Resuscitation and circulatory support using extracorporeal membrane oxygenation for fulminant pulmonary embolism

Fulminant pulmonary embolism (PE) with circulatory collapse is associated with a high mortality rate due to acute right ventricular failure and hypoxia. Immediate and appropriate resuscitation and circulatory support in the perioperative period is mandatory to prevent sudden death. Extracorporeal membrane oxygenation (ECMO) was recently introduced for extracorporeal life support in patients with circulatory collapse and has provided an excellent outcome. We report on the effectiveness of ECMO support for fulminant PE. Seven patients were placed on veno-arterial ECMO for circulatory collapse caused by fulminant PE refractory to conventional treatment. After resuscitation, all patients underwent pulmonary angiography, and thrombolytic therapy was administered in all 7 patients under ECMO support. Three patients who did not improve by thrombolysis underwent embolectomy with standard cardiopulmonary bypass. Two thrombolysis and 2 surgery patients were weaned from bypass and survived. The duration of support ranged from 18-168 h (mean = 67.8 +/- 67.1 h), with maximum bypass flow rates of 2.0-4.5 (mean = 3.5 +/- 0.9). There were no device-related complications during support. In total, 4 patients (57%) were successfully weaned from support and discharged from the hospital in good condition. All patients who survived required prolonged support (27, 82, 151, and 168 h). We conclude that resuscitation and circulatory support using ECMO can be effective, life-saving measures in cases of circulatory collapse caused by fulminant PE.     

An infant with Costelio syndrome complicated with fatal hypertrophic obstructive cardiomyopathy

We report a 3-month-old girl with Costelio syndrome complicating fatal hypertrophic obstructive cardio-myopathy. She had typical findings of this syndrome, slight dyspnea and persistent wheezing. Doppler echocardiography revealed asymmetric septal hypertrophy and systolic anterior movement of the anterior mitral leaflet. There was grade 1 mitral regurgitation. Although once her heart failure had been controlled medically, she died suddenly following deterioration of her heart condition. Costelio syndrome can complicate fatal hypertrophic obstructive cardiomyopathy.     

P-glycoprotein plays a major role in the efflux of fexofenadine in the small intestine and blood-brain barrier, but only a limited role in its biliary excretion.

Fexofenadine is a selective, nonsedating H(1)-receptor antagonist approved for symptoms of allergic conditions, which is mainly excreted into feces via biliary excretion. The purpose of this study is to investigate its pharmacokinetics in mice and rats to determine the role of P-glycoprotein (P-gp) in its biliary excretion. In mice, biliary excretion clearance (17 ml/min/kg) accounted for almost 60% of the total body clearance (30 ml/min/kg). Comparing the pharmacokinetics after intravenous and oral administration indicated that the bioavailability of fexofenadine was at most 2% in mice. Knockout of Mdr1a/1b P-gp did not affect the biliary excretion clearance with regard to both plasma and liver concentrations, whereas the absence of P-gp caused a 6-fold increase in the plasma concentration after oral administration. In addition, the steady-state brain-to-plasma concentration ratio of fexofenadine was approximately 3-fold higher in Mdr1a/1b P-gp knockout mice than in wild-type mice. Together, these results show that P-glycoprotein plays an important role in efflux transport in the brain and small intestine but only a limited role in biliary excretion in mice. In addition, there was no difference in the biliary excretion between normal and hereditarily multidrug resistance-associated protein 2 (Mrp2)-deficient mutant rats (Eisai hyperbilirubinemic rats) and between wild-type and breast cancer resistance protein (Bcrp) knockout mice. These results suggest that the biliary excretion of fexofenadine is mediated by unknown transporters distinct from P-gp, Mrp2, and Bcrp.     

Galectin-9 as a prognostic factor with antimetastatic potential in breast cancer.

PURPOSE: Galectin-9, a member of the beta-galactoside-binding galectin family, induces aggregation of certain cell types. We assessed the contribution of galectin-9 to the aggregation of breast cancer cells as well as the relation between galectin-9 expression in tumor tissue and distant metastasis in patients with breast cancer. EXPERIMENTAL DESIGN: Subclones of MCF-7 breast cancer cells with high or low levels of galectin-9 expression were established and either cultured on plastic dishes or transplanted into nude mice. The tumors of 84 patients with breast cancer were tested for galectin-9 expression by immunohistochemistry. The patients were followed up for 14 years. RESULTS: MCF-7 subclones with a high level of galectin-9 expression formed tight clusters during proliferation in vitro, whereas a subclone (K10) with the lowest level of galectin-9 expression did not. However, K10 cells stably transfected with a galectin-9 expression vector aggregated in culture and in nude mice. Ectopic expression of galectin-9 also reduced MCF-7 cell adhesion to extracellular matrix proteins. Tumors of 42 of the 84 patients were galectin-9 positive, and those of 19 of the 21 patients with distant metastasis were galectin-9 negative. None of the 13 patients with galectin-9-positive tumors and lymph node metastasis up to level II manifested distant metastasis. The cumulative disease-free survival ratio for galectin-9-positive patients was more favorable than that for the galectin-9-negative group (P < 0.0001). Multivariate analysis revealed that galectin-9 status influenced distant metastasis independently of and to a greater extent than lymph node metastasis. CONCLUSIONS: Galectin-9 is a possible prognostic factor with antimetastatic potential in breast cancer.     

