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Biomedical subjects

M Stevenson

Publications and source records attributed to M Stevenson.

At least 37 records · Page 2Linked to original sources

HIV-1 Nef promotes survival of myeloid cells by a Stat3-dependent pathway.

Human immunodeficiency virus Nef is a small myristylated protein that plays a critical role in AIDS progression. Nef binds with high affinity to the SH3 domain of the myeloid-restricted tyrosine kinase Hck in vitro, identifying this Src-related kinase as a possible cellular target for Nef in macrophages. Here we show that Nef activates endogenous Hck in the granulocyte-macrophage colony-stimulating factor-dependent myeloid cell line, TF-1. Unexpectedly, Nef induced cytokine-independent TF-1 cell outgrowth and constitutive activation of the Stat3 transcription factor. Induction of survival required the Nef SH3 binding and membrane-targeting motifs and was blocked by dominant-negative Stat3 mutants. Nef also stimulated Stat3 activation in primary human macrophages, providing evidence for Stat3 as a Nef effector in a target cell for human immunodeficiency virus.

Cell Survival↗

Clinical decision support systems for intensive care units: using artificial neural networks.

The paper provides an overview of applications of artificial neural networks (ANNs) to various medical problems, with a particular focus on the intensive care unit environment (ICU). Several technical approaches were tested to see whether they improve the ANN performance in estimating medical outcomes and resource utilization in adult ICUs. These experiments include: (1) use of the weight-elimination cost function; (2) use of 'high' and 'low' nodes for input variables; (3) verifying the effect of the total number of input variables on the results; (4) testing the impact of the value of the constant predictor on the performance of the ANNs. The developments presented intend to help medical and nursing personnel to assess patient status, assist in making a diagnosis, and facilitate the selection of a course of therapy.

APACHE↗

Intraoperative motor evoked potentials to transcranial electrical stimulation during two anaesthetic regimens.

OBJECTIVES: To study motor evoked potentials (MEPs) to multi-pulse transcranial electrical stimulation (MP-TES) during orthopaedic spinal surgery under different anaesthetic regimens. METHODS: MEPs to MP-TES were recorded from tibialis anterior and abductor hallucis bilaterally in 50 operations. Anaesthesia was maintained with propofol and nitrous oxide in 29 operations and isoflurane (0.78+/-0.17% end-tidal) and nitrous oxide in 23 (two patients received both regimens). Analgesia was provided with fentanyl or remifentanil. RESULTS: Motor stimulation caused neither EEG changes nor seizures. MEPs were obtained in 97% of patients during propofol anaesthesia. The median amplitude and coefficient of variation (CV) at baseline (across all muscles) were 198 microV and 22%, respectively. Amplitudes throughout the operation paralleled the degree of neuromuscular block and were reduced after fentanyl bolus, isoflurane or morphine. Loss of MEPs or persistent amplitude decrements were associated with neurological complications in one patient and severe blood loss in another two patients. MEPs were obtainable in 61% of patients during isoflurane anaesthesia and became inconsistent for end-tidal concentrations >0.87+/-0.08%. Amplitudes were smaller (85 microV) and baseline variability higher (coefficient of variation 29%) than in the propofol group. The decrease in the number of recordings was greater for isoflurane than propofol when the number of pulses/train decreased from 4 to 2. CONCLUSIONS: Muscle MEPs to MP-TES are a safe, sensitive and reliable method for monitoring motor pathways during propofol/nitrous oxide and fentanyl or remifentanil anaesthesia. MEPs are also obtainable in the majority of patients during isoflurane/nitrous oxide anaesthesia, but quantitative monitoring is not always possible with this regimen.

Adolescent↗

Sequence-specific interaction between HIV-1 matrix protein and viral genomic RNA revealed by in vitro genetic selection.

