The septal area, site for the central regulation of penile erection during waking and rapid eye movement sleep in rats: a stimulation study.

The effects of electrical stimulation to the septum on penile erections in rats were examined to clarify the mechanisms for regulation of erectile responses during different states of vigilance. Penile responses were assessed by changes in pressure in the corpus spongiosum of penis (CSP) and electromyography (EMG) of the bulbospongiosus (BS) muscle. In anesthetized and un-anesthetized rats, stimulation in and around the septum induced three erectile patterns; 1) a Normal type response, which was indistinguishable from a spontaneous erection, characterized by a slow increase in CSP pressure with sharp CSP pressure peaks associated with BS muscle bursts, 2) Mixed type response, in which high frequency CSP pressure peaks were followed by a Normal type response, and 3) a Prolonged type response, evoked only in the anesthetized rat, consisting of a single sharp CSP peak followed by a slow increase in CSP pressure and a return to baseline with multiple subsequent events repeated for up to 960 s. In addition, a Micturition type response was also observed involving high frequency CSP pressure oscillations similar to the pressure pattern seen during spontaneous micturition. We found that erections were induced after stimulation to the lateral septum (LS), but not from the medial septum (MS). In anesthetized rats, a few responses were also obtained following stimulation of the horizontal limb of diagonal band (HDB). In un-anesthetized rats, responses were also induced from the HDB and the ventral limb of diagonal band (VDB) and the adjoining areas. The effective sites for eliciting erection during rapid eye movement (REM) sleep were located in the dorsal and intermediate parts of the LS, whereas the ventral part of the LS was the most effective site for eliciting erections during wakefulness. These results suggest a functional role for penile erection in the septum, and further suggest that subdivisions of the LS may have different roles in the regulation of penile erection during wakefulness and REM sleep.

Metabotropic glutamate receptor subtype 7 has critical roles in regulation of the endocrine system and social behaviours.

Metabotropic glutamate receptor subtype 7 (mGluR7) is one of the group III mGluRs, which are negatively coupled to adenylate cyclase via Gi/Go proteins and localised to presynaptic active zones of the mammalian central nervous system. We previously reported that mGluR7 is essential for intermale aggression and amygdala-dependent fear learning. To elucidate the role of mGluR7 in the neuroendocrine system, we performed biochemical analyses and found a significant reduction of testosterone levels in mGluR7 knockout (KO) mice. Testosterone replacement restored intermale aggressive behaviour in castrated wild-type mice to the level of gonadally intact wild-type mice. However, given the same dosage of testosterone replacement, mGluR7 KO mice showed almost no aggressive behaviour. These results indicate that reduction of plasma testosterone is unrelated to the deficit in intermale aggression in mGluR7 KO mice. Social investigating behaviour of intact mGluR7 KO mice also differed from that of wild-type mice; e.g. the KO mice showing less frequent anogenital sniffing and more frequent grooming behaviour. Testosterone replacement increased anogenital sniffing and grooming behaviour in castrated mGluR7 KO mice, while the differences were still present between castrated wild-type mice and KO mice after both underwent testosterone replacement. These results imply that reduction of plasma testosterone may partially inhibit social investigating behaviours in intact mGluR7 KO mice. Furthermore, castrated mGluR7 KO mice have smaller seminal vesicles than those of castrated wild-type mice, although seminal vesicle weights were normal in intact mice. These observations suggest that, besides testicular testosterone, some other hormone levels may be dysregulated in mGluR7 KO mice, and indicate a critical role of mGluR7 in the endocrine system. Taken together, our findings demonstrate that mGluR7 is essential for the regulation of the endocrine system, in addition to innate behaviours such as intermale aggression and fear response.

Do motorcyclists have erectile dysfunction? A preliminary study.

