Cortical plasticity as a basis of phantom limb pain: Fact or fiction?

Cortical reorganization has been proposed as a major factor involved in phantom pain with prior nociceptive input to the deafferented region and input from the non-deafferented cortex creating neuronal activity that is perceived as phantom pain. There is substantial evidence that these processes play a role in neuropathic pain, although causal evidence is lacking. Recently it has been suggested that a maintenance of the cortical representation of the former hand area is related to phantom pain. Although interesting, evidence for this process is so far scarce. In addition, peripheral factors have been proposed as important for phantom limb pain. Although often introduced as contradictory, we suggest that cortical reorganization, preserved limb function and peripheral factors interact to create the various painful and nonpainful aspects of the phantom limb experience. In addition, the type of task (sensory versus motor), the interaction of injury- and use-dependent plasticity, the type of data analysis, contextual factors such as the body representation and psychological variables determine the outcome and need to be considered in models of phantom limb pain. Longitudinal studies are needed to determine the formation of the phantom pain experience.

Neural correlates of evoked phantom limb sensations.

Previous work showed the existence of changes in the topographic organization within the somatosensory cortex (SI) in amputees with phantom limb pain, however, the link between nonpainful phantom sensations such as cramping or tingling or the percept of the limb and cortical changes is less clear. We used functional magnetic resonance imaging (fMRI) in a highly selective group of limb amputees who experienced inducible and reproducible nonpainful phantom sensations. A standardized procedure was used to locate body sites eliciting phantom sensations in each amputee. Selected body sites that could systematically evoke phantom sensations were stimulated using electrical pulses in order to induce phasic phantom sensations. Homologous body parts were also stimulated in a group of matched controls. Activations related to evoked phantom sensations were found bilaterally in SI and the intraparietal sulci (IPS), which significantly correlated with the intensity of evoked phantom sensations. In addition, we found differences in intra- and interhemispheric interaction between amputees and controls during evoked phantom sensations. We assume that phantom sensations might be associated with a functional decoupling between bilateral SI and IPS, possibly resulting from transcallosal reorganization mechanisms following amputation.

Active and placebo transcranial magnetic stimulation effects on external and internal auditory hallucinations of schizophrenia.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) over the left temporo-parietal region has been proposed as a treatment for resistant auditory verbal hallucinations (AVH), but which patients are more likely to benefit from rTMS is still unclear. This study sought to assess the effects of rTMS on AVH, with a focus on hallucination phenomenology. METHOD: Twenty-seven patients with schizophrenia and medication-resistant AVH participated to a randomized, double-blind, placebo-controlled, add-on rTMS study. The stimulation targeted a language-perception area individually determined using functional magnetic resonance imaging and a language recognition task. AVH were assessed using the hallucination subscale of the Scale for the Assessment of Positive Symptoms (SAPS). The spatial location of AVH was assessed using the Psychotic Symptom Rating Scales. RESULTS: A significant improvement in SAPS hallucination subscale score was observed in both actively treated and placebo-treated groups with no difference between both modalities. Patients with external AVH were significantly more improved than patients with internal AVH, with both modalities. CONCLUSIONS: A marked placebo effect of rTMS was observed in patients with resistant AVH. Patients with prominent external AVH may be more likely to benefit from both active and placebo interventions. Cortical effects related to non-magnetic stimulation of the auditory cortex are suggested.

How restful is it with all that noise? Comparison of Interleaved silent steady state (ISSS) and conventional imaging in resting-state fMRI.

Resting-state fMRI studies have become very important in cognitive neuroscience because they are able to identify BOLD fluctuations in brain circuits involved in motor, cognitive, or perceptual processes without the use of an explicit task. Such approaches have been fruitful when applied to various disordered populations, or to children or the elderly. However, insufficient attention has been paid to the consequences of the loud acoustic scanner noise associated with conventional fMRI acquisition, which could be an important confounding factor affecting auditory and/or cognitive networks in resting-state fMRI. Several approaches have been developed to mitigate the effects of acoustic noise on fMRI signals, including sparse sampling protocols and interleaved silent steady state (ISSS) acquisition methods, the latter being used only for task-based fMRI. Here, we developed an ISSS protocol for resting-state fMRI (rs-ISSS) consisting of rapid acquisition of a set of echo planar imaging volumes following each silent period, during which the steady state longitudinal magnetization was maintained with a train of relatively silent slice-selective excitation pulses. We evaluated the test-retest reliability of intensity and spatial extent of connectivity networks of fMRI BOLD signal across three different days for rs-ISSS and compared it with a standard resting-state fMRI (rs-STD). We also compared the strength and distribution of connectivity networks between rs-ISSS and rs-STD. We found that both rs-ISSS and rs-STD showed high reproducibility of fMRI signal across days. In addition, rs-ISSS showed a more robust pattern of functional connectivity within the somatosensory and motor networks, as well as an auditory network compared with rs-STD. An increased connectivity between the default mode network and the language network and with the anterior cingulate cortex (ACC) network was also found for rs-ISSS compared with rs-STD. Finally, region of interest analysis showed higher interhemispheric connectivity in Heschl's gyri in rs-ISSS compared with rs-STD, with lower variability across days. The present findings suggest that rs-ISSS may be advantageous for detecting network connectivity in a less noisy environment, and that resting-state studies carried out with standard scanning protocols should consider the potential effects of loud noise on the measured networks.

