Targeting lung macrophages for fungal and parasitic pulmonary infections with innovative amphotericin B dry powder inhalers.

The incidence of fungal pulmonary infections is known to be on the increase, and yet there is an alarming gap in terms of marketed antifungal therapies that are available for pulmonary administration. Amphotericin B (AmB) is a highly efficient broad-spectrum antifungal only marketed as an intravenous formulation. Based on the lack of effective antifungal and antiparasitic pulmonary treatments, the aim of this study was to develop a carbohydrate-based AmB dry powder inhaler (DPI) formulation, prepared by spray drying. Amorphous AmB microparticles were developed by combining 39.7 % AmB with 39.7 % γ-cyclodextrin, 8.1 % mannose and 12.5 % leucine. An increase in the mannose concentration from 8.1 to 29.8 %, led to partial drug crystallisation. Both formulations showed good in vitro lung deposition characteristics (80 % FPF < 5 µm and MMAD < 3 µm) at different air flow rates (60 and 30 L/min) when used with a DPI, but also during nebulisation upon reconstitution in water.

Sedentary behaviour patterns and arterial stiffness in a Spanish adult population - The EVIDENT trial.

OBJECTIVE: Arterial stiffness is a contributor to the development of atherosclerosis and cardiovascular disease. The aim of the study was to analyse the relationship between sedentary behaviour and arterial stiffness in a Spanish adult population. METHODS: This cross-sectional study included 1365 subjects belonging to the EVIDENT project. Physical activity and sedentary behaviour were measured objectively over 7 days using ActiGraph accelerometers. Thresholds of 10 consecutive minutes were used to estimate the daily sedentary time in bouts ≥10 min. Each interruption in sedentary time (counts/min ≥100) was considered a break. Arterial stiffness was evaluated using the B-pro device through the following indicators: radial Augmentation Index (rAIx), Ambulatory Arterial Stiffness Index (AASI), and central and peripheral pulse pressure (PP). RESULTS: We found a positive relationship between central and peripheral pulse pressure (office, 24 h, awake and sleep PP) and total sedentary time. These arterial stiffness parameters were also associated with sedentary time in bouts ≥10 min. Significance disappeared in both cases, however, after adjusting for MVPA and breaks per sedentary hour. Adults who reported fewer breaks per sedentary hour (25th percentile < 2 n/day) had higher levels of AASI, awake and sleep PP. CONCLUSIONS: In a medium-sized sample of adult attenders of community clinics our data showed that it seems to be important to avoid prolonged uninterrupted periods of sedentary time.

Glycemic index, glycemic load, and pulse wave reflection in adults.

BACKGROUND AND AIMS: Diets with a high glycemic index (GI), high glycemic load (GL), or both, increase the risk of cardiovascular disease. This study examined the association of GI and GL in a regular diet with the peripheral augmentation index (i.e., a marker of vascular aging) in a sample of adults. METHODS AND RESULTS: Cross-sectional study. The findings presented in this manuscript are a subanalysis of the EVIDENT study whose purpose was to analyze the relationship between lifestyle and arterial aging. For the sample population, 1553 individuals aged 20-80 years were selected through random sampling from the patients of general practitioners at six health centers in Spain. GI and GL for each patient's diet were calculated from a previously validated, semi-quantitative, 137-item food frequency questionnaire. The peripheral augmentation index corrected for a heart rate of 75 bpm (PAIx75) was measured with pulse-wave application software (A-Pulse CASP). Based on a risk factor adjusted regression model, for every 5 unit increase in GI, the PAIx75 increased by 0.11 units (95% CI: 0.04-0.19). Similarly, for every increase in 10 units in GL, the PAIx75 increased by 1.13 (95% CI: 0.21-2.05). High PAIx75 values were observed in individuals with diets in the third GI tertile (i.e., the highest), and lower PAIx75 values in those with diets in the first tertile (i.e., the lowest), (93.1 vs. 87.5, respectively, p = 0.001). CONCLUSIONS: GI and GL were directly associated with PAIx75 values in adults without cardiovascular diseases regardless of age, gender, physical activity, and other confounders.

