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Congestive heart failure is a common and serious complication in patients undergoing chronic dialysis. However, there have been no studies on preferential medical therapies to improve left ventricular function in haemodialysis patients. Beta-blocker treatment is known to improve left ventricular function in patients with dilated cardiomyopathy; moreover, plasma levels of noradrenaline and natriuretic peptides are sensitive markers of left ventricular dysfunction. The present study investigated whether beta-blocker treatment could improve left ventricular function in haemodialysis patients with a dilated left ventricle. Our study group comprised 14 haemodialysis patients with a dilated left ventricle, who had undergone maintenance haemodialysis for a mean of 11 years. The following haemodynamic parameters were evaluated before and after 4 months of treatment with the beta-blocker metoprolol: left ventricular dimension at end-systole and end-diastole, and fractional shortening. Plasma levels of noradrenaline, atrial natriuretic peptide and brain natriuretic peptide were also determined. Dry body weight and haemoglobin concentration showed no significant change after compared with before treatment with metoprolol. Heart rate decreased significantly, from 79+/-9 beats/min to 69+/-9 beats/min, but systolic blood pressure remained unchanged. The left ventricular dimension both at end-systole and at end-diastole was decreased, and fractional shortening increased significantly. Plasma levels of noradrenaline did not change significantly, but those of atrial natriuretic peptide and brain natriuretic peptide decreased markedly [from 100+/-89 pg/ml to 46+/-29 pg/ml (P=0.0051) and from 549+/-516 pg/ml to 140+/-128 pg/ml (P=0.0035) respectively]. In conclusion, beta-blocker therapy with metoprolol can markedly attenuate left ventricular remodelling and decrease the plasma levels of natriuretic peptides in haemodialysis patients with a dilated left ventricle.

To assess the effect of antihypertensive drugs on aortic distensibility, we evaluated the aortic distensibility of 33 hypertensive patients before and after antihypertensive treatment by using cine magnetic resonance imaging. Thirty three hypertensive patients were divided into three groups and treated for 12 weeks with 2-4 mg trichlormethiazide per day (n = 10), 80 mg nicardipine per day (n = 13) and 50 mg alacepril per day (n = 10). There were no significant differences in mean age and mean blood pressure among the three groups. Cine magnetic resonance was performed at ascending and descending aortic levels. Aortic area was measured at the maximum and minimum frames. The effect of antihypertensive therapy on aortic distensibility was evaluated as the percent change from before treatment to after treatment. There were no significant differences in pulse pressure before and after treatment with trichlormethiazide, nicardipine and alacepril. After treatment with these drugs, mean blood pressure in all groups decreased (trichlormethiazide and nicardipine, P.01; alacepril, P.05), (the maximum area--the minimum area) and aortic distensibility in all groups increased significantly (each P.01). Percent changes in aortic distensibility after treatment were significantly higher with nicardipine (ascending, 346.6 +/- 255.9%; descending, 338.8 +/- 246.5%, each P.05) and alacepril (ascending, 369.7 +/- 238.8%, P.05; descending, 306.9 +/- 123.3%, P.01) than with trichlormethiazide (ascending, 146.0 +/- 139.6%; descending, 129.3 +/- 97.5%). In conclusion, nicardipine and alacepril have a beneficial effect on aortic distensibility.

The effects of a new dihydropyridine calcium antagonist, benidipine hydrochloride, on 24-hour blood pressure and blood pressure response to mental arithmetic test were investigated.Ten elderly patients with essential hypertension (mean age: 65+/-4 years; 7 male and 3 female).After a control period of 4 weeks, 4 mg benidipine was administered once daily in the morning for 12 weeks. Ambulatory blood pressure was monitored using a non-invasive automatic portable device with the cuff-oscillometric method at the end of both the control and treatment periods.Benidipine administration significantly decreased 24-hour blood pressure, while little change was noted in heart rate. Daytime blood pressure decreased significantly, from 148.2+/-11.5/90.8+/-8.8 to 133.8+/-9.2/82.5+/-10.8 mmHg. However, no significant decrease in nighttime diastolic blood pressure was noted, and the decrease in nighttime systolic blood pressure was small (from 129.8+/-9.9/77.1+/-7.6 to 121.8+/-10.1/74.7+/-9.1 mmHg). No significant changes were observed in diurnal variability of blood pressure and heart rate. The decrease in systolic blood pressure by benidipine administration showed a significant positive correlation with systolic blood pressure before treatment in the 24-hour and daytime periods. Single cosinor analysis showed that benidipine administration significantly decreased MESOR of both systolic and diastolic blood pressure, without an increase in amplitude. Both systolic and diastolic blood pressure during mental arithmetic test were significantly decreased after treatment with benidipine, and the increase in systolic blood pressure induced by mental arithmetic test was also significantly attenuated.These findings indicate that administration of benidipine once daily in the morning effectively decreases blood pressure and attenuates blood pressure response to mental stress. Neither reflex tachycardia, deterioration of diurnal blood pressure change, nor excessive lowering of nighttime blood pressure was observed after benidipine administration. It is suggested that benidipine is a potent and long-lasting calcium antagonist which may be useful for the treatment of elderly hypertensive patients with cardiovascular disease.

