Effect of atrial pressure increase on sinus node automaticity

There is evidence suggesting that atrial electrophysiological properties may be changed by an acute increase in atrial pressure. The aim of the present study was to investigate the effect of alteration, in atrial pressure on sinus node recovery time. Twelve patients (8 men and 4 women, mean age 61.3 ± 14.1 years) were included in this study. None of the patients had organic heart disease. Sinus node recovery time (SNRT) was measured following atrial pacing and atrioventricular (AV) pacing at sequential cycle lengths of 600, 545, 500, 461, 428, and 400ms with two different AV intervals (150, 0ms). Peak and minimal atrial pressure increased significantly from 8.5 ± 2.8 to 20.1 ± 2.9mmHg (11.56 ± 3.8 to 27.3 ± 3.9cmH₂O) (P = 0.001) and from 2.06 ± 1.69 to 5.33 ± 2.9mmHg (2.8 ± 2.29 to 7.2 ± 3.9cmH₂O), respectively (P = 0.002) during AV interval modification. Sinus node recovery time did not change despite the increase in atrial pressure. Autonomic blockade had no effect on SNRT. This study demonstrates that atrial pressure increase does not significantly affect sinus node automaticity expressed by SNRT.     

Anatomical structure of the isthmus between the inferior vena cava and tricuspid annulus investigated with a three-dimensional electroanatomical mapping system

We studied the anatomical structure of the isthmus between the inferior vena cava and tricuspid annulus in humans with a three-dimensional electroanatomical mapping system (CARTO, Biosense, Haifa, Israel). Fifteen patients with atrial flutter were studied. Thirteen patients had underlying heart disease. We investigated the anatomical structure of the isthmus with cross sections made from the three-dimensional right atrial map. The cross sections of the isthmus showed a concave shape in 7 patients (47%: group A), convex shape in 2 (13%: group B), and complex shape in 6 (40%: group C). The distance between the IVC and TA was 34 ± 17mm (group A), 25 ± 2mm (group B), 34 ± 16mm (group C), and 32 ± 15mm (Total), respectively. The distance between the top and bottom was 6 ± 5mm (group A), 3mm (group B), 6 ± 3mm (group C), and 6 ± 4mm (total), respectively. Seven of 15 patients exhibited an uneven surface of more than 5mm in depth and 4 of 15 patients had one of more than 10mm. The anatomical structure of the isthmus varies. To carry out precise catheter ablation, these variations should be taken into consideration to ensure an effective procedure.     

A Three-dimensional Analysis of Blood Vessels in Bronchioloalveolar Carcinoma

The three-dimensional architecture of blood vessels within lung adenocarcinomas has not been well studied. In 19 cases with bronchioloalveolar carcinoma with central fibrosis, we three-dimensionally examined blood vessel architecture in 150 m thick sections stained with elastin staining and anti-CD34 antibody. We examined four regions: normal alveoli and three regions within the tumor including an area adjacent to the normal alveoli (external area), an area in which tumor cells were replacing epithelial cells (replacement area), and a central fibrotic area (fibrotic area). Elastin staining showed that elastic fibers formed the framework of the alveoli, and the alveolar structure shrank more strongly to the center of the tumor due to folding of alveolar walls invaded by adenocarcinoma cells. We also measured three vessel parameters in these four regions. The vessel diameters were 4.08±1.10 m, 3.95±1.02 m, 5.04±1.56 m, and 6.11±2.23 m, the circumferences of those vessels seen as complete circles were 43.11±12.78 m, 43.71±12.87 m, 95.21±39.32 m, and 126.77±54.65 m; the lengths between vessel bifurcations were 13.28±3.08 m, 13.47±4.58 m, 24.91±9.66 m, and 41.82±28.08 m in the normal alveoli, and the external, replacement, and fibrotic areas, respectively. Blood vessel architecture changed such that the vessels became larger and coarser towards the center of the tumor. Our three-dimensional analysis suggests continuous remodeling of alveolar capillaries rather than angiogenesis within bronchioloalveolar carcinoma.     