Dispositivo supraglótico I-gel® en cirugía ginecológical aparoscópica ambulatoria / No disponible

Objetivo: La cánula I-gel® es un dispositivo de ventilación supraglótico de reciente aparición que incorpora un canal de acceso gástrico. En este estudio valoramos su eficacia en cirugía ginecológica laparoscópica. Material y métodos: Estudio descriptivo prospectivo de 30 pacientes intervenidos de cirugía ginecológica la paroscópica mediante anestesia general. Tras la inducción se colocó la mascarilla asignada y se valoró la facilidad de inserción. Se midieron los siguientes parámetros ventilatorios: presión pico (Pp), presión media(Pm), complianza, volumen corriente y frecuencia respiratoria (VT/FR) al inicio, y a los 10, 30 y 60 minutos de iniciada la intervención. Se comprobaron las condiciones del paso de una sonda nasogástrica y la visualización mediante la cámara de laparoscopia del tamaño del estómago (al comienzo y final de la cirugía) deforma directa. Los datos se tomaron con el paciente en posición de Trendelenburg y con un neumoperitoneo que no superó los 15 mmHg. Resultados: La cánula I-gel® se colocó al primer intento en el 95% de los pacientes. El tiempo medio de colocación fue de 14 segundos. Se colocó la sonda nasogástrica en el 85% de los pacientes. La presión de fuga de la vía aérea era parecida al principio y al final de la cirugía 25 ± 9 cm H2O y en todos los casos se mantuvieron las presiones pico por debajo de 21. La media de valoración por parte del cirujano en el tamaño del estómago al comienzo de la cirugía fue de 2 y al final de 3,5. Coincidió en un único caso la diferencia al final y al principio, donde se describió un vómito al despertar. Conclusión: La cánula I-gel® es un dispositivo fácil de colocar al primer intento. Asimismo resultó un dispositivo seguro para el sellado de la vía aérea y la minimización de las fugas en la ventilación para la cirugía laparoscópica ginecológica (AU)

Background: The I-gel® is a new single-use supraglottic airway device with a non inflatable cuff and an esophageal vent. In this study we evaluated the I-gel® in gynecological laparoscopic surgery. Material and methods: 30 women, ASA I-II undergoing gynaecological laparoscopic surgery in the Trendelenburg position were included in this prospective, observational study. We evaluated ease in inserting the I-gel®, seal pressure, gastric leak, complications during insertion and removal, ease in inserting the gastric tube and ventilatory parameters during positive pressure ventilation. Results: Insertion was easy and performed at the first attempt in 95% of cases. After creation of the pneumoperitoneum average peak pressure was 19,40 mmHg and average plateau pressure 18,20 mmHg. The gastric tube insertion was easily achieved 85%of cases. One case of vomiting occurred. Conclusion: The I-gel® is a reliable, easily inserted airway device that provides an adequate seal, and very few complications. It seems to be an efficient and safe device for gynecological laparoscopicsurgery (AU)

[Analysis of the poisonings by lithium in a department of internal medicine]. / Análisis de las intoxicaciones por litio ingresadas en un servicio de medicina interna.

INTRODUCTION: Lithium salts have been mainly used in the treatment of bipolar disorder. Because of its narrow therapeutic range, and several well characterised adverse effects, serum lithium levels must be monitored regularly in patients given lithium treatment in order to prevent intoxication. OBJECTIVE: To describe the clinic and toxic characteristics in inpatients at our Clinic Toxicologic Unit. MATERIAL AND METHODS: Descriptive and retrospective study of lithium intoxications in 150 inpatients between 2003 and 2006. Patients were classified based on their neuropsychiathric symptom profile and serum lithium levels. RESULTS: Sixteen of 150 inpatients had lithium intoxication: 58.3% women and 43.8% men; 49.19% +/- 18.49% years old. Lithium was used as treatment of bipolar disorder in 87.5% of cases. The most frequent cause of intoxication was attempted suicide. Using neuropsychiatric parametres, intoxication was moderate in 50% of cases, and mild in 25% and severe or very severe in 25%. Using serum lithium levels, intoxication was very severe in 31.35%, severe in 25%, and slight-moderate in 43.7%. Conservative measures were used as the most frequent treatment (50%), and haemodialfiltration was needed in 37.5%. Mean stay was 4,8 days in acute intoxication, and 11.2 days in chronic. Sequelaes were found in two patients (ataxia). Death was not present. CONCLUSIONS: Lithium intoxications can involve severe complications, even death. Narrow control is encouraged in polymedicated and elderly patients, and in concommitant treatment with antidepressant and neuroleptics.

