Decreased cyclosporin A absorption after treatment with GoLytely lavage solution in rats

Abstract— Recently we observed a case in which the cyclosporin A absorption decreased after treatment with GoLytely lavage solution in a kidney transplant patient. In this study, we confirmed the decrease of the blood concentration of cyclosporin A after oral administration by GoLytely (Macrogol 3350) based on experiments with rats. The peak blood cyclosporin A concentration, and the area under the blood drug concentration-time curve from 0 to 24 h in the GoLytely-administered group were significantly lower than the control group. In the case of gastrointestinal dysfunction such as diarrhoea, or in treatment with laxatives such as GoLytely lavage solution, whole blood cyclosporin levels must be carefully monitored, and intravenous cyclosporin A may be more suitable for providing adequate immunosuppression.     

Clinical Evaluation of Brushing Cytology and Biopsy of the Pancreatic Duct in Patients with Mucin Producing Tumor of the Pancreas

Abstract: A cytological study of pure pancreatic juice obtained endoscopically after brushing the lesion of the pancreatic duct urns performed in 10 patients with mucin producing tumors of the pancreas. In 6 of these 10 patients, biopsies from the lesion in the pancreatic duct were also carried out endoscopically. The brushing cytology in all 6 patients with mucin producing carcinoma of the pancreas, except for the sidebranch type, showed cellular atypism and the cytological diagnoses were Class IV or Class V. The results of the brushing cytology in the patients assumed clinically benign were Class I ? Class III. Biopsy results in 4 patients with mucin producing carcinoma of the pancreas indicated that one of them had adenocarcinoma, and the other 3 had atypical hyperplasia which suggests the existence of malignancy. In the patient with adenoma, diagnosis of the biopsy specimen revealed hyperplasia only. It was concluded that cytology and biopsy of lesions in the pancreatic duct are a valuable way of assessing mucin producing tumors of the pancreas before surgery.     

Significance of Initial Induction Therapy to Long-Term Survival in Malignant Lymphoma

Seven patients with malignant lymphoma had complete remissionsof from more than 50 to more than 81mo. These patients showeda direct relationship between length of initial remission andsurvival. Six patients had survival periods after cessationof maintenance therapy that extended from more than 38 to morethan 71 mo. The histologic subtypes of the patients were: inHodgkin's disease, two cases of mixed cellularity and one ofnodular sclerosis, and in non-Hodgkin's lymphoma, three casesof diffuse large cell type and one of diffuse medium-sized celltype.     

The differences of self-ratings of sleep quality associated with epinephrine and wake time during 4 hour sleep

Abstract The present study examined the differences of self-ratings of 4h sleep in three states: L-WE, where the percentage of waking time and urinary epinephrine are low (< 20% waking time); H-W, where the percentage of waking time and epinephrine levels increase along the basal regression line as determined by a previous study (20–100% waking time and < 7 ng/min); H-E, where epinephrine levels increase more than expected from the basal regression line for the two parameters (> 7 ng/min). Eight healthy male subjects participated twice in a 4 h polysomnograph experiment with four types of sleep onset (total of 64 observations). In group L-WE (52 observations for eight subjects), there were no excessively negative feelings on sleep latency, sleep depth, and feelings of sleep compared with usual sleep according to the questionnaire. Subjective sleep diagrams in group L-WE were similar to polysomnographic findings. Thus, group L-WE was thought objectively and subjectively to have a good sleep state. Groups H-W (eight observations for four subjects) and H-E (four observations for two subjects) had negative feelings regarding sleep depth and feelings of sleep compared with usual sleep. Approximately half the group H-W underrated their sleep compared with objective diagrams, while all cases in group H-E remarkably underrated their sleep in the subjective diagrams. The state of remarkable adrenal medullary secretory activity seen in group H-E and that of the slightly increased activity shown in group H-W were included in poor sleep states objectively and subjectively.     

