Delphi consensus on recommendations for the treatment of spinal muscular atrophy in Spain (RET-AME consensus).

INTRODUCTION: Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by a biallelic mutation of the SMN1 gene, located on the long arm of chromosome 5, and predominantly affects the motor neurons of the anterior horn of the spinal cord, causing progressive muscle weakness and atrophy. The development of disease-modifying treatments is significantly changing the natural history of SMA, but uncertainty remains about which patients can benefit from these treatments and how that benefit should be measured. METHODOLOGY: A group of experts specialised in neurology, neuropediatrics, and rehabilitation and representatives of the Spanish association of patients with SMA followed the Delphi method to reach a consensus on 5 issues related to the use of these new treatments: general aspects, treatment objectives, outcome assessment tools, requirements of the treating centres, and regulation of their use. Consensus was considered to be achieved when a response received at least 80% of votes. RESULTS: Treatment protocols are useful for regulating the use of high-impact medications and should guide treatment, but should be updated regularly to take into account the most recent evidence available, and their implementation should be assessed on an individual basis. Age, baseline functional status, and, in the case of children, the type of SMA and the number of copies of SMN2 are characteristics that should be considered when establishing therapeutic objectives, assessment tools, and the use of such treatments. The cost-effectiveness of these treatments in paediatric patients is mainly influenced by early treatment onset; therefore, the implementation of neonatal screening is recommended. CONCLUSIONS: The RET-AME consensus recommendations provide a frame of reference for the appropriate use of disease-modifying treatments in patients with SMA.

Spanish translation and linguistic validation of the North Star Ambulatory Assessment for Duchenne muscular dystrophy functional evaluation. / Traducción al español y validación lingüística de la escala North Star Ambulatory Assessment para la evaluación funcional de la distrofia muscular de Duchenne.

INTRODUCTION: There is a need for reliable and properly validated outcome measures in Duchenne muscular dystrophy, both to monitor functional impairment and to assess the impact of new therapies. OBJECTIVE: We aimed to perform a translation of the North Star Ambulatory Assessment scale into Spanish and a linguistic validation of the resulting Spanish version. MATERIALS AND METHODS: A structured multistage process based on international guidelines was used, with the following steps: translation (preparation, forward translation, reconciliation, back translation, back translation review, clinicians' review), linguistic validation though pilot testing (cognitive interviewing, medical review, review of results and final changes), and finalization (proofreading, final report). RESULTS: No major difficulties were found during translation steps. Few changes were needed to reconcile forward translations. The linguistic validation process required several meetings to solve comprehension difficulties due to subtle nuances in the meaning of some words. The pilot study was carried out in 10 practitioners from different places in Spain, including both physiotherapists and specialists and registrars in physical medicine and rehabilitation. A total of 6 comments were obtained, including 2 comments on starting positions for items 4-5 (stand on one leg) and item 10 (stand on heels) and 2 comments on scoring instructions for item 3 (stand up from chair) and item 14 (jump). CONCLUSION: Our study has resulted in a convenient and reliable instrument for the quantification of functional abilities in boys with Duchenne muscular dystrophy in Spain. Our innovations in methods and our results could be used as a suggested template for the North Star Ambulatory Assessment linguistic validation in other languages.

