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We have developed a guinea pig model of trimellitic anhydride-induced airway hypersensitivity responses. In one group of guinea pigs, injected intradermally with 0.1 ml 30% trimellitic anhydride (TMA), we examined the specificity of the bronchopulmonary response to TMA comparing the effect of intravenous TMA conjugated to guinea pig serum albumin (GPSA) with a control hapten (procion dye) protein conjugate (PD-GPSA). A significant increase in pulmonary inflation pressure (PIP) was provoked in sensitized animals following intravenous injection with TMA-GPSA (20%; 0-400, median; range) as compared to intravenous injection of PD-GPSA. In the second group we compared three different methods of sensitization: single injection of 0.1 ml of 0.3% TMA; four injections of 0.1 ml of 0.1% TMA; and a single high dose injection of 30% TMA. Following intravenous TMA-GPSA guinea pigs sensitized with a single injection 0.3% TMA had an increase in PIP of 395%; 220-600, while those given four repeat injections of 0.1% TMA had an increase in PIP of 343%; 315-490. These results were significantly higher than the increase in PIP (160%; 0-220) which occurred in guinea pigs sensitized with a single dose of 30% TMA. Four of 11 guinea pigs given low dose injections of TMA had bronchopulmonary responses to inhaled TMA-GPSA. All sensitized guinea pigs had specific IgG1 antibodies demonstrated by enzyme linked immunosorbent assay (ELISA) and confirmed by ELISA inhibition. Four guinea pigs sensitized by low dose injections of TMA had IgE antibodies demonstrated by passive cutaneous anaphylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract Background Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness. Methods We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. Results 146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. Conclusion Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection. (Funded by Oxford NIHR Biomedical Research Centre and AstraZeneca; ClinicalTrials.gov number, NCT04416399 ) Research in context Evidence before this study The majority of interventions studied for the COVID-19 pandemic are focused on hospitalised patients. Widely available and broadly relevant interventions for mild COVID-19 are urgently needed. Added value of this study In this open label randomised controlled trial, inhaled budesonide, when given to adults with early COVID-19 illness, reduces the likelihood of requiring urgent care, emergency department consultation or hospitalisation. There was also a quicker resolution of fever, a known poor prognostic marker in COVID-19 and a faster self-reported and questionnaire reported symptom resolution. There were fewer participants with persistent COVID-19 symptoms at 14 and 28 days after budesonide therapy compared to usual care. Implications of all the available evidence The STOIC trial potentially provides the first easily accessible effective intervention in early COVID-19. By assessing health care resource utilisation, the study provides an exciting option to help with the worldwide pressure on health care systems due to the COVID-19 pandemic. Data from this study also suggests a potentially effective treatment to prevent the long term morbidity from persistent COVID-19 symptoms.

No abstract is provided for this article.

No abstract is provided for this article.

Because many ongoing clinical restenosis prevention trials are using quantitative angiography to assess whether a drug is capable of reducing the amount of intimal hyperplasia, quantitative angiographic risk factors for angiographic luminal narrowing after balloon angioplasty were determined, including stretch and elastic recoil at the dilatation site. Quantitative analysis was performed on 666 lesions in 575 patients during angioplasty and at 6-month follow-up. Stretch was defined as balloon diameter minus minimal luminal diameter (MLD) before angioplasty/reference diameter, and recoil as balloon diameter minus MLD after angioplasty/reference diameter. Multivariate analysis was used to yield independent risk factors for luminal narrowing at follow-up. Predictors of absolute change in MLD were (1) relative gain at angioplasty (gain in millimeters normalized for reference diameter) and (2) lesion length. To allow risk stratification, logistic regression analysis was applied using the decrease in MLD as a binary outcome variable. A decrease in MLD at follow-up of ≥ 0.72 mm was considered significant. Variables retained in the model were: relative gain > 0.3 mm (rate ratio 2.9), relative gain 0.2 to 0.3 (rate ratio 2.1), stenosis length ≥ 6.8 (rate ratio 1.7), and thrombus after angioplasty (rate ratio 2.6). Although stretch was significantly related to luminal narrowing at univariate analysis, it was not retained in the multivariate models. A large gain in lumen diameter at angioplasty, dilation of long lesions, and angiographically determined thrombus after angioplasty were found to be accompanied by more severe luminal narrowing at follow-up.

