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Biomedical subjects

J R Buchanan

Publications and source records attributed to J R Buchanan.

At least 19 recordsLinked to original sources

Hemodynamics simulation and identification of susceptible sites of atherosclerotic lesion formation in a model abdominal aorta.

Employing the rabbit's abdominal aorta as a suitable atherosclerotic model, transient three-dimensional blood flow simulations and monocyte deposition patterns were used to evaluate the following hypotheses: (i) simulation of monocyte transport through a model of the rabbit abdominal aorta yields cell deposition patterns similar to those seen in vivo, and (ii) those deposition patterns are correlated with hemodynamic wall parameters related to atherosclerosis. The deposition pattern traces a helical shape down the aorta with local elevation in monocyte adhesion around vessel branches. The cell deposition pattern was altered by an exercise waveform with fewer cells attaching in the upper abdominal aorta but more attaching around the renal orifices. Monocyte deposition was correlated with the wall shear stress gradient and the wall shear stress angle gradient. The wall stress gradient, the wall shear stress angle gradient and the normalized monocyte deposition fraction were correlated with the distribution of monocytes along the abdominal aorta and monocyte deposition is correlated with the measured distribution of monocytes around the major abdominal branches in the cholesterol-fed rabbit. These results suggest that the transport and deposition pattern of monocytes to arterial endothelium plays a significant role in the localization of lesions.

Animals↗

Optimization of phosphorus precipitation from swine manure slurries to enhance recovery.

Laboratory experiments were conducted using magnesium chloride (MgCl2 x 6H2O, 64% solution) to force the precipitation of phosphorus and reduce the concentration of soluble phosphorus (PO4(3-)) in two swine wastes. One of the swine wastes tested contained a high concentration of PO4(3-) (initially approximately 1,000 mg/L), and the other swine waste tested contained a low concentration of PO4(3-) (initially approximately 230 mg/L). The precipitation reactions were performed to determine the required reaction time, pH, magnesium addition rate and seed material for future precipitate recovery work. For the high and low concentration waste, a 10-minute reaction time at a pH of 8.6 was sufficient to remove 98 and 96% of the PO4(3-) from solution. A molar ratio of Mg2+:PO4(3-) of 1.6:1 was determined to be effective for PO4(3-) removal from both the low and high strength wastes. At a molar ratio of 1.6:1, the PO3- in the high concentration waste was reduced from 590 to 12 mg/L. In the low concentration waste, the PO4(3-) concentration was reduced from 157 to 15 mg/L. Seeding the reaction did not significantly enhance the recovery process.

Animals↗

Hemodynamic parameters and early intimal thickening in branching blood vessels.

Intimal thickening due to atherosclerotic lesions or intimal hyperplasia in medium to large blood vessels is a major contributor to heart disease, the leading cause of death in the Western World. Balloon angioplasty with stenting, bypass surgery, and endarterectomy (with or without patch reconstruction) are some of the techniques currently applied to occluded blood vessels. On the basis of the preponderance of clinical evidence that disturbed flow patterns play a key role in the onset and progression of atherosclerosis and intimal hyperplasia, it is of interest to analyze suitable hemodynamic wall parameters that indicate susceptible sites of intimal thickening and/or favorable conditions for thrombi formation. These parameters, based on the wall shear stress, wall pressure, or particle deposition, are applied to interpret experimental/clinical observations of intimal thickening. Utilizing the parameters as "indicator" functions, internal branching blood vessel geometries are analyzed and possibly altered for different purposes: early detection of possibly highly stenosed vessel segments, prediction of future disease progression, and vessel redesign to potentially improve long-term patency rates. At the present time, the focus is on the identification of susceptible sites in branching blood vessels and their subsequent redesign, employing hemodynamic wall parameters. Specifically, the time-averaged wall shear stress (WSS), its spatial gradient (WSSG), the oscillatory shear index (OSI), and the wall shear stress angle gradient (WSSAG) are compared with experimental data for an aortoceliac junction. Then, the OSI, wall particle density (WPD), and WSSAG are segmentally averaged for different carotid artery bifurcations and compared with clinical data of intimal thickening. The third branching blood vessel under consideration is the graft-to-vein anastomosis of a vascular access graft. Suggested redesigns reduce several hemodynamic parameters (i.e., the WSSG, WSSAG, and normal pressure gradient [NPG]), thereby reducing the likelihood of restenosis, especially near the critical toe region.

