Abstract: PURPOSE: We investigated the effects of intrathecal application of gamma-aminobutyric acid A and B receptor agonists on detrusor overactivity in spinal cord injured rats. MATERIALS AND METHODS: Adult female Sprague-Dawley rats were used. At 4 weeks after Th9-10 spinal cord transection awake cystometry and recordings of external urethral sphincter electromyogram were performed to examine the effect of intrathecal application of the gamma-aminobutyric acid A and B agonists muscimol and baclofen or the gamma-aminobutyric acid A and B antagonists bicuculline and saclofen (Tocris Cookson, Ellisville, Missouri), respectively, at the level of the L6-S1 spinal cord. The expression of glutamate decarboxylase 67 mRNA in the L6-S1 spinal cord and dorsal root ganglia was also assessed. RESULTS: Muscimol and baclofen produced a dose dependent inhibition of the number (51% to 73% decrease) and amplitude (35% to 93% decrease) of nonvoiding bladder contractions and a decrease in micturition pressure. The effects of muscimol and baclofen were antagonized by bicuculline and saclofen, respectively. Bursting activity of external urethral sphincter electromyogram was inhibited, corresponding to the inhibition of bladder activity by muscimol and baclofen. Glutamate decarboxylase 67 mRNA levels in the spinal cord and dorsal root ganglia were decreased after spinal cord transection (55% and 84%, respectively). CONCLUSIONS: These results indicate that gamma-aminobutyric acid A and B receptor activation in the spinal cord inhibits detrusor overactivity. The decrease in glutamate decarboxylase 67 mRNA suggests hypofunction of GABAergic inhibitory mechanisms in the spinal cord. Therefore, stimulation of spinal GABAergic mechanisms could be effective for the treatment of detrusor overactivity after spinal cord injury.
Abstract: PURPOSE: We investigated the mechanisms by which Eviprostat, a phytotherapeutic drug for benign prostatic hyperplasia, influences bladder activity in rats. MATERIALS AND METHODS: A total of 42 female rats were divided into a control group and an Eviprostat group. Rats in the control group were fed a standard diet, while animals in the Eviprostat group were fed a diet containing 0.1% Eviprostat. After 2 weeks 14 rats (7 rats per group) underwent continuous cystometry with physiological saline or 0.1% acetic acid solution and bladder activity was recorded. Body weight, blood pressure, plasma monoamines and adenosine triphosphate were measured in another 14 rats (7 per group). In the remaining 14 rats (7 per group) 0.1% acetic acid solution was infused into the bladder and urinary adenosine triphosphate was measured before and after stimulation. RESULTS: During cystometry with acetic acid the interval between bladder contractions was shorter and maximum bladder contraction pressure was higher in the control group compared with results obtained using physiological saline but such differences were not seen in the Eviprostat group. Plasma adrenaline and noradrenaline were lower in the Eviprostat group than the control group but no difference in blood pressure was observed. Urinary adenosine triphosphate was higher in the 2 groups than before stimulation but the increase was smaller in the Eviprostat group than in the control group. CONCLUSIONS: These results suggest that Eviprostat acts to maintain low catecholamine and also inhibit pathological bladder activity by decreasing adenosine triphosphate release from the bladder.
Abstract: We compared the serum cholinesterase (ChE) level and various parameters between patients with or without overactive bladder (OAB) and/or neurogenic bladder (NB). A total of 258 patients who met the following criteria were enrolled: the presence/absence of OAB and/or NB was documented, laboratory data were available, and liver and renal functions were normal. Patients were divided into the 3 groups: 1) a NB+/OAB+ group who had both NB and OAB, 2) a NB-/OAB+ group who had OAB alone, and 3) an OAB- group who did not have OAB. The relationship between the presence of OAB and various biochemical parameters were examined, as well as the therapeutic outcome in relation to the same biochemical parameters. Forty-three patients had both NB and OAB (NB+/OAB+), 66 patients had OAB without NB (NB-/OAB+), and 149 patients had no OAB (OAB-). Serum ChE, total protein, and albumin levels were lower in the NB-/OAB+ group than the NB+/OAB+ group or the OAB- group. In the NB-/OAB+ group, a higher serum albumin or ChE level was associated with a better therapeutic outcome. These results suggest that a decrease of serum ChE level is related to the occurrence of OAB and the poor response to treatment in OAB patients without NB.
Abstract: We investigated whether nocturia in the elderly was improved by walking exercise, which involved walking rapidly for 30 min or more in the evening or night for 8 weeks. A questionnaire related to micturition and exercise, blood pressure, body composition analysis, blood biochemistry tests, and urinalysis were performed before and after 8 weeks of exercise to investigate the effects of walking. Thirty men (71 years old on average) continued the walking exercise for long enough to undergo evaluation. The number of episodes of nocturia decreased significantly (p < 0.001) from 3.3 +/- 0.7 to 1.9 +/- 0.8 after 8 weeks of walking exercise. The daytime urinary frequency, blood pressure, body weight, body fat ratio, edema ratio, serum catecholamines, triglycerides, and total cholesterol were also decreased. After 8 weeks of exercise, 20 of the subjects (67%) stated that sleep was deeper than before exercise. Assessment of the overall improvement showed that excellent or good results were obtained in 18 patients (60%). The main factor related to the influence of walking exercise on nocturia was that sleep became deeper, which increased the arousal threshold bladder volume. Walking exercise may also have a preventive effect on lifestyle-related diseases.
Abstract: BACKGROUND: The mean age of starting hemodialysis (HD) in patients with end-stage renal failure is gradually increasing in Japan. It is not uncommon for HD to be commenced in bedridden elderly patients who cannot give informed consent, because of brain damage. However, we have not been able to provide useful advice to their families because there was no relevant information available about the prognosis of bedridden patients on HD. Therefore, we examined the prognosis of bedridden HD patients. METHODS: Two hundred and nineteen patients who received HD were enrolled. These subjects were divided into five groups; (aged <50, 50-59, 60-69, 70-79, and >or=80 years at the commencement of HD), and we compared the overall prognosis between bedridden and nonbedridden patients, as well as that for each age group. RESULTS: There were 76 bedridden patients among the 219 HD patients, and the main cause of their bedridden state before starting HD was cerebrovascular disease. The 50% survival time after the start of HD was 120 months for the nonbedridden patients versus 56 months for bedridden patients. However, the mean (+/-SD) age of the bedridden patients was higher than that of nonbedridden patients (70 +/- 13 versus 64 +/- 14 years). In patients under age 50 years at the start of dialysis, the survival rate was lower in the bedridden than in the nonbedridden patients, but there were no differences between survival rates for bedridden and nonbedridden patients in the other four age groups. CONCLUSIONS: The prognosis of HD patients is poor compared with the general life expectancy of the Japanese population, but whether these patients are bedridden or not has little influence on their survival.
