[First case series of femoral lengthening using a Precice® intramedullary nail in our center]. / Primera serie de casos de alargamiento femoral mediante clavo intramedular Precice® en nuestro centro.

INTRODUCTION: femoral lengthening using an intramedullary nail is one of the surgical options in the treatment of severe lower limb dysmetria in routine clinical practice. MATERIAL AND METHODS: a retrospective descriptive study was carried out on a series of five patients with a mean age of 15.4 years, who underwent femoral lengthening surgery using a Precice® intramedullary nail. The etiology in all cases was idiopathic. Preoperative and definitive postoperative theoretical lengthening or dysmetry was measured, as well as lengthening accuracy, distraction rate and index (mm/day and days/cm, respectively) and consolidation index (days/cm). Intraoperative and postoperative complications were identified in all cases. RESULTS: mean follow-up was 21 months (12-42), with no loss to follow-up. The mean duration of the surgical procedure was 126 minutes (105-160). The preoperative theoretical dysmetry was 38 ± 2.7 mm. The final mean lengthening was 41 ± 7.5 mm. The mean accuracy was 108% (91-125) and the distraction rate was 0.9 ± 0.4 mm/day. The distraction rate was 13.9 ± 5.1 days/cm and the consolidation rate was 26.6 ± 9.1 days/cm. Bone consolidation was observed in all patients with a mean of 113 ± 58 days. Regarding complications, a total of four minor muscular complications were found. CONCLUSION: the Precice® intramedullary nail is a good treatment option for cases of severe femoral shortening, providing good clinical and radiological results with a low rate of complications and implant failure.

INTRODUCCIÓN: el alargamiento femoral mediante clavo intramedular es una de las opciones quirúrgicas en el tratamiento de las dismetrías severas de miembros inferiores en la práctica clínica habitual. MATERIAL Y MÉTODOS: se realizó un estudio descriptivo retrospectivo de una serie de cinco pacientes con una media de edad de 15.4 años, intervenidos de alargamiento femoral mediante clavo intramedular Precice®. La etiología en todos los casos fue idiopática. Se midió la dismetría o alargamiento teórico prequirúrgico y el definitivo postquirúrgico, así como la precisión del alargamiento, la tasa y el índice de distracción (mm/día y días/cm respectivamente) y el índice de consolidación (días/cm). Se identificaron las complicaciones intra y postoperatorias en todos los casos. RESULTADOS: la media de seguimiento fue de 21 meses (12-42), sin pérdidas en el seguimiento. La duración media del procedimiento quirúrgico fue de 126 minutos (105-160). La dismetría teórica prequirúrgica fue de 38 ± 2.7 mm. El alargamiento medio final fue de 41 ± 7.5 mm. La precisión media fue de 108% (91-125) y la tasa de distracción de 0.9 ± 0.4 mm/día. El índice de distracción fue de 13.9 ± 5.1 días/cm y el índice de consolidación, de 26.6 ± 9.1 días/cm. La consolidación ósea se observó en la totalidad de los pacientes con una media de 113 ± 58 días. Con respecto a las complicaciones, se encontraron un total de cuatro complicaciones menores de índole muscular. CONCLUSIÓN: el clavo intramedular Precice® es una buena opción de tratamiento para casos de acortamiento femoral severo aportando buenos resultados clínicos y radiológicos con una baja tasa de complicaciones y fallo del implante.

Primera serie de casos de alargamiento femoral mediante clavo intramedular Precice® en nuestro centro / First case series of femoral lengthening using a Precice® intramedullary nail in our center

