Experiencia clínica con el antipsicótico clozapina en niños y adolescentes menores de 18 años en Chile / Clinical experience in Chile with clozapine in child and adolescents under 18 years

Objective: Increase in severe psychopathology in adolescents who are resistant to common treatment creates a need to search new alternatives in pharmacological treatment. Background: To describe a sample 47 child and adolescent patients treated with clozapine between 1985 and 2010, indicating: age, gender, diagnoses, hospitalization, electroconvulsive therapy, dosing, adverse effects specially hematological ones. Methods: 47patients between the ages of 10 and 18 were treated with clozapine. Review of clinical charts, protocol investigation and Excel statistic analysis. Results: The sample consisted in: male: 40 percent, female: 60 percent, the youngest was 10 and the oldest 17years and 11 months old; the most frequent age was 15 years. The mean number of hospitalization was 1.5. Diagnosis Axis I,DSM IV: Affective disorders 64 percent, Schizophreniform disorder 23 percent. Electroconvulsive Therapy: 57 percent. Treatment indications: irreducible psychosis 23 percent, suicidability: 33 percent. Average dosing 200 mg. Adverse effects: sedation: 76 percent, hypersalivation: 68 percent, increase in weight: 66 percent. Neutropenia: not severe (more than 2000/ mm³): 17 percent; severe 1:15 percent, severe II: 2 percent, severe III: 2 percent. Conclusions: Clozapine appears as an effective drug, with moderate but frequent adverse effects. Hematologic adverse effects where transient; only one in 47 patients presented a severe neutropenia and require cancellation of treatment, which was reinstalled after three month without mayor side effects. There is a need for control studies with larger population and a longer period of time.

Introducción: El aumento de psicopatología severa en la clínica infanto-juvenil y la resistencia a los tratamientos habituales, lleva a los clínicos buscar nuevas alternativas farmacológicas. Surge entonces la clozapina como una alternativa útil, avalada por la literatura para tratamiento de estas patologías. Objetivos: Describir una muestra de 47 pacientes niños y adolescentes entre 10 y 18 años tratados con clozapina entre los años 1985 y 2010. Se indican: variables demográficas, diagnósticos, hospitalizaciones, dosis y efectos adversos, especialmente los hematológicos. Material y Método: Estudio descriptivo, retrospectivo consistente en revisión de fichas clínicas, protocolo de investigación y análisis estadístico con plantilla Excel. Resultados: Muestra de 47 pacientes; 40 por ciento hombres, 60 por ciento mujeres, el menor de 10 años y el mayor de 17 años y 11 meses; la edad más frecuente fue de 15 años. El 80 por ciento presentó al menos una hospitalización. Diagnósticos agrupados: Trastornos a predominio afectivo el 64 por ciento, Trastornos esquizomorfo el 23 por ciento y Trastornos a predominio del descontrol de los impulsos y agresión 9 por ciento. Un 57 por ciento recibió TEC. Causa de indicación: psicosis irreductible 36 por ciento, suicidalidad alta 33 por ciento, conducta heteroagrsiva 25 por ciento, efectos laterales con otros fármacos 23 por ciento. La dosis promedio de mantención fue de 200 mg. Los efectos adversos más frecuentes fueron: sedación 76 por ciento, salivación 68 por ciento, alza peso 66 por ciento. Baja inespecífica de neutrófilos: 17 por ciento, alarma 1:15 por ciento, alarma II: 2 por ciento, alarma III: 2 por ciento. Discusión: Clozapina aparece como fármaco útil, con efectos adversos frecuentes, pero en nuestra muestra fueron graves no y transitorios. Hubo un caso con alarma III que requirió de suspensión, pero se reinstaló 3 meses después; sin reincidir, ni presentar otros efectos adversos de gravedad...