Efficacy of mizoribine treatment in patients with SjÖgren’s syndrome: an open pilot trial

The aim of this study was to evaluate the efficacy and safety of mizoribine in patients with SjÖgrens syndrome. Forty patients with sicca syndrome, whose conditions were definitely diagnosed as SjÖgrens syndrome, were given mizoribine orally at a dosage of 150mg/day for 12 months. The percentage change in salivary secretion after 3, 6, and 12 months of the therapy increased to +112.2% (P 0.001), +119.9% (P 0.01), and +147.3% (P 0.001), respectively, compared with the baseline. Serum IgG levels decreased significantly throughout the study, and the level was 1969.4 ± 620.0mg/dl after treatment for 12 months compared with the pretreatment value of 2094.3 ± 746.6mg/dl (P 0.05). The patients assessment of clinical signs and symptoms on a 10-cm visual analog scale improved significantly from 7.2 ± 2.3cm at the start of the treatment to 5.0 ± 1.9cm after 12 months (P 0.001). There was a similar improvement in the physicians assessment using the 10-cm visual analog scale: 7.1 ± 1.6cm at the start of the treatment and 5.2 ± 1.9cm after 12 months (P 0.001). With regard to safety, no serious adverse reactions were observed. Although a controlled study would be required to clarify the efficacy of mizoribine, these preliminary observations indicate its efficacy for ameliorating glandular symptoms through improvements in immune abnormalities in patients with SjÖgrens syndrome.     

Pulsed Doppler tissue imaging can help to identify patients with right ventricular infarction

This study was planned to assess whether tissue Doppler imaging is a useful method for the detection of the right ventricular myocardial infarction. Forty-eight patients with acute inferior myocardial infarction and 24 age- and sex-matched healthy controls were included in this study. Twenty-four patients had electrocardiographic signs of inferior myocardial infarction without right ventricular infarction (group I), and the other 24 patients had electrocardiographic signs of inferior myocardial infarction with right ventricular infarction (group II). From the echocardiographic apical four-chamber view, peak systolic, early diastolic, and late diastolic velocities of the tricuspid annulus at the right ventricular free wall were recorded with the use of pulsed-wave Doppler tissue imaging. The tricuspid annular peak tissue Doppler imaging systolic velocity was significantly lower in group I (14.03 ± 2.57cm/s, P 0.005) and in group II (8.50 ± 0.84cm/s, P 0.005) than in controls (16.63 ± 2.31cm/s). The tricuspid annular peak systolic (8.50 ± 0.84cm/s vs 16.63 ± 2.31cm/s) and peak early diastolic (10.99 ± 3.28cm/s vs 19.39 ± 4.3cm/s) velocities were significantly lower in group II than in group I, as compared with controls (P 0.001). Peak early diastolic velocity of tricuspid annulus (10.99 ± 3.28cm/s vs 19.39 ± 4.3cm/s) was significantly lower in group I than in controls (P 0.001); however, late diastolic velocity was significantly lower in group II (15.98 ± 5.08cm/s, P 0.05) than in group I (18.21 ± 2.63cm/s, P 0.05) and in controls (19.02 ± 5.29cm/s). The results of this study indicate that tricuspid annular peak systolic and early diastolic velocities are reduced in patients with right ventricular infarction. The velocity of the tricuspid annulus by tissue Doppler imaging is simple and can be used to distinguish whether patients with inferior myocardial infarction have right ventricular infarction.This study was presented at the XXIII. Congress of the European Society of Cardiology, Stockholm, Sweden, 1–5 September 2001     

The Role of Pleural Fluid-Serum Gradient of Tumor Necrosis Factor-α Concentration in Discrimination Between Complicated and Uncomplicated Parapneumonic Effusion

