Uso de vasopresina en el postoperatorio de cirugía de Fontan: inferencias sobre morbimortalidad / Vasopressin use in postoperative Fontan surgery: implications for morbidity and mortality

Introducción: Se ha postulado que el uso de vasopresina tendría efectos beneficiosos en el postoperatorio de cirugía cardiovascular. Objetivo: Evaluar la respuesta a la vasopresina en el postoperatorio (POP) de cirugía de Fontan de nuestra población. Métodos: Estudio de casos y controles anidados en una cohorte retrospectiva. Se incluyeron pacientes con cirugía de Fontan entre 2014 y 2019. Se registraron variables demográficas, datos del cateterismo pre-Fontan, días de asistencia respiratoria mecánica (ARM), necesidad de inotrópicos, diuréticos, diálisis, dieta hipograsa, octreotide, sildenafil y nutrición parenteral total (NPT); balance de fluidos al primer y segundo día POP, necesidad de cateterismo en el POP, días de permanencia de tubo pleural, días de internación, necesidad de reinternación y mortalidad. Se compararon los grupos con y sin vasopresina utilizando la prueba de Mann- Whitney-Wilcoxon test. Se consideró significativa una p < 0.05. Resultados: Del total analizado, 35 pacientes recibieron vasopresina. En el grupo control fueron 58 pacientes con características similares de gravedad sin vasopresina. No se encontraron diferencias en la evolución postoperatoria entre ambos grupos. El grupo con vasopresina recibió en mayor proporción dieta hipograsa. Conclusiones: En nuestra serie el uso de vasopresina no marcó diferencias significativas en términos de morbimortalidad con relación al grupo control (AU)

Introduction: The use of vasopressin has been suggested to have beneficial effects in the postoperative period after cardiovascular surgery. Objective: To evaluate the response to vasopressin in the postoperative period (POP) of Fontan surgery in our population. Methods: Nested case-control study in a retrospective cohort. Patients who underwent Fontan surgery between 2014 and 2019 were included. Demographic variables, pre-Fontan catheterization data, days of mechanical ventilation (MRA), need for inotropics, diuretics, dialysis, low-fat diet, octreotide, sildenafil and total parenteral nutrition (TPN); fluid balance at first and second day POP, need for catheterization at POP, duration of chest tube drainage, days of hospitalization, need for readmission, and mortality were recorded. Groups with and without vasopressin were compared using the Mann-Whitney- Wilcoxon test. A p < 0.05 was considered significant. Results: Of all patients analyzed, 35 received vasopressin. The control group consisted of 58 patients with similar severity characteristics who did not receive vasopressin. No differences were found in the postoperative outcome between the two groups. The vasopressin group received a higher proportion of low-fat diet. Conclusions: In our series the use of vasopressin did not show significant differences in terms of morbidity and mortality compared to the control group (AU)

El espacio muerto (VD/VT) como predictor de éxito en la extubación de pacientes postquirúrgicos de cirugía cardiovascular pediátrica / Dead space (VD/VT) as a predictor of successful extubation of patients after pediatric cardiovascular surgery

Introducción: La ventilación mecánica (VM) forma parte de la recuperación postoperatoria (PO) de niños con cirugía de cardiopatía congénita, pero su uso no está exento de riesgos. El fracaso de extubación (FE) se ha asociado con internaciones prolongadas, aumento de complicaciones y mortalidad. El objetivo es determinar un valor de Vd/Vt predictor de extubación exitosa (EE). Material y métodos: estudio de cohorte prospectivo y observacional realizado del 1 de Enero al 31 de Diciembre de 2016 en niños menores de 6 meses cursando PO de cirugía cardiovascular con circulación extracorpórea (CEC) con requerimientos de VM por más de 48 horas. En los mismo se analizó el éxito o fracaso de extubación. Previo a la extubación se registraron valores de mecánica respiratoria; Vd/Vt, CO2 espiratoria final, Vt/kg, etc. Otras variables registradas: edad, sexo, peso, requerimiento de VM antes de la cirugía, fisiología de ventrículo único, duración de VM, complicaciones, duración de la internación y mortalidad. Las variables continuas se describieron como mediana y rango intercuartilo (25-75) y se compararon con prueba de Wilcoxon, las categóricas como proporciones o porcentajes y se analizaron con chi2 . Se efectuó un análisis bivariado con diferentes puntos de corte de Vd/Vt pre extubación para realizar un análisis de sensibilidad del valor predictivo de EE. Resultados: Se evaluó Vd/Vt en 67 pacientes, tres se eliminaron por parálisis cordal (1) y parálisis del diafragma (2). Mediana de edad 23 días (10-55), peso 3.2 Kg (2.89- 3.88), días de VM 5 (3-7), días de internación 15 (2- 128), mortalidad 7,8%. Se extubaron con éxito 76% de los pacientes (50/64). Las características demográficas de los pacientes, la mecánica respiratoria, gases de sangre arterial y EtCO2 no tuvieron asociación significativa con EE. Un Vd/Vt pre extubación < 0,53 se asoció con EE. Conclusión: En la población estudiada un valor de Vd/Vt <0,53 se asoció con EE. Los pacientes con ventrículo único presentaron mayor FE.(AU)