In order to examine the current status of antihypertensive drug therapy for elderly hypertensive patients, and the effect of clinical characteristics and drugs on their prognosis, 1669 hypertensive patients in the Chugoku and Shikoku districts, aged between 65 and 84 years, were enrolled and followed for 3 years. Of the 1669 patients enrolled, 1459 were selected for evaluation and 1127 patients were followed. Group A comprised 955 patients who had not suffered from any accident, group B comprised 139 patients who had suffered from a cerebral, cardiac, renal or other non-fatal accident, and group C comprised 33 patients who died. The mortality rate was 10.7/1000 patient.years and the morbidity rate was 55.6/1000 patient.years. The number of patients who received monotherapy was 736 (calcium channel blockers: #436, beta blockers: #100, angiotensin converting enzyme inhibitors: #80, diuretics: #64, alpha blockers: #16; others: #13). In group C, there were more male, and the patients were older and showed a higher level of serum creatinine concentration at enrollment compared with other groups. The use of diuretics and beta blockers tended to be low in this group. Among the three groups, however, there was no difference in blood pressure, heart rate or the use of each drug at enrollment. In summary, it is suggested that the different antihypertensive drug therapies die not influence the prognosis of elderly hypertensive patients.

The aim of this study was to compare the effects of a calcium antagonist, nicardipine SR, with an angiotensin-converting enzyme (ACE) inhibitor, alacepril, on the regression of left ventricular hypertrophy (LVH) and function. Twenty patients with LVH, aged 42-78 years, were treated with nicardipine SR or alacepril. Ten patients were treated with nicardipine SR (40-80 mg) for 21 months, and the other 10 patients were treated with alacepril (25-100 mg) for 18 months. All patients underwent echocardiography to assess left ventricular structure and function before and after the treatment. After nicardipine SR or alacepril treatment, blood pressure was decreased significantly from 176.0 +/- 13.9/97.0 +/- 5.3 mmHg to 140.0 +/- 14.0/77.4 +/- 7.2 mmHg and from 168.2 +/- 22.3/99.0 +/- 5.5 mmHg to 138.4 +/- 12.5/85.2 +/- 9.7 mmHg, respectively (both p0.01), whereas heart rate did not change (73.8 +/- 14.6 beats/min vs. 69.9 +/- 13.5 beats/min and 71.6 +/- 9.7 vs. 65.8 +/- 8.1 beats/min, respectively). The left ventricular mass index decreased significantly from 133.2 +/- 11.7 g/m2 to 114.4 +/- 15.7 g/m2 with nicardipine SR and from 137.1 +/- 14.8 g/m2 to 99.3 +/- 23.0 g/m2 with alacepril (both p0.01). The fractional shortening, peak shortening rate, and peak lengthening rate all improved significantly after each treatment. The end-systolic wall stress/left ventricular end-systolic volume index, as an index of left ventricular contractility, was decreased significantly after treatment with nicardipine SR but was not changed after treatment with alacepril. In conclusion, both nicardipine SR and alacepril similarly reduced LVH and improved left ventricular systolic and diastolic function. However, alacepril did not alter left ventricular contractility, whereas nicardipine SR decreased left ventricular contractility.

A 38-year-old man was admitted to our hospital for detailed examination of fever, cough and yellow sputum. At the age of 32, be had mitral prosthesis for the first time, because of mitral regurgitation due to mitral valve prolapse. Four years previously, he had again undergone mitral prosthetic valve replacement due to prosthetic valve endocarditis due to staphylococcus epidemidis. This occasion, staphylococcus aureus was isolated by arterial blood culture. Transesophageal echocardiography detected vegetation attached to the mitral prosthetic valve and paravalvular leakage. The diagnosis was prosthetic valve endocarditis. He underwent a third mitral prosthetic valve replacement. Detection of the source of infection was difficult only by transthoracic echocardiography, and immediate transesophageal echocardiography seemed mandatory to diagnose bacterial endocarditis.

