[Electromyographic assessment of the temporalis muscle prior to a lengthening myoplasty in patients with Moebius syndrome]. / Étude électromyographique du muscle temporalis avant une myoplastie d'allongement dans le syndrome de Moebius.

BACKGROUND/OBJECTIVES: Temporalis muscle lengthening myoplasty improves tightening of the lips and rehabilitates smile for patients with congenital facial palsies. Because Moebius syndrome is heterogeneous, a careful evaluation is mandatory before deciding to perform myoplasty. This series shows the role of electromyography for investigating temporalis muscle and trigeminal nerve motor functions. METHODS: We conducted a retrospective study of 18 patients with no upward movements of the labial commissure and absent or unsightly smile. Electromyography was used to study the temporalis muscle bilaterally. Analysis focused on the recruitment pattern of voluntary contraction and electrical silence or activity at rest. Traces were classified as normal, neurogenic, or low-amplitude. Functional outcomes of myoplasty were evaluated by measuring the upward movement of the commissure (mm), and qualified as high (≥10), medium (>5), or little (≤5). RESULTS: Surgery was cancelled for 5 patients with abnormal electromyographic signs, neurogenic (2) or low-amplitude (3). Myoplasty was performed in 7 patients (age: 8-17 years), unilaterally (3) or bilaterally (4). Preoperative electromyogram was normal (3), or showed moderate neurogenic (2) or low-amplitude (2) changes. Follow-up period after surgery was from 2 to 12 years; functional outcomes were high (5), medium (1), or little (1). CONCLUSION: Electromyographic study of the temporalis can detect muscle denervation or atrophy, or dyspraxia, and guide decision to encourage or discourage performing myoplasty, or enhance rehabilitation programme and make the patient aware of possibly modest outcome.

Visual neurophysiological dysfunction in infants exposed to hydroxychloroquine in utero.

AIM: Hydroxychloroquine therapy during pregnancy is thought to be safe for foetuses. Normal visual function has been showed on clinical grounds in infants exposed in utero to hydroxychloroquine, but there are few visual neurophysiological data. Our study was designed to assess retina and visual pathways using electroretinogram and visual evoked potentials in a series of infants born to mothers treated by hydroxychloroquine for connective tissue diseases. METHODS: Twenty-one infants (3-7 months of age) were consecutively examined between June 2002 and May 2007. Full-field electroretinogram was recorded by contact lens electrodes and visual evoked potentials were recorded by occipital surface electrodes using flash stimulation in mesopic condition. Analysis was focused on the amplitudes and latencies of the a- and b-waves of electroretinogram and the latency of the P(100) component of visual evoked potentials. RESULTS: Electroretinogram abnormalities were detected in six infants, associated with delayed visual evoked potentials in four of them. CONCLUSION: Early electroretinogram and visual evoked potentials testing evidenced neurophysiological visual disturbances in a subset of infants born to mothers treated by hydroxychloroquine. Systematic clinical and neurophysiological vision testing during childhood is needed to detect possible consequences of antenatal exposure to hydroxychloroquine.

An unexpected plasma cholinesterase activity rebound after challenge with a high dose of the nerve agent VX.

