences in hopes of improving quality and controlling costs. Patient-centered practices are intended to involve patients in treatment decisions, increase communication between patients and care-givers, and increase interaction with family members and friends. Rapid adoption of these practices has occurred, even though little is known about the effects of patient-centered care on outcomes and cost. METHODS: A simultaneous equations regression model was developed to examine the reciprocal relationships between patient-centeredness, outcomes, and cost. A consortium of employers obtained data from 52 hospital units in southeastern Michigan. Two hundred randomly selected patients were sampled from all discharges on the medical, surgical, and obstetric units at each hospital for the first three months of 1997; the patients were sent the survey in May. Patient-centeredness was measured by patient reports of whether key clinical events occurred (The Picker Inpatient Survey). Outcomes were assessed by rates of unexpected mortality and complications. Cost was defined by self-insured purchaser payments. RESULTS: Hospital units that were more patient centered were associated with statistically significantly better outcomes and higher costs than those that were less patient centered. The joint relations between outcomes and cost were insignificant. CONCLUSIONS: Patient-centeredness was associated with better outcomes and higher cost. For either the short run or long run, managers, patients, and purchasers should determine whether the improvement in outcomes and patient satisfaction associated with becoming patient centered is worth the investment in costs.

Cost-Benefit Analysis↗
PubMed2000

Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription.

BACKGROUND: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase, the activity of which is inhibited by a variety of extracellular stimuli including insulin, growth factors, cell specification factors and cell adhesion. Consequently, inhibition of GSK-3 activity has been proposed to play a role in the regulation of numerous signalling pathways that elicit pleiotropic cellular responses. This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3. RESULTS: SB-216763 and SB-415286 are structurally distinct maleimides that inhibit GSK-3alpha in vitro, with K(i)s of 9 nM and 31 nM respectively, in an ATP competitive manner. These compounds inhibited GSK-3beta with similar potency. However, neither compound significantly inhibited any member of a panel of 24 other protein kinases. Furthermore, treatment of cells with either compound stimulated responses characteristic of extracellular stimuli that are known to inhibit GSK-3 activity. Thus, SB-216763 and SB-415286 stimulated glycogen synthesis in human liver cells and induced expression of a beta-catenin-LEF/TCF regulated reporter gene in HEK293 cells. In both cases, compound treatment was demonstrated to inhibit cellular GSK-3 activity as assessed by activation of glycogen synthase, which is a direct target of this kinase. CONCLUSIONS: SB-216763 and SB-415286 are novel, potent and selective cell permeable inhibitors of GSK-3. Therefore, these compounds represent valuable pharmacological tools with which the role of GSK-3 in cellular signalling can be further elucidated. Furthermore, development of similar compounds may be of use therapeutically in disease states associated with elevated GSK-3 activity such as non-insulin dependent diabetes mellitus and neurodegenerative disease.

Adenosine Triphosphate↗
PubMed2000

An assessment of the accuracy of ridge-mapping in planning implant therapy for the anterior maxilla.

The use of ridge-mapping to assess bone levels available for implant placement in the anterior maxilla avoids some of the problems associated with CT scanning. The aim of this study was to assess the accuracy of ridge-mapping callipers in determining body ridge widths in the anterior maxilla prior to dental implant surgery. A modified surgical stent was designed to locate the beaks of ridge-mapping callipers at the same points on the jaw before and after mucoperiosteal flap reflection. Eleven subjects were included in the study. Measurements (n = 100) were made at 25 implant sites, 50 "pre-operative" and 50 "intra-operative" at 3 mm and 6 mm distances from the crest of the ridge. There were statistically significant (P < 0.0001) differences between pre- and intra-operative measurements. Based on pre-operative measurements, clinical judgements were made as to whether supplementary procedures such as guided bone regeneration would be required. Unanticipated supplementary procedures were required at 10 fixture sites. The findings indicate that ridge-mapping alone is insufficient to accurately predict bone available for implantation in the anterior maxilla. It is suggested that ridge-mapping may provide reliable information about bone levels when the labial aspect of the anterior ridge is not markedly concave.

Alveolar Process↗
PubMed2000

Chronic phantom sensations, phantom pain, residual limb pain, and other regional pain after lower limb amputation.

OBJECTIVES: To determine the characteristics of phantom limb sensation, phantom limb pain, and residual limb pain, and to evaluate pain-related disability associated with phantom limb pain. DESIGN: Retrospective, cross-sectional survey. Six or more months after lower limb amputation, participants (n = 255) completed an amputation pain questionnaire that included several standardized pain measures. SETTING: Community-based survey from clinical databases. PARTICIPANTS: A community-based sample of persons with lower limb amputations. MAIN OUTCOME MEASURES: Frequency, duration, intensity, and quality of phantom limb and residual limb pain, and pain-related disability as measured by the Chronic Pain Grade. RESULTS: Of the respondents, 79% reported phantom limb sensations, 72% reported phantom limb pain, and 74% reported residual limb pain. Many described their phantom limb and residual limb pain as episodic and not particularly bothersome. Most participants with phantom limb pain were classified into the two low pain-related disability categories: grade I, low disability/low pain intensity (47%) or grade II, low disability/high pain intensity (28%). Many participants reported having pain in other anatomic locations, including the back (52%). CONCLUSIONS: Phantom limb and residual limb pain are common after a lower limb amputation. For most, the pain is episodic and not particularly disabling. However, for a notable subset, the pain may be quite disabling. Pain after amputation should be viewed from a broad perspective that considers other anatomic sites as well as the impact of pain on functioning.

