Les mélanomes du tronc ont-ils un pronostic individualisable? À propos d'une série de 77 cas

AimsTruncal melanoma is characterized by lymphatic drainage to single or multiple basins, affecting different anatomic regions. Since the introduction of sentinel lymph node biopsy (SLN) several questions have aroused in regard to this particular drainage. However, published data available on SLN anatomic distribution and on the prognostic value of multiple-nodal drainage is controversial. The aim of the present study was to provide further evidence based on our own experience.MethodsFrom January 2003 through December 2006, a total of 77 melanoma of the trunk were diagnosed and treated at our institution. Systematic lymphoscintigraphy was obtained for all patients, followed by removal of SLN and in-transit lesions. When SLN metastasis was detected a complete lymphadenectomy was performed and adjuvant immunotherapy with interferon was administered. Statistical analysis was performed using Chi² and Fisher's exact tests for categoric variables and Kaplan-Meier curves for survival.ResultsLymphoscintigraphy visualized 70.1% of single and 28.6% of multiple-nodal drainage (uninterpretable data). The rate of SLN macrometastasis ranged from 7.8 to 14.3%. Micrometastasis were found in 6.5% of patients. Positive SLN were discovered in 12.9% (17/54) of single-nodal and 18.6% (2/22) of multiple-nodal drainage. Melanoma's topography significantly influenced lymphatic drainage distribution, with 28.6% of single-nodal and 71.4% of multiple-nodal drainage for central tumors, and with 79.4% of single-nodal and 19.1% of multiple-nodal drainage for lateral tumors. The group with multiple-nodal drainage was associated non-significantly with primary tumor ulceration, 39 vs 24%. The Breslow thickness did not associate to multiple-nodal drainage. There were no differences in the rate of lymph node metastasis between both groups, 18 vs 12.9%. After a median follow-up of 47 months, prognosis was similar regardless of SLN status, with 80.3% overall survival for negative SLN and 81.3% for positive SLN. Single or multiple drainage did not affect survival rates significantly, with 84% survival for single-nodal drainage and 95% for multiple-nodal drainage.ConclusionsPrimary tumor location (medial location) was the principal risk factor for multi-nodal drainage: lymphoscintigraphy was the best technique for lymphatic drainage assessment. Primary tumor location with single or multi-nodal drainage did not influence the rate of positive SLN and had similar disease-free and overall survival. For us, truncal melanoma has not a different prognosis than melanoma of extremities.     

A computational neuroscience approach to schizophrenia and its onset

Computational neuroscience integrate-and-fire attractor network models can be used to understand the factors that alter the stability of cortical networks in the face of noise caused for example by neuronal spiking times. A reduction of the firing rates of cortical neurons caused for example by reduced NMDA receptor function (present in schizophrenia) can lead to instability of the high firing rate attractor states that normally implement short-term memory and attention, contributing to the cognitive and negative symptoms of schizophrenia. Reduced cortical inhibition caused by a reduction of GABA neurotransmission (present in schizophrenia) can lead to instability of the spontaneous firing states of cortical networks, leading to a noise-induced jump to a high firing rate attractor state even in the absence of external inputs, contributing to the positive symptoms of schizophrenia. We consider how effects occurring at the time of late adolescence including synaptic pruning, decreases in grey matter volume, and changes in GABA-mediated inhibition and dopamine may contribute to the onset in some individuals of schizophrenia at this time.     

Nonlinear analyses of heart rate variability in normal and growth-restricted fetuses

BACKGROUND: Many studies on the physiology of the cardiovascular system reported that nonlinear chaotic dynamics may govern the generation of the heart rate signal. OBJECTIVE: To examine whether the heart rate dynamics of an intrauterine growth restricted (IUGR) fetus is different from a healthy normal fetus by nonlinear methods of time series analysis. DESIGN OF THE STUDY: One hundred nineteen fetal heart rate (FHR) recordings from healthy normal fetuses, and 69 recordings from IUGR fetuses were analyzed. Nonlinear analyses included attractor reconstruction, calculation of the largest Lyapunov exponents using the Wolf algorithm, and estimation of correlation dimension. The largest Lyapunov exponents from normal fetuses were checked by means of surrogate-data test. RESULTS: Abnormal FHR patterns of IUGR fetuses such as decreased variability and repetitive late decelerations presented a remarkably different structure in the reconstructed attractor. Surrogate data suggest that the FHR of healthy normal fetuses has unique nonlinear characteristics. The largest Lyapunov exponents were positive for all of 119 healthy normal fetuses, indicating that the FHR control system is sensitive to initial conditions. The values of IUGR fetuses were significantly lower than those of normal subjects. In normal fetuses, significant changes of correlation dimension according to gestational age were observed. In IUGR fetuses, however, such changes were not found. CONCLUSIONS: The heart rate dynamics of IUGR fetuses is less chaotic than that of normal fetuses. Decreased system complexity suggested by correlation dimension may limit the IUGR fetuses' ability to maintain cardiovascular integrity, and therefore, to adapt to the variety of internal and external cardiovascular stresses.     