Transgene delivery to endothelial cultures derived from porcine carotid artery ex vivo.

Carotid artery disease is a widespread cause of morbidity and mortality. Porcine models of vascular disease are well established in vivo, but existing endothelial systems in vitro (e.g. human umbilical vein endothelial cells, rat aortic endothelial cultures) poorly reflect carotid endothelium. A reliable in vitro assay would improve design of in vivo experiments and allow reduction and refinement of animal use. This study aimed (1) to develop ex vivo endothelial cultures from porcine carotid and (2) to test whether these were suitable for lentivector-mediated transgene delivery. Surplus carotid arteries were harvested from young adult female Large White pigs within 10 min post-mortem. Small sectors of carotid artery wall (approximately 4 mm×4 mm squares) were immobilised in a stable gel matrix. Cultures were exposed to HIV-derived lentivector (LV) encoding a reporter transgene or the equivalent integration-deficient vector (IDLV). After 7-14 days in vitro, cultures were fixed and labelled histochemically. Thread-like multicellular outgrowths were observed that were positive for endothelial cell markers (CD31, VEGFR2, von Willebrand factor). A minority of cells co-labelled for smooth muscle markers. Sensitivity to cytotoxic agents (paclitaxel, cycloheximide, staurosporine) was comparable to that in cell cultures, indicating that the gel matrix permits diffusive access of small pharmacological molecules. Transgene-expressing cells were more abundant following exposure to LV than IDLV (4.7, 0.1% of cells, respectively). In conclusion, ex vivo adult porcine carotid artery produced endothelial cell outgrowths that were effectively transduced by LV. This system will facilitate translation of novel therapies to clinical trials, with reduction and refinement of in vivo experiments.

[Knowledge and practices of the mothers of children from 6 to 18 months relative to the conduct of weaning: cases from the general hospital of Marcory]. / Connaissances et pratiques des meres d'enfants de 6 a 18 mois relatives à la conduite du sevrage: cas de l' hôpital général de Marcory.

Weaning is a high-risk phase in the life of infants around the world, because poorly managed, it raises protein-energy malnutrition to levels causing crucial problems to the health of infants. AIMS: The purpose is to estimate the knowledge and the practices of the mothers regarding the conduct of food weaning of their children aged 6 to 18 months. MATERIALS AND METHODS: We conducted a descriptive cross-sectional survey at the general hospital of Marcory in Abidjan-CI on a sample of 100 mother-child pairs who came to consult. RESULTS: It emerges from this survey that.The mothers are young, with 94% younger than 35 years old. 88% of the mothers were of a low socioeconomic level. Dietary restrictions still remained a real obstacle to a better practice of weaning.The vast majority of the mothers (74%) ignore the notion of weaning and 40% of them had no information regarding this process. Food weaning was not conventional with an early weaning at 1 to 6 months in 38% of the cases and a late weaning (30%) after 13 months. CONCLUSION: It is necessary to set up a program focusing on the adequate conduct of weaning in infants to improve mothers' knowledge and the practices.

Le sevrage constitue une phase à haut risque dans la vie des nourrissons dans le monde , car mal conduit, le sevrage hisse la malnutrition protéino énergétique au rang des problèmes cruciaux de santé chez les nourrissons. OBJECTIF: Le but est d'évaluer les connaissances et les pratiques des mères concernant la conduite du sevrage alimentaire de leurs enfants âgés de 6 à 18 mois. MATERIEL: Nous avons réalisé une enquête transversale descriptive à l'hôpital général de Marcory à Abidjan-CI sur un échantillon de 100 couples mères enfants venus consulter. RESULTATS: Il ressort de cette enquête que.Les mères sont jeunes puisque 94% des mères avaient moins de 35 ans.88% des mères étaient d'un niveau socio économique bas. Les interdits alimentaires restaient encore un réel obstacle à une meilleure pratique du sevrage.La grande majorité des mamans (74%) méconnaissent la notion de sevrage et 40 % d'entre elles ne disposaient d'aucune information. Le sevrage alimentaire n'était pas conventionnel avec un sevrage précoce d'1 à 6 mois dans 38% des cas et un sevrage tardif (30%) au delà de 13 mois. CONCLUSION: Il faut mettre en place un programme axé sur la conduite adéquate du sevrage des nourrissons pour améliorer les connaissances et pratiques des mères.

