The total synthesis of renierone, mimocin, renierol, renierol acetate, renierol propionate, and 7-methoxy-1,6-dimethylisoquinoline-5,8-dione was successfully achieved by the regioselective oxidation of 5-oxygenated isoquinoline. The synthetic method of the 5-oxygenated isoquinoline is based on the thermal electrocyclic reaction of 1-azahexatriene system involving the benzene 1,2-bond.

AIM:Milrinone, a phosphodiesterase III inhibitor, exerts positive inotropic effects which induce an increase in the intracellular calcium concentration by raising the cyclic adenosine monophosphate level in cardiac muscle. Milrinone was also reported to inhibit platelet aggregation, however, its mechanism remains unknown. Therefore, we investigated the effects of milrinone on intracellular calcium mobilization when platelets were activated.METHODS:Washed platelets, obtained from six healthy volunteers, were preincubated with milrinone (0.9 micro M) for 1 min and then exposed to 0.015 i micro ml-1 thrombin for 5 min. The effect of milrinone on changes in the intracellular calcium level using a fluorescent dye, fura-2, was also observed. Calcium mobilizations via plasma membrane calcium channels and the dense tubular system were assessed differentially.RESULTS:Milrinone (0.9 micro M) significantly suppressed the aggregation ratios at 5 min compared with those in controls (86+/-5%) to 75+/-8%. The increase in the intracellular calcium concentration was also significantly suppressed (controls, 915+/-293 nM vs. 405+/-240 nM) when stimulated by thrombin. Milrinone also significantly inhibited the release of calcium from the dense tubular system (controls, 284+/-111 nM vs. 158+/-51 nM). Calcium influx through the plasma membrane was suppressed by milrinone 2.4 micro M.CONCLUSION:Milrinone (0.9 micro M) inhibited thrombin-induced platelet aggregation. This inhibitory effect was mainly mediated by suppressing calcium release from the dense tubular system.

We describe the development of intention myoclonus following severe cardiopulmonary failure in three paediatric patients. Symptoms occurred during the withdrawal of midazolam and fentanyl, which were used for prolonged sedation, and resolved spontaneously. Because the three patients had concomitant brain injury secondary to cardiopulmonary failure-related hypoxia, we propose that the combination of hypoxic brain injury and sedative withdrawal may predispose to intention myoclonus. (Critical Care and Resuscitation 2002; 4: 104-106)

Purpose: The purpose of this study was to assess whether the arterial ketone body ratio (AKBR) can be effectively used to evaluate the severity of illness in children following cardiac surgery. Materials and Methods: AKBR was measured in 157 consecutive pediatric patients following heart surgery on the odd numbers of postoperative days. The relationship between AKBR and patient outcome was analyzed using the data of 141 patients with cardiopulmonary bypass. Results: Initial AKBR was frequently lower than 1.0, and this was associated with the increases in total ketone body counts. Insufficient glucose metabolism appeared to contribute to the low initial AKBR. As a result, the specificity of initial AKBR as a mortality predictor was lower than that of initial blood lactate. In the sequential analysis of AKBR for the 48 patients with PICU stay longer than 5 days, patients showing a sustained lower level <1.0 had significantly higher development of organ dysfunction (liver, heart) and greater mortality (56%). Conclusions: Sustained postoperative decrease in AKBR <1.0 represents lethal outcome. The analysis of AKBR trend in combination with a measurement of blood lactate level in early postoperative period appears to be useful for the assessment of the severity of illness in pediatric patients following heart surgery. Copyright © 2001 by W.B. Saunders Company

A fatal hyperthermic syndrome occurred in a patient with myokymia. The patient suffered acute circulatory collapse and severe rhabdomyolysis associated with hyperthermia. Although these symptoms were similar to neuroleptic malignant syndrome or malignant hyperthermia, he did not have a history of antipsychotic medication or anesthesia. Continuous muscular contraction due to myokymia likely led to the development of hyperthermic syndrome.

Nasal carriage of MRSA is a significant risk-factor for the endogenous MRSA infection in immunocompromised patients. MRSA infection in ICU patients is thus mostly endogenous infection. To evaluate the impact of mupirocin use on the incidence of endogenous infection caused by MRSA in an intensive care unit, we prospectively treated all patients in the unit with mupirocin, 3 times daily for 3 days. This routine use of mupirocin led to eradication of nasal MRSA carriage in 81.8% of surveillance cultures and to a significant reduction in the total incidence of MRSA infection among MRSA carrier patients (0 episode in 11 patients) when compared to historical controls prior to the use of mupirocin (3 episodes in 7 patients). Mupirocin nasal ointment was significantly effective to prevent endogenous MRSA infection.

