Effects of benidipine hydrochloride on 24-hour blood pressure and blood pressure response to mental stress in elderly patients with essential hypertension.

OBJECTIVE: 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. SUBJECTS: Ten elderly patients with essential hypertension (mean age: 65+/-4 years; 7 male and 3 female). METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

[Malignant syndrome associated with disseminated intravascular coagulation and a high level of amylase in serum, followed by diabetic coma in an elderly patient with Parkinson's disease during L-dopa therapy].

A 66-year-old woman with a 7-year history of Parkinsons' disease was admitted to our hospital because of a high fever and disturbance of consciousness. She had been treated with levodopa/benserazide hydrochloride and trihexyphenidyl hydrochloride until admission. On admission, the patient was comatose, her temperature was 40.5 degrees C, her blood pressure was 54/-mmHg, and her pulse rate was 130 beats/min. Laboratory tests showed leukocytosis, a high level of creatine kinase in serum and evidence of hyperosmolar non-ketotic diabetic coma (blood glucose, 1,080 mg/dl) and of disseminated intravascular coagulation (DIC). A continuous insulin infusion, antibiotics, nafamostat mesilate, and urinastatin were given, after which the DIC, hyperglycemia, and the level of consciousness were improved. However, levels of creatine kinase, myoglobin, transaminase, and amylase in serum continued to increase, and multiple organ failure was suspected. Furthermore, she became less responsive, diaphoretic, and tremulous; fever and mild rigidity developed. The peak creatine kinase and myoglobin were 11,095 U/l and 12,520 ng/ml, respectively. A diagnosis of malignant syndrome was made, and treatment with levodopa/carbidopa and dantrolene was begun. Within several days, the clinical and laboratory findings improved. We report here a rare case of malignant syndrome associated with DIC followed by diabetic coma in an elderly patient with Parkinsons' disease during L-dopa therapy. Timely diagnosis and treatment of malignant syndrome are important in the management of elderly patients with Parkinsons' disease, because DIC and multiple organ failure may occur in the early stages of malignant syndrome.

[Septicemia due to methicillin-resistant Staphylococcus aureus from chronic prurigo in an elderly woman].

An 80-year-old woman being treated with anti-hypertensive drugs developed eruption and itching of the skin. High fever and lymph node enlargement subsequently developed in spite of discontinuing all antihypertensive drugs, and she was admitted to our hospital. At the initial examination, multiple papules were noted over the entire body, and the skin showed thickening and lichenification with scratch marks. There was also generalized enlargement of the superficial lymph nodes. From these findings, her condition was diagnosed as chronic prurigo due to drug allergy. Laboratory tests showed inflammatory findings, anemia and a high serum level of IgE. Analysis of the surface marker of peripheral lymphocytes revealed no abnormalities. Bacteriologic cultures of blood revealed methicillin-resistant Staphylococcus aureus (MRSA). Histologic examination of the lymph nodes revealed chronic reactive lymphadenitis with a follicular pattern. She was strongly suspected of having MRSA septicemia, and so combination chemotherapy with vancomycin, minocycline and cefoperazone/sulbactam was started. However, 1 month after initiation of chemotherapy, the low-grade fever, eruption and moderate inflammatory findings persisted, and culture of the eruptions revealed MRSA. The prurigo was therefore considered to be the source of the septicemia, and daily application of diflucortolone ointment containing 3% acetic acid was started. Thereafter, the clinical and laboratory findings showed a rapid improvement. MRSA infections usually occur in compromised patients who are receiving antibiotics during prolonged hospitalization. The present case, who did not have any underlying disease, indicates that old-age is also an important factor for the development of MRSA septicemia.

Personality characteristics of patients with "white coat" hypertension.

