Influence of Apolipoprotein E Plasma Levels and Tobacco Smoking on the Induction of Neutralising Antibodies to Interferon-Beta

Interferon-beta (IFN-beta) therapy for multiple sclerosis (MS) is associated with a potential for induction of neutralizing antibodies (NAbs). Because immune reactivity depends on changes in lipoprotein metabolism, we investigated whether plasma lipoprotein profiles could be associated with the development of NAbs. Thirty-one female MS patients treated with subcutaneously administered IFN-beta were included. Demographic and clinical characteristics were compared between NAbs response groups using t tests for continuous and logistic regression analysis and Fisher's exact tests for categorical data, respectively. Multivariate logistic regression was used to evaluate the effect of potential confounders. Patients who developed NAbs had lower apoE levels before treatment, 67 (47-74) mg/L median (interquartile range), and at the moment of NAb analysis, 53 (50-84) mg/L, in comparison to those who remained NAb-negative, 83 (68-107) mg/L, P = 0.03, and 76 (66-87) mg/L, P = 0.04, respectively. When adjusting for age and smoking for a one-standard deviation decrease in apoE levels, a 5.6-fold increase in the odds of becoming NAb-positive was detected: odds ratios (OR) 0.18 (95% CI 0.04-0.77), P = 0.04. When adjusting for apoE, smoking habit became associated with NAb induction: OR 5.6 (95% CI 1.3-87), P = 0.03. These results suggest that apoE-containing lipoprotein metabolism and, possibly, tobacco smoking may be associated with risk of NAb production in female MS patients treated with IFN-beta.

Skin Prick Tests and Allergy Diagnosis

Skin testing remains an essential diagnostic tool in modern allergy practice. A signifi cant variability has been reported regarding technical procedures, interpretation of results and documentation. This review has the aim of consolidating methodological recommendations through a critical analysis on past and recent data. This will allow a better understanding on skin prick test (SPT) history; technique; (contra-) indications; interpretation of results; diagnostic pitfalls; adverse reactions; and variability factors.

Methacholine Dose-Response Slopes from Maximal Bronchial Challenge Tests in Asthmatic Children: Methodological Aspects

To determine whether the slope of a maximal bronchial challenge test (in which FEV1 falls by over 50%) could be extrapolated from a standard bronchial challenge test (in which FEV1 falls up to 20%), 14 asthmatic children performed a single maximal bronchial challenge test with methacholin(dose range: 0.097–30.08 umol) by the dosimeter method. Maximal dose-response curves were included according to the following criteria: (1) at least one more dose beyond a FEV1 ù 20%; and (2) a MFEV1 ù 50%. PD20 FEV1 was calculated, and the slopes of the early part of the dose-response curve (standard dose-response slopes) and of the entire curve (maximal dose-response slopes) were calculated by two methods: the two-point slope (DRR) and the least squares method (LSS) in % FEV1 × umol−1. Maximal dose-response slopes were compared with the corresponding standard dose-response slopes by a paired Student’s t test after logarithmic transformation of the data; the goodness of fit of the LSS was also determined. Maximal dose-response slopes were significantly different (p < 0.0001) from those calculated on the early part of the curve: DRR20% (91.2 ± 2.7 FEV1% z umol−1)was 2.88 times higher than DRR50% (31.6 ± 3.4 DFEV1% z umol−1), and the LSS20% (89.1 ± 2.8% FEV1 z umol−1) was 3.10 times higher than LSS 50% (28.8 ± 1.5%FEV1 z umol−1). The goodness of fit of LSS 50% was significant in all cases, whereas LSS 20% failed to be significant in one. These results suggest that maximal dose-response slopes cannot be predicted from the data of standard bronchial challenge tests.

A Comparative Study of Cardiovascular Tolerability with Slow Extended Dialysis Versus Continuous Haemodiafiltration in the Critical Patient

Background: In the haemodynamically unstable patient the method of treatment of acute renal failure is still largely controversial. The purpose of our study was to compare slow extended dialysis with continuous haemodiafiltration in the critical patient with indication for renal replacement therapy and haemodynamic instability. Patients and Methods: This is a cohort study comparing in 63 ventilated critical patients a 12 month period when only continuous haemodiafiltration was used (n=25) with an equal period of slow extended dialysis (n=38). Our primary objective was to evaluate the impact of the dialytic procedure on cardiovascular stability in those patients. As secondary aims we considered system coagulation/thrombosis and predictors of mortality. In the two groups we analysed the first session performed, the second session performed and the average of all the sessions performed in each patient. Results: In these patients, mortality in the intensive care unit was high (68% in the continuous haemodiafiltration group and 63% in the slow extended dialysis group). We did not find any association between the dialytic technique used and death; only the APACHE score was a predictor of death. Slow extended dialysis was a predictor of haemodynamic stability, a negative predictor of sessions that had to be interrupted for haemodynamic instability, and a predictor of achieving the volume removal initially sought. Slow extended dialysis was also associated with less coagulation of the system. Conclusions: Our data suggested that slow extended dialysis use was not inferior to continuous haemodiafiltration use in terms of cardiovascular tolerability.