Organophosphorus chemical warfare agents (nerve agents) are to be feared in military operations as well as in terrorist attacks. Among them, VX (O-ethyl-S-[2-(diisopropylamino)ethyl] methylphosphonothioate) is a low volatility liquid that represents a percutaneous as well as an inhalation hazard if aerosolized. It is a potent irreversible cholinesterase (ChE) inhibitor that causes severe signs and symptoms, including respiratory dysfunction that stems from different mechanisms. VX-induced pulmonary oedema was previously reported in dogs but mechanisms involved are not well understood, and its clinical significance remains to be assessed. An experimental model was thus developed to study VX-induced cardiovascular changes and pulmonary oedema in isoflurane-anaesthetized swine. In the course of this study, we observed a fast and unexpected rebound of plasma ChE activity following inhibition provoked by the intravenous injection of 6 and 12 microg kg(-1) of VX. In whole blood ChE activity, the rebound could stay unnoticed. Further investigations showed that the rebound of plasma esterase activity was neither related to spontaneous reactivation of ChE nor to VX-induced increase in paraoxonase/carboxylesterase activities. A bias in Ellman assay, haemoconcentration or severe liver cytolysis were also ruled out. All in all, these results suggest that the rebound was likely due to the release of butyrylcholinesterase into the blood stream from ChE producing organs. Nature of the organ(s) and mechanisms involved in enzyme release will need further investigations as it may represent a mechanism of defence, i.e. VX scavenging, that could advantageously be exploited.

Respiratory-related evoked potentials in children with asthma.

AIMS OF THE STUDY: Respiratory-related evoked potentials (RREPs) are a method of recording brain activities in response to respiratory stimuli. Although data in childhood are scarce, the absence of the early P1 component of RREPs has been reported in children with a history of life-threatening asthma. This study was focused on the presence, latencies, and amplitudes of the P1, N1, P2, and N2 components of the RREPs in a paediatric series of asthmatic patients. PATIENTS AND METHODS: RREPs were recorded in 21 patients with stable asthma, age range 8-17 years, 11 healthy children, age range 6-16 years, and 24 healthy adults, age range 20-28 years. The signals from left (C3-Cz) and right (C4-Cz) central (rolandic) location were recorded separately, using surface electrodes. Evoked responses to two series of 80 consecutive mid-inspiratory occlusions were averaged. Recordings were analysed manually. RESULTS: All 4 RREPs components were significantly more often absent in asthmatic children than in healthy children and adults (P1, p=0.01; N1, p=0.008; P2, p=0.008, N2, p=0.01). The latencies and amplitudes of the four components were similar in patients and healthy subjects. CONCLUSION: RREPs components were less frequently present in children with asthma than in healthy subjects. This finding should promote the recording of RREPs in other acute and chronic respiratory diseases in children in order to search for possible electroclinical correlations.

[Discovery and crystallographic structure of human apolipoprotein]. / Découverte et structure cristallographique d'une apolipoprotéine humaine.

We report the serendipitous discovery of a human plasma phosphate binding protein (HPBP). This 38 kDa protein is co-purified with paraoxonase (PON1). The association between HPON1 and HPBP is modulated by phosphate and calcium concentrations. The HPBP X-ray structure solved at 1.9 A resolution is similar to the prokaryotic phosphate solute-binding proteins (SBPs) associated with ATP binding cassette transmembrane transporters, though phosphate-SBPs have never been characterized or predicted from nucleic acid databases in eukaryotes. However, HPBP belongs to the family of ubiquitous eukaryotic proteins named DING, meaning that phosphate-SBPs are also widespread in eukaryotes. The absence of complete genes for eukaryotic phosphate-SBP from databases is intriguing, but the astonishing 90% sequence conservation of genes between evolutionary distant species suggests that the corresponding proteins play an important function. HPBP is the first identified transporter capable of binding phosphate ions in human plasma. Thus it is thought to become a new predictor and a potential therapeutic agent for phosphate-related diseases such as atherosclerosis.

Raman spectroscopic study of conjugates of butyrylcholinesterase with organophosphates.

