Naoki Imada

Clinical utility of ursodeoxycholic acid in preventing flutamide-induced hepatopathy in patients with prostate cancer: A preliminary study

The present study was designed to ascertain retrospectively the validity of ursodeoxycholic acid (UDCA) in the treatment of prostate cancer in terms of prophylactic effects on the occurrence of flutamide‐induced hepatopathy in a large number of patients surveyed in a multi‐center cooperative study.

How does the distention of urinary bladder cause arousal

Abstract Under urethane anesthesia, the urinary bladder of male rats was distended by 0.3‐0.5 mL of saline. When the animals displayed large amplitude delta waves, the distention caused tonic excitation in 76% (19/25) of the noradrenergic neurons in the locus coeruleus and in 53% (16/30) of the cholinergic neurons in the laterodorsal tegmental nucleus. The response was followed by a shift of electroencephalogram (EEG) pattern to faster waves of smaller amplitude. When EEG amplitude was faster and smaller, the same stimuli caused no response. Neurons in Barringtons nucleus were excited by a small amount of bladder distention independent of EEG patterns. These results suggest that the transition of state, caused by bladder distention, from deep sleep to light sleep is mediated by noradrenergic and cholinergic neurons in the brainstem.

Prognostic utility of plasma S100A12 levels to establish a novel scoring system for predicting mortality in maintenance hemodialysis patients: a two-year prospective observational study in Japan

BackgroundS100A12 protein is an endogenous receptor ligand for advanced glycation end products. In this study, the plasma S100A12 level was assessed as an independent predictor of mortality, and its utility in clinical settings was examined.MethodsIn a previous cross-sectional study, plasma S100A12 levels were measured in 550 maintenance hemodialysis patients to determine the association between S100A12 and the prevalence of cardiovascular diseases (CVD). In this prospective study, the risk of mortality within a two-year period was determined. An integer scoring system was developed to predict mortality on the basis of the plasma S100A12 levels.ResultsHigher plasma S100A12 levels (≥18.79 ng/mL) were more closely associated with higher all-cause mortality than lower plasma S100A12 levels (<18.79 ng/mL; P = 0.001). Multivariate Cox proportional hazards analysis revealed higher plasma S100A12 levels [hazard ratio (HR), 2.267; 95% confidence interval (CI), 1.195–4.302; P = 0.012], age ≥65 years (HR, 1.961; 95%CI, 1.017–3.781; P = 0.044), serum albumin levels <3.5 g/dL (HR, 2.198; 95%CI, 1.218–3.968; P = 0.012), and history of CVD (HR, 2.068; 95%CI, 1.146–3.732; P = 0.016) to be independent predictors of two-year all-cause mortality. The integer score was derived by assigning points to these factors and determining total scores. The scoring system revealed trends across increasing scores for predicting the all-cause mortality [c-statistic = 0.730 (0.656–0.804)]. The resulting model demonstrated good discriminative power for distinguishing the validation population of 303 hemodialysis patients [c-statistic = 0.721 (0.627–0.815)].ConclusionThe results indicate that plasma S100A12 level is an independent predictor for two-year all-cause mortality. A simple integer scoring system was therefore established for predicting mortality on the basis of plasma S100A12 levels.

Firing of putative cholinergic neurons and micturition center neurons in the rat laterodorsal tegmentum during distention and contraction of urinary bladder

The relation between unit activity in the laterodorsal tegmental (LDT) area and the state of the urinary bladder was examined in urethane-anesthetized rats. Neurons in the LDT area can be classified into two populations: broad-spike (possibly cholinergic) and brief-spike (non-cholinergic). When the rats showed cortical electroencephalographic activity with large amplitude lower frequency, indicative of deep anesthesia, more than 40% of the broad-spike neurons was excited and about 10% was inhibited by infusion of saline into the bladder. The response was followed by decrease in amplitude and slight increase in frequency of the cortical activity, i.e., lightening of anesthesia. During light anesthesia, excitation was observed only in less than 10% of the units, while 17% was inhibited. In the brief-spike neurons, a similar proportion (about 20%) was excited and less than 10% was inhibited by the distention during either state of anesthesia. About 10% of the broad-spike neurons in the LDT area and 30% of the brief-spike neurons examined were discharged prior to the bladder contraction. Such neurons of the brief-spike category were encountered frequently outside of the central gray; lateral, caudal and ventral to the main mass of cholinergic neurons in the LDT area. These results suggest the possible involvement of the broad-spike (cholinergic) neurons in the elevation of vigilance level caused by bladder distention. The brief-spike (non-cholinergic) neurons firing with relation to bladder contraction may be part of the micturition reflex center.

