Physiological levels of interleukin-18 stimulate multiple neutrophil functions through p38 MAP kinase activation

Patients with sepsis and acute lung injury have increased interleukin (IL)-18 levels systemically. We hypothesize that IL-18 stimulates neutrophils (PMNs) at physiologic concentrations. IL-18 primed the oxidase at 15 min (10-100 ng/ml), 30 min (0.1-100 ng/ml), and 60 min (100 ng/ml; P<0.05) and caused translocation of p47(phox) to the membrane similar to lipopolysaccharides. CD11b surface expression was increased by IL-18 in a time- and concentration-dependent manner. IL-18 caused up-regulation of the formyl-Met-Leu-Phe receptor, changes in PMN size, and elastase release. Investigation of signaling demonstrated IL-18-mediated activation of p38 mitogen-activated protein (MAP) kinase in a concentration (0.1-100 ng/ml)-, time (5-15 min)-, and Ca2+-dependent manner. IL-18 directly increased cytosolic Ca2+ concentration. IL-18 activation of PMNs was blocked by inhibition of p38 MAP kinase activity (SB203580) or by inhibition of p38 MAP kinase activation by chelation of cytosolic Ca2+. We conclude that IL-18, at physiologic concentrations, is an effective PMN priming agent that requires p38 MAP kinase activity.     

Increased numbers of sodium channels form along demyelinated axons

Sodium channels, which are largely localized to the nodes of Ranvier in myelinated axons, appear to form new distributions along demyelinated axons. In this study a sensitive radioimmunoassay (RIA) was used to examine the changes in the total number of sodium channels that occur in nerves experimentally demyelinated in vivo with doxorubicin (adriamycin). The results clearly illustrate the development of an increased number of sodium channels during demyelination, suggesting that this process is associated with the formation of new sodium channels.     

History of migraine and risk of pregnancy-induced hypertension.

This analysis assesses the relation between a history of migraine and the risk of preeclampsia or gestational hypertension. Cases (172 women with preeclampsia and 254 with gestational hypertension) and controls (505) were primiparae with no history of hypertension before pregnancy. Information on migraine attacks in the year before pregnancy was obtained after delivery. Migraine was reported by 16% of preeclamptic women, 12% of women with gestational hypertension, and 8% of the controls. Adjusted odds ratios (95% confidence interval) of preeclampsia and gestational hypertension were 2.44 (1.42-4.20) and 1.70 (1.02-2.85), respectively. We conclude that women who have a recent history of migraine may be at higher risk of pregnancy-induced hypertension.     

The effect of cigarette smoking on the risk of preeclampsia and gestational hypertension

This case-control study assessed the relation of cigarette smoking during pregnancy to the risk of preeclampsia and gestational hypertension. All subjects were primiparous women without a history of high blood pressure who gave birth in Quebec City or Montreal, Canada, hospitals between 1984 and 1986. Cases (172 women with preeclampsia and 251 with gestational hypertension) and 505 controls were interviewed at the hospital after delivery. Adjusted relative risks were estimated by polychotomous logistic regression. Compared with women who had never smoked, women who were smokers at the onset of pregnancy had a reduced risk of preeclampsia (relative risk = 0.51, 95% confidence interval 0.34-0.77). Relative risks of preeclampsia decreased with increases in the number of cigarettes smoked daily at the onset of pregnancy: Relative risks among smokers of less than 11, 11-20, and more than 20 cigarettes per day were 0.79, 0.56, and 0.38, respectively (test for trend: p = 0.0002). The protective effect of smoking on preeclampsia was stronger for women who continued to smoke after 20 weeks of pregnancy. While smoking tended to reduce the risk of gestational hypertension, this effect was less evident than that for preeclampsia. Relative risks varied little with severity of disease as based on gestational age at the onset of hypertension, maximal blood pressure and, for preeclampsia, amount of proteinuria. The reduction in mean birth weight attributable to smoking during pregnancy was similar among cases and controls. Nicotine inhibition of thromboxane A2 production might explain the decreased risk of pregnancy-induced hypertension among smokers. Despite these findings, the harmful consequences of smoking on pregnancy outcome outweigh its protective effect against pregnancy-induced hypertension.     

