Otolaryngologists
32 years of experience
Video profile
Accepting new patients
613 23rd St
Ste 420
Ashland, KY 41101
606-408-3415
Locations and availability (6)

Education ?

Medical School
University Of Alberta Faculty Of Medicine And Dentistry (1978)
Foreign school

Awards & Distinctions ?

Associations
American Board of Otolaryngology
American Academy of Otolaryngology: Head and Neck Surgery

Affiliations ?

Dr. Baker is affiliated with 2 hospitals.

Hospital Affilations

Score

Rankings

  • King's Daughters' Medical Center
    Otolaryngology
    2201 Lexington Ave, Ashland, KY 41101
    • Currently 4 of 4 crosses
    Top 25%
  • Our Lady of Bellefonte Hospital
    Otolaryngology
    1300 Saint Christopher Dr, Ashland, KY 41101
    • Currently 3 of 4 crosses
    Top 50%
  • Publications & Research

    Dr. Baker has contributed to 116 publications.
    Title Confocal Microscopy for the Analysis of Sirna Delivery by Polymeric Nanoparticles.
    Date December 2010
    Journal Microscopy Research and Technique
    Excerpt

    Clinical applications of genetic therapies, including delivery of short, interfering RNAs (siRNAs) for RNA interference (RNAi), are limited due to the difficulty of delivering nucleic acids to specific cells of interest while at the same time minimizing toxicity and immunogenicity. The use of cationic polymers to deliver nucleic acid therapeutics has the potential to address these complex issues but is currently limited by low-delivery efficiencies. Although cell culture studies have shown that some polymers can be used to deliver siRNAs and achieve silencing, it is still not clear what physical or chemical properties are needed to ensure that the polymers form active polymer-siRNA complexes. In this study, we used multicolor fluorescence confocal microscopy to analyze the cellular uptake of siRNAs delivered by novel propargyl glycolide polymeric nanoparticles (NPs). Delivery by these vehicles was compared with delivery by linear polyethyleneimine (LPEI) and Lipofectamine 2000 (LF2K), which are both known as effective delivery vehicles for siRNAs. Our results showed that when LF2K and LPEI were used, large quantities of siRNA were delivered rapidly, presumably overwhelming the basal levels of mRNA to initiate silencing. In contrast, our novel polymeric NPs showed delivery of siRNAs but at concentrations that were initially too low to achieve silencing. Nonetheless, the exceptionally low cytotoxicity of our NPs, and the simplicity with which they can be modified, makes them good candidates for further study to optimize their delivery profiles and, in turn, achieve efficient silencing.

    Title Creation of Functional Membranes Using Polyelectrolyte Multilayers and Polymer Brushes.
    Date September 2008
    Journal Langmuir : the Acs Journal of Surfaces and Colloids
    Excerpt

    Over the last 15 years, the layer-by-layer deposition of polyelectrolytes and the growth of polymer brushes from surfaces have become established techniques for the formation of a wide range of thin films. This article discusses the use of these techniques in creating the skin layer of nanofiltration or gas-separation membranes and in functionalizing the interior of membranes for protein adsorption or catalysis. In the case of separation membranes for nanofiltration, the minimal thickness of layer-by-layer films allows for high flux, and the wide range of available polyelectrolytes that can form these films permits the tailoring of membranes for separations such as water softening, the reduction of F (-) concentrations, and the removal of dyes from wastewater. For gas separation, polymers grown from surfaces are more attractive than layer-by-layer coatings because most polyelectrolyte films are not highly gas-selective. Cross-linked poly(ethylene glycol dimethacrylate) films grown from porous alumina exhibit CO(2)/CH(4) selectivities of around 20, and the careful selection of monomers should further improve the selectivity of similar membranes. Both layer-by-layer methods and polymer brushes can also be employed to modify the interior of membranes, and we have utilized these techniques to create catalysts, antibody arrays in membranes, and membrane absorbers for protein purification. Polymer brushes are particularly attractive because they allow the absorption of multilayers of protein to yield membranes with binding capacities as high as 150 mg protein/cm(3). Some challenges in the practical implementation of these systems, such as the economical formation of membranes using highly permeable polymeric supports, and future directions in research on membrane modification with multilayer films and polymer brushes are also discussed herein.

    Title Inhalation Toxicity and Lung Toxicokinetics of C60 Fullerene Nanoparticles and Microparticles.
    Date February 2008
    Journal Toxicological Sciences : an Official Journal of the Society of Toxicology
    Excerpt

    While several recent reports have described the toxicity of water-soluble C60 fullerene nanoparticles, none have reported the toxicity resulting from the inhalation exposures to C60 fullerene nanoparticles or microparticles. To address this knowledge gap, we exposed male rats to C60 fullerene nanoparticles (2.22 mg/m3, 55 nm diameter) and microparticles (2.35 mg/m3, 0.93 microm diameter) for 3 h a day, for 10 consecutive days using a nose-only exposure system. Nanoparticles were created utilizing an aerosol vaporization and condensation process. Nanoparticles and microparticles were subjected to high-pressure liquid chromatography (HPLC), XRD, and scanning laser Raman spectroscopy, which cumulatively indicated no chemical modification of the C60 fullerenes occurred during the aerosol generation. At necropsy, no gross or microscopic lesions were observed in either group of C60 fullerene exposures rats. Hematology and serum chemistry results found statistically significant differences, although small in magnitude, in both exposure groups. Comparisons of bronchoalveolar (BAL) lavage fluid parameters identified a significant increase in protein concentration in rats exposed to C60 fullerene nanoparticles. BAL fluid macrophages from both exposure groups contained brown pigments, consistent with C60 fullerenes. C60 lung particle burdens were greater in nanoparticle-exposed rats than in microparticle-exposed rats. The calculated lung deposition rate and deposition fraction were 41 and 50% greater, respectively, in C60 fullerene nanoparticle-exposed group than the C60 fullerene microparticle-exposed group. Lung half-lives for C60 fullerene nanoparticles and microparticles were 26 and 29 days, respectively. In summary, this first in vivo assessment of the toxicity resulting from inhalation exposures to C60 fullerene nanoparticles and microparticles found minimal changes in the toxicological endpoints examined. Additional toxicological assessments involving longer duration inhalation exposures are needed to develop a better and more conclusive understanding of the potential toxicity of inhaled C60 fullerenes whether in nanoparticle or microparticle form.

    Title Completely Aqueous Procedure for the Growth of Polymer Brushes on Polymeric Substrates.
    Date January 2008
    Journal Langmuir : the Acs Journal of Surfaces and Colloids
    Excerpt

    The growth of polymer brushes on polymer substrates is often challenging because of substrate incompatibility with the organic solvents used for initiator attachment. This letter reports the use of layer-by-layer adsorption of macroinitiators and subsequent aqueous ATRP from these immobilized initiators to prepare polymer brushes on polymeric substrates. Polyethersulfone (PES) films and porous membranes were modified with polyelectrolyte multilayer films, and a previously developed polycationic initiator, poly(2-(trimethylammonium iodide)ethyl methacrylate-co-2-(2-bromoisobutyryloxy)ethyl acrylate), was then electrostatically adsorbed onto these polyelectrolyte films. The immobilized macroinitiator is very efficient in initiating the growth of polymer brushes on PES, as demonstrated by aqueous syntheses of poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) films. PHEMA (250 nm thick) and PDMAEMA (40 nm thick) brushes were grown in 2 h from surfaces modified with polycationic initiators. Moreover, this procedure is effective for growing brushes in the pores of PES membranes.

    Title High-capacity Purification of His-tagged Proteins by Affinity Membranes Containing Functionalized Polymer Brushes.
    Date December 2007
    Journal Biomacromolecules
    Excerpt

    Porous membrane absorbers are attractive for increasing the rate of protein purification, but their binding capacity is low relative to porous beads. Modification of membranes with functionalized polymer brushes, however, can greatly enhance capacity. This work demonstrates that membrane modification with poly(2-hydroxyethyl methacrylate) (PHEMA) brushes derivatized with nitrilotriacetate-Ni2+ (NTA-Ni2+) complexes allows purification of polyhistidine-tagged ubiquitin (HisU) in less than 30 min with a binding capacity of 120 mg of HisU/cm3 of porous alumina membrane. Adsorption isotherms show that saturation of the brushes occurs at HisU concentrations as low as 0.04 mg/mL and that these brushes can bind up to 23 monolayers of HisU. Gel electrophoresis reveals that the purity of eluted HisU is more than 99%, even when the initial feed solution contains 10% bovine serum or a 20-fold excess of BSA. Thus, reusable porous membranes modified by PHEMA-NTA-Ni2+ brushes are attractive candidates for rapid purification of polyhistidine-tagged proteins.

    Title The Lxcxe Prb Interaction Domain of Cyclin D1 is Dispensable for Murine Development.
    Date October 2007
    Journal Cancer Research
    Excerpt

    Cyclin D1 is a multifunctional, tumor-associated protein that interacts with pRb via a conserved LxCxE motif, activates a kinase partner, directs the phosphorylation of pRb, activates cyclin E-cyclin-dependent kinase 2 (cdk2) by titrating Cip/Kip cdk inhibitors, and modulates the activity of a variety of transcription factors. It is thought that some of the proproliferative function of cyclin D1 is exerted by LxCxE-dependent binding to the pRb pocket domain, which might interfere with the ability of pRb to repress transcription by recruiting cellular chromatin remodeling proteins to E2F-dependent promoters. To test the importance of the LxCxE domain in vivo, we have generated a "knock-in" mouse by replacing the wild-type cyclin D1 gene with a mutant allele precisely lacking the nucleotides encoding the LxCxE domain. Analysis of this mouse has shown that the LxCxE protein is biochemically similar to wild-type cyclin D1 in all tested respects. Moreover, we were unable to detect abnormalities in growth, retinal development, mammary gland development, or tumorigenesis, all of which are affected by deleting cyclin D1. Although we cannot exclude the presence of subtle defects, these results suggest that the LxCxE domain of cyclin D1 is not necessary for function despite the absolute conservation of this motif in the D-type cyclins from plants and vertebrates.

    Title Rapid Growth of Polymer Brushes from Immobilized Initiators.
    Date August 2007
    Journal Journal of the American Chemical Society
    Excerpt

    This report describes the remarkably rapid synthesis of polymer brushes under mild conditions (50 degrees C) using surface-initiated polymerization. The highly active atom transfer radical polymerization catalyst Cu(I)-1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane allows synthesis of 100 nm thick poly(tert-butyl acrylate) brushes from initiator-modified Au surfaces in just 5 min. Using the same catalyst, polymerization of 2-hydroxyethyl methacrylate and methyl methacrylate yielded 100 nm thick films in 10 and 60 min, respectively. Such growth rates are an order of magnitude greater than those for traditional free-radical polymerizations initiated from surfaces. These polymerizations also retain some features of controlled radical polymerizations, such as the ability to form block copolymer brushes.

    Title High-capacity Binding of Proteins by Poly(acrylic Acid) Brushes and Their Derivatives.
    Date July 2007
    Journal Langmuir : the Acs Journal of Surfaces and Colloids
    Excerpt

    Polymeric coatings with high protein-binding capacities are important for increasing the output of affinity-based protein purification and decreasing the detection limits of antibody microarrays. This report describes the use of thick poly(acrylic acid) (PAA) brushes to immobilize as much as 80 monolayers of protein. The brushes were prepared using a recently developed procedure that allows polymerization of 100-nm-thick poly(tert-butyl acrylate) films from a surface in just 5 min along with hydrolysis of these films to PAA in 15 min. Covalent binding of bovine serum albumin (BSA) to PAA brushes that were activated using standard coupling agents, however, resulted in immobilization of less than two monolayers of BSA because of competitive hydrolysis of the esters in the activated film. In contrast, derivatization of PAA with nitrilotriacetate (NTA)-Cu2+ complexes yielded films capable of binding many monolayers of protein via metal-ion affinity interactions. For example, derivatization of 55-nm-thick PAA films with NTA-Cu2+ allowed immobilization of about 15 monolayers (5.8 microg/cm2 or 58 nm) of BSA. The binding capacity was even higher for myoglobin (7.7 microg/cm2) and anti-IgG (9.6 microg/cm2). Remarkably, electrostatic adsorption of lysozyme in 55-nm-thick, underivatized PAA resulted in as much as 80 monolayers (16.2 microg/cm2 or 162 nm) of adsorbed protein. Polymer synthesis, derivatization, and swelling, as well as BSA immobilization kinetics and thermodynamics were characterized using reflectance FT-IR spectroscopy, ellipsometry, and protein assays.

    Title Use of Porous Membranes Modified with Polyelectrolyte Multilayers As Substrates for Protein Arrays with Low Nonspecific Adsorption.
    Date April 2007
    Journal Analytical Chemistry
    Excerpt

    Coating of substrates with polyelectrolyte multilayers terminated with poly(acrylic acid) (PAA) followed by activation of the free -COOH groups of PAA provides a surface that readily reacts with amine groups to allow covalent immobilization of antibodies. The use of this procedure to prepare arrays of antibodies in porous alumina supports facilitates construction of a flow-through system for analysis of fluorescently labeled antigens. Detection limits in the analysis of Cy5-labeled IgG are 0.02 ng/mL because of the high surface area of the alumina membrane, and the minimal diameter of the substrate pores results in binding limited by kinetics, not mass transport. Moreover, PAA-terminated films resist nonspecific protein adsorption, so blocking of antibody arrays with bovine serum albumin is not necessary. These microarrays are capable of effective analysis in 10% fetal bovine serum.

