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Showing papers by "King's College London published in 1997"


Journal ArticleDOI
TL;DR: This paper analyses critically purposeful and theoretical sampling and offers clarification on the use of theoretical sampling for nursing research to enhance understanding of the differences between purposefuland theoretical sampling in nursing research.
Abstract: Sampling is a very complex issue in qualitative research as there are many variations of qualitative sampling described in the literature and much confusion and overlapping of types of sampling, particularly in the case of purposeful and theoretical sampling. The terms purposeful and theoretical are viewed synonomously and used interchangeably in the literature. Many of the most frequent misinterpretations relate to the disparate meanings and usage of the terminology. It is important that the terminology is examined so that underlying assumptions be made more explicit. Lack of shared meanings and terminology in the nursing discourse creates confusion for the neophyte researcher and increases the production of studies with weak methodologies. This paper analyses critically purposeful and theoretical sampling and offers clarification on the use of theoretical sampling for nursing research. The aim is not to make prescriptive statements on sampling; rather, to enhance understanding of the differences between purposeful and theoretical sampling for nursing research.

2,130 citations


Journal ArticleDOI
TL;DR: The results suggest that NO2−, at physiological or pathological levels, is a substrate for the mammalian peroxidases MPO and lactoperoxidase and that formation of NO2· via per oxidase-catalyzed oxidation ofNO2− may provide an additional pathway contributing to cytotoxicity or host defense associated with increased NO· production.

778 citations


Journal ArticleDOI
15 May 1997-Nature
TL;DR: Mechanical experiments on single molecules of titin are done to determine their visco-elastic properties, showing that there are two main sources of elasticity: one deriving from the entropy of straightening the molecule; the other consistent with extension of the polypeptide chain in the PEVK region.
Abstract: The giant muscle protein titin, also called connectin, is responsible for the elasticity of relaxed striated muscle, as well as acting as the molecular scaffold for thick-filament formation. The titin molecule consists largely of tandem domains of the immunoglobulin and fibronectin-III types, together with specialized binding regions and a putative elastic region, the PEVK domain. We have done mechanical experiments on single molecules of titin to determine their visco-elastic properties, using an optical-tweezers technique. On a fast (0.1s) timescale titin is elastic and force-extension data can be fitted with standard random-coil polymer models, showing that there are two main sources of elasticity: one deriving from the entropy of straightening the molecule; the other consistent with extension of the polypeptide chain in the PEVK region. On a slower timescale and above a certain force threshold, the molecule displays stress-relaxation, which occurs in rapid steps of a few piconewtons, corresponding to yielding of internal structures by about 20 nm. This stress-relaxation probably derives from unfolding of immunoglobulin and fibronectin domains.

734 citations


Journal Article
TL;DR: This paper examined differences in mortality from various causes among regions in Europe related to cold weather conditions and found that mortality increased to a greater extent with given fall of temperature in regions with warm winters.

691 citations


Journal ArticleDOI
TL;DR: Compared with developmentally delayed and normally developing children, 20-month-old children with autism were specifically impaired on some aspects of empathy, joint attention, and imitation.
Abstract: Systematic studies of infants with autism have not been previously carried out. Taking advantage of a new prospective screening instrument for autism in infancy (S. Baron-Cohen et al., 1996), the present study found that, compared with developmentally delayed and normally developing children, 20-month-old children with autism were specifically impaired on some aspects of empathy, joint attention, and imitation. Infants with autism failed to use social gaze in the empathy and joint attention tasks. Both the infants with autism and the infants with developmental delay demonstrated functional play, but very few participants in either group produced spontaneous pretend play. In the developmental delay group, but not the autism group, pretend play was shown following prompting. The implications of these findings for developmental accounts of autism and for the early diagnosis of the disorder are discussed.

