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Biomedical subjects

David Bates

Publications and source records attributed to David Bates.

At least 19 recordsLinked to original sources
PubMed2006

Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation.

Neuroferritinopathy is a progressive potentially treatable adult-onset movement disorder caused by mutations in the ferritin light chain gene (FTL1). Features overlap with common extrapyramidal disorders: idiopathic torsion dystonia, idiopathic Parkinson's disease and Huntington's disease, but the phenotype and natural history have not been defined. We studied a genetically homogeneous group of 41 subjects with the 460InsA mutation in FTL1, documenting the presentation, clinical course, biochemistry and neuroimaging. The mean age of onset was 39.4 years (SD = 13.3, range 13-63), beginning with chorea in 50%, focal lower limb dystonia in 42.5% and parkinsonism in 7.5%. The majority reported a family history of a movement disorder often misdiagnosed as Huntington's disease. The disease progressed relentlessly, becoming generalized over a 5-10 year period, eventually leading to aphonia, dysphagia and severe motor disability with subcortical/frontal cognitive dysfunction as a late feature. A characteristic action-specific facial dystonia was common (65%), and in 63% there was asymmetry throughout the disease course. Serum ferritin levels were low in the majority of males and post-menopausal females, but within normal limits for pre-menopausal females. MR brain imaging was abnormal on all affected individuals and one presymptomatic carrier. In conclusion, isolated parkinsonism is unusual in neuroferritinopathy, and unlike Huntington's disease, cognitive changes are absent or subtle in the early stages. Depressed serum ferritin is common and provides a useful screening test in routine practice, and gradient echo brain MRI will identify all symptomatic cases.

Adolescent↗
PubMed2006

Increased axonal mitochondrial activity as an adaptation to myelin deficiency in the Shiverer mouse.

Axonal pathology in multiple sclerosis (MS) has been described for over a century, but new insights into axonal loss and disability have refocused interest in this area. There is evidence of oxidative damage to mitochondrial DNA in chronic MS plaques, suggesting that mitochondrial failure may play a role in MS pathology. We propose that in the chronic absence of myelin the maintenance of conduction relies partially on an increase in mitochondria to provide energy. This increased energy requirement also promotes reactive oxygen species (ROS), because most intraaxonal ROS are generated by mitochondria. If antioxidant defenses are overwhelmed by an excess of ROS, this may result in damage to the axon. Our aim was to investigate whether a chronic lack of myelin results in adaptive changes involving mitochondria within the axon. We investigated this in the shiverer mouse. This myelin basic protein gene mutant provides a model of how adult central nervous system (CNS) axons cope with the chronic absence of a compact myelin sheath. Cytochrome c histochemistry demonstrated a twofold increase in mitochondrial activity in white matter tracts of shiverer, and electron microscopy confirmed a significantly higher number of mitochondria within the dysmyelinated axons. Our data demonstrate that there are adaptive changes involving mitochondria occurring within CNS axons in shiverer mice in response to a lack of myelin. This work contributes to our understanding of the adaptive changes occurring in response to a lack of myelin in a noninflammatory environment similar to the situation seen in chronically demyelinated MS plaques.

Adaptation, Physiological↗
PubMed2006

Selecting indicators for patient safety at the health system level in OECD countries.

BACKGROUND: Concerns about patient safety have arisen with growing documentation of the extent and nature of harm. Yet there are no robust and meaningful data that can be used internationally to assess the extent of the problem and considerable methodological difficulties. PURPOSE: This article describes a project undertaken as part of the Organization for Economic Cooperation and Development (OECD) Quality Indicator Project, which aimed at developing an initial set of patient safety indicators. METHODS: Patient safety indicators from OECD countries were identified and then rated against three principal criteria: importance to patient safety, scientific soundness, and potential feasibility. Although some countries are developing multi-source monitoring systems, these are not yet mature enough for international exchange. This project reviewed routine data collections as a starting point. RESULTS: Of an initial set of 59 candidate indicators identified, 21 were selected which cover known areas of harm to patients. CONCLUSIONS: This project is an important initial step towards defining a usable set of patient safety indicators that will allow comparisons to be made internationally and will support mutual learning and quality improvement in health care. Measures of harm should be complemented over time with measures of effective improvement factors.

Benchmarking↗
PubMed2005

Health care IT collaboration in Massachusetts: the experience of creating regional connectivity.

The state of Massachusetts has significant early experience in planning for and implementing interoperability networks for exchange of clinical and financial data. Members of our evolving data-sharing organizations gained valuable experience that is of potential benefit to others regarding the governance, policies, and technologies underpinning regional health information organizations. We describe the history, roles, and evolution of organizations and their plans for and success with pilot projects.

Clinical Pharmacy Information Systems↗
PubMed2005

Chromosome and replisome dynamics in E. coli: loss of sister cohesion triggers global chromosome movement and mediates chromosome segregation.