Abstract: OBJECTIVE: We examined whether the existence of spina bifida occulta or ultrasonographic bladder abnormalities was related to the outcome of treatment for primary nocturnal enuresis in children. METHODS: Between April 1996 and September 2005, a total of 77 subjects (53 boys and 24 girls, aged 5-18 years; mean age, 9.9 years) with primary nocturnal enuresis were studied. Plain X-ray films of the spine and ultrasonographic bladder measurements (bladder wall thickness, bladder neck descent and bladder neck opening) were obtained and the correlations with the outcome of treatment using imipramine hydrochloride were assessed. RESULTS: On plain X-ray films of the spine, spina bifida occulta (lumbar vertebrae in three, lumbosacral vertebrae in 19 and sacral vertebrae in 31) was recognized in 53 children (69%). Ultrasonographic bladder abnormalities were recognized in 40 children (52%). Children with lumbar and lumbosacral spina bifida occulta showed a higher rate of concomitant ultrasonographic bladder abnormalities (P = 0.006) and had a poorer response to treatment (P = 0.041) compared with the children who had sacral spina bifida occulta. Children with ultrasonographic bladder abnormalities had a worse response to treatment (P = 0.005) compared to the children without bladder abnormalities. CONCLUSIONS: The presence of lumbar spina bifida occulta and ultrasonographic bladder abnormalities was related to the outcome of treatment for primary nocturnal enuresis in children, suggesting that spinal radiography and vesical ultrasonography may be useful predictive tests.
Abstract: AIMS: Nocturia is a common symptom in the elderly, and various contributing factors have been suggested. Therefore, in order to investigate which factors are strongly related to occurrence of nocturia, we performed a suite of examinations. METHODS: One hundred eighty volunteers were divided into three groups: a young adult control group (60 healthy persons without nocturia), an elderly control group (60 healthy persons with a low mean frequency of nocturnal urination, i.e., <once per night), and an elderly nocturia group (60 healthy persons with a high mean frequency of nocturnal urination, i.e., more than twice per night). Biochemistry tests, measurement of the osmotic pressure of plasma and urine, and body composition analysis were performed in three groups during the daytime and nighttime. In the elderly control group and the elderly nocturia group, measurement of blood pressure and recording of urinary frequency-volume charts were performed. RESULTS: The features specific to the elderly nocturia group are as follows: (1) a decrease of the nighttime plasma melatonin level, (2) an increase of nighttime plasma catecholamine levels, (3) an increase of daytime and nighttime plasma natriuretic peptide levels, (4) an increase of blood pressure, (5) a decrease of daytime and nighttime urinary osmotic pressure, (6) an increase of total urine volume, and (7) an increase of the edema ratio before sleeping. CONCLUSIONS: These results suggest that sleep disturbance, hypertension, and excessive fluid intake are major factors contributing to an increased frequency of nocturnal urination (>twice per night) in the elderly. Neurourol. Urodynam. (c) 2007 Wiley-Liss, Inc.
Abstract: PURPOSE: We investigated the effect of the blended herbal medicine Gosha-jinki-gan on bladder activity and the autonomic nervous system in rats. MATERIALS AND METHODS: A total of 42 female rats were divided into a control diet group of 21 and a Gosha-jinki-gan diet group of 21. Rats in the control diet group were fed a standard diet, while animals in the Gosha-jinki-gan were fed a special diet containing 1.08% Gosha-jinki-gan (TJ107, Tsumura Co., Tokyo, Japan). After 4 weeks 28 rats, including 14 in the control and 14 in the Gosha-jinki-gan group, underwent continuous cystometry with physiological saline or 0.1% acetic acid solution and bladder activity was recorded. The remaining 14 rats were anesthetized with halothane, and body weight, serum amino acid (glutamate and glycine) and plasma monoamine (noradrenaline, adrenaline, dopamine and serotonin) levels were measured. RESULTS: The amplitude of bladder contraction on continuous cystometry with physiological saline was lower in the Gosha-jinki-gan diet group than in the control diet group, and plasma dopamine and serotonin levels were also lower in the Gosha-jinki-gan group. When cystometry was done with 0.1% acetic acid, the interval between bladder contractions was shortened in the control and Gosha-jinki-gan groups. However, the interval and duration of bladder contractions were longer in the Gosha-jinki-gan than in the control group. CONCLUSIONS: These results suggest that Gosha-jinki-gan inhibits bladder activity by maintaining the balance of the sympathetic and parasympathetic nervous systems at a low level.
Abstract: Physicians recommend a high water intake to prevent cerebral infarction by decreasing blood viscosity. However, there is no evidence that high water intake decreases viscosity, although it increases urinary frequency. Therefore, we investigated the change of blood viscosity and urinary frequency by high water intake. We examined the change of blood viscosity after acute water intake, the circadian rhythm of blood viscosity, and the change of early morning blood viscosity and urinary frequency after high water intake for 1 week in healthy volunteers aged 31-75 years. Blood viscosity decreased transiently by acute water intake, but remained within the range of its circadian rhythm. Morning blood viscosity did not alter by high water intake for 1 week, although urinary frequency increased. Because excessive water intake increases urinary frequency without decreasing blood viscosity, a high water intake should not be recommended in persons with urinary frequency.