The effect of administration of an angiotensin-converting enzyme inhibitor, alacepril, on 24-hour blood pressure in the elderly hypertensive patients was investigated. Thirteen elderly hypertensive patients (mean age 71 +/- 5; 6 male and 7 female) participated in the present study. After 2 weeks of control period alacepril was administered 25-50 mg/day for 8 weeks. Ambulatory blood pressure monitoring with cuff-oscillometric method was performed at the end of both control and treatment periods. Alacepril administration for 8 weeks significantly decreased 24-hour blood pressure while it had little effect on heart rate. Daytime blood pressure was significantly decreased from 154 +/- 10/91 +/- 5 mmHg to 145 +/- 8/85 +/- 5 mmHg, while the change in nocturnal blood pressure was not significant: from 137 +/- 17/79 +/- 7 mmHg to 130 +/- 15/75 +/- 9 mmHg. Hyperbaric area of systolic blood pressure was also significantly decreased (from 295 +/- 185 mmHg x hour/day to 172 +/- 111 mmHg x hour/day), indicating that pressure load to the heart was effectively reduced. Administration of alacepril did not cause tachycardia in response to the decrease in blood pressure. Acrophase of both blood pressure and heart rate was changed to 11:00 a.m. These findings indicate that blockade of the renin-angiotensin system in the elderly hypertensive patients decreased blood pressure effectively without causing tachycardia or deterioration of diurnal variations of blood pressure. These hemodynamic changes produced by alacepril administration are favorable for the treatment of the elderly patients with cardiovascular disease.

KL-6 is a mucinous glycoprotein expressed on Type 2 pneumonocytes, and serum levels of KL-6 are reported to be abnormally high in patients with interstitial pneumonia. A new assay kit for serum KL-6 (ED046) was used in the evaluation of patients with pneumonitis. To clarify whether KL-6 is a useful marker of pneumonitis activity, 649 subjects were studied, including 185 healthy controls, 187 patients with 3 types of interstitial lung diseases, and 277 patients with 4 types of non-interstitial lung diseases. The serum KL-6 level was significantly higher in the patients with pneumonitis (1285 +/- 1196 U/ml) than in the patients without pneumonitis (307 +/- 232 U/ml). The KL-6 level was also significantly higher in patients with clinically active pneumonitis (1708 +/- 1338 U/ml) than in those with inactive pneumonitis (820 +/- 796 U/ml) (p0.0001). Serum KL-6 levels correlated significantly with serum c-reactive protein, lactic dehydrogenase, and PaO2 values. These results suggest that the ED046 assay is useful for measuring KL-6 as a marker of pneumonitis activity.

A 37-year-old man with multiple nodules on a chest X-ray film, hypertension, and proteinuria was admitted to our hospital in September, 1993. Thirteen years earlier, he had been admitted to another hospital because of bloody sputum, fever, and dyspnea. He also had slight oral aphthae and slight iridocyclitis. A chest X-ray film at that time showed bilateral diffuse reticular shadows, and his illness was diagnosed as acute interstitial pneumonitis. Since that time, he had been continuously receiving tapering doses of prednisolone. His chest symptoms were relieved, and the findings on the chest X-ray film resolved with that treatment. In 1993, he also had positive tests for HBs antigen and for HLA-B51, and he was found to have renal vascular hypertension. Chest CT films and a pulmonary angiogram showed multiple aneurysms and occlusions of pulmonary arteries. A renal angiogram showed multiple intraparenchymal aneurysms of renal arteries. A specimen taken by open-lung biopsy showed healed endoarteritis obliterans of muscular arteries and no alveolitis. His illness was diagnosed as polyangiitis overlap syndrome, because of the unclassified systemic necrotizing vasculitis.

To elucidate the characteristics of end-organ damage in essential hypertension in the elderly, the progression of end-organ damage, with respect to deterioration of renal function and changes in the optic fundi, were compared between young and elderly essential hypertensive patients with the same left ventricular mass index (LVMI). Forty five elderly hypertensive patients (ageor = 65 years) were matched with 40 young patients (ageor = 55 years) for sex and LVMI. All studies were performed under hospitalisation to uniform the background of diet and daily activity. Compared with young hypertensive patients, elderly patients were characterised to have advanced end-organ damage. In young patients, the levels of progression of end-organ damage were significantly correlated with each other, while in elderly patients no relation was observed. In young patients, LVMI was significantly correlated with urinary and plasma noradrenaline, PRA and 24 h blood pressure. In elderly patients, LVMI correlated only with 24 h systolic blood pressure.