Resumen: Introducción: el alargamiento femoral mediante clavo intramedular es una de las opciones quirúrgicas en el tratamiento de las dismetrías severas de miembros inferiores en la práctica clínica habitual. Material y métodos: se realizó un estudio descriptivo retrospectivo de una serie de cinco pacientes con una media de edad de 15.4 años, intervenidos de alargamiento femoral mediante clavo intramedular Precice®. La etiología en todos los casos fue idiopática. Se midió la dismetría o alargamiento teórico prequirúrgico y el definitivo postquirúrgico, así como la precisión del alargamiento, la tasa y el índice de distracción (mm/día y días/cm respectivamente) y el índice de consolidación (días/cm). Se identificaron las complicaciones intra y postoperatorias en todos los casos. Resultados: la media de seguimiento fue de 21 meses (12-42), sin pérdidas en el seguimiento. La duración media del procedimiento quirúrgico fue de 126 minutos (105-160). La dismetría teórica prequirúrgica fue de 38 ± 2.7 mm. El alargamiento medio final fue de 41 ± 7.5 mm. La precisión media fue de 108% (91-125) y la tasa de distracción de 0.9 ± 0.4 mm/día. El índice de distracción fue de 13.9 ± 5.1 días/cm y el índice de consolidación, de 26.6 ± 9.1 días/cm. La consolidación ósea se observó en la totalidad de los pacientes con una media de 113 ± 58 días. Con respecto a las complicaciones, se encontraron un total de cuatro complicaciones menores de índole muscular. Conclusión: el clavo intramedular Precice® es una buena opción de tratamiento para casos de acortamiento femoral severo aportando buenos resultados clínicos y radiológicos con una baja tasa de complicaciones y fallo del implante.

Abstract: Introduction: femoral lengthening using an intramedullary nail is one of the surgical options in the treatment of severe lower limb dysmetria in routine clinical practice. Material and methods: a retrospective descriptive study was carried out on a series of five patients with a mean age of 15.4 years, who underwent femoral lengthening surgery using a Precice® intramedullary nail. The etiology in all cases was idiopathic. Preoperative and definitive postoperative theoretical lengthening or dysmetry was measured, as well as lengthening accuracy, distraction rate and index (mm/day and days/cm, respectively) and consolidation index (days/cm). Intraoperative and postoperative complications were identified in all cases. Results: mean follow-up was 21 months (12-42), with no loss to follow-up. The mean duration of the surgical procedure was 126 minutes (105-160). The preoperative theoretical dysmetry was 38 ± 2.7 mm. The final mean lengthening was 41 ± 7.5 mm. The mean accuracy was 108% (91-125) and the distraction rate was 0.9 ± 0.4 mm/day. The distraction rate was 13.9 ± 5.1 days/cm and the consolidation rate was 26.6 ± 9.1 days/cm. Bone consolidation was observed in all patients with a mean of 113 ± 58 days. Regarding complications, a total of four minor muscular complications were found. Conclusion: the Precice® intramedullary nail is a good treatment option for cases of severe femoral shortening, providing good clinical and radiological results with a low rate of complications and implant failure.

[Treatment of intrinsic brain tumors located in motor eloquent areas. Results of a protocol based in navigation, tractography and neurophysiological monitoring of cortical and subcortical structures]. / Tratamiento de los tumores cerebrales intrínsecos de áreas motoras elocuentes. Resultados de un protocolo basado en la navegación, tractografía y monitorización neurofisiológica de estructuras corticales y subcorticales.

