[Systemic nocardiosis with mediastinal lymph node involvement proven by endoscopic ultrasound]. / Nocardiose systémique avec atteinte ganglionnaire médiastinale prouvée par échoendoscopie.

INTRODUCTION: Systemic nocardiosis is an infectious disease that is rarely associated with mediastinal lymph nodes. CASE REPORT: We report the case of a 72-year-old male patient treated with a high dose of oral corticosteroids for rheumatoid polyarthritis. This patient presented with rapid overall deterioration associated with mediastinal lymph nodes. Endobronchial ultrasound enabled us to establish a diagnosis of systemic nocardiosis. The patient recovered after having received suitable antibiotic treatment for four months. CONCLUSION: This work reports on a rare clinical presentation of systemic nocardiosis associated with mediastinal lymphadenopathies and highlights the key role of endobronchial ultrasound in diagnosing mediastinal lymph nodes, especially in differential diagnosis for lung cancer.

Body mass index variations in patients with Parkinson's disease treated with levodopa-carbidopa intestinal gel infusion: A case control study versus standard of care and subthalamic nucleus deep brain stimulation.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is an advanced therapy for patients with Parkinson Disease (PD). Weight loss has been pointed out as an adverse event of LCIG infusion. AIMS OF THE STUDY: To compare weight changes between three groups of PD patients: patients treated with LCIG, patients within the first year of subthalamic deep brain stimulation (STN-DBS) and patients treated exclusively with oral treatment during 1 year of follow up. METHODS: Patients treated with LCIG were retrospectively matched by age, gender, disease duration and Hoehn and Yahr to patients undergoing STN-DBS and to patients both receiving the standard of care treatment and unwilling advanced therapies (SOC). Clinical features and weight were collected at baseline, and 12 months after introducing the treatment (LCIG and STN-DBS groups) or for one year of treatment (SOC). RESULTS: Eighteen patients were included in each group. They had no differences in clinical and demographic features, except for cognitive impairment. There was a mean weight (-5.8kg ±6.8) and BMI (-2.1kg/m2±2.6) reduction in the LCIG group after 12 months, while there was a slight weight loss in the SOC (-1.4kg ±3.1) and a weight increase in the STN-DBS group (5.4kg ±4.7). Differences of weight were statistically different between, LCIG and STN-DBS (P<0.001), LCIG and SOC (P=0.002) and STN-DBS and SOC (P<0.001). CONCLUSIONS: The study shows a significant weight reduction after starting LCIG infusion compared to the other groups. Weight loss should be closely monitored in patients treated with LCIG.

Cognitive complaint in early Parkinson's disease: A pilot study.

BACKGROUND: Subjective cognitive complaint (SCC) is a criterion recommended by the Movement Disorder Society (MDS) task force for the diagnosis of mild cognitive impairment (MCI). Until now there were few specific tools for detecting SCC in PD. We sought to develop a new tool to assess SCC specifically dedicated for PD. MATERIALS AND METHODS: We set a group of experts in movements disorders and neurocognition to develop an easy-to-use tool based on a visual analogue scale (VAS) for five cognitive domains: memory, executive functions, spatial orientation, attention, and language. We use it to assess SCC twice (at a one-month interval) in PD patients with disease duration of less than 5 years. Comprehensibility of the VAS was assessed. Controls were assessed with the same VAS. Patients with PD also underwent neuropsychological testing. RESULTS: VAS was easily understandable by the 70 patients with PD. We found significant SCC for the patients with PD vs controls in three cognitive domains: executive functions (1.7 ± 1.9 vs 0.8 ± 1.1; P < .001), language (2.3 ± 2.5 vs 1.0 ± 1.3, P < .001), and attention (2.1 ± 2.2 vs 1.2 ± 1.2; P < .01). Reproducibility between the two evaluations of patients with PD was good. There was no relationship between SCC and the results of neuropsychological testing. CONCLUSIONS: SCC seems to appear early in PD, in three cognitive domains (executive functions, language, and attention), and VAS might be a good way to detect SCC in PD, but need to be validated.

Abnormal pain perception in patients with Multiple System Atrophy.

