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Biomedical subjects

A Hayes

Publications and source records attributed to A Hayes.

At least 55 records · Page 3Linked to original sources

Comparison of sevoflurane and propofol with rocuronium for modified rapid-sequence induction of anaesthesia.

We compared the use of sevoflurane and propofol with three different doses of rocuronium for modified rapid-sequence induction of anaesthesia. One hundred and forty adult patients were randomly allocated to have a rapid-sequence intravenous induction with propofol 2-3 mg.kg-1 (group P) or an inhalational induction with sevoflurane 8% in oxygen, using a vital capacity technique (group S). Following loss of the eyelash reflex, cricoid pressure was applied and 20 patients in each group were administered rocuronium 0.3 (groups P/0.3 and S/0.3), 0.45 (groups P/0.45 and S/0.45) or 0.6 (groups P/0.6 and S/0.6) mg.kg-1. An additional 10 patients in each group received only saline placebo in place of the muscle relaxant (groups P/Saline and S/Saline). Laryngoscopy was started 60 s later and intubating conditions evaluated by a blinded anaesthetist according to a standard scoring system. Intubating conditions were acceptable in one patient and no patient, respectively, following induction with sevoflurane and propofol without the muscle relaxant. The conditions were acceptable in 30, 55 and 90% of subjects with sevoflurane induction, and in 45, 80 and 90% of subjects with propofol induction following 0.3, 0.45 and 0.6 mg.kg-1 of rocuronium, respectively (no significant difference for each dose of rocuronium). The present study shows that intubating conditions during a rapid-sequence induction using rocuronium 0.6 mg.kg-1 following induction of anaesthesia with sevoflurane or propofol are similar.

Adolescent↗

Muscle protection following motor nerve repair in combination with leukemia inhibitory factor.

Leukemia inhibitory factor (LIF) has been shown to stimulate growth of muscle and nerve cells. In this rat study, in which the nerve to the medial head of the gastrocnemius was divided and repaired and slow-release LIF was administered at the repair site, we evaluated recovery by measuring the force of muscle contraction and of muscle bulk. Thirty-five male Sprague-Dawley rats (325-375 g) were randomly divided into 5 different groups according to type of treatment: denervated, end-to-end nerve repair, end-to-end nerve repair with LIF, neurotization, and neurotization with LIF. The contralateral side served as a nonoperated control group. Leukemia inhibitory factor was administered for 28 days to the site of the nerve repair via an implanted osmotic infusion pump. Muscle mass and muscular function were evaluated at 6 weeks using electrophysiologic techniques. The medial gastrocnemius muscle mass of the repair + LIF group was greater than the repair-alone group. The peak twitch, relative twitch, relative tetanic, and tetanic forces generated from the repair + LIF group were also significantly higher than those in the repair-alone group. Although neurotization was almost as effective as end-to-end nerve repair for reinnervating muscle, LIF had no increased effect on neurotization. These data suggest that LIF protects muscular function and reduces denervation atrophy following end-to-end nerve repair.

Animals↗

12-year outcome after modified Watson-Jones tenodesis for ankle instability.

In a retrospective study, the long term outcome of the modified Watson-Jones tenodesis according to Lemberger and Kramer was determined using a questionnaire, clinical examination, radiographic data, including stress views, measurement of plantar pressure distribution, and peroneal reaction times on a tilt board. Twenty-five male patients (mean age, 34 years) with a mean followup of 12 years from surgery were available for examination. Eighteen patients (72%) were classified clinically as having excellent or good results. The higher presence of osteophytes in the surgically treated ankle in comparison with the opposite side indicated the progression of arthrosis with time, but this finding could not be related to the reconstruction method. Anterior drawer and talar tilt were reduced significantly in comparison with the preoperative stress radiographs. No differences in plantar pressure distribution were seen between the patients' surgically treated and nonsurgically treated feet. The peroneal reaction times of the peroneus brevis and peroneus longus muscles were significantly shorter in the surgically treated foot compared with the opposite side. It was concluded that the modified Watson-Jones tenodesis effectively corrected lateral ankle instability with no clinical deterioration with time and no influence on gait.

Adolescent↗

Examining potential drug therapies for muscular dystrophy utilising the dy/dy mouse: I. Clenbuterol.

