Recent advances in the synthesis of the carbocyclic nucleosides as potential antiviral agents

Compared with 4'-oxonucleosides, there have been far fewer systematic structure-activity relationship studies on carbocyclic nucleosides as antiviral and antitumour agents. This is mainly because of the synthetic problems in preparing the carbasugars. However, the recent discovery of the ring-closing metathesis (RCM) (a powerful tool for the preparation of 5-membered carbasugar via C-C bond formation) has made it possible to synthesize the key carbasugars to a preparative scale. This review summarizes the asymmetric syntheses of carbasugars and carbocyclic nucleosides, using an RCM reaction as a key step. Furthermore, the review includes valuable information for designing and synthesizing novel carbocyclic nucleosides.     

Elastic properties of the ascending aorta in young children after successful coarctoplasty in infancy

BACKGROUND: Based on the hypothesis that vascular dysfunction in the ascending aorta can cause morbidity, we undertook this study on the elastic properties of ascending aorta and left ventricular (LV) function in young children who received coarctoplasty in early infancy. METHODS: Blood pressures (BP) in the right arm and ascending aortic internal diameters determined by M-mode ultrasound at rest and after exercise were measured in 25 patients (mean age, 6.4+/-3 years) and 22 control subjects (mean age, 5.8+/-2.4 years). Ascending aortic stiffness index and distensibility were calculated using BP measurements and ascending aortic internal diameters. In addition, LV parameters (systolic and diastolic function, mass index) were evaluated. RESULTS: Compared with control subjects, patients had increased stiffness index (at rest: 4.87+/-1.94 versus 3.57+/-1.19, P=0.021; after exercise: 4.33+/-1.91 versus 3.2+/-1.26, P=0.034) and decreased distensibility (at rest: 6.90+/-3.15 versus 8.72+/-2.77, P=0.02; after exercise: 5.69+/-2.39 versus 7.88+/-3.44 cm2 dyn(-1) 10(-6), P=0.023). BP and LV parameters showed no consistent differences between the two groups. In patients, distensibility was significantly correlated with systolic BP (at rest: P=0.008; after exercise: P=0.014) and pulse pressure (at rest: P=0.013; after exercise: P=0.001). CONCLUSIONS: This study suggests that vasculopathy of ascending aorta is possible in some young children despite early correction. However, long-term tracking study is needed to clarify the significance of the study.     

Transarterial chemo-lipiodolization can reactivate hepatitis B virus replication in patients with hepatocellular carcinoma

BACKGROUND/AIMS: Reactivation of hepatitis B virus (HBV) replication is a well-known complication in cancer patients receiving chemotherapy. The aims of this study were to determine the incidence of HBV reactivation in hepatocellular carcinoma (HCC) patients undergoing transarterial chemo-lipiodolization, and to clarify factors contributing to HBV reactivation. METHODS: From April 2001 to September 2002, 146 HBsAg positive patients newly diagnosed as HCC were enrolled in the study. Among these, 83 patients underwent transarterial chemo-lipiodolization using epirubicin and/or cisplatin, and 63 received other treatments. RESULTS: In total, HBV reactivation occurred in 30 (20.5%) patients (28 with chemo-lipiodolization and 2 with other treatments), and of the 30 patients, 19 (13.0%) (18 with chemo-lipiodolization and 1 with other treatments) developed hepatitis. Chemo-lipiodolization was significantly correlated with a higher incidence of hepatitis attributed to HBV reactivation than other treatments (21.7% vs. 1.6%, P<0.001), irrespective of HBeAg or HBV DNA. Among 83 patients undergoing chemo-lipiodolization, HBV reactivation occurred in 28 (33.7%) patients, and HBeAg seropositivity was the only independent predictor of HBV reactivation (P=0.013). Three (10.7%) of them died of hepatic decompensation resulting from HBV reactivation. CONCLUSIONS: Transarterial chemo-lipiodolization can reactivate HBV, and HBeAg-positive HCC patients receiving chemo-lipiodolization should be closely monitored for HBV reactivation.     