    Title Regulation of Osteoblast Gene Expression and Phenotype by Polylactide-fatty Acid Surfaces.
    Date January 2007
    Journal Molecular Biology Reports
    Excerpt

    Cell function is influenced by surface structure and molecules. Molecules that enhance cellular differentiation can be applied to tissue scaffold surfaces to stimulate endogenous tissue regeneration. The application of this approach to bone implants yields surfaces coated with factors (proteins, peptides, etc...) that promote the differentiation of osteoblasts, the cells that make bone. Increased bone formation leads to increased healing and union of the implant with endogenous bone. To obtain better control over surface coating we developed PLLA copolymers with allyl (PLLA-co-DAG) and 3-hydroxypropyl (PLLA-co-HP) side chains to which we can attach functional groups. Given the potential of fatty acids being able to incorporate into lipid bilayers and/or influence gene expression, we grafted different fatty acid side chains to PLLA-co-HP by esterifying the corresponding fatty acids with the PLLA-co-HP 3-hydroxypropyl side chains. The effects of the polymer modifications on osteoblasts were then evaluated. While cellular morphology differed between surface coatings, they did not reflect changes in cellular phenotype. Changes in gene expression were most evident with arachidonate and 3-hydroxypropyl side-chains which exhibited osteoblast differentiating capabilities. Linoleate, myristate, oleate, and stearate ester side-chains did not have a significant influence on osteoblast phenotype. Growth characteristics of osteoblasts did not differ between the fatty acid copolymer films, although cells grown on PLLA-co-HP exhibited a trend toward increased growth. Taken together our findings demonstrate that surface fatty acid composition can impact osteoblast phenotype.

    Title Estrous Cycle Alters Naphthalene Metabolism in Female Mouse Airways.
    Date August 2006
    Journal Drug Metabolism and Disposition: the Biological Fate of Chemicals
    Excerpt

    Previous studies have shown variability in naphthalene cytotoxicity, expression of CYP2F2 gene and protein, and naphthalene metabolism in random cycling female mice (NIH:Swiss). CYP2F2 metabolizes naphthalene to cytotoxic metabolites in lungs of mice. This study was designed to address the question: do hormonal changes associated with the estrous cycle alter metabolism of naphthalene in the lung? Adult virgin female mice were manipulated into defined stages of the reproductive cycle: estrus, proestrus, and noncycling. Cycling was confirmed by cytology on vaginal swabs. At specific cycle times, extrapulmonary (tracheal and bronchial) and intrapulmonary (bronchiolar) conducting airways were microdissected from the lung parenchyma and incubated with naphthalene, and the products of naphthalene metabolism were trapped and measured using high-performance liquid chromatography. Circulating estradiol levels were measured at necropsy using an enzyme-linked immunosorbent assay. CYP2F2 gene expression was determined by airway level using real-time reverse transcription-polymerase chain reaction and did not vary by estrous cycle stage in intrapulmonary airways but did in extrapulmonary airways. Metabolism of naphthalene varied significantly by estrous cycle stage with the highest level of total metabolism occurring in proestrus (when estrogen is lowest) in intrapulmonary airways. Total activity and metabolite profiles in both extrapulmonary and intrapulmonary airways were affected by cycle stage. We conclude that the hormonal patterns associated with different stages of the estrous cycle 1) alter metabolism of naphthalene in the lungs of mice and 2) alter naphthalene metabolism differentially in extrapulmonary versus intrapulmonary airways.

    Title Multiple Functions of D-type Cyclins Can Antagonize Prb-mediated Suppression of Proliferation.
    Date March 2006
    Journal Cell Cycle (georgetown, Tex.)
    Excerpt

    The most well understood function of the D-type cyclins is to activate the G(1) kinases, cdk4 and cdk6, and target the retinoblastoma gene product (pRb) for phosphorylation and inactivation. pRb can suppress S phase entry, cause a transient G(1) arrest following DNA damage, and is critical in establishing terminal cell cycle withdrawal in cells exposed to differentiation or senescence-inducing signals. Each of these functions of pRb can be demonstrated in cultured cells derived from human tumors that have suffered RB1 gene inactivation. In such in vitro assays, coexpression of D type cyclins has been shown to inhibit the function of pRb, likely reflecting an oncogenic role of cyclin D1 in vivo. Two regions of cyclin D, the LxCxE pRb-binding motif, and the cyclin box, are thought to be critical for the proper function of cyclin D. Here we show that the LxCxE motif is dispensable in cyclin D1 for all functions tested, but is required by cyclin D2. This observation suggests that there is a functional difference between cyclins D1 and D2 in pRb regulation, and argues against complete functional redundancy of these D cyclins. In addition, the ability of cyclins D1 and D2 to activate cdk partners is required for induction of pRb phosphorylation and S phase entry. However, mutant forms of cyclins D1 and D2 that are incapable of activating kinase partners were still able to prevent pRb-induced senescence. Thus, D cyclins have both kinase-dependent and kinase-independent mechanisms of interfering with proliferation arrest and senescence.

    Title Characterization of a Structurally Intact in Situ Lung Model and Comparison of Naphthalene Protein Adducts Generated in This Model Vs Lung Microsomes.
    Date October 2005
    Journal Chemical Research in Toxicology
    Excerpt

    Airway epithelial cells are a susceptible site for injury by ambient air toxicants such as naphthalene that undergo P450-dependent metabolic activation. The metabolism of naphthalene in Clara cells to reactive intermediates that bind covalently to proteins correlates with cell toxicity. Although several proteins adducted by reactive naphthalene metabolites were identified in microsomal incubations, new methods that maintain the structural integrity of the lung are needed to examine protein targets. Therefore, we developed a method that involves inflation of the lungs via the trachea with medium containing (14)C-naphthalene followed by incubation in situ. The viability of this preparation is supported by maintenance of glutathione levels, rates of naphthalene metabolism, and exclusion of ethidium homodimer-1 from airway epithelium. Following in situ incubation, the levels of adduct per milligram of protein were measured in proteins obtained from bronchoalveolar lavage, epithelial cells, and remaining lung. The levels of adducted proteins obtained in lavage and epithelial cells were similar and were 20-fold higher than those in residual lung tissue. (14)C-Labeled adducted proteins were identified by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry (MS) and quadrupole-TOF MS/MS. Major adducted proteins include cytoskeletal proteins, proteins involved in folding and translocation, ATP synthase, extracellular proteins, redox proteins, and selenium binding proteins. We conclude that in situ incubation maintains structural integrity of the lung while allowing examination of reactive intermediate activation and interaction with target cell proteins of the lung. The proteins adducted and identified from in situ incubations were not the same proteins identified from microsomal incubations.

    Title Immunostimulatory Oligonucleotides Attenuate Airways Remodeling in Allergic Monkeys.
    Date April 2005
    Journal American Journal of Respiratory and Critical Care Medicine
    Excerpt

    To determine whether inhaled immunostimulatory DNA sequence oligonucleotides containing CpG motifs mitigate the pathophysiologic manifestation of the asthmatic phenotype (airways hyperresponsiveness and airways remodeling), rhesus monkeys with experimentally induced allergic airways disease were treated seven times with inhaled immunostimulatory oligonucleotides (or sham) periodically for 33 weeks. Airways hyperresponsiveness was reduced twofold in immunostimulatory DNA sequence-treated compared with sham-treated monkeys. Airways from immunostimulatory oligonucleotide-treated monkeys had thinner reticular basement membranes, fewer mucous cells, fewer eosinophils, and fewer mast cells than sham-treated allergic monkeys. We conclude that inhaled immunostimulatory oligonucleotides can attenuate the magnitude of airway hyperreactivity and airways remodeling produced in nonhuman primates with experimentally induced allergic airways disease.

    Title Epithelial Cell Distribution and Abundance in Rhesus Monkey Airways During Postnatal Lung Growth and Development.
    Date April 2005
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    Lung development is both a pre- and postnatal process. Although many lung diseases have their origins in early childhood, few quantitative data are available on the normal growth and differentiation of both the conducting airways and the airway epithelium during the postnatal period. We examined rhesus monkey lungs from five postnatal ages: 4-6 days and 1, 2, 3, and 6 mo. Airways increase significantly in both length and circumference as monkeys increase significantly in body weight from 5 days to 6 mo. In this study we asked: as basement membrane surface area increases, does the epithelial cell organization change? To answer this question, we quantified total epithelial cell mass using high-resolution light micrographs and morphometric techniques on sections from defined airway regions: trachea, proximal intrapulmonary bronchus (generations 1 or 2), and distal intrapulmonary bronchus (generations 6-8). Epithelial thickness decreased in the smaller, more distal, airways compared with trachea but did not change with age in the trachea and proximal bronchus. The volume fraction of all cell types measured did not change significantly. Ciliated cells in the distal bronchus and goblet cells in the trachea both decreased in abundance with increasing age. Overall, the epithelial cell populations changed little in terms of mass or relative abundance to each other during this period of active postnatal lung growth. Regarding the proximal conducting airway epithelium, we conclude that 1) the steady-state abundance is tightly regulated to keep the proportion of cell types constant, and 2) establishment of these cell types occurs before 4-6 days postnatal age. We conclude that growth of the proximal airways occurs primarily in length and lags behind that of the lung parenchyma.

    Title Polymer-brush Stationary Phases for Open-tubular Capillary Electrochromatography.
    Date February 2005
    Journal Journal of Chromatography. A
    Excerpt

    Synthesis of poly(2-hydroxyethyl methacrylate) (PHEMA) brushes from the inside of silica capillaries by surface-initiated atom transfer radical polymerization (ATRP) yields unique stationary phases for open-tubular capillary electrochromatography (OT-CEC). Although PHEMA brushes have only a small effect on the separation of a set of phenols and anilines, derivatization of PHEMA with ethylenediamine (en) allows baseline resolution of several anilines that co-elute from bare silica capillaries. Derivatization of PHEMA with octanoyl chloride (C8-PHEMA films) affords even better resolution in the separation of a series of phenols and anilines. Increasing the thickness of C8-PHEMA coatings by a factor of 2 enhances resolution for several solute pairs, presumably because of an increase in the effective stationary phase to mobile phase volume ratio. Thus, this work demonstrates that thick polymer brushes provide a tunable stationary phase with a much larger phase ratio than is available from monolayer wall coatings. Through appropriate choice of derivatizing reagents, these polymer brushes should allow separation of a wide range of neutral molecules as well as compounds with similar electrophoretic mobilities.

    Title The Remodelled Tracheal Basement Membrane Zone of Infant Rhesus Monkeys After 6 Months of Recovery.
    Date November 2004
    Journal Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology
    Excerpt

    BACKGROUND: In previous studies, we showed that repeated exposure to (1) house dust mite allergen (HDMA) (Dermatophagoides farinae) caused thickening of the basement membrane zone (BMZ) and (2) HDMA+ozone (O3) caused depletion of BMZ perlecan and atypical development of BMZ collagen (irregular thin areas<2.0 microm in width). OBJECTIVE: The purpose of this study was to determine if these remodelling changes were reversible after 6 months of recovery. METHODS: Rhesus monkeys were exposed to a regimen of HDMA and or O3 or filtered air (FA) for 6 months. After the exposure protocol was completed FA and O3 groups were allowed to recover in FA for 6 months. The HDMA and HDMA+O3 exposure groups recovered in a modified environment. They were re-exposed to HDMA aerosol for 2 h at monthly intervals during recovery in order to maintain sensitization for pulmonary function testing. To detect structural changes in the BMZ, collagen I and perlecan immunoreactivity were measured and compared to data from the previous papers. RESULTS: The remodelled HDMA group had a significantly thicker BMZ and after 6 months of recovery the width had not regressed. In the remodelled BMZ of the HDMA+O3 group, perlecan had returned to the BMZ after 6 months of the recovery protocol, and the thin, irregular, collagen BMZ had been resolved. CONCLUSION: In summary, this study has shown that: (1) The width of the remodelled HDMA BMZ did not regress during a recovery protocol that included a sensitizing dose of HDMA. (2) The atypical collagen BMZ in the HDMA+O3 BMZ was resolved in the absence of O3. (3) Depletion of perlecan from the BMZ by O3 was reversed by recovery in the absence of O3.