As a potent promoter of muscle growth, clenbuterol has been proposed as a treatment for muscle wasting diseases. Thus, the effects of clenbuterol on dystrophic skeletal muscle was examined. Male dystrophic (dy/dy) mice aged 4-5 weeks were treated with clenbuterol for 3 weeks, and the isometric contractile, fatigue and histochemical properties of the slow-twitch soleus and fast-twitch plantaris muscles measured. Muscles of dystrophic animals produced lower forces, contracted more slowly and exhibited greater fatigue resistance than age-matched normal animals. Dystrophic soleus muscles also had higher proportions of type I fibres than normal mice. Clenbuterol significantly reduced the natural death rate of dystrophic mice, as 3 of 11 untreated animals died prior to completion of the 3-week experimental period, whereas none of the 9 clenbuterol-treated animals died. Clenbuterol treatment significantly increased the relative mass (P<0.001) and relative tetanic force production (P<0.01) of the soleus of dystrophic animals, most likely due to increases in protein accretion and improved regeneration. The plantaris of clenbuterol-treated dystrophic animals also exhibited higher mass (P<0.05) and higher absolute forces than untreated mice. The results from this study show that clenbuterol could be a valuable adjunct to treatments of muscle wasting diseases such as muscular dystrophy.

Administration, Oral↗

Quantitative analysis of yeast gene function using competition experiments in continuous culture.

One possible route to the evaluation of gene function is a quantitative approach based on the concepts of metabolic control analysis (MCA). An important first step in such an analysis is to determine the effect of deleting individual genes on the growth rate (or fitness) of S. cerevisiae. Since the specific growth-rate effects of most genes are likely to be small, we employed competition experiments in chemostat culture to measure the proportion of deletion mutants relative to that of a standard strain by using a quantitative PCR method. In this paper, we show that both densitometry and GeneScan analysis can be used with similar accuracy and reproducibility to determine the proportions of (at least) two strains simultaneously, in the range 10-90% of the total cell population. Furthermore, we report on a model competition experiment between two diploid nuclear petite mutants, homozygous for deletions in the cox5a or pet191 genes, and the standard strain (ho::kanMX4/ho::kanMX4) in chemostat cultures under six different physiological conditions. The results indicate that competition experiments is continuous culture are a suitable method to distinguish quantitatively between deletion mutants that qualitatively exhibit the same phenotype.

Culture Media↗

Contractile function and low-intensity exercise effects of old dystrophic (mdx) mice.

Old mdx mice display a severe myopathy almost identical to Duchenne's muscular dystrophy. This study examined the contractile properties of old mdx muscles and investigated any effects of low-intensity exercise. Isometric contractile properties of the extensor digitorum longus (EDL) and soleus muscles were tested in adult (8-10 mo) and old (24 mo, split into sedentary and exercised groups) mdx mice. The EDL and soleus from old mdx mice exhibited decreased absolute twitch and tetanic forces, and the soleus exhibited a > 50% decrease in relative forces (13.4 +/- 0.4 vs. 6.0 +/- 0.9 N/cm2) compared with adult mice. Old mdx muscles also showed longer contraction times and a higher percentage of type I fibers. Normal and mdx mice completed 10 wk of swimming, but mdx mice spent significantly less time swimming than normal animals (7.8 +/- 0.4 vs. 15.8 +/- 1.1 min, respectively). However, despite their severe dystrophy, mdx muscles responded positively to the low-intensity exercise. Relative tetanic tensions were increased (approximately 25% and approximately 45% for the EDL and soleus, respectively) after the swimming, although absolute forces were unaffected. Thus these results indicate that, even with a dystrophin-deficient myopathy, mdx muscles can still respond to low-intensity exercise. This study shows that the contractile function of muscles of old mdx mice displays many similarities to that of human dystrophic patients and provides further evidence that the use of non-weight-bearing, low-intensity exercises, such as swimming, has no detrimental effect on dystrophic muscle and could be a useful therapeutic aid for sufferers of muscular dystrophy.

Aging↗

Molecular characterization of abLIM, a novel actin-binding and double zinc finger protein.

