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1.
Resuscitation ; 118: 82-88, 2017 09.
Article in English | MEDLINE | ID: mdl-28689046

ABSTRACT

BACKGROUND: The PARAMEDIC cluster randomised trial evaluated the LUCAS mechanical chest compression device, and did not find evidence that use of mechanical chest compression led to an improvement in survival at 30 days. This paper reports patient outcomes from admission to hospital to 12 months after randomisation. METHODS: Information about hospital length of stay and intensive care management was obtained through linkage with Hospital Episode Statistics and the Intensive Care National Audit and Research Centre. Patients surviving to hospital discharge were approached to complete questionnaires (SF-12v2, EQ-5D, MMSE, HADS and PTSD-CL) at 90days and 12 months. The study is registered with Current Controlled Trials, number ISRCTN08233942. RESULTS: 377 patients in the LUCAS arm and 658 patients in the manual chest compression were admitted to hospital. Hospital and intensive care length of stay were similar. Long term follow-up assessments were limited by poor response rates (53.7% at 3 months and 55.6% at 12 months). Follow-up rates were lower in those with worse neurological function. Among respondents, long term health related quality of life outcomes and emotional well-being was similar between groups. Cognitive function, measured by MMSE, was marginally lower in the LUCAS arm mean 26.9 (SD 3.7) compared to control mean 28.0 (SD 2.3), adjusted mean difference -1.5 (95% CI -2.6 to -0.4). CONCLUSION: There were no clinically important differences identified in outcomes at long term follow-up between those allocated to the mechanical chest compression compared to those receiving manual chest compression.


Subject(s)
Cardiopulmonary Resuscitation/methods , Heart Massage/methods , Out-of-Hospital Cardiac Arrest/therapy , Patient Reported Outcome Measures , Quality of Life , Cardiopulmonary Resuscitation/instrumentation , Case-Control Studies , Heart Massage/instrumentation , Humans , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Odds Ratio , Out-of-Hospital Cardiac Arrest/mortality , Prospective Studies , Surveys and Questionnaires , Survivors/statistics & numerical data
2.
J Vet Intern Med ; 30(6): 1882-1886, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27731908

ABSTRACT

BACKGROUND: Infection control is critical to providing high-quality patient care. Many veterinary teaching hospitals (VTHs) utilize footbaths or footmats at entrances and key control points throughout the facility to decrease trafficking of pathogenic microorganism on contaminated footwear. HYPOTHESIS/OBJECTIVES: To compare efficacy of 4 disinfectants used in footmats for decreasing bacterial contamination of footwear in a large animal hospital. ANIMALS: A single adult dairy cow was housed in a stall for 4 days to facilitate stall contamination with fecal material. METHODS: Overboots were experimentally contaminated with organic material in a standardized manner. Each boot was randomly assigned to 1 of 5 treatments (no treatment, or exposure to 1 of 4 disinfectants: an accelerated peroxygen [AHP], a peroxygen [VIRKON], a quaternary ammonium [QUAT], and a phenolic disinfectant [PHENOLIC]) by stepping on a soaked footmat and collecting samples from boot soles. Generalized linear modeling was used to analyze differences in bacterial counts. RESULTS: Reductions in colony-forming units (CFUs) on treated boots ranged from no detectable reduction to 0.45 log10 and varied by disinfectant. Percentage reductions in total bacterial counts generally were larger (albeit still modest) for AHP and QUAT disinfectants (range 37-45%) and smallest for the PHENOLIC (no detectable reduction). CONCLUSIONS AND CLINICAL IMPORTANCE: In general, use of disinfectant footmats was associated with significant reductions in viable bacteria on overboots-albeit with variable efficacy. Footmats may be useful adjuncts to cleaning and disinfection programs for decreasing trafficking of microorganisms throughout VTHs but should not be considered as a sole prevention method.