BACKGROUND:Sevoflurane reportedly inhibits adenosine diphosphate-induced platelet aggregation by suppressing thromboxane A2 formation. The increase in intracellular calcium concentration that fosters platelet aggregation, however, is also induced by other cell signaling pathways, such as activation of the production of inositol 1,4,5-triphosphate by thrombin. The current study aimed to clarify the net influence of sevoflurane on thrombin-induced platelet aggregation.METHODS:Washed platelets were stimulated by thrombin after incubation with 0.5, 1.0, or 1.5 mM sevoflurane, halothane, or isoflurane. Aggregation curves were measured by an aggregometer. Intracellular calcium concentration was measured fluorometrically using fura-2. Calcium mobilization via plasma membrane calcium channels and the dense tubular system was assessed differentially. Intracellular inositol 1,4,5-triphosphate was measured by radioimmunoassay.RESULTS:Halothane significantly suppressed aggregation ratios at 5 min compared with those in controls (89 +/- 7%) to 71 +/- 10% (1.0 mM) and 60 +/- 11% (1.5 mM) and the increase in intracellular calcium concentration (controls, 821 +/- 95 nM vs. 440 +/- 124 nM [1.0 mM] or 410 +/- 74 nM [1.5 mM]). Halothane also significantly inhibited release of calcium from the dense tubular system (controls, 220 +/- 48 nM vs. 142 +/- 31 nM [1.0 mM]). Neither sevoflurane nor isoflurane produced a net change in aggregation ratios, intracellular calcium concentration, or calcium mobilization. Halothane (1 mM) significantly suppressed inositol 1,4,5-triphosphate concentrations, whereas neither 1 mM isoflurane nor 1 mM sevoflurane had any effect.CONCLUSIONS:Although sevoflurane has been reported to inhibit human platelet aggregation induced by weak agonists such as adenosine diphosphate, it does not inhibit human platelet aggregation induced by strong agonists such as thrombin.

New total syntheses of renierol (3), renierol acetate (4), and renierol propionate (5) were completed by the synthesis of 5-oxygenated isoquinoline (6) based on the thermal electrocyclic reaction of the 1-azahexatriene system followed by regioselective oxidations of 5-hydroxyisoquinolines (6).

OBJECTIVE: To evaluate the efficacy of hypoxic gas therapy using nitrogen, where the fraction of inspired oxygen (Fio2) was reduced to <0.21 in patients with univentricular parallel circulation. DESIGN: Case report. SETTING: A pediatric intensive care unit at a university hospital. PATIENTS: Two neonatal patients with hypoplastic left heart syndrome admitted to the pediatric intensive care unit preoperatively. INTERVENTIONS: Nitrogen insufflation by using continuous-flow respiratory support. MEASUREMENTS AND MAIN RESULTS: We reduced the Fio2 in these patients by giving additional nitrogen to relieve pulmonary overcirculation and systemic hypoperfusion suspected by transcutaneous arterial oxygen saturation >90%, systemic arterial hypotension, and low urine output in the preoperative course. The improvement of systemic hemodynamics concomitant with decreases in transcutaneous arterial oxygen saturation <85% was accomplished by controlling Fio2 between 0.14 and 0.18. These infants were able to undergo Norwood's surgery after several days without complications relating to Fio2 reduction. CONCLUSION: Hypoxic gas therapy with nitrogen was effective clinically in preventing pulmonary overcirculation in neonatal patients with univentricular and parallel circulation.

New total syntheses of renierol (3), renierol acetate (4), and renierol propionate (5) were completed by the synthesis of 5-oxygenated isoquinoline (6) based on the thermal electrocyclic reaction of the 1-azahexatriene system followed by regioselective oxidations of 5-hydroxyisoquinolines (6).

BACKGROUND:The inhibitory effects of propofol on platelet aggregation are controversial because the fat emulsion used as the solvent for propofol may affect platelet function. The effects of propofol on platelet intracellular calcium ion concentration and on aggregation were investigated.METHODS:Platelet aggregation was measured in 10 patients who received an intravenous infusion of propofol. Intralipos, the propofol solvent, was infused in 10 healthy volunteers and platelet aggregation were measured. The in vitro effects of propofol and Intralipos on platelets were also investigated. The inhibitory effects of various concentrations of propofol were studied. The effects of propofol on the changes in intracellular calcium level using a fluorescent dye, fura-2, were also observed. Template bleeding time was measured to determine the effect of propofol in clinical use.RESULTS:Platelet aggregation was significantly inhibited by infusion of propofol, although bleeding time was not prolonged. Intralipos did not inhibit platelets either in vivo or in vitro. Propofol significantly inhibited platelet aggregation in vitro and at 5.81 +/- 2.73 microg/ml but not at 2.08 +/- 1.14 microg/ml. The increase of intracellular calcium concentration was inhibited both in influx and discharge of calcium.CONCLUSIONS:Propofol inhibited platelet aggregation both in vivo and in vitro. Inhibition of platelet aggregation appeared to be caused by propofol itself and not by the fat emulsion. This inhibitory effect was also supported by the suppressed influx and discharge of calcium. No change in the bleeding time suggests that this inhibitory effect does not impair hemostasis clinically.