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Biomedical subjects

Robert J Adams

Publications and source records attributed to Robert J Adams.

At least 37 records · Page 2Linked to original sources

Elevated blood flow velocity in the anterior cerebral artery and stroke risk in sickle cell disease: extended analysis from the STOP trial.

Elevated velocity in the internal carotid artery (ICA) or middle cerebral artery (MCA), detected by transcranial Doppler (TCD) ultrasonography, predicts an increased risk of stroke in children with sickle cell disease (SCD). Although strokes also occur in an anterior cerebral artery (ACA) distribution, the significance of elevated velocity in this vessel has not been determined previously. We assessed the effect of elevated ACA velocity on stroke risk using the results of the first adequate TCD study performed on 1975 children as part of The Stroke Prevention Trial in Sickle Cell Anemia (STOP). Elevated ACA velocity (> or =170 cm/s) was associated with an increased risk of stroke (P = 0.0013) after adjusting for the ICA/MCA classification. Among subjects with normal ICA/MCA velocity, the risk of stroke was more than 10-fold greater in those with elevated compared with normal ACA velocity (2.13 and 0.20 per 100 patient-years, respectively, P < 0.001); risk more than doubled with elevated compared with normal ACA velocity in those already at high risk due to abnormal ICA/MCA findings (7.56 vs. 3.22 per 100 patient-years, P = 0.042). Few of the strokes in those with elevated ACA velocity occurred in an ACA distribution, suggesting changes in blood flow velocity in anterior vessels may be associated with diffuse arterial disease or, alternatively, manifest collateral flow from compromised middle cerebral vessels.

Adolescent↗

How valid are self-reported height and weight? A comparison between CATI self-report and clinic measurements using a large cohort study.

OBJECTIVE: To examine the relationship between self-reported and clinical measurements for height and weight in adults aged 18 years and over and to determine the bias associated with using household telephone surveys. METHOD: A representative population sample of adults aged 18 years and over living in the north-west region of Adelaide (n = 1,537) were recruited to the biomedical cohort study in 2002/03. A computer-assisted telephone interviewing (CATI) system was used to collect self-reported height and weight. Clinical measures were obtained when the cohort study participants attended a clinic for biomedical tests. RESULT: Adults over-estimated their height (by 1.4 cm) and under-estimated their weight (by 1.7 kg). Using the self-report figures the prevalence of overweight/ obese was 56.0% but this prevalence estimate increased to 65.3% when clinical measurements were used. The discrepancy in self-reported height and weight is partly explained by 1) a rounding effect (rounding height and weight to the nearest 0 or 5) and 2) older persons (65+ years) considerably over-estimating their height. CONCLUSION: Self-report is important in monitoring overweight and obesity; however, it must be recognised that prevalence estimates obtained are likely to understate the problem. IMPLICATIONS: The public health focus on obesity is warranted, but self-report estimates, commonly used to highlight the obesity epidemic, are likely to be underestimations. Self-report would be a more reliable measure if people did not round their measurements and if older persons more accurately knew their height.

Adolescent↗

Titanium surface modification and its effect on the adherence of Porphyromonas gingivalis: an in vitro study.

AIM: Titanium dental implants are an important treatment option in the replacement of missing teeth. Implant failures can, however, occur and may be promoted by the loss of tissue as a result of local bacterial infection (peri-implantitis). OBJECTIVES: Bacterial adherence to implant surfaces is believed to be influenced by material surface roughness and surface-free energy parameters. Consequently, the aim of this study was to modify these properties of titanium and identify what effect these modifications had on subsequent bacterial adherence. MATERIALS AND METHODS: In this study, 16 titanium samples of different roughness (R(a) 34.57-449.42 nm) were prepared using specific polishing procedures. A further six samples were chemically altered by argon plasma discharge treatment and immersion in silane solutions to produce different surface hydrophobicities. An in vitro adhesion assay using Porphyromonas gingivalis was used to assess the effect of modification on bacterial adherence. RESULTS: A significant reduction in adhesion to materials categorised as being 'very smooth' (R(a) 34.57+/-5.79 nm) was evident. This reduction did not occur with 'smooth' (R(a) 155.00+/-33.36 nm), 'rough' (R(a) 223.24+/-9.86 nm) or 'very rough' (R(a) 449.42+/-32.97 nm) surfaces. Changing material surface hydrophobicity was also not found to effect bacterial adhesion. CONCLUSIONS: Adhesion of P. gingivalis to titanium was inhibited at surface roughness levels below those generally encountered for implant collars/abutments (R(a) 350 nm). Considerations of these findings may be beneficial in the production of titanium implants in order to reduce bacterial colonisation.