On the intrinsic inevitability of cancer: from foetal to fatal attraction

The cracks in the paradigm of oncogenic mutations and somatic evolution as driving force of tumorigenesis, lucidly exposed by the dynamic heterogeneity of “cancer stem cells” or the diffuse results of cancer genome sequencing projects, indicate the need for a more encompassing theory of cancer that reaches beyond the current proximate explanations based on individual genetic pathways. One such integrative concept, derived from first principles of the dynamics of gene regulatory networks, is that cancerous cell states are attractor states, just like normal cell types are. Here we extend the concept of cancer attractors to illuminate a more profound property of cancer initiation: its inherent inevitability in the light of metazoan evolution. Using Waddington's Epigenetic Landscape as a conceptual aid, for which we present a mathematical and evolutionary foundation, we propose that cancer is intrinsically linked to ontogenesis and phylogenesis. This explanatory rather than enumerating review uses a formal argumentation structure that is atypical in modern experimental biology but may hopefully offer a new coherent perspective to reconcile many conflicts between new findings and the old thinking in the categories of linear oncogenic pathways.     

Reduction in dengue cases observed during mass control of Aedes (Stegomyia) in street catch basins in an endemic urban area in Colombia

Dengue incidence continues to increase globally and, in the absence of an efficacious vaccine, prevention strategies are limited to vector control. It has been suggested that targeting the most productive breeding sites instead of all water-holding containers could be a cost-effective vector control strategy. We sought to identify and continuously control the most productive Aedes (Stegomyia) breeding site in an endemic urban area in Colombia and followed the subsequent incidence of dengue. In the urban area of Guadalajara de Buga, southwestern Colombia, potential breeding sites inside and outside houses were first characterized, and local personnel trained to assess their productivity based on the pupae/person index. Simultaneously, training and monitoring were implemented to improve the dengue case surveillance system. Entomological data and insecticide resistance studies were used to define the targeted intervention. Then, a quasi-experimental design was used to assess the efficacy of the intervention in terms of the positivity index of the targeted and non- targeted breeding sites, and the impact on dengue cases. Street catch basins (storm drains) were the potential breeding site most frequently found containing Aedes immature stages in the baseline (58.3% of 108). Due to the high resistance to temephos (0% mortality after 24 h), the intervention consisted of monthly application of pyriproxyfen in all the street catch basins (n = 4800). A significant decrease in catch basins positivity for Aedes larvae was observed after each monthly treatment (p < 0.001). Over the intervention period, a reduction in the dengue incidence in Buga was observed (rate ratio 0.19, 95% CI 0.12–0.30, p < 0.0001) after adjusting for autocorrelation and controlling with a neighboring town, Palmira, This study highlights the importance of street catch basins as Aedes breeding sites and suggests that their targeted control could help to decrease dengue transmission in such areas.     

Automatic segmentation of amyloid plaques in MR images using unsupervised support vector machines

Deposition of the β-amyloid peptide (Aβ) is an important pathological hallmark of Alzheimer's disease (AD). However, reliable quantification of amyloid plaques in both human and animal brains remains a challenge. We present here a novel automatic plaque segmentation algorithm based on the intrinsic MR signal characteristics of plaques. This algorithm identifies plaque candidates in MR data by using watershed transform, which extracts regions with low intensities completely surrounded by higher intensity neighbors. These candidates are classified as plaque or nonplaque by an unsupervised learning method using features derived from the MR data intensity. The algorithm performance is validated by comparison with histology. We also demonstrate the algorithm's ability to detect age-related changes in plaque load ex vivo in amyloid precursor protein (APP) transgenic mice that coexpress five familial AD mutations (5xFAD mice). To our knowledge, this study represents the first quantitative method for characterizing amyloid plaques in MRI data. The proposed method can be used to describe the spatiotemporal progression of amyloid deposition, which is necessary for understanding the evolution of plaque pathology in mouse models of Alzheimer's disease and to evaluate the efficacy of emergent amyloid-targeting therapies in preclinical trials.