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Biomedical subjects

A J Frew

Publications and source records attributed to A J Frew.

At least 127 records · Page 7Linked to original sources
PubMed1988

The pattern of human late-phase skin reactions to extracts of aeroallergens.

The kinetics and dose response of cutaneous late phase reactions (LPR) (defined as greater than 5 mm induration 6 hours after intradermal challenge with allergen) were studied in 20 randomly selected subjects with atopic rhinitis. When subjects were challenged intradermally with 0.2 biologic unit (BU) of Dermatophagoides pteronyssinus or grass pollen, wheal-and-flare reactions were elicited without subsequent LPRs. With 30 BU, all subjects developed LPRs, whereas 1 and 10 BU provoked LPRs in 28% and 64%, respectively. No biphasic responses were detected. At all concentrations which progressed to form an LPR, a palpable skin reaction was continuously present and either remained constant or increased steadily in magnitude during 6 hours. Skin reactions of similar diameter provoked by histamine resolved fully within 2 hours. Thus, we confirm that the development of a macroscopic cutaneous LPR requires a higher concentration of allergen than the wheal-and-flare reaction. Together with our other findings, these results suggest that all untreated atopic individuals are capable of mounting an LPR if they are challenged with sufficient allergen. In contrast to the asthmatic response to inhaled allergen, the cutaneous wheal and LPR are not biphasic.

Adult↗
PubMed1988

MHC class II restriction specificity of cloned human T lymphocytes reactive with Dermatophagoides farinae (house dust mite).

In this report the antigen and restriction specificity of human T-cell clones induced with Dermatophagoides farinae (D. farinae) and isolated from an atopic individual with perennial rhinitis has been investigated. Of the six clones analysed, four were species specific and two showed cross-reactivity for the closely related Dermatophagoides pteronyssinus (D. pteronyssinus). Inhibition of antigen-dependent proliferation by murine monoclonal antibodies directed against HLA-D-region gene products revealed that all the clones were restricted by HLA-DR molecules. The restriction specificity was investigated further using a panel of histocompatible and allogeneic-presenting cells. Of the clones tested, one appeared to be DR5 restricted while the remainder showed complex patterns suggesting that DRw52 and DRw53 supertypic specificities may be the restriction elements presenting antigen.

Allergens↗
PubMed1987

An outbreak of tuberculosis in an Oxfordshire school.

A primary school teacher was found to have pulmonary tuberculosis. Subsequent investigations showed that nine of her 32 pupils had been infected. The problem is discussed in the light of current recommendations designed to protect schoolchildren.

Adult↗
PubMed1987

A comparison of symptoms and intra-arterial ambulatory blood pressure during long term dual chamber atrioventricular synchronous (DDD) and ventricular demand (VVI) pacing.

Fifteen patients with dual chamber pacemakers implanted for atrioventricular block (11) or sinoatrial disease (4) completed a single blind within-patient comparison of symptoms and 24 hour intra-arterial blood pressure during long term atrioventricular synchronous (DDD) pacing and long term ventricular demand (VVI) pacing. The patients reported significantly less breathlessness, fatigue, and dizziness and a significantly greater sense of general well-being during DDD pacing than during VVI pacing. Twelve of the fifteen patients expressed a strong preference for DDD pacing. Systolic blood pressure tended to be lower and was significantly more variable during VVI pacing than during DDD pacing (mean (SD) daytime systolic blood pressure 132.4 (17.1) and 140.4 (13.1) mm Hg respectively). Accordingly, episodes of hypotension were more common during VVI pacing, which may partly explain why the patients reported more symptoms during this mode of pacing.

Aged↗
PubMed1985

Changes in ventilation and its components in normal subjects during sleep.

Non-invasive measurements were made of ventilation, its derivatives, the contributions of abdomen and rib cage and arterial oxygen saturation in six healthy normal men whilst awake and during sleep. Minute ventilation fell significantly during slow wave (SW) sleep and rapid eye movement (REM) sleep (awake = 6.3 1 min-1, SW sleep = 5.7 1 min-1, REM sleep = 5.4 1 min-1; p less than 0.04). Mean inspiratory flow also fell significantly but timing was unchanged. The abdominal (diaphragmatic) contribution to ventilation fell very significantly during SW sleep but returned to awake levels during REM sleep (awake 54%, SW sleep 38%, REM sleep 56%; p less than 0.007). There were also significant falls in arterial oxygen saturation during SW and REM sleep (awake 97.3%, SW sleep 96.5%, REM sleep 96.2%; p less than 0.002). These falls represent reductions in arterial oxygen tension similar to those seen in patients with chronic airways obstruction and can be accounted for entirely by the associated reduction in ventilation.

Abdomen↗
PubMed1980

Proliferative response of lymphocytes of normal individuals to wheat proteins (gliadins).

Preparations of gliadin, extracted from wheat gluten, were shown to stimulate a proliferative response by lymphocytes of normal donors. Not all donors responded to gliadin. In all but one case responder or non-responder status remained consistent on retesting. There was no association of ability to respond with HLA A or B type.

