Diarrea aguda en el lactante y preescolar / Acute diarrhea in toddlers and infants

Acute diarrhea (AD) is the increase in frequency and volume of bowel movements with decrease in their consistency that lasts less than 14 days. AD is a major public health problem and is still nowadays a cause of significant morbidity and mortality during childhood, especially in children with nutritional deficits. At a younger age, there is a greater susceptibility to diarrhea, which is more intense and more likely cause dehydration. The prevention and management of dehydration is the mainstay of treatment. The use of medications must be used with caution, analyzing individual cases and based on the best available evidence. We will analyze the subject with special emphasis on treatment according to scientific evidence.

La diarrea aguda (DA) se define como el aumento en la frecuencia y volumen de las deposiciones con disminución de la consistencia y que dura menos de 14 días. La DA es un gran problema de salud pública y es aún hoy en día una causa de importante morbimortalidad durante la infancia en especial en niños con déficits nutricionales. A menor edad hay mayor susceptibilidad de presentar diarrea, siendo ésta de mayor intensidad y con mayores posibilidades de producir deshidratación. La prevención y el manejo de la deshidratación es el pilar fundamental del tratamiento. El uso de medicamentos debe ser criterioso, analizando cada caso individual y basado en la mejor evidencia disponible. Analizaremos el tema con especial énfasis en el tratamiento según evidencia científica.

[Breath tests in children with suspected lactose intolerance]. / Análisis de test de aire espirado en niños con sospecha de intolerancia a la lactosa.

INTRODUCTION: Up to 70% of the world population is lactose intolerance. However, there are no epidemiological studies among Chilean pediatric population affected by this condition. OBJECTIVES: Clinical characterization of a series of children who underwent the lactose intolerance breath test for lactose intolerance study, establishing intolerance and malabsorption frequencies, the most frequent symptoms, and test performance depending on the origin. PATIENTS AND METHODS: Patients under 18 years old who took the lactose intolerance breath test in the Gastroenterology Laboratory of the Catholic University of Chile, and who were admitted due to clinically suspected lactose intolerance. Malabsorption was considered when there was as an increase of ≥20ppm above the baseline (H2) or ≥34ppm of H2 and methane (CH4) combined. Intolerance was considered when the above was associated with a symptom intensity score ≥7 during registration. RESULTS: The analysis included194 patients aged 1 to17 years of age. Of these, 102 (53%) presented with malabsorption, and 53 (27%) were intolerant. The frequency of lactose intolerance varied from 7.1 to 45.4%, and it occurred more frequently at older ages. The most common reported symptoms were abdominal pain, bloating and rumbling. DISCUSSION: Lactose malabsorption and intolerance can be investigated from the first years of life using the lactose breath test plus a symptom questionnaire. An increase in the frequency of intolerance with age, and a greater number of positive tests, if they were requested by a gastroenterologist, were observed.

Análisis de test de aire espirado en niños con sospecha de intolerancia a la lactosa / Breath tests in children with suspected lactose intolerance

Introducción: Un 70% de la población general presenta intolerancia a la lactosa; sin embargo, no existen estudios epidemiológicos en la población pediátrica chilena afectada por esta condición. Objetivos: Caracterizar una serie clínica de niños que acude a realizarse el test de aire espirado con lactosa para estudio de intolerancia a la lactosa, determinando la frecuencia de intolerancia y malabsorción, síntomas más frecuentes y rendimiento del test dependiendo de su origen. Pacientes y Método: Pacientes menores de 18 años que acudieron a realizarse el test de aire espirado con lactosa al Laboratorio de Gastroenterología de la Pontificia Universidad Católica de Chile, por sospecha clínica de intolerancia a la lactosa. Se consideró malabsorción un aumento ≥ 20 ppm sobre el nivel basal de hidrógeno (H2) o ≥ 34 ppm de H2 y metano (CH4) en conjunto y como intolerancia cuando lo anterior se asoció a la sumatoria de intensidad de síntomas ≥ 7 en el registro. Resultados: Se analizaron 194 pacientes entre 1 y 17 años de edad. De ellos, 102 (53%) pacientes resultaron malabsorbedores y 53 (27%) intolerantes. La frecuencia de intolerancia a la lactosa varió de un 7,1 a un 45,4%, con una mayor frecuencia a edades mayores. Los síntomas más reportados fueron dolor abdominal, meteorismo y borborigmo. Discusión: La malabsorción e intolerancia a lactosa se pueden pesquisar desde los primeros años de vida utilizando el test de aire espirado con lactosa asociado al cuestionario simultáneo de síntomas. Se puede observar un aumento en la frecuencia de intolerancia con la edad, además de una mayor positividad del examen si es solicitado por un gastroenterólogo.

