In 2013, we prescribed daiuzusen for 3 patients with intractable pain; pain from complex regional pain syndrome, colic pain of unknown origin after an abdominal operation, and colic pain from advanced colon cancer and ileus. A dose of daiuzusen (containing uzu 0.5-2 g) quickly relieved their pain in several minutes. Another common symptom was “cold” in their bowel or extremities when they were feeling pain. Aconite levels in drugs and patients' serum after taking daiuzusen were analyzed by liquid chromatography tandem mass spectrometry. Daiuzusen per 1 g of uzu contained aconitine 1.28 μg, mesaconitine 2.31 μg, and hypaconitine 92.89 μg, while jesaconitine was not detected; this was about 5 to 35 times the level of tsumyakushigyakuto per 1 g of uzu. Serum concentrations of hypaconitine peaked in the study at 1.11 ng/mL after about an hour of taking daiuzusen (1 g of uzu). We posit that the immediate effect after taking daiuzusen was due to transmucosal absorption of uzu components. However serum hypaconitine, which we are now able to monitor, is at least one practical way of indicating the use of uzu or bushi containing prescriptions.

Objective : Carvedilol is a non-selective β blocker with an α blocking activity. Since this drug is highly fat-soluble, it can pass through the blood-brain barrier, and thus may induce depression and lower QOL. In the present study, physicians and pharmacists collaborated to evaluate the antihypertension effect of carvedilol and post-administration changes in QOL. Furthermore, the relationship between QOL and antihypertension effect was analyzed.
Design : Self-controlled study.
Patients and Methods : Subjects were outpatients with hypertension above the age of 70 years who visited one of 42 medical institutions in Japan between April 1995 and March 1996. A total of 243 patients were registered, and 10-20 mg of carvedilol was administered once a day for six months. Pharmacists assessed the QOL of these patients by asking 82 questions on three separate occasions : before administration and one and six months after administration. The antihypertensive effect of this drug was investigated in patients in whom all three QOL questionnaires were collected. The main test items were antihypertensive effect, changes in QOL (subjective QOL with a special emphasis on patient psychology), and the relationship between antihypertensive effect and QOL. The antihypertensive effect of this drug was statistically analyzed by a paired t-test, and changes in QOL were statistically analyzed using generalized estimating equations.
Results : All three QOL questionnaires were collected from a total of 146 patients. Their pre-administration systolic blood pressure was 159.6±1.4 mmHg, and diastolic blood pressure 94.0±0.9 mmHg, and their blood pressure decreased significantly one month after the start of administration. This antihypertensive effect of carvedilol persisted, and the systolic and diastolic blood pressure of these patients six months after the start of administration was 141.1±1.2 and 85.2±0.7 mmHg, respectively (significant decreases when compared to pre-administration levels ; both p<0.05).
Subjective QOL improved significantly after carvedilol administration. And, changes were not seen in sexual function. Changes in the five categories of subjective QOL were as follows : psychological stability, disease-induced inconvenience, and independence improved significantly after carvedilol administration, but changes were not seen in gratification or vitality. However, improvements in subjective QOL did not correlate with improvements in blood pressure.
Conclusions : The results of the present study showed that carvedilol improved QOL without negatively affecting sexual function. Subjective QOL reflects the psychological well-being of patients. In the present study, psychological stability, disease-induced inconvenience, and independence improved significantly, but changes were not seen in gratification or vitality. Since β blockers can suppress the central nervous system, they can reduce psychological stability, gratification and vitality. Even though carvedilol is highly fat-soluble, the results of non-clinical studies have shown that it does not suppress the central nervous system as much as propranolol. The results of the present study showed that carvedilol does not strongly suppress the central nervous system of humans. Moreover, significant changes in QOL were not seen between one and six months after the start of administration of carvedilol, suggesting that it is possible to estimate the QOL of patients on antihypertensive therapy after six months of administration by assessing their QOL one month after administration.

Poor eating is a life-threatening condition in senior citizens. Herein, we report a case of poor eating due to stomach yin deficiency (wei yin xu), which was successfully treated with bakumondoto. The patient was a 91-year-old woman who expected treatment for her poor food intake. She was diagnosed as poor eating with stomach yin deficiency and was administered with bakumondoto, which increased her food intake and weight. To treat poor eating with Kampo medicine, rikkunshito and various other Kampo drugs are commonly used. In this case, bakumondoto, which is usually used for respiratory diseases such as dry cough, was effective. Bakumondoto is useful for stomach yin deficiency of poor eating.

