Magnetic resonance imaging study of the brain in aged volunteers: T2 high intensity lesions and higher order cortical function

Abstract The aims of the present study were to clarify the findings of magnetic resonance imaging (MRI) in the aging brain, and to relate the MRI findings to higher order cortical function. A total of 118 healthy aged volunteers (41 men, 77 women) underwent cranial MRI electroencephalography (EEG), Benton visual retention test (BVRT) and interview. The subjects had no past history or clinical evidence of cerebrovascular disorder, head trauma or dementia and were living at home without any difficulty. The majority of the subjects have participated in this series of studies since 1982. Using a 1.5 T superconductive MR instrument, T1-weighted, proton density and T2-weighted images were obtained. The MRI data were rated visually by regarding 12 items according to fixed criteria. T2 high signal intensity (T2HSI) lesions were found in 69.5% of subjects, the prevalence of which increased with age. T2HSI lesions were most frequently found in the basal ganglia (61.9%), followed by the thalamus (39.0%), parietal lobe (37.0%), temporal lobe (12.7%) and pons (8.5%). Among these lesions, lacunar infarction showed low signal intensity in T1-weighted images and was found in 24.6% of subjects, the prevalence also increasing with age. These findings, including brain atrophy determined according to similar criteria, were correlated closely with the subjects' age. The results of BVRT showed a close relation with T2HSI, suggesting that T2HSI may influence cognitive function. When the subjects were classified according to the presence of T2HSI, lacunar infarction and EEG abnormalities, brain atrophy was significantly milder in a group of subjects with T2HSI(-), lacunar infarction(-) and normal EEG than in the other groups. This suggests that changes seemingly representing physiological aging may be promoted by another pathological which also exerts influences on higher order cerebral function.     

A Case of Pachydermoperiostosis with Watery Diarrhea,Giant Gastri Rugae,and Endocrine Disorder

Abstract: A 31-year-old man, cook, who had had persistent watery diarrhea for about a month visited our hospital. He had already been diagnosed as having pachydermoperiostosis. An examination of the upper gastrointestinal tract revealed that he had giant gastric rugae. The histology was compatible with hypertrophic gastritis accompanied with marked hyperplasia of the fundic gland and foveolar epithelia. The output of gastric juice was high in volume, although its acidity normal. The barium transit time of the small intestine was reduced to 15 minutes. His diarrhea was, thus, considered to be induced by gastrointestinal hyperfunction. The patient's glucose tolerance was abnormal and basal Cortisol secretion level was high. Pachydermoperiostosis has been the focus of attention for skin and bone changes, and the frequency of this disease with endocrine disorders seems rather high, but accompanying gastrointestinal disorders have so far not often been reported in Japan. The results of our investigation strongly suggest that pachydermoperiostosis is a systemic disease.     

Solitary nodular Langerhans cell histiocytosis

We report a 3-month-old girl with a solitary variant of congenital self-healing reticulohistiocytosis, one type of Langerhans cell histiocytosis.     

Alteration of Activities of Hepatic Antioxidant Defence Enzymes in Developing Chick Embryos After Glucocorticoid Administration - A Factor to Produce Some Adverse Effects?

Liver tissue is one of the principal targets of glucocorticoids, therefore changes in the balance between hepatic oxidative and reductive capacity may greatly influence adverse effects of glucocorticoid therapy. In this study, effects of glucocorticoid on the activities of hepatic antioxidant defence enzymes were examined by using developing chick embryos. After the administration of 0.25 μmol hydrocortisone sodium succinate, a typical glucocorticoid, to 15-day-old chick embryos, glutathione peroxidase, glutathione reductase, catalase and superoxide dismutase in the liver generally began to decrease at around 4 h, reaching 60–70% of control levels between 24 and 48 h. These changes were observed much earlier than the elevation of the hepatic thiobarbituric acid reacting substance (TBARS) level which began to increase from 20 h, reaching about six times the control level at 48 h after hydrocortisone administration. Conversely, the elevated TBARS level decreased back to the normal level with the recoveries of these enzyme activities. Furthermore, it was found that the aniline hydroxylase activity, measured as a marker of oxidative activity, began to increase after around 12 h. These results suggested that TBARS levels were possibly produced by the suppression of antioxidant defence abilities and the significant induction of oxidative activity in the liver by glucocorticoid. As the elevated TBARS in the liver can be distributed to tissues, TBARS will be involved in the occurrence of some of the glucocorticoid-induced adverse effects such as cataract formation.     

Pharmacokinetics and pharmacodynamics of ()-sotalol in healthy male volunteers

1 We investigated the pharmacokinetics and pharmacodynamics of (±)-sotalol administered orally to healthy male volunteers in single doses of 40, 80 and 160 mg and in multiple doses of 80 mg twice daily for 7 consecutive days.
2 In the single dose studies, the half-life of (-)-sotalol (7.2-8.5 h) was significantly ( P < 0.01) shorter than that of (+)-sotalol (9.1-11.4 h) while the renal clearance of (-)-sotalol (110.6-126.4 ml min^-1) was significantly ( P < 0.01) faster than that of (+)-sotalol (102.2-110.1 ml min^-1). In the multiple dose studies, similar differences in the pharmacokinetics of (+)- and (-)-sotalol were observed. In addition, the pharmacokinetics of both (+)- and (-)-sotalol on day 4 were shown to be essentially the same as those on day 7.
3 In pharmacodynamic examinations, (±)-sotalol prolonged QTc intervals on electrocardiograms dose-dependently after single doses of 80 and 160 mg (3.81 ± 2.96%, 13.23 ± 5.66%). The correlation between the plasma concentration of (±)-sotalol and prolongation of QTc intervals was nearly linear, and showed no hysteresis.
4 In conclusion, we demonstrated that QTc interval was prolonged with a linear correlation to the plasma concentration of (±)-sotalol. In addition, our study suggested that differences in the pharmacokinetics of (+)- and (-)-sotalol may be attributable to faster urinary excretion of (-)-sotalol.     

Thymic Hypoplasia due to a Bis-diamine

Bis(dichloroacetyl)diamine is capable of producing characteristic congenital malformations in high incidence. Wistar rats were given 200 mg/day of bis-diamine via a gastric tube on gestation days 9, 10 and 11. The fetuses of 14, 16, 18, 20 days and new born rats were examined using light and electron microscopes as well as rat T-cell surface markers. The thymus rudiment in rats treated with bis-diamine has been compared to the normal at each stages. A high incidence of aplasia or hypoplasia of the thymus was observed in treated groups. Histological studies of those revealed a short delay in appearance of lymphocytic cells in the thymus, which initially were blast like and later small lymphocytes, and also a delay in cortical and medullary differentiation of the thymus. Immunohistological studies using anti rat T-cell monoclonal antibodies confirmed the histological findings which show a delay of the development of the thymus. Bis-diamine induced anomalies were similar to those of the human primary immunodeficiency syndrome, particularly the DiGeorge syndrome.