Introduction: Up to 70% of the world population is lactose intolerance. However, there are no epidemiological studies among Chilean pediatric population affected by this condition. Objectives: Clinical characterization of a series of children who underwent the lactose intolerance breath test for lactose intolerance study, establishing intolerance and malabsorption frequencies, the most frequent symptoms, and test performance depending on the origin. Patients and Methods: Patients under 18 years old who took the lactose intolerance breath test in the Gastroenterology Laboratory of the Catholic University of Chile, and who were admitted due to clinically suspected lactose intolerance. Malabsorption was considered when there was as an increase of ≥ 20 ppm above the baseline (H2) or ≥ 34 ppm of H2 and methane (CH4) combined. Intolerance was considered when the above was associated with a symptom intensity score ≥ 7 during registration. Results: The analysis included194 patients aged 1 to17 years of age. Of these, 102 (53%) presented with malabsorption, and 53 (27%) were intolerant. The frequency of lactose intolerance varied from 7.1 to 45.4%, and it occurred more frequently at older ages. The most common reported symptoms were abdominal pain, bloating and rumbling. Discussion: Lactose malabsorption and intolerance can be investigated from the first years of life using the lactose breath test plus a symptom questionnaire. An increase in the frequency of intolerance with age, and a greater number of positive tests, if they were requested by a gastroenterologist, were observed.

Evaluación de los niveles de orientación empática en estudiantes de odontología de la Universidad Finis Terrae de Santiago, Chile / Evaluation of empathetic orientation in dentistry students of Finis Terrae University in Santiago, Chile

Objetivo: Evaluar el nivel de orientación empática en los alumnos de la Facultad de Odontología de la Universidad Finis Terrae. Materiales y Métodos: Se realizó un estudio no experimental, descriptivo, transversal y ex post facto causa-efecto. Participaron 309 alumnos, de un universo de 430, correspondientes a los niveles 1º, 2º, 3º, 4º y 5º de la Facultad de Odontología de la Universidad Finis Terrae (Chile) en 2012, a quienes se aplicó la Escala de Empatía Médica de Jefferson (EEMJ). Para el análisis de los datos obtenidos se realizó la prueba de normalidad de Shapiro-Wilk y la prueba de homocedasticidad de Levene. Posteriormente se estimaron los estadígrafos descriptivos en todos los factores estudiados, y finalmente la comparación de las medias se realizó mediante un Análisis de Varianza Bifactorial y una prueba de comparación múltiple de Duncan. Resultados: Las mujeres obtuvieron mayores puntuaciones en la EEMJ con significación estadística en en relación a los hombres (p<0.05). No se observaron diferencias significativas en el factor nivel de carrera. Conclusiones: Las mujeres tienen niveles mayores de orientación empática durante toda la carrera en relación a los hombres y, en ambos, es mayor el valor de orientación empática en la medida que aumenta el curso examinado. Tal efecto es más pronunciado en las mujeres que en los hombres.