To clarify psychological factors related to white coat hypertension, we examined personality characteristics of patients with mild essential hypertension by psychological testing. Patients with essential hypertension were taught to measure their own blood pressure (BP) with a semi-automatic oscillometric BP measuring device and were asked to measure BP at home in the sitting position before going to sleep. The duration of the study was 8 wk. Patients were defined as "white coat" hypertensive patients (WCHT) (n = 49) if home systolic BP was 135 mmHg or less and home diastolic BP was 85 mmHg or less, and as "sustained" hypertensive patients (SHT) (n = 53) if home systolic BP was 140 mmHg or more or home diastolic BP was 90 mmHg or more. All the patients underwent the following psychometric tests: self-rating questionnaire for depression, MMPI alexithymia scale, type A behavior pattern check list, general health questionnaire (GHQ), and egogram check list. WCHT did not differ from SHT in the scores for depression, alexithymia, type A behavior pattern, or GHQ. However, WCHT showed an abnormal pattern on egograms, as compared with SHT. On egograms, SHT showed a normal hill-shaped pattern with a peak in "nurturing parent (NP)", and "free child (FC)" was higher than "adapted child (AC)" in both genders. In contrast, WCHT showed significantly lower FC and significantly higher AC than SHT, and AC was higher than FC in both genders. These findings suggested that WCHT tend to suppress their own emotions and become over-adaptive to their surroundings, as compared with SHT.

Both a calcium antagonist and ACE inhibitor reverse hypertrophy in hypertension but a calcium antagonist also depresses contractility.

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 p < 0.01), 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 p < 0.01). 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.

Effect of alacepril on 24-hour blood pressure in elderly hypertensive patients.

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.

Fatal cerebral infarction in an asymptomatic young patient with primary antiphospholipid syndrome.

An 18-year-old woman with primary antiphospholipid syndrome developed a major cerebral infarction leading to brain death despite intensive treatment with steroids, urokinase, glyceol and heparin. Fatal strokes associated with this syndrome are rare. A computed tomographic scan of the brain suggested occlusion of the main trunk of the right middle cerebral artery. The titer of antibodies against cardiolipin/ beta 2-glycoprotein I complex in serum was extremely high.

Asterixis and astatic seizures in association with bilateral insular lesions in a patient with viral encephalitis.

We report a 48-year-old man who suffered from viral encephalitis and developed involuntary movements of the hands and astatic seizures as sequelae. T2-weighted magnetic resonance imaging of the brain showed high intensity areas in the bilateral insulae. Electroencephalography (EEG) revealed spike and slow wave complexes and high-amplitude slow waves. The involuntary movements of the hands were diagnosed as asterixis by electromyography. Asterixis affected both hands. Administration of sodium valproate aggravated asterixis and EEG findings, but treatment with clonazepam markedly improved these findings and astatic seizures. The present case indicates that insular lesions might be also responsible for the development of asterixis.

Response of plasma renin-angiotensin system to a single captopril administration in patients receiving long-term treatment with captopril.

1. The responses of angiotensin II (AII), AIII, aldosterone and plasma renin activity (PRA) to a single dose of captopril were investigated in hypertensive patients receiving long-term (more than 1 year) captopril therapy (CT patients) and compared with those of non-treated hypertensive patients (NT patients). 2. Baseline levels of AII and aldosterone were significantly lower in CT patients than in NT patients. AIII tended to be lower and PRA was slightly higher in CT than in NT patients, but these differences were not significant. 3. A single administration of captopril (50 mg orally) significantly decreased plasma levels of AII, AIII and aldosterone as well as blood pressure in both CT and NT patients. 4. These results demonstrate that chronically repeated administration of captopril to hypertensive patients effectively reduces the daily blood pressure and concomitantly the plasma AII level to acceptable levels in patients with no experience of ACE inhibition.

Polysplenia syndrome with various visceral anomalies in an adult: embryological and clinical considerations.

A 26-year-old female with polysplenia syndrome is reported. She had numerous visceral anomalies including polysplenia, a short pancreas, a preduodenal portal vein, malrotation of the bowel, azygos continuation of the inferior vena cava, bilateral hyparterial bronchi and symmetrical liver lobation. Embryological and clinical considerations of polysplenia syndrome are described.

Prolonged partial remission of malignant fibrous histiocytoma in posterior mediastinum by immunotherapy.