Chromosome and replisome dynamics were examined in synchronized E. coli cells undergoing a eukaryotic-like cell cycle. Sister chromosomes remain tightly colocalized for much of S phase and then separate, in a single coordinate transition. Origin and terminus regions behave differently, as functionally independent domains. During separation, sister loci move far apart and the nucleoid becomes bilobed. Origins and terminus regions also move. We infer that sisters are initially linked and that loss of cohesion triggers global chromosome reorganization. This reorganization creates the 2-fold symmetric, ter-in/ori-out conformation which, for E. coli, comprises sister segregation. Analogies with eukaryotic prometaphase suggest that this could be a primordial segregation mechanism to which microtubule-based processes were later added. We see no long-lived replication "factory"; replication initiation timing does not covary with cell mass, and we identify changes in nucleoid position and state that are tightly linked to cell division. We propose that cell division licenses the next round of replication initiation via these changes.

Chromosome Mapping↗
PubMed2005

Spectrum of movement disorders in neuroferritinopathy.

Neuroferritinopathy is a recently recognized, dominantly inherited movement disorder caused by a mutation of the ferritin light chain gene. We present video case reports of 4 individuals with neuroferritinopathy chosen to illustrate how this disorder can present and subsequently progress clinically. The clinical phenotype of this disorder is highly variable with symptoms beginning in the third to sixth decades. Chorea, dystonia, or an akinetic-rigid syndrome can predominate in different individuals. Neuroferritinopathy is not restricted to the UK and it has been described in apparently sporadic cases. The diagnosis should therefore be considered in patients with a wide variety of different movement disorders. Characteristic neuroimaging assists in identifying affected individuals.

Ferritins↗
PubMed2005

Subclinical semitendinosus and obturator externus involvement defines an autosomal dominant myopathy with early respiratory failure.

We recently described a dominant limb myopathy characterised by early respiratory failure whilst affected individuals were still ambulant (autosomal dominant myopathy with early respiratory failure). Early diagnosis and exclusion of this disorder is difficult because of the insidious onset in late adult life and the highly selective muscle involvement, both clinically and pathologically. We performed muscle magnetic resonance imaging on seven cases of autosomal dominant myopathy with early respiratory failure (age range 37-66 years, 4 male) and show selective early involvement of semitendinosus and obturator externus on magnetic resonance imaging that cannot be detected clinically, with different rates of progression in closely related muscles. These findings are specific to autosomal dominant myopathy with early respiratory failure and enable early non-invasive diagnosis for individuals at risk.

Female↗
PubMed2005

The Escherichia coli baby cell column: a novel cell synchronization method provides new insight into the bacterial cell cycle.

We describe a new method for synchronizing bacterial cells. Cells that have transiently expressed an inducible mutant 'sticky' flagellin are adhered to a volume of glass beads suspended in a chromatography column though which growth medium is pumped. Following repression of flagellin synthesis, newborn cells are eluted from the column in large quantities exceeding that of current baby machine techniques by approximately 10-fold. Eluted cultures of 'baby cells' are highly synchronous as determined by analysis of DNA replication, cell division and other events, over time after elution from the column. We also show that use of 'minutes after elution' as a time metric permits much greater temporal resolution among sequential chromosomal events than the commonly used metric of cell size (length). The former approach reveals the existence of transient intermediate stages that are missed by the latter approach. This finding has two important implications. First, at a practical level, the baby cell column is a particularly powerful method for temporal analysis. Second, at a conceptual level, replication-related events are more tightly linked to cell birth (i.e. cell division) than to absolute cell mass.

Adhesins, Bacterial↗
PubMed2004

The effect of air pollution on lung development from 10 to 18 years of age.

BACKGROUND: Whether exposure to air pollution adversely affects the growth of lung function during the period of rapid lung development that occurs between the ages of 10 and 18 years is unknown. METHODS: In this prospective study, we recruited 1759 children (average age, 10 years) from schools in 12 southern California communities and measured lung function annually for eight years. The rate of attrition was approximately 10 percent per year. The communities represented a wide range of ambient exposures to ozone, acid vapor, nitrogen dioxide, and particulate matter. Linear regression was used to examine the relationship of air pollution to the forced expiratory volume in one second (FEV(1)) and other spirometric measures. RESULTS: Over the eight-year period, deficits in the growth of FEV(1) were associated with exposure to nitrogen dioxide (P=0.005), acid vapor (P=0.004), particulate matter with an aerodynamic diameter of less than 2.5 microm (PM(2.5)) (P=0.04), and elemental carbon (P=0.007), even after adjustment for several potential confounders and effect modifiers. Associations were also observed for other spirometric measures. Exposure to pollutants was associated with clinically and statistically significant deficits in the FEV(1) attained at the age of 18 years. For example, the estimated proportion of 18-year-old subjects with a low FEV(1) (defined as a ratio of observed to expected FEV(1) of less than 80 percent) was 4.9 times as great at the highest level of exposure to PM(2.5) as at the lowest level of exposure (7.9 percent vs. 1.6 percent, P=0.002). CONCLUSIONS: The results of this study indicate that current levels of air pollution have chronic, adverse effects on lung development in children from the age of 10 to 18 years, leading to clinically significant deficits in attained FEV(1) as children reach adulthood.

