When the obvious is not so obvious.
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Diagnostic Errors↗
Biomedical subjects
D Russell
Publications and source records attributed to D Russell.
The use of multiple imputation for the analysis of missing data.
This article provides a comprehensive review of multiple imputation (MI), a technique for analyzing data sets with missing values. Formally, MI is the process of replacing each missing data point with a set of m > 1 plausible values to generate m complete data sets. These complete data sets are then analyzed by standard statistical software, and the results combined, to give parameter estimates and standard errors that take into account the uncertainty due to the missing data values. This article introduces the idea behind MI, discusses the advantages of MI over existing techniques for addressing missing data, describes how to do MI for real problems, reviews the software available to implement MI, and discusses the results of a simulation study aimed at finding out how assumptions regarding the imputation model affect the parameter estimates provided by MI.
Bias↗
Using the gross motor function measure to evaluate motor development in children with Down syndrome.
The purpose of this article is to describe our clinical experiences in using the Gross Motor Function Measure (GMFM) to evaluate motor development in children with Down syndrome and to provide strategies we found helpful in enhancing a child's adherence to standardized testing. The issues discussed are: (1) strategies for test administration; (2) modifications in administration and scoring; (3) reliability of the GMFM using the modified administration and scoring procedures; and (4) applications of the GMFM for clinical practice. The strategies and recommendations address the particular characteristics of children with Down syndrome and allow for their progress to be monitored relative to other children with Down syndrome rather than to children without motor delays. Future studies validating the use of specific goal areas for the administration and scoring of the GMFM for children with Down syndrome are recommended.
Activities of Daily Living↗
MEK kinase 1 gene disruption alters cell migration and c-Jun NH2-terminal kinase regulation but does not cause a measurable defect in NF-kappa B activation.
MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase that, in addition to regulating the c-Jun NH(2)-terminal kinase (JNK) pathway, is involved in the control of cell motility. MEKK1(-/-) mice are defective in eyelid closure, a TGFalpha-directed process involving the migration of epithelial cells. MEKK1 expression in epithelial cells stimulates lamellipodia formation, a process required for cell movement. In addition, mouse embryo fibroblasts derived from MEKK1(-/-) mice are inhibited in their migration relative to MEKK1(+/+) fibroblasts. MEKK1 is required for JNK but not NF-kappaB activation in response to virus infection, microtubule disruption, and stimulation of embryonic stem cells with lysophosphatidic acid. MEKK1 is not required for TNFalpha or IL-1 regulation of JNK or NF-kappaB activation in macrophages or fibroblasts. Thus, MEKK1 senses microtubule integrity, contributes to the regulation of fibroblast and epithelial cell migration, and is required for activation of JNK but not NF-kappaB in response to selected stress stimuli.
Animals↗
Pharmacological analysis of extracellular dopamine and metabolites in the striatum of conscious as/agu rats, mutants with locomotor disorder.
The as/agu rat is a spontaneously occurring mutation which exhibits locomotor abnormalities, reduced tyrosine hydroxylase levels in the substantia nigra and lower extracellular levels of dopamine. The animal could represent a model of some human locomotor disorders. High-potassium medium evoked a 460% rise of dopamine levels in control rats but double this in mutants. Amphetamine increased extracellular dopamine by 710% in controls and 1480% in mutants. Clorgyline produced a small increase of dopamine levels in controls but an 1170% increase in mutants. The uptake inhibitor nomifensine increased dopamine levels by 910% in controls but only 270% in mutants. After treatment with benserazide plus L-DOPA, an acute injection of L-DOPA evoked a release of dopamine which was twice as large in the as/agu rats compared with controls. The results show reduced extracellular dopamine in as/agu rats when the locomotor disorder is apparent, but there has been little loss of tyrosine hydroxylase. The responses to drugs are qualitatively different from those obtained using 6-hydroxydopamine.Overall, the effects of compounds affecting aminergic neurons suggest that one possible mechanism for the neuronal abnormality in as/agu rats is a defective regulation of dopamine release from striatal terminals.
Amphetamine↗
The AS/AGU rat: a spontaneous model of disruption and degeneration in the nigrostriatal dopaminergic system.