The human immunodeficiency virus type-1 matrix protein (HIV-1 MA) is a multifunctional structural protein synthesized as part of the Pr55 gag polyprotein. We have used in vitro genetic selection to identify an RNA consensus sequence that specifically interacts with MA (Kd = 5 x 10(-7) M). This 13-nt MA binding consensus sequence bears a high degree of homology (77%) to a region (nt 1433-1446) within the POL open reading frame of the HIV-1 genome (consensus sequence from 38 HIV-1 strains). Chemical interference experiments identified the nucleotides within the MA binding consensus sequence involved in direct contact with MA. We further demonstrate that this RNA-protein interaction is mediated through a stretch of basic amino acids within MA. Mutations that disrupt the interaction between MA and its RNA binding site within the HIV-1 genome resulted in a measurable decrease in viral replication.

Base Sequence↗

Community participation in road safety: barriers and enablers.

The objectives of the paper were to identify barriers to community participation in road safety activities and to recommend strategies to reduce those barriers. Information was obtained from: a review of relevant literature, from the authors' extensive community-based experiences, from undertaking community-based research, and from interviews with key stakeholders in road safety in Western Australia. Ten significant barriers to community participation were identified. These are classified into two groups: personnel and planning issues. The former includes: reasons why people are often reluctant to become involved in projects in their communities, a lack of leadership, and a lack of skills. The latter includes: inappropriate program foci, inappropriate program evaluation, lack of resources, and a lack of sustainability. It was concluded that the barriers to community involvement in road safety initiatives are similar in many parts of Australia and overseas and apply to a wide range of health promotion interventions besides road safety. Awareness of the barriers and knowledge of their solutions can ensure that appropriate steps are taken to maximise the likelihood of community participation.

Accidents, Traffic↗

Professional perceptions of the benefits of orthodontic treatment.

The aim of this study was to assess general dental practitioners' and orthodontists' perceptions of the benefits of orthodontic treatment. A specially designed questionnaire was sent to a random sample of 150 general dental practitioners (GDPs) and all orthodontists in Northern Ireland (excluding hospital practitioners) with a postgraduate qualification (n = 29). There was a 93 per cent response rate by the general dental practitioners and all but one specialist practitioner returned the questionnaire. The questionnaire comprised 14 visual analogue scales (VAS) whereby participants were asked to rate the importance of various possible dental health and psychosocial benefits of orthodontic treatment. In addition to the VAS, the influence of dentist variables such as number of years since qualification, orthodontic cases completed, referral rates and attendance at postgraduate lectures were examined. When ratings on the 14 dental health and psychosocial scales were examined overall, GDPs rated an improvement in self-esteem while orthodontists considered an improvement in physical attractiveness as the most important benefit of orthodontic treatment. Even though psychosocial variables received the highest ratings, examination of the mean ratings (and 95 per cent confidence intervals) revealed that some dental health factors were also rated highly by both groups. While the results do indicate an encouraging awareness of the psychosocial benefits of orthodontic treatment, they also suggest that both GDPs and orthodontists have an unrealistic expectation of the dental health gain likely to result from orthodontic treatment.

Dentists↗

Two long terminal repeat circles and persistent HIV-1 replication.

Building on the success of combination antiretroviral drug therapy will require a better understanding of the underlying basis for viral persistence. Characterization of the therapeutic, viral, and immunological factors that influence the size and stability of viral reservoirs will foster the development of strategies to control or eliminate HIV-1 from infected individuals. Here we review recent work aimed at delineating the complex interplay between viral replication, the immune system, and viral reservoirs. Finally, we address the implications and clinical significance of the residual replication that persists in infected individuals on potent antiretroviral therapy to evaluate both the possible risks and benefits of ongoing HIV-1 replication.

CD4-Positive T-Lymphocytes↗

Bipolar scissors versus cold dissection tonsillectomy: a prospective, randomized, multi-unit study.

