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Biomedical subjects

R Johnston

Publications and source records attributed to R Johnston.

At least 19 recordsLinked to original sources

Chlorine spot treatment of flooded tube wells, an efficacy trial.

AIMS: To evaluate the water quality of recently flooded tube wells in Bangladesh and the effect of spot chlorination on improving bacteriological quality. METHODS AND RESULTS: The study team identified and tested water samples from 127 tube wells that were flooded within the preceding 4 weeks. Twenty-six of the tube wells with the highest concentration of thermotolerant coliform bacteria were randomly assigned to spot chlorination vs control. On initial screening, water samples from 56 recently inundated tube wells (44%) were contaminated with thermotolerant coliforms. Among the 13 wells randomized to chlorination, there was no change in the proportion of water samples that had no detectable thermotolerant coliform bacteria immediately before chlorine treatment (n = 4, 23%) and 60 min following chlorine treatment (n = 4, 23%). Similarly, there was no difference in the proportion of water samples that had no detectable thermotolerant coliforms between chlorine spot treated and control tube wells 7-18 days later (31 vs 23%P = 0.66). CONCLUSIONS: Spot chlorine treatment of inundated tube wells in Bangladesh three to 6 weeks after the flooding did not improve drinking water quality. SIGNIFICANCE AND IMPACT OF THE STUDY: Unless modified methods improve effectiveness, resources should not be spent promoting spot chlorination of flooded tube wells.

Bangladesh↗

Creating SunSmart schools.

Kidskin was a sun-protection intervention study involving 1776 children attending 33 primary schools in Perth, Western Australia. There were three study groups: a control group, a moderate intervention group and a high intervention group. In addition to receiving a specially designed curricular intervention (1995-1998), the moderate and high intervention groups received an environmental intervention aimed at creating SunSmart schools (1996-1998). The environmental intervention focused on encouraging implementation of 'No hat, no play' policies and reducing sun exposure at lunchtime. In 1995 and 1998, observational methods were used to measure children's lunchtime sun exposure (i.e. polysulfone film badges) and hat wearing (i.e. video-taping of children). The proportion of children wearing broad-brimmed hats or legionnaire caps increased in seven of the eight high intervention schools between 1995 and 1998. In three schools, however, the impact was very positive with almost all children wearing these hats in 1998. There was no improvement in wearing these types of hats in either the moderate intervention group or the control group. In terms of sun exposure, there were only small non-significant differences among the three groups in terms of lunchtime sun exposure. The Kidskin program had a positive effect on hat wearing in the playground, but did not change children's use of shade at lunchtime. In this study, disseminating policy guidelines to schools using a mail-only strategy was ineffective, even when combined with an awards program. More information on 'champions' who bring about change in schools is required.

Child↗

Insulin-treated diabetes and driving in the UK.

Diabetes, and particularly insulin-treated diabetes, has important implications for motor vehicle driving, largely because of its association with potential hypoglycaemia. For this reason, most countries operate some driving restrictions on insulin-treated diabetic patients, as well as systems of intermittent reassessment of hypoglycaemic risk. In the UK, regulations are operated by the Driver and Vehicle Licensing Agency (DVLA), which is an agency of the Department of the Environment, Transport and the Regions (DETR). They are supported by an Expert Panel which advises the Secretary of State on diabetes-related issues relating to fitness to drive. The patient organization Diabetes UK is also concerned with diabetes and driving issues, largely from a position of lobbying policy-influencers and supporting individual cases. All parties involved with diabetes and driving issues recognize the need for more research on the subject, as the current literature is flawed in design, though no convincing excess of accidents amongst diabetic drivers has been conclusively demonstrated. Currently in the UK, Class 2 vehicles (large trucks and passenger vehicles) are barred to diabetic drivers on insulin. European law has recently extended this to so-called C1 (large vans and small lorries) and D1 (minibuses) vehicles, though the law has recently been revised to allow individual consideration for potential diabetic C1 drivers on insulin treatment. Diabetes and insulin-treated diabetes is an emotive and difficult issue, for which a stronger evidence base is urgently needed.

Automobile Driving↗

An evaluation of the performance of cDNA microarrays for detecting changes in global mRNA expression.

