[The pain-emotion: Advocating pain as an emotion]. / L'émotion­douleur : de l'intérêt de considérer la douleur comme une émotion.

OBJECTIVES: Pain is a common experience, both physical and emotional. However we often feel powerless with our patients suffering pain. This paper aims to give a new heuristic and psychological understanding of pain. METHODOLOGY: According to new theories, recent researches as well as different points of view, we form an analogy between pain and emotion. Throughout historical considerations pain has always been perceived through theories and beliefs, changing its definition. This is also the case for emotion. Could they be two ways of expressing a single phenomenon? RESULTS: First, we must clarify the definition of emotion. In past, emotion was considered as a multiple-conditioned notion. To be considered as an emotion the pain had to fill numerous features, which differ according to the scientific opinions. The emotion may be considered as a physical expression or perceived only as the consequences of a real emotion, i.e., the subjective feeling. We propose as a way of thinking that emotion brings together these two concepts. We support a flexible vision of emotion. To investigate the field of the emotion different mental steps may be thought of: we should conceive of the emotion as a stimulus, as an emotional evaluation and as a tendency to action, which becomes an emotional response. These steps are colored by subjective feelings. It can be summarized in three levels: the situation decoding (1), the response organization (2) and the effectiveness of the response (3). Second pain can be considered as a complex notion involving personal and subjective feelings. We can use multidimensional patterns and consider emotion with its multiple features: the generating mechanisms, the pain perception, the pain behavior and the environment. Each stage can be divided in different ways. Hence pain treatment could be approached as an emotional treatment. Indeed, we can make a link between generating mechanisms and emotion situation decoding, between pain perception and emotion situation decoding and response organization, between pain behavior and environment and emotion response effectiveness and consequences. A heuristic analogy can be formed enriching therapeutic possibilities. First, emotion and pain could be considered as a unique phenomenon that can be expressed in different ways. We can let aside the opposition between psychological and physiological: these are two different levels of a same phenomenon. This point of view can be helpful to treat pain disorders because the skills to manage emotion disorders are well known.

An electrodynamics-Langevin dynamics (ED-LD) approach to simulate metal nanoparticle interactions and motion.

Understanding the formation of electrodynamically interacting assemblies of metal nanoparticles requires accurate computational methods for determining the forces and propagating trajectories. However, since computation of electromagnetic forces occurs on attosecond to femtosecond timescales, simulating the motion of colloidal nanoparticles on milliseconds to seconds timescales is a challenging multi-scale computational problem. Here, we present a computational technique for performing accurate simulations of laser-illuminated metal nanoparticles. In the simulation, we self-consistently combine the finite-difference time-domain method for electrodynamics (ED) with Langevin dynamics (LD) for the particle motions. We demonstrate the ED-LD method by calculating the 3D trajectories of a single 100-nm-diameter Ag nanoparticle and optical trapping and optical binding of two and three 150-nm-diameter Ag nanoparticles in simulated optical tweezers. We show that surface charge on the colloidal metal nanoparticles plays an important role in their optically driven self-organization. In fact, these simulations provide a more complete understanding of the assembly of different structures of two and three Ag nanoparticles that have been observed experimentally, demonstrating that the ED-LD method will be a very useful tool for understanding the self-organization of optical matter.

Integrated copy number and gene expression analysis detects a CREB1 association with Alzheimer's disease.

Genetic variation, both single-nucleotide variations and copy number variations (CNV), contribute to changes in gene expression. In some cases these variations are meaningfully correlated with disease states. We hypothesized that in a genetically heterogeneous disorder such as sporadic Alzheimer's disease (AD), utilizing gene expression as a quantitative trait and CNVs as a genetic marker map within the same individuals in the context of case-control status may increase the power to detect relevant loci. Using this approach an 8-kb deletion was identified that contains a PAX6-binding site on chr2q33.3 upstream of CREB1 encoding the cAMP responsive element-binding protein1 transcription factor. The association of the CNV to AD was confirmed by a case-control association study consisting of the Texas Alzheimer Research and Care Consortium and NIA-LOAD Family Study data sets.

Surgical repair of a post-traumatic arteriovenous fistula complicated by stent-graft misplacement.

An arteriovenous fistula (AVF) is an abnormal connection between an artery and a vein which may result from a traumatic injury or occur as a congenital abnormality. It may be asymptomatic or may present with a variety of symptoms. Surgical or endovascular treatment can be preferred. We present a case of unsuccessful percutaneous treatment of a femoral AVF due to misplacement of the stent-grafts, necessitating surgical correction.

Increased blood-brain barrier permeability with thymidine phosphorylase deficiency.

Mitochondrial neurogastrointestinal encephalomyopathy is an autosomal recessive multisystemic disorder caused by thymidine phosphorylase deficiency. Whereas the pathomechanism of the secondary mitochondrial dysfunction has been extensively studied, that of the leukoencephalopathy has not been elucidated. We hypothesized that the white matter hyperintensities on T2-weighted magnetic resonance images reflect disturbance of blood-brain barrier function. Albumin immunohistochemistry disclosed quantitative (p < 0.01) and qualitative differences between the mitochondrial neurogastrointestinal encephalomyopathy and control brains, indicating that loss of thymidine phosphorylase function impairs the integrity of the blood-brain barrier.