In a previous preliminary study an excess of tumor necrosis factor- (TNF) was found in pleural fluid of patients with complicated parapneumonic effusion (CPPE), and its levels in pleural fluid of these patients were shown to be significantly higher than those in patients with uncomplicated parapneumonic effusion (UCPPE). This larger population study was undertaken to investigate, for the first time, the role of pleural fluid-serum gradient of TNF (TNFgradient) in discrimination between UCPPE and CPPE. Using a commercially available high sensitivity ELISA kit, levels of TNF were measured in serum and pleural fluid of 51 patients with UCPPE and 30 patients with nonempyemic CPPE. The mean±SEM values of serum TNF (TNFserum), pleural fluid TNF (TNFpf), and TNFgradient in the UCPPE group were 6.65±0.48 pg/mL, 10.85±0.74 pg/mL, and 4.2±0.38 pg/mL respectively, and in the CPPE group they were 7.59±0.87 pg/mL, 54.02±5.43 pg/mL, and 46.43±5.34 pg/mL, respectively. While no significant difference was found between the two groups regarding levels of TNFserum (p=0.31), a highly significant difference between these two groups was found regarding levels of TNFpf and TNFgradient (p < 0.0001 for both variables). A significant correlation was found between levels of TNFserum and levels of TNFpf in the UCPPE group (r=0.89, p < 0.0001), but not in the CPPE group (r=0.18, p < 0.33). TNFgradient at an optimal cut-off level of 9.0 pg/mL was found to be a good marker for discrimination between UCPPE and CPPE (sensitivity, 96.7%, specificity, 98%, accuracy, 97.5%, and p < 0.0001). In conclusion, levels of TNFpf but not TNFserum are significantly higher in CPPEs than those in UCPPEs where TNFgradient at an optimal cut-off level of 9.0 pg/mL is a good marker for discrimination between UCPPE and CPPE.     

Percutaneous radiofrequency ablation with cooled electrodes combined with hepatic arterial balloon occlusion in hepatocellular carcinoma

Background We have reported that percutaneous radiofrequency ablation (RFA) with balloon occlusion of the hepatic artery (balloon-occluded RFA), using an expandable electrode, increases the coagulation area. In this study, we investigated the efficacy of balloon-occluded RFA and balloon-microcatheter-occluded RFA, using a cool RF single electrode.Methods We studies 41 patients with 47 hepatocellular carcinoma (HCC) lesions. We treated 28 patients (32 nodules) with balloon-occluded RFA, 5 patients (6 nodules) with balloon-microcatheter-occluded RFA, and 8 patients (9 nodules) with standard RFA. Initial therapeutic efficacy was evaluated with dynamic computed tomography performed 1 week after one session of treatment.Results One session of treatment was done for 20 nodules (62.5%) in the balloon-occluded RFA group and for 4 nodules (66.7%) in the balloon-microcatheter-occluded RFA group. We compared the coagulation diameter for balloon-occluded RFA (7 nodules), balloon-microcatheter-occluded RFA (6 nodules), and standard RFA (9 nodules) after one application cycle (12min). The greatest dimension of the area coagulated by balloon-occluded RFA was significantly larger (greatest long-axis dimension, 47.6 ± 7.8mm; greatest short-axis dimension, 33.4 ± 7.5mm) than that coagulated by standard RFA (greatest long-axis dimension, 35.3 ± 4.7mm; greatest short-axis dimension, 25.9 ± 3.7mm; P = 0.002 for greatest long-axis dimension; P = 0.041 for greatest short-axis dimension). However, there was significant difference only in the greatest short-axis dimension of the area coagulated comparing balloon-microcatheter-occluded RFA and standard RFA.Conclusions We consider balloon-occluded RFA using a cool RF electrode to be superior to standard RFA for the treatment of HCC, especially when larger coagulation volumes are required.     

Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Maldistribution of exogenous surfactant may preclude any clinical response in acute lung injury associated with surfactant dysfunction. Our previous studies have shown the effectiveness of surfactant lavage after homogenous lung injury. The present study utilizes a histologically confirmed non-homogeneous lung injury model induced by saline lung-lavage followed by meconium injected into a mainstem bronchus. Piglets were then treated with Infasurf® or Exosurf® by lavage (I-LAVAGE, n=7; E-LAVAGE, n=5) or bolus (I-BOLUS, n=8; E-BOLUS, n=5), or went untreated (CONTROL, n=4). Lavage administration utilized a dilute surfactant (35 ml/kg; 4 mg phospholipid/ml) instilled into the lung, followed by gravity drainage. The retained doses of the respective surfactant in the lavage and bolus groups were similar. Results showed that the surfactant distribution was more uniform in the lavage groups compared to the bolus groups. Significant and consistent increases in PaO₂ were observed in the lavage groups compared to the bolus groups and the controls. PaO₂ (mmHg) at 240 min posttreatment: I-LAVAGE=297±54, E-LAVAGE= 280±57; I-BOLUS=139±31; E-BOLUS=152±29; C=119±73 (mean± SEM). Other improved pulmonary function parameters favored lavage administration. We conclude that better surfactant distribution achieved by lavage administration can be more effective than bolus administration in this type of non-homogeneous lung injury.     