Objetive: To evaluate the empathetic orientation of the dentistry students of Finis Terrae University. Materials and Methods: This investigation is a non experimental, descriptive, cross-sectional research. 309 out of 430 students participated. They belonged to the 1º, 2º, 3º, 4º and 5º grade of the Dentistry School of Finis Terrae University (Chile) in 2012. The Jefferson Scale of Physician Empathy was applied. Shapiro-Wilk normality test and Levene homoscedasticity test were performed for the analysis of the data obtained. Subsequently, descriptive statigraphs were considered in all the studied factors and finally average comparison was made through Bifactorial analysis of variance and a Duncan multiple comparison test. Results: Higher scores in the JSPE with statistical significance were obtained in women when compared with men (p<0.05). No significant differences were found in the scores related to the grade. Conclusions: Women had higher levels of empathetic orientation than men during their educational program. Both, women and men had shown changes in their scores as the curriculum develops. That effect is more pronounced in women than men.

D-lactoacidosis como complicación del síndrome de intestino corto / D-lactoacidosis as short bowel syndrome complication

Short bowel syndrome is defined as the loss, congenital or acquired, anatomical or functional, of a large part of the small intestine that generates inadequate absorption of nutrients and the frequent need of prolonged parenteral nutrition. The etiology of short bowel is diverse and varies with age. The necrotizing enterocolitisis and the midgut volvulus are among the most frequent causes. The bacterial overgrowth is frequently observed in children with short bowel, due to the secondary dilation of the remaining small bowel and to the associated intestinal dysmotility. It is more frequent in absence of the ileocecal valve. We present a 6-year-old boy with short bowel syndrome secondary to extensive intestinal resection after a volvulous of the medium small intestine, 9 months before admission to the hospital, and who was on cyclical parenteral nutrition at home. The child developed ataxia, disarthria, dizziness and conscience compromise been admitted to de intensive care unit in deep sopor. An extensive work up including metabolic, infectious, toxicology and SNC imaging was negative except for metabolic acidosis. He was discharged on good conditions. Even though the child was on supportive therapy, the patient was readmitted few hours later with similar symptoms. D-lacto acidosis was suspected and confirmed with a value of 6.69 mmol/1 (normal range: 0,0-0,25). Literature about this uncommon complication and its mechanism is reviewed. D-lacto acidosis should be suspected in every patient with short bowel syndrome and unexplained metabolic acidosis associated with neurological symptoms.

El síndrome de intestino corto se define como la pérdida, congénita o adquirida, anatómica o funcional, de una extensa área del intestino delgado que genera inadecuada absorción de nutrientes y la frecuente necesidad de nutrición parenteral prolongada. Su etiología varía con la edad. Entre las causas más frecuentes están la enterocolitis necrotizante y el vólvulo de intestino medio. El sobrecrecimiento bacteriano es frecuente en estos pacientes, debido a la dilatación secundaria del remanente de intestino delgado y a la dismotilidad intestinal asociada. Objetivo: Comunicar un caso de acidosis D-láctica en un niño con Intestino corto. Caso clínico: Niño de 6 años con antecedente de intestino corto secundario a resección intestinal por vólvulo de intestino medio 9 meses previos al ingreso y que estaba recibiendo nutrición parenteral domiciliaria ciclada. El niño desarrolló ataxia, disartria, mareos y compromiso de conciencia, ingresando a la unidad de cuidados intensivos en sopor profundo. Un extenso estudio metabólico, infectológico, toxicológico y de neuroimágenes fue negativo, excepto por acidosis metabólica. Fue dado de alta en buenas condiciones. A pesar del tratamiento de soporte vuelve a ingresar horas después con similar cuadro clínico. Se sospecha y confirma elevación de D-lactato en sangre (6,69 mmol/1 con rango normal de 0,0-0,25). Se revisa la literatura acerca de esta infrecuente complicación y su mecanismo de producción. La D-lactoacidosis debiera ser sospechada en todos los pacientes portadores de intestino corto que presenten un cuadro de acidosis metabólica no explicada, especialmente si se acompaña de compromiso de conciencia y síntomas cerebelosos.

