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Biomedical subjects

J Middleton

Publications and source records attributed to J Middleton.

At least 37 records · Page 2Linked to original sources
PubMed1999

Accuracy of centre of pressure measurement using a piezoelectric force platform.

OBJECTIVE: To evaluate the accuracy in determining centre of pressure when using a force platform for stabilometry research. DESIGN: Technical report. BACKGROUND: Previous studies have determined the accuracy of locating the centre of pressure by applying force through a single point. In human stabilometry research however, force is distributed across two feet and the centre of pressure located between the feet. METHODS: Forces were applied to a Kistler force platform using a force applied through a single point as well as when force was distributed between two metal blocks. RESULTS: Errors in calculating centre of pressure were substantially larger when force was applied through a single point than when the force was distributed between two blocks. CONCLUSIONS: Evaluating centre of pressure accuracy by applying force through a single point overestimates the errors inherent in human stabilometry research. RELEVANCE: Evaluating changes in the centre of pressure of human subjects standing on a force platform is a common tool for evaluating control mechanisms of balance. Accurate information regarding the centre of pressure is essential for the validity of this research.

Biomechanical Phenomena↗
PubMed1999

Changes in serum chondroitin sulphate epitopes 3-B-3 and 7-D-4 in early rheumatoid arthritis.

OBJECTIVES: The aims of the present rheumatoid arthritis (RA) study were (1) to examine the levels of serum 3-B-3 and 7-D-4 to find out whether they are different from controls, (2) to find out whether the concentrations of these epitopes change with disease duration in early RA and (3) whether the serum concentrations of 3-B-3 and 7-D-4 in early RA are prognostic for subsequent disease progression. METHODS: The concentrations of 3-B-3 and 7-D-4 in sera were quantitated by immunoassays. RESULTS: The levels of 3-B-3 and 7-D-4 were significantly lower in RA than in controls (3- to 30-fold, P < 0.001). Changes in 3-B-3 and 7-D-4 were apparent with disease duration. At first presentation, the 3-B-3 concentration was lowest and increased at 12 months (3-fold, P < 0.001). This increase was transient since by 24 and 36 months the concentrations were not different to those at first presentation. The level of 7-D-4 was also lowest when the patients first presented at clinic and increased with time at 6 months (2-fold, P < 0.001). The increase was more prolonged for 7-D-4, remaining elevated at 12, 24 and 36 months. The lack of correlations of serum 3-B-3 and 7-D-4 with clinical measurements showed that these markers were not prognostic for disease severity. CONCLUSIONS: The levels of 3-B-3 and 7-D-4 differed between RA and control sera, and changed with disease duration. These markers were not prognostic in predicting disease outcome.

Adult↗
PubMed1999

Patient's lists.

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed1998

Endothelial cell "memory" of inflammatory stimulation: human venular endothelial cells store interleukin 8 in Weibel-Palade bodies.

The expression and secretion of interleukin (IL)-8, the prototype member of the C-X-C subfamily of chemokines, can be induced by diverse inflammatory stimuli in many cells, including endothelial cells (EC). Upon de novo synthesis, IL-8 localizes intracellularly in the Golgi apparatus, from where it is secreted. In addition to this constitutive secretory pathway, we describe a depot storage and separate regulated secretory pathway of IL-8 in EC. The prolonged stimulation of primary human EC with inflammatory mediators resulted in the accumulation of IL-8 in Weibel-Palade bodies, where it colocalized with von Willebrand factor. IL-8 was retained in these storage organelles for several days after the removal of the stimulus and could be released by EC secretagogues such as phorbol myristate acetate, the calcium ionophore A23187, and histamine. These findings suggest that storage of IL-8 in Weibel-Palade bodies may serve as the EC "memory" of a preceding inflammatory insult, which then enables the cells to secrete IL-8 immediately without de novo protein synthesis.

Calcimycin↗
PubMed1998

Mortality following spinal cord injury.

This study analyzed the mortality in 1453 spinal cord injured patients admitted early after injury to a specialised Spinal Injuries Unit within a University teaching hospital over a 40-year period. The cohort comprised 55.3% patients with cervical lesions and 44.7% patients with thoracic/lumbar lesions. Those patients who died within 18 months of the spinal injury (132) were excluded from the final analysis. Standardised Mortality Ratios, survival rates and life expectancy ratios were calculated for specific ranges of current attained age and duration since injury with reference to level and degree of spinal cord injury. The projected mean life expectancy of spinal cord injured people compared to that of the whole population was then estimated to approach 70% of normal for individuals with complete tetraplegia and 84% of normal for complete paraplegia (Frankel grade A). Patients with an incomplete lesion and motor functional capabilities (Frankel grade D) are projected to have a life expectancy of at least 92% of the normal population.