OBJECTIVE: To evaluate bipolar scissors tonsillectomy by comparing it with traditional cold dissection tonsillectomy. STUDY DESIGN: A prospective, randomized, multi-unit study. SETTINGS: Belfast City Hospital, Royal Victoria Hospital Belfast, and Ulster Hospital Dundonald. PATIENTS: Two hundred consecutive patients undergoing tonsillectomy for recurrent or chronic tonsillitis between March 2000 and September 2000. OUTCOME MEASURES: (1) Intraoperative bleeding, (2) operative time, (3) postoperative pain, and (4) complication rates, including primary and secondary hemorrhage. RESULTS: Seventeen patients were excluded from the study for various reasons. The mean age of the study population was 22 years (range, 10-54 y). Seventy-two percent of patients were female. Twenty-seven percent of patients were children aged 16 years or under. Median intraoperative blood loss was 5 mL for bipolar scissors tonsillectomy and 115 mL for cold dissection tonsillectomy (P < .001). The mean operative time was 13 minutes for bipolar scissors tonsillectomy compared with 20 minutes for the cold dissection method (P < .001). There was no statistically significant difference in the pain scores between the two methods (independent samples t = 1.35; P > .05). The overall primary hemorrhage rate was 2.1%, whereas the overall secondary hemorrhage rate was 16.9%. The hospital readmission rate was 10.3%. The primary and secondary hemorrhage rates were unaffected by the surgical method. CONCLUSIONS: Bipolar scissors tonsillectomy is a safe technique with a similar morbidity to the cold dissection method. Its use is associated with a significant decrease in both surgical time and blood loss compared with the cold dissection method.

Adolescent↗

Drink and drug driving: what's the skipper up to?

OBJECTIVE: Since the introduction of random breath testing (RBT) in Australia there has been a significant reduction in drink driving, as measured by alcohol-related crashes. In contrast, the prevalence of drug-related road fatalities is on the increase. One strategy that targets drink- and/or drug-driving is the promotion of a designated driver or 'skipper'. This paper determines to what extent the 'skipper' is driving alcohol or drug-free. METHODS: A convenience sample of university students from The University of Western Australia completed a questionnaire that included questions on drug and alcohol use while driving as the designated 'skipper'. RESULTS: The mean age of the 286 participants was 21 years. Among the students who reported acting as the designated 'skipper' during the past 12 months, 26% of the students drove, as the designated 'skipper,' while feeling the effects of alcohol. Similarly, 18% of students who reported using drugs drove, as the 'skipper', while feeling the effects of the drug. Multivariate analysis identified that the presence of random drug testing would act as a deterrent for drug driving while the designated 'skipper'. CONCLUSION: Although three-quarters of designated 'skippers' do not drink and/or drug drive, a sizeable proportion of young drivers continue to place themselves and, more importantly, their passengers and the entire community at an elevated risk of injury. IMPLICATIONS: Campaigns that target the responsibility of the 'skipper' and that are included as part of drink-driving campaigns would be beneficial. It is premature to be making recommendations on random drug testing for drivers.

Adult↗

Relation between macular morphology and visual function in patients with choroidal neovascularisation of age related macular degeneration.

AIM: To examine the relation between three measures of visual function (distance acuity, near acuity, and contrast sensitivity) and specific fluorescein angiographic characteristics of the macular lesion in patients with subfoveal choroidal neovascularisation (CNV) due to age related macular degeneration (AMD). METHODS: Visual evaluation and digital fundus fluorescein angiography were performed in 93 patients with subfoveal CNV. Standard morphometric techniques were used on two frames from the angiographic series closest to 30 seconds and 60 seconds respectively, to ascertain total lesion size (defined as the entire area of abnormal fluorescence), the size of the classic component, and the distance from the fovea to the closest point of healthy retina. Correlations were sought using Pearson's correlation coefficients. Stepwise regression was used to minimise multiple colinearity. RESULTS: When the study eye was the better eye of a patient's pair of eyes, the strongest correlation was between the size of the classic component and contrast sensitivity (r= 0.48, p <0.001) and was highly significant. When the study eye was the worse eye, significant correlations were observed between total lesion size and all three measures of visual function. The strongest correlation was observed between overall lesion size and contrast sensitivity (r = 0.52, p <0.001). CONCLUSIONS: This study has shown that the status of the study eye (that is, better or worse eye of a pair of eyes) influences the impact of macular pathology in AMD on visual function. The distance of the fovea from healthy retina was found to be an important factor in predicting visual function.

