The role of ADAMTS-13 activity and complement mutational analysis in differentiating acute thrombotic microangiopathies.

UNLABELLED: ESSENTIALS: Molecular diagnostics has improved the differentiation of acute thrombotic microangiopathys (TMAs). Atypical hemolytic uremic syndrome may have features mimicking thrombotic thrombocytopenic purpura. We identified novel complement mutations and a high incidence of CD46, with favorable long term outcomes. Complement mutation analysis in TMA where the diagnosis is unclear and ADAMTS-13 activity is >10%. BACKGROUND: Differentiation of acute thrombotic microangiopathy (TMA) at presentation has historically been dependent on clinical parameters. Confirmation of thrombotic thrombocytopenic purpura (TTP) is increasingly reliant on demonstrating deficient ADAMTS-13 activity. The identification of alternative complement pathway abnormalities in atypical hemolytic uremic syndrome (aHUS), along with the proven efficacy of terminal complement inhibitors in treatment, has increased the need for rapid differentiation of TTP from aHUS. OBJECTIVES: We describe the clinical phenotype and nature of complement mutations in a cohort of aHUS patients referred as acute TMAs. PATIENTS/METHODS: Fourteen consecutive aHUS patients were screened for mutations in C3, CD46, CFH, CFI, and CFB, as well as factor H (FH) antibodies. All aHUS patients had ADAMTS-13 activity > 10%. RESULTS: Of 14 aHUS patients, 11 (79%) had platelet counts < 30 × 10(9) /L during the acute phase. Median presenting creatinine level was 295 µmol L(-1) , while five (36%) of 14 presented with a serum creatinine level < 200 µmol L(-1) . Alternative complement pathway mutations were detected in 9 (64%) of 14 patients, including CD46 mutations in five (36%) of 14 patients. Patients were identified with novel mutations in CFB and C3 that have not been previously reported. CONCLUSIONS: We demonstrate that diagnostic differentiation based on platelet count and renal function is insufficient to predict an underlying complement mutation in some aHUS cases. Specifically, we demonstrate a high frequency of functionally significant CD46 mutations which may mimic TTP. ADAMTS-13 activity > 10% in a patient with a TMA should necessitate genetic screening for complement abnormalities.

LRIG1 opposes epithelial-to-mesenchymal transition and inhibits invasion of basal-like breast cancer cells.

LRIG1 (leucine-rich repeat and immunoglobulin-like domain containing), a member of the LRIG family of transmembrane leucine-rich repeat-containing proteins, is a negative regulator of receptor tyrosine kinase signaling and a tumor suppressor. LRIG1 expression is broadly decreased in human cancer and in breast cancer and low expression of LRIG1 has been linked to decreased relapse-free survival. Recently, low expression of LRIG1 was revealed to be an independent risk factor for breast cancer metastasis and death. These findings suggest that LRIG1 may oppose breast cancer cell motility and invasion, cellular processes that are fundamental to metastasis. However, very little is known of LRIG1 function in this regard. In this study, we demonstrate that LRIG1 is downregulated during epithelial-to-mesenchymal transition (EMT) of human mammary epithelial cells, suggesting that LRIG1 expression may represent a barrier to EMT. Indeed, depletion of endogenous LRIG1 in human mammary epithelial cells expands the stem cell population, augments mammosphere formation and accelerates EMT. Conversely, expression of LRIG1 in highly invasive Basal B breast cancer cells provokes a mesenchymal-to-epithelial transition accompanied by a dramatic suppression of tumorsphere formation and a striking loss of invasive growth in three-dimensional culture. LRIG1 expression perturbs multiple signaling pathways and represses markers and effectors of the mesenchymal state. Furthermore, LRIG1 expression in MDA-MB-231 breast cancer cells significantly slows their growth as tumors, providing the first in vivo evidence that LRIG1 functions as a growth suppressor in breast cancer.

Mueller-matrix polarimeter using analysis of the nonlinear voltage-retardance relationship for liquid-crystal variable retarders.