A 70-year-old man was admitted for diagnosis of an abnormal shadow on chest X-ray film. Chest X-ray films and chest tomograms showed a club-like shadow close to the pulmonary artery. The tumor was diagnosed as a small cell lung cancer, after transbronchial biopsy. The patient underwent chemotherapy and radiation therapy. This patient had small cell lung cancer that appeared on chest X-ray films to have a strange shape.

We encountered a 63-year-old man whose dry cough due to interstitial pneumonia had been successfully with an anti-thrombin drug, argatroban, which was given to treat exacerbated Buerger's disease. We therefore prospectively evaluated fibrinogen, fibrin-degradating product D-dimer, thrombin anti-thrombin III complex, and plasmin anti-plasmin complex in patients with interstitisal lung diseases. In a preliminary study, we found that some patients actually had elevated levels of these markers. These findings suggested that increased coagulability was involved in the pathophysiology of interstitial pneumonia. In this study, we measured the levels of serum-soluble thrombomodulin as a marker of endothelial cell damages that lead to hemostasis. We found that serum levels of thrombomodulin were high in about 35% of patients with sarcoidosis, interstitial pneumonia associated with collagen diseases, or idiopathic interstitial pneumonia. Furthermore, these levels decreased as the patients' conditions improved. Although further evaluation is needed, these results suggest that endothelial cell damage and hemostasis are involved in the pathophysiology of interstitial pneumonia.

To evaluate the biosynthesis of the type-1 angiotensin II (AT1) receptor and the regulation of AT1 receptor subtypes in the rat adrenal gland, we performed non-radioisotope in situ hybridisation histochemistry with an AT1 receptor complementary RNA (cRNA) probe and a messenger RNA (mRNA) probe. The levels of AT1A and AT1B receptor mRNAs were measured by the reverse transcriptase-polymerase chain reaction method after 4-week treatment with a selective AT1 receptor antagonist, TCV-116, and an angiotensin-converting enzyme inhibitor, delapril. Specific hybridisation signals were observed with the cRNA probe in both the cortex and medulla of the rat adrenal gland. An especially strong signal was observed in the zona glomerulosa. TCV-116 did not affect the levels of expression of AT1A and AT1B receptor mRNAs in the adrenal gland. Delapril, on the other hand, significantly reduced the levels of expression of AT1A and AT1B receptor mRNAs. These results indicate that the sites of biosynthesis of the AT1 receptor are mainly distributed in the adrenal zona glomerulosa. The observed differences in levels of expression of AT1 receptor mRNAs following treatment with TCV-116 and delapril suggest the involvement of the AT2 receptor in the regulation of AT1 receptor subtypes.

The aim of this study was to elucidate whether human renin gene restriction fragment length polymorphism (RFLP) is associated with essential hypertension. We sampled randomly 45 inpatients at our hospital and divided them into two groups according to a family history of essential hypertension, FH(-) and FH(+) groups. The FH(+) group was further divided into two subgroups based on the level of BP, FH(+) x HT(-) and FH(+) x HT(+) groups. The frequencies of renin gene RFLP patterns were compared among three groups: FH(-), FH(+) x HT(-) and FH(+) x HT(-). Among 18 restriction endonucleases tested, renin gene RFLPs were detected by three restriction endonucleases, Mbo I, Bg I and Hind III, digestion. There was a significant difference in the distribution of renin gene Mbo I genotypes among the three groups (chi 2 = 13.284, P0.01). The distribution of Mbo I genotypes in the FH(-) group was different from FH(+) x HT(-) group (chi 2 = 5.990, P0.05) and FH(+) x HT(+) group (chi = 9.210, P0.01), but there was no significant difference between the FH(+) x HT(-) and FH(+) x HT(+) groups. The distribution of renin gene Bgl I and Hind III genotypes were similar in the three groups, FH(-), FH(+) x HT(-) and FH(+) x HT(+). These results indicate that human renin gene Mbo I RFLP is significantly associated with a family history of essential hypertension.

