Intravenous immunoglobulin (IVIG) has the potential to regulate Ig production, but the mechanism(s) responsible for this effect is unknown. In experiments reported here, we examined the ability of IVIG to regulate Ig production in human peripheral blood mononuclear cells (PBMCs) stimulated with pokeweed mitogen (PWM). IVIG (2–10 mg/ml) showed a potent (80–85%) inhibition of PWM-stimulated IgG, IgM, and IgA production. To determine more precisely how IVIG mediated the inhibition of Ig production, we studied Ig promoting cytokine gene expression after PWM stimulation with or without IVIG (2 and 10 mg/ml) using dot-blot techniques. RNA was isolated from PBMCs at predetermined time points and probed with cDNAs specific for human cytokines (IL-1-, IL-2, IL-2R, IL-4, IL-5, IL-6, -IFN, and TNF-). IL-6 mRNA accumulation was maximal at 4.5 hr post-PWM stimulation and was inhibited 64–75% when IVIG (10 mg/ml) was present. -IFN mRNA levels peaked at 72 hr poststimulation and were also 68–75% inhibited by IVIG. IL-2 mRNA levels peaked at 4.5 hr and were 23–46% inhibited by IVIG. The inhibitory effect of IVIG on production of these cytokines (IL-6 and -IFN) was also observed at the protein level in sonicated PBMCs after incubation with PWM and IVIG. The mRNA levels for other cytokines were not or only minimally inhibited by IVIG. Addition of IL-6, -IFN, or IL-2 partially restored Ig production in IVIG-treated PWM-stimulated cultures, suggesting that inhibition of other cytokines or another mechanism(s) independent of cytokine inhibition might also be involved, although inhibition of IL-6, -IFN, and IL-2 may be one of the critical factors in the suppression of Ig production by IVIG. 相似文献
A randomized, double-blind study was undertaken to determine the dose requirements, recovery characteristics, and pharmacokinetic variables of midazolam given by continuous infusion for sedation in patients following abdominal aortic surgery. Thirty subjects, 50–75 yr, scheduled to undergo aortic reconstructive surgery, entered the study. Following a nitrous oxide-isoflurane-opioid anaesthetic technique, patients were randomly allocated to receive one of three loading doses (0.03, 0.06 or 0.1 mg · kg?1) and initial infusion rates (0.5, 1.0 or 1.5 μg · kg?1 · min?1) of midazolam, corresponding to groups low (L), moderate (M) and high (H). The infusion of midazolam was adjusted to maintain sedation levels of “3, 4 or 5,“ which permitted eye opening in response to either verbal command or a light shoulder tap, using a seven-point scale ranging from “0” (awake, agitated) to “6” (asleep, non-responsive). Additionally, morphine was given in increments of 2.0 mg iv prn for analgesia. On the morning after surgery, midazolam was discontinued, and the tracheas were extubated when patients were awake. Blood samples were taken during, and at increasing intervals for 48 hr following discontinuation of the infusion, and analyzed by gas chromatography. The desired level of sedation was maintained during more than 94% of the infusion period in all three groups, with a maximum of three dose adjustments per patient, for treatment which lasted 16.3 ± 0.6 hr. There was, however, an increase in both the infusion rates and mean plasma concentrations from Group L to Group H (P < 0.05), which corresponded to an inverse relationship of morphine requirements during the period of sedation (P < 0.05, Group H vs Group L). Optimal midazolam infusion rates and resulting plasma concentrations at the times the infusions were discontinued (in parentheses) were as follows — Group L: 0.60 ± 0.18 μg · kg?1 min?1 (76 ± 32 ng · mL?1), Group M: 0.90 ± 0.52 μg · kg?1 · min?1 (133 ± 71 ng · mL?1), and Group H: 1.34 ± 0.69 μg · kg?1 · min?1 (206 ± 106 ng · mL?1). Times to awakening were longer in Group H: 3.1 ± 3.4 hr, than in Group L: 1.1 ± 0.8 h, P < 0.05. Pharmacokinetic variables were found to be dose- independent over the range of infusion rates. Mean values were t1/2β = 4.4 ± 1.5 hr, CL = 5.94 ± 1.69 mL · min?1 · kg?1, Vd = 3.13 ± 1.07 L · kg?1. It is concluded that midazolam, infused between 0.6–0.9 μg · kg?1 · min?1, provides a stable level of sedation, when administered in conjunction with intermittent iv morphine following AAS. This sedation technique, which costs $1.65 ± 0.73 hr?1 ($Can), is associated with rapid recovery and minimal side effects. 相似文献
We present a model to estimate the infection curve of the human immunodeficiency virus in intravenous drug users in Lombardia. We based estimates on AIDS incidence data, according to a backcalculation model accounting for therapy and changes in the surveillance definition of AIDS. 相似文献
Introduction: Helicopter transport of the combative patient is a major safety hazard facing air medical teams. Although physical restraints alone are helpful, the addition of chemical restraint (CR) often is necessary to control these patients while in flight.