Subject(s)
Bacteria/isolation & purification , Colony Count, Microbial/veterinary , Disinfectants , Floors and Floorcoverings , Hospitals, Animal , Animals , Cattle/microbiology , Feces/microbiology , Female , Humans , Infection Control/methods , Peroxides , Phenols , Quaternary Ammonium Compounds , Shoes
3.
Equine Vet J ; 48(4): 485-9, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26101083

ABSTRACT

REASONS FOR PERFORMING STUDY: Effective decontamination of animal holding environments is critical for providing high quality patient care and maintaining a safe working environment. Disinfection of animal holding environments is a significant challenge during times of epidemic disease. OBJECTIVES: The purpose of this study was to evaluate the disinfectant efficacy of 3 strategies for high-volume directed mist application of accelerated hydrogen peroxide and peroxymonosulfate disinfectants; 4.25% accelerated hydrogen peroxide (Accel(®) ; AHP) at a 1:16 dilution and single and double applications of 2% peroxymonosulfate solution (Virkon-S(®) ; VIR-1 and VIR-2) for decontamination of a large animal hospital environment. STUDY DESIGN: Experiment. METHODS: After cleaning and disinfection of the hospital environment, transparencies experimentally contaminated with known concentrations of Staphylococcus aureus, Salmonella enterica and Pseudomonas aeruginosa were placed on vertical surfaces. Disinfectant solution was applied by directed mist application and, after 30 min of contact time, transparencies were collected and individually placed into tubes containing 10 ml Dey-Engley broth. The process was repeated for each disinfectant. Tenfold dilutions of each sample were plated onto tryptic soy blood agar with 5% sheep blood. Bacterial counts from transparencies exposed to disinfectants were compared with counts from control transparencies (unexposed to disinfectants) to evaluate reduction in colony forming units. RESULTS: The least squares mean reduction (log10 ) in colony forming units (CFUs) for S. aureus and P. aeruginosa was 1.5-2.5 logs and approximately 0.8-1.0 logs for S. enterica. Reductions were generally largest for VIR-2 and smallest for AHP, although these differences were not all statistically significant and the magnitude of differences may not be clinically relevant. CONCLUSIONS: For the organisms evaluated, all 3 disinfectants applied as a directed mist were effective at reducing CFUs in a veterinary hospital environment. Effective disinfection using this method of application is dependent on adequate cleaning prior to application, and use of adequate volumes of disinfectant.


Subject(s)
Disinfectants/pharmacology , Hospitals, Animal/standards , Hydrogen Peroxide/pharmacology , Peroxides/pharmacology , Aerosols , Animals , Bacteria/drug effects , Colony Count, Microbial/veterinary , Environmental Microbiology , Horses , Infection Control/methods
4.
J Vet Intern Med ; 28(5): 1613-20, 2014.
Article in English | MEDLINE | ID: mdl-24965884

ABSTRACT

BACKGROUND: Persistent hyperglycemia is common in alpacas and typically requires insulin administration for resolution; however, little is known about alpacas' response to different insulin formulations. OBJECTIVES: To evaluate the effects of 3 insulin formulations on blood glucose concentrations and the use of a continuous glucose monitoring (CGM) system in alpacas. ANIMALS: Six healthy alpacas. METHODS: The CGM was installed in the left paralumbar fossa at the start of this crossover study and recorded data every 5 minutes. Regular insulin, NPH insulin, insulin glargine, and dextrose were administered to each alpaca over a 2-week period. Blood samples were collected for glucose testing at 0, 1, 2, 4, 6, 8, and 12 hours, and then every 6 hours after each administration of insulin or dextrose. Data were compared by using method comparison techniques, error grid plots, and ANOVA. RESULTS: Blood glucose concentrations decreased most rapidly after regular insulin administration when administered IV or SC as compared to the other formulations. The NPH insulin produced the longest suppression of blood glucose. The mean CGM interstitial compartment glucose concentrations were typically lower than the intravascular compartment glucose concentrations. The alpacas had no adverse reactions to the different insulin formulations. CONCLUSIONS AND CLINICAL IMPORTANCE: The NPH insulin might be more appropriate for long-term use in hyperglycemic alpacas because of its extended duration of action. A CGM is useful in monitoring glucose trends and reducing blood collection events, but it should not be the sole method for determining treatment protocols.


