Cirugía del sueño: Definición de una especialidad emergente, propuesta de una clasificación anatomofuncional integral e indicaciones

Resumen Los trastornos respiratorios del sueño (ronquido primario y síndrome de apnea-hipopnea obstructiva del sueño) han sido tratados mediante múltiples modalidades a lo largo de la historia. Sin embargo, la cirugía de la vía aérea superior siempre ha estado presente, dando cabida a la aparición de múltiples técnicas para este fin. El estudio adecuado de los sitios anatómicos de estrechez o colapso de la vía aérea superior y sus contribuyentes (bajo el concepto de topodiagnóstico) y el mejor entendimiento de los mecanismos de acción de los diferentes procedimientos descritos, ha permitido el nacimiento de una nueva disciplina, dedicada al manejo quirúrgico planificado de este grupo de patologías: la cirugía del sueño.

Abstract Sleep-related breathing disorders (primary snoring and obstructive sleep apnea-hypopnea syndrome) have been treated with multiple modalities throughout history. However, upper airway surgery has always been present, giving appearance of multiple techniques for this purpose. The adequate study of the anatomical sites of upper airway narrowness or collapse and its contributors (under the concept of topodiagnosis) and a better understanding of the different procedures, has allowed the birth of a new discipline, dedicated to a planned surgical management for this group of pathologies: sleep surgery.

Tomografía de Coherencia Óptica. Uso en Dermatología / Optical Coherence Tomography. Use in Dermatology

RESUMEN La Tomografía de Coherencia Óptica (OCT) ha sido recientemente muy usada en diversas patologías de piel. Es una técnica no invasiva para la investigación morfológica de los tejidos, comparable con una biopsia virtual, capaz de generar imágenes en sección transversal de la microestructura del tejido; esta técnica se basa principalmente en el esparcimiento de la luz en los medios a estudiar y gracias a las fibras de colágeno hace que pueda utilizarse en la piel. Con el uso de OCT, es posible caracterizar la morfología normal y patológica de la piel, similar a la arquitectura del tejido que se observa en la histología de rutina, así como la progresión de la enfermedad, la cual se puede investigar in situ. Representa un enfoque no traumático y eficiente en el tiempo para el diagnóstico y seguimiento de un amplio número de enfermedades dermatológicas.

SUMMARY The Optical Coherence Tomography (OCT) has recently been widely used in various skin pathologies. It is a non-invasive technique for the morphological research of tissues, comparable with a virtual biopsy, capable of generating cross-sectional images of the tissue microstructure; this technique is based mainly on the scattering of light in the media to be studied and thanks to the collagen fibers it can be used on the skin. With the use of OTC, it is possible to characterize the normal and pathological morphology of the skin, similar to the tissue architecture observed in routine histology, as well as the progression of the disease which can be investigated in situ. Representing a non-traumatic and time-efficient approach for the diagnosis and monitoring of a large number of dermatological diseases.

La lente dermatológica… historia y algo más / Dermatological vision lens... history and something else

El microscopio es un instrumento, que desde hace muchos años es herramienta diagnóstica en Dermatología. La evolución del microscopio ha ido en sinergia con el avance de la tecnología, siendo el desarrollo de imágenes microscópicas digitalizadas, fuente de estudio en la época actual. El uso de estas imágenes en Dermatología ha permitido realizar diagnósticos en tiempo real; situación que vence la celeridad diagnóstica y aminora tanto para el médico como para el paciente, la lentitud de otras técnicas. El conocimiento sobre los diferentes métodos que se utilizan actualmente, para confirmar diagnósticos de enfermedades cutáneas, como: la dermatoscopía, la dermatoscopía multiespectral y la microscopía confocal de reflectancia, son imprescindibles para la formación del dermatólogo de hoy en día, ya que, con ellos se resumen pasos para el manejo definitivo de los pacientes. Con esta disertación, realizaremos un breve análisis de la historia de la microscopía, desde sus inicios hasta la era digital y los beneficios que se obtienen, con el uso de cada una de estas técnicas diagnósticas.

