STUDY OBJECTIVES: To determine whether childhood sleep-disordered breathing (SDB) is associated with elevated levels of plasma adhesion molecules. DESIGN: Prospective, observational study. SETTING: Sleep Medicine Center of Kosair Children's Hospital. PARTICIPANTS: Thirty-nine children with SDB (apnea-hypopnea index [AHI] > 5/h), 47 children with mild SDB (AHI 1 to 5/h), and 42 healthy control subjects (AHI < 1/h). MEASUREMENTS AND RESULTS: One hundred twenty-eight children underwent a standard polysomnographic assessment with a blood draw the following morning. Plasma levels of CRP and the adhesion molecules intercellular adhesion molecule (ICAM)-1 and P-selectin were measured. No differences were observed in ICAM-1 levels among the groups; however, obese children had higher ICAM-1 levels than nonobese children (425.0 +/- 123.0 ng/mL vs 375.6 +/- 107.1 ng/mL, p = 0.04) [mean +/- SD]. P-selectin levels were significantly higher in the SDB group (84.0 +/- 52.2 ng/mL) and the mild SDB group (89.3 +/- 49.9 ng/mL) when compared to control subjects (49.5 +/- 22.3 ng/mL; p < 0.001 for both groups). Furthermore, P-selectin correlated with AHI (r = 0.32, p < 0.001), respiratory arousal index (r = 0.27, p = 0.002), and nadir of oxygen saturation as measured by pulse oximetry (r = - 0.19, p = 0.038). Plasma CRP levels were found to correlate with P-selectin even after controlling for BMI (r = 0.20, p = 0.05). No correlations were found between CRP and ICAM-1. CONCLUSIONS: Children with SDB have plasma elevations of P-selectin, a marker of platelet activation, lending support to the premise that inflammatory processes are elicited by SDB in children, and may contribute to accelerated risk for cardiovascular morbidity. In contrast, elevations in ICAM-1 are primarily associated with obesity rather than SDB. 相似文献
The antithrombotic efficacy of lepirudin in patients with heparin-induced thrombocytopenia (HIT) is compromised by an increased risk for bleeding. A retrospective observational analysis in 181 patients (median age, 67 years) with confirmed HIT treated in routine practice with lepirudin was performed to identify predictive factors for thrombotic and bleeding complications. Lepirudin was administered at a mean (+/- SD) dose of 0.06 +/- 0.04 mg/kg/h (compared with a recommended initial dose of 0.15 mg/kg/h). Mean activated partial thromboplastin time was greater than 1.5 times baseline value in 99.4% of patients. Median treatment duration was 7.7 days. Until discharge from the hospital, 13.8% and 20.4% of patients experienced a thrombotic or a major bleeding event, respectively. On multivariate analysis, mean lepirudin dose was not a significant predictive factor for thrombosis. In contrast, mean lepirudin dose greater than 0.07 mg/kg/h, long duration of lepirudin treatment, and moderate to severe renal impairment were significant positive factors for major bleeding. Overall, these results suggest that the recommended dose of lepirudin in patients with HIT is too high; the use of reduced doses may be safer with regard to bleeding risk and does not compromise antithrombotic efficacy. 相似文献
Sleep promotes the integration of recently acquired spatial memories into cerebral networks for the long term. In this study, we examined how sleep deprivation hinders this consolidation process. Using functional MRI, we mapped regional cerebral activity during place-finding navigation in a virtual town, immediately after learning and 3 days later, in subjects either allowed regular sleep (RS) or totally sleep-deprived (TSD) on the first posttraining night. At immediate and delayed retrieval, place-finding navigation elicited increased brain activity in an extended hippocampo-neocortical network in both RS and TSD subjects. Behavioral performance was equivalent between groups. However, striatal navigation-related activity increased more at delayed retrieval in RS than in TSD subjects. Furthermore, correlations between striatal response and behavioral performance, as well as functional connectivity between the striatum and the hippocampus, were modulated by posttraining sleep. These data suggest that brain activity is restructured during sleep in such a way that navigation in the virtual environment, initially related to a hippocampus-dependent spatial strategy, becomes progressively contingent in part on a response-based strategy mediated by the striatum. Both neural strategies eventually relate to equivalent performance levels, indicating that covert reorganization of brain patterns underlying navigation after sleep is not necessarily accompanied by overt changes in behavior. 相似文献