Infecciones virales intestinales en pediatría / Intestinal viral infections in pediatrics

Los virus que causan diarrea en humanos generalmente muestran gran trofismo por las células epiteliales del intestino delgado. El mecanismo tradicionalmente aceptado es que estos agentes causan enfermedad destruyendo gran cantidad de entericitos maduros, (sea por lisis directa o induciendo la apoptosis) los que son reemplazados por células inmaduras provenientes de las criptas. Esto lleva a una absorción inadecuada de agua, electrolitos y nutrientes, con capacidad conservada de secretar cloro y agua. A diferencia de lo que ocurre frente a patógenos bacterianos invasores, la respuesta inflamatoria del huésped es leve y no contribuye significativamente en el mecanismo de la diarrea viral. Estudios posteriores han llevado a postular mecanismos adicionales, que no serían autoexcluyentes. Se ha descrito que algunas proteínas virales no estructurales actuarían como enterotoxina. Además, jugaría un rol la alteración de las uniones estrechas con aumento del flujo paracelular de agua y electrolitos, el aumento de la secreción intestinal mediada por neurotransmisores, y la microisquemia vellositaria. El impacto de la enteritis viral es mayor y la recuperación más lenta en niños previamente desnutridos. Se ha demostrado en animales de experimentación desnutridos un notorio retraso en la recuperación de la capacidad enzimática y absortiva de la mucosa intestinal frente a una enteritis viral, lo que refuerza la necesidad de una temprana y efectiva rehabilitación nutricional durante los episodios agudos de diarrea. Es ampliamente conocido que la lactancia materna, disminuye la incidencia y severidad de las diarreas virales en niños, los primeros meses de vida.

Viruses that cause diarrhea in humans generally show great tropism due to epithelial cells of the small intestine. The traditionally accepted mechanism is that these agents cause illness by destroying large number of mature enterocytes (via direct lysis or by inducing apoptosis), which are replaced by immature cells coming from the crypts. This leads to an inadequate absorption of water, electrolytes and nutritients with conserved chloride and water secretion. In contrast to invasive bacterial pathogens, the host infl amatory response is mild and it does not contribute significantly to the mechanism of viral diarrhea. Subsequent studies have leaded to postulate additional mechanisms that would not exclude each other. It has been described that some non-structural viral proteins may act as enterotoxin. In addition, the alteration of the tight junctions with an enhanced paracellular flow of water and electrolytes, the increase of neurotransmitter mediated intestinal secretion, and the micro-ischemia of villi would also play a role. The impact of viral enteritis is larger and the recovery slower in previously undernourished children. Studies carried out on undernourished experimentation animals have demonstrated a notorious delay in the recovery of the enzymaticand absorptive capacity of intestinal mucosa after viral enteritis, which reinforces the need for early and effective nutritional rehabilitation during episodes of acute diarrhea. It is well-known that the breastfeeding reduces the incidence and severity of viral diarrheas in children during the first months of life.

Bioavailability of a controlled-release cyclobenzaprine tablet and influence of a high fat meal on bioavailability.

OBJECTIVE: To evaluate the systemic bioavailability of a new controlled release cyclobenzaprine tablet, and the influence of a high fat meal on its bioavailability. SUBJECTS, MATERIALS AND METHODS: 24 and 12 healthy male subjects were recruited for the bioavailability and influence of diet studies, respectively. Experimental design for both studies was an open randomized, 2-period, single dose, crossover study. In the bioavailability study, each subject received in different occasions, a single oral dose of cyclobenzaprine of immediate (10 mg) or controlled release (20 mg) tablet, followed by a 2-week washout period. In the influence of diet study, the volunteers received the controlled-release tablet concomitantly with a high fat meal or in a state of fasting. RESULTS: In the bioavailability study, plasma cyclobenzaprine profiles were in agreement with a controlled release system. This formulation presented a 92.8% of relative bioavailability (IC 85.5 - 105%) and a significant reduction in Cmax (IC 58 - 65.5%), when compared with equal dose of the immediate release tablet. The presence of food increased AUC (11.6%) and Cmax (48%). For both parameters the calculated 90% confidence interval was not in the bioequivalence interval, 97.4 - 125.8% for AUC and 111.7 - 184.2% for Cmax. CONCLUSIONS: The controlled release tablet showed a relative bioavailability comparable with equal dose of the immediate release product and produced a significantly lower Cmax, as expected in a controlled release formulation. The concomitant administration of the tablet with a high fat meal produced an increase on its bioavailability, mainly in Cmax, with no evidence of dose-dumping.