The AS/AGU rat provides an alternative to experimentally produced laboratory models of basal ganglia disorders. This mutant is characterised by disturbances of movement including clumsy gait, whole body tremor, rigidity and difficulty in initiating movement. From an early age, there is a profound depletion of extracellular dopamine in the dorsal caudate-putamen as measured via in vivo microdialysis; levels are only 10-20% of those found in the parent Albino Swiss (AS) strain. Subsequently a depletion of whole tissue dopamine levels occurs and, later still, loss of dopaminergic cells in the substantia nigra pars compacta. The dysfunction in movement and the nigrostriatal dopaminergic system are clearly linked, since movement can be ameliorated by L-DOPA administration. Furthermore, there are depletions in glucose utilisation in several regions of the basal ganglia circuitry, including the substantia nigra pars compacta, the subthalamic nucleus and the ventrolateral thalamus. The AS/AGU rat represents a unique opportunity to investigate the intrinsic factors controlling the integrity of dopaminergic systems and the recent successful positional cloning of the agu gene will allow the molecular mechanisms underlying this interesting phenotype to be analysed.
Animals↗
Capturing the paradigm shift in HIV treatment: changing attitudes in the choice of combination antiretroviral drugs by high HIV caseload Australian GPs (1996-1997).
The use of combination antiretroviral therapy for HIV infection is a rapidly changing field. To assess the impact of recent studies on prescribing patterns, two surveys of 21 high HIV caseload Australian GPs were undertaken in June 1996 and June 1997 to plot changes in the choice of combination antiviral therapy. Of the 17 GPs who responded to the survey in each year, the number of HIV-infected patients seen at their practices were estimated to be 5,061 in 1996 and 5,912 in 1997. In 1996, 40% of their patients were estimated to be on antiretroviral therapy compared to 60% in 1997 (p < 0.05). In 1996, most GPs preferred using dual combination therapy (59%); whereas in 1997, triple combination therapy was preferred (82%). Between 1996 and 1997, there was a significant change by high caseload Australian GPs in the choice of antiretroviral drugs with many combinations being preferred prior to presentation of efficacy data for those combinations, or recommendation through national guidelines.
Anti-HIV Agents↗
Cp50 of propofol with and without nitrous oxide 67%.
The target concentration of propofol required to prevent response to surgical incision was determined in 60 unpremedicated ASA I or II patients, who breathed either oxygen-enriched air or nitrous oxide 67% in oxygen. Propofol was infused using a target-controlled infusion system incorporating the standard 'Diprifusor' pharmacokinetic model, with the target concentration for each patient decided by up/down sequential allocation. Presence or absence of movement in response to a groin incision was determined by the surgeon. The calculated blood concentration at which 50% of patients responded (Cp50calc), determined by probit analysis, was 6.8 micrograms ml-1 for patients who breathed oxygen-enriched air and 4.9 micrograms ml-1 for those who breathed nitrous oxide 67% in oxygen.
Adolescent↗
Characterization of ovarian carbonyl reductase gene expression during ovulation in the gonadotropin-primed immature Rat.
In this differential-display polymerase chain reaction-based study, four different primer sets generated cDNA fragments of ovarian carbonyl reductase genes that were uniquely expressed during the ovulatory process in eCG-primed immature rats. The temporal pattern of expression of this aldo-keto reductase gene was delineated by extracting ovarian RNA at 0, 2, 4, 8, 12, and 24 h after induction of ovulation via injection of the primed animals with hCG. The results showed that at least four homologous forms of this gene were transcribed during ovulation. Northern blot analyses indicated a 14-fold increase in ovarian mRNA for carbonyl reductase, with expression reaching a peak at 8 h after hCG treatment and then declining to negligible levels during the next 16 h. In situ hybridization revealed that most of the transcription was in the thecal connective tissue of the ovary and was absent from the granulosa layer of ovarian follicles. Treatment of the animals with ovulation-blocking doses of epostane (an inhibitor of progesterone synthesis) or indomethacin (an inhibitor of prostanoid synthesis) did not reduce the expression of ovarian carbonyl reductase. Nevertheless, the temporal pattern of expression of carbonyl reductase after the induction of ovulation suggests that this enzyme activity is at least indirectly associated with the ovulatory process.