TITLE: Traducción al español y validación lingüística de la escala North Star Ambulatory Assessment para la evaluación funcional de la distrofia muscular de Duchenne.Introducción. En la distrofia muscular de Duchenne son necesarias medidas de evaluación fiables y validadas para el seguimiento del deterioro funcional y de los efectos de los nuevos tratamientos. Objetivo. Se realizó una traducción, seguida de validación lingüística, de la escala North Star Ambulatory Assessment al español. Materiales y métodos. Se utilizó un proceso estructurado, de múltiples etapas, basado en las guías internacionales, con los siguientes pasos: traducción (preparación, traducción directa, reconciliación, retrotraducción, revisión de la retrotraducción y revisión por médicos clínicos), validación lingüística mediante una prueba piloto (entrevista cognitiva, revisión médica, revisión de resultados y ajustes finales) y finalización (revisión de pruebas e informe final). Resultados. No surgieron dificultades importantes durante los pasos de traducción. La reconciliación de las traducciones directas requirió pocos cambios. En la validación lingüística fueron precisas varias reuniones para resolver dificultades de comprensión, en matices sutiles, en el significado de algunas palabras. El estudio piloto se realizó con 10 especialistas clínicos de diferentes lugares de España (fisioterapeutas y especialistas o residentes de medicina física y rehabilitación). Hubo seis comentarios, dos de ellos sobre las posiciones de partida en los ítems 4-5 (de pie sobre un solo pie) y 13 (de pie sobre los talones), y dos sobre las instrucciones de puntuación para los ítems 3 (levantarse de la silla) y 14 (saltar). Conclusión. Nuestro estudio ha proporcionado un instrumento cómodo y fiable para cuantificar las capacidades funcionales en niños con distrofia muscular de Duchenne en España. Las innovaciones en el método y nuestros resultados podrían usarse como modelo para la validación lingüística en otros idiomas.

Traducción al español y validación lingüística de la escala North Star Ambulatory Assessment para la evaluación funcional de la distrofia muscular de Duchenne / Spanish translation and linguistic validation of the North Star Ambulatory Assessment for Duchenne muscular dystrophy functional evaluation

Introducción: En la distrofia muscular de Duchenne son necesarias medidas de evaluación fiables y validadas para el seguimiento del deterioro funcional y de los efectos de los nuevos tratamientos. Objetivo: Se realizó una traducción, seguida de validación lingüística, de la escala North Star Ambulatory Assessment al español. Materiales y métodos: Se utilizó un proceso estructurado, de múltiples etapas, basado en las guías internacionales, con los siguientes pasos: traducción (preparación, traducción directa, reconciliación, retrotraducción, revisión de la retrotraducción y revisión por médicos clínicos), validación lingüística mediante una prueba piloto (entrevista cognitiva, revisión médica, revisión de resultados y ajustes finales) y finalización (revisión de pruebas e informe final). Resultados: No surgieron dificultades importantes durante los pasos de traducción. La reconciliación de las traducciones directas requirió pocos cambios. En la validación lingüística fueron precisas varias reuniones para resolver dificultades de comprensión, en matices sutiles, en el significado de algunas palabras. El estudio piloto se realizó con 10 especialistas clínicos de diferentes lugares de España (fisioterapeutas y especialistas o residentes de medicina física y rehabilitación). Hubo seis comentarios, dos de ellos sobre las posiciones de partida en los ítems 4-5 (de pie sobre un solo pie) y 13 (de pie sobre los talones), y dos sobre las instrucciones de puntuación para los ítems 3 (levantarse de la silla) y 14 (saltar). Conclusión: Nuestro estudio ha proporcionado un instrumento cómodo y fiable para cuantificar las capacidades funcionales en niños con distrofia muscular de Duchenne en España. Las innovaciones en el método y nuestros resultados podrían usarse como modelo para la validación lingüística en otros idiomas.(AU)

Introduction: There is a need for reliable and properly validated outcome measures in Duchenne muscular dystrophy, both to monitor functional impairment and to assess the impact of new therapies.Objective: We aimed to perform a translation of the North Star Ambulatory Assessment scale into Spanish and a linguistic validation of the resulting Spanish version. Materials and methods. A structured multistage process based on international guidelines was used, with the following steps: translation (preparation, forward translation, reconciliation, back translation, back translation review, clinicians’ review), linguistic validation though pilot testing (cognitive interviewing, medical review, review of results and final changes), and finalization (proofreading, final report). Results: No major difficulties were found during translation steps. Few changes were needed to reconcile forward translations. The linguistic validation process required several meetings to solve comprehension difficulties due to subtle nuances in the meaning of some words. The pilot study was carried out in 10 practitioners from different places in Spain, including both physiotherapists and specialists and registrars in physical medicine and rehabilitation. A total of 6 comments were obtained, including 2 comments on starting positions for items 4-5 (stand on one leg) and item 10 (stand on heels) and 2 comments on scoring instructions for item 3 (stand up from chair) and item 14 (jump). Conclusion: Our study has resulted in a convenient and reliable instrument for the quantification of functional abilities in boys with Duchenne muscular dystrophy in Spain. Our innovations in methods and our results could be used as a suggested template for the North Star Ambulatory Assessment linguistic validation in other languages.(AU)