INTRODUCTION: Patients with Parkinson's disease or Multiple System Atrophy frequently experience painful sensations. The few studies investigating pain mechanisms in Multiple System Atrophy patients have reported contradictory results. In our study, we compared pain thresholds in Multiple System Atrophy and Parkinson's disease patients and healthy controls and evaluated the effect of l-DOPA on pain thresholds. METHODS: We assessed subjective and objective pain thresholds (using a thermotest and RIII reflex), and pain tolerance in OFF and ON conditions, clinical pain, motor and psychological evaluation. RESULTS: Pain was reported in 78.6% of Multiple System Atrophy patients and in 37.5% of Parkinson's disease patients. In the OFF condition, subjective and objective pain thresholds were significantly lower in Multiple System Atrophy patients than in healthy controls (43.8 °C ± 1.3 vs 45.7 °C ± 0.8; p = 0.0005 and 7.4 mA ± 3.8 vs 13.7 mA ± 2.8; p = 0.002, respectively). They were also significantly reduced in Multiple System Atrophy compared to Parkinson's disease patients. No significant difference was found in pain tolerance for the 3 groups and in the effect of l-DOPA on pain thresholds in Multiple System Atrophy and Parkinson's disease patients. In the ON condition, pain tolerance tended to be reduced in Multiple System Atrophy versus Parkinson's disease patients (p = 0.05). CONCLUSION: Multiple System Atrophy patients had an increase in pain perception compared to Parkinson's disease patients and healthy controls. The l-DOPA effect was similar for pain thresholds in Multiple System Atrophy and Parkinson's disease patients, but tended to worsen pain tolerance in Multiple System Atrophy.

Exchangeable copper: a reflection of the neurological severity in Wilson's disease.

BACKGROUND AND PURPOSE: The severity of Wilson's disease (WD) is linked to free copper accumulating in the liver and brain. Exchangeable copper (CuEXC) is a new technique to determine plasmatic copper and is useful in the diagnosis of WD. It is hypothesized that it may also enable a good evaluation of extra-hepatic involvement and its severity. METHODS: Forty-eight newly diagnosed WD patients were prospectively evaluated using hepatic, neurological, ophthalmological and brain magnetic resonance imaging (MRI) scores. Three phenotypic presentations were distinguished: pre-symptomatic, hepatic and extra-hepatic. CuEXC was determined in addition to standard copper assays before decoppering therapy. Correlations between biological parameters and the different scores were determined and compared in the hepatic and extra-hepatic groups. RESULTS: Extra-hepatic patients had significantly higher CuEXC values than those with the hepatic form (P < 0.0001). The overall ability of CuEXC to separate the two forms was satisfactory, with an area under the curve of 0.883 (95% confidence interval 0.771-0.996) and an optimal threshold for extra-hepatic diagnosis of 2.08 µmol/l (sensitivity 85.7%; specificity 94.1%). In extra-hepatic patients, CuEXC was the only biological marker to be positively correlated with the Unified Wilson Disease Rating Score (r = 0.45, P = 0.016), the Kayser-Fleischer ring score (r = 0.46, P = 0.014) and the brain MRI score (r = 0.38, P = 0.048), but it was not correlated with the hepatic score. CONCLUSIONS: Exchangeable copper determination is useful when diagnosing WD as a value >2.08 µmol/l is indicative of the severity of the extra-hepatic involvement. In the case of purely hepatic presentation, atypical or mild neurological signs, it should encourage physicians to search for lesions in the brain and eyes.

[Effects of fine particulate matter from on bronchial epithelial cells]. / Effets des particules fines sur les cellules épithéliales bronchiques.

INTRODUCTION: Ambient air contains a variety of pollutants including solid particles. Human bronchial epithelial cells (HBEC) play a key role following inhalation of these toxic particles. In a cell culture system of HBEC, we investigated the effects of several fractions of Lyons air-derived particles on cell viability/proliferation and production of the inflammatory mediators IL-8 and TGF-ß. METHODS: Air particles were collected in Lyon (France) by filtration of the air and impaction on filters located on a tapered element oscillating microbalance. Several diameter-based fractions of particles were prepared. HBEC were then exposed to different concentrations of these fractions. RESULTS: HBEC survival was not altered after 48hours of culture in the presence of particles regardless of their diameter and concentration. A dose-dependent inhibitory effect on cell growth was observed for all fractions. The particles caused an increase of both TGF-ß and Il-8 protein levels as a function of their diameters and/or concentrations. CONCLUSION: Air-derived particle fractions exhibit both an inhibitory effect on cell proliferation and a pro-inflammatory activity on HBEC.

An individual rehabilitation program: evaluation by Parkinsonian patients and their physiotherapists.

