The acute and chronic effects of H1 receptor blockade with astemizole on indocyanine green clearance

The effects of acute and chronic (3 months) dosing with astemizole on indocyanine green kinetics have been investigated in normal volunteers and patients. A single dose of astemizole 40 mg produced significant reduction in indocyanine green clearance (P less than 0.02) and volume of distribution (P less than 0.02) when assessed at 48 h, but not at 24 h. In six volunteers who did not receive astemizole there was no significant change in indocyanine green kinetics over a 48 h period. In seven patients on chronic treatment with astemizole there was no significant change in indocyanine green kinetics when these were measured at 1 month and 3 months and compared to pre-treatment values. The change in indocyanine green clearance and volume of distribution following acute astemizole treatment did not correlate with H1-receptor antagonism. Change in indocyanine green clearance following acute drug administration may not be due to changes in liver blood flow and should therefore be interpreted with caution.     

Radiation-induced cell death and dendritic cells: potential for cancer immunotherapy?

Dendritic cells are key orchestrators of the immune system. There is considerable interest in their use for treating cancer. Whether they initiate an effective cytotoxic response against antigen-bearing cells, or produce tolerance, depends on the context in which those antigens are presented. Ionising radiation, and the cell death it causes, has several properties that may facilitate such an effective response. A range of in-vitro and in-vivo data supports this, although potential problems exist that may require concurrent strategies.     

Phytostanol tablets reduce human LDL-cholesterol

The feasibility of using solid dosage forms containing stanol lecithin to lower human LDL-cholesterol was investigated. The particle size distribution of a coarse aqueous dispersion of a stanol lecithin mixture was determined at various weight ratios of the components. At a stanol-to-lecithin weight ratio of 1.00-1.50, dispersions could be spray dried and the solid reconstituted with water to produce a particle size distribution that was similar to that of the aqueous dispersion from which it was derived. Two solid dosage forms containing this spray-dried stanol lecithin preparation had different disintegration times--tablets less than 10 min and capsules greater than 45 min. Each delivery system was then tested for LDL-cholesterol reduction activity in a placebo-controlled, double-blind clinical trial containing a total of 52 subjects. After a six-week treatment period, the group that received rapidly disintegrating stanol lecithin tablets (1.26 g stanols daily) experienced a decrease in both LDL-cholesterol and the ratio of LDL-cholesterol to HDL-cholesterol by 10.4% (P = 0.01) and 11.5% (P = 0.03), respectively, relative to placebo. On the other hand, with slowly disintegrating capsules (1.01 g daily) there was no statistically significant difference in any lipid parameter between the active group and placebo group. Taken together, these studies demonstrate that for maximum LDL-cholesterol reduction activity the stanol lecithin formulation must be delivered in a rapidly dispersible form to reach the site of cholesterol absorption.     

Value of attenuation correction on ECG-gated SPECT myocardial perfusion imaging related to body mass index

BACKGROUND: Obesity is a growing problem in the United States, and attenuation artifacts are more prevalent in this patient group. This study evaluated the impact of attenuation correction in patients with a high body mass index (BMI). METHODS AND RESULTS: Three readers interpreted gated attenuation-corrected and non-attenuation-corrected rest/stress technetium 99m sestamibi myocardial perfusion imaging results in 116 patients (BMI <30, n = 60; BMI > or =30, n = 56) who had coronary angiography no more than 60 days after imaging. Readers were blinded to all clinical information and as to whether myocardial perfusion imaging was attenuation-corrected or non-attenuation-corrected. Sensitivity, specificity, and accuracy for detection of coronary artery disease of 70% or greater for attenuation-corrected versus non-attenuation-corrected single photon emission computed tomography (SPECT) were 86% versus 89%, 79% versus 50%, and 84% versus 79%, respectively. Sensitivity, specificity, and accuracy for attenuation-corrected versus non-attenuation-corrected SPECT for patients with BMI less than 30 were 90% versus 90%, 82% versus 64%, and 88% versus 85%, respectively. For BMI of 30 or greater, the results were 82% versus 87%, 76% versus 41%, and 80% versus 73%, respectively. There was a significant difference in specificity overall ( P = .02) and for the category of BMI of 30 or greater ( P = .03). CONCLUSIONS: This study demonstrates that electrocardiography-gated attenuation-corrected Tc-99m sestamibi SPECT myocardial perfusion imaging improves specificity compared with electrocardiography-gated non-attenuation-corrected SPECT myocardial perfusion imaging, especially in patients with BMI of 30 or greater.