Effects of arotinolol on exercise capacity and humoral factors during exercise in normal subjects

Summary A placebo-controlled, double-blind crossover study was undertaken in 10 normal subjects to examine the effects of arotinolol (10 mg bid), a nonselective beta blocker with alpha-blocking activity, on exercise capacity and hormone levels during exercise after a 2-week treatment period. Maximal oxygen uptake (VO₂ max) and blood lactic acid concentration (LA) were measured during progressive exercise testing. An exercise intensity equivalent to 4 mmol/l of LA was used for the constant workload exercise test. Humoral factors were measured after 20 minutes of constant workload exercise. The administration of arotinolol significantly decreased systolic blood pressure and heart rate at rest and during exercise, but diastolic blood pressure did not change. No significant difference was found between arotinolol and placebo with regard to VO₂ max and maximal workload. Plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (NE) levels at rest and during exercise did not differ between the two treatments. In contrast, plasma epinephrine (EN) levels at rest and during exercise were significantly greater with arotinolol. Atrial natriuretic peptide (ANP) at rest did not differ between the two treatments. However, exercise caused a significant increase in ANP after arotinolol treatment. These findings suggest that arotinolol decreases blood pressure and heart rate without affecting exercise capacity.     

Angiogenesis in hepatocellular carcinoma as evaluated by CD34 immunohistochemistry

ABSTRACT— To clarify the relationship between angiogenesis and hepatocarcinogenesis on progression of hepatocellular carcinoma (HCC), we quantitatively evaluated angiogenesis by CD34 immunohistochemistry in liver cirrhosis (LC), adenomatous hyperplasia (AH), and HCC, and proliferative activity estimated by Ki-67 immunohistochemistry. Angiogenesis was evaluated by CD34 immunohistochemistry using monoclonal antibody HPCA-2, and tumor proliferative activity was evaluated using monoclonal antibody MIB-1. We used an image analysis system to assess the microvessel density as the area percentage of the endothelial area. Angiogenesis was generally observed in HCC and there was no significant difference among all clinical stages and histological grades of HCC. On the other hand, the staining of CD34 was partly observed in sinusoids of AH, although no positive staining was seen in any sinusoids of LC. The proliferative activity was significantly correlated with the clinical stage and histological grade of HCC. Our results indicate that the quantitation of angiogenesis does not provide significant prognostic information in HCC, but that it may have diagnostic value in distinguishing HCC from non-HCC. Meanwhile, AH, which is not morphologically diagnosed as cancer, shows positive staining for CD34, suggesting that some portion of AH contains cancerous characteristics.     

Partial tarsal arthrodesis for rheumatoid feet

Partial intertarsal joint arthrodesis was performed on 12 feet of 11 patients as a surgical treatment for planovalgus deformity of the foot and lesions of the intertarsal joints caused by rheumatoid arthritis. Single arthrodesis was performed on the talocalcaneal joint in eight feet, two of which underwent simultaneous total ankle arthroplasty, and on the talonavicular joint in two feet. Double arthrodesis was done on the talocalcaneal and talonavicular joints in one foot and on the talonavicular and calcaneocuboid joints in one foot. Screws or staples were used for fixation. Patients were followed for 2 years to 8 years 7 months (average 4 years 3 months). Osseous fusion was achieved in all feet, and satisfactory pain relief was obtained in all cases except one. We performed this surgery in patients who were relatively active, and the results indicated that arthrodesis of a small number of joints that caused pain and deformity was effective in reducing pain and correcting the deformity. We concluded that partial tarsal arthrodesis should be performed on a limited number of joints during the early stages of planovalgus deformity of the foot because more joints are found to be fixed during the advanced stages. However, progression of the osteoarthritis was found in the neighboring joints. Close follow-up observation is needed.     

CD30-positive lymphoma in human T-cell leukaemia virus type 1 carrier without monoclonal integration of HTLV-1

Summary. CD30, Ki-1 antigen, an activated T-cell antigen, is a member of the nerve growth factor receptor family. This antigen is expressed on the lymphoma cells of some adult T-cell leukaemia/lymphoma (ATL/L) patients and some patients with Epstein-Barr virus infection. CD30-positive large cell cutaneous T-cell lymphomas occasionally integrate a defective HTLV-1 provirus. We describe here an HTLV-1 carrier who developed Ki-1 lymphoma with no evidence of monoclonal integration of the HTLV-1 proviral sequence.     