OBJECTIVES: The purpose of this work was to study the feasibility of an individual Parkinson disease (PD) rehabilitation program based on each patient's prevalent symptoms and to determine the effects of this program on patient's quality of life as well as the level of patient's and physiotherapist's satisfaction with the program. PATIENTS AND METHODS: In association with physiotherapists with expertise in PD, a physical medicine and rehabilitation physician, we elaborated a physical therapy program based on the core areas for physical therapy in PD: transfers; posture; balance and falls; physical capacity and inactivity. Within this program, we selected exercises tailored to each patient's main impairment and proposed this selection to their local physiotherapist for three months. Quality of life was evaluated with PDQ-39 at baseline and after three months of the individualized physical therapy program. We built an anonymous satisfaction questionnaire for patients and physiotherapists that was filled out at the end of the program. RESULTS: One hundred and three individuals with moderately advanced but clinically stable idiopathic PD were included. Significant improvement was found for the emotional well-being, bodily discomfort and stigma domain (P ≤ 0.05). No significant improvement was found for the other PDQ-39 domains. The mean global satisfaction figures for this program were 6.0 ± 2.4 and 7.2 ± 2.1 for patients and physiotherapists respectively. Most of the patients felt improved by the physiotherapy program and especially for transfer, balance, gait, and mobility. CONCLUSION: Our study found evidence of the potential benefits of a patient-tailored physiotherapy program. Such a program was feasible and had a favorable impact on patients' quality of life and on physiotherapists' practices for PD patients. Specific physiotherapy may be effective to limit physical mobility impairment. Our results also pointed out that physiotherapy may be efficient to confine the negative impact of social isolation, pain and emotional reactions. Such a program should be associated with a therapeutic education intervention such as encouraging patients to perform physical therapy exercises alone.

[A therapeutic educational program in Parkinson's disease: ETPARK]. / Éducation thérapeutique chez le patient parkinsonien: le programme ETPARK.

We developed a therapeutic educational program in Parkinson's disease (PD). The needs analysis for this program was performed through a survey involving 41 PD patients. This survey questionnaire was elaborated through the analysis of 395 patients' semi-directive interviews, performed in our specialized hospitalisation unit during explanation workshops between 2005 and 2007. We managed to design an educational program tailored to specificities of PD and according to the recommendations of the High Authority of Health in France (HAS). This program was based on individual sessions conducted by a nurse experienced in PD and trained in education. Collective workshops concerning specific themes such as physical therapy, communication, social supports, sleep disorders, stress management, therapies in PD could be proposed to volunteer patients and were performed by the nurse, a physiotherapist and a specialized practitioner. This program focused on skills structured in knowledge, expertise, and learning. It was intended for patients without any motor or cognitive severe impairment. We educated 231 patients between 2008 and 2012 individually and 113 in collective workshops. Patients had an interesting improvement in their self-esteem (6.2±1.4 before and 7.3±1.1 after one year of this educational program). This program has been validated by our regional medical agency and we performed a medico-economic study demonstrating a significant improvement in quality-of-life of educated patients without extra costs.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Both L-DOPA and HFS-STN restore the enhanced group II spinal reflex excitation to a normal level in patients with Parkinson's disease.

OBJECTIVE: To investigate the contribution of group II spinal pathways in Parkinsonian upper limb rigidity and the modulation of spinal excitability of group I and group II pathways by L-DOPA and subthalamic nucleus-high-frequency stimulation (STN-HFS). METHODS: The effect of ulnar nerve electrical stimulation on Flexor Carpi Radialis Electromyogram (FCR EMG) was investigated in two groups of patients: patients receiving medication (MED group) and chronically surgically implanted patients (DBS group). Results were compared in patients ON and OFF treatment, and between patients and control subjects. RESULTS: The resulting long-lasting facilitation in FCR EMG had similar characteristics in all groups, and surface area was assessed in analysis windows corresponding to the parts supposed to be mediated by non-monosynaptic spinal pathways to FCR motoneurones, fed by hand muscle group I and group II afferents (Lourenço et al., 2006). In both the MED and DBS groups, the group I excitation was not altered but the group II excitation was particularly enhanced when OFF treatment, compared to controls, and both L-DOPA and STN-HFS restored the group II spinal excitation to normal level. CONCLUSION: Both L-DOPA and STN-HFS influence the metabolism of monoamines in the midbrain, and restore the descending neuromodulation on group II spinal reflex. SIGNIFICANCE: These results further support a group II contribution to the enhanced long latency response (LLR) to muscle stretch observed in wrist muscles of rigid Parkinson's disease (PD) patients.

Motor activation in multiple system atrophy and Parkinson disease: a PET study.

