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An automated method for measuring beta-hydroxybutyrate was adapted to the Ciba-Corning 550 Express trade mark random access analyzer. The assay was based on a kinetic reaction utilizing hydroxybutyrate-dehydrogenase. Beta-hydroxybutyrate concentration (mmol/L) was calculated ratiometrically using a 1.0 mmol/l standard. Canine serum, plasma, and urine were used without prior deproteinization and only a 30-microliter sample was required. The method demonstrated good linearity between 0 to 2 mmol/l of beta-hydroxybutyrate. Analytical recovery (accuracy) within these concentrations ranged from 85.8 to 113.3%. Both within-run and day-to-day precision were determined, as was specificity of the assay in the presence of a variety of interfering substances. The automated assay was rapid and economical, with reagent stability maintained for at least 2 weeks at 4 degrees C. This assay can readily be applied toward the assessment of ketoacidosis in dogs, and with further validation, other species.

Adaptation, Psychological, Adult, Chronic Disease, Factor Analysis, Statistical, Female, Humans, Male, Regression Analysis, Social Support, Socioeconomic Factors, Surveys and Questionnaires, Life Change Events, Pain psychology, and Quality of Life

Cognitive appraisal processes or the meaning a person gives a stressful event are believed to mediate an individual's reaction to an event and, as such, have been demonstrated to explain adjustment to illness. The purpose of this paper is to test this cognitive as well as other social and illness variables to explain the variance in a person's adjustment to chronic pain. Two hundred and twenty-two patients, who were randomly selected from an original sample of referrals to a chronic pain specialty clinic, completed a questionnaire by telephone interview or mail. The questionnaire consisted of psychosocial scales (PAIS-SR; Social Support) and cognitions including the Meaning of Illness Questionnaire (MIQ). Fifty-six percent of the sample had poor psychosocial adjustment to their pain problem. Seventy percent of the variance in adjustment was explained by social and cognitive variables which corroborates their importance. The MIQ 5-factor structure was supported and provides credible evidence of the role of cognitions in differentiating between the poor and well adjusted.

Adolescent, Adult, Age of Onset, Alleles, Child, Disease Progression, Female, Haplotypes genetics, Heterozygote, Humans, Male, Middle Aged, Molecular Sequence Data, Multiple Sclerosis pathology, Phenotype, Polymorphism, Single Nucleotide genetics, Probability, Survival Analysis, Apolipoproteins E genetics, Genetic Predisposition to Disease, Multiple Sclerosis genetics, Multiple Sclerosis physiopathology, and Polymorphism, Genetic genetics

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, with a complex etiology that includes a strong genetic component. The contribution of the major histocompatibility complex (MHC) has been established in numerous genetic linkage and association studies. In addition to the MHC, the chromosome 19q13 region surrounding the apolipoprotein E (APOE) gene has shown consistent evidence of involvement in MS when family-based analyses were conducted. Furthermore, several clinical reports have suggested that the APOE-4 allele may be associated with more-severe disease and faster progression of disability. To thoroughly examine the role of APOE in MS, we genotyped its functional alleles, as well as seven single-nucleotide polymorphisms (SNPs) located primarily within 13 kb of APOE, in a data set of 398 families. Using family-based association analysis, we found statistically significant evidence that an SNP haplotype near APOE is associated with MS susceptibility (P=.005). An analysis of disease progression in 614 patients with MS from 379 families indicated that APOE-4 carriers are more likely to be affected with severe disease (P=.03), whereas a higher proportion of APOE-2 carriers exhibit a mild disease course (P=.02).

