[Autism of unknown aetiology]. / El autismo de etiología desconocida.

OBJECTIVE: To review the origin, development and present state of autism, pervasive developmental disorders, progress in diagnostic tools, genetic advances, neurobiological bases, the possible causes of the increased prevalence of autism and the present treatment of the autistic condition. DEVELOPMENT: Autism is a neurobiological, life-long disorder characterized by abnormal social skills, deficient verbal and not verbal communication, symbolic and imaginative play, reasoning and related complex behaviour. Autism is 4 times more frequent in males. 70% are mentally retarded (30% mild and the rest moderate and severely retarded). Approximately 25% have convulsions and around 65% inspecific EGG abnormalities. Other conditions like ADHD, anxiety, depression may be associated. RMN: increased subarachnoidal spaces, moderate ventricular enlargement, 20% have megaloencephaly. PET and 31 PMMR show increased glucose metabolism and decreased functional links with association cortex. Mental level and language are the best prognostic indices for outcome. Pathology: reduced size of nerve cells in hippocampus, subiculum, sections of the amygdala, mamillary bodies, medial septal nucleus, decreased size of cerebellar hemispheres, posterior vermis, VI VII neocerebellar lobules. Evolution: in a small group about 9-31% live independently, 11-50% attend college. CONCLUSION: Autism is a disorder of multi-factorial origin with a genetic polygenic component and the influence of environmental elements. Treatment with risperidone improves symptoms.

[A system of multidimensional behavior assessment. A scale for parents of children from 6 to 11 years of age. Colombian version]. / Sistema de evaluación multidimensional de la conducta. Escala para padres de niños de 6 a 11 años, versión colombiana.

INTRODUCTION: Behavioral Assessment System for Children (BASC) has demonstrated to be useful in the diagnosis of Attention Deficit Disorder (ADD). PATIENTS AND METHODS: A randomized sample of 120 children, 6 to 11-year-old, participants from the school of the city of Medellín, Colombia, was selected. The sample was stratified by sex and two socioeconomic status (SES). Parents were asked to answer the BASC Parent Rating Scale (PRS) 6-11, authorized Spanish version. RESULTS: Cronbach's alpha coefficient was 0.85 for the clinical scale (9 items). It was 0.75 for the Adaptive Scale (3 items). A scale designed with 4 items to assess ADD (hyperactivity, attention problems, aggression, and conduct problems) showed an alpha coefficient of 0.82. Male children scored significantly higher than female (ANOVA, p < 0.05) in hyperactivity, conduct problems, and atypicality. Children from low SES scored significantly higher than children of high SES on the most of clinical measures (p < 0.05) and lower on the three adaptive measures. Cluster analysis selecting six clusters found a prevalence of 61.6% for normal male children. In the total sample there were a 4% at risk of DDA type II (inattentive) and 14% at risk of DDA type I (combined). CONCLUSIONS: BASC PRS (6-11) showed reliability and validity to assessing the behavior in Spanish speaking Colombian children.

Trauma cervicofacial en niños / Facial injuries in children

Se revisaron las historias clínicas de 263 pacientes pediátricos que ingresaron al Hospital Universitario del Valle (HUV) con diagnósticos de lesión cervicofacial por causa externa durante un período de 50 meses (1 de marzo de 1990 a 30 de abril de 1994). La relación masculino: femenino fue de 2 :1 y el promedio de edad 6,5 años. Durante el período estudiado la mayoría de lesiones ocurrieron en día de semana (lunes a viernes). Según el origen de la lesión, los accidentes de tránsito ocuparon el primer lugar con un 49 por ciento, seguido de los accidentes domésticos con un 27 por ciento. El 31 por ciento de los accidentes de tránsito ocurrieron en automotor, 13 por ciento en moto y el 3 por ciento en bicicleta. Los agentes de lesión más frecuentes fueron los traumas contusos 51 por ciento, seguidos por trauma mixto. El maltrato infantil ocurrió en el 9,1 por ciento de casos. 153 niños (58,2 por ciento) sufrieron trauma de tejidos blandos, siendo las heridas en cara las más frecuentes con 102 casos (38,8 por ciento) y las heridas en oreja (13,5 por ciento). El 15 por ciento de los pacientes presentó complicaciones con una mortalidad del 0,8 por ciento. El promedio de estancia en urgencias fue de 2 días y el promedio de hospitalización de 4,4 días