Análisis de las intoxicaciones por litio ingresadas en un servicio de medicina interna / Analysis of the poisoning by lithium in a department of internal medicine

Introducción: El litio, utilizado principalmente en el tratamiento de los trastornos bipolares, presenta un estrecho margen terapéutico, que junto a sus múltiples interacciones y farmacocinética obliga a una monitorización estrecha de concentraciones plasmáticas para evitar intoxicaciones. Objetivo: Describir características clínicas y toxicológicas de los pacientes ingresados en la Unidad Toxicología Clínica (2003-2006). Material y métodos: Estudio descriptivo y retrospectivo de 16 intoxicaciones por litio, de 150 pacientes ingresados entre los años 2003-2006. Se han utilizado dos escalas: según la clínica y los valores séricos de litio. Resultados: Dieciséis pacientes incluidos (58,3 mujeres y 43,8% hombres, 49,19 ± 18,49 años). Trastorno psiquiátrico más frecuente asociado bipolar (87,5%). Causa más frecuente de intoxicación, intento autolisis (56,3%). Según escala neurológica, 50% intoxicación moderada, 25% leve y grave o muy grave el 25% restante. En relación a los niveles de litemia, 31,35% muy grave, 25% graves, 43.7 % leve-moderado.Tratamiento más utilizado en un 50% conservador, hemodiálisis 37,5%, estancia media 4,8 días en intoxicaciones aguda, y 11,2 días en crónicas. Secuelas sólo en dos pacientes (ataxia), sin ninguna muerte. Conclusiones: Las intoxicaciones por litio conllevan gravedad clínica, complicaciones y graves secuelas, incluso la muerte. Se recomienda vigilancia estrecha en pacientes polimedicados, edad avanzada o en tratamiento concomitante de antidepresivos y neurolépticos

Introduction: Lithium salts have been mainly used in the treatment of bipolar disorder. Because of its narrow therapeutic range, and several well characterised adverse effects, serum lithium levels must be monitored regularly in patients given lithium treatment in order to prevent intoxication. Objetive: To describe the clinic and toxic characteristics in inpatients at our Clinic Toxicologic Unit. Material and methods: Descriptive and retrospective study of lithium intoxications in 150 inpatients between 2003 and 2006. Patients were classified based on their neuropsychiathric symptom profile and serum lithium levels. Results: Sixteen of 150 inpatients had lithium intoxication: 58.3% women and 43.8% men; 49.19% ± 18.49% years old. Lithium was used as treatment of bipolar disorder in 87.5% of cases. The most frequent cause of intoxication was attempted suicide. Using neuropsychiatric parametres, intoxication was moderate in 50% of cases, and mild in 25% and severe or very severe in 25%. Using serum lithium levels, intoxication was very severe in 31.35%, severe in 25%, and slight-moderate in 43.7%. Conservative measures were used as the most frequent treatment (50%), and haemodial filtration was needed in 37.5%. Mean stay was 4,8 days in acute intoxication, and 11.2 days in chronic. Sequelaes were found in two patients (ataxia). Death was not present. Conclusions: Lithium intoxications can involve severe complications, even death. Narrow control is encouraged in polymedicated and elderly patients, and in concommitant treatment with antidepressant and neuroleptics

[Lyme disease and SAPHO syndrome]. / Enfermedad de Lyme y síndrome SAPHO.

Joint manifestation in Lyme disease hare shown similarities to those in reactive arthritis. SAPHO syndrome can also be included into the group of seronegative spondyloarthrophaties. It is presented a patient with joint, ocular and serological features proper of Lyme disease and after ones suggestive of SAPHO syndrome, who responds properly to an antibiotic treatment. It is considered the possibility that some patients suffering from SAPHO syndrome can also be suffering from Lyme disease.