Phase III trial of doxorubicin plus cyclophosphamide (AC), docetaxel, and alternating AC and docetaxel as front-line chemotherapy for metastatic breast cancer: Japan Clinical Oncology Group trial (JCOG9802).

BACKGROUND: This randomized, multicenter, phase III trial compared doxorubicin plus cyclophosphamide (AC), single-agent docetaxel (D), and an alternating regimen of AC and docetaxel (AC-D) as first-line chemotherapy in metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients with MBC resistant to endocrine therapy were entered in a randomized study to receive either six cycles of AC (doxorubicin 40 mg/m2 plus cyclophosphamide 500 mg/m2), D (60 mg/m2), or alternating treatment with AC-D (i.e. three cycles of AC and three cycles of D). Treatment was administered every 3 weeks. RESULTS: A total of 441 patients were entered in a randomized study. Response rates were 30% for AC, 41% for D, and 35% for AC-D. The median times to treatment failure (TTFs) were 6.4, 6.4, and 6.7 months (one-sided log-rank test, P = 0.13 for AC versus D, P = 0.14 for AC versus AC-D) and median overall survival (OS) was 22.6, 25.7, and 25.0 months (P = 0.09 for AC versus D, P = 0.13 for AC versus AC-D) in the AC, D, and AC-D, respectively. CONCLUSION: There was no difference in the TTF among the three arms. However, there was a trend toward a better response and better OS in the D than in the AC.

[The psychological experience of the mothers whose babies were born deformed in the neonatological ward of the academic hospital center of Treichville (Côte-d'Ivoire)]. / Vécu psychologique des mères de nouveau-nés malformés dans le centre hospitalier et universitaire de Treichville (Côte-d'Ivoire).

OBJECTIVE: When a baby is born deformed, his birth breaks up plans his family has made for his life as well as for the family itself. So, our objective was to describe the experience undergone by the mothers who gave birth to babies with serious deformities. METHOD: A prospective and descriptive study was carried out during 12 months about 35 mothers whose babies were born seriously deformed. The data were collected from newborn's medical file and from a well-conducted interview with volunteered mothers. RESULTS: The incidence of the major deformities was 1.4% and the antenatal diagnosis was carried out on only 6 cases. The announcement of deformities in the 30 cases discovered at birth by the clinical staff brought about a shock among mothers. In fact, 28 mothers were disappointed, while 23 experienced fear and 10 others felt guilty. Six mothers thought in terms of aborting, followed by 25 mothers who without any psychological aid felt lonely. Furthermore, 30 mothers suffered from a lack of communication with nurses and with medical staff concerning deformities. The anxiety of mothers was linked, respectively to fear of their husband (33 cases), to the social environment (35 cases) and to the health care (10 cases). CONCLUSION: Mothers facing congenital deformity experienced painful and violent emotional distress. Therefore, the emphasis must be put on the improvement of the neonatal diagnosis and of relationship between physicians and parents in order to achieve a close support toward mothers.

Vecu psychologique des parents accompagneurs d'enfant hospitalises en oncologie pediatrique

La survenue d'un cancer chez un enfant entraine de nombreux bouleversements de la structure familiale. Il nous a paru important d'etudier les contours psychologiques de cette situation en milieu hospitalier a Abidjan. L'etude a ete retrospective; descriptive; sur une periode de douze mois. Elle a concerne 30 accompagnateurs majeurs d'enfants hospitalises dans l'unite d'oncologie du service de pediatrie du CHU de Treichville. Les donnees ont ete recueillies a partir des entretiens isoles ou en groupe avec des accompagnateurs et du dossier medical de l'enfant. 33;4 pour cent des parents accompagnateurs ont attribue l'origine de la maladie a un mauvais sort ou a une malediction; pour 66;6 pour cent il s'etait agi d'une maladie comme une autre. Notre objectif a ete de decrire les aspects psychologiques engendres par ce vecu hospitalier afin d'aider a l'amelioration de l'atmosphere autour de l'enfant lors de sa prise en charge

[Treatment of childhood cancer in Africa. Action of the Franco-African childhood cancer group]. / Le traitement des cancers de l'enfant en Afrique. Travaux du groupe franco-africain d'oncologie pédiatrique.