Raman spectra of human butyrylcholinesterase (BuChE; E.C. 3.1.1.8) were analyzed in the native state and after conjugation with organophosphates (soman, DFP and paraoxon). The secondary structure of the native BuChE in Tris-HCl buffer (pH 7.5), determined from analysis of the amide I polypeptide vibration band, indicates 47% alpha-helices, 26% beta-sheets, 16% turns and 12% undefined structure. We obtained the same values for paraoxon-phosphorylated BuChE, but 39% helical structure, 31% beta-sheets, 17% turns and 13% undefined structure for 'aged' DFP-BuChE conjugates and 36% helical structure, 34% beta-sheets, 20% turns and 10% undefined structure for 'aged' soman-BuChE conjugates. The approximately 10% decrease of alpha-helical structure observed upon phosphorylation by DFP and phosphonylation by soman, probably corresponds to the 'aging' process, which does not take place in the case of paraoxon. Considerable differences have been observed between native, paraoxon inhibited and 'aged' BuChE in aromatic ring vibrations, suggesting that the dealkylation of organophosphate conjugates modifies the environment or the interactions of aromatic amino-acid residues. In the aliphatic side chains an increase of the number of gauche configurations has been observed in 'aged' DFP-BuChE and soman-BuChE.

Combined pressure/heat-induced inactivation of butyrylcholinesterase.

The combined effects of pressure and temperature on the activity of butyrylcholinesterase (BuChE) were investigated in the pressure range from 10(-3) to 5 kbar and temperature range from -10 degrees C to 70 degrees C. Inactivation of the enzyme showed a complex dependence on pressure and temperature. Under moderate pressures (1-3 kbar) at temperatures 40-65 degrees C BuChE was resistant to heat inactivation; under other conditions of pressure and temperature, the action of both parameters was synergistic and caused inactivation. Results allowed to construct a pressure-temperature kinetic phase diagram for the enzyme inactivation. The elliptic diagram for the irreversible transition active-->inactive BuChE as a function of both pressure and temperature has a positive angular coefficient. This indicates that pressure acts as a stabilizer of BuChE against heat denaturation.

Purification, molecular characterization and catalytic properties of a Pseudomonas fluorescens enzyme having cholinesterase-like activity.

An enzyme with a cholinesterase (ChE) activity, produced by Pseudomonas fluorescens, was purified to homogeneity in a three-step procedure. Analysis by non-denaturing and SDS-PAGE, and by isoelectric focusing, indicated that the enzyme was a monomer of 43 kDa, with a pI of 6.1. The N-terminal sequence, AEPLKAVGAGEGQLDIVAWPGYIEA, showed some similarities with proteins of the ChE family and a strong similarity with a protein from Escherichia coli with unknown structure and function. Cholinesterase activity at pH 7.0 and 25 degreesC was maximum with propionylthiocholine as substrate (kcat,app=670 min-1), followed by acetylthiocholine, and significantly lower with butyrylthiocholine. Catalytic specificity (kcat/Km) was the same for propionylthiocholine and acetylthiocholine, but was two orders of magnitude lower for butyrylthiocholine. Kinetics of thiocholine ester hydrolysis showed inhibition by excess substrate which was ascribed to binding of a second substrate molecule, leading to non-productive ternary complex (Km=35 microM, KSS=0.49 mM with propionylthiocholine). There was low or no reactivity with organophosphates and carbamates. The enzyme inhibited by echothiophate (kII=0.44x102 M-1 min-1) was not reactivated by pralidoxime methiodide. However, the P. fluorescens enzyme had affinity for procainamide and decamethonium, two reversible ChE inhibitors used as affinity chromatography ligand and eluant, respectively. Although similarity of the N-terminal amino acid sequence of the enzyme with an internal sequence of ChEs is weak, its catalytic activity towards thiocholine esters, and its affinity for positively charged ligands supports the contention that this enzyme may belong to the ChE family. However, we cannot rule out that the enzyme belongs to another structural family of proteins having cholinesterase-like properties. The reaction of the enzyme with organophosphates suggests that it is a serine esterase, and currently this enzyme may be termed as having a cholinesterase-like activity.

[How to manage my patients' psychological disturbances?]. / Comment gérer les troubles psychologiques de mes patients?