The cDNA microarray is one technological approach that has the potential to accurately measure changes in global mRNA expression levels. We report an assessment of an optimized cDNA microarray platform to generate accurate, precise and reliable data consistent with the objective of using microarrays as an acquisition platform to populate gene expression databases. The study design consisted of two independent evaluations with 70 arrays from two different manufactured lots and used three human tissue sources as samples: placenta, brain and heart. Overall signal response was linear over three orders of magnitude and the sensitivity for any element was estimated to be 2 pg mRNA. The calculated coefficient of variation for differential expression for all non-differentiated elements was 12-14% across the entire signal range and did not vary with array batch or tissue source. The minimum detectable fold change for differential expression was 1.4. Accuracy, in terms of bias (observed minus expected differential expression ratio), was less than 1 part in 10 000 for all non-differentiated elements. The results presented in this report demonstrate the reproducible performance of the cDNA microarray technology platform and the methods provide a useful framework for evaluating other technologies that monitor changes in global mRNA expression.

Analysis of Variance↗

Physical and transcript map of the dominant optic atrophy (OPA1) gene critical region at 3q28-q29.

The dominant optic atrophy gene (OPA1) has previously been mapped to chromosome 3q28-q29. We have now constructed a physical and transcriptional map across the OPA1 critical region between markers D3S3557 and D3S3346. It comprises 21 sequence-tagged sites (STSs), 4 single nucleotide polymorphisms, 29 expressed sequence tags, 2 known genes, and 12 newly generated STSs anchored onto 21 yeast artificial chromosome, 22 bacterial artificial chromosome, 48 P1 phage artificial chromosome, and 42 cosmid overlapping clones spanning 2.5 Mb. The map has allowed us to order many of the markers hitherto only roughly defined and to exclude 23 of the putative candidate genes assigned to the region. We found the OPA1 critical interval to be 450-550 kb. It contains 2 known genes, RPL35a and SDHA, which thus constitute candidate genes.

Chromosomes, Human, Pair 3↗

Complications and prognostic factors in Vogt-Koyanagi-Harada disease.

PURPOSE: To identify associations between complications of disease and final visual acuity in patients with Vogt-Koyanagi-Harada disease and to identify prognostic factors for disease outcome. METHODS: All patients diagnosed with Vogt-Koyanagi-Harada disease at the Doheny Eye Institute or the Los Angeles County/University of Southern California Medical Center between 1983 and 1997 were reviewed. Data extracted included initial and final visual acuities, age, gender, ethnicity, complications, treatment, duration of disease, and number of recurrences. RESULTS: One hundred one patients with Vogt-Koyanagi-Harada disease were identified, 68 (67%) of which were female. Mean age was 34 +/- 14 years (range, 8 to 75 years). Asians presented at a significantly older age than all other groups. One hundred three eyes (51%) developed at least one complication, including cataract in 84 eyes (42%), glaucoma in 54 eyes (27%), choroidal neovascular membranes in 22 eyes (11%), and subretinal fibrosis in 13 eyes (6%). Patients who developed at least one complication had a significantly longer median duration of disease and number of recurrent episodes of inflammation (P =.0001 for each) than did those patients who developed no complications. Statistically significant associations existed between poor final visual acuity and greater numbers of complications (P =.001), greater age at onset (P =.03), a longer median duration of disease (P =.03), and greater number of recurrent episodes of inflammation (P =.0004). Eyes possessing a better visual acuity at presentation were more likely to have a better visual acuity at final follow-up (P =.001). CONCLUSIONS: Factors associated with a worse final acuity included increasing numbers of complications, greater age at onset, and worse acuity at presentation.

Adolescent↗

Reduced sun exposure and tanning in children after 2 years of a school-based intervention (Australia).

OBJECTIVE: This paper presents the results of the evaluation of measured suntan and parent-reported sun exposure in participating children after 2 years of the Kidskin study, a 5-year school-based sun protection intervention undertaken in Perth, Western Australia (1995-1999). METHODS: The study involves three groups: a control, a "moderate", and a "high" intervention group. Participants were 5 or 6 years of age at the beginning of the study. Control schools received the standard Health Education curriculum, while intervention schools received a multicomponent intervention including a specially designed curriculum. Children in the high intervention group also received program materials over the summer vacation and were offered sun-protective swimwear at low cost. At the end of the second summer, suntan was measured and parents completed a questionnaire about their child's sun-related behavior. RESULTS: Children in the intervention groups--especially the high group--were less tanned at the end of the summer; this effect was greater for the back than for the forearms. These children were also reported to have received less sun exposure and made greater use of sun protection measures. CONCLUSION: Intensive school-based interventions can reduce tanning and reported sun exposure in children.

Child↗

Analysis of chimaerism in thalassaemic children undergoing stem cell transplantation.