599 citations


Journal ArticleDOI
TL;DR: The arthrogenic impairment in quadriceps sensorimotor function and decreased postural stability was associated with reduced functional performance of the patients, and the most important predictors of disability were objective functional performance and quad riceps strength.
Abstract: OBJECTIVE Muscles are essential components of our sensorimotor system that help maintain balance and perform a smooth gait, but it is unclear whether arthritic damage adversely affects muscle sensorimotor function. Quadriceps sensorimotor function in patients with knee osteoarthritis (OA) was investigated, and whether these changes were associated with impairment of functional performance. METHODS Quadriceps strength, voluntary activation, and proprioceptive acuity (joint position sense acuity) were assessed in 103 patients with knee OA and compared with 25 healthy control subjects. In addition, their postural stability, objective functional performance (the aggregate time for four activities of daily living), and disabilities (Lequesne index) were also investigated. RESULTS Compared with the control subjects, the patients with knee OA had weaker quadriceps (differences between group mean 100N, CI 136, 63N), poorer voluntary activation (20% CI 13, 25%) that was associated with quadriceps weakness, and impaired acuity of knee joint position sense (1.28°, CI 0.84, 1.73°). As a group the patients were more unstable (p=0.0017), disabled (10, CI 7, 11), and had poorer functional performance (19.6 seconds, CI 14.3, 24.9 seconds). The most important predictors of disability were objective functional performance and quadriceps strength. CONCLUSIONS In patients with knee OA, articular damage may reduce quadriceps motoneurone excitability, which decreases voluntary quadriceps activation thus contributing to quadriceps weakness, and diminishes proprioceptive acuity. The arthrogenic impairment in quadriceps sensorimotor function and decreased postural stability was associated with reduced functional performance of the patients.

557 citations


Journal ArticleDOI
TL;DR: In this article, it is argued that the public sector has been transformed from a Keynsian Welfare State to a Schumpeterian Workfare State, which involves fundamental changes to forms of provision, patterns of access, forms of work, client relations, worker relations, interinstitutional relations and values and ethics.
Abstract: The paper undertakes two related exercises; one substantive and one meta‐analytical. The first concerns changes in public sector provision. It is argued that the public sector has been ‘transformed’, in Jessop's terms, from a Keynsian Welfare State to a Schumpeterian Workfare State. This transformation involves fundamental changes to forms of provision, patterns of access, forms of work, client — worker relations, inter‐institutional relations and values and ethics. The constitution of citizenship has also been affected. The second concerns the conception of and engagement with social policy by educational researchers. A template for examination of the ‘surface epistemology’ of education policy research is presented — that is the relationships between conceptualisation, research design and conduct and the interpretation of data. It is argued that there is a basic tension at the heart of education policy research, between a commitment to the pursuit of efficiency and a commitment to the pursuit of...

493 citations


Journal Article
TL;DR: 18FDG PET is superior to bone scintigraphy in the detection of osteolytic breast cancer metastases, which led to a poorer prognosis than conventional PET, and osteoblastic metastases show lower metabolic activity and are frequently undetectable by PET.

478 citations


Journal ArticleDOI
TL;DR: GRABHER as mentioned in this paper examines the innovative character, born of necessity, in which actors in the postsocialist setting are restructuring by redefining and recombining resources instead of conceiving these recombinations as accidental aberrations.
Abstract: GRABHER G. and STARK D. (1997) Organizing diversity: evolutionary theory, network analysis and postsocialism, Reg. Studies 31, 533‐544. In contrast to the dominant transition framework that examines organizational forms in Eastern Europe according to the degree to which they conform to, or depart from the blueprints of already existing capitalisms, this paper examines the innovative character, born of necessity, in which actors in the postsocialist setting are restructuring by redefining and recombining resources. Instead of conceiving these recombinations as accidental aberrations, it explores their evolutionary potentials. Its starting premise is that the actual unit of entrepreneurship is not the isolated individual personality but the social networks that link firms and the actors within them. Drawing on recent developments in evolutionary theory, it cautions that although allencompassing privatization and marketization might foster adaptation in the short run, the consequent loss of organizational di...

