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Biomedical subjects

M Stevenson

Publications and source records attributed to M Stevenson.

At least 91 records · Page 5Linked to original sources
PubMed1999

Immune activation and virologic response to immunization in recent HIV type 1 seroconverters.

Antigenic stimulation from invasive bacterial infections, and the vaccines designed to prevent them, may promote T cell activation and enhancement of HIV-1 replication. Changes in viral load have been correlated with antigen-specific responses. We prospectively determined the impact of immunization with 23-valent pneumococcal vaccine (PVAX) and Haemophilus influenzae type b (Hib)-modified diphtheria toxoid CRM197 (DT) vaccine on HIV-1 replication in recent HIV-1 seroconverters (n = 14; median, 5.5 months from infection; median CD4+ T cells, 535 microl), and correlated results with vaccine-related immune activation. Specific antibody responses, markers of CD4+ T cell activation (transferrin and interleukin 2 receptors), and viral burden were measured at weeks -2 (pre), 0, 1, 2, 6, and 12 after immunization. By week 2, levels of IgG had increased significantly over baseline in both HIV-1-infected patients and HIV-1-seronegative control subjects (n = 9) for each antigen (geometric mean fold rise: PVAX, 10.1 versus 5.3; Hib, 16.0 versus 11.7; and DT, 26.2 versus 24.5, respectively). Despite these vigorous responses to both polysaccharide and protein antigens, HIV-1-infected patients showed limited evidence of CD4+ T cell activation at 1 week, no consistent rise in HIV-1 burden at any point, and no decline in CD4+ T cell number over time. We conclude that recent HIV-1 seroconverters show vigorous humoral responses to vaccine antigens and limited early evidence of T cell activation, but no substantial or sustained increase in viral replication or decline in CD4+ T cell number. Thus, respiratory bacterial vaccines appear immunogenic and safe early in HIV-1 infection.

Adult↗
PubMed1999

Predictors of outcome among patients with class II division 1 malocclusion treated with fixed appliances in the permanent dentition.

This retrospective study investigated the outcomes achieved in 212 consecutively completed patients with Class II Division 1 malocclusion (overjet > 6 mm). All patients were treated in the permanent dentition with upper and lower fixed appliances. A composite outcome measure was used to identify those cases with an excellent outcome (posttreatment PAR </= 5, posttreatment upper incisor to maxillary plane angle between 104.7 degrees and 115.3 degrees, and anterior movement of the lower incisors </= 2 mm). Logistic regression analysis with patient group as the dependent variable was used to evaluate the predictive value of 32 patient and treatment variables. The three outcome measures (posttreatment PAR score, posttreatment upper incisor inclination, and anterior movement of lower incisors) were ranked and combined to form a single continuous outcome variable. This was used as the dependent variable to carry out further analysis with the linear regression method. Both methods of analysis identified pretreatment overjet and pretreatment upper incisor inclination as significant predictors of outcome. The results revealed that in patients with large overjets an excellent outcome can only be predicted if the upper incisors are very proclined. Every 2 mm increase in overjet (above 4 mm) required approximately a 5 degrees increase in incisor proclination to achieve an excellent outcome.

Adolescent↗
PubMed1999

Variation in periodontal referral in 2 regions in the UK.

This study investigated the periodontal referral patterns of general dental practitioners (GDPs) in Northern Ireland (NI) and North West England (NWE). A questionnaire dealing with periodontal referral was sent to all 520 GDPs registered in NI and to 274 GDPs in NWE. A usable return was made by 355 (68%) in NI and 189 (70%) in NWE. The NI dentists made significantly more periodontal referrals (median 5, range 0-80) in the year preceding the survey than those in NWE (median 2, range 0-50), p<0.001. Distance was the only factor significantly related to the referral rate in both regions with those who practised more than 25 miles from a specialist referring significantly fewer patients in both regions. In NI, there was a trend towards increased periodontal referral by GDPs who had attended more postgraduate courses; however, in NWE, this was not the case. The GDPs in NWE were significantly less likely than those in NI to refer patients with medical conditions. It is concluded that there is considerable variation in periodontal referral both within and between the 2 regions studied. It is further concluded that in many cases, non-disease factors, such as the accessibility of the specialist service, have powerful effects on the decisions made by dentists and patients in these regions (NI and NWE) in relation to periodontal referral. Much of the variance in referral in North West England, as in Northern Ireland, remains unexplained.

