The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis

BACKGROUND. In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease. METHODS. We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Children's Hospital, San José, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days. RESULTS. The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5). CONCLUSIONS. The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis.     

The effect of intravenous administration of dexamethasone on intraocular pressure in clinically normal dogs

The purpose of this study was to determine the effect of intravenous administration of dexamethasone on intraocular pressure (IOP) in clinically normal dogs. Ten ophthalmoscopically and clinically healthy mixed-breed dogs were included in this study. Dogs received intravenous dexamethasone (4 mg/kg). Applanation tonometry was performed on both eyes of all dogs prior to treatment and then at 15, 30, 60, 120, 240, and 360 min post-drug administration. Statistical comparisons between the pre-treatment mean values of IOP and post-treatment values revealed significant increase at 15 (P = 0.001), 30 (P = 0.001), 60 (P = 0.004), 120 (P = 0.004), 180 (P = 0.003), and 360 min (P = 0.024) after dexamethasone administration. In summary, this observation confirms that dexamethasone increases IOP shortly after intravenous administration in dogs. Based on these results, dogs with weak or thin corneas, glaucoma, or any condition for which an increase in IOP could be harmful should not receive systemic dexamethasone.     

The significance of timing of FTY720 administration on the immunosuppressive effect to prolong rat skin allograft survival

FTY720, a potent immunosuppressant, dramatically decreases the number of peripheral blood lymphocytes within a few hours after administration. The current study assessed the significance of timing of FTY720 administration on the immunosuppressive effect to prolong rat skin allograft survival (WKAH donor to F344 recipient). The median survival time of allografts was 7 days in the control recipients. FTY720 (1 mg/kg/day) significantly prolonged allograft survival when administered from days 0 and 3, but failed to exert an immunosuppressive effect when administered from day 4. Intragraft T cells, especially CD8(+) T cells, were markedly increased in number from day 4 to 6, peaking on day 5 in control recipients. FTY720 markedly decreased the number of intragraft CD8(+) T cells on day 5 when administered from days 0 and 3. In recipients administered with FTY720 from day 4, the number of intragraft CD8(+) T cells were only partially decreased on day 5. Intragraft CD8(+) T-cell number in those recipients on day 5 was almost the same as that in control recipients on day 4. In addition, FTY720 did not affect the increase in frequency of CD25(+) cells in the CD8(+) T-cell subset in allografts. It is likely that recipients treated with FTY720 from day 4 reject allografts by intragraft immune responses involved in CD8(+) T cells which had infiltrated before day 4, similar to control recipients. These findings suggest that FTY720 should be administered before increase in T cell infiltration into grafts to inhibit acute allograft rejection.     

Prostacyclin administration as a beneficial supplement to the conventional cancer chemotherapy

Prostacyclin (PGI(2)) and its analogues protect from cardiovascular disease through pleiotropic effects such as vasodilation, inhibition of platelet aggregation, leukocyte adhesion, and vascular smooth muscle cell (VSMC) proliferation. Additionally, prostacyclin synthase (PGIS) and PGI(2) also possess anti-cancer properties. As of late (2009-2010), numerous studies have identified the deleterious side-effects of chemotherapy on the cardiovascular system, which have been deemed as a serious clinical issue. Cardiomyocyte damage, induced by oxidative stress, is one of the clinical consequences caused by routine cancer chemotherapy. Previous studies indicate iloprost, a PGI(2) analogue, can protect against doxorubicin-induced (DOX) cardiomyocyte injury in vitro and in vivo without compromising tumor suppression. Therefore, we hypothesize PGI(2) can be used as a cardioprotective supplement to attenuate the damaging cardiac effects caused by the traditional cancer chemotherapy regimen.     

Effects of dexamethasone on the pharmacokinetics of adriamycin after intravenous administration to rats

Adriamycin was metabolized to adriamycinol by the cytoplasmic aldo-keto reductase and adriamycin and adriamycinol were further metabolized to their deglycosylated aglycones, M3 and M4, respectively, by cytochrome P450. SKF-525A (a cytochrome P450 inhibitor) and dexamethasone (a cytochrome P450 inducer) were pretreated to rats. Adriamycin, 16 mg/kg, was infused over 1-min via the jugular vein of each rat. After pretreatment with SKF-525A, the area under the plasma concentration-time curve of adriamycin from time zero to the last measured time in plasma, 8 h (537 versus 155 microg x min/ml) was significantly greater, and the 24-h urinary excretion of M3 (1.65 versus 23.8 microg), and M3, M4, and their glucuronide and/or sulfate conjugates (33.7 versus 3.38 microg) were significantly smaller than those in control rats suggesting that the formation of M3 and M4 were inhibited by SKF-525A. After pretreatment with dexamethasone, the 24-h urinary excretion of M3 (94.5 versus 23.8 microg), M4 (8.43 versus 2.78 microg), and M3, M4, and their glucuronide and/or sulfate conjugates (116 versus 33.7 microg) were significantly greater than those in control rats, suggesting that the formation of M3 and M4 seemed to be induced by dexamethasone.     

The effects of dexamethasone administration on EEG sleep in depressed patients

Since DST non-suppression and sleep abnormalities have been shown to co-exist in depressive states, it seems important to examine what effects dexamethasone administration might have on the sleep of depressed patients. Therefore, the effects of 1 mg dexamethasone p.o. administered at 11 p.m. to a group of 12 depressed outpatients was examined. In this series of patients, the hypothesis of no significant changes in sleep continuity, sleep architecture or REM sleep features was confirmed aside from an increase in Stage 2 sleep percent and decrease in Stage 1 REM percent in these patients (both variables stayed in the normal range). It can be concluded that acute administration of dexamethasone does not influence the sleep of depressed patients in a major way.     