BACKGROUND/AIMS: The effects of Histamine-2 receptor antagonists and proton pump inhibitors on the gastrointestinal motility have not yet been sufficiently investigated. The aim of this study was to determine the effects of intravenous bolus administration of famotidine and omeprazole on the rate of gastric emptying using the continuous 13C breath test (BreathID system, Exalenz Bioscience Ltd, Israel). METHODS: Twelve healthy male volunteers participated in this randomized, 3-way crossover study. After fasting overnight, the subjects were randomly assigned to receive 20 mg of famotidine, 20 mg of omeprazole or 20 mL of saline alone by intravenous bolus injection before a test meal (200 kcal per 200 mL, containing 100 mg of 13C-acetate). Gastric emptying was monitored for 4 hours after the ingestion of test meal by the 13C-acetic acid breath test performed using the BreathID system. RESULTS: No significant differences in the calculated parameters, namely, the T1/2, Tlag, GEC, beta and kappa, were observed among the 3 test conditions. CONCLUSIONS: The study revealed that intravenous administration of gastric acid suppressant drugs had no significant influence on the rate of gastric emptying in comparison with that of saline alone as a placebo. Our results indicating the absence of any effect of either famotidine or omeprazole on accelerating the rate of gastric emptying suggest that both medications can be administered safely to patients suffering from hemorrhagic peptic ulcers who need to be kept nil by mouth from the viewpoint of possible acceleration of gastrointestinal motility in the clinical setting.
Acceleration ; Administration, Intravenous ; Breath Tests ; Cross-Over Studies ; Eating ; Famotidine ; Fasting ; Gastric Acid ; Gastric Emptying ; Gastrointestinal Motility ; Humans ; Male ; Meals ; Mouth ; Omeprazole ; Peptic Ulcer ; Proton Pump Inhibitors ; Proton Pumps ; Protons ; Stress, Psychological

BACKGROUND/AIMS: The gastrointestinal motility effects of endogenous incretin hormones enhanced by dipeptidyl peptidase-IV (DPP-IV) inhibitors have not yet been sufficiently investigated. The aim of this study was to determine whether single pre-prandial sitagliptin, the DPP-IV inhibitor, administration might have an effect on the rate of liquid gastric emptying using the 13C-acetic acid breath test. METHODS: Ten healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted for overnight and were randomly assigned to receive 50 mg sitagliptin 2 hours before ingestion of the liquid test meal (200 kcal per 200 mL, containing 100 mg 13C-acetate) or the test meal alone. Under both conditions, breath samples were collected for 150 minutes following the meal. Liquid gastric emptying was estimated by the values of the following parameters: the time required for 50% emptying of the labeled meal (T1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (Tlag), the gastric emptying coefficient and the regression-estimated constants (beta and kappa), calculated by using the 13CO2 breath excretion curve using the conventional formulae. The parameters between the 2 test conditions were compared statistically. RESULTS: No significant differences in the calculated parameters, including T1/2, Tlag, gastric emptying coefficient or beta and kappa, were observed between the 2 test conditions. CONCLUSIONS: The present study revealed that single-dose sitagliptin intake had no significant influence on the rate of liquid gastric emptying in asymptomatic volunteers.
Breath Tests ; Cross-Over Studies ; Eating ; Gastric Emptying ; Gastrointestinal Motility ; Humans ; Incretins ; Male ; Meals ; Pyrazines ; Triazoles ; Sitagliptin Phosphate