Adult↗
PubMed1998

Pain and cognitive status in the institutionalized elderly: perceptions & interventions.

The purposes of this study were to examine the relationship between: (1) nurses' ratings of pain and corresponding administration of pain medication to elderly long-term care residents, and (2) cognitive status of the elderly and pain medication orders/administration. Participants were 83 residents, 60 years of age and older, in two groups: cognitively impaired (n = 64), and cognitively intact (n = 19). For comparison purposes, 19 of the cognitively impaired subjects were matched on age and diagnosis to provide control for potentially painful conditions. A retrospective medication review of the resident's charts was conducted to compare medication orders and administration on analgesics that were scheduled and p.r.n. (given as needed). The pain ratings of 25 RNs using a visual analogue scale were correlated with pain medications given to the resident on the day of the rating. Results indicated that RNs' ratings of resident pain and the administration of pain medications were not significantly correlated. In addition, cognitively impaired residents were prescribed significantly less scheduled medication and received significantly less pain medication (either p.r.n. or scheduled) than the cognitively intact elderly. Implications for practice and research are discussed.

Aged↗
PubMed1998

Vibration perception threshold: are multiple sites of testing superior to single site testing on diabetic foot examination?

Vibration perception threshold (VPT) values, measured at different anatomic locations on the foot and ankle, and the time to assess VPT and sensory perception using two difference modalities in 102 diabetic patients were compared. VPT was evaluated at the great toe, fifth metatarsal and ankle. Differences in VPT at these three sites, in addition to differences in duration of testing comparing single site (great toe) to multiple sites, and to standard SWMF testing were assessed. No significant difference in VPT between the great toe and fifth metatarsal was found for patients both with and without loss of protective sensation (LOPS). Mean VPT was significantly higher at the ankle compared with both the great toes and fifth metatarsals. However, the difference between ankle and great toe was not significant between patients with and without LOPS [3.9 +/- 11.2 (12%) vs. 3.0 +/- 10.8 (16%) volts, respectively, p > 0.6]. Testing of one site took approximately half the time of Semmes-Weinstein 10-gram monofilament wire SWMF testing (40.5 +/- 16.9 vs. 22.3 +/- 9.1 seconds, p < 0.01) and less than one third the time of three-site VPT testing (10.5 +/- 26.1 vs. 22.3 +/- 9.1 seconds, p < 0.01). There may not be a significant practical benefit in multiple site VPT testing when compared with single site testing on the great toe alone. The value of multiple site testing is further called into question when one notes that the great toe VPT remains the only site tested for sensitivity and specificity for ulceration.

Diabetic Foot↗
PubMed1997

Transcytosis and surface presentation of IL-8 by venular endothelial cells.

Chemokines have been convincingly implicated in actuating inflammatory leukocyte emigration. To affect the circulating leukocytes, tissue-derived chemokines have to traverse the endothelial cells (ECs). This was thought to be accomplished by chemokine diffusion through the intercellular gaps. On the contrary, we show by electron microscopy that the prototype chemokine IL-8 is internalized by venular ECs abluminally and transcytosed to the luminal surface. Here, it is presented to the adherent leukocytes on the EC membrane, predominantly in association with the EC projections. The intact C terminus of IL-8, the molecule's "immobilization" domain, is required for the EC binding, transcytosis, and consequently, the in vivo proemigratory activity of IL-8, indicating that the described subcellular interactions of IL-8 with the ECs are functionally relevant.

Animals↗
PubMed1997

Neonatally wounded skin induces NGF-independent sensory neurite outgrowth in vitro.

An in vitro model was established to investigate factors underlying the sensory hyperinnervation of neonatal rat skin wounds that has been observed in vivo (Reynolds and Fitzgerald, J. Comp. Neurol. 358 (1995) 487-489). Explants of normal and wounded rat dorsal foot skin were co-cultured with explants of embryonic chick or newborn rat dorsal root ganglia for 24 h and the number of sensory neurites counted. Explants of skin surrounding a wound made at birth were taken 3 (P3) or 10 (P10) days later and compared with normal skin of the same age. In addition, explants were taken from adult skin wounded 3 and 10 days earlier. At P3, normal skin induced weak neurite outgrowth (mean 13.1 +/- 2.1 neurites per ganglion explant) but skin that had been wounded 3 days earlier, at birth, induced three times more neurite outgrowth (37.8 +/- 3.3). Ten days after wounding at birth, neurite outgrowth was still substantial (40.9 +/- 3.3) although at that age (P10), even normal skin stimulates substantial growth (37.4 +/- 2.9). Normal adult skin also stimulated neurite outgrowth (28.7 +/- 0.45) but this was not increased by wounding 3 or 10 days earlier, and this was enhanced 3 days but not 10 days after wounding. Anti-NGF (nerve growth factor) added to the culture medium blocked the constitutive neurite stimulating activity from normal P10 and adult skin but was ineffective in blocking the neurite stimulating activity produced by neonatal wounding. It is concluded that skin wounding at birth results in release of one or more sensory neurotrophic factors that stimulate rat and chick dorsal root ganglia neurite outgrowth for at least 10 days, but which do not include NGF.

