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Biomedical subjects

J McNeil

Publications and source records attributed to J McNeil.

At least 19 recordsLinked to original sources

Bispectral index monitoring to prevent awareness during anaesthesia: the B-Aware randomised controlled trial.

BACKGROUND: Awareness is an uncommon complication of anaesthesia, affecting 0.1-0.2% of all surgical patients. Bispectral index (BIS) monitoring measures the depth of anaesthesia and facilitates anaesthetic titration. In this trial we determined whether BIS-guided anaesthesia reduced the incidence of awareness during surgery in adults. METHODS: We did a prospective, randomised, double-blind, multicentre trial. Adult patients at high risk of awareness were randomly allocated to BIS-guided anaesthesia or routine care. Patients were assessed by a blinded observer for awareness at 2-6 h, 24-36 h, and 30 days after surgery. An independent committee, blinded to group identity, assessed every report of awareness. The primary outcome measure was confirmed awareness under anaesthesia at any time. FINDINGS: Of 2463 eligible and consenting patients, 1225 were assigned to the BIS group and 1238 to the routine care group. There were two reports of awareness in the BIS-guided group and 11 reports in the routine care group (p=0.022). BIS-guided anaesthesia reduced the risk of awareness by 82% (95% CI 17-98%). INTERPRETATION: BIS-guided anaesthesia reduces the risk of awareness in at-risk adult surgical patients undergoing relaxant general anaesthesia. With a cost of routine BIS monitoring at US16 dollars per use in Australia and a number needed to treat of 138, the cost of preventing one case of awareness in high-risk patients is about 2200 dollars.

Anesthesia Recovery Period↗

Methodology of the Cardiovascular Health and Age-Related Maculopathy (CHARM) Study.

Age-related macular degeneration (AMD) is responsible for the majority of visual impairment in the Western world. Epidemiological studies examining risk factors for AMD are needed to develop strategies for the prevention of blindness from this condition. A number of potentially modifiable risk factors for AMD have been identified; however, only smoking has been a consistent risk factor across the numerous studies. A growing body of evidence suggests that AMD and cardiovascular disease may have common risk factors. The Cardiovascular Health and Age Related Maculopathy (CHARM) Study was established to examine the risk factors for AMD and its progression, in particular risk factors associated with cardiovascular disease. Examining risk factors for prevalent AMD, cases with AMD were compared with age and gender matched controls with no AMD features. For the assessment of AMD progression, the study examined in 2001 and 2002 those participants with early AMD, or age-related maculopathy (ARM), who had undergone baseline examination between 1992 and 1995 and compared the characteristics of those who had progression of AMD with those who did not. The CHARM study involved both ophthalmic and cardiovascular examinations. Standardised clinical eye examination and grading of the macular stereo photographs were used to determine the AMD status and progression. To examine cardiovascular status, carotid artery ultrasound imaging analysis of systemic arterial compliance, augmentation index and pulse wave velocity were performed. The traditional and novel risk factors for CVD such as levels of glucose, cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, fibrinogen, C-reactive protein, immunoglobulins A and M, homocysteine, oxidized LDL and the exposure to the Chlamydia Pneumonia infection were determined. DNA was collected for apolipoprotein E genotyping. The present paper outlines the primary aims of the CHARM study, the methodology involved and the recruitment results.

Age Factors↗

Celiac disease.

Explore the source record for details and available documents.

Adult↗

Prism adaptation can improve contralesional tactile perception in neglect.

The authors show that prismatic adaptation can reduce tactile inattention in stroke patients with unilateral neglect. Four patients with visuospatial neglect and tactile extinction underwent 10-minute application of 20 degrees right-shifting prismatic lenses during pointing. This improved contralesional tactile perception in all patients, even for a task requiring no exploration or spatial motor responses. This finding suggests a potential role for prismatic adaptation in the rehabilitation of multiple sensory modalities in patients with neglect.

Adaptation, Physiological↗

Reduced frequency of high cholesterol levels among patients with intracerebral haemorrhage.