Animals↗

Relation between non-uniform hemodynamics and sites of altered permeability and lesion growth at the rabbit aorto-celiac junction.

Using the rabbit's aorto-celiac junction as a representative atherosclerotic model, the hemodynamics of a bifurcating blood vessel are numerically simulated and three hemodynamic parameters are compared. The wall shear stress (WSS), the oscillatory shear index (OSI), and the spatial wall shear stress gradient (WSSG) are considered in this study. Locally enhanced wall permeabilities and intimal macrophages are generally considered to be involved in atherogenesis, and here the primary concern is with the hemodynamic influence on these early stages of the disease process. In comparing the segmental averages of the indicator functions and previously published intimal white blood cell densities, only the WSSG shows a statistically significant correlation. All three indicators have selective strengths in determining sites of early lesion growth around the aorto-celiac flow divider. At the proximal end of the flow divider on the lateral side of the orifice, there are elevated values of the OSI as well as WSSG and low WSS values. Regions of elevated wall permeabilities compare with the regions of elevated WSSG along the lateral and distal portions of the flow divider. Largely dependent upon the present input pulse with reverse flow, the OSI indicates relatively high values throughout the flow domain, however, it is important when utilized in conjunction with low WSS regions. This study presents a rationale for further quantitative correlative studies in the rabbit model based on additional histological data sets.

Animals↗

Performance improvement: the organization's quest.

In today's health care marketplace, quality has become an expectation. Stakeholders are demanding quality clinical outcomes, and accrediting bodies are requiring clinical performance data. The Roosevelt Institute's quest was to define and quantify quality outcomes, develop an organizational culture of performance improvement, and ensure customer satisfaction. Several of the organization's leaders volunteered to work as a team to develop a specific performance improvement approach tailored to the organization. To date, over 200 employees have received an orientation to the model and its philosophy and nine problem action and process improvement teams have been formed.

Georgia↗

Simulation of particle-hemodynamics in a partially occluded artery segment with implications to the initiation of microemboli and secondary stenoses.

Computational results of laminar incompressible blood-particle flow analyses in an axisymmetric artery segment with a smooth local area constriction of 75 percent have been presented. The flow input waveform was sinusoidal with a nonzero average. The non-Newtonian behavior of blood was simulated with a modified Quemada model, platelet concentrations were calculated with a drift-flux model, and monocyte trajectories were described and compared for both Newtonian and Quemada rheologies. Indicators of "disturbed flow" included the time-averaged wall shear stress (WSS), the oscillatory shear index (OSI), and the wall shear stress gradient (WSSG). Implications of the vortical flow patterns behind the primary stenosis to the formation of microemboli and downstream stenoses are as follows. Elevated platelet concentrations due to accumulation in recirculation zones mixed with thrombin and ADP complexes assumed to be released upstream in high wall shear stress regions, could form microemboli, which are convected downstream. Distinct near-wall vortices causing a local increase in the WSSG and OSI as well as blood-particle entrainment with possible wall deposition, indicate sites susceptible to the onset of an additional stenosis proximal to the initial geometric disturbance.

Algorithms↗

Purpose and guidelines for toxicokinetic studies within the National Toxicology Program.

Toxicokinetic studies undertaken within the National Toxicology Program are intended to aid the design of toxicology and carcinogenicity studies, help interpret the results of toxicology and carcinogenicity studies with respect to the relationship between toxic effects and external exposure, and define the parameters of dose, distribution, metabolism, and elimination that can be used in human risk assessment. Descriptions of two study designs presented here represent the possible extremes in approaches to toxicokinetic studies. The comprehensive approach is geared toward the development of physiology based pharmacokinetic models that relate external exposure to target organ dosimetry and addresses the questions: Is the chemical absorbed? How is the chemical metabolized? Where are the chemical and/or metabolites distributed in the body? What are the elimination rate and route of the chemical? What is the effect of dose on absorption, distribution, metabolism, and elimination? The minimal study design is more limited in scope than the comprehensive design and addresses primarily the issues of absorption, distribution, and elimination of the parent chemical. Study protocols for most chemicals lie somewhere between these two extreme approaches. An increased understanding of the relationships between external exposure, target organ dosimetry, and adverse effects should provide greater confidence in making low-dose extrapolations of human risk. This paper focuses on the collection of data from animal toxicokinetic studies. The construction of comparable models to characterize target organ dosimetry in exposed humans would certainly require the use of human parameter values obtained from human tissue samples and volunteers.

