Shin-ichiro Ohkawa

Improvement of thrombocytopenia with disappearance of HCV RNA in patients treated by interferon‐α therapy: possible etiology of HCV‐associated immune thrombocytopenia

Abstract:  We evaluated the relationship between the severity of thrombocytopenia and the serum hepatitis C virus (HCV) RNA level to investigate the mechanism of thrombocytopenia in patients with HCV infection. Patients who had chronic hepatitis without splenomegaly were divided into two groups according to the platelet count, which were 18 patients with a platelet count ≤150 × 109/L and 22 patients with a platelet count >150 × 109/L. HCV RNA, platelet‐associated immunoglobulin G (PAIgG), rheumatoid factor (RF), and other immunological parameters were measured and correlations were investigated. Patients in the low platelet group had higher levels of PAIgG, Th1 cells, thrombopoietin (TPO), and RF than those in the normal platelet group (textitP < 0.05). Twenty‐two patients completed 6 months of IFN therapy and were followed for more than 1 yr afterwards. Twelve patients who responded to IFN therapy with clearance of HCV showed an increase of the platelet count, whereas the 10 patients who did not respond to IFN showed a decrease of the platelet count. The improvement of thrombocytopenia after interferon therapy suggests a contribution of HCV infection to this condition.

Lewy bodies in the sinoatrial nodal ganglion : Clinicopathological studies

Lewy bodies (LB) are characteristic pathological findings for idiopathic Parkinson disease, and extracranial organs have also been known to exhibit these structures. Clinically, the possible involvement of LB in cardiac dysfunction has attracted attention based on the findings of studies using [123I] metaiodobenzyl guanidine (MIBG) scintigraphy. The purpose of the present study was to investigate the possible involvement of LB in heart disease. A total of 40 autopsy cases consisting of Lewy body disease and Parkinson syndrome were examined. The former were cases with intracranial LB regardless of clinical symptoms, and the latter were cases with parkinsonism but without intracranial LB. The presence of heart disease or an atrial arrhythmia and the results of an MIBG scintigraphy study were clinically examined. The sinoatrial node was examined microscopically and immunohistochemically. The results showed that heart disease and atrial arrhythmia complications were more frequent in cases with Lewy body disease than in cases with Parkinson syndrome and that LB were frequently found in extracranial organs, especially in the sinoatrial nodal ganglion, in cases with Lewy body disease. In the current report, we hypothesized that neuronal changes involving LB in the sinoatrial nodal ganglion may cause arrhythmia and ischemic heart disease as a result of vasoconstriction.

Pathologic implications of restored positive T waves and persistent negative T waves after Q wave myocardial infarction

OBJECTIVES We sought to study the pathologic implications of restored positive T waves and persistent negative T waves in the chronic stage of Q wave myocardial infarction. BACKGROUND Some inverted T waves (coronary T waves) become positive after acute myocardial infarction; others retain their negative T wave component for a long time. The pathologic implications of the difference between restored positive T waves and persistent negative T waves in leads with Q waves has not, until now, been given much careful study. METHODS Of 17 patients with anterior or anteroseptal myocardial infarction confirmed by autopsy, 8 (group P) had positive and 9 (group N) had negative T waves in precordial leads with Q waves > or = 1 year after the onset of myocardial infarction. The appearance and extent of the infarct area and the degree of coronary artery stenosis were evaluated in both groups. RESULTS At autopsy, seven of eight patients in group P had nontransmural fibrotic changes in the anteroseptal or anterior wall. However, seven of nine patients in group N had a transmural myocardial infarction consisting of only a thin fibrotic layer in the anteroseptal or anterior wall. The left anterior descending coronary artery showed 75% stenosis in 1 patient in each group but > 90% stenosis in the remaining 15 patients. CONCLUSIONS Persistent negative T waves in leads with Q waves in the chronic stage of myocardial infarction indicate the presence of a transmural infarction with a thin fibrotic layer, whereas positive T waves indicate a nontransmural infarct containing viable myocardium within the layer.

Low-sulfated chondroitin sulfate in human blood and urine.

