Munehiko Morishita

The clinical course and prognosis of patients with severe, moderate or mild sarcoidosis

During 1978-1990, 346 patients with sarcoidosis were enrolled in our institute. Of 346 patients, 295 patients were eligible for evaluation on the clinical course and prognosis. According of their clinical presentations, they were classified into 3 groups; severe, moderate and mild sarcoidosis. Of the 295 patients, 27 (9.2%) were classified as severe sarcoidosis who developed serious illness including involvement of the heart (8), lung (6), muscles (5), eyes (3), central nervous system (CNS) (3) or liver (2). The mean interval between the onset of disease to severe disability was 58.3 months. The interval was particularly long in those patients who presented with either pulmonary (100.8 months) or liver sarcoidosis (108 months). Of the 27 patients with severe sarcoidosis, 8 (29.6%) gradually became worse towards the end of their clinical course despite only mild clinical signs and symptoms at the first presentation. Therefore, the initial clinical symptoms and findings, including ocular involvement. ECG abnormalities, negative reaction to PPD, high value of serum angiotensin converting enzyme (ACE) and a small number of lymphocytes in peripheral blood, were not useful in predicting prognosis. The relationship between the maximum serum ACE value during the clinical course and the duration of the active phase was statistically significant in the 123 patients who were monitored throughout their course, suggesting that the maximum serum ACE may be a marker for assessing prognosis. Corticosteroid was administered to 76 patients (22%) with serious systemic involvement. They included 26 (96.4%) of the 27 severe sarcoidosis and 50 (37.9%) of the 132 moderate sarcoidosis. Patients with mild sarcoidosis did not receive corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum Lysozyme Levels and Clinical Features of Sarcoidosis

Abstract. Serum lysozyme is used as a marker of sarcoidosis disease activity. In this study we examined the association between lysozyme levels and the clinical features of sarcoidosis and thus the clinical usability of this parameter in a large population. One hundred ten sarcoidosis patients from central Japan were examined for clinical features and serum lysozyme level at the first visit to our hospital and on a regular basis thereafter. The sensitivity of lysozyme for predicting sarcoidosis was 79.1%, whereas that of serum angiotensin-converting enzyme (ACE) was 59.0%. Even in the cases without an elevated serum ACE level, a value of 72.1% was obtained. The serum lysozyme level demonstrated a significant tendency to increase with the number of organs involved (p < 0.01). There were significant differences among the four radiographic stages (p < 0.05). The maximum serum lysozyme levels of patients without a disappearance of abnormal shadows on chest radiography within 5 years were significantly greater than those of individuals with a disappearance (p < 0.05). A positive correlation between serum lysozyme and serum ACE levels was observed. Because serum lysozyme is much less specific for sarcoidosis than serum ACE, its diagnostic value may be limited. However, the sensitivity was high even when serum ACE levels were within normal limits and correlated well with clinical features in sarcoidosis. Therefore, this parameter seems suitable for disease monitoring in proven cases.

Pioglitazone-induced body weight gain is prevented by combined administration with the lipoprotein lipase activator NO-1886.

Pioglitazone improves insulin resistance in diabetics but often causes body weight gain. The lipoprotein lipase activator NO-1886 has been shown to exert both anti-obesity and anti-insulin-resistance effects. In this study, we investigated the effect of the combined administration of pioglitazone with NO-1886 (pioglitazone+NO-1886) in preventing body weight gain in insulin-resistant, high-fat fed rats. The rats were fed a standard or high-fat diet for 16 weeks. The high-fat fed rats were randomized at week 9 into 4 groups (i.e., control, pioglitazone (30 mg/kg/day), NO-1886 (100mg/kg/day), and pioglitazone+NO-1886 (30 and 100mg/kg/day, respectively)). The high-fat fed control rats developed obesity and insulin resistance. After 7 weeks of drug treatment, pioglitazone+NO-1886 was found to prevent the body weight gain caused by pioglitazone alone (pioglitazone+NO-1886: Δ76.0 ± 16.8 g vs. pioglitazone: Δ127.8 ± 39.5 g, P<0.05) and to increase glucose infusion rate during insulin clamp, compared with the results in the high-fat fed control group. No differences in plasma nonesterified fatty acid, leptin, adiponectin, glucose, or insulin levels were observed between the pioglitazone+NO-1886 and the pioglitazone-alone groups. However, plasma total cholesterol and HDL-cholesterol levels were significantly increased and plasma triglyceride levels were slightly decreased in the pioglitazone+NO-1886 group, compared with the values in the pioglitazone-alone group. In summary, the combined administration of pioglitazone and NO-1886 prevented the pioglitazone-induced body weight gains and ameliorated insulin resistance observed in high-fat fed rats. These results indicate that combined therapy with pioglitazone and NO-1886 may be beneficial for the treatment of type 2 diabetes.

Activation of lipoprotein lipase increases serum high density lipoprotein 2 cholesterol and enlarges high density lipoprotein 2 particles in rats.

It is known that postheparin plasma lipoprotein lipase (LPL) activity correlates with serum high density lipoprotein cholesterol (HDL-C) levels in humans and animals. Furthermore, LPL has been reported to cause enlargement of HDL particle size in vitro. However, these effects have not yet been experimentally proven. The aim of this study was to determine whether LPL has a role in increase in HDL-C and enlargement of HDL particle by activating the LPL function with NO-1886, the LPL promoting agent. NO-1886 administration increased postheparin plasma LPL activity without influencing hepatic triglyceride lipase activity. NO-1886 increased serum HDL(2)-cholesterol (HDL(2)-C) concentration and enlarged HDL(2) particle size, but did not increase serum HDL(3)-cholesterol concentration or enlarge HDL(3) particle size. Also, serum HDL(2)-C concentrations were positively correlated with HDL(2) particle size (r=0.910). Our study demonstrates that the LPL activation induced with NO-1886 may cause production of HDL(2)-C by catabolism of triglyceride-rich lipoproteins and enlarges HDL(2) particle size in rats.

Use of a Data Management System to Provide Glycemic Control Instructions to Diabetic Patients Based on Patient Self-Measured Blood Glucose

To make the treatment for diabetes more effective, we assessed the effects of a data management system for glycemic control. This system enables physicians at distant medical institutions to obtain the fluctuations in blood glucose (BG) measured daily by patients themselves at home and then to give instruction for treatment based on the BG. Use of the system for 2 months resulted in decreases in the hemoglobin A1c (HbA1c) level (from 6.8% ± 0.9% to 6.6% ± 0.8% [M ± SD], p < .05) and the incidences of preprandial hypoglycemia and postprandial hyperglycemia. These effects can be concluded to have resulted from the fact that physicians become able to give patients appropriate instructions quickly. Also, these effects are considered to have resulted from patient awareness of the importance of self-management of BG.