The case of a 16-year-old female patient with the giant cell type of malignant fibrous histiocytoma (MFH) in the left posterior mediastinum is reported. This is a very unusual site for MFH. Immunotherapy induced a prolonged partial remission lasting 15 months with a marked reduction in tumor size. The usefulness of immunotherapy for MFH needs to be evaluated.

Effect of L-threo-3, 4-dihydroxyphenylserine on orthostatic hypotension in a patient with spinal cord injury.

A 72-year-old female who underwent the extirpation of metastatic intraspinal tumor showed an extremely wide variation of blood pressure with recurrent episodes of syncope due to paroxysmal hypotension. Treatment of the patient with salt supplement and L-threo-3, 4-dihydroxyphenylserine, an exogenous precursor of norepinephrine, markedly improved the syncopal attack as well as the daily activity.

Impairment of baroreceptor reflex in patients with phaeochromocytoma.

We examined the baroreceptor reflex sensitivity (BRS) in two patients with adrenal phaeochromocytoma because of their wide BP fluctuations. These patients showed greatly reduced values for BRS, which returned to normal with marked improvements of BP fluctuations soon after the removal of phaeochromocytoma. In these patients, circulating blood volume was normal and episodic rises in BP occurred without detectable increases in plasma catecholamines. From these observations, a marked impairment of baroreceptor function is considered to be one of the determinants for the wide BP fluctuation in patients with phaeochromocytoma.

Influence of age and severity of hypertension on blood pressure response to isometric handgrip exercise.

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.

Blood pressure and heart rate variability in elderly patients with isolated systolic hypertension.

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.

Kidney renin gene expression after renin inhibition in the marmoset.

1. The effects of renin inhibitor ES-8891 on renin synthesis and its secretion by the kidney were investigated in normotensive sodium-depleted marmosets. We measured plasma renin activity, plasma immunoreactive renin concentration, plasma angiotensin II concentration and kidney renin mRNA content after oral administration of ES-8891 (60 mg day-1 kg-1) for 1 week. 2. The mean blood pressure was significantly decreased (P less than 0.01) on day 7 after oral administration of ES-8891. There was no significant change in heart rate during the administration. 3. Oral administration of ES-8891 for 1 week markedly decreased the plasma renin activity, the plasma immunoreactive renin concentration and the plasma angiotensin II concentration (to 18%, 41% and 24% of the corresponding control values; P less than 0.05 for each, n = 5). 4. The kidney renin mRNA content in ES-8891-treated marmosets was significantly lower than that in normal controls (4.2 +/- 3.5 versus 12.8 +/- 5.5 pg/micrograms of total RNA, means +/- SD, P less than 0.05, n = 5). 5. Oral administration of the renin inhibitor ES-8891 for 1 week not only inhibited plasma renin activity but also decreased renin synthesis and its secretion by the kidney.

Effect of renal denervation on the development of hypertension in Dahl-Iwai salt-sensitive rats.

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.

The effect of the renin inhibitor ES-1005 on the expression of the kidney renin gene in sodium-depleted marmosets.

The effect of the renin inhibitor ES-1005 or captopril on the expression of the kidney renin gene was investigated in sodium-depleted marmosets. We measured the level of kidney renin messenger RNA (mRNA) after continuous administration of ES-1005 (48 mg/kg per day) or captopril (2 mg/kg per day) intraperitoneally, via an osmotic mini-pump, for one week. The level of kidney renin mRNA was measured by densitometric Northern blot analysis using an alpha-32P-labelled human renin cDNA fragment as the hybridization probe. Captopril treatment markedly increased plasma renin activity and the level of kidney renin mRNA by 4.7-fold and 6.3-fold, respectively. ES-1005 treatment completely inhibited plasma renin activity and significantly decreased the level of kidney renin mRNA (46% of the normal control P less than 0.01). However, plasma immunoreactive renin concentration was significantly increased by the treatment with ES-1005 (P less than 0.05). These results suggest that the treatment with the renin inhibitor ES-1005 for one week has a paradoxical effect on kidney renin gene expression and renin release from the kidney in sodium-depleted marmosets.