We examined the left ventricular cardiac structure and the diastolic function in patients with isolated systolic hypertension (ISH; SBPor = 160 mmHg and DBP90 mmHg) in the elderly. We studied 17 patients with ISH, 24 age-matched patients with essential hypertension (EHT; DBPor = 90 mmHg) and 17 normotensive controls (NT; SBP140 mmHg and DBP90 mmHg). EHT were divided into two groups based on the mean wall thickness (MWT) of the left ventricle. Group 1 patients (EHT-I, n = 12) had a MWT10 mm and group 2 patients (EHT-II, n = 12) had a MWTor = 10 mm. We measured left ventricular end-diastolic dimension (LVDd), end-systolic dimensions (LVDs), left ventricular mass index (LVMi) and left ventricular isovolumic relaxation time (IRT) to assess the left ventricular cardiac structure and the diastolic function by M-mode echocardiography. LVDd was significantly smaller in ISH than in NT, EHT-I and EHT-II (P0.01). Relative wall thickness was greatest in ISH because of both the decreased chamber size and the increased left ventricular wall thickness. LVMi in ISH was similar to that in EHT-I, but IRT in ISH was significantly longer than that in EHT-I (P0.05). These results suggest that ISH in the elderly shows a left ventricular concentric hypertrophy and a severely impaired diastolic function.

A 28-year-old man was admitted to our hospital for further evaluation of a loop-like abnormal shadow in the middle lower lung field on chest X-ray film. Pulmonary angiograms demonstrated staining of the abnormal shadow during the venous phase. The abnormal vein descended from the right upper lobe to the middle lobe and then tortuously made a loop upward to drain into the left atrium. A part of the right apical vein was stenosed. The right apical segmental bronchus directly branched from the trachea. These observations indicate that the abnormalities may have originated in the prenatal period. Cases of anomalous course of the pulmonary vein are very rare.

To evaluate the myocardial damage associated with aortic regurgitation, thallium-201 myocardial scintigraphy was performed in 13 patients with aortic regurgitation. The data obtained by thallium-201 single photon emission computed tomography were expressed as the extent score, and were compared with data by echocardiography. The results were as follows: 1. In 11 of 13 patients, there were moderate Tl defects in the distribution of bull's eye map, 80% in the apex, 50% in the inferior and lateral regions, 30% in the anterior region and 10% in the septal region. The mean extent score was 22.3 +/- 11.0%. 2. The extent score correlated with the increase in aortic regurgitant flow volume. The extent score according to the Sellers' classifications II, III, and IV was 13.8 +/- 3.7%, 20.1 +/- 9.8% and 31.9 +/- 10.2%, respectively. 3. There was a good negative correlation between the extent score and fractional shortening (r = -0.66, p0.01), however, no significant correlation was observed between the extent score and the left ventricular end-diastolic volume. These results suggest that Tl defects in patients with aortic regurgitation are mainly due to myocardial ischemia associated with a decrease in coronary perfusion pressure and that the extent score may sensitively reflect the severity of myocardial damage in cases with aortic regurgitation.

1. Familial aggregation of hypertension was determined in 187 Japanese nuclear families. The necessary data on family and case history particularly concerning the hypertensive status were obtained by personal interviews of outpatients at six local hospitals, using a specifically designed questionnaire. 2. From the family history of the 187 living index children (single ascertainment), 134 pairs of parents were informative. Of 819 children, excluding index cases, the number of hypertensives, normotensives and status unknown were 224, 274 and 187, respectively. Individuals under 30 were classified as unknown. 3. For a child given the birth order, empirical risk to be hypertensive was calculated from the proportion of hypertensives to normotensives plus hypertensives. 4. Irrespective of parental mating types, among a simplex family of hypertension the index cases of the first-born child were more than the others. 5. There was no birth order effect in risk among multiplex families of hypertension. 6. There was no increase of hypertensive offsprings observed when the mother was hypertensive.

To study the effect of antihypertensive therapy on the regulation of renin gene expression, the levels of tissue renin messenger RNA (mRNA) were measured after treatment with a calcium channel blocker (manidipine hydrochloride 3 mg/kg/day) or an angiotensin-converting enzyme inhibitor (delapril hydrochloride 30 mg/kg/day), administered orally for 1 week, in spontaneously hypertensive rats (SHR). Male SHR, aged 15 weeks old, were used in this study (n = 5 per group). Control rats were administered the vehicle alone. Tissue total RNA was isolated from kidney, adrenal gland, heart, and brain tissue, and tissue RNA was reverse-transcribed to complementary DNA (cDNA), which was specifically amplified by polymerase chain reaction with labeled-primers for the rat renin gene. The radioactivity of the cDNA products was measured directly. Although delapril increased plasma renin activity (PRA) about 5-fold compared with the control group, manidipine did not change PRA. The kidney renin mRNA content was increased about 6-fold by treatment with delapril. Manidipine and delapril significantly decreased the renin mRNA content in the heart (p0.01 and p0.05, respectively). The level of renin mRNA in the adrenal gland and brain tissues was not significantly changed by treatment with either drug. These results suggest that tissue renin gene expression in SHR is regulated by a tissue-specific process independent of the circulating renin-angiotensin system.