To determine whether a relationship exists between high cholesterol levels and intracerebral haemorrhage (ICH) a case-control study was undertaken on 331 consecutive cases of first-episode primary ICH, verified by computed tomography, and 331 age- and sex-matched community controls. Using conditional logistic regression the adjusted odds ratio (OR) of ICH among individuals reporting a high cholesterol level was 0.45 [95% confidence interval (CI), 0.28-0.73]. A similar finding was observed when the analysis was limited to those using cholesterol-lowering drugs (OR 0.25; 95% CI, 0.08-0.80). These data provide support for an inverse relationship between high cholesterol levels and ICH. When considered together with previous findings, in which low cholesterol levels have been associated with an increased risk of haemorrhagic stroke, these data provide evidence that this inverse relationship may extend into a higher range of cholesterol values.

Aged↗

Effects of sediment bulk properties on erosion rates.

Considerable work has been done recently on the effects of sediment bulk properties on erosion rates. From this it is known that erosion rates depend on at least the following parameters: bulk density, average particle size, particle size distribution, mineralogy, organic content, volume of gas in the sediment, salinity of the pore waters, and time after deposition. This work is reviewed and discussed here with the purpose of presenting a quantitative overview of the effects of each of these parameters. This information is then used to demonstrate a procedure for estimating erosion rates of sediments based on a knowledge of their bulk properties.

Journal Article↗

Acceptance of a medical first-responder role by fire fighters.

STUDY OBJECTIVE: In July 1998, a pilot trial which used fire fighters as medical first-responders for the first time in Australia, was implemented in Melbourne. We aimed to assess the impact of the introduction of a medical first-responder role to the fire service, on the fire fighters both professionally and personally. METHODS: Focus groups were conducted at the fire stations located in the study area. Data from the focus groups was collated and examined for themes. The issues identified as important through the focus groups were then incorporated into a questionnaire. RESULTS: The fire fighters located at the pilot stations involved in the first-responder programme appear to view their new role as first-responders as a positive addition to their emergency profession. Some areas of the programme were identified by this study as in need of improvement. Some aspects of the communication strategies utilised by the Fire Brigade were highly criticised. Some aspects of the support system offered by the Fire Brigade also appear to be regarded as unfavourable. CONCLUSION: Results from this study provide useful information on professional fire fighter first-responder programmes and their impact on participating personnel. These results can be used to improve training modules, communication strategies and support services.

Adaptation, Psychological↗

A systematic review of predictors of maintenance of normotension after withdrawal of antihypertensive drugs.

BACKGROUND: The identification and treatment of hypertension in the general community has contributed to the reduction in strokes and coronary heart disease observed during the past 30 years. However, concerns have arisen that some patients may be receiving unnecessary antihypertensive drug therapy leading to wasted resources and the potential for adverse drug effects. Once therapy has been started, treating physicians have difficulty in selecting patients for withdrawal and have concerns regarding patient safety and their own legal liability. PROCEDURES: This study reviews and consolidates information from published studies to identify known predictors of the successful maintenance of normotension after antihypertensive drug withdrawal. The predictors were identified by determining the proportion of subjects with various baseline characteristics who remained normotensive while off medication for at least 12 months. From these data we have developed a clinical algorithm to help identify patients in whom antihypertensive drug withdrawal might be considered. This may assist primary care physicians in achieving successful withdrawal of antihypertensive therapy among selected hypertensive patients. RESULTS: The most consistent predictors identified were blood pressure (BP) (lower pretreatment, on treatment, and after withdrawal), nature of pharmacotherapy (fewer agents and lower dose), and preparedness to accept dietary intervention (weight and sodium reduction). CONCLUSIONS: On the basis of this information, a trial of withdrawal of antihypertensive medication might be recommended for patients who have mildly elevated, uncomplicated BP that is well controlled on a single agent, and who are motivated and likely to accept lifestyle changes.

