Search PubMed⌕ Search

Biomedical subjects

J Middleton

Publications and source records attributed to J Middleton.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1995

Adaptive finite-element approach for analysis of bone/prosthesis interaction.

The study uses the finite-element method to analyse the stress field in a perfectly bonded hip prosthesis arising from loading through body weight. Special attention is paid to the accuracy of the numerical analysis, and adaptive mesh refinement is introduced to reduce the discretisation error. The finite-element procedure developed is especially well suited to analyse the behaviour of a bonded interface as it is capable of calculating accurately the stress at the nodal positions while satisfying the natural discontinuity in the stress field at this location. An orthotropic material model is used for the representation of the behaviour of the bone, and an axisymmetric geometry with non-symmetrical loading is adopted for the analysis. The results demonstrate the usefulness of adaptive mesh refinement and the significance of adopting anisotropic material modelling in the context of tissue/prosthesis interaction.

Anisotropy↗
PubMed1995

Osteoblasts and osteoclasts in adult human osteophyte tissue express the mRNAs for insulin-like growth factors I and II and the type 1 IGF receptor.

Insulin-like growth factors (IGFs) are among the most abundant growth factors present in bone. In vitro, bone-derived cells both produce and respond to IGFs I and II, suggesting that these growth factors play an autocrine role in the regulation of bone turnover. In vivo, however, particularly in adult bone, their sites of expression have not been well documented. We have used, therefore, the technique of in situ hybridization to study the expression of the mRNAs for IGFs I and II and the type 1 IGF receptor in adult human osteophyte tissue. Throughout the developing osteophyte there was a strong association between osteogenesis and the expression of all three mRNA transcripts. The highest levels of expression were observed in active osteoblasts. Hybridization signals were weak or absent in flat cells lining quiescent surfaces and in cells of the bone marrow, including those that expressed alkaline phosphatase activity. Osteocytes and cells of the periosteum were negative. At sites of endochondral bone formation newly differentiated and hypertrophic chondrocytes expressed the mRNAs for IGFs and IGF receptor whereas cells of the perichondrium were negative. A striking finding of this investigation was that osteoclasts at sites of bone and calcified cartilage resorption expressed high levels of all three mRNA transcripts. These results support the hypothesis that locally produced IGFs are important regulators of bone formation. The differential expression of all three transcripts among cells of the osteoblast lineage suggests that IGFs may be involved in the maintenance of the mature osteoblast phenotype rather than in inducing the differentiation of marrow precursors or controlling the osteoblast-osteocyte transition.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow↗
PubMed1994

Muscle performance, voluntary activation and perceived effort in normal subjects and patients with prior poliomyelitis.

Many people previously affected by polio complain of increased fatigue, weakness and pain many years after the initial illness. Although electromyographic abnormalities have been found in these patients, the cause of their increased weakness is not well understood. Previous studies have shown decreased strength and impaired exercise performance in those with prior polio, but the level of voluntary drive to the muscle has not been investigated. The present study investigated maximal voluntary activation without fatigue and both peripheral and central components of muscle fatigue during exercise in 21 subjects with poliomyelitis 20-40 years previously, and 20 healthy, age-matched control subjects. Voluntary activation and strength of the elbow flexors were quantified using twitch interpolation during maximal isometric voluntary contractions both at rest, and during fatigue induced by 45 min of repeated isometric contractions. Compared with the control subjects, patients with prior polio had impaired voluntary activation both when the elbow flexors were not fatigued and during fatiguing submaximal exercise. During exercise, polio subjects also had lower twitch amplitudes and increased subjective fatigue. Central and peripheral fatigue were more marked in those with the post-polio syndrome. The impaired voluntary activation with unfatigued muscles in polio subjects indicates that defective central or reflex drive may contribute to their new weakness.

Adult↗
PubMed1994

The finite element analysis of stress in the periodontal ligament when subject to vertical orthodontic forces.