Localización histoquímica e inmunohistoquímica de fibrocitos en la cóclea de la rata / Histochemical and immunohistochemical location of fibrocyts in the cochlea of rats

El fibrocito, célula de origen mesenquimal del ligamento espiral de la coclea, ha sido investigado usando tecnicas inmunohistoquimicas que al intentar reproducirlas fallan debido a la impredecible alteracion de sitios antigenicos introducidos durante el procesamiento de la muestra. El presente estudio describe la estandarizacion de una tecnica histoquimica e inmunohistoquimica para la localizacion del fibrocito en la coclea de la rata. Dos ejemplares, bajo anestesia general con nembutal recibieron una inyeccion intracardiaca de fijadores tipo aldehidos, buffer salino fosfato y sales precipitantes. Luego de la muerte del animal su cabeza se sometio a postfijacion y decalcificacion, para realizarle cortes con microtomo cada 5 micrometros y tincion cada decima placa con hematoxilina-eosina. Finalmente, se utilizó inmunohistoquimica indirecta con el metodo Avidina-biotina conjugada y marcador monoclonal anti-vimentina y la proteina S100, lográndose la identificacion de los fibrocitos y demás componentes del organo de corti murino. La estandarizacion de esta tecnica es un hecho trascendental para el proceso de investigacion histopatologica del oido interno, aplicable al estudio de patologias que afecten a los fibrocitos del ligamento espiral

Long distance runners and body-builders exhibit elevated plasma levels of lipoprotein(a).

A one-point cross-sectional study of 20 sedentary individuals, 20 low-aerobic athletes (body-builders), and 20 high-aerobic athletes (long distance, endurance runners) was conducted in Mexico City, Mexico to determine the influence of these diverse life-styles on the plasma levels of Lp(a). Only non-obese male subjects, aged 23-33, who were nonsmokers, non-alcoholics, and had never used anabolic steroids were included in this study. Blood samples were drawn 24 h following the last period of physical activity, and after a 12-14-h fast-period and a 15-min sitting-rest. Plasma levels of Lp(a) and other parameters, including postheparin lipoprotein lipase (LPL) and hepatic lipase (HL) activities, triglycerides (TG), total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C), as well as % body fat and muscle mass, and maximum aerobic capacity (VO2max) were measured to determine possible correlations with Lp(a) and to serve as convenient internal standards. Mean Lp(a) concentrations were significantly higher in the runners (52 +/- 19 mg/dl) than in the body-builders (40 +/- 6.4 mg/dl, P < 0.05) and the sedentary subjects (24 +/- 5 mg/dl, P < 0.001). Positive correlations between Lp(a) and Vo2max (P < 0.001), HDL-C (P < 0.005) and HDL2-C subfraction (P < 0.005), and a negative correlation with TG were determined. Agglomerative cluster methods suggested three close-distance clusters and a fourth cluster which is composed of four runners who exhibited low LDL-C/HDL-C and high LPL/HL ratios, high mean Lp(a), HDL2-C, and Vo2max levels, but low TG levels. These data show that some individuals who maintain a life-style of very high level physical exertion may have remarkably elevated plasma Lp(a) concentrations. The highly increased concentrations of Lp(a) in high exercise athletes may represent a normal metabolic response to repeated small tissue injuries resulting from frequent and prolonged large muscle movement.

Calcium transport sensitive to ruthenium red in cytochrome oxidase vesicles reconstituted with mitochondrial proteins.

We describe a calcium transport that is sensitive to ruthenium red in liposomes reconstituted with mitochondrial extracts. This system is able to build an internally negative membrane potential, which allows the electrogenic influx of Ca2+ and Sr2+. Proteins with molecular weights higher than 35 kDa were incorporated to the vesicles, and enhanced the accumulation of the cation in an energy-dependent fashion.

Protective behavior of captopril on Hg(++)-induced toxicity on kidney mitochondria. In vivo and in vitro experiments.