Alcohol Oxidoreductases↗
Diagnostic dilemmas in Cushing's syndrome.
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Adult↗
High stakes testing: what is at stake?
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Deafness↗
Clinical and para-clinical tests in the routine examination of headache patients.
Para-clinical examinations in the diagnosis and treatment control of headache patients vary considerably between clinics and headache centers. Among the neurological societies in Europe there has been a consensus that some common procedures and recommendations should be created. In the Fall of 1998, the European Federation of Neurological Societies (EFNS) commissioned a Task Force on Neurophysiological Tests and Imaging Procedures in Headache Patients. Members of the Task Force are the present authors and we have reviewed the literature on 1) neurophysiological tests (EEG and evoked potentials), 2) autonomic nervous system and clinical tests and 3) imaging and cerebrovascular tests (X-ray, CT, MR, fMRI, PET, SPECT and transcranial Doppler). The literature was carefully evaluated with respect to validity and strength of the data. The task was to reach conclusions about each technique in the form of guidelines for clinical use. Finally, selected areas for future research will be outlined. The extensive review and the guidelines will be published by the EFNS during 2000.
Electroencephalography↗
Roundway, Wiltshire County Asylum attendants and nurses, 1881-1905: a window onto Victorian sobriety.
The only detailed surving Male and Female Registers of Roundway provide a rich documentary glimpse of nineteenth century mental health care staff. An analysis is made of what constituted desirable behavior and problems occurring in the workplace. More primary source material has been gathered from visitors books, medical superintendents' reports, patient case records, admission/discharge registers and account books. An attempt will be made to show how the dominant characteristics of Victorianism shaped the lives of the staff. Religion, morality and personal qualities appear more influential than scientific inquiry in determining the pattern of events. The 'Asylum for the Pauper Insane of the County of Wiltshire' later came to be called 'Roundway Hospital'. It is commonly remembered as 'Roundway' and that is how it is referred to here. The nursing staff changed their titles in minor ways during the period considered, but for convenience the dominant titles - 'attendants' for men and 'nurses' for women - are used. The period chosen, 1881-1905, begins from when Dr John Bowes was appointed Medical Superintendent and started to write in the new Staff Registers. The period finishes when he ceased to make entries. There are no detailed registers for any other nineteenth century period.
England↗
Comparative biotransformation studies of MeIQx and PhIP in animal models and humans.
MeIQx and PhIP are putative carcinogenic heterocyclic amines formed during the cooking of meat and fish. Using accelerator mass spectrometry, we have investigated the metabolism and macromolecule binding of 14C-labelled MeIQx and PhIP in human cancer patients compared to the rat. Following oral administration of MeIQx and PhIP, more DNA adducts were formed in human colon tissue compared with rats. Differences were also observed between rats and humans in the metabolite profile and urine excretion for these compounds. These results suggest humans metabolise heterocyclic amines differently to laboratory rodents and question their use as models of human risk.
Animals↗
Measuring outcomes in children's rehabilitation: a decision protocol.
OBJECTIVE: To develop and test the feasibility and clinical utility of a computerized self-directed software program designed to enable service providers in children's rehabilitation to make decisions about the most appropriate outcome measures to use in client and program evaluation. DESIGN: A before-and-after design was used to test the feasibility and initial impact of the decision-making outcome software in improving knowledge and use of clinical outcome measures. SETTING: A children's rehabilitation center in a city of 50,000. PARTICIPANTS: All service providers in the children's rehabilitation center. Disciplines represented included early childhood education, occupational therapy, physical therapy, speech and language pathology, audiology, social work, and psychology. INTERVENTION: Using a conceptual framework based on the International Classification of Impairment, Disability, and Handicap (ICIDH), an outcome measurement decision-making protocol was developed. The decision-making protocol was computerized in an educational software program with an attached database of critically appraised measures. Participants learned about outcome measures through the program and selected outcome measures that met their specifications. The computer software was tested for feasibility in the children's rehabilitation center for 6 months. OUTCOME MEASURES: Knowledge and use of clinical outcome measures were determined before and after the feasibility testing using a survey of all service providers currently at the centre and audits of 30 randomly selected rehabilitation records (at pretest, posttest, and follow-up). RESULTS: Service providers indicated that the outcomes software was easy to follow and believed that the use of the ICIDH framework helped them in making decisions about selecting outcome measures. Results of the survey indicated that there were significant changes in the service providers' level of comfort with selecting measures and knowing what measures were available. Use of outcome measures as identified through the audit did not change. CONCLUSIONS: The "All About Outcomes" software is clinically useful. Further research should evaluate whether using the software affects the use of outcome measures in clinical practice.