OBJECTIVES: The role of the microsurgical management of intrinsic brain tumors is to maximize the volumetric resection of the tumoral tissue minimizing the postoperative morbidity. The purpose of our paper has been to study the benefits of an original protocol developed for the microsurgical treatment of tumors located in eloquent motor areas where the navigation and electrical stimulation of motor subcortical pathways have been implemented. MATERIALS AND METHODS: A total of 17 patients operated on for resection of cortical or subcortical tumors in motor areas were included in the series. Preoperative planning for multimodal navigation was done integrating anatomic studies, motor functional MRI (f-MRI) and subcortical pathways volumes generated by diffusion tensor imaging (DTI). Intraoperative neuromonitorization included motor mapping by direct cortical and subcortical electrical stimulation (CS and sCS) and localization of the central sulcus using cortical multipolar electrodes and the N20 wave inversion technique. The location of all cortical and subcortical stimulated points with positive motor response was stored in the navigator and correlated with the cortical or subcortical motor functional structures defined preoperatively. RESULTS: The mean tumoral volumetric resection was 89.1±14.2% of the preoperative volume, with a total resection (≥100%) in twelve patients. Preoperatively a total of 58.8% of the patients had some motor deficit, increasing 24 hours after surgery to 76.5% and decreasing to 41.1% a month later. There was a great correlation between anatomic and functional data, both cortically and subcortically. However, in six cases it was not possible to identify the central sulcus and in many cases fMRI gave contradictory information. A total of 52 cortical points submitted to CS had positive motor response, with a positive correlation of 83.7%. Also, a total of 55 subcortical points had positive motor response, being in these cases 7.3±3.1 mm the mean distance from the stimulated point to the subcortical tract. CONCLUSIONS: The integration of preoperative and intraoperative anatomic and functional studies allows a safe functional resection of the brain tumors located in eloquent areas, compared to the tumoral resection based on anatomic imaging studies. Multimodal navigation allows the integration and correlation among preoperative and intraoperative anatomic and functional data. Cortical motor functional areas are anatomically and functionally located preoperatively thanks to MRI and fMRI and subcortical motor pathways with TDI and tractography. Intraoperative confirmation is done with CS and N20 inversion wave for cortical structures and with sCS for subcortical pathways. With this protocol we achieved a mean of 90% of volumetric resection in cortical and subcortical tumors located in eloquent motor areas with an increase of neurological deficits in the immediate postoperative period that significantly decreased one month later. Ongoing studies will define the safe limits for functional resection taking into account the intraoperative brain shift. Finally, it must be demonstrated if this protocol has any benefit for patients concerning disease free or overall survival.

Tratamiento de los tumores cerebrales intrínsecos de áreas motoras elocuentes. Resultados de un protocolo basado en la navegación, tractografía y monitorizaciónneurofisiológica de estructuras corticales y subcorticales / Treatment of intrinsic brain tumors located in motor eloquent areas. results of a protocol based in navegation, tractography and neurophysiological monitoring of cortical and subcortical structures

Objetivos. El papel actual del tratamiento microquirúrgicode los tumores cerebrales intrínsecos se basaen alcanzar la máxima resección volumétrica del tumorminimizando la morbilidad postoperatoria. El propósitodel trabajo es estudiar los beneficios de un protocolodiseñado para tratar tumores localizados en áreaselocuentes motoras, en el que se incluye la navegación yla estimulación de tractos motores subcorticales.Material y métodos. Se han incluido 17 pacientescon tumores corticales y subcorticales de área motoratratados quirúrgicamente. Para la planificación preoperatoriase fusionaron en el sistema de navegaciónestudios anatómicos, de resonancia funcional motora(RNM-f) y los tractos subcorticales generados porestudios de tensor de difusión (DTI). La monitorizaciónintraoperatoria incluía el mapeo motor por estimulacióncortical y subcortical directa (ECD y EsCD) e identificacióndel surco central por inversión de la onda N20con electrodos corticales multipolares. La localizaciónde los puntos con respuesta positiva a la ECD o EsCD secorrelacionaba con las áreas corticales o tractos funcionalesmotores definidos en los estudios preoperatoriosgracias al navegador.Resultados. La resección volumétrica tumoral mediafue del 89.1±14.2% del volumen tumoral calculado enlos estudios preoperatorios, con resección total (≥100%)en doce pacientes. En el preoperatorio había focalidadneurológica deficitaria motora en el 58.8% de lospacientes, que aumentó al 76.5% a las 24 horas de lacirugía y se redujo a los 30 días al 41.1%. Hubo una (..) (AU)

Objectives. The role of the microsurgical managementof intrinsic brain tumors is to maximize the volumetricresection of the tumoral tissue minimizing thepostoperative morbidity. The purpose of our paper hasbeen to study the benefits of an original protocol developedfor the microsurgical treatment of tumors locatedin eloquent motor areas where the navigation and electricalstimulation of motor subcortical pathways havebeen implemented.Materials and methods. A total of 17 patients operatedon for resection of cortical or subcortical tumors inmotor areas were included in the series. Preoperativeplanning for multimodal navigation was done integratinganatomic studies, motor functional MRI (f-MRI)and subcortical pathways volumes generated by diffusiontensor imaging (DTI). Intraoperative neuromonitorizationincluded motor mapping by direct corticaland subcortical electrical stimulation (CS and sCS) andlocalization of the central sulcus using cortical multipolarelectrodes and the N20 wave inversion technique.The location of all cortical and subcortical stimulatedpoints with positive motor response was stored in thenavigator and correlated with the cortical or subcorticalmotor functional structures defined preoperatively.Results. The mean tumoral volumetric resection (..) (AU)