Abstract: We attempted to increase bladder contraction by bone marrow cell transplantation in rats with underactive bladder due to bladder outlet obstruction (BOO). Twelve female rats were anesthetized with halothane to create BOO. After 1 month, the urethral obstruction was removed and they were divided into a transplant group and a sham-operated group (n = 6 each). Bone marrow cells (1 x 10(7) / 0.2 mL) isolated from green fluorescent protein transgenic rats were injected into the bladder wall of the transplant group. Rats from the sham-operated group received injection of culture medium alone. One month after transplantation, isovolumetric cystometry parameters and histological features of bladder were observed as well as intact control rats (n = 6). The amplitude of bladder contractions was larger and the interval between contractions was shorter in the transplant group than the sham-operated group, and there were no differences in these parameters between the transplant group and the control group. Some green fluorescent muscle layers were found in the bladder wall of the transplant group, and these layers were also labeled by anti alpha-smooth muscle actin antibody. These results suggest that transplanted bone marrow cells may improve bladder contractility by differentiating into smooth muscle-like cells.
Abstract: We investigated the factors related to nocturnal urination that was not considered bothersome by comparing various parameters between subjects who felt nocturnal urination as bothersome and those who did not. A total of 94 persons (50 males and 44 females) were enrolled. They urinated >or= once per night. Each subject's perception of nocturnal urination was examined, and the subjects were divided into a bothersome group and a non-bothersome group. Blood biochemical data and urinary condition were compared between the two groups and various subgroups. There were 60 subjects (56 +/- 17 years old) in the non-bothersome group, and 34 subjects (57 +/- 17 years old) in the bothersome group. The serum melatonin level was significantly lower and the total score of the International Prostatic Symptom Score questionnaire (IPSS) and the quality of life (QOL) score were significantly higher in the bothersome group than in the non-bothersome group. Among 50 subjects with nocturnal urination >or= twice per night, the serum melatonin level was also significantly lower and the QOL score was significantly higher in the bothersome group than in the non-bothersome group. In conclusion, nocturnal urination might be not considered bothersome when subjects maintain sufficient levels of melatonin.
Abstract: We examined the effects of propiverine hydrochloride and naftopidil on the urinary ATP level and bladder activity after bladder stimulation in rats. Thirty-nine female rats were divided into a control group, a propiverine group, and a naftopidil group. Rats in the propiverine and naftopidil groups were administered 1 ml/day of propiverine or naftopidil dissolved in water at 5mg/ml, while animals in the control group were administered 1 ml of water only. After 2 weeks, 18 rats (6 per group) underwent continuous cystometry with physiological saline or 0.1% acetic acid solution and their bladder activity was recorded. In the remaining 21 rats (7 per group), 0.1% acetic acid solution was infused into the bladder and the urinary ATP level was measured before and after stimulation (days 0-7). During cystometry with acetic acid in the control group, the interval between bladder contractions was shorter and the maximum bladder contraction pressure was higher than the results for cystometry with physiological saline. The maximum bladder contraction pressure was also increased in the naftopidil group, but such a change was not seen in the propiverine group. The urinary ATP level increased significantly in all three groups after the infusion of acetic acid, but the increase of ATP was smaller in the propiverine group (45% of control) and the naftopidil group (62% of control) than in the control group on day 0. Therefore, the inhibitory effect of propiverine and naftopidil on bladder activity may be partly due to blocking ATP release from the bladder epithelium.
Abstract: Urethral polyps are rarely found in young girls. A total of 12 urethral polyps have been described in young girls in the English literature to date. Here we present a case of urethral polyp that was detected in the distal urethra of a 12-year-girl. Her chief complaint was a sudden blood discharge. On examination, a 15 x 9 mm polypoid mass with a 7 mm pedicle was seen protruding from the urethral meatus. The mass was excised under general anesthesia. Histopathologically, the polyp was covered with urothelium and squamous epithelium, and was composed of congested blood vessels and inflammatory infiltrates. These findings were similar to those of urethral caruncles in postmenopausal female. She has been free from recurrence and has had no complications, as of 12 months after excision.
Abstract: The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. During urine storage, the outlet is closed, and the bladder smooth muscle is quiescent. When bladder volume reaches the micturition threshold, activation of a micturition center in the dorsolateral pons (the pontine micturition center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. These peripheral systems are integrated by excitatory and inhibitory regulation at the levels of the spinal cord and the brain. Injury or diseases of the nervous system, as well as drugs and disorders of the peripheral organs, can produce lower urinary tract dysfunction. In the overactive bladder (OAB) condition, therapeutic targets for facilitation of urine storage can be found at the levels of the urothelium, detrusor muscles, autonomic and afferent pathways, spinal cord, and brain. There is increasing evidence showing that the urothelium has specialized sensory and signaling properties including: (1) expression of nicotinic, muscarinic, tachykinin, adrenergic, bradykinin, and transient receptor potential (TRP) receptors, (2) close physical association with afferent nerves, and (3) ability to release chemical molecules such as adenosine triphosphate (ATP), acetylcholine, and nitric oxide. Increased expression and/or sensitivity of these urothelial-sensory molecules that lead to afferent sensitization have been documented as possible pathogenesis of OAB. Targeting afferent pathways and/or bladder smooth muscles by modulating activity of ligand receptors (e.g., neurokinin, ATP, or beta(3)-adrenergic receptors) and ion channels (e.g., TRPV1 or K) could be effective to suppress OAB. In the stress urinary incontinence condition, pharmacotherapies targeting the neurally mediated urethral continence reflex during stress conditions such as sneezing or coughing could be effective for increasing the outlet resistance. Therapeutic targets include adrenergic and serotonergic receptors in the spinal cord as well as adrenergic receptors at the urethral sphincter, which can enhance urethral reflex activity during stress conditions and increase baseline urethral pressure, respectively.
Abstract: We compared the effects of melatonin, an antioxidant and sleep inducer in humans, and rilmazafone hydrochloride, a hypnotic, in elderly patients with nocturia. Patients received either melatonin (2 mg/day; n = 20) or rilmazafone (2 mg/day; n = 22) for 4 weeks. There were no significant differences in the mean age, the quality of life (QoL) score and the serum melatonin levels between the two groups at baseline. After 4 weeks' treatment, the number of nocturnal urinations was significantly decreased and the QoL score was significantly improved in both groups. There was no significant difference between the patient-reported effectiveness ratings between the two groups. The serum melatonin level was significantly increased in the melatonin-treated group, but it remained unchanged in the rilmazafone-treated group. Melatonin and rilmazafone were equally effective for nocturia in the elderly. We recommend that the problems of sleep disturbance should be considered when choosing a therapy for nocturia.