A method for using liquid-crystal variable retarders (LCVRs) with continually varying voltage to measure the complete Mueller matrix of a general sample is presented. The LCVRs are usually employed with fixed retardance values due to the nonlinear voltage-retardance behavior that they show. For the measurement method presented here, the nonlinear voltage-retardance relationship is first measured, and then a linear fit of the known retardance terms to the detected signal is performed. For a gap of air, the measurement error in the Mueller-matrix polarimeter is estimated at 1%-10%, depending on the Mueller-matrix element. Also, we present experimental results for a Glan-Thompson prism polarizer as a test sample, and we use the measured Mueller parameters as functions of the orientation of the optical axes of the polarizer as an indication of the quality of the polarimeter. In addition, results are compared to a typical step-voltage method to measure the Mueller matrix. Both methods give good results.

Stokes polarimetry using analysis of the nonlinear voltage-retardance relationship for liquid-crystal variable retarders.

We present a method for using liquid-crystal variable retarders (LCVR's) with continually varying voltage to measure the Stokes vector of a light beam. The LCVR's are usually employed with fixed retardance values due to the nonlinear voltage-retardance behavior that they show. The nonlinear voltage-retardance relationship is first measured and then a linear fit of the known retardance terms to the detected signal is performed. We use known waveplates (half-wave and quarter-wave) as devices to provide controlled polarization states to the Stokes polarimeter and we use the measured Stokes parameters as functions of the orientation of the axes of the waveplates as an indication of the quality of the polarimeter. Results are compared to a Fourier analysis method that does not take into account the nonlinear voltage-retardance relationship and also to a Fourier analysis method that uses experimental voltage values to give a linear retardance function with time. Also, we present results of simulations for comparison.

Postpartum aHUS secondary to a genetic abnormality in factor H acquired through liver transplantation.

We report here a young female who underwent a successful deceased donor liver transplant for hepatic vein thrombosis. Five years after transplantation she developed postpartum atypical hemolytic uremic syndrome (aHUS). She did not recover renal function. Mutation screening of complement genes in her DNA did not show any abnormality. Mutation screening of DNA available from the donor showed a nonsense CFH mutation leading to factor H deficiency. Genotyping of the patient showed that she was homozygous for an aHUS CD46 at-risk haplotype. In this individual, the development of aHUS has been facilitated by the combination of a trigger (pregnancy), an acquired rare genetic variant (CFH mutation) and a common susceptibility factor (CD46 haplotype).

Monitoring of the West Nile virus epidemic in Spain between 2010 and 2011.

West Nile virus (WNV) is a mosquito-transmitted flavivirus recognized as an emerging and re-emerging pathogen in different countries. This study describes the monitoring of the first WNV epidemic in Spain between 2010 and 2011. Between September and December 2010, 36 outbreaks of WNV in horses were reported in three different provinces of Andalusia (southern Spain), with no apparent spread outside this area. The temporal distribution and the clinical signs observed during the WNV epidemic in Spain were, in general, similar to those reported in Europe and in the Mediterranean Basin. Morbidity, mortality and fatality rate in the affected herds were 4.6, 1.4 and 35.3%, respectively. Thirty-six of 75 (47.4%) suspected herds investigated presented at least one IgM seropositive animal. The individual seroprevalence in unvaccinated animals from the infected holdings was 51.7%. RNA WNV lineage 1 virus was confirmed from blood and cerebrospinal fluid samples in a lethally infected horse. The entomological survey showed that the most abundant mosquito species detected in the affected area was Culex pipiens. A cross-sectional study was carried out in non-suspected herds between April 2010 and February 2011 in the affected area. The individual seroprevalence was 11.0%, and six of the 38 herds sampled (15.8%) presented at least one seropositive animal. The results showed active WNV circulation several months before the first outbreak was reported in horses. The seropositivity found in municipalities where clinical cases were not reported indicates a higher geographical dissemination of the virus. Significantly higher seroprevalences were detected in areas close to Morocco. Furthermore, 90 wild ruminants were tested for the presence of antibodies against WNV, but the results were all negative.

A role for nucleotides in support of breast cancer angiogenesis: heterologous receptor signalling.

