General Principles. Obstructive Airway Diseases. Respiratory Failure. Respiratory Infections. Opportunistic Infections in the Acquired Immune Deficiency Syndrome. Tuberculosis. Lung Cancer. Pulmonary Vascular Disease. Treatment of Cough and Breathlessness. Drug-Induced Pulmonary Disease. Index
This paper presents the behaviour and design of axially loaded concrete filled stainless steel elliptical hollow sections. The experimental investigation was conducted using normal and high strength concrete of 30 and 100 MPa. The current study is based on stub column tests and is therefore limited to cross-section capacity. Based on the existing design guidance in Eurocode 4 for composite columns, the proposed design equations use the continuous strength method to determine the strength of the stainless steel material. It is found to provide the most accurate and consistent prediction of the axial capacity of the composite concrete filled stainless steel elliptical hollow sections due largely to the more precise assessment of the contribution of the stainless steel tube to the composite resistance.
Chronic total occlusions remain one of the last frontiers in interventional cardiology, with far lower procedural success rates compared with other lesion subsets. The benefits of successful treatment include improvements in angina and survival. One method, which may improve technical success rates, is the use of a retrograde approach. We report three cases employing a retrograde approach and describe the technique in detail.
This volume covers the recent advances in our understanding of the pathophysiology and treatment of asthma. Our understanding of asthma has changed dramatically in recent years, and much of this information is brought together by internationally recognised authorities. They review the changing concepts of the inflammatory processes in asthma and discuss the implications for research and future therapy of this common chronic disease. Each chapter is illustrated with diagrams and photographs. Many of the advances in our understanding of asthma have originated from a pharmacological approach, and these options for pharmacological intervention are highlighted. This volume aims to be useful for research scientists and clinicians involved in asthma research and a reference resource for chest physicians and those involved in the development of novel pharmaceutical entities. This monograph on pharmacology, immunology is intended for researchers and clinicians.
The likelihood of restenosis is a major limitation of coronary angioplasty. We studied whether hirudin, a highly selective inhibitor of thrombin with irreversible effects, would prevent restenosis after angioplasty. We compared two regimens of recombinant hirudin with heparin.
Drug eluting stents represent one of the fastest growing fields in interventional cardiology today. At the congress of the European Society of Cardiology in Amsterdam in 2000, I (PWS) was asked to give the Andreas Gruentzig Lecture. In the week preceding the lecture, we re-angiographied patients 32 and 33 of the initial cohort of patients who had received a rapamycin eluting stent in Sao Paulo and in Rotterdam. Scrutinising the 4–6 month angiographic and ultrasonic results of these patients, I became overwhelmingly convinced that we were the privileged witnesses of a new phenomenon: the almost complete abolition of intra-stent neointimal proliferation. Colleagues, invasive and non-invasive cardiologists, old friends, and financial analysts were surprised by the unusual “excess of enthusiasm” coming from somebody who has built over the years a reputation as a critical assessor, never one to be carried away by the hype of a new wave in interventional cardiology. In the history of this field I have recognised (and “got excited” by, as my American colleagues used to put it) only two revolutionary developments: the introduction of the moveable and steerable guidewire by John Simpson, and the advent of the stent (Palmaz-Schatz, Wallstent). The drug eluting stent is the third such development, and almost one year later I would like to restate the fact that we are entering a new era in interventional cardiology. Why? Because the principle of an eluting stent is sound, and because the three major technical challenges have been mastered—the controlled release of an efficient drug from a stable coating. Drug administration for the prevention of restenosis has been tested in the past—with disappointing results throughout. A proposed explanation for the repeated failure of clinical drug studies has been that agents given systematically cannot reach sufficient concentrations in injured arteries, which has a signficant impact …
