The purpose of this study was to eliminate factors of accidents during Japanese style bathing of the elderly.
We investigated the age-related changes in cardiovascular and thermoregulatory function in response to the bathing at 40°C. We measured the blood pressure and the heart rate using an automatic spygmomanometer, the skin blood flow at the forearm using laser Doppler flowmetry, the tympanic temperature using a thermistor, and the sweat rate at dorsum manus using the ventilated capsule method during bathing at 40°C for 20min in 10 aged (73.5±8.4, mean±SD) and 10 young subjects (19.8±1.8).
Aged subjects failed to maintain a stable blood pressure during the immersion in the bathtub. While the heart rate during the bathing significantly changed in the young subjects, no change was observed in the aged subjects. Skin blood flow, tympanic temperature, and sweat rate increased during the bathing for both in the aged and the young subjects, though with smaller changes among aged subjects.
These findings suggest that the adaptability of cardiovascular and thermoregulatory functions to heating and hydrostatic pressure during Japanese style bathing decreases with age.

A 75-year-old man with underlying arteriosclerosis obliterans presented with acute heart failure secondary to rest pain of the right lower extremity. Echocardiogram showed severe mitral regurgitation, moderate tricuspid regurgitation and a low cardiac function (ejection fraction : 27%). Right toe gangrene developed in association with continuous acute heart failure. He underwent mitral valve replacement, tricuspid annuloplasty, right common femoral artery-posterior tibial artery bypass and amputation of the right toes in single-stage surgery. There were no major complications during his hospital stay. After surgery, his symptoms significantly improved.

The purpose of this study was to clarify the effects of ingesting spa water on electrogastrography and heart rate variability in humans. The subjects were eight youths (average age 22.3 years old). We measured three and six circles per minute (cpm) power of electrogastrography (EGG), the high-frequency (HF: 0.15-0.4Hz) components, and the ratio of low-frequency (LF: 0.04-0.15Hz) components to HF components in heart rate variability (HRV) during 90 minutes. We also assessed the taste of water, pain or abnormalities in the stomach by questionnaire. The subjects ingested the spa water or purified water after thirty minutes, and ingested no water on a different day. The six cpm power of EGG, presumably reflecting instestinal activity, was significantly increased with spa water ingestion. The three cpm power of EGG, presumably reflecting stomach activity, did not change under any conditions. The HF components in HRV, presumably reflecting cardiac parasympathetic activity, tended to increase with ingestion of spa water. The ratio of LF to HF components in HRV, presumably reflecting cardiac sympathetic activity, significantly decreased with ingestion of spa and purified water. There was no difference in the answers of the questionnaire. These findings suggest that spa water ingestion activates instestinal activity, increasing parasympathetic nerve activity and suppressing sympathetic nerve activity in humans.

Long term physical training is known to cause a change of cardiac functions and this effect is observed at various levels of the heart (from whole heart to subcellular level), although its mechanism is not fully understood. It is reported that cardiac hypertrophy and decreased heart rate can be observed as effects of long term physical training, but change of the catecholamine content in heart tissue induced by training is controversial.
In the present experiment, long schedule of short daily swimming episodes was employed to observe the effect of mild physical training on cardiac functions of rats in the growing stage. We measured body weight, heart weight, heart rate under light anesthesia, variation of R-R-interval of electrocardiogram, and catecholamine contents in cardiac muscle.
1) Wister rats were divided into 2 groups 3 weeks after birth. One group rats was kept sedentary in cages, and the other group was required to free swim in a tank containing water at 30°C. At the beginning of the programme, swimming time was 10 min. Swimming was applied 5 days a week for up to 14 weeks, and swimming time was gradually increased to 30 min.
2) Body weight of rats in the trained group was significantly less than that of the controls, and the heart weight to body weight ratio in the trained rats was significantly higher than in the controls.
3) In the exercised rats, the R-R interval of the ECG was longer than that of the controls, and there was a tendency for the variation of R-R interval in the trained group to be larger than that of the controls.
4) At 10 and 17 weeks, rats from each group were sacrificed after or without a 30 min test swim for measurement of catecholamine content of the ventricular muscle. One time swimming for 30 min increased dopamine content, but did not change norepinephrine content except for the trained group at 10 weeks. There was no significant difference in cardiac catecholamine contents in the rested state of the control and trained groups at 10 and 17 weeks.
5) Results were interpreted as follows: One time swimming for 30 min influences the activity of the autonomic nervous system innervating the heart, and catecholamine metabolism at nerve terminals of the sympathetic nervous system. Long term mild swimming does not cause permanent change of catecholamine contents, and the low heart rate in the trained group cannot be soley explained by the decreased activity of the sympathetic nervous system.