Animals, Carcinogens, Environmental toxicity, Environmental Monitoring, Gasoline toxicity, Mollusca, Petroleum toxicity, and Polycyclic Aromatic Hydrocarbons toxicity

Fish and shellfish are exposed to a wide range of polycyclic aromatic hydrocarbons (PAH) following oil spills at sea, and can become contaminated as a result. Finfish have a more effective mixed-function oxidase enzyme system than shellfish, and are therefore able to metabolise and excrete PAH more effectively than the invertebrates. Thus, contamination by high-molecular weight PAH, including those with carcinogenic potential and so of concern with regard to human consumers, is therefore usually observed in shellfish, and particularly in bivalve molluscs. Oil spills are not the sole source of PAH, however, as parent compounds are also generated by a wide range of combustion processes. In this paper, consideration is given to monitoring data gathered following recent oil spills (both of crude oil and diesel fuel), alongside data from other studies. These include studies conducted around a former gasworks site and downstream of an aluminium smelter in the UK, and from mussel monitoring studies undertaken in the UK and the USA (including the Exxon Valdez oil spill and the National Status and Trends programme), and in other countries in Europe. For comparative purposes the PAH concentrations are summed and also expressed as benzo[a]pyrene equivalents, their relative concentrations being weighted in relation to the carcinogenic potential of individual PAH compounds using toxic equivalency factors (TEF). Our aim was to assess the utility of this approach in fishery resource monitoring and control following oil spills. Certainly this approach seems useful from the data assessed in this study. and the relative ranking of the various studies seems to reflect the relative degree of concern for human consumers due to the differing contamination sources. As a simple tool for control purposes it is equally applicable to PAH derived from oil spills, and from industrial and combustion sources.

Animals, Dose-Response Relationship, Drug, Drug Administration Schedule, Endothelin Receptor Antagonists, Endothelium, Vascular physiology, Enzyme Inhibitors pharmacology, Female, In Vitro Techniques, Infusion Pumps, Implantable, Nitric Oxide Synthase antagonists inhibitors, Peptides, Cyclic pharmacology, Pregnancy, Rats, Rats, Long-Evans, Receptor, Endothelin B, Vascular Patency drug effects, Vasoconstrictor Agents pharmacology, Vasodilator Agents pharmacology, Vasomotor System physiology, Arteries drug effects, Arteries physiology, Kidney blood supply, Relaxin pharmacology, and Vasomotor System drug effects

Administration of the ovarian hormone relaxin to nonpregnant rats vasodilates the renal circulation comparable to pregnancy. This vasodilation is mediated by endothelin (ET), the ET(B) receptor, and nitric oxide. Furthermore, endogenous relaxin mediates the renal vasodilation and hyperfiltration that occur during gestation. The goal of this study was to investigate whether myogenic reactivity of small renal and mesenteric arteries is reduced in relaxin-treated rats comparable to the pregnant condition. Relaxin or vehicle was administered to virgin female Long-Evans rats for 5 days at 4 microg/h, thereby producing midgestational blood levels of the hormone. The myogenic responses of small renal arteries (200-300 microm in diameter) isolated from these animals were evaluated in an isobaric arteriograph system. Myogenic reactivity was significantly reduced in the small renal arteries from relaxin-treated compared with vehicle-treated rats. The reduced myogenic responses were mediated by the ET(B) receptor and nitric oxide since the selective ET(B) receptor antagonist RES-701-1 and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester restored myogenic reactivity to virgin levels. The influence of relaxin was not limited to the renal circulation because myogenic reactivity was also reduced in small mesenteric arteries isolated from relaxin-treated rats. Thus relaxin administration to nonpregnant rats mimics pregnancy, insofar as myogenic reactivity of small renal and mesenteric arteries is reduced in both conditions.

Animals, Antithrombin III metabolism, Binding Sites, Brain Ischemia blood, Cattle, DNA Mutational Analysis, Factor Xa Inhibitors, Family Health, Genetic Variation, Humans, Hypercholesterolemia blood, Male, Middle Aged, Mutation, Missense, Protein Binding genetics, Antithrombin III chemistry, Antithrombin III genetics, and Heparin metabolism

Here we report the finding of a new natural antithrombin mutation that confirms the critical contribution of lysine 114 to the binding of the core heparin pentasaccharide, with the replacement of lysine 114 by glutamate causing a complete loss in affinity. The variant was identified in a father and son, the father having been investigated for an episode of cerebral ischaemia associated with hypercholesterolaemia. The variant forms SDS-stable complexes with activated factor X (fXa) and its thermal stability and rate of factor Xa inhibition in the absence of heparin are identical to those of normal antithrombin. Normal antithrombin binds to the high affinity heparin pentasaccharide with a Kd of 1nM, as detected by a 45% change in intrinsic fluorescence, resulting in a 230-fold increase in rate of factor Xa inhibition. However, no change in fluorescence was detected for the variant when titrated with heparin or the heparin pentasaccharide, nor was there detectable activation towards factor Xa, indicating a complete loss of heparin binding.

Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 6, Chromosomes, Human, Pair 7, Genetic Heterogeneity, HLA-DR2 Antigen genetics, Humans, Lod Score, Multiple Sclerosis etiology, Genetic Linkage, Genetic Predisposition to Disease, and Multiple Sclerosis genetics

Multiple sclerosis (MS) is a common and frequently disabling autoimmune disorder mediated by autoaggressive T cells and autoantibodies that target central nervous system myelin. While numerous studies have demonstrated a strong genetic component to MS, it has been difficult to identify the specific genes involved. Several genomic screens have been undertaken to locate such genes, but have not provided consistent gene localization, except for the MHC on chromosome 6p21 and a locus on chromosome 19q13. To determine which of the original genomic locations presented in the US genome screen could be replicated, a more detailed analysis of additional families was performed. The results, derived from a population of 266 affected individuals belonging to 98 multiplex families, continue to support linkage to chromosomes 6p21, 6q27, and 19q13 with LOD scores>3.0, and suggest that regions on chromosomes 12q23-24 and 16p13 may also harbor susceptibility loci for MS. Analysis taking into account the known HLA-DR2 association identified two additional potential linkage regions on chromosomes 7q21-22 and 13q33-34. These regions can now be targeted for detailed study to identify the underlying MS susceptibility genes.

Consultants, Humans, Librarians, Personnel Staffing and Scheduling standards, Societies, Workforce, Information Management standards, Libraries, Hospital standards, Library Services standards, and Professional Role

The Medical Library Association's "Standards for Hospital Libraries 2002" have been developed as a guide for hospital administrators, librarians, and accrediting bodies to ensure that hospitals have the resources and services to effectively meet their needs for knowledge-based information. Specific requirements for knowledge-based information include that the library be a separate department with its own budget. Knowledge-based information in the library should be directed by a qualified librarian who functions as a department head and is a member of the Academy of Health Information Professionals. The standards define the role of the medical librarian and the links between knowledge-based information and other functions such as patient care, patient education, performance improvement, and education. In addition, the standards address the development and implementation of the knowledge-based information needs assessment and plans, the promotion and publicity of the knowledge-based information services, and the physical space and staffing requirements. The role, qualifications, and functions of a hospital library consultant are outlined. The health sciences library is positioned to play a key role in the hospital. The increasing use of the Internet and new information technologies by medical, nursing, and allied health staffs; patients; and the community require new strategies, strategic planning, allocation of adequate resources, and selection and evaluation of appropriate information resources and technologies. The Hospital Library Standards Committee has developed this document as a guideline to be used in facing these challenges.

Air Pollutants analysis, Aircraft, Humans, Musculoskeletal Diseases etiology, Musculoskeletal Diseases psychology, New York City, Occupational Diseases psychology, Occupational Health, Pilot Projects, Respiratory Tract Diseases psychology, Air Pollutants adverse effects, Occupational Diseases etiology, Occupational Exposure adverse effects, Rescue Work, Respiratory Tract Diseases etiology, and Terrorism

Aspergillus genetics, Aspergillus growth development, Blotting, Northern, Blotting, Southern, Fermentation, Heme metabolism, Mitosporic Fungi genetics, Peroxidase metabolism, Plasmids, Promoter Regions, Genetic, Aspergillus enzymology, Biotechnology methods, Mitosporic Fungi enzymology, and Peroxidase genetics

The heterologous production of Arthromyces ramosus peroxidase (ARP) was analysed in the filamentous fungus Aspergillus awamori under control of the inducible endoxylanase promoter. Secretion of active ARP was achieved up to 800 mg l(-1) in shake flask cultures. Western blot analysis showed that an rARP product of the correct molecular weight was produced. In contrast to several other studies about heterologous production of heme containing peroxidases, our results suggest that in A. awamori no heme limitation exists during overproduction of ARP.