Long-term follow-up of atrioventricular delay optimization in patients with biventricular pacing.

BACKGROUND: Atrioventricular (AV) delay optimization may be important in patients with biventricular pacing and the optimal AV delay can be predicted using Doppler echocardiography and the formula: optimal AV delay = AV delay-the interval between the end of A wave and complete closure of the mitral valve when the AV delay is set at slightly prolonged AV delay. METHODS AND RESULTS: In the present study the efficacy of this method was evaluated in 5 patients (67.4+/-8.0 (SD) years old) with biventricular pacing. Cardiac output (CO) and diastolic filling time were measured by Doppler echocardiography. When the AV delay was set at the predicted optimal AV delay -25 ms, the predicted optimal AV delay (133+/-66 ms) and predicted optimal AV delay + 25 ms, the respective CO were 4.5+/-0.9, 5.3+/-1.0, 4.8+/-1.0 L/min (p<0.05, ANOVA) and the diastolic filling times were 364 +/-100, 373+/-105, 335+/-84 ms (p<0.05, ANOVA). Congestive heart failure improved from New York Heart Association class 3.6+/-0.5 to 1.4+/-0.5 (p<0.001). CONCLUSIONS: AV delay optimization is important in patients with biventricular pacing and can be easily achieved by the new method.     

Multi-Step Regulation of Interferon Induction by Hepatitis C Virus

Acute hepatitis C virus (HCV) infection evokes several distinct innate immune responses in host, but the virus usually propagates by circumventing these responses. Although a replication intermediate double-stranded RNA is produced in infected cells, type I interferon (IFN) induction and immediate cell death are largely blocked in infected cells. In vitro studies suggested that type I and III IFNs are mainly produced in HCV-infected hepatocytes if the MAVS pathway is functional, and dysfunction of this pathway may lead to cellular permissiveness to HCV replication and production. Cellular immunity, including natural killer cell activation and antigen-specific CD8 T-cell proliferation, occurs following innate immune activation in response to HCV, but is often ineffective for eradication of HCV. Constitutive dsRNA stimulation differs in output from type I IFN therapy, which has been an authentic therapy for patients with HCV. Host innate immune responses to HCV RNA/proteins may be associated with progressive hepatic fibrosis and carcinogenesis once persistent HCV infection is established in opposition to the IFN system. Hence, innate RNA sensing exerts pivotal functions against HCV genome replication and host pathogenesis through modulation of the IFN system. Molecules participating in the RIG-I and Toll-like receptor 3 pathways are the main targets for HCV, disabling the anti-viral functions of these IFN-inducing molecules. We discuss the mechanisms that abolish type I and type III IFN production in HCV-infected cells, which may contribute to understanding the mechanism of virus persistence and resistance to the IFN therapy.     

Early non-convulsive seizures are associated with the development of acute encephalopathy with biphasic seizures and late reduced diffusion

IntroductionChildren with either febrile seizure or acute encephalopathy exhibit seizures and/or impaired consciousness accompanied by fever of unknown etiology (SICF). Among children with SICF, we previously reported those who have refractory status epilepticus or prolonged neurological abnormalities with normal AST levels are at a high risk for the development of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), considered to be caused by excitotoxicity. Non-convulsive seizures (NCS) are common in critically ill children and cause excitotoxic neuronal injury. The aim of this study was to elucidate the prevalence of NCS in the acute phase of children at a high risk for developing AESD and the relationship between NCS in the acute phase and neurological outcomes.MethodsWe studied 137 children with SICF at a high risk for developing AESD and who underwent continuous electroencephalogram monitoring (cEEG) upon admission to a tertiary pediatric care center at Hyogo Prefectural Kobe Children’s Hospital between October 2007 and August 2018. Patient characteristics and outcomes were compared between patients with NCS and without NCS.ResultsOf the 137 children, NCS occurred in 30 children; the first NCS were detected in cEEG at the beginning in 63.3%, during the first hour in 90%, and within 12 h in 96.7%. Neurological sequelae were more common in NCS patients (20.0%) than in non-NCS patients (1.9%; p = 0.001). Five in 30 NCS patients (16.7%) and 3 in 107 non-NCS patients (2.8%) developed AESD (p = 0.013).ConclusionThe occurrence of NCS is associated with subsequent neurological sequelae, especially the development of AESD.