Background/Aims: Acute cholangitis (AC) is a potentially life-threatening bacterial infection, and timely antimicrobial treatment, faster than that achieved with bacterial cultures, is recommended.Although the current guidelines refer to empirical antimicrobial treatment, various kinds of antimicrobial agents have been cited because of insufficient analyses on the spectrum of pathogens in AC. Enterococcus spp. is one of the most frequently isolated Gram-positive bacteria from the bile of patients with AC, but its risk factors have not been extensively studied. This study aimed to analyze the risk factors of AC caused by Enterococcus faecalis and Enterococcus faecium. Methods: Patients with AC who were hospitalized in a Japanese tertiary center between 2010 and 2015 were retrospectively analyzed. Patients’ first AC episodes in the hospital were evaluated. Results: A total of 266 patients with AC were identified. E. faecalis and/or E. faecium was isolated in 56 (21%) episodes of AC. Prior endoscopic sphincterotomy (EST), the presence of a biliary stent, prior cholecystectomy, and past intensive care unit admission were more frequently observed in AC patients with E. faecalis and/orE. faecium than in those without such bacteria. Prior EST was identified as an independent risk factor for AC caused by E. faecalis and/or E. faecium in the multivariate analysis. Conclusions Given the intrinsic resistance of E. faecalis and E. faecium to antibiotics, clinicians should consider empirical therapy with anti-enterococcal antibiotics for patients with prior EST.

Background/Aims: Acute cholangitis (AC) is a potentially life-threatening bacterial infection, and timely antimicrobial treatment, faster than that achieved with bacterial cultures, is recommended.Although the current guidelines refer to empirical antimicrobial treatment, various kinds of antimicrobial agents have been cited because of insufficient analyses on the spectrum of pathogens in AC. Enterococcus spp. is one of the most frequently isolated Gram-positive bacteria from the bile of patients with AC, but its risk factors have not been extensively studied. This study aimed to analyze the risk factors of AC caused by Enterococcus faecalis and Enterococcus faecium. Methods: Patients with AC who were hospitalized in a Japanese tertiary center between 2010 and 2015 were retrospectively analyzed. Patients’ first AC episodes in the hospital were evaluated. Results: A total of 266 patients with AC were identified. E. faecalis and/or E. faecium was isolated in 56 (21%) episodes of AC. Prior endoscopic sphincterotomy (EST), the presence of a biliary stent, prior cholecystectomy, and past intensive care unit admission were more frequently observed in AC patients with E. faecalis and/orE. faecium than in those without such bacteria. Prior EST was identified as an independent risk factor for AC caused by E. faecalis and/or E. faecium in the multivariate analysis. Conclusions Given the intrinsic resistance of E. faecalis and E. faecium to antibiotics, clinicians should consider empirical therapy with anti-enterococcal antibiotics for patients with prior EST.

BACKGROUND/AIMS: Noninvasive liver fibrosis evaluation was performed in patients with nonalcoholic fatty liver disease (NAFLD). We used a quantitative method based on the hepatic volume acquired from gadoxetate disodium-enhanced (Gd-EOB-DTPA-enhanced) magnetic resonance imaging (MRI) for diagnosing advanced fibrosis in patients with NAFLD. METHODS: A total of 130 patients who were diagnosed with NAFLD and underwent Gd-EOB-DTPA-enhanced MRI were retrospectively included. Histological data were available for 118 patients. Hepatic volumetric parameters, including the left hepatic lobe to right hepatic lobe volume ratio (L/R ratio), were measured. The usefulness of the L/R ratio for diagnosing fibrosis ≥F3–4 and F4 was assessed using the area under the receiver operating characteristic (AUROC) curve. Multiple regression analysis was performed to identify variables (age, body mass index, serum fibrosis markers, and histological features) that were associated with the L/R ratio. RESULTS: The L/R ratio demonstrated good performance in differentiating advanced fibrosis (AUROC, 0.80; 95% confidence interval, 0.72 to 0.88) from cirrhosis (AUROC, 0.87; 95% confidence interval, 0.75 to 0.99). Multiple regression analysis showed that only fibrosis was significantly associated with the L/R ratio (coefficient, 0.121; p<0.0001). CONCLUSIONS: The L/R ratio, which is not influenced by pathological parameters other than fibrosis, is useful for diagnosing cirrhosis in patients with NAFLD.
Body Mass Index ; Fibrosis* ; Humans ; Liver Cirrhosis ; Magnetic Resonance Imaging ; Methods ; Non-alcoholic Fatty Liver Disease* ; Retrospective Studies ; ROC Curve

