Objective : To get first-hand information on and understand MEDWatch, a newly created program of the US FDA, on safety information reporting and management.
Design and Method : Through a visit to the FDA office by Japanese members of the ICH M1 (Medical Terminology) Expert Working Group (EWG) and other concerned experts, and discussion with relevant FDA staffs.
Results and Conclusion : (1) The MEDWatch program was introduced in June 1993, to accelerate the spontaneous reporting of adverse events (AE) to FDA by developing a single Adverse Event Reporting Form, i.e., FDA 3500, for (1) drugs, (2) biologics (except vaccine), (3) medical devices, (4) food, and (5) veterinary medicines; (2) Five responsible sectors in FDA have been working together to develop a smooth flow of information from health care professionals and industries; (3) The remarkable result from the development of this new program is the increased reporting of serious AE; (4) Much efforts have been exerted by FDA on the education of health professionals through various health societies and through publications; (5) Some of the issues which remain unresolved include database integration of NDA and PMS information; (6) Advocacy of the AE concept and importance of reporting thereof by health care professionals and the use of simple, easy-to-fill-out form is recommended in Japan.

A study was conducted to clarify the validity and availability of inclination of exponential curve-fitting model for oxygen uptake (VO₂) and heart rate (HR) during incremental exercise (IECOH) as an index of cardio-pulmonary functional reserve in healthy subjects. A treadmill exercise test was used to measure the VO₂ (L/kg/min) and HR (beat /min) during incremental exercise of all subjects. The IECOH was derived from the following equation : HR=A⋅exp^B·VO₂. The constant “B” represents the IECOH. The following three identifications were made : 1) the relationship between maximal oxygen uptake (VO₂max) and IECOH in 82 healthy males ; 2) the relationship between IECOH and age in 428 healthy males and females ; 3) the effect of physical training in 8 healthy males.
There was inverse correlation between IECOH and VO₂max (r= -0.824) . And also, there were inverse correlations between IECOH detected from submaximal tests and VO₂max (above r=-0.6) . There were no differences in the IECOH detected from maximal and submaximal tests. In Bland-Altman plot method, accuracy of measurment in the IECOH detected from submaximal exercise test was precise. There was a significant relationship between IECOH and age in male and female subjects (r=0.499 and r=0.310, respectively) . Physical training increased VO₂max and decreased IECOH significantly. The VO₂max before and after physical training correlated inversely with the IECOH before and after physical training (r=-0.514) .
In conclusion, these results suggest that IECOH is adequate and useful as an index of cardio-pulmonary functional reserve which can be measured by the submaximal exercise test in healthy subjects.

Rikkunshito is comprised of 8 crude drugs and is used for the treatment of gastrointestinal dysfunctions such as anorexia and heavy stomach feeling. These symptoms are often caused by delay in gastric emptying. Cisplatin is a representative cancer chemotherapeutic drug with severe adverse effects such as anorexia and nausea, that gives rise to a delay in gastric emptying. However, it is still unknown whether rikkunshito has effects on improving the delayed gastric emptying induced by cisplatin. In the present study, we examined the effects of rikkunshito (an Atractylodis rhizoma-containing formula) on cisplatin-induced delay in gastric emptying in the rat. Rikkunshito improved this. Among the crude drugs that comprise rikkunshito, Atractylodis rhizoma, Ginseng radix, Poria and Aurantii nobilis pericarpium individually improved the delay in gastric emptying, suggesting that they all contribute to the action of rikkunshito. Moreover, the effects of these 4 crude drugs in combinations were also examined, and as a result, tended to be stronger when Atractylodis rhizoma was included. On the other hand, when Atractylodis rhizoma was excluded from rikkunshito, the effects were weaker. Meanwhile, atractylenolide III, a specific chemical constituent of Atractylodis rhizoma, improved delay in gastric emptying in a manner similar to that of rikkunshito with Atractylodis rhizoma. These results, taken together, suggest that Atractylodis rhizoma likely contributes greatly to the improving effect of rikkunshito on cisplatin-induced delay in gastric emptying.