413 citations


Journal ArticleDOI
TL;DR: The reproducibility and accuracy for the ECM is acceptable while radiographs miss early occlusal lesions, and the new visual system appears promising, but takes time to learn.
Abstract: This laboratory study of 100 occlusal surfaces investigated the reproducibility and accuracy of a visual ranked caries scoring system, an electronic caries scoring system (ECM) using a continuous conductance scale, and a radiographic ranked caries scoring system. Histological examination of the teeth served as a gold standard to validate the ability of each system to assess lesion depth and predict softened, demineralized dentine. After training, 3 examiners carried out each scoring system on two separate occasions. Kappa values for visual, ECM and radiographic ranked scoring systems showed good inter- and intra-examiner reproducibility levels and acceptable limits of agreement for ECM readings. When scoring systems were tabulated against histological scores there was a high correlation between the visual and ECM methods and lesion depth in both enamel and dentine, but radiographic examination could not detect enamel caries. When compared to the histological scoring, the Spearman correlation coefficients for the visual scoring ranged between 0.87 and 0.93, for the ECM between 0.80 and 0.85 and for the radiographic scoring system between 0.76 and 0.78. No tooth scored as visually sound had histological evidence of dentine caries. Soft dentine corresponded to demineralization involving the middle third of the dentine or more which was related to visual cavity formation or an ECM reading above 9 (score 3 or 4). The radiograph was an excellent predictor of soft dentine. In conclusion, the new visual system appears promising, but takes time to learn. The reproducibility and accuracy for the ECM is acceptable while radiographs miss early occlusal lesions.

412 citations


Journal ArticleDOI
TL;DR: A system is set up to analyze the stability of the core domain of the tumor suppressor p53 and its mutants and the possibility of rescue and there are excellent two-state denaturation curves on the addition of urea that may be analyzed quantitatively.
Abstract: Some 50% of human cancers are associated with mutations in the core domain of the tumor suppressor p53. Many mutations are thought just to destabilize the protein. To assess this and the possibility of rescue, we have set up a system to analyze the stability of the core domain and its mutants. The use of differential scanning calorimetry or spectroscopy to measure its melting temperature leads to irreversible denaturation and aggregation and so is useful as only a qualitative guide to stability. There are excellent two-state denaturation curves on the addition of urea that may be analyzed quantitatively. One Zn2+ ion remains tightly bound in the holo-form of p53 throughout the denaturation curve. The stability of wild type is 6.0 kcal (1 kcal = 4.18 kJ)/mol at 25°C and 9.8 kcal/mol at 10°C. The oncogenic mutants R175H, C242S, R248Q, R249S, and R273H are destabilized by 3.0, 2.9, 1.9, 1.9, and 0.4 kcal/mol, respectively. Under certain denaturing conditions, the wild-type domain forms an aggregate that is relatively highly fluorescent at 340 nm on excitation at 280 nm. The destabilized mutants give this fluorescence under milder denaturation conditions.

Journal ArticleDOI
TL;DR: A prototype PET detector which is compatible with a clinical MRI system to provide simultaneous PET and MR imaging was developed, and simultaneousPET and MR phantom images were successfully acquired.
Abstract: We have developed a prototype PET detector which is compatible with a clinical MRI system to provide simultaneous PET and MR imaging. This single-slice PET system consists of 48 2 x 2 x 10 mm3 LSO crystals in a 38 mm diameter ring configuration that can be placed inside the receiver coil of the MRI system, coupled to three multi-channel photomultipliers housed outside the main magnetic field via 4 m long and 2 mm diameter optical fibres. The PET system exhibits 2 mm spatial resolution, 41% energy resolution at 511 keV and 20 ns timing resolution. Simultaneous PET and MR phantom images were successfully acquired.

Journal ArticleDOI
TL;DR: In this paper, a new model for the inclusion of such material is proposed that directly ad- dresses both children's alternative frameworks and the historical and sociocultural context of the discovery.
Abstract: This article focuses on two of the principal issues for science curriculum developers who wish to introduce the history and philosophy of science into the teaching of science — the jus- tification for, and the placement of, historical materials within teachers' schemes of work. First, it is argued that the history and philosophy of science must have a rationale that is integral to, and con- sistent with, teachers' main aims to have any chance of being considered for inclusion in a program of study. Second, the justification must point to places in schemes of work where the inclusion of history of science will directly contribute to students learning of science concepts and satisfy that principal objective. A new model for the inclusion of such material is proposed that directly ad- dresses both children's alternative frameworks and the historical and sociocultural context of the discovery. It is argued that this model offers potential for improved learning of the concepts of sci- ence and for learning about science. ©1997 John Wiley & Sons, Inc. Sci Ed 81:405 - 424, 1997.