Adolescent↗
PubMed1999

HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages.

Infection of macrophage lineage cells is a feature of primate lentivirus replication, and several properties of primate lentiviruses seem to have evolved to promote the infection of macrophages. Here we demonstrate that the accessory gene product Nef induces the production of two CC-chemokines, macrophage inflammatory proteins 1alpha and 1beta, by HIV-1-infected macrophages. Adenovirus-mediated expression of Nef in primary macrophages was sufficient for chemokine induction. Supernatants from Nef-expressing macrophages induced both the chemotaxis and activation of resting T lymphocytes, permitting productive HIV-1 infection. These results indicate a role for Nef in lymphocyte recruitment and activation at sites of virus replication.

Adenoviridae↗
PubMed1999

Immunosuppressive therapy for ulcerative colitis: results of a nation-wide survey among consultant physician members of the British Society of Gastroenterology.

BACKGROUND: The role of immunosuppressive therapy in ulcerative colitis remains controversial. There is little information available on how frequently immunosuppressives are used, the circumstances, dose and duration of use and perceived benefit. METHODS: A postal survey was sent to consultant gastroenterologist members of the British Society of Gastroenterology. RESULTS: Questionnaires were returned by 81% of the 496 UK consultants approached. Azathioprine use was frequent, with 93% reporting previous use and 86% use within the past year. Although 95% usually prescribed a < or =2 mg/kg dose, only 39% were prepared to prescribe higher doses. There was marked variation in duration of use, with 46% using azathioprine for <2 years and 17% continuing it for 4 years or longer. Consultants with more experience of azathioprine in ulcerative colitis used it at higher maintenance doses for longer periods, and in patients with less extensive disease. Cyclosporin use was reported by 47% of those caring for ulcerative colitis patients, with 36% having used it at least once in the past year. However, 65% of users estimated that fewer than 50% of patients subsequently avoided colectomy. On stopping cyclosporin only 21% always introduced an alternative immunosuppressive, while 23% never did so. Potentially serious side-effects attributable to azathioprine and cyclosporin were reported by 36% and 45% of users of each drug, respectively. CONCLUSIONS: This survey reveals considerable variation in the amount and pattern of immunosuppressive use in ulcerative colitis, with serious side-effects commonly seen. There is a pressing need for further randomized controlled trials to provide reliable evidence as to how immunosuppressive therapy should be used in ulcerative colitis.

Azathioprine↗
PubMed1999

Measuring community/environmental interventions: the Child Pedestrian Injury Prevention Project.

OBJECTIVES: To assess the effectiveness of community/environmental interventions undertaken as part of the Child Pedestrian Injury Prevention Project (CPIPP). SETTING: Three communities (local government areas) in the Perth metropolitan area, Western Australia. METHODS: A quasiexperimental community intervention trial was undertaken over three years (1995-97). Three communities were assigned to either: a community/environmental road safety intervention and a school based road/pedestrian safety education program (intervention group 1); a school based road/pedestrian safety education program only (intervention group 2); or to no road safety intervention (comparison group). Quantification of the various road safety community/environmental activities undertaken in each community during the trial was measured, and a cumulative community activity index developed. Estimates of the volume and speed of vehicular traffic were monitored over a two year period. RESULTS: Greater road safety activity was observed in intervention group 1 compared with the other groups. A significant reduction in the volume of traffic on local access roads was also observed over the period of the trial in intervention group 1, but not in the remaining groups. CONCLUSIONS: The findings indicate that the various community/environmental interventions initiated in collaboration with CPIPP in intervention group 1 contributed, in part, to the observed reduction in the volume of traffic. A combination of community/environmental interventions and education are likely to reduce the rate of childhood pedestrian injury.