Introduction: Mechanical ventilation (MV) is part of postoperative (PO) recovery of children with congenital heart disease surgery, but is not without risks. Extubation failure (EF) has been associated with prolonged hospital stays and increased complication and mortality rates. The goal is to determine the value of Vd/Vt as a predictor of successful extubation (SE). Material and methods: A prospective and observational cohort study was conducted from January 1 to December 31, 2016, in children under 6 months of age undergoing cardiovascular surgery with extracorporeal circulation (ECC) and requiring MV for more than 48 hours. Intubation success or failure was evaluated. Prior to extubation, respiratory mechanics values, such as Vd/Vt, final expiratory CO2, and Vt/kg, were recorded. Other variables, including age, sex, weight, VM requirement before surgery, single ventricle physiology, VM duration, complications, length of hospital stay, and mortality were also recorded. Continuous variables were described as median and interquartile range (25-75) and compared with the Wilcoxon test. Categorical variables were described as proportions or percentages and analyzed with chi2. Bivariate analysis was performed with different pre-extubation Vd/Vt cut-off points to analyze the sensitivity of the predictive value for SE. Results: Vd/Vt was evaluated in 67 patients; three were excluded because of vocal fold (1) and diaphragm paralysis (2). Median age was 23 days (10-55), weight 3.2 Kg (2.89- 3.88), days on MV 5 (3-7), length of hospital stay 15 (2- 128), and mortality rate 7.8%. Overall, 76% of patients (50/64) were successfully extubated. Patient demographics, respiratory mechanics, arterial blood gases, and EtCO2 were not significantly associated with SE. A pre-extubation Vd/ Vt < 0.53 was associated with SE. Conclusion: In this series of patients, a Vd/Vt value of <0.53 was associated with SE. EF was increased in patients with a single ventricle (AU)

Regional venous oxygen saturation versus mixed venous saturation after paediatric cardiac surgery.

BACKGROUND: Central venous oxygen saturation (ScvO2) remains the gold standard surrogate for tissue oxygen extraction in paediatric cardiac surgery. Near-infrared spectroscopy (NIRS) has been developed as a non-invasive diagnostic tool for regional oxygen saturation. The aim was to compare regional oxygen saturation measured by NIRS with ScvO2 in postoperative paediatric cardiac patients. METHODS: In this prospective study, we included newborns and infants younger than 45 days undergoing heart surgery. We recorded continuous ScvO2 and NIRS regional saturation placed on the forehead (B) and right flank (S) for 48 h postoperatively. A Bland-Altman's analysis was used to assess the agreement between these measurements. RESULTS: A total of 23 patients were included with a median age of 12 days (2-46) and median weight of 3.1 kg (2.3-4.47). The mean difference (MD) ScvO2- B NIRS was 10.45% with limits of agreement (LOA) -17.23 to 38.13% and ScvO2- S NIRS MD 7.16% with LOA: -25.51 to 39.84%. The single ventricle ScvO2- S NIRS subgroup had MD within ± 5%; however, wide LOA was observed. The remaining subgroups showed MD nearly above ± 5%, with wide LOA. CONCLUSIONS: The regional oxygen saturation of brain and kidney did not match ScvO2 as estimation of global tissue perfusion. Nevertheless, NIRS may still provide information regarding regional circulation that may help in the management of neonatal cardiac surgery patients.

Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes.