Comparación de susceptibilidad de especies de shigella a antimicrobianos de uso habitual en el Hospital Regional de Temuco, Chile 1990-2001 / Shigella species susceptibility to commonly used antimicrobials in the Temuco Regional Hospital, Chile 1990-2001

Background: The permanent surveillance of antimicrobial susceptibility of Shigella sp in the Temuco Regional Hospital, allowed us to define the empirical use of antimicrobials in dysenteric syndrome. Aim: To study antimicrobial susceptibility of Shigella strains collected from 1997 to May 2001 and compare the results with those reported in 1990. Material and methods: Two hundred and seventeen Shigella strains, coming from stool cultures of pediatric patients, were studied. Results: In the period 1989-1990 Shigella flexneri was the main species isolated (83 percent) whereas, in the period 1997-2001, Shigella sonnei (55.8 percent) predominated. In the second period, an increase of antimicrobial resistance, as compared with the period 1989-1990, was observed for ampicillin (74.5 and 42 percent respectively), for cotrimoxazol (57.5 and 45 percent respectively) and tetracycline (64 and 8 percent respectively). Chloramphenicol resistance increased from 0 to 57.5 percent. In the second period no resistance to ciprofloxacin was detected. There was simultaneous resistance to four drugs in 30 percent of the strains, predominating multiresistance in S flexneri (52.1 percent). Conclusions: In the two periods studied, a significant increase was detected in the resistance of Shigella strains to antimicrobials

The host range phenotype displayed by a Sindbis virus glycoprotein variant results from virion aggregation and retention on the surface of mosquito cells.

The Sindbis virus variant NE2G216 is a PE2-containing host range mutant that is growth restricted in cultured mosquito cells (C6/36) due to inefficient release of virions from this cell type. The maturation defect of NE2G216 has been linked to the structures of N-linked oligosaccharides synthesized by arthropod cells. Analysis of C6/36 cells infected with NE2G216 by transmission electron microscopy revealed the presence of dense virus aggregates within cytoplasmic vacuoles and virus aggregates adhered to the cell surface. The virus aggregation phenotype of NE2G216 was reproduced in vertebrate cells (Pro-5) by the addition of 1-deoxymannojirimycin, an inhibitor of carbohydrate processing which limits the processing of N-linked oligosaccharides to structures that are structurally similar, albeit not identical, to those synthesized in C6/36 cells. We conclude that defective maturation of NE2G216 in mosquito cells is due to virion aggregation and retention on the cell surface and that this phenotype is directly linked to the carbohydrate-processing properties of these cells.

Linkage of an alphavirus host-range restriction to the carbohydrate-processing phenotypes of the host cell.

The Sindbis virus mutant NE2G216 retains PE2 in place of E2 in its virion structure. NE2G216 is a host-range mutant that replicates with near-normal kinetics in vertebrate cells, but displays severely restricted growth in cultured mosquito cells (C6/36) due to defects in the virus maturation process. In this study we tested the hypothesis that the host-range phenotype of NE2G216 was linked to the differences in carbohydrate-processing phenotypes between vertebrate and arthropod cells. Arthropod cell-derived glycoproteins are distinguishable from those synthesized in vertebrate cells by the absence of complex- and hybrid-type N-linked oligosaccharides. To test our hypothesis we compared the growth of the wild-type virus, TRSB, NE2G216 and three PE2-containing, C6/36 cell-adapted variants, in vertebrate cells treated with 1-deoxymannojirimycin (1-dMM). 1-dMM inhibits the Golgi alpha-mannosidase I enzyme and limits oligosaccharide processing to high-mannose forms (Man(8-9)GlcNAc(2)). The growth of TRSB was not restricted by the action of 1-dMM; however, NE2G216 was restricted in a dose-dependent manner. In contrast, the growth of each PE2-containing, C6/36 cell-adapted mutant was enhanced by low concentrations of 1-dMM (up to 1500%) and was only slightly affected by the higher concentrations. These results demonstrate that virion maturation functions of NE2G216 are sensitive to the structure of cis-linked oligosaccharides, and indicate that the carbohydrate-processing phenotypes of the host cell can influence viral host-range and function as a selective pressure in alphavirus evolution.

Resistencia de especies de shigella a antimicrobianos de uso habitual en el Hospital Regional Temuco, Chile / Resistance of the shigella species to regular antibiotics in the Regional Hospital of Temuco, Chile