Accidents, Traffic↗
PubMed1999

Good gene hunting: commercializing safety and efficacy of home genetic test kits.

The rapid advancement of genetic identification as a means of diagnosing or identifying the existence of a genetic trait for preventative and reproductive concerns should compel legal experts to determine whether there is sufficient safety and efficacy in genetic tests. Genetic testing has been used by physicians for a number of years to enhance their allopathic practice. Specifically, genetic tests are now being considered as aids in understanding the development and proliferation of certain diseases in society as a whole, and in specific ethnic and familial groups. The purposes of this paper are to: (1) articulate what genetic testing offers, by way of definition and scope; (2) identify statutory and regulatory limitations on the development, distribution, and use of genetic tests; and (3) consider whether the potential availability of home genetic tests should be made accessible to the American public. This paper will further provide a proposed regulation to encourage the development and distribution of home genetic tests.

Biotechnology↗
PubMed1998

Establishment of a functional human immunodeficiency virus type 1 (HIV-1) reverse transcription complex involves the cytoskeleton.

After interaction of human immunodeficiency virus type 1 (HIV-1) virions with cell surface receptors, a series of poorly characterized events results in establishment of a viral reverse transcription complex in the host cell cytoplasm. This process is coordinated in such a way that reverse transcription is initiated shortly after formation of the viral reverse transcription complex. However, the mechanism through which virus entry and initiation of reverse transcription are coordinated and how these events are compartmentalized in the infected cell are not known. In this study, we demonstrate that viral reverse transcription complexes associate rapidly with the host cell cytoskeleton during HIV-1 infection and that reverse transcription occurs almost entirely in the cytoskeletal compartment. Interruption of actin polymerization before virus infection reduced association of viral reverse transcription complexes with the cytoskeleton. In addition, efficient reverse transcription was dependent on intact actin microfilaments. The localization of reverse transcription to actin microfilaments was mediated by the interaction of a reverse transcription complex component (gag MA) with actin but not vimentin (intermediate filaments) or tubulin (microtubules). In addition, fusion, but not endocytosis-mediated HIV-1 infectivity, was impaired when actin depolymerizing agents were added to target cells before infection but not when added after infection. These results point to a previously unsuspected role for the host cell cytoskeleton in HIV-1 entry and suggest that components of the cytoskeleton promote establishment of the reverse transcription complex in the host cell and also the process of reverse transcription within this complex.

Cell Line↗
PubMed1998

Differential association of uracil DNA glycosylase with SIVSM Vpr and Vpx proteins.

The HIV-1 Vpr protein is a virion-associated protein which has been shown to facilitate infection of nondividing macrophages and additionally to alter cell cycle and proliferation status of the infected host cell. HIV-1 Vpr also was recently shown to associate with the DNA repair enzyme uracil DNA glycosylase (UDG). This association with a DNA repair enzyme is intriguing given that nonprimate lentiviruses encode a dUTPase, which, like UDG, minimizes the misincorporation of uracil into DNA and is important for virus replication in primary nondividing macrophages but not in dividing cells. This raises the possibility that the dependence upon Vpr for infection of nondividing macrophages may relate to its ability to interact with UDG. Members of the HIV-2/SIVSM group encode, in addition to Vpr, a related protein called Vpx. We previously demonstrated (Fletcher et al., 1996) that Vpx of HIV-2/SIVSM is necessary and sufficient for infection of primary macaque macrophages, while Vpr is not required for macrophage infection but governs cell cycle arrest. Here, we extend on these observations by demonstrating that Vpr, but not Vpx of HIV-2/SIVSM, associates with UDG, which suggests that Vpx facilitates infection of macrophages by a UDG-independent mechanism.