Escolar con displasia cleidocraneal: importancia del diagnóstico precoz / No disponible

La displasia cleidocraneal (DCC) es una enfermedad autosómica dominante poco frecuente,con alta penetrancia y expresión variable, caracterizada por la presencia de suturas cranealesabiertas, hipoplasia o aplasia clavicular y anormalidades dentarias complejas.En el presente artículo se expone un caso de DCC en un escolar con antecedentes familiaresde hipoacusia. Este niño fue diagnosticado a los tres meses de vida, por presentar macrocefalia,braquicefalia, fontanela anterior amplia, diástasis de suturas e hipertelorismo. En la exploraciónfísica, los hombros podían aproximarse a la línea media. Las radiografías revelaron hipoplasia declavículas. Se resalta la importancia del diagnóstico precoz para evitar acciones innecesarias, comosobredosificación de vitamina D. Por otro lado, se recomienda actuar convenientemente sobrelos trastornos dentales con un equipo multidisciplinario. El objetivo final es proveer una aparienciafacial estética y conseguir una oclusión funcional en la adolescencia tardía o adulteztemprana. La inteligencia y la esperanza de vida son normales sin complicaciones serias

Cleidocraneal dysplasia (CCD) is an infrequent autosomal dominant disease with high penetranceand variable expression characterized by open skull sutures, hypoplastic or aplasticclavicles and complex dental abnormalities.In this article we report a case of CCD in a school age child with a family history of hearingloss. The child was diagnosed due to the presentation of a macrocephalic and braquicephalicskull with large fontanelle, open sutures and hypertelorism at three months of age. On examinationthe shoulders have the ability to come together at the midline. Plain radiographs revealedhypoplastic clavicles.The early diagnosis is remarked to avoid unnecessary proceedings as overdosification of vitaminD. On the other hand it is recommended a multidisciplinary team to treat appropriately dental abnormalities. The overall goal is to provide an esthetical appearance of the face and toget a functional occlusion by late adolescence or young adulthood. Intelligence and life expectancyare normal with not serious complications

[Holt-Oram syndrome: characterization of a novel mutation]. / Síndrome de Holt-Oram: caracterización de una nueva mutación.

INTRODUCTION: Cardiomyelic syndromes encompass congenital heart disease and skeletal malformations of the upper limbs and are related to mutations in transcription factors with T-Box domains. Holt-Oram syndrome is caused by a dominant mutation in the TBX5 gene that alters the three-dimensional structure of the protein and its DNA binding function. Several point mutations and deletions in TBX5 have been reported in patients with the Holt-Oram syndrome phenotype. PATIENTS AND METHODS: The proband was a boy with a large atrial septal defect ostium secundum type and a ventricular septal defect, diagnosed by clinical findings (heart murmur) and echocardiography. He also presented slightly hypoplastic thumbs with distal bilateral placement and an implantation index of 0.19 (compared with an average of 0.50 for his gestational age at birth). The boy was referred to the department of medical genetics to rule out 22q11.2 microdeletion syndrome. RESULTS: Karyotype and fluorescence in situ hybridization at locus D22S75 were both normal. Because of his clinical findings, molecular study for Holt-Oram syndrome was indicated, leading to the finding of a mutation at intron 7 of TBX5, probably producing a splicing alteration of the gene and resulting in a protein truncated at its C-terminal end. The proband's parents presented the wild type sequence of the gene, thus indicating that the mutation was produced de novo, although a possible germinal mosaicism in the parents could not be ruled out. CONCLUSIONS: Holt-Oram syndrome is the most frequent cause of cardiomyelic syndrome. All children with heart malformations and abnormalities of the upper limbs such as absent, hypoplastic, distally placed or triphalangic thumbs should undergo molecular studies for this syndrome.