BACKGROUND: Multiple system atrophy (MSA) is an atypical parkinsonian syndrome including cerebellar impairment and poor response to levodopa. We assessed right hand motor activation in patients with MSA before and after an acute levodopa challenge in comparison with patients with PD and healthy volunteers (HVs). METHODS: Eighteen patients with MSA, 8 patients with PD, and 10 age-matched HVs were included. Regional cerebral blood flow measurements with H(2)(15)O PET were performed at rest and during a right hand movement. Statistical parametric mapping was used to analyze motor vs rest in OFF and ON conditions and the effect of levodopa on motor activation. RESULTS: Before levodopa, patients with MSA activated most known cerebral motor areas. Compared with HVs, patients with MSA exhibited less bilateral cerebellar activation and greater left superior parietal activation. They also had less bilateral cerebellar and greater supplementary motor and left superior parietal activation than patients with PD. Conversely, patients with PD had greater activation than HVs in the right cerebellum and less in the supplementary motor cortex. After levodopa, patients with MSA exhibited reduced activation in anterior cingulate, whereas patients with PD had greater activation in the right cerebellum. CONCLUSION: Patients with MSA and patients with PD recruited different motor networks. Patients with PD preferentially activated cerebellar pathways, possibly to compensate for basal ganglia dysfunction. This was not observed in patients with MSA, probably because of cerebellar dysfunction; other frontoparietal cortical areas were recruited.

Short-chain fatty acids and commensal microbiota in the faeces of severely malnourished children with cholera rehydrated with three different carbohydrates.

BACKGROUND: Short-chain fatty acids (SCFAs) liberated by fermentation of complex carbohydrates might stimulate water and salt absorption, and provide energy. The aim of the study was to assess the number and proportion of faecal bacteria and the concentration of SCFAs of severely malnourished children with cholera receiving oral rehydration solution (ORS) containing glucose, amylase-resistant starch (ARS) or rice. METHODS: Serial faecal samples were collected from 30 malnourished children with cholera until rehydration and partial nutritional recovery. SCFAs were identified and quantitated by high-performance liquid chromatography. In situ hybridization combined with flow cytometry was used to analyse the microbiota in the faeces. RESULTS: Before treatment the concentration of total SCFA in faecal sample of cholera children was found to be 4.7±0.6 mmol/kg and it increased steadily until 95.0±8.7 mmol/kg at day 28. Among different ORS groups, concentration was significantly higher in the Rice-ORS group at day 1 (P<0.011) and at day 2 (P<0.025). During recovery faecal output was significantly reduced and the number of bacteria also increased faster in the Rice-ORS group than in the glucose-ORS group at day 1 and day 2 (P<0.01), and a modest increase in bacterial number was observed in the glucose-ORS plus ARS group (day 1, P=0.07; day 2, P=0.09). CONCLUSION: Clinical recovery was associated with an increase in bacterial and SCFA concentrations with all three carbohydrates in ORS. However, the increases were significantly higher in children receiving Rice-ORS.

Phylogeny of ladybirds (Coleoptera: Coccinellidae): are the subfamilies monophyletic?

The Coccinellidae (ladybirds) is a highly speciose family of the Coleoptera. Ladybirds are well known because of their use as biocontrol agents, and are the subject of many ecological studies. However, little is known about phylogenetic relationships of the Coccinellidae, and a precise evolutionary framework is needed for the family. This paper provides the first phylogenetic reconstruction of the relationships within the Coccinellidae based on analysis of five genes: the 18S and 28S rRNA nuclear genes and the mitochondrial 12S, 16S rRNA and cytochrome oxidase subunit I (COI) genes. The phylogenetic relationships of 67 terminal taxa, representative of all the subfamilies of the Coccinellidae (61 species, 37 genera), and relevant outgroups, were reconstructed using multiple approaches, including Bayesian inference with partitioning strategies. The recovered phylogenies are congruent and show that the Coccinellinae is monophyletic but the Coccidulinae, Epilachninae, Scymninae and Chilocorinae are paraphyletic. The tribe Chilocorini is identified as the sister-group of the Coccinellinae for the first time.

Levodopa raises objective pain threshold in Parkinson's disease: a RIII reflex study.

BACKGROUND: Patients suffering from Parkinson's disease (PD) describe painful sensations that could be related to neuropathic pain. Experimental data have indicated the involvement of basal ganglia and dopaminergic pathways in central nociceptive processing. AIM: The objective of this study was to assess and compare the effect of levodopa on the objective pain threshold in patients with PD and healthy subjects. METHODS: The objective pain threshold was assessed by the nociceptive flexion reflex (RIII) in 13 PD patients and 10 healthy subjects. Patients and healthy subjects were evaluated under two randomised conditions: with levodopa (ON) and without (OFF). RESULTS: Levodopa significantly increased the RIII threshold of PD patients (6.9 (1.2) mA in the OFF condition vs 8 (1.1) mA in the ON position; p = 0.02). RIII threshold was significantly lower in PD patients than in healthy subjects in the OFF condition (6.9 (1.2) mA vs 9.7 (3.4) mA; p = 0.02). RIII threshold did not change after levodopa administration in healthy subjects. CONCLUSION: These results provide evidence of a dopaminergic modulation of objective pain threshold in PD patients. In addition, the decrease in RIII threshold in PD patients, in the OFF condition, compared with controls, confirms the existence of an objective pain perception disturbance in PD.

