Risk factors for coronary artery disease in patients with elevated high-density lipoprotein cholesterol

High high-density lipoprotein (HDL) levels protect against coronary artery disease (CAD) development. We hypothesized that patients with CAD and high HDL levels would have higher prevalence of other CAD risk factors compared with patients with CAD and normal HDL. We identified 41,982 patients from a single center with normal levels (40 to 60 mg/dl in men, 50 to 70 mg/dl in women) or high HDL levels (> or =70 mg/dl in men, > or =80 mg/dl in women) when last measured between January 2000 and April 2004. From this overall population, we characterized a cohort of 1,610 patients with CAD, including 98 patients with high HDL levels. We measured prevalence of traditional CAD risk factors by comparing these 98 patients with patients with CAD and normal HDL levels (n = 1,512). We performed manual chart review in patients (n = 196) matched 1:1 by age, gender, and HDL level to obtain further detail with regard to differences in family history and lifestyle factors. In patients with CAD, those with high HDL levels (98 of 1,610, 6.1%) were of similar age (71.1 vs 69.6 years, p = 0.23), had similar prevalence of hypertension (78.6% vs 88.7%, p = 0.30), lower levels of low-density lipoprotein (85.3 vs 90.9 mg/dl, p = 0.04) and triglycerides (87.1 vs 141.2 mg/dl, p <0.01), and a lower prevalence of diabetes (28.6% vs 38.4%, p = 0.05) compared with patients with normal HDL levels. In logistic regression models, patients with high HDL levels and CAD were less likely to have diabetes (adjusted odds ratio 0.60, 95% confidence interval 0.38 to 0.95, p = 0.03) or obesity (adjusted odds ratio 0.50, 95% confidence interval 0.25 to 0.99, p = 0.046) than patients with normal HDL levels and CAD. In conclusion, patients with high HDL and CAD had a similar or lower prevalence of traditional CAD risk factors compared with patients with normal HDL levels and CAD.     

High dose dexmedetomidine as the sole sedative for pediatric MRI

Objective: This large-scale retrospective review evaluates the sedation profile of dexmedetomidine. Aim: To determine the hemodynamic responses, efficacy and adverse events associated with the use of high dose dexmedetomidine as the sole sedative for magnetic resonance imaging (MRI) studies. Background: Dexmedetomidine has been used at our institution since 2005 to provide sedation for pediatric radiological imaging studies. Over time, an effective protocol utilizing high dose dexmedetomidine as the sole sedative agent has evolved. Methods/Materials: As part of the ongoing Quality Assurance process, data on all sedations are reviewed monthly and protocols modified as needed. Data were analyzed from all 747 consecutive patients who received dexmedetomidine for MRI sedation from April 2005 to April 2007. Results: Since 2005, the 10-min loading dose of our dexmedetomidine protocol increased from 2 to 3 μg·kg⁻¹, and the infusion rate increased from 1 to 1.5 to 2 μg·kg⁻¹·h⁻¹. The current sedation protocol progressively increased the rate of successful sedation (able to complete the imaging study) when using dexmedetomidine alone from 91.8% to 97.6% (P = 0.009), reducing the requirement for adjuvant pentobarbital in the event of sedation failure with dexmedetomidine alone and decreased the mean recovery time by 10 min (P < 0.001). Although dexmedetomidine sedation was associated with a 16% incidence of bradycardia, all concomitant mean arterial blood pressures were within 20% of age-adjusted normal range and oxygen saturations were 95% or higher. Conclusion: Dexmedetomidine in high doses provides adequate sedation for pediatric MRI studies. While use of high dose dexmedetomidine is associated with decreases in heart rate and blood pressure outside the established ‘awake’ norms, this deviation is generally within 20% of norms, and is not associated with adverse sequelae. Dexmedetomidine is useful as the sole sedative for pediatric MRI.     

