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Biomedical subjects

G R Johnson

Publications and source records attributed to G R Johnson.

At least 19 recordsLinked to original sources

A systematic review of the Tardieu Scale for the measurement of spasticity.

BACKGROUND: The Tardieu Scale has been suggested a more appropriate clinical measure of spasticity than the Ashworth or modified Ashworth Scales. It appears to adhere more closely to Lance's definition of spasticity as it involves assessment of resistance to passive movement at both slow and fast speeds. OBJECTIVE: To review the available literature in which the Tardieu Scale has been used or discussed as a measure of spasticity, with a view to determining its validity and reliability. STUDY DESIGN: A systematic review of all literature found related to the Tardieu Scale (keywords: Tardieu scale, spasticity) from Pubmed and Ovid databases, including medline, CINAHL, EMBASE, Journals at Ovid full text, EBM reviews and Cochrane database of systematic reviews. Hand searching was also used to track the source literature. CONCLUSIONS: In theory, we can acknowledge that the Tardieu Scale does, in fact, adhere more closely to Lance's definition of spasticity. However, there is a dearth of literature investigating validity and reliability of the scale. Some studies have identified the Tardieu Scale to be more sensitive than other measures, to change following treatment with botulinum toxin. Further studies need to be undertaken to clarify the validity and reliability of the scale for a variety of muscle groups in adult neurological patients.

Disability Evaluation↗

Particle number emissions and source signatures of an industrial facility.

The work presented was conducted within the scope of a larger study investigating impacts of the Stuart Oil Shale project, a facility operating to the north of the industrial city of Gladstone, Australia. The aims of the investigations were threefold: (a) the identification of the plant signatures in terms of particle size distributions in the submicrometer range (13-830 nm) through stack measurements, (b) exploring the applicability of these signatures in tracing the source contributions at locations of interest, at a distance from the plant, and (c) assessing the contribution of the plant to the total particle number concentration at locations of interest. The stack measurements conducted for three different conditions of plant operation showed that the particle size distributions were bimodal with average modal count median diameters (CMDs) of 24 (SD 4) and 52 (SD 9) nm. The average of all the particle size distributions recorded within the plant sector at a site located 4.5 km from the plant, over the sampling period when the plant was operating, also showed a bimodal distribution. The modal CMDs in this case were 27 and 50 nm, similar to those at the stack. This bimodal size distribution is distinct from the size distribution of the most common ambient anthropogenic emission source, which is vehicle emissions, and can be considered as a signature of this source. The average contribution of the plant (for plant sector winds) was estimated to be (10.0 +/- 3.8) x 10(2) particles cm(-3) and constituted approximately a 50% increase overthe local particle ambient concentration for plant sector winds. This increase in particle number concentration compared to the local background concentration, while high compared to the clean environment concentration, is not significant when compared to concentrations generally encountered in the urban environment of Brisbane.

Air Pollutants↗

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Aged↗

Correlation of virus replication in tissues with histologic lesions in Atlantic salmon experimentally infected with infectious salmon anemia virus.

We have studied the replication of virus in tissues and development of lesions associated with infectious salmon anemia virus (ISAV) infection in Atlantic salmon using in situ hybridization (ISH) with a riboprobe targeting ISAV RNA segment 7 messenger RNA. Fish were infected with three ISAV isolates (U5575-1, RPC-01-0593-1, Norway 810/9/99) and then euthanatized sequentially at 3, 6, 10, and 13 days postinoculation (dpi) and thereafter once a week for 8 weeks. Severe histopathologic lesions were observed in tissues from all groups beginning at the onset of mortality. The severe histopathologic lesions correlated with maximum intensity and frequency of ISH signals (P < 0.001). There was a strong association between the hybridization signals and severity of lesions in the liver, kidney, and heart (R = 0.81, 0.70, and 0.78, respectively; P < 0.001). The distribution of ISH signals indicated the presence of a viremia because signals were observed predominantly in individual blood cells and endothelial cells, and possibly hematopoietic cells of head kidney, but not in the necrotic hepatocytes and renal epithelium. Of the organs sampled, the heart was the first and last to show ISH signals, possibly because of increased activity of the endocardial endothelial cells and the underlining macrophages, which continuously trap and remove circulating virus, and therefore represents the best tissue sample for screening of suspected infected fish. On the basis of mortality, severity of lesions, and intensity and frequency of ISH signals, ISAV isolate Norway 810/9/99 was the most virulent and U5575-1 the least virulent isolate studied.

Animals↗

Does spasticity result from hyperactive stretch reflexes? Preliminary findings from a stretch reflex characterization study.