Síndrome de Holt-Oram: caracterización de una nueva mutación / Holt-Oram syndrome: characterization of a novel mutation

Introducción Los síndromes cardiomiélicos comprenden cardiopatías congénitas y malformaciones esqueléticas de los miembros superiores, y están relacionados con mutaciones deletéreas de factores de transcripción con dominios del tipo T-Box. El síndrome de Holt-Oram se debe a una mutación dominante en el gen TBX5 que altera la estructura tridimensional de la proteína impidiendo su correcta unión al ADN. Se han descrito varias mutaciones puntuales y deleciones de TBX5 en pacientes con fenotipo de síndrome de Holt-Oram. Pacientes y métodos El paciente es un niño con una comunicación interauricular (CIA) del tipo ostium secundum grande y una comunicación interventricular (CIV) diagnosticados por clínica (soplo) y ecocardiografía. Presenta además unos dedos pulgares algo hipoplásicos y con un emplazamiento distal bilateral, con un índice de implantación de 0,19 frente a una media normal de 0,50 para su edad gestacional al nacer. Es remitido a la consulta de Genética para descartar microdeleción 22q11.2. Resultados El cariotipo y la hibridación in situ de fluorescencia (FISH) con sonda D22S75 resultaron normales y debido a los hallazgos clínicos se realizó un estudio molecular para el síndrome de Holt-Oram. Se encontró una mutación en el intrón 7 de TBX5 que produce una probable alteración del splicing del gen que da lugar a una proteína truncada en su extremo C-terminal. Los padres del propósito presentan una secuencia normal para el gen, lo que indica que la mutación se produjo de novo, sin que pueda descartarse un mosaicismo germinal en los padres. Conclusiones El síndrome de Holt-Oram es la causa más frecuente de síndrome cardiomiélico. Debería ser objeto de estudio molecular todo niño con malformaciones cardíacas y alteraciones de las extremidades superiores como pulgares ausentes, hipoplásicos, distalmente emplazados o trifalángicos

Introduction Cardiomyelic syndromes encompass congenital heart disease and skeletal malformations of the upper limbs and are related to mutations in transcription factors with T-Box domains. Holt-Oram syndrome is caused by a dominant mutation in the TBX5 gene that alters the three-dimensional structure of the protein and its DNA binding function. Several point mutations and deletions in TBX5 have been reported in patients with the Holt-Oram syndrome phenotype. Patients and methods The proband was a boy with a large atrial septal defect ostium secundum type and a ventricular septal defect, diagnosed by clinical findings (heart murmur) and echocardiography. He also presented slightly hypoplastic thumbs with distal bilateral placement and an implantation index of 0.19 (compared with an average of 0.50 for his gestational age at birth). The boy was referred to the department of medical genetics to rule out 22q11.2 microdeletion syndrome. Results Karyotype and fluorescence in situ hybridization at locus D22S75 were both normal. Because of his clinical findings, molecular study for Holt-Oram syndrome was indicated, leading to the finding of a mutation at intron 7 of TBX5, probably producing a splicing alteration of the gene and resulting in a protein truncated at its C-terminal end. The proband's parents presented the wild type sequence of the gene, thus indicating that the mutation was produced de novo, although a possible germinal mosaicism in the parents could not be ruled out. Conclusions Holt-Oram syndrome is the most frequent cause of cardiomyelic syndrome. All children with heart malformations and abnormalities of the upper limbs such as absent, hypoplastic, distally placed or triphalangic thumbs should undergo molecular studies for this syndrome

[Clinical guide to the management of patients with Beckwith-Wiedemann syndrome]. / Guía clínica para el seguimiento de pacientes con síndrome de Beckwith-Wiedemann.

Beckwith-Wiedemann syndrome (BWS) is characterized by congenital overgrowth, macroglossia and omphalocele or umbilical hernia. Children with BWS may also have all or some of the following features: asymmetry (hemihypertrophy) of the limbs, torso or face, hypoglycemia, organomegaly, ear pits or creases, and embryonal tumors. The frequency of BWS is approximately 1:14,000 births. We present a guide for the management of children with BWS aimed at helping pediatricians and general practitioners or specialists in the clinical follow-up of these patients. This guide has been structured according to different age groups and is based on published evidence.