Dose-Response Relationship, Immunologic↗
PubMed1977

Relationship between the HLA associated specifities 4a and 4b and the lymphocyte C3 receptor.

Contrary to previous reports, we have obtained no evidence that 4a and 4b antisera specifically inhibit C3 rosette formation by human lymphocytes. Pretreatment of lymphocytes with various whole 4a and 4b antisera resulted in partial inhibition which was often nonsepcific. Ultracentrifugation of the sera to remove immune complexes removed C3 rosette inhibitory activity although specific cytotoxic activity remained. It is probable that immune complexes in antisera will have fixed C3 which will have been converted to C3d and so be able to block the C3d receptor. This is the receptor mainly measured in these and in the previous experiments.

Complement C3↗
PubMedDate not supplied

Mapping therapeutic response in a patient with malignant glioma.

Short-interval scanning of patients offers a detailed understanding of the natural progression of tumor tissue, as revealed through imaging markers such as contrast enhancement and edema, prior to therapy. Following treatment, short-interval scanning can also provide evidence of attenuation of growth rates. We present a longitudinal imaging study of a patient with glioblastoma multiforme (GBM) scanned 15 times in 104 days on a 3 T MR scanner. Images were analyzed independently by two automated algorithms capable of creating detailed maps of tumor changes as well as volumetric analysis. The algorithms, a nearest-neighbor-based tissue segmentation and a surface-modeling algorithm, tracked the patient's response to temozolomide, showing an attenuation of growth. The need for surrogate imaging end-points, of which growth rates are an example, is discussed. Further, the strengths of these algorithms, the insight gained by short-interval scanning, and the need for a better understanding of imaging markers are also described.

Algorithms↗
PubMedDate not supplied

Genetic and environmental influences on airway inflammation in asthma.

The clear recognition that asthma has an inflammatory basis has led to a search for genetic and environmental causes. Genetic linkage studies provide evidence for allelic association between polymorphic markers of interleukin-9 on chromosome 5 and a principal component of the allergic phenotype, log IgE. Further studies that intrauterine environmental factors are an important determinant of the allergic phenotype in addition to allergen exposure during the first year of life. Once sensitised, the respiratory mucosa provides the allergic interface between the environment and internal milieux involving autacoid and cytokine release from mast cells. Up-regulation of endothelial cell adhesion molecules, specifically E-selectin and ICAM-1, is responsible for the leucocyte recruitment of the late-phase asthmatic response, while recruitment of T cells and their subsequent activation contribute to the ongoing inflammatory response of asthma. The epithelium is the origin and target tissue for the inflammatory response, resulting in detachment of suprabasal cells, up-regulation of adhesion molecules and enhanced mediator and cytokine secretion. These latter findings, being more evident in severe chronic disease, suggest that the 'formed' airway elements are also important in mediating the ongoing inflammation characteristic of asthma.

Allergens↗
PubMedDate not supplied

Cardiovascular safety of second-generation antihistamines.

Reports of serious cardiac arrhythmia associated with some second-generation antihistamines have prompted concern for their prescription. This article reviews the nature of the adverse events reported and concludes that the blockade of potassium channels, particularly the subtype responsible for the rapid component of the delayed rectifier current (IKr), is largely responsible for such adverse cardiac events. Consequently, antihistamines with little or no interaction with these channels are expected to have the greatest safety margin. The main cardiac arrhythmia of concern is that of torsades de pointes, a potentially fatal phenomenon characterized by prolonged ventricular depolarization that manifests as a prolonged QT interval and polymorphic ventricular tachycardia, with twisting of the QRS complexes. Based on pre-clinical and clinical evidence, it appears that loratadine, cetirizine, and fexofenadine are safe from cardiac arrhythmia via the IKr channel, whereas astemizole and terfenadine have a propensity to cause ventricular tachyarrhythmias.

Animals↗
PubMedDate not supplied

Toxicological mechanisms underlying oxidant pollutant-induced airway injury.

The health effect of atmospheric pollution is causing increasing public concern. Several controlled human-exposure studies have clearly. shown that oxidant pollutants, including ozone, nitrogen dioxide, and diesel exhaust, induce an acute inflammatory response in human airways. The main component of this response involves the influx of polymorphonuclear leukocytes (PMN) and is mediated via the upregulation of transcription factors NF-kappa B, AP-1, and NF-IL6; leukocyte-endothelial adhesion molecules, and chemokine secretion, including IL-8 and Gro-alpha. The results of recent studies also suggest that short-term exposure to ozone leads to neurogenic inflammation by causing damage to the bronchial epithelium and stimulating subepithelial sensory nerves to release substance P. In addition, such exposures lead to the consumption of endogenous antioxidants that are present in the airway lining fluid. Studies in asthmatics have shown that oxidant pollutants, including ozone and nitrogen dioxide, induce PMN influx in the airways and potentiate responses to inhaled aero-allergens. This article will review various studies addressing the toxicological mechanisms underlying oxidant pollutant-induced airways injury.

Air Pollution↗