The microscope, is an instrument that for many years is used as a diagnostic tool in Dermatology. The evolution of the microscope has gone in synergy with the advancement of technology, being the development of digitized microscopic images a source of study and research in the present time. The use of these images in Dermatology has carried out diagnoses in real time; situation that overcomes the diagnostic speed and reduces for both the doctor and the patient the slowness of other techniques. The knowledge about the different methods currently used to confirm skin diseases, such as dermatoscopy, multispectral dermoscopy and confocal reflectance microscopy, is essential for the formation of today's dermatologist, since they summarize the steps for the definitive management of patients. With this dissertation, we will make a brief analysis of the history of microscopy from its beginnings to the digital age, and the benefits obtained with the use of each of these diagnostic techniques.

Morfea localizada en cuero cabelludo / Localized morphea on the scalp

La morfea o esclerodermia localizada, es una enfermedad del tejido conectivo, benigna, crónica y autoinmune, que se caracteriza por un endurecimiento de la piel, debido a una síntesis aumentada de colágeno. La incidencia anual varía entre 0,4 y 2,7 por 100.000 personas, con un predominio femenino de 2,4 a 4,2:1 y es dos a tres veces más frecuente que la esclerosis sistémica. Existen diversas formas de presentación, siendo la morfea en placas la más común en los adultos y la afectación del cuero cabelludo, en niños. El diagnóstico es clínico y se confirma mediante biopsia.

Morphea or localized scleroderma, is a benign, chronic, and autoimmune connective tissue disease, characterized by a hardening of the skin, due to an increased synthesis of collagen. The annual incidence varies from 0.4 to 2.7 per 100.000 people, with a female predominance of 2.4 to 4.2: 1 and is two to three times more frequent than systemic sclerosis. There are several forms of presentation, with plaque morphea being the most common in adults and the scalp involvement, in children. The diagnosis is clinical and confirmed by biopsy.

Paradojas del color en dermatología / Paradoxes of color in dermatology

La lógica dermatológica, ha encontrado el rompimiento de los paradigmas semiológicos, desde la incorporación de la imagen digital al estudio de las lesiones de piel, características como: forma, límites, contraste, estructura y profundidad están ligadas al color. Su percepción puede objetivarse, con la ayuda de instrumentos como el dermato-colorímetro, el derma-espectrofotómetro e inclusive el dermatoscopio digital, que permiten corregir los errores de metamerismo. En esta disertación pretendemos abrir nuevas ideas, sobre la importancia de estudiar el color de la piel más allá del fototipo cutáneo, así como, reconocer el color estructurado como una variante de la semiología pigmentaria y la incorporación del estudio heurístico, en el diseño de modelos enseñanza-aprendizaje para los programas de Dermatología.

The dermatological logic study has found breaking out paradigms since the introduction of digital imaging for the study of skin disease, features like shape, boundaries, contrast, depth and structure are related to color, color perception can be objectified through instruments such as derm-colorimeter, derm-spectrophotometer and even digital dermatoscopy, which can correct the metamerism phenomenon. In this dissertation, we intend to open mind and give new ideas about the importance of studying the skin color beyond the skin phototype, recognize the structured color as a variant of the semiology of color, as well as the incorporation of models of study design teaching-learning heuristic for dermatology programs.

Acute oral, pulmonary and intravenous toxicity/pathogenicity testing of a new formulation of Bacillus thuringiensis var israelensis SH-14 in rats.

During the last decades, efforts are being made to develop microbial insecticides as biological control agents. Bacillus thuringiensis has been one of the most consistent and significant biopesticides for using on crops as an insecticidal spray. The aim of this study was to assess and to compare the pathogenicity of a new formulation of B.thuringiensis var israelensis SH-14 in rats through oral, intranasal and intravenous single dosing. Through 21 days after administration, clinical examinations were performed daily, and body weight gain was evaluated. Clearance was estimated by means of collection of feces or examination of lungs and blood, and infectivity was evaluated enumerating microorganisms from organs of Bti SH-14 treated animals sacrificed at intervals. Gross necropsy of animals was performed at interim or final sacrifice. There were no treatment-related mortalities, and no evidence of pathogenicity or treatment related toxicity, although in the intravenous study, the microorganism was capable of achieving persistence in organs after administration, and the Bti SH-14 treated animals developed skin ulcerations and hemorrhages at the injection site. It could be concluded that the tested microorganism was not toxic or pathogenic to rats via oral or intranasal route, although it was capable of achieving persistence in organs after intravenous administration, eliciting local effects at the injection site.