Journal ArticleDOI
TL;DR: It is suggested that Shh acts to induce myoblasts committed to slow muscle differentiation from uncommitted presomitic mesoderm to induce slow muscle from medial cells of the somite.
Abstract: The patterning of vertebrate somitic muscle is regulated by signals from neighboring tissues. We examined the generation of slow and fast muscle in zebrafish embryos and show that Sonic hedgehog (Shh) secreted from the notochord can induce slow muscle from medial cells of the somite. Slow muscle derives from medial adaxial myoblasts that differentiate early, whereas fast muscle arises later from a separate myoblast pool. Mutant fish lacking shh expression fail to form slow muscle but do form fast muscle. Ectopic expression of shh, either in wild-type or mutant embryos, leads to ectopic slow muscle at the expense of fast. We suggest that Shh acts to induce myoblasts committed to slow muscle differentiation from uncommitted presomitic mesoderm.

Journal ArticleDOI
TL;DR: Findings from this laboratory confirm that NIDDM is associated with increased oxidative stress as assessed by plasma ROOHs and suggest that oxidative stress is an early stage in the disease pathology, which may contribute to the development of complications.
Abstract: Diabetes mellitus may be associated with increased lipid peroxidation which may contribute to long-term tissue damage. To test this hypothesis, we measured hydroperoxides (ROOHs) as well as α-tocopherol in plasma from healthy subjects and individuals with non-insulin-dependent diabetes mellitus (NIDDM) (n = 41 and 87, respectively). ROOHs were analysed using the ferrous oxidation with xylenol orange version II (FOX2) assay in conjunction with a specific ROOH reductant, triphenylphosphine. α-Tocopherol was analysed by HPLC with fluorimetric detection. NIDDM patients had lower cholesterol standardised α-tocopherol levels as compared to control subjects (3.3 ± 1.0 vs 5.1 ± 2.3 (μmol/l)/(mmol/l); p < 0.0005, Mann-Whitney test): range (1.5–6.5 vs 1.9–13.0, respectively). Plasma ROOHs were substantially higher in the diabetic subjects compared to those of the control subjects (9.4 ± 3.3 vs 4.1 ± 2.2 μmol/l; p < 0.0005 Mann-Whitney test: range 2.7–16.8 vs 0.4–10.3, respectively). ROOH/cholesterol standardised α-tocopherol ratio was significantly higher in the diabetic patients compared to control subjects (3.2 ± 1.6 vs 0.9 ± 0.6; p < 0.0005, Mann-Whitney test: range 0.7–8.3 and 0.1–2.7, respectively). Plasma levels of ROOHs and α-tocopherol were similar in diabetic patients with or without complications as well as in smokers and non-smokers. The present study confirms previous findings from this laboratory that NIDDM is associated with increased oxidative stress as assessed by plasma ROOHs. Increased oxidative stress in diabetic patients appears to be related to the underlying metabolic abnormalities in diabetes, rather than to the complications of this disease. We therefore suggest that oxidative stress is an early stage in the disease pathology, which may contribute to the development of complications. [Diabetologia (1997) 40: 647–653]

