Change in inflammation in out-patient COPD patients from stable phase to a subsequent exacerbation

BACKGROUND: Inflammation increases during exacerbations of COPD, but only a few studies systematically assessed these changes. Better identification of these changes will increase our knowledge and potentially guide therapy, for instance by helping with quicker distinction of bacterially induced exacerbations from other causes. AIM: To identify which inflammatory parameters increase during COPD exacerbations compared to stable disease, and to compare bacterial and non-bacterial exacerbations. METHODS: In 45 COPD patients (37 male/8 female, 21 current smokers, mean age 65, FEV(1) 52% predicted, pack years 38) sputum was collected during a stable phase and subsequently during an exacerbation. RESULTS: Sputum total cell counts (9.0 versus 7.9 x 10(6)/mL), eosinophils (0.3 versus 0.2 x 10(6)/mL), neutrophils (6.1 versus 5.8 x 10(6)/mL), and lymphocytes (0.07 versus 0.02 x 10(6)/mL) increased significantly during an exacerbation compared to stable disease. A bacterial infection was demonstrated by culture in 8 sputum samples obtained during an exacerbation. These exacerbations had significantly increased sputum total cell and neutrophil counts, leukotriene-B4, myeloperoxidase, interleukin-8 and interleukin-6, and tumor necrosis factor-alpha (TNF-alpha) levels, and were also associated with more systemic inflammation compared to exacerbations without a bacterial infection. Sputum TNF-alpha level during an exacerbation had the best test characteristics to predict a bacterial infection. CONCLUSION: Sputum eosinophil, neutrophil, and lymphocyte counts increase during COPD exacerbations. The increase in systemic inflammation during exacerbations seems to be limited to exacerbations caused by bacterial infections of the lower airways. Sputum TNF-alpha is a candidate marker for predicting airway bacterial infection

End-stage extension of the knee and its influence on tibial tuberosity-trochlear groove distance (TTTG) in asymptomatic volunteers

PURPOSE: Increased tibial tuberosity-trochlear groove distance (TTTG) is one potential correcting parameter in patients suffering from lateral patellar instability. It was hypothesized that end-stage extension of the knee might influence the TTTG distance on MR images. METHODS: Transverse T1-weighted MR images of the knee were acquired at full extension, 15° and 30° flexion of the knee in 30 asymptomatic volunteers. MRI parameters: slice thickness: 3 mm, matrix: 256 × 384, FOV: 150 × 150 mm. Two observers independently measured the TTTG at all positions. RESULTS: Mean TTTG for observer 1 was 15.1 ± 3.2 mm at full extension, 10.0 ± 3.5 mm at 15° flexion and 8.1 ± 3.4 mm at 30° flexion. Mean TTTG for observer 2: 14.8 ± 3.3 mm at full extension, 9.4 ± 3.0 mm at 15° flexion, 8.6 ± 3.4 mm at 30° flexion. Mean values were significantly different (p < 0.001) between full extension and 15° as well as 30° flexion for both observers. Mean values were significantly different (p < 0.001) between 15° and 30° for observer 1, but not for observer 2 (n.s.). Interobserver agreement was very good (intraclass correlation coefficient: 0.87-0.88; p < 0.001). CONCLUSIONS: The TTTG increases significantly at the end-stage extension of the knee. Therefore, the comparability of published TTTG values measured on radiographs, CT and MRI at various flexion/extension angles of the knee are limited. LEVEL OF EVIDENCE: Development of diagnostic criteria in a consecutive series of patients and a universally applied 'gold' standard, Level II

Letter to the editor in reponse to Louboutin, Wascher, and Neyret in management of patellar problems in skeletally mature patients with nail-patella syndrome. KSSTA 2017 Oct;25(10):3012-3016. https://doi.org/10.1007/s00167-016-4044-y. Epub 2016 Feb 12

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Effects of propranolol inhalation on the diurnal increase in FEV1 and on propranolol airways responsiveness in atopic subjects with asthma.

BACKGROUND--Propranolol inhalation provocation tests are used to measure indirect airways responsiveness in the investigation of asthma. In this study the effects of repeated propranolol inhalation provocation tests within the same day on normal diurnal variation in the forced expiratory volume in one second (FEV1) and subsequent propranolol airways responsiveness were investigated. METHODS--Fifteen atopic asthmatic subjects were challenged with doubling concentrations of propranolol at 08.00 and 16.00 hours on the same study day and at 16.00 hours on a control day to exclude changes related to normal diurnal variation. RESULTS--Mean (SD) baseline FEV1 at 16.00 hours on the study day was 3.38 (0.23) 1, significantly lower than the value at 16.00 hours on the control day of 3.70 (0.24) 1 (p = 0.001). No differences were found between the geometric mean provocative concentration of propranolol causing a 20% fall in FEV1 (PC20) measured on the study day (08.00 hours, 9.3 mg/ml; 16.00 hours, 11.3 mg/ml) and on the control day (16.00 hours 9.3 mg/ml). CONCLUSIONS--The results suggest that propranolol provocation at 08.00 hours has a long lasting effect on FEV1, thereby counteracting the normal diurnal increase in diameter of the airways. This makes propranolol challenge tests less suitable for studying indirect airways responsiveness in the course of one day. Because the FEV1 does not return to control values, it is not possible to determine whether tachyphylaxis to repeated propranolol challenge with a time interval of up to eight hours occurs

&quot;Target Debt ratios: The impact of equity mis-pricing&quot; &quot;Target Debt ratios: differential rates of adjustment and market timing&quot;

Abstract Previous studies disagree on the rate of speed with which firms adjust their leverage toward a target leverage. We argue that a portion of this variance is caused by two factors. First, firms face a &apos;hard&apos; boundary when over levered. This is due to the present value of bankruptcy costs increasing at an increasing rate. These firms will adjust toward a target debt ratio more rapidly than under levered firms which face a &apos;soft&apos; boundary. Second, if a firm&apos;s equity is mis-priced, the cost of issuing equity may be reduced/increased. Our empirical findings support the above conjectures. The findings are robust to various means of measuring leverage and mis-pricing. &quot;Target Debt ratios: differential rates of adjustment and market timing&quot; Abstract Previous studies disagree on the rate of speed with which firms adjust their leverage toward a target leverage. We argue that a portion of this variance is caused by two factors. First, firms face a &apos;hard&apos; boundary when over levered. This is due to the present value of bankruptcy costs increasing at an increasing rate. These firms will adjust toward a target debt ratio more rapidly than under levered firms which face a &apos;soft&apos; boundary. Second, if a firm&apos;s equity is mis-priced, the cost of issuing equity may be reduced/increased. Our empirical findings support the above conjectures. The findings are robust to various means of measuring leverage and mis-pricing