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Michael Crooks - Top 30 Publications

Continuous Cough Monitoring Using Ambient Sound Recording During Convalescence from a COPD Exacerbation.

Cough is common in chronic obstructive pulmonary disease (COPD) and is associated with frequent exacerbations and increased mortality. Cough increases during acute exacerbations (AE-COPD), representing a possible metric of clinical deterioration. Conventional cough monitors accurately report cough counts over short time periods. We describe a novel monitoring system which we used to record cough continuously for up to 45 days during AE-COPD convalescence.

Bleomycin increases neutrophil adhesion to human vascular endothelial cells independently of upregulation of ICAM-1 and E-selectin.

Bleomycin-induced lung disease is a serious complication of therapy characterized by alveolar injury, cytokine release, inflammatory cell recruitment, and eventually pulmonary fibrosis. The mechanisms underlying bleomycin-induced pulmonary fibrosis may be relevant to other progressive scarring diseases of the lungs. Pulmonary vascular endothelial cells are critically involved in immune cell extravasation at sites of injury through adhesion molecule expression and cytokine release. We sought to determine the effects of bleomycin on adhesion molecule expression and cytokine release by pulmonary vascular endothelial cells, and their functional relevance to inflammatory cell recruitment.

Idiopathic Pulmonary Fibrosis and Prothrombotic State.

Coagulation and anticoagulation in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an incurable, progressive interstitial lung disease with a prognosis that is worse than that of many cancers. Epidemiological studies have demonstrated a link between IPF and thrombotic vascular events. Coagulation and fibrinolytic systems play central roles in wound healing and repair, processes hypothesised to be abnormal within the IPF lung. Animal models of pulmonary fibrosis have demonstrated an imbalance between thrombosis and fibrinolysis within the alveolar compartment, a finding that is also observed in IPF patients. A systemic prothrombotic state also occurs in IPF and is associated with increased mortality, but trials of anticoagulation in IPF have provided conflicting results. Differences in methodology, intervention and study populations may contribute to the inconsistent trial outcomes. The new oral anticoagulants have properties that may prove advantageous in targeting both thrombotic risk and progression of lung fibrosis.

Objective Measurement of Cough Frequency During COPD Exacerbation Convalescence.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Cough and sputum production are associated with adverse outcomes in COPD and are common during COPD exacerbation (AE-COPD). This study of objective cough monitoring using the Hull Automated Cough Counter and Leicester Cough Monitor software confirms that this system has the ability to detect a significant decrease in cough frequency during AE-COPD convalescence. The ability to detect clinically meaningful change indicates a potential role in home monitoring of COPD patients.

Biomarkers in idiopathic pulmonary fibrosis: picking the winners for trials.

The value of telehealth in the early detection of chronic obstructive pulmonary disease exacerbations: A prospective observational study.

We aim to establish the value of telemonitoring in the early detection of chronic obstructive pulmonary disease exacerbations. We followed up patients undergoing chronic obstructive pulmonary disease telemonitoring for 4 months. We studied changes in the telemonitored data in the week prior to admission or to community chronic obstructive pulmonary disease exacerbation. A total of 183 patients were studied. In all, 30 chronic obstructive pulmonary disease-related hospital admissions and 68 chronic obstructive pulmonary disease community exacerbations were recorded. Changes in telehealth parameters occurred in 80 per cent (24/30) of admissions and 82 per cent (56/68) of community exacerbations. Although changes in telehealth data occurred in the majority of exacerbations, most individual symptoms was present in less than half the exacerbations and almost 20 per cent of exacerbations were not preceded by any change in telemonitoring data. Cough created significantly more alerts by those treated in the community (p = 0.008), whereas a drop in oxygen saturation created significantly more alerts pre-hospitalisation (p = 0.049). We conclude that further work is required to develop methods of identifying impending chronic obstructive pulmonary disease exacerbations with greater sensitivity and specificity.

A new era of drug therapy for idiopathic pulmonary fibrosis.

Increased platelet reactivity in idiopathic pulmonary fibrosis is mediated by a plasma factor.

Idiopathic Pulmonary Fibrosis (IPF) is a progressive, incurable fibrotic interstitial lung disease with a prognosis worse than many cancers. Its pathogenesis is poorly understood. Activated platelets can release pro-fibrotic mediators that have the potential to contribute to lung fibrosis. We determine platelet reactivity in subjects with IPF compared to age-matched controls.

Increased platelet binding to circulating monocytes in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and its prognosis is poor. Epidemiological evidence suggests an association of IPF with vascular disease and thrombotic tendency, which may be related to platelet activation.

