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Biomedical subjects

Andrew Clarke

Publications and source records attributed to Andrew Clarke.

At least 19 recordsLinked to original sources

Climate, energy and diversity.

In recent years, a number of species-energy hypotheses have been developed to explain global patterns in plant and animal diversity. These hypotheses frequently fail to distinguish between fundamentally different forms of energy which influence diversity in dissimilar ways. Photosynthetically active radiation (PAR) can be utilized only by plants, though their abundance and growth rate is also greatly influenced by water. The Gibbs free energy (chemical energy) retained in the reduced organic compounds of tissue can be utilized by all heterotrophic organisms. Neither PAR nor chemical energy influences diversity directly. Both, however, influence biomass and/or abundance; diversity may then increase as a result of secondary population dynamic or evolutionary processes. Temperature is not a form of energy, though it is often used loosely by ecologists as a proxy for energy; it does, however, influence the rate of utilization of chemical energy by organisms. It may also influence diversity by allowing a greater range of energetic lifestyles at warmer temperatures (the metabolic niche hypothesis). We conclude that there is no single species/energy mechanism; fundamentally different processes link energy to abundance in plants and animals, and diversity is affected secondarily. If we are to make progress in elucidating these mechanisms, it is important to distinguish climatic effects on species' distribution and abundance from processes linking energy supply to plant and animal diversity.

Animals↗

Blood audit evidenced-based cross-match requesting for lumbar spine surgery.

STUDY DESIGN: Complete audit cycle. OBJECTIVE: Radical overhaul of the blood ordering practices made by the spinal surgery department, in order to maximize the efficient use of blood products. SUMMARY OF BACKGROUND DATA: Spinal surgeons request blood-based on historical practice and not evidence. Blood is a scarce resource. Provision relies on voluntary donations from the general population. However, the donor population has been reduced because of the risks of variant Creutzfeldt-Jakob disease. Hence, the responsibility rests with clinicians to optimize their management of blood. METHODS: The spinal surgery department database was accessed to identify all patients who underwent elective lumbar spine operations (excluding deformity) during 2002 to 2003. These records were then cross-referenced with the blood transfusion department database. From the results the cross-match to transfusion (C:T) ratios and transfusion indexes (TI) were calculated for the procedures. A new tariff was agreed between the surgeons, anesthetists, and transfusion department. This was then audited prospectively. RESULTS: There were 664 cross-match requests made during 2002 to 2003, and only 40 U was transfused. This gave a C:T ratio of 16.6:1. The prospective audit resulted in only 58 U being cross-matched and 5 were transfused. This reduced the C:T ratio to 11.5:1. CONCLUSION: Implementing evidence based cross-match protocols can make significant savings in time, manpower, and money.

Blood Grouping and Crossmatching↗

Nonlocal hydrodynamic influence on the dynamic contact angle: slip models versus experiment.

Experiments reported by Blake [Phys. Fluids., 11, 1995 (1999)] suggest that the dynamic contact angle formed between the free surface of a liquid and a moving solid boundary at a fixed contact-line speed depends on the flow field and geometry near the moving contact line. We examine quantitatively whether or not it is possible to attribute this effect to the bending of the free surface due to hydrodynamic stresses acting upon it and hence interpret the results in terms of the so-called "apparent" contact angle. It is shown that this is not the case. Numerical analysis of the problem demonstrates that, at the spatial resolution reported in the experiments, the variations of the "apparent" contact angle (defined in two different ways) caused by variations in the flow field, at a fixed contact-line speed, are too small to account for the observed effect. The results clearly indicate that the actual (macroscopic) dynamic contact angle--i.e., the one used in fluid mechanics as a boundary condition for the equation determining the free surface shape--must be regarded as dependent not only on the contact-line speed but also on the flow field and geometry in the vicinity of the moving contact line.

Journal Article↗

Trade-offs in thermal adaptation: the need for a molecular to ecological integration.