STATE DEPENDENT RESPONSE OF THE LOCUS CAERULEUS NEURONS TO BLADDER DISTENTION

PURPOSE The precise mechanism by which normal persons wake upon urinary sensation is unclear. The locus caeruleus in the pons is suggested to be involved in the activating systems for arousal. We evaluated the effects of bladder distention on the neural activity in the l. caeruleus under different states of anesthesia. MATERIALS AND METHODS Experiments were performed on 20 male Sprague-Dawley rats. The spontaneous discharge rate of single neurons in and around the l. caeruleus was recorded with the rat under urethane anesthesia administered intraperitoneally, while the electroencephalogram was monitored simultaneously. The changes of the discharge rate of the neurons were observed during saline infusion into the bladder or during tail pinch stimulation. After recording the location of the neurons was confirmed histologically. RESULTS Of 42 l. coeruleus neurons whose response was examined during deep anesthesia 31 showed an excitatory response to bladder distention, followed by a change in electroencephalogram pattern to a faster and smaller rate, while the remaining 11 showed no response. Of 28 l. coeruleus neurons examined during light anesthesia only 1 neuron was excited and the remaining 27 showed no response. Virtually all of the l. coeruleus neurons unresponsive to bladder distention were responsive to tail pinch stimulation. Of the nonnoradrenergic neurons ventromedial to the l. coeruleus 4 of 7 during deep anesthesia and 5 of 8 during light anesthesia showed an excitatory response to distention. CONCLUSIONS The excitatory response of the l. coeruleus neurons to bladder distention was strongly affected by the state of anesthesia. The response was observed only during deep anesthesia and was accompanied by lightening of the anesthesia. L. coeruleus may be involved in arousal which is mediated by bladder distention.

Effects of systematic treatment based on overnight simultaneous monitoring of electroencephalography and cystometry

Objective: To clarify the effects of systematic treatment based on overnight simultaneous monitoring by electroencephalography (EEG) and cystometry (CM) on each type of enuresis. Methods: For enuresis type I, the change in the awakening response during the conditioning treatment with a therapeutic machine was observed. For enuresis type IIa, the effect of imipramine on the EEG was observed. For enuresis type IIb, the effect of oxybutynin hydrochloride on the cystometrogram (CMG) was observed. Results: Values, in which the awakening score on the second night was subtracted from the score on the last night, were significantly higher in the effective cases than in the unchanged cases. Out of the 3 patients in whom imipramine was effective, an awakening response on the EEG was observed in 2. Neither of the 2 unchanged cases showed an awakening response. Out of 4 patients in whom oxybutynin hydrochloride was effective, uninhibited contractions (UIC) on the CMG disappeared in 3. UIC stopped in neither of the 2 unchanged cases. Conclusions: Improvement of the awakening response plays an important role in the effectiveness of conditioning treatment with our therapeutic machine. The generation of awakening response is thought to be the most important result of imipramine directly concerned with its clinical effect on enuresis type IIa. The main result with oxybutynin hydrochloride in enuresis type IIb is thought to be related to its antispasmodic effect.

Relationship between nocturnal urinary frequency and sleep disturbances in aged men

Abstract The relationship between nocturnal urinary frequency and sleep disturbances is investigated in aged men in 12 rural towns in Kyoto and Shiga Prefectures. The subjects were 178 men who did not have diseases or symptoms that were likely to affect urinary condition or sleep. There were no significant differences in sleep disturbances, except sleep maintenance, between the normal group (nocturnal urinary frequency below twice per night) and the abnormal group (nocturnal urinary frequency twice or more per night). In healthy aged men, nocturnal urinary frequency only caused disturbance in sleep maintenance, but did not cause any other sleep disturbance.

Systematic treatment for nocturnal urinary frequency following a sleep–micturition chart

Seven patients complaining of nocturnal urinary frequency were treated following a sleep–micturition chart. By clinical analysis of the data, the causes of nocturnal urinary frequency were divided into three diagnostic categories: a small bladder capacity group, a sleep disorder group and a large nocturnal urinary volume group. The three groups were treated by anti‐cholinergic agents, sleeping pills and restriction of water intake at night respectively. With the administration of anti‐cholinergic agents or sleeping pills nocturnal bladder capacity increased. By restriction of water intake at night nocturnal urinary volume decreased. In all patients nocturnal urinary frequency decreased and sleep efficiency was improved.