It has been found that CDKL5 gene mutations are responsible for early-onset epilepsy and drug resistance. We screened a population of 92 patients with classic/atypical Rett syndrome, 17 Angelman/Angelman-like patients and six idiopathic autistic patients for CDKL5 mutations and exon deletions and identified seven novel mutations: six in the Rett subset and one in an Angelman patient. This last, an insertion in exon 11, c.903_904 dupGA, p.Leu302Aspfx49X, is associated with a relatively mild clinical presentation as the patient is the only one capable of sitting and walking alone. Of the six mutations, two are de novo missense changes affecting highly conserved aminoacid residues, c.215 T > C p.Ile72Thr and c.380A > G p.His127Arg (present in a mosaic condition) found in two girls with the most severe clinical presentation, while the remaining are the splicing c.145 + 2 T > C and c.2376 + 5G > A, the c.1648C > T p.Arg550X and the MPLA-identified c.162_99del261 mutation. RNA characterisation of four mutations revealed the aberrant transcript of the missense allele (case 2) and not the stop mutation (case 3), but also allowed the splicing mutation (case 1) and the c.-162_99del261 (case 4) to be categorised as truncating. The obtained data reinforce the view that a more severe phenotype is due more to an altered protein than haploinsufficiency. Furthermore, the mutational repertoire of the CDKL5 gene is shown to be expanded by testing patients with phenotypical overlap to Rett syndrome and applying multiplex ligation-dependent probe amplification.

Transitory, spontaneously recovering, peripheral facial nerve palsy after vinorelbine administration.

Childhood intrinsic brain-stem gliomas have a dismal prognosis. Different treatment strategies have been adopted over the years without changing the final outcome of this ominous disease. Due to this grim prognosis, experimental therapeutic designs are worthwhile. Vinorelbine is a semi-synthetic vinca alkaloid that has demonstrated a broad spectrum of activity both in in vitro and in vivo experimental systems. By adopting vinorelbine during and after focal radiotherapy in the last two years, we have tried to evocate its known synergistic effect in brain-stem tumour control. Vinorelbine was administered intravenously before, during and after radiotherapy on tumour bed for a total duration of 10 months. All the consecutive patients whose clinical and radiological features corresponded to the diagnosis of an intrinsic brain-stem tumour, i.e., diffuse pontine glioma, have been accrued to this treatment protocol since July 2002. A histological assessment was not required. All patients were treated during hospital stay or in the outpatient clinic at the Istituto Nazionale Tumori of Milan (n=12) and at the Pediatric Clinic of Policlinico in Catania (n=1). Two of the thirteen patients so far treated have developed multiple subsequent, and transitory, episodes of monolateral peripheral facial nerve palsy during vinorelbine administration. The palsy always completely and spontaneously resolved at a short interval-around 30 min-after the end of the drug infusion. Obvious tumour progression was excluded by means of MRI; therefore the drug was administered as scheduled until the end of the treatment. We describe possible neurological and oncological implications of this unusual side effect, until now not reported in any other series dealing with vinorelbine as adjuvant treatment.

GJA12 mutations in children with recessive hypomyelinating leukoencephalopathy.

BACKGROUND: Pelizaeus-Merzbacher-like disease (PMLD) is an inherited hypomyelinating leukoencephalopathy with onset in early infancy. Like Pelizaeus-Merzbacher disease (PMD), PMLD is characterized clinically by nystagmus, cerebellar ataxia, and spasticity, due to a permanent lack of myelin deposition in the brain. Mutations in the GJA12 gene, encoding connexin 47 (Cx47), were recently reported in five children with autosomal recessive PMLD. OBJECTIVES: To evaluate the impact of mutations in the GJA12 gene in, and define the clinical and neuroimaging features of, autosomal recessive PMLD. RESULTS: The authors screened for GJA12 mutations in 10 additional PMLD families originating from Italy, Pakistan, and Saudi Arabia. Three novel homozygous GJA12 mutations were identified in 12 mutant cases distributed in 3 of 10 families. The mutations segregated with the disease according to an autosomal recessive trait and included one missense (G236S) and two nonsense (L281fs285X and P131fs144X) changes. CONCLUSIONS: The identification of homozygous mutations predicting the synthesis of aberrant and truncated polypeptides, and their tight segregation with the disease in very large families, clearly demonstrate that the loss of Cx47 function is the cause of the disease. The phenotype of GJA12-related Pelizaeus-Merzbacher-like disease is fairly homogeneous and similar to that of Pelizaeus-Merzbacher disease. However, slower progression of symptoms, greater preservation of cognitive functions, and partial myelination of corticospinal tracts at MRI were distinctive features, which could help in the differential diagnosis.