Guía clínica para el seguimiento de pacientes con síndrome de Beckwith-Wiedemann / Clinical guide to the management of patients with Beckwith Wiedemann syndrome

Los pacientes con síndrome de Beckwith-Wiedemann (SBW) suelen identificarse al nacer por la presencia de macrosomía, macroglosia y onfalocele o hernia umbilical. Muchos de estos niños pueden tener además todos o algunos de los siguientes hallazgos: asimetría (hemihipertrofia) de miembros, torso o cara, hipoglucemia, organomegalia, alteraciones de las orejas (apéndices auriculares, fosetas en el hélix o surcos en la región del lóbulo de la oreja) y tumores embrionarios. La frecuencia del SBW es aproximadamente de 1:14.000 nacimientos. Presentamos una guía cronológica de seguimiento clínico para pacientes con SBW con el objeto de facilitar al pediatra y al médico general o especialista el seguimiento clínico de los pacientes con esta patología. La guía ha sido estructurada para diferentes períodos de edad y está basada principalmente en las evidencias publicadas

Beckwith-Wiedemann syndrome (BWS) is characterized by congenital overgrowth, macroglossia and omphalocele or umbilical hernia. Children with BWS may also have all or some of the following features: asymmetry (hemihypertrophy) of the limbs, torso or face, hypoglycemia, organomegaly, ear pits or creases, and embryonal tumors. The frequency of BWS is approximately 1:14,000 births. We present a guide for the management of children with BWS aimed at helping pediatricians and general practitioners or specialists in the clinical follow-up of these patients. This guide has been structured according to different age groups and is based on published evidence

Acute effects of bright light and caffeine on nighttime melatonin and temperature levels in women taking and not taking oral contraceptives.

Caffeine and bright light effects on nighttime melatonin and temperature levels in women were tested during the luteal phase of the menstrual cycle (n=30) or the pseudo luteal phase for oral contraceptive users (n=32). Participants were randomly assigned to receive either bright (5000 lux) or dim room light (<88 lux) between 20:00 and 08:00 h under a modified constant routine protocol. Half the subjects in each lighting condition were administered either caffeine (100 mg) or placebo in a double-blind manner at 20:00, 23:00, 02:00 and 05:00 h. Results showed that the combination of bright light and caffeine enhanced nighttime temperature levels to a greater extent than did either caffeine or bright light alone. Both of the latter groups had higher temperature levels relative to the dim light placebo condition and the two groups did not differ. Temperature levels in the bright light caffeine condition were maintained at near peak circadian levels the entire night in the luteal and pseudo luteal phase. Melatonin levels were reduced throughout the duration of bright light exposure for all women. Caffeine reduced the onset of melatonin levels for women in the luteal phase, but it had little effect on melatonin levels for oral contraceptive users. The results for women in the luteal phase of the menstrual cycle are consistent with our previous findings in men. The results also suggest that oral contraceptives may alter the effects of caffeine on nighttime melatonin levels.

Trombosis de grandes vasos en el recién nacido / Thrombosis involving large vessels in the new born

En este estudio se revisan las historias clínicas de un periodo de cuatro años de los recién nacidos diagnosticados de trombosis en el Hospital 'Son Dureta' de Palma de Mallorca. Se registraron cuatro casos, lo que representa una incidencia de 1,28/10.000 nacidos vivos. La localización fue en la vena renal en dos casos, intracardiaca y aórtica. El diagnóstico se estableció en todos los casos mediante ecografía Doppler. Los cuatro pacientes sobrevivieron tras un cuadro agudo y fueron sometidos a tratamiento fibrinolítico con urocinasa. La trombosis neonatal presenta una incidencia variable, más elevada en estudios prospectivos de pacientes canalizados. Los déficits congénitos o transitorios de sustancias del sistema fibrinolítico pueden favorecer su aparición. El tratamiento varía entre los diferentes centros, aunque la urocinasa es el agente trombolítico más utilizado (AU)

Effects of menstrual cycle phase and oral contraceptives on alertness, cognitive performance, and circadian rhythms during sleep deprivation.