Animals↗
PubMed1997

Quantitative assessments of elbow flexor muscle performance using twitch interpolation in post-polio patients: no evidence for deterioration.

A large number of patients previously affected by polio have symptoms, including increased weakness and fatigue, which are collectively known as a post-polio syndrome. Prospective measurements of strength and endurance using twitch interpolation in post-polio patients are lacking and hence the exact rate of decline in muscle function in these patients is not well defined. We therefore measured performance of the elbow flexor muscles twice, at a mean of 2.5 years apart in a group of selected post-polio subjects (Group A, n = 13) and matched control subjects (n = 11), and in a second group of unselected polio patients from a post-polio clinic (Group B, n = 40) at a mean of 1.7 years apart. All subjects performed 10 attempted maximal voluntary isometric contractions of the elbow flexor muscles, during which voluntary activation of the elbow flexor muscles was measured using a sensitive form of twitch interpolation. The first group of selected polio subjects (Group A) and matched control subjects also performed 45 min of submaximal exercise. During this time, at 5-min intervals, maximal voluntary force, voluntary activation and the amplitude of twitch responses to single and paired stimuli were measured in order to investigate central and peripheral components of muscle fatigue. There was no change in the polio patients' strength, voluntary activation or peripheral muscle endurance between testing sessions, despite an 80% probability of detecting a 2.5% change per year in these variables. The unselected group of patients from the post-polio clinic (Group B) showed no change in maximal voluntary strength or voluntary activation between the first and second test. There was an absence of decline in muscle performance in these polio patients over the test interval, despite a subjective deterioration in muscle function consistent with the 'post-polio syndrome'. This supports the view that symptoms of the post-polio syndrome are not due to a progressive neuronal dysfunction.

Adult↗
PubMed1997

Paying for water.

Water has been taken for granted as an essential public health need since the Victorian sanitary revolution. Water has come back on to the public health agenda in the United Kingdom because of recent policy changes and their untoward environmental and social impacts; along with water privatization and tough new environmental directives, there have been serious water pollution incidents, water shortages, water debt and disconnection. Along with concern about protecting individual rights to a clean safe water supply, there is concern about the ability of national water resources to meet all our communities' needs, without unacceptable environmental damage. A national plan is needed for the conservation of water and protection of water resources and the environment; adequate central funds are needed to see that this happens. There should be greater emphasis on local water management and a key role for local authorities; there should be fair pricing, protection of water supplies for the poorest and most vulnerable, and a ban on water disconnection to domestic users, on public health grounds. More research is needed into the potential adverse health impact of people on prepayment meters disconnecting themselves. There is a place for water metering as the most rapidly deliverable means of controlling peak demand, reducing overall consumption and avoiding a large-scale environmentally damaging solution to supply more water. However, control of leakage offers the largest potential saving and is the most cost-effective means to protect existing water supply. We question whether private water companies, geared to maximizing profit and share dividends, can deliver a national plan for the protection and management of water resources, for the good of the environment and future generations. The public health lobby must become more actively engaged in the debate about the supply, protection and price of our most precious public health asset-water.

Environmental Health↗
PubMed1996

Some aspects of IL-8 pathophysiology. III: Chemokine interaction with endothelial cells.