The prostanoid receptor(s) that mediates inhibition of bacterial lipopolysaccharide (LPS)‐induced tumour necrosis factor‐α (TNFα) generation from human peripheral blood monocytes was classified by use of naturally occurring and synthetic prostanoid agonists and antagonists. In human monocytes that were adherent to plastic, neither prostaglandin D 2 (PGD 2 ), prostaglandin E 2 (PGE 2 ), prostaglandin F 2α (PGF 2α ) nor the stable prostacyclin and thromboxane mimetics, cicaprost and U‐46619, respectively, promoted the elaboration of TNFα‐like immunoreactivity, as assessed with a specific ELISA, indicating the absence of excitatory prostanoid receptors on these cells. Exposure of human monocytes to LPS (3 ng ml −1 , ∼ EC 84 ) resulted in a time‐dependent elaboration of TNFα which was suppressed in cells pretreated with prostaglandin E 1 (PGE 1 ), PGE 2 and cicaprost. This effect was concentration‐dependent with mean pIC 50 values of 7.14, 7.34 and 8.00 for PGE 1 , PGE 2 and cicaprost, respectively. PGD 2 , PGF 2α and U‐46619 failed to inhibit the generation of TNFα at concentrations up to 10 μ M . With respect to PGE 2 , the EP‐receptor agonists, 16,16‐dimethyl PGE 2 (non‐selective), misoprostol (EP 2 /EP 3 ‐selective), 11‐deoxy PGE 1 (EP 2 ‐selective) and butaprost (EP 2 ‐selective) were essentially full agonists as inhibitors of LPS‐induced TNFα generation with mean pIC 50 values of 6.21, 6.02, 5.67 and 5.59, respectively. In contrast to the results obtained with butaprost and 11‐deoxy PGE 1 , another EP 2 ‐selective agonist, AH 13205, inhibited TNFα generation by only 21% at the highest concentration (10 μ M ) examined. EP‐receptor agonists which have selectivity for the EP 1 ‐ (17‐phenyl‐ω‐trinor PGE 2 ) and EP 3 ‐receptor (MB 28,767, sulprostone) were inactive or only weakly active as inhibitors of TNFα generation. Pretreatment of human monocytes with the TP/EP 4 ‐receptor antagonist, AH 23848B, at 10, 30 and 100 μ M suppressed LPS‐induced TNFα generation by 10%, 28% and 77%, respectively, but failed to shift significantly the location of the PGE 2 concentration‐response curves. Given that AH 13205 was a poor inhibitor of TNFα generation, studies were performed to determine if it was a partial agonist and whether it could antagonize the inhibitory effect of PGE 2 . Pretreatment of human monocytes with 10 and 30 μ M AH 13205 inhibited the generation of TNFα by 31% and 53%, respectively, but failed to shift significantly the location of the PGE 2 concentration‐response curves at either concentration examined. Since PGD 2 and 17‐phenyl‐ω‐trinor PGE 2 (EP 1 ‐agonist) did not suppress TNFα generation, the EP 1 /EP 2 /DP‐receptor antagonist, AH 6809, was employed to assess if EP 2 ‐receptors mediated the inhibitory effect of PGE 2 . Pretreatment of human monocytes with 10 μ M AH 6809 did not affect LPS‐induced TNFα generation but produced a parallel 3.5 fold rightwards shift of the PGE 2 concentration‐response curve. Collectively, these data suggest that human peripheral blood monocytes express at least two distinct populations of inhibitory prostanoid receptors that mediate inhibition of LPS‐induced TNFα generation. One of these probably represents IP receptors based upon the selectivity of cicaprost for this subtype. The other population has the pharmacology of EP‐receptors, but the rank order of potency for a range of synthetic EP‐receptor agonists was inconsistent with an interaction with any of the currently defined subtypes. Given the pharmacological behaviour of butaprost, AH 6809 and AH 23848B in these cells, we propose that multiple (EP 2 ‐ and/or EP 4 ‐ and/or IP) or novel EP‐receptors mediate the inhibitory effect of PGE 2 on TNFα generation. British Journal of Pharmacology (1997) 122 , 149–157; doi: 10.1038/sj.bjp.0701360
