American journal of respiratory and critical care medicine
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The initial enzymatic steps in leukotriene synthesis occur at the nuclear envelope. Cytosolic phospholipase A2 translocates from the cytoplasm to selectively hydrolyze nuclear envelope phospholipids, releasing free arachidonate. 5-Lipoxygenase-activating protein, an arachidonate transfer protein, then binds arachidonate and presents it to 5-lipoxygenase (5-LO), which catalyzes a two-step reaction to produce leukotriene A4. ⋯ Immunofluorescence microscopy studies demonstrate that both cytoplasmic and nuclear 5-LO move to the nuclear envelope following cell activation. Many questions remain unanswered regarding the significance of nuclear 5-LO, potential autocrine actions of leukotrienes, and intracellular trafficking of these enzymes and their products.
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Am. J. Respir. Crit. Care Med. · Jun 1998
Randomized Controlled Trial Clinical TrialWeight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease.
The objective of the study was to further unravel the prognostic significance of body weight changes in patients with COPD. Two survival analyses were performed: (1) a retrospective study, including 400 patients with COPD none of whom had received nutritional therapy; (2) a post hoc analysis of a prospective study, including 203 patients with COPD who had participated in a randomized placebo-controlled trial. There was no overlap between the patient groups. ⋯ On Cox regression analysis weight change entered as a time-dependent covariate remained an independent predictor of mortality in addition to all variables that were entered in the retrospective study. The combined results of the two survival analyses provide evidence to support the hypothesis that body weight has an independent effect on survival in COPD. Moreover the negative effect of low body weight can be reversed by appropriate therapy in some of the patients with COPD.
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Am. J. Respir. Crit. Care Med. · Jun 1998
The use of a neural network to detect upper airway obstruction caused by goiter.
Goiter is a common condition and can cause upper airway obstruction (UAO), which may be difficult to detect. We have studied maximal expiratory and inspiratory flow volume loops using a neural network to see if this offers a better way to identify patients with UAO. The flow-volume loops from 155 patients with goiter were assessed by a human expert and sorted into those with and without UAO. ⋯ The kappa score for agreement between each of the observers and the original classification were 0.5 and 0.46, respectively, with the agreement between the observers at each reading of 0.58 and 0.68. The neural network found that a combination of four novel scores for flatness of the expiratory loop, the moment ratio, and the FEV1/PEF ratio was best at identifying UAO with a kappa score of 0.81, a sensitivity of 88%, specificity of 94% and an accuracy of 92%. We conclude that a neural network using only six indices taken from the expiratory limb of a flow-volume loop was better than human experts at identifying flow loops with UAO.
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Am. J. Respir. Crit. Care Med. · Jun 1998
Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. Risk to relatives for airflow obstruction and chronic bronchitis.
Severe alpha-1-antitrypsin deficiency is the only proven genetic risk factor for chronic obstructive pulmonary disease (COPD). We have assembled a cohort of 44 probands with severe, early-onset COPD, who do not have severe alpha-1-antitrypsin deficiency. A surprisingly high prevalence of females (79.6%) was found. ⋯ Generalized estimating equations, adjusting for age and pack-years of smoking, demonstrated increased odds of reduced FEV1 and chronic bronchitis in current or ex-smoking first-degree relatives of early-onset COPD probands. Using a new method to estimate relative risk from relative odds, we estimate that the relative risks for FEV1 below 60%, FEV1 below 80%, and chronic bronchitis are each approximately three in current or ex-smoking first-degree relatives of early-onset COPD probands. The increased risk to relatives of early-onset COPD probands for reduced FEV1 and chronic bronchitis, limited to current or ex-smokers, suggests genetic risk factor(s) for COPD that are expressed in response to cigarette smoking.
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Am. J. Respir. Crit. Care Med. · Jun 1998
Pulmonary gas exchange improves in the prone position with abdominal distension.
Arterial blood oxygenation in patients with adult respiratory distress syndrome is often improved in the prone position. Critically ill patients often have abdominal distension and whether similar improvements in gas exchange occur with the prone position is not known. We therefore studied the effect of posture on gas exchange in eight ketamine-anesthetized pigs with abdominal distension. ⋯ In the presence of abdominal distension, the prone position increased Pa O2 by 26 +/- 18 mm Hg (p < 0.01) and decreased AaPO2 (p < 0.05) and V A/Q heterogeneity as measured by the log standard deviation of the perfusion distribution (p < 0.01) and the arterial-alveolar difference area (p < 0.05). In addition, intragastric pressure was lower in the prone position (p < 0.01). We conclude that in anesthetized, mechanically ventilated pigs, the prone position improves pulmonary gas exchange to a greater degree in the presence of abdominal distension than when the abdomen is normal.