Serum carcinoembryonic antigen correlates with severity of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the commonest idiopathic interstitial pneumonia and carries a poor prognosis. Epidemiological evidence suggests that patients with IPF have an increased risk of developing lung cancer. Carcinoembryonic antigen (CEA) has a close association with epithelial malignancy. The aim of this study was to evaluate serum CEA concentrations in patients with IPF and to perform correlation with pulmonary function.

Idiopathic pulmonary fibrosis is associated with circulating antiepithelial antibodies.

Idiopathic pulmonary fibrosis (IPF) is a restrictive fibrotic lung disease of uncertain etiology. Alveolar epithelial injury may be one of the inciting triggers in the pathogenesis of this disorder. We hypothesized that circulating antibodies to alveolar epithelial and endothelial cells may be involved in the pathogenesis of IPF.

Azithromycin for prevention of exacerbations of COPD.

Gastroesophageal reflux and idiopathic pulmonary fibrosis: a review.

The histological counterpart of idiopathic pulmonary fibrosis is usual interstitial pneumonia, in which areas of fibrosis of various ages are interspersed with normal lung. This pattern could be explained by repeated episodes of lung injury followed by abnormal wound healing responses. The cause of the initiating alveolar epithelial injury is unknown, but postulated mechanisms include immunological, microbial, or chemical injury, including aspirated gastric refluxate. Reflux is promoted by low basal pressure in the lower oesophageal sphincter and frequent relaxations, potentiated by hiatus hernia or oesophageal dysmotility. In susceptible individuals, repeated microaspiration of gastric refluxate may contribute to the pathogenesis of IPF. Microaspiration of nonacid or gaseous refluxate is poorly detected by current tests for gastroesophageal reflux which were developed for investigating oesophageal symptoms. Further studies using pharyngeal pH probes, high-resolution impedance manometry, and measurement of pepsin in the lung should clarify the impact of reflux and microaspiration in the pathogenesis of IPF.

Tuberculous paraspinal abscess: a case of mistaken identity.

We present the case of a 35-year-old man of Pakistani origin presenting with a history suggestive of tuberculosis. Chest x-ray revealed left upper zone consolidation and mediastinal widening felt to be consistent with mediastinal lymphadenopathy. Bronchoalveolar lavage failed to yield acid-fast bacilli (AFB) and therefore CT thorax was requested with a view to surgical referral for mediastinal node biopsy. CT thorax revealed a large paravertebral abscess to be the cause of apparent mediastinal widening. CT guided biopsy confirmed Mycobacterium tuberculosis on culture. On reflection, there was preservation of the right paratracheal stripe on chest x-ray indicating that this was not mediastinal lymphadenopathy but a paravertebral mass as illustrated on CT.

The generation of promoter-mediated transcriptional noise in bacteria.

Noise in the expression of a gene produces fluctuations in the concentration of the gene product. These fluctuations can interfere with optimal function or can be exploited to generate beneficial diversity between cells; gene expression noise is therefore expected to be subject to evolutionary pressure. Shifts between modes of high and low rates of transcription initiation at a promoter appear to contribute to this noise both in eukaryotes and prokaryotes. However, models invoked for eukaryotic promoter noise such as stable activation scaffolds or persistent nucleosome alterations seem unlikely to apply to prokaryotic promoters. We consider the relative importance of the steps required for transcription initiation. The 3-step transcription initiation model of McClure is extended into a mathematical model that can be used to predict consequences of additional promoter properties. We show in principle that the transcriptional bursting observed at an E. coli promoter by Golding et al. (2005) can be explained by stimulation of initiation by the negative supercoiling behind a transcribing RNA polymerase (RNAP) or by the formation of moribund or dead-end RNAP-promoter complexes. Both mechanisms are tunable by the alteration of promoter kinetics and therefore allow the optimization of promoter mediated noise.

Mullerian papilloma-like proliferation arising in cystic pelvic endosalpingiosis.

This report describes an unusual epithelial proliferation occurring in pelvic cystic endosalpingiosis. A cyst mass lined by a layer of ciliated epithelial cells involved the posterior surface of the cervix and vagina. The epithelial proliferation within the wall resembled a mullerian papilloma with fibrous and fibrovascular cores lined by bland cuboidal epithelial cells. Other areas had a microglandular growth pattern resembling cervical microglandular hyperplasia, and focally there was a solid growth pattern. Foci of typical endosalpingiosis involved the surface of both ovaries and pelvic soft tissues. The cystic lesion recurred after partial cystectomy and drainage and was followed up radiologically and with periodic fine-needle aspiration. Part of the wall of the cyst removed 11 years after the original surgery showed an identical epithelial proliferation. MIB1 staining showed a proliferation index of less than 5%, contrasting with the higher proliferation index of a typical serous borderline tumor. The differential diagnosis is discussed. As far as we are aware, this is the first report of such a benign epithelial proliferation involving cystic endosalpingiosis.