Consenso para el diagnóstico, tratamiento y seguimiento del paciente con distrofia muscular de Duchenne / Consensus on the diagnosis, treatment and follow-up of patients with Duchenne muscular dystrophy

Introducción: La distrofia muscular de Duchenne (DMD) es la miopatía más frecuente en niños, con una prevalencia mundial de aproximadamente 0,5 por cada 10.000 varones. Se caracteriza por una debilidad muscular progresiva al inicio de la infancia con aparición posterior de complicaciones musculoesqueléticas, respiratorias y cardíacas que ocasionan discapacidad, dependencia y muerte prematura. Actualmente su tratamiento se fundamenta en medidas sintomáticas multidisciplinares que han modificado favorablemente el curso de la enfermedad, por lo que resulta crucial establecer unas directrices claras y actualizadas que permitan tanto una detección temprana de la enfermedad como un adecuado tratamiento y seguimiento de sus posibles complicaciones. Desarrollo: Con el fin de obtener una visión general de los aspectos abordados por las guías actuales y detectar aquellos en los que todavía no existe un consenso y su abordaje sea relevante, se realizó una revisión de la literatura en la base de datos biomédicas de los últimos 10 años. El grado de evidencia y el nivel de recomendación de la información obtenida se clasificaron y ordenaron de acuerdo con los criterios de la American Academy of Neurology (AAN). Conclusiones: El abordaje de la DMD debe ser multidisciplinar y ajustado al perfil del paciente y su grado de evolución clínica, comprendiendo, además del tratamiento basado en corticoides, medidas a nivel gastrointestinal, respiratorio, cardiaco, fisioterapéutico y ortopédico dirigidas a mejorar la calidad de vida de los pacientes. Los estudios genéticos desempeñan un papel clave en el manejo de la enfermedad, tanto en la detección de casos y posibles portadoras como en la caracterización de la mutación implicada y el desarrollo de nuevas terapias

Introduction: Duchenne muscular dystrophy (DMD) is the most common myopathy in children, with a worldwide prevalence of approximately 0.5 cases per 10,000 male births. It is characterised by a progressive muscular weakness manifesting in early childhood, with the subsequent appearance of musculoskeletal, respiratory, and cardiac complications, causing disability, dependence, and premature death. Currently, DMD is mainly managed with multidisciplinary symptomatic treatment, with favourable results in terms of the progression of the disease. It is therefore crucial to establish clear, up-to-date guidelines enabling early detection, appropriate treatment, and monitoring of possible complications. Development: We performed a literature search of the main biomedical databases for articles published in the last 10 years in order to obtain an overview of the issues addressed by current guidelines and to identify relevant issues for which no consensus has yet been established. The degree of evidence and level of recommendation of the information obtained were classified and ordered according to the criteria of the American Academy of Neurology. Conclusions: DMD management should be multidisciplinary and adapted to the patient's profile and the stage of clinical progression. In addition to corticotherapy, treatment targeting gastrointestinal, respiratory, cardiac, and orthopaedic problems, as well as physiotherapy, should be provided with a view to improving patients' quality of life. Genetic studies play a key role in the management of the disease, both in detecting cases and potential carriers and in characterising the mutation involved and developing new therapies