Regulation of the gene expression of type-1 angiotensin II receptor (AT1) by treatment with manidipine, a calcium channel blocker, or delapril, an angiotensin converting enzyme inhibitor, for one week was assessed in the adrenal gland, heart, kidney, and brain from spontaneously hypertensive rats (SHR). Tissue AT1 receptor messenger RNA (mRNA) content was measured by reverse transcriptase-polymerase chain reaction. Treatment with manidipine (3 mg/kg/day) or delapril (30 mg/kg/day) lowered systolic blood pressure (SBP) significantly (p0.01) (delta SBP; -73 mmHg or -67 mmHg, respectively). Although delapril markedly increased plasma renin activity (PRA), manidipine did not alter PRA. AT1 receptor mRNA content in the adrenal gland was significantly (p0.01) decreased by treatment with manidipine or delapril. In contrast, cardiac AT1 receptor mRNA content was significantly (p0.01) increased by treatment with either agent. There was no significant change in renal and brain AT1 receptor mRNA contents. These findings suggest that although the expression of AT1 receptor gene depends on the circulating renin-angiotensin system (RAS), it is regulated independently in a tissue-specific manner via the local RAS in each tissue of SHR.

To investigate the circadian profiles of BP and heart rate in elderly patients with isolated systolic hypertension (ISH), the variability of BP and heart rate during day time (daytime) and the amplitudes of nocturnal fall were evaluated in ISH (n = 19) comparing with those of essential hypertensive patients (EHT, n = 18) and normotensive subjects (NT, n = 16) in the same age range. ISH showed a significantly wider BP variability during the day time and a greater amplitude of nocturnal fall compared with EHT and NT. However, the heart rate variability during the daytime and the amplitude of nocturnal fall were similar among the three groups. ISH showed a stronger correlation between BP and heart rate during 24 hours compared with EHT and NT. Approximately 80% of ISH showed a significant positive correlation between BP and heart rate. These results suggest that the BP of ISH patients is susceptible to fluctuations in autonomic nerve activity.

The influence of age and severity of hypertension on the blood pressure response to isometric handgrip exercise (IHG) was studied in essential hypertensive patients (n = 122). The change in blood pressure during IHG in elderly patients with isolated systolic hypertension (ISH) (n = 12) was also studied. Left ventricular hypertrophy due to hypertension was used as an index of the severity of hypertension. The change in systolic blood pressure (SBP) during IHG was markedly greater in essential hypertensives than in normotensive subjects (n = 36). Among hypertensive patients, the change in SBP increased with increasing severity of hypertension. This change in SBP was not influenced by age. The change in SBP during IHG in patients with ISH was significantly smaller than that in essential hypertensive patients and was similar to that in normotensive subjects in the elderly. These results demonstrate that age does not affect the increased blood pressure response to IHG in essential hypertensive patients but the greater the severity of hypertension, the greater the increase in SBP during IHG. Elderly patients with ISH do not have an enhanced blood pressure response to IHG.

Plasma immunoreactive atrial natriuretic factor (ANF) and urinary sodium excretion were measured in elderly patients with isolated systolic hypertension (ISH) (n = 11), age-matched essential hypertensive patients (EHT; n = 16) and normotensive subjects (NT; n = 9) before and during a 60 min infusion of hypertonic saline (120 mEq of Na+). An exaggerated natriuresis during the sodium load was observed only in ISH. Baseline plasma ANF levels in ISH were significantly lower (P less than 0.05) than those of EHT and NT. There was no significant change in plasma ANF in EHT and NT subjects after the saline load. In contrast, there was a significant increase in plasma ANF (P less than 0.05) after the saline load in ISH. The change in urinary sodium excretion was significantly correlated with the change in plasma ANF (r = 0.75, P less than 0.01) in ISH. We conclude that an exaggerated natriuresis during a hypertonic saline infusion may be linked to an increase in plasma ANF in elderly ISH patients.

