Instability of anticoagulation intensity contributes to occurrence of ischemic stroke in patients with non-rheumatic atrial fibrillation

The efficacy of anticoagulation in reducing the risk of cardiogenic embolism has been demonstrated in patients with atrial fibrillation (AF), but there are few prospective studies assessing the influence of anticoagulation stability on ischemic stroke in such patients. Accordingly, the present study investigated prospectively whether an instability of the anticoagulation intensity would affect the efficacy of the therapy in a total of 156 patients with non-rheumatic AF (NRAF) who received oral anticoagulation with warfarin. During a 2-year follow-up period, the annual event rate of ischemic stroke was 2.1%. In patients without a history of prior stroke, no ischemic stroke occurred at a higher international normalized ratio (INR> or =2.0). In contrast, patients who had had a prior stroke had no INR-dependent reduction of incidence. The coefficient of variation (CV) of measured INRs was significantly greater in patients with ischemic stroke than in those without. By multivariate analysis, only greater CV (> or =0.3) of INRs was an independent risk for ischemic stroke, although New York Heart Association functional class > or =II and treatment with diuretics were of borderline significance by univariate analysis. The present results suggest that stability of anticoagulation intensity is important to protect thromboembolic events in patients with NRAF.     

Contribution of Irf-1 promoter polymorphisms to the Th1-type cell response and interferon-beta monotherapy for chronic hepatitis C.

We recently reported promoter polymorphisms in the IRF-1 gene, an interferon-inducible gene that plays an important role in host antiviral function. The promoter activity was shown to be different between different polymorphisms. In this study, we investigated the relationship between IRF-1 promoter polymorphisms and the response to interferon monotherapy for chronic hepatitis C. Eighteen patients with a low initial viral load or hepatitis C virus (HCV) genotype non-1b received 6-months course of interferon-beta monotherapy. IRF-1 gene mutations and the treatment response were investigated. The IRF-1 promoter type possessing a higher promoter activity (-415C/-410A/-300A) was found in only three patients, all of which had a lower viral load than those with other promoter types and were able to obtain a sustained viral response. Flow cytometric analysis of peripheral blood mononuclear cells showed that the patients with a higher promoter activity of the IRF-1 had a significantly higher proportion of T helper 1-type CD4(+) cells after interferon administration than those of other promoter types. These results suggest that IRF-1 promoter polymorphisms may contribute, at least partially, to host antiviral activity for chronic hepatitis C.     

Time-varying spectral analysis of heart rate and left ventricular pressure variability during balloon coronary occlusion in humans: a sympathoexicitatory response to myocardial ischemia

OBJECTIVES

We assessed time-varying spectral components of heart rate and left ventricular (LV) pressure variability during coronary angioplasty to elucidate dynamic autonomic responses to transient myocardial ischemia.

BACKGROUND

Sympathoexcitatory reflexes elicited by acute coronary occlusion are rarely addressed in the clinical settings because of a lack of technique to monitor transient changes in sympathetic activation.

METHODS

RR interval and LV pressure and volume were serially recorded in 14 patients with effort angina during balloon coronary angioplasty. Wavelet analysis was applied for determination of nonstationary spectral components of RR interval and LV peak pressure variability.

RESULTS

The wavelet analysis revealed that coronary occlusion provoked low-frequency (LF) fluctuations of RR interval (seven patients) and LV peak pressure (six patients) at 0.06 ± 0.01 Hz, but not in the remaining patients. Following the balloon inflation, the LF component of RR interval began to increase after the onset of myocardial ischemia, peaked at about 80 s, and then declined in the late phase of inflation. Consequently, the ratio of low to high frequency component rose to be significantly greater in the LF augmentation group than in the no LF augmentation group in the middle phase of coronary occlusion. The patients with no LF augmentation had little evidence of myocardial ischemia as reflected by changes in ST segment and LV systolic function during coronary occlusion.

CONCLUSIONS

The wavelet analysis of RR interval and LV pressure variability clearly showed a dynamic profile of spectral components in response to transient coronary artery occlusion. The resultant regional myocardial ischemia elicited a profound sympathoexcitatory response followed by a gradual suppression. This method provides a useful tool to gain a new insight into the nonstationary autonomic influence on the cardiovascular system.     

