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Biomedical subjects

E R Chilvers

Publications and source records attributed to E R Chilvers.

80 records · Page 5Linked to original sources
PubMed1989

Absence of circulating products of oxygen derived free radicals in acute severe asthma.

Oxygen derived free radicals (ODFRs), generated by eosinophils, neutrophils, alveolar macrophages and mast cells, have been proposed as important mediators of inflammatory damage in asthma. We attempted to assess the role of these free radicals in patients with acute asthma by determining serum concentrations of phospholipid-esterified 9, 11 and the parent 9, 12-linoleic acid isomers (9, 11-LA, 9, 12-LA), using HPLC and diode array detection. The diene conjugate, 9, 11-LA, has been shown to be a sensitive and specific marker of free radical activity in other inflammatory conditions. Eight patients (6 female, aged 19-42 years) with acute asthma (mean peak expiratory flow 92 +/- (26) m (SEM) l.min-1, mean PaO2 8.4 (1.0) kPa were studied at 0, 6, 12, 24 and 48 hours after admission to hospital and again 4-6 weeks later. Initial blood samples were taken prior to the administration of oxygen or drug therapy. On admission, mean concentrations of 9, 11-LA and 9, 12-LA were normal at 18.0 (2.8) and 1024 (118) mumol.l-1. All subsequent 9, 11-LA serum concentrations were likewise in the normal range. The serum 9, 11-LA/9, 12-LA ratio was 1.9 (0.4) on admission and 1.6 (0.2) in convalescence (Normal Range 1.0-3.8). These findings in peripheral blood do not support a major role or oxygen derived free radical production in acute asthma, but local airway production cannot be excluded.

Adult↗
PubMed1988

Quantification of right to left shunt through pulmonary arteriovenous malformations using 99Tcm albumin microspheres.

Calculation of the right-to-left shunt through pulmonary arteriovenous malformations (PAVMs) is important in assessing the effect of therapeutic embolisation or surgical resection. Previously, complicated physiological techniques using radiolabelled inert gases or the 100% oxygen breathing method were required. We describe a new method for quantitating the systemic uptake of intravenously injected 99Tcm albumin microspheres (99Tcm MS) which reflects shunt fraction since these particles do not normally traverse the pulmonary capillary bed. Seven patients with PAVMs were studied and shunt values obtained using 99Tcm MS were validated by simultaneous measurement of shunt fraction using the 100% oxygen method. By comparing radioactive counts in the injection dose to subsequent counts in the right kidney, which was taken as an index of systemic activity, accurate quantification of right-to-left shunt over a wide range of values was obtained (correlation coefficient against 100% oxygen method r = 0.993). The comparison of right kidney counts with total lung counts and total lung counts with injected dose counts, also indicators of shunt fraction, correlated less well with the oxygen method (r = 0.942 and r = 0.88 respectively). Use of 99Tcm labelled microspheres allows simple and precise measurement of right-to-left shunt in patients with PAVMs during routine isotope lung scanning.

Adult↗
PubMed1988

Effect of peptide histidine valine on cardiovascular and respiratory function in normal subjects.

Non-adrenergic inhibitory nerves may have an important role in regulating airway calibre. A recently discovered peptide, peptide histidine valine, is a potent relaxer of airway smooth muscle in vitro and has been proposed as a possible neurotransmitter in this tissue. The cardiovascular and respiratory effects of graded infusions of this peptide (2.5-10 pmol kg-1 min-1) have been examined in six normal subjects in a placebo controlled, randomised double blind study. The mean (SEM) peak plasma concentration of peptide histidine valine during the highest infusion rate was 2392 (170) pmol/l, representing a 29 fold increase above the basal concentration. This was accompanied by flushing, a significant increase in heart rate of 28 (3.7) beats/min and skin temperature of 1.8 degrees (0.16 degrees) C, but no effect on systolic or diastolic blood pressure. Despite these high plasma concentrations of the peptide and the substantial tachycardia and increase in skin blood flow, there was no change in partial expiratory flow at 40% of vital capacity (Vp40) or in the airway response to inhaled histamine (geometric PD40 9.37 and 9.73 mumol during saline and peptide histidine valine infusion respectively). Although these findings provide no support for a physiological role of peptide histidine valine in controlling airway function in healthy subjects, important effects of locally released peptides in the vasoactive intestinal peptide family cannot be excluded.

Adult↗
PubMed1988

Clinical and physiological aspects of pulmonary arteriovenous malformations.

In view of the high morbidity and mortality associated with unrecognized or untreated pulmonary arteriovenous malformations it is essential that a provisional diagnosis is followed by definitive investigation and prompt intervention. Careful physiological monitoring, including measurement of the right-to-left shunt, is required.

Angiography↗
PubMed1983

The blood supply of the islets of Langerhans in the Mongolian gerbil.

Ink injection studies and point counting have been used to follow and quantify the development of vascularity in the islets of Langerhans of the Mongolian gerbil. Vascularization is essentially a postnatal event in this species. Initially, islet capillaries form part of the general capillary bed of the gland, but subsequently they develop a direct arteriolar supply and venous drainage. The capillary connections with the exocrine bed are retained to form the basis of an insulo-acinar portal system. The volume fraction of islet vascularity remains constant at 19% from birth to adulthood, while the volume fraction of the intra-insular capillaries increases gradually in the first week; it accounts for half the total islet vascularity by day 14 and two thirds of total islet vascularity in the adult.

Aging↗
PubMedDate not supplied

Phosphoinositide metabolism in airway smooth muscle.

Agonist-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate, which generates inositol 1,4,5-trisphosphate and sn-1,2-diacylglycerol, is thought to be one of the major mechanisms underlying pharmacomechanical coupling in airway smooth muscle. This article is a review of the currently available information on phosphoinositide and inositol 1,4,5-trisphosphate metabolism in this tissue and includes data on inositol 1,4,5-trisphosphate-induced Ca2+ release and the receptor mediating this effect. The final section outlines the potential mechanisms underlying physiological regulation of phosphoinositide metabolism by other second-messenger pathways operative in this tissue.

Animals↗
PubMedDate not supplied

The function and fate of neutrophils at the inflamed site: prospects for therapeutic intervention.

Neutrophils play a key role in the immediate non-specific immune response, and defects in their function increase host susceptibility to a range of infective agents. However, excess activation and/or delayed clearance of these cells from an inflamed site can lead to significant tissue damage. Neutrophil priming by agents such as endotoxin, granulocyte macrophage colony stimulating factor (GM-CSF), platelet activating factor (PAF) and tumour necrosis factor-alpha (TNF alpha) may play a pivotal role in modulating the adhesive and secretory properties of these cells. Priming also appears to affect the survival of neutrophils by delaying constitutive apoptosis. The unique signal transduction events that control neutrophil priming and apoptosis, and particularly the importance of the phospholipase C and phosphoinositide 3-kinase pathways, suggest opportunities for selective pharmacological intervention.

Apoptosis↗