Psychological disturbances are frequently encountered in obese patients. The physician specialised in nutrition should take them into account within the therapeutic project and all along the patient's management. This review describe, according to the main obese patients' profiles (typology), the conditions for an optimal adequation between hopes and expectations from both the patient and the physician, as well as the psychiatrist role within the therapeutic project and during the management period.

Pressure-induced molten globule state of cholinesterase.

The denaturing effect of pressure on the structure of human butyrylcholinesterase was examined by gel electrophoresis under pressure and by 8-anilino-1-naphthalene sulfonate (ANS) binding. It was found that the fluorescence intensity of bound ANS is increased by pressure between 0.5 and 1.5 kbar and that the hydrodynamic volume of the enzyme swells when pressures around 1.5 kbar are applied. These findings indicate that pressure denaturation of butyrylcholinesterase is a multi-step process and that the observed transient pressure-denatured states have characteristics of molten globules.

The expression of PEA-15 (phosphoprotein enriched in astrocytes of 15 kDa) defines subpopulations of astrocytes and neurons throughout the adult mouse brain.

Phosphoprotein enriched in astrocytes of 15 kDa (PEA-15) is an abundant phosphoprotein in primary cultures of mouse brain astrocytes. Its capability to interact with members of the apoptotic and mitogen activated protein (MAP) kinase cascades endows PEA-15 with anti-apoptotic and anti-proliferative properties. We analyzed the in vivo cellular sources of PEA-15 in the normal adult mouse brain using a novel polyclonal antibody. Immunohistochemical assays revealed numerous PEA-15-immunoreactive cells throughout the brain of wild-type adult mice while no immunoreactive signal was observed in the brain of PEA-15 -/- mice. Cell morphology and double immunofluorescent staining showed that both astrocytes and neurons could be cellular sources of PEA-15. Closer examination revealed that in a given area only part of the astrocytes expressed the protein. The hippocampus was the most striking example of this heterogeneity, a spatial segregation restricting PEA-15 positive astrocytes to the CA1 and CA3 regions. A PEA-15 immunoreactive signal was also observed in a few cells within the subventricular zone and the rostral migratory stream. In vivo analysis of an eventual PEA-15 regulation in astrocytes was performed using a model of astrogliosis occurring along motor neurons degeneration, the transgenic mouse expressing the mutant G93A human superoxyde-dismutase-1, a model of amyotrophic lateral sclerosis. We observed a marked up-regulation of PEA-15 in reactive astrocytes that had developed throughout the ventral horn of the lumbar spinal cord of the transgenic mice. The heterogeneous cellular expression of the protein and its increased expression in pathological situations, combined with the known properties of PEA-15, suggest that PEA-15 expression is associated with a particular metabolic status of cells challenged with potentially apoptotic and/or proliferative signals.

An outbreak of Ochrobactrum anthropi bacteraemia in five organ transplant patients.

Nosocomial bacteraemia caused by Ochrobactrum anthropi occurred over a 1-month period in five organ transplant recipients, four of whom were in the same renal and pancreatic transplant unit. Bacteraemia occurred with cyclosporin A, azathioprine and steroids, and with a rabbit anti-thymocyte globulin (RATG) during the induction phase. RATG appeared to be the only common factor among the five cases. Over the period described, 71.4% of all patients receiving RATG developed O. anthropi bacteraemia. Three patients presented with fever and chills during or shortly after RATG infusion. Analysis of residues of the infusion, and the used vials of RATG, showed the presence of O. anthropi in concentrations of between 20 and 1000 cfu ml-1 in 5.3% of samples. Unused vials were found to be heavily contaminated with either O. anthropi or Microbacterium spp. in 23.5% of samples. All positive vials were of one particular lot number suggesting a malfunction in the manufacturing process. Many parenteral drugs such as the RATG used here do not contain preservatives and, although aseptically prepared, will not withstand thermal sterilization. Bacterial contamination of these small volume medications is not always easily detectable by conventional methods. This outbreak highlights the need for accurate quality control testing to detect small inocula that may occur during or after the manufacturing process.