Animals↗

The past as prologue.

What has the Association of American Medical Colleges (AAMC) accomplished in the last 25 years in its efforts to advance medical education, biomedical research, and health delivery in this country? Can the AAMC's past accomplishments help predict how it will respond to future challenges? To answer these questions, the author traces in detail the recent history of the AAMC, focusing on the expansion of the association's role and constituencies and how these and other changes were precipitated by recommendations in the AAMC's 1965 "Coggeshall Report." He also recounts how the AAMC has responded to the pressures and needs of recent years (such as fostering an increase in the number of practicing physicians) and describes in detail the organization and functions of the AAMC's staff, with emphasis on its six divisions and the fact that many of the complex issues that confront the AAMC transcend the boundaries of governance councils and staff divisions and dictate that association policy be based on broad consensus. Looking ahead, he sees at least four important activities that the AAMC will continue to be involved with: fostering the education of more minority students; promoting health services research; finding an appropriate role in the evolution of health care reform; and addressing the need for academic medicine to be more socially responsive. The author concludes that the AAMC's highly regarded record, its organization, and its financial stability all indicate that it will do well as it tackles the issues on the horizon and others not yet in view.(ABSTRACT TRUNCATED AT 250 WORDS)

Education, Medical, Undergraduate↗

A vaccinia-vectored rabies vaccine field trial: ante- and post-mortem biomarkers.

During the field safety evaluation of a vaccinia-rabies glycoprotein recombinant virus vaccine for wildlife, two biomarkers were used to identify potential contact with vaccine-laden baits. Tetracycline, a commonly used and reliable calciphilic tissue marker, was included in a fish-meal polymer bait matrix and was evaluated from post-mortem bone samples. Additionally, an ante-mortem marker was needed to identify, for prospective study, raccoons which had contacted baits and thus, potentially, vaccine. Sulfadimethoxine (SDM) was included in an attractant slurry surrounding the bait, as a novel short-term seromarker. Preliminary laboratory studies in raccoons demonstrated SDM residues for up to one week following ingestion of a single 250 mg dose. During the first six days after bait distribution, 49 individual raccoons were live-trapped in the vaccination area. SDM was detectable in 38 of 49 (77.5%) serum samples. Similarly, 47 of 56 (83.9%) bone samples from raccoons collected in the vaccination area throughout the twelve-month study were tetracycline-positive. Conversely, none of the serum samples (n = 12) from the first six days of the trial nor any of the bone samples (n = 34) from raccoons in the surveillance area were biomarker-positive.

Administration, Oral↗

Recombinant rabies vaccines: efficacy assessment in free-ranging animals.

With the advancement of recombinant DNA techniques, a number of potent biologicals are available for the oral vaccination of free-ranging animals. Once oral immunogenicity and vaccine safety have been demonstrated, efficacy then becomes of paramount importance. Classical assessment of efficacy is conducted under carefully controlled laboratory conditions, whereas efficacy of oral wildlife rabies vaccination programs, to date, have been assessed by the lack (or occurrence) of field cases of rabies in a vaccinated area. This communication describes an intermediate vaccine efficacy strategy in which self-vaccinated, free-ranging animals from a study site were captured seven months after vaccine-laden bait distribution for laboratory rabies challenge. This technique is specifically reviewed in the context of available recombinant products for the consideration of extension towards dog rabies control.

Animals↗

Long-term oral contraceptive use does not affect trabecular bone density.