PURPOSE: To characterize the stretch reflex response of the biceps brachii in stroke patients with elbow spasticity (prior to or within 15 min of treatment with botulinum toxin) and non-impaired volunteers with the aim of quantifying the stretch reflex excitability and observe the differences between the groups. METHODS: A cross-sectional study. Stretch reflexes from the biceps brachii were elicited following a controlled elbow extension. The amplitude, latency, rise time and duration, calculated from surface EMG recordings from the biceps brachii, were used to characterize the stretch reflex response. RESULTS: Seventeen non-impaired and 14 stroke patients participated. The amplitude was significantly lower in stroke patients than in non-impaired volunteers (p<0.05). The latency was significantly shorter in stroke patients than in non-impaired volunteers (p<0.05). There were no significant differences in rise time or duration (p>0.10). DISCUSSION: Reduction in the amplitude in stroke patients was unexpected suggesting the stretch reflex is not necessarily hyper-excitable in people with clinically diagnosed spasticity. Latency differences suggest decreased presynaptic inhibition and/or increased motor neurone excitability can occur following a stroke. However, carry over effects from previous botulinum toxin treatment may have confounded amplitude measurements. Further work evaluating the excitability of the stretch reflex independent of Botulinum toxin and its contribution to resistance to passive stretching is being conducted.

Adult↗

Performance specification for lower limb orthotic devices.

OBJECTIVE: To establish the range of forces and moments applied to lower limb orthoses during ambulation by routine users. DESIGN: Well-established gait analysis techniques were used to determine the loading at the major joints. It was assumed that the joint moments were transmitted by the orthosis encompassing any particular joint. Two hundred and five assessments of 164 patients were successfully completed by a consortium of four gait laboratories in Europe. The orthosis specification and patient clinical data were also recorded. BACKGROUND: The design and development of orthoses has occurred largely by evolution rather than by formal engineering methods. In particular, formal design has been hampered by a lack of information on the forces and moments applied during ambulation. METHODS: A standard gait analysis procedure was employed to capture the data. In-house biomechanical models were used to calculate the joint loading. Data were normalised with respect to patient weight and leg length. RESULTS: It was found that the median maximum normalised ankle moment transmitted by an ankle foot orthosis was 0.15 and the maximum knee moment was 0.09. The greatest moment transmitted by the hip joint of a hip knee ankle foot orthosis was also 0.09. There was a wide variation in the data due to differences in the impairments of the test subjects. CONCLUSION: It is possible to estimate the loads transmitted by an orthosis using established gait analysis procedures without the need for load measurement transducers. There is now a need both to collect a larger representative dataset and to perform validation studies with transducers.

Adolescent↗

Evolution of catabolic pathways for synthetic compounds: bacterial pathways for degradation of 2,4-dinitrotoluene and nitrobenzene.

The pathways for 2,4-dinitrotoluene (2,4-DNT) and nitrobenzene offer fine illustrations of how the ability to assimilate new carbon sources evolves in bacteria. Studies of the degradation pathways provide insight about two principal strategies for overcoming the metabolic block imposed by nitro- substituents on aromatic compounds. The 2,4-DNT pathway uses novel oxygenases for oxidative denitration and subsequent ring-fission. The nitrobenzene pathway links facile reduction of the nitro- substituent, a novel mutase enzyme, and a conserved operon encoding aminophenol degradation for mineralization of nitrobenzene. Molecular genetic analysis with comparative biochemistry reveals how the pathways were assembled in response to the recent appearance of the two synthetic chemicals in the biosphere.

Bacteria↗

The effect of local-scale physical heterogeneity and nonlinear, rate-limited sorption/desorption on contaminant transport in porous media.

Nonideal transport of contaminants in porous media has often been observed in laboratory characterization studies. It has long been recognized that multiple processes associated with both physical and chemical factors can contribute to this nonideal transport behavior. To fully understand system behavior, it is important to determine the relative contributions of these multiple factors when conducting contaminant transport and fate studies. In this study, the relative contribution of physical-heterogeneity-related processes versus those of nonlinear, rate-limited sorption/desorption to the observed nonideal transport of trichloroethene in an undisturbed aquifer core was determined through a series of miscible-displacement experiments. The results of experiments conducted using the undisturbed core, collected from a Superfund site in Tucson, AZ, were compared to those obtained from experiments conducted using the same aquifer material packed homogeneously. The results indicate that both physical and chemical factors, specifically preferential flow and associated rate-limited diffusive mass-transfer and rate-limited sorption/desorption, respectively, contributed to the nonideal behavior observed for trichloroethene transport in the undisturbed core. A successful prediction of trichloroethene transport in the undisturbed core was made employing a mathematical model incorporating multiple sources of nonideal transport, using independently determined model parameters to account for the multiple factors contributing to the nonideal transport behavior. The simulation results indicate that local-scale physical heterogeneity controlled the nonideal transport behavior of trichloroethene in the undisturbed core, and that nonlinear, rate-limited sorption/desorption were of secondary importance.

