The effect of nitrogen mustards on enzymes and tissue metabolism; the effect on enzymes

Nitrogen mustards are powerful inhibitors for choline oxidase, acetylcholine esterase, and choline acetylase, half-inhibition of the first enzyme being produced with concentrations around 1 x 10(-6)M; i.e., ten times less than the LD(50) values. Acetylcholine esterase and choline acetylase required higher concentrations. This inhibition seems to be due to the structural similarity of the ethylenimonium derivatives with choline and acetylcholine. A list of enzyme systems inhibited by nitrogen mustards is given.     

Gemfibrozil increases apolipoprotein A-I and cholesterol concentrations in human peripheral lymph

Abstract. Peripheral lymph lipoproteins were studied in four hyperlipidaemic men before and after 6 weeks of treatment with gemfibrozil, a drug which is known to increase the fractional catabolic rate of very low density lipoproteins (VLDL) by raising lipoprotein lipase activity in peripheral tissues. Decreases in plasma triglycerides of 18–60% (mean, 45%) were accompanied by increases in lymph apolipoprotein (apo) A-I concentration of 30–108% (mean, 66%; P<0.01), and in lymph cholesterol concentration of 35–100% (mean, 59%; P< 0.05). The additional lymph cholesterol was distributed over a broad range of lipoprotein particle sizes. Effects on plasma apo A-I concentration (mean, +7%) and plasma total cholesterol concentration (- 7%)) were not statistically significant. No changes were observed in four untreated control subjects. These findings are compatible with the hypothesis that lipolysis of VLDL at the blood-endothelium interface increases the transfer of apo A-I from plasma to interstitial fluids, and thereby promotes cholesterol efflux from cells.     

Lymphocyte phenotypes in the abomasal mucosa of sheep infected with Haemonchus contortus

Lymphocyte subpopulations in the abomasal mucosa of worm-free and parasitized sheep were assessed in situ. A preponderance of T-lymphocytes, with approximately equal numbers of cells expressing CD5, CD4 and CD8 antigens, was found. Most of the lymphocytes expressing CD8 lacked CD5. Using a panel of 15 monoclonal antibodies to ovine leucocyte antigens, abomasal lymphoid follicles in the mucosa were shown to resemble lymph node follicles phenotypically. Abomasal epithelial cells contained major histocompatibility complex (MHC) class II antigen. Infection or hyperimmunization of pasture-reared sheep with the gastric nematode Haemonchus contortus increased the numbers of mucosal mast cells and eosinophils but did not alter the phenotypic composition or number of mucosal lymphocytes or the pattern of expression of MHC class II antigens.     

Demonstration of an Excitable Gap in the Common Form of Atrioventricular Nodal Reentrant Tachycardia

Premature ventricular depolarizations were introduced during sustained atrioventricular nodal reentrant tachycardia ("slow-fast" type) in a single patient during electrophysiological study. Preexcitation of the atrium with retrograde His bundle capture occurred over an 85 msec range of coupling intervals between the last antegmde His bundle depolarization and the first retrograde His bundle depolarimtion associated luith the premature beat (H₁ - H₂ interval). The interval between the retrograde His bundle depolarization (H₂) and the retrograde atrial depolarization (A₂) remained constant over this 85 msec excitable gap as the H₁-H₂ interval decreased. This indicates the presence of fully excitable tissue luithin the retrograde fast pathway of the reentrant circuit during the tachycardia and demonstrates the utility of this technique for defining the extent and conduction properties of the excitable gap in reentrant arrhythmias     

Acute Termination of Human Atrial Fibrillation by Identification and Catheter Ablation of Localized Rotors and Sources: First Multicenter Experience of Focal Impulse and Rotor Modulation (FIRM) Ablation

FIRM Ablation of Human AF Rotors. Introduction: Catheter ablation of atrial fibrillation (AF) currently relies on eliminating triggers, and no reliable method exists to map the arrhythmia itself to identify ablation targets. The aim of this multicenter study was to define the use of Focal Impulse and Rotor Modulation (FIRM) for identifying ablation targets. Methods: We prospectively enrolled the first (n = 14, 11 males) consecutive patients undergoing FIRM‐guided ablation for persistent (n = 11) and paroxysmal AF at 5 centers. A 64‐pole basket catheter was used for panoramic right and left atrial mapping during AF. AF electrograms were analyzed using a novel system to identify sustained rotors (spiral waves), or focal beats (centrifugal activation to surrounding atrium). Ablation was performed first at identified sources. The primary endpoints were acute AF termination or organization (>10% cycle length prolongation). Conventional ablation was performed only after FIRM‐guided ablation. Results: Twelve out of 14 cases were mapped. AF sources were demonstrated in all patients (average of 1.9 ± 0.8 per patient). Sources were left atrial in 18 cases, and right atrial in 5 cases, and 21/23 were rotors. FIRM‐guided ablation achieved the acute endpoint in all patients, consisting of AF termination in n = 8 (4.9 ± 3.9 minutes at the primary source), and organization in n = 4. Total FIRM time for all patients was 12.3 ± 8.6 minutes. Conclusions: FIRM‐guided ablation revealed localized AF rotors/focal sources in patients with paroxysmal, persistent and longstanding persistent AF. Brief targeted FIRM‐guided ablation at a priori identified sites terminated or substantially organized AF in all cases prior to any other ablation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1277‐1285, December 2012)     

Body composition in older orthopaedic rehabilitation inpatients: Are field methods valid?

Aim: The assessment of body composition is an important aspect of the determination of nutritional health. This cross-sectional measurement study aimed to assess the relative validity of a range of field techniques for the measurement of body composition in a sample of older orthopaedic inpatients participating in rehabilitation. Methods: Assessment of percent fat-free mass of 31 adults, aged 65 years and over, was conducted under fasting conditions by two types of bioelectrical impedance analysis (multi-frequency and single frequency—using manufacturer's pre-programmed prediction equation) and compared with percent fat-free mass estimated by dual energy X-ray absorptiometry, a reference technique. Data from multi-frequency bioelectrical impedance analysis were also used to calculate percent fat-free mass from the prediction equation of Dey et al. for comparison. Skeletal muscle mass was derived from assessment of corrected arm muscle area and compared with skeletal muscle mass from dual energy X-ray absorptiometry analysis. Bland-Altman analysis was performed to determine the level of agreement between each field technique and dual energy X-ray absorptiometry. Results: Mean bias and limits of agreement between single frequency bioelectrical impedance analysis and dual energy X-ray absorptiometry were −5.7% (−24.0, 12.6), between multi-frequency bioelectrical impedance analysis (manufacturer's pre-programmed prediction equation) and dual energy X-ray absorptiometry were 1.4% (−13.4, 16.1), between multi-frequency bioelectrical impedance analysis (Dey et al. prediction equation) and dual energy X-ray absorptiometry were −5.0% (−16.6, 6.6) and between skeletal muscle mass as derived from assessment of corrected arm muscle area and skeletal muscle mass from dual energy X-ray absorptiometry analysis −0.97 kg (−8.37, 6.43). Conclusion: None of the methods assessed are clinically acceptable for assessment of body composition in older orthopaedic rehabilitation patients; however, estimation of skeletal muscle mass, as derived from corrected arm muscle area, is likely to be of more use in the clinical setting as there is no requirement for patients to be fasted.