Adult↗
PubMed2000

Better Medicare Cost Report data are needed to help hospitals benchmark costs and performance.

To evaluate costs and achieve cost control in the face of new technology and demands for efficiency from both managed care and governmental payers, hospitals need to benchmark their costs against those of other comparable hospitals. Since they typically use Medicare Cost Report (MCR) data for this purpose, a variety of cost accounting problems with the MCR may hamper hospitals' understanding of their relative costs and performance. Managers and researchers alike need to investigate the validity, accuracy, and timeliness of the MCR's cost accounting data.

Accounting↗
PubMed2000

Gamma interferon influences intestinal epithelial hyperplasia caused by Lawsonia intracellularis infection in mice.

Lawsonia intracellularis is a recently identified bacterial pathogen which causes disease in a broad range of animals. Invasion of intestinal epithelial cells and the resultant hyperplasia of infected cells are central processes in disease pathogenesis. In this study, we aimed to establish whether immunocompetent mice were susceptible to infection and whether gamma interferon (IFN-gamma) contributed to the pathogenesis of infection. Wild-type 129-Sv-Ev mice (129 mice) and IFN-gamma receptor knockout mice based on the 129 background (IFN-gammaR(-)) were challenged orally with approximately 5.5 x 10(7) L. intracellularis cells. Both 129 and IFN-gammaR(-) mice became infected, although the extent of infection (as determined by the proportion of infected crypts) was substantially lower in 129 mice than in IFN-gammaR(-) mice. Despite these differences, infected crypts showed characteristics typical of proliferative enteropathies of other animals, i.e., intracellular colonization of epithelial cells by L. intracellularis with resultant epithelial hyperplasia. Infection in 129 mice was cleared between days 21 and 28 postchallenge, whereas infection in IFN-gammaR(-) mice was evident in 100% of animals from day 21 onward. Additionally, in IFN-gammaR(-) mice the infection was so extensive that fatalities resulted. IFN-gamma therefore plays a significant role in limiting intracellular infection and increased cellular proliferation associated with L. intracellularis. L. intracellularis infection is generally associated with modest cellular infiltration; therefore, further comparative examinations will be necessary to determine pathogenicity factors and define the role of IFN-gamma in controlling this infection.

Animals↗
PubMed2000

Characterisation of kynurenine pathway metabolism in human astrocytes and implications in neuropathogenesis.

The role of astrocytes in the production of the neurotoxin quinolinic acid (QUIN) and other products of the kynurenine pathway (KP) is controversial. Using cytokine-stimulated human astrocytes, we assayed key enzymes and products of the KP. We found that astrocytes lack kynurenine-hydroxylase so that large amounts of kynurenine (KYN) and kynurenic acid (KYNA) were produced, while minor amounts of QUIN were synthesised that were completely degraded. We then showed that kynurenine added to macrophages led to significant production of QUIN. These results suggest that astrocytes alone are neuroprotective by minimising QUIN production and maximising synthesis of KYNA. However, it is likely that, in the presence of macrophages and/or microglia, astrocytes are neurotoxic by producing large concentrations of KYN that can be metabolised by neighbouring monocytic cells to QUIN.

Astrocytes↗
PubMed2000

Financial management in leading health care systems.

To understand better the financial management practices and strategies of modern health care organizations, we conducted interviews with chief financial officers (CFOs) of several leading health care systems. In this introduction, we present an overview of the project and summary responses on corporate financial structures and strategic challenges facing CFOs.

Accounts Payable and Receivable↗
PubMed2000

Capital investment strategies in health care systems.

Capital investment decisions are among the most important decisions made by firms. They determine the firm's capacity for providing services and commit the firm's cash for an extended period of time. Interviews with chief financial officers of leading health care systems reveal capital investment strategies that generally follow the recommendations of modern finance theory. Still, there is substantial variation in capital budgeting techniques, methods of risk adjustment, and the importance of qualitative considerations in investment decision making. There is also variation in delegation of investment decision making to operating units and methods of performance evaluation. Health care systems face the same challenges as other organizations in developing and implementing capital investment strategies that use consistent methods for evaluation of projects that have inconsistent aims and outcomes.

Budgets↗
PubMed2000

Capital structure strategy in health care systems.

The capital structures (the relative use of debt and equity to support assets) of leading health care systems are viewed as a strategic component of their financial plans. While not-for-profit hospitals as a group have maintained nearly constant levels of debt over the past decade, investor-owned hospitals and a group of leading health care systems have reduced their relative use of debt. Chief financial officers indicated that in addition to reducing debt because of less favorable reimbursement incentives, there was a focus on maintaining high bond ratings. Debt levels have not been reduced as sharply in these health care systems as they have in investor-owned hospitals, in part due to the use of debt to support investments in financial markets. Because these health care systems do not have easy access to equity, high bond ratings and solid investment earnings are central to their capital structure policies of preserving access to debt markets.

Capital Financing↗
PubMed2000

Sources of project financing in health care systems.

Through discussions with chief financial officers of leading health care systems, insights are offered on preferences for project financing and development efforts. Data from these same systems provide at least anecdotal evidence in support of pecking-order theory.

Capital Financing↗