Journal ArticleDOI
TL;DR: Evidence of convergent evolution among diverse bacterial groups to achieve the end of energy-yielding sulfur compound oxidation (to drive autotrophic growth on carbon dioxide) but using a variety of enzymological systems, which share some common features is presented.
Abstract: The history of the elucidation of the microbiology and biochemistry of the oxidation of inorganic sulfur compounds in chemolithotrophic bacteria is briefly reviewed, and the contribution of Martinus Beijerinck to the study of sulfur-oxidizing bacteria highlighted. Recent developments in the biochemistry, enzymology and molecular biology of sulfur oxidation in obligately and facultatively lithotrophic bacteria are summarized, and the existence of at least two major pathways of thiosulfate (sulfur and sulfide) oxidation confirmed. These are identified as the ‘Paracoccus sulfur oxidation’ (or PSO) pathway and the ‘S4intermediate’ (or S4I) pathway respectively. The former occurs in organisms such as Paracoccus (Thiobacillus) versutus and P. denitrificans, and possibly in Thiobacillus novellus and Xanthobacter spp. The latter pathway is characteristic of the obligate chemolithotrophs (e.g. Thiobacillus tepidarius, T. neapolitanus, T. ferrooxidans, T. thiooxidans) and facultative species such as T. acidophilus and T. aquaesulis, all of which can produce or oxidize tetrathionate when grown on thiosulfate. The central problem, as yet incompletely resolved in all cases, is the enzymology of the conversion of sulfane-sulfur (as in the outer [S-] atom of thiosulfate [-S-SO3-]), or sulfur itself, to sulfate, and whether sulfite is involved as a free intermediate in this process in all, or only some, cases. The study of inorganic sulfur compound oxidation for energetic purposes in bacteria (i.e. chemolithotrophy and sulfur photolithotrophy) poses challenges for comparative biochemistry. It also provides evidence of convergent evolution among diverse bacterial groups to achieve the end of energy-yielding sulfur compound oxidation (to drive autotrophic growth on carbon dioxide) but using a variety of enzymological systems, which share some common features. Some new data are presented on the oxidation of 35S-thiosulfate, and on the effect of other anions (selenate, molybdate, tu ngstate, chromate, vanadate) on sulfur compound oxidation, including observations which relate to the roles of polythionates and elemental sulfur as intermediates.

Journal ArticleDOI
TL;DR: The results suggest that schizophrenia is associated with a reduced left and increased right temporal cortical response to auditory perception of speech, with little distinction between patients who differ in their vulnerability to hallucinations.
Abstract: OBJECTIVE: The authors explored whether abnormal functional lateralization of temporal cortical language areas in schizophrenia was associated with a predisposition to auditory hallucinations and whether the auditory hallucinatory state would reduce the temporal cortical response to external speech. METHOD: Functional magnetic resonance imaging was used to measure the blood-oxygenation-level-dependent signal induced by auditory perception of speech in three groups of male subjects: eight schizophrenic patients with a history of auditory hallucinations (trait-positive), none of whom was currently hallucinating; seven schizophrenic patients without such a history (trait-negative); and eight healthy volunteers. Seven schizophrenic patients were also examined while they were actually experiencing severe auditory verbal hallucinations and again after their hallucinations had diminished. RESULTS: Voxel-by-voxel comparison of the median power of subjects' responses to periodic external speech revealed that this ...

Journal ArticleDOI
TL;DR: The catechin polyphenols were found to offer protection from peroxynitrite-induced modification of critical amino acids of apolipoprotein B-100 of LDL which contribute towards its surface charge.

Journal ArticleDOI
TL;DR: In this article, the authors investigated factors influencing farmers' motivations for participation in the Cambrian Mountains ESA scheme (Wales, UK) and concluded that a behavioural approach offers a valuable insight into farmers' decision-making behaviour with regard to participation in agri-environmental schemes.

Journal ArticleDOI
01 Mar 1997-Stroke
TL;DR: The levels of both health and social service provision are likely to be inadequate for this population of stroke patients and there is a clear need for a coordinated policy to guide assessment and management across sectors.
Abstract: Background and Purpose Two hundred ninety-one residents of southeast London, younger than 75 years, suffered their first stroke in 1989/1990. The objectives of this study were to determine the long-term outcome of this cohort of stroke patients in terms of impairment, disability, handicap, and quality of life and their use of services and prevention measures subsequent to their stroke. Methods The survivors and their identified caregivers were traced and completed a structured interview questionnaire that included the Barthel Index, modified Rankin Scale, Hospital Anxiety and Depression Scale (HAD), Mini-Mental State Examination, Frenchay Activities Index, and Caregiver Strain Index. Results One hundred twenty-three people (42%) were alive, of whom 106 were interviewed. The mean interval between the stroke and the long-term follow-up was 4.9 years. Thirty-one of the survivors (29%) were severely or moderately disabled, 39 (37%) were mildly disabled, and 36 (34%) were functionally independent. Of the 96 pe...

