Eight-year nationwide survival analysis in relatives of patients with hepatocellular carcinoma: role of viral infection

BACKGROUND: Families of patients with hepatocellular carcinoma (HCC) carry a high risk of developing HCC. We determine the number of fatalities in relatives of HCC patients during an 8-year period to understand the risk and cause of HCC in relatives of patients with HCC. METHODS: From 1992 to 1997, 15 410 relatives of HCC patients in three generations were screened prospectively for HCC by ultrasonography, alpha-fetoprotein, liver biochemistry and viral markers. By using national citizen identification numbers, we searched the total fatalities in relatives of HCC patients between 1992 and 1999 from the national mortality data bank. The results were compared among different viral infection groups. RESULTS: Of the relatives studied, 37.8% were hepatitis B s antigen (HBsAg) positive (+), 4.3% were anti-hepatitis C virus (HCV) (+) and 1.7% were both HBsAg (+) and anti-HCV (+). A total of 399 fatalities, including 139 because of HCC (34.8%), 37 because of liver diseases (9.3%), 88 because of other cancers (22.1%) and 135 because of other diseases (33.8%), were found. Relatives who were HBsAg (+) or anti-HCV (+)showed a lower cumulative survival than did relatives who were negative for both HBsAg and anti-HCV. Relatives with dual infection of hepatitis B and C virus showed the highest mortality due to HCC or terminal liver diseases. CONCLUSIONS: Chronic viral infection rather than a hereditary factor is the main cause of a familial tendency for HCC. Dual infection of hepatitis B and C virus increases the risk of HCC or decompensated liver diseases.     

Amelioration of proteolipid protein 139-151-induced encephalomyelitis in SJL mice by modified amino acid copolymers and their mechanisms

Copolymer 1 [Cop1, glatiramer acetate, Copaxone, poly(Y,E,A,K)n] is widely used in the treatment of relapsing/remitting multiple sclerosis in which it reduces the frequency of relapses by approximately 30%. In the present study, copolymers with modified amino acid compositions (based on the binding motif of myelin basic protein 85-99 to HLA-DR2) have been developed with the aim of suppressing multiple sclerosis more effectively. The enhanced efficacy of these copolymers in experimental autoimmune encephalomyelitis (EAE) induced in SJL/J mice with proteolipid protein 139-151 was demonstrated by using three protocols: (i) simultaneous administration of autoantigen and copolymer (termed prevention), (ii) pretreatment with copolymers (vaccination), or (iii) administration of copolymers after disease onset (treatment). Strikingly, in the treatment protocol administration of soluble VWAK and FYAK after onset of disease led to stasis of its progression and suppression of histopathological evidence of EAE. The mechanisms by which these effects are achieved have been examined in several types of assays: binding of copolymers to I-A(s) in competition with proteolipid protein 139-151 (blocking), cytokine production by T cells (T helper 2 polarization), and transfer of protection by CD3(+) splenocytes or, notably, by copolymer-specific T cell lines (induction of regulatory T cells). The generation of these copolymer-specific regulatory T cells that secrete IL-4 and IL-10 and are independent of the immunizing autoantigen is very prominent among the multiple mechanisms that account for the observed suppressive effect of copolymers in EAE.     

Measurement of cytosolic free calcium concentration in isolated rat ventricular myocytes with quin 2

Cytosolic free calcium concentration was determined in isolated ventricular myocytes from adult rats with the calcium-sensitive indicator, quin 2. The fluorescence signal from resting cells indicated that cytosolic free calcium concentration was 181 +/- 18 nM (mean +/- SEM, n = 18). Inhibition of the sodium-potassium pump with strophanthidin (0.1 mM) resulted in an increase of cytosolic free calcium concentration from 186 +/- 17 to 736 +/- 129 nM (n = 6). The results indicate that it is possible to measure cytosolic free calcium concentration in cardiac muscle cells that have been isolated enzymatically. Moreover, they confirm the observation that inhibition of the sodium-potassium pump increases cytosolic free calcium concentration, presumably via the sodium-calcium exchange mechanism.     

Direct implantation versus platelet-rich fibrin-embedded adipose-derived mesenchymal stem cells in treating rat acute myocardial infarction

Background

This study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation.

Methods

Twenty-eight male adult Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI only), group 3 (AMI + direct ADMSC implantation), and group 4 (AMI + PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI.

Results

LV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p < 0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p < 0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31 +, CXCR4 +, SDF-1α +), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit +, Sca-1 +) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p < 0.005).

Conclusion

PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling.     