BACKGROUND: Human breast carcinoma cells secrete an adenosine 5'-diphosphate transphosphorylase (sNDPK) known to induce endothelial cell tubulogenesis in a P2Y receptor-dependent manner. We examined sNDPK secretion and its effects on human endothelial cells. METHODS: Nucleoside diphosphate kinase (NDPK) secretion was measured by western blot and enzyme-linked immunosorbent assay, while transphosphorylase activity was measured using the luciferin-luciferase ATP assay. Activation of MAPK was determined by western blot analysis, immunofluorescence and endothelial cell proliferation and migration. RESULTS: A panel of breast cancer cell lines with origin as ductal carcinoma, adenocarcinoma or medullary carcinoma, secrete sNDPK-A/B. Addition of purified NDPK-B to endothelial cultures activated VEGFR-2 and Erk(1/2), both of which were blocked by inhibitors of NDPK and P2Y receptors. Activation of VEGFR-2 and ErK(1/2) by 2-methylthio-ATP (2MeS-ATP) was blocked by pretreatment with the P2Y(1)-specific antagonist MRS2179, the proto-oncogene non-receptor tyrosine kinase (Src) inhibitor PP2 or the VEGFR-2 antagonist SU1498. Nucleoside diphosphate kinase-B stimulates cell growth and migration in a concentration-dependent manner comparable to the effect of vascular endothelial growth factor. Treatment of endothelial cells with either NDPK-B or 2MeS-ATP induced migration, blocked by P2Y(1), Src or VEGFR-2 antagonists. CONCLUSION: sNDPK supports angiogenesis. Understanding the mechanism of action of sNDPK and P2Y(1) nucleotide signalling in metastasis and angiogenesis represent new therapeutic targets for anti-angiogenic therapies to benefit patients.

Molecular architecture of the human specialised atrioventricular conduction axis.

The atrioventricular conduction axis, located in the septal component of the atrioventricular junctions, is arguably the most complex structure in the heart. It fulfils a multitude of functions, including the introduction of a delay between atrial and ventricular systole and backup pacemaking. Like any other multifunctional tissue, complexity is a key feature of this specialised tissue in the heart, and this complexity is both anatomical and electrophysiological, with the two being inextricably linked. We used quantitative PCR, histology and immunohistochemistry to analyse the axis from six human subjects. mRNAs for ~50 ion and gap junction channels, Ca(2+)-handling proteins and markers were measured in the atrial muscle (AM), a transitional area (TA), inferior nodal extension (INE), compact node (CN), penetrating bundle (PB) and ventricular muscle (VM). When compared to the AM, we found a lower expression of Na(v)1.5, K(ir)2.1, Cx43 and ANP mRNAs in the CN for example, but a higher expression of HCN1, HCN4, Ca(v)1.3, Ca(v)3.1, K(ir)3.4, Cx40 and Tbx3 mRNAs. Expression of some related proteins was in agreement with the expression of the corresponding mRNAs. There is a complex and heterogeneous pattern of expression of ion and gap junction channels and Ca(2+)-handling proteins in the human atrioventricular conduction axis that explains the function of this crucial pathway.

The lymphovascular embolus of inflammatory breast cancer exhibits a Notch 3 addiction.

Inflammatory breast carcinoma (IBC) is characterized by exaggerated lymphovascular invasion (LVI), recapitulated in our human xenograft, MARY-X. This model exhibited lymphovascular emboli in vivo and corresponding spheroids in vitro. Owing to the morphological and gene profile resemblance of these spheroids to embryonal blastocysts, we wondered whether they might exhibit embryonic stem cell signaling. Specifically we investigated Notch and observed selective Notch 3 activation by expression profiling, reverse transcriptase- and real-time PCR, western blot and immunofluorescence in vitro, and immunohistochemistry in vivo. Notch 3 intracellular domain (N3icd) and six target genes, HES-5, HEY-1, c-Myc, Deltex-1, NRARP and PBX1, markedly increased in MARY-X. In addition, a significant percentage of MARY-X cells expressed aldehyde dehydrogenase (ALDH), a stem cell marker. Only the ALDH(+) cells were capable of secondary spheroidgenesis, tumorigenicity and self-renewal. Inhibiting Notch 3 activation in vitro with γ-secretase inhibitors (GSIs) or small interfering RNA resulted in a downregulation of Notch target genes, including CD133, and an induction of caspase 3-mediated apoptosis. Transfection of N3icd but not Notch 1 intracellular domain into normal human mammary epithelial cells resulted in increased expression of Notch target genes and induction of spheroidgenesis. GSI in vivo resulted in inhibitory but diffusion-limited effects on Notch 3 signaling, resulting in xenograft growth reduction. The lymphovascular emboli of human IBC exhibited dual N3icd and ALDH1 immunoreactivities independently of molecular subtype. This Notch 3 addiction of lymphovascular emboli might be exploited in future therapeutic strategies.