Animals↗
PubMed1998

Modulation of HIV-1 infectivity by MAPK, a virion-associated kinase.

Infection of a cell by human immunodeficiency virus type 1 (HIV-1) results in the formation of a reverse transcription complex in which viral nucleic acids are synthesized. Efficient disengagement of the reverse transcription complex from the cell membrane and subsequent nuclear translocation require phosphorylation of reverse transcription complex components by a virion-associated kinase. In this study, we identify the virion-associated kinase as mitogen-activated protein kinase (ERK/MAPK). Upon density gradient fractionation, MAPK, but not its activating kinase MEK, co-sedimented with viral particles. Expression of a constitutively active, but not kinase-inactive, MEK1 in virus producer cells was able to activate virion-associated MAPK in trans. Stimulation of virion-associated MAPK activity in trans by the mitogen phorbol myristate acetate (PMA) increased viral infectivity. Conversely, suppression of virion-associated MAPK by specific inhibitors of the MAPK cascade markedly impaired viral infectivity. These studies demonstrate regulation of an early step in HIV-1 infection by the host cell MAPK signal transduction pathway.

CD4 Antigens↗
PubMed1998

Comparative analysis of crossover exchanges and chiasmata in Allium cepa x fistulosum after genomic in situ hybridization (GISH).

Genomic in situ hybridization (GISH) successfully differentiated homoeologous genomes in the inter-specific hybrid Allium cepa x fistulosum, thus allowing the detection of reciprocal crossover events as label exchanges in separating anaphase I chromosomes. Three of the eight chromosome pairs were positively identified by fluorescence in situ hybridization (FISH) to rDNA sequences. There was a general similarity of the GISH-based label exchange frequencies and metaphase I chiasma frequencies, but with a 20% deficit of chiasmata. Reasons for this apparent deficit are discussed. The locations of chiasmata and label exchanges are in broad agreement.

Allium↗
PubMed1998

Vpx is required for dissemination and pathogenesis of SIV(SM) PBj: evidence of macrophage-dependent viral amplification.

The viral accessory protein Vpx is required for productive in vitro infection of macrophages by simian immunodeficiency virus from sooty mangabey monkeys (SIV(SM)). To evaluate the roles of Vpx and macrophage infection in vivo, we inoculated pigtailed macaques intravenously or intrarectally with the molecularly cloned, macrophage tropic, acutely pathogenic virus SIV(SM) PBj 6.6, or accessory gene deletion mutants (deltaVpr or deltaVpx) of this virus. Both wild-type and SIV(SM) PBj deltaVpx viruses were readily transmitted across the rectal mucosa. A subsequent 'stepwise' process of local amplification of infection and dissemination was observed for wild-type virus, but not for SIV(SM) PBj deltaVpx, which also showed considerable impairment of the overall kinetics and extent of its replication. In animals co-inoculated with equivalent amounts of wild-type and SIV(SM) Pbj deltaVpx intravenously or intrarectally, the deltaVpx mutant was at a strong competitive disadvantage. Vpx-dependent viral amplification at local sites of initial infection, perhaps through a macrophage-dependent mechanism, may be a prerequisite for efficient dissemination of infection and pathogenic consequences after exposure through either mucosal or intravenous routes.

Animals↗
PubMed1998

The two communities in Northern Ireland: deprivation and ill health.