Subject(s)
Blood Glucose/analysis , Camelids, New World/blood , Insulin, Isophane/pharmacology , Insulin, Long-Acting/pharmacology , Insulin/pharmacology , Animals , Camelids, New World/metabolism , Insulin Glargine , Male , Monitoring, Physiologic/methods , Monitoring, Physiologic/veterinary
5.
J Vet Intern Med ; 27(4): 990-5, 2013.
Article in English | MEDLINE | ID: mdl-23734626

ABSTRACT

PURPOSE: Hospitalized alpacas are often hyperglycemic requiring frequent blood glucose testing. OBJECTIVES: To compare the performance of 4 brands of glucometers with a laboratory-based analyzer (LCA) over a range of glucose concentrations in alpacas. ANIMALS: Four healthy male alpacas. METHODS: A 2-treatment cross-over study was utilized. The alpacas were given 0.4 U/kg of regular insulin intravenously and then 500 mg/kg of dextrose intravenously with a 1 week washout period between treatments. Blood samples were collected from 10 minutes before until 6 hours after drug administration. Glucose concentrations were measured in whole blood and plasma samples on 4 glucometers, and serum glucose was measured on an LCA. RESULTS: Glucometer performance varied depending on whether glucose concentrations were measured in plasma or whole blood. Based on error grid analysis, the Precision Xtra and One Touch Ultra 2 glucometers were clinically acceptable for testing whole blood samples, whereas the Accu-Chek Aviva and Nova StatStrip Xpress glucometers were clinically acceptable for testing plasma samples in comparison with serum glucose concentrations determined by the LCA. All glucometers had systematic and proportional biases that varied based on sample type. CONCLUSIONS AND CLINICAL IMPORTANCE: Human-based glucometers in alpacas should be used cautiously, particularly at higher blood glucose concentrations. The blood sample type (plasma or whole blood) can alter meter performance when compared with serum glucose concentrations and potentially lead to errors in clinical decisions.


Subject(s)
Blood Glucose/physiology , Camelids, New World/blood , Point-of-Care Systems , Animals , Blood Glucose/drug effects , Cross-Over Studies , Glucose/pharmacology , Insulin/pharmacology , Male
6.
J Vet Intern Med ; 25(2): 380-5, 2011.
Article in English | MEDLINE | ID: mdl-21281346

ABSTRACT

BACKGROUND: Diaphragmatic paralysis is a relatively uncommon medical condition in animals not reported in alpacas. OBJECTIVES: Describe the signalment, physical examination, diagnostic testing, clinical, and histopathologic findings related to diaphragmatic paralysis in alpacas. ANIMALS: Eleven alpacas with spontaneous diaphragmatic paralysis. METHODS: A retrospective study examined medical records from a 10-year period and identified 11 alpacas with confirmed diaphragmatic paralysis admitted to Washington State University and Colorado State University Veterinary Teaching Hospitals between September 2003 and October 2009. RESULTS: The 11 alpacas ranged in age from 2 to 12 months. Fluoroscopic imaging confirmed the presence of bilateral diaphragmatic paralysis in the 7 alpacas that were imaged. Arterial blood gas analyses showed hypercapnea, hypoxemia, and low oxygen saturation. Seven alpacas died or were euthanized between 2 and 60 days after onset of respiratory signs. Histopathologic examination of tissues found phrenic nerve degeneration in the 6 alpacas that were necropsied and additional long nerves examined demonstrated degeneration in 2 of these animals. Two animals had spinal cord lesions and 2 had diaphragm muscle abnormalities. No etiologic agent was identified in the alpacas. CONCLUSIONS AND CLINICAL IMPORTANCE: The etiology for diaphragmatic paralysis in these alpacas is unknown. A variety of medical treatments did not appear to alter the outcome.


Subject(s)
Blood Gas Analysis/veterinary , Camelids, New World , Diaphragm/innervation , Diaphragm/physiopathology , Respiratory Paralysis/veterinary , Animals , Female , Male , Respiratory Paralysis/diagnosis , Respiratory Paralysis/mortality , Respiratory Paralysis/pathology , Retrospective Studies
7.
Oncogene ; 27(6): 755-62, 2008 Jan 31.
Article in English | MEDLINE | ID: mdl-17667944

ABSTRACT

Eukaryotic initiation factor 6 (eIF6), an essential protein important in ribosome biosynthesis and assembly, was identified as an interacting partner of the beta-catenin C terminus in the yeast two-hybrid assay. Independent studies identified Drosophila eIF6 (DeIF6) in a genetic screen designed to detect new genes involved in the regulation of the Wnt/Wg (wingless) pathway. Ectopic expression of DeIF6 in wing discs results in a Wg phenotype. Expression of eIF6 in adenomatous polyposis coli (APC)-mutant colon cancer cells, which express high levels of active beta-catenin, showed that eIF6 selectively inhibits the Wnt pathway at the level of beta-catenin protein independently of proteasomal degradation. Incorporation of radiolabeled amino acids into beta-catenin was selectively decreased in cells that overexpressed eIF6. A similar inverse relationship of the two proteins was observed in the APC(min/+) mouse intestine, in which beta-catenin levels are very high. Taken together these data reveal a link between eIF6 and Wnt signaling, perhaps at the level of ribosome recycling on beta-catenin mRNA.