East Coast fever, caused by the tick-borne intracellular apicomplexan parasite Theileria parva, is a highly fatal lymphoproliferative disease of cattle. The pathogenic schizont-induced lymphocyte transformation is a unique cancer-like condition that is reversible with parasite removal. Schizont-infected cell-directed CD8(+) cytotoxic T lymphocytes (CTL) constitute the dominant protective bovine immune response after a single exposure to infection. However, the schizont antigens targeted by T. parva-specific CTL are undefined. Here we show the identification of five candidate vaccine antigens that are the targets of MHC class I-restricted CD8(+) CTL from immune cattle. CD8(+) T cell responses to these antigens were boosted in T. parva-immune cattle resolving a challenge infection and, when used to immunize na?ve cattle, induced CTL responses that significantly correlated with survival from a lethal parasite challenge. These data provide a basis for developing a CTL-targeted anti-East Coast fever subunit vaccine. In addition, orthologs of these antigens may be vaccine targets for other apicomplexan parasites. 相似文献
Background: Opioid-induced delayed hyperalgesia and allodynia have been reported in human and animal models. The authors evaluated the influence of different opioids used during clinical anesthesia on nociceptive sensitivity and incisional pain in mice. The role of the inducible nitric oxide synthase on surgical pain and opioid-induced pronociception also was investigated.
Methods: CD1 mice were used to study the efficacy of opioids inducing pronociception and enhancing incisional pain. The implication of nitric oxide generated from the inducible nitric oxide synthase was investigated using knockout mice (C57/BL6) for its gene. Mice underwent right hind paw surgery under sevoflurane anesthesia combined with subcutaneous administration of saline or the opioids fentanyl (0.05 mg/kg), alfentanil (1 mg/kg), and remifentanil (0.04 mg/kg). Nociception was evaluated daily for 7 days using paw-pressure, plantar, and von Frey tests.
Results: The antinociceptive effect of opioids was followed by long-lasting thermal hyperalgesia and mechanical allodynia (each lasting between 2 and 7 days), but not mechanical hyperalgesia. Intraoperative infusion of opioids significantly enhanced incisional pain in all tests. The most prominent effects were observed with remifentanil. The inducible nitric oxide synthase gene deletion attenuated both remifentanil- and incision-induced pronociceptive effects. In mutant mice for the inducible nitric oxide synthase gene, remifentanil was still efficient in enhancing incisional pain, but the global pronociceptive effect was attenuated significantly as compared with wild-type mice. 相似文献
Background: The goal of the current study was to assess the effects of flumazenil, a benzodiazepine receptor antagonist, in limiting infarct size and in reducing hydroxyl free radical production.
Methods: After intravenous salicylate (100 mg/kg) administration, rabbits were subjected to 40 min of regional myocardial ischemia and 2 h of reperfusion. In one group, flumazenil (0.05 mg/kg) and, in another, midazolam (0.05 mg/kg) was administered 15 min before 40 min of ischemia. Ischemic preconditioning (IP) was elicited by 5 min of ischemia followed by 10 min of reperfusion (before the 40-min ischemia period). In two other groups, midazolam was added to flumazenil and IP. Infarct size was determined using triphenyl tetrazolium chloride staining. The authors quantified the hydroxyl-mediated conversion of salicylate to its 2,3- and 2,5-dihydroxybenzoate derivatives during reperfusion by high-performance liquid chromatography coupled with electrochemical detection. Results are expressed as mean +/- SEM.
Results: Flumazenil, like IP, significantly decreased infarct size (23 +/- 4 and 22 +/- 5%, respectively, vs. 57 +/- 6% in control group; P < 0.01). Midazolam inhibited the effects of flumazenil and IP. Flumazenil and IP significantly limited the increase in the normalized concentrations of 2,3- and 2,5-dihydroxybenzoic acids. With midazolam, however, the increase was comparable to that of the control group. 5-Hydroxydecanoate, a selective mitochondrial adenosine triphosphate-sensitive K+ channel blocker, given with flumazenil, abolished the protection obtained with the latter. 相似文献