    Title Assessing Gene Expression in Lung Subcompartments Utilizing in Situ Rna Preservation.
    Date August 2004
    Journal Toxicological Sciences : an Official Journal of the Society of Toxicology
    Excerpt

    The mechanisms of toxicant-mediated lung injury and repair are influenced by the considerable spatial heterogeneity that exists within the conducting airways of the lungs. As a result of this heterogeneity, significant differences and similarities in gene expression are observed throughout lung subcompartments. RNA-based technologies such as real-time reverse transcription polymerase chain reaction (real-time RT-PCR) and cDNA microarray analysis of gene expression provide valuable clues to understanding the mechanisms of toxicant-induced injury. Isolating RNA from lung subcompartments has previously involved considerable time and labor-intensive processes that limit the number of animals that could be processed in a day. The aim of this study was to determine if intact, high-quality RNA could be preserved in situ over a period of time to delay the need to immediately perform site-specific lung subcompartment microdissections and RNA isolations. Two hours after 1-nitronaphthalene treatment, rat lungs were inflated with and stored in RNA preservation solution and stored at 4 degrees C for 7 days. RNA was isolated from the lung subcompartments isolated by microdissection. After 7 days of storage, the RNA was intact, of high quality, and could be used for real-time RT-PCR to examine heterogeneous gene expression in the lung subcompartments. In summary, this simplified technique of in situ RNA preservation and site-specific lung subcompartment microdissection allows the isolation of intact, high-quality RNA that may be used with molecular RNA-based technologies that will significantly accelerate our understanding of pulmonary injury and repair mechanisms.

    Title Hepatic Microcirculatory Dysfunction During Cholestatic Liver Injury in Rats.
    Date August 2004
    Journal Microcirculation (new York, N.y. : 1994)
    Excerpt

    OBJECTIVE:: The present study was conducted to elucidate the sequential alterations in the hepatic microvascular inflammatory response to extrahepatic biliary obstruction. METHODS:: The hepatic microvasculature in anesthetized Sprague-Dawley rats was studied by in vivo microscopy 3, 7, and 14 days after bile duct ligation (BDL) or sham operation. RESULTS:: The numbers of adhering leukocytes and swollen sinusoidal endothelial cells were significantly increased at 3, 7, and 14 days after BDL when compared with sham-operated controls. Concomitantly, the numbers of sinusoids containing blood flow were significantly and progressively decreased by up to 30%. The phagocytic activity of hepatic macrophages was significantly elevated during the development of biliary cholestasis. In particular, centrilobular phagocytosis at 14 days after BDL was significantly increased 1.4- to 2.0-fold when compared with that at 3 and 7 days after BDL. Electron microscopy also revealed evidence of activated Kupffer cells reflected by numerous filopodia and ruffles. CONCLUSIONS:: These results suggest that hepatic microcirculatory dysfunction subsequent to BDL contributes to cholestatic liver injury.Microcirculation (2003) 10, 421-432. doi:10.1038/sj.mn.7800208

    Title Gene Expression Analysis in Response to Lung Toxicants: I. Sequencing and Microarray Development.
    Date March 2004
    Journal American Journal of Respiratory Cell and Molecular Biology
    Excerpt

    A key challenge in measuring gene expression changes in the lung in response to site-selective toxicants is differentiating between target and nontarget areas. The toxicity for the cytotoxicant 1-nitronaphthalene is highly localized in the airway epithelium. Target cells comprise but a fraction of the total lung cell mass; measurements from whole lung homogenates are not likely to reflect what occurs at the target site. Additionally, the use of generic microarrays to measure expression in airway epithelium may not provide a good representation of transcripts present at the site of toxic action. cDNA libraries from airway and alveolar subcompartments of rat lung were sequenced for the development of a custom microarray representative of these lung regions. We identified 7,460 nonredundant rat lung sequences. Nearly 30% of the sequences on this array are not present on the Affymetrix Rat GeneChip 230. A 20,000-element microarray was developed that delineates differences in gene expression between subcompartments. This is the first in a series of articles employing this microarray for detecting gene expression changes during acute injury produced by 1-nitronaphthalene and subsequent repair.

    Title Dental Malocclusion and Upper Airway Obstruction, an Otolaryngologist's Perspective.
    Date October 2003
    Journal International Journal of Pediatric Otorhinolaryngology
    Excerpt

    INTRODUCTION: This paper, through the presentation of eight case reports and a limited literature review, attempts to illustrate the negative effect that upper airway obstruction can have on developing dental occlusion and the positive effect that upper airway relief can have on the 'normalization' of various malocclusion patterns believed to be related to chronic obligate mouth breathing. OBJECTIVE: To study the effect of airway relief (usually through tonsillectomy and/or adenoidectomy) on various patterns of dental malocclusion. METHODS: Children coming to the office of the lead author (D.J.W.) found to be obligate mouth breathers and who also had dental malocclusion had Polaroid 'bite' pictures taken at the time of their initial visit. One year or more after their surgery for upper airway relief (tonsillectomy and adenoidectomy in these cases) a second 'bite' photograph was taken and compared to the first. RESULTS: In all cases selected in this study there was observed improvement in their dental occlusion within a year following surgery to improve their breathing. CONCLUSION: It is the opinion of the authors of this paper that upper airway obstruction may have a negative effect on the developing transitional dental occlusion and that eliminating the cause of upper airway obstruction can lead to 'normalization' of occlusion in such children. Further orthodontic corrective modalities may be required for optimal occlusal results.

    Title Atypical Development of the Tracheal Basement Membrane Zone of Infant Rhesus Monkeys Exposed to Ozone and Allergen.
    Date October 2003
    Journal American Journal of Physiology. Lung Cellular and Molecular Physiology
    Excerpt

    Development of the basement membrane zone (BMZ) occurs postnatally in the rhesus monkey. The purpose of this study was to determine whether house dust mite allergen (HDMA) plus ozone altered this process. Rhesus monkeys were exposed to a regimen of HDMA and/or ozone or filtered air for 6 mo. To detect structural changes in the BMZ, we measured immunoreactivity of collagen I. To detect functional changes in the BMZ, we measured perlecan and fibroblast growth factor-2 (FGF-2). We also measured components of the FGF-2 ternary signaling complex [fibroblast growth factor receptor-1 (FGFR-1) and syndecan-4]. The width of the BMZ was irregular in the ozone groups, suggesting atypical development of the BMZ. Perlecan was also absent from the BMZ. In the absence of perlecan, FGF-2 was not bound to the BMZ. However, FGF-2 immunoreactivity was present in basal cells, the lateral intercellular space (LIS), and attenuated fibroblasts. FGFR-1 immunoreactivity was downregulated, and syndecan-4 immunoreactivity was upregulated in the basal cells. This suggests that FGF-2 in basal cells and LIS may be bound to the syndecan-4. We conclude that ozone and HDMA plus ozone effected incorporation of perlecan into the BMZ, resulting in atypical development of the BMZ. These changes are associated with specific alterations in the regulation of FGF-2, FGFR-1, and syndecan-4 in the airway epithelial-mesenchymal trophic unit, which may be associated with the developmental problems of lungs associated with exposure to ozone.

    Title Repeated Episodes of Ozone Inhalation Amplifies the Effects of Allergen Sensitization and Inhalation on Airway Immune and Structural Development in Rhesus Monkeys.
    Date September 2003
    Journal Toxicology and Applied Pharmacology
    Excerpt

    Twenty-four infant rhesus monkeys (30 days old) were exposed to 11 episodes of filtered air (FA), house dust mite allergen aerosol (HDMA), ozone (O3), or HDMA + O3 (5 days each followed by 9 days of FA). Ozone was delivered for 8 h/day at 0.5 ppm. Twelve of the monkeys were sensitized to house dust mite allergen (Dermatophagoides farinae) at ages 14 and 28 days by subcutaneous inoculation (SQ) of HDMA in alum and intraperitoneal injection of heat-killed Bordetella pertussis cells. Sensitized monkeys were exposed to HDMA aerosol for 2 h/day on days 3-5 of either FA (n = 6) or O3 (n = 6) exposure. Nonsensitized monkeys were exposed to either FA (n = 6) or O3 (n = 6). During the exposure regimen, parameters of allergy (i.e., serum IgE, histamine, and eosinophilia), airways resistance, reactivity, and structural remodeling were evaluated. Eleven repeated 5-day cycles of inhaling 0.5 ppm ozone over a 6-month period had only mild effects on the airways of nonsensitized infant rhesus monkeys. Similarly, the repeated inhalation of HDMA by HDMA-sensitized infant monkeys resulted in only mild airway effects, with the exception of a marked increase in proximal airway and terminal bronchiole content of eosinophils. In contrast, the combined cyclic inhalation of ozone and HDMA by HDMA sensitized infants monkeys resulted in a marked increase in serum IgE, serum histamine, and airways eosinophilia. Furthermore, combined cyclic inhalation of ozone and HDMA resulted in even greater alterations in airway structure and content that were associated with a significant elevation in baseline airways resistance and reactivity. These results suggest that ozone can amplify the allergic and structural remodeling effects of HDMA sensitization and inhalation.

    Title Fibroblast Growth Factor-2 in Remodeling of the Developing Basement Membrane Zone in the Trachea of Infant Rhesus Monkeys Sensitized and Challenged with Allergen.
    Date January 2003
    Journal Laboratory Investigation; a Journal of Technical Methods and Pathology
    Excerpt

    SUMMARY: Remodeling of the epithelial basement membrane zone (BMZ) involves increased deposition of collagen, resulting in thickening of the BMZ. The current study focuses on fibroblast growth factor-2 (FGF-2) in the tracheal BMZ in house dust mite allergen (HDMA)-sensitized infant rhesus monkeys, challenged with HDMA at a time when the BMZ is undergoing active postnatal development. To detect structural changes in the BMZ, we measured collagens I, III, and V. To detect changes in the function of the BMZ, we measured immunoreactivity of the heparan sulfate proteoglycan, perlecan, and FGF-2. We found significant thickening of the tracheal BMZ (p < 0.05) with each of these parameters. We also found that all HDMA tracheal samples expressed thin focal areas of the BMZ associated with leukocyte trafficking. These areas were depleted of perlecan and FGF-2; however, increased FGF-2 immunoreactivity was present in the adjacent basal cells. We conclude that basal cells and FGF-2 are involved with significant remodeling of the BMZ in the developing trachea of infant rhesus monkeys exposed to HDMA.

    Title Fibroblast Growth Factor-2 During Postnatal Development of the Tracheal Basement Membrane Zone.
    Date December 2002
    Journal American Journal of Physiology. Lung Cellular and Molecular Physiology
    Excerpt

    Thickening of the basement membrane zone (BMZ) is a characteristic of several airway diseases; however, very little is known about how this process occurs. The purpose of this study was to define development of the BMZ in the trachea of growing rhesus monkeys at 1, 2, 3, and 6 mo of age. We measured immunoreactivity of collagen types I, III, and V to detect structural changes in the developing BMZ. To detect more dynamic, functional components of the epithelial-mesenchymal trophic unit, we evaluated the distribution of perlecan, fibroblast growth factor-2 (FGF-2), and fibroblast growth factor receptor-1 (FGFR-1). One-month-old monkeys had a mean collagen BMZ width of 1.5 +/- 0.7 microm that increased to 4.4 +/- 0.4 microm in 6-mo-old monkeys. Perlecan was localized in the BMZ of the epithelium at all ages. FGF-2 was strongly expressed in basal cells at 1-3 mo. At 6 mo, FGF-2 was expressed throughout the BMZ and weakly in basal cells. FGFR-1 immunoreactivity was expressed by basal cells and cilia and weakly in the nuclei of columnar cells at all time points. These data indicate that development of the BMZ is a postnatal event in the rhesus monkey that involves FGF-2.

    Title Effect of Curcuminoids As Anti-inflammatory Agents on the Hepatic Microvascular Response to Endotoxin.
    Date November 2002
    Journal Shock (augusta, Ga.)
    Excerpt

    Curcuminoids, derived from the plant Curcuma domestica Val., have been shown to be free radical scavengers that suppress the production of superoxide by macrophages and potent anti-inflammatory agents that inhibit the lipopolysacharide (LPS)-induced production of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and the activation of nuclear factor (NF)-kappaB in human monocytic derived cells. The present study was undertaken to determine the efficacy of curcuminoids in inhibiting the hepatic microvascular inflammatory response elicited by LPS. BALB/C mice were gavaged intragastricly with curcuminoids [40 mg/kg body weight (bw) or 80 mg/kg bw] 1 h before intravenous injection of LPS (Escherichia coli, O111:B4, 100 microg/kg bw). The liver was examined 2 h after LPS injection using in vivo microscopic methods. LPS-treated mice showed significantly increased phagocytic activity of centrilobular Kupffer cells. The numbers of leukocytes adhering to the sinusoidal wall and swollen endothelial cells increased significantly in both the periportal and centrilobular regions, concomitant with a reduction in the numbers of sinusoids containing flow. Pretreatment with curcuminoids at the doses of 40 mg/kg bw or 80 mg/kg bw to endotoxemic mice significantly reduced the phagocytic activity of Kupffer cells, the numbers of adhering leukocytes and swollen endothelial cells. As a result, the number of sinusoids containing flow was increased in animals treated with 40 mg/kg curcuminoids and restored to control levels with 80 mg/kg curcuminoids. Neutrophil sequestration was reduced when measured in sections stained with naphtol AS-D chloroacetate esterase technique. These results demonstrate that curcuminoids are effective in suppressing the hepatic microvascular inflammatory response to LPS and may be a natural alternative anti-inflammatory substance.

