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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 199 records · Page 11Linked to original sources
PubMed1998

Influence of antimicrobial chemotherapy on spirometric parameters and pro-inflammatory indices in severe pulmonary tuberculosis.

Patients who have completed a treatment for severe pulmonary tuberculosis (TB) are often left with severe respiratory disability. There have been few prospective studies assessing the effect of treatment on lung function in such patients. The influence of antimicrobial chemotherapy on lung function was investigated over a six month period in patients with newly diagnosed pulmonary TB to test the hypothesis that treatment improves lung function, as well as to identify factors that may influence lung function outcome. Seventy-six patients were recruited into the study, of whom 74 completed the treatment programme. Forty-two were current smokers and 13 seropositive for the human immunodeficiency virus. Improvement in lung function occurred in 54% of patients, but residual airflow limitation or a restrictive pattern was evident in 28% and 24% of patients, respectively. The extent of lung infiltration (radiographic score) both at the outset and after chemotherapy was significantly and negatively related to forced expiratory volume in one second (FEV1) (% pred) (r=-0.41, and r=-0.46, respectively). The post-treatment serum C-reactive protein and alpha1-protease inhibitor levels were negatively associated with FEV1 (% pred) (r=-0.30 and r=-0.35, respectively). These findings demonstrate that, while antimicrobial chemotherapy may lead to improved lung function in patients with pulmonary tuberculosis, a large proportion of patients has residual impairment. The most significant factor influencing post-treatment lung function status, as measured by forced expiratory volume in one second (% predicted), is the pretreatment and post-treatment radiographic score, which acts as a marker of the extent of pulmonary parenchymal involvement in tuberculosis.

Adult↗
PubMed1998

The Internet comes to home care.

The Internet can provide home care agencies access to information, patients, physicians, payors, hospitals, pharmacists, durable medical equipment (DME) companies--virtually anyone participating in the delivery of care. Agencies that wish to take advantage of these capabilities need to take a hard look at what services the Internet can help them deliver.

Communication↗
PubMed1998

Oral health systems in Europe. Part I: Finance and entitlement to care.

OBJECTIVE: To describe and compare the oral health systems in 18 European countries. BASIC RESEARCH DESIGN: Semi-structured, in-depth validation interviews were carried out with key informants from the main national dental associations of EU and associated countries. The interviews were structured around the responses to a previously completed questionnaire, the topics and terminology of which had been agreed in advance with the collaborating associations. The resulting descriptions of dental practice and the dental workforce in each country were returned for further validation and correction by the collaborating associations. Ultimate editorial control over the review of each country's oral health system rested with the authors. RESULTS AND CONCLUSIONS: Oral health care is mainly financed by government-regulated or compulsory social insurance in seven of the 18 countries examined here: Austria, Belgium, France, Germany, Luxembourg, The Netherlands and Switzerland. Providing universal or near-universal coverage by membership of insurance institutions, these systems provide oral health care for about 180 million people across Europe, and almost half of all EU citizens. In the Nordic countries and the UK entitlement to care is typically based upon residence or citizenship, and apart from in Norway and Iceland is provided within a tax-funded and government-organised health service. In southern Europe, Norway, Ireland and Iceland oral health care is largely financed directly by the patient, with occasional support through private insurance. Some publicly-funded and organised services do exist in these countries but generally only for specific population groups (e.g. children, unemployed), or in particular regions.

Child↗
PubMed1998

Influence of antimicrobial chemotherapy and smoking status on the plasma concentrations of vitamin C, vitamin E, beta-carotene, acute phase reactants, iron and lipid peroxides in patients with pulmonary tuberculosis.