Effects of acetyl strophanthidin on duration of atrial fibrillation in the neurally-intact and blockaded dog

Summary Although the inotropic and dromotropic effects of cardiac glycosides in atrial fibrillation (AF) are well recognized, their action on AF itself is not clear. Accordingly, to determine whether cardiac glycosides prolong AF, the duration of electrically induced AF, atrioventricular conduction, and left ventricular function were assessed for 30 minutes before and for 30 minutes following intravenous administration of acetyl strophanthidin (AS), 20 g/kg, in neurally intact, -blocked, and -blocked and vagotomized dogs. In the intact dog, AS, 20 g/kg, increased peak dp/dt by 132±35 mmHg·sec^-1, p<0.05, and slowed ventricular response by 16±7 min^-1, p<0.05, but had a variable effect on Af duration. While the increased left ventricular peak dp/dt persisted for 15 minutes after AS, an increased duration of AF was evident only at 20 minutes, when the effects of AS on left ventricular (LV) inotropy were no longer apparent. Moreover, the subset of dogs that did not demonstrate prolongation of average duration of AF after AS had a greater increment of peak dp/dt than those that showed prolongation, 237±52 versus 53±31 mmHg·sec^-1, p<0.05. An additional 20 g/kg, which produced ventricular extrasystoles, prolonged AF duration when compared to both control and 30-minute measurements. Acetyl strophanthidin, 20 g/kg, had a variable effect on duration of AF with -blockde but prolonged duration by 114±34%, p<0.05, with both vagotomy and -blockade. Thus the conclusion is reached that, at a clinically relevant dosage, cardiac glycosides did not exert a statistically significant influence on duration of AF; at a toxic dosage, however, an AF-enhancing effect was apparent. The inotropic effects of cardiac glycosides appear to obscure this effect. An AF-enhancing action of cardiac glycosides in the presence of neurohumoral blockade suggests that the effects on AF may not only be vagally mediated.     

Microemboli at the Different Stages of Percutaneous Transluminal Carotid Angioplasty and Stenting in Patients with Post–carotid Endarterectomy Restenosis Compared to Primary Stenosis

Microembolization to cerebral arteries during percutaneous transluminal carotid angioplasty (PTCA) and stenting is well described, as well as different mural pathology in primary versus post–carotid endarterectomy (CEA) restenosis lesions. The purpose of this study is to investigate possible different patterns of embolization in regards to number and distribution of microembolic signals (high-intensity transient signals (HITS)) in patients with primary carotid stenosis and restenosis after CEA. We used transcranial Doppler (TCD) to monitor the ipsilateral middle cerebral artery (MCA) of 13 patients (13 procedures) with restenosis after CEA and six patients (seven procedures) with primary stenosis of the internal carotid artery (ICA) during PTCA and stenting. All the procedures were performed without protection devices. The total number of HITS recorded in all patients was 2692, including 1563 microemboli in patients with restenosis and 1129 in patients with primary stenosis. The mean number of microemboli per procedure was 120.2±65 and 161.3±70 (p=0.05) respectively. The average number of microembolic signals during the various stages of PTCA and stenting in the two groups was as follows: 1. Crossing the stenotic region with the guidewire and positioning the balloon inside the stenosis 33±6.9 and 73.4±9.4 (restenosis patients versus primary–stenosis patients, respectively, (p=0.011); 2. angioplasty, balloon inflation and deflation, 19.l±6.9 and 38.9±9.4 (restenosis versus primary lesions, respectively, p=0.09); 3. stent deployment, 39.5±6.9 and 27.3±9.4 (restenosis versus primary lesions, respectively, p=0.3); and 4. Post-stent dilatation, 29±6.9 and 21.7±9.4 (restenosis versus primary lesions, respectively, p=0.53). Microembolic signals are detected through all stages of PTCA and stenting in patients with primary or post-CEA-restenosis lesions. The number of HITS was significantly higher in patients with primary stenosis than with restenosis of ICA in stages prior to stenting. This probably stems from the difference in pathomorphologic structure between the lesions. There was no significant difference between groups during stent deployment and post-stent dilatation. The clinical significance of the phenomenon of microembolism during carotid stenting is still not clear, but our results suggest the importance of using protection devices to reduce the incidence of these events in both primary and post-CEA lesions.     