To determine whether long-term exposure to exogenous estrogen in oral contraceptives influences trabecular bone mass in premenopausal women, we studied 25 closely matched, healthy, premenopausal women, who were recruited from an active obstetrics and gynecology practice. Eleven women had never used oral contraceptives, and 14 women had used oral contraceptives for a minimum of 67 months. All oral contraceptive users had used preparations that provided a minimum of 50 micrograms mestranol per day. Trabecular bone density was determined by quantitative single-energy computerized tomography of the L1-3 lumbar vertebral bodies. Trabecular bone density was similar for both the control group and the oral contraceptive users, 160.6 +/- 6.9 versus 161.2 +/- 7.4 mg/ml, respectively. The power to detect a 15% difference in bone density between these two samples was 0.87. We concluded that long-term, premenopausal oral contraceptive use has no effect on vertebral bone density.

Absorptiometry, Photon↗

Determination of peak trabecular bone density: interplay of dietary fiber, carbohydrate, and androgens.

To elucidate mechanisms linking nutrition and sex hormones to magnitude of peak trabecular bone density, we studied 11 normal women aged 19-21 y. Trabecular bone density was related inversely to dietary fiber (r = -0.69, p = 0.02) and carbohydrate (r = -0.70, p = 0.02) and directly to serum free-and-albumin-bound testosterone (fab T) (r = -0.70, p = 0.02) and total testosterone (total T) (r = 0.66, p = 0.03). Dietary fiber was correlated negatively with fab T (r = -0.74, p = 0.009), total T (r = -0.70, p = 0.02), and androstenedione (Adione) (r = -0.72, p = 0.01). Controlling for the effect of fab T or Adione weakened the relationship between dietary fiber and bone density and the relationship was no longer statistically significant. Conversely, controlling for sex hormones did not abolish the effect of carbohydrate on bone density. The contributions of fab T and carbohydrate to bone density were independent. These results suggest that dietary fiber may depress serum androgens which in turn decrease trabecular bone density. Carbohydrate may also depress bone density but independently of sex steroid hormones.

Adult↗

Resources and limitations of medical centers in the United States.

A profile is provided of the range of opportunities and limitations for foreign nationals who seek access to the U.S. health care education and training system. The system is complicated, and entry depends on numerous variables. Facility in the English language is considered a prerequisite. Among opportunities, clinical training is probably most sought in the form of either residencies or clinical fellowships. Many major medical centers are eager to host earnest students and trainees from abroad. Yet such opportunities are limited, since most programs are unable to accept additional trainees once the first year of the program has been filled. Additional residency positions are not likely to be created and funded. In general, the larger academic medical centers tend to be the first to introduce new technologies and newer diagnostic and therapeutic modalities. Other settings may offer better, or at least equally good, environments for other kinds of post-M.D.-degree training. U.S. educational opportunities also exist in health policy and health systems education, nursing education, allied health and non-physician education, and research. All those seeking to study in the United States are urged to consult one of the several agencies that are knowledgeable about the opportunities and requirements for entering the programs offered.

Academic Medical Centers↗

Early vertebral trabecular bone loss in normal premenopausal women.

The precise timing for the onset of trabecular bone loss in women is a matter of controversy. To address this issue, we studied the relationship between age and vertebral trabecular bone density (measured by computed tomography) in 74 healthy premenopausal women from 18 to 48 years old. We also measured radial cortical bone density (by single photon absorptiometry) in 28 of these subjects. Trabecular bone density levels (milligrams per milliliter, mean +/- standard error of the mean, SEM) were significantly (p less than 0.05) higher in the second (178 +/- 8) and third (171 +/- 6) decades than in the fourth (158 +/- 4) or fifth (140 +/- 12) decades, and were inversely correlated with age (r = -0.39, p = 0.0006), diminishing at a rate of 1.3 mg/ml (0.73%) per year. Radial cortical bone density levels (grams per square centimeter) were similar in the third (0.711 +/- 0.021), fourth (0.721 +/- 0.012), and fifth (0.736 +/- 0.012) decades and were not related to age (r = 0.17, p = 0.39). We conclude that vertebral trabecular bone loss in women commences during or prior to the third decade. In contrast, radial cortical bone density does not decline during the premenopausal years.

Adolescent↗

Determinants of peak trabecular bone density in women: the role of androgens, estrogen, and exercise.