The present study was conducted to obtain basic information about blood glucose fluctuation and relation with race performance during 100 km marathon. Subcutaneous glucose of one well-trained runner was measured by continuous glucose monitoring system (CGMS) at 5 min interval and blood samples for biochemical analysis were drawn at pre, middle and post of the race. Energy balance during one week prior to the 100 km race was recorded, and the whole energy and fluid intake during the race was analyzed. Blood glucose fluctuated reflecting duration of exercise and energy supply during the race. During the latter part of the race (65–70 km), abrupt declines in blood glucose level, which reflected insufficient carbohydrate intake before the race (119 g), were accompanied by decrease in running speed. The present report suggests that continuous glucose monitoring supplemented with standard nutritional and physiological measurement provides precise and valuable information on runner’s energy state during the ultra-endurance race, and that athletes need to reassess their preparation for the race and planning of energy intake during the race.

The present study was conducted to obtain basic information about blood glucose fluctuation and relation with race performance during 100 km marathon. Subcutaneous glucose of one well-trained runner was measured by continuous glucose monitoring system (CGMS) at 5 min interval and blood samples for biochemical analysis were drawn at pre, middle and post of the race. Energy balance during one week prior to the 100 km race was recorded, and the whole energy and fluid intake during the race was analyzed. Blood glucose fluctuated reflecting duration of exercise and energy supply during the race. During the latter part of the race (65–70 km), abrupt declines in blood glucose level, which reflected insufficient carbohydrate intake before the race (119 g), were accompanied by decrease in running speed. The present report suggests that continuous glucose monitoring supplemented with standard nutritional and physiological measurement provides precise and valuable information on runner’s energy state during the ultra-endurance race, and that athletes need to reassess their preparation for the race and planning of energy intake during the race.

Polysaccharide sulfate (PSS) is a new type of antiatherosclerotic medicine for its effects of anticoagulation, anti-thrombosis and modulation of dyslipidemia. However, it is still uncertain whether PSS could modulate the diabetic dyslipidemia or not. Here, the rat model of diabetic dyslipidemia was developed and the effects of PSS on glucose and lipid levels were investigated in this animal model. Wistar rats were iv injected with streptozotocin 20 mg·kg-1 after feeding with high fat diet for one and a half month. Then, rats received orally PSS (30, 90, and 180 mg·kg-1) for 1 month. After oral treatment with PSS (90 and 180 mg·kg-1) for 1 month, the levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) were significantly reduced and the level of high density lipoprotein-cholesterol (HDL-C) increased, compared with diabetic control rats. Moreover, PSS (30, 90, and 180 mg·kg-1) had a tendency to reduce glucose and insulin levels, and significantly increased insulin sensitivity index. Our results suggest that PSS could improve insulin sensitivity and relieve dyslipidemia in diabetic dyslipidemic rats.

This study examined the effects of physical training on exercise hyperpnea (EH) in patients on hemodialysis (HD) . In baseline, 17 (trained group) and 12 (control group) patients on HD performed symptom limited exercise test using a treadmill. Trained group, but not control group, exercised 2 to 3 times weekly on non-dialysis days under medical supervision. Exercise testing was repeated 20 weeks after the baseline. Ventilatory response to exercise was evaluated using the regression slope relating minute ventilation (VE) to carbon dioxide output (VCO₂ ) during incremental exercise (VE/VCO₂ slope) below the point of respiratory compensation. In trained group, VE, oxygen uptake ( VO₂) and VCO₂ at peak exercise increased and VE/VO₂ and VE/VCO₂ decreased after physical training, respectively. No change was observed in control group. VO₂ at the anaerobic threshold increased in trained group, but not in control group. The post training VE/VCO₂ slope (33.9±5.0) was significantly (p<0.05) lower than the pre-training slope (38.0± 4.8) and remained constant in control group. In trained group, changes in the VE/VCO₂ slope correlated with those in peak VO₂ (p<0.05) . These results suggest that physical training decreases EH in patients on HD and that it correlates with changes in exercise tolerance.