Antihypertensive Agents↗

Predicted impact on Victoria's ambulance services of a new major trauma system.

BACKGROUND: In 1999, a new major trauma system was proposed for the state of Victoria, Australia. The guidelines for the new system were aimed at delivering major trauma cases to definitive trauma care in the least time possible. The aim of the present study was to analyse the potential effect of this system on Victoria's ambulance services. METHODS: The present study modelled the workload of major trauma cases in Victoria's ambulance service for one year pre- and post-introduction of the guidelines. Cases were analysed regarding whether their first hospital destination would change under the proposed guidelines, and, subsequently, whether they would require interhospital transport to a higher level trauma service. The impact on the ambulance services was modelled as annual changes in distances travelled due to predicted changes in hospital destinations. RESULTS: Analysis of the predicted changes indicated that, in general, Victoria's metropolitan and rural road ambulance crews would not be greatly affected. However, some metropolitan road crews may have to travel extra distances for up to 110 cases per year. The major impact was on air retrieval crews, where the annual number of interhospital transfers is predicted to increase from approximately 150 to 330. CONCLUSIONS: The present study demonstrated that most of the impact of a new trauma system on Victoria's ambulance services could be readily absorbed into the current workload. However, it also highlighted areas affected disproportionately within the ambulance services; in particular, air retrieval. Such studies are important to enable the effective implementation of new trauma systems.

Aged↗

Developing an information pack for the Asian carers of people with autism spectrum disorders.

An investigation is described which forms the basis for the development of an information package for the Asian carers of people with autism spectrum disorders (ASD) and learning disabilities. The results of semi-structured interviews and planning for questionnaires with three different linguistic Asian groups (Urdu, Gujarati and Bengali) are presented. The views, attitudes and awareness of autism, knowledge of support services and perceived priority of needs are analysed for the three different communities. The investigation concludes with recommendations as to whether separate information is needed by each culture or whether a single information pack can be used and presented in each language format. The possible presentation format in which the information can be produced is also discussed.

Asia↗

Compliance of Victorian dairy farmers with current calf rearing recommendations for control of Johne's disease.

Questionnaires were posted to 800 randomly selected registered Victorian dairy farmers in 1996. Five hundred and thirty-four responses were received and analysed. Johne's disease (JD) had been diagnosed on the farm of 13.2% of respondents in the last 5 years. JD was rated second only to neonatal diarrhoea in importance as a disease of calves, even though other diseases occurred more frequently. However, there was a low level of compliance with JD control recommendations by the respondents. There was no significant difference in the number of JD control recommendations adopted by farmers between the three major Victorian regions. There was a significant difference in compliance between farms having had a diagnosed case of JD and those that had not. Although there is awareness among dairy farmers of the importance of JD, there appears to be a poor implementation of measures by farmers to prevent the spread of the disease. Current JD control recommendations and the method of information transfer to Victorian dairy farms should be reassessed to ensure that dairy heifers are reared with minimal risk of transmission of JD.

Animals↗

Tracking COL1A1 RNA in osteogenesis imperfecta. splice-defective transcripts initiate transport from the gene but are retained within the SC35 domain.

This study illuminates the intra-nuclear fate of COL1A1 RNA in osteogenesis imperfecta (OI) Type I. Patient fibroblasts were shown to carry a heterozygous defect in splicing of intron 26, blocking mRNA export. Both the normal and mutant allele associated with a nuclear RNA track, a localized accumulation of posttranscriptional RNA emanating to one side of the gene. Both tracks had slightly elongated or globular morphology, but mutant tracks were cytologically distinct in that they lacked the normal polar distribution of intron 26. Normal COL1A1 RNA tracks distribute throughout an SC-35 domain, from the gene at the periphery. Normally, almost all 50 COL1A1 introns are spliced at or adjacent to the gene, before mRNA transits thru the domain. Normal COL1A1 transcripts may undergo maturation needed for export within the domain such as removal of a slow-splicing intron (shown for intron 24), after which they may disperse. Splice-defective transcripts still distribute thru the SC-35 domain, moving approximately 1-3 micrometer from the gene. However, microfluorimetric analyses demonstrate mutant transcripts accumulate to abnormal levels within the track and domain. Hence, mutant transcripts initiate transport from the gene, but are impeded in exit from the SC-35 domain. This identifies a previously undefined step in mRNA export, involving movement through an SC-35 domain. A model is presented in which maturation and release for export of COL1A1 mRNA is linked to rapid cycling of metabolic complexes within the splicing factor domain, adjacent to the gene. This paradigm may apply to SC-35 domains more generally, which we suggest may be nucleated at sites of high demand and comprise factors being actively used to facilitate expression of associated loci.