Dual effect of high electric field in capillary electrophoresis study of the conformational stability of Bungarus fasciatus acetylcholinesterase.

The effect of high electric field in capillary zone electrophoresis (CZE) was evaluated for the study of the thermally induced unfolding of Bungarus fasciatus acetylcholinesterase. This monomer enzyme is characterised by two interdependent uncommon structural features, the asymmetrical distribution of charged residues and a relatively low thermal denaturation temperature. Both traits were presumed to interfere in the thermal unfolding of this enzyme as investigated by CZE. This paper analyses the effect of high electric field on the behaviour of the enzyme native state. It is shown that increasing the applied field causes denaturation-like transition of the enzyme at a current power which does not induce excessive Joule heating in the capillary. The susceptibility to electric field of proteins like cholinesterases, with charge distribution anisotropy, large permanent dipole moment and notable molecular flexibility associated with moderate thermal stability, was subsequently discussed.

Neurophysiological brainstem investigations in isolated Pierre Robin sequence.

Polysomnography, electromyography (EMG) of the face, tongue, and soft palate, blink reflexes (BRs), EMG during bottle-feeding, and brainstem auditory evoked responses (BAERs) were performed in 25 newborn babies with isolated Pierre Robin sequence (PRS) to aid in evaluation and management. Obstructive apneas were found in 23/24 patients (the 25th having undergone tracheotomy). Number and duration of central respiratory pauses were always normal, as well as electroencephalographic and clinical organization of sleep stages. EMG recruitment pattern in facial and lingual muscles, and BRs were normal in all cases. EMG recruitment pattern in muscles of the soft palate was normal in 14/25 patients, showed a reduced average amplitude with short-duration and low amplitude motor unit potentials in 10/25, and showed signs of denervation in 1/25. EMG during bottle-feeding showed sucking-swallowing disorders in 20/25 patients. BAERs showed a bilateral conductive impairment with increased latencies and thresholds in 5/19 patients, but with normal and symmetric I-III and I-V interpeak latencies in 19/19. These neurophysiological findings suggest that in isolated PRS a dysfunction of the lingual and pharyngeal motor organization exists without any structural impairment in brainstem nuclei and pathways.

[Infantile spinal amyotrophy with myotonia. Electromyographic study]. / Amyotrophie spinale infantile avec myotonie. Etude electromyographique.

An unusual feature was observed in a 7-year-old boy presenting with type II infantile spinal muscular atrophy: percussion myotonia, clinical expression of pseudomyotonic volleys (bizarre high frequency discharge or complex repetitive discharge).

[Early electromyographic signs in congenital myotonic dystrophy. A study of ten cases]. / Les signes électromyographiques précoces de la dystrophie myotonique congénitale. Etude de dix cas.

Ten cases of congenital myotonic dystrophy have been reported and EMG findings described. In 5 neonates, EMG was performed between the 4th and 27th d of life. Four very severe cases had a fatal outcome, the 6 others were of mild severity, showed hypotonia, motor delay and mental handicap. In 9 cases, diagnosis was not established before birth. The EMG myogenic criteria were present in 2 muscles or more in each case, and were predominantly present in the proximal muscles. Clinical myotonia was absent in all cases but electrical myotonia was provoked by motor nerve stimulation using a current of long duration. The authors emphasize the interest of this stimulation-detection method which was able to exhibit myotonic discharge in 6 patients including 3 neonates.

Muscle complications of malnutrition in children: a clinical and electromyographic study.

