Intravesical resiniferatoxin for patients with neurogenic detrusor overactivity

BACKGROUND: Resiniferatoxin