Subject(s)
Peptide Initiation Factors/metabolism , Wnt Proteins/metabolism , beta Catenin/metabolism , Adenomatous Polyposis Coli Protein/genetics , Amino Acids/metabolism , Animals , Drosophila/growth & development , Drosophila/metabolism , Drosophila Proteins/metabolism , Intestinal Mucosa/metabolism , Mice , Mice, Mutant Strains , Peptide Initiation Factors/analysis , Protein Biosynthesis , Protein Structure, Tertiary , RNA, Messenger/metabolism , Signal Transduction , Wings, Animal/growth & development , Wnt Proteins/antagonists & inhibitors , beta Catenin/analysis , beta Catenin/genetics
8.
Cell Mol Life Sci ; 65(3): 395-413, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17965830

ABSTRACT

Hyaluronan (HA) is a large but simple glycosaminoglycan composed of repeating D-glucuronic acid, beta1-3 linked to N-acetyl-D-glucosamine beta1-4, found in body fluids and tissues, in both intra- and extracellular compartments. Despite its structural simplicity, HA has diverse functions in skeletal biology. In development, HA-rich matrices facilitate migration and condensation of mesenchymal cells, and HA participates in joint cavity formation and longitudinal bone growth. In adult cartilage, HA binding to aggrecan immobilises aggrecan, retaining it at the high concentrations required for compressive resilience. HA also appears to regulate bone remodelling by controlling osteoclast, osteoblast and osteocyte behaviour. The functions of HA depend on its intrinsic properties, which in turn rely on the degree of polymerisation by HA synthases, depolymerisation by hyaluronidases, and interactions with HA-binding proteins. HA synthesis and degradation are closely regulated in skeletal tissues and aberrant synthetic or degradative activity causes disease. The role and regulation of HA synthesis and degradation in cartilage, bone and skeletal development is discussed.


Subject(s)
Bone Development/physiology , Bone and Bones/metabolism , Cartilage/metabolism , Hyaluronic Acid/metabolism , Animals , Bone and Bones/cytology , Extracellular Matrix/chemistry , Glucuronosyltransferase/genetics , Glucuronosyltransferase/metabolism , Humans , Hyaluronan Receptors/metabolism , Hyaluronan Synthases , Morphogenesis , Synovial Membrane/metabolism , Tissue Distribution
9.
J Orthop Res ; 23(6): 1336-44, 2005 Nov.
Article in English | MEDLINE | ID: mdl-15946820

ABSTRACT

Injuries to the growth plate in children can result in bone bridge formation, which ultimately lead to limb length and angular deformities. The histological and molecular changes associated with growth plate repair following the Langenskiöld procedure, a surgical technique used to remove impeding bone bridges, in conjunction with administration of recombinant human osteogenic protein-1 (rhOP-1) were examined using a sheep model. Following treatment with rhOP-1 there was an increase in the height of the growth plate immediately adjacent to the defect compared to untreated animals. The expression of type I collagen, osteopontin and decorin were observed in the growth plate adjacent to the defect in the untreated animals at day 56, but this response was accelerated in the rhOP-1 treated animals, with these molecules seen as early as day 7. Therefore, treatment with rhOP-1 initiated a complex response that was both chondrogenic and osteogenic in nature.