Evaluación de la patogenicidad en ratas del Paecilomyces lilacinus LPL-01 utilizando vías diferentes de exposición / Pathogenicity evaluation of Paecilomyces lilacinus to rats

Los nemátodos parásitos de las plantas, conocidos como plagas agrícolas desde el siglo XIX, causan un 9% de pérdidas de cultivos en los países desarrollados y un 14% en los países en desarrollo. El Paecilomyces lilacinus es un hongo parásito que ataca formas sedentarias de los nemátodos, como los huevos. Su valoración como agente microbiano de control debe incluir una evaluación de su virulencia hacia organismos no-diana, tomando en consideración las vías posibles de exposición de los humanos. Para evaluar la patogenicidad de la cepa LPL-01 del P. lilacinus en ratas, se administró por las vías oral, pulmonar e intravenosa. Las observaciones clínicas fueron diarias, y se evaluó el comportamiento del peso corporal. Se estimó el aclaramiento mediante recolección de las heces fecales y análisis de muestras de los pulmones y de la sangre, según la vía de administración, y se evaluó la infectividad mediante toma de muestras de órganos de animales inoculados sacrificados a intervalos. Durante estos sacrificios, y al final de los ensayos, se realizó la necropsia de los animales. No ocurrieron mortalidades, ni evidencias de patogenicidad relacionada con el tratamiento en los ensayos oral y pulmonar, no provocando el hongo una infestación significativa. Por vía endovenosa, el microorganismo provocó alteraciones anátomo-patológicas en hígado y bazo, coincidiendo con el período de máxima infestación. Se concluyó que la cepa LPL-01 del P. lilacinus, a las dosis evaluadas, no es patogénica por las vías oral y pulmonar, siendo levemente patogénica por vía endovenosa

Plant parasitic nematodes have been recognized as agricultural pests in Europe as early as the late 19th century. It has been estimated that plant parasitic nematodes cause crop yield losses of nearly 9% in the developed world, and over 14% in developing countries. The Paecilomyces lilacinus is a parasitic fungi attacking sedentary stages of nematodes, e.g. eggs. Evaluation of this fungus as a microbial control agent, must include an evaluation of its virulence towards non-target organisms, especially vertebrates, with consideration given to potential human exposure scenarios. With the aim of assessing the pathogenicity in rats of the strain LPL-01 of Paecilomyces lilacinus, this fungus was given using several routes of exposure (oral, pulmonary and intravenous route). In all of the assays, clinical examinations were performed daily after administration, and body weight gain of animals was evaluated. Clearance was estimated by means of collection of feces and examination of lungs and blood, depending on the route used, and ineffectiveness was evaluated by enumerating microorganisms from organs and corporal fluids in animals sacrifice at intervals. A gross necropsy of all animals was performed at interim or final sacrifice. There were no mortalities, and no evidence of pathogenicity or treatment-related toxicity either in oral or pulmonary toxicity/pathogenicity tests, without significant infection of test animals. In the intravenous toxicity/pathogenicity test, P. lilacinus caused anatomopathological changes in liver and spleen at the same period when higher infectivity was achieved. It was concluded that P. lilacinus is not pathogenic by oral and pulmonary route, but has some pathogenic effects when intravenous injection is performed

Migration of bisphenol A (BPA) from can coatings into a fatty-food simulant and tuna fish.

The effect of heat processing, storage time and temperature on the migration of bisphenol A (BPA) from organosol and epoxy can coatings to a fatty-food simulant and tuna was determined. Analyses of BPA were performed by RP-HPLC with fluorescence detection. Four migration experiments, performed between 2000 and 2003, using cans with organosol, epoxy and a combination of both types of coatings were performed under different processing conditions and storage times. Migration levels as high as 646.5 microg kg(-1) BPA from an organosol coating of tuna fish cans were found using a fatty-food simulant following the heat processing of the simulant-filled cans. Levels ranging from 11.3 to 138.4 microg kg(-1) BPA from tuna cans coated with an epoxy resin migrated to the fatty-food simulant during 1 year at 25 degrees C. Levels of BPA migration into a fatty-food simulant from thermally processed and stored tuna cans coated with a combination of organosol and epoxy resins and from vegetable cans coated with an epoxy resin were below the limit of quantitation of 10.0 microg kg(-1). Migration of BPA to tuna ranged from <7.1 to 105.4 microg kg(-1) during long-term storage at 25 degrees C. BPA levels in tuna cans purchased from three local supermarkets ranged from <7.1 to 102.7 microg kg(-1). The highest migration levels were found following heat processing at temperatures as high as 121 degrees C and at times as long as 90 min. Coatings from different can batches can give different levels of BPA migration. The migration levels of BPA found in this work are below the present European Union migration limit, except the 646.5 microg kg(-1) found after the commercial heating process was applied to the simulant-filled cans coated with the organosol resin.