Blood and urinary low-sulfated chondroitin sulfate from healthy young and aged volunteers have been characterized by gel chromatography, two-dimensional electrophoresis on cellulose acetate strips and by chemical and enzymatic analysis. No difference in content of the material (24 nmol hexosamine per ml plasma) was observed regardless of age. Chemical composition (approximately 40% sulfation at 4-position of galactosamine) and molecular weight (about 8000) of blood and urinary low-sulfated chondroitin sulfates were found to be the same, though urinary excretion of the material was much higher in the aged than in the young adults (Ohkawa et al. (1972) J. Biochem. 72, 1495--1501). Low-sulfated chondroitin sulfate in serum was in a bound form with a molecular weight of more than 100000, irrespective of age. These results suggest that increase in urinary excretion of low-sulfated chondroitin sulfate in the aged is mainly due to renal dysfunction. Low-sulfated chondroitin sulfate was also the main component of acidic glycosaminoglycans in blood from patients with Hurlers syndrome who excreted excessive amounts of dermatan sulfate and heparan sulfate in urine. This suggests that low sulfated chondroitin sulfate in blood is not merely a precursor of urinary glycosaminoglycans in the case of healthy young adults.

A Case of Pacemaker Lead Fracture Associated with Thoracic Outlet Syndrome

A pacemaker lead fracture in the left subclavian vein was caused by compression of the clavicle and the first rib; subsequent coil elongation at the same site on the right side was observed in the replacement lead in a patient with thoracic outlet syndrome. Venography showed narrowing of the subclavian vein at the site where the lead abnormalities were observed. This case illustrates that a lead in the subclavian vein can be easily damaged when a patient has thoracic outlet syndrome.

Weekly Variation of Home and Ambulatory Blood Pressure and Relation Between Arterial Stiffness and Blood Pressure Measurements in Community-Dwelling Hypertensives

Although blood pressure (BP) is a major determinant of pulse wave velocity (PWV), some treatments have independent effects on BP and arterial stiffness. Although both ambulatory BP (ABP) and self-measured BP at home (HBP) have become important measures for the diagnosis and management of hypertension, single day recordings may be insufficient for a proper diagnosis of hypertension or the evaluation of treatment efficacy. To evaluate weekly variations in BP using 7-day HBP and 7-day ABP monitoring and to determine the relation between arterial stiffness and BP measurements in community-dwelling patients with hypertension. We enrolled 68 community-dwelling hypertensive subjects in this study. Significant weekly variations in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were found in the awake ABP data (p < .01, respectively), while no significant weekly variations in the asleep ABP or the morning and evening HBP data were observed. In untreated subjects, significant correlations were obtained between the brachial-ankle PWV and the average awake SBP, the average asleep SBP and the average SBP measured by HBP in the evening. In treated subjects, only the average SBP measured by HBP in the morning was significantly correlated with the baPWV. Differences in the weekly variations in BP were observed between HBP and ABP monitoring. In addition, the morning systolic HBP was not correlated with arterial stiffness in untreated subjectswith hypertension but was correlated in treated subjects. Relations between the morning HBP and arterial stiffness might be attributed to morning surges in BP and/or trough levels of antihypertensive drugs.

A morphological study of the normally aging heart

A morphological examination of aging was performed on 141 normal hearts selected from a total of 972 consecutive autopsies on persons aged 60 years or over. The average heart weight was 270 ± 41 g. The circumference of the valvular ring was 99 ± 10 mm in the tricuspid valve, 68 ± 8 mm in the pulmonic valve, 83 ± 10 mm in the mitral valve, and 73 ± 7 mm in the aortic valve. The thickness of the tricuspid valve (anterior leaflet) was 0.9 ± 0.3 mm, pulmonic (anterior cusp) 0.4 ± 0.3 mm, mitral (anterior leaflet) 1.3 ± 0.6 mm, and aortic (posterior cusp) 1.0 ± 0.6 mm. Cardiac chamber volumes were as follows: 40 ± 14 mL in the right atrium, 22 ± 7 mL in the right ventricle, 37 ± 12 mL in the left atrium, and 7.3 ± 3.4 mL in the left ventricle. The circumference of the tricuspid ring was the largest. Left-sided valves were thicker than right-sides valves, and atrioventricular valves were thicker than semilunar valves. Cardiac chamber volumes were generally larger on the right side. Because this study was limited to hearts from persons aged 60 years or over, age-related changes were observed in only four parameters: (i) the circumference of the aortic valvular ring, (ii) the thickness of the aortic posterior cusp, (iii) the thickness of the pulmonic anterior cusp, and (iv) the volume of the left ventricle. With increasing age the aortic valvular ring dilated, the aortic posterior cusp and the pulmonic anterior cusp thickened, and the left ventricular volume diminished.A morphological examination of aging was performed on 141 normal hearts selected from a total of 972 consecutive autopsies on persons aged 60 years or over. The average heart weight was 270 ± 41 g. The circumference of the valvular ring was 99 ± 10 mm in the tricuspid valve, 68 ± 8 mm in the pulmonic valve, 83 ± 10 mm in the mitral valve, and 73 ± 7 mm in the aortic valve. The thickness of the tricuspid valve (anterior leaflet) was 0.9 ± 0.3 mm, pulmonic (anterior cusp) 0.4 ± 0.3 mm, mitral (anterior leaflet) 1.3 ± 0.6 mm, and aortic (posterior cusp) 1.0 ± 0.6 mm. Cardiac chamber volumes were as follows: 40 ± 14 mL in the right atrium, 22 ± 7 mL in the right ventricle, 37 ± 12 mL in the left atrium, and 7.3 ± 3.4 mL in the left ventricle. The circumference of the tricuspid ring was the largest. Left-sided valves were thicker than right-sides valves, and atrioventricular valves were thicker than semilunar valves. Cardiac chamber volumes were generally larger on the right side. Because this study was limited to hearts from persons aged 60 years or over, age-related changes were observed in only four parameters: (i) the circumference of the aortic valvular ring, (ii) the thickness of the aortic posterior cusp, (iii) the thickness of the pulmonic anterior cusp, and (iv) the volume of the left ventricle. With increasing age the aortic valvular ring dilated, the aortic posterior cusp and the pulmonic anterior cusp thickened, and the left ventricular volume diminished.