Aged↗

An overview of the injury severity score and the new injury severity score.

OBJECTIVE: The research was undertaken to describe the injury severity score (ISS) and the new injury severity score (NISS) and to illustrate their statistical properties. DESIGN: Descriptive analysis and assessment of the distribution of these scales. METHODS: Three data sources--the National Pediatric Trauma Registry; the Massachusetts Uniform Hospital Discharge Data Set; and a trauma registry from an urban level I trauma center in Massachusetts--were used to describe the distribution of the ISS and NISS among injured patients. RESULTS: The ISS/NISS was found to have a positively skewed distribution and transformation did not improve their skewness. CONCLUSION: The findings suggest that for statistical or analytical purposes the ISS/ NISS should not be considered a continuous variable, particularly if ISS/NISS is treated as a continuous variable for correlation with an outcome measure.

Adolescent↗

Intestinal disappearance and mesenteric and portal appearance of amino acids in dairy cows fed ruminally protected methionine.

An experiment was conducted to compare the rates of disappearance of amino acids (AA) from the small intestine and their net appearance in the blood draining only the small intestine (mesenteric-drained viscera) and the whole gastrointestinal tract (portal-drained viscera) of cows fed a silage-based diet supplemented or not with ruminally protected Met. Five lactating dairy cows (118+/-4 DIM) equipped with duodenal and ileal cannulae (n = 2) or a duodenal cannula only (n = 3), two of which were multicatheterized, were fed a TMR top dressed with 0 or 72 g of ruminally protected Met per day. The addition of ruminally protected Met to the diet increased the duodenal flux of Met leading to a higher apparent digestibility of Met in the small intestine. Sixty-six percent of Met from ruminally protected Met bypassed the rumen and 82% of that Met disappeared from the small intestine. Arterial plasma Met concentrations numerically increased with ruminally protected Met (45 vs. 18 microM), while total AA concentration decreased. Feeding ruminally protected Met resulted in higher concentrations of urea-N and glucose in arterial plasma. Milk production and milk composition were unaffected. The disappearance of essential AA across the small intestine was equivalent (101%) to their flux through the mesenteric-drained viscera while the portal:mesenteric-drained viscera flux ratio for each essential AA varied from 38% for Thr to 76% for Phe. The portal:mesenteric-drained viscera flux ratio for Met was 66%. These results confirm observations made with pigs and sheep.

Amino Acids↗

General practice out-of-hours service, variations in use and equality in access to a doctor: a cross-sectional study.

BACKGROUND: There is increasing dissatisfaction among general practitioners (GPs) with their 24 hour commitment despite the demand for GP services outside ordinary working hours. The creation of out-of-hours co-operatives has been welcomed by participating GPs and their families and patient satisfaction is generally high. However, there have been concerns about the lack of patient consultation in their development and on the quality of care provided. OBJECTIVES: To examine geographical variation in the rates of out-of-hours calls and to see if there is any systematic variation in how the co-operative that covers the area responds to calls. DESIGN OF STUDY: A secondary data analysis of 110,357 calls received by the co-operative during the second year of its operation. SETTING: A co-operative with four centres providing out-of-hours care for one mostly rural Health Board in Northern Ireland. METHOD: Deprivation score and mortality and long-term illness ratios provided indicators of need at an area level. Proximity to the four co-operative centres was measured as the distance in kilometres and estimated travel time (in minutes) along the road network. RESULTS: Out-of-hours call ratios were proportional to the area deprivation score and proximity to the co-operative centres, though not to area indicators of ill health. Older patients were more likely to be seen by the GP and females over the age of 15 years were more likely to receive telephone advice only (adjusted odds ratio [OR] = 0.785, 95% confidence intervals [CI] 0.756-0.816, P < 0.001). Each kilometre from the centres reduced the likelihood of seeing the GP (OR = 0.978, 95% CI = 0.976-0.979, P < 0.001). Even after controlling for potential confounders a large difference remained in how centres responded to calls. CONCLUSIONS: It is not certain whether these inequalities in services delivery represent inequity as the apposite level or type of response cannot be determined until more is known about the appropriateness of the demand for out-of-hours medical care.