    Title Gender Differences in Naphthalene Metabolism and Naphthalene-induced Acute Lung Injury.
    Date May 2002
    Journal American Journal of Physiology. Lung Cellular and Molecular Physiology
    Excerpt

    Humans are widely exposed to polycyclic aromatic hydrocarbons, commonly found in cigarette smoke and diesel exhaust. These can undergo site- and cell-specific metabolism to cytotoxic intermediates. Metabolism of naphthalene and Clara cell cytotoxicity have been extensively studied in male animals. To address whether male and female mice are equally susceptible to naphthalene, mice were injected with naphthalene, and lungs were examined 1, 2, 3, 6, and 24 h after treatment. By analysis of acute injury using differential permeability to fluorescent nuclear dyes and high-resolution histopathology, injury in female mice was found to be more extensive, occur earlier, and include permeable cells in proximal airways, including airway bifurcations. HPLC analysis of the products of cytochrome P-450 (CYP)-mediated metabolism in microdissected airways indicated that although both genders produced a predominance of products from CYP2F2, female mice produced more naphthalene dihydrodiol in distal airways, the primary sites of injury. We conclude that there are clear gender differences in susceptibility to naphthalene-induced injury and that differences in metabolism of naphthalene may play a role in elevated susceptibility in female mice.

    Title Poly(phenyllactide): Synthesis, Characterization, and Hydrolytic Degradation.
    Date January 2002
    Journal Biomacromolecules
    Excerpt

    Poly(phenyllactide) was synthesized via the ring-opening polymerization of phenyllactide, the dimer of phenyllactic acid. Phenyllactide was synthesized by two methods, the solution phase condensation of L-phenyllactic acid and by thermal cracking of low molecular weight phenyllactic acid oligomers. The poor solubility of the monomer limited solution polymerizations of phenyllactide to low yields and low molecular weights, but melt polymerization of phenyllactide with Sn(Oct)2/tert-butylbenzyl alcohol at 180 degrees C gave high molecular weight polymers in high yields. The resulting polymers were amorphous due to epimerization of approximately 10% of the stereocenters during polymerization. Poly(phenyllactide) has a glass transition temperature of 50 degrees C and degrades to monomer at 320 degrees C. Experiments run at 55 degrees C at pH 7.4 show that poly(phenyllactide) degrades at approximately 1/5 the rate of rac-polylactide.

    Title High Doses of Intravenous Immunoglobulin G Enhance Kupffer Cell Phagocytic Function During the Late Phase of Sepsis and Endotoxemia in Rats.
    Date November 2000
    Journal Shock (augusta, Ga.)
    Excerpt

    The effect of intravenous immunoglobuln G (ivIG) on the hepatic microvascular inflammatory response during the late phase of sepsis and endotoxemia in rats was studied by using in vivo microscopy. One hour after administration of a clinically relevant dose of ivIG (0.5 g/kg body weight, Sandoglobulin), rats were subjected to polymicrobial sepsis induced by cecal ligation and puncture (CLP) or were injected intravenously with lipopolysaccharide (LPS, 0.1 mg/kg body weight). Twenty-four hours after CLP or LPS, the number of leukocytes adhering to the sinusoidal wall was increased 11.0-fold in CLP-treated animals and 5.6-fold in LPS-treated animals, respectively, compared with the controls. Concomitantly, the numbers of swollen sinusoidal endothelial cells were increased 4.2-fold and 3.2-fold. The number of perfused sinusoids was decreased by 35% and by 24%. These responses were minimized by pretreatment with high doses of ivIG. Kupffer cell phagocytic activity in the periportal sinusoids in CLP-treated animals was decreased by 41%, whereas that in the centrilobular sinusoids in LPS-treated animals was increased by 72%. IvIG significantly elevated this activity in both CLP- and LPS-treated animals and the number of ED2-positive Kupffer cells in tissue sections. The results suggest that ivIG limits the hepatic microvascular inflammatory response during the late phase of sepsis and endotoxemia by affecting Kupffer cell function.

    Title Cdk6 Can Shorten G(1) Phase Dependent Upon the N-terminal Ink4 Interaction Domain.
    Date November 1999
    Journal The Journal of Biological Chemistry
    Excerpt

    Deregulated activity of cdk4 or cdk6 can lead to inappropriate cellular proliferation and tumorigenesis accompanied by unchecked inactivation of the retinoblastoma tumor suppressor protein. Certain tumor types preferentially activate either cdk4 or cdk6, suggesting that these kinases may not be equivalently oncogenic in all cell types. Although it is clear that cdk4 can act as an oncogene at least in part by evading inhibition by p16(INK4a), the role of cdk6 in tumorigenesis is less well understood. To investigate the consequences of aberrant expression of cdk6, the requirements for proliferation caused by cdk6 overexpression were studied. cdk6-transfected U2OS cells displayed an accelerated progression through G(1) phase that was dependent on kinase activity and that did not correlate with p27 binding. Furthermore, a mutation that prevents cdk6 interaction with INK4 proteins (cdk6R31C) was found to inactivate the proliferative effect of cdk6 and increase cytoplasmic localization, despite the fact that this mutant could phosphorylate the retinoblastoma protein in vitro. Together, these data suggest a role for the cdk6 INK4 interaction domain in the generation of functional, nuclear cdk6 complexes and demonstrate the importance of elevated cdk6 kinase activity in G(1) acceleration.

    Title Effect of Intravenous Immunoglobulin G on the Tnfalpha-mediated Hepatic Microvascular Inflammatory Response.
    Date June 1999
    Journal Shock (augusta, Ga.)
    Excerpt

    The effect of intravenous immunoglobulin G (ivIG) on the hepatic microvascular inflammatory response elicited by tumor necrosis factor alpha (TNFalpha) in rats was studied by means of in vivo microscopy and histological examination. One hour after the portal infusion of TNFalpha, the average number of leukocytes adhering to the sinusoidal endothelium was increased sevenfold, and the average number of the perfused sinusoids was decreased by 15% when compared with controls. Concomitantly, the expression of intercellular adhesion molecule-1 (ICAM-1) on the hepatic sinusoidal endothelium and that of the central vein was increased. The phagocytic activity of Kupffer cells in centrilobular sinusoids was increased by 54%, as were the number of ED2-positive Kupffer cells in tissue sections. Pretreatment with a clinically relevant high dose of ivIG (1 g/kg body weight, Sandoglobulin) minimized these responses by reducing leukocyte-endothelial interactions and Kupffer cell phagocytic function. The results suggest that high doses of ivIG limit the hepatic microvascular inflammatory response by inhibiting the action of the proinflammatory cytokine TNFalpha.

    Title Re: Treatment of Scars: a Review.
    Date February 1999
    Journal Annals of Plastic Surgery
    Title Effect of Immunoglobulin G on the Hepatic Microvascular Inflammatory Response During Sepsis.
    Date November 1996
    Journal Shock (augusta, Ga.)
    Excerpt

    The effects of intravenous immunoglobulin G (ivIG) on the hepatic microvascular inflammatory response to sepsis were studied in rats by in vivo microscopy. High doses of ivIG (300 mg/kg bw) (Sandoglobulin or rat IgG) significantly improved the 48 h survival of septic rats from 25-66% when ivIG was given before or immediately after cecal ligation and puncture. Circulating endotoxin also was significantly reduced. Eight hours after inducing sepsis, the average number of leukocytes adhering to the sinusoidal endothelium increased 15-fold and the average decrease in the number of perfused sinusoids was 22%. IvIG administration minimized these responses. In both septic and nonseptic animals, ivIG also reduced the phagocytic activity of Kupffer cells. The results suggest that high doses of ivIG not only reduce lethality but also limit hepatic microcirculatory dysfunction during sepsis by minimizing leukocyte-endothelial interactions that may be a result of reducing circulating endotoxin and modifying Kupffer cell function.

    Title Role of Endotoxin in the Hepatic Microvascular Inflammatory Response to Ethanol.
    Date March 1996
    Journal Journal of Gastroenterology and Hepatology
    Excerpt

    Kupffer cells (KC) and gut-derived bacterial endotoxin have been implicated in the aetiology of alcoholic liver disease. Using in vivo microscopic methods, we have shown that ethanol ingestion in mice causes a dose dependent increase in leucocyte adhesion and endothelial cell swelling in hepatic sinusoids. Activation of KC is elicited at low doses while depression occurs at high doses and with chronic exposure. The responses are exacerbated in the presence of endotoxaemia or sepsis and are not seen in endotoxin-resistant animals, implicating a role for endotoxin in the ethanol-induced inflammatory response. In addition, the responses are abolished with anti-TNF alpha suggesting that TNF alpha is a primary mediator of these events. Nitric oxide (NO) initially appears to play an important role in these events by stabilizing the TNF alpha-mediated hepatic microvascular inflammatory response to acute ethanol ingestion, thereby helping to protect the liver from ischaemia and leucocyte induced oxidative injury. Finally, an ongoing clinical study has confirmed a mild systemic endotoxaemia in patients hospitalized for alcoholic liver disease. All of these results support important roles for endotoxin, cytokines, nitric oxide and sinusoidal lining cells in the pathophysiology of liver injury resulting from ethanol alone or in combination with infection.

    Title Effects of Cyclophosphamide on the Development of Malignancy and on Long-term Survival of Patients with Rheumatoid Arthritis. A 20-year Followup Study.
    Date September 1995
    Journal Arthritis and Rheumatism
    Excerpt

    OBJECTIVE. To examine the effects of cyclophosphamide (CYC) on the development of malignancies and on the long-term survival of patients with rheumatoid arthritis (RA). METHODS. We used a longitudinal cohort design in which 119 patients (76 women and 43 men) with refractory RA who were treated with oral CYC between 1968 and 1973 were compared with 119 control patients with RA (matched for age, sex, disease duration, and functional class) who were evaluated during the same time period but did not receive CYC. RESULTS. There was increased risk of malignancy in the CYC-treated group, with 50 cancers found in 37 patients in the CYC group compared with 26 cancers in 25 of the control patients (P < 0.05). The relative risk of cancer for those treated with CYC was 1.5 (95% confidence interval 0.93-5.5). Nine of the malignancies in the CYC group were bladder cancers and 19 were skin cancers, compared with no bladder cancers and 6 skin cancers in the control group. The total dose of CYC was higher in those who developed cancer, particularly in those with bladder cancer. Three of the bladder cancers occurred 14, 16, and 17 years after CYC had been discontinued. CONCLUSION. The risk of malignancy, particularly bladder cancer, in RA patients treated with oral CYC continues even 17 years after discontinuation of the drug.

    Title Digit Replantation in Infants and Young Children: Determinants of Survival.
    Date July 1994
    Journal Plastic and Reconstructive Surgery
    Excerpt

    Thirty-three children under 34 months of age with 41 digits amputated over a 15-year period were reviewed. There were 3 primary amputations, 6 composite grafts, and 32 replantations. Twenty-one variables were evaluated for their influence on 4-week digit survival. The overall survival rate of 32 replanted digits was 69 percent. Favorable uncontrollable variables were clean-cut injury and body weight greater than 11 kg. Favorable controllable variables included more than one vein repaired, bone shortening, interosseous bone fixation, and vein grafting of arteries or veins. Forty-one percent of children required a blood transfusion. Children with trauma to more than one digit were most likely to be transfused (p < 0.05). The combination of prompt digit reperfusion after successful arterial repair and at least one successful venous anastomosis resulted in a 95 percent digit survival rate, significantly higher than the 0 percent survival of digits lacking one or the other of these features.

    Title Effects of Cholinesterase Inhibitors on the Neuromuscular Blocking Action of Suxamethonium.
    Date March 1994
    Journal British Journal of Anaesthesia
    Excerpt

    Prolonged neuromuscular block occurs when suxamethonium is given after neostigmine or pyridostigmine; however, studies of edrophonium and suxamethonium have yielded conflicting results. We have studied, therefore, interactions between suxamethonium and all three anticholinesterases in rats anaesthetized with pentobarbitone. After recovery from an initial bolus of suxamethonium, saline, edrophonium, pyridostigmine or neostigmine was administered and a second dose of suxamethonium was then given. All three anticholinesterases prolonged the duration of neuromuscular block (90% suppression to 50% twitch recovery) to 127 (SEM 9)%, 127(10)% and 138 (11)% of baseline for edrophonium, pyridostigmine and neostigmine, respectively. Recovery index (25% to 75% twitch recovery) was increased also to 125 (9)%; 149 (10%) and 185 (15)% of baseline, respectively for the three drugs.

    Title Visual and Auditory Cortical Lesions Following Acquisition of an Intensity Discrimination in Rats Fail to Disrupt Cross-modal Transfer.
    Date December 1993
    Journal Neuropsychologia
    Excerpt

    The effect of visual or auditory decortication on cross-modal transfer of an intensity discrimination was examined in rats. Twenty animals were first trained under either visual-auditory (V-A) or auditory-visual (A-V) cross-modal transfer (CMT) in a shuttlebox using a shock avoidance pardigm. Prior to the second training session, five of the A-V animals received auditory ablations and five V-A animals received visual ablations. The other 10 animals served as controls and received sham operations. The results reveal that CMT occurred in both experimental groups following cortical ablations. It is possible that information regarding stimulus intensity was transferred from a cortical region used during the original training session to the cortex used in the second or retraining session, prior to surgery. Alternatively, it may be that some subcortical structure (e.g. the amygdala, superior colliculus, or reticular formation) may be involved in CMT of intensity.