To elucidate determinants of peak trabecular bone density, we studied the role of androgens, estrogen, and aerobic exercise in 30 women from 18 to 22 years old. The women were divided into three groups: Sedentary, 11 normal women who did not exercise regularly; eumenorrheic, 10 athletes with normal menstrual function; and oligomenorrheic, 9 athletes with exercise-induced oligomenorrhea. All athletes participated in aerobic sports that did not involve selective resistance loading of the back. Serum free and albumin-bound testosterone (fab T), androstenedione (A), and estradiol (E2) were measured on four separate occasions at consecutive 7 day intervals and averaged. Trabecular density was measured by quantitative computed tomography of the lumbar spine. Peak trabecular bone density was related to fab T (r = 0.48, p = 0.007), A (r = 0.40, p = 0.03), and E2 (r = 0.40, p = 0.04). When taken in combination, androgens and estrogen each accounted independently for significant portions of the variance in bone density [fab T and E2 (R2 = 0.38, p = 0.002) and A and E2 (R2 = 0.27, p = 0.01)]. Bone density (mg/ml, mean +/- standard error of the mean, SEM) in the sedentary group (174 +/- 6) was not significantly different from that in the eumenorrheic (183 +/- 12, p = 0.47) or oligomenorrheic (161 +/- 11, p = 0.32) subjects. We conclude that androgens and estrogen function as independent and additive determinants of peak trabecular bone density in young women. The quantitative impact of aerobic exercise (without resistance loading) and exercise-induced menstrual dysfunction appears to be less important than that of the hormones.

Adolescent↗

Effect of declining renal function on bone density in aging women.

The factors that are responsible for trabecular bone loss in aging women are not completely understood. To evaluate declining renal function as a possible factor, we studied 19 Caucasian women (average age 67) who were from 6 to 41 years postmenopausal. Trabecular bone density was quantitated by computerized tomography of the spine. Serum calcium, phosphorus, and creatinine were normal in all subjects. Creatinine clearance averaged 74 ml/min (range 38-122), decreased with age (r = -0.60, P = 0.003), and was inversely related to serum creatinine (r = -0.51, P = 0.01). Bivariate regression demonstrated that bone density decreased with age (r = -0.59, P = 0.004); controlling for the effect of creatinine clearance weakened this correlation to r = -0.45 (P = 0.03); controlling additionally for 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) reduced the correlation coefficient to r = -0.34 (P = 0.11). Bone density also decreased in direct proportion to the decrement in creatinine clearance (r = 0.44, P = 0.03); controlling for the effects of 1,25(OH)2D and PTH reduced this correlation coefficient to r = 0.34 (P = 0.11). These results suggest that occult renal insufficiency may contribute to bone loss in aging women, and that this effect may be mediated in part by 1,25(OH)2D and PTH. In this age group renal function should be assessed by measuring creatinine clearance rather than the serum creatinine concentration since renal insufficiency can be masked by apparently normal circulating creatinine levels.

Aged↗

Determinants of atraumatic vertebral fracture rates in menopausal women: biologic v mechanical factors.

In menopausal women, the susceptibility to atraumatic vertebral fractures is thought to be governed by both mechanical factors (as represented by bone density) and by biologic factors such as age, body size, and dietary calcium. Whether these biologic factors independently influence fracture rates beyond the effect of bone density is a matter of controversy. To compare the relative importance of mechanical and biologic factors on vertebral fractures, we elucidated the determinants of atraumatic compression fractures in 63 menopausal women who had no chronic diseases other than osteopenia. Trabecular bone density was determined by quantitative computerized tomography of the spine. Fracture frequency was expressed as the number of compressed vertebrae per person between T5 and L4. The analysis showed that fracture frequency, bone density, and the biologic factors were closely interrelated. Fracture frequency was inversely correlated to bone density [R2 (spline model) = .40, P less than .0001], body size (r = -.26, P = .05), and dietary calcium (r = -.28, P = .04), and directly correlated with age (r = .46, P = .0002). Bone density decreased with age (r = -.65, P less than .0001), increased with body size (r = .37, P = .004), and tended to increase with dietary calcium (r = .24, P = .08). After controlling for bone density, there was no perceptible residual relationship between fracture frequency and any of these biologic factors. We conclude that mechanical factors overshadow age, body size, and dietary calcium as determinants of vertebral fracture frequency. The apparent influence of these biologic factors on fracture frequency is explained by their surrogate effects on bone density.

Aged↗