El Hospital Regional de Temuco realiza vigilancia permanente de susceptibilidad a antimicrobianos en shigella detectándose desde 1996 resistencia progresiva a cloranfenicol, droga de elección en el tratamiento empírico frente a la sospecha de shigellosis. Se estudiaron 200 cepas de shigella aisladas de pacientes pediátricos que consultaron por diarrea entre julio 1997 y octubre 2000. La identificación bioquímica y serológica de las especies se realizó mediante metodología tradicional. La susceptibilidad a antimicrobianos de uso habitual, se midió mediante método de difusión en agar (Kirby-Bauer). Distribución por especies: shigella sonnei 64,5 por ciento y S. flexneri 35,5 por ciento. Se detectó 73 por ciento de resistencia a ampicilina, 56,5 por ciento a cloranfenicol, 45 por ciento a cotrimoxazol y 0 por ciento a ciprofloxacino. S. flexneri presentó resistencia y multirresistencia significativamente mayor. La resistencia limita las posibilidades terapéuticas, lo que incentiva a continuar con la vigilancia, para establecer normas de tratamiento y controlar la selección y diseminación de cepas multirresistentes

European study on dose-response relationship of acarbose as a first-line drug in non-insulin-dependent diabetes mellitus: efficacy and safety of low and high doses.

The aim of this double-blind, placebo-controlled, multinational, five-arm study was to investigate the dose-response relationship of acarbose as a first-line drug in the treatment of type 2 diabetes (non-insulin dependent) over a range of minimal and maximal doses according to the European recommendations. The study included 495 patients from 7 countries who were insufficiently controlled with diet alone (glycosylated haemoglobin HbA1C 6.5%-9%). Acarbose, 25, 50, 100 or 200 mg t.i.d., or placebo t.i.d. was given for 24 weeks. Even a low dosage of 25 mg t.i.d. acarbose reduced fasting and postprandial blood glucose levels (1 h postprandial -11.6%; 2 h postprandial -11.3%). Acarbose in a dosage of 200 mg t.i.d. had the greatest effect on these parameters. In the placebo group the mean 2 h postprandial area under the curve (AUC) value for blood glucose was 22.6 mmol/l after 24 weeks' therapy. The mean 2 h postprandial AUC values in the patients given acarbose at doses of 25, 50, 100 and 200 mg t.i.d. were found to be 21.2, 19.6, 20.3 and 18.5 mmol/l, respectively. The corresponding HbA1C values for the placebo and acarbose groups were 7.83%, 7.37%, 7.08%, 6.98% and 6.79%. Interestingly, there was a plateau of blood glucose level at a dosage of 50-100 mg t.i.d. The frequency of flatulence decreased with the duration of drug therapy, but we could not find a linear relationship between doses of acarbose and the gastrointestinal side effects. Less than 3% of patients stopped tablet intake due to adverse events.

Tuberculosis infantil: experiencia regional en la Araucanía en veinte años / Pediatric tuberculosis: experience at the Araucania region during 20 years

Entre 1979 y 1998 se trataron con diagnóstico de tuberculosis (TBC), 120 pacientes menores de 15 años en el Servicio de Pediatría del Hospital Regional de Temuco. Todos recibieron isoniacida + rifampicina + pirazinamida diariamente por 1 a 2 meses. En TBC meníngea o grave se adicionó estreptomicina como cuarto fármaco antituberculoso. En fase intermitente, generalmente ambulatoria, se empleó isoniacida + rifampicina bimensual por 5 a 7 meses. El diagnóstico de tuberculosis fue bacteriológica en 65 pacientes (54 POR CIENTO), en el resto tuvo fundamentación clínica-epidemiológica. La enfermedad predominó en escolares de origen rural y ascendencia mapuche. En 48 por ciento se obtuvo el antecedente de TBC familiar. En 50 por ciento no se encontró cicatriz BCG. En 70 por ciento hubo compromiso pulmonar exclusivo, en 20 por ciento extrapulmonar solamente y en 10 por ciento asociación. El compromiso del SNC y aparato osteoarticular siguieron en frecuencia al pulmón. Fallecieron 5 pacientes (letalidad 4,1 por ciento). Hubo elevación transitoria de transaminasas en 4,1 por ciento. Se observó recidiva en un paciente. La vacunación BCG, el adecuado manejo de la TBC del adulto y control de los contactos son estrategias fundamentales en la reducción y eliminación de la TBC infantil en Chile.

Efficacy of 6 months monotherapy with glucosidase inhibitor Acarbose versus sulphonylurea glibenclamide on metabolic control of dietary treated type II diabetics (NIDDM).

Six months monotherapy with Acarbose vs. glibenclamide led to a marked improvement of BG and HbA1 in NIDDM, insufficiently controlled with diet. Beneficial effects of these distinct principles of action were statistically not different.