    Title Justifying Budget Requests for Ftes.
    Date November 1993
    Journal Journal of Healthcare Protection Management : Publication of the International Association for Hospital Security
    Title Superior Vena Cava Syndrome: Etiology, Diagnosis, and Treatment.
    Date September 1993
    Journal American Journal of Critical Care : an Official Publication, American Association of Critical-care Nurses
    Excerpt

    Superior vena cava (SVC) syndrome is a critical condition in which an intrathoracic mass lesion compresses the SVC and promotes the development of head and upper body edema and cyanosis. SVC syndrome develops in 10% of patients with a right-sided malignant intrathoracic mass lesion. Diagnostic evaluation and emergency therapy are always necessary to assess and alleviate airway obstruction, cerebral venous hypertension and symptoms secondary to mediastinal compression. Radiation therapy and venous bypass of the obstructed SVC are both used successfully as early treatment. Although radiation therapy to the malignant process may provide initial decompression, a more sustained decrease in venous pressure occurs in patients who also undergo decompressive SVC surgical bypass. SVC bypass should be considered early in the course of patients with profound cerebral or laryngeal edema, patients with extensive thrombosis of the SVC, and in rare patients afflicted with severe venous hypertension and in whom a tissue diagnosis requires a mediastinal exploration.

    Title Elevator Modification: Enhancement for Safety and Confidence During Orbital Exploration.
    Date August 1993
    Journal Plastic and Reconstructive Surgery
    Title Infant Cardiorespiratory Monitor Burn.
    Date May 1993
    Journal Kansas Medicine : the Journal of the Kansas Medical Society
    Title Infant Monitoring Resulting in Burns-tissue Damage: Literature Review and Case Report.
    Date April 1993
    Journal The Journal of Burn Care & Rehabilitation
    Excerpt

    Noninvasive infant monitoring occasionally results in burns and tissue damage. The medical literature now contains 14 isolated reports that were summarized for this review. All 14 victims were less than 24 months of age, and of these 14, two died by electrocution. Burns and tissue damage resulted from infant respiratory monitors (six), pulse oximeters (four), electrocardiographic monitors (two), an anal myoneural junction monitor (one), and a fetal scalp monitor (one). Infant extremities were injured most often (40%), and the trunk was burned somewhat less frequently (23%). Infants were burned in the hospital (57%) only slightly more often than at home (43%). Household burns involved only infant cardiorespiratory monitors. The most common mechanism of injury was the misapplication or improper connection of electrode lead wires (57%). A full one third of infants with burns required a reconstructive surgical procedure, usually a skin graft. Risk factors related to monitor-induced burns and tissue damage have been identified and presented. Injury prevention principles are also outlined.

    Title Microvascular Digit Transposition Following a Two-digit Amputation in an Infant.
    Date June 1992
    Journal Journal of Reconstructive Microsurgery
    Excerpt

    Multiple digit amputations in children demand special consideration to make subsequent hand function optimal. Replanted digits in children have a comparatively lower viability rate, but those that do survive usually go on to excellent function. In this case, an amputated thumb was severely mangled and not suitable for replantation. An amputated index finger was transposed to the thumb position. A six-month postoperative follow-up of the transposed digit confirmed satisfactory joint motion, restored sensibility, and unimpaired digit growth. The 11-month-old infant described is the youngest patient ever reported to have undergone a successful emergency microvascular digit transposition.

    Title Management of Arginine Monohydrochloride Extravasation in the Forearm.
    Date April 1991
    Journal Southern Medical Journal
    Excerpt

    We initially observed our patient, who had subcutaneous arginine monohydrochloride extravasation in the volar forearm, until his wound demarcation was complete. After wound demarcation, we proceeded with debridement and partial-thickness skin grafting. Upper extremity function was totally normal 3 months after this therapy. This is the first case report in the literature that describes a child with an arginine monohydrochloride-induced extravasation necrosis.

    Title Plasma Amino Acid Concentrations and Amino Acid Ratios in Normal Adults and Adults Heterozygous for Phenylketonuria Ingesting a Hamburger and Milk Shake Meal.
    Date April 1991
    Journal The American Journal of Clinical Nutrition
    Excerpt

    Plasma amino acid concentrations were measured and selected amino acid ratios were calculated in 12 normal adults and 12 adults heterozygous for phenylketonuria (PKU) ingesting a hamburger and milk shake meal providing 1 g protein/kg body wt. Plasma concentrations of all amino acids increased significantly over baseline after meal ingestion in both groups, reaching the highest mean values 3-5 h after meal ingestion. Plasma phenylalanine concentrations were significantly higher in heterozygous than in normal subjects both before and at all times after meal ingestion. The absolute increase in plasma phenylalanine concentration over baseline and the area under the plasma phenylalanine concentration-time curve were approximately twice as large in heterozygous as in normal subjects. However, the molar ratio of the plasma phenylalanine concentration to the sum of the plasma concentrations of the other large neutral amino acids did not increase significantly over baseline, but rather decreased.

    Title Fasciocutaneous Island Flap Based on the Medial Plantar Artery: Clinical Applications for Leg, Ankle, and Forefoot.
    Date January 1990
    Journal Plastic and Reconstructive Surgery
    Excerpt

    Soft-tissue deficits over the plantar forefoot, plantar heel, tendo calcaneus, and lower leg are often impossible to cover with a simple skin graft. The previously developed medial plantar fasciocutaneous island flap has been adapted to cover soft-tissue defects over these areas. This fasciocutaneous flap based on the medial plantar neurovascular bundle is capable of providing sensate and structurally similar local tissue. Application of this fasciocutaneous island flap is demonstrated in 12 clinical cases. Successful soft-tissue cover was achieved on the plantar calcaneus (four patients), tendo calcaneus (four patients), lower leg (two patients), and plantar forefoot (two patients). Follow-up ranged from 6 months to 5 years. All flaps were viable at follow-up. Protective sensation was present in 11 of 12 flaps evaluated at 6 months. In addition, all 11 patients were able to ambulate in normal footwear. The medial plantar island flap seems to be more durable than a skin graft, and the donor site on the non-weight-bearing instep is well tolerated. This study demonstrates that the medial plantar fasciocutaneous island flap should be considered as another valuable tool in reconstructive efforts directed at the plantar forefoot, plantar heel, posterior ankle, and lower leg.

    Title Partitioning of Ventilation Between Nose and Mouth: the Role of Nasal Resistance.
    Date June 1989
    Journal American Journal of Orthodontics and Dentofacial Orthopedics : Official Publication of the American Association of Orthodontists, Its Constituent Societies, and the American Board of Orthodontics
    Excerpt

    We have examined the relationship between nasal resistance (Rna) and the distribution of ventilation between the nose and mouth in 10 normal breathing children and 15 children who met clinical criteria of mouth breathing. We studied Rna by posterior rhinometry. We used a face mask divided into separate oral and nasal chambers to measure oral and nasal components of ventilation. Each chamber of the mask was connected to a separate pneumotachograph. We measured oral and nasal tidal volumes (VTna) by integration of the oral and nasal flow, and calculated the total tidal volume (VTtot) by summing the oral and nasal components. The nasal fraction of ventilation (F-VTna) was calculated by dividing VTna by VTtot. We found a weak inverse correlation between Rna and F-VTna, but eight of 25 children did not breathe as one might predict on the basis of Rna, and eight of 15 children who appeared to be mouth breathers actually breathed through the nose. We administered a vasoconstricting nasal spray and a placebo nasal spray to the children and, although Rna changed significantly, we observed no change in the distribution of flow between the nose and mouth. In summary we found that clinical criteria of mouth breathing do not accurately identify children who actually breathe mainly through the mouth. Moreover Rna is only a weak predictor of the pattern of breathing; hence other factors may be important determinants of the distribution of flow between the nose and mouth.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Repeated Ingestion of Aspartame-sweetened Beverage: Effect on Plasma Amino Acid Concentrations in Individuals Heterozygous for Phenylketonuria.
    Date January 1989
    Journal Metabolism: Clinical and Experimental
    Excerpt

    It has been suggested that excessive use of aspartame (APM) (N-L-alpha-aspartyl-L-phenylalanine methyl ester) might grossly elevate plasma aspartate and phenylalanine concentrations in individuals heterozygous for phenylketonuria (PKUH). In study 1 six adult PKUH (three males; three females) ingested three successive 12-oz servings of beverage at 2-h intervals. The study was carried out in two parts in a randomized crossover design. In one arm the beverage was not sweetened. In the other the beverage provided 10 mg APM/kg body weight per serving. The addition of APM to the beverage did not significantly increase plasma aspartate concentration but did increase plasma phenylalanine levels 2.3 to 4.1 mumol/dL above baseline values 30 to 45 min after each dose. The high mean plasma phenylalanine level after repeated APM dosing (13.9 +/- 2.15 mumol/dL) was slightly, but not significantly, above the normal postprandial range for PKUH (12.6 +/- 2.11 mumol/dL). In study 2 six different adult PKUH ingested beverage providing 30 mg APM/kg body weight as a single bolus. The high mean plasma phenylalanine concentration and the phenylalanine to large neutral amino acid ratio were significantly higher when APM was ingested as a single bolus than when ingested as a divided dose.

    Title Repeated Ingestion of Aspartame-sweetened Beverage: Effect on Plasma Amino Acid Concentrations in Normal Adults.
    Date April 1988
    Journal Metabolism: Clinical and Experimental
    Excerpt

    Aspartame (APM) is a dipeptide sweetener (L-aspartyl-L-phenylalanine methyl ester). It has been suggested that excessive use of the product might elevate plasma aspartate and phenylalanine concentrations. Eight normal adults (four male, four female) ingested three successive 12-oz servings of APM-sweetened beverage at two-hour intervals. The study was carried out in two parts in a randomized cross-over design. In one study the beverage was not sweetened. In the other, the beverage provided 10 mg APM/kg body weight per serving. Plasma amino acid concentrations were measured throughout the six-hour study period. The addition of APM to the beverage had no significant effect on plasma aspartate concentration. APM addition did increase plasma phenylalanine levels 1.64 to 2.05 mumol/dL above baseline values (5.09 +/- 0.82 mumol/dL) 30 to 45 minutes after each dose. However, plasma phenylalanine levels did not exceed normal postprandial values at any time. The data indicate ready metabolism of APM's amino acid content when administered at levels likely to be ingested by individuals who are heavy users of such beverages.

    Title Plasma Amino Acid Concentrations in Normal Adults Ingesting Aspartame and Monosodium L-glutamate As Part of a Soup/beverage Meal.
    Date December 1987
    Journal Metabolism: Clinical and Experimental
    Excerpt

    We tested the hypothesis that ingestion of monosodium L-glutamate with aspartame produces a marked increase in plasma glutamate and aspartate concentrations. Twelve normal adults (6 males, 6 females) ingested three different soup/beverage meals in a balanced Latin square design. One meal (A) provided no aspartame (APM) or monosodium L-glutamate (MSG); a second (B) provided 50 mg MSG/kg body weight; while the third (C) provided 50 mg MSG and 34 mg APM per kg body weight. Plasma glutamate (Glu) concentrations were not significantly affected by meal A but increased significantly after meals B and C (no significant difference between B and C). Plasma aspartate (Asp) concentrations were not significantly affected by meal A but increased significantly after meals B and C (values significantly higher after meal C than meal B). Plasma Glu + Asp concentrations were not significantly affected by meal A but increased significantly from a mean (+/- SD) baseline value of 5.64 +/- 2.62 mumol/dL to high mean values of 23.1 +/- 7.29 and 26.8 +/- 9.74 mumol/dL after ingestion of meals B and C, respectively (no significant difference between meals B and C). Similarly, the area under the plasma Glu + Asp concentration-time curve did not differ significantly between meals B and C (624 +/- 197 v 763 +/- 277 mumol/dL x min, respectively). Peak plasma Glu + Asp concentrations for each subject (ignoring time) were also examined. The mean peak plasma Glu + Asp concentrations were 7.39 +/- 2.77, 23.0 +/- 6.61, and 27.3 +/- 9.07 mumol/dL, respectively after meals A, B, and C.

    Title Malignancy Following Treatment of Rheumatoid Arthritis with Cyclophosphamide. Long-term Case-control Follow-up Study.
    Date August 1987
    Journal The American Journal of Medicine
    Excerpt

    A long-term retrospective case-control study was performed comparing 119 patients with rheumatoid arthritis treated with cyclophosphamide and 119 matched control patients with rheumatoid arthritis not treated with cyclophosphamide to determine the risk of subsequent malignancy. Thirty-seven malignancies were detected in 29 cyclophosphamide-treated patients, while 16 malignancies were found in 16 control patients (p less than 0.05) during a mean follow-up period of more than 11 years. Urinary bladder cancer (six cyclophosphamide-treated patients, no control patients) and skin cancer (eight cyclophosphamide-treated patients, no control patients) were identified as differing statistically between the groups, and hematologic malignancy (five cyclophosphamide-treated patients, one control patient) showed a similar trend. Survival analysis indicated that the rate of development of malignancy in the cyclophosphamide-treated patients was significantly greater than in the control patients at six years following drug initiation, and that this increased rate persisted even at 13 years (p less than 0.01). Of the many risk factors evaluated, mean total cyclophosphamide dose and duration and tobacco use were significantly increased in patients in whom cancer subsequently developed. These long-term complications must be considered seriously when cyclophosphamide or other cytotoxic drugs are initiated for the treatment of rheumatoid arthritis.