The aim of the present study was to evaluate the relationship between motorcycling and erectile dysfunction (ED). We investigated the relationship between motorcycling and erectile function using the 5-items version of the International Index of Erectile Function (IIEF5) in 234 motorcyclists (response rate 75%) and 752 healthy controls (response rate 66%). In all, 161 (69%) of 234 motorcyclists were diagnosed as ED based on IIEF5. The prevalence of ED in the motorcycle group increased by age as: 58, 63, 76 and 93%, for motorcyclists in 20-29, 30-39, 40-49 and 50-59 years, respectively. There was a significant difference in the prevalence of ED between the motorcycle group and the control group in all age groups. On stepwise logistic regression analysis, motorcycling was the strongest risk factor for ED. Although the severity of ED in motorcyclists was not so severe, motorcycling may be one of risk factors for ED.

Restless legs syndrome in hemodialysis patients: health-related quality of life and laboratory data analysis.

AIMS: To compare clinical data, sleep quality and health-related quality of life (HRQOL) with and without RLS in HD patients. MATERIALS AND METHODS: The international RLS study group diagnosis questionnaire was completed by 228 HD patients. The Pittsburg Sleep Quality Index (PSQI) for the evaluation of sleep quality and the Kidney Disease Quality of Life (KDQOL-SF) for the analysis of HRQOL were also used. RESULTS: 53 (23%) patients were diagnosed as RLS. Age and age at the initiation of HD were significantly younger in the RLS group. Serum calcium concentration (Ca) was significantly higher in the RLS group. Sleep quality evaluated by PSQI was significantly lower in the RLS group. In SF-36 domains of KDQOL-SF, bodily pain, general health perceptions, vitality, role functioning emotional, mental health and mental component score were significantly lower in the RLS group. In kidney targeted scales of KDQOL-SF, symptoms/problems, burden of kidney disease, cognitive function, quality of social interaction, sleep and patient satisfaction were significantly lower in the RLS group. CONCLUSION: High Ca was possibly connected to the pathophysiology of RLS which impaired sleep quality as well as HRQOL including mental health and many kidney disease related scales.

Efficacy of sildenafil as the first-step therapeutic tool for Japanese patients with erectile dysfunction.

The aim of this study was to assess the efficacy of sildenafil as the first-step tool for erectile dysfunction (ED) in Japanese males. Between March 1999 and March 2003, 281 patients were prescribed five tablets of sildenafil (50 mg) as the first step in the therapeutic management of ED. Of the 281 patients, 206 were evaluable patients. The overall success rate in achieving sexual intercourse in subjects after taking sildenafil was 77.2% (159/206), while 22.8% (47/206) were unsuccessful. The success rates in men with functional ED and organic ED were 91.4% (85/93) and 65.5% (74/113), respectively (P<0.0001). Overall, transient adverse effects of sildenafil occurred in 16 (8%) males. Intolerable adverse effects (edema and dizziness) occurred in only 1% of patients (2/206). Sildenafil citrate may be recommended as the first choice drug for ED because of its high success rate and low invasiveness.

The significance of dihydropyrimidine dehydrogenase (DPD) activity in bladder cancer.

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the pathway of uracil and thymine catabolism. DPD is also the principal enzyme involved in the degradation of 5-fluorouracil (5-FU), which is one of the anticancer chemotherapeutic agents currently used in the treatment of bladder cancer. Little is known about the significance of DPD activity in human cancers. We investigated the activity of DPD in 74 bladder cancers and the relationship between the DPD activity and the sensitivity to 5-FU. The levels of DPD activity in bladder cancer and normal bladder tissues were determined by the 5-FU degradation assay. The sensitivity to 5-FU was assessed by the microculture tetrazolium dye (dimethylthiazolyl-2-5-diphenyltetrazolium bromide; MTT) assay. The activity of DPD was approximately 2-fold higher in bladder cancer tissues compared with normal bladder tissues. DPD activity in invasive bladder cancers was approximately 2-fold higher than that in superficial cancers. In addition, the levels of DPD activity in grade 2 and grade 3 bladder cancers were approximately 3-fold and 4-fold higher than that in grade 1 cancers, respectively. Patients with superficial bladder cancer with a low DPD activity had a slightly longer postoperative tumour-free period than those with a high DPD activity over a 2-year follow-up period, but this was not significant. There was an inverse correlation between DPD activity in bladder cancer cells and their sensitivity to 5-FU. Furthermore, 5-chloro-2,4-dihydroxypyridine (CDHP), a potent DPD inhibitor, enhanced the sensitivity to 5-FU. The present study has demonstrated that the level of DPD activity correlated with the progression of the stage and an increase in the grade of the bladder cancer. These results suggest that an elevated DPD activity might be associated with the malignant potential of the bladder cancer. In addition, it might be possible to overcome 5-FU insensitivity by using DPD inhibitors in the treatment protocols of 5-FU-based chemotherapy for bladder cancers.

