Cicletanine is a new antihypertensive drug that stimulates renal and vascular synthesis of prostaglandin (PG) I2 in experimental animals. However, there is little evidence that cicletanine increases the level of PGI2 in systemic blood of human subjects. To investigate the short-term antihypertensive mechanism of cicletanine, we measured serially the systemic blood pressure, the levels of 6-keto-PGF1 alpha (a stable metabolite of PGI2) and PGE2, and renin activity in plasma after administration of the drug. Nine patients with essential hypertension on a diet without severe sodium restriction took 100 mg of the drug by mouth. Systemic blood pressure was measured hourly for 24 h before and after cicletanine administration. The two PGs of interest were extracted, purified by high pressure liquid chromatography, and measured by radioimmunoassay. Cicletanine decreased blood pressure 3 and 6 h after administration and increased the plasma level of 6-keto-PGF1 alpha. The increase in 6-keto-PGF1 alpha was small but significant (mean +/- SD, from 3.21 +/- 1.26 to 3.88 +/- 1.44 and later 4.15 +/- 1.08 pg/mL by 3 and 6 h after administration; P < .05 and .01, respectively). The level of PGE2 had increased at 3 h after administration but returned to baseline by 6 h. Plasma renin activity was increased only at 24 h after administration. Cicletanine increased systemic PGI2 levels short-term, producing an antihypertensive effect in patients with essential hypertension.

6-Ketoprostaglandin F1 alpha↗

PubMed1995

Effect of nafamostat mesilate on bradykinin generation and hemodynamics during LDL apheresis.

Dextran-sulfate (DS) cellulose used for low-density lipoprotein (LDL) apheresis seems to be a weak activator of the contact phase of the intrinsic coagulation pathway because the surface of this substance has negative charges. Heparin, a commonly used anticoagulant, has no effect on this process whereas the process is inhibited by a newly developed anticoagulant, nafamostat mesilate (NM). The effects on bradykinin generation were compared between heparin and NM. Five patients with severe hypercholesterolemia were treated with LDL apheresis using either heparin or NM on a different day. During apheresis with heparin, factor XII, high molecular weight kininogen, and prekallikrein were markedly decreased by passing through the DS column. A distinct generation of bradykinin was observed by passing plasma through the DS column, and this led to the rise of bradykinin levels from 12 +/- 5 (mean +/- SE) to 72 +/- 14 pg/ml after treatment of 1,000 ml of plasma. NM suppressed almost completely the rise of bradykinin levels. Although blood pressure was apt to decrease during apheresis with heparin, there was no significant difference in blood pressure between heparin and NM. Since an angiotensin-converting enzyme inhibitor may lead to a marked rise in blood levels of bradykinin by suppressing its degradation, the use of NM is recommended for apheresis in patients taking this drug.

Adolescent↗

PubMed1995

Comparison of first-line antihypertensive drugs by a randomized cross-over method--a preliminary report.

The present study was undertaken to compare the effects of first-line antihypertensive drugs in Japanese patients. Four antihypertensive drugs were studied: trichlormethiazide (TCT), nifedipine retard (NIF), atenolol (ATN), and enalapril malate (ENP). Thirty-eight patients (16 men and 22 women; age, 53.3 +/- 8.8 years, mean +/- SD) were enrolled in the study. After a control period of 2 to 4 weeks, the four drugs were administered according to a randomized, cross-over design, the duration of each treatment period being 8 to 12 weeks. The initial dose of each drug was increased until blood pressure (BP) fell to less than 150/90 mmHg. The maximum doses of TCT, NIF, ATN, and ENP were 4, 40, 50, and 20 mg/day, respectively. The protocol was completed in 25 of the 38 patients. The BPs (SBP/DBP) at the end of each period were 168 +/- 3 (mean +/- SEM)/105 +/- 1 (control), 149 +/- 4/ 98 +/- 2 (TCT), 138 +/- 3/89 +/- 2 (NIF), 151 +/- 4/94 +/- 2 (ATN), and 152 +/- 4/97 +/- 2 mmHg (ENP). The BP during NIF treatment was significantly lower than during the other treatments. This finding suggests that the calcium antagonist had a greater hypotensive effect than the other first-line antihypertensive drugs studied. The subjects seem to more closely resemble black rather than white populations with respect to their response to antihypertensive treatment.