    Title Pasteurella Multocida Polyarticular Septic Arthritis.
    Date August 1987
    Journal The Journal of Rheumatology
    Excerpt

    Pasteurella multocida is an unusual cause of septic arthritis with most patients having underlying joint damage or altered host defenses. We report 2 cases of polyarticular sepsis with this bacteria. Predisposing factors in our patients included alcoholic cirrhosis, end stage renal disease and metastatic malignancy. Heightened awareness of this organism's involvement in polyarticular septic arthritis in the immunocompromised patient is emphasized.

    Title Effect of Sucrose Ingestion on Plasma Glutamate Concentrations in Humans Administered Monosodium L-glutamate.
    Date May 1986
    Journal The American Journal of Clinical Nutrition
    Excerpt

    Plasma glutamate concentrations in human subjects are markedly lower when monosodium L-glutamate (MSG) is ingested in consomme with starch than when ingested in consomme alone. This study investigated whether sucrose had a similar effect. Six normal adult subjects (three male, three female) ingested two servings of beef consomme each providing 50 mg MSG/kg body weight in a randomized crossover design. One serving of consomme contained no added carbohydrate; the other provided 0.5 g sucrose/kg body weight. Ingestion of the consomme without sucrose significantly (p less than 0.05) increased the mean plasma glutamate concentration from baseline (4.44 +/- 0.97 mumol/dl) to a peak value of 18.1 +/- 6.99 mumol/dl 30 min after dosing. The area under the plasma glutamate concentration-time curve was 553 +/- 238 mumol/dl X min. When the consomme contained 0.5 g sucrose/kg body weight, both the mean peak plasma glutamate concentration (5.48 +/- 2.19 mumol/dl) and the area under the curve (105 +/- 46 mumol/dl X min) were significantly lower. These data confirm that metabolizable carbohydrate has a significant effect on plasma glutamate concentration response after MSG loading.

    Title Plasma Glutamate Concentrations in 1-year-old Infants and Adults Ingesting Monosodium L-glutamate in Consommé.
    Date March 1986
    Journal Pediatric Research
    Excerpt

    This study tested the hypothesis that infants metabolize glutamate more slowly than adults. Eight 1-yr-old infants ingested 160 ml of a beef consommé providing monosodium L-glutamate at 0, 25, and 50 mg/kg body weight. Plasma glutamate and aspartate concentrations were measured sequentially for the next 2 h. The results were compared to values noted in nine adult subjects ingesting equivalent doses of monosodium L-glutamate in consommé. In adults, mean (+/- SD) peak plasma glutamate concentrations were 5.59 +/- 1.56, 10.2 +/- 2.08, and 17.0 +/- 8.06 mumol/dl, respectively; the area under the plasma glutamate concentration time curves were 96 +/- 42, 257 +/- 80, and 442 +/- 303 mumol/dl X min, respectively. In infants, the mean (+/- SD) peak plasma glutamate concentrations were 6.94 +/- 1.43, 10.6 +/- 2.36, and 12.0 +/- 1.16 mumol/dl, respectively; the plasma glutamate area under the curve values were 47 +/- 28, 191 +/- 85, and 358 +/- 105 mumol/dl X min, respectively. The data indicate that the plasma glutamate concentration response in 1-yr-old infants ingesting MSG at these glutamate doses is no higher than values observed in adult subjects.

    Title The Hypothenar Hammer Syndrome.
    Date March 1986
    Journal The Journal of Rheumatology
    Title Effect of Allopurinol on Kidneys After Ischemia and Reperfusion.
    Date February 1986
    Journal Current Surgery
    Title Ankylosis of the Temporomandibular Joint from Psoriatic Arthritis.
    Date December 1985
    Journal The Journal of Otolaryngology
    Excerpt

    A review of 27 cases of temporomandibular joint arthritis in patients with psoriasis reveals the main pathologic features to be condylar erosions, condylar osteoporosis, calcification of the articular disc, and subchondral cyst formation. We present another pathological process, temporomandibular joint bony ankylosis in a patient with psoriasis. Surgical management consisted of a high condylectomy, with a silastic implant to maintain the vertical dimension of the ramus. A very good functional result was obtained and 21/2 years later her incisive distance is 44 mm.

    Title Oxygen Free Radical Induced Damage in Kidneys Subjected to Warm Ischemia and Reperfusion. Protective Effect of Superoxide Dismutase.
    Date November 1985
    Journal Annals of Surgery
    Excerpt

    Superoxide anion free radical (O2-.) has been implicated in the pathogenesis of tissue injury consequent to ischemia/reperfusion in several different organs, including heart and bowel. Superoxide dismutase (SOD), an enzyme free radical scavenger specific for O2-., has been used successfully to protect these organs from structural damage during reoxygenation of ischemic tissue. It has been suggested that the catalytic action of xanthine oxidase in injured tissue is an important source of O2-. during reoxygenation. In order to evaluate the potential of SOD to protect against kidney damage resulting from transient ischemia followed by reperfusion with oxygenated blood, a model of warm renal ischemia was studied. LBNF1 rats underwent right nephrectomy and occlusion of the left renal artery for 45 minutes. Survival in the group of ischemic untreated rats (N = 30) was 56% at 7 days and serum creatinine was greatly elevated (p less than 0.01) in rats remaining alive over the full 7-day period. In strong contrast to these results, all of the animals treated with SOD before reperfusion (N = 18) were alive after 7 days similar to sham operated control rats (N = 8). Serum creatinine in the SOD treated rats was significantly elevated only to postoperative day 3 and thereafter returned to normal. Rats treated with inactive SOD (N = 4) or SOD before ischemia (N = 4) had decreased survival rates compared to ischemic untreated animals and prolonged elevation of serum creatinine. When the ischemia time was extended to 60 minutes, only 19% of the untreated animals (N = 16) survived at 7 days whereas nearly 60% of the SOD-treated animals survived (N = 19). Serum creatinine was greatly elevated during the full 7-day observation period in all surviving rats in the untreated ischemic group, whereas serum creatinine returned to normal (p less than 0.05) after 4 days in the surviving rats treated with SOD. To test whether the action of xanthine oxidase contributed to the kidney damage after reoxygenation, 45 min. ischemic rat kidneys were treated with allopurinol. All of the animals treated with allopurinol (N = 12) were alive at 7 days. Serum creatinine values returned to normal after the episode of ischemia and reperfusion but more slowly than after SOD treatment. Histologic evaluation of kidney tissue taken from animals after ischemia alone showed extensive renal tubular damage, which was essentially absent in kidneys from SOD-treated animals.(ABSTRACT TRUNCATED AT 400 WORDS)

    Title Plasma Glutamate Concentrations in Adult Subjects Ingesting Monosodium L-glutamate in Consomme.
    Date September 1985
    Journal The American Journal of Clinical Nutrition
    Excerpt

    The effect of MSG ingestion in consomme on the plasma glutamate concentration response was studied in normal adult subjects. In the first study nine subjects ingested three different consomme servings (providing 0, 25 and 50 mg/kg body weight MSG) in a Latin square design. Plasma glutamate concentrations were not significantly increased over baseline (3.69 +/- 1.08 mumol/dl) when no added MSG was present. However, mean peak plasma glutamate levels increased proportional to dose when MSG was added (10.2 +/- 2.00 and 17.0 +/- 8.06 mumol/dl at 25 and 50 mg/kg body weight respectively). Since six of the nine subjects in this study reported an idiosyncratic symptom response when tested with MSG at 150 mg/kg body weight, nine additional subjects were also studied. They ingested consomme providing MSG at 0 and 50 mg/kg body weight. No significant differences in plasma amino acid responses were noted between the two groups of subjects.

    Title Effect of Starch Ingestion on Plasma Glutamate Concentrations in Humans Ingesting Monosodium L-glutamate in Soup.
    Date March 1985
    Journal The Journal of Nutrition
    Excerpt

    Plasma glutamate concentrations in human subjects are markedly lower when monosodium L-glutamate is ingested in a water solution containing partially hydrolyzed starch than when ingested in water alone. This study was carried out to investigate whether starch ingested as crackers had a similar effect. Eight normal adult subjects (four male, four female) ingested three servings of a beef consommé providing 50 mg/kg body weight monosodium L-glutamate. One serving was consommé alone, the other two were accompanied by sufficient crackers to provide 0.25 or 0.5 g starch per kilogram body weight, respectively. Ingestion of consommé containing glutamate significantly increased the mean plasma glutamate concentration above baseline to a mean peak value 30 min later. The peak after consumption of 0.5 g starch per kilogram body weight, but not 0.25 g/kg body weight, was significantly lower than when consommé alone was ingested. These data indicate that simultaneous ingestion of metabolizable carbohydrate with glutamate has a marked effect on the plasma glutamate response and indicate that the threshold value for carbohydrate is greater than 0.25 g/kg body weight.

    Title Plasma Amino Acid Concentrations in Normal Adults Fed Meals with Added Monosodium L-glutamate and Aspartame.
    Date October 1983
    Journal The Journal of Nutrition
    Excerpt

    Aspartame is a dipeptide sweetener containing aspartate. It has been suggested that aspartame addition to meals containing large amounts of monosodium L-glutamate (MSG) would result in a rapid rise in plasma glutamate and/or aspartate concentrations and increase the potential for dicarboxylic amino acid--induced toxicity. Sic normal adult subjects were fed three hamburger and milk shake meals providing protein at 1 g/kg body weight in a Latin square design. One meal had no additions, the second provided MSG at 150 mg/kg body weight, and the third provided MSG at 150 mg/kg body weight and aspartame at 23 mg/kg body weight. The addition of MSG alone significantly increased plasma glutamate + aspartate concentration above values noted after ingestion of the meal alone. Aspartame addition to meals already containing MSG did not further significantly increase plasma glutamate + aspartate concentration above values noted when only MSG was added. However, aspartame addition did significantly increase the mean plasma phenylalanine concentration above values noted after ingestion of the meal alone or the meal with added MSG, reflecting aspartame's phenylalanine content. The data do not support the suggestion that aspartame addition to high protein meals already containing large amounts of MSG, will promote a rapid and dangerous rise in plasma glutamate and aspartate concentrations.

    Title Effect of Aspartame Loading on Plasma and Erythrocyte Free Amino Acid Concentrations in One-year-old Infants.
    Date September 1983
    Journal The Journal of Nutrition
    Excerpt

    Aspartame is a new dipeptide sweetener. It has been suggested that infants metabolize its constituent amino acids (aspartate and phenylalanine) less well than adults. To test this hypothesis, 24 1-year-old infants were administered 34, 50 and 100 mg/kg body weight aspartame in cherry-flavored beverage mix. Plasma amino acid concentrations and the areas under the plasma concentration-time curves (AUC) were determined and were compared with values in adults administered equivalent doses. The doses studied include the 99th percentile of projected ingestion for adults (34 mg/kg), a very high use dose (50 mg/kg body weight), and a potentially abusive dose (100 mg/kg body weight). Plasma aspartate concentrations did not change significantly (P greater than 0.05) at aspartame doses of 34 and 50 mg/kg body weight, but did increase significantly at the 100 mg/kg body weight dose. The change over base line was similar in infants and adults. Aspartame dosing significantly increased both the mean peak plasma phenylalanine concentration and the plasma phenylalanine AUC value in proportion to dose. Mean (+/- SD) peak plasma phenylalanine concentrations in infants were 9.37 +/- 1.44, 11.6 +/- 4.44 and 22.3 +/- 11.5 mumol/100 ml at aspartame doses of 34, 50 and 100 mg/kg body weight, respectively. Values in infants were similar to those noted in adults. The data do not support the suggestion that infants metabolize the amino acids of aspartame less well than adults.

    Title Blood Methanol Concentrations in One-year-old Infants Administered Graded Doses of Aspartame.
    Date September 1983
    Journal The Journal of Nutrition
    Excerpt

    Blood methanol concentrations were measured in 24 1-year-old infants administered aspartame, a dipeptide methyl ester sweetener. The doses studied included a dose projected to be the 99th percentile of daily ingestion for adults (34 mg/kg body weight), a very high use dose (50 mg/kg body weight) and a dose considered to be in the abuse range (100 mg/kg body weight). Blood methanol values in infants were compared to values observed previously in adults administered equivalent doses of aspartame. Methanol concentrations were below the level of detection (0.35 mg/dl) in the blood of 10 infants administered aspartame at 34 mg/kg body weight, but were significantly elevated (P less than or equal to 0.05) after ingestion of aspartame at 50 and 100 mg/kg body weight. At the latter doses, mean peak blood methanol concentrations and the area under the blood methanol concentration-time curve increased in proportion to dose. Mean (+/- SEM) peak blood methanol concentration was 0.30 +/- 0.10 mg/100 ml at a 50 mg/kg body weight aspartame dose (n = 6) and 1.02 +/- 0.28 mg/ml at the 100 mg/kg body weight dose (n = 8). Blood methanol values in infants were similar to those observed in normal adults.