Subject(s)
Bone Morphogenetic Proteins/pharmacology , Growth Plate/drug effects , Salter-Harris Fractures , Transforming Growth Factor beta/pharmacology , Animals , Bone Morphogenetic Protein 7 , Chondrogenesis/drug effects , Collagen Type I/analysis , Decorin , Extracellular Matrix Proteins , Extremities/growth & development , Growth Plate/pathology , Growth Plate/surgery , Immunohistochemistry , Models, Animal , Osteogenesis/drug effects , Osteopontin , Proteoglycans/analysis , Recombinant Proteins/pharmacology , Sheep , Sialoglycoproteins/analysis
10.
Cancer Res ; 61(21): 7978-84, 2001 Nov 01.
Article in English | MEDLINE | ID: mdl-11691822

ABSTRACT

A second adenomatous polyposis coli (APC)-like gene, APC2/APCL, was recently described and localized to chromosome 19. We have fine mapped APC2 to a small region of chromosome 19p13.3 containing markers D19S883 and WI-19632, a region commonly lost in a variety of cancers, particularly ovarian cancer. Interphase fluorescence in situ hybridization analysis revealed an APC2 allelic imbalance in 19 of 20 ovarian cancers screened and indicates that APC2 could be a potential tumor suppressor gene in ovarian cancer. When overexpressed in SKOV3 ovarian cancer cells, which express low levels of APC2, exogenous APC2 localized to the Golgi apparatus, actin-containing structures, and occasionally to microtubules. Antibodies against the NH2 terminus of human APC2 show that endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. APC2 remained associated with actin filaments after treatment with the actin-disrupting agent, cytochalasin D. These results suggest that APC2 is involved in actin-associated events and could influence cell motility or adhesion through interaction with actin filaments, as well as functioning independently or in cooperation with APC to down-regulate beta-catenin signaling.


Subject(s)
Allelic Imbalance , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , Actin Cytoskeleton/metabolism , Animals , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Chromosomes, Human, Pair 19/genetics , Cytoskeletal Proteins/biosynthesis , Dogs , Female , Gene Expression , Genes, APC , Genes, Tumor Suppressor , Golgi Apparatus/metabolism , Humans , In Situ Hybridization, Fluorescence , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Radiation Hybrid Mapping , Transfection , Tumor Cells, Cultured
11.
J Biol Chem ; 276(45): 42276-86, 2001 Nov 09.
Article in English | MEDLINE | ID: mdl-11527961

ABSTRACT

Both the beta-catenin and the nuclear factor kappaB (NF-kappaB) proteins are important regulators of gene expression and cellular proliferation. Two kinases, IKKalpha and IKKbeta, are critical activators of the NF-kappaB pathway. Here we present evidence that these kinases are also important in the regulation of beta-catenin function. IKKalpha- and IKKbeta-deficient mouse embryo fibroblasts exhibited different patterns of beta-catenin cellular localization. IKKbeta decreases beta-catenin-dependent transcriptional activation, while IKKalpha increases beta-catenin-dependent transcriptional activity. IKKalpha and IKKbeta interact with and phosphorylate beta-catenin using both in vitro and in vivo assays. Our results suggest that differential interactions of beta-catenin with IKKalpha and IKKbeta may in part be responsible for regulating beta-catenin protein levels and cellular localization and integrating signaling events between the NF-kappaB and Wingless pathways.


Subject(s)
Cytoskeletal Proteins/physiology , Protein Serine-Threonine Kinases/physiology , Trans-Activators , Animals , COS Cells , Cytoskeletal Proteins/analysis , I-kappa B Kinase , Mice , NF-kappa B/physiology , Phosphorylation , Transcriptional Activation , Tumor Necrosis Factor-alpha/pharmacology , beta Catenin
12.
Bone ; 27(4): 495-501, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11033444

ABSTRACT

Longitudinal bone growth occurs via the transformation of growth plate cartilage into bone through a series of cell and matrix changes, termed endochondral ossification. In this study, we characterize the development of trabecular bone from growth plate cartilage in the human rib from birth to adolescence. The height of the proliferative and hypertrophic zones within the growth plate and the primary bone spongiosa decreased with increasing age, with the greatest change observed in the first year of postnatal life. Within these zones, an internal rearrangement of tissue structure occurred. The matrix volume fraction (either cartilage or bone) increased with age in each of the zones. A concomitant increase in cartilage septae thickness and bone trabecular thickness was observed. A decrease in cartilage septae number was seen in the proliferative zone and a decrease in bone trabeculae number was also observed in the primary spongiosa. However, no difference in cartilage septae number was noted in the hypertrophic zone, the region at which cartilage is transformed into bone. Together the proliferative and hypertrophic regions of the growth plate and the bone primary spongiosa appear to constitute the active growth region, with concomitant changes observed that result in longitudinal growth. In contrast, bone mineral volume in the secondary spongiosa was stable over the ages examined; however, trabecular architecture underwent consolidation as trabecular number decreased and trabecular thickness increased. The integration of the structural transformation from cartilage to bone is crucial in achieving the dual purposes of longitudinal growth and peak bone mass. The structure developed during childhood will have an important bearing on the response to bone-altering disease in later life.