Adult↗

PubMed1995

Glomerular hemodynamics during supraventricular tachycardia.

Supraventricular tachycardia (SVT) was induced in 7 patients by programmed cardiac stimulation via an esophageal lead. Blood pressure, renal function, and hormonal factors were measured before, during, and after SVT. The glomerular filtration rate increased during SVT, while renal blood flow did not change. The parameters of glomerular hemodynamics were calculated according to the method of Gomez. Glomerular pressure was 64 +/- 3 (mean +/- SE) mmHg before SVT, and rose significantly (p < 0.01) to 76 +/- 5 during SVT. This rise in glomerular pressure was associated with a decrease in afferent vascular resistance (from 3355 +/- 610 to 1770 +/- 517 dynes x sec/cm5, p < 0.05) and an increase in efferent vascular resistance (from 3726 +/- 758 to 4814 +/- 780 dynes x sec/cm5, p < 0.05). Since atrial natriuretic peptide (ANP) increased during SVT (from 40 +/- 15 to 208 +/- 72 pg/ml, p < 0.01), these changes in glomerular hemodynamics may be attributed to the physiologic action of ANP. Despite the changes in glomerular hemodynamics during SVT, natriuresis appeared after SVT and not during SVT. This suggests that natriuresis accompanying SVT could not be attributed to the changes in glomerular hemodynamics.

Adult↗

PubMed1995

[Secondary signs of anterior cruciate ligament tear at MR imaging].

The value of secondary signs of anterior cruciate ligament (ACL) tear was evaluated MR images of 47 knees, 15 with normal, 6 with acutely torn and 26 with chronically torn ACLs confirmed at arthroscopy, were reviewed. Lateral and medial anterior tibial translocations (ATT), posterior cruciate ligament (PCL) bowing ratio and depth of lateral femoral notch (LFN) were measured. The degrees of lateral and medial ATTs and the PCL bowing ratio of the chronically torn ACLs were significantly higher than those of normal ACLs. With cutoff values of 5-mm lateral ATT, 2.5-mm medial ATT and 0.35-PCL bowing ratio, torn ligaments were distinguished from intact ligaments with accuracies of over 80%. Depth of LFN was less sensitive and less accurate. All knees with lateral ATT of 6.4 mm, medial ATT of 3.5 mm, PCL bowing ratio of 0.43 and LFN depth of 1.5 mm or more had torn ACLs. Higher correlations were revealed between lateral ATT and medial ATT, and also between lateral ATT and PCL bowing ratio. Combined criteria of lateral ATT and PCL bowing ratio indicated the highest diagnostic value as a reliable secondary sign of torn ACLs.

Adolescent↗

PubMed1995

[MR imaging features of chronically torn anterior cruciate ligament].

Magnetic resonance (MR) images of 40 knee joints with arthroscopically proved chronic anterior cruciate ligament (ACL) tears were retrospectively evaluated. MRI demonstrated various features of chronic ACL tears: 19 knees revealed with no identifiable ligamentous structure, and 21 had residual ligamentous structures. These pseudoligaments, 14 discontinuous bands and seven continuous bands with elongation, were residual torn ligamentous fibers and/or synovial tissues. All the discontinuous bands were disrupted from the femoral attachment and were likely to traverse the lower intercondylar space. Six disrupted ligaments were attached to the lateral aspect of the posterior cruciate ligament (PCL). Coronal T2-weighted gradient echo images showed better delineation of the disrupted femoral attachment and adhesion to the PCL. A chronic ACL tear with minimal elongation or with PCL attachment at a higher position may occasionally be difficult to distinguish from an intact ligament.

Adolescent↗

PubMed1995

Imidapril hydrochloride in essential hypertension: a double-blind comparative study using enalapril maleate as a control.