SETTING: Inflammation-related oxidative stress has been implicated in the pathogenesis of lung fibrosis and dysfunction in patients with pulmonary tuberculosis. OBJECTIVE: To investigate the effects of antimicrobial chemotherapy and smoking status on the plasma concentrations of the anti-oxidative nutrients vitamin C, vitamin E and beta-carotene, as well as those of iron, lipid peroxides and the acute phase reactants C-reactive protein (CRP) and ferritin. DESIGN: A total of 41 patients with active pulmonary tuberculosis were studied at the outset and after 6 months of antimicrobial chemotherapy. RESULTS: Initial plasma concentrations of vitamin C and beta-carotene were low, returning to normal values after chemotherapy in the non-smokers, but not in the smokers, while those of vitamin E remained low throughout in both groups. Ferritin and CRP concentrations decreased significantly following chemotherapy, with the former higher in smokers than in non-smokers. Serum lipid peroxides were elevated in patients with pulmonary tuberculosis and were unaffected by chemotherapy or smoking habits, while iron levels were not significantly affected by chemotherapy. Although residual dysfunction and infiltration were evident, pulmonary function (FEV1) and radiographic score improved equally in both smokers and non-smokers following antimicrobial chemotherapy. CONCLUSIONS: Even after 6 months of apparently successful antimicrobial chemotherapy, pulmonary tuberculosis is associated with increased oxidative stress, which is unrelated to cigarette smoking and characterized by increased levels of circulating lipid peroxides and low concentrations of plasma vitamin E.

Acute-Phase Proteins↗
PubMed1998

A study of young people's perceptions of their orthodontic need and their experience of orthodontic services.

A study investigating young people's perceptions of their orthodontic needs, demands and their experience of orthodontic services was conducted in Walsall and Dudley health districts, using a self-completed questionnaire. The subjects were 4812 individuals in year 10 of education (average age 15.0 years). Overall, the level of malocclusion perceived by the young people was similar to that identified by dentists in the 1993 national survey of children's dental health. The level of reported malocclusion by boys and girls, white and non-white students and students from the two districts was the same; however fewer students from the less prosperous neighborhoods reported having straight teeth, and more non-white students with irregularities wanted to have straight teeth. Although many young people reported having a malocclusion, the majority were not concerned about it. The study revealed significant differences in experience of treatment. Boys, non-white students and students from less prosperous areas were less likely to report having active orthodontic treatment. Access to specialist services was lower for the non-white students and students from less prosperous areas. A higher proportion of students treated with fixed appliances reported straight teeth after treatment than those treated by extractions alone or by removable appliance therapy.

Adolescent↗
PubMed1998

Oral health systems in Europe. Part II: The dental workforce.

OBJECTIVE: To describe and compare the practice of dentistry and the dental workforce in eighteen European countries. BASIC RESEARCH DESIGN: Semi-structured, in-depth validation interviews were carried out with key-informants from the main national dental associations of EU and associated countries. The interviews were structured around the responses to a previously completed questionnaire, whose topics and terminology had been agreed in advance with the collaborating associations. The resulting descriptions of dental practice and the dental workforce in each country were returned for further validation and correction by the collaborating associations. Ultimate editorial control over the review of each country's oral health system rested with the academic unit from which the associations jointly commissioned the study. RESULTS AND CONCLUSIONS: With the exception of Austria the primary training and registration of dentists is now more or less standard across Europe. However, wide international variation exists in the official recognition of dental specialists and auxiliaries. The Nordic countries of Sweden, Finland and Iceland recognise the broadest range of specialties. In contrast Spain, Portugal, Luxembourg and Belgium currently do not formally recognise any types of specialist practice. Fee-for-service is the dominant form of remuneration for dentists across Europe, but considerable variation exists in the level of fees, how they are decided and the proportion paid by the patient. When based upon standard questionnaires, semi-structured interviews with key informants are an effective method for capturing both the specifics of how an oral health system works, and the general similarities and differences between countries.

Delivery of Health Care↗
PubMed1997

Solar ultraviolet radiation exposure does not appear to exacerbate HIV infection in homosexual men. The Multicenter AIDS Cohort Study.