Evaluación de la toxicidad/patogenicidad de una formulación de Bacillus thuringiensis var israelensis (Bactivec) / Toxicity/pathogenicity evaluation of a Bacillus sphaericus 2362 formulation (Griselesf)

Existen varios agentes microbianos, incluyendo hongos, protozoos, virus y bacterias, que han sido utilizados como mosquiticidas. No obstante, entre esos agentes, el Bacillus thuringiensis es el más potente y ha sido el más ampliamente utilizado. El Bactivec es un biolarvicida producido en Cuba, que contiene Bacillus thuringiensis variedad israelensis como agente activo. Con el objetivo de evaluar su toxicidad/patogenicidad, se administró el Bactivec en una dosis única de 5 x 108 unidades formadoras de colonias por vía oral a ratas, y por vía dérmica a dos grupos de conejos albinos, uno recibiendo una dosis de Bactivec de l x 109 unidades formadoras de colonia por animal, y el otro una dosis de 9.2 x 108 de unidades formadoras de colonia de Bacillus thuringiensis variedad israelensis por animal. En ambos ensayos las observaciones clínicas fueron diarias, y se evaluó el comportamiento del peso corporal. Además, en el ensayo por vía oral se estimó el aclaramiento mediante recolección de las heces fecales, y se evaluó la infectividad mediante toma de muestras de fluidos y órganos. Al final de los ensayos se realizó la necropsia ä todos los animales. No ocurrieron mortalidades, ni evidencias de patogenicidad o toxicidad relacionada con el tratamiento en ninguno de los ensayos. En el ensayo de toxicidad/patogenicidad aguda oral se obtuvo que el microorganismo fue eliminado rápidamente sin provocar infección significativa. Se concluyó que el Bactivec no es patogénico por las vías oral y dérmica a las dosis evaluadas. (AU)

Ausencia de toxicidad / patogenicidad de una formulación de Bacillus sphaericus 2362 (Griselesf) / Lack of toxicity/pathogenicity of a Bacillus sphaericus 2362 formulation (Griselesf)

Los insecticidas microbianos ofrecen alternativas efectivas para el control de muchas plagas de insectos, siendo uno de sus mayores atractivos su especificidad. El Griselesf es un biolarvicida producido en Cuba, que contiene Bacillus sphaericus cepa 2362 como ingrediente activo. Con el objetivo de evaluar su toxicidad/patogenicidad, se administró el Griselesf en una dosis única de 5.6 x 108 unidades formadoras de colonia por vía oral a ratas, y por vía dérmica a dos grupos de conejos albinos, uno recibiendo una dosis de Griselesf de 1.12 x 109 unidades formadoras de colonia por animal, y el otro una dosis de 8.4 x 108 unidades formadoras de colonia de Bacillus sphaericus cepa 2362 por animal. En ambos ensayos, las observaciones clínicas fueron diarias, y se evaluó el comportamiento del peso corporal. Además, en el ensayo por vía oral se estimó el aclaramiento mediante recolección de las heces fecales, y se evaluó la infectividad mediante toma de muestras de fluidos y órganos. Al final de los ensayos se realizó la necropsia a todos los animales. No ocurrieron mortalidades, ni evidencias de patogenicidad o toxicidad relacionada con el tratamiento en ninguno de los ensayos. En el ensayo de toxicidad/patogenicidad aguda oral, el microorganismo fue aclarado rápidamente sin provocar infección significativa. Se concluyó que el Griselesf no es patogénico por las vías oral y dérmica. (AU)

[Epidemiological study of the hepatitis C virus in our population and vaccine coverage]. / Estudio epidemiológico del virus de la hepatitis C en nuestra población y cobertura vacunal.