Effects of Piclamilast,a Selective Phosphodiesterase-4 Inhibitor,on Oxidative Burst of Sputum Cells From Mild Asthmatics and Stable COPD Patients

Oxidative stress associated with increased presence of neutrophils is an important feature of inflammatory airways diseases like asthma or chronic obstructive pulmonary disease. We studied the in vitro effect of piclamilast (RP73401), a selective phosphodiesterase (PDE)-4 inhibitor, compared to theophylline and prednisolone, on respiratory burst of sputum cells from mild asthmatics and COPD patients. Sputum cells were harvested from mild asthmatics and stable COPD patients and treated with piclamilast, theophylline or prednisolone. Respiratory burst was assessed by luminol-dependent chemoluminescence after stimulation with 10 M n-formyl-met-leu-phe (FMLP). Piclamilast inhibited FMLP-induced respiratory burst of sputum cells in a concentration-dependent manner (asthma: EC₅₀ approximately 100 nM, max. inhibition: 97.5±5% at 100 M; COPD: EC₅₀ approximately 1 M, max. inhibition: 70.6±4.5% at 100 M), whereas maximal inhibition observed with theophylline (asthma: max. inhib. 27±15%; COPD: 6±2%, both p < 0.05 vs. piclamilast) and prednisolone (asthma: 16±6%; COPD: 7.8±6.2%, both p < 0.05 vs. piclamilast) was weaker. Inhibition by piclamilast was largely reversed through pretreatment of cells with the adenylcyclase inhibitor SQ22536. We concluded that piclamilast, a selective PDE-4 inhibitor, attenuates the respiratory burst of sputum cells from mild asthmatics and COPD patients in vitro. These data underline the potential of PDE-4 inhibition as a novel therapeutic approach to inflammatory airway diseases like asthma or COPD.     

The effects of parabiosis on serum and kidney glycosidase activities in spontaneously diabetic mice

Summary Spontaneously diabetic non-obese mice of the ICR strain were newly inbred in Shionogi laboratory, Japan. Animals became diabetic suddenly, more frequently and severely in females. Blood glucose levels were 452±73 mg/100 ml with serum insulin levels of < 1.0 U/ml in the fed state. Parabiosis with normal control ICR mice for 2 weeks decreased the blood glucose level to 260±51 mg/ 100ml (P<0.01) and resulted in serum insulin levels of 46.0±18.0 U/ml (P<0.01). Kidney homogenate -N-acetylglucosaminidase and -galactosidase activities were reduced in diabetic mice (42% and 44% decrease respectively) (P<0.025 and P<0.001), and restored almost to normal after 2 weeks of parabiosis. Renal -mannosidase activity was decreased 43% (P<0.001) in the diabetic mice but unaffected by parabiosis. Serum -N-acetylglucosaminidase, -galactosidase and -glucosidase activities were significantly increased in diabetic mice (179%; 233% and 58% increase respectively) (P<0.005, P<0.001 and P<0.001), and returned to normal with parabiosis.     

Block of HERG current expressed in HEK293 cells by the Na<Superscript>+</Superscript>-channel blocker cibenzoline

A Na⁺-channel blocker, cibenzoline, blocks the delayed rectifier potassium current (I_k), but its detailed action on the rapidly activating component (I_kr) of I_k encoded by the human ether-a-go-go-related gene (HERG) has not been clarified. We examined the effects of cibenzoline on stably expressed HERG current in HEK293 cells recorded by the patch-clamp technique of whole-cell configuration. Cibenzoline blocked HERG current expressed in HEK293 cells with IC₅₀ = 3.7 ± 0.963µM and Hill coefficient = 0.74 ± 0.12. Voltage-depended activation was shifted in a negative direction by cibenzoline. No block or minor block was induced at test depolarization of –40 to –30mV, and the block increased with depolarization reaching a plateau at 0mV without a further increase at positive voltages. Voltage-dependent activation of HERG currents became faster at negative test voltages but there were no changes at positive voltages after cibenzoline. No frequency-dependent block of HERG tail current by cibenzoline after equilibration was noted between 1.33 and 0.2Hz. Steady-state inactivation of the HERG current was shifted in a negative direction by 8mV but the time constants of fast inactivation were little affected by cibenzoline. Cibenzoline blocks the I_kr-like current reconstituted by HERG clone transfection with an IC₅₀ value comparable to therapeutic concentrations. Cibenzoline has a preferential affinity, at least, to the open state of the HERG channel with a rapid access to the binding site.     