Clinical evaluation of nanofill and nanohybrid composite in Class I restorations: a 12-month randomized trial

This randomized trial evaluated the 12-month clinical performance of nanofill, a nanohybrid, and a microhybrid composite in restorations in occlusal cavities of posterior teeth. This study utilized 41 patients, each of whom had three molars affected by primary caries or the need to replace restorations. All restorations were performed in accordance with the manufacturer's recommendations and evaluated in accordance with U.S. Public Health Service-modified criteria. Based on the results of the present study, the material investigated demonstrated acceptable clinical performance after 12 months of clinical service. Long-term re-evaluations are necessary for a more detailed analysis of these composites.     

790 Kb microduplication in chromosome band 17p13.1 associated with intellectual disability, afebrile seizures, dysmorphic features, diabetes, and hypothyroidism

We report a patient with a moderate mental retardation, afebrile seizure, mild dysmorphic features and type 2 diabetes mellitus with mild obesity and metabolic syndrome. Array-CGH analysis revealed a de novo 790–830 kb duplication on chromosome 17p13.1, not reported so far. Among the approximately 50 genes involved in the rearrangement, neuroligin 2 (NLGN2) and ephrin B3 (EFNB3) are candidates for the mental retardation phenotype. NLGN2 may therefore be a novel candidate gene for mental retardation or autistic spectrum disorder, joining other members of the neurexin/neuroligin network. Moreover, GLUT4, a member of the solute carrier family 2, may play a role in the patient’s type 2 diabetes.     

Relaxation versus fractionation as hypnotic deepening: do they differ in physiological changes?

After rapid hypnotic induction, 12 healthy volunteers underwent hypnotic deepening with relaxation or with fractionation (without relaxation) in a random latin-square protocol. Electroencephalographic occipital alpha activity was measured, low-resolution brain electromagnetic tomography was performed, and hemodynamics (stroke volume, heart rate, cardiac output, mean arterial blood pressure, forearm arterial flow and resistance) were monitored in basal conditions and after deepening. After relaxation, both forearm flow (-18%) and blood pressure (-4%) decreased; forearm resistance remained unchanged. After fractionation, a forearm flow decrease comparable to that recorded after relaxation was observed, but blood pressure remained unchanged, leading to an increase of forearm resistance (+51%). Central hemodynamics did not change. Alpha activity increased in the precuneus after fractionation only. In conclusion, both relaxation and fractionation have vasoconstrictor effects, but fractionation is also associated with an increase in peripheral resistance.     

Respiratory failure after pediatric scald injury

Objective

A subset of children with scald burns develops respiratory failure despite no direct injury to the lungs. We examined these patients in an effort to elucidate the etiology of the respiratory failure.

Methods

The charts of pediatric patients with greater than 10% total body surface area (TBSA) scald burns were reviewed. Age, weight, burn distribution, percentage of TBSA burned, resuscitation volumes, Injury Severity Score, evidence of abuse, length of stay, days in the intensive care unit, and time and duration of intubation were recorded.

Results

Two hundred thirty-two patients met our inclusion criteria. Of these, 220 patients did not require intubation, and 12 of the patients did. No patient older than 3 years or with burns less than 15% TBSA required intubation. Fluid over resuscitation was not directly associated with respiratory failure requiring mechanical ventilation.

Conclusions

We report the largest published series of patients with scald burns requiring mechanical ventilation in the absence of direct airway injury. Five percent of pediatric patients required mechanical ventilation after scald injury. We believe that a combination of causes including fluid resuscitation, young patient age, small patient size, and possible activation of the systemic inflammatory immune response may be responsible for the respiratory failure.