Adolescent↗

Telerheumatology--diagnostic accuracy and acceptability to patient, specialist, and general practitioner.

This study examines the diagnostic accuracy and acceptability of telemedicine in the field of rheumatology. One hundred patients had a telephone and televisual consultation and the results were compared with a face-to-face consultation. While the telephone consultations were often unsatisfactory, the televisual consultations were highly accurate (97%) and acceptable to patients, general practitioners, and specialists.

Adult↗

DepoFoam technology: a vehicle for controlled delivery of protein and peptide drugs.

A major challenge in the development of sustained-release formulations for protein and peptide drugs is to achieve high drug loading sufficient for prolonged therapeutic effect coupled with a high recovery of the protein/peptide. This challenge has been successfully met in the formulation of several peptide and protein drugs using the DepoFoam, multivesicular lipid-based drug delivery system. DepoFoam technology consists of novel multivesicular liposomes characterized by their unique structure of multiple non-concentric aqueous chambers surrounded by a network of lipid membranes. The objective of this paper is to demonstrate that DepoFoam technology can be used to develop sustained-release formulations of therapeutic proteins and peptides with high loading. DepoFoam formulations of a protein such as insulin, and peptides such as leuprolide, enkephalin and octreotide have been developed and characterized. The data show that these formulations have high drug loading, high encapsulation efficiency, low content of free drug in the suspension, little chemical change in the drug caused by the formulation process, narrow particle size distribution, and spherical particle morphology. Drug release assays conducted in vitro in biological suspending media such as human plasma indicate that these formulations provide sustained release of encapsulated drug over a period from a few days to several weeks, and that the rate of release can be modulated. In vivo pharmacodynamic studies in rats also show a sustained therapeutic effect over a prolonged period. These results demonstrate that the DepoFoam system is capable of efficiently encapsulating therapeutic proteins and peptides and effectively providing controlled delivery of these biologically active macromolecules.

Animals↗

Child pedestrian injury prevention project: student results.

BACKGROUND: Few comprehensive pedestrian safety interventions for primary-school-age children have been developed and evaluated. This paper reports the impact of the 3-year (1995-1997) Child Pedestrian In jury Prevention Project (CPIPP) on a cohort of 1603 children followed from age 6 to 9 years. This multicomponent project comprised an educational intervention for students, their parents and teachers, and the local community, as well as several environmental interventions. The primary aim of CPIPP was to improve children's road-related behavior and to enhance the safety of their road environment. METHODS: Three communities were assigned to the treatment conditions: (1) high-education, community, and environmental interventions; (2) moderate-education intervention only; and (3) comparison (usual road safety education). Children's pedestrian knowledge and road crossing and playing behaviors were assessed using a pre- and posttest self-report questionnaire. Their self-reported road crossing behaviors were validated using an observational schedule and brief interview. RESULTS: Children in the high and moderate intervention groups were significantly more likely to cross the road with adult supervision (P = 0.013) and play away from the road (P = 0.000) than the comparison group. No differences were detected in children's pedestrian safety knowledge between the intervention and comparison groups. CONCLUSIONS: While several methodological limitations may have influenced the study outcomes, these data nonetheless indicate that in the study sample the CPIPP educational intervention deaccelerated the natural increase in children's pedestrian-related risk behavior.

Accident Prevention↗