[Levodopa modifies pain thresholds in Parkinson's disease patients]. / La lévodopa modifie les seuils nociceptifs chez le patient parkinsonien.

OBJECTIVE: To assess levodopa dose effect on pain thresholds in Parkinson's disease (PD) patients using an experimental nociceptive thermal stimulation. PATIENTS AND METHODS: We evaluated pain thresholds in 20 PD patients treated by dopaminergic drugs. We assessed heat and cold pain thresholds by using 2 different methods (method of limits and method of levels), intensity-response curve and tolerance threshold. Each PD patient was evaluated in two conditions: ON (after administration of leovdopa and OFF (after acute levodopa withdrawal). The order was randomized. RESULTS: The mean age of patients was 652+/-9.9 years and the mean duration was 9.3+/-3.3 years. Heat pain thresholds were statistically higher in ON versus OFF condition using both methods (44.1+/-3,6 degrees C versus 42.3+/-3,1 degrees C, method of levels, p=0.02). Cold pain thresholds were statistically higher in ON versus OFF condition only using method of levels (17.9+/-4,4 degrees C versus 19.6+/-4,2 degrees C, p=0.02). Heat pain tolerance was statistically higher in ON versus OFF condition (21.4+/-21.6 seconds versus 14.7+/-20.3 seconds, p=0.02). CONCLUSION: This study showed that levodopa increased heat and cold pain thresholds and heat pain tolrance in PD patients. This suggests that dopaminergic drugs could have an analgesic effects on PD related pain.

Exploration of the Drosophila acetylcholinesterase substrate activation site using a reversible inhibitor (Triton X-100) and mutated enzymes.

Cholinesterases are activated at low substrate concentration, and this is followed by inhibition as the level of substrate increases. However, one of these two components is sometimes lacking. In Drosophila acetylcholinesterase, the two phases are present, allowing both phenomena to be studied. Several kinetic schemes can explain this complex kinetic behavior. Among them, one model assumes that activation results from the binding of a substrate molecule to a non-productive site affecting the entrance of a substrate molecule into the active site. To test this hypothesis, we looked for an inhibitor competitive for activation and we found Triton X-100. Using organophosphates or carbamates as hemisubstrates, we showed that Triton X-100 inhibits or increases phosphorylation or carbamoylation of the enzyme. In vitro mutagenesis of the residues lining the active site gorge allowed us to locate the Triton X-100 binding site at the rim of the gorge with glutamate 107 playing the major role. These results led to the hypothesis that substrate binding at this site affects the entrance of another substrate molecule into the active site cleft.

Chronic biliary drainage corrects liver atrophy induced by portacaval shunt in the rat.

Portacaval shunt induces a severe liver atrophy. The relative liver hypertrophy induced by chronic biliary drainage was studied by electron microscopy. Rats with either portacaval or sham portacaval shunt had a 4-day chronic bile fistula. Compared with rats not submitted to chronic bile fistula, liver weight/body weight ratio increased from 1.84 to +/- 0.12 to 3.54 +/- 0.48 (p less than 0.05) in portacaval shunt and from 3.52 +/- 0.15 to 3.64 +/- 0.40 (p less than 0.05) in sham portacaval shunt (controls). Chronic bile fistula stimulated bile acid synthesis in the two groups. Furthermore, the initial low bile flow observed in portacaval shunt (rats) reached control values after chronic bile fistula. Ultrastructural abnormalities observed in portacaval shunt: atrophy of the hepatocyte mainly related to the atrophy of the rough and smooth endoplasmic reticulum, irregularity of the nucleus, dilatation of the nuclear envelope and of the rough endoplasmic reticulum, and swelling of mitochondria, were greatly modified by chronic bile fistula. The hepatocyte size increased, mitochondria appeared smaller than normal, the nuclear envelope and the rough endoplasmic reticulum were not dilated, and the rough and smooth endoplasmic reticulum were expanded. Chronic bile fistula had no noticeable effect on the liver in sham portacaval shunt. Either stimulation of bile salts synthesis or removal of bile salts, which could be toxic for the atrophic liver, are possible explanations for the relative hypertrophy of the liver.