Abstract: We examined the relationship between the Arg16Gly polymorphism of beta2-adrenoceptor (ADRB2) and the efficacy of tricyclic antidepressant therapy in patients with interstitial cystitis (IC). We studied 55 IC patients and 113 controls. The IC patients were treated with imipramine hydrochloride, and the efficacy of treatment was categorized by patients' satisfaction (no change, fair, or good). Genomic DNA was extracted from the controls and IC patients, and the Arg16Gly polymorphism of ADRB2 was analyzed. The Arg16Gly polymorphism showed a significant difference in prevalence between IC patients and controls, and Arg/Arg was associated with increase in the risk of IC than Arg/Gly or Gly/Gly. Regarding the tricyclic antidepressant therapy, there was a significant difference in the prevalence of this polymorphism between IC patients with no change or a fair response to treatment and controls, and Arg/Arg was associated with decrease in the response rate to tricyclic antidepressant therapy than Arg/Gly or Gly/Gly. Therefore, these results suggest that the Arg16Gly polymorphism of ADRB2 is related to down-regulation of ADRB2 expression in the detrusor muscle, so that the response of IC to tricyclic antidepressant therapy depends on the Arg16Gly polymorphism.
Abstract: We examined the effect of 18alpha-glycyrrhetinic acid (18alpha-GA), a gap junction blocker, or propiverine hydrochloride on the activity of isolated whole bladders obtained from intact rats and rats with partial bladder outlet obstruction (BOO). Thirty-two female Sprague-Dawley rats were divided into an intact group and a BOO group. The whole bladder was harvested from each rat and isovolumetric cystometry was performed in Krebs solution. Changes of bladder activity were recorded after addition of 18alpha-GA or propiverine hydrochloride to the perfusate. Propiverine hydrochloride inhibited the amplitude and duration of contraction in both intact and BOO groups. Propiverine hydrochloride also reduced the baseline bladder pressure in the BOO group, but not in the intact group. In contrast, 18alpha-GA inhibited the amplitude and duration of bladder contraction, and also reduced the baseline pressure, in both intact and BOO groups. BOO bladders showed inhibition of the amplitude and duration of bladder contraction at lower concentrations of 18alpha-GA than intact bladders. A gap junction blocker suppressed the in vitro activity of BOO bladders more effectively than that of intact bladders. Therefore, inhibition of intercellular communication in the bladder via gap junctions may be useful for treating detrusor overactivity, as well as propiverine hydrochloride.
Abstract: OBJECTIVES: In order to clarify the role of glutamate in the micturition reflex and in glutamatergic and glycinergic neuronal activity, we examined the effects of intrathecal (IT) injection of glutamate or MK-801 (an N-methyl-D-aspartate receptor antagonist) on bladder activity and on the glutamate and glycine levels in the lumbosacral cord of female rats with or without acute lower thoracic spinal cord injury (SCI). METHODS: Under urethane anesthesia, isovolumetric cystometry was performed in rats with or without SCI before and after IT injection of glutamate or MK-801 at the lumbosacral cord level. The glutamate and glycine levels of the whole lumbosacral cord were measured after IT injection of glutamate or MK-801 in both groups. RESULTS: In intact rats, IT glutamate (100 microg) prolonged the interval between bladder contractions and decreased the amplitude of contractions. IT MK-801 (3-100 microg) also prolonged the interval between bladder contractions and decreased the amplitude in intact rats. In SCI rats, cystometry demonstrated the disappearance of bladder contractions, and the glycine level in the lumbosacral cord was elevated. In intact rats, IT glutamate (0.3-100 microg) increased the glycine level in the lumbosacral cord. On the other hand, IT MK-801 (3-100 microg) decreased both glutamate and glycine levels in intact and SCI rats. CONCLUSIONS: These results suggest that glutamatergic neurons have stimulatory projections to both glutamatergic and glycinergic neurons in the lumbosacral cord, and that glutamatergic neurons inhibit the micturition reflex by stimulating glycinergic neurons.
Abstract: The influence of the nucleus reticularis pontis oralis (PoO) on the pontine micturition center (PMC) and pontine urine storage center (PUSC) was examined in decerebrate cats by electrical and chemical stimulations of the PMC, PUSC or PoO. Microinjection of carbachol into the rostral and dorsolateral part of the PoO rapidly inhibited reflex micturition and external urethral sphincter (EUS) activity. After confirming the inhibition of reflex micturition and EUS activity by microinjection of carbachol into the PoO, intravenous injection of atropine sulfate or its microinjection into the PoO recovered both reflex micturition and EUS activity. Microinjection of carbachol into the PMC evoked micturition and then inhibited reflex micturition, but intravenous injection of atropine or its microinjection into the PoO recovered reflex micturition. After confi rming the inhibition of reflex micturition and EUS activity by microinjection of carbachol into the PoO, electrical stimulation of the PUSC enhanced EUS activity, but electrical stimulation of the PMC failed to evoke micturition. However, electrical stimulation of the PMC evoked micturition after microinjection of atropine into the PoO. These results suggest that the PoO strongly inhibits the PMC and less strongly inhibits the PUSC. Therefore, the PoO seems to be the pontine micturition inhibitory area.
Abstract: OBJECTIVE: Our previous study showed that the spinal glycine level in rats was changed by spinal injury or bladder outlet obstruction, and this change was reflected by serum glycine levels. Therefore, we measured the serum glutamate and glycine levels in healthy volunteers and patients with cerebrospinal damage or benign prostatic hyperplasia (BPH) to confirm whether the change of serum amino acid levels was obtained from these patients as well as the animal experiment. METHODS: We measured the serum glutamate and glycine levels in 170 healthy controls, 57 patients with cerebrovascular disease (CVD), 68 patients with spinal cord injury (SCI), and 70 patients with BPH. Amino acid levels were compared between the controls and patients, according to gender, level of spinal injury and the type of bladder activity. RESULTS: In the healthy controls, glutamate levels were higher and glycine levels were lower in men than in women. On group comparison of each gender, there were no differences of glutamate levels. However, glycine levels were lower in male and female SCI patients and BPH patients than in controls. According to the level of spinal injury or the pattern of bladder activity and amino acid levels, there were no relationships among them. CONCLUSIONS: Serum glutamate and glycine levels were not related to the spinal injury level or bladder activity. However, serum glycine levels changed in patients with SCI or BPH patients, so it may be possible to use it as an indicator of spinal glycinergic neuronal activity.