Apoptosis drug effects, Butyrates pharmacology, Caco-2 Cells, Carcinoma drug therapy, Carcinoma metabolism, Carcinoma physiopathology, Caspase 3, Caspases drug effects, Caspases metabolism, Cell Adhesion drug effects, Cell Differentiation drug effects, Colonic Neoplasms drug therapy, Colonic Neoplasms metabolism, Colonic Neoplasms physiopathology, Down-Regulation drug effects, Down-Regulation physiology, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, Humans, Integrin beta1 drug effects, Integrin beta1 metabolism, Integrins drug effects, Intestinal Mucosa drug effects, NF-kappa B drug effects, NF-kappa B metabolism, Phosphatidylinositol 3-Kinases drug effects, Phosphatidylinositol 3-Kinases metabolism, Phosphorylation drug effects, Protein-Tyrosine Kinases drug effects, Protein-Tyrosine Kinases metabolism, Proto-Oncogene Proteins drug effects, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-bcl-2 drug effects, Proto-Oncogene Proteins c-bcl-2 metabolism, Signal Transduction drug effects, Signal Transduction physiology, Sucrase drug effects, Sucrase metabolism, Apoptosis physiology, Cell Adhesion physiology, Cell Differentiation physiology, Integrins metabolism, Intestinal Mucosa metabolism, and Protein Serine-Threonine Kinases

We previously reported that the enterocytic differentiation of human colonic Caco-2 cells correlated with alterations in integrin signaling. We now investigated whether differentiation and apoptosis of Caco-2 cells induced by the short-chain fatty acid butyrate (NaBT) was associated with alterations in the integrin-mediated signaling pathway with special interest in the expression and activity of focal adhesion kinase (FAK), of the downstream phosphatidylinositol 3'-kinase (PI 3-kinase)-Akt pathway and in the role of the nuclear factor kappaB (NF-kappaB). NaBT increased the level of sucrase. It induced apoptosis as shown by: (1) decreased Bcl-2 and Bcl-X(L) proteins and increased Bax protein; (2) activation of caspase-3; and (3) increased shedding of apoptotic cells in the medium. This effect was associated with defective integrin-mediated signaling as shown by: (1) down-regulation of beta1 integrin expression; 2) decreased FAK expression and tyrosine phosphorylation; (3) concerted alterations in cytoskeletal and structural focal adhesions proteins (talin, ezrin); and (4) decreased FAK ability to associate with PI 3-kinase. However, in Caco-2 cells, beta1-mediated signaling failed to be activated downstream of FAK and PI 3-kinase at the level of Akt. Transfection studies show that NaBT treatment of Caco-2 cells promoted a significant activation of the NF-kappaB which was probably involved in the NaBT-induced apoptosis. Our results indicate that the prodifferentiating agent NaBT induced apoptosis of Caco-2 cells probably through NF-kappaB activation together with a defective beta1 integrin-FAK-PI 3-kinase pathways signaling.

Action Potentials physiology, Animals, Cells, Cultured, Cochlear Nerve physiology, Culture Techniques, Electric Stimulation methods, Immunohistochemistry, Kv1.1 Potassium Channel, Mice, Mice, Inbred CBA, Neurons classification, Neurons metabolism, Patch-Clamp Techniques, Potassium Channels biosynthesis, Protein Subunits biosynthesis, Reaction Time physiology, Neurons physiology, Potassium Channels, Voltage-Gated, and Spiral Ganglion cytology