The effect of ultrasound on Escherichia coli viability

The effect of continuous-wave ultrasound on the viability of Escherichia coli HB101 was assessed using a 20 kHz ultrasonic processor. A standardised cell suspension of fixed concentration was used to investigate the influence of different physical and environmental conditions on ultrasound susceptibility. Cell viability decreased exponentially with time at different intensities of ultrasound. Increasing intensity caused a decrease in decimal reduction times. Loss of cell viability occurred primarily from the mechanical effects of ultrasound rather than free radical damage. E. coli susceptibility was also shown to vary with growth conditions, whereby cells cultivated either on agar or harvested from the stationary phase of liquid culture were significantly more susceptible to ultrasound than an equivalent population obtained from the exponential phase of liquid growth. The implication of these results is discussed in relation to the use of ultrasound as a novel means of bacterial transformation.     

The effect of dexamethasone dosage upon plasma cortisol and dexamethasone during the DST

To investigate the effect of dexamethasone dosage upon the outcome of the dexamethasone suppression test (DST) and the role of concurrent plasma dexamethasone concentrations, four different dexamethasone dosages were administered to 119 hospitalized depressed patients (0.5 mg: n = 12; 1.0 mg: n = 30; 1.5 mg: n = 42; 2.0 mg: n = 35). Independent of the dosage, dexamethasone plasma concentrations at 4.00 p.m. were lower in DST non-suppressors than in suppressors, although differences were statistically significant only for the 1.5-mg and 2.0-mg dosages. Our findings confirm recent reports that the actual plasma concentration of dexamethasone at 4.00 p.m. does not determine DST outcome.     

皮瓣修复四肢深度电烧伤创面的临床观察

目的探讨四肢深度电烧伤创面处理的最佳手术时机及手术方式。方法回顾性分析32例共48个四肢深度电烧伤创面的修复。在病情稳定后尽早手术清创,清除坏死组织,保留有活力的间生态组织,即刻采用皮瓣修复。结果48个接受治疗的创面,包括轴型皮瓣修复26处,随意皮瓣修复8处,肌皮瓣修复8处,游离皮瓣修复4处,交肢皮瓣修复2处。其中1例游离皮瓣由于基底感染血管栓塞而发生坏死,待肉芽组织生长后游离植皮修复。其余创面一期修复成功,较好地保存了患肢功能。结论四肢深度电烧伤创面应尽早手术清创,一期修复创面,酌情选择轴型皮瓣、随意皮瓣、肌皮瓣,必要时可选用游离皮瓣或交肢皮瓣,最大限度地保存患肢功能,降低伤残率。     

前列环素对随意皮瓣血液流变学的影响

目的：探讨前列环素对随意皮瓣血液流变状态以及成活情况的影响。方法：以ＳＤ大鼠为模型，于其背部设计蒂在尾部长９ｃｍ、宽３ｃｍ的随意皮瓣。术前及术后经尾静脉注射一定量的前列环素，对照组给等量生理盐水，观察术后７ｄ皮瓣的成活面积，并测定了术后不同时刻的血液流变学变化。结果：术后给药组皮瓣的成活面积显著大于对照组。结论：前列环素可以通过降低术后皮瓣的血小板聚集率、血浆纤维蛋白原浓度以及全血还原比粘度，改善皮瓣的微循环状态，从而促使皮瓣成活。     

轴型真皮下血管网皮瓣的应用解剖

目的　为临床应用轴型真皮下血管网皮瓣 (ASVNF)提供解剖学依据。方法　对 12侧下肢标本进行了解剖学观察。重点解剖观察股前外侧ASVNF和隐血管ASVNF的轴心血管在浅筋膜层的走行、分支、真皮下血管网 (SVN)的构筑和皮瓣超薄范围等情况。结果　肌皮穿支穿出深筋膜层后向周围不同方向发出三种分支 ,其中SVN分支斜穿较少浅筋膜后很快进入真皮下层形成吻合稠密的SVN ,制备股前外侧ASVNF应采用“圆形”超薄法。直接皮肤血管在浅筋膜层纵行途中主要向两侧及浅面发出分支 ,制备隐血管ASVNF应采用“U形”超薄法。SVN分支在真皮下层反复分支形成“血管树”或“蜘蛛痣”状血管网 ,且血管网之间稠密吻合。结论　不同血供类型ASVNF的超薄方法应不同。     

The effect of dexamethasone on organ-cultured human trabecular meshwork

The effect of dexamethasone (DEX) on the organ-cultured human trabecular meshwork (HTM) was studied with morphometric, autoradiographical, biochemical and immunohistochemical techniques. In approximately 36% of the cases examined, a statistically significant increase in extracellular materials in the endothelial meshwork was found with occurrence of vacuolated trabecular cells. Silver grains showing the presence of the proteins and glycoproteins labeled with³H-methionine were observed in vacuoles of the trabecular cells. In addition, elastin was identified on the surface of the vacuolated trabecular cells. The alterations of the proteins/glycoproteins and elastin in the HTM induced by DEX treatment may play a role in the reduction in aqueous outflow facility.     

The effect of cytochrome c on the myocardium during reperfusion

Experimental and clinical trials have shown high effectiveness of cytochrome c (0.5 mg/kg) in prevention of reperfusion myocardial disorders in cardiosurgical patients. Cytochrome c inhibits development of myocardial ischemic contracture, depression of coronary circulation, activation of lipid peroxidation. It reduces myocardial consumption of oxygen and promotes earlier restoration of fatty acids metabolism under lower glucose consumption by the heart muscle. By correction of myocardial metabolism, the drug suppresses fermentemia in early reperfusion.