Abstract: BACKGROUND: We examined the influence of rectal distention on the spinal micturition reflex and the mechanism underlying its inhibition of bladder contraction. METHODS: Fourteen conscious female Sprague-Dawley rats were used in this study after transection of the lower thoracic cord. Isovolumetric cystometry was performed before and after distention of the rectum by inflation of a rectal balloon, followed by intrathecal injection of strychnine (a selective glycine receptor antagonist) or bicuculline (a GABA(A) receptor antagonist) into the lumbosacral cord. RESULTS: Rectal distention (1.0-3.0 cm(3)) prolonged the interval, decreased the amplitude, and shortened the duration of bladder contraction, and eventually almost abolished bladder activity. After intrathecal injection of strychnine (0.001-10 microg) or bicuculline (0.001-1 microg) in animals with inhibition of bladder activity by rectal distention, the interval, amplitude, and duration of bladder contraction returned to baseline. CONCLUSION: These results suggest that there is an inhibitory rectovesical reflex in the lumbosacral cord of rats with spinal cord injury, which modulates the spinal micturition reflex via glycinergic or GABAergic mechanisms.
Abstract: PURPOSE: We examined the mechanism involved in the inhibition of bladder activity in rats by stimulating the rostral pontine reticular formation (RPRF) using carbachol, flavoxate and propiverine, and by analysis of amino acid levels in the lumbosacral cord. MATERIALS AND METHODS: A total of 82 female rats were anesthetized with urethane. Under isovolumetric conditions physiological saline, carbachol, flavoxate or propiverine was injected into the RPRF or intravenously. Changes in bladder activity and amino acid levels in the lumbosacral cord were examined. RESULTS: Injection of carbachol or flavoxate (0.3 microM each) into the RPRF abolished bladder contraction but there was no change after injection of physiological saline or propiverine. Intravenous injection of flavoxate or propiverine (0.1 to 10 mg/kg each) inhibited bladder contraction. Amino acid analysis revealed that injection of carbachol into the RPRF increased glutamate and glycine levels in the lumbosacral cord, while injection of flavoxate into the RPRF or intravenously caused an increase in glycine the lumbosacral cord. Injection of propiverine into the RPRF or intravenously did not influence lumbosacral cord amino acid levels. CONCLUSIONS: These results suggest that the RPRF has an important role in the inhibition of bladder contraction and carbachol or flavoxate can activate descending RPRF neurons and inhibit bladder contraction via spinal glycinergic neurons.
Abstract: PURPOSE: The influence of dietary glycine on bladder activity, and on glutamate and glycine levels in the serum and lumbosacral cord was examined in rats with or without spinal cord injury (SCI). MATERIALS AND METHODS: A total of 84 female rats were divided into an intact and an SCI group. Each group of rats was divided into 7 subgroups. Two intact and 2 SCI subgroups were fed a standard diet and the remaining subgroups were fed diets containing 0.1% to 3% glycine. After 4 weeks isovolumetric cystometry was performed with rats under urethane anesthesia. Following cystometry glutamate and glycine levels in the serum and lumbosacral cord were measured as well as the glycine receptor alpha1 mRNA level in the lumbosacral cord. RESULTS: Dietary glycine (1% to 3%) prolonged the interval between bladder contractions in intact rats but did not change the amplitude of contractions. On the other hand, dietary glycine (1% to 3%) prolonged the interval and decreased the amplitude of bladder contractions in SCI rats. The glycine levels in the serum and lumbosacral cord of SCI rats on the standard diet were respectively 43% and 45% lower than those in intact rats on the standard diet. Dietary glycine (1% to 3%) increased the serum glycine level in intact and SCI rats but the glycine receptor alpha1 mRNA level in the lumbosacral cord was unchanged. CONCLUSIONS: Dietary glycine crosses the blood-brain barrier and inhibits the micturition reflex pathway in the lumbosacral cord but SCI and/or dietary glycine do not influence glycine receptor expression.
Abstract: PURPOSE: We examined the influence of intrathecal or dietary glycine on bladder and urethral activity in rats with spinal cord injury. MATERIALS AND METHODS: A total of 20 female Sprague-Dawley rats were used 4 weeks after lower thoracic spinal cord injury. The rats were divided into standard and 1% glycine diet groups. In the standard diet group isovolumetric cystometry and urethral pressure measurement were performed before and after intrathecal injection of glycine. In the 1% glycine diet group bladder and urethral activity were compared with control recordings in the standard diet group. RESULTS: In the standard diet group intrathecal injection of glycine prolonged the interval and decreased the amplitude of bladder contractions, decreased baseline urethral pressure and altered urethral activity during bladder contraction from a pattern of detrusor-sphincter dyssynergia to detrusor-sphincter synergy at 100 mug glycine. In the 1% glycine diet group the interval and amplitude of bladder contractions were prolonged and decreased, respectively, compared with those in the standard diet group. Baseline urethral pressure was lower than in the standard diet group even after intrathecal injection of 100 mug glycine. Urethral pressure did not change during bladder contraction and it was the same as baseline pressure. Residual urine volume was lower than in the standard diet group. CONCLUSIONS: Intrathecal or dietary glycine inhibits bladder and urethral activity, and improves detrusor hyperreflexia and detrusor-sphincter dyssynergia.