Through functional analyses, integrative physiology is able to link molecular biology with ecology as well as evolutionary biology and is thereby expected to provide access to the evolution of molecular, cellular, and organismic functions; the genetic basis of adaptability; and the shaping of ecological patterns. This paper compiles several exemplary studies of thermal physiology and ecology, carried out at various levels of biological organization from single genes (proteins) to ecosystems. In each of those examples, trade-offs and constraints in thermal adaptation are addressed; these trade-offs and constraints may limit species' distribution and define their level of fitness. For a more comprehensive understanding, the paper sets out to elaborate the functional and conceptual connections among these independent studies and the various organizational levels addressed. This effort illustrates the need for an overarching concept of thermal adaptation that encompasses molecular, organellar, cellular, and whole-organism information as well as the mechanistic links between fitness, ecological success, and organismal physiology. For this data, the hypothesis of oxygen- and capacity-limited thermal tolerance in animals provides such a conceptual framework and allows interpreting the mechanisms of thermal limitation of animals as relevant at the ecological level. While, ideally, evolutionary studies over multiple generations, illustrated by an example study in bacteria, are necessary to test the validity of such complex concepts and underlying hypotheses, animal physiology frequently is constrained to functional studies within one generation. Comparisons of populations in a latitudinal cline, closely related species from different climates, and ontogenetic stages from riverine clines illustrate how evolutionary information can still be gained. An understanding of temperature-dependent shifts in energy turnover, associated with adjustments in aerobic scope and performance, will result. This understanding builds on a mechanistic analysis of the width and location of thermal windows on the temperature scale and also on study of the functional properties of relevant proteins and associated gene expression mechanisms.

Acclimatization↗

Genetic mapping of a major gene affecting onion bulb fructan content.

The non-structural dry matter content of onion bulbs consists principally of fructose, glucose, sucrose and fructans. The objective of this study was to understand the genetic basis for the wide variation observed in the relative amounts of these carbohydrates. Bulb carbohydrate composition was evaluated in progeny from crosses between high dry matter storage onion varieties and sweet, low dry matter varieties. When samples were analysed on a dry weight basis, reducing sugar and fructan content exhibited high negative correlations and bimodal segregation suggestive of the action of a major gene. A polymorphic SSR marker, ACM235, was identified which exhibited strong disequilibrium with bulb fructan content in F(2:3) families from the 'W202A' x 'Texas Grano 438' mapping population evaluated in two environments. This marker was mapped to chromosome 8 in the interspecific population 'Allium cepa x A. roylei'. Mapping in the 'Colossal Grano PVP' x 'Early Longkeeper P12' F2 population showed that a dominant major gene conditioning high-fructan content lay in the same genomic region. QTL analysis of total bulb fructan content in the intraspecific mapping population 'BYG15-23' x 'AC43' using a complete molecular marker map revealed only one significant QTL in the same chromosomal region. This locus, provisionally named Frc, may account for the major phenotypic differences in bulb carbohydrate content between storage and sweet onion varieties.

Breeding↗

Harpin modulates the accumulation of salicylic acid by Arabidopsis cells via apoplastic alkalization.

It is reported here that salicylic acid (SA) is rapidly taken up by Arabidopsis cells, and its uptake is accompanied by media alkalization and cytosolic acidification, and it is inhibited by the ionophore nigericin, suggesting that its import is linked with that of H+ and driven by a proton gradient. Such import and accumulation declined sharply within a narrow physiological pH range (pH 5.7-6.1), corresponding to a reduction in the [H+] of the media from 1.99 micromol l(-1) to 0.79 micromol l(-1). Following the initial uptake, SA was exported back into the media as free SA against a continued [H+]-dependent import. Since the uptake and accumulation of SA declines sharply within a narrow pH range and cell wall alkalization is an early response during incompatible plant/pathogen interactions, the bacterial elicitor harpin(Pss) was used to investigate how SA transport may be modulated during defence responses. Harpin induced a rapid and sustained alkalization of the cell suspension media, reaching the critical pH (pH 5.9-6.1) at which SA import is inhibited at c. 60 min. Such media alkalization corresponded with a reduction in the SA associated with cells co-treated with harpin, and an inhibition of SA uptake in cells pretreated with harpin. Scavengers of ROS, or compounds which generate H2O2 or NO had little effect on the import or net export of SA, suggesting that media alkalization induced by harpin is sufficient to modulate the kinetics of SA transport.

Alkalies↗

The Modic classification: inter- and intraobserver error in clinical practice.