Molecules that couple the actin-based cytoskeleton to intracellular signaling pathways are central to the processes of cellular morphogenesis and differentiation. We have characterized a novel protein, the actin-binding LIM (abLIM) protein, which could mediate such interactions between actin filaments and cytoplasmic targets. abLIM protein consists of a COOH-terminal cytoskeletal domain that is fused to an NH2-terminal domain consisting of four double zinc finger motifs. The cytoskeletal domain is approximately 50% identical to erythrocyte dematin, an actin-bundling protein of the red cell membrane skeleton, while the zinc finger domains conform to the LIM motif consensus sequence. In vitro expression studies demonstrate that abLIM protein can bind to F-actin through the dematin-like domain. Transcripts corresponding to three distinct isoforms have a widespread tissue distribution. However, a polypeptide corresponding to the full-length isoform is found exclusively in the retina and is enriched in biochemical extracts of retinal rod inner segments. abLIM protein also undergoes extensive phosphorylation in light-adapted retinas in vivo, and its developmental expression in the retina coincides with the elaboration of photoreceptor inner and outer segments. Based on the composite primary structure of abLIM protein, actin-binding capacity, potential regulation via phosphorylation, and isoform expression pattern, we speculate that abLIM may play a general role in bridging the actin-based cytoskeleton with an array of potential LIM protein-binding partners. The developmental time course of abLIM expression in the retina suggests that the retina-specific isoform may have a specialized role in the development or elaboration of photoreceptor inner and outer segments.

Actins↗

Suitability of replacement markers for functional analysis studies in Saccharomyces cerevisiae.

The complete yeast sequence contains a large proportion of genes whose biological function is completely unknown. One approach to elucidating the function of these novel genes is by quantitative methods that exploit the concepts of metabolic control analysis. An important first step in such an analysis is to determine the effects of deleting individual genes on the growth rate (or fitness) of Saccharomyces cerevisiae. Since the specific growth-rate effects of most genes are likely to be small, they are most readily determined by competition against a standard strain in chemostat cultures where the true steady state demanded by metabolic control analysis may be achieved. We have constructed two different standard strains in which the HO gene is replaced by either HIS3 or kanMX. We demonstrate that HO is a selectively neutral site for gene replacement. However, there is a significant marker effect associated with HIS3 which, moreover, is dependent on the physiological conditions used for the competition experiments. In contrast, the kanMX marker exhibited only a small effect on specific growth rate (< or = +/- 4%). These data suggest that nutritional markers should not be used to generate deletion mutants for the quantitative analysis of gene function in yeast but that kanMX replacements may be used, with confidence, for such studies.

Anti-Bacterial Agents↗

Integrating contours within and through depth.

To better understand the role of disparity in contour integration we compared detection performance of "paths" composed of elements confined either to a single depth plane, or spanning multiple depth planes. In both cases paths defined by alignment of elements were embedded in a noise background-field made up of similar, but randomly positioned, elements covering the same depth range as the path elements. We show that a systematic disparity cue can enhance the detectability of paths which traverse depth, but that this detectability is weak compared to paths made up of elements of the same disparity. These results suggest that the outputs of disparity detectors tuned to different disparities can be linked to define contours.

Depth Perception↗

The average pressure distribution of the diabetic foot: can it be used as a clinical diagnostic aid?