In the past, vertical intrusive movement of teeth has been considered difficult and most routine clinical vertical movement of teeth has been confined to extrusion. It has been suggested that attempts at intrusion may result in an increased incidence of root resorption and also in occasional devitalization. The displacement and resulting stress fields associated with such treatment can be successfully studied using the finite element method. In the case being considered initial movements are known to be small; therefore, the assumption in the study that the material behaves linear-elastically is considered to be reasonable. This study of vertical tooth movement demonstrated that the maximum cervical margin stress in the periodontal ligament was 0.0046 N/mm2, whilst the highest apical stress was 0.00205 N/mm2 when intrusive and extrusive forces of 1 Newton were applied to the buccal surface of the crown of a tooth model. These stresses were evaluated in the light of previous studies and found to be within the suggested clinical optimum level. However, the periodontal stress distribution following orthodontic loading within this three-dimensional finite element model was found to be highly complex.

Cuspid↗
PubMed1994

Written lists in the consultation: attitudes of general practitioners to lists and the patients who bring them.

BACKGROUND: Written lists of patients' concerns could help to improve doctor-patient communication in primary care consultations. AIM: This study set out to explore the attitudes of doctors to written lists, and to the patients who bring them. METHOD: A piloted questionnaire was sent to all 58 trainers in the Leicester sub-region--49 (84%) responded. RESULTS: There was evidence of ambiguity in doctors' attitudes to lists--71% thought that they were an aid to clarifying problems, but 67% felt that they would be time consuming, and 45% thought that more patients should bring lists. Doctors also appeared to have a negative stereotype of the patients who bring lists, with 90% endorsing the description obsessional, and over 50% the descriptions heartsink and neurotic. Also, over 75% thought such patients were middle aged and female. CONCLUSION: If patients were to be encouraged to bring lists to consultations, in order to improve communication, it might be necessary to overcome some negative perceptions of doctors, which are perhaps engendered by a small number of patients.

Adult↗
PubMed1993

Street talk.

Explore the source record for details and available documents.

City Planning↗
PubMed1993

Cl- and K+ transport in human biliary cell lines.

BACKGROUND: The cellular mechanisms which contribute to billing secretion and absorption are not fully defined. The purpose of these studies was to evaluate the membrane ion transport properties of Mz-ChA-1 and Sk-ChA-1 cell lines derived from human biliary tumors. METHODS: In cultured cells, 125I and 36Cl efflux rates were used to assess membrane anion permeability, and 86Rb efflux rates were used to assess K+ permeability. RESULTS: Sections of tumors grown on BALB/Urd mice were used for morphological evaluation and for detection of cystic fibrosis transmembrane conductance regulator (CFTR), the protein product of the cystic fibrosis gene. There was organized development of ductular structures and cells stained for gamma-glutamyl transpeptidase and CK-19. Immunoperoxidase staining for CFTR, which is likely a Cl- channel, was also present. Increases in intracellular Ca2+ stimulated by exposure to ionomycin or thapsigargin increased efflux of 125I, 36Cl, and 86Rb. Efflux of 125I was greater than 36Cl, and anion efflux was inhibited by the Cl- channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. Increases in 5'-cyclic adenosine monophosphate increased efflux of 36Cl greater than 125I but had no effect on 86Rb efflux. Both cell lines possess bumetanide-sensitive 86Rb uptake consistent with possible Na+/K+/2Cl- cotransport. CONCLUSIONS: These human cell lines retain certain phenotypic features of differentiated biliary cells and may be useful for further investigation of biliary fluid and electrolyte transport.

Animals↗
PubMed1993

An adaptive finite-element approach for the analysis of dental restorations.

The present paper deals with the problem of stresses generated during the setting process of polymer tooth fillings. A finite element procedure capable of accurately predicting the stresses along an interface between two different materials is presented. Adaptation of the finite element mesh is carried out based on a simple error estimator. The procedure is tested against benchmark problems and then applied to polymer tooth fillings. The results of the study are relevant in understanding and improving the behaviour of dental restorations.

Dental Cavity Preparation↗