Clinical usefulness of edaravone for acute liver injury

BACKGROUND: Edaravone, a newly synthesized radical scavenger, has shown an excellent effect on treating stroke patients. The effect of edaravone on carbon tetrachloride (CCl4)-induced acute liver injury was examined. METHODS: Six rats were injected with CCl4 alone and six rats were intravenously injected with edaravone immediately after and 3 h after injection of CCl4. Another six rats were injected with olive oil alone. The animals were killed at 24 h after the CCl4 injection. RESULTS: Injection of CCl4 was followed by a marked increase in serum alanine aminotranferase (ALT) level (CCl4, 1630.6 +/- 606.8 IU/L; olive oil, 21.0 +/- 2.6 IU/L; P < 0.001), lactate dehydrogenase (LDH) level (CCl4, 5068.0 +/- 2956.4 IU/L; olive oil, 203.6 +/- 30.5 IU/L; P < 0.005), and total bilirubin (TB) level (CCl4, 0.88 +/- 0.48 mg/dL; olive oil, 0.37 +/- 0.05 mg/dL; P < 0.01), whereas in the edaravone-treated rats, the ALT (119.4 +/- 113.5 IU/L, P < 0.001), LDH (369.7 +/- 288.2 IU/L, P < 0.005), and TB values (0.29 +/- 0.16 mg/dL, P < 0.01) were significantly decreased. Histological examination of the liver by hematoxylin and eosin and oil red O staining showed a marked reduction of steatosis in the CCl4 and edaravone-treated rats compared with the CCl4-injected rats. Significant inhibition of hepatocytic apoptosis was demonstrated by the terminal deoxynucleotidyl transferase-mediated UTP nick-end labeling (TUNEL) method in the edaravone-treated rats. CONCLUSIONS: These results suggest that edaravone has a marked preventive effect on oxidative stress-induced acute liver injury.     

Left atrial appendage function and abnormal hypercoagulability in patients with atrial flutter

STUDY OBJECTIVES: The prevalence of thromboembolism might be higher than previously recognized in patients with atrial flutter (AFL) based on findings of transesophageal echocardiography (TEE). To evaluate the potential prothrombotic state in patients with AFL, TEE findings and hemostatic markers were compared among patient groups with AFL, normal sinus rhythm (NSR) and chronic nonvalvular atrial fibrillation (AF). DESIGN AND SETTINGS: Cross-sectional study at a university hospital. METHODS: In 28 patients (mean age, 63 years) with AFL, 58 patients (mean age, 66 years) with AF, and 27 patients (mean age, 61 years) with NSR who underwent TEE, plasma levels of markers for platelet activity (platelet factor 4 and beta-thromboglobulin [beta-TG]), thrombotic status (thrombin-antithrombin III complex and prothrombin fragments 1 and 2) and fibrinolytic status (d-dimer and plasmin-alpha(2)-plasmin inhibitor complex) were determined. RESULTS: Left atrial appendage (LAA) blood flow velocity in patients with AFL was higher (p < 0.05) than that in patients with AF, but was lower (p < 0.05) than that in patients with NSR (AF, 25 +/- 2; AFL, 44 +/- 4; NSR, 60 +/- 4 cm/s). Dense left atrial spontaneous echo contrast (SEC) was found in 4 patients (14%) with AFL and 16 patients (28%) with AF. There was no significant difference in plasma levels of hemostatic markers between the AFL group and the NSR group. AFL patients with impaired LAA function (LAA flow < 30cm/s, dense SEC, or both), however, showed higher level of d-dimer and beta-TG than those without impaired LAA function (d-dimer, 1.9 +/- 0.6 microg/mL vs 0.4 +/- 0.1 microg/mL; beta-TG, 73 +/- 17 ng/mL vs 33 +/- 5 ng/mL, p < 0.05). CONCLUSIONS: Patients with AFL as a whole are not in the prothrombotic state as compared with those with AF. However, patients with AFL and impaired LAA function are at potentially high risk for thromboembolism and might require anticoagulation.     