Subject(s)
Aging/physiology , Growth Plate/anatomy & histology , Adolescent , Anthropometry , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male
13.
Cancer Res ; 60(17): 4709-13, 2000 Sep 01.
Article in English | MEDLINE | ID: mdl-10987273

ABSTRACT

beta-Catenin is a multifunctional molecule with important roles in intercellular adhesion and signal transduction. We reported previously that beta-catenin is mutated in human prostate cancer. In this study, we investigated the role of beta-catenin mutations on androgen receptor (AR) signaling. beta-Catenin significantly enhanced androgen-stimulated transcriptional activation by the AR. beta-Catenin also increased AR transcriptional activation by androstenedione and estradiol and diminished the antagonism of bicalutamide. Coimmunoprecipitation of beta-catenin with AR from LNCaP prostate cancer cells showed that the two molecules are present in the same complex. The amount of beta-catenin in complex with AR was increased by androgen. These findings implicate beta-catenin in the regulation of AR function and support a role for beta-catenin mutations in the pathogenesis of prostate cancer.


Subject(s)
Cytoskeletal Proteins/physiology , Receptors, Androgen/physiology , Trans-Activators , Transcriptional Activation/physiology , Androgen Antagonists/pharmacology , Androgens/physiology , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , Humans , Ligands , Male , Mutation , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Substrate Specificity , Tumor Cells, Cultured , beta Catenin
14.
J Orthop Sci ; 5(3): 294-301, 2000.
Article in English | MEDLINE | ID: mdl-10982672

ABSTRACT

Using laser confocal microscopy and 5-chloromethyl-fluoresceindiacetate (CMFDA) loading of chondrocytes we have investigated the structure of the ovine physis during late fetal development and its relationship to the structure observed in the primary spongiosa. Chondrocytes within the ovine growth plate form nests that together span the growth plate. We propose that all growth plates may be composed of nests of cells, but that the length of the individual nests changes between growth plates and with gestational age. The continuous column of cells seen within some growth plates is a nest of cells that is in the process of being absorbed by the invading metaphyseal front. Scanning electron microscopy of the mineralized portion of the primary spongiosa revealed structures that were consistent with the hypothesis that the cartilage surrounding the nest structure gives rise to the structure in the primary spongiosa. Although mineralization does not occur between cells within a nest, bands of mineral form between nests in the lower hypertrophic region and around the end of the nest as it reaches the hypertrophic region. This pattern of mineralization around and between nest termini yields the complex three-dimensional network of mineralized trabeculae observed in the primary spongosia.


Subject(s)
Bone Development/physiology , Cartilage, Articular/anatomy & histology , Chondrocytes/ultrastructure , Epiphyses/anatomy & histology , Osteogenesis/physiology , Animals , Female , Fetus , Fluoresceins , Fluorescent Dyes , Microscopy, Confocal , Microscopy, Electron, Scanning , Pregnancy , Sheep
15.
Stat Med ; 19(17-18): 2243-9, 2000.
Article in English | MEDLINE | ID: mdl-10960850

ABSTRACT

This paper describes a method for estimating the risk from a disease over a set of contiguous geographical regions, when data on a potentially important covariate, such as race, are not available. Conditions under which the extra margin can be recovered are suggested. An application to prostate cancer mortality among the non-white population in the counties of the U.S.A. is discussed.