Abstract: A large cystic mass that occupied more than half of the abdomen was identified by ultrasound in a 10-month-old boy. Intravenous pyelography failed to visualize the right kidney, so we created a loop ureterocutaneostomy followed by temporary nephrostomy to improve renal function. Exploratory surgery revealed complete atresia of the distal right ureter. A ureteral stricture developed after ureteroneocystostomy and undiversion of the loop, so a second reconstruction procedure was required (pelvi-ureteroplasty and reimplantation of the right ureter with a psoas hitch) to free the patient from dependence on catheters. Despite the occurrence of giant hydronephrosis secondary to complete ureteral obstruction at the age of 10 months, the function of the right kidney could be preserved. Accordingly, aggressive attempts to promote functional recovery may be justified even when patients have advanced hydronephrosis.
Abstract: The micturition reflex is one of the autonomic reflexes, but the release of urine is regulated by voluntary neural mechanisms that involve centers in the brain and spinal cord. The micturition reflex is a bladder-to-bladder contraction reflex for which the reflex center is located in the rostral pontine tegmentum (pontine micturition center: PMC). There are two afferent pathways from the bladder to the brain. One is the dorsal system and the other is the spinothalamic tract. Afferents to the PMC ascend in the spinotegmental tract, which run through the lateral funiculus of the spinal cord. The efferent pathway from the PMC also runs through the lateral funiculus of the spinal cord to inhibit the thoracolumbar sympathetic nucleus and the sacral pudendal nerve nucleus, while promoting the activity of the sacral parasymapathetic nucleus. Inhibition of the sympathetic nucleus and pudendal nerve nucleus induces relaxation of the bladder neck and the external urethral sphincter, respectively. There are two centers that inhibit micturition in the pons, which are the pontine urine storage center and the rostral pontine reticular formation. In the lumbosacral cord, excitatory glutamatergic and inhibitory glycinergic/GABAergic neurons influence both the afferent and efferent limbs of the micturition reflex. The activity of these neurons is affected by the pontine activity. There are various excitatory and inhibitory areas co-existing in the brain, but the brain has an overall inhibitory effect on micturition, and thus maintains continence. For micturition to occur, the cerebrum must abate its inhibitory influence on the PMC.
Abstract: PURPOSE: We examined the influence of rectal distention on the spinobulbospinal micturition reflex and the mechanism underlying the inhibition of bladder contraction. MATERIALS AND METHODS: A total of 22 female Sprague-Dawley rats were used in this study. Using urethane anesthesia isovolumetric cystometry was performed before and after distention of the rectum by inflation of a rectal balloon (0 to 3 cm3), followed by the intrathecal injection of strychnine (a glycine receptor antagonist, 0.001 to 10 microg) and/or bicuculline (a gamma-aminobutyric acid(A) receptor antagonist, 0.001 to 1 microg) at the lumbosacral level of the spinal cord. RESULTS: Rectal distention (1.5 to 3.0 cm3) prolonged the interval, decreased the amplitude and shortened the duration of bladder contraction and finally almost abolished bladder activity. After intrathecal injection of strychnine or bicuculline in animals with inhibition of the bladder by rectal distention the interval and duration of bladder contraction returned to baseline but amplitude only recovered to 47% to 54% of the control level. However, simultaneous intrathecal injection of strychnine and bicuculline (0.001 microg each) restored amplitude to the control level. There were no differences between strychnine and bicuculline with respect to their effects on the interval, amplitude and duration of bladder contraction. CONCLUSIONS: An inhibitory rectovesical reflex exists in the lumbosacral cord of rats. The afferent limb of the spinobulbospinal micturition reflex pathway may be additionally and redundantly inhibited by glycinergic and GABAergic mechanisms, while the efferent limb of this pathway may be synergistically inhibited by these mechanisms.
Abstract: BACKGROUND: Transabdominal ultrasonography was used to study the bladder neck morphology in women with urethral syndrome or stress urinary incontinence, in order to determine the ultrasonographic findings of these conditions. METHODS: A total of 210 female patients with a normal bladder, asymptomatic trigonitis, urethral syndrome, and stress incontinence were studied. The mucosal thickness around the bladder neck, the length of the anterior base plate of the bladder, and the anteroposterior vesical wall angle (APVA) at the bladder neck were measured on sagittal transabdominal vesical ultrasonograms with the patient in the supine position. RESULTS: Patients with asymptomatic trigonitis or urethral syndrome had thicker mucosa around the bladder neck than the subjects with a normal bladder, and the subjects with stress incontinence had normal mucosa. The APVA was 158 +/- 17 (mean +/- SD) degrees in the subjects with a normal bladder. It was smaller in symptomatic patients and decreased to 109 +/- 10 degrees in those with conservative therapy-resistant incontinence. The anterior edge of the vesical base plate was visible approximately 2 cm from the bladder neck in subjects without incontinence, while it tended to be absent in patients with incontinence and an APVA of less than 126 degrees. CONCLUSION: A small APVA appears to reflect bladder neck descent, while a small APVA without a visible anterior base plate edge may reflect hypotonia of the vesical base plate. Transabdominal vesical ultrasonography with the patient in the supine position provides useful information and can be carried out as a routine examination in female patients with micturition disorders.
Abstract: We examined the influence of lumbosacral glycinergic neurons on the spinobulbospinal and spinal micturition reflexes. Female rats were divided into intact rats, rats with acute injury to the lower thoracic spinal cord (SCI), and rats with chronic SCI. Under urethane anesthesia, isovolumetric cystometry was performed in each group before and after intrathecal (IT) injection of glycine or strychnine into the lumbosacral cord level. The glutamate and glycine levels of the lumbosacral cord were measured after injection of glycine or strychnine in intact and chronic SCI rats. Expression of strychnine-sensitive glycine receptor alpha-1 (GlyR alpha1) mRNA in the lumbosacral cord was also assessed in both rats. In chronic SCI rats, the interval and amplitude of bladder contractions were shorter and smaller when compared with intact rats. IT glycine (0.1-100 microg) prolonged the interval and decreased the amplitude of bladder contractions in both intact rats and chronic SCI rats. IT strychnine (0.01-10 microg) elevated the baseline pressure in intact rats and induced bladder contraction in acute SCI rats. On amino acid analysis, IT glycine (0.01-100 microg) decreased the glutamate level of the lumbosacral cord in intact rats, but not in chronic SCI rats. The glycine level of the lumbosacral cord was 54% lower in chronic SCI rats when compared with intact rats, while the GlyR alpha1 mRNA level did not change after SCI. These results suggest that glycinergic neurons may have an important inhibitory effect on the spinobulbospinal and spinal micturition reflexes at the level of the lumbosacral cord.
