Estimation of base blood pressure by using a new device in the outpatient clinic.

Direct measurement of intra-arterial blood pressure (BP) for 24-h provides approximately 100,000 values that vary enormously, but each (BPi) can be expressed by the equation BPi = BP0 + DeltaBPi (BP0, base BP; DeltaBPi, BP increment, i=1, 2, ..., 100 x 10(3)). About 20% of outpatients with hypertension exhibit white-coat hypertension (WCH). In such patients, DeltaBPc (i = c; c, time at the clinic) is surmised to be large. A method for explaining the physiological factors in DeltaBPc and the estimation of base BP in the outpatient clinic is important. This study addresses this issue. A total of 293 subjects were divided into four groups: 1) WCH group, 45 individuals (office BP > or = 140/90 mmHg and 24-h indirect BP < 125/80 mmHg); 2) normotensive (NT) group, 84 controls matched for age and sex; 3) WHO-I group, 95 hypertensive patients with WHO stage I (office BP > or = 140/90 mmHg and 24-h BP > or = 125/80 mmHg); and 4) WHO-II group, 69 hypertensive patients with WHO stage II. Their BPc and heart rate (HR; HRc, clinic HR) values were measured by a BP-ECG monitoring device in the outpatient clinic. Power-spectral analysis was used to obtain the ratio between the low-frequency component (LF) and high-frequency component (HF) of ECG-RR variability (LF/HF = LH). Twenty-four-hour indirect BP (and BP0) and base HR (HR0) were measured by a portable device (TM2425) at 30-min intervals. Then, DeltaBPc (= BPc - BP0) was estimated by performing linear multivariate analysis applying the model equation DeltaBPc = (BPc -alphaLH)(1-betaHR0/HRc) + epsilon to the above variables (alpha and beta, constant values; epsilon, error). This model equation made it possible to estimate BP0 (and DeltaBPc) with a high coefficient of correlation (r > or = 0.85, mean of error less than 0.82 +/- 5.9 mmHg). The predictive accuracy for discrimination between WCH and sustained hypertension (WHO-I and WHO-II groups) by this equation was 88%. The new DeltaBP-estimation device (BP-ECG monitor) enabled us to infer BP0 and is therefore useful in estimating WCH in the outpatient clinic.     

Pharmacological properties of MO-8282, a novel antidepressant

The pharmacological properties of MO-8282 (1,2,3,4-tetrahydro-2-methyl-9H-dibenzo [3,4: 6,7]cyclohepta [1,2-c]pyridine maleate) as an antidepressant were investigated. At doses 10 times less than those of amitriptyline, MO-8282 showed similar potencies in reducing the duration of immobility during forced swimming in rats and in potentiating stereotype induced by L-DOPA. Intermediate doses of MO-8282 reduced the duration of immobility during forced swimming, in mice as well, suppressed muricide behavior of olfactory-bulbectomized rats and antagonized clonidine-induced suppression of exploratory activity in mice. MO-8282 moderately antagonized the ptosis but not the hypothermia induced by reserpine in mice. MO-8282 exhibited weak antagonism against the tremor, lacrimation and diarrhea induced by tremorine, but its activity was milder than that of amitriptyline. The uptake of noradrenaline into rat hypothalamic synaptosomes was inhibited by MO-8282 at concentrations 20 times less than equally effective doses of amitriptyline, but the uptake of dopamine or serotonin was unaffected by MO-8282. A single oral administration of MO-8282 at a dose of 30 mg/kg accelerated noradrenaline turnover, but did not affect dopamine and serotonin turnover in the rat brain. MO-8282 strongly inhibited noradrenaline-, histamine- or adenosine-sensitive adenylate cyclase activity of guinea pig brain. Its mode of action differed from that of imipramine, rather resembling that of mianserin. MO-8282 did not affect monoamine oxidase activity of rat liver. These results suggest that the pharmacological characteristics of MO-8282 are different from those of tricyclic antidepressants and rather similar to those of mianserin, but more potent. The results, therefore, indicate that MO-8282 is possibly a novel antidepressant.     

A case of parathyroid hormone-related peptide producing gallbladder carcinoma presenting humoral hypercalcemia of malignancy]

Humoral hypercalcemia of malignancy (HHM) in neoplastic syndrome has been most commonly reported in squamous cell carcinoma. Gallbladder carcinoma with HHM is uncommon. In this report, we describe a male case of gallbladder carcinoma with marked hypercalcemia and a high level of serum parathyroid hormone-related peptide (PTHrP). An immunohistochemical examination using PTHrP was also positive.     

Epinephrine is an enhancer of rat intestinal absorption.

Some physiological substances, including acetylcholine and nitric oxide, are useful candidates for stimulation of intestinal absorption of drugs. In the present study, we elucidated the ability of epinephrine (Epi) to stimulate the intestinal absorption of drugs. We evaluated the ability of Epi to enhance absorption of macromolecules using dextran (Mw 4000 Da), which is poorly absorbed from the intestine, as a model compound in situ in a closed loop of the rat jejunum. Treatment of the jejunum with Epi resulted in significant increase in absorption of dextran in a dose-dependent fashion. The area under the curve (AUC) from 0 to 4 h in the Epi-treated jejunum was 13-fold higher than that in the vehicle-treated jejunum. The absorption-enhancing activity of Epi was 40-fold higher than that of caprate, a clinically used absorption-enhancer of drugs. In the experimental conditions used in this study, histological injury of the mucosa and perturbation of the mucosal membrane were not observed in the Epi-treated jejunum. Treatment with an antagonist of alpha-adrenergic receptors attenuated the stimulation of intestinal absorption by Epi, and treatment with an agonist of alpha-adrenergic receptors resulted in enhancement of intestinal absorption. While an antagonist of beta-adrenergic receptors enhanced the absorption-enhancing effect of Epi, an agonist of beta-adrenergic receptors stimulated intestinal absorption. These results indicate that stimulation of adrenergic receptors may be a novel strategy for intestinal absorption of drugs.     

ENDOSCOPIC OBSERVATION OF MUCOSAL SPREAD LESION OF CHOLANGIOCARCINOMA USING PERORAL CHOLANGIOSCOPY WITH NARROW BAND IMAGING

A 69‐year‐old man was admitted to Toho University Omori Medical Center complaining of icterus. Abdominal computed tomography, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography were suspicious of cholangioma of inferior bile duct. Peroral cholangioscopy using narrow band imaging (NBI) was performed and it was possible to diagnose the mucosal spread lesions of cholangioma. Histological findings reflected the endoscopic findings. Mucosal spread lesions of cholangiocarcinoma were successfully diagnosed using the CHF‐B260 for NBI.