Hemodynamic effects of dexmedetomidine sedation for CT imaging studies

Background: Dexmedetomidine sedation for radiological imaging studies is a relatively recent application for this drug. Previous studies have demonstrated some haemodynamic effects of dexmedetomidine, however, the effects remain poorly described in children. The aim of this study was to better define the effect of age on heart rate (HR) and blood pressure changes in children sedated for CT imaging with dexmedetomidine. Methods/materials: At our institution dexmedetomidine is given for sedation for CT imaging as a bolus of 2 mcg·kg⁻¹ over 10 min followed by an infusion of 1 mcg·kg⁻¹·h⁻¹ with a second bolus if required. Detailed quality assurance data sheets document patient demographics, sedation outcomes, adverse events, and hemodynamic data are recorded for each patient. Results: A total of 250 patients (range 0.1–10.6 years) received dexmedetomidine. anova revealed strong evidence for changes in HR and mean arterial blood pressure during bolus and infusion relative to presedation values (P < 0.001). These changes were apparent in each age group and similar between groups. During the first bolus and during infusion, 82% and 93% of patients respectively were within the age-based normal range for HR. For mean arterial blood pressure, 70% of patients were within the normal range during first bolus and 78% during infusion. Conclusion: In the pediatric population studied, intravenous dexmedetomidine sedation was associated with modest fluctuations in HR and blood pressure. Hemodynamic changes were independent of age, required no pharmacologic interventions and did not result in any adverse events. By anticipating these possible hemodynamic effects and avoiding dexmedetomidine in those patients who may not tolerate such fluctuations in HR and blood pressure, dexmedetomidine is an appropriate sedative for children undergoing CT imaging.     

Salivary gland morphology and virus transmission during long-term cytopathologic West Nile virus infection in Culex mosquitoes

The effect of long-term West Nile virus (WNV) infection on Culex salivary gland morphology and viability was evaluated by transmission electron microscopy during a four week period post-blood feeding. These studies showed that apoptosis and other cytopathologic changes occurred more frequently in WNV-infected mosquitoes compared with uninfected controls. The effect of long-term infection on WNV transmission was evaluated by titering virus in saliva over the same time period. Although the mean titer of WNV in mosquito saliva did not change significantly over time, the percentage of saliva samples containing WNV decreased. Because of the importance of saliva in blood meal acquisition and virus delivery, salivary gland pathology has the potential to affect mosquito feeding behavior and virus transmission. Results from this study add to a growing body of evidence that arbovirus infections in mosquito vectors can be cytopathic, and offer a potential mechanism for virus-induced cell death in mosquitoes.     

Combination of radiotherapy with EGFR antagonists for head and neck carcinoma

The introduction of biologically sound radiation fractionation regimens and combinations of radiotherapy with chemotherapy have gradually improved both the survival of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) and the prospect of organ preservation. Long-term follow-up, however, has shown that some of the radiation–chemotherapy combinations are associated with increased late toxicity. This observation, in conjunction with advances in tumor biology, has led to the launch of investigations into molecular markers and targets for therapeutic interventions. Research on the epidermal growth factor receptor (EGFR)-mediated signaling pathway has enriched our understanding of the biology of HNSCC, in terms of carcinogenesis and cellular processes governing tumor response to therapy. The finding that the addition of an antibody-based inhibitor of the EGFR pathway to radiotherapy significantly improves locoregional control and overall survival rates in patients with locally advanced HNSCC, without increasing radiation-induced toxicity, has resulted in the growing acceptance of such combined regimens as a frontline therapy option for locally advanced HNSCC. Because such therapy has benefited only an additional 10%-15% of patients, studies are being undertaken to identify markers and mechanisms of resistance to EGFR antagonists that are essential for the further refinement of therapy. Overall, preclinical and clinical studies on EGFR have validated the concept that selective tumor radiation sensitization can be achieved by modulating a specific perturbed signaling pathway, and these studies have increased the enthusiasm for developing and investigating other novel agents targeting other cellular processes. Dr. L. Milas has received research funding from Imclone Systems Inc. and Sanofi-Aventis. Dr. K.K. Ang has served on Advisory Boards of AstraZeneca, Bristol-Myers Squibb, Imclone Systems Inc., and Sanofi-Aventis.