Fast multipole acceleration of the MEG/EEG boundary element method

The accurate solution of the forward electrostatic problem is an essential first step before solving the inverse problem of magneto- and electroencephalography (MEG/EEG). The symmetric Galerkin boundary element method is accurate but cannot be used for very large problems because of its computational complexity and memory requirements. We describe a fast multipole-based acceleration for the symmetric boundary element method (BEM). It creates a hierarchical structure of the elements and approximates far interactions using spherical harmonics expansions. The accelerated method is shown to be as accurate as the direct method, yet for large problems it is both faster and more economical in terms of memory consumption.     

EGFR mutation and resistance of non-small-cell lung cancer to gefitinib

Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in specimens from patients with non-small-cell lung cancer who have a response to anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to such inhibitors, most patients ultimately have a relapse. The mechanism of the drug resistance is unknown. Here we report the case of a patient with EGFR-mutant, gefitinib-responsive, advanced non-small-cell lung cancer who had a relapse after two years of complete remission during treatment with gefitinib. The DNA sequence of the EGFR gene in his tumor biopsy specimen at relapse revealed the presence of a second point mutation, resulting in threonine-to-methionine amino acid change at position 790 of EGFR. Structural modeling and biochemical studies showed that this second mutation led to gefitinib resistance.     

Individual differences in male rat ejaculatory behaviour: searching for models to study ejaculation disorders

In addition to investigating sexual function in rats that display normal ejaculatory behaviour, studying rats that are either 'hyposexual' or 'hypersexual' may provide important insights into the aetiology of ejaculatory dysfunctions in men, such as premature and retarded ejaculation. To this end, rats were matched into groups of 'sluggish', 'normal' and 'rapid' ejaculators based on their ejaculation frequencies displayed in a series of weekly sexual behaviour tests. Selecting rats on this parameter revealed large and stable differences in other parameters of sexual behaviour as well, including ejaculation latency and mount frequency but not intromission frequency and mount latency, putative indices of sexual motivation. Neuroanatomically, Fos immunoreactivity as a measure of neuronal activation was increased in rapid ejaculators compared with sluggish ejaculators in ejaculation-related brain areas, presumably associated with the differences in ejaculatory behaviour. Although the total number of oxytocin neurones within subregions of the hypothalamus did not differ between groups, in the supraoptic nucleus of the hypothalamus more oxytocin neurones were activated in rapid ejaculators compared with the other groups. Apart from the differences observed in ejaculatory behaviour, groups did not differ with respect to their locomotor activity and approach-avoidance behaviour as measured in the elevated plus-maze. Finally, apomorphine-induced stereotypy was similar in sluggish and rapid ejaculators, suggesting no large differences in dopamine susceptibility. Altogether, the present results suggest stable differences in male rat ejaculatory behaviour. Further exploring the neurobiological mechanisms underlying these differences may be a promising approach to gain insights into the aetiology of sexual dysfunctions such as premature, retarded or an-ejaculation.     

Olanzapine versus risperidone in the treatment of post-psychotic depression in schizophrenic patients

OBJECTIVE: To compare the efficacy of two atypical antipsychotic drugs, olanzapine and risperidone, in schizophrenic patients with post-psychotic depression. RESULTS: A clinically significant decrease of MADRS scores occurred in patients treated with both drugs for 8 weeks. CONCLUSION: Atypical antipsychotic drugs may be particularly appropriate when treating schizophrenic patients with depression.     

Topiramate prevents excitotoxic damage in the newborn rodent brain

Brain lesions induced in newborn mice by the glutamatergic agonists ibotenate (acting on NMDA and metabotropic receptors) and S-bromowillardiine (acting on AMPA-kainate receptors) mimic some aspects of white matter cysts and transcortical necrosis observed in human perinatal brain damage. Topiramate (TPM), already used in children to manage newly diagnosed and refractory epilepsy, has potential neuroprotective effects that may be useful in human perinatal brain lesions. In the excitotoxic newborn mouse model, TPM provided dose-dependent and long-lasting protection of developing white matter and cortical plate against S-bromowillardiine. TPM had no significant effect on ibotenate-induced brain lesions. TPM-induced neuroprotection potentially involved increased survival of pre-oligodendrocytes, decreased neuronal apoptosis, inhibition of microglial activation and astrogliosis, and decreased seizure activity. Diazepam, phenytoin, and carbamazepine had no neuroprotective effect in this model. The present study provides experimental support for the consideration of TPM as a candidate therapy for excitotoxic perinatal brain lesions.     