Adsorption↗

Outcome measures of spasticity.

Spasticity is characterized by a velocity-dependent increase in muscle resistance, in response to a passive stretch. Whilst clinical scales probably represent the most common approach to its measurement, these are limited by poor reliability and difficulties with some definitions. However, recently, a simple system has been used to provide the clinician with a measure of the force applied during the Ashworth Test. The Wartenberg Pendulum Test has been devised for measuring spasticity at the knee, but has been shown to be unsuitable for measuring more severe spasticity. Powered systems have been used in research studies, but are rarely considered suitable for routine clinical use. However, one method of interest, using a low inertia torque motor to measuring stiffness at the wrist, has been shown to provide rapid measurements which correspond to the degree of spasticity defined by other scales. Clinical gait analysis may have an important role to play in assessing spasticity - since there are clear associations between lower limb spasticity and gait problems - but it does not provide a true measure of the condition. In summary, while scales remain the most common method of measuring spasticity, there is considerable potential in instrumented techniques that can provide greater reliability and precision of measurement.

Biomechanical Phenomena↗

The tyrosine phosphatase SHP-2 is required for mediating phosphatidylinositol 3-kinase/Akt activation by growth factors.

SHP-2 is a ubiquitously expressed non-transmembrane tyrosine phosphatase with two SH2 domains. Multiple reverse-genetic studies have indicated that SHP-2 is a required component for organ and animal development. SHP-2 wild-type and homozygous mutant mouse fibroblast cells in which the N-terminal SH2 domain was target-deleted were used to examine the function of SHP-2 in regulating Phosphatidylinositol 3-Kinase (PI3K) activation by growth factors. In addition, SHP-2 and various mutants were introduced into human glioblastoma cells as well as SHP-2(-/-) mouse fibroblasts. We found that EGF stimulation and EGFR oncoprotein (DeltaEGFR) expression independently induced the co-immunoprecipitation of the p85 subunit of PI3K with SHP-2. Targeted deletion of the N-terminal SH2 domain of SHP-2 severely impaired PDGF- and IGF-induced Akt phosphorylation. Ectopic expression of SHP-2 in U87MG gliobastoma cells elevated EGF-induced Akt phosphorylation, and the effect was abolished by mutation of its N-terminal SH2 domain. Likewise, the reconstitution of SHP-2 expression in the SHP-2(-/-) cells enhanced Akt phosphorylation induced by EGF while rescuing that induced by PDGF and IGF. Further lipid kinase activity assays confirmed that SHP-2 modulation of Akt phosphorylation correlated with its regulation of PI3K activation. Based on these results, we conclude that SHP-2 is required for mediating PI3K/Akt activation, and the N-terminal SH2 domain is critically important for a "positive" role of SHP-2 in regulating PI3K pathway activation.

Animals↗

Epidermal growth factor (EGF) receptor kinase-independent signaling by EGF.

The ErbB family of receptors, which includes the epidermal growth factor receptor (EGFR), ErbB2, ErbB3, and ErbB4, mediate signaling by EGF-like polypeptides. To better understand the role of the EGFR tyrosine kinase, we analyzed signaling by a kinase-inactive EGFR (K721M) in ErbB-devoid 32D cells. K721M alone exhibited no detectable signaling capacity, whereas coexpression of K721M with ErbB2, but not ErbB3 or ErbB4, resulted in EGF-dependent mitogen-activated protein kinase (MAPK) activation. The kinase activity, but not tyrosine phosphorylation, of ErbB2 was required for EGF-induced MAPK activation. The presence of tyrosine phosphorylation sites in K721M was not a requisite for signaling, indicating that transphosphorylation of K721M by ErbB2 was not an essential mechanism of receptor activation. Conversely, the mutated kinase domain of K721M (residues 648-973) and tyrosine phosphorylation of at least one of the receptors were necessary. EGF was found to activate the pro-survival protein kinase Akt in stable cell lines expressing K721M and ErbB2 but, unlike cells expressing wild-type EGFR, was incapable of activating signal transducers and activators of transcription (STAT) or driving cell proliferation. These results demonstrate that EGFR-ErbB2 oligomers are potent activators of MAPK and Akt, and this signaling does not require EGFR kinase activity.