Journal ArticleDOI
TL;DR: Comparing, on consecutive sections, the distribution c-fos messenger RNA (mRNA) with that of mRNAs for peptides synthesized in arcuate cells, including neuropeptide Y (NPY), GH-releasing factor (GRF), tyrosine hydroxylase, POMC, and somatostatin indicated the majority of cells expressing c- fos mRNA following GHRP-6 injection are NPY and GRF-containing cells.
Abstract: In this study we investigated the neurochemical identity of the arcuate cells activated following GH-releasing peptide-6 (GHRP-6) injection by comparing, on consecutive sections, the distribution c-fos messenger RNA (mRNA) with that of mRNAs for peptides synthesized in arcuate cells, including neuropeptide Y (NPY), GH-releasing factor (GRF), tyrosine hydroxylase, POMC, and somatostatin. Rats bearing chronically implanted jugular catheters were injected with either 50 μg GHRP-6 or vehicle. Thirty minutes later they were terminally anesthetized and perfused with fixative. Paraffin-embedded sections of 7 μm thickness were processed using in situ hybridization for either c-fos mRNA or mRNAs for the neurochemical markers. In GHRP-6-treated rats the mean (± sem) number of cells expressing c-fos mRNA in the arcuate nucleus (23 ± 2 cells/section per rat; n = 5) was significantly higher than for vehicle-treated controls (2 ± 1 cells/section per rat; n = 5; P < 0.001, Mann-Whitney U test). Superimposed camera lucid...

Journal ArticleDOI
TL;DR: The component form of the equations of motion for the 5-brane in eleven dimensions is derived from the superspace equations in this article, which are fully covariant in six dimensions.

Journal ArticleDOI
TL;DR: It is reported here that Wnt-7a is expressed in cerebellar granule cell neurons as they begin to extend processes and form synapses, and it is proposed that WNT proteins have a novel function in the formation of neuronal connections.

Journal ArticleDOI
TL;DR: The authors dealt with the following questions: 1) The "Literacy Debate" and 2) Why do such apparently arcane accounts of language and literacy have such a high profile in popular culture?
Abstract: This paper deals with the following questions:1. The ‘problem’: what is the ‘Literacy Debate’ and why do such apparently arcane accounts of language and literacy have such a high profile in popular...

Journal ArticleDOI
TL;DR: These findings provide the first evidence that V EGF can stimulate PGI2 synthesis via cPLA2‐mediated arachidonic acid release and indicate that VEGF stimulation of this biosynthetic pathway may occur, at least in part, via activation of p42/p44 MAP kinases.

Journal ArticleDOI
TL;DR: In this article, a variety of bioassessment metrics were tested using family-level macroinvertebrate data, gathered by standard colonization units, and associated physicochemical data from pollution gradients in three rivers in developing countries.
Abstract: 1. A variety of bioassessment metrics were tested using family-level macroinvertebrate data, gathered by standard colonization units, and associated physicochemical data from pollution gradients in three rivers in developing countries. 2. Graphical methods of evaluation were used to evaluate the metrics with respect to these pollution gradients. 3. In general, the macroinvertebrate communities sampled displayed a similar response to pollution to that observed in well-studied temperate areas. 4. Of the twenty metrics tested seven described the pollution gradients adequately. Four of these seven metrics, which do not supply duplicate information, were selected for use in a multimetric system of bioassessment. 5. A multimetric system is proposed and tested using the original macroinvertebrate data. It performs well in the assessment of the pollution status of the study sites and the description of the pollution gradient. However, local modifications are likely to enhance its performance.

Journal ArticleDOI
TL;DR: In this article, the minimum energy path for photoisomerization of the minimal retinal protonated Shiff base model tZt-penta-3,5-dieniminium cation (cis-C5H6NH2+) is computed using MC−SCF and multireference Moller−Plesset methods.
Abstract: The minimum energy path for photoisomerization of the minimal retinal protonated Shiff base model tZt-penta-3,5-dieniminium cation (cis-C5H6NH2+) is computed using MC−SCF and multireference Moller−Plesset methods. The results show that, upon excitation to the spectroscopic state, this molecule undergoes a barrierless relaxation toward a configuration where the excited and ground states are conically intersecting. The intersection point has a ∼80° twisted central double bond which provides a route for fully efficient nonadiabatic cis → trans isomerization. This mechanism suggests that cis-C5H6NH2+ provides a suitable “ab initio” model for rationalizing the observed “ultrafast” (sub-picosecond) isomerization dynamics of the retinal chromophore in rhodopsin. The detailed analysis of the computed reaction coordinate provides information on the changes in molecular structure and charge distribution along the isomerization path. It is shown that the initial excited state motion is dominated by stretching modes ...