Bacterial Adhesion↗

Coexistent chronic conditions and asthma quality of life: a population-based study.

OBJECTIVE: Reports of the prevalence and impact of comorbid conditions among people with asthma have been limited to certain population groups or convenience samples. Our aim was to examine the prevalence of major comorbidity in asthma and associations with quality of life and functional status in the general population. STUDY DESIGN/SETTING: The WANTS Health and Well-being Survey is a cross-sectional representative population household telephone interview survey in three Australian states. PARTICIPANTS: Representative sample of noninstitutionalized adults in three Australian states. MEASUREMENT AND RESULTS: From the available sample of 10,080 patients, 7,619 interviews were completed (participation rate, 74.8%), with 834 people reporting current doctor-diagnosed asthma (11.2%). People with asthma were more likely to report one of the selected comorbid conditions: diabetes, arthritis, heart disease, stroke, cancer, osteoporosis (adjusted odds ratio, 1.9; 95% confidence interval, 1.5 to 2.2). Among people with asthma, there were statistically and clinically significant decreases in usual activity levels and in Short Form-12 physical component summary scores when another chronic condition was also present. For those with any of the chronic conditions, the additional presence of asthma was associated with significant further impairment in quality of life in those aged > 35 years but not in younger adults. CONCLUSION: The significant reduction in quality of life associated with comorbidity in asthma has implications for disease management and organization of care, as well as for the design and external validity of single-disease clinical trials.

Activities of Daily Living↗

Characterization of an anti-lymphocyte function-associated antigen-1 antibody in a simian immunodeficiency virus-pig-tailed macaque (Macaca nemestrina) model.

The simian immunodeficiency virus (SIV)/pig-tailed macaque (Macaca nemestrina) model of acquired immune deficiency syndrome (AIDS) is a powerful system in which to study cell adhesion molecules and retroviral pathogenesis in vivo. Preliminary experiments were conducted to examine the role of lymphocyte function-associated antigen 1 (LFA-1) in early SIV infection in vivo by using an LFA-1 monoclonal antibody (MHM.23) specific to human LFA-1. In vitro studies revealed that at concentrations of > or = 20 microg/ml, MHM.23 blocked LFA-1-mediated adhesion and T-cell activation (>90%) of pig-tailed macaque peripheral blood mononuclear cells (PBMCs). In addition, SIVmac239 infection of macaque cells was inhibited in a dose-dependant manner by MHM.23. Administration of MHM.23 to pig-tailed macaques inhibited LFA-1-ICAM-1-mediated activity in vivo and maintained binding on macaque cells for < or = 4 d. Our in vitro studies indicated that at an MHM.23 concentration of 20 microg/ml, macaque PBMCs were completely saturated. Our in vivo studies determined that 5 mg/kg MHM.23 intravenously every 24 h was required to maintain saturating levels and inhibit LFA-1-ICAM-1 function in pig-tailed macaques.

Acquired Immunodeficiency Syndrome↗

Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease.