A Pharmacodynamic Study of Clopidogrel in Chronic Hemodialysis Patients

Combination antiplatelet agents, particularly aspirin and ticlopidine, have found increased use in the prevention of arterial thrombosis. Clopidogrel, a thienopyridine derivative, like ticlopidine was recently approved by the U.S. Food and Drug Administration (FDA) for the reduction of ischemic events in patients with myocardial infarction, stroke, or peripheral arterial disease and appears to have much less hematologic toxicity than ticlopidine has. Thrombosis of hemodialysis access grafts is a major cause of morbidity in this patient population. Combination antiplatelet agents may be particularly useful in the prevention of hemodialysis access graft thrombosis. In preparation for such a study, we have performed a pharmacodynamic study of the platelet inhibitory effects of clopidogrel in patients on maintenance hemodialysis. Nine chronic hemodialysis patients were studied. Baseline platelet aggregation studies were performed, after which the subjects were begun on clopidogrel 75mg daily. Platelet aggregation studies were repeated after 14 days of therapy. Drug was stopped and a final set of platelet aggregation studies were performed 7 days later. Because clopidogrel acts by inhibiting adenosine diphosphate (ADP)-induced platelet aggregation, we used ADP as the agonist in the platelet aggregation studies. We also measured the time required to achieve hemostasis after removing the dialysis needles at the termination of a dialysis session. Patients were carefully monitored for any adverse reaction to clopidogrel. Fourteen days' treatment with clopidogrel inhibited ADP-induced platelet aggregation from 48 to 23% with ADP 2M (P=0.0113), from 59 to 38% with ADP 5M (P=0.0166), and from 66 to 44% with ADP 10M (P=0.0172). This inhibition of platelet aggregation was reversed 7 days after stopping clopidogrel. Clopidogrel administration did not affect the time required to achieve hemostasis after removal of the dialysis needles. No adverse reactions were noted. No patient had evidence of bleeding, rash or gastro-intestinal (GI) upset. Clopidogrel inhibits ADP-induced platelet aggregation in subjects receiving chronic maintenance hemodialysis. The magnitude of inhibition is similar to that reported in nonuremic subjects with atherosclerosis. This inhibition is reversible within 7 days of discontinuing the drug. No adverse reactions to the drug were noted in this short-term (14-day) trial.     

Wave intensity analysis from the common carotid artery: a new noninvasive index of cerebral vasomotor tone

Cerebral vasomotor tone is difficult to assess in patients. Wave intensity analysis has been applied to resolve complex upstream and downstream events within the vascular system. We hypothesized that the backward-traveling wave measured in the common carotid artery was caused by reflection from the cerebrovascular beach, and that the magnitude of this reflected wave would be altered by changes in cerebral vasomotor tone. We measured common carotid arterial diameter and velocity of flow to calculate wave intensity in ten healthy male volunteers (age mean 31 ± 3 years). Applying a rebreathing technique, we were able to increase the inspired carbon dioxide concentration to a mean of 5.9% ± 1.7% and to compare baseline wave intensity readings to those recorded during hypercapnia. The magnitude of the reflected wave decreased significantly after CO₂ rebreathing, from –43.0 ± 27.1 to –25.0 ± 16.9mmHgms^–2, P = 0.02. This reduction in regative wave reflections in mid-systole during hypercapnia remained significant when it was analyzed as the reflection coefficient (the magnitude of the reflected wave normalized for the magnitude of the initiating forward wave, which fell from –2.8 ± 1.5 to –1.6 ± 1.4ms (P = 0.01). Carotid wave reflection was significantly decreased during cerebral vasodilatation induced by increased arterial pCO₂. Wave intensity may provide a simple noninvasive means of assessing changes in cerebral vasomotor tone in vivo.     