Cell Line↗

Application of spherical and cylindrical wrapping algorithms in a musculoskeletal model of the upper limb.

In the modelling of the upper limb, many muscles cannot be represented as a straight line from origin to insertion due to the complex morphology causing them to wrap around passive structures. The majority of bony contours that form these obstructions can be described adequately as simple geometric shapes such as spheres and cylinders.A novel technique for the parameterisation of muscle paths as they wrap around such shapes has been developed for use in an upper limb model. The new method involves the definition of moving co-ordinate systems in which the path of a wrapped muscle does not move, allowing simplified specification. In addition, an analytical calculation of the wrapping path around a cylinder is presented over previous approximate methods. Muscle moment arms were pre-calculated from vector considerations and within SIMM by tendon excursion. Close agreement between the two suggests that the proposed implementations accurately follow the theoretical relationship and can be used with confidence in musculoskeletal models.

Algorithms↗

Biomechanical examination of a commonly used measure of spasticity.

BACKGROUND: An increase in the prevalence of neurological disability puts pressure on service providers to restrict costs associated with rehabilitation. Spasticity is an important neurological impairment for which many novel and expensive treatment options now exist. The antispastic effects of these techniques remain unexplored due to a paucity of valid outcome measures. AIM: To develop a biomechanical measure of resistance to passive movement, which could be used in routine clinical practice, and to examine the validity of the modified Ashworth scale. STUDY DESIGN: Repeated measure cross-section study on 16 subjects who had a unilateral stroke one-week previously and had no elbow contractures. OUTCOME MEASURES: Simultaneous measurement of resistance to passive movement using a custom built measuring device and the modified Ashworth scale. Passive range of movement and velocity were also measured. The "catch", a phenomenon associated with the modified Ashworth scale, was identified by the assessor using a horizontal visual analogue scale and biomechanically quantified using the residual calculated from a linear regression technique. RESULTS: Half the study population had a modified Ashworth score greater than zero. The association between the two measures was poor (kappa=0.366). The speed and range of passive movement were greater in subjects with modified Ashworth score "0" (P<0.05). Resistance to passive movement was higher in the impaired arm (P<0.05) and tended to decrease with repeated measures and increasing speeds. CONCLUSIONS: A device to measure resistance to passive movement at the elbow was developed. The modified Ashworth scale may not provide a valid measure of spasticity but a measure of resistance to passive movement in an acute stroke population. RELEVANCE: Spasticity is an important neurological impairment for which many novel and expensive treatment options are being made available. There is a paucity of clinically usable outcomes to measure spasticity. A device to measure resistance to passive movement at the elbow, which was more reliable than the modified Ashworth scale was developed. This device may provide a much needed objective clinical measure to evaluate the efficacy of antispasticity treatment.

Aged↗

Glenohumeral subluxation, scapula resting position, and scapula rotation after stroke: a noninvasive evaluation.

OBJECTIVES: To determine whether scapular downward tilt (ScDT) and dynamic scapular lateral rotation (ScLR) in subjects with and without stroke is associated with subluxation, and to prove the reliability of a Scapula Locator System in an elderly population. DESIGN: Repeated measures of ScLR by 2 observers. SETTING: Outpatient rehabilitation department of a district general hospital. PARTICIPANTS: To test device reliability, 5 healthy men (mean age +/- standard deviation, 72 +/- 5 yr). To test scapula position, 30 stroke patients (19 men, 11 women; mean age, 73 +/- 6 yr) and 15 healthy controls (12 men, 3 women; mean age, 62 +/- 6 yr). INTERVENTIONS: The control subjects' ScDT was compared with stroke subjects' ScDT after stratification according to 3 patterns of ScLR symmetry and the presence of palpable glenohumeral subluxation. MAIN OUTCOME MEASURES: For device reliability, 3-way analysis of variance. For scapula position, triangulated location by Scapula Locator System of acromion, inferior angle, and root of the scapular spine; then measurement of scapula motion to determine symmetry, lag, or lead. RESULTS: The inter- and intraobserver reliability of the Scapula Locator System device was high (1% of variance each). Normal ScDT was positive (left side: 10.94 degrees +/- 2.62 degrees; right side: 9.69 degrees +/- 4.36 degrees ), indicating a downward-facing glenoid fossa. This finding was unchanged by stroke (10.46 degrees +/- 2.42 degrees ). All controls and 16 stroke subjects had symmetry between shoulders for ScLR rate and ScDT. Two other patterns (p <.01) of ScLR were found after stroke: 8 subjects had a slower rate of affected arm ScLR (lag) with a correspondingly greater ScDT on the affected side (2.61 degrees +/- 6.7 degrees ); 6 subjects had a faster rate of affected arm ScLR (lead) but with an upward-facing glenoid fossa on the affected side (ScDT: -11.84 degrees +/- 8.48 degrees ). No significant inter- or intrasubject difference in ScDT existed in the 6 cases of glenohumeral subluxation. CONCLUSIONS: The scapula normally tilts downward with or without stroke. The effect of stroke is similar on tonic (ScDT) and phasic (ScLR) control of scapula position. Subluxation is not linked with a particular scapular resting position after stroke.