Type I and type II spiral ganglion neurons convey auditory information from the sensory receptors in the cochlea to the CNS. The numerous type I neurons have been extensively characterized, but the small population of type II neurons with their unmyelinated axons are undetectable with most recording methods. Despite the paucity of information about the type II neurons, it is clear that they must have a significant role in sound processing because they innervate the large number of outer hair cells that are critical for maintaining normal responses to stimuli. To elucidate the function of type II neurons, we have developed an approach for studying their electrophysiological features in vitro. Type II neurons obtained from postnatal day 6-7 mice displayed distinctly different firing properties than type I neurons. They showed slower accommodation, lower action potential thresholds, and more prolonged responses to depolarizing current injection than the type I neurons. These differences were most evident in neurons from the basal, high-frequency region of the cochlea. The basal type I neurons displayed uniformly fast firing features, whereas the basal type II neurons showed particularly slow accommodation and responses to depolarization. Interestingly, neurons from the apical, low-frequency region of the cochlea showed the opposite trend. These data suggest that the type I and type II neurons have specialized electrophysiological characteristics tailored to their different roles in auditory signal processing. In particular, the type II neuron properties are consistent with cells in other sensory systems that receive convergent synaptic input for high-sensitivity stimulus detection.

Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, Chromosomes, Human, Pair 3, Cooperative Behavior, France, Genetic Predisposition to Disease, HLA-DR Antigens genetics, HLA-DR Serological Subtypes, Humans, United States, Genetic Linkage genetics, and Multiple Sclerosis genetics

Multiple sclerosis (MS) is a demyelinating autoimmune disease with a strong yet complex genetic component. To date only the HLA-DR locus, and specifically the HLA-DR15 allele, has been identified and confirmed as influencing the risk of developing MS. Genomic screens on several datasets have been performed and have identified several chromosomal regions with interesting results, but none have yet been confirmed. We tested seven of the most-promising regions (on chromosomes 1p, 2p, 3p, 3q, 5q, 19q, and Xp) identified from several genomic screens in a dataset of 98 multiplex MS families from the United States and 90 multiplex MS families from France. The results did not confirm linkage to 2p, 3q, 5q, or Xp in the overall dataset, or in subsets defined by geographic origin or HLA-DR15 status. Regions on 1p34, 3p14, and 19q13 produced lod scores >0.90 in at least one subset of the data, suggesting that these regions should be examined in more detail.

Anxiety Disorders physiopathology, Brain physiopathology, Humans, Obsessive-Compulsive Disorder epidemiology, Panic Disorder epidemiology, Phobic Disorders epidemiology, Schizophrenia physiopathology, Stress Disorders, Post-Traumatic epidemiology, Anxiety Disorders epidemiology, and Schizophrenia epidemiology

Anxiety symptoms and disorders have long been described in schizophrenia. This article reviews the epidemiology, phenomenology, and neurobiologic underpinnings of comorbid anxiety symptoms and disorders in schizophrenia. Recent literature was obtained by Medline searches using key words relating to schizophrenia and anxiety symptoms or disorders. There is some evidence that anxiety may be a core symptom dimension in schizophrenia, although further work is required. There is evidence that comorbid obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, and social anxiety disorder are all more common than expected by chance in schizophrenia, although additional work is needed to determine the mechanisms that underlie these associations and their clinical implications. In the interim, however, the data emphasize the importance of assessing and treating comorbid anxiety symptoms and disorders in schizophrenia.

Genetic Linkage, Genetic Markers, Genetic Predisposition to Disease, Humans, Lod Score, Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 9, Cleft Lip genetics, and Cleft Palate genetics

Isolated or nonsyndromic cleft lip with or without cleft palate (CL/P) is a common birth defect with a complex etiology. A 10-cM genome scan of 388 extended multiplex families with CL/P from seven diverse populations (2,551 genotyped individuals) revealed CL/P genes in six chromosomal regions, including a novel region at 9q21 (heterogeneity LOD score [HLOD]=6.6). In addition, meta-analyses with the addition of results from 186 more families (six populations; 1,033 genotyped individuals) showed genomewide significance for 10 more regions, including another novel region at 2q32-35 (P=.0004). These are the first genomewide significant linkage results ever reported for CL/P, and they represent an unprecedented demonstration of the power of linkage analysis to detect multiple genes simultaneously for a complex disorder.