Consensus on the diagnosis, treatment and follow-up of patients with Duchenne muscular dystrophy. / Consenso para el diagnóstico, tratamiento y seguimiento del paciente con distrofia muscular de Duchenne.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is the most common myopathy in children, with a worldwide prevalence of approximately 0.5 cases per 10,000 male births. It is characterised by a progressive muscular weakness manifesting in early childhood, with the subsequent appearance of musculoskeletal, respiratory, and cardiac complications, causing disability, dependence, and premature death. Currently, DMD is mainly managed with multidisciplinary symptomatic treatment, with favourable results in terms of the progression of the disease. It is therefore crucial to establish clear, up-to-date guidelines enabling early detection, appropriate treatment, and monitoring of possible complications. DEVELOPMENT: We performed a literature search of the main biomedical databases for articles published in the last 10years in order to obtain an overview of the issues addressed by current guidelines and to identify relevant issues for which no consensus has yet been established. The degree of evidence and level of recommendation of the information obtained were classified and ordered according to the criteria of the American Academy of Neurology. CONCLUSIONS: DMD management should be multidisciplinary and adapted to the patient's profile and the stage of clinical progression. In addition to corticotherapy, treatment targeting gastrointestinal, respiratory, cardiac, and orthopaedic problems, as well as physiotherapy, should be provided with a view to improving patients' quality of life. Genetic studies play a key role in the management of the disease, both in detecting cases and potential carriers and in characterising the mutation involved and developing new therapies.

Allergenome characterization of the mosquito Aedes aegypti.

BACKGROUND: Saliva and muscle-derived mosquito allergens have been purified and characterized. However, the complete set of allergens remains to be elucidated. In this study, we identified and characterized IgE-binding proteins from the mosquito species Aedes aegypti. METHODS: Serum was obtained from 15 allergic individuals with asthma and/or rhinitis and sensitized to mosquito. IgE binding was determined by ELISA. Total proteins from freeze-dried bodies of A. aegypti were extracted and IgE-reactive proteins were identified by 2D gel electrophoresis, followed by Western blot with pooled or individual sera. IgE-reactive spots were further characterized by mass spectrometry. RESULTS: Twenty-five IgE-reactive spots were identified, corresponding to 10 different proteins, some of which appeared as different variants or isoforms. Heat-shock cognate 70 (HSC-70) and tropomyosin showed IgE reactivity with 60% of the sera, lysosomal aspartic protease, and "AAEL006070-PA" (Uniprot: Q177P3) with 40% and the other proteins with <33.3% of the sera. Different variants or isoforms of tropomyosin, arginine or creatine kinase, glyceraldehyde-3-phosphate dehydrogenase (GPDH), calcium-binding protein, and phosphoglycerate mutase were also identified. The mixture of three allergens (Aed a 6, Aed a 8, and Aed a 10) seems to identify more than 80% of A. aegypti-sensitized individuals, indicating that these allergens should be considered when designing of improved mosquito allergy diagnostic tools. CONCLUSIONS: The newly identified allergens may play a role in the pathophysiology of mosquito allergy in the tropics, and some of them might be important arthropod-related proteins involved in cross-reactivity between A. aegypti and other allergenic arthropods.

Escoliosis en enfermedades neuromusculares infantiles / Scoliosis in chilhood neuromuscular diseases

Objetivo. La escoliosis es una complicaciónfrecuente y grave en la mayoría de las enfermedades neuromuscularesde la infancia. Nuestro objetivo es realizar unaactualización del tema, describiendo su historia natural y elmanejo global de la misma.Estrategia de búsqueda. Se ha revisado la base de datosMedline, completada con una búsqueda en la Biblioteca Cochrane,en lo que se refiere al tratamiento ortésico y quirúrgico,sus complicaciones y manejo multidisciplinar. Serevisan también las citas bibliográficas de los artículos seleccionados.Selección de estudios. Se han seleccionado los artículosrelativos al manejo de la escoliosis en estas enfermedades.Entre ellos destacamos dos revisiones Cochrane, una específicasobre cirugía de la escoliosis en la distrofia muscularde Duchenne (DMD), publicada en 2007 y actualizadaen 2009, y otra relativa al tratamiento con corticoidespara la misma enfermedad, publicada en 2008, un documentode consenso para pacientes con atrofia muscularespinal y una guía de práctica clínica para enfermedadesneuromusculares.Síntesis de resultados. Ante la ausencia de artículos que demuestrenla evidencia científica del manejo actual de la escoliosisse da especial importancia a los artículos de consenso.Conclusiones. Las ortesis no impiden la evolución de laescoliosis, aunque pueden mejorar la sedestación. Actualmentela cirugía es considerada como la única intervencióncapaz de frenar la evolución de la curva y debe realizarse encentros especializados, siendo necesario un abordaje multidisciplinaren el pre y postoperatorio(AU)

