Assessment of myocardial viability in rats: Evaluation of a new method using superparamagnetic iron oxide nanoparticles and Gd-DOTA at high magnetic field.

The aim of this study was to detect salvageable peri-infarction myocardium by MRI in rats after infarction, using with a double contrast agent (CA) protocol at 7 Tesla. Intravascular superparamagnetic iron oxide (SPIO) nanoparticles and an extracellular paramagnetic CA (Gd-DOTA) were used to characterize the peri-infarction zone, which may recover function after reperfusion occurs. Infarcted areas measured from T1-weighted (T1-w) images post Gd-DOTA administration were overestimated compared to histological TTC staining (52% +/- 3% of LV surface area vs. 40% +/- 3%, P=0.03) or to T2-w images post SPIO administration (41% +/- 4%, P=0.04), whereas areas measured from T2-w images post SPIO administration were not significantly different from those measured histologically (P=0.7). Viable and nonviable myocardium portions of ischemically injured myocardium were enhanced after diffusive Gd-DOTA injection. The subsequent injection of vascular SPIO nanoparticles enables the discrimination of viable peri-infarction regions by specifically altering the signal of the still-vascularized myocardium.     

Exclusive elemental enteral diet in cortico-resistant and cortico-dependent forms of Crohn's disease

The aim of this study was to investigate the value of elemental diet in steroid-resistant and steroid-dependent Crohn's disease. Elemental diet (Vivonex HN, 39.4 +/- 9.2 kcal/kg/d) was delivered through a nasogastric tube at a constant rate. Twenty therapeutic periods lasting from 20 to 74 days (median, 32 days) were undertaken in 18 patients. Elemental diet was well tolerated. Mean values of hemoglobin, serum albumin, and serum transferrin increased significantly through the therapeutic period; body weight and anthropometric data did not change significantly. The short-term response to elemental diet was excellent in 11 cases, demonstrated by achievement of clinical remission and steroid withdrawal; six patients had an incomplete remission and remained slightly active or had to be maintained under low dose steroids; three patients did not respond to therapy and had to be operated upon. During the follow-up (6-30 months), 8 patients out of 17 had a relapse. Relapse was controlled by medical therapy in 5 cases and led to surgery in the 3 other cases. We conclude that elemental diet, as total parenteral nutrition, is an effective therapy of steroid-resistant and steroid-dependent Crohn's disease. However, elemental diet does not prevent relapse.     

Evaluation of a Bayesian method of amikacin dosing in intensive care unit patients with normal or impaired renal function

Our study was designed to determine the population pharmacokinetic parameters of amikacin in intensive care unit patients and to develop a Bayesian method allowing individual estimation of pharmacokinetic parameters. A two-stage method was used for estimating the population characteristics of the pharmacokinetic parameters. Calculations of optimum doses and dosing intervals were based on individual parameters. Our results indicate that the Bayesian method is capable of estimating the individual pharmacokinetic parameters with no significant bias and good precision. Individualization of amikacin dosage was assessed 70 times in 52 patients. To determine the predictive performance of the method, observed peak and trough levels were compared with predicted values by computing precision, bias, and correlation. The amikacin dosing method was unbiased and showed a high correlation coefficient (r = 0.962) between measured and predicted drug serum concentrations. No significant differences were found between the predicted and observed peak (17.3 +/- 3.5 and 17.3 +/- 3.8 micrograms/ml, respectively) and trough (2.86 +/- 0.93 and 3.08 +/- 1.41 micrograms/ml, respectively) amikacin serum concentrations. Among the 52 patients, wide variations were observed in the pharmacokinetic parameters (Vd = 0.21-0.50 L/kg; t 1/2 = 1.1-22 h) and the daily doses (2.8-42 mg/kg/day).     

Bronchial and cardiovascular effects of ocular topical B-antagonists in asthmatic subjects: comparison of timolol, carteolol, and metipranolol

B antagonists eye drops are most effective for the treatment of chronic open angle glaucoma. By this way of administration they have a very good systemic bioavailability. Bronchial, and cardiovascular effects of three of these topicals: timolol, carteolol and metipranolol have been evaluated in three parallel groups of asthmatic patients. The three topics induce bronchoconstriction without significant difference between them, and lower heart rate (sometimes very intensely) whatever the B antagonist studied. From these data, it is recommended to practitioners to follow carefully the rules of administration of B blockers, even in eye drops.     

Transmyocardial revascularization ameliorates ischemia by attenuating paradoxical catecholamine-induced vasoconstriction

Background  The mechanism by which transmyocardial revascularization (TMR) offers clinical benefit is controversial. We hypothesized that TMR ameliorates ischemia by reversing paradoxical catecholamine-induced vasoconstriction. Methods and Results  Chronic ischemic cardiomyopathy was created in 11 dogs by placing ameroid constrictors on the proximal coronary arteries and their major branches. Six weeks later, 35 channels were created percutaneously in the left circumflex artery region, with the left anterior descending artery region serving as control. At rest, wall thickening and myocardial blood flow did not change in the treated region, whereas they deteriorated in the control bed. Contractile and myocardial blood flow reserve increased in the treated region but deteriorated in the control region. There was diminished iodine 123 metaiodobenzylguanidine uptake and a significant reduction in noradrenergic nerves in the treated region compared with the control region, with a corresponding reduction in tissue tyrosine hydroxylase activity. Conclusions  We conclude that the absence of a catecholamine-induced reduction in MBF reserve and contractile reserve in the TMR-treated region with associated evidence of neuronal injury indicates that the relief of exercise-induced ischemia after TMR most likely results from reversal of paradoxical catecholamine-induced vasoconstriction. These findings may have implications in selecting patients who would benefit from TMR. Supported in part by grants from the National Institutes of Health (R01-HL66034 and K-08-HL074290-01). Bethesda. Md. The radio-labeled microspheres were provided by DuPont Pharmaceuticals, North Billerica. Mass, and the ultrasound equipment was supplied by Philips. Andover, Mass. Dr Leong-Poi was the recipient of a Fellowship Training Grant from the Canadian Institute of Health Research and the Heart and Stroke Foundation of Canada.