Mercurials are known to induce morphological and functional modifications in kidney mitochondria. In this work we studied in vitro and in vivo the protective effect of captopril on the deleterious effect of Hg(++)-induced nonspecific membrane permeability changes to Ca++ and membrane de-energization. In vivo the administration of captopril prevented the toxic effects of mercury poisoning on membrane permeability, oxidative phosphorylation and Ca++ homeostasis. Moreover, captopril preserves kidney tissue morphology from Hg(++)-induced damage. The protective effect of captopril is most likely related to the existence of a sulfhydryl group in the drug.

Induction of mitochondrial Ca2+ uptake by mersalyl.

1. The addition of mersalyl to aged mitochondria from rat kidneys, is followed by induction of an ATP-driven Ca2+ uptake which is sensitive to Ruthenium Red. 2. This Ca2+ influx requires Mg2+, albumin, and is accomplished by membrane energization. 3. The activation of Ca2+ uptake by the mercurial in the presence of ATP can be explained if it is assumed that the inorganic phosphate generated by ATPase activity, and trapped in the matrix by the thiol reagent, provides the negative potential which results in an electrophoresis cation influx.

Ionophoretic and inhibitory action of the analgesic, diflunisal, on sarcoplasmic reticulum.

Diflunisal decreased the ATP-dependent transport rate and calcium accumulation by the sarcoplasmic reticulum. Inhibition of calcium transport by diflunisal was pH dependent, and a pKa of 6.7 to 6.9 was observed for the carboxylic acid group. In sealed sarcoplasmic reticulum vesicles, diflunisal at concentrations below 1 mM increased the rate of Ca2+-dependent hydrolysis of ATP; above 1 mM, the Ca2+-ATPase activity was inhibited. In purified Ca2+-ATPase, diflunisal acted only as an inhibitor. Methylation of the phenolic group of diflunisal eliminated both its analgesic and ionophoretic properties.

Mitochondrial calcium release as induced by Hg2+.

Addition of Hg2+ to mitochondria of rat kidney induces efflux of intramitochondrial Ca2+. This reaction is accompanied by a diminution of the NAD(P)H/NAD(P) ratio and a decrease of the internal negative membrane potential. These effects were enhanced by dithiothreitol. The binding of mercuric ions to mitochondria saturates with a maximal binding of 9 nmol min-1 mg-1. The stoichiometry between Ca2+ released and Hg2+ bound showed that in the presence of dithiothreitol, the binding of approximately 1 nmol of Hg2+/mg of protein suffices to induce the release of the accumulated Ca2+. In the electrophoretic analysis of Hg-labeled mitochondrial proteins it was found that 203Hg2+ bound mainly to proteins that have molecular masses of 20 and 30 kDa. It is proposed that Hg2+-induced Ca2+ release is due to modification of--SH groups of these latter proteins.

Metabolite transport in mitochondria as a function of osmolarity.

The effect of increasing sucrose concentrations on some mitochondrial functions was studied. The results showed that high osmolarity inhibits oxidative phosphorylation as well as ATPase activity and ATP-dependent delta phi formation as a consequence of adenine nucleotide translocase inhibition. It is also shown that high osmolarity does not affect delta phi formation and energy-dependent Ca2+ uptake as driven by succinate oxidation. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of membrane proteins showed a different reactivity to o-phenantroline/Cu2+ as function of osmolarity. It is proposed that high sucrose concentrations induce a collapse of the matrix compartment that results in a restricted diffusion of some metabolites.

Cooperative effects of Ca2+ and Sr2+ on sarcoplasmic reticulum adenosine triphosphatase.

The intrinsic fluorescence of purified Ca-ATPase from skeletal sarcoplasmic reticulum was measured in the presence of various concentrations of Ca2+, Sr2+, and Ba2+. Ca2+ and Sr2+ induce positive cooperative fluorescence enhancement, whereas Ba2+ does not change the fluorescence of ATPase. ATP does not seem to modify the kinetic parameters of Ca2+ and Sr2+ binding to ATPase. Nevertheless, p-nitrophenylphosphate hydrolysis, activated by Ca2+ or Sr2+ at various pHs, changes the affinity and the cooperative behavior for both cations and two components appear in the Hill plots. For Ca2+, nH of 1.6 to 3.5 were obtained, and 1.06 to 1.83 for Sr2+; nH changes of the second component seem to be pH dependent. Differences in the ratio between rates of Ca2+ transport and substrate hydrolysis by sarcoplasmic reticulum were found, i.e., two for ATP and one for p-nitrophenylphosphate. For Sr2+ this ratio was one for either ATP or p-nitrophenylphosphate.