Pharmacokinetics of prednisolone in man during acute and chronic exposure to high altitude.

INTRODUCTION: The exposure to high altitude (H) produces several physiologic alterations which may induce changes in the pharmacokinetics of drugs. This hypothesis has been confirmed in previous studies which suggest that drugs which are highly bound to plasma proteins are most likely to exhibit altered pharmacokinetics. OBJECTIVES: To further elucidate the influence of H on pharmacokinetics, prednisolone was selected, since it is highly bound to plasma proteins, renally excreted and poorly bound to red blood cells. SUBJECTS, MATERIALS AND METHODS: Prednisolone (80 mg) was given orally to three groups of young healthy volunteers. One group was residing at sea level (L): the same volunteers were studied again after 15 hours of exposure to high altitude (3600 m, HA group), and volunteers living at H for at least six months (group HC). RESULTS: There were no statistically significant differences in the pharmacokinetic parameters calculated from plasma data in the three situations studied. When calculated from whole blood data, however, AUC and Cmax were increased and both volume of distribution and clearance diminished after exposure to H, either acute or chronically. Binding to proteins increased significantly after H exposure from 57% in group L to 75% and 94% in group H and HC, respectively. Binding to erythrocytes also increased with H exposure from 43.7% in group L to 50.6% and 61.6% in group HA and HC, respectively. The prednisolone/prednisone ratio in urine was 11.1 in group L, 7.3 in group HA and 45.6 in group HC. CONCLUSION: Since prednisone has very little intrinsic glucocorticoid activity and has to be converted to prednisolone for therapeutic effect, the alteration of the prednisolone/prednisone ratio, as a result of high altitude exposure could be clinically relevant. Additional experiments are desirable to further evaluate this observation.

Effects of high altitude exposure on the pharmacokinetics of furosemide in healthy volunteers.

INTRODUCTION: A cascade of pathophysiological events occurs with the ascension to high altitude (H). We have performed studies on the effects of exposure to H on the pharmacokinetics of drugs. The hypothesis behind these studies has been that the exposure to H, which produces marked physiological changes in the body, may alter pharmacokinetics, and consequently, pharmacodynamics. Our previous studies suggest that drugs highly bound to plasma proteins are most likely to exhibit altered disposition. OBJECTIVE: In continuation of our research, we selected furosemide which is about 98% bound to plasma proteins, renally excreted and has low binding to red blood cells. SUBJECTS, MATERIALS AND METHODS: Furosemide (40 mg) was administered orally to 3 groups of young healthy volunteers. One group who had been residing at sea level (group L), the same group after 15 hours of exposure to high altitude (3,600 m, group HA) and a group of volunteers living at H for at least 6 months (group HC). RESULTS: Our results are in accordance with the most recent pharmacokinetic studies on furosemide in which a terminal half-life of approximately 20-30 h was reported. Total proteins were 9.3% and 12.7% higher in groups HA and HC, respectively, than in group L. Albumin in group HC was 8.2% higher than group L. Bilirubin increased 17.7% and 41.2% in groups HA and HC, respectively, in comparison with group L. A rapid disposition rate constant in groups HA and HC was the only pharmacokinetic parameter that was significantly different from those in group L. Concentration of furosemide in plasma water increased significantly after H exposure, thus, the binding diminished from 97.2% in group L to 95.1% and 91.1% in groups HA and HC, respectively. CONCLUSION: Exposure to H produces an increase in the free fraction of furosemide in humans, which could be of therapeutic importance.

Validated HPLC method for the determination of ranitidine in plasma.