Chemokines have been convincingly implicated in driving leukocyte emigration in different inflammatory reactions. However, the cellular and molecular mechanisms of chemokine involvement in leukocyte emigration are not clear. We and others suggested that leukocyte adhesion to the endothelium and transmigration are induced by chemokines immobilized on the endothelial cell surface. This would require the presence of specific chemokine binding sites in this microanatomical location. Using an in situ binding assay we demonstrated the presence of binding sites for interleukin-8 (IL-8) and RANTES, but not monocyte inflammatory protein-1 alpha on the endothelium of postcapillary venules and small veins in human skin. In contrast, venules and veins in various anatomical locations showed dramatically differing IL-8 binding patterns. The subcellular distribution of IL-8 in the venular endothelial cells following its in vivo and ex vivo injections was studied by use of electron microscopy. Our results suggest that IL-8 was internalized by the endothelial cells, transported transcellularly via plasmalemmal vesicles, and released onto the luminal surface where it appeared located preferentially on tips of membrane protrusions. We were unable to study the endothelial IL-8 binding or transport in vitro because all the in vitro propagated endothelial cell lines and primary endothelial cells tested lacked IL-8 binding sites. This includes human umbilical vein endothelial cells (HUVECs), which also did not bind IL-8 in situ. However, HUVECs provided a satisfactory in vitro system to study the secretion of IL-8 by the endothelial cells. Two possible alternative pathways were described: secretion directly from the Golgi apparatus or following storage in Weibel-Palade bodies.

Animals↗
PubMed1996

The role of the periodontal ligament in bone modeling: the initial development of a time-dependent finite element model.

Current remodeling theories, as applied to long bones, suggest that such processes are controlled by mechanical strains either within or on the bone surface. In this study, the stresses and strains within the periodontal ligament and surrounding bone, consequent to orthodontic loading of a tooth, were investigated by application of the finite element method. Previously, various authors have applied two and three dimensional instantaneous (essentially static) models to analyze the problems. The study reported in this article describes an initial time-dependent (continuous/dynamic) finite element model for tooth movement that uses newly developed software, the results being cross-referenced against historical data. These early results, from a two-dimensional mathematical model of a loaded canine tooth, suggest that the remodeling process may be controlled by the periodontal ligament rather than the bone. In the finite element model, bone was found to experience a low strain of 1 x 10(-5), whereas the periodontal ligament experienced a strain of 0.1 when the "tooth model" is loaded. Only this latter figure is above the threshold usually reported to be necessary to initiate the remodeling process. Further developments in this rapidly advancing area of biomechanical research should facilitate a greater increase in our knowledge of tissue stress and strain after loading.

Bone Remodeling↗
PubMed1996

Insulin-like growth factor (IGF) receptor, IGF-I, interleukin-1 beta (IL-1 beta), and IL-6 mRNA expression in osteoarthritic and normal human cartilage.

Insulin-like growth factor-I (IGF-I) stimulates the production of extracellular matrix by cartilage cells and this action is mediated through the Type 1 IGF receptor. Expression of the genes for the IGF receptor and for IGF-I was examined in normal and osteoarthritic (OA) human articular cartilage by in situ hybridization. RNA transcripts for Type 1 receptor were detected in all 73 tissue samples and in 80-100% of chondrocytes per section. Signal for the receptor was present in normal and OA cells, and the highest message levels were in the tissues exhibiting advanced pathology. Strong message signals in the cells of the more advanced lesions were also noted for IGF-I, whereas little or no IGF-I mRNA was detected in normal samples. Interleukin-1 beta (IL-1 beta) induces degradation of extracellular matrix by cartilage cells, and expression of this gene was examined with digoxygenin-labeled oligonucleotide probes. mRNA transcripts were detected in only one in five of the cartilage samples taken from OA joints. Unlike IGF-I, expression did not correlate with the degree of OA pathology and positive cells were demonstrated also in samples from young normal cartilage. IL-6 mRNA was present both in surface and deep cells of fibrillated OA cartilage, but no signal was evident in histologically normal cartilage from OA tissue or in normal young joints.

Adult↗
PubMed1996

The expression of mRNA for insulin-like growth factors and their receptor in giant cell tumors of human bone.

Insulin-like growth factors I and II are among the most abundant growth factors found in bone, and their expression also has been reported in a variety of neoplastic tissues. Using the technique of in situ hybridization, the authors have studied the expression of the messenger ribonucleic acid (mRNA) for insulin-like growth factors I and II and the Type I insulin-like growth factor receptor in giant cell tumors of human bone (n = 8). The expression of the mRNA for insulin-like growth factors I and II and the Type 1 insulin-like growth factor receptor was observed in giant cells and in the mononuclear stromal cell component but not in cells of the fibrous connective tissue at the growing edge of the tumor. The multinucleated cells expressed tartrate resistant acid phosphatase and showed reactivity with osteoclast selective monoclonal antibodies, confirming the close relationship between these giant cells and osteoclasts. Thus, these results are consistent with the possibility that locally produced insulin-like growth factors have an important regulatory role in the growth and development of giant cell tumors of bone. In addition, they suggest that these growth factors may function as autocrine or paracrine regulators of the proliferation of differentiation of cells of the osteoclast lineage.

Adolescent↗