Methods: A survey was conducted to determine the current practices of using nonparalyzing CR in air medical transport programs nationwide. The survey consisted of 24 questions on the use of CR during transport. Each U.S. program belonging to the Association of Air Medical Services was contacted by telephone, and a flight nurse or paramedic provided answers based on personal experience and statistics compiled by his or her individual program.
Results: Of the 100 programs responding, benzodiazepines were used most commonly to control agitation with 51% using midazolam. Patients with a head injury required CR more frequently than any other condition (73%). Crews flying larger aircraft reported less need for CR. A physician order was required by only 30% of the programs, but delays infrequently endangered the patient (2%). Only 7% of the responding programs had a patient whose condition deteriorated because of CR.
Conclusion: CR is necessary in air medical transport. Most programs use short-acting benzodiazepines. Crews in smaller aircraft use CR more frequently, and head injury is the most common condition requiring such restraint. 相似文献
Dexmedetomidine, a highly selective and potent alpha2-adrenergic agonist, has a potentially useful role as a sedative agent in patients requiring intensive care. As part of a larger European multicentre trial, a total of 119 postoperative cardiac and general surgical patients requiring ventilation and sedation in an intensive care unit were enrolled in four centres in the United Kingdom. One hundred and five patients were randomly allocated to receive either dexmedetomidine or placebo with rescue sedation and analgesia provided by midazolam and morphine, respectively. Compared with the control group, intubated patients receiving dexmedetomidine required 80% less midazolam [mean 4.9 (5.8) microg.kg-1.h-1 vs. 23.7 (27.5) microg.kg-1.h-1, p < 0.0001], and 50% less morphine [11.2 (13.4) microg.kg-1.h-1 vs. 21.5 (19.4) microg.kg-1.h-1,p = 0.0006]. Cardiovascular effects and adverse events could be predicted from the known properties of alpha-2 agonists. In conclusion, dexmedetomidine is a useful agent for the provision of postoperative analgesia and sedation. 相似文献
Rationale: The neurochemical effects of psychostimulant exposure may depend on how these drugs are encountered. A useful method for examining
this issue is to compare neurotransmitter release following response-dependent, or self-administered, drug exposure and response-independent
exposure. Objectives: This experiment examined the effect of active and passive cocaine administration on acetylcholine (ACh) efflux in the shell
region of the nucleus accumbens (NAc) in rats. Methods: One group of rats (CSA: cocaine self-administration) was trained to lever-press for intravenous infusions of cocaine (0.42
mg/kg per infusion) on a fixed-ratio-1 schedule of reinforcement. Cocaine infusions were accompanied by the onset of a stimulus
light that signaled a 20-s time-out period. Control rats received intravenous cocaine (cocaine non-contingent: CNC) or saline
(SAL) in a manner that was not contingent upon their behavior. Drug infusions in these groups were determined by the lever-press
behavior of the animals in the CSA group, i.e. they were yoked to rats in the self-administration group such that CNC animals
received equal amounts of cocaine as CSA rats. Animals received cocaine or saline in 3-h sessions for 13 consecutive days
before testing. On day 14, extracellular ACh was measured in 15-min intervals before, during and after a 3-h session of cocaine
exposure using unilateral microdialysis probes located in the NAc shell coupled with HPLC. Results: ACh efflux was significantly increased above baseline in both groups of rats that received cocaine but CSA rats had significantly
higher ACh levels during the self-administration period compared to their yoked counterparts. In addition, ACh efflux remained
elevated longer in CSA animals relative to CNC rats following cessation of cocaine exposure. Conclusions: These results demonstrate that ACh interneurons in the NAc shell are responsive to cocaine exposure. In addition, these findings
suggest that the manner in which the drug is administered (i.e. either by active self-administration or passive exposure)
may be relevant to the magnitude of the neural response.
Received: 28 April 1998 / Final version: 4 November 1998 相似文献