INTRODUCTION:: The aim of this study was to investigate whether averaged data obtained from pressure distribution measurements could be used to distinguish differences between diabetic feet with normal and no sensation. The calculated parameters most sensitive to any differences were established, and the potential of the averaged maximum pressure picture as a quick recognition pattern of a neuropathic diabetic foot was assessed for clinical use. METHODS:: Dynamic pressure distribution data was collected from 56 diabetics using an emed SF2 platform. The first step method was used, and only one step per subject was recorded for this set of data. Each subject completed a questionnaire which included a grading of the sensitivity to vibration on the plantar surface of the foot evaluated by a clinician. The subjects were subsequently divided into four groups depending on this sensitivity, but only data from the two groups with normal (n=16) and no sensation (n=12) were evaluated in this study. Control data were obtained from two separate sources: for adults (n=40) using an emed SF4 platform and for teenagers (n=73) using a mini-emed platform. The groupmask evaluation program from the novel-win software and the average program from the novel-ortho software were used to evaluate the data. Each dynamic pressure distribution was automatically masked using the foot recognition algorithms of the 'novel' mask, which divided the foot into ten areas: the heel, midfoot, first, second, third, fourth and fifth metatarsal heads (MTH), hallux, second toe, and remaining toes. The parameters analysed for each of these masks included: the mean peak pressure, maximum force, contact time, beginning of contact time, pressure-time integral and force-time integral. RESULTS AND DISCUSSION:: The results showed clearly that both pressure and contact time are important parameters in differentiating a neuropathic from a non-neuropathic diabetic foot. Values of the maximum force in each area of the foot showed no difference between the two groups. Owing to the small sample sizes for the two diabetic groups the 95% confidence limits were relatively large, however, clear differences existed between the two sets of data for the mean peak pressure and the mean pressure-time integral for the total foot and the forefoot. Based upon this data, peak pressure values above 56 N/cm(2) for the 1st MTH, 46 N/cm(2) for the 3rd MTH, 35 N/cm(2) for the 4th MTH and 26 N/cm(2) for the 5th MTH, and pressure-time integrals above 31 Ns/cm(2) for the 1st MTH, 21 Ns/cm(2) for the 2nd MTH, 24 Ns/cm(2) for the 3rd MTH, 19 Ns/cm(2) for the 4th MTH and 12 Ns/cm(2) for the 5th MTH would suggest the possibility of a neuropathic diabetic foot. The averaged maximum pressure distribution picture for each group showed some differences between diabetic feet with normal sensation and those with no sensation. However, owing to the small size of the groups, it was felt that the averaged pressure pictures were, at the moment, limited in their use as a quick recognition pattern for the clinician. Although further data has already been collected and will be added to the databank in the near future. CONCLUSIONS:: These data show that averaged maximum pressure pictures alone do not provide sufficient information to differentiate clearly between a non-neuropathic and a neuropathic diabetic foot. Parameters obtained from the dynamic process, in particular, the pressure-time integral, must also be taken into account. It is anticipated that this work will be continued in order to investigate differences between other dynamic processes of potential importance, such as the location and speed of the gait line. ACKNOWLEDGEMENTS:: The authors would like to thank Dr M Morlock and Dr T Tsvetkova for the control data.

Journal Article↗

Reproducibility test on a children's insole for measuring the dynamic plantar pressure distribution.

INTRODUCTION:: This study aimed to establish the reproducibility of a insole measuring system specifically designed for use inside children's shoes. It is important to carry out such an investigation before any measurements are taken in order to ensure that any errors associated with the system are known and quantified. The children's insole had 84 pressure sensors, compared to the adult insoles, with 99 pressure sensors. The sensor technology was essentially the same as used in the adult Pedar system, and incorporated capacitance-based pressure transducers. MATERIALS AND METHOD:: An eight year old boy, height 123 cm, weight 29 kg, was used in the study. Dynamic tests were carried out with the Pedar insole measuring system. The subject walked on a treadmill, at a speed comfortable for him (3 km/h), with the insoles placed between the foot and the shoe. No fixation of the insole to the shoe was used. Seven runs were completed, each with four tests recorded of more than twenty steps. In between each run the insoles were completely removed from the shoe and then replaced. A zero measurement was also taken before the continuation of the next run. Before analysis of the data, twenty steps were selected. The first two steps in each sequence were ignored and the following twenty steps were used in the analysis, ten each for the left and the right foot. Any additional steps recorded were also ignored. The average force for the test data file was initially noted, together with the local pressure for each of the forefoot, midfoot, heel and toe regions, for both the left and the right foot, separately. RESULTS:: The within test data and in-between test data when walking on a treadmill at constant speed was found to be reproducible (F(0.01)) for 6 out of 7 tests for the left and the right foot. The standard deviation of the average force for the left and the right foot was 3%. The 95% confidence intervals for the mean of the peak pressure in the total object was within 6% for the treadmill and free walking data. There was no significant difference between these data. The 95% confidence intervals for the mean of the peak pressure under the big toe was 9% for the treadmill data and 16% for the free walking data. CONCLUSIONS:: These results, together with other published data (McPoil et al. 1995) show that the pedar children's insole system provides accurate and reproducible measurements of the dynamic plantar pressure distribution. The clinician can therefore use this system with confidence as a therapeutic or rehabilitative tool.

Journal Article↗

An investigation of the stress distribution generated in articular cartilage by crystal aggregates of varying material properties.