CXCL12 expression is predictive of a shorter time to tumor progression in low-grade glioma: a single-institution study in 50 patients.

The clinical course of 50 patients with low-grade glioma (31 male, 19 female) undergoing surgery at a single Institution from 1992 to 1996 was analyzed in relationship with known prognostic factors as far as time to tumor progression (TTP) and survival time (ST) are concerned. Moreover, microvessel density (MVD) and expression of the angiogenesis-related chemokine CXCL12 were investigated in surgical specimens. Age at diagnosis ranged from 1 to 68 years (median 30). Histology revealed 11 fibrillary, 6 protoplasmatic, 5 gemistocytic astrocytoma, 18 oligoastrocytoma and 10 oligodendroglioma. Mean follow-up was 86 months. Four patients were lost to follow-up. Of the remaining 46, twenty-four have shown disease progression and 14 have died. Median overall survival was not achieved; an estimated 75% percentage of survivors was found at 78 months. Complete gross tumor removal was associated to a longer TTP (P = 0.04 logrank). Of the investigated immunohistochemical parameters, while MVD was not predictive of subsequent TTP, expression of CXCL12 was associated with a significantly shorter TTP (P = 0.01 logrank): this predictive value remained significant (P = 0.02) at multivariate analysis. The data suggest the possible prognostic value for CXCL-12 (an angiogenesis- and tumor-growth-related chemokine) on TTP in low-grade gliomas.

Sites of phosphorylation by protein kinase A in CDC25Mm/GRF1, a guanine nucleotide exchange factor for Ras.

Activation of the neuronal Ras GDP/GTP exchange factor (GEF) CDC25Mm/GRF1 is known to be associated with phosphorylation of serine/threonine. To increase our knowledge of the mechanism involved, we have analyzed the ability of several serine/threonine kinases to phosphorylate CDC25Mm in vivo and in vitro. We could demonstrate the involvement of cAMP-dependent protein kinase (PKA) in the phosphorylation of CDC25Mm in fibroblasts overexpressing this RasGEF as well as in mouse brain synaptosomal membranes. In vitro, PKA was found to phosphorylate multiple sites on purified CDC25Mm, in contrast to protein kinase C, calmodulin kinase II, and casein kinase II, which were virtually inactive. Eight phosphorylated serines and one threonine were identified by mass spectrometry and Edman degradation. Most of them were clustered around the Ras exchanger motif/PEST motifs situated in the C-terminal moiety (residues 631-978) preceding the catalytic domain. Ser745 and Ser822 were the most heavily phosphorylated residues and the only ones coinciding with PKA consensus sequences. Substitutions S745D and S822D showed that the latter mutation strongly inhibited the exchange activity of CDC25Mm on Ha-Ras. The multiple PKA-dependent phosphorylation sites on CDC25Mm suggest a complex regulatory picture of this RasGEF. The results are discussed in the light of structural and/or functional similarities with other members of this RasGEF family.

Calcium and calmodulin are essential for Ras-GRF1-mediated activation of the Ras pathway by lysophosphatidic acid.

The exchange factor Ras-GRF1, also called CDC25Mm, couples calcium signaling and G-protein-coupled receptors to Ras and downstream effectors. Here we show that when expressed in different cell lines Ras-GRF1 strongly enhances the level of active Ras (Ras-GTP) and the activity of mitogen-activated protein kinases (MAPK). Moreover, in NIH 3T3 fibroblasts it potentiates the effect of lysophosphatidic acid (LPA) on Ras protein and MAPK activity. Calmodulin and cytosolic free calcium are essential for Ras and MAPK activation induced by LPA and mediated by Ras-GRF1, as shown by the finding that BAPTA-AM, an intracellular calcium chelator, and calmodulin inhibitors completely abolished this effect. This report demonstrates the relevance of calmodulin in addition to calcium for the response of Ras-GRF1 to LPA.