The childhood cancer survival rate is currently 75% in industrialized countries. Rates in developing countries are much lower. The Franco-African Childhood Cancer Group (French acronym, GFAOP) was founded in 2000 with aim of reducing this unfavorable situation in Africa. The GFAOP has developed two forms of action. The main form consists of organizing two- to twelve-month training sessions for physicians and nurses in France and Morocco. The other form involves assessing the feasibility of modern treatment protocols for various cancers in Africa. The first feasibility trials were carried out on nephroblastoma and Burkitt's lymphoma in 12 pilot units in North Africa, West Africa, and Madagascar. In the first study from 2001 to 2005 we treated 306 cases of Burkitt's lymphoma using French LMB protocols adapted to the African setting and achieved a survival rate of 61%. A second study started in 2005 using Endoxan alone achieved a highly satisfactory survival rate of 73% for neuroblastoma in all stages except bilateral. Altogether from 2001 to 2007 more than 1000 cases of nephroblastoma and Burkitt's lymphoma were treated in African hospitals by African doctors and nurses. No patients were transferred to Europe. The GFAOP supplied drugs when necessary and took care of most travel expenses. African and French doctors worked together on protocol design, trial management, and data analysis. These promising results show that the latest therapeutic techniques can be used to treat childhood cancer in Africa by adapting the protocol to conditions in developing countries. Sanofi-Aventis Laboratories in association with the International Union against Cancer has launched a major campaign to improve Pediatric Oncology in developing countries. Projects in four GFAOP units are being financed through this campaign. In 2006 the GFAOP began assessment of two new treatment protocols, i.e., one for acute lymphoblastic leukemia and the other for Hodgkin's disease. Two other projects are being planned, i.e., one for treatment of retinoblastoma and the other for treatment of some types of brain tumors.

Modulation of language areas with functional MR image-guided magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) can interfere with linguistic performance when delivered over language areas. At low frequency (1 Hz), rTMS is assumed to decrease cortical excitability; however, the degree of TMS effect on cortical language areas may depend on the localization of the stimulation coil with respect to the inter-individual anatomo-functional variations. Hence, we aimed at investigating individual brain areas involved in semantic and phonological auditory processes. We hypothesized that active rTMS targeted over Wernicke's area might modify the performance during a language-fragment-detection task. Sentences in native or foreign languages were presented to 12 right-handed male healthy volunteers during functional magnetic resonance imaging (fMRI). 3D-functional maps localized the posterior temporal activation (Wernicke) in each subject and MRI anatomical cortical landmarks were used to define Broca's pars opercularis (F3Op). A frameless stereotaxy system was used to guide the TMS coil position over Wernicke's and F3Op areas in each subject. Active and placebo randomized rTMS sessions were applied at 1 Hz, 110% of motor threshold, during the same language-fragment-detection task. Accuracy and response time (RT) were recorded. RT was significantly decreased by active rTMS compared to placebo over Wernicke's area, and was more decreased for native than for foreign languages. No significant RT change was observed for F3Op area. rTMS conditions did not impair participants' accuracy. Thus, low-frequency rTMS over Wernicke's area can speed-up the response to a task tapping on native language perception in healthy volunteers. This individually-guided stimulation study confirms that facilitatory effects are not confined to high-frequency rTMS.

[Bacterial pneumopathies of the newborn: diagnostic and therapeutic aspects]. / Pneumopathies bactériennes du nouveau-né: aspects diagnostiques et thérapeutiques.

OBJECTIVES: To describe the diagnosis and therapeutic management of bacterial pneumopathies in a neonatology unit located in a tropical area. METHODS: Transverse and prospective survey over an 18-month period. The diagnosis was based on the comparison of anamnestic features with clinical, biological and radiological features. A research was made in order to determine the causal agent in the blood, in cerebrospinal fluid, in urines, in pleural liquid and skin lesions. A treatment by two antibiotics was administered through parenteral route. RESULTS: Risk factors were found in 61 selected patients. Polypnea was associated with signs of respiratory distress in 53 patients. Blood abnormalities were present in 47, 5% of the cases. All the patients showed a positive C reactive protein and abnormal X-rays. The diagnosis was confirmed bacteriologically in 32, 8% of the cases. The association of a third-generation cephalosporin with an aminoside was prescribed in 44 cases. The initial antibiotic therapy was not relevant in 19, 7% of the cases. The lethality rate was 24, 6%. The scarcity of bacteriological confirmation led us to consider the combination of radiological abnormalities with respiratory distress as significant symptoms of bacterial pneumopathy. Biological and anamnestic features were considered as extra elements. CONCLUSION: The severity of clinical features, the nature of germs and their sensitivity to antibiotics in our local environment led us to recommend a large prescription of third-generation cephalosporins combined to aminoglycosides.