Efficacy and Safety of Orally Administered Intravenous Midazolam Versus a Commercially Prepared Syrup

Background:

Among different categories of sedative agents, benzodiazepines have been prescribed for more than three decades to patients of all ages. The effective and predictable sedative and amnestic effects of benzodiazepines support their use in pediatric patients. Midazolam is one of the most extensively used benzodiazepines in this age group. Oral form of drug is the best accepted route of administration in children.

Objectives:

The purpose of this study was to compare the efficacy and safety of a commercially midazolam syrup versus orally administered IV midazolam in uncooperative dental patients. Second objective was to determine whether differences concerning sedation success can be explained by child‘s behavioral problems and dental fear.

Patients and Methods:

Eighty eight uncooperative dental patients (Frankl Scales 1,2) aged 3 to 6 years, and ASA I participated in this double blind, parallel randomized, controlled clinical trial. Midazolam was administered in a dose of 0.5 mg/kg for children under the age 5 and 0.2 mg/kg in patients over 5 years of age. Physiologic parameters including heart rate, respiratory rate, oxygen saturation and blood pressure were recorded. Behavior assessment was conducted throughout the course of treatment using Houpt Sedation Rating Scale and at critical moments of treatment (injection and cavity preparation) by North Carolina Scale. Dental fear and behavioral problems were evaluated using Child Fear Schedule Survey-Dental Subscale (CFSS-DS), and Strength and Difficulties Questionnaire (SDQ). Independent t-test, Chi-Square, and Pearson correlation were used for statistical analysis.

Results:

Acceptable overall sedation ratings were observed in 90% and 86% of syrup and IV/Oral group respectively; Chi-Square P = 0.5. Other domains of Houpt Scale including: sleep, crying and movement were also not significantly different between groups. Physiological parameters remained in normal limits during study without significant difference between groups.

Conclusions:

“Orally administered IV midazolam” preparation can be used as an alternative for commercially midazolam syrup.     

Diesel exhaust exposure enhances the expression of IL-13 in the bronchial epithelium of healthy subjects

Epidemiological studies have demonstrated adverse health effects of environmental pollution. Diesel exhaust (DE) is an important contributor to ambient particulate matter pollution. DE exposure has been shown to induce a pronounced inflammatory response in the airways, with an enhanced epithelial expression of IL-8, and Gro-alpha in healthy subjects. The present investigation was aimed to further characterise the epithelial response to DE in vivo, with particular reference to possible TH2 response, in non-atopic healthy subjects. To determine this response, 15 healthy, non-atopic non-smoking subjects with normal lung function were exposed to DE (PM10 300 microg/m3) and filtered air during 1 h on two separate randomised occasions. Bronchoscopy sampling of bronchial mucosal biopsies was performed 6 h after exposure. Immunohistochemical staining were performed using mAb for IL-10, IL-13 and IL-18 expression. DE exposure induced a significant increase in the expression of IL-13 in the bronchial epithelium cells, 2.1 (1.35-4.88) Md (Q1-Q3) vs. air 0.94 (0.53-1.23); P = 0.009. No significant changes were seen in IL-10 and IL-18 expression. This finding suggests an TH2-inflammatory response in the airways of non-atopic healthy individuals.     

Optimal β-blocker for prevention of atrial fibrillation after on-pump coronary artery bypass graft surgery: Carvedilol versus metoprolol

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia after coronary artery bypass graft (CABG) surgery. It has been shown that prophylactic oral beta-blocker administration reduces the incidence of post-CABG AF. However, the optimal beta-blocker has not been identified. OBJECTIVE: This study sought to determine whether oral carvedilol (with its unique anti-inflammatory and antioxidant properties) is more effective than oral metoprolol for prevention of AF after CABG surgery. METHODS: Between April 2006 and December 2006, 120 patients (63 men, mean age 61 +/- 9.4 years) who were scheduled to undergo their first on-pump CABG were enrolled in this study. The patients were randomized in a prospective 1:1 manner to receive either oral carvedilol (n = 60) or oral metoprolol (n = 60). The end point of the study was the occurrence of the new-onset AF during the first 5 days after CABG. RESULTS: AF occurred in 29 of 120 patients (24.0%). The incidence of postoperative AF was 15.0% (9 of 60) in the carvedilol group and 33% (20 of 60) in the metoprolol group (P = .022). The carvedilol group was treated with mean daily dose of 46 +/- 9 mg and metoprolol group with mean daily dose of 93 +/- 11 mg. There were no differences between the study groups regarding any known preoperative, perioperative, or postoperative characteristics (all values were P >.05). No significant adverse effect was observed in either group. CONCLUSION: This prospective study suggested that oral carvedilol is more effective than oral metoprolol in the prevention of AF after on-pump CABG. It is well tolerated when started before and continued after the surgery. However, further prospective studies are needed to clarify this issue.     

The assembly of single domain antibodies into bispecific decavalent molecules

Bispecific antibodies present unique opportunities in terms of new applications for engineered antibodies. However, designing ideal bispecific antibodies remains a challenge. Here we describe a novel bispecific antibody model in which five single domain antibodies (sdAbs) are fused via a linker sequence to the N-terminus of the verotoxin B (VTB) subunit, a pentamerization domain, and five sdAbs are fused via a linker sequence to the VTB C-terminus. Fifteen such decavalent bispecific molecules, termed decabodies, were constructed and characterized for the purpose of identifying an optimal decabody design. One of the fifteen molecules existed in a non-aggregated decavalent form. In conjunction with the isolation of sdAbs with the desired specificities from non-immune phage display libraries, the decabody strategy provides a means of generating high avidity bispecific antibody reagents, with good physical properties, relatively quickly.