Pharmacoeconomics.

Today, spiraling costs of medical care coupled with limited resources have led to an explosive increase in the number of pharmacoeconomic analyses being carried out. The first step in a pharmacoeconomic analysis is to measure the costs and benefits of the therapeutic regimens being compared. Then one compares these costs and benefits by calculating a cost: benefit ratio for each regimen. Four types of economic analyses are commonly used for this purpose. While cost minimization analysis ignores the benefits and focuses only on costs of treatment, cost-effectiveness analysis measures costs in monetary terms and benefits or outcome in their natural clinical units. Cost benefit analysis on the other hand, places monetary values on both-costs and outcome of therapy. Finally, cost utility analysis measures costs in monetary terms, and outcome in a single utility-based unit of measurement. Utility based measures like quality adjusted life-years (QALY) measure the contribution made by the regimens to the patient's quality of life. Finally study designs generally used for generating data for a pharmacoeconomic analysis are mentioned, and concepts like marginal analysis, sensitivity analysis and discounting are explained in the context of health economics.

High frequency of immunophenotype changes in acute myeloid leukemia at relapse: implications for residual disease detection (Cancer and Leukemia Group B Study 8361).

Multiparameter flow cytometry (MFC) has the potential to allow for sensitive and specific monitoring of residual disease (RD) in acute myeloid leukemia (AML). The use of MFC for RD monitoring assumes that AML cells identified by their immunophenotype at diagnosis can be detected during remission and at relapse. AML cells from 136 patients were immunophenotyped by MFC at diagnosis and at first relapse using 9 panels of 3 monoclonal antibodies. Immunophenotype changes occurred in 124 patients (91%); they consisted of gains or losses of discrete leukemia cell populations resolved by MFC (42 patients) and gains or losses of antigens on leukemia cell populations present at both time points (108 patients). Antigen expression defining unusual phenotypes changed frequently: CD13, CD33, and CD34, absent at diagnosis in 3, 33, and 47 cases, respectively, were gained at relapse in 2 (67%), 15 (45%), and 17 (36%); CD56, CD19, and CD14, present at diagnosis in 5, 16, and 20 cases, were lost at relapse in 2 (40%), 6 (38%), and 8 (40%). Leukemia cell gates created in pretreatment samples using each 3-antibody panel allowed identification of relapse AML cells in only 68% to 91% of cases, but use of 8 3-antibody panels, which included antibodies to a total of 16 antigens, allowed identification of relapse AML cells in all cases. Thus, the immunophenotype of AML cells is markedly unstable; nevertheless, despite this instability, MFC has the potential to identify RD in AML if multiple antibody panels are used at all time points. (Blood. 2001;97:3574-3580)

Interleukin-2 as a therapeutic agent.

Interleukin-2 (IL-2) belongs to a class of soluble, regulatory proteins known as cytokines. It is a 133 amino acid glycoprotein secreted by T(H) lymphocytes and other cells following activation by antigens, mitogens and other cytokines. It stimulates the proliferation and cytotoxicity of T lymphocytes. It also enhances the microbicidal and cytotoxic activities of NK cells, B lymphocytes, macrophages and monocytes. IL-2 can now be produced in unlimited quantities by recombinant DNA technology and used therapeutically to modulate the immune system in a number of diseases. A number of different studies have demonstrated its therapeutic value in HIV +ve and AIDS patients. It has been approved by US-FDA for treatment of metastatic renal cell carcinoma (RCC) and metastatic melanoma. Routine detection of soluble IL-2 receptor in blood could be useful as a diagnostic marker in some autoimmune diseases. Agents that antagonize IL-2 find application as immunosuppressants. The main adverse effect of IL-2 is capillary leak syndrome caused by increased capillary permeability and extravasation of fluid. In days to come, IL-2 is likely to play an increasingly important role in management of viral infections, malignancies and a number of other diseases conditions.

Adrenergic and peptidergic control of the regulation of cAMP efflux and melatonin secretion from perifused rat pineal gland.

Mammalian pineal gland receives peptidergic (e.g., vasoactive intestinal peptide [VIP]; peptide histidine isoleucine [PHI]; neuropeptide Y, NPY; substance P, calcitonin gene-related peptide [CGRP], arginine vasopressin [AVP] and oxytocin [OXT]) fibers in addition to sympathetic innervation. The dynamics of cAMP efflux and melatonin (MT) secretion were compared during the infusion of these peptides in our long-term perifusion system. VIP and PHI enhanced both pineal cAMP efflux and MT secretion in a dose-dependent manner (10 nM to 10 microM). However, the potency of PHI was slightly less. The peak of cAMP release always precedes that of MT production. The possible interactions between adrenergic and peptidergic compounds in the regulation of pineal cAMP efflux and MT secretion were also studied. VIP acts on specific peptidergic receptors, since its stimulatory effect could only be reduced by a VIP receptor antagonist. VIP has an additive effect at a lower (100 nM) concentration combined with norepinephrine (NE). NPY (100 nM) can completely block NE-induced MT secretion, but the decrease in cAMP efflux is less. However, NPY does not significantly influence VIP-stimulated cAMP efflux or MT secretion. These data suggest that NE, VIP, and NPY are differently involved in the cAMP and calcium signaling. The other neuropeptides are ineffective.