[Effects of acidosis and alkalosis on the sarcoplasmic reticulum of the heart]. / Efectos de la acidosis y alcalosis en retículo sarcoplásmico de corazón.

Some functions of dog cardiac sarcoplasmic reticulum have been studied in acidosis and alkalosis conditions in a range of pH from 6.0 to 7.8. Intravesicular water content at pH 6.0 is 4.7 microliter per mg of protein and diminished to 4 microliter, (15%) at pH 8.0; this correlates with a drop of 13.5% in turbidity. Ca2+-dependent ATPase has an optimal pH of 7.2 and a specific activity of 580 nanomoles of ATP hydrolyzed/min/mg protein. The activity of Basal ATPase or Mg2+-dependent is insensitive to changes of pH. Maximal calcium uptake attains 45.1 +/- 1.4 nanomoles per mg protein between pH 6.0 and 6.6. The accumulated calcium diminished progressively when pH was raised. The rate of calcium transport in steady state shows an optimal pH of 6.7. The calcium transport kinetics constants shows that reticulum has a maximal affinity for calcium between pH 6.87 and 7.02. The maximal velocity for transport diminished progressively between pH 6.1 to 7.16. During the calcium transport process pH is changed from acid to alkaline and the accumulated calcium is release proportionally to the pH increment. This effect shows to be reversible. Calcium accumulation and ATP hydrolysis are uncoupled at pH values higher than 6.6 because to the increase in the rate of calcium release. Values of pK and number of protons per mg of protein that dissociates from ionizable residues are 6.53 and 0.68 respectively for calcium dependent ATPase; 7.09 and 0.60 for calcium transport and 7.41 and 0.39 for calcium release. We conclude that the rate of transport and affinity of cardiac sarcoplasmic reticulum for calcium are optimal between pH 6.8 and 7.0 that is the reported range of intracellular pH of normal cardiac tissue. The data are in close agreement with the fall of contractility in acidosis. It is proposed a calcium release pathway sensitive to pH and different from that of calcium pump, exclusively for entrance.

[Mechanism of the antiarrhythmic effect of inorganic phosphates in digitalis poisoning]. / Mecanismo del efecto antiarrítmico de los fosfatos inorgánicos en la intoxicación digitálica.

THe synergistic effects between calcium and the therapeutic and toxic actions of the cardiac glycosides have suggested that a way of treating digitalis intoxication could be through a decrease in free plasma calcium. In 1966, Burckhardt and La-Due published a study based on the inverse relationship that exists between plasma phosphates and calcium. It was shown then that potassium phosphate had a pronounced antiarrhythmic effect on digitalis induced arrhythmias. The use of potassium phosphate for this study prevented the analysis of the role of the phosphates in these effects, since the actions of potassium in digitalis toxicity precluded any conclusion. The purpose of the present paper is to study the effect of phosphates on digitalis intoxication and its possible mechanism of action. The results obtained demonstrated: 1) Phosphates have a marked antiarrhythmic effect in digitalis induced arrhythmias. 2) This effect is due to a decrease in free plasma calcium. 3) The lowering of this calcium pool occurs in the blood and is not mediated by hormonal or renal mechanisms. 4) The ions that disappear from the free calcium pool do not precipitate. 5) The use of phosphates could be useful in the treatment of some clinical cases of advanced digitalis intoxication.

[Mechanism of the decrease in free plasma calcium produced by the administration of inorganic phosphates]. / Mecanismo de la disminución de calcio libre plasmático producida por la administración de fosfatos inorgánicos.