Efficiency of gene transfection reagents in NG108-15, SH-SY5Y and CHO-K1 cell lines.

Several gene delivery reagents were analyzed for their transfection efficiency. Genes studied belonged to the class of mammalian proteins termed regulators of G-protein signaling (RGS), ranged in size up to 2.2 Kb long and were transfected into the NG108-15, SH-SY5Y and CHO-K1 cell lines. Prior to transfection, genes were cloned into a nonviral vector pcDNA 6.2/EmGFP, so as to express a green fluorescent protein tag at the 3' end. Flow cytometry was used to analyze cell fluorescent activity and thereby transfection efficiency. Gene delivery reagents Lipofectamine 2000 and ExGen 500 produced more effective transfection in NG108-15 cells whereas Lipofectamine 2000, ExGen 500 and TurboFectin 8.0 were more effective in CHO-K1 cells. In both these cell lines, transfection efficiency reached 60-80%. In SH-SY5Y cells, TurboFectin 8.0 produced the best transfection result; however efficiency level was only 5%. Gene size had no effect on transfection efficiency. Unlike Lipofectamine 2000, cells transfected using ExGen 500 showed morphological deformation. Our results suggest that Lipofectamine 2000 is the most suitable transfection medium for gene delivery to NG108-15 and CHO-K1 cells.

Structural remodelling of the sinoatrial node in obese old rats.

During ageing, the function of sinoatrial node (SAN), the pacemaker of the heart, declines, and the incidence of sick sinus syndrome increases markedly. The aim of the study was to investigate structural and functional remodelling of the SAN during ageing. Rats, 3 and 24 months old (equivalent to young adult and approximately 69-year-old humans), were studied. Extracellular potential recording from right atrial preparations showed that (as expected) the intrinsic heart rate was slower in the old animals. It also showed a shift of the leading pacemaker site towards the inferior vena cava in the old animals. Consistent with this, intracellular potential recording showed that slow pacemaker action potentials were more widespread and extended further towards the inferior vena cava in old animals. Immunohistochemistry demonstrated that SAN tissue expressing HCN4, but lacking the expression of Na(v)1.5 (lack of Na(v)1.5 explains why pacemaker action potential is slow), was also more widespread and extended further towards the inferior vena cava in the old animals. Immunolabelling of caveolin3 (expressed in cell membrane of cardiac myocytes) demonstrated that there was a hypertrophy of the SAN cells in the old animals. Histology, quantitative PCR, and immunohistochemistry revealed evidence of a substantial age-dependent remodelling of the extracellular matrix (e.g. approximately 79% downregulation of genes responsible for collagens 1 and 3 and approximately 52% downregulation of gene responsible for elastin). It is concluded that the age- (and/or obesity-) dependent decline in SAN function is associated with a structural remodelling of the SAN: an enlargement of the SAN, a hypertrophy of the SAN cells, and a remodelling of the extracellular matrix.

Cellular localization and distribution of dopamine D(4) receptors in the rat cerebral cortex and their relationship with the cortical dopaminergic and noradrenergic nerve terminal networks.

The role of the dopamine D(4) receptor in cognitive processes and its association with several neuropsychiatric disorders have been related to its preferential localization in the cerebral cortex. In the present work we have studied in detail the regional and cellular localization of the dopamine D(4) receptor immunoreactivity (IR) in the rat cerebral cortex and its relationship to the dopaminergic and noradrenergic nerve terminal networks, since both dopamine and noradrenaline have a high affinity for this receptor. High levels of D(4) IR were found in motor, somatosensory, visual, auditory, temporal association, cingulate, retrosplenial and granular insular cortices, whereas agranular insular, piriform, perirhinal and entorhinal cortices showed low levels. D(4) IR was present in both pyramidal and non-pyramidal like neurons, with the receptor being mainly concentrated to layers II/III. Layer I was observed to be exclusively enriched in D(4) IR branches of apical dendrites. Finally, mismatches were observed between D(4) IR and tyrosine hydroxylase and dopamine beta-hydroxylase IR nerve terminal plexuses, indicating that these receptors may be activated at least in part by dopamine and noradrenaline operating as volume transmission signals. The present findings support a major role of the dopamine D(4) receptor in mediating the transmission of cortical dopamine and noradrenaline nerve terminal plexuses.

Effects of streptozotocin-induced diabetes on connexin43 mRNA and protein expression in ventricular muscle.