BACKGROUND: The aim of this study was to examine differences in socio-economic standing and ill health between the two communities in Northern Ireland. METHODS: This was a descriptive epidemiological study. Deaths from 1991 to 1995 inclusive were used to calculate standardized mortality rates (SMR, under 75 years) at small level using the 1991 Census population estimates. The standardized limiting long-term illness ratios (SIR) were based on the appropriate Census question. Regression models were tested with SMR and SIR as dependent variables and a wide range of socio-economic indicators, including income support and family credit uptake, as independent predictors. RESULTS: Northern Ireland is a very polarized society. More than 60 per cent of the population live in areas which have more than 80 per cent of one religion. Areas with a preponderance of Catholics tend to be more deprived. Unemployment rates, percentage renting, car availability, and education attainment are all worse in Catholic areas. However, there is considerable heterogeneity between areas with similar levels of religious affiliation and the overall pattern varies with the indicator chosen. SMRs rise stepwise with increasing percentage of Catholics. SIRs increase with increasing polarization of areas, but this is much more marked in those with a predominantly Catholic affiliation. Altogether 46.8 per cent of the variance in SMR and 77.9 per cent of that of SIRs could be explained by socio-economic variables alone. Denomination did not have any residual predictive value. CONCLUSIONS: Policy-makers should continue to periodically monitor for differences between the two communities including any differences in service accessibility and uptake. Efforts should be directed towards reducing the inequalities in health for all sections of the community.

Adolescent↗
PubMed1998

A retrospective comparison of craniofacial form in Northern Irish children with unilateral cleft lip and palate.

OBJECTIVE: This study evaluated the craniofacial form of a sample of Northern Irish children with unilateral cleft lip and palate (UCLP). The quality of the outcomes achieved was compared with the outcomes reported for the six centers involved in the European multicenter study (Mars et al., 1992; Mølsted et al, 1992). DESIGN: Retrospective analysis. PATIENTS: All children born with complete skeletal UCLP in Northern Ireland during the years 1983 to 1987. MAIN OUTCOME MEASURES: Cephalometric analysis was used to determine the craniofacial form and soft tissue profile. The quality of the dental arch relationships was independently assessed using the Goslon ranking system. RESULTS: The sample comprised 25 children with complete skeletal UCLP who had cephalometric radiographs and study casts recorded at a mean age of 9.4 years (range, 8 to 11 years). Cephalometric analysis revealed no important skeletal differences between the Northern Irish UCLP children and the published results from the six Eurocleft centers. The soft tissue profile of the Northern Irish UCLP children was significantly more convex than the soft tissue profile recorded for center D in the Eurocleft study. The Goslon ranking system revealed that 18 (72%) of the Northern Irish UCLP children had good or satisfactory dental arch relationships. CONCLUSIONS: No clinically important differences were detected between the mean cephalometric skeletal parameters of the Northern Irish UCLP children and those published for the six cleft centers involved in the Eurocleft study. On average, the Northern Irish UCLP children were found to differ significantly from Eurocleft's center D in their soft tissue facial contour and sagittal lip profile. The quality of the dental arch relationships of the Northern Irish sample was between the best and the less good Eurocleft centers.

Cephalometry↗
PubMed1998

Can patients predict which consultations can be dealt with by telephone?

The use of telephone consultations to reduce the workload of general practitioners is well established both in this country and abroad. The principal aim of this study was to discover the proportion of consultations currently carried out in the surgery that would be suitable, for both doctor and patient, to be managed over the telephone. The second aim was to establish what proportion of such consultations could be predicted.

England↗
PubMed1998

New advances and validation of knowledge management tools for critical care using classifier techniques.

An earlier version (2.0) of the case-based reasoning (CBR) tool, called IDEAS for ICU's, allowed users to compare the ten closest matching cases to the newest patient admission, using a large database of intensive care patient records, and physician-selected matching-weights [1,2]. The new version incorporates matching-weights, which have been determined quantitatively. A faster CBR matching engine has also been incorporated into the new CBR. In a second approach, a back-propagation, feed-forward artificial neural network estimated two classes of the outcome "duration of artificial ventilation" for a subset of the database used for the CBR work. Weight-elimination was successfully applied to reduce the number of input variables and speed-up the estimation of outcomes. New experiments examined the impact of using a different number of input variables on the performance of the ANN, measured by correct classification rates (CCR) and the Average Squared Error (ASE).

Critical Care↗