PREDICTION OF THE THERAPEUTIC DOSE FOR BENZODIAZEPINE ANXIOLYTICS BASED ON RECEPTOR OCCUPANCY THEORY

Many benzodiazepines (BZPs) are now used as anxiolytics with nearly 200-fold variety of therapeutic doses. The variation of the doses of BZPs is due to differences both in their pharmacokinetics and in their receptor binding characteristics. The purpose of this study is to clarify the mechanism of the differences in therapeutic dose by retrospective analyses and to develop a system for the quantitative estimation of optimal doses of BZPs. The values of receptor dissociation constant (K_d), which indicates the binding affinity of each BZP at the receptor site, were obtained from a number of works based on in vitro binding experiments. The plasma unbound concentrations of the BZPs and their active metabolites were calculated using the reported values of their total plasma concentrations after average oral doses of the BZPs and the values of their plasma unbound fractions, which were also taken from the literature. There were log-linear relationships between the K_d values of BZPs and their average therapeutic doses or maximum plasma concentrations, but the correlation coefficients were relatively small (r >0·77). In contrast, a good log-linearity (r =0·96) was observed in the correlation between their K_d values and the effective plasma unbound concentrations considering the active metabolites. This finding indicates that the receptor occupancy after administration of therapeutic dose of BZPs is consistent (52·3±3·2%) among the BZPs. In this study, we also develop a possible system for estimating the appropriate doses of BZPs based on receptor occupancy theory. ©1997 by John Wiley & Sons, Ltd.     

Genetic contribution to the relationship between social role function and depressive symptoms in Japanese elderly twins: a twin study

Background: Social role function is the capacity to maintain interpersonal relationships and is essential for being independent in the community. Limitations in social role function often coexist with depressive symptoms, suggesting a possible common mechanistic basis. We investigated whether the observed association between these traits is mainly a result of genetic or environmental influences. Methods: In 2008, a questionnaire was sent to 745 male twins aged 65 years and older. Our sample included 397 male twins. The number of monozygotic twins was 302, and dizygotic was 95. Among the twin pairs for whom data were available for both twins, 75 twin pairs (150 individuals) were monozygotic and 28 pairs (56 individuals) were dizygotic. Social role function was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Depressive symptoms were measured by the 15‐item version of the Geriatric Depression Scale. Relative importance of genes and environments for the phenotypes was calculated using structural equation analyses. Results: Our results show that genetic influence was the major contributor to the relationship between social role function and depressive symptoms, and non‐shared environmental influence was important for overall variation in each trait. Conclusions: We concluded that focusing on a non‐shared environment is an essential approach for maintaining social role function and psychological well‐being. It is suggested that treatments specific to depressive symptoms are more effective than indirect intervention targeting social role function.     

A Comparative Pharmacokinetic-Pharmacodynamic Study of the Electrocardiographic Effects of Epinastine and Terfenadine in Rats

The effects of epinastine hydrochloride and terfenadine on electrocardiographic (ECG) parameters in rats were investigated from a pharmacokinetic and pharmacodynamic perspective. Epinastine hydrochloride (1 or 3 mg kg^?1 h^?1) or terfenadine (5, 10 or 15 mg kg^?1 h^?1) was intravenously infused into rats anaesthetized with urethane and α-chloralose. The changes in the QT interval derived from limb lead II and the chest lead, heart rate and PR interval were analysed. The time-course of the plasma drug-concentration of each drug was also investigated. Terfenadine prolonged the QT interval in an infusion-rate-dependent manner; its EC50 value was 792–1039 ng mL^?1. An obvious QT prolongation was, moreover, observed even at a plasma terfenadine concentration of 100–200 ng mL^?1, which is clinically quite high, but might be achieved under a definite condition such as a restrained terfenadine metabolism. Terfenadine also induced PR prolongation and bradycardia in an infusion-rate dependent manner. Epinastine slightly increased the heart rate, but did not affect any of the other ECG parameters even at a plasma concentration of 400 ng mL^?1, which is more than 10 times the maximum concentration attained after an ordinary dosage regimen in man. We conclude that epinastine might have an advantage over terfenadine in avoiding adverse electrocardiographic reactions.