Abnormal QT prolongation with the associated arrhythmias is a significant predictor of mortality in diabetic patients. Gap junctional intercellular communication allows electrical coupling between heart muscle cells. The effects of streptozotocin (STZ)-induced diabetes mellitus on the expression and distribution of connexin 43 (Cx43) in ventricular muscle have been investigated. Cx43 mRNA expression was measured in ventricular muscle by quantitative PCR. The distribution of total Cx43, phosphorylated Cx43 (at serine 368) and non-phosphorylated Cx43 was measured in ventricular myocytes and ventricular muscle by immunocytochemistry and confocal microscopy. There was no significant difference in Cx43 mRNA between diabetic rat ventricle and controls. Total and phosphorylated Cx43 were significantly increased in ventricular myocytes and ventricular muscle and dephosphorylated Cx43 was not significantly altered in ventricular muscle from diabetic rat hearts compared to controls. Disturbances in gap junctional intercellular communication, which in turn may be attributed to alterations in balance between total, phosphorylated and dephosporylated Cx43, might partly underlie prolongation of QRS and QT intervals in diabetic heart.

Glutaminase activity is confined to the mantle of the islets of Langerhans.

Glutamatergic signalling plays an important role in the coordination of hormone secretion from the endocrine pancreas. Thus, glutamate production must be a process exquisitely regulated to ensure a proper transmitter function. Recently we have reported that the endocrine pancreas co-expresses two isoforms of the protein glutaminase (GA), denoted as kidney-type (KGA) and liver-type (LGA). However, how GA activity, and therefore glutamate production, is regulated in the islets represents a critical issue that remains unresolved. Since the purification of these enzymes from rat islets is a daunting task, in order to characterize each isoform we have taken advantage of the spatial segregation of these isoenzymes in pancreas. To assist us with this goal, we have developed a new procedure that enables us to assay GA activity in situ. The assay is highly specific for GA as indicated by its dependence on glutamine and orthophosphate. Surprisingly, LGA, which is abundantly expressed by beta-cells, did not show detectable activity under the assay conditions. All the GA activity detected in pancreatic islets was attributed to KGA and was confined to the mantle of the islets. Double labelling analyses strongly suggested that alpha-cells should be regarded as the site of glutamate production in the endocrine pancreas.

Expression of Kir2.1 and Kir6.2 transgenes under the control of the alpha-MHC promoter in the sinoatrial and atrioventricular nodes in transgenic mice.

Kir2.1 and Kir6.2 are ion channel subunits partly responsible for the background inward rectifier and ATP-sensitive K(+) currents (I(K1) and I(KATP)) in the heart. Very little is known about how the distribution of ion channel subunits is controlled. In this study, we have investigated the expression (at protein and mRNA levels) of GFP-tagged Kir2.1 and Kir6.2 transgenes under the control of the alpha-MHC promoter in the sinoatrial node (SAN), atrioventricular node (AVN), His bundle and working myocardium of transgenic mice. After dissection, serial 10-microm cryosections were cut. Histological staining was carried out to identify tissues, confocal microscopy was carried out to map the distribution of the GFP-tagged ion channel subunits and in situ hybridization was carried out to map the distribution of corresponding mRNAs. We demonstrate heterologous expression of the ion channel subunits in the working myocardium, but not necessarily in the SAN, AVN or His bundle; the distribution of the subunits does not correspond to the expected distribution of alpha-MHC. Both protein and mRNA expression does, however, correspond to the expected distributions of native Kir6.2 and Kir2.1 in the SAN, AVN, His bundle and working myocardium. The data demonstrate novel transcriptional and/or post-transcriptional control of ion channel subunit expression and raise important questions about the control of regional expression of ion channels.

Connexins in the sinoatrial and atrioventricular nodes.

The sinoatrial node (SAN) and the atrioventricular node (AVN) are specialized tissues in the heart: the SAN is specialized for pacemaking (it is the pacemaker of the heart), whereas the AVN is specialized for slow conduction of the action potential (to introduce a delay between atrial and ventricular activation during the cardiac cycle). These functions have special requirements regarding electrical coupling and, therefore, expression of connexin isoforms. Electrical coupling in the center of the SAN should be weak to protect it from the inhibitory electrotonic influence of the more hyperpolarized non-pacemaking atrial muscle surrounding the SAN. However, for the SAN to be able to drive the atrial muscle, electrical coupling should be strong in the periphery of the SAN. Consistent with this, in the center of the SAN there is no expression of Cx43 (the principal connexin of the working myocardium) and little expression of Cx40, but there is expression of Cx45 and Cx30.2, whereas in the periphery of the SAN Cx43 as well Cx45 is expressed. In the AVN, there is a similar pattern of expression of connexins as in the center of the SAN and this is likely to be in large part responsible for the slow conduction of the action potential.