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.

Significant decrease of the International Index of Erectile Function in male renal failure patients treated with hemodialysis.

In order to evaluate the erectile function in male renal failure patients treated with hemodialysis (HD), we investigated the International Index of Erectile Function (IIEF) in patients and healthy controls. The subjects were 174 male patients treated with HD, of whom 43 had diabetes mellitus (DM) and the remaining 131 patients did not have DM. The controls were 1133 healthy males. We evaluated the prevalence of erectile dysfunction (ED) using the erectile function (EF) score, which is one of the five domains of the IIEF, in each age group (upto 39 y old, 40-49 y old, 50-59 y old, 60-69 y old). The severity of ED was classified into five categories using EF in each age group. The univariate logistic regression analysis and multiple variate analysis of IIEF in HD patients were performed. The prevalence of ED in HD patients was significantly higher than that in the controls in each age group. The severity of ED in HD patients was also significantly higher than that in the controls in each age group. In the logistic regression analysis and multiple variate analysis of IIEF in HD patients, DM and age were significant risk factors on sexual dysfunction. ED was more prevalent in male renal failure patients treated with HD than in the controls. In the patient group, ED was more prevalent in older DM patients.

Erythrocyte aldose reductase correlates with erectile dysfunction in diabetic patients.

Erectile dysfunction (ED) is a common complication of diabetes mellitus. Erythrocyte aldose reductase (AR) has been implicated in a variety of diabetic complications. The subjects were 62 diabetic patients, of whom 25 were treated with hemodialysis (chronic renal failure CRF group) and the remaining 37 did not have chronic renal failure (DM group). The controls were 20 healthy volunteers age-matched to the patients. The level of AR was measured by the quantitative determination kit for AR in all patients and controls. In this study, ED was diagnosed by 5-item version of the International Index of Erectile Function (IIEF-5). The average level of AR in the CRF group was significantly higher than that in the DM group and controls (P<0.001). The average level of AR in the DM group without ED was significantly lower than that in the DM group with ED and controls (P<0.005). These results suggest that the level of AR may be a useful modality for prediction of ED in diabetic patients.

Possible use of ultrasound estimated bladder weight in evaluating vesicoureteral reflux in children.

The present study was designed to reveal the possible use of ultrasound estimated bladder weight (UEBW) in evaluating vesicoureteral reflux (VUR) in children in terms of possible implication of bladder hypertrophy in VUR. In 27 children with VUR, UEBW was measured by transabdominal ultrasound. The UEBW in an individual patient was evaluated quantitatively using the percent deviation from age matched UEBW. There was a significant difference noted in the percent deviation from age-matched UEBW between patients (n = 17) with primary VUR and those (n = 10) with secondary VUR (p <.05). When analyzed together in 27 patients, a significant positive correlation (p <.05) was recognized between the percent deviation from age-matched UEBW and VUR grade. This was also the case in ten patients with secondary VUR (p <.01), but not for 17 patients with primary VUR. The measurement of UEBW might be of clinical use in evaluating the pathogenesis as well as the severity of VUR in children.

Intracranial vessels with color Doppler echoencephalography in infants.