OBJECTIVE: To determine the effect of sun exposure on HIV progression. DESIGN: Cross-sectional survey nested within a longitudinal cohort study. SETTING: The Multicenter AIDS Cohort Study. PARTICIPANTS: A total of 1155 white HIV-seronegative and 496 white HIV-seropositive homosexual men, of whom 142 seroconverted during the study. MAIN OUTCOME MEASURES: T-helper lymphocyte decline and AIDS. RESULTS: No positive correlation was found between the development of AIDS or loss of T-helper lymphocytes and (i) phenotypic characteristics associated with enhanced ultraviolet radiation (UVR) sensitivity (hair or eye color, skin type), or (ii) reported UVR exposure (sun lamp/tanning bed use, frequency of beach vacations, sunscreen use), or (iii) composite score of UVR sensitivity and exposure history. The composite scores and individual measures of risk were not correlated with rate of T-helper lymphocyte decline (slope) based upon rank correlation (correlation coefficient, 0.04; P = 0.32). In fact, individuals purposefully seeking the sun had slower T-helper lymphocyte declines. Sensitivity to UVR was also not significantly associated with AIDS [odds ratio (OR), 1.11 per unit of higher composite score; 95% confidence interval (CI), 0.66-1.88; P = 0.63]. Among individuals who were HIV-infected at baseline, those who have been purposely seeking sun exposure were less likely to have AIDS (OR, 0.67; 95% CI, 0.39-1.11; P = 0.12). CONCLUSIONS: These data suggest that phenotypic characteristics of high UVR sensitivity and exposure are not highly correlated with decline in T-helper lymphocyte count or with progression to AIDS.

Adult↗
PubMed1997

Interactions between germ cells and extracellular matrix glycoproteins during migration and gonad assembly in the mouse embryo.

Cells are known to bind to individual extracellular matrix glycoproteins in a complex and poorly understood way. Overall strength of adhesion is thought to be mediated by a combinatorial mechanism, involving adhesion of a cell to a variety of binding sites on the target glycoproteins. During migration in embryos, cells must alter their overall adhesiveness to the substrate to allow locomotion. The mechanism by which this is accomplished is not well understood. During early development, the cells destined to form the gametes, the primordial germ cells (PGCs), migrate from the developing hind gut to the site where the gonad will form. We have used whole-mount immunocytochemistry to study the changing distribution of three extracellular matrix glycoproteins, collagen IV, fibronectin, and laminin, during PGC migration and correlated this with quantitative assays of adhesiveness of PGCs to each of these. We show that PGCs change their strength of adhesion to each glycoprotein differentially during these stages. Furthermore, we show that PGCs interact with a discrete tract of laminin at the end of migration. Closer analysis of the adhesion of PGCs to laminin revealed that PGCs adhere particularly strongly to the E3 domain of laminin, and blocking experiments in vitro suggest that they adhere to this domain using a cell surface proteoglycan.

Animals↗
PubMed1997

Construction and biological characterization of an interleukin-12 fusion protein (Flexi-12): delivery to acute myeloid leukemic blasts using adeno-associated virus.

Interleukin-12 (IL-12) is a cytokine that exhibits pleiotropic effects on lymphocytes and natural killer cells and has been shown to have promise for the immunotherapy of cancer. The combination of the immune costimulatory molecule B7.1 and IL-12 has been shown to be synergistic for T cell activation. By transfecting tumor cells with both IL-12 and B7.1 cDNAs, it may be possible to use these modified targets as vaccines. A major obstacle in designing a vector to deliver these genes results from the structure of IL-12. Functional IL-12 is a heterodimer composed of two distinct subunits that are encoded by separate genes on different chromosomes. Production of functional IL-12 requires the coordinated expression of both genes. This presents several problems in vectors, particularly those in which additional genes, either a co-stimulatory gene or a selectable marker, are inserted. Therefore, we have constructed a single cDNA that encodes a single-chain protein, called Flexi-12, which retains all of the biological characteristics of recombinant IL-12 (rIL-12). The monomeric polypeptide Flexi-12 is able to induce the proliferation of phytohemagglutinin (PHA) blasts, induce PHA blasts to secrete interferon-gamma (IFN-gamma) and additionally, by preincubation, enhance the killing of K562 targets by PBLs. These phenomena are in a dose-dependent manner comparable to that seen with rIL-12. We have also shown that tyrosine phosphorylation of the STAT 4 transcription factor, which has been shown to be unique to the IL-12 signaling pathway, occurs with Flexi-12 at levels similar to those seen with rIL-12. We have packaged Flexi-12 into a recombinant adeno-associated virus (AAV) and used this vector to infect acute myeloid leukemic (AML) blasts. Infected AML blasts produced between 2 and 6 ng of IL-12/10(6) cells per ml per 48 hr. These studies also confirm that AAV is an efficient delivery vehicle for cytokines to leukemic cells. Direct analysis of these modified cells acting as tumor vaccines is underway.