    Title Effect of Carbohydrate on Plasma and Erythrocyte Glutamate Levels in Humans Ingesting Large Doses of Monosodium L-glutamate in Water.
    Date June 1983
    Journal The American Journal of Clinical Nutrition
    Excerpt

    In previous studies, plasma glutamate concentration was lower when equivalent doses of monosodium L-glutamate (MSG) were given with a ready-to-feed liquid formula meal (Sustagen; 0.4 g protein, 1.1 g carbohydrate, 0.06 g fat, 6.6 kcal energy/kg body weight) rather than in water. This difference was suggested to reflect a carbohydrate effect on mucosal cell glutamate metabolism. To test this hypothesis, a large dose of monosodium L-glutamate (150 mg/kg body weight) dissolved in water, with or without added carbohydrate, was administered to eight healthy adult subjects. Carbohydrate was administered at 1.1 g/kg body weight in the form of partially hydrolyzed corn starch (Polycose). In the absence of carbohydrate, the mean (+/- SD) peak plasma glutamate concentration was 59.4 +/- 46.5 mumol/dl, and the incremental area under the plasma glutamate concentration time curve was 3391 +/- 2360 mumol/(dl x min). The addition of carbohydrate to the glutamate solution significantly decreased (p = 0.001) both the mean peak plasma glutamate concentration (7.18 +/- 3.48 mumol/dl) and the incremental area under the plasma glutamate concentration-time-curve (451 +/- 20.8 mumol/(dl x min). Erythrocyte glutamate and aspartate concentrations were not affected by glutamate loading in either test. Delayed gastric emptying did not account for the carbohydrate effect. Carbohydrate is postulated to serve as a pyruvate source for mucosal cells, facilitating the transamination of glutamate and its subsequent metabolism. This process would reduce the release of glutamate to the peripheral circulation.

    Title Modulating Effect of Sustagen on Plasma Glutamate Concentration in Humans Ingesting Monosodium L-glutamate.
    Date March 1983
    Journal The American Journal of Clinical Nutrition
    Excerpt

    It has been suggested that monosodium L-glutamate (MSG) addition to meals would significantly increase plasma glutamate concentrations compared to values noted after ingestion of protein-bound glutamate. To test this hypothesis, plasma amino acid concentrations were measured in six normal adults ingesting a ready-to-feed liquid meal (Sustagen) containing added MSG at 0, 100, and 150 mg/kg body weight (Latin square design), and compared to plasma values noted after ingestion of 150 mg/kg body weight MSG in water. The mean (+/- SD) peak plasma glutamate concentrations after ingestion of meals providing 0, 100, and 150 mg/kg body weight MSG were 6.64 +/- 1.99, 11.2 +/- 4.89 and 10.8 +/- 3.10 mumol/dl, respectively. Erythrocyte glutamate concentrations were unchanged after each meal. Peak plasma glutamate concentrations after ingestion of meals with added MSG were similar to those noted in normal adults ingesting a similar quantity of protein-bound glutamate. In contrast, ingestion of MSG in water (150 mg/kg body weight) markedly increased the mean (+/- SD) peak plasma glutamate concentration to 71.8 +/- 35.7 mumol/dl. Similarly, the area under the plasma glutamate concentration-time-curve was significantly higher. MSG ingestion with meals results in lower plasma glutamate concentrations than ingestion of equivalent doses in water.

    Title Effect of Aspartame Plus Monosodium L-glutamate Ingestion on Plasma and Erythrocyte Amino Acid Levels in Normal Adult Subjects Fed a High Protein Meal.
    Date January 1983
    Journal The American Journal of Clinical Nutrition
    Excerpt

    It has been suggested that aspartame addition to meals already containing large amounts of monosodium L-glutamate would result in an early rapid rise in plasma glutamate and/or aspartate concentrations and increase the potential for dicarboxylic amino acid-induced toxicity. Six normal adult subjects were fed hamburger and milk shake meals providing protein at 1 g/kg body weight in a randomized cross-over design. One meal had no additions while the other contained added monosodium L-glutamate and aspartame (each present at 34 mg/kg body weight). The addition of aspartame plus glutamate had little effect on either plasma or erythrocyte concentrations of glutamate or aspartate beyond those arising from the meal itself. Plasma phenylalanine concentrations were significantly higher (p less than 0.05, paired t test) after ingestion of meals containing aspartame plus glutamate reflecting the increased phenylalanine load.

    Title Effect of Sampling Site on Plasma Amino Acid Concentrations of Infants: Effect of Skin Amino Acids.
    Date December 1982
    Journal The American Journal of Clinical Nutrition
    Excerpt

    Plasma taurine, aspartate, threonine, serine, glycine, alanine, valine, leucine, tyrosine, phenylalanine, tryptophan, lysine, histidine, and ornithine concentrations are significantly greater (p less than 0.05, "Student's" t test) in blood samples obtained by conventional heel skin puncture techniques from 1-yr-old infants than values in venous plasma. Differences in plasma concentrations of taurine, aspartate, serine, glycine, and ornithine were particularly striking, with levels in plasma collected from the heel being 1.6 to 6.7 times higher than levels in venous plasma. These increased plasma amino acid concentrations were shown to result primarily from contamination of the plasma with amino acids present on the skin surface. Thorough washing and stimulation of blood flow to the heel by warming prior to skin puncture reduced observed differences. Plasma amino acid concentrations of blood samples obtained by conventional heel skin puncture procedures can be "normalized" to venous values through the use of data on the amino acid composition of heel skin washings.

    Title Plasma and Erythrocyte Amino Acid Levels in Normal Adult Subjects Fed a High Protein Meal with and Without Added Monosodium Glutamate.
    Date December 1982
    Journal The Journal of Nutrition
    Excerpt

    It has been suggested that the addition of free glutamate to meals already containing large amounts of protein-bound glutamate would produce an early rapid rise in plasma glutamate and/or aspartate concentrations, increasing the potential for glutamate-induced adverse effects. Normal adult subjects were fed a hamburger and milk shake meal providing protein at 1 g/kg body weight with and without added monosodium L-glutamate (34 mg/kg body weight). The addition of glutamate to the meal at this level had no significant effect on either plasma or erythrocyte concentrations of glutamate or aspartate beyond those arising from the meal itself. Free glutamate added to a hamburger and milk shake meal at this level is rapidly metabolized and does not elevate plasma concentrations of these dicarboxylic amino acids.

    Title The 1981 Entering Class.
    Date September 1982
    Journal Journal of the Iowa Medical Society
    Title Plasma and Urinary Methionine Levels in One-year-old Infants After Oral Loading with L-methionine and N-acetyl-l-methionine.
    Date June 1982
    Journal The Journal of Nutrition
    Excerpt

    N-acetyl-L-methionine has been proposed as a replacement for methionine in supplementing food products low in this amino acid. Previous studies in adult subjects administered equimolar quantities (0.0605 mmoles/kg body weight) of L-methionine and N-acetyl-L-methionine showed equivalent overall release of methionine to the blood as judged by area under the plasma methionine time--absorption curve. In the present study, similar doses (0.0605 mmoles/kg body weight) of L-methionine and N-acetyl-L-methionine were administered to fasting 1-year-old infants in a randomized crossover design. The two compounds produced an equivalent overall release of methionine to the blood as judged by plasma methionine concentrations and by the area under the plasma methionine concentration--time curves. No evidence was obtained that indicated release of N-acetyl-L-methionine to plasma or its excretion in urine after loading. However, peak plasma methionine concentrations, and the areas under the plasma methionine concentration--time curves for infants were approximately one-half the values observed in normal adults administered equimolar doses of each compound on a per kilogram body weight basis. The data suggest more rapid metabolism of methionine and N-acetyl-L-methionine by infants than adults.

    Title Effect of Aspartame and Sucrose Loading in Glutamate-susceptible Subjects.
    Date November 1981
    Journal The American Journal of Clinical Nutrition
    Excerpt

    It has been postulated that individuals reporting an idiosyncratic symptom response after glutamate ingestion might also experience such symptoms after aspartame ingestion. Such sensitive subjects might have been missed in earlier studies of aspartame. In the present study, six subjects reporting various symptoms after glutamate ingestion, but not after placebo, were administered aspartame (34 mg/kg body weight) or sucrose (1 g/kg body weight) dissolved in orange juice in a randomized, cross-over, double-blind study. No subject reported symptoms typical of a glutamate response after either sucrose or aspartame loading. One subject reported slight nausea approximately 1.5 h after aspartame ingestion, but indicated that the symptoms were not those of a glutamate response. Plasma phenylalanine and aspartate levels were similar to those noted in normal subjects administered identical doses of aspartame. The data indicate no effect of aspartame loading in glutamate-susceptible subjects.

    Title Plasma Phenylalanine Levels in Phenylketonuric Heterozygous and Normal Adults Administered Aspartame at 34 Mg/kg Body Weight.
    Date October 1981
    Journal Toxicology
    Excerpt

    Following administration of aspartame (34 mg/kg body wt) in orange juice, plasma concentrations of free amino acids were measured in 12 female subjects known to be heterozygous for phenylketonuria and 22 normal subjects (12 male, 10 female). No change in fasting plasma aspartate concentrations were noted after aspartame loading in either group. In normal male subjects, the mean (+/-S.D.) plasma phenylalanine concentration increased from a fasting value of 5.86 +/- 1.25 mumol/dl. Plasma phenylalanine levels in normal female subjects increased from a mean fasting concentration of 4.83 +/- 0.84 mumol/dl to a men peak value of 8.95 +/- 1.49 mumol/dl suggesting a more rapid absorption, metabolism, and/or clearance of phenylalanine by females. In female heterozygous subjects, the mean peak plasma phenylalanine concentration was significantly higher than in normal females. Plasma phenylalanine values increased from a mean fasting value of 5.92 +/- 1.51 mumol/dl to a mean peak value of 15.1 +/- 4.76 mumol/dl. Similarly, the area under the plasma phenylalanine concentration-time curve was significantly greater in heterozygous female subjects (21.36 +/- 5.10 IU) than in normal female subjects (10.84 +/- 2.32 IU). However, peak plasma phenylalanine levels were well below those associated with toxic effects in all cases.

    Title Blood Methanol Concentrations in Normal Adult Subjects Administered Abuse Doses of Aspartame.
    Date July 1981
    Journal Journal of Toxicology and Environmental Health
    Excerpt

    Blood methanol concentrations were measured in 30 normal adult subjects administered aspartame, a dipeptide methyl ester. The doses studied included the 99th percentile of projected daily ingestion (34 mg/kg body weight) and three doses considered to be in the abuse range (100, 150, and 200 mg/kg body weight). Methanol concentrations were below the level of detection (0.4 mg/dl) in the blood of the 12 normal subjects who ingested aspartame at 34 mg/kg. They were significantly elevated (p less than or equal to 0 .001) after ingestion of each abuse dose, with the mean peak blood methanol concentrations and the areas under the blood methanol concentration-time curve increasing in proportion to dose. Mean (+/- SD) peak blood methanol concentrations were 1.27 +/- 0.48 mg/dl at the 100 mg/kg dose, 2.14 +/- 0.35 mg/dl at the 150 mg/kg dose, and 2.58 +/- 0.78 mg/dl at the 200 mg/kg dose. Blood methanol concentrations returned to predosing levels by 8 h after administration of the 100 mg/kg dose. Methanol was still detected in the blood 8 h after the subjects had ingested aspartame at 150 or 200 mg/kg. Blood formate analyses were carried out in the 6 subjects who ingested aspartame at 200 mg/kg, since recent studies indicate that the toxic effects of methanol are due to formate accumulation. No significant increase in blood formate concentrations over predosing concentrations was noted. No changes were noted in any of the blood chemistry profile parameters measured 24 h after aspartame ingestion, compared to values noted before administration. Similarly, no differences were noted in ophthalmologic examinations carried out before and after aspartame loading.

    Title Plasma and Erythrocyte Concentrations of Free Amino Acids in Adult Humans Administered Abuse Doses of Aspartame.
    Date July 1981
    Journal Journal of Toxicology and Environmental Health
    Excerpt

    Plasma and erythrocyte concentrations of amino acids were measured in 18 fasting adult subjects (9 male, 9 female) administered abuse doses of aspartame (100, 150, and 200 mg/kg body weight) dissolved in 500 ml orange juice. Six subjects were studied at each dose. Plasma aspartate concentrations increased significantly (p less than or equal to 0.05) over baseline values after ingestion of each dose. However, the increase was small in each case, and maximal levels observed were below those noted postprandially in formula-fed infants. No significant changes (p greater than 0.05) were noted in erythrocyte glutamate, or erythrocyte aspartate concentrations after any dose. Plasma phenylalanine concentrations increased significantly over fasting concentrations (p less than 0.01) from 15 min to 6 h after each dose, and the increase was proportional to dose. Mean (+/- SD) peak plasma phenylalanine concentrations were 20.3 +/- 2.03, 35.1 +/- 11.3, and 48.7 +/- 15.5 mumol/dl, respectively, after aspartame doses of 100, 150, and 200 mg/kg. Erythrocyte phenylalanine concentrations showed similar changes. Although these phenylalanine concentrations are considerably above the normal postprandial range (12 +/- 3 mumol/dl), they are below values associated with toxic findings. These data indicate little risk to normal subjects from excessive aspartate or phenylalanine levels after ingestion of single abuse loads of aspartame.