Slow abnormal conduction in the low right atrium : its anatomic basis and relevance to atrial reentry

To characterize slow abnormal conduction in the low right atrium, which is known to be responsible for atrial flutter, electrophysiologic findings were correlated with anatomic features in a canine model of atrial flutter with ligation of the crista terminalis in the midright atrium. Activation in the low right atrium was mapped with a patch electrode containing 52 bipolar electrodes and a multiplexing system. A particular region in the low right atrium showed atrioventricular node-like electrophysiologic properties, a rate-dependent conduction delay, and Wenckebach periodicity. This area coincided with an area responsible for slow conduction during atrial flutter and unidirectional block at its initiation. Both pilsicainide and E-4031 preferentially blocked conduction in the specific area, leading to the termination of atrial flutter. Although refractoriness could not explain the abnormal conduction, anatomic studies consistently found the specific region to be in or around a thick muscle bundle, that is, the crista terminalis, or a thick pectinate muscle branching from the crista, located perpendicular to the wavefront of the pacing impulse and atrial flutter. These electrophysiologic and anatomic findings suggest that slow abnormal and atrioventricular node-like conduction over a thick muscle bundle, which is a normal anatomic feature of the low right atrium, plays a role in the initiation, maintenance, and termination of atrial reentry.

Type C chronic hepatitis with the discovery of a small hepatocellular carcinoma 7 years after successful interferon therapy

The patient, a 61-year-old man, had sustained injuries in a traffic accident at the age of 26, for which he received a blood transfusion. Since 1988 (age, 49 years), abnormal hepatic function had been detected, and, because of the presence of hepatitis C virus antibodies, he was diagnosed as having type C chronic hepatitis. Based on a liver biopsy that was conducted in July 1992 (age, 53), a histological diagnosis of chronic active hepatitis (F1/A2) was made. Over a period of 6 months, starting in 1992, the patient was treated with interferon (IFNα-2a; total dosage, 720 MU). At the end of this regimen, the alanine aminotransferase level was normalized and serum hepatitis C virus—ribonucleic acid was negative. This condition was maintained until August 1996 (age, 57), after which the patient stopped reporting to our hospital. In June 2000 (age, 61) when he was hospitalized for an adhesive ileus, a small hepatocellular carcinoma (a solitary lesion measuring 18 mm in diameter) at S8 was found, and it was extirpated by a segmental excision in July. The case is introduced to call attention to the need for longterm follow-up observation, even after effective IFN therapy.

DOES SODIUM SENSITIVITY AFFECT NOCTURNAL BLOOD PRESSURE VARIATION IN OUTPATIENTS WITH HYPERTENSION

We investigated the relationship between sodium sensitivity and diurnal variation of blood pressure in outpatients with hypertension. Twenty hypertensives were maintained on both a regular sodium diet for a period of 2 weeks and a low salt (7 g/day) diet for a period of one or two weeks. Ambulatory blood pressure was recorded at thirty minute intervals for 24 hours by automatic device before and during low salt diet. Patients were classified by nocturnal fall in blood pressure. 14 patients were classified as sodium sensitive, whereas 6 were classified as non-sodium sensitive on the basis of a ≥ 0 in salt sensitive index caused by sodium restriction. Incidence of reversed dipper and non-dipper in systolic blood pressure was reduced by sodium restriction, however, dipper and extreme dipper were increased. In conclusion, the results of this study show that patients with high sodium sensitivity index have strong sodium sensitivity and non-dipper is not always changed by sodium restriction.