A validated HPLC method for the determination of ranitidine in human plasma is presented. Sulfanilamide as internal standard (IS) was used. Plasma samples were purified by solid phase extraction (SPE) using a copolymeric [poly(divinyl-benzene-co-N-vinylpyrrolidone)] column ("Oasis Waters"). Mobile phase consisting of dibasic potasium phosphate 0.08 M/acetonitrile/methanol/triethylamine 0.05% (89.5:3:7:0.05) pH5 was used at a flow rate of 0.9 ml/min on a C18 column (Nova-Pack, 3,9 x 300 mm, Waters). The eluate was monitored using an UVNis detector set at 300 nm. Ratio of peak area of ranitidine to sulfanilamide was used for the quantitation of plasma samples. FDA criteria for bioanalytical validation was used to validate the method. Linearity was assessed between 100-1600 ng/ml, the limit of quantitation was 100 ng/ml and recovery was greater than 94%. Accuracy, precision and selectivity met the current recommendations for bioanalytical method validation. The method was successfully used in a bioavailability study of a ranitidine tablet in healthy volunteers.

Pharmacokinetics of lithium in healthy volunteers after exposure to high altitude.

INTRODUCTION: Exposure of the human body to high altitude causes a number of physiological changes. In previous studies, we observed that these changes may alter the pharmacokinetics of drugs. The number of erythrocytes/mm3 increases both, after acute exposure to high altitude (HA), i.e. within 12 - 24 h after reaching high altitude (H), as well as in chronic exposure (HC) (> 10 months) to H. Also binding of drugs to biologic material may change with exposure to HA and/or HC. OBJECTIVE: Since lithium is transported into and out of erythrocytes and binds strongly to erythrocytes, but is not plasma protein-bound, we selected this drug as candidate for the present study. SUBJECTS, MATERIAL AND METHODS: Lithium carbonate 300 mg were administered orally to young healthy volunteers. One group residing at low altitude (Santiago, Chile, 600 m, group L), these same volunteers after 15 hours of exposure to high altitude (4,360 m, group HA), and volunteers living at high altitude for at least 10 months (group HC). RESULTS: We found a significant increase of both hematocrit and red blood cell count (RBC) after exposure to H, both, acute or chronic. Elimination half-life increased 64.1% in group HA and 111.4% in group HC in comparison to group L. We also found an increase in volume of distribution: + 18.9% in group HA, and + 35.8% in group HC when measured in plasma, and + 16.9% in group HA and + 18.8% in group HC when measured in whole blood. Lithium uptake by the erythrocytes increases: the value of 36.7 +/- 22.7% in Group L rose to 54.8 +/- 21.1% and to 54.6 +/- 24.2% in groups HA and HC, respectively. Total clearance decreases at high altitude, though the differences were significant only in group HC (37%). CONCLUSION: Results indicate that exposure to H produces alterations in the pharmacokinetics of lithium and that these variations may be clinically relevant.

[Acute cholangitis caused by choledocholithiasis: traditional surgery or endoscopic biliary drainage]. / Colangitis aguda debida a coledocolitiasis: cirugía tradicional o drenaje biliar endoscópico?

BACKGROUND: Endoscopic drainage of the biliary tree for acute cholangitis is a therapeutic modality with a lower mortality and complication rates. AIM: To compare endoscopic drainage with surgical treatment in the emergency management of acute cholangitis. PATIENTS AND METHODS: Between 1995 and 1998, sixty five patients with acute cholangitis were subjected to an endoscopic drainage of the biliary tree. In the same period, 40 patients were treated with traditional surgical procedures. The evolution of both groups of patients were compared. RESULTS: Sixty two patients (95.4%) subjected to endoscopic treatment had a satisfactory evolution, compared with 23 (58%) of those operated (p < 0.001). Five operated patients and no individual subjected to endoscopic drainage died (p < 0.01). Mean postoperative hospital stay of operated patients was 15.5 +/- 19.6 days compared to 5.8 +/- 4.2 days in those subjected to endoscopic drainage (p < 0.001). Definitive resolution of biliary obstruction was achieved in 83% of patients subjected to endoscopic drainage or traditional surgery. CONCLUSIONS: Endoscopic drainage has a lower rate of complications and mortality than traditional surgery, in the treatment of acute cholangitis.