An association between plasma levels of 8-isoprostane and alcohol drinking habits in Japanese volunteers]

Lipid peroxidation and oxidative stress may play a certain role in the pathogenesis of pressure-induced atherosclerosis, and alcohol related diseases. Recently, 8-isoprostane in biological fluids has been reported to be a reliable marker for lipid peroxidation and oxidative stress in vivo. In the present study, we developed an ELISA method for 8-isoprostane which has high sensitivity, intra- and inter-assay reproducibility and wide dynamic assay range. Using this method, we examined the effects of drinking and smoking habits on plasma levels of 8-isoprostane in healthy subjects. A total of 157 apparently healthy volunteers was assayed for plasma 8-isoprostane. Subjects were divided into three groups according to their alcohol consumption. Group I is non- or few-drinkers, Group II includes subjects who drink once or twice a week, and subjects of Group III intake 3 to 5 times a week or almost every day. In addition, the same population was divided into two groups, 96 non-smokers and 61 smokers. Plasma 8-isoprostane was extracted with ODS gel followed by NH2 Sep-Pak column. The 8-isoprostane fractions thus separated were assayed by a commercial ELISA kit (Cayman Chemical). The plasma 8-isoprostane was estimated to be 20.9 +/- 93 pg/ml in a total of 157 volunteers (83 male, 74 female). The plasma 8-isoprostane levels were elevated in the Group III (26.6 +/- 9.5 pg/ml) compared with Group I (20.3 +/- 6.1 pg/mL, p<0.0001) and Group II (20.9 +/- 5.7 pg/ml, p<0.001). Significant increase of the plasma 8-isoprostane was observed only in habitual drinkers of females, but not in those of males. On the other hand, no significant difference of the plasma 8-isoprostane levels were observed between non-smokers (21.5 +/- 7.3 pg/ml) and smokers (22.8 +/- 7.4 pg/ml, p>0.05). We suppose that plasma 8-isoprostane may increase in the habitual drinkers due to the oxidization stress induced by alcohol intake, and it may become a useful marker to estimate drinking habit     

Enlargement of Intrathoracic Goiter with Unilateral Phrenic Nerve Paralysis Leading to Cardiopulmonary Arrest

As an intrathoracic goiter expands, it causes airway stenosis and phrenic nerve paralysis, and slight respiratory stimuli can trigger sudden life-threatening hypoventilation. A 78-year-old obese woman with a large intrathoracic goiter was found unconscious with agonal breathing in her room early in the morning. Cardiopulmonary resuscitation restored spontaneous circulation. She underwent surgical removal of the goiter; however, she required long-term mechanical ventilation because of atelectasis due to phrenic nerve paralysis. In patients with large intrathoracic goiters, difficulty breathing on exertion and diaphragm elevation on chest X-ray may be significant findings predicting future respiratory failure.     

Short-term prognostic value of initial serum levels of interleukin-10 in patients with acute myocarditis

The disease course of acute myocarditis has a wide spectrum and the predictors of the prognosis in patients with acute myocarditis have not yet been established. In the pathogenesis of myocarditis, the cytokine environment is important. In this study, we examined the predictive values of serum levels of interleukin-10 (IL-10) and IL-12 in the short-term prognosis of patients with acute myocarditis. Twenty-four consecutive patients who had been diagnosed as having acute active myocarditis were analyzed and monitored for 2 months. The patients with myocarditis were divided into the survival group (n=16) and the non-survival group (n=8). Initial serum levels of IL-10 (P=0.0015) and IL-12 (P=0.012) in the non-survival group were significantly higher than those of the survival group, and there was a significant correlation between IL-10 and IL-12 levels (P<0.0001). The univariate analyses showed that increased serum levels of IL-10 (hazard ratio 1.041, P=0.0004) and IL-12 (hazard ratio 1.128, P=0.0346) were significant predictors of mortality. In the Kaplan-Meier analysis, high levels of IL-10 (>or=7.0 pg/ml) (P=0.0239) strongly predicted high mortality. In conclusion, the elevation in serum IL-10 levels at the initial phase appeared to predict poor short-term prognosis in patients with acute myocarditis.