Ralph T. Kiefer

A Placebo-Controlled Randomized Crossover Trial of the N-Methyl-D-Aspartic Acid Receptor Antagonist, Memantine, in Patients with Chronic Phantom Limb Pain

In the present study we investigated the effect of the N-methyl-d-aspartic acid (NMDA) receptor antagonist memantine (30 mg/d) on the intensity of chronic phantom limb pain (PLP) and cortical reorganization. In 8 patients with chronic PLP, memantine was tested in a placebo-controlled double-blinded crossover trial of 4 wk duration per trial. The intensity of PLP was rated hourly by the patients on a visual analog scale during baseline and both treatment periods. At the same time points, the functional organization of the primary somatosensory cortex (SI) was determined by neuromagnetic source imaging. In comparison to baseline and placebo, the NMDA receptor antagonist had no effect on the intensity of chronic PLP. In none of the periods were significant changes in the functional organization of SI observed. Although the conclusions regarding the clinical effect are limited because of the small sample size, the data indicate that in the studied dosage the NMDA receptor antagonist memantine is ineffective in the treatment of chronic PLP and is also ineffective for the reduction of associated neural plasticity in the primary SI.

Role of cross-allergies to latex in clinical routine of anesthesia

STUDY OBJECTIVE To determine the applicability and reliability of a screening questionnaire to detect patients at high-risk of latex allergy; to assess the importance of other allergies such as profilin allergies (pollinosis) for presence of latex sensitization; and to determine the clinical effectiveness of preemptive avoidance of latex exposure in high-risk patients. DESIGN Prospective, clinical trial. SETTING Operative theater of a university hospital. PATIENTS 95 adult patients. INTERVENTIONS Patients were preoperatively screened and classified for present latex allergy (high-risk and low-risk group) according to a specially designed screening questionnaire. Anesthesia and surgery in the high-risk group were performed strictly avoiding latex-containing materials. The low-risk group (other allergies including pollinosis) received routine treatment, without latex-avoidance. Effects of latex avoidance or exposure were evaluated by measuring specific IgE titers perioperatively. MEASUREMENTS AND MAIN RESULTS According to the questionnaire, 45 patients at high risk were defined. Validity of classification of high-risk patients is supported by significantly higher total IgE and latex and grass profilin specific IgE compared to the low-risk group. There were no significant differences in other profilin-specific IgEs. In one case of severe anaphylactic reaction a drop of latex-specific IgE during surgery could be observed. CONCLUSION The questionnaire allowed the identification of most patients at high risk for latex allergy. In isolated pollinosis no changes in any specific IgE levels were detectable. Strict avoidance of perioperative latex exposure in high-risk patients increases safety during anesthesia and surgery.

Thiopental and Nuclear Factor κB: Some Questions

To the Editor:—In their very interesting study, Loop et al. demonstrate an inhibitory effect of thiopental on nuclear factor B (NFB) activation in T cells. However, we missed some essential background information in the discussion. First, the concentration of thiopental used in this study is much higher than plasma concentrations noted in clinical practice or in other models presenting inhibitory effects of thiopental on interferon (IFN) production. Second, the fact that thiopental suppresses NFB translocation in T cells may not directly reflect general immune suppression. Regulation of cytokines in T cells is simplified in this article and may lead to false interpretation. Therefore, it would be helpful to give some more information beyond that provided by the authors in their statement that “other transcription factors may be involved.” Cytokine expression is regulated in a cell-type and stimuli-specific manner. This might explain why Loop et al. were not able to demonstrate any effect of propofol on cytokine production or NFB activation, whereas Takaono et al. describe inhibition of interleukin 6 (IL-6) production in lipopolysaccharide-stimulated peripheral blood mononuclear cells after propofol treatment. In the same study, thiopental (up to 200 g/ l) had no significant effect on IL-6 production. Furthermore, the ability of transcription factors to bind DNA and modulate gene transcriptions is tightly regulated in normal cells. There are four transcription factors that play a major role in the regulation of inflammatory gene expression: activator protein 1, activating transcription factor 2, signal transducers and activators of transcription, and NFB (and, in T cells, nuclear factor of activated T cells [NFAT]). The pattern of their activation regulates expression of inflammatory mediators. Inhibition of one transcription factor may include enhanced activation of another factor. Loop et al. show that thiopental reduces the production of IL-2, IL-6, and IFNin phorbol-12-myristate-13acetate–stimulated peripheral blood mononuclear cells. The authors conclude that this is due to the inhibitory effect of thiopental on NFB activation. However, the transcription of IL-2 and IFNrequires the activation of NFAT and activator protein 1 more than that of NFB. This is of importance since NFAT is also required for transcription of IL-10, an antiinflammatory cytokine induced by thiopental. In this regard it also must be mentioned that the regulation of IFNseems to be different in Jurkat cells than in “normal” T cells. In addition, the presentation of NFAT binding in the presence of other anesthetics would have been very interesting since it has been shown that ketamine decreases cytokine production in whole blood preparations at concentrations comparable to those used by Loop et al. Furthermore, it has been shown that ketamine suppresses endotoxin-induced NFB activation in other models. Therefore, it is surprising that Loop et al. do not see any effect of ketamine on NFB activation in T cells or on cytokine production in peripheral blood mononuclear cells.