Electronegative LDL induces priming and inflammasome activation leading to IL-1ß release in human monocytes and macrophages.

BACKGROUND: Electronegative LDL (LDL(−)), a modified LDL fraction found in blood, induces the release of inflammatory mediators in endothelial cells and leukocytes. However, the inflammatory pathways activated by LDL(−) have not been fully defined. We aim to study whether LDL(−) induced release of the first-wave proinflammatory IL-1ß in monocytes and monocyte-derived macrophages (MDM) and the mechanisms involved. METHODS: LDL(−) was isolated from total LDL by anion exchange chromatography. Monocytes and MDM were isolated from healthy donors and stimulated with LDL(+) and LDL(−) (100 mg apoB/L). RESULTS: In monocytes, LDL(−) promoted IL-1ß release in a time-dependent manner, obtaining at 20 h-incubation the double of IL-1ß release induced by LDL(−) than by native LDL. LDL(−)-induced IL-1ß release involved activation of the CD14-TLR4 receptor complex. LDL(−) induced priming, the first step of IL-1ß release, since it increased the transcription of pro-IL-1ß (8-fold) and NLRP3 (3-fold) compared to native LDL. Several findings show that LDL(−) induced inflammasome activation, the second step necessary for IL-1ß release. Preincubation of monocytes with K+ channel inhibitors decreased LDL(−)-induced IL-1ß release. LDL(−) induced formation of the NLRP3-ASC complex. LDL(−) triggered 2-fold caspase-1 activation compared to native LDL and IL-1ß release was strongly diminished in the presence of the caspase-1 inhibitor Z-YVAD. In MDM, LDL(−) promoted IL-1ß release, which was also associated with caspase-1 activation. CONCLUSIONS: LDL(−) promotes release of biologically active IL-1ß in monocytes and MDM by induction of the two steps involved: priming and NLRP3 inflammasome activation. SIGNIFICANCE: By IL-1ß release, LDL(−) could regulate inflammation in atherosclerosis.

[Parental presence in the operating room: effect on the quality of anesthetic induction and postoperative agitation in children]. / Efectos de la presencia paterna en quirófano sobre la calidad de la inducción anestésica y agitación postoperatoria en niños.

BACKGROUND AND OBJECTIVE: Various nonpharmacologic strategies for reducing anxiety in children and improving cooperation during induction of anesthesia have been investigated. Parental presence during anesthetic induction has been the alternative studied most often, especially in English-speaking populations. Mixed results have been reported, however. The aim of this study was to evaluate the quality of anesthetic induction and the development of postoperative agitation in Spanish children undergoing ear, nose, or throat surgery with or without parental presence in the operating room. PATIENTS AND METHODS: Children in American Society of Anesthesiologists class 1 or 2 who were scheduled for ear, nose or throat surgery under inhalation anesthesia were randomized to 2 groups for presence or absence of a parent in the operating room. The induction experience was classified as easy, carried out with moderate resistance, or traumatic. The postoperative period was assessed as easy or traumatic. RESULTS: Forty children were randomized. Time to onset of anesthesia was similar in the 2 groups. Induction was easy for 65% of the children with parental presence and for 25% of the children without a parent present (P < .05). Induction was traumatic for 25% in the parental presence group and for 35% in the parental absence group (P < .05). The incidence of moderate resistance during induction was similar in the 2 groups; the quality of the postoperative experience was also similar. CONCLUSIONS: Parental presence during induction of inhalation anesthesia improves the induction experience of nonpremeditated Spanish children, increasing the incidence of easy induction and decreasing the presence of traumatic induction. The quality of the postoperative experience is similar.

Efectos de la presencia paterna en quirófano sobre la calidad de la inducción anestésica y agitación postoperatoria en niños / Parental presence in the operating room: effect on the quality of anesthetic induction and postoperative agitation in children

Objetivos: Se han investigado diversas alternativas no farmacológicas para reducir el estrés y mejorar la cooperación de los niños durante la inducción anestésica. La presencia de los padres durante la inducción anestésica ha sido la intervención más comúnmente estudiada, sobre todo en la población anglosajona y con resultados contradictorios. El objetivo del presente trabajo es evaluar la calidad de la inducción anestésica y del postoperatorio según la presencia paterna o no durante la misma en niños españoles no premedicados sometidos a cirugía otorrinolaringológica. Pacientes y métodos: Niños ASA I-II programados para cirugía otorrinolaringológica con inducción inhalatoria, asignados de forma aleatoria a dos grupos, según entraran los padres (grupo P) o no (grupo C) en el quirófano. La calidad de la inducción anestésica fue valorada como suave, moderada o traumática y el postoperatorio como suave o traumático. Resultados: Se incluyeron 40 niños. El tiempo de inducción anestésica fue similar en ambos grupos. Hubo una inducción suave en el 65% de los niños del grupo P frente al 25% en el grupo C (p<0,05), y una inducción traumática en el 25% de los niños del grupo P, frente al 35% del grupo C (p<0,05). La incidencia de inducción moderada y la calidad de postoperatorio fueron similares en ambos grupos. Conclusión: La presencia paterna durante la inducción de la anestesia inhalatoria mejora la calidad de la inducción del niño no premedicado, aumentando la incidencia de inducciones suaves frente a las traumáticas. No se han encontrado diferencias en la calidad del postoperatorio(AU)