Effect of three different diets on the bioavailability of a sustained release lithium carbonate matrix tablet.

BACKGROUND: Food-induced changes on the bioavailability of a sustained release lithium carbonate matrix tablet, which uses an acrylic matrix of Eudragit RSPM as sustaining agent, have been studied in healthy male volunteers. The tablet was developed in our laboratory using conventional technology. SUBJECTS, MATERIALS AND METHODS: The study design was a 4 x 4 Latin square involving 12 subjects who received a single dose of the tablet while fasting or with a standardized normal, high fat or high fat/high protein meal. RESULTS: The results showed no differences in half-lifebeta, renal clearance, Vdbeta, AUC, tmax, Xinfinite(u), fraction absorbed and MRT. Higher Cmax (mg/l) were obtained when the tablet was administered with any kind of meal: 2.09 +/- 0.47 (fast), 2.95 +/- 1.04 (normal diet), 2.64 +/- 0.54 (high fat diet) and 2.87 +/- 0.67 (high fat/high protein diet). The analysis of the ratio Cmax/AUC indicated that changes in Cmax were more probably due to changes in the rate of absorption. To evaluate if the magnitude of the change could be clinically relevant, Cmax and C at 12 hours (dosing interval) were treated by the superposition method in order to establish maximum and minimum concentrations at steady-state. For all the experimental conditions both concentrations would remain in the therapeutic range (4.2 10 mg/l or 0.6 - 1.4 mEq/l). CONCLUSION: The behavior of the formulation is appropriate for a sustained release tablet and fasting or non-fasting state seems not to be a major consideration for bioavailability when deciding on the regimen administration.

Pharmacokinetics of acetazolamide in healthy volunteers after short- and long-term exposure to high altitude.

Exposure to high altitude results in significant physiologic changes and may precipitate mountain sickness, ranging from mild symptoms above 2,500 m to severe symptoms above 4,000 m. In a previous study, changes in the pharmacokinetics of meperidine were observed after exposure to high altitude. This study was conducted to investigate whether similar changes occur for acetazolamide, which is prescribed for prophylaxis of acute mountain sickness. Acetazolamide 250 mg was administered orally to young, healthy male volunteers in groups of 12 each: those residing at sea level (group L), these same volunteers on the day after arrival at high altitude (4,360 m, group HA), and volunteers living at high altitude for 10 months or longer (group HC). Serial blood samples were collected for 24 hours and acetazolamide concentrations were measured in whole blood, plasma, and plasma water. The elimination rate constant (lambda z) was significantly increased in group HA compared with group L. Clearance uncorrected for bioavailability (Cl/F) increased significantly in group HA compared with group L, and further increased in group HC. Apparent volume of distribution (Vz/F) was decreased by 17% in group HA compared with group L, and increased by 37% in group HC compared with group HA. Mean residence time (MRT) was significantly decreased in group HA compared with groups L and HC. Erythrocyte (RBC) uptake increased significantly after a significant increase in RBC count in group HC compared with group L. The extent of protein binding (EPB), however, was significantly decreased in group HA compared with groups L and HC. Free acetazolamide concentrations were significantly lower in group HC than in group L 12 hours after administration. Based on these observations, it is suggested that patients travelling to high altitude, especially altitudes above 4,000 m, should be closely monitored and acetazolamide dosage adjusted as necessary.

Urinary excretion of acetazolamide in healthy volunteers after short- and long-term exposure to high altitude.