BACKGROUND/AIMS: The administration of liquid nutrients to patients is often accompanied by complications such as gastroesophageal reflux. To prevent gastroesophageal reflux, high-viscosity liquid meals are used widely, however, it still remains controversial whether high-viscosity liquid meals have any effect on the rate of gastric emptying. The present study was conducted with the aim of determining whether high-viscosity liquid meals had any effect on the rate of gastric emptying and mosapride might accelerate the rate of gastric emptying of high-viscosity liquid meals. METHODS: Six healthy male volunteers underwent 3 tests at intervals of > 1 week. After fasting for > 8 hours, each subject received one of three test meals (liquid meal only, high-viscosity liquid meal [liquid meal plus pectin] only, or high-viscosity liquid meal 30 minutes after intake of mosapride). A 13C-acetic acid breath test was performed, which monitored the rate of gastric emptying for 4 hours. Using the Oridion Research Software (beta version), breath test parameters were calculated. The study parameters were examined for all the 3 test conditions and compared using the Freidman test. RESULTS: Gastric emptying was significantly delayed following intake of a high-viscosity liquid meal alone as compared with a liquid meal alone; however, intake of mosapride prior to a high-viscosity liquid meal was associated with a significantly accelerated rate of gastric emptying as compared with a high-viscosity liquid meal alone. CONCLUSIONS: This study showed that high-viscosity liquid meals delayed gastric emptying: however, mosapride recovered the delayed rate of gastric emptying by high-viscosity liquid meals.
Benzamides ; Breath Tests ; Cross-Over Studies ; Fasting ; Gastric Emptying ; Gastroesophageal Reflux ; Humans ; Male ; Meals ; Morpholines ; Pectins

BACKGROUND/AIMS: There are few reports on the correlation between chewing gum and the gastrointestinal functions. But previous report showed use of chewing gum to be an effective method for controlling gastrointestinal symptoms. The aim of this study was to determine the correlation between chewing gum and gastric emptying using the continuous real time 13C breath test (BreathID system). METHODS: Ten healthy male volunteers participated in this randomized, 2-way crossover study. The subjects fasted overnight and were randomly assigned to chewing gum (Xylish, 2-3/1 tablet) for an hour following intake of a test meal (200 kcal/200 mL) or intake of the test meal alone. Gastric emptying was monitored for 4 hours after administration of the test meal by the 13C-acetic acid breath test performed continually using the BreathID system. RESULTS: No significant differences in the calculated parameters, namely, T1/2 (median, 111.82 vs 109.26 minutes; P = 0.575), Tlag (median, 53.28 vs 56.53 minutes; P = 0.333), gastric emptying coefficient (median, 3.58 vs 3.65; P = 0.285), regression-estimated constant beta (median, 1.85 vs 1.80; P = 0.575) and regression-estimated constant kappa (median, 0.61 vs 0.62; P = 0.959) were observed between the test meal alone group and the test meal and chewing gum group. CONCLUSIONS: This study showed that chewing gum had no effect on the rate of gastric emptying. Therefore, since chewing gum did not enhance the speed of gastric emptying, it may ameliorate gastrointestinal symptoms through other mechanisms, such as saliva and autonomic nervous system.
Autonomic Nervous System ; Breath Tests ; Chewing Gum ; Cross-Over Studies ; Gastric Emptying ; Humans ; Male ; Mastication ; Meals ; Saliva

Objective: The addition of maintenance olaparib to bevacizumab demonstrated a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the PAOLA-1/ENGOT-ov25 trial (NCT02477644). We evaluated maintenance olaparib plus bevacizumab in the Japan subset of PAOLA-1. Methods: PAOLA-1 was a randomized, double-blind, phase III trial. Patients received maintenance olaparib tablets 300 mg twice daily or placebo twice daily for up to 24 months, plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total. This prespecified subgroup analysis evaluated investigator-assessed PFS (primary endpoint). Results: Of 24 randomized Japanese patients, 15 were assigned to olaparib and 9 to placebo. After a median follow-up for PFS of 27.7 months for olaparib plus bevacizumab and 24.0 months for placebo plus bevacizumab, median PFS was 27.4 versus 19.4 months, respectively (hazard ratio [HR]=0.34; 95% confidence interval [CI]=0.11–1.00). In patients with tumors positive for homologous recombination deficiency, the HR for PFS was 0.57 (95% CI=0.16–2.09). Adverse events in the Japan subset were generally consistent with those of the PAOLA-1 overall population and with the established safety and tolerability profiles of olaparib and bevacizumab. Conclusion: Results in the Japan subset of PAOLA-1 support the overall conclusion of the PAOLA-1 trial demonstrating that the addition of maintenance olaparib to bevacizumab provides a PFS benefit in patients with newly diagnosed, advanced ovarian cancer.