Renal denervation has been shown to delay the onset of hypertension in spontaneously hypertensive rats and DOCA-salt sensitive rats. We investigated the contribution of the renal nerves to the development of hypertension in Dahl-Iwai salt-sensitive (DS) rats. Bilateral renal denervation or sham-operation was carried out in DS rats, and animals were then kept on a high salt diet (study I) or on a normal salt diet (study II). DS rats became severely hypertensive (207 +/- 8 mmHg) after 4 weeks on a high salt diet. They became mildly hypertensive (156 +/- 3 mmHg) after 4 weeks on a normal salt diet. In both studies, renal denervation exerted no effect on the development of hypertension in the DS rats. The urinary sodium excretion, urinary volume, heart rate and body weight were unaltered by renal denervation. These results indicate that the renal nerves do not make a major contribution to the development of hypertension in DS rats.

A case of malignant mesothelioma originated from pericardium was reported. A 76 year-old male who complained of dyspnea showed cardiomegaly (CTR = 68%) and bilateral pleural effusion in chest plain X-ray film. Gallium-67 (67Ga) scintigraphy revealed doughnut-like accumulation on cardiac apical site and mediastinal accumulation. Cytological examination of pericardial effusion revealed class V. Autopsy confirmed diagnosis of malignant pericardial mesothelioma. 67Ga scintigraphy may be useful in diagnosis of malignant pericardial mesothelioma.

A patient with a mycotic aneurysm of the sinus of Valsalva and heart block secondary to infectious endocarditis was described. This 46-year-old man was admitted to our hospital on May 9, 1990, because of fever and progressive general malaise after extraction of a tooth. Physical examination on admission revealed blood pressure of 98/62 mmHg, pulse rate 96 per min, temperature 37.7 degrees C and respiration 35 per min. Auscultation of the heart revealed a grade 3/6 systolic murmur and a grade 2/6 diastolic murmur at the third left intercostal space. Chest radiograph showed mild cardiomegaly with moderate lung congestion. Electrocardiography revealed the first grade atrioventricular block. Echocardiography demonstrated vegetations on the aortic valve, and perforation of the non-coronary sinus of Valsalva. The prolapsed non-coronary sinus of Valsalva extended into the right atrium. Doppler echocardiography revealed a severe aortic regurgitant jet in the diastolic phase. We diagnosed the patient as having aortic regurgitation with a mycotic aneurysm of the non-coronary sinus of Valsalva due to infectious endocarditis. His condition remained severely ill despite intensive medical treatment. On May 14, 1990, aortic valve replacement and excision of the mycotic aneurysm were performed. The commissural portions of the aortic cusps were heavily thickened and calcified. The mycotic aneurysm was very fragile. During manipulating the mycotic aneurysm, the sinus accidentally perforated into the right atrium. The cardioaortic fistula was closed with a goretex patch. A demand pacemaker was implanted because of postoperative complete atrioventricular block.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic arterial compliance, baroreflex sensitivity index and cardiac function were studied in elderly patients with isolated systolic hypertension (ISH, n = 12) comparing values with those of essential hypertensive patients (EHT, n = 12) and normotensive subjects (NT, n = 7) in the same age range. Systemic arterial compliance of the ISH group was markedly decreased. Baroreflex sensitivity indices of ISH and EHT were similarly decreased. Pre-ejection period index (PEPI) of ISH was normal, whereas PEPI of EHT was significantly longer than that of NT. These results demonstrate that of the haemodynamic characteristics of ISH, the predominant features are a decrease in compliance of large arteries with a disturbance of baroreflex sensitivity and normal cardiac function.

Angiotensin converting enzyme (ACE) activities of bronchoalveolar lavage fluid (BALF) and serum in patients with sarcoidosis and with silicosis were measured. Serum ACE was measured by enzymic assay and radioimmunoassay. There was a close relationship between ACE activity and content (r = 0.78). Serum ACE activities in patients with active sarcoidosis (37.5 +/- 11.1 nmol/min/ml, mean +/- SD) and with silicosis (25.5 +/- 9.3) were significantly elevated from the control (18.6 +/- 6.0). BALF ACE activities in the control, patients with active sarcoidosis and with silicosis were 0.23 +/- 0.19 nmol/min/ml, 0.94 +/- 0.97 and 0.38 +/- 0.05, respectively. BALF ACE in patients with active sarcoidosis and with silicosis were significantly different from the control. When BALF ACE was corrected by the cell count of alveolar macrophage (per 10(6) cells), activity was significantly different from control only in the patients with sarcoidosis. Moreover, only the alveolar macrophages in sarcoidosis were stained by immunofluorescence and immunocytochemistry using rabbit antihuman ACE antibody. Induction of ACE in alveolar macrophage might have an important role for the activity or progression of sarcoidosis.