Identification of three novel mutations in the major human skeletal muscle chloride channel gene (CLCN1), causing myotonia congenita.

Myotonia congenita (MC) is a genetic disease characterized by mutations in the CLCN1 gene (OMIM*118425) encoding the skeletal muscle voltage-gated chloride channel (ClC-1). Autosomal dominant and recessive forms are observed, characterized by impaired muscle relaxation after forceful contraction (myotonia), which is more pronounced after inactivity and improves with exercise. We report three novel and one known mutations of the CLCN1 gene in four unrelated MC families. In two families the mutations were missense: 803C>T (T268M) and 1272C>G (I424M) in exons 7 and 12, respectively. The third was a splice mutation in intron 5 (696+2T>A), which induced a frame shift with a stop codon in exon 6 (fs213X). In the fourth family the previously-reported missense mutation 689G>A (G230E) was found. We also report two known polymorphisms: 261C>T (T87T) and 2154T>C (D718D) in exons 2 and 17 of two MC families; also found in 14 (33%) and 28 (67%) of 42 healthy controls, respectively. These findings expand our knowledge of mutations responsible for myotonia congenita, reducing the proportion of MC patients in whom genetic alterations have not been found.

Oxido nítrico: ensayo clínico en niños con hipertensión pulmonar grave en el post-operatorio de cardiopatías congénitas / Nitric oxide: clinical trial in children with severe pulmonary hypertension after cardiac surgery for congenital heartdisease

jetivo: evaluar en un ensayo clínico a muestras relacionadas la respuesta al óxido nítrico (NO) en niños con hipertensión pulmonar (HP) grave post cirugía cardiovascular. Pacientes y Métodos: 24 pacientes (5 por ciento) internados en la unidad de recuperación cardiovascular entre agosto de 1996 y agosto de 1997 recibieron NO inhalado por padecer HP grave postoperatoria y fracaso al tratamiento convencional. Las indicaciones se categorizaron en 4 grupos: 1) Tratamiento con monitoreo directo de la presión arterial pulmonar (PAP). 2) Sin monitoreo directo, con evaluación clínica y ecocardiográfica. 3) Con gradiente transpulmonar >15 mmhg. 4) Uso preventivo. Se controlaron presión arterial y pulmonar, gases en sangre antes y después de la administración, metahemoglobinemia cada 12 hs, control ambiental de NO y NO2 cada 4 hs y ecocardiograma pre y post-no. En el análisis estadístico se compararon los valores de la pao2 antes y después de la administración del NO utilizando el wilcoxon rank test para dos colas (gpis).Se consideró significativa una p<0.05. Resultados: la mediana de edad fue de 8.7m, y la de peso de 4.2 kg., la mediana del tiempo de administración fue 69 hs (2-317 hs) con una dosis máximapromedio de 26 +- 22 ppm. Diez y nueve pacientes (80 por ciento) tuvieron una respuesta favorable; en 12 de ellos se observó un incremento de la pao2 basal superior al 30 por ciento. La mediana de la pao2 previa fue de 94 torr (r=36-428) con una posterior de 155 torr (r=34-683), p=0.009. Los niveles promedio de metahemoglobinemia fueron de 2 por ciento. Los niveles de NO y NO2 ambientales fueron menores de 1 ppm. No se observaron fenómenos de hipotensión arterial sistémica asociados a la administración del NO. La sobrevida fue de 18/24 pacientes (75 porciento). Conclusiones: el uso terapéutico de NO inhalado en pacientes críticamente enfermos con HP, dentro de un protocolo de administración y monitoreo, es seguro, mejora la oxigenación y/o disminuye los episodios de HP constituyendo una valiosa herramienta en el tratamiento de este grupo de pacientes.