Subject(s)
Epidemiologic Methods , Models, Statistical , Prostatic Neoplasms/epidemiology , Age Factors , Humans , Incidence , Male , Poisson Distribution , Prostatic Neoplasms/ethnology , Risk Assessment , Risk Factors , United States/epidemiology
16.
Biol Reprod ; 63(3): 913-24, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10952939

ABSTRACT

Proteoglycans (PGs) consist of a core protein and attached glycosaminoglycans (GAGs) and have diverse roles in cell and tissue biology. In follicles PGs have been detected only in follicular fluid and in cultured granulosa cells, and the composition of their GAGs has been determined. To identify PGs in whole ovarian follicles, not just in follicular fluid and granulosa cells, small (1-3-mm) bovine follicles were harvested. A proportion of these was incubated with (35)SO(4) for 24 h to incorporate radiolabel into the GAGs. The freshly harvested and cultured follicles were sequentially extracted with 6 M urea buffer, the same buffer with 0.1% Triton X-100 and then with 0.1 M NaOH. Proteoglycans were subjected to ion-exchange and size-exclusion chromatography. The GAGs were analyzed by chemical and enzymic digestion, and on the basis of their composition, we chose a list of known PGs to measure by ELISA analyses. Versican, perlecan, decorin, but not aggrecan or biglycan, were identified. These, excluding decorin for technical reasons, as well as a basal lamina glycoprotein, nidogen/entactin, were immunolocalized. Versican was localized to the thecal layers, including externa and the interna particularly in an area adjacent to the follicular basal lamina. Perlecan and nidogen were localized to the follicular basal lamina of antral follicles, both healthy and atretic, but not to that of preantral follicles. Both were localized to subendothelial basal laminas, but the former was not readily detected in arteriole smooth muscle layers. This study has confirmed the presence of versican and perlecan, but not the latter as a component of follicular fluid, and identified decorin and nidogen in ovarian antral follicles.


Subject(s)
Chondroitin Sulfate Proteoglycans/analysis , Heparan Sulfate Proteoglycans/analysis , Membrane Glycoproteins/analysis , Ovarian Follicle/chemistry , Proteoglycans/analysis , Animals , Cattle , Chromatography, Gel , Chromatography, Ion Exchange , Decorin , Extracellular Matrix Proteins , Female , Glycosaminoglycans/analysis , Glycosaminoglycans/metabolism , Immunohistochemistry , Lectins, C-Type , Versicans
17.
Pediatr Res ; 47(6): 743-9, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10832731

ABSTRACT

Enzyme replacement therapy (ERT) in the MPS VI cat is effective at reducing or eliminating pathology in most connective tissues. One exception is that cartilage and chondrocytes remained distended with extensive lysosomal vacuolation after long-term, high-dose ERT. In this study, we demonstrate that recombinant human N-acetylgalactosamine-4-sulphatase (4S) is taken up by chondrocytes via a mannose-6-phosphate-dependent mechanism and is effective at removing MPS storage. In vitro, the penetration of 4S into articular cartilage is low (partitioning coefficient = 0.06) and i.v. administered enzyme does not distribute significantly into articular cartilage in vivo. To alter the tissue distribution of 4S, the enzyme was coupled to ethylene diamine or poly-L-lysine, increasing its overall charge and diffusion into cartilage, and the dosing frequency of unmodified 4S was increased. Modification resulted in active 4S that maintained its ability to correct MPS storage and increased the partitioning coefficient of 4S into cartilage by 77% and 50% for ethylene diamine and poly-L-lysine, respectively. However, in vivo ERT studies demonstrated that response to therapy was not significantly improved by either the enzyme modifications or change to the dosing regimen, when compared with ERT with unmodified enzyme. Distribution experiments indicated the majority of enzyme is taken up by the liver irrespective of modification. To optimize therapy and improve the amount of enzyme reaching cartilage and other tissues demonstrating poor uptake, it may be necessary to bypass the liver or prolong plasma half-life so that proportionately more enzyme is delivered to other tissues.


Subject(s)
Disease Models, Animal , Mucopolysaccharidosis VI/drug therapy , N-Acetylgalactosamine-4-Sulfatase/therapeutic use , Animals , CHO Cells , Cats , Cricetinae , Drug Administration Schedule , Humans , N-Acetylgalactosamine-4-Sulfatase/administration & dosage , N-Acetylgalactosamine-4-Sulfatase/chemistry , Protein Conformation , Recombinant Proteins/administration & dosage , Recombinant Proteins/chemistry , Recombinant Proteins/therapeutic use
18.
Am J Phys Anthropol ; 111(2): 283-9, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10640952

ABSTRACT

This paper presents a look at the underused procedure of testing for Type II errors when "negative" results are encountered during research. It recommends setting a statistical alternative hypothesis based on anthropologically derived information and calculating the probability of committing this type of error. In this manner, the process is similar to that used for testing Type I errors, which is clarified by examples from the literature. It is hoped that researchers will use the information presented here as a means of attaching levels of probability to acceptance of null hypotheses.


