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1.

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Methods

Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.

Results

Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).

Conclusions

Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF.  相似文献   
2.

Objective

The teaching hospital of Nancy, France, implemented a specific multidisciplinary care pathway (French acronym AMDPL) to improve the management of patients presenting with Lyme borreliosis (LB) suspicion. We aimed to assess the first year of activity of this care pathway.

Patients and methods

We included all patients managed in the AMDPL pathway from November 1, 2016 to October 31, 2017. The first step was a dedicated Lyme disease consultation with an infectious disease specialist. Following this consultation, the LB diagnosis was either confirmed and adequate treatment was prescribed, or a differential diagnosis was established and patients received adequate management, or further investigations were required and patients were offered multidisciplinary management as part of a day hospitalization.

Results

A total of 468 patients were included. LB diagnosis was confirmed in 15% of patients (69/468), 49% of patients received a differential diagnosis, and 26% (122/468) of patients had the LB diagnosis ruled out without receiving any other diagnosis.

Conclusions

This is to our knowledge the first multidisciplinary center implemented in France for the management of patients presenting with LB suspicion related to polymorphous signs and symptoms. Several diagnoses could be confirmed or corrected, although some symptoms and complaints could not be explained. This cohort could improve our knowledge of LB and its differential diagnoses.  相似文献   
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Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125I]AII binding to rabbit aortic membranes (AT, receptors) and [125I][Sar1, Ile8]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study.  相似文献   
5.
D-xylose disposition was examined in 24 healthy men between 32 and 85 years of age. Xylose was administered as a 5 gm iv infusion and as a 25 gm po solution. Serum xylose concentrations and urinary excretion of intact xylose were determined. There were statistically significant inverse relationships with age for each of the following parameters after intravenous infusion: elimination rate constant (r2 = 0.71); systemic clearance (r2 = 0.66); renal clearance (r2 = 0.66); and nonrenal clearance (r2 = 0.35). Similar inverse relationships were found after oral dosing for the elimination rate constant (r2 = 0.69) and renal clearance (r2 = 0.54). There was no significant age relationship for the apparent volume of distribution or the steady-state volume of distribution. The percentage of the oral and intravenous dose recovered in urine up to 5 hours after dosing was significantly and inversely correlated with age. The implications of the latter finding are discussed with regard to the interpretation of the xylose tolerance test used to assess gastrointestinal absorptive capacity.  相似文献   
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A vertically integrated health care system is an arrangement whereby a health care organization offers, either directly or through others, a broad range of patient care and support services. This article discusses the market forces and strategic considerations driving the recent trend toward vertical linkages in health care markets and examines some of the managerial implications and issues associated with this vertical restructuring trend.  相似文献   
10.
Aorto-femoral angiography carried out in 839 patients revealed that 139 males and females had uni- or bilateral occlusion of the common or external iliac arteries. Pelvic or lumbar/intercostal arteries served as collaterals in 786 patients. In the remaining 53 patients the collateral blood supply originated from the thoracic arteries. Among the 53 patients, only 7 were females. A chi 2-test revealed the difference to be significant (p less than 0.0005), indicating a sex-linked difference, a male preponderance, in the development of collateral circulation of thoracic origin.  相似文献   
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