Circulating soluble Fas levels in patients with hepatitis C virus infection and interferon therapy

Background The clinical relevance of the circulating soluble form of the Fas-Receptor (sFas) was investigated in patients with hepatitis C receiving type 1 interferon (IFN) therapy.Methods sFas was quantified by enzyme-linked immunosorbent assay in 66 hepatitis C virus (HCV) carriers and 30 HCV-naive or previously infected controls. The levels were then monitored during enhanced treatment with type 1 IFNs in 15 chronic hepatitis C patients.Results The HCV carriers had high levels of sFas compared with controls (3.8 ± 1.3 vs 2.7 ± 0.8ng/ml; P < 0.001). sFas levels in patients with chronic HCV infection were directly related to serum alanine aminotransferase levels (r = 0.440; P < 0.001) and the histological grade (r = 0.403; P = 0.019). Among necroinflammatory reactions, only piecemeal necrosis showed a correlation with sFas levels (r = 0.556; P = 0.001). Pretreatment sFas levels, however, were not predictive of therapeutic outcomes. A sustained virological response to enhanced IFN therapy showed a relation to only the pretreatment HCV load. Interestingly, circulating sFas was upregulated when IFN- was administered at short intervals (3MU/every 12h). This upregulation was accompanied by parallel aminotransferase elevation, which was observed regardless of a virological response.Conclusions sFas elevation, in parallel with the severity of liver injury, suggests the possible upregulation of hepatic Fas expression and the Fas-mediated pathway in both HCV- and type 1 IFN-induced liver injury. The essential function of sFas to protect hepatocytes against Fas-mediated liver injury was not evident in these clinical settings.     

Percutaneous ultrasound-guided radiofrequency ablation with artificial pleural effusion for hepatocellular carcinoma in the hepatic dome

Background Nodules of hepatocellular carcinoma (HCC) located in the hepatic dome cannot be depicted on ultrasography because of pulmonary air. Therefore, percutaneous treatment is not possible in such cases. The purpose of this study was to clarify the feasibility and safety of percutaneous sonographically guided radiofrequency (RF) ablation with the concurrent use of artificial pleural effusion for HCC located in the right subphrenic region.Methods Between May 2001 and June 2002, 24 patients with 28 HCC nodules located directly below the diaphragm were enrolled in this study. The patient population included 17 men and 7 women (age range, 51–87 years; mean age, 66.5 years). The maximum diameter of the HCC nodules ranged from 1.0cm to 4cm (mean ± SD, 2.1 ± 0.8cm).Results We infused 200–1100ml of 5% glucose solution intrathoracically to separate the lung and liver; thus, obtaining an image of the whole tumor was impossible on gray-scale sonography. Complete tumor necrosis was achieved in a single session of RF ablation in 27 (96.4%) of the 28 lesions, while two sessions of RF ablation were required for the remaining lesion (3.6%). During treatment, no dyspnea or other complications concerned with the respiratory system were observed. Clinical courses have been satisfactory without recurrences at 1–13 months after treatment (mean, 7.9 months).Conclusions Percutaneous RF ablation with artificial pleural effusion in patients with HCC in the hepatic dome may be a safe and feasible therapy.     

Effects of glycoprotein IIb/IIIa inhibition on clinical stabilization parameters in patients with unstable angina and non-Q-wave myocardial infarction