Animals, Animals, Newborn, Biopsy, Needle, Cell Movement, Disease Models, Animal, Female, Immunohistochemistry, Lung Compliance, Male, Positron-Emission Tomography, Probability, Pulmonary Ventilation, Random Allocation, Respiratory Distress Syndrome diagnostic imaging, Sensitivity and Specificity, Tidal Volume, Neutrophils physiology, Positive-Pressure Respiration methods, Respiratory Distress Syndrome pathology, and Respiratory Distress Syndrome therapy

Objectives: To compare the effects of low vs. high tidal volume (Vt) with three positive end-expiratory pressure (PEEP) strategies on activated neutrophil influx into the lung.
Design: Prospective, randomized controlled animal study.
Setting: Animal laboratory in a university hospital.
Subjects: Newborn piglets.
Interventions: Surfactant-depleted piglets were randomized in littermate pairs; to PEEP of either 0 (zero end-expiratory pressure [ZEEP]; n = 6), 8 cm H2O (PEEP 8; n = 5), or 1 cm H2O above the lower inflection point (LIP) (PEEP>LIP; n = 6). Within each pair piglets were randomized to a low VT (5-7 mL/kg) or high VT strategy (17-19 mL/kg). After 4 hrs of mechanical ventilation, 18-fluorodeoxyglucose (18FDG) was injected and positron emission tomography scanning was performed.
Measurements and Main Results: VT and PEEP changes on influx constants of 18FDG were assessed by analysis of variance. A within-litter comparison of Vt was nonsignificant (p = .50). A between-litter comparison, ordered in linear trend rank, from ZEEP, to PEEP 8, to PEEP>LIP, showed a strong effect of PEEP on influx constant (p = .019).
Conclusions: PEEP set above the LIP on the inspiratory limb of the pressure-volume curve affords a stronger lung protection than VT strategy.

Adult, Comorbidity, Ethnicity, Female, Humans, Interview, Psychological, Male, Obsessive-Compulsive Disorder complications, Prevalence, Schizophrenia epidemiology, Schizophrenia ethnology, Schizophrenic Psychology, South Africa epidemiology, Obsessive-Compulsive Disorder epidemiology, and Schizophrenia complications

Obsessive compulsive disorder (OCD) has been reported in up to 31% of schizophrenia sufferers. This study evaluated the presence of OCD in a Xhosa-speaking schizophrenia group. Xhosa patients (N = 509, including 100 sibships) with schizophrenia were recruited from hospital and community settings. The patients underwent a structured clinical interview for the presence of lifetime co-morbid schizophrenia and OCD. Only 3 patients (0.5%) fulfilled criteria for OCD. No concordance for OCD was noted in the sibship group. Our findings differ from those in other parts of the world, and if replicated, might suggest unique protective environmental or genetic factors for OCD in certain ethnic groups.

Adaptation, Psychological, Adult, Age Distribution, Comorbidity, Female, HIV Infections psychology, Health Care Costs statistics numerical data, Health Care Surveys, Health Expenditures statistics numerical data, Health Services statistics numerical data, Health Status, Health Surveys, Humans, Male, Middle Aged, Ontario epidemiology, Prevalence, Quality of Life, Risk Factors, Sex Distribution, Socioeconomic Factors, Depression economics, Depression epidemiology, HIV Infections economics, and HIV Infections epidemiology

As new technologies extend the lives of people living with HIV/AIDS (PHA), the need increases for services that optimize their quality-of-life cost effectively. This study of PHAs (n = 297) in Ontario, Canada, examined the prevalence of depression, and its association with quality-of-life, coping strategies, social support, and use of health and social services. Results showed that depression was widespread (54.2%) and largely unrelated to demographic characteristics, but associated with diminished health status, health-related quality-of-life, and coping strategies. Depressed PHAs used significantly more crisis health care and related services, and community-based HIV/AIDS service organizations (ASOs). Findings suggest quality-of-life of PHAs may be improved by expanding the capacity of ASO workers to recognize and address depression, including helping depressed PHA access appropriate medication and sustain medication regimes.

Humans, Information Management standards, Library Associations standards, Professional Role, United States, Information Storage and Retrieval standards, Librarians, Libraries, Hospital standards, and Library Services standards