The influence of menstrual cycle phase and oral contraceptive use on neurobehavioral function and circadian rhythms were studied in healthy young women (n = 25) using a modified constant routine procedure during 24 h of sleep deprivation. Alertness and performance worsened across sleep deprivation and also varied with circadian phase. Entrained circadian rhythms of melatonin and body temperature were evident in women regardless of menstrual phase or oral contraceptive use. No significant difference in melatonin levels, duration, or phase was observed between women in the luteal and follicular phases, whereas oral contraceptives appeared to increase melatonin levels. Temperature levels were higher in the luteal phase and in oral contraceptive users compared to women in the follicular phase. Alertness on the maintenance of wakefulness test and some tests of cognitive performance were poorest for women in the follicular phase especially near the circadian trough of body temperature. These observations suggest that hormonal changes associated with the menstrual cycle and the use of oral contraceptives contribute to changes in nighttime waking neurobehavioral function and temperature level whereas these factors do not appear to affect circadian phase.

Combination of bright light and caffeine as a countermeasure for impaired alertness and performance during extended sleep deprivation.

Effects of four conditions (Dim Light-Placebo, Dim Light-Caffeine, Bright Light-Placebo and Bright Light-Caffeine) on alertness, and performance were studied during the night-time hours across 45.5 h of sleep deprivation. Caffeine (200 mg) was administered at 20.00 and 02.00 hours and bright-light exposure (> 2000 lux) was from 20.00 to 08.00 hours each night. The three treatment conditions, compared to the Dim Light-Placebo condition, enhanced night-time performance. Further, the combined treatment of caffeine and all-night bright light (Bright Light-Caffeine) enhanced performance to a larger degree than either the Dim Light-Caffeine or the Bright Light-Placebo condition. Beneficial effects of the treatments on performance were largest during the early morning hours (e.g. after 02.00 hours) when performance in the Dim Light-Placebo group was at its worst. Notably, the Bright Light-Caffeine condition was able to overcome the circadian drop in performance for most tasks measured. Both caffeine conditions improved objective alertness on the Maintenance of Wakefulness Test. Taken together, the above results suggest that the combined treatment of bright light and caffeine provides an effective intervention for enhancing alertness and performance during sleep loss.

Sleep-promoting and hypothermic effects of daytime melatonin administration in humans.

Sleep-promoting and hypothermic effects of orally administered melatonin during the daytime were assessed using a placebo-controlled, double-blind, cross-over design. Following a 7-hour nighttime sleep opportunity, healthy young male subjects (n = 8) were given either a placebo or one of three doses of melatonin (1 mg, 10 mg, and 40 mg) at 1000 hours. Sleep was polygraphically assessed in a 4-hour sleep opportunity from 1200 to 1600 hours. All doses of melatonin significantly shortened the latency to sleep onset. Melatonin also significantly increased total sleep time and decreased wake after sleep onset (WASO). Sleep following melatonin administration contained significantly more stage 2 and less stage 3-4, while stage 1 and rapid eye movement (REM) sleep were unaffected. In addition to the sleep-promoting effects, melatonin completely suppressed the normal diurnal rise of core body temperature. These data suggest that melatonin may be an effective method of promoting sleep for individuals attempting to sleep during their subjective day, such as shiftworkers and individuals rapidly traveling across multiple time zones.

Caffeine and light effects on nighttime melatonin and temperature levels in sleep-deprived humans.

The effects of caffeine ingestion and exposure to bright light, both separately and in combination, on salivary melatonin and tympanic temperature were assessed in humans. Four treatments during a 45.5 h sleep deprivation period were compared: Dim Light-Placebo, Dim Light-Caffeine, Bright Light-Placebo and Bright-Light Caffeine. The Dim Light-Caffeine condition (200 mg twice each night) relative to the Dim Light-Placebo condition suppressed nighttime melatonin levels and attenuated the normal decrease in temperature. Combining caffeine ingestion with bright light exposure (> or = 2000 lux) suppressed melatonin and attenuated the normal nighttime drop in temperature to a larger degree than either condition alone; i.e. effects were additive. Circadian effects were also observed in that the amplitude and phase of the temperature rhythm were altered during treatment. These findings establish that the human melatonin system is responsive to caffeine. Other evidence suggests that caffeine may influence melatonin and temperature levels through antagonism of the neuromodulator adenosine.