A technique for imaging of the intracranial vessels in infants was described, which used high resolution, commercially available, color Doppler ultrasonography (real-time two-dimensional Doppler). On 12 normal infants, serial scans were obtained in sagittal, coronal, and axial plains. A large number of intracranial arteries and veins could be clearly demonstrated in real-time, including anterior cerebral artery, pericallosal artery, middle cerebral artery, posterior cerebral artery, basilar artery, communicating artery, internal cerebral vein, inferior and superior sagittal sinuses, great cerebral vein, straight sinus, occipital sinus and transverse sinus. In conclusion, color Doppler examination is useful in the detection of vessels in infants and in the measurement of intracranial blood flow velocity.

Color Doppler flow imaging of CSF flow in an infant with intraventricular hemorrhage.

Evaluation of CSF flow was performed by means of the color Doppler flow imaging (CDFI) technique. The motion of CSF was examined in an infant with intraventricular hemorrhage (IVH). With the aid of CDFI, CSF flow in the aqueduct, 3rd ventricle and foramen of Monro could be demonstrated. CSF flow in both upward and downward directions was clearly visualized, primarily reflecting cardiac pulsation and respiration. When he was subjected with intermittent positive pressure ventilation, during inspiration there was upward flow in the aqueduct, while during expiration there was downward flow. Our experience indicates that CDFI is a useful technique for examining the CSF circulation in infants with IVH.

[A study of the intraorbital blood flow using ultrasound color Doppler mapping images in optic canal fracture cases].

Ultrasound color Doppler flow mapping image (CFMI) equipment, SSA-270A (Toshiba Co) was used to measure the blood flow velocity of the ophthalmic artery (OA) and the central retinal artery (CA) in eyes with optic canal fracture. The maximal blood flow velocity (V max), the minimal blood flow velocity (V min), the mean blood flow velocity (V mean), and the resistance index (RI) before and after transethmoidal decompression of the optic nerve were compared. The examination was conducted on 13 patients. There was no difference in blood flow velocity in the CA after the operation. Pre-operative V max and RI of the OA in the damaged eyes were lower than in normal eyes, but they increased the day after the operation. We measured the intraorbital blood flow velocity by CFMI because ultrasound does not penetrate bone. Since the peripheral artery from the optic foramen did not change after the operation, we concluded that the peripheral blood flow of OA had been quantitatively improved by the trans-ethmoidal decompression of the optic nerve.

[A fundamental study on expansive splitter lithotripsy].

The application of expansive splitter for industrial use to lithotripsy was studied. A natural rubber latex catheter 350 mm in length, 3.5 mm in diameter and 0.1 mm in thickness was newly developed for prevention from alkalization by expansive splitter. Expansive pressure generated by expansive splitter was measured to calculate the fragmentation time of urinary stones. Urinary stones 20, 30 or 40 mm in diameter were expected to be fragmented in 7.5, 9 and 11 minutes. Human bladder stone 55 x 54 x 33 mm in size was divided into two parts in 24 minutes using expansive splitter. The fragmentation test of model calculi was performed to decide the boring length necessary for the fragmentation of urinary stones. The necessary boring length was a half of the stone diameter in stones smaller than 20 mm in diameter and was 3/4 of it in stones larger than 30 mm in diameter. A tolerance test of the catheter was performed. When the used catheters for splitting were immersed in water, no change was observed in pH, in spite of the elevation of pH from 6.6 to 12.3 when the splitter itself was immersed in water. No leakage of water from the catheter was observed in this tolerance test. Histological change on the epithelium of the bladder and the renal pelvis by expansive splitter was examined. The mucosa of the dog; bladder and the pig renal pelvis, to which expansive splitter was made contact, showed no histological change after 30, 45 or 60 minutes after the contact. In conclusion, expansive splitter enclosed in the natural rubber latex catheter can be employed for clinical use to fragment urinary calculi in endourological procedures.

[Vesico-prostatic calculi treated by microexplosion lithotripsy: a case report].