STUDY DESIGN: A reliability study of the Modic classification. OBJECTIVE: To determine the reliability and reproducibility of the Modic classification for lumbar vertebral marrow changes. SUMMARY OF BACKGROUND DATA: In 1988, Modic et al described two degenerative stages of vertebral marrow and endplate morphology. These were type 1 (inflammatory phase) and type 2 (a fatty phase). Later in 1988, he added a third variety: type 3 where there was marked sclerosis adjacent to the endplates. No formal reliability or reproducibility studies had been performed on this Modic classification. METHODS: This study involved five independent observers of differing spinal experience using the Modic classification to grade 50 sagittal T1- and T2-weighted magnetic resonance imaging scans. The observers repeated the assessment at 3 weeks. Intra- and interobserver reliabilities were assessed using kappa statistics. RESULTS: There were 7 type 1, 40 type 2, 1 type 3, and 2 normal levels. The individual intraobserver agreement was substantial or excellent with kappa values ranging from 0.71 to 1. The overall interobserver agreement was excellent with a kappa value of 0.85. There was complete agreement in 78% of the levels, a difference of one type in 14% and a difference of two or more in 8% of levels. The level of experience of the observer did not correlate with a better score. CONCLUSIONS: We have shown that the classification is both reliable and reproducible. It is simple and easy to apply for observers of varying clinical experience. We therefore recommend its use in clinical research and practice.

Adult↗

Using video-oculography for galvanic evoked vestibulo-ocular monitoring in comatose patients.

Binocular eye movement responses to galvanic vestibular stimulation were measured in comatose patients. Healthy persons have been demonstrated to show a consistent and reproducible relationship between eye movement and galvanic vestibular stimulation. Any pathology of the vestibular integrating structures (brainstem and to some degree the cerebellum and cortex) is assumed to influence this response pathognomonically. A monitoring facility was designed to record eye movements during galvanic labyrinth polarization (GaLa) in order to examine the vestibular response in comatose patients. GaLa was applied by means of two pairs of electrodes attached between the mastoid and interscapular region. A custom-built, battery-driven current-source stimulator served to generate sinusoidal stimuli that could be applied either unilaterally or simultaneously and independently to the left and right labyrinths. The resultant binocular eye movements were recorded using a Chronos Eye Tracker and the digital image sequences stored for subsequent analysis. Repeated testing was performed in five comatose patients with a Glasgow Coma Score of 3, who were intubated and ventilated (subarachnoid hemorrhage (n = 3), traumatic injury (n = 2)). The observed ocular movements varied. In four cases ocular movements in response to GaLa were observed, while one patient showed neither spontaneous nor galvanic-induced eye movements. The latter was diagnosed as brain-dead 2 days after testing. In contrast, the patients who showed ocular movements synchronous with galvanic stimulation left the intensive care unit (ICU) for rehabilitation. These data indicate that it is possible to assess brain function in comatose patients by evaluating the vestibulo-ocular response to galvanic stimulation. The designed monitoring facility can be used on the ICU ward without disconnection of other monitoring equipment.

Brain↗

Postural control in otolith disorders.

It was the aim of the present paper to investigate the influence of otolith disorders on human postural control by different methods. The 33 patients of our study had undergone a minor head injury and suffered subsequently from an utricular or sacculo-utricular disorder as evidenced by vestibular evoked myogenic potential recordings and eccentric rotation recordings of the otolith-ocular responses. Postural control was assessed by performing stance/gait tests (standard balance deficit test, SBDT) and by evaluating trunk sway (using angular velocity sensors). Moreover, classical tests of the posterior column of the spinal tract (Romberg/Unterberger) and the dynamic posturography (sensory organization test, SOT) were included. It could be shown that SBDT tasks with reduced proprioceptive and visual cues (e.g. standing on foam, eyes closed) are most sensitive for an otolith disorder. The patients showed an increased trunk sway in the pitch plane (i.e. linear motion as adequate utricular stimulus) and an increase in sway velocities (i.e. tilting movements as adequate saccular stimulus) compared to controls. The SOT was most sensitive for combined (sacculo-utricular) otolith disorders (78%) while vestibulospinal tests are not enough sensitive. In essence, otolith disorders evidently impair human postural control and have been possibly underestimated as a source of posttraumatic postural imbalance as yet.

Adult↗

Management of posttraumatic vertigo.