Amino Acid Sequence↗
PubMed1997

Preferential translation of reovirus mRNA by a sigma3-dependent mechanism.

We have characterized reovirus strains that differ in the degree to which they inhibit cellular protein synthesis and used them to investigate mechanisms regulating gene expression in infected cells. A previous genetic study associated distinct effects of reovirus strains on cellular translation with polymorphisms in viral protein sigma3. In cell extracts, sigma3 sequesters double-stranded RNA (dsRNA) and blocks activation of the dsRNA-activated protein kinase (PKR), an interferon-induced enzyme that inhibits translational initiation by phosphorylating elF-2alpha. We found that in infected cells, cellular protein synthesis is translationally regulated in a strain-specific manner. Using immunoprecipitation and indirect immunofluorescence we showed that the effect of a strain on cellular translation is not determined by the level of sigma3, but appears to result from differences in sigma3 localization. In cells infected with a strain that spares cellular translation, sigma3 is present throughout the cytoplasm, whereas in cells infected with inhibitory strains, sigma3 is restricted to perinuclear viral factories. Biochemical studies suggested that diffuse localization of sigma3 is a consequence of low affinity for capsid protein mu1. Our findings are consistent with a model in which the efficiency of cellular translation is determined by the cytoplasmic level of sigma3 that is not complexed with mu1.

Amino Acid Sequence↗
PubMed1997

Pneumococcal vaccine campaign based in general practice.

OBJECTIVE: To show whether a general practice setting is a practical and effective medium for increasing uptake of pneumococcal vaccine. DESIGN: Follow up study of responses of general practices (debriefing by questionnaire or small group session) and patients (questionnaire sent to 429 patients vaccinated in a two week period) to vaccination campaign. SETTING AND SUBJECTS: Patients registered with general practices of one family health services authority. INTERVENTIONS: Pneumococcal vaccination campaign including clinical guidelines and support materials. MAIN OUTCOME MEASURES: Proportion of general practitioners offering pneumococcal vaccine; proportion of patients at risk who were vaccinated between 1 May and 31 December 1995; number of splenectomised patients identified and vaccinated in same period; views of patients who were vaccinated. RESULTS: Proportion of general practitioners offering pneumococcal vaccine increased from 17% to 89% during the campaign. Estimated number of patients at risk who were vaccinated increased from 656 (4%) to 5982 (33%) during campaign. Of 61 splenectomised patients identified, 30 had been vaccinated previously and 27 were vaccinated during campaign. Practices in which a general practitioner took or shared the lead had higher vaccination rates and used vaccine up faster. Of the 384 patients whose questionnaires were used in analysis, only 35 had heard of pneumococcal vaccine before the campaign, 198 reported side effects (mostly minor and local, but systemic and severe local reactions were more common than expected), and 337 were pleased they had been vaccinated (only five expressed dissatisfaction). CONCLUSION: A practice based campaign is an effective method of increasing uptake of pneumococcal vaccine by high risk groups.

Adult↗
PubMed1997

Respiratory syncytial virus triggers synthesis of IL-6 in BALB/c mouse alveolar macrophages in the absence of virus replication.