Aged↗

Abdominal aortic aneurysm in women.

OBJECTIVE: The purpose of this study was to compare abdominal aortic aneurysm (AAA) associations in men and women. METHODS: Veterans aged 50 to 79 years without a previous history of AAA underwent ultrasound screening for AAA after completing a questionnaire on demographic information and potential risk factors. RESULTS: A total of 122,272 men and 3450 women were successfully screened. An AAA of 3.0 cm or greater in diameter was found in 4.3% of men and 1.0% of women (P <.001). Contrary to a previous report, we did not find suprarenal aortic enlargement accompanying AAA to be more common in women. The principal associations that we have previously reported for AAA in this cohort (age, smoking, family history of AAA, and a negative association with diabetes) were all similar in women compared with men. In age- and smoking-adjusted models, the interaction terms indicated that black race and cancer were more strongly associated with AAA in women than men (P <.05). Height and cerebral vascular disease were also more strongly associated with AAA in women than in men, but these interaction terms did not reach statistical significance (P <.10). Although the other differences were unexpected and require confirmation, the trend toward a stronger association of cerebral vascular disease with AAA in women is consistent with two previous reports. CONCLUSIONS: Despite the much lower prevalence of AAA in women, the most important associations with AAA are similar to those seen in men. Our data provide some support for a previous finding that cerebrovascular disease may be more closely associated with AAA in women than in men.

Aged↗

Oxidative transformation of aminodinitrotoluene isomers by multicomponent dioxygenases.

The electron-withdrawing nitro substituents of 2,4,6-trinitrotoluene (TNT) make the aromatic ring highly resistant to oxidative transformation. The typical biological transformation of TNT involves reduction of one or more of the nitro groups of the ring to produce the corresponding amine. Reduction of a single nitro substituent of TNT to an amino substituent increases the electron density of the aromatic nucleus considerably. The comparatively electron-dense nuclei of the aminodinitrotoluene (ADNT) isomers would be expected to be more susceptible to oxygenase attack than TNT. The hypothesis was tested by evaluating three nitroarene dioxygenases for the ability to hydroxylate the ADNT isomers. The predominant reaction was dioxygenation of the ring to yield nitrite and the corresponding aminomethylnitrocatechol. A secondary reaction was benzylic monooxygenation to form aminodinitrobenzyl alcohol. The substrate preferences and catalytic specificities of the three enzymes differed considerably. The discovery that the ADNT isomers are substrates for the nitroarene dioxygenases reveals the potential for extensive bacterial transformation of TNT under aerobic conditions.

Escherichia coli↗

Assessing motor deficits in neurological rehabilitation: patterns of instrument usage.

To describe current patterns in the use of clinical scales and measurement technology for the assessment of motor deficits in neurological rehabilitation. Questionnaire, sent to the 2,556 members of the World Forum for Neurological Rehabilitation, distributed over 75 countries. Sixty-eight questionnaires were returned. Generally, participants indicated that the centres where they were based used a number of different clinical assessment scales (median, three), most frequently with a small proportion of patients. The (Modified) Ashworth Scale, the FIM, and the Fugl-Meyer were used most frequently. Only 35 respondents stated that their centre used one or more scales in >75% of their patients, but the choice of such routinely applied instruments varied between centres. The application of measurement technology was restricted, with video and goniometry being used most frequently. The main barriers to more frequent use of assessment tools were perceived to be a lack of resources, information, and training. The (albeit limited) results from this survey suggest that the assessment of motor deficits in neurological rehabilitation is currently mostly qualitative and lacks standardisation. More resources and education are required to support a more routine application of assessment tools and to integrate measurement technology further in neurological rehabilitation to assist in the process of quantification of outcomes.

Disability Evaluation↗