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.     

An increase in water content of mouse erythrocytes infected with Plasmodium yoelii

Mean cell volume and mean cell water content were examined in Plasmodium yoelii-infected mouse erythrocytes by gas chromatography and 3H-sucrose. Mean cell volume increased by 16% in infected erythrocytes with late trophozoites and schizonts. Mean cell water content further increased by 23% in the infected erythrocytes. Measurement of the erythrocyte potassium and sodium concentrations by an atomic absorption spectrophotometer revealed that the infected erythrocytes contained highly elevated sodium and slightly reduced potassium levels when calculated per single erythrocyte. It is suggested that membrane transport processes of sodium and potassium are changed in P. yoelii-infected erythrocytes and that a passive inflow of sodium takes place, which results in an increase in intra-erythrocytic water content.     

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.     

Anti-tumor activity of human recombinant TNF against human malignant glioma cell lines and combined effect with Hu INF-beta

Human TNF was detected fairly recently and at present the anti-tumor activity of human recombinant TNF is being examined against various malignant tumors of human origin. In the present study, we report the anti-tumor activity of recombinant human TNF against human malignant glioma cell lines in vitro and in vivo, in addition to its combined effects with HuIFN-beta. The in vitro study was conducted as follows. Thirteen human glioma cell lines were exposed to 100 U/ml TNF, 1,000 IU/ml HuIFN-beta, or both, and the suppression rate was calculated on days 3, 5 and 7. In the in vivo study, nude mice carrying a human glioma cell line, KMS II, in the subcutaneous tissues were divided into groups and drugs were administered intratumorally as described below. 1) control, 2) TNF 5,000 U single administration, 3) TNF 5,000 U, intermittently administered (once/week for two weeks), 4) TNF 5,000 U, continuously administered (3/week for two weeks), 5) HuIFN-beta 50 X 10(4) IU (3/week for two weeks), and 6) combination of 4) with 5). Results of the in vitro study revealed some suppressive effects on proliferation of tumor cells on day 7 in all 13 glioma cell lines examined with 100 U/ml TNF. And also, especially in 8 of 13 cell lines, the suppression rate was more than 30%. The suppressive effects of TNF were augmented by combined use of HuIFN-beta in all cell lines, giving a range of suppression of 67.8 to 99.3%. The in vivo study revealed that the mean tumor weight ratios (control = 100%) on day 19 (the end of the experiment) were as follows; single administration of TNF: 41.3%, intermittent: 46.7%, continuous: 26.7%, HuIFN-beta: 65.9%, combination: 18.5%. Statistical analysis disclosed significant suppressive effects on tumor proliferation between the control group and 3 TNF-administered groups (single, intermittent, and continuous) and that suppression in the continuously administered group was more severe in comparison with the group given single administration. Moreover, it was suggested that combination therapy with TNF and Hu IFN-beta was more effective than a single therapy with TNF only or HuIFN-beta only. From the results described above, it was found that human recombinant TNF had some cytotoxic effects against human malignant gliomas in vitro and in vivo, although the degree of cytotoxicity was not always higher in comparison with the effects of TNF.     

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.     

Periodic oscillation of intracranial pressure in ventricular dilation: a preliminary report

Artificial pressure waves (PWs) were generated by manual inflation of a balloon in the trigonum of the lateral ventricle in seven adult mongrel dogs with normal cerebrospinal fluid (CSF) circulation. In 14 of 16 series of continuous appearances of artificial PWs, local shifts of the brain were successfully monitored using small strain-gauge sensors at the periventricular structures in these animals. Of the 14 series, 13 showed displacements of the periventricular structures, suggesting ventricular dilation. These results did not always correlate with macroscopic findings. They are thought to be due largely to periventricular oedemas and, in part, non-uniform dilations of the ventricles during PWs. We conclude that a water hammer formed by reflection of an increased pulse pressure of PWs at the site of CSF absorption causes a shift of CSF from the ventricle to the periventricular structures through the wall of the ventricle. This phenomenon appears amplified in patients with impaired CSF absorption. Thus, PWs have a pathological role in the progress of ventricular dilation in patients with normal pressure hydrocephalus.