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.     

Relationship between in vivo first-order intestinal absorption rate constant and the membrane permeability clearance

An attempt was made to explore the quantitative relationship between the intestinal absorption data obtained from in vivo studies and in situ perfusion studies. The time course of the fraction remaining to be absorbed of L-glucose, erythritol, and urea in the small intestine following the intrajejunal administration to rats was described by a one-compartment model. Thus derived first-order intestinal absorption rate constants (ka) obtained from the in vivo studies in rats were compared with the membrane permeability clearances (CLa,m) estimated in a single-pass perfusion system. Not only were ka and CLa,m in the same increasing order of L-glucose less than erythritol less than urea, but also the operational luminal volumes given as CLa,m/ka were in agreement with the in vivo luminal volume of jejunum estimated by an inulin dilution method. This result suggests that the in vivo intestinal absorption rate (or ka) can be correlated with the intestinal membrane permeability (or CLa,m) by taking the in vivo luminal volume into account.     

The relationship between jaw deformity and scoliosis

Objectives To analyze the relationship between lateral displacement of the mandible and scoliosis. Methods From April 2002 through July 2003, we examined posteroanterior cephalometric radiographs and chest X-rays from 85 patients with jaw deformities and a control group of 20 patients with no jaw deformities. To measure the lateral shift of the mandible, we drew a horizontal baseline (X axis) on the cephalogram connecting the intersection of the external margins of the orbits and the most lateral points of the greater wings of the sphenoid. A vertical baseline (Y axis) was then marked perpendicular to the X axis, intersecting the ethmoid crista galli. Then, we measured the lateral displacement of the mandibular mentum from the Y axis. Displacement to the right was designated positive; that to the left was designated negative. Cobb's method was used to measure scoliosis curves on chest X-rays; the direction of the curve was designated similarly. Results Of the 85 patients with jaw deformity, 23 (27.1%) had a Cobb angle exceeding 10°. None of the control group had scoliosis exceeding 10°. No correlation was found between the direction of mandibular displacement and the direction of scoliosis. Conclusion This study suggests a relationship between jaw deformities and scoliosis, as scoliosis was found in 27.1% of the patients with a main complaint of jaw deformity.     

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.     

Preparation of two-drug composite microparticles to improve the dissolution of insoluble drug in water for use with a 4-fluid nozzle spray drier.

In this study, we used a novel 4-fluid nozzle spray drier to prepare composite microparticles of a water-insoluble drug, flurbiprofen (FP), and a water-soluble drug, sodium salicylate (SS), for the purpose of improving the water solubility of FP. An ethanol solution of FP and an aqueous SS solution were simultaneously introduced through different liquid passages in the 4-fluid nozzle spray drier and then spray-dried. Quantitative elemental analysis suggested that the FP/SS ratio in each composite microparticle was nearly the same as the formulation ratio. We also found that SS and FP exist in a low crystallinity state in the composite particles. Release of FP from dissolved composite microparticles was markedly improved because of an increase in the effective surface area following rapid dissolution of SS. This study shows that it is possible to prepare FP-SS composite microparticles using a 4-fluid nozzle spray drier in single process and that this can improve the ability of FP to dissolve in water.     

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.