OBJECTIVE: To assess the value of using imidapril hydrochloride (ACE/TA-6366), a long-acting angiotensin converting enzyme (ACE) inhibitor developed in Japan, to treat patients with essential hypertension. PATIENTS AND METHODS: A double-blind, comparative, phase III study was carried out using enalapril maleate as a control, with a 4-week observation period and a 12-week treatment period. Both drugs were started at a dose of 5 mg once a day, increasing to 10 mg in patients whose antihypertensive response was insufficient after 4 weeks. The study included 231 outpatients aged 30-74 years; of these, 108 in the imidapril group and 115 in the enalapril group were assessed. There were no differences in background factors between groups. RESULTS: An adequate antihypertensive effect was observed in 71.3% (77/108) in the imidapril group in in 66.1% (76/115) in the enalapril group, with no significant difference between groups. The pulse rate was unchanged in both groups. The drug had no adverse effects in 86.1% (93/108) of the imidapril group and 79.1% (91/115) of the enalapril group, with no significant difference between groups. Adverse drug effects were observed din 5.6% (6/108) of the imidapril group and 12.2% (14/115) of the enalapril group. Cough was the most frequent side effect, reported in 0.9% (1/108) of the imidapril group and 7.0% (8/115) of the enalapril group. Other side effects were reported in 4.6% (5/108) of the imidapril group and 5.2% (6/115) of the enalapril group. Abnormal laboratory values were observed in 3.7% (4/108) of the imidapril group and 0.9% (1/115) of the enalapril group. CONCLUSIONS: Imidapril showed excellent clinical efficacy and safety compared to enalapril. The low incidence of cough is of particular interest.

Adult↗

PubMed1994

The efficacy of monatepil, a new calcium antagonist, in the treatment of essential hypertension.

A multicenter, open-label trial in Japan examined the efficacy, safety, and optimal dose of monatepil (AJ-2615) as monotherapy and in combination therapy with angiotensin-converting enzyme (ACE) inhibitors or beta-blockers. Patients with essential hypertension who had never been treated or had been refractory to conventional antihypertensive agents were enrolled in the trial. During a 4-week control period patients assigned to monotherapy received placebo and those assigned to combination therapy received an ACE inhibitor or beta-blocker and placebo. Patients with systolic blood pressure (BP) > or = 160 mm Hg and diastolic BP > or = 95 mm Hg at the end of the control period were enrolled in the study. The initial dose of monatepil was 30 mg/day in monotherapy and 15 mg/day in combination therapy; the daily dose was titrated to 60 mg/day according to the antihypertensive response. The treatment period was 8 to 12 weeks. Blood pressure decreased from 168 +/- 8/100 +/- 6 to 142 +/- 9/85 +/- 7 mm Hg (SD) with monatepil monotherapy, from 171 +/- 11/102 +/- 6 to 141 +/- 9/84 +/- 6 mm Hg in combination with ACE inhibitors, and from 175 +/- 13/102 +/- 7 to 153 +/- 21/91 +/- 9 mm Hg in combination with beta-blockers (P < .001). When patients in whom mean BP decreased by > or = 13 mm Hg were defined as responders, the response rate was 80.4%, 78.1%, and 51.6% in the respective groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1994

Biphasic effects of repeated alcohol intake on 24-hour blood pressure in hypertensive patients.

BACKGROUND: The association between alcohol and blood pressure (BP) may be related to the temporal sequencing of alcohol use and BP measurement. We investigated the effects of single and repeated intakes of alcohol on 24-hour BP. METHODS AND RESULTS: Fourteen male habitual drinkers with essential hypertension were placed sequentially on a 4-day control phase: a nonalcoholic drink with the same calories as alcohol was given at dinner (5 PM to 6 PM) and a 7-day drinking phase: alcohol (ethanol, 1 mL/kg) was given at dinner under standardized conditions. Ambulatory BP measurements were performed on day 3 of the control phase and on days 1 and 7 of the alcohol phase. The average 24-hour systolic and diastolic BPs on day 1 were significantly lower than those in the control phase and on day 7. Between 6 PM and midnight, both systolic and diastolic BPs on days 1 and 7 (121 +/- 2/73 +/- 1 and 126 +/- 4/75 +/- 2 mm Hg, respectively) were significantly lower than those in the control phase (139 +/- 4/83 +/- 2 mm Hg). Between midnight and 8 AM (6 to 14 hours after the last drink), both systolic and diastolic BPs on day 7 (138 +/- 4/83 +/- 2 mm Hg) were significantly higher than those in the control phase (131 +/- 4/79 +/- 2 mm Hg) and day 1 (129 +/- 3/77 +/- 1 mm Hg). Between 8 AM and 3 PM, BPs showed no difference among the three phases. CONCLUSIONS: A single intake of alcohol has a depressor effect on BP that lasts for several hours after drinking, while repeated intakes for 7 days have both depressor and pressor effects according to the differences in time intervals after the last drink. This study suggests that the chronic effects of alcohol on BP might be overestimated when based on casual BP measurements alone.