An Infected Popliteal Aneurysm after Plain Old Balloon Angioplasty

The case was a 76-year-old man with chronic limb-threatening ischemia. Plain old balloon angioplasty (POBA) was performed on the popliteal artery. Subsequently, he suffered from cellulitis around the POBA site, followed by reocclusion. Staphylococcus aureus was detected in a blood culture. After re-revascularization with POBA, both purulent gonitis and an infected popliteal aneurysm were observed to occur. We performed aneurysmectomy and bypass grafting with the saphenous vein and then continued antibiotic therapy. Although treatment consisted of endovascular therapy (EVT) with nothing left behind, management was difficult because of secondary infectious complications. We conclude that prophylactic antibiotics before EVT should be considered in such cases.     

Importance of collateral circulation for prevention of left ventricular aneurysm formation in acute myocardial infarction

The effect of preexistent coronary collateral perfusion on the prevention of left ventricular aneurysm formation was examined in 47 patients undergoing an intracoronary thrombolysis within 6 hours after the onset of a first acute anterior myocardial infarction. Left ventricular aneurysm formation and wall motion were analyzed with cineventriculography. A left ventricular aneurysm was determined as well-defined demarcation of the infarcted segment from normally contracting myocardium. In 25 patients with successful thrombolysis (group A), a left ventricular aneurysm was observed in one patient (4%) during the chronic stage of infarction. In 10 patients who had a significant collateral circulation to the infarct-related coronary artery and unsuccessful reperfusion (group B), the left ventricular aneurysm was observed in only one patient (10%). In the remaining 12 patients with unsuccessful recanalization in the absence of a significant collateral perfusion (group C), there was a higher incidence (seven of 12, 58%) of left ventricular aneurysm formation than in groups A and B (p less than 0.05). In group A, both the global ejection fraction and regional wall motion in the infarct areas improved significantly (p less than 0.05) between the acute and chronic stages of infarction. By contrast, in groups B and C, these indexes on the ventricular function did not change significantly during the convalescent period. Thus, although the collateral perfusion existing at the onset of acute myocardial infarction may not improve ventricular function, it exerts a beneficial effect on the prevention of left ventricular aneurysm formation.     

Impact of a bidirectional approach via radial and popliteal arteries for the treatment of chronic total occlusion of lower limb artery: A case report

A 49-year-old man with poorly controlled diabetes was admitted to Kushiro Rosai Hospital, Hokkaido, Japan after scalding both feet with boiling water. Because of poor healing, he was assessed for peripheral arterial disease. Angiography revealed total occlusion of the right common and external iliac arteries, diffuse stenosis of the right superficial femoral artery, focal stenosis of the left common iliac artery and chronic total occlusion of the left superficial femoral artery. A staged procedure with bidirectional approach via the radial and popliteal arteries was attempted. During the procedures, the patient was in the prone position on the catheterization table, and bidirectional guidewire manipulation was performed. All of the lesions were successfully stented. The patient was not required to change positions during the procedure, which can be performed by a single operator. The bidirectional approach is effective in the setting of transcatheter treatment of chronic total occlusive disease.     

Proton beam therapy for aged patients with hepatocellular carcinoma

PURPOSE: To investigate the safety and efficacy of proton beam therapy for aged patients with hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Twenty-one patients aged > or =80 years with HCC underwent proton beam therapy. At the time of irradiation, patient age ranged from 80 to 85 years (median, 81 years). Hepatic tumors were solitary in 17 patients and multiple in 4. Tumor size ranged from 10 to 135 mm (median, 40 mm) in maximum diameter. Ten, 5, and 6 patients received proton beam irradiation with total doses of 60 Gy in 10 fractions, 66 Gy in 22 fractions, and 70 Gy in 35 fractions, respectively, according to tumor location. RESULTS: All irradiated tumors were controlled during the follow-up period of 6-49 months (median, 16 months). Five patients showed new hepatic tumors outside the irradiated volume, 2-13 months after treatment, and 1 of them also had lung metastasis. The local progression-free and disease-free rates were 100% and 72% at 3 years, respectively. Of 21 patients, 7 died 6-49 months after treatment; 2 patients each died of trauma and old age, and 1 patient each died of HCC, pneumonia, and arrhythmia. The 3-year overall, cause-specific, and disease-free survival rates were 62%, 88%, and 51%, respectively. No therapy-related toxicity of Grade > or = 3 but thrombocytopenia in 2 patients was observed. CONCLUSIONS: Proton beam therapy seems to be tolerable, effective, and safe for aged patients with HCC. It may contribute to prolonged survival due to tumor control.