Adolescent↗

Efficacy testing of recombinant human immunodeficiency virus (HIV) gp160 as a therapeutic vaccine in early-stage HIV-1-infected volunteers. rgp160 Phase II Vaccine Investigators.

A phase II efficacy trial was conducted with recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein gp160 (rgp160) in 608 HIV-infected, asymptomatic volunteers with CD4+ cell counts >400 cells/mm3. During a 5-year study, volunteers received a 6-shot primary series of immunizations with either rgp160 or placebo over 6 months, followed by booster immunizations every 2 months. Repeated vaccination with rgp160 was safe and persistently immunogenic. Adequate follow-up and acquisition of endpoints allowed for definitive interpretation of the trial results. There was no evidence that rgp160 has efficacy as a therapeutic vaccine in early-stage HIV infection, as measured at primary endpoints (50% decline in CD4+ cell count or disease progression to Walter Reed stage 4, 5, or 6) or secondary endpoints. A transient improvement was seen in the secondary CD4 endpoint for the vaccination compared with the placebo arm, but this did not translate into improved clinical outcome.

AIDS Vaccines↗

Respiratory symptoms and lung function in two prebake aluminum smelters.

BACKGROUND: Respiratory symptoms are known to occur in some aluminum smelter employees working in the potroom department but little is known about the respiratory health of employees in other departments. METHODS: This cross-sectional study examined the prevalence of work-related respiratory symptoms and levels of lung function in different departments of two aluminum smelters compared to administration employees. Multiple logistic regression was performed with each of four work-related symptoms as outcomes and multiple linear regressions were performed with FEV1 and FVC as outcomes. RESULTS: There were 1,529 male participants in the two smelters representing a response rate of 89.6%. After adjusting for age and smoking, work-related respiratory symptoms were reported significantly more often among the ingot mill, anode, and potroom groups in Smelter A. In Smelter B, ingot employees were more likely to report work-related wheeze and potroom employees were more likely to report work-related rhinitis. Symptoms tended to increase with increasing time in the potrooms but were more likely to occur in new employees in the ingot mill and anode process groups. After adjusting for age, height, and smoking, there were no significant differences between the process groups for either FEV1 or FVC at Smelter A, and at Smelter B potroom employees had slightly greater FEV1 and FVC than the administration employees. CONCLUSIONS: Work-related respiratory symptoms among aluminum smelter workers are not reported only by potroom employees but also by ingot mill and anode employees.

Adult↗

Cross-subtype neutralizing antibodies induced in baboons by a subtype E gp120 immunogen based on an R5 primary human immunodeficiency virus type 1 envelope.

