Abstract The behaviour and design of cylindrically‐pinned stainless steel equal‐leg angle section members under compression and compression combined with strong‐axis bending are investigated herein. Numerical models are developed by means of shell finite element modelling formulated within ABAQUS and validated against experimental data. A numerical parametric study is then presented considering both hot‐rolled and cold‐formed stainless steel equal‐leg angle section columns alongside beam‐columns with a wide range of cross‐section and member geometries. Finally, new design proposals for pin‐ended stainless steel equal‐leg angle section members under compression and compression plus major‐axis bending are developed and verified against the results of physical experiments and numerical simulations. The proposed design rules are shown to offer substantially more accurate and consistent resistance predictions compared to existing codified design rules.
Macrophages (mф) in the lungs of COPD patients show a pro-inflammatory phenotype and fail to clear pathogens and apoptotic cells. Whether this is due to local pulmonary environmental or to an inherent mф defect is not clear. We have shown that monocyte-derived macrophages (MDM) from COPD patients show similar defects, with reduced phagocytosis and increased release of pro-inflammatory cytokines and proteases. Kruppel-like factor (KLF)-4 is a transcription factor that is important in the differentiation of mф. This study aimed to examine whether KLF-4 expression was altered during differentiation of monocytes to mф in COPD. Monocytes from control (C=7) and COPD patients (COPD=5) were cultured in GM-CSF (pro-inflammatory phenotype) or M-CSF (resolving phenotype) for 18d, and <i>KLF4</i> gene expression measured using qPCR. <i>KLF4</i> increased during differentiation from 0d to 12d in both subject groups, but was markedly higher in controls compared to COPD MDM. This was observed in both GM and M cultured cells, although GM-MDM expressed twice as much <i>KLF4</i> than M-MDM. In control cells, <i>KLF4</i> decreased by day 18, but remained the same in COPD MDM (Fig. 1). These data indicate a role for KLF4 in mф differentiation. Furthermore, low gene expression in COPD MDM suggests that these cells are unable to differentiate correctly, or take longer to do so, resulting in dysfunctional mф phenotype.
In 1981 we initiated a randomized trial at the Thoraxcenter in Rotterdam which was later extended to include four other hospitals cooperating in the Netherlands Interuniversity Cardiology Institute: the Zuiderziekenhuis in Rotterdam, the Free University in Amsterdam, the St. Annadal Hospital in Maastricht and the Leiden University Hospital. Since the global results of the study have been published in the Lancet (4) and in other journals (3, 5) we present a summary of the findings and discuss the clinical consequences of the trial.
Dr Rutherford asks: When you first heard that Andreas Grüentzig had successfully performed a transluminal coronary dilation in September 1977, what were your thoughts?Did it seem a sustainable therapy at the time?Dr Serruys replies: In 1975 at a meeting in Frankfurt, a key opinion leader at that time, Professor Paul Lichtlen, Chief of Cardiology at Hannover, was describing during a keynote lecture a significant coronary lesion with a thin fibrous cap and a large atheromatous core; today, we call this a vulnerable plaque.He mentioned somewhat sarcastically that Dr Andreas Grüentzig had developed a procedure he believed could dilate that type of lesion.There was of course a lot of skepticism whether the procedure could be performed without major distal embolization.I went to see Andreas Grüentzig and to look at his poster.He had tied a ligature with catgut around the coronary artery of a dog, and he was using his balloon to open this artificial narrowing.Honestly, I could not foresee the future of this therapeutic approach.At that time, the Department of Cardiology in Zürich (where Grüentzig worked) was headed by 2 cardiologists, Hans Peter Krayenbühl and Wilhelm Rutishauser.Krayenbühl was not in favor of attempting the procedure, but Rutishauser was more enthusiastic about it.The famous Chief of Cardiovascular Surgery, Dr Åke Senning, told the Board of the hospital that he would help Andreas and be present in the cardiac catheterization laboratory to back up a potential catastrophe.The story is that when Andreas deflated the balloon and the gradient disappeared, Senning left the laboratory, without even looking at the angiogram, convinced the result was good.In 1978, Grüentzig reported successful dilation of an 85% left anterior descending coronary stenosis by PTCA in a 38-year-old man with severe angina and theThe Birth, and Evolution,