Objective. Scoliosis is a frequent, seriouscomplication in the majority of childhood neuromusculardiseases. Our objective was to carry out an updating surveyon the topic, describing its natural history and its globalmanagement.Search strategy. We reviewed the Medline database,complemented by a search in the Cochrane Library, withreference to orthopedic devices and surgical treatment,com plications, and multidisciplinary management. Wealso reviewed the bibliographic citations of the selectedarticles.Study selection. Selected were those articles related tothe management of scoliosis in these diseases. Of note weretwo Cochrane reviews, one specifically on surgery for scoliosisin Duchenne’s muscular dystrophy, published in 2007and updated in 2009, and another relating to treatment ofthe same disease with corticoids, published in 2008, as wellas a consensus document for patients with spinal muscularatrophy and a practical clinical guide for neuromuscular disorders.Synthesis of results. Given the lack of articles with scientificevidence on the current management of scoliosis, theconsensus articles are of particular importance.Conclusions. Orthopedic devices do not limit the evolutionof scoliosis although they may improve sedestation.Currently surgery is considered to be the only interventioncapable of stopping the evolution of the curvature. It mustbe carried out in specialized centers and it requires a multidisciplinaryapproach both pre- and post-operative(AU)

Influencia de la recuperación de la marcha sobre el tiempo de ingreso hospitalario en el niño y adolescente con traumatismo craneoencefálico / Influence of the recovery of walking on the hospital impatient time in children and adolescents with traumatica brain injury

Introducción. El traumatismo craneoencefálico (TCE) es la primera causa de discapacidad adquirida entrela población infantil y juvenil, y la recuperación de la marchauno de los principales objetivos de los programas de rehabilitación. La finalidad de este trabajo es estudiar la influencia de la capacidad de la marcha en el momento del alta hospitalaria,y su repercusión sobre el tiempo de estancia hospitalaria en un grupo de niños y adolescentes con TCE ingresadosen el Servicio de Rehabilitación de un hospital infantil. Pacientes y métodos. Evaluamos 40 niños con TCE y conuna edad media de 13,5 años ingresados en la planta de Rehabilitaciónde un hospital infantil desde el año 2001 hasta el 2006. En el momento del alta hospitalaria la marcha se clasificó de forma cuantitativa por su presencia o ausencia, y de forma cualitativa por ser autónoma o asistida. Las variablesanalizadas fueron: tipo de lesión según la neuroimagen, lesiones asociadas en extremidades inferiores y/o pelvis, días de estancia en la Unidad de Cuidados Intensivos (UCI), en la planta de Rehabilitación y días de estancia total, presencia del síndrome de disfunción autonómica (SDA) y pronóstico funcionalal alta según la escala de resultados de Glasgow (GOS). Resultados. En el momento del alta hospitalaria 35 niños(87,5 %) realizaban marcha; 29 de ellos (72,5 %) lo hacían de forma autónoma y 6 (15,0 %) de forma asistida. Los 5 restantes (12,5 %) no deambulaban. Tres pacientes presentaron el síndrome de disfunción autonómica, ninguno de los cualescaminaba. La estancia media hospitalaria fue de 32,15 días enlos ambulantes y de 46,35 en los no ambulantes. Se encontró correlación entre la capacidad de marcha, el tiempo medio de coma y los días de estancia en la UCI. Otras variables correlacionadas,aunque estadísticamente menos significativas, fueron los días de estancia en la planta de Rehabilitación y el tiempo total de ingreso (AU)