Miriplatin is a novel lipophilic platinum complex that was developed to treat hepatocellular carcinoma (HCC). Although HCC patients frequently have coexisting chronic renal failure, little prospective data are available regarding the clinical toxicity of chemotherapeutic agents used to treat HCC patients with chronic renal failure. In a phase II study, the plasma concentration of total platinum in patients who received miriplatin was very low, and no severe renal toxicity caused by miriplatin injection was reported. Here, we present three cases of HCC with stage 4 chronic renal failure who received transcatheter arterial chemotherapy with miriplatin. All cases were male, ages 72, 84, and 83 years, and had serum creatinine levels of 2.3, 1.6, and 1.9 mg/dL, respectively. Their estimated glomerular filtration rates were 21.9, 20.3, and 22.2 mL/min, respectively. All cases were treated for unresectable HCC with transcatheter arterial chemotherapy with miriplatin. No serious adverse events were observed, and serum creatinine levels did not elevate, even in the patient who experienced renal failure caused by cisplatin administration. These results might suggest that transcatheter arterial chemotherapy with miriplatin can be safely used in HCC patients with chronic renal failure.
Carcinoma, Hepatocellular ; Cisplatin ; Creatinine ; Glomerular Filtration Rate ; Humans ; Kidney Failure, Chronic ; Male ; Organoplatinum Compounds ; Plasma ; Platinum ; Renal Insufficiency

BACKGROUND/AIMS: It is important to determine the noninvasive parameters of histological features in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the value of genetic variations as surrogate markers of histological features. METHODS: The parameters that affected the histological features of NAFLD were investigated in 211 Japanese patients with biopsy-proven NAFLD. The relationships between genetic variations in PNPLA3 rs738409 or TM6SF2 rs58542926 and histological features were analyzed. Furthermore, the impact of genetic variations that affected the pathological criteria for the diagnosis of nonalcoholic steatohepatitis (NASH) (Matteoni classification and NAFLD activity score) was evaluated. RESULTS: The fibrosis stage of PNPLA3 GG was significantly more progressive than that of CG by multiple comparisons. Multivariate analysis identified PNPLA3 genotypes as predictors of fibrosis of stage 2 or more, but the impact tended to decrease at stage 3 or greater. There were no significant differences among the histological features of the three genotypes of TM6SF2. PNPLA3 genotypes partly affected the definition of NASH by the NAFLD activity score, but TM6SF2 genotypes did not affect the definition of NASH. CONCLUSIONS: In Japanese patients with biopsy-proven NAFLD, PNPLA3 genotypes may partly affect histological features, including stage of fibrosis, but the TM6SF2 genotype does not affect histological features.
Asian Continental Ancestry Group ; Biological Markers ; Classification ; Diagnosis ; Fatty Liver* ; Fibrosis ; Genetic Variation* ; Genotype ; Humans ; Japan* ; Multivariate Analysis

BACKGROUND/AIMS: The aim of this study was to determine the pharmacodynamics of cisplatin following three different treatment procedures for intrahepatic arterial infusion therapy for hepatocellular carcinoma (HCC). METHODS: We divided 13 HCC patients into the following three groups: group A, lone injection of cisplatin (n=3); group B, combined injection of cisplatin and lipiodol, with embolization using small gelatin cubes (GCs) (n=5); and group C, injection of suspended lipiodol with cisplatin powder, with embolization using small GCs (n=5). In each group, the free cisplatin concentration in the hepatic vein was measured at 0, 5, 10, and 30 minutes. RESULTS: The mean free cisplatin concentrations were as follows. For group A, the mean was 48.58 microg/mL at 0 minute, 7.31 microg/mL at 5 minutes, 5.70 microg/mL at 10 minutes, and 7.15 microg/mL at 30 minutes. For the same time points, for group B, the concentrations were 8.66, 4.23, 3.22, and 1.65 microg/mL, respectively, and for group C, the concentrations were 4.81, 2.61, 2.52, and 1.75 microg/mL, respectively. The mean area under the curve (AUC)0-infinity for the free cisplatin concentration was 7.80 in group A, 2.48 in group B, and 2.27 in group C. The AUC0-infinity for the free cisplatin concentration gradually decreased, from group A to group C. CONCLUSIONS: These results indicate that the combination of lipiodol and small GCs may be useful for delaying cisplatin drainage from the liver.
Carcinoma, Hepatocellular ; Cisplatin ; Drainage ; Drug Delivery Systems ; Ethiodized Oil ; Gelatin ; Hepatic Veins ; Humans ; Liver ; Pilot Projects