Bone involvement in generalized crystal-storing histiocytosis

The abnormal secretion of monoclonal immunoglobulins observed with monoclonal gammopathies and other clonal B cell dyscrasias can be responsible for a spectrum of deposition disorders. Crystal-storing histiocytosis (CSH) is a rare disease affecting patients with B cell dyscrasias and monoclonal gammopathies, characterized by the accumulation of histiocytes that have phagocytosed an abnormal crystalline immunoglobulin. We describe 2 cases of this rare disorder with multiorgan involvement and prominent bone involvement. Magnetic resonance imaging showed bone marrow infiltration and images of avascular necrosis. Bone specimen analysis gave histological proof of diffuse bone infiltration by the abnormal histiocytes. Bone involvement, which appears to be a specific feature of CSH, links this entity to other storage disorders, such as Gaucher disease. Because the accumulation of abnormal immunoglobulin-loaded histiocytes is clearly pivotal, CSH should be considered not only as an immunoglobulin deposition disease but also as a storage histiocytic disorder.     

Chemotherapy and radiotherapy: Cryptic anticancer vaccines

An attractive, yet hitherto unproven concept predicts that the promotion of tumor regression should elicit the host's immune response against residual tumor cells to achieve an optimal therapeutic effect. In a way, chemo- or radiotherapy must trigger “danger signals” emitted from immunogenic cell death and hence elicit “danger associated molecular patterns” to stimulate powerful anticancer immune responses. Here, based on the recent experimental and clinical evidence, we will discuss the molecular identity of the multiple checkpoints that dictate the success of “immunogenic chemotherapy” at the levels of the drug, of the tumor cell and of the host immune system.     

Negative emotion-driven impulsivity predicts substance dependence problems

Impulsivity is predominant among users of several drugs of abuse including alcohol, cocaine, and amphetamines, and it is considered a risk factor for later development of alcohol and substance abuse and dependence. However, there is little consensus on how impulsivity should be defined and measured, and there are few studies on the relationship between separate dimensions of impulsivity and substance dependence. We used a multidimensional measure of impulsivity (the UPPS scale) to examine differences between 36 individuals with substance dependence (ISD) and 36 drug-free controls on the dimensions of urgency, lack of premeditation, lack of perseverance, and sensation seeking. In addition, we examined which dimensions of impulsivity better predicted addiction-related problems as measured with the addiction severity index. Results revealed that ISD show high scores on dimensions of urgency, lack of perseverance, and lack of premeditation (effect sizes ranging from 1.10 to 1.96), but not on sensation seeking. Among the different impulsivity dimensions, urgency was the best predictor of severity of medical, employment, alcohol, drug, family/social, legal and psychiatric problems in ISD, explaining 13-48% of the total variance of these indices. Furthermore, urgency scores alone correctly classified 83% of the participants in the ISD group. Urgency is characterized by a tendency to act impulsively in response to negative emotional states. Thus, our results could have important implications for novel treatment approaches for substance dependence focused on emotional regulation.     

pfmdr1 Amplification Associated with Clinical Resistance to Mefloquine in West Africa: Implications for Efficacy of Artemisinin Combination Therapies

We describe here a clinical failure in the treatment with mefloquine of acute falciparum malaria contracted in Africa and associated with in vitro mefloquine resistance and pfmdr1 copy number amplification. This case raises the question of the presence and the evolution of this genotype in Africa, which is also known to alter the susceptibility to artemisinin combination therapy (ACT).