Oxido nítrico: ensayo clínico en niños con hipertensión pulmonar grave en el post-operatorio de cardiopatías congénitas / Nitric oxide: clinical trial in children with severe pulmonary hypertension after cardiac surgery for congenital heartdisease

jetivo: evaluar en un ensayo clínico a muestras relacionadas la respuesta al óxido nítrico (NO) en niños con hipertensión pulmonar (HP) grave post cirugía cardiovascular. Pacientes y Métodos: 24 pacientes (5 por ciento) internados en la unidad de recuperación cardiovascular entre agosto de 1996 y agosto de 1997 recibieron NO inhalado por padecer HP grave postoperatoria y fracaso al tratamiento convencional. Las indicaciones se categorizaron en 4 grupos: 1) Tratamiento con monitoreo directo de la presión arterial pulmonar (PAP). 2) Sin monitoreo directo, con evaluación clínica y ecocardiográfica. 3) Con gradiente transpulmonar >15 mmhg. 4) Uso preventivo. Se controlaron presión arterial y pulmonar, gases en sangre antes y después de la administración, metahemoglobinemia cada 12 hs, control ambiental de NO y NO2 cada 4 hs y ecocardiograma pre y post-no. En el análisis estadístico se compararon los valores de la pao2 antes y después de la administración del NO utilizando el wilcoxon rank test para dos colas (gpis).Se consideró significativa una p<0.05. Resultados: la mediana de edad fue de 8.7m, y la de peso de 4.2 kg., la mediana del tiempo de administración fue 69 hs (2-317 hs) con una dosis máximapromedio de 26 +- 22 ppm. Diez y nueve pacientes (80 por ciento) tuvieron una respuesta favorable; en 12 de ellos se observó un incremento de la pao2 basal superior al 30 por ciento. La mediana de la pao2 previa fue de 94 torr (r=36-428) con una posterior de 155 torr (r=34-683), p=0.009. Los niveles promedio de metahemoglobinemia fueron de 2 por ciento. Los niveles de NO y NO2 ambientales fueron menores de 1 ppm. No se observaron fenómenos de hipotensión arterial sistémica asociados a la administración del NO. La sobrevida fue de 18/24 pacientes (75 porciento). Conclusiones: el uso terapéutico de NO inhalado en pacientes críticamente enfermos con HP, dentro de un protocolo de administración y monitoreo, es seguro, mejora la oxigenación y/o disminuye los episodios de HP constituyendo una valiosa herramienta en el tratamiento de este grupo de pacientes. (AU)

Expression of Ras-GRF in the SK-N-BE neuroblastoma accelerates retinoic-acid-induced neuronal differentiation and increases the functional expression of the IRK1 potassium channel.

Ras-GRF, a neuron-specific Ras exchange factor of the central nervous system, was transfected in the SK-N-BE neuroblastoma cell line and stable clones were obtained. When exposed to retinoic acid, these clones showed a remarkable enhancement of Ras-GRF expression with a concomitant high increase in the level of active (GTP-bound) Ras already after 24 h of treatment. In the presence of retinoic acid, the transfected cells stopped growing and acquired a differentiated neuronal-like phenotype more rapidly than the parental ones. Cells expressing Ras-GRF also exhibited a more hyperpolarized membrane potential. Moreover, treatment with retinoic acid led to the appearance of an inward rectifying potassium channel with electrophysiological properties similar to IRK1. This current was present in a large number of cells expressing Ras-GRF, while only a small percentage of parental cells exhibited this current. However, Northern analysis with a murine cDNA probe indicated that IRK1 mRNA was induced by retinoic acid at a similar level in both kinds of cells. Brief treatment with a specific inhibitor of the mitogen-activated protein kinase (MAPK) pathway reduced the number of transfected cells showing IRK1 activity. These findings suggest that activation of the Ras pathway accelerates neuronal differentiation of this cell line. In addition, our results suggest that Ras-GRF and/or Ras-pathway may have a modulatory effect on IRK1 channel activity.

Ketamina más Benzodiazepina para procedimienos dolorosos en niños: eficacia y seguridad / Ketamine plus a benzodiazepine for painful procedures in children. Efficacy and safety