Rosiglitazone improves insulin sensitivity and glucose tolerance in subjects with impaired glucose tolerance

OBJECTIVE: This study was designed to evaluate the effects of rosiglitazone (ROS) on insulin sensitivity, beta-cell function, and glycaemic response to glucose challenge and meal in subjects with impaired glucose tolerance (IGT). METHODS: Thirty patients with IGT (ages between 30 and 75 years and BMI (body mass index) < or = 27 kg/m2) were randomly assigned to receive either placebo (n = 15) or ROS (4 mg/day) (n = 15). All participants underwent a 75-g oral glucose tolerance test (OGTT), meal test, and frequently sampled intravenous glucose tolerance test (FSIGT) before and after the 12-week treatment. RESULTS: After 12 weeks of ROS treatment, there were significant increases in total cholesterol (TC) (4.25 +/- 0.22 vs 4.80 +/- 0.17 mmol/l, P < 0.001), high-density lipoprotein cholesterol (HDL-C) (1.25 +/- 0.07 vs 1.43 +/- 0.06 mmol/l, P < 0.05), and low-density lipoprotein cholesterol (LDL-C) (2.70 +/- 0.15 vs 3.37 +/- 0.17 mmol/l, P < 0.05) without changes in triglyceride concentration, TC/HDL-C and LDL-C/HDL-C ratio. Although the acute insulin response (AIR) to intravenous glucose and disposition index (measured as the ability of pancreatic beta-cell compensation in the presence of insulin resistance) remained unchanged, the insulin sensitivity (SI) and glucose effectiveness (SG) were remarkably elevated (0.38 +/- 0.06 vs 0.54 +/- 0.09 x 10(-5) min(-1)/pmol, P < 0.05; 0.017 +/- 0.002 vs 0.021 +/- 0.001 min(-1), P < 0.05, respectively) in the ROS group. The glucose, insulin, and c-peptide areas under curve (AUC) in response to OGTT and the glucose and insulin AUC during meal were significantly ameliorated in the ROS group. Five out of 15 (33%) and two out of 15 (13%) subjects treated with ROS and placebo, respectively, reversed to normal response during OGTT (P < 0.05). CONCLUSION: Rosiglitazone treatment significantly improved insulin resistance and reduced postchallenge glucose and insulin concentrations in patients with impaired glucose tolerance without remarkable effects on beta-cell secretory function.     

Dual resistance to adamantanes and oseltamivir among seasonal influenza A(H1N1) viruses: 2008-2010

Two distinct genetic clades of seasonal influenza A(H1N1) viruses have cocirculated in the recent seasons: clade 2B oseltamivir-resistant and adamantane-susceptible viruses, and clade 2C viruses that are resistant to adamantanes and susceptible to oseltamivir. We tested seasonal influenza A(H1N1) viruses collected in 2008-2010 from the United States and globally for resistance to antivirals approved by the Food and Drug Administration. We report 28 viruses with both adamantane and oseltamivir (dual) resistance from 5 countries belonging to 4 distinct genotypes. Because of limited options for antiviral treatment, emergence of dual-resistant influenza viruses poses a public health concern, and their circulation needs to be closely monitored.     

Successful retrieval of dislodged paclitaxel-eluting stent with a nitinol loop snare: a case report

Coronary stent dislodgment or embolization before deployment is a rare but challenging complication in interventional cardiology. Intracoronary embolization of the dislodged stent is associated with a high risk of coronary occlusion, due to thrombus formation and subsequent myocardial infarction. Furthermore, systemic embolization may cause severe cerebrovascular events. Nonsurgical retrieval strategies for this complication have been suggested, but bailout cardiac surgery may be indicated if percutaneous retrieval attempts fail. To our knowledge, this is the first case report of intracoronary drug-eluting stent dislodgment, and successful retrieval was accomplished by a loop snare technique. With the increasing trend of using drug-eluting stents in percutaneous coronary intervention, the likelihood of stent dislodgment or embolization may increase. It should be kept in mind, especially by coronary interventionists, how to manage this complication.     

Anatomic characteristics of the left atrial isthmus in patients with atrial fibrillation: lessons from computed tomographic images

Introduction: Left atrial (LA) isthmus ablation was reported to improve the success rate of catheter ablation of paroxysmal atrial fibrillation (AF). LA isthmus ablation could also cure a subset of LA flutter. Therefore, understanding the anatomy of the LA isthmus is important for performing the ablation effectively.
Methods and Results: Group I included 45 patients (40 male, mean age = 50 ± 13 years) with paroxysmal AF who underwent catheter ablation. Group II included 45 patients (37 male, mean age = 54 ± 10 years) without a history of AF. They underwent a 16-slice multidetector computed tomography (MDCT) scan to delineate the LA structures before the ablation procedure. The average length of the LA isthmus was longer in group I than in group II (lateral isthmus: 3.30 ± 0.68 vs 2.71 ± 0.60 cm, P < 0.001; medial isthmus: 5.12 ± 0.94 vs 4.45 ± 0.63 cm, P < 0.001), and morphological patterns of lateral and medial isthmus were similar between groups. In addition, the average depth of lateral isthmus was similar between groups (0.62 ± 0.32 vs 0.55 ± 0.33 cm, P = 0.41), but the average depth of medial isthmus was larger in group I than in group II (0.60 ± 0.32 vs 0.44 ± 0.25 cm, P = 0.01). The medial isthmus had more ridges, as compared to the lateral isthmus (13% vs 0%, P = 0.026). Furthermore, the distances between esophagus and lateral isthmus were longer in group I than in group II (at the middle of isthmus and mitral annulus level: 21.0 ± 4.8 vs 18.4 ± 6.0 mm, P < 0.001; and 37.1 ± 5.7 vs 29.6 ± 8.1 mm, P < 0.001, respectively).
Conclusion: The LA isthmus was longer in the AF patients. The morphology of the isthmus was variable. Compared with the lateral isthmus, the medial isthmus was longer and had more ridges. A peculiar configuration of the isthmus provided by CT images could influence the ablation strategy.