We have prospectively assessed the relative contribution of host and donor to haemopoiesis following stem cell transplantation (SCT) in children with beta-thalassaemia major (n = 35), using karyotype analysis or Southern blot/polymerase chain reaction analysis of variable number tandem repeats on genomic DNA from peripheral blood. Early haemopoiesis was fully donor in origin in 24 out of 35 cases and remained so throughout the post-transplant course in all but one patient, who evolved to stable mixed chimaerism. The remaining 11 cases (31%) initially showed mixed chimaerism: four of these rejected, one eventually eradicated host haemopoiesis to become fully donor haemopoietic, and the remaining six had persistent mixed chimaerism, with 5--38% host haemopoiesis. The risk of graft rejection was high when > 15% host haemopoiesis was present at 3 months post transplant: four out of six such patients rejected their grafts; conversely, zero out of 29 patients with < 15% host haemopoiesis at 3 months rejected (P < 0.0001). There was a higher incidence of significant acute and chronic graft-versus-host disease in patients with full donor chimaerism. These studies confirm that the mixed chimaeric state is common following SCT for thalassaemia, often persists (with up to 4 years follow-up) and is compatible with long-term cure. Analysis of chimaerism in patients undergoing SCT for beta-thalassaemia enables monitoring of engraftment in the early post-transplant period, provides insight into the biology of engraftment and may be useful in identifying patients at high risk of rejection.

ABO Blood-Group System↗

[Monetary value of breast milk in Bolivia].

OBJECTIVE: To estimate the volume of breast milk consumed by Bolivian children under 36 months of age, and the monetary value of replacing that volume of breast milk with commercial substitutes. METHODS: The analysis took into account the distribution of the infant population by age groups, the prevalence of breast-feeding practices (exclusive or partial) in every age group, the average volume of breast milk consumed by the infants of a given age group, and the cost of breast milk production and replacement. RESULTS: Bolivian infants annually consume more than 161 million liters of breast milk, which represents an average volume of 573 mL/day per infant under 1 year of age. The monetary value of breast milk consumed by the Bolivian infants amounts to US$ 274 million annually. The average cost of replacing breast milk with commercial substitutes for an infant adequately breast-fed for the first year of life would be US$ 407. DISCUSSION: For the formulation and consolidation of policies and programs to protect, promote, and support breast-feeding to become a reality, it is necessary that the political leaders of Bolivia be aware of the enormous monetary value of breast milk.

Bolivia↗

Influenza virus (A/HK/156/97) hemagglutinin expressed by an alphavirus replicon system protects chickens against lethal infection with Hong Kong-origin H5N1 viruses.

Venezuelan equine encephalitis virus replicon particles (VRP) containing the gene expressing hemagglutinin (HA) from the human Hong Kong Influenza A isolate (A/HK/156/97) were evaluated as vaccines in chicken embryos and young chicks. Expressed HA was readily detected in bird-tissue staining with anti-H5 HA antibody and in chicken cells infected with the replicon preparations following immunoprecipitation with monoclonal antibody. Birds challenged with a dose of the lethal parent virus were protected to different extents depending on the age of the bird. In ovo and 1-day-old inoculated animals that received no boost with the VRP were partially protected; birds 2 weeks of age were completely protected with a single dose of VRP.

Age Factors↗

Development of a toxicological gene array and quantitative assessment of this technology.

High-density arrays of DNA bound to solid substrates offer a powerful approach to identifying changes in gene expression in response to toxicants. While DNA arrays have been used to explore qualitative changes in gene regulation, less attention has focused on the quantitative aspects of this technology. Arrays containing expressed sequence tags for xenobiotic metabolizing enzymes, proteins associated with glutathione regulation, DNA repair enzymes, heat shock proteins, and housekeeping genes were used to examine gene expression in response to beta-naphthoflavone (beta-NF). Upregulation of cytochrome P4501a1 (Cyp1a1) and 1a2 in mouse liver was maximal 8 h after beta-NF administration. Significant upregulation of Cyp1a2 was noted at beta-NF doses as low as 0.62 and 1.2 mg/kg when gene expression was measured by microarray or Northern blotting, respectively. Maximal Cyp1a2 induction is 5-fold by Northern analysis and 10-fold by microarray. Induction of Cyp1a1 was 15- and 20-fold by Northern and microarray analysis, respectively. The coefficient of variation for spot to spot and slide to slide comparisons was <15%; this variability was smaller than interanimal variability (18-60%). Comparison of mRNA expression in control animals indicated that there are differences in labeling/detection associated with Cy3/Cy5 dyes; accordingly, experiments must include methods for establishing baseline signals for all genes. We conclude that the dynamic range and sensitivity of DNA microarrays on glass slides is comparable to Northern blotting analysis and that variability of the data introduced during spotting and hybridization is less than the interanimal variability.