BACKGROUND: Prophylactic transfusion prevents strokes in children with sickle cell anemia who have abnormalities on transcranial Doppler ultrasonographic examination. However, it is not known how long transfusion should be continued in these children. METHODS: We studied children with sickle cell disease who had a high risk of stroke on the basis of a transcranial Doppler screening examination and who had received transfusions for 30 months or longer, during which time the Doppler readings became normal. The children were randomly assigned to continued transfusion or no continued transfusion. Children with severe stenotic lesions on cerebral magnetic resonance angiography were excluded. The composite primary end point was stroke or reversion to a result on Doppler examination indicative of a high risk of stroke. RESULTS: The study was stopped after 79 children of a planned enrollment of 100 underwent randomization. Among the 41 children in the transfusion-halted group, high-risk Doppler results developed in 14 and stroke in 2 others within a mean (+/-SD) of 4.5+/-2.6 months (range, 2.1 to 10.1) of the last transfusion. Neither of these events of the composite end point occurred in the 38 children who continued to receive transfusions. The average of the last two transcranial Doppler results before transfusion was started was the only predictor of the composite end point (P=0.05). CONCLUSIONS: Discontinuation of transfusion for the prevention of stroke in children with sickle cell disease results in a high rate of reversion to abnormal blood-flow velocities on Doppler studies and stroke. (ClinicalTrials.gov number, NCT00006182.)

Adolescent↗

Acute manganese administration alters dopamine transporter levels in the non-human primate striatum.

We used positron emission tomography (PET) to measure non-invasively the effect of acute systemic administration to manganese sulfate (MnSO4) on dopamine transporter (DAT) levels in the living non-human primate brain. Baboons received [11C]-WIN 35,428 PET scans to measure DAT levels before and after acute MnSO4 administration. In one animal, we observed a 46% increase in DAT binding potential (BP), a measure of DAT binding site availability, 1 week after Mn administration. DAT levels returned to baseline values at 4 months and remained constant at 10 months after treatment. A subsequent single MnSO4 injection to the same animal also resulted in a 57% increase in DAT-BP, 2 days after administration. In a second animal, a 76% increase in DAT-BP relative to baseline was observed at 3 days after Mn injection. In this animal, the DAT-BP returned to baseline levels after 1 month. Using in vitro receptor binding assays, we found that Mn inhibits [3H]-WIN 35,428 binding to rat striatal DAT with an inhibitory constant (Ki) of 2.0+/-0.3mM (n=4). Saturation isotherms and Scatchard analysis of [3H]-WIN 35,428 binding to rat striatal DAT showed a significant decrease (30%, p<0.001) in the maximal number of binding sites (Bmax) in the presence of 2mM MnSO4. No significant effect of Mn was found on binding affinity (Kd). We also found that Mn inhibits [3H]-dopamine uptake with an IC50 of 11.4+/-1.5mM (n=4). Kinetic studies and Lineweaver-Burk analysis showed a significant decrease (40%, p<0.001) in the maximal velocity of uptake (Vmax) with 5mM MnSO4. No significant effect of Mn was found on Michaelis-Menten constant (Km). These in vitro findings suggest that the increase in DAT levels in vivo following acute Mn administration may be a compensatory response to its inhibitory action on DAT. These findings provide helpful insights on potential mechanisms of Mn-induced neurotoxicity and indicate that the DAT in the striatum is a target for Mn in the brain.

Animals↗

REACH: clinical feasibility of a rural telestroke network.

BACKGROUND AND PURPOSE: Development of stroke networks is critical to bringing guideline-driven stroke care to rural, underserved areas. METHODS: A Web-based telestroke tool, REACH, was developed to provide a foundation for a rural stroke network that delivered acute stroke consults 24 hours per day 7 days per week to 8 rural community hospitals in Georgia. RESULTS: There were 194 acute stroke consults delivered. Thirty patients were treated with tissue plasminogen activator (tPA). The mean National Institutes of Health Stroke Score (NIHSS) was 15.4, and the median NIHSS was 12.5. The mean onset to treatment time (OTT) was 122 minutes. The OTT dropped from 143 minutes in the first 10 patients treated to 111 minutes in last 20 patients. Of the 30 patients treated with tPA, 23% (7) were treated in < or =90 minutes and 60% (18) were treated within 2 hours. There were no symptomatic intracerebral hemorrhages. CONCLUSIONS: The REACH telestroke system permits the rapid and safe use of tPA in rural community hospitals. Over time, the system became more efficient and OTT decreased.

Aged↗

Modulation of disease, T cell responses, and measles virus clearance in monkeys vaccinated with H-encoding alphavirus replicon particles.