OBJECTIVE: To evaluate patients after blunt trauma of the head, neck, and craniocervical junction (without fractures) with vertigo and to report the results of treatment after extensive diagnostics. STUDY DESIGN: Prospective study of consecutive new cases with vertigo after trauma at different periods of onset. During 2000-2002, 63 patients were examined and treated. SETTING: Regional trauma medical center for the greater Berlin Area, tertiary referral unit. RESULTS: The primary disorders included labyrinthine concussion (18), rupture of the round window membrane (6), and cervicogenic vertigo (12). The secondary disorders included otolith disorders (5), delayed endolymphatic hydrops (12), and canalolithiasis (9). The patients were free of vertigo symptoms (except cervicogenic and otolith disorder) after treatment, which consisted of habituation training, medical and surgical therapy options. The follow-up was 1 year. CONCLUSION: Posttraumatic vertigo can be treated with a high success rate once the underlying disorder has been identified. The extent of the neurotological test battery determines the precision and quality of diagnostics. Surgical measures should be an integral part of treatment modalities if conservative treatment is not effective. SIGNIFICANCE: Minor trauma of the head, neck, and craniocervical junction can have major impact on the vestibular system at different sites. Patients need to be carefully diagnosed, even if the onset of vertigo occurs a few weeks or months after the initial trauma.

Adolescent↗

How isolated is Antarctica?

The traditional view of Antarctica and the surrounding Southern Ocean as an isolated system is now being challenged by the recent discovery at the Antarctic Peninsula of adult spider crabs Hyas areneus from the North Atlantic and of larvae of subpolar marine invertebrates. These observations question whether the well described biogeographical similarities between the benthic fauna of the Antarctic Peninsula and the Magellan region of South America result from history (the two regions were once contiguous), or from a previously unrecognized low level of faunal exchange. Such exchange might be influenced by regional climate change, and also exacerbated by changes in human impact.

Journal Article↗

Disability prevention and communication among workers, physicians, employers, and insurers--current models and opportunities for improvement.

PURPOSE: To review prevailing models of disability management and prevention with respect to communication, and to suggest alternative approaches. METHOD: Review of selected articles. RESULTS: Effective disability management and return to work strategies have been the focus of an increasing number of intervention programmes and associated research studies, spanning a variety of worker populations and provider and business perspectives. Although primary and secondary disability prevention approaches have addressed theoretical basis, methods and costs, few identify communication as a key factor influencing disability outcomes. Four prevailing models of disability management and prevention (medical model, physical rehabilitation model, job-match model, and managed care model) are identified. The medical model emphasizes the physician's role to define functional limitations and job restrictions. In the physical rehabilitation model, rehabilitation professionals communicate the importance of exercise and muscle reconditioning for resuming normal work activities. The job-match model relies on the ability of employers to accurately communicate physical job requirements. The managed care model focuses on dissemination of acceptable standards for medical treatment and duration of work absence, and interventions by case managers when these standards are exceeded. Despite contrary evidence for many health impairments, these models share a common assumption that medical disability outcomes are highly predictable and unaffected by either individual or contextual factors. As a result, communication is often authoritative and unidirectional, with workers and employers in a passive role. CONCLUSION: Improvements in communication may be responsible for successes across a variety of new interventions. Communication-based interventions may further improve disability outcomes, reduce adversarial relationships, and prove cost-effective; however, controlled trials are needed.

Communication↗

The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein.

Mitogen and stress-activated kinase-1 (MSK1) is a serine/threonine protein kinase that is activated by either p38 or p42ERK MAPKs in response to stress or mitogenic extracellular stimuli. MSK1 belongs to a family of protein kinases that contain two distinct kinase domains in one polypeptide chain. We report the 1.8 A crystal structure of the N-terminal kinase domain of MSK1. The crystal structure reveals a unique inactive conformation with the ATP binding site blocked by the nucleotide binding loop. This inactive conformation is stabilized by the formation of a new three-stranded beta sheet on the N lobe of the kinase domain. The three beta strands come from residues at the N terminus of the kinase domain, what would be the alphaB helix in the active conformation, and the activation loop. The new three-stranded beta sheet occupies a position equivalent to the N terminus of the alphaC helix in active protein kinases.

Adenosine Triphosphate↗

Experimentally induced motion sickness in fish: possible role of the otolith organs.