Animals↗

Simvastatin-induced rhabdomyolysis in an HIV-infected patient with coronary artery disease.

As greater numbers of human immunodeficiency virus (HIV)-infected individuals live to middle-age and beyond, there is growing concern that elevated cholesterol and lipid values will lead to cardiovascular complications in such patients. Furthermore, several of the highly active antiretroviral therapies (HAART) used to reduce levels of circulating HIV and extend acquired immunodeficiency syndrome (AIDS)-related survival are associated with a rise in plasma lipids. Anecdotal reports suggest such rises may be linked to cardiovascular complications. Herein, we review the case of a 74-year-old HIV-infected man with advanced coronary artery disease. He was prescribed simvastatin for control of hyperlipidemia and within 4 weeks developed muscle pain, proximal muscle weakness, myoglobinuria, and a markedly elevated creatinine phosphokinase (CPK). Simvastatin was discontinued, and rhabdomyolysis improved rapidly with conservative care. This report emphasizes this rare, but potentially significant, side effect of statin anticholesterol agents. Medical providers who prescribe statins must remember to check CPK levels when their HIV-infected patients complain of muscle pain. Discontinuing the offending drug will usually result in rapid diminution of muscle pain and inflammation and improve muscle strength.

Aged↗

An industry, clinical, and academic telehealth partnership venture: progress, goals achieved, and lessons learned.

The goal of this project was to develop and test a multi-application telehealth workstation with an interface seamless to the end-users. This project required collaboration among the private sector, a clinical regional referral setting, a clinical tertiary receiving center, and a university academic unit. The project applied the usability testing methodology to design and test the workstation: (1) the developmental phase focused on planning, prototype workstation development, and end-user trials in the private sector research and development environment, and (2) the operational testing phase moved the workstation into the clinical setting. The latter included training of end-users and addressing policy and ethical issues. In addition, the partners documented the goals achieved and lessons learned. The project resulted in the refinement of the workstation for clinical applications. The unique, diverse, and at times complementary goals and lessons learned by each partner are noted. Collaboration around a shared goal was a key element in achieving the refined workstation. Collaborators reported that the lessons learned will aid them as they pursue telehealth activities.

Alberta↗

Improved sun protection behaviour in children after two years of the Kidskin intervention.

OBJECTIVE: To evaluate a school-based intervention in terms of reducing children's sun exposure and improving their use of sun protection measures. METHODS: 'Kidskin' is a five-year, school-based intervention study in Perth, Western Australia, of a cohort of children who were five or six years old in 1995. The study involves three groups: control, 'moderate' and 'high' intervention. Children in the control schools received the standard health curriculum; those in the intervention schools received a multicomponent intervention, including a specially designed curriculum. Children in the high intervention group also received program materials over the summer holidays and were offered sun-protective swimwear at a low cost. After two years, parents completed a questionnaire about their child's sun-related behavior. RESULTS: Children in the intervention groups--especially the 'high' group--were reported to have had less sun exposure. This involved covering the back more often, spending more time in the shade when outdoors and wearing a style of swimsuit that covered the trunk. There was also evidence that children in the intervention groups spent less time outdoors in the middle of the day. There was little difference between groups in the wearing of hats or sunscreen. CONCLUSIONS: Our school-based intervention improved children's sun protection, but had little effect on specific behaviours that have already been vigorously promoted. IMPLICATIONS: School-based prevention campaigns would benefit from focusing on sun protection using clothing and shade, and reducing sun exposure in the middle of the day. There may be little potential to improve hat and sunscreen use.

Child↗

Telelearning in a partnership between a university faculty and a regional health authority: benefits, challenges and strategies.

The University of Calgary's Faculty of Medicine and the Calgary Regional Health Authority understand that telehealth is an evolving field requiring both academic enquiry and operational readiness. Both parties are committed to quality educational programmes--the Faculty through its commitment to excellence and the Authority with its charge to maintain and enhance such programmes. There are shared applications, multi-learner user groups, shared strategies to overcome distances and shared infrastructure--technologies, communication pathways and resources. Having embarked on a joint telelearning venture, we have learned a number of lessons. Central to progress has been an appreciation and respect for unique mandates, a spirit of trust and flexibility, an agreement on a set of principles, ongoing communication between and participation from the users and, at times, redirection. Questions being answered include the following. How well is this collaborative model working? How functional is it at this time of health reform and restructuring? Can one meet complementary telelearning goals within a faculty-health authority relationship? These all have implications for future success.

Canada↗