Cytokines produced by alveolar macrophages are likely involved in the regulation of the immune response arising from respiratory syncytial virus (RSV) infection. Both infectious and UV-inactivated RSV were effective in inducing BALB/c mouse alveolar macrophages to synthesize increased levels of IL-6 mRNA and secreted IL-6 protein. No increase in IL-1beta (either mRNA or secreted protein) was observed. The augmented production of IL-6 was activated by purified virus and was reduced by pretreating virus with virus-neutralizing antiserum, demonstrating a requirement for virus in the enhanced IL-6 response. The results suggest that the exposure of BALB/c alveolar macrophages to small quantities of RSV (in the absence of detectable virus replication) is sufficient to trigger IL-6 production. The finding that UV-inactivated virus was effective in triggering IL-6 production by mouse alveolar macrophages is similar to that reported in human alveolar macrophages, providing further validation of the BALB/c mouse as a useful animal model for human RSV infection.

Animals↗
PubMed1997

Absence of central cholinergic deficits in ApoE knockout mice.

ApolipoproteinE (ApoE) genotype has recently been identified as a major risk factor for Alzheimer's disease (AD) but the mechanism(s) by which ApoE isoforms influence this disease remain unclear. Recent studies suggest that mice deficient in ApoE may exhibit impaired central cholinergic function. Since this neurotransmitter system has traditionally been associated with the pathogenesis of AD, we have further investigated the impact of ApoE gene deletion on this system. Female ApoE knockout (ko) mice, age 12 months, were compared with wild type littermate controls using a range of behavioural, biochemical and histochemical techniques. Pre-treatment with the cholinomimetic, donepezil (E2020; 2.5-5 mg kg-1 IP), produced significant hypothermia and induction of tremor in both wild type and ApoE ko mice. The magnitude of change did not significantly differ between the groups. Cognitive testing in the Morris water maze revealed that both wild type and ApoE ko mice could learn the location of a hidden escape platform with similar rates of acquisition and accuracy. Similarly, the behaviour of both genotypes proved indistinguishable in a Y-maze spontaneous alteration procedure. The protocols used for both cognitive tests were then shown to be sensitive to the disruptive effects of scopolamine (but not scopolamine methyl bromide). Following behavioural testing, choline acetyltransferase (ChAT) activity was measured in the hippocampus, frontal and entorhinal cortex and striatum. In each case there was no difference between the genotypes. In addition, coronal sections of striatum and anterior hippocampal regions of ApoE ko and wild type mice showed similar patterns of acetylcholinesterase (AChE) staining, with no qualitative or obvious quantitative difference. Finally, analysis of plasma cholesterol levels confirmed ApoE genotype. In conclusion, using a combination of behavioural, histochemical and biochemical measurements, we have failed to detect any significant differences in central cholinergic activity between wild type and ApoE ko mice.

Acetylcholinesterase↗
PubMed1997

The perils of permanent punctal plugs.

PURPOSE: To describe previously unreported complications associated with permanent lacrimal punctal plugs. METHOD: Five oculoplastic practices reviewed patients referred to them over the preceding 2 years for permanent lacrimal punctal plug complications. RESULTS: In 12 patients, 14 lacrimal punctal plugs migrated distally within the lacrimal drainage system, causing symptoms and necessitating surgical removal. CONCLUSION: Luxation of permanent punctal plugs into the distal lacrimal drainage system can occur, sometimes requiring complex surgical intervention.

Foreign-Body Migration↗
PubMed1997

Immunization of mice with DNA encoding fragment C of tetanus toxin.

Immunization of mice with Fragment C protein, the non-toxic C-terminal domain of tetanus toxin, will protect mice against lethal challenge with tetanus toxin. A plasmid, pcDNA3/tetC, which encodes a synthetic tetC gene expressed under the control of the human cytomegalovirus major intermediate early promoter/enhancer region, was constructed. Fragment C expression was observed in Chinese hamster ovary cells following transfection with pcDNA3/tetC. The immune response induced by intramuscular immunization with pure pcDNA3/tetC DNA was evaluated in a murine model. Anti-Fragment C serum immunoglobulin and proliferative responses in splenocytes were observed following two immunizations with pcDNA3/tetC. The major IgG subclass that recognized Fragment C was IgG2a and the stimulated splenocytes secreted high levels of interferon-gamma. Sufficient anti-Fragment C serum immunoglobulins were induced by DNA-mediated immunization to protect mice against lethal challenge with tetanus toxin.

Animals↗