La ketamina es la única droga que produce por si sola tres efectos buscados en la medicación para realizar un procedimiento doloroso de corta duración: sedación, analgesia y amnesia. A estos efectos se le suman la depresión respiratoria leve, la frecuente preservación de los reflejos protectores de la vía aérea y la estabilidad hemodinámica, perfil que ha hecho de esta droga de las más usada para los procedimientos dolorosos relizados fuera del quirófano. Sin embargo, para evitar las alucinaciones y reacciones disfóricas (S. de Emergencia) que con frecuencia causa la Ketamina se recomienda la co-administración de una benzodiacepina. El objetivo de este trabajo fue evaluar en forma prospectiva, la eficiencia y seguridad de ketamina más benzodiacepina pra la sedación de niños que requieren la realización de procedimientos dolorosos de corta duración. Se ralizaron 25 procedimientos dolorosos de corta duración. Se realizaron 25 procedimientos (23 catéteres venosos centrales y 2 drenajes pleurales) en niños con rago de edad entre 8 y 204 meses (mediana de 36 neses). La droga fue efectiva (permitió la realización del procedimiento bajo sedación) en todos los pacientes; un 32 por ciento (8/25) requirieron una dosis adicional. El monitoreo estuvo siempre a cargo de uno de los investigadores y consistió en vigilancia clínica, grado de sedación), registro de frecuencia cardíaca y de la Sat O2 en forma continua, toma de la tensión arterial cada 5 minutos y registro de ocurrencia y grado de Sindrome del Despertar. Ocurrieron 8 episodios (16 por ciento) de desaturación de oxigeno por debajo de 95 por ciento. que corrigieron con mascarilla de O2, y un episodio (4 por ciento) de apnea prolongada que requirió intubación endotraqueal durante aproximadamente 15 minutos. Solo 2 pacientes (8 por ciento) presentaron Síndrome del Despertar que requirieron contención física pero no famacológica.

[Cerebral tumors in children with neurofibromatosis type 1]. / Tumori cerebrali in neurofibromatosi tipo 1 in età pediatrica.

Twenty-eight children (mean age 8 years) with neurofibromatosis type 1 (NF1) and cerebral tumor were studied from 1975 to 1992 (mean follow-up 8.1 years) considering the biological behaviour of the tumor and the patient's quality of life, in order to identify retrospectively the best management. All, except one, tumors were benign gliomas, 76% of the optic nerve/chiasm (NCO), just 10% infratentorial. Sixteen children (57%) did not receive any treatment, 2 radiotherapy (RT) only and 4 symptomatic treatment only; in 6 patients the tumor resection was performed. 92% of the 25 survivors had sufficient autonomy in daily life at last follow-up. Considering the risk of cerebral tumors in patients with NF1, we conclude that cerebral magnetic resonance should be performed also in the asymptomatic ones. If neuroradiological findings are characteristic of benign glioma, histologic confirmation seems unnecessary. Surgical resection is recommended only in tumors confined to a single optic nerve, with severe or progressive symptoms. In chiasmatic tumors we suggest partial resection or symptomatic treatment only with close clinical and radiological observation. RT is only recommended if there is unequivocal evidence of tumor progression. Chemotherapy can delay the use of RT in very young children. Cerebral tumors different from NCO gliomas seem to have a similar natural history in patients with or without NF1 and therefore the management should be the same for both groups.

Triventricular hydrocephalus: review of 71 cases evaluated at the Istituto Neurologico "C. Besta" Milan over the last 10 years.

The authors review 71 patients with triventricular hydrocephalus in whom a contrast-enhanced CT scan did not show any tumoral or vascular lesion that could have caused the hydrocephalus. The patients were subdivided into three age groups. The results of the neuroradiological examination, the surgical treatment, and the complications of the shunt procedure are analyzed, with special reference to the high number (13) of periaqueductal alterations of signal pattern found on MRI (interpreted as a "slow growing" neoplasm) and to the incidence and causes of shunt malfunction.

Brain tumors with symptomatic onset in the first two years of life.

Eighty children who in the first 2 years of life had signs and symptoms relating to a cerebral neoplasm were studied over an 18-year period (1970-1987), the mean follow-up being 8.2 years. In each case age at onset, clinical presentation, tumor location and pathological diagnosis, extent of surgical resection, postoperative mortality, adjuvant therapy length of survival and quality of life were assessed. Supratentorial tumors (59%) were more common than infratentorial. The most frequent clinical presenting feature (70%) was increased intracranial pressure. Sixty-three patients (79%) were operated on and in all of these cases a histological diagnosis was obtained. Astrocytomas (41%) and medulloblastomas (20%) were the most common oncotypes. Surgical mortality was 17.4% and the 5-year survival rate was 54%. Quality of life was assessed for all long-term surviving patients using a specifically designed protocol. Normal physical and intellectual performances were found in 46% of cases, and all together 75% of the patients had sufficient autonomy in daily life. The prognosis is more closely related to tumor location and type of treatment than to histological diagnosis or age at onset.