Blood Pressure↗

PubMed1994

The association between salt sensitivity of blood pressure and some polymorphic factors.

OBJECTIVE: To examine the association in Japanese subjects between the salt sensitivity of blood pressure and polymorphic factors. DESIGN AND METHODS: One hundred and four patients with essential hypertension were classified as salt-sensitive or non-salt-sensitive depending on their blood pressure response to salt restriction. An insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene was examined by detecting an alu sequence in intron 16. The ACE genotype was classified as II, ID or DD depending on whether each allele had this sequence. The haptoglobin phenotype was determined by the starch-gel electrophoresis method, and was classified as three phenotypes, 1-1, 2-1 or 2-2 form. RESULTS: The response of plasma renin activity to salt restriction was greater in patients with the DD form than in those with other forms, although there were no significant differences in the ratio salt-sensitive: non-salt-sensitive patients among the three ACE genotype groups. However, the ratio was significantly larger in the haptoglobin 2-1 phenotype group than in the 2-2 group. CONCLUSIONS: The salt sensitivity of blood pressure was associated with the haptoglobin phenotype, but was not associated with the ACE genotype. However, the response of plasma renin activity to salt restriction was different according to the ACE genotype.

Adult↗

PubMed1993

Effects of aspirin DL-lysine on thrombin generation in unstable angina pectoris.

To evaluate the effects of aspirin on thrombin generation in patients with unstable angina, plasma levels of thrombin-antithrombin III complex (TAT) as a new marker of thrombin generation and of 11-dehydro-thromboxane B2 (11-dehydro-TXB2) as an indicator of platelet activation were measured in 18 patients with unstable angina, including 8 patients with prolonged rest angina (> 15 minutes). Aspirin DL-lysine (900 mg) was administered intravenously to 9 of the 18 patients (aspirin group); the other 9 were not given aspirin during the first 24 hours of hospitalization (non-aspirin group). Clinical characteristics, angiographic features and medications other than aspirin were similar between the 2 groups. Levels of plasma TAT and 11-dehydro-TXB2 were significantly higher (p < 0.05) in patients with prolonged rest angina than in those without the condition (n = 10). In 5 patients with prolonged rest angina who received aspirin, plasma TAT levels (ng/ml) were significantly decreased (4.52 +/- 1.18 at baseline, 2.50 +/- 0.65 at 1 hour and 2.16 +/- 0.42 at 24 hours after aspirin administration, p < 0.01) with a significant decrease in plasma 11-dehydro-TXB2 levels. However, the reduction in TAT after aspirin administration was slight in patients without prolonged rest angina (n = 4). In contrast, levels of plasma TAT and 11-dehydro-TXB2 in the non-aspirin group remained unchanged during the study period. These results suggest that aspirin rapidly reduces thrombin generation through inhibition of platelet activity in patients with unstable angina with prolonged rest angina.

Aged↗

PubMed1993

Effects of hemodialysis on body surface maps in patients with chronic renal failure.

