Electrical stimulation of the globus pallidus internus in patients with primary generalized dystonia: long-term results

OBJECT: Primary generalized dystonia (PGD) is a medically refractory disease of the brain causing twisting or spasmodic movements and abnormal postures. In more than 30% of cases it is associated with the autosomal DYT1 mutation. Continuous electrical stimulation of the globus pallidus internus (GPi) has been used successfully in the treatment of PGD. The aim of this study was to examine the long-term efficacy and safety of deep brain stimulation (DBS) in the treatment of PGD in children and adults with and without the DYT1 mutation. METHODS: Thirty-one patients with PGD were selected for surgery. Electrodes were bilaterally implanted under stereotactic guidance and connected to neurostimulators that were inserted subcutaneously. Efficacy was evaluated by comparing scores on the clinical and functional Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) before and after implantation. The efficacy of stimulation improved with time. After 2 years, compared with preoperative values, the mean (+/- standard deviation) clinical and functional BFMDRS scores had improved by 79 +/- 19% and 65 +/- 33%, respectively. At the 2-year follow-up examination the improvement was comparable in patients with and without the DYT1 mutation in both the functional (p = 0.12) and clinical (p = 0.33) scores. Children displayed greater improvements in the clinical score than adult patients (p = 0.04) at 2 years of follow up. In contrast, there was no significant difference in functional scores between children and adults (p = 0.95). CONCLUSIONS: Electrical stimulation of the GPi is an effective, reversible, and adaptable treatment for PGD and should be considered for conditions refractory to pharmaceutical therapies.     

The nature of unilateral motor commands in between-hand choice tasks as revealed by surface Laplacian estimation

From electroencephalographic recordings, we estimated the surface Laplacian over motor areas in a Stroop-like between-hand choice reaction time task in humans. Response-locked averages showed a (negative) "motor potential" over the primary motor areas contralateral to the response. At the same time, a positive wave was observed over the primary motor areas ipsilateral to the response. These data suggest that, when a between-hand choice is required, an inhibition of the primary motor cortex ipsilateral to the nonresponding hand is implemented. This observation is relevant to the interpretation of the lateralized readiness potential (LRP) because the LRP is blind to the respective contribution of the contralateral and ipsilateral motor cortices. In addition, a negative wave beginning about 200 ms before EMG onset and peaking about 50 ms before it occurred over the supplementary motor areas (FCz). This wave preceded the motor potential, which supports the view that the supplementary motor areas are upstream in a hierarchy of the motor command.     

Etiologic diagnosis of 204 pericardial effusions

The etiologic evaluation of pericardial effusion is frequently unsuccessful when noninvasive methods are used. To determine the cause of the current episode, all patients with echographically identified pericardial effusion from May 1998 to December 2002 underwent noninvasive diagnostic testing of blood, throat, and stool samples. Patients with postpericardiotomy syndrome were excluded. To analyze the value of our tests, we tested randomly selected blood donors as negative controls. Among 204 included patients, 107 (52.4%) had a final etiologic diagnosis: the etiology of 52 was highly suspected at first examination and later confirmed (thyroid deficiency, 5 cases; systemic lupus erythematous, 7; rheumatoid arthritis, 7; scleroderma, 3; cancer, 25; and renal insufficiency, 5). A definite etiologic diagnosis was made in 11 patients from pericardial fluid analysis (cancer, 5 cases; tuberculosis, 3; Streptococcus pneumoniae, Citrobacter freundii, and Actinomyces, 1 case each). Among 141 patients considered to have idiopathic pericarditis, 44 (32.1%) gained an etiologic diagnosis by our systematic testing strategy. This included serologic evaluation of serum (Coxiella burnetii, 10 cases; Bartonella quintana, 1; Legionella pneumophila, 1; Mycoplasma pneumoniae, 4; influenza virus, 1), viral culture of throat swabs (enterovirus, 8 cases; and adenovirus, 1), high-level antinuclear antibodies (>1/400, 3 cases), and thyroid-stimulating hormone (15 abnormal results). Antibodies to Toxoplasma and cytomegalovirus, enterovirus recovered from rectal swabs, and low-level antinuclear antibodies were seen with equal frequency in patients and controls.Using our evaluation strategy, the number of pericardial effusions classified as idiopathic was less than in other series. Systematic testing for Q fever, Mycoplasma pneumoniae, thyroid abnormalities, and antinuclear antibodies, accompanied by viral throat cultures, frequently enabled us to diagnose diseases not initially suspected in patients with pericardial effusion.     

Gamma irradiation induces acetylcholine-evoked, endothelium-independent relaxation and activates K-channels of isolated pulmonary artery of rats

PURPOSE: To test the effects of irradiation (R*) on the pulmonary artery (PA). METHODS AND MATERIALS: Isolated PA rings were submitted to gamma irradiation (cesium, 8 Gy/min(-1)) at doses of 20 Gy-140 Gy. Rings were placed in an organ chamber, contracted with serotonin (10(-4) M 5-hydroxytryptamine [5-HT]), then exposed to acetylcholine (ACh) in incremental concentrations. Smooth muscle cell (SMC) membrane potential was measured with microelectrodes. RESULTS: A high dose of irradiation (60 Gy) increased 5HT contraction by 20%, whereas lower (20 Gy) doses slightly decreased it compared with control. In the absence of the endothelium, 5-HT precontracted rings exposed to 20 Gy irradiation developed a dose-dependent relaxation induced by acetylcholine (EI-ACh) with maximal relaxation of 60 +/- 17% (n = 13). This was totally blocked by L-NAME (10(-4) M), partly by 7-nitro indazole; it was abolished by hypoxia and iberiotoxin, decreased by tetra-ethyl-ammonium, and not affected by free radical scavengers. In irradiated rings, hypoxia induced a slight contraction which was never observed in control rings. No differences in SMC membrane potential were observed between irradiated and nonirradiated PA rings. CONCLUSION: Irradiation mediates endothelium independent relaxation by a mechanism involving the nitric oxide pathway and K-channels.     