Computer three-dimensional reconstruction of the sinoatrial node.

BACKGROUND: There is an effort to build an anatomically and biophysically detailed virtual heart, and, although there are models for the atria and ventricles, there is no model for the sinoatrial node (SAN). For the SAN to show pacemaking and drive atrial muscle, theoretically, there should be a gradient in electrical coupling from the center to the periphery of the SAN and an interdigitation of SAN and atrial cells at the periphery. Any model should include such features. METHODS AND RESULTS: Staining of rabbit SAN preparations for histology, middle neurofilament, atrial natriuretic peptide, and connexin (Cx) 43 revealed multiple cell types within and around the SAN (SAN and atrial cells, fibroblasts, and adipocytes). In contrast to atrial cells, all SAN cells expressed middle neurofilament (but not atrial natriuretic peptide) mRNA and protein. However, 2 distinct SAN cell types were observed: cells in the center (leading pacemaker site) were small, were organized in a mesh, and did not express Cx43. In contrast, cells in the periphery (exit pathway from the SAN) were large, were arranged predominantly in parallel, often expressed Cx43, and were mixed with atrial cells. An approximately 2.5-million-element array model of the SAN and surrounding atrium, incorporating all cell types, was constructed. CONCLUSIONS: For the first time, a 3D anatomically detailed mathematical model of the SAN has been constructed, and this shows the presence of a specialized interface between the SAN and atrial muscle.

Clinical significance of nuclear matrix-estradiol receptor complex in human sperm.

Estrogen receptor levels were determined in nuclear matrix of human spermatozoa of normospermic fertile men and idiopathic infertile men. In noncapacitated sperm cells, the distribution of the estrogen receptor in normospermic fertile men was present in 50% of the cases, whereas in idiopathic infertile men was present in 19% of the cases. In capacitated sperm cells, the distribution of the estrogen receptor in normospermic fertile men was present in 80% of cases, whereas in idiopathic infertile men was present in 31% of the cases. The values of estrogen receptors in capacitated and noncapacitated sperm cells of normospermic fertile men were 91 +/- 21 and 26 +/- 7 fmol/10(8) sperm cells, respectively, whereas in capacitated and noncapacitated sperm cells of idiopathic infertile men, the estrogen receptor values were 50 +/- 17 and 22.5 +/- 9 fmol/10(8) sperm cells, respectively. The diminution of the estrogen receptor levels in the nuclear matrix could be a biochemical indicator of male factor infertility.

Normativa para la realización e interpretación de potenciales evocados visuales en edades pediátricas / Standards for carrying out and interpreting visual evoked potentials in children

Introducción. Un paso previo indispensable para la introducción en la clínica pediátrica de los potenciales evocados visuales (PEV) provocados por estimulación con diodos emisores de luz (LED) es su caracterización a través de las diferentes etapas de maduración del sistema nervioso. Pacientes y métodos. Hemos obtenido PEV a LED en una muestra de 60 niños de entre 1 y 5 años, funcionalmente sanos, distribuida homogéneamente por edad y sexo. En cada niño se registraron las respuestas a la estimulación monocular (derecha e izquierda), binocular y sin estimulación (réplicas de cada condición). Los registros se realizaron bajo sedación con secobarbital a 3 mg/kg de peso corporal. Resultados. De acuerdo con nuestros resultados se comprueba una reducción significativa de la latencia de todos los componentes (excepto P3) y de la amplitud de N1 y P1 en función de la edad. La respuesta a LED es replicable (sobre todo intraindividuos), observándose hasta tres variantes morfológicas. La sedación no afectó la detectabilidad de la respuesta, el único efecto significativo fue una reducción de la amplitud de P1. Conclusiones. Comprobamos cambios maduracionales, reflejados en la reducción significativa de los valores de latencias de la mayoría de los componentes con el incremento de la edad, alcanzándose valores similares al adulto entre los 4 y 6 años de edad. Los resultados obtenidos nos brindan la posibilidad de difundir estos datos normativos para una mejor utilización e interpretación de los PEV a LED a edades tempranas (AU)