OBJECTIVE: Epidemiological study of patients with chronic hepatitis C and its serological status in relation to the hepatitis A (HA) and B (HB) viruses. DESIGN: Descriptive cross-sectional study. SETTING: Two urban health centres. Participants. 291 patients with chronic hepatitis C. VARIABLES: age, sex, year and reason for diagnosis, personal histories, alcohol intake, serological status of the HA and HB viruses and HIV, and initial level of transaminases. RESULTS: Mean age, 55 +/- 16. Sex, 52% women. Prevalence, 0.98%. Reason for diagnosis, 41% health study, 15% study of hepatic pathology, 18% study of other pathologies. Personal histories, surgical intervention, 37.5%; intravenous drug users, 21.4%; transfusion, 14%; high-risk sexual conduct, 2.4%; health material used more than once, 2.4%; family member HC positive, 1.4%; no personal history recorded, 26.5%. Alcoholism, 17.9%. Mean transaminases: AST, 79.7 +/- 100 (9-920); ALT, 114.8 +/- 160 (6-1640). HB serological status: natural immunity, 22%; chronic, 9%; vaccine immunity, 3%; negative, 44%; not recorded, 21%. HA serological status: natural immunity, 2%; vaccine immunity, 2.5%; negative, 9%; not recorded, 87%. HIV-positive: 4.5%. CONCLUSIONS: Prevalence was below the expected level. Knowledge of serological status needs to be improved, especially for HA. The degree of vaccine coverage in these patients for HA and HB should be increased.

Estudio epidemiológico del virus de la hepatitis C en nuestra población y cobertura vacunal / Epidemiological study of the hepatitis C virus in our population and vaccine coverage

Objetivo. Estudio epidemiológico de los pacientes con hepatitis C crónica y su estado serológico en cuanto a los virus de la hepatitis A (VHA) y B (VHB).Diseño. Estudio transversal descriptivo. Emplazamiento. Dos centros de salud urbanos. Participantes. Un total de 291 pacientes afectados de hepatitis C crónica. Mediciones principales. Variables: edad, sexo, año y motivo del diagnóstico, antecedentes personales, enolismo, estado serológico de los VHA, VHB y VIH, y concentración de transaminasas inicial. Resultados. Edad media: 55 ñ 16. Sexo: 52 por ciento mujeres. Prevalencia: 0,98 por ciento. Motivo del diagnóstico: 41 por ciento estudio de salud, 15 por ciento estudio de enfermedad hepática, 18 por ciento estudio de otras enfermedades. Antecedentes personales: intervención quirúrgica 37,5 por ciento, usuarios de drogas por vía parenteral 21,4 por ciento, transfusión 14 por ciento, conducta de riesgo sexual 2,4 por ciento, material sanitario de más de un uso 2,4 por ciento, familiar VHC positivo 1,4 por ciento, no consta ningún antecedente personal 26,5 por ciento. Enolismo: 17,9 por ciento. Media de transaminasas: AST 79,7 ñ 100 (9-920), ALT 114,8 ñ 160 (6-1.640). Estado serológico VHB: inmunidad natural 22 por ciento, crónica 9 por ciento, inmunidad vacunal 3 por ciento, negativo 44 por ciento, no consta 21 por ciento. Estado serológico VHA: inmunidad natural 2 por ciento, inmunidad vacunal 2,5 por ciento, negativo 9 por ciento, no consta 87 por ciento. VIH-positivos: 4,5 por ciento. Conclusiones. La prevalencia fue inferior a la esperada. Es necesario mejorar el conocimiento del estado serológico, sobre todo del VHA. Sería importante aumentar el grado de cobertura vacunal de los VHB y VHA en estos pacientes (AU)

Demographics, Prevalence, and Clinical Features of the Schizo-obsessive Subtype of Schizophrenia.