Mechanisms of membrane potential sensing with second-harmonic generation microscopy

We characterize the transmembrane voltage response of a novel second-harmonic generation (SHG) marker using a screening protocol with giant unilamellar vesicles. Two mechanisms are found to contribute to the voltage response: (1) an electro-optic-induced alteration of the molecular hyperpolarizability and (2) an electric-field-induced alteration of the degree of molecular alignment. We quantify the relative weights and of these contributions and provide an upper limit to their response time, which is found to be submillisecond. The identification of two voltage response mechanisms leads to new strategies for the molecular design of membrane potential markers.     

Blood-tissue barriers in the male reproductive tract of the dog: a morphological study using lanthanum nitrate as an electron-opaque tracer

Blood-tissue barriers preventing an uncontrolled exchange of larger molecules between adjacent but metabolically separate compartments have been demonstrated in various organs. One prominent example is the blood-testis barrier which has been investigated in a number of species. A key function of this barrier is to shield developing germ cells from the immune system in order to avoid autoimmune reactions. This requirement also applies to the male excurrent duct system. Yet, very few investigations have addressed the morphology of the blood-epididymal barrier. The goal of the present study, therefore, was to revisit the blood-testis barrier in the dog and to identify the structures constituting the blood-epididymal barrier in this species. Lanthanum nitrate was used as a tracer for electron microscopy. In the testis, lanthanum had free access to the intercellular space of the seminiferous epithelium up to the Sertoli cell junctions. Similarly, epithelial tight junctions were found to represent the permeability barrier in the epididymis. The present study highlights species differences with respect to the blood-testis barrier and extends the knowledge of the blood-epididymal barrier by providing morphofunctional data in this domestic species.     

Rapid detection of the deltaF508 mutation in single cells using DHPLC: implications for preimplantation genetic diagnosis

Purpose: Practice of preimplantation genetic diagnosis (PGD) requires efficient amplification and analysis techniques. We have tested Denaturing High Performance Liquid Chromatography (DHPLC) to screen the F508 mutation in heterozygous single cells in order to assess its usefulness for PGD of cystic fibrosis. Methods: One hundred and two single lymphocytes—including N/N and N/F508—were studied. F508 locus was amplified by nested PCR followed by the analysis of PCR products by DHPLC in non-denaturing conditions. Results: On the basis of PCR-amplified product analysis, total efficiency of amplification was 98.78% (101/102), and allele dropout (ADO) rate was 3.7% (3/81). For each sample, results were obtained in less than 4 min with high resolution. Conclusions: DHPLC is a rapid and efficient technique to detect the F508 mutation in single cells and is therefore appropriate for clinical application of preimplantation genetic diagnosis of cystic fibrosis.     

Caffeic acid phenethyl ester (CAPE) prevents inflammatory stress in organotypic hippocampal slice cultures

Caffeic acid phenethyl ester (CAPE) is an antioxidant component of propolis, a natural product secreted by honeybee. Recent literature shows that CAPE inhibits nuclear factor kappa B (NFkappaB) activation in cell lines. Since NFkappaB was shown to be a crucial factor in neuroinflammation and to be associated with some neuropathologies, CAPE might reduce these disorders in brain too and have therapeutic applications. To test this hypothesis we used a model of endotoxic insult (interferon-gamma, followed by lipopolysaccharide) on rat organotypic hippocampal cultures. Cerebral inflammatory responses were strongly inhibited by CAPE (100 microM): reductions of NFkappaB nuclear activity, tumor necrosis factor alpha and nitric oxide productions were observed. At the dose of maximal effects (100 microM), an increase of cAMP-responsive element binding protein (CREB) activity, which anti-inflammatory role is well known, was seen. We compared CAPE effects with those of other drugs: anti-inflammatory as acetyl-salicylate and dexamethasone (glucocorticoid), antioxidant as pyrrolidine dithiocarbamate, or selective permeant inhibitor of NFkappaB as SN 50 peptide. These studies lead us to conclude that CAPE presents an interesting and original neuropharmacological profile compared to these drugs and might be helpful in the prevention of neurotoxic events due to excessive inflammatory reaction in brain. CAPE interferes with several effectors of neuroinflammation that might have complementary and synergic effects and allows a rather durable control since an acute treatment at the time of endotoxin exposure allows to control inflammatory factors for over 48 h.     

Transient restless legs-like syndrome as a complication of opiate withrawal

In most cases, restless legs syndrome (RLS) is an idiopathic disorder affecting patients of middle and older age. Usually, the intensity of symptoms is constant or progressive. Here, we describe two opiate addicts developing RLS during opiate withdrawal. Their RLS disappeared along with the remission of withdrawal symptoms. Both cases responded well to a treatment with Madopar (L-dopa plus benserazid). This observation encouraged us to perform a retrospective analysis of all cases of opiate addicts detoxified in our unit during a 5-month period. This analysis revealed 15 out of 120 patients who had described the symptoms of transient RLS emerging during opiate detoxification treatment. Transient RLS during opiate detoxification merits further interst in order to improve the treatment of sleep disturbances during detoxification and as a model of interaction of the dopaminergic and endorphine system in motor activity.