Acetazolamide is recommended for the prophylaxis of acute mountain sickness symptoms which sets in on climbing to high altitudes (H) above 2,500 m. It is primarily excreted unchanged in urine. In a previous study, we reported on the changes in urinary excretion of meperidine and its metabolite normeperidine on exposure to high altitude. In this study, we investigated the effect on urinary excretion of acetazolamide. The study was carried out in three groups of 12 healthy male volunteers each: at sea level (group L), these same volunteers the day after arrival at high altitude of 4,360 m (group HA), and subjects residing for approximately 10 months at high altitude (group HC). Urine was collected for the periods of 0-2, 2-4, 4-8, 8-12, 12-24 and 24-36 h after peroral administration of a single 250 mg dose. Urinary pH was measured and the concentrations of acetazolamide were determined. There were no significant changes observed in the amount of acetazolamide excreted in urine over 36 h. The urinary pH ranged from 4.5 to 7.8 for L, from 4.2 to 6.9 for HA and from 3.1 to 6.7 for HC. The Fel (fraction eliminated unchanged in urine) was calculated from the amount excreted in 36 h in urine and dose, assuming a bioavailability of 1 based on literature data. No significant changes in Fel were seen.

Evaluación retrospectiva de fracturas orbitarias / Orbital fracture retrospective assessment

Los traumatismos faciales comprometen en un alto porcentaje a la región orbitaria determinando en ésta distintos tipos de fracturas. Para conocer la realidad del Hospital Carlos Van Buren en cuanto a los principales atributos de la población afectada por Fracturas Orbitarias (F.O.), su clínica y manejo general, se realizó un estudio descriptivo desde el año 1993 al año 1996. Se seleccionaron 30 pacientes que ingresaron al Servicio de Otorrinolaringología durante este período. La relación hombre: mujer fue de 5:1. El grupo más afectado correspondió a varones jóvenes. Las causas más frecuentes fueron agresiones y accidentes de tránsito. Utilizando la clasificiación de Nolasco y Mathog, se encontró un 70 por ciento de fracturas tipo III, un 17 por ciento de fracturas tipo IV, y un 13 por ciento de fracturas tipo II. No se encontraron fracturas tipo I. Las manifestaciones clínicas más constantes fueron la hemorragia subconjuntival y el hundimiento facial en las fracturas malares. El tratamiento fue casi exclusivamente quirúrgico (86,6 por ciento). Los abordajes quirúrgicos más usados fueron el subpalpebral en combinación al subciliar externo y Caldwell-Luc. Como material de osteosíntesis se usó preferentemente alambre. Las complicaciones más frecuentes fueron ectropion, díplopia y consolidación viciosa

Pharmacokinetics of meperidine in healthy volunteers after short- and long-term exposure to high altitude.

Increased numbers of erythrocytes have been shown ex vivo to increase meperidine uptake, and one of the major physiologic changes that occurs at high altitude is an increase in hematocrit and erythrocytes. A study was therefore conducted to evaluate the effects of high altitude on the pharmacokinetics of meperidine. Intramuscular doses (0.75 mg/kg) of meperidine were given to three groups of healthy volunteers (age range, 18-20 years): participants living at sea level (group L), those same participants the day after arrival at high altitude (4,360 m; group HA), and participants who had lived at high altitude for > or = 10 months (group HC). Blood samples were collected for 12 hours after drug administration. Meperidine was measured in whole blood, plasma, and plasma water. Elimination rate constant (lambda z) and clearance uncorrected for bioavailability (Cl/F) were significantly lower at high altitudes than at sea level in plasma (HA and HC) and in whole blood (HA only). Mean residence time (MRT) was significantly higher at high altitudes than at sea level in plasma (HA and HC) and in whole blood (HA only). Hematocrit was significantly increased at both time points at high altitude in comparison to values at sea level, and was also higher after a long-term stay at high altitude than after arrival at high altitude. Erythrocyte binding increased significantly from 41.3% at sea level to 43.8% at arrival at high altitude to 50.9% after a long-term stay at high altitude. The extent of protein binding tended to decrease with high altitude, but this decrease was not significant. Free concentrations of meperidine in plasma water measured 1, 2, and 4 hours after administration were significantly increased after 2 and 4 hours.