Multireader, multicase receiver operating characteristic analysis: an empirical comparison of five methods

RATIONALE AND OBJECTIVES: Several statistical methods have been developed for analyzing multireader, multicase (MRMC) receiver operating characteristic (ROC) studies. The objective of this article is to increase awareness of these methods and determine if their results are concordant for published datasets. MATERIALS AND METHODS: Data from three previously published studies were reanalyzed using five MRMC methods. For each method the 95% confidence intervals (CIs) for the mean of the readers' ROC areas for each diagnostic test, the P value for the comparison of the diagnostic tests' mean accuracies, and the 95% CIs for the mean difference in ROC areas of the diagnostic tests were reported. RESULTS: Important differences in P values and CIs were seen when using parametric versus nonparametric estimates of accuracy, and there were the expected differences for random-reader versus fixed-reader models. Controlling for these differences, the Dorfman-Berbaum-Metz (DBM), Obuchowski-Rockette, Beiden-Wagner-Campbell, and Song's multivariate Wilcoxon-Mann-Whitney (WMW) methods gave almost identical results for the fixed-reader model. For the random-reader model, the DBM, Obuchowski-Rockette, and Beiden-Wagner-Campbell methods yielded approximately the same inferences, but the CIs for the Beiden-Wagner-Campbell method tend to be broader. Ishwaran's hierarchical ROC sometimes yielded significance not found with other methods. Song's modification of DBM's jack-knifing algorithm sometimes led to different conclusions than the original DBM algorithm. CONCLUSION: In choosing and applying MRMC methods, it is important to recognize: (1) the distinction between random-reader and fixed-reader models, the uncertainties accounted for by each, and thus the level of generalizeability expected from each; (2) assumptions made by the various MRMC methods; and (3) limitations of a five- or six-reader study when the reader variability is great.     

Cystic Changes in Intraabdominal Extrahepatic Metastases from Gastrointestinal Stromal Tumors Treated with Imatinib

Objective

This study was undertaken for the purpose of describing the CT features of intra-abdominal extra-hepatic metastases from gastrointestinal stromal tumors in patients who were treated with imatinib.

Materials and Methods

Eleven patients with intra-abdominal extra-hepatic metastases from gastrointestinal stromal tumors, who were treated with imatinib between May 2001 and December 2003, were included in this study. The clinical findings and CT scans were retrospectively reviewed. The metastatic lesions were assessed according to the location, size (greatest diameter), attenuation, and the enhancing pattern before and after imatinib treatment.

Results

Prior to the treatment, the sizes and attenuation values of the metastatic lesions ranged from 5 to 20 cm and from 63 to 131 H, respectively. The metastatic lesions showed a heterogeneous enhancement pattern on the contrast-enhanced CT scans. After the treatment, the metastatic lesions became smaller in all 11 patients, and the corresponding attenuation value ranged from 15 to 51 H. The metastatic lesions became homogeneous and cystic in appearance on the follow-up CT scans, mimicking ascites.

Conclusion

Intra-abdominal extra-hepatic metastases of patients with gastrointestinal stromal tumors treated with imatinib may appear as well-circumscribed cystic lesions on contrast-enhanced CT. These metastases are likely to become smaller and resemble ascites, but may persist indefinitely on the follow-up CT.     

Causes of Arterial Bleeding After Living Donor Liver Transplantation and the Results of Transcatheter Arterial Embolization

Objective

To analyze the causes of arterial bleeding after living donor liver transplantation (LDLT) and to evaluate the efficacy of transcatheter arterial embolization (TAE).

Materials and Methods

Forty-two sessions of conventional arteriography were performed in 32 of the 195 patients who underwent LDLT during the past 2 years. This was done in search of bleeding foci of arterial origin. TAE was performed with microcoils or gelatin sponge particles. The causes of arterial bleeding, the technical and clinical success rates of TAE and the complications were retrospectively evaluated.

Results

Forty-two bleeding foci of arterial origin were identified on 30 sessions of arteriography in 21 patients. The most common cause of bleeding was percutaneous procedures in 40% of the patients (17 of the 42 bleeding foci) followed by surgical procedures in 36% (15/42). The overall technical and clinical success rates of TAE were 21 (70%) and 20 (67%) of the 30 sessions, respectively. The overall technical success rate of TAE for the treatment of bleeding from the hepatic resection margin, hepatic artery anastomotic site and hepaticojejunostomy was only 18% (2/11), whereas for the treatment of bleeding in the other locations the technical and clinical success rates of TAE were 100% and 95%, respectively. No procedure-related major complications occurred.

Conclusion

In the case of arterial bleeding after LDLT, percutaneous procedure-related hemorrhages were as common as surgery-related hemorrhages. There were technical difficulties in using TAE for the treatment of hepatic arterial bleeding. However, in the other locations, TAE seems to be safe and effective for the control of arterial bleeding in LDLT recipients.