The schizo-obsessive subtype of schizophrenia has been proposed to describe the condition of patients with chronic psychotic disorders and prominent obsessive-compulsive (OC) symptoms. These patients differ from others with schizophrenia not only in their psychopathology, but perhaps also in their prognosis and pharmacotherapeutic response. Potent serotonin reuptake blockers, such as clomipramine, fluvoxamine, and fluoxetine, in conjunction with antipsychotics, can prove helpful in improving these patients' OC symptoms. The current study to access the demographics, prevalence, and clinical features of the schizo-obsessive subtype included established outpatients with a principal diagnosis of schizophrenia or schizoaffective disorder treated at a large urban public hospital. More than 50% of the hospital's psychiatric population is Hispanic. The Modified Maudsley Obsessive Compulsive Inventory (MMOCI) was used to identify prominent compulsive symptoms. Of the 52 patients who fulfilled the specific screening criteria, 17 (33%) also had prominent OC symptoms. Surprisingly, there was a statistical trend (P=0.06) for Hispanic patients to meet our threshold for the schizo-obsessive subtype. The MMOCI proved to be an adequate and efficient self-rated screening tool. The prevalence of the schizo-obsessive subtype, especially among Hispanic patients, highlights the importance for mental health professionals working with this population to identify and appropriately treat this group of patients.

Pharmacokinetics and pharmacodynamics of mivacurium stereoisomers in beagle dogs using twitch height and train-of-four response.

Mivacurium, a non-depolarizing neuromuscular blocking agent, consists of three isomers; trans-trans (57%), cis-trans (36%) and cis-cis (7%). The purpose of this study was to characterize the pharmacokinetics and pharmacodynamics of mivacurium after various inputs. Four beagle dogs weighing between 7.95 and 9.89 kg were anesthetized with isofluorane (5%) and received a bolus dose (0.010-0.020 mg kg(-1)) and two constant rate infusions (1.0-1.5 microg kg(-1) min(-1)) of mivacurium via the saphenous vein. Single twitch height (TH) and train-of-four (TOF) were evaluated every 15 and 30 s, respectively. Arterial blood samples were collected, processed and analysed for mivacurium using a stereospecific HPLC-fluorescence method. The disposition of mivacurium isomers was best described by a two compartment model. Mean Cl for the cis-trans, trans-trans and cis-cis isomers were 19.98, 13.53 and 3.47 mL min(-1) kg(-1) respectively and the corresponding mean Vdss were 0.29, 0.24 and 1.00 L kg(-1). The measurement of onset showed dose dependence as evidenced by a rapid onset at the higher doses. TOF measurements were more sensitive to the onset of action and required a longer period of time to recover to baseline values as compared with TH measurements.

Rapid method for the quantitation of mivacurium isomers in human and dog plasma by using liquid chromatography with fluorescence detection: application to pharmacokinetic studies.

A simple, selective and specific liquid chromatography method was used to simultaneously determine the cis-cis, cis-trans and trans-trans isomers of mivacurium in human and dog plasma. Solid phase extraction was used to separate interfering endogenous products from the compounds of interest. Fluorometric detection was evaluated at excitation and emission maxima of 280 and 325 nm. The calibration curves were found to be linear in the range 50-500 ng ml-1. The method was applied to plasma samples collected from a human and dog study and was found to be satisfactory. Excellent recovery, linearity, accuracy and precision were achieved by the assay for each isomer.

Dose-dependent caffeine pharmacokinetics during severe sleep deprivation in humans.

Following 49 h of sleep deprivation, 37 healthy males ingested either 2.1, 4.3, or 8.6 mg*kg-1 body weight of caffeine in a randomized double-blind design. Subjects were sleep deprived for additional 12 h and venous blood samples were collected intermittently. Caffeine and primary metabolite concentrations were determined by HPLC. Pharmacokinetics were computed using the Lagran computer program. The ratio of the primary human metabolite, paraxanthine, to caffeine was used to estimate the rate of metabolism. There was a significant (p < 0.05) and disproportional increase in the dose normalized caffeine AUC and a significant decrease in its clearance associated with increasing dose. In addition, the paraxanthine to caffeine ratio significantly decreased with an increase in dose, indicating that the rate of caffeine metabolism decreased. These results demonstrate that under the conditions of severe sleep deprivation caffeine exhibits dose-dependent pharmacokinetics. In addition, these results are consistent with a model of capacity-limited metabolism.

Effects of chronic hypoxia on the pharmacokinetics of caffeine and cardio-green in micro swine.