Normativa para la realización e interpretación de potenciales evocados visuales en edades pediátricas / Standards for carrying out and interpreting visual evoked potentials in children

Introducción. Un paso previo indispensable para la introducción en la clínica pediátrica de los potenciales evocados visuales (PEV) provocados por estimulación con diodos emisores de luz (LED) es su caracterización a través de las diferentes etapas de maduración del sistema nervioso. Pacientes y métodos. Hemos obtenido PEV a LED en una muestra de 60 niños de entre 1 y 5 años, funcionalmente sanos, distribuida homogéneamente por edad y sexo. En cada niño se registraron las respuestas a la estimulación monocular (derecha e izquierda), binocular y sin estimulación (réplicas de cada condición). Los registros se realizaron bajo sedación con secobarbital a 3 mg/kg de peso corporal. Resultados. De acuerdo con nuestros resultados se comprueba una reducción significativa de la latencia de todos los componentes (excepto P3) y de la amplitud de N1 y P1 en función de la edad. La respuesta a LED es replicable (sobre todo intraindividuos), observándose hasta tres variantes morfológicas. La sedación no afectó la detectabilidad de la respuesta, el único efecto significativo fue una reducción de la amplitud de P1. Conclusiones. Comprobamos cambios maduracionales, reflejados en la reducción significativa de los valores de latencias de la mayoría de los componentes con el incremento de la edad, alcanzándose valores similares al adulto entre los 4 y 6 años de edad. Los resultados obtenidos nos brindan la posibilidad de difundir estos datos normativos para una mejor utilización e interpretación de los PEV a LED a edades tempranas(AU)

Introduction: An essential step, prior to the introduction into paediatric practice of visual evoked potentials (VEP) caused by stimulation with light emitting diodes (LED) is their description at different stages of maturity of the nervous system. Patients and Methods: We obtained VEP to LED in a group of 60 children aged between 1 and 5 years, who were functionally healthy and equally distributed with regard to age and sex. In each case we recorded the responses to monocular stimulation (right and left), binocular stimulation and without stimulation (replicas of each condition). The recordings were made under sedation with secobarbital at a dose of 3 mg/kg body weight. Results: Our results showed a significant reduction in the latency of all components (except P3) and the amplitude of N1 and P1, as a function of the age of the child. The response to LED is reproducible (especially intra-individual) with up to three types of morphology observed. Sedation did not affect detection of the response. The only significant effect was a reduction in the amplitude of P1. Conclusions: We confirmed the changes due to maturity, reflected in a significant reduction of the latency of most components with increasing age. By between 4 and 6 years old the figures obtained were similar to those in adults. The results obtained give us the opportunity chance of publishing this standard data so that better use and interpretation of VEP to LED at an early age may be possible(AU)

Introdução. Um passo inicial indispensável para a introdução, na clínica pediátrica, dos potenciais evocados visuais (PEV) provocados por estimulação com díodos emissores de luz (LED), é a sua caracterização através das diferentes etapas de desenvolvimento do sistema nervoso. Doentes e métodos. Obtivemos PEV por LED numa amostra de 60 crianças com idade compreendida entre 1 e 5 anos, distribuída homogeneamente por idade e por sexo. Em cada criança registaram-se as respostas à estimulação monocular (direita e esquerda), binocular e sem estimulação (réplicas de cada condição). Os registos realizaram-se sob sedação com secobarbital a 3 mg/kg de peso corporal. Resultados. De acordo com os nossos resultados, é comprovada uma redução significativa da latência de todos os componentes (excepto P3) e da amplitude de N1 e P1 em função da idade. A resposta ao LED é reprodutível (sobretudo intra?indivíduos), sendo observada em três variantes morfológicas. A sedação não afectou a detecção da resposta, sendo o único efeito significativo, uma redução da amplitude de P1. Conclusões. Comprovamos alterações de desenvolvimento, que se reflectem na redução significativa dos valores de latências da maioria dos componentes, à medida que a idade aumenta, sendo alcançados valores similares aos dos adulto entre os 4 e os 6 anos de idade. Os resultados obtidos não permitem difundir estes dados normativos para uma melhor utilização e interpretação dos PEV por LED em idades baixas(AU)