To examine the effects of hemodialysis on the electrocardiogram, 87-lead body surface maps were performed in 38 patients with chronic renal failure, before and after hemodialysis. The patients were divided into two groups; 16 patients with coronary artery disease (CAD group), and 22 patients without ischemic heart disease (control group). Three maps were analyzed, QRS isopotential maps, isochrone maps, and QRS isointegral maps. Parameters measured were maximal R wave voltage (Peak R), minimal QRS wave voltage (Peak S), maximal ventricular activation time (VATmax) and QRS duration (QRSd). In the control group, Peak R and Peak S increased but VATmax decreased after hemodialysis. There were negative correlations between the changes of body weight and the changes in Peak R (r = -0.67, p < 0.01) and Peak S (r = -0.87, p < 0.001), although there were no correlations between changes in left ventricular diastolic dimension and the changes in Peak R and Peak S. In the CAD group, Peak S increased but Peak R and VATmax did not change significantly. There were negative correlations between the change of body weight and the change of Peak S (r = -0.73, p < 0.01). The most pronounced changes in mean QRS isointegral maps on hemodialysis were an increased magnitude of positivity in the control group and negativity in the CAD group on the anterior thorax. These findings suggested that the increase in the QRS amplitude after hemodialysis was influenced by the changes of the conductivity of extracardiac thorax and the relative heart position to the chest wall rather than myocardial ischemia or ventricular conduction delay.

Adult↗

PubMed1993

[Risk factors for contrast nephropathy in diabetic patients undergoing cardioangiography].

Risk factors for contrast nephropathy were prospectively studied in 17 patients with non-insulin dependent diabetes mellitus undergoing cardioangiography. Contrast nephropathy, defined as a serum creatinine increase of greater than 25% at 3 day after angiography, occurred in 29.4% of diabetic patients. Patients who developed contrast nephropathy had significantly higher serum creatinine (Cr), fractional excretion of sodium (FENa), urinary albumin excretion rate (AER), and lower 24hr Ccr than patients who did not (Cr: 1.5 +/- 0.3 mg/dl vs. 0.8 +/- 0.1 mg/dl, FENa: 1.9 +/- 0.5% vs. 0.6 +/- 0.1%, AER: 522 +/- 335 micrograms/min vs. 27 +/- 13 micrograms/min, 24hr Ccr: 39.1 +/- 11.6 ml/min vs. 86.2 +/- 9.3 ml/min, P < 0.05). Contrast nephropathy developed in all of two patients with overt proteinuria (AER more than 200 micrograms/min), but none of eight patients with normoalbuminuria (AER below 15 micrograms/min). Three of seven patients with microalbuminuria developed contrast nephropathy, and two of them had advanced nephropathy. FENa obtained next day was significantly elevated over baseline in patients with contrast nephropathy (1.9 +/- 0.5% vs. 9.7 +/- 4.5%, P < 0.05), but unchanged in patients without contrast nephropathy. The rise in C beta 2-microglobulin/Ccr and enzymuria was noted in both group. Percentage decrease of Ccr on the next day was positively correlated with FENa before angiography (r = 0.645, p < 0.01). Of 24hr Ccr, AER, and FENa before angiography, FENa was revealed as a statistically significant discriminant factor for contrast nephropathy by stepwise discriminant analysis (p = 0.0008). These results suggest that contrast nephropathy develops predominantly in the stage not of incipient but of overt diabetic nephropathy indicated by a decline of glomerular filtration, overt proteinuria, and tubular dysfunction. Of them, tubular dysfunction may be the most important risk factor for contrast nephropathy.

Aged↗

PubMed1993

[IgA nephropathy with acute exacerbation of idiopathic interstitial pneumonia: an autopsy case].

A 73-year old man was admitted to the hospital because of dyspnea. His proteinuria was pointed out in 1981. He felt dyspnea after exertion and abnormal chest X-ray shadow was pointed out in 1984. He was admitted to our hospital for further examination for the first time in 1988. He was diagnosed as IgA nephropathy by renal biopsy, and idiopathic interstitial pneumonia (IIP) by transbronchial lung biopsy. Then steroid therapy was begun because of progression of renal dysfunction in November 1990. But thereafter dyspnea, hypoxia and fine diffuse reticulonodular shadow on chest X-ray film was exacerbated. And he died because of respiratory failure. In this case, progression of IgA nephropathy seemed associated with exacerbation of IIP.

Aged↗