Measles remains a major worldwide problem partly because of difficulties with vaccination of young infants. New vaccine strategies need to be safe and to provide sustained protective immunity. We have developed Sindbis virus replicon particles that express the measles virus (MV) hemagglutinin (SIN-H) or fusion (SIN-F) proteins. In mice, SIN-H induced high-titered, dose-dependent, MV-neutralizing antibody after a single vaccination. SIN-F, or SIN-H and SIN-F combined, induced somewhat lower responses. To assess protective efficacy, juvenile macaques were vaccinated with a single dose of 10(6) or 10(8) SIN-H particles and infant macaques with two doses of 10(8) particles. A dose of 10(8) particles induced sustained levels of high-titered, MV-neutralizing antibody and IFN-gamma-producing memory T cells, and most monkeys were protected from rash when challenged with wild-type MV 18 months later. After challenge, there was a biphasic appearance of H- and F-specific IFN-gamma-secreting CD4+ and CD8+ T cells in vaccinated monkeys, with peaks approximately 1 and 3-4 months after challenge. Viremia was cleared within 14 days, but MV RNA was detectable for 4-5 months. These studies suggest that complete clearance of MV after infection is a prolonged, phased, and complex process influenced by prior vaccination.

Aging↗

Undiagnosed asthma in older people: an underestimated problem.

WHAT WE NEED TO KNOW: Are older people with respiratory symptoms aware this could be asthma? Which explanations for undiagnosed asthma apply most commonly in older Australians with asthma? Can we improve awareness of asthma in older people with undiagnosed asthma? Is the possibility of asthma in older people firmly established on the general practitioners' radar screen? What reasons most often determine whether GPs perform spirometry in their practice? WHAT WE NEED TO DO: Conduct a representative population study to assess whether older Australians recognise respiratory symptoms as being asthma and are reporting these symptoms. Conduct and evaluate a pilot asthma health promotion program for older people. Conduct a controlled therapeutic trial of people with undiagnosed asthma to assess treatment benefits and produce treatment recommendations. Identify whether the prominence of asthma in older people can be brought to the attention of GPs. Analyse more carefully the issues associated with innovation of office spirometry.

Age Distribution↗

An algorithmic approach to diagnosing asthma in older patients in general practice.

WHAT WE NEED TO KNOW: How effective would an algorithm be in helping general practitioners diagnose asthma? What proportion of older people with undiagnosed asthma fail to recognise symptoms? What proportion of the population believe asthma does not occur in the older population? What systems or supports do GPs need to diagnose asthma more effectively? WHAT WE NEED TO DO: Work on developing a gold standard for asthma diagnosis. Develop prototype algorithms for general practice discussion. Conduct a general practice study to assess the effectiveness of an algorithm. In conjunction with GPs, develop a pilot program to increase awareness of the current asthma problem. Conduct focus-group research to identify why some people do not believe they can develop asthma for the first time in adult life. Conduct focus-group research to identify why some adults do not attribute asthma symptoms to asthma. Conduct focus groups with GPs to identify what support is needed to diagnose asthma more effectively. Consult with all stakeholders before an intervention is used. Evaluate any interventions used.

Aged↗

TCD in sickle cell disease: an important and useful test.

Sickle cell disease is associated with a high risk of stroke in the early years of childhood. The risk of a secondary stroke can be significantly reduced through chronic blood transfusions. Prevention of the first stroke (primary prevention) was made possible through the use of transcranial Doppler (TCD) US and demonstrated in a randomized clinical trial called the stroke prevention trial in sickle cell anemia (STOP). TCD results were classified as normal, conditional, abnormal or inadequate based on velocity readings in specific arterial segments. The MCA and ICA were carefully searched to find the highest velocity, and this was used to stratify patients as to stroke risk. Those with abnormal or high-risk TCD received either monthly blood transfusions or no transfusions, and those randomized to transfusion had a much better outcome in terms of stroke (one stroke, versus ten in the control group) and also fewer other medical problems while transfused. TCD screening is recommended for SCD patients to begin at 24 months of age and should be repeated every 6-12 months during early childhood. Transcranial Doppler imaging (TCDI) can be easier to use and learn and with a few adjustments can provide equivalent predictive power. Currently, TCD is the only recommended method for treatment selection for primary-stroke prevention. MRI and MRA can provide important information on the status of the brain and the blood vessels and, when abnormal, indicate greater risk. Although TCD cannot predict all strokes, TCD and TCDI offer an opportunity to apply an effective therapy for patients in this risk group and reduce many first-time strokes.

