Trafficking in blood vessel development

Angiogenesis - Blood vessels demonstrate a multitude of complex signaling programs that work in concert to produce functional vasculature networks during development. A known, but less widely...     

Furosemide and the progression of left ventricular dysfunction in experimental heart failure

OBJECTIVES: We tested the hypothesis that furosemide accelerates the progression of left ventricular systolic dysfunction in a tachycardia-induced porcine model of heart failure. BACKGROUND: Furosemide activates the renin-angiotensin-aldosterone system in patients with congestive heart failure (CHF). Such activation may contribute to CHF progression, but prospective data are lacking. METHODS: Thirty-two Yorkshire pigs were randomized to furosemide (1 mg/kg intramuscularly daily, mean 16.1 +/- 0.9 mg) or placebo. Thereafter, a pacing model of heart failure was utilized to produce systolic dysfunction in both sets of animals (fractional shortening <0.16 by echocardiogram). The goal was to determine if furosemide would accelerate the progression of left ventricular dysfunction in the "treated" group. After sacrifice, sodium-calcium exchanger currents and their responsiveness to isoproterenol were measured during voltage clamp. All investigators were blinded to treatment assignment. RESULTS: Furosemide shortened the time to left ventricular dysfunction (35.1 +/- 5.1 days in placebo versus 21.4 +/- 3.2 days for furosemide animals; p = 0.038, log-rank test). By day 14, aldosterone levels were significantly higher in furosemide animals (43.0 +/- 11.8 ng/dl vs. 17.6 +/- 4.5 ng/dl; p < 0.05). Serum sodium was reduced (133.0 +/- 0.9 mmol/l furosemide vs. 135.7 +/- 0.8 mmol/l placebo; p < 0.05), but no difference in norepinephrine, potassium, magnesium, creatinine, or urea nitrogen was present. Basal sodium-calcium exchanger currents were significantly increased and isoproterenol responsiveness depressed by furosemide. CONCLUSIONS: Tachycardic pigs given furosemide had significant acceleration of both contractile and metabolic features of CHF, including left ventricular systolic dysfunction, elevated serum aldosterone levels, and altered calcium handling in a controlled experimental model of heart failure.     

Albuminuria and sodiuria in IUGR children

Objective: Intrauterine growth restriction (IUGR) is associated with hyperfiltration, glomerulosclerosis and albuminuria. Albuminuria may further lead to tubulointerstitial inflammation, fibrosis and tubular atrophy. The time at which this may occur is unknown. This study was designed to assess the relationship between glomerular and tubular damage in IUGR children.

Methods: We enrolled 50 children, 25 IUGR, categorized by estimated fetal weight <10th percentile and umbilical artery pulsatility index >2 SD, and 25 appropriate for gestational age (AGA) controls at 18 months of age. We compared albuminuria among IUGR and AGA children, to assess the relationship between albuminuria and contemporary sodium and lysozyme excretion, as a measure of tubular damage.

Results: The albumin-creatinine (mg/g) and sodium-creatinine (μM/L) ratios (3.12 and 441.3, versus 1.39 and 226.1 in AGA; p?=?0.002 and p?=?0.012, respectively) were significantly higher in the IUGR subjects compared with AGA children, and significantly correlated (rho?=?0.593, p?=?0.002). Conversely, urinary lysozyme was undetectable or in normal excretion range.

Conclusions: Our results show glomerulosclerosis and albuminuria in IUGR children aged 18 months. Elevated sodium excretion in the absence of abnormal lysozymuria may represent a epiphenomenon of glomerulosclerosis and of albuminuria.     

Urinary albumin excretion in patients with rheumatoid arthritis in a large cross-sectional study

While there is a lot of evidence published on the association of cardiovascular (CV) disease and rheumatoid arthritis (RA), little is known about urinary albumin excretion (UAE)—a marker of CV risk—in this particular high-risk population. Therefore, we investigated UAE in a large cross-sectional study. We used data from the US National Health and Nutrition Examination Survey (NHANES), including the years 2007–2012. Primary outcome was the proportion of patients with a urinary albumin-creatinine ratio (ACR) >30 mg/g. A total of 14,648 study participants (representing a population size of 174,663,008) with available ACR were included in the study (14,179 without RA and 469 with RA). In the RA group, the proportion of patients with an ACR >30 mg/g was 10.46 % (95 % CI 7.47–14.45 %) and in the non-RA group this proportion was 13.39 % (95 % CI 12.65–14.16 %; p?=?0.09). There was a strong association between RA and DM (OR 5.84; 95 % CI 4.48–7.62). In the RA group, significantly more patients had a former CV event (OR 3.01; 95 % CI 2.28–3.97). Adjustments for DM, smoking status, former CV event, age, systolic blood pressure, and gender did not substantially alter the association between RA and ACR >30 mg/g (OR 0.82; 95 % CI 0.51–1.33). We did not find evidence for a difference in UAE in patients with or without RA, despite the fact that RA was associated with DM and, in addition, RA patients more often had a previous CV event. These findings may support the assumption that despite an increased CV risk, UAE does not play a major role in RA patients.     

Thrombus precursor protein,endogenous thrombin potential,von‐Willebrand factor and activated factor VII in suspected deep vein thrombosis: is there a place for new parameters?

Because of its high negative predictive value, D-Dimer is an important parameter in the exclusion of deep vein thrombosis (DVT) but it produces a high number of false-positive results. We therefore evaluated different blood parameters in 74 consecutive patients with suspected DVT, whose final diagnosis was based on the results of Duplex ultrasound or venography. DVT was diagnosed in 52.7%. While D-Dimer, thrombin-antithrombin complexes, prothrombin fragment 1+2, von-Willebrand factor and thrombus precursor protein were significantly increased in patients with DVT, there was no influence concerning endogenous thrombin potential and activated factor VII. There was no significant correlation between the thrombus extension or the duration of symptoms with any of these parameters. D-Dimer showed the best sensitivity (94.9%) to specificity (45.7%) ratio and neither the sole nor the additional evaluation of any other investigated parameter increased its diagnostic performance. We, therefore, conclude that the determination of D-Dimer remains the 'gold standard' in the laboratory testing of patients with suspected DVT.     

Acute Granulomatous <Emphasis Type="Italic">Acanthamoeba</Emphasis> Encephalitis in an Immunocompetent Patient

Background  

Acanthamoeba sp. are known to cause fatal granulomatous Acanthamoeba encephalitis (GAE) in immunocompromised patients.