Introduction. Traumatic brain injury (TBI) is the most important cause of acquired disability in children and young people. Restoring walking ability is one of the primary purposes of our rehabilitation program. This work has aimed to study the incidence of the walking ability on hospital discharge time and its effects on the average hospital stay in children and young people with TBI admitted to a Children¿s Hospital Rehabilitation Service. Patients and methods. Forty children with TBI and an average age of 13.5 were admitted to the rehabilitation service between 2001 and 2006. Walking was evaluated at the time of discharge quantitatively (presence or absence of walking ability) and qualitatively (independent or device assisted walking). The variables analyzed were: lesion type through neuroimaging, associated lower limb injuries, average stay in ICU (Intensive care Unit) and Rehabilitation Service, presence of Autonomic Dysfunction Syndrome (SDA) and functional outcome on discharge by Glasgow Outcome Scale (GOS). Results. Thirty-five (87.5 %) of the 40 children and adolescents were walkers on discharge, 29(72.5 %) as independent walkers, 6(15.0 %) walked with device assistance and 5 (12.5 %) were non-walkers. Average Hospital stay was 32.15 days for walking children and 46.35 for non-walking ones. A correlation was found between walking ability, length of coma and length of the impatient stay in the ICU. Other correlated variables but with less statistical significance were average Rehabilitation service stay and total length of impatient stay. We did not find any correlation with initial TBI severity or with lower limb or pelvis injuries. Conclusions. Most of the children were walkers at discharge. The average Rehabilitation impatient stay and total average inpatient stay were lower in non-walking patients. We conclude that walking ability has an influence over total average Hospital inpatient stay (AU)

Dose of compound A, not sevoflurane, determines changes in the biochemical markers of renal injury in healthy volunteers.

UNLABELLED: Administration of sevoflurane in a circle absorption system generates Compound A, a nephrotoxin in rats. Reports examining the potential of Compound A to produce renal injury in humans have provided conflicting results. We tested the possibility that there is a threshold to Compound A-induced renal injury in humans and that, above this threshold, renal injury increases with increasing doses of Compound A. Eleven volunteers received 3% sevoflurane for 8 h at 2 L/min, and three volunteers received 3% sevoflurane for 8 h at 4-6 L/min. We measured inspired and expired concentrations of Compound A and urinary excretion of albumin, alpha-glutathione-S-transferase (GST), and glucose. The median urinary excretion of albumin, glucose, and alpha-GST for the first 3 days after anesthesia increased significantly from preanesthetic values in the 2-L/min group. Compound A doses < 240 ppm-h resulted in normal urinary excretion of albumin, glucose, and alpha-GST. Five of seven subjects who received doses > 240 ppm-h had abnormal excretion of albumin, and six of seven had abnormal alpha-GST urinary excretion (P < 0.05). Urinary excretion of albumin, alpha-GST, and glucose was normal by 14 days after exposure. We conclude that sevoflurane administration for 8 h at 2 L/min results in albuminuria and enzymuria when the dose of Compound A exceeds 240 ppm-h. That is, a Compound A concentration of 30 ppm breathed for > or = 8 h may produce transient renal injury. IMPLICATIONS: We examined the dose-response relationship of sevoflurane/Compound A and urinary excretion of albumin, glucose, and alpha-GST. Sevoflurane exposure for 8 h at a 2-L/min inflow rate produces transient albuminuria and enzymuria in healthy volunteers when the dose of Compound A exceeds 240 ppm-h (30 ppm for 8 h).

Difficult intubation from gastroesophageal reflux disease in adults.