The authors report the clinical and electromyographic (EMG) findings in a series of 13 children with a pseudomyopathic motor deficit in the context of malnutrition (Body Mass Index < or = 3rd percentile) caused by primary protein-calorie deficiency or secondary to chronic disease. The infants (nine cases) manifested a regression or stagnation of motor abilities, with hypotonia and amyotrophy; older children and adolescents (four cases) presented clear amyotrophy with a deficit in muscle strength consisting primarily of proximal muscular weakness. Detection and stimulation-detection EMG demonstrated myogenic signs in at least two muscles in all patients. Myogenic signs were dominant in all proximal muscles. Latencies were normal in all patients. Motor nerve conduction velocities were slowed in three infants and in one adolescent. A temporal dispersion of motor responses was observed in 11 proximal muscles. The muscle biopsy, performed in five cases, revealed an inequality in the calibre of fibres, with atrophy dominating in type II fibres. The authors emphasize the value of EMG in disclosing the myopathic process, thereby contributing to the etiological diagnosis of motor difficulties in children suffering from malnutrition or a chronic disease.

[Facial, lingual and pharyngeal electromyography in children: a method to study sucking and swallowing disorders and their pathophysiology]. / Electromyographie faciale, linguale et pharyngée chez l'enfant: une méthode d'étude des troubles de succion-déglutition et de leur physiopathologie.

The authors describe an electromyogaphic protocol developed with the aim of evaluating the sucking-swallowing function and of studying the pathophysiology of its disturbances in the newborn and in infants. This protocol consists of associating several techniques. Some of them are traditional: EMG of the facial muscles and nerves and blink reflex, while others are original: EMG of the tongue and hypoglossal nerve, EMG of the velum palatinum, and a dynamic study using a baby bottle, of the sucking and swallowing reflex for a liquid meal. For each technique, practical procedures are described together with normal results observed between birth and 3 years of age. The authors report on abnormalities observed in pathological conditions and discuss their significance in major nosological contexts. They emphasize the value of this EMG protocol in assessing the sucking-swallowing reflex, in revealing anatomo-functional disturbances in the brainstem and in tackling the pathophysiological aspects of aspiration pneumopathies, feeding difficulties and bucco-facial malformations.

[Contribution of the electromyogram in the diagnosis of infantile spinal muscular atrophy in the neonatal period]. / Apport de l'électromyogramme au diagnostic d'amyotrophie spinale infantile en période néonatale.

BACKGROUND: The acute form of Werdnig-Hoffman disease, infantile spinal muscular atrophy type I (SMA I), is characterized by severe paralytic hypotonia with neurogenic electromyographic (EMG) pattern and specific histologic features. PATIENTS: Four cases of very severe SMA I suffering from generalized muscle weakness at birth were included in the study. RESULTS: The neurogenic EMG pattern was observed at the first exam performed between D2 and D46. The muscular biopsy performed between D18 and D45 showed only a mild decrease of the muscle fiber size without grouping of fiber types. CONCLUSION: In those forms of SMA I with a neonatal clinical onset, the diagnosis is assessed by clinical and EMG findings while early muscular biopsy can be misleading. EMG is the relevant diagnostic test which confirms the anterior horn cell disease and can justify the DNA study.

[Pigmentary retinopathy of neonates and infants. Their examination using electroretinography and visual evoked potentials]. / Rétinopathies pigmentaires du nourrisson et de l'enfant. Leur exploration par l'électrorétinogramme et les potentiels évoqués visuels.

A method of neurophysiological investigation (electroretinography and visual evoked potentials) is described as a non invasive exploration used in awake children. E.R.G. and V.E.P. normal patterns are described in relation to age. The data obtained in pigmentary retinopathies are referred to the physiopathology of these diseases. Usefulness of both neurophysiological tests is showed in the early diagnosis. Significative abnormalities are seen even before any detectable ophthalmoscopic symptom. In pigmentary retinopathies, V.E.P. are normal while E.R.G. is slightly then severely altered. E.R.G. and V.E.P. are also helpful in the differential diagnosis: in macular diseases, E.R.G. is usually normal while V.E.P. are altered. Repeated examinations have a prognostical value: when a disease is progressing, E.R.G. becomes more and more altered and V.E.P.'s abnormalities appear.