METHODS: The pharmacokinetics of caffeine and cardio-green (ICG) were examined in four micro swine at sea level (SEA) and following 21 d continuous exposure to 4600 m (ALT) in a hypobaric chamber. Caffeine (84.7 mg) and ICG (10 mg) were administered as separate intravenous boluses and sequential blood samples collected. RESULTS: Caffeine clearance significantly (p < 0.05) increased in ALT (96.8 +/- 20.0 ml.min-1) as compared to SEA (53.6 +/- 24.8 ml.min-1), demonstrating that liver function increased in ALT. There was no significant change in the ratio of primary metabolites to caffeine, suggesting that the increase in clearance was not due to a change in the rate of caffeine metabolism. ICG clearance significantly increased in ALT (179.8 +/- 57.4 ml.min-1) as compared to SEA (84.4 +/- 28.9 ml.min-1) indicating that hepatic blood flow (HBF) increased. CONCLUSION: These results demonstrate that chronic exposure to 4600 m increases the clearance of caffeine and ICG in the micro swine model and suggests that the increase in caffeine clearance is related to HBF.

Effects of altitude (4300 m) on the pharmacokinetics of caffeine and cardio-green in humans.

The effects of chronic exposure to high altitude on the pharmacokinetics of caffeine and cardio-green (ICG) were examined in eight healthy males (23-35 y) at sea level (SEA) and following 16 days residence at 4300 m (ALT). ICG (0.5 mg. kg-1) was administered as an intravenous bolus and caffeine (4 mg. kg-1) in an orally ingested solution. The concentration of ICG, caffeine, and the primary metabolites of caffeine (MET) were determined in serial blood samples and their pharmacokinetics computed. In comparison to SEA, ALT resulted in a significant decrease in a caffeine half-life (t1/2, 4.7 vs 6.7 h) and area under the curve (2.5 vs 3.7 g.l-1.min-1), and increased clearance (117 vs 86 ml.min-1.70 kg-1). In ALT the area under the curve the ICG significantly decreased (85 vs 207 mg.l-1.min-1) and the volume of distribution and clearance increased (5.2 vs 2.4 l and 532 vs 234 ml.min-1 respectively) compared to SEA. There was a significant increase in the AUC ratio of MET to caffeine indicating that either metabolite formation or elimination was increased in ALT. These results demonstrate that in humans, chronic exposure to 4300 m results in the modification of the pharmacokinetics of caffeine and ICG.

Anti-class II antibodies in AIDS patients and AIDS-risk groups.

The specificity of anti-lymphocyte antibodies was evaluated in AIDS patients and in individuals at risk of AIDS [R-AIDS: male homosexuals (Ho) and haemophiliacs (He)]. Antibodies capable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) against non-T cells and lymphoblastoid cell lines (P3HR-1K and Raji) were detected in AIDS patients and in R-AIDS with positive or negative human immune deficiency virus (HIV) serology. Anti-class II antigen specificity was revealed by experiments in which class II antigens on target cells were blocked with monoclonal anti-class II antibody (DA6,231) and the cytotoxic reaction induced by patient's sera was abolished. In contrast, ADCC was not impaired by preincubating the target cells with anti-class I monoclonal antibody (W6/32). Prevalence of antibodies to non-T cells was confirmed by standard C-mediated microlymphocytotoxicity. However, with this technique anti-T lymphocyte cytotoxicity was also observed in three AIDS patients with haemophilia. R-AIDS peripheral blood mononuclear cells (PBMC) were also cytotoxic against autologous non-T cells, and lysis was slightly increased by sensitization of the target cells with autologous serum. In addition to ADCC and C-mediated cytotoxicity, the specificity of anti-lymphocyte antibodies was assayed by their ability to interfere the binding of fluorescein-labelled anti-class II (HLA-DR) and anti-class I (W6/32) monoclonal antibodies to PBMC, non-T cells, P3HR-1K and Raji. Anti-class II specificity was confirmed, and antibody titres tended to be higher in Ho than in He R-AIDS, using non-T cells and Raji as targets. Higher titres of anti-class II antibodies in the Ho group could play a role in the different susceptibility of HIV-infected Ho when compared to HIV (+) He to develop AIDS.