We studied the Nobori coronary stent coated with a bioabsorbable polymer and the anti-proliferative agent Biolimus A9 which may reduce neointimal formation.Patients undergoing percutaneous coronary intervention for de novo lesions in up to two native coronary arteries, in 29 centres across Europe, Asia and Australia were randomly (2:1) assigned to receive the Biolimus A9 eluting stent Nobori (85 patients) or paclitaxel eluting stent Taxus(R) (35 patients). The two groups were well matched in baseline characteristics. The primary end point of non-inferiority for in-stent late loss of Nobori stent versus Taxus(R) stent, at 9 months, was reached with the values of 0.15+/-0.27 mm with Nobori stent and 0.32+/-0.33 mm with Taxus(R) stent (p=0.006). Neointimal volume obstruction was 2.2+/-6.0% and 8.9+/-9.2% for Nobori and Taxus(R) stent respectively (p=0.017). The rates of death, myocardial infarction and any target vessel revascularisation at 9 months were 0%, 4.7%, and 7.1% respectively for Nobori stent, and 0%, 8.6% and 14.3% respectively for Taxus(R) stent. Clinically-driven target lesion revascularisation rate was 0% for Nobori stent and 2.9% for Taxus(R) stent. Stent thrombosis rates at 9 months were 0% in both groups.In this trial the Nobori Biolimus A9 eluting stent proved to be safe and effective in reducing neointimal proliferation. The long term safety remains to be confirmed during the extended follow-up period of 5 years.
The effect of thiazide duretics on neurally and agonist-induced contractile responses of guinea pig airways in vitro were investigated. Tracheal or bronchial strips were suspended in organ baths and isometric tension recorded. Chlorothiazide (CTZ, 10−4 to 3 × 10−3 M), hydrochlorothiazide (HCTZ, 10−3 M), and dichlorphenamide (DCPM, 10−3 M) significantly potentiated contraction of tracheal strips induced by electrical field stimulation (EFS). They also increased acetylcholine (ACh)- but not carbachol-induced tracheal contraction. In the presence of atropine and propranolol, on the other hand, CTZ and DCPM but not HCTZ significantly inhibited EFS-induced contraction in bronchial strips. We determined whether carbonic anhydrase inhibition could mimic the effects of CTZ and DCPM. Acetazolamide (ATZ), an inhibitor of carbonic anhydrase, had no effect on either EFS- or ACh-induced contraction in tracheal strips but significantly inhibited nonadrenergic, noncholinergic (NANC) contractile responses induced by EFS in bronchial strips. CTZ, DCPM, and ATZ did not affect substance P-induced contractile responses in the bronchi. We conclude that CTZ, DCPM, and ATZ attenuate NANC neurally mediated bronchial contraction by preventing the release of contractile neuropeptides from sensory nerve endings. This effect may occur through inhibition of carbonic anhydrase activity. In addition, thiazide diuretics potentiate contractile responses to ACh in the trachea, probably through inhibition of acetylcholinesterase activity.
We investigated the role of endogenous nitric oxide (NO) and superoxide anions in recombinant human interleukin-1 beta (rhIL-1 beta)-induced bronchial hyperresponsiveness (BHR) and neutrophilia in Brown-Norway rats. Aminoguanidine (100 mg/kg/d) administered subcutaneously for 3 d, an inhibitor of inducible NO synthase, L-arginine (100 mg/kg/d administered subcutaneously for 3 d, a specific precursor for the synthesis of NO, and apocynin (5 mg/kg/orally), an inhibitor of superoxide anion (O2-)-generating NADPH oxidase in macrophages and neutrophils, were administered prior to administration of rhIL-1 beta (500 U) intratracheally. Aminoguanidine in addition to another inhibitor of NO synthase, NW-nitro-L-arginine methyl ester (L-NAME) 100 mg kg/d administered subcutaneously for 3 d augmented bronchial responsiveness to inhaled bradykinin (BK) but not to acetylcholine (ACh), an effect reversed by L-arginine. rhIL-1 beta-treated rats also demonstrated BHR to BK but not to ACh, associated with neutrophilia in bronchoalveolar lavage fluid (BALF). rhIL-1 beta-induced BHR and neutrophilia were neither further increased by aminoguanidine nor inhibited by L-arginine. Apocynin, however, significantly inhibited rhIL-1 beta-induced BHR but not the BALF neutrophilia. Suppression of NO generation and generation of O2- from macrophages and infiltrating neutrophils may be important in rhIL-1 beta-induced airway hyperresponsiveness to bradykinin.