Child↗
Anaesthesia for daycase gynaecological laparoscopy: a survey of clinical practice in the United Kingdom.
Gynaecological laparoscopy is a daycase procedure that can be associated with significant morbidity and patients may require admission to hospital for overnight stay. Following a decision to administer intraperitoneal bupivacaine routinely to such patients in our day surgery unit, we wished to establish whether this was routine practice elsewhere. We therefore carried out a postal survey of consultant anaesthetists in the UK who regularly anaesthetise patients undergoing daycase gynaecological laparoscopy, addressing a number of clinical issues. The results of the survey are presented, discussed and compared with published advice.
Ambulatory Surgical Procedures↗
Contrast enhanced pulsed Doppler and colour-coded duplex studies of the cranial vasculature.
INTRODUCTION: The aim of this study was to assess the effect of Albunex, a vascular contrast agent based on albumin-coated air microbubbles, on pulsed Doppler and colour-coded duplex sonography of the cranial vasculature. METHODS: Twenty healthy male volunteers received intravenous injections of contrast in single doses ranging from 0.08 to 0.30 ml/kg. Pulsed wave Doppler sonography examination and colour-coded duplex sonography were carried out in the right internal carotid artery (ICA) and middle cerebral artery (MCA) before and after i.v. contrast. The relative intensity increase of the Doppler signal was measured in decibels. RESULTS: Transpulmonary passage of contrast occurred in sufficient amounts to enhance the intensity of the Doppler signal significantly, but the duration of this effect was short. Contrast enhancement also improved visualization of both the ICA and MCA in all subjects. For the transcranial examinations, this resulted in visualization of a greater length of the middle cerebral arteries and additional vessels in the Circle of Willis. CONCLUSIONS: These results confirm that contrast enhancement can significantly improve the quality of Doppler examination and colour-coded duplex sonography of both the intracranial and extracranial vessels. However, the use of Albunex in neurosonology will be of limited value due to its relatively short duration.
Adult↗
Double blind clinical trial of a remineralizing dentifrice in the prevention of caries in a radiation therapy population.
OBJECTIVES: The purpose of this study is to determine the efficacy and safety of a specially formulated remineralizing toothpaste in controlling caries in a group of high risk, head and neck radiation patients. DESIGN: The study compares the performance of the remineralizing toothpaste with a leading conventional fluoride dentifrice using double-blind randomization. TEST PRODUCTS: The products compared both contain equivalent quantities of fluoride (1150 ppm). The remineralizing toothpaste also delivers soluble calcium and phosphate ions, the essential components of teeth. SUBJECTS: On completion, 50 subjects who received > 50 Gy of radiation to the head and neck. MEASUREMENTS: Examinations include coronal and root caries using the Pitts Diagnostic Criteria, salivary flow rate, plaque and gingival indices and microbiological counts over one year. RESULTS: At this point subjects are enrolled in the study at various phases. However, the current average for the net increment per month per subject is -0.12 (+/- 1.30) for coronal caries and 0.06 (+/- 0.73) for root caries in subjects using the remineralizing toothpaste and 0.53 (+/- 1.62) for coronal caries and 0.45 (+/- 0.98) for root caries in subjects using the conventional fluoride dentifrice. Non-parametric analysis of rank scores for net root surface increments/month was statistically significant (p = 0.02), suggesting lower net root surface increment/month for the remineralizing toothpaste relative to the conventional toothpaste. No significant differences were noted on coronal surfaces. CONCLUSIONS: The results to date indicate that the remineralizing toothpaste is significantly superior to the conventional fluoride dentifrice in preventing root caries in high risk patients.
Adult↗