Adolescent↗
PubMed2003

Breathless in Los Angeles: the exhausting search for clean air.

Population growth and the proliferation of roadways in Southern California have facilitated a glut of mobile air pollution sources (cars and trucks), resulting in substantial atmospheric pollution. Despite successful efforts over the past 40 years to reduce pollution, an alarming set of health effects attributable to air pollution have been described in Southern California. The Children's Health Study indicates that reduced lung function growth, increased school absences, asthma exacerbation, and new-onset asthma are occurring at current levels of air pollution, with sizable economic consequences. We describe these findings and urge a more aggressive effort to reduce air pollution exposures to protect our children's health. Lessons from this "case study" have national implications.

Absenteeism↗
PubMed2003

Controversies across continents. Report from the MS Forum Symposium, September 2002, Baltimore, USA.

The personal views of speakers from North America and Europe concerning the diagnosis and management of people with multiple sclerosis (MS) were presented at an MS Forum symposium before ACTRIM/ECTRIMS Meeting in Baltimore, USA. There were more areas of agreement than controversy and the overall impression was that MS is managed similarly across the continents. Four topics were discussed: diagnosing the clinically isolated syndrome; guidelines for using disease-modifying therapy; people who fail to respond to disease-modifying treatment; and treating the patient with rapid deterioration to disability.

Attitude of Health Personnel↗
PubMed2003

ZD-6474. AstraZeneca.

ZD-6474, one of a series of inhibitors of vascular endothelial growth factor receptor tyrosine kinase, which also has activity against the epidermal growth factor receptor tyrosine kinase, is under development by AstraZeneca for the potential treatment of solid tumors. Phase II trials in non-small-cell lung cancer, small-cell lung cancer and myeloma were ongoing in January 2003.

Animals↗
PubMed2002

Clinical use of bone densitometry: scientific review.

CONTEXT: Osteoporosis causes substantial morbidity and costs $13.8 billion annually in the United States. Measurement of bone mass by densitometry is a primary part of diagnosing osteoporosis and deciding a preventive treatment course. Bone mineral densitometry has become more widely available and commonly used in practice. OBJECTIVE: To review evidence about the value of various clinical applications of bone densitometry. DATA SOURCES: A MEDLINE search was performed to update previous meta-analyses of the relationship between various measurements of bone density and risk of vertebral and hip fracture. We used data from the prospective Study of Osteoporotic Fractures to estimate risk of fracture from bone density and age in postmenopausal women. STUDY SELECTION AND DATA EXTRACTION: When available, meta-analyses and systematic reviews are emphasized in the review. DATA SYNTHESIS: Bone mineral density (BMD) predicts fracture and can be used in combination with age to estimate absolute risk of fractures in postmenopausal white women. Hip BMD predicts hip fracture more strongly than other measurements of BMD. There are insufficient data to translate BMD results into risk of fracture for men and nonwhite women. The benefits of treatments to prevent fractures depend on BMD: women with osteoporosis have a greater risk of fractures and greater benefit from treatments than women without osteoporosis. CONCLUSIONS: Guidelines based on systematic reviews and a cost-effectiveness analysis have suggested that it is worthwhile to measure BMD in white women older than 65 years and perhaps to use risk factors to select younger postmenopausal women for densitometry. Other potential clinical applications of BMD that have not yet been adequately studied include screening men or nonwhite women, monitoring BMD in patients receiving treatment, and using BMD to identify patients who should be evaluated for secondary causes of osteoporosis.

Absorptiometry, Photon↗
PubMed2002

Normokalemic periodic paralysis revisited: does it exist?

Normokalemic periodic paralysis (normoKPP) is well established in the literature, but there are doubts as to whether it exists as a discrete entity. Retrospective clinical and molecular analysis has confirmed suspicions that most normoKPP families actually have a variant of hyperkalemic periodic paralysis (hyperKPP) due to a mutation of the muscle-specific sodium channel gene (SCN4A). However, the original normoKPP family described by Poskanzer and Kerr (Poskanzer DC, Kerr DNS. A third type of periodic paralysis, with normokalemia and favourable response to sodium chloride. Am J Med 1961;31:328-342) has remained unchallenged. We identified the Met1592Val mutation of SCN4A in an affected descendent of this original normoKPP family. This is the final piece in the puzzle: normoKPP is actually a variant of hyperKPP and is not a distinct disorder.

Adult↗