We measured the activity of angiotensin converting enzyme (ED 3.4.15.1) in urine samples from normal subjects and patients with nephrotic syndrome and chronic glomerulonephritis. Urinary excretion of angiotensin converting enzyme in patients with nephrotic syndrome (1.58 +/- 0.50 (SD) units/day; n = 15) and chronic glomerulonephritis (1.01 +/- 0.45 units/day; n = 12) was significantly increased compared with normal subjects (0.38 +/- 0.10 units/day; n = 18). It was demonstrated that a high molecular weight form of the enzyme (more than 400000) was mainly excreted in urines from patients with nephrotic syndrome. After trypsin treatment, this form was altered to a low molecular weight form (290000). These two different forms of urinary angiotensin converting enzyme were compared with the enzyme purified from human kidney, and found to be identical with respect to Km values (2 mmol/l), pH optimum (pH 8.3), chloride ion dependency (0.8 mol/l), inhibitory effect of captopril (I50, 21 nmol/l), and behavior towards antiserum to human kidney angiotensin converting enzyme.

We found a family with a high activity for hydrolyzing L-alanyl-beta-naphthylamide in their serum. This enzyme was confirmed to be aminopeptidase (microsomal) (EC 3.4.11.2) by means of immunological experiments involving anti-human kidney aminopeptidase (microsomal) antibody. We could not find the cause of the increased activity from the results of clinical and laboratory examinations. The enzyme from the propositus resembled that from the serum of normal subjects in molecular mass (240 000 Da), Km value (87 mumol/L), and degree of inhibition by antiserum to human kidney aminopeptidase (microsomal). It differed from the normal enzyme with respect to electrophoretic mobility (R1 value, 0.58; normal, 0.51), isoelectric point (pI, pH 3.4; normal, pH 3.8), and heat stability (more labile than normal). From information on this family and another one reported in the Japanese literature, we suggest that the mode of inheritance of a high activity of serum aminopeptidase (microsomal) may be autosomal dominant.

Angiotensin converting enzyme [EC 3.4.15.1] was solubilized from the membrane fraction of human kidney cortex using trypsin and purified to homogeneity by DEAE-cellulose, hydroxylapatite and DEAE-Sephadex A-50 column chromatographies, preparative isoelectric focusing, and Sephadex G-200 gel filtration. The final recovery of the enzyme was 13.9%. The molecular weight of the enzyme was estimated to be 199,000 by a sedimentation equilibrium method. A value of 170,000 was obtained for the reduced and denatured enzyme by dodecylsulfate-polyacrylamide gel electrophoresis. The enzyme was a glycoprotein consisting of a single polypeptide chain with an isoelectric point of 5.10. Neutral sugar accounted for 13% per weight of the enzyme. The purified enzyme had a specific activity of 96.9 mumol/min/mg protein for hippurylhistidylleucine. The Km value, Kcat value and hydrolytic coefficient (Kcat/Km) of the enzyme for hippurylhistidylleucine were 2.0 mM, 545 s-1 and 273 mM-1 . s-1, respectively. Rabbit antibody against the human kidney converting enzyme inhibited the activities of the enzymes from human lung and serum as equally as that from human kidney, but not those from sheep, dog, or rat sera. The human kidney and lung converting enzymes were immunologically identical on double immunodiffusion analysis.

A 52-year-old man with olivopontocerebellar atrophy was admitted to Ehime University Hospital for examination of sleep apnea. Overnight polysomnographic study revealed that his sleep apnea was predominantly the central type. With progress of the disease, the dominance of apnea pattern changed from the central type to the obstructive type. After tracheostomy, the apnea index decreased from 15 per hour to 12.4 per hour. However, the apnea index of the central type increased from 1.5 per hour to 12.4 per hour. These findings suggest that the effect of tracheostomy is not always beneficial in sleep apnea, and that the frequency and the pattern of apnea are not always indicators of tracheostomy.

Angiotensin-converting enzyme (ACE, EC 3.4.15.1) was demonstrated in the tissue of human renal cell carcinoma and its cultured cells by immunofluorescence and immunohistochemistry using a specific rabbit antibody to human kidney ACE. The biochemical properties of the partially purified enzyme from the tumor tissue were identical with the pure enzyme from normal kidney with respect to Km, optimal pH, chloride ion activation and heat sensitivity. Catalytic activities of tumor and normal kidney enzymes were similarly inhibited by an ACE inhibitor, captopril, and by the antibody to human kidney ACE. However, double immunodiffusion analysis showed spur-forming immunoprecipitin bands between the tumor and normal kidney enzyme. These data suggest that human renal cell carcinomas have a new isozyme of ACE differing in part immunologically from the enzyme of normal kidney.