OBJECTIVE: Although the occurrence of motion sickness is largely attributed to sensory conflict, the reasons for the highly variable inter-individual susceptibility to motion sickness remain unclear. One cause may be asymmetry between otoconial masses in the right and left inner ear. This hypothesis has been supported by experiments in fish under conditions of prolonged weightlessness and parabolic flight. In swordtail fish (Xiphophorus helleri) we examined the extent to which a Coriolis force environment, which has a strong motion sickness-triggering effect, disturbs swimming behaviour or produces motion sickness. MATERIAL AND METHODS: In a sealed aquarium, fish (n = 22) were subjected to Coriolis stimulation by constant vertical axis rotation, combined with pendular oscillation around a horizontal axis. RESULTS: Initially, at low stimulus intensity, all fish showed active compensatory swimming behaviour. However, while the majority (n = 19) maintained active compensation movements at higher stimulus levels, the others (n = 3) entered a passive uncoordinated state, from which they recovered again after reduction of stimulus intensity. On examination of the otoconial mass, we found asymmetries between the right and left utricles in all three cases and between the saccules in one case. CONCLUSION: We conclude that a lateral preponderance of the otoconial masses in the utricle or saccule promotes motion sickness under experimental conditions. The utricle appears to play a more important role in this than the saccule.

Animals↗

Myogenic cell cycle duration in Harpagifer species with sub-Antarctic and Antarctic distributions: evidence for cold compensation.

In teleosts, the proliferation of myogenic progenitor cells is required for muscle growth and nuclear turnover. We measured the cell cycle and S-phase duration of myogenic cells in the fast myotomal muscle of two closely related Harpagifer species by cumulative S-phase labelling with 5-bromo-2'-deoxyuridine (BrdU). Harpagifer antarcticus is a stenothermal species from the Antarctic peninsula (experiencing temperatures of -2 degrees C to +1 degrees C) and Harpagifer bispinis is a eurythermal species from the Beagle Channel, Tierra del Fuego (living at +4 degrees C in winter and up to 11 degrees C in summer). Specific growth rates in the adult stages studied were not significantly different from zero. Myogenic progenitor cells were identified using an antibody against c-met. Seventy-five percent of the c-met(+ve) cells were in a proliferative state in both species. Cell cycle time was 150 h at 5 degrees C and 81.3 h at 10 degrees C in H. bispinis (Q(10)=3.4). Cell cycle duration was 35% shorter in H. antarcticus at 0 degrees C (111 h) than in H. bispinis at 5 degrees C. The predicted cell cycle time for H. bispinis at 0 degrees C (based on the Q(10) relationship) was 277 h, which was more than double that measured for the Antarctic species at this temperature. The results obtained are compatible with an evolutionary adjustment of cell cycle time for function at low temperature in the Antarctic species.

Acclimatization↗

Low-temperature protein metabolism: seasonal changes in protein synthesis and RNA dynamics in the Antarctic limpet Nacella concinna Strebel 1908.

Protein synthesis is a fundamental and energetically expensive physiological process in all living organisms. Very few studies have examined the specific challenges of manufacturing proteins at low ambient temperatures. At high southern latitudes, water temperatures are continually below or near freezing and are highly stable, while food availability is very seasonal. To examine the effects of low temperature and a highly seasonal food supply on protein metabolism, we have measured wholebody protein synthesis, RNA concentrations, RNA:protein ratios and RNA translational efficiencies in the Antarctic limpet Nacella concinna at four times of the year. From summer to winter, protein synthesis rates decreased by 52%, RNA concentrations decreased by 55% and RNA:protein ratios decreased by 68%, while RNA translational efficiencies were low and very variable. Protein synthesis rates in N. concinna approached those measured in temperate mussels, while RNA:protein ratios were considerably higher than in temperate species. Interspecific comparisons show that species living at low temperatures have elevated RNA:protein ratios, which are probably needed to counteract a thermally induced reduction in RNA translational efficiency. Calculations using theoretical energetic costs of protein synthesis suggest that Antarctic species may allocate a larger proportion of their metabolic budget to protein synthesis than do temperate or tropical species.

Animals↗

Hydrogen peroxide and nitric oxide as signalling molecules in plants.

It is now clear that hydrogen peroxide (H(2)O(2)) and nitric oxide (NO) function as signalling molecules in plants. A wide range of abiotic and biotic stresses results in H(2)O(2) generation, from a variety of sources. H(2)O(2) is removed from cells via a number of antioxidant mechanisms, both enzymatic and non-enzymatic. Both biotic and abiotic stresses can induce NO synthesis, but the biosynthetic origins of NO in plants have not yet been resolved. Cellular responses to H(2)O(2) and NO are complex, with considerable cross-talk between responses to several stimuli. In this review the potential roles of H(2)O(2) and NO during various stresses and the signalling pathways they activate are discussed. Key signalling components that might provide targets for enhancing crop production are also identified.

Apoptosis↗