Experimental investigations of nonlinearities and destruction mechanisms of an experimental phospholipid-based ultrasound contrast agent.

OBJECTIVES: We sought to characterize the acoustical behavior of the experimental ultrasound contrast agent BR14 by determining the acoustic pressure threshold above which nonlinear oscillation becomes significant and investigating microbubble destruction mechanisms. MATERIALS AND METHODS: We used a custom-designed in vitro setup to conduct broadband attenuation measurements at 3.5 MHz varying acoustic pressure (range, 50-190 kPa). We also performed granulometric analyses on contrast agent solutions to accurately measure microbubble size distribution and to evaluate insonification effects. RESULTS: Attenuation did not depend on acoustic pressure less than 100 kPa, indicating this pressure as the threshold for the appearance of microbubble nonlinear behavior. At the lowest excitation amplitude, attenuation increased during insonification, while, at higher excitation levels, the attenuation decreased over time, indicating microbubble destruction. The destruction rate changed with pressure amplitude suggesting different destruction mechanisms, as it was confirmed by granulometric analysis. CONCLUSIONS: Microbubbles showed a linear behavior until 100 kPa, whereas beyond this value significant nonlinearities occurred. Observed destruction phenomena seem to be mainly due to gas diffusion and bubble fragmentation mechanisms.

Long-term follow-up of atherosclerotic renovascular disease. Beneficial effect of ACE inhibition.

BACKGROUND: Patients with atherosclerotic renovascular disease (ARVD) are almost invariably treated by revascularization. However, the long-term outcomes of this approach on survival and progression to renal failure have not been investigated and have not been compared with that of a purely medical treatment. The aim of this observational study was to investigate factors affecting long-term (over 5 years) outcome, survival and renal function of patients with ARVD treated invasively or medically. METHODS: ARVD was demonstrated angiographically in 195 patients who were consecutively enrolled into a follow-up study. Patient age was 65.6+/-11.2 years, serum creatinine was 1.74+/-1.22 mg/dl and renal artery lumen narrowing was 73.5+/-17.5%. A revascularization was performed in 136 patients, whereas 54 subjects having comparable characteristics were maintained on a medical treatment throughout the study; five patients were lost during follow-up. RESULTS: The main follow-up was 54.4+/-40.4 months. The assessment of cardiovascular survival and renal survival at the end of follow-up revealed 46 cardiovascular deaths, 20 patients with end-stage renal disease (ESRD) and 41 patients with an increase in serum creatinine of over one-third. The multivariate analysis showed that renal revascularization did not affect mortality or renal survival compared with medical treatment. Revascularization produced slightly lower increases in serum creatinine and a better control of blood pressure. A longer survival was associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) (P = 0.002) in both revascularized and medically treated patients. The only significant predictor of ESRD was an abnormal baseline serum creatinine. CONCLUSIONS: On long-term follow-up, ARVD was associated with a poor prognosis due to a high cardiovascular mortality and a high rate of ESRD. In our non-randomized study, revascularization was not a major advantage over medical treatment in terms of mortality or renal survival. The use of ACEIs was associated with improved survival.

Association of the -159C/T polymorphism of the endotoxin receptor (CD14) with carotid artery disease and cardiovascular mortality in dialysis patients.

BACKGROUND: Atherosclerosis is a major problem in end-stage renal disease (ESRD) patients treated by hemodialysis and the prevalence of carotid artery disease is much higher in this group than in the general population. Repeated exposure to cytokine-inducing material, derived from dialysate, may induce a chronic inflammatory state, that could contribute to the atherosclerotic process. Endotoxin is mainly cleared from plasma by the sCD14, the soluble form of the endotoxin receptor CD14. The levels of sCD14 are associated with a polymorphism, -159 C/T, of the CD14 gene. METHODS AND RESULTS: We determined the genotype for the -159 C/T polymorphism in 158 haemodialysis patients and 168 healthy controls. In patients we investigated the association between the CD14 polymorphism and carotid artery disease. With a prospective follow-up study we assessed whether the CD14 polymorphism shows any relationship with cardiovascular mortality. The polymorphic frequency was comparable between patients and controls. In patients, we found a significant difference in the prevalence of carotid artery disease between groups divided by genotype: CC 87.0%, CT 71.7%, TT 48.9% (p = 0.0093). In dialysis patients with hypertension the CC polymorphism was associated with an increased cardiovascular mortality. CONCLUSIONS: These results demonstrate an association between the -159 C/T polymorphism of the CD14 gene and carotid artery disease in dialysis patients. We hypothesize that the low plasma clearance of endotoxin associated with the CC genotype facilitates the atherogenic action of endotoxin-derived cytokines in haemodialysis patients.