The prevalence of asthma has increased worldwide. Asthma exacerbations triggered by upper respiratory tract viral infections remain a major clinical problem and account for hospital admissions and time lost from work. Virus-induced asthma exacerbations cause airway inflammation, resulting in worsening asthma and deterioration in the patients' quality of life, which may require systemic corticosteroid therapy. Despite recent advances in understanding the cellular and molecular mechanisms underlying asthma exacerbations, current therapeutic modalities are inadequate for complete prevention and treatment of these episodes. The pathological role of cellular senescence, especially that involving the silent information regulator 2 homolog sirtuin (SIRT) protein family, has recently been demonstrated in stable and exacerbated chronic respiratory disease states. This review discusses the role of SIRT1 in the pathogenesis of bronchial asthma. It also discusses the role of SIRT1 in inflammatory cells that play an important role in virus-induced asthma exacerbations. Recent studies have hypothesized that SIRT1 is one of major contributors to cellular senescence. SIRT1 levels decrease in Th2 and non-Th2-related airway inflammation, indicating the role of SIRT1 in several endotypes and phenotypes of asthma. Moreover, several models have demonstrated relationships between viral infection and SIRT1. Therefore, targeting SIRT1 is a novel strategy that may be effective for treating virus-induced asthma exacerbations in the future.

Journal Article Immediate PTCA after successful thrombolysis with intracoronary streptokinase, three years follow-up: A matched pair analysis of the effect of PTCA in the randomized multicentre trial of intracoronary streptokinase, conducted by the Interuniversity Cardiology Institute of the Netherlands Get access F. VERMEER, F. VERMEER Address for reprints and correspondence: F Vermeer, Department of Cardiology, University Hospital Maastricht, University of Limburg, P. O. Box 1918, 6201 BX Maastricht, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar M. L. SIMOONS, M. L. SIMOONS Search for other works by this author on: Oxford Academic PubMed Google Scholar P. I. DE FEYTER, P. I. DE FEYTER Search for other works by this author on: Oxford Academic PubMed Google Scholar F. W. BÄR, F. W. BÄR Search for other works by this author on: Oxford Academic PubMed Google Scholar H. SURYAPRANATA, H. SURYAPRANATA Search for other works by this author on: Oxford Academic PubMed Google Scholar P. FIORETTI, P. FIORETTI Search for other works by this author on: Oxford Academic PubMed Google Scholar P. W. SERRUYS, P. W. SERRUYS Search for other works by this author on: Oxford Academic PubMed Google Scholar B. BUIS, B. BUIS Search for other works by this author on: Oxford Academic PubMed Google Scholar J. C. J. RES, J. C. J. RES Search for other works by this author on: Oxford Academic PubMed Google Scholar S. H. BRAAT, S. H. BRAAT Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more J. LUBSEN, J. LUBSEN Search for other works by this author on: Oxford Academic PubMed Google Scholar P. G. HUGENHOLTZ P. G. HUGENHOLTZ Search for other works by this author on: Oxford Academic PubMed Google Scholar European Heart Journal, Volume 9, Issue 4, April 1988, Pages 346–353, https://doi.org/10.1093/oxfordjournals.eurheartj.a062510 Published: 01 April 1988 Article history Received: 13 July 1987 Revision received: 28 September 1987 Published: 01 April 1988

No abstract is provided for this article.

A previous Task Force of the European Society of Cardiology (ESC) and European Association of Percutaneous Cardiovascular Interventions (EAPCI) provided a report on recommendations for the non-clinical and clinical evaluation of coronary stents. Following dialogue with the European Commission, the Task Force was asked to prepare an additional report on the class of devices known as bioresorbable scaffolds (BRS). Five BRS have CE-mark approval for use in Europe. Only one device-the Absorb bioresorbable vascular scaffold-has published randomized clinical trial data and this data show inferior outcomes to conventional drug-eluting stents (DES) at 2-3 years. For this reason, at present BRS should not be preferred to conventional DES in clinical practice. The Task Force recommends that new BRS devices should undergo systematic non-clinical testing according to standardized criteria prior to evaluation in clinical studies. A clinical evaluation plan should include data from a medium sized, randomized trial against DES powered for a surrogate end point of clinical efficacy. Manufacturers of successful devices receive CE-mark approval for use and must have an approved plan for a large-scale randomized clinical trial with planned long-term follow-up.

No abstract is provided for this article.