Contribution of sleep research to the development of new antidepressants

Several sleep anomalies are known to accompany depression and other psychiatric disorders, and to be partially modified by drugs efficient on clinical symptoms. Many puzzling theoretical questions remain, even after 30 years of research, because these drugs do not act in a uniform way: some reduce slow-wave sleep while others increase it some prolong rapid-eye movement sleep latency, while others do not. The relationship between insomnia and depression is likely to be a close one, since a large majority of patients with depression suffer insomnia, and that insomnia can predate depression by a few years. However, questions remain here, too, since sleep deprivation is also an effective means to combat depression, and some patients present with hypersomnia rather than insomnia. This review details the action of all current classes of antidepressants on sleep. It examines the predictive value of baseline electronencephalographic sleep symptoms or early modifications due to treatment for eventual clinical efficiency. We will also discuss the two main theories on the relationship between sleep and depression. The action on sleep of all new drugs-and antidepressants in particular-is carefully examined during development, for insomnia is currently considered to be a major health con-insomnia is currently considered to be a major health concern in industrialized countries.     

Neuroinflammatory processes in Parkinson's disease

In Parkinson's disease (PD), post-mortem examination reveals a loss of dopaminergic (DA) neurons in the substantia nigra (SN) associated with a massive astrogliosis and the presence of activated microglial cells. Similarly, microglial activation has also been reported to be associated with the loss of DA neurons in animal models of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, annonacine and lipopolysaccharide (LPS). Recent evidence suggests that the disease may progress even when the initial cause of neuronal degeneration has disappeared, raising the possibility that toxic substances released by glial cells could be involved in the propagation of neuronal degeneration. Inhibition of the glial reaction and the inflammatory processes may thus represent a therapeutic target to reduce neuronal degeneration in PD.     

Interference by Cellular Telephone with an Implantable Loop Recorder

We report the observation of interference between an implanted loop recorder and a cellular telephone when the latter was placed over the subcutaneous pocket. The artifact produced during the ringing of the telephone was automatically recorded and stored in the device memory. A similar interference was documented during ex vivo testing.     

Effect of perinatal alcohol exposure on ibotenic acid-induced excitotoxic cortical lesions in newborn hamsters

Alcohol is one of the most common noxious substance to which fetuses are exposed. The aim of the study was to determine the effects of in utero alcohol exposure on excitotoxin-induced neuronal migration disorders. Female hamsters received alcohol (7%) for 3-5 mo or for the last 9-12 d of gestation. Alcohol diet was continued for 5 d during lactation in both groups. Drinking behavior was monitored. Peak plasma alcohol levels were 104+/-12 mg/dL and 225+/-6 mg/dL after 30 min for hamsters receiving an intragastric dose of 3 mL or 5 mL alcohol, respectively. At birth, pups received intrapallial injections ibotenic acid (1 ng, 100 ng, or 10 microg). Histology and N-methyl-D-aspartic acid (NMDA) receptor labeling by 3H-MK-801 in the pups cortices were studied. Short-term-alcohol-exposed pups had normal body and brain weights at birth, but their body growth was retarded postnatally. Ibotenic acid induced similar neuronal migration impairments in control and alcohol-exposed pups (nodular heterotopia in the white matter and/or deep cortical layers, subpial ectopia, and micro- or polymicrogyria). The size of lesions induced by 100 ng ibotenic acid was increased in alcohol-exposed pups; the 10 microg dose was lethal. The density of 3H-MK-801 binding sites was similar in the three groups, indicating that exacerbated ibotenic acid excitotoxicity in alcohol-exposed pups did not result from increased NMDA receptor density. This study shows that alcohol exposure at levels that do not induce neuron migration disorders is sufficient to enhance the effects of the hypoxia-ischemia mimicking effects of ibotenic acid.