Glycoprotein IIb/IIIa receptor inhibition prevents the major cardiac events and improves the prognosis of patients with acute coronary syndromes. The purpose of the study was to evaluate the effects of tirofiban on clinical stabilization parameters in patients with unstable angina (UA) and non-Q-wave myocardial infarction (MI). Eighty-three patients presenting with prolonged ongoing chest pain and ST segment depression were included in the study. Forty-two patients were randomized to aspirin and heparin therapy, and 41 patients to tirofiban therapy in addition to the aspirin and heparin therapy. The interval between the initiation of the treatment and the disappearance of angina, recovery time of ST segment depression, creatine kinase-MB (CK-MB) levels, onset of decrease and normalization of CK-MB, and frequency of in-hospital major cardiac events were compared. The interval between initiation of the treatment and the disappearance of angina was significantly shorter in the tirofiban group (3.5 ± 4.2 vs 9.1 ± 8.6h, P 0.001). Recovery time of ST depression was also significantly shorter in the tirofiban group (5.1 ± 7.3 vs 12.3 ± 11.5h, P 0.05). The peak CK-MB values were significantly lower in the non-Q-wave MI and UA subgroups of tirofiban than in the heparin group (P = 0.04 for both). The onset of the CK-MB decrease was significantly earlier in the tirofiban group (15 ± 14 vs 24 ± 15h, P = 0.02). The normalization time of the CK-MB was relatively shorter in the tirofiban group but without statistical significance (50 ± 22 vs 60 ± 25h). The tirofiban group had a lower frequency of total major cardiac events (26% vs 54%, P = 0.01), acute MI (2.4% vs 19%, P = 0.03), and recurrent angina (26% vs 50%, P = 0.04). The frequency of death and urgent revascularization did not differ between the groups. Tirofiban, in addition to heparin, provides earlier clinical stability and prevents major in-hospital cardiac events in patients with UA and non-Q-wave MI as compared to heparin therapy alone.     

Improvement of arterial stiffness by the antioxidant and anti-inflammatory effects of short-term statin therapy in patients with hypercholesterolemia

The preventive effect of statins on coronary events is not only associated with the cholesterol-lowering effect of these drugs, but also various direct effects on the vascular wall, which include improvement of endothelial function, antioxidant activity, and anti-inflammatory activity. We investigated whether short-term statin therapy could improve arterial stiffness and assessed its mechanism of action in patients with hypercholesterolemia. We assessed arterial stiffness in 10 patients (mean age: 62.9 ± 9.0 years) with hypercholesterolemia (total cholesterol 220mg/dl). The patients were treated with cerivastatin (0.15mg/day) for 4 weeks. Before and after 4 weeks of treatment, we determined arterial stiffness from brachial-ankle pulse wave velocity and the ankle-brachial blood pressure index (ABI) using a FORM apparatus (Colin, Komaki, Japan). We also measured the blood levels of high-sensitivity C-reactive protein (hsCRP) and malondialdehyde low-density lipoprotein (MDA-LDL) as markers of inflammation and oxidation, respectively. After statin therapy, both the right and left abPWV were significantly decreased from 1544.6 ± 157.1 to 1349.0 ± 223.9cm/s and from 1592.1 ± 164.8 to 1424.8 ± 245.2cm/s, respectively (P < 0.05). However, the ABI was unchanged after 4 weeks of cerivastatin therapy. MDA-LDL decreased significantly (from 161.2 ± 42.4 to 119.4 ± 33.5U/l, P < 0.05) and hsCRP also decreased. Total cholesterol and LDL-cholesterol decreased, while triglycerides and high-density lipoprotein-cholesterol were unchanged. Blood pressure was not significantly altered from the baseline value by statin therapy. These results suggest that the preventive effect of statins on coronary events is partly associated with the various actions of these drugs on the vascular wall, and that statins are not only cholesterol-lowering agents but also antiatherosclerotic agents.     

Left ventricular remodeling and aortic distensibility in elite power athletes

The aim of this study was to determine left ventricular (LV) morphology and aortic function in power athletes and to compare them with normal subjects. Thirty-two elite male wrestlers and 15 age-matched healthy male controls were included. All subjects underwent echocardiographic examination. Measurements included LV cavity dimension at systole and diastole, wall thickness, diastolic parameters, and aortic diameter, 3cm above aortic valve, at systole and diastole. Left ventricular mass and mass index were found to be higher in the athletes than in control subjects. The aortic distensibility index was found to be reduced in the athletes compared with controls (2.53 ± 0.91 vs 3.94 ± 1.77cm²dyne^–1 10^–6, P = 0.003), while the aortic stiffness index was significantly higher in the athletes than in controls (9.12 ± 3.23 vs 6.65 ± 2.35, P = 0.02). However, LV end-systolic wall stress was lower in the athletes than in controls. Furthermore, transmitral early (E) and late (A) peak velocity, peak velocity of the myocardial systolic wave (S _m), and early (E _m) and atrial (A _m) diastolic waves at the inferior wall were higher in the athletes than in controls. Reduced aortic distensibility in elite power athletes may be one of the cardiovascular adaptation factors which affect LV hypertrophy.