Macrophage migration inhibitory factor: a therapeutic target across inflammatory diseases

Macrophage migration inhibitory factor (MIF), a cytokine originally reported in the 1960s as the prototypic T lymphokine, has emerged in recent years as a key factor regulating inflammatory responses. Both by directly activating immune cells, and by participating in activation entrained by other stimuli, MIF is important in innate and adaptive immune responses as well as tissue-specific mechanisms of damage. As a consequence of its involvement in multiple stages of the immune-inflammatory response, MIF has the potential to be involved in the pathogenesis of a range of immune-mediated inflammatory diseases affecting multiple organ systems. Diseases in which a role for MIF has been strongly validated include rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, atherosclerosis, asthma, inflammatory liver disease, and most recently systemic lupus erythematosus. Recent data have provided mechanisms of action for MIF which further support its suitability as a therapeutic target. Finally, MIF has a unique relationship with glucocorticoids, acting to counter-regulate their anti-inflammatory effects, such that MIF antagonist therapy may be a direct route to 'steroid-sparing'. Methods of targeting MIF therapeutically have also emerged in recent years, based on the unique protein structure of MIF which affords opportunities for direct antagonism by small molecules, as well as by protein therapeutics such as monoclonal antibodies. Clinical trials of MIF antagonist therapies are likely before the end of the current decade.     

Diagnostic yield of CT angiography performed for suspected cervical artery dissection in the emergency department

Emergency Radiology - Computed tomography angiographies are frequently performed in the emergency department (ED) for the assessment of cervical artery dissection (CeAD) due to the high risk of...     

Influence of diet complexity on intestinal adaptation following massive small bowel resection in a preclinical model

AIMS: To investigate the effect of dietary complexity on intestinal adaptation using a preclinical model. METHODS: Four-week-old piglets underwent a 75% proximal small bowel resection or transection operation (control). Post-operatively, animals received either pig chow (n = 15), polymeric formula (n = 9), polymeric formula plus fiber (n = 6), or elemental formula (n = 7). RESULTS: The weight gain of all groups was reduced compared with controls that were fed the same diet. Animals that had a resection, which were fed elemental formula, had significantly reduced weight gain compared with the other groups (4.7 4.2 vs 30.7 7.1 kg chow and 11.5 1.3 kg polymeric formula). Villus height was increased in the jejunum, ileum and terminal ileum of resected animals compared with controls in animals fed with pig chow, polymeric formula and elemental formula. The animals that had a resection had a significant reduction in the transepithelial conductance (10.4 5.5 vs 25.4 6.5 mS/cm2) and 51Chromium-EDTA flux (2.8 1.9 vs 4.8 4.9 microL/h per cm2) compared with the controls. CONCLUSIONS: A complex diet was found to be superior to an elemental diet in terms of the morphological and functional features of adaptation following massive small bowel resection.     

The relationship between nighttime dipping in blood pressure and cerebral hemodynamics in nonstroke patients

Inadequate dipping in nighttime blood pressure (BP) is associated with cerebrovascular disease. The authors aimed to determine whether inadequate nocturnal dipping was associated with abnormalities in cerebrovascular hemodynamics in individuals without stroke. Participants in this study underwent 24-hour ambulatory BP monitoring followed by morning transcranial Doppler measurements of blood flow velocities (BFVs) in the middle cerebral artery during supine rest, head-up tilt, hypocapnia, and hypercapnia. Nighttime BP decline by <10% was considered nondipping. Of the 102 nonstroke participants (mean age, 53.6 years), 35 (34%) were dippers. Although nondippers had similar BFV and cerebrovascular resistance (CVR) while supine, they had a lower BFV (P=.04) and greater CVR (P=.02) during head-up tilt compared with dippers. Moreover, greater nighttime dipping in both systolic BP (P=.006) and diastolic BP (P=.03) were associated with higher daytime BFV and lower CVR (P=.01 for systolic BP; P=.02 for diastolic BP). Inadequate nocturnal BP dipping is associated with lower daytime cerebral blood flow, especially during head-up tilt.     

Pre-discharge and early post-discharge management of patients hospitalized for acute heart failure: A scientific statement by the Heart Failure Association of the ESC

Acute heart failure is a major cause of urgent hospitalizations. These are followed by marked increases in death and rehospitalization rates, which then decline exponentially though they remain higher than in patients without a recent hospitalization. Therefore, optimal management of patients with acute heart failure before discharge and in the early post-discharge phase is critical. First, it may prevent rehospitalizations through the early detection and effective treatment of residual or recurrent congestion, the main manifestation of decompensation. Second, initiation at pre-discharge and titration to target doses in the early post-discharge period, of guideline-directed medical therapy may improve both short- and long-term outcomes. Third, in chronic heart failure, medical treatment is often left unchanged, so the acute heart failure hospitalization presents an opportunity for implementation of therapy. The aim of this scientific statement by the Heart Failure Association of the European Society of Cardiology is to summarize recent findings that have implications for clinical management both in the pre-discharge and the early post-discharge phase after a hospitalization for acute heart failure.     

Assessment of left internal mammary artery graft patency by transthoracic Doppler echocardiography

BACKGROUND: The successful application of noninvasive Doppler spectrum analysis has been reported for the hemodynamic assessment of LIMA graft after myocardial revascularization. HYPOTHESIS: The objective of this study was to assess the utility of transthoracic Doppler echocardiography (TTE) in providing information on LIMA flow in patients after coronary artery bypass graft surgery. METHODS: In all, 22 patients (aged 62 +/- 8 years) with LIMA graft to the left anterior descending (LAD) coronary artery who underwent coronary angiography were assessed using high-frequency (5 MHz) transthoracic Doppler echocardiography. They were compared with 25 patients with angina (control group A, aged 59 +/- 12 years), in whom an ungrafted LIMA was assessed, and with 17 patients (control group B, aged 59 +/- 9 years) with angiographically normal coronary arteries, in whom the LAD was assessed. RESULTS: A biphasic pattern (systolic and diastolic) was recorded in all cases. In 14 patients with a normal graft or < 70% stenosis (Group 1) and in control group B, blood flow was maximal during diastole. In eight patients with severe graft stenosis > 70% (Group 2) and control group B, blood flow was maximal during systole, with low diastolic flow. The diastolic fraction of the velocity time integrals was 0.81 +/- 0.11 for Group 1 and 0.25 +/-0.06 for Group 2 (p < 0.05). A diastolic velocity time integral fraction < 0.5 predicted > 70% stenosis with a sensitivity and specificity of 100%. The ratio of systolic/diastolic peak velocities was 0.61 +/- 0.31 for Group 1 and 3.21 +/- 0.49 for Group 2 (p < 0.05). A systolic/diastolic peak velocity > 1 predicted stenosis > 70% with a sensitivity and specificity of 100 and 90%, respectively. CONCLUSIONS: High-frequency TTE is a useful noninvasive method for detecting LIMA graft blood flow. Severe graft stenoses exhibited Doppler velocity patterns, which were different from those of patent grafts, or grafts with moderate stenoses.