A 48-year-old male suffering from neurogenic bladder due to spinal injury was admitted to our clinic with a chief complaint of macrohematuria. Examinations revealed some calculi located in the bladder and in the prostate. Microexplosion lithotripsy for the prostatic calculi (29 x 23 mm etc.) was performed via the urethra and for the vesical calculus (65 x 55 mm) via the suprapubic cystostomy channel. The calculi were fragmented and removed out completely.

[A case of recurrent stones in the urinary bladder after extensive panhysterectomy].

A 71-year-old female suffered from recurrent stones in the urinary bladder, caused by bladder injury due to extensive panhysterectomy. The stones were crushed successfully by micro-explosion lithotripsy (MEL). This newly established treatment is recommended for such recurrent stones in the urinary bladder.

[Ofloxacin concentration in prostatic tissue].

The concentration of ofloxacin in prostatic tissue and serum was determined in order to evaluate the permeability of ofloxacin into prostatic tissue in patients with benign prostatic hypertrophy. Ofloxacin was administered orally at a dose of 200 mg several hours before subcapsular prostatectomy. The determination was performed in the surgically removed adenoma and in the serum taken one hour before and at the removal of the adenoma. The peak level in the prostatic tissue was 1.46 microgram/g at 4.5 hour after the administration. The ratio of prostatic tissue level to the serum level was 1.00. In conclusion, ofloxacin was thought to be very useful for the treatment of acute and chronic prostatitis.

[A case of primary adenocarcinoma of the female urethra].

A 53-year-old female visited our hospital with a complaint of acute urinary retention. Transvaginal ultrasonography, computed tomography and magnetic resonance imaging showed extreme thickening of the urethral wall. Histopathological examination of the transvaginal needle biopsy suggested well-differentiated adenocarcinoma. She underwent total cysto-urethrectomy with partial vaginal wall resection and ileal conduit urinary diversion. Pathological diagnosis of the tumor was columnar adenocarcinoma invading into the vaginal wall and periurethral connective tissue. Fifty-eight cases of primary adenocarcinoma of the female urethra in the Japanease literature are briefly reviewed.

[Two cases of rhabdomyosarcoma of the bladder in children].

A 1-year-old boy was admitted to our hospital with chief complaint of urinary retention and a lower abdominal large mass. The mass was shown in the bladder by computerized tomography (CT) associated with paraaortic lymph node swelling. Tumor biopsy revealed rhabdomyosarcoma, embryonal type. Complete remission (CR) was obtained by chemotherapy based on STS' 88. He has been healthy 40 months without recurrence. A similar case of rhabdomyosarcoma, embryonal type, in the bladder in a 3-year-old girl with a chief complaint of macrohematuria was verified by CT and tumor biopsy. The same chemotherapy was performed, resulting in partial remission (PR). A complete resection of the tumor was achieved by partial cystectomy. She is alive without recurrence 18 months after the cystectomy.

[Influential factors on the therapeutic response in the conditioning treatment of enuresis with an original therapeutic machine].

The conditioning treatment of enuresis with our original therapeutic machine, that is to awake the patient before enuresis may occur, has been performed since 1987. Influential factors on the therapeutic response were investigated. Twenty two patients with enuresis Type I were admitted and were treated for 5 nights with the therapeutic machine. Seven patients were cured (the cured group) and a certain effectiveness (decrease of the frequency of enuresis of more than 50%) was observed in 8 patients (the effective group). No effectiveness was obtained in 7 patients (the no change group). The average age of the cured group was higher than that of the no change group, and the difference was significant. No significant differences were found among the three groups in sex, the frequency of enuresis or the past experience of awakening before enuresis. Significant differences among the three groups were found in the average awakening score (how easily the patient awoke when a nurse called the patient after the machine alarmed) and the change of awakening score during treatment. The average awakening score of the cured group was the highest and that of the no change group was the lowest. The change of awakening score during treatment of the no change group was significantly lower than that of the cured group or that of the effective group. The desire to cure, scored 0-2 points at the time of discharge, was significantly stronger in the cured group than in the no change group. No significant differences were noticed among the three groups in the sleeping condition and the remembrance of awakening at the next morning.