Global human immunodeficiency virus type 1 (HIV-1) diversity may require engineering vaccines to express antigens representing strains prevalent in the target population of vaccine testing. The majority (90%) of incident infections in Thailand are genetic subtype E, with a small percentage of subtype B infections in the intravenous drug user populations. We have evaluated and compared the binding and HIV-1 neutralizing properties of serum antibodies induced in baboons by CHO cell-expressed monomeric gp120 derived from a CCR5-using (R5) subtype E primary HIV-1CM235 or a CXCR4-using (X4) subtype B T-cell line-adapted (TCLA) HIV-1SF2 isolate. In contrast to the subtype-specific HIV-1 neutralizing antibodies induced with recombinant HIV-1SF2 gp120 (rgp120SF2), rgp120CM235 immunization induced antibodies capable of neutralizing both subtype E and subtype B TCLA HIV-1 isolates. However, neither immunogen induced antibodies capable of neutralizing primary HIV-1 isolates. Antibody induced by rgp120CM235 preferentially bound natively folded gp120 and retained strong cross-reactivity against multiple gp120 strains within subtype E as well as subtype B. In contrast, antibody responses to rgp120SF2 were directed predominantly to linear epitopes poorly exposed on native gp120 and had more limited cross-recognition of divergent gp120. Fine epitope mapping revealed differences in antibody specificities. While both rgp120CM235 and rgp120SF2 induced antibodies to regions within C1, V1/V2, V3, and C5, unique responses were induced by rgp120CM235 to multiple epitopes within C2 and by rgp120SF2 to multiple epitopes within C3, V4, and C4. These data demonstrate that strain and/or phenotypic differences of HIV-1 subunit gp120 immunogens can substantially alter antibody binding specificities and subsequent HIV-1 neutralizing capacity.

AIDS Vaccines↗

The oxidative inactivation of tissue inhibitor of metalloproteinase-1 (TIMP-1) by hypochlorous acid (HOCI) is suppressed by anti-rheumatic drugs.

Tissue inhibitors of metalloproteinases (TIMPs) prevent uncontrolled connective tissue destruction by limiting the activity of matrix metalloproteinases (MMPs). That TIMPs should be susceptible to oxidative inactivation is suggested by their complex tertiary structure which is dependent upon 6 disulphide bonds. We examined the oxidative inactivation of human recombinant TIMP-1 (hr TIMP-1) by HOCl and the inhibition of this process by anti-rheumatic agents. TIMP-1 was exposed to HOCl in the presence of a variety of disease modifying anti-rheumatic drugs. TIMP-1 activity was measured by its ability to inhibit BC1 collagenase activity as measured by a fluorimetric assay using the synthetic peptide substrate (DNP-Pro-Leu-Ala-Leu-Trp-Ala-Arg), best cleaved by MMP-1. The neutrophil derived oxidant HOCl, but not the derived oxidant N-chlorotaurine, can inactivate TIMP-1 at concentrations achieved at sites of inflammation. Anti-rheumatic drugs have the ability to protect hrTIMP-1 from inactivation by HOCl. For D-penicillamine, this effect occurs at plasma levels achieved with patients taking the drug but for other anti-rheumatic drugs tested this occurs at relatively high concentrations that are unlikely to be achieved in vivo, except possibly in a microenvironment. These results are in keeping with the concept that biologically derived oxidants can potentiate tissue damage by inactivating key but susceptible protein inhibitors such as TIMP-1 which form the major local defence against MMP induced tissue breakdown.

Animals↗

Localization of three genes in the hook-shaped hamster sperm nucleus by fluorescent in situ hybridization.

We mapped the positions of three different genes in the flat, hook-shaped hamster sperm nucleus to determine the specificity of sperm DNA positioning. The positions of the 5S rRNA gene cluster, the CAD gene, and the class I 1.6 gene were determined by fluorescent in situ hybridization (FISH) in over 50 hamster sperm nuclei for each gene. We first demonstrated by FISH with mitotic chromosomes that the latter two genes were localized on the same chromosome. Within the sperm nuclei, we found that the precise position was variable for each of the three genes, but that there were two areas of preferred localization that contained 26-31% of the nuclear area and within which 80% of the signals were located. Nuclei were then hybridized to two genes simultaneously, using either two genes located on the same chromosome or two genes located on different chromosomes. We found no preference for orientation of one gene relative to the other for either pair of genes examined. This suggested that the relative arrangements of chromosomes within the sperm nucleus are flexible. These data demonstrate that the topographical arrangements of genes within the hamster sperm nucleus have a limited plasticity allowing for a relatively large range of possible localization.

Animals↗