Abstract: AIM: Many patients with stress urinary incontinence do not have enough motivation to continue pelvic floor muscle training (PFMT) by themselves. Therefore, a device was created to support PFMT, and its effect was examined. METHODS: Forty-six women with stress urinary incontinence were assigned to a control group or a device group in order of presentation. A pamphlet on PFMT was given to control patients, while the same pamphlet plus the device and instructions on its use were given to patients in the device group. The device had a chime that was set to sound three times a day when exercise sessions were scheduled. PFMT consisted of fast and slow pelvic floor muscle contraction exercises that were performed for 2 min and followed a rhythm set by the device. RESULTS: After 8 weeks, 20 patients from the control group and 21 patients from the device group could be evaluated. In the control group, only the quality of life (QOL) index improved significantly. In the device group, however, the daily number of incontinence episodes, the number of pads used daily, the QOL index, and the pad weight in the pad test improved significantly. Patients in the device group said that they felt obligated to perform PFMT when the chime sounded. Forty-eight percent of patients from the device group were satisfied with the outcome of PFMT, while only 15% were satisfied in the control group. CONCLUSION: This device may be useful to support the management of stress urinary incontinence.
Abstract: The effects of intrathecal injection of tamsulosin (an alpha-1A adrenergic receptor antagonist) and naftopidil (an alpha-1D adrenergic receptor antagonist) on isovolumetric bladder contraction were investigated in rats under urethane anesthesia. Intrathecal injection of tamsulosin (10-30 microg) or naftopidil (0.1-30 microg) transiently abolished isovolumetric rhythmic bladder contraction. Following the recovery of bladder contraction, the interval between contractions was the same as the control value before the injection. The amplitude of bladder contraction was decreased by intrathecal injection of naftopidil (3-30 microg), but not by tamsulosin. Therefore, in addition to the antagonistic action of these agents on the alpha-1 adrenergic receptors of prostatic smooth muscle, both agents (especially naftopidil) may also act on the lumbosacral cord, and thus may improve collecting disorders in patients with benign prostatic hyperplasia.
Abstract: A 10-year-old boy presented to our hospital with pain in the flank and was subsequently diagnosed as having a retrocaval ureter. He underwent retroperitoneoscopic surgery, during which the retrocaval segment of the right ureter was divided and reanastomosed anterior to the inferior vena cava using 5-0 polyglactin. He returned to normal activities from three days after the procedure. Hydronephrosis was markedly decreased on excretory urography at 6 months after surgery. To the best of our knowledge, this is the eighth case report on retroperitoneoscopic surgery for retrocaval ureter in the English and Japanese literature.
Abstract: PURPOSE: Interstitial cystitis is a chronic and sterile inflammatory disease of the bladder. Clinically many patients with interstitial cystitis also have allergic or autoimmune diseases. Recent studies have suggested that allelic variations in the adrenergic receptor beta2 gene, the interleukin (IL)-4 gene and its receptor gene are closely associated with immune diseases. Therefore, we studied adrenergic receptor genes alpha1d (ADRA1d), beta2 (ADRB2) and beta3 (ADRB3), and IL-4/IL-4 receptor genes in patients with interstitial cystitis. MATERIALS AND METHODS: We studied 55 patients with interstitial cystitis and 228 controls. Genomic DNA was extracted from a whole blood sample collected from each subject. We analyzed 5 gene polymorphisms (G404781T, Arg16Gly, Trp64Arg, C589T and Ile50Val) per gene (ADRA1d, ADRB2, ADRB3, IL-4 and IL-4 receptor, respectively) and their relationship to interstitial cystitis. RESULTS: The frequency of the Arg/Arg genotype of the ADRB2 gene and the TT genotype of the IL-4 gene were significantly higher in patients with interstitial cystitis than in controls. A significant difference of ADRA1d genotype prevalence was also observed. However, there were no remarkable differences of IL-4 receptor or ADRB3 genotype prevalences. CONCLUSIONS: Variants of the ADRB2, ADRA1d and IL-4 genes may be related to a predisposition to interstitial cystitis.
Abstract: BACKGROUND: Our previous study showed that the anteroposterior vesical wall angle (APVA) at the bladder neck on transabdominal ultrasonography varied widely between women. The present study examines whether the APVA changes during development in girls with a normal bladder. METHODS: Seventy-four females aged 0-29 years with normal bladders were examined by transabdominal ultrasonography. They were divided into six age groups and their APVA was measured in the supine position by sagittal ultrasonography. Intravenous urography was conducted to examine bladder neck descent and bladder neck opening. RESULTS: The APVA ranged from 85 to 200 degrees. The mean APVA in girls aged 0-4 years was 129 +/- 30 degrees (+/-SD) and the mean APVA in girls aged 5-9 years was 135 +/- 25 degrees. The mean APVA at ages 10-14 years was 161 +/- 26 degrees; at 15-19 years, 164 +/- 33 degrees; at 20-24 years, 164 +/- 18 degrees; and at 25-29 years, 163 +/- 16 degrees. The APVA values of these four groups were significantly larger (P < 0.05) than those of the two younger groups. No bladder abnormalities were found on intravenous urography. CONCLUSION: The APVA was small in some girls under 10 years of age, but the APVA of girls aged over 10 years was similar to that in young adults. The APVA may reflect bladder base plate tone and be partially related to hormonal changes in females during development.
Abstract: A 19-year-old man with a history of histologically-proven Goodpasture's syndrome (hemoptysis, rapidly progressive glomerulonephritis, and positive anti-glomerular basement membrane (anti-GBM) antibody) was maintained on hemodialysis for 21 months. After steroid pulse therapy and plasmapheresis, his anti-GBM antibody disappeared. His stable condition on dialysis and a session of plasmapheresis prior to surgery allowed him to undergo cadaveric renal transplantation from a 34-year-old man. The blood type was identical (group A and Rh (+)), and there was 1 and 0 mismatch of HLA class 1 and 2, respectively. The initial immunosuppressants included cyclosporine, methylprednisolone, mizoribine, azathioprine, and anti-lymphocyte globulin (ALG). The transplanted kidney regained function on day 6 and he was free from hemodialysis. Circulating anti-GBM antibody was negative after surgery. The graft has functioned well for almost 4 years after transplantation without any episodes of renal or pulmonary complications. To the best of our knowledge, this is the first report of renal transplantation for Goodpasture's syndrome in the Japanese literature.