Subject(s)
Anthropology, Physical , Mathematical Computing , Animals , Humans , Reproducibility of Results
19.
J Orthop Sci ; 5(6): 593-9, 2000.
Article in English | MEDLINE | ID: mdl-11180924

ABSTRACT

Our hypothesis is that physiological mineralization within the mammalian growth plate is a consequence of communication between cartilage chondrocytes and cells within metaphyseal bone. To test this hypothesis, chondrocytes were isolated from the proliferative region of the fetal ovine physis and co-cultured with cells or conditioned medium from cells characteristic of those in metaphyseal bone. The mineralization potential of chondrocytes alone and in the presence of other cells or conditioned medium was determined by 45calcium incorporation. Co-culture of chondrocytes with a crude cell isolate from metaphyseal bone resulted in a stimulation of 45calcium incorporation of 93% above that observed in the individual cell populations alone. Conditioned medium from metaphyseal bone cultures also stimulated 45calcium incorporation. This response to conditioned medium was dose-dependent and stable to 90 degrees C. Vascular endothelial cells and conditioned medium from chondrocyte and osteoblast cultures did not stimulate 45calcium incorporation by physeal chondrocytes. Thus, cells found in the metaphyseal bone produce a soluble factor, which promote calcium incorporation by physeal chondrocytes. The source of this factor is not chondrocytic, osteoblastic, or endothelial in origin.


Subject(s)
Calcification, Physiologic/physiology , Calcium/metabolism , Cell Culture Techniques , Chondrocytes/metabolism , Animals
20.
J Appl Toxicol ; 20 Suppl 1: S129-32, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11428623

ABSTRACT

An in vivo sulfur mustard (HD) vapor exposure model followed by bronchoalveolar lavage was developed previously in this laboratory to study biochemical indicators of HD-induced lung injury. This model was used to test two treatment compounds--niacinamide (NIA) and N-acetyl cysteine (NAC)--for their ability to ameliorate HD-induced biochemical changes. Anesthetized rats were intratracheally intubated and exposed to 0.35 mg of HD in 0.1 ml of ethanol or ethanol alone for 50 min. At the beginning of the exposure (t = 0), the rats were treated with either NIA (750 mg kg(-1)) or NAC (816 mg kg(-1)), i.p. At 24 h post-exposure, rats were euthanized and the lungs were lavaged with saline (three 5-ml washes). One milliliter of the recovered lavage fluid was analyzed for cellular components. The remaining fluid was centrifuged (10 min at 300 g) and the supernatant was assayed on a Cobas FARA clinical analyzer for lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), albumin (ALB), total protein (TP) and glutathione peroxidase (GP). The HD alone and HD+NIA treatment caused significant increases in all of the biochemical parameters compared with control levels. The NAC treatment yielded LDH, ALB and TP values that, although elevated, were not significantly different from the control. The GP levels were significantly higher than the control but significantly lower than the HD alone levels, indicating some protection compared with the HD alone group. The GGT levels were unaffected by NAC compared with HD alone. Cytological analysis of lavage fluid showed that the percentages of neutrophils were 5.3 +/- 1.0 (mean +/- SEM) for control, 46.6 +/- 4.5 for HD, 31.4 +/- 4.7 for HD + NIA and 21.6 +/- 4.7 for HD + NAC, respectively. The neutrophil counts were significantly higher for the three HD-exposed groups vs controls; however, the NAC-treated group had neutrophil counts lower than HD alone, indicating decreased inflammatory response. These results show that NAC may be useful as a potential treatment compound for HD-induced lung injury.


Subject(s)
Acetylcysteine/pharmacology , Dermatologic Agents/toxicity , Free Radical Scavengers/pharmacology , Lung Diseases/chemically induced , Lung/pathology , Mustard Gas/toxicity , Niacinamide/pharmacology , Acetylcysteine/administration & dosage , Animals , Bronchoalveolar Lavage , Free Radical Scavengers/administration & dosage , Lung/drug effects , Lung/immunology , Lung Diseases/drug therapy , Lung Diseases/prevention & control , Male , Neutrophils , Niacinamide/administration & dosage , Rats , gamma-Glutamyltransferase/analysis
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