Several joint diseases are associated with the deposition of crystals within the articular cartilage. A variety of crystal aggregates have previously been identified throughout the thickness of the cartilage. A linear elastic finite element model representing instantaneous, or short-term, loading conditions has been developed of a large crystal aggregate surrounded by articular cartilage. The material properties of the aggregate and the cartilage were varied and the resultant shear stress and equivalent strain distribution in the surrounding cartilage studied in order to provide some indication of the relative potential of various types of crystal aggregate to cause damage to the articular cartilage. Results indicated that aggregates with a Young's modulus either much less, or much greater, than that of the surrounding cartilage generated the maximum shear stress and equivalent strain concentrations at the interface between the aggregate and the cartilage. Also, that highly compressible aggregates, with a very low Poisson's ratio, generated higher shear stress and equivalent strain concentrations in the surrounding cartilage than aggregates of a more incompressible nature. Under conditions of short-term loading these results suggest that crystal aggregates present within the cartilage layer will increase the shear stress and equivalent strain concentrations in the surrounding cartilage, and therefore have the potential to cause damage to the cartilage.

Biomechanical Phenomena↗

How should public health policy be developed? A case study in European public health.

BACKGROUND: Article 129 of the Treaty of Rome (as amended at Maastricht) gave new powers to the European Union (EU) institutions to develop and implement public health programmes at EU level. The authors were invited by the cabinet of Commissioner Flynn to assist the Commission by developing new policy proposals in certain specific areas. METHODS: The approach was agreed with officials of the Public Health Unit (now the Public Health and Safety Directorate) in DG V. Working groups of experts were appointed to review policy options in five discrete areas. The experts were resident in 13 of the 15 current EU member states, and were employed in academic departments, in health ministries, in local government, and in non-governmental organizations. Draft reports were presented to an evaluation panel of additional experts, whose comments contributed to the final report to the Commission. RESULTS: The final report consisted of five main chapters, corresponding to the work of the five working groups. The recommendations were grouped into those for which implementation would be short term, medium term or longer term, and these were summarized as a Plan of Action. CONCLUSION: Five criteria for good public health policy development were satisfied, but the approach used was excessively expensive and time-consuming. Some further lessons for future policy development work have also been recorded. This work provided a fascinating insight into the workings of the EU institutions.

European Union↗

Environmental signals triggering methylenomycin production by Streptomyces coelicolor A3(2).

Methylenomycin production by Streptomyces coelicolor A3(2) may be triggered by either of two environmental signals: alanine growth-rate-limiting conditions and/or an acidic pH shock. The production of this SCP1-encoded antibiotic was studied by using batch and chemostat cultures. Batch cultures indicated a role for both nutritional status and culture pH in its regulation. Steady-state methylenomycin production and transcription of an mmy gene under alanine but not glucose growth-rate-limiting conditions was demonstrated in chemostat culture. Transient mmy expression and methylenomycin production occurred following an acidic pH shock. This stimulation of methylenomycin production occurred independently of the nutritional status of the growth environment. Antibiotic production was partially suppressed under alanine compared with glucose growth-rate-limiting conditions following the acidic pH shock. A low specific growth rate was a prerequisite for both steady-state and transient production of methylenomycin.

Acids↗

Contractile properties of clenbuterol-treated mdx muscle are enhanced by low-intensity swimming.

The beta 2-agonist clenbuterol has potent anabolic properties in normal and denervated muscle and, as such, may be of use in muscle wasting diseases such as muscular dystrophy. However, potential side effects such as the transformation of the fiber type pool toward increased proportions of fast-twitch fibers must be balanced with the beneficial anabolic properties. In the present report, we clearly show that extensor digitorum longus and soleus muscles from dystrophic mdx mice exposed to a combination of clenbuterol and low-intensity endurance swimming exercise did not undergo the slow- fast-twitch fiber transformations caused by clenbuterol administration alone, yet increases in the force-generating capacity of the soleus (30-40%) that resulted from the clenbuterol treatment were maintained after the swimming program. The increased sensitivity of dystrophin-deficient dystrophic muscle to clenbuterol and low-intensity exercise that is evident in this study may have therapeutic implications in the treatment of muscle wasting diseases.

Animals↗