Background and objective: Various nonpharmacologic strategies for reducing anxiety in children and improving cooperation during induction of anesthesia have been investigated. Parental presence during anesthetic induction has been the alternative studied most often, especially in English-speaking populations. Mixed results have been reported, however. The aim of this study was to evaluate the quality of anesthetic induction and the development of postoperative agitation in Spanish children undergoing ear, nose, or throat surgery with or without parental presence in the operating room. Patients and methods: Children in American Society of Anesthesiologists class 1 or 2 who were scheduled for ear, nose or throat surgery under inhalation anesthesia were randomized to 2 groups for presence or absence of a parent in the operating room. The induction experience was classified as easy, carried out with moderate resistance, or traumatic. The postoperative period was assessed as easy or traumatic. Results: Forty children were randomized. Time to onset of anesthesia was similar in the 2 groups. Induction was easy for 65% of the children with parental presence and for 25% of the children without a parent present (P<.05). Induction was traumatic for 25% in the parental presence group and for 35% in the parental absence group (P<.05). The incidence of moderate resistance during induction was similar in the 2 groups; the quality of the postoperative experience was also similar. Conclusions: Parental presence during induction of inhalation anesthesia improves the induction experience of nonpremeditated Spanish children, increasing the incidence of easy induction and decreasing the presence of traumatic induction. The quality of the postoperative experience is similar(AU)

[Therapeutic errors and dose measuring devices]. / Errores terapéuticos con dosificadores domésticos.

In order to investigate the possibilities of therapeutical error in syrups administration, authors have measured the capacity of 158 home spoons (x +/- SD). They classified spoons in four groups: group I (table spoons), 49 units (11.65 +/- 2.10 cc); group II (tea spoons), 41 units (4.70+/-1.04 cc); group III (coffee spoons), 41 units (2.60 +/- 0.59 cc), and group IV (miscellaneous), 27 units. They have compared the first three groups with theoreticals values of 15, 5 and 2.5 cc, respectively, ensuring, in the first group, significant statistical differences. In this way, they analyzed information that paediatricians receive from "vademecums", which they usually consult and have studied two points: If syrup has a meter or not, and if it indicates drug concentration or not. Only a 18% of the syrups have a meter and about 88% of the drugs indicate their concentration (mg/cc). They conclude that to prevent errors of dosage, the pharmacological industry must include meters in their products. If they haven't the safest thing is to use syringes.

Management of anticoagulation in outpatients: experience with an anticoagulation service in a municipal hospital setting.

In 66 months, a general hospital's outpatient Anticoagulation Service (ACS) monitored 263 patients who received 280 courses of warfarin sodium totalling 254 patient treatment years. Major hemorrhagic morbidity was 4% of courses and there was no mortality attributable to warfarin therapy. Major hemorrhage occurred in patients with increased anatomic risk of bleeding (diverticulosis, hemorrhoids, cystitis), and was not a function of patient age, sex, anticoagulation control, or medications administered concurrently with warfarin. Control of anticoagulation was not correlated with age or other medications, but was worsened significantly by the presence of congestive heart failure. We attribute a favorable experience with outpatient ACS to careful patient selection, patient education and monitoring, attention to duration of anticoagulation, and continuing communication with primary physicians who retained responsibility for medical care. An ACS offers safety, consistency, efficiency, and a unified approach to outpatient anticoagulation in the general hospital setting.

Outpatient management of anticoagulation.

The Anticoagulation Service insures uniformity of approach to the regulation of anticoagulation for patients of hospital-based primary physicians. There has been no anticoagulant-related mortality in 254 patient treatment-years, and the major complication rate is 4% of treatment courses. There is a relatively low complication rate because of the systematic approach to anticoagulation therapy, recognition of the importance of patient education, communication with the primary physician, and flexibility of drug dosage and patient visit regimens. Achieving the therapeutic range of the prothrombin time with minimum complications is the goal of this Service. The hallmark of adequate control is predictable response of the prothrombin time to adjustments in drug dosage. Statistical analysis of six years' experience has provided support for the thesis that control of anticoagulation and incidence of complications are not significantly altered by patient age, sex, or the presence of concurrent nonthromboembolic medical illness.