Anemia, Sickle Cell↗

Spirometric criteria for asthma: adding further evidence to the debate.

BACKGROUND: Objective assessments of pulmonary function are considered essential for the diagnosis of asthma. The degree of reversibility of FEV(1) considered supportive of asthma varies between international asthma guidelines. OBJECTIVE: We sought to compare the relative performance of international guideline reversibility criteria for identifying impairment in persons with a significant bronchodilator response (SBR) without an asthma diagnosis. METHODS: The North West Adelaide Health (Cohort) Study, a population biomedical study of 4060 subjects, conducted spirometry according to American Thoracic Society criteria. SBR was defined as postbronchodilator FEV(1) responses of at least 12% or 15% of baseline values, 9% of predicted values, or 400 mL. A self-completed questionnaire assessed current asthma (CA), respiratory symptoms, and participant demographics. RESULTS: The prevalence of CA was 9.4% (n = 380), whereas 1.3% (>/=400 mL) to 4.5% (>/=9% of predicted value) of participants demonstrated an SBR in the absence of CA. With the exception of the 9% predicted criterion, prebronchodilator mean FEV(1) (percent predicted) in those demonstrating an SBR but no CA was significantly worse than that in the CA group. Significantly more respiratory symptoms were experienced by the SBR groups than the group without asthma. Logistic regression analyses identified different characteristics of those classified by the following criteria: 12% and 15%, age of 40 years or greater and household income of less than $40,000; 9% predicted, household income of less than $40,000; 400 mL, male sex (odds ratio, 4.5; 95% CI, 2.1-9.3). CONCLUSIONS: Different criteria identify different persons, but SBR by any criteria was associated with significant respiratory impairment, some of which might be attributable to asthma. Postbronchodilator change as a percentage of predicted value was the least biased of the criteria.

Adult↗

Assessing patient satisfaction: implications for South Australian public hospitals.

This paper reports on the results from 2620 South Australians who participated in the 2003 Patient Evaluation of Hospital Services. Patients were found to be generally satisfied with the care, services and amenities provided, with a statewide overall score of 86.3. Satisfaction was lowest in the patients' assessment of their involvement in their own care and treatment. Three demographic factors (younger age, female sex or tertiary education) predicted lower levels of satisfaction in the multivariate analysis, whereas living with others, non-emergency admission or admission to smaller hospitals were found to predict higher satisfaction. Despite administrative and organisational difficulties, and limited current evidence of increased quality or satisfaction, it is considered important to continue satisfaction research with the goal of encouraging the development of action plans for improvement of care, services and amenities.

Adolescent↗

Participatory decision making, asthma action plans, and use of asthma medication: a population survey.

Use of controller asthma medication and possession of asthma action plans remains suboptimal. Our aim was to investigate the association of the propensity of physicians to involve patients in their care (participatory decision-making style) and their asthma management in a representative population sample of 3015 adults. Current doctor-diagnosed asthma was reported by 393 (13.0%). People who rated their doctors as more participatory were significantly more likely to report more regular use of controller medications and possession of a written asthma action plan, but not less asthma morbidity. Possession of a written action plan was associated with more participatory interactions (OR 2.3; 95% CI 1.1-4.7, for upper tertile scores compared to lowest tertile); more severe symptoms (OR 4.8; 95% CI 1.7-13.0), being female (OR 2.2; 95% CI 1.2-4.3), those with higher education, and residence outside the metropolitan area (OR 2.1; 95% CI 1.1-4.0). Increasing patient participation in their own care is associated with better asthma management, independent of asthma symptoms. Longitudinal studies are needed to examine if increasing participation in decisions can also improve asthma outcomes.

Adolescent↗