Dot immunobinding assay para la detección de anticuerpos antigonocócicos / Dot immunobinding assay for antigonoccocal antibodies detection

Se desarrolló un ELISA modificado, Dot immunobinding assay para detectar anticuerpos antigonocócicos en el suero de pacientes con infección gonocócica. Fueron analizadas 20 muestras provenientes de hombres con gonorrea confirmada mediante técnicas bacteriológicas tradicionales y otras 20 de niños mayores de 1 año sin antecedentes de infección. Todos los sueros de hombres infectados presentaron reacción positiva en alguna dilución. El grupo control fue negativo con excepción de una muestra. La sensibilidad del test fue 1 y la especificidad 0,95. El valor predictivo positivo 0,95 y el valor predictivo negativo igual a 1

Uso de la nimodipina (Nimotop) en psicogeriatría / Use of the nimodipine (Nimotop) in psychogeriatric

La nimodipina (Nimotop) es una droga prometedora para el anciano demente y para pacientes no dementes. Varios estudios doble ciego han demostrado que la droga puede ser efectiva para los déficit cognitivos, rendimiento, afectividad e integración social. Las conclusiones derivadas de los resultados de varios experimentos sobre conducta en animales son significativos para predecir los efectos clínicos de la nimodipina (Nimotop)

[Stomach tolerance of acetylsalicylic acid by addition of calcium carbonate. A study of a 2-treatment/3-period cross-over design]. / Magenverträglichkeit von Acetylsalicylsäure bei Zusatz von Calciumcarbonat. Eine Studie im Zwei-Behandlungen-/Drei-Perioden-Cross-over-Design.

18 male volunteers (age 24 +/- 4 years; Broca index 0.94 +/- 0.08; mean +/- SD) underwent six upper endoscopies (three control and three test investigations) in a single blind two treatments-crossover designed study which evaluated the effect of buffering on aspirin-induced (one single oral dose of 0.5 g aspirin to fasted subjects) gastroduodenal mucosal injury. All subjects had a normal endoscopy prior to applications of 0.5 g plain aspirin (group A; swallowed) or 0.5 g aspirin + 0.3 g calcium carbonate (group B; chewed before swallowing). The sequence groups were A-B-B (n = 9) or B-A-A (n = 9). In advance fo the performed tests a washout period of six days was chosen. Endoscopies were performed two hours after ingestion of the respective tablets. The appearance of corpus, antrum, and duodenum was scored. Biopsies were taken for histological examinations. 15 volunteers experienced no gastrointestinal side effects. Three complained short-lasting gastric burning (two of group A, one of group B). In both treatment groups no significant lesions of the duodenum were found. Buffering significantly (p less than 0.0005) reduced mucosal injuries which occurred mainly as submucosal hemorrhage but without histological alterations of the mucosal architecture after aspirin ingestion. These findings suggest that oral administration of calcium carbonate buffered, chewable aspirin tablets is less harmful to the gastric mucosa than plain aspirin.

The effect of new alpha-glucosidase inhibitors (BAY m 1099 and BAY o 1248) on meal-stimulated increases in glucose and insulin levels in man.

To confirm findings obtained from animal experiments demonstrating the metabolic effect of two new glucosidase inhibitors, 7 single blind cross-over studies with 42 healthy male volunteers were performed. In each group 6 subjects received 25, 50, 100 and 200 mg BAY m 1099 and 10, 20, and 40 mg BAY o 1248 or placebo with a standardized breakfast. Blood glucose and serum insulin were measured in venous blood before and 30, 60, 90, 120 and 180 min after each of 3 meals. ECG, blood pressure, body weight, monitor ECG and haematological and clinico-chemical parameters were also examined. The postprandial increase in blood glucose and serum insulin after breakfast were significantly and dose-dependently reduced by BAY m 1099. 10 and 20 mg BAY o 1248 not only reduced the increases in blood glucose and serum insulin after breakfast, but also after lunch (10 mg). 40 mg BAY o 1248 prevented the postprandial increase in both metabolic parameters after breakfast (p less than 0.05), an effect which was sustained after lunch. Intestinal problems occurred (flatulence, meteorism, diarrhoea) in 25 of 42 volunteers. Objective tolerability was good. The results of these first clinical pharmacological studies with two new glucosidase inhibitors justify studies on patients with diabetes mellitus.