Two cases of difficult intubation are presented. Both cases presented with red swollen arytenoids, swollen false vocal cords, and subglottic stenosis. Tracheal intubation could not be achieved for these reasons. Both patients were placed on gastrointestinal prokinetic drugs and histamine-two blocker, as a diagnosis of gastroesophageal reflux disease (GERD) was made. In one case, follow-up by an otolaryngotic surgeon showed reversal of the above findings. In the other case, one tracheal intubation was achieved eventually. GERD occurs frequently. Clinicians need to maintain a high index of suspicion for GERD-related airway changes so as to avoid potential difficult intubations.

Recovery parameters after sevoflurane and isoflurane anesthesia.

We compared recovery times in patients with American Society of Anesthesiologists physical status I-III receiving sevoflurane or isoflurane during surgical procedures longer than 1 hour in duration. Of the 50 patients enrolled, 23 received sevoflurane and 27 received isoflurane. Anesthetic gases were discontinued abruptly at the end of the surgical procedure. The following parameters were recorded: time to emergence (opens eyes), time to extubation, response to verbal command (squeezes hand of observer), and orientation (time and place). Exposure times to the agents were similar. The time to emergence was significantly less with sevoflurane than with isoflurane (5.6 vs 11.2 min, respectively). There were no significant differences in time to extubation, response to verbal command, or orientation between the groups. Our data support more rapid emergence with sevoflurane than with isoflurane in surgical procedures longer than 1 hour in duration.

Sevoflurane versus isoflurane for maintenance of anesthesia: are serum inorganic fluoride ion concentrations of concern?

Sevoflurane administration can result in increased serum inorganic fluoride ion concentrations, which have been associated with inhibition of renal concentrating ability. We measured serum fluoride levels, renal function, and recovery variables as a function of time in ASA grade I-III patients administered general anesthesia with isoflurane or sevoflurane for at least 1 h. Fifty patients were exposed to sevoflurane (< or = 2.4% inspired concentration) or isoflurane (< or = 1.9% inspired concentration) for maintenance of anesthesia as part of a multicenter trial. Blood was collected for determination of serum fluoride ion concentration, electrolytes, blood urea nitrogen, and creatinine at various time points pre- and postoperatively. Mean serum fluoride levels were significantly increased in sevoflurane versus isoflurane groups at all time points; the mean peak serum levels were 28.2 +/- 14 mumol/L at 1 h for sevoflurane and 5.08 +/- 4.35 mumol/L at 12 h for isoflurane. Sevoflurane-mediated increases in serum fluoride levels peaked at 1 h and, in general, decreased rapidly after discontinuation of the anesthesia. Three of 24 patients exposed to sevoflurane had one or more fluoride levels > 50 mumol/L. One of these patients had a serum inorganic fluoride ion level > 50 mumol/L at 12 h after sevoflurane, and an additional patient had fluoride levels > 33 mumol/L for up to 24 h after sevoflurane discontinuation. Those two patients also demonstrated an increase in serum blood urea nitrogen and creatinine at 24 h after sevoflurane administration compared with baseline. The elimination half-life of serum fluoride ion was 21.6 h. The results of this study suggest the possibility of sevoflurane induced nephrotoxicity.

Natural history of spinal cord infarction caused by nucleus pulposus embolism.

Nucleus pulposus embolism causing spinal cord infarction is exceptional. A 16-year-old girl was seen with sudden onset of interscapular pain and paraplegia from fatal ischemic transverse myelopathy due to arterial and venous occlusions by fibrocartilaginous embolism. In 32 cases of nucleus pulposus embolism, females predominated (69%) and age distribution was bimodal with peaks at 22 and 60 years (median, 38.5). Embolization was either arterial and venous (50%) or purely arterial (50%). Myelopathy predominated in cervical (69%) and lumbosacral (22%) segments. Schmorl's nodes, larger volume and vascularization of nucleus pulposus in the young, and spinal arteriovenous communications, trauma, and degenerative changes in older patients could be important pathogenetic factors. Diagnosis requires histopathologic confirmation. Nucleus pulposus embolism may be an underlying cause in cases diagnosed as transverse myelitis and ischemic infarction of spinal cord.