    Title Effect of an Abuse Dose of Aspartame Upon Plasma and Erythrocyte Levels of Amino Acids in Phenylketonuric Heterozygous and Normal Adults.
    Date January 1981
    Journal The Journal of Nutrition
    Excerpt

    Plasma and erythrocyte levels of free amino acids were measured in five female subjects known to be heterozygous for phenylketonuria and six subjects assumed to be normal (three male, three female) who were administered an abuse dose of aspartame (100 mg/kg) in orange juice. Small increases in plasma aspartate levels were noted 30 minutes after aspartame loading in both groups, with mean (+/- SD) levels increasing from 0.15 +/- 0.05 mumoles/100 ml to 0.43 +/- 0.23 mumoles/100 ml in normal subjects (P = 0.02), and from 0.49 +/- 0.23 mumoles/100 ml to 0.80 +/- 0.56 mumoles/100 ml in heterozygous subjects (P > 0.05). However, plasma aspartate levels remained within normal postprandial levels in each case. Erythrocyte aspartate levels were unchanged in both groups. In normal subjects, plasma phenylalanine levels (mean +/- SD) increased from fasting levels (5.40 +/- 1.05 mumoles/100 ml) to mean peak values of 20.2 +/- 6.77 mumoles/100 ml. In heterozygous subjects, mean peak plasma phenylalanine levels were approximately twice as high (41.7 +/- 2.33 mumoles/100 ml), and the area under the plasma concentration-time curve twice as large. Peak plasma phenylalanine levels, however, were below those associated with toxic effects. The data indicate slower, but adequate metabolism and clearance of an abuse dose of aspartame by the phenylketonuric heterozygote.

    Title The Medical Curriculum--from the 70's into the 80's.
    Date July 1980
    Journal Journal of the Iowa Medical Society
    Title Plasma and Erythrocyte Amino Acid Levels of Adult Humans Given 100 Mg/kg Body Weight Aspartame.
    Date May 1980
    Journal Toxicology
    Title Plasma Methionine Levels in Normal Adult Subjects After Oral Loading with L-methionine and N-acetyl-l-methionine.
    Date April 1980
    Journal The Journal of Nutrition
    Excerpt

    The biological quality of soy protein isolates is limited by methionine content but can be enhanced by methionine addition. Since supplemental methionine may undergo chemical modification during processing, producing objectionable odors, N-acetyl-L-methionine has been proposed as a methionine replacement. Plasma and erythrocyte methionine levels and the area under the plasma and erythrocyte methionine absorption curve were compared in five normal adult subjects administered equimolar quantities (0.0605 mmoles/kg) of L-methionine and N-acetyl-L-methionine. The two compounds produced an equivalent overall release of L-methionine to the blood as judged by the area under the plasma and erythrocyte methionine time-absorption curves. There was a difference in the early part of both absorption curves (15 to 45 minutes), with plasma and erythrocyte levels higher after L-methionine administration than after N-acetyl-L-methionine administration. However, this difference was only statistically significant at 15 minutes (P = 0.03). Gastric emptying did not account for this difference apparently reflecting a slower rate of absorption of N-acetyl-L-methionine by mucosal cells. No evidence was obtained that indicated release of N-acetyl-L-methionine to the plasma or its excretion in urine after loading. The data are consistent with previous data showing L-methionine and N-acetyl-L-methionine to be equivalent sources of methionine.

    Title Plasma, Erythrocyte and Human Milk Levels of Free Amino Acids in Lactating Women Administered Aspartame or Lactose.
    Date February 1980
    Journal The Journal of Nutrition
    Title Assessing the Moral Development of Medical Students: an Empirical Study.
    Date December 1979
    Journal Annual Conference on Research in Medical Education. Conference on Research in Medical Education
    Title Bacteremia and Meningitis Following Fiberoptic Bronchoscopy.
    Date July 1979
    Journal Archives of Internal Medicine
    Excerpt

    Bacteremia and meningitis due to Streptococcus pneumoniae developed in a 52-year-old man 28 hours after an otherwise uncomplicated fiberoptic bronchoscopy. The patient responded to antimicrobial therapy and supportive care and later underwent pneumonectomy for carcinoma. This report reinforces previous observations that bacteremia may occasionally be associated with the performance of fiberoptic bronchoscopy.

    Title Effect of Aspartame Loading Upon Plasma and Erythrocyte Amino Acid Levels in Phenylketonuric Heterozygotes and Normal Adult Subjects.
    Date June 1979
    Journal The Journal of Nutrition
    Title Admissions Matters.
    Date November 1978
    Journal Journal of the Iowa Medical Society
    Title Effect of Aspartame and Aspartate Loading Upon Plasma and Erythrocyte Free Amino Acid Levels in Normal Adult Volunteers.
    Date November 1977
    Journal The Journal of Nutrition
    Excerpt

    Aspartame is a dipeptide (L-aspartyl-L-phenylalanyl-methyl ester) with a sweeting potential 180 to 200 times that of sucrose. Questions have been raised about potential toxic effects of its constituent amino acids, aspartate and phenylalanine when the compound is ingested in large amounts. Plasma and erythrocyte amino acid levels were measured in 12 normal subjects after administration of either Aspartame (34 mg/kg) or equimolar quantities of aspartate (13 mg/kg) in a crossover design. No changes in either plasma or erythrocyte aspartate levels were noted at any time after either Aspartame or aspartate ingestion. Plasma phenylalanine levels decrease slightly after aspartate loading, and increased from fasting levels (4.9 +/- 1 mumoles/100 ml) to 10.7 +/- 1.9 mumoles/100 ml about 45 to 60 minutes after Aspartame loading. Phenylalanine levels returned to baseline by 4 hours. Erythrocyte phenylalanine levels showed similar changes.

    Title Largest Ever Graduating Class.
    Date May 1977
    Journal Journal of the Iowa Medical Society
    Title Automatic Systems for Monitoring Vinyl Chloride in Working Atmospheres.
    Date April 1977
    Journal American Industrial Hygiene Association Journal
    Excerpt

    During the past two years, Union Carbide Corporation (UCC) has developed completely automatic systems for monitoring 0-25 ppm vinyl chloride monomer (VCM) in working atmospheres and for processing the data obtained. Each system includes a process gas chromatograph, a sampling system capable of monitoring up to 19 points and data processing equipment. The data systems compute and print out statistical summaries on shift, daily and monthly bases and estimate the maximum exposure to VCM for each job. These systems are now essential operating tools at several UCC production units.

    Title Outcome at Ages 1, 3, and 5 Years of Children Born to Diabetic Women.
    Date March 1977
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    A prospective study of infants born to women with diabetes mellitus is reported. The children were examined at birth and followed at 1, 3, and 5 years of age. Medical and psychological information was obtained through follow-up examinations. Intrauterine growth was atypical and there was an increase in neonatal problems and congenital malformations. There was an increased incidence of intellectual delay at 3 and 5 years of age. The presence of acetone in the urine during pregnancy had a significant, adverse effect on intellectual status of the offspring at 5 years of age. Birth weight was negatively related to intellectual status at both 3 and 5 years of age.

    Title Optical Rotation and the Dna Helix-to-coil Transition. An Undergraduate Project.
    Date December 1974
    Journal Journal of Chemical Education
    Title College-wide Development of Educational Objectives for a Medical Curriculum.
    Date September 1974
    Journal Journal of Medical Education
    Title Monosodium Glutamate Metabolism in the Neonatal Pig: Effect of Load on Plasma, Brain, Muscle and Spinal Fluid Free Amino Acid Levels.
    Date September 1973
    Journal The Journal of Nutrition
    Title Iowa's Medical Curriculum--1973.
    Date May 1973
    Journal Journal of the Iowa Medical Society
    Title Monosodium Glutamate: Effect of Plasma and Breast Milk Amino Acid Levels in Lactating Women.
    Date August 1972
    Journal Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (new York, N.y.)
    Title Infusion of Protein Hydrolysates in the Newborn Infant: Plasma Amino Acid Concentrations.
    Date April 1971
    Journal The Journal of Pediatrics
    Title Serum Amino Acid Levels of Northern Alaskan Eskimo Infants and Children.
    Date January 1971
    Journal The American Journal of Clinical Nutrition
    Title Care of the Low Birth Weight Infant.
    Date November 1970
    Journal Journal of the Iowa Medical Society
    Title Effect of Diet on Fatty Acid Composition of Miniature Swine Adipose Tissue Lipids.
    Date October 1970
    Journal The American Journal of Clinical Nutrition
    Title Design and Operation of a Van for the Transport of Sick Infants.
    Date December 1969
    Journal American Journal of Diseases of Children (1960)
    Title Management of Neonatal Bacterial Infections. Rx: Continual Alertness, Specific Treatment, and Ampicillin with Kanamycin Until the Culture Reports Are Back.
    Date December 1969
    Journal Clinical Pediatrics
    Title Human Adipose Tissue Composition and Age.
    Date September 1969
    Journal The American Journal of Clinical Nutrition
    Title Nutritional Survey of Northern Eskimo Infants and Children.
    Date July 1969
    Journal The American Journal of Clinical Nutrition
    Title Picosecond Dynamics of Photogenerated Charged Solitons in Trans-polyacetylene.
    Date
    Journal Physical Review. B, Condensed Matter
    Title Influence of Disorder on the Field-modulated Spectra of Polydiacetylene Films.
    Date
    Journal Physical Review. B, Condensed Matter
    Title Interchain Dynamics and Side-group Modulation of Excitons in a Polydiacetylene.
    Date
    Journal Physical Review. B, Condensed Matter
    Title Resonant-raman-scattering Studies of Disorder in Solution-cast Polydiacetylene Films.
    Date
    Journal Physical Review. B, Condensed Matter
    Title Resonant Raman-scattering Spectroscopy of Polydiacetylene Films at High Pressure.
    Date
    Journal Physical Review. B, Condensed Matter
    Title Charged-soliton Dynamics in Trans-polyacetylene.
    Date
    Journal Physical Review Letters
    Title Soliton Pinning in Polyacetylene Revealed by Multiple-quantum Spin Coherences.
    Date
    Journal Physical Review Letters
    Title Spectrum of Chi (3)(-3 Omega; Omega, Omega, Omega ) in Polyacetylene: An Application of Free-electron Laser in Nonlinear Optical Spectroscopy.
    Date
    Journal Physical Review Letters
    Title Excitonic and Phonon-mediated Optical Stark Effects in a Conjugated Polymer.
    Date
    Journal Physical Review Letters
    Title Femtosecond Dynamics of Photogenerated Solitons and Polarons in Trans-polyacetylene.
    Date
    Journal Physical Review Letters
    Title High-pressure Effects on Ultrafast-relaxation Kinetics of Excitons in Polydiacetylene 4bcmu.
    Date
    Journal Physical Review Letters
    Title Controlled Synthesis of Cross-linked Ultrathin Polymer Films by Using Surface-initiated Atom Transfer Radical Polymerization We Thank the Nsf Center for Sensor Materials at Michigan State University for Financial Support.
    Date
    Journal Angewandte Chemie (international Ed. in English)
    Title Synthesis and Properties of Aba Amphiphiles.
    Date
    Journal The Journal of Organic Chemistry
    Title Inverting Chaos: Extracting System Parameters from Experimental Data.
    Date
    Journal Chaos (woodbury, N.y.)
    Excerpt

    Given a set of experimental or numerical chaotic data and a set of model differential equations with several parameters, is it possible to determine the numerical values for these parameters using a least-squares approach, and thereby to test the model against the data? We explore this question (a) with simulated data from model equations for the Rossler, Lorenz, and pendulum attractors, and (b) with experimental data produced by a physical chaotic pendulum. For the systems considered in this paper, the least-squares approach provides values of model parameters that agree well with values obtained in other ways, even in the presence of modest amounts of added noise. For experimental data, the "fitted" and experimental attractors are found to have the same correlation dimension and the same positive Lyapunov exponent. (c) 1996 American Institute of Physics.

    Title Fatty Acid Methyl Esters in Grasshopper Eggs.
    Date
    Journal Lipids

    Similar doctors nearby

    Dr. Charles Watson

    Otolaryngology
    41 years experience
    Ashland, KY

    Dr. William Van Beneden

    Otolaryngology
    6 years experience
    Ashland, KY

    Dr. Stephen Wolfe

    Otolaryngology
    39 years experience
    Huntington, WV

    Dr. Thomas Jung

    Otolaryngology
    20 years experience
    Huntington, WV

    Dr. Mark Sheridan

    Otolaryngology
    23 years experience
    Huntington, WV

    Dr. Phillip Stevens

    Otolaryngology
    27 years experience
    Huntington, WV
    Search All Similar Doctors