Abstract: A 47-year-old man presented with a left renal incidentaloma without hematuria. The tumor was complicated by inferior vena cava (IVC) thrombus extending from Th11 to L4. A temporary IVC filter was introduced prior to surgery. A midline incision was used to perform a left radical nephrectomy and en bloc lymphadenectomy with excision of the inferior vena cava from above the level of the left renal vein to 2.5 cm above the confluence of the common iliac veins. The pathological diagnosis was invasive transitional cell carcinoma. The tumor thrombus consisted of transitional cell carcinoma that histologically invaded the walls of the IVC. He died of cancer 17 months after the operation for the liver metastases. This is the 18th case report of such a presentation in the literature.
Abstract: A 5-year-old girl with a history of recurrent urinary tract infection since the age of 14 months was diagnosed as having a right duplicated urinary collecting system with the upper ureter ectopically opening in the urethra. She underwent retroperitoneoscopic heminephrectomy for a right dysplastic kidney and open ureterocelectomy and reimplantation of the refluxing lower ureter via Pfannenstiel incision. She survived the procedure without serious complications and resumed normal daily activities by day 6. To the best of our knowledge, this case is the 16th case of laparoscopic heminephrectomy for pediatric patients and the first case treated by the retroperitoneal approach in the English literature.
Abstract: Bilateral hydronephrosis identified by a local physician brought a 65-year-old man to our hospital. Emergency percutaneous nephrostomy was bilaterally established for obstructive renal failure. After recovering renal function, the patient underwent radical cystectomy under the diagnosis of invasive bladder cancer and the construction of an ileal conduit. The pathology reported well differentiated adenocarcinoma (pT2, pL1, pV1). Five years after the surgery, gross hematuria developed. A computed tomographic scan revealed right hydronephrosis with a solid mass in the upper calyx. The urinary cytology was negative. The patient underwent right nephrectomy in May, 1999. The pathology then revealed well differentiated adenocarcinoma in the renal pelvis and ureter (pT3, pL0, pV0 and pT1, pL0, pV0, respectively). He is alive with mild chronic renal insufficiency with evidence of tumor at ten months after surgery. To our knowledge, this is the first case of metachronous adenocarcinoma of the urinary bladder and the upper urinary tract reported in the Japanese literature.
Abstract: Benign prostate hypertrophy weighing more than 200 g is defined as giant prostatic hypertrophy. An 81-year-old man presented with urinary retention and underwent retropubic prostatectomy. Blood loss was 1,850 ml and he received 800 ml of autologous blood. The removed specimen weighed 267 g and pathology revealed benign hyperplasia of the prostate. We collected 32 such cases from the Japanese literature.
Abstract: A 67-year-old woman presented with upper abdominal pain and was found to have a suprarenal tumor by ultrasonography and CT scanning. Under a diagnosis of non-functioning adrenal tumor, we made an extraperitoneal approach via a lumbar incision and removed the tumor together with the left adrenal gland. There was minimal blood loss. The resected tumor was firm and had a yellowish-white cut surface. The lesion measured 60 x 40 x 35 mm and weighed 50 g. The pathological diagnosis was benign schwannoma, mainly of the Antoni type A. This is the 27th case of benign schwannoma in the adrenal area reported in the Japanese literature.
Abstract: Renal transplantation for patients with systemic lupus erythematosus (SLE) remains controversial. We performed living-tissue related renal transplantation on a 45-year-old woman with SLE and an eight-month history of hemodialysis. We also did cadaveric renal transplantation on a 41-year-old man with SLE and a 12-year history of hemodialysis. Serological tests including tests for antinuclear antibodies and complements were negative prior to surgery and throughout the course in both cases. The latter patients survived herpes-zoster virus infection in month 6 and bacterial pneumonia in month 9 after transplantation. Neither patient experienced any rejection or relapse of lupus nephritis after the procedure, and both maintained good renal allograft functions. The recurrence of lupus nephritis is reportedly extremely rare, i.e., with a possibility rate of less than 1% in transplant patients with burnt-out SLE. To the best of our knowledge, these cases are the 27th and 28th case reports of renal transplantation for SLE patients in Japanese literature.
Abstract: BACKGROUND: It is difficult to diagnose intermittent hydronephrosis and to decide the indication of surgical intervention. We investigated 23 cases of intermittent hydronephrosis. METHODS: From 1978 to 1995, a total of 23 patients were diagnosed as intermittent hydronephrosis in our institution. We inspected their clinical features and treatment which had been performed to them. RESULTS: Our study comprised 21 boys and 2 girls, whose mean age was 6 year old. Their chief complaint was intermittent flank pain (left: 21, right: 1, bilateral: 1) accompanied with gross hematuria (30%) and vomiting (39%). When they were asymptomatic, an excretory urogram revealed only mild pelvic dilatation without calyceal distension and kinking of ureteropelvic junction. Split renal function study by RI showed no difference between the affected side and the normal side except one case. When pelvic or calyceal enlargement was confirmed on ultrasonography while they were symptomatic, surgery was indicated. Surgery was performed in 17 cases (74%) including dismembered pyeloplasty in 14 cases, resection of aberrant vessel in 1, relocation of lower pole renal vessel in 1 and nephrectomy in 1. In surgical and histological view points, intrinsic stenosis was seen in 10 cases, extrinsic obstruction caused by aberrant vessels was seen in 4 and ureteral polyp was seen in 3 (bilateral polyp in 1 case). CONCLUSION: They had no more symptoms after operation. Of 23 among followed up cases without surgery, we experienced 2 cases unexpectedly advancing irreversible hydronephrotic change after the last attack, 1 case of gradually progressing hydronephrotic change and 1 case of severe renal dysfunction after many attacks. Therefore intermittent hydronephrosis should be followed up carefully.