Journal ArticleDOI
TL;DR: The concept thatIL-5 may determine asthma clinical expression and severity is supported, and by inference they support the development of IL-5 targeted therapies.
Abstract: Atopic asthma is characterized by chronic inflammation of the bronchial mucosa in which eosinophil- and immunoglobulin E (IgE)–dependent mechanisms are believed to be prominent. Therefore, specific proeosinophilic mediators such as interleukin (IL)-5 and essential cofactors for IgE switching in B-lymphocytes such as IL-4 could play a pivotal role in asthma. However, the exact role that individual inflammatory mediators play in the development of the disease in humans is still unknown. Using semiquantitative reverse transcriptase-polymerase chain reaction amplification in bronchial biopsies from 10 atopic asthmatics, we have tested the hypothesis that IL-4 and IL-5 mRNA expression relative to β -actin mRNA correlates with validated indicators of disease severity. IL-4 and IL-5 mRNA copies relative to β -actin mRNA were detected in bronchial biopsies from atopic asthmatics. The numbers of IL-5 mRNA copies relative to β -actin mRNA correlated with disease severity assessed by the Aas asthma score (r = 0.70, ...

Journal ArticleDOI
TL;DR: Evidence that the neuropeptides substance P and CGRP, acting via tachykinin NK1 and NK2 receptors, play a pro-inflammatory role in disease and a beneficial role in wound healing are concentrated on.

Journal ArticleDOI
01 Dec 1997-Brain
TL;DR: Interictal epileptiform discharges may originate from a complex interaction between separate regions, resulting in propagation and recruitment of neuronal activity along specific neural pathways, and identification of such leading regions could be used to improve seizure control and reduce neurological, neuropsychological and psychiatric post-surgical morbidity.
Abstract: Although acute electrocorticography (ECoG) is routinely performed during epilepsy surgery there is little evidence that the extent of the discharging regions is a useful guide to tailoring the resection or that the findings are predictive of outcome or pathology. Patterns of discharge propagation have, however, rarely been considered in assessing the ECoG. We hypothesize that regions where discharges show earliest peaks ('leading regions') are located in the epileptogenic zone, whereas sites in which late, secondary, propagated activity occurs have less epileptogenic potential and do not need to be excised. To allow intraoperative topographic ECoG analysis, a computer program has been developed to identify leading regions and the sites showing greatest rates or amplitudes of spikes. Their topography has been compared retrospectively with pathology and seizure control in 42 consecutive patients following temporal lobe surgery. Leading regions were most often found in the hippocampus, the subtemporal cortex and the superior temporal gyrus. The most common propagation patterns were from hippocampus to subtemporal cortex and vice versa. There was no association between seizure outcome and the location of regions with greatest incidence or amplitude of spikes or location of leading regions. There was, however, a strong and significant association between poor outcome and non-removal of leading regions other than those in the posterior subtemporal cortex. All leading regions (other than posterior subtemporal) were resected in 27 patients of whom 25 had a favourable outcome. Leading regions (other than posterior subtemporal) remained in 14 patients of whom only four had a good outcome. One patient had no epileptiform activity in the ECoG and good outcome. Persistent posterior subtemporal leading regions remained in nine subjects; all had favourable outcome (Grades I or II) but only three were seizure free. These results suggest that: (i) interictal epileptiform discharges may originate from a complex interaction between separate regions, resulting in propagation and recruitment of neuronal activity along specific neural pathways; (ii) removal of all discharging areas appears unnecessary to achieve seizure control provided that leading regions (other than posterior subtemporal) are removed; and (iii) identification of such leading regions could be used to tailor resections in order to improve seizure control and reduce neurological, neuropsychological and psychiatric post-surgical morbidity.