The preceding paper (published in the issue) demonstrated that the administration of sodium phosphates exerted a marked antiarrhythmic effect on several models of digitalis intoxication; this action being due to a decrease in the free calcium fraction. THe purpose of the present paper is to analyze the effects that several concentrations of phosphates have on the different calcium fractions and determine the fate of the ions that are disappearing from the calcium pool. This study was done using two models of digitalis intoxication, one in the intact dog and the other in the heart-lung preparation and two protocols in which the experiments were carried out using blood in vitro. The results show: 1) the administration of phosphates into the intact dog produces a small decrease in the total calcium content of plasma and blood. 2) the increase in phosphate concentration runs parallel to an important decrease in free calcium. 3) In the heart-lung preparation, phosphate administration markedly decreases free calcium but does not lower total calcium in plasma or blood. 4) An increase in phosphate concentration of plasma in in vitro conditions does not alter total calcium and decreases free calcium in a linear relationship with the levels of phosphates. 5) A fraction of the phosphates added to the plasma and the ions that are disappearing from the free calcium pool are binding to a plasmatic macromolecule (most probably a protein) which prevents them from precipitating.

Mecanismo del efecto antiarritmico de los fosfatos inorganicos en la intoxicacion digitalica. / Mechanism of antiarrhythmic effect of the inorganic phosphate in digitalis intoxication

El sinergismo existente entre el calcio y las acciones terapeuticas y toxicas de los digitalicos, ha sugerido la posibilidad de tratar la intoxicacion digitalica mediante una disminucion de calcio plasmatico. En base a la relacion inversa entre los fosfatos y el calcio plasmatico, en 1966, Burckhardt y La Due estudiaron las acciones de los fosfatos de potasio sobre la intoxicacion digitalica, con resultados que mostraron un claro efecto anti-arritmico.El uso de fosfatos de potasio no permitio determinar el papel de los fosfatos en este efecto, ya que el uso del potasio oscurecia los resultados. El objeto del presente trabajo es el de determinar, usando diversos metodos experimentales, si los fosfatos tienen efecto sobre la intoxicacion digitalica y el mecanismo de su accion. Los resultados demostraran: 1) Los fosfatos ejercen un marcado efecto antiarritmico en la intoxicacion digitalica. 2) Este efecto es secundario a una disminucion en el calcio libre. 3) La disminucion en el calcio ocurre en la sangre y no esta mediada por un efecto hormonal o renal. 4) Los iones que desaparecem en la fraccion de calcio libre no se estan precipitando. 5) La administracion de fosfatos podria ser de utilidad en algunos casos de intoxicacion digitalica severa en la clinica

[Changes induced by hypertonic solutions in the transportation of calcium by the cardiac reticular sarcoplasma]. / Cambios inducidos por soluciones hipertónicas en el transporte de calcio por el reticulo sarcoplásmico del corazón.

In the sarcoplasmic reticulum of the myocardium, celular organell which function is to regulate the cytoplasmic concentration of calcium in contraction and relaxation, we have studied the effect of hypertonic solutions of sucrose between 1 and 6.96 times the normal tonicity in order to observe the behavior of the internal linked or free calcium of this structure, as well as to prove the hypothesis that hypertonic solutions encourage the calcium exit of the sarcoplasmatic reticulum with the resulting signs of contractures. The following results were obtained: 1. The ATP hydrolisis and calcium transport rate are 14% and 90% respectively of the maximum speeds of 10(-5) M in calcium, while for concentrations of 10(-7) M or ess of the said cation, the transport rates and the ATPase do not reach 5% of the maximum values. 2. Between 1 and 2.54 times of the normal tonicity the calcium uptake remains between 400 and 500 nmoles of calcium/mg protein/min, the transported amount of calcium varies between 14 and 16 nmoles/mg protein and the rate of the ATP hydrolysis increases a 37% to 0.4 M in sucrose. 3. Between 0.4 and 1.2 M in sucrose of 2.54 to 6.96 times the isotonicity, the calcium transport rate velocity as well as the ATP hydrolisis are strongly inhibited. The vesicles volume minimizes and the amount of linked calcium remains within the control values, proving that the capacity of linking this cathion is independent from sarcoplasmic reticulum volume. These results show that the sarcoplasmic reticulum is involved in the contractures induced by hypertonic solutions in intact cells, since the osmolarity increase produces changes of volume which results in a decrease of the calcium transportation velocity or in an increase of the exit of said cathion.