Fenoldopam infusion for the treatment of postoperative hypertension.

STUDY OBJECTIVE: To examine the safety and efficacy of intravenous fenoldopam as compared to placebo for the treatment of postoperative hypertension. DESIGN: Randomized, placebo-controlled, double-blind study. SETTING: Community hospital. PATIENTS: 16 ASA I-III hypertensive patients scheduled for noncardiac surgical procedures. INTERVENTIONS: Treatment with fenoldopam or placebo was initiated immediately after other causes of hypertension had been ruled out. Hypertension was defined as a supine systolic blood pressure (SBP) or diastolic blood pressure (DBP) greater than 20% over the patient's preoperative baseline, which was obtained 6 hours prior to the procedure with the patient lying quietly. The baseline consisted of 3 consecutive blood pressure (BP) measurements obtained at 5-minute intervals and not varying by more than 10%. Fenoldopam or placebo infusion was initiated at 0.1 microgram/kg/min and increased and decreased as necessary until the therapeutic goal BP was reached or treatment failure had occurred. The therapeutic goal BP was a decrease to at least 10% above the preoperative baseline, and failure of treatment was defined as inability to reach this BP level after 15 minutes at 1.5 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: BP and heart rate (HR) data were collected consistently throughout the study and 1 hour after termination of infusion. Laboratory studies and 12-lead electrocardiographic results were obtained at the start of the study and repeated 24 hours after termination of infusion. Blood samples were obtained for the measurement of epinephrine, norepinephrine, and dopamine levels and were analyzed using high-performance liquid chromatography with electrochemical detection. Pretreatment BP measurements were significantly elevated from baseline in both groups. Fenoldopam treatment significantly reduced BP to the therapeutic goal in 8 of 8 patients; placebo reduced BP to this goal in only 4 of 8 patients (p < 0.05). At the end of the titration period, the therapeutic goal BP was not significantly different from baseline in the fenoldopam group. HR was significantly elevated (p < 0.05) at goal in the fenoldopam group as compared with the placebo group. Fenoldopam administration lowered SBP and DBP to goal in a mean time of 28 minutes versus 42.5 minutes in the placebo group. There were no significant differences in catecholamine levels at any of the measurement periods. CONCLUSION: Fenoldopam is an effective drug for reducing BP following hypertensive episodes in the postoperative setting. Fenoldopam use is associated with an increase in HR versus placebo.

Acute ischemic stroke from fibrocartilaginous embolism to the middle cerebral artery.

BACKGROUND AND PURPOSE: Fibrocartilaginous embolism from the nucleus pulposus has been reported as a rare cause of spinal cord ischemia. We were unable to find previous reports of embolism from this source to cerebral arteries. CASE DESCRIPTION: A previously healthy 17-year-old girl fell during a basketball game. Left hemiparesis and unresponsiveness developed followed by signs of right uncal herniation and death over a 3-day period. There was no evidence of neck, head, or spine trauma, and cardiac evaluation was normal. Neuropathological examination showed extensive ischemic infarction of the right middle cerebral artery territory, brain edema, and herniation. Complete embolic occlusion of the right middle cerebral artery by fibrocartilaginous material, consistent with nucleus pulposus, was documented. Small, terminal coronary artery branches also showed embolism by the same material and limited areas of myocardial infarction. CONCLUSIONS: Acute cerebral embolism after minor trauma in a young patient may be rarely due to fibrocartilaginous embolism from the nucleus pulposus. The pathogenesis of this problem remains poorly understood, but systemic embolism appeared to have occurred in this case.

Perioperative arrhythmias with a propofol-based anesthetic.

Propofol was used for the induction and maintenance of anesthesia in a patient undergoing a laparoscopic tubal ligation. This new anesthetic has not been associated with postoperative ventricular arrhythmias. This report demonstrates the occurrence of supraventricular tachycardia deteriorating to ventricular tachycardia in a patient who received propofol. Included is a discussion of the possible causes of this event.