Comparison of anticonvulsant effects of valproic acid entrapped in positively and negatively charged liposomes in amygdaloid-kindled rats

Intraperitoneal injection of free valproic acid (VPA) suppressed amygdaloid-kindled seizure 1 h after injection in rats, but had no effect at 24 h. VPA entrapped in positively charged liposomes showed a prolonged anticonvulsant effect lasting for 2 days, while the effect evaluated at 1 h was not different from that with free VPA. VPA entrapped in negatively charged liposomes exerted a significantly stronger effect at 1 h than did free VPA, while it had no significant effect at 24 h. These results suggest that surface charges on liposomes play an important role in modifying the anticonvulsant effect of VPA.     

Altered gastric emptying in the head-injured patient: relationship to feeding intolerance

Most patients with moderate to severe head injury initially do not tolerate enteral feedings postinjury. This intolerance is more prolonged than that found in patients suffering other types of trauma. The authors prospectively evaluated 12 patients with moderate to severe head injury (Glasgow Coma Scale score between 4 and 10) throughout their hospitalization for liquid gastric emptying as a possible mechanism for intolerance to enteral feeding. During Week 1, the majority of patients displayed a delay in gastric emptying. Patients also displayed an abnormal biphasic response (gastric emptying faster than normal during the early stage but prolonged later). By Week 2, many patients still had delayed and abnormal biphasic responses to gastric emptying. By Week 3, an improvement was observed with the majority of patients exhibiting rapid gastric emptying, but delays and abnormal biphasic responses were still seen. Patients who initially had rapid or normal gastric emptying tolerated full-strength full-rate feedings significantly earlier compared with those who experienced delayed gastric emptying (8.5 +/- 0.5 days vs. 13.7 +/- 3.2 days, p less than 0.001). All patients tolerated full-strength full-rate feedings by Day 16 postinjury (range 7 to 16 days) except the two patients who displayed delayed gastric emptying for prolonged periods of time (mean 25 days). This is the first study to longitudinally evaluate gastric emptying following head injury. The authors suggest that patients with moderate to severe head injury often experience alterations in gastric emptying which may affect their ability to tolerate enteral feedings.     

Intestinal active absorption of sugar-conjugated compounds by glucose transport system: implication of improvement of poorly absorbable drugs.

The intestinal absorption of glucose- and galactose-conjugated compounds was studied in the everted sac of the rat small intestine. The absorption clearance of p-nitrophenyl beta-D-glucopyranoside (p-NPglc) at 250 microM in the mucosal side (4.45 +/- 0.34 microL/min/cm, mean +/- SE, N = 4), calculated by dividing the absorption rate by the drug concentration, was significantly decreased (0.476 +/- 0.036 microL/min/cm) in the presence of 1 mM phloridzin, an inhibitor of glucose transport, and in the absence of Na+, a cosubstrate of the glucose transport carrier (0.424 +/- 0.018 microL/min/cm). The absorption clearance of p-NPglc was decreased as its concentration increased. In the same experiment, the absorption clearance of p-nitrophenyl beta-D-galactopyranoside (1.99 +/- 0.23 microL/min/cm) was also significantly decreased in the presence of phloridzin and in the absence of Na+. However, the absorption clearance of p-nitrophenyl beta-D-mannopyranoside (0.811 +/- 0.013 microL/min/cm) was low and not significantly decreased in the presence of phloridzin (P greater than 0.1). Furthermore, the absorption clearance of beta-naphthyl beta-D-glucopyranoside and beta-naphthyl beta-D-galactopyranoside was also significantly decreased in the presence of phloridzin (P less than 0.001). These results indicated that the glucose and galactose moieties provided these compounds with a new route by way of the glucose transport carrier for intestinal absorption.     

Periodic psychosis of puberty: a review on near-monthly episodes.

Published cases of periodic psychosis of puberty and related papers were reviewed. The clinical picture is near-monthly recurrence of episodes of stupor or excitement lasting about 1 or 2 weeks, which are accompanied by delusion and in some cases also by hallucinations or confusion. This condition was found to occur more commonly in girls than in boys, and in half of the girls reported the episodes tended to start a few days before menses. Adolescents with mental retardation were more commonly affected, and this suggests that organic brain damage may play a role in the etiology in some cases. Short-term prognosis is usually favorable, but at long-term follow-up, nearly half of them were found to be suffering from affective or schizophrenic illness. The clinical importance of recognizing this psychosis early in the course of illness is emphasized.     

Serum immunoreactive beta-glucuronidase determined by an enzyme-linked immunosorbent assay in patients with hepatic diseases.

An enzyme-linked immunosorbent assay (ELISA) was developed for human beta-glucuronidase, using a specific polyclonal antibody raised against the purified enzyme. beta-Glucuronidase from human liver consisted of three subunits with molecular mass of 76, 64 and 18 kDa. The assay offered a specific, sensitive and convenient means of measuring immunoreactive beta-glucuronidase in human sera. beta-Glucuronidase activity determined by the conventional method appeared to be extremely low, indicating that in human sera beta-glucuronidase exists in an enzymatically inactive form. The sensitivity of the assay permitted the detection of 1-100 ng of purified beta-glucuronidase. A mean serum level in normal subjects was 108 +/- 25 ng/ml (mean +/- S.D.). A high level of beta-glucuronidase was found in sera of patients with severe hepatocellular necrosis, including liver cirrhosis (152 +/- 130 ng/ml) and chronic active hepatitis (220 +/- 99 ng/ml), whereas no significant increase of the enzyme protein was observed in chronic persistent hepatitis (102 +/- 42 ng/ml). beta-Glucuronidase was also increased in sera of patients with primary hepatoma (156 +/- 125 ng/ml). The immunoreactive beta-glucuronidase determined in this assay was thought to be a supplementary serological indicator for hepatocellular necrosis.     

Papillary thyroid cancer and its surgical management.

The surgical management in papillary thyroid cancer has been highly controversial. In the Department of Surgery (II), Kanazawa University Hospital, the surgical management especially for cervical lymph node metastases has changed since 1973 from a conservative approach to an aggressive one. In order to determine whether an aggressive approach is warranted, a retrospective multivariate analysis was carried out on 106 cases of papillary thyroid cancer. The patients have been followed for 10-28 years. Multivariate analysis was conducted following Cox's model. By this analysis, aggressive management appeared to have no impact on survival or relapse-free survival. However, age, sex, tumor size, and cervical lymphadenopathy were confirmed to be important prognostic factors in survival and/or relapse-free survival.     

The effect of oral appliance therapy on blood pressure in patients with obstructive sleep apnea

The objective of the study was to investigate the effects of oral appliance (OA) therapy on ambulatory blood pressure in patients with obstructive sleep apnea (OSA). Eleven OSA patients who received OA therapy were prospectively investigated. Ambulatory blood pressure was measured for 20 h from 4:00 p.m. to 12:00 noon the next day using an ambulatory blood pressure monitor. The Respiratory Disturbance Index (RDI) was measured in the pretreatment and posttitration periods. The OA was titrated to reach a therapeutic jaw position over 2 to 8 months, and posttitration measurements were repeated. At posttitration, the RDI was significantly decreased from a mean (SD) of 24.7 (20.1) to 6.1 (4.5). Significant reductions in diastolic blood pressure (DBP) and mean arterial pressure (MAP) were found for the 20-h periods, and systolic blood pressure (SBP), DBP, and MAP while asleep. The mean values were 79.5 (5.5) to 74.6 (6.0) for DBP and 95.9 (5.4) to 91.2 (5.9) for MAP, for over a 20-h period, and 118.4 (10.0) to 113.7 (9.1) for SBP, 71.6 (8.0) to 67.2 (7.9) for DBP, and 88.4 (8.0) to 83.9 (7.5) for MAP, while asleep. This study suggests that successful OSA treatment with an OA may also be beneficial to lower blood pressure in OSA patients, as previously suggested for nasal continuous positive airway pressure therapy. This study was conducted in the Division of Orthodontics, The University of British Columbia, Canada     

Case of Heerfordt's syndrome with prolonged peripheral nerve involvement]

A 28-year-old man complaining of myiodesopsia was given a diagnosis of uveitis. Subsequently he complained facial nerve palsy and enlargement of parotid gland. Heerfordt's syndrome was diagnosed based on the results of several examinations. Facial nerve palsy, enlargement of the parotid gland and uveitis were improved by systemic corticosteroid therapy. At present he is receiving systemic corticosteroid therapy, but numbness in the mouth, thought to be the involvement of the trigeminal nerve, remains. Systemic corticosteroid therapy is usually effective for most cases with Heerford's syndrome. On the other hand, there are some cases with the prolonged peripheral nerve involvement despite systemic corticosteroid therapy, as seen in this case. If peripheral nerve involvement is prolonged, it is necessary to consider small-fibre neuropathy as one possible cause.     

Pathogenesis of progressive muscular dystrophy: studies on free radical metabolism in an animal model

Evidence to suggest the presence of abnormal metabolism of oxygen free radicals in progressive muscular dystrophy is presented using an animal model. In the superficial pectoral muscles of dystrophic chickens, enzyme activities regulating the metabolism of oxygen free radicals, i.e., catalase, superoxide dismutases and glutathione peroxidase, were significantly elevated within 1 week of hatching. Activities of related enzymes, i.e., glutathione reductase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase were also elevated. In contrast, the specific activity of phosphofructokinase, the rate-limiting enzyme of the glycolytic pathway, was normal during the first 4-week period. These results suggest that there is an increased turnover of oxygen free radicals in the dystrophic muscle. This concept appears important in a further investigation of the pathogenesis and treatment of progressive muscular dystrophies.     

Infantile subcortical leukohypodensity demonstrated by computed tomography

We reviewed the computed tomography scans of 126 term infants, ages 1-6 months; leukohypodensity was found just under the cerebral cortex (subcortical leukohypodensity [SLD]) in 3 infants (2.4%) at 1-3 months of age. On subsequent computed tomography at over 4 months of age, SLD had disappeared and anterior horn predominant dilatation of the lateral ventricles had appeared. Only 1 patient with a distinct SLD had a poor neurodevelopmental outcome: spastic diplegia. SLD in our patients is believed to be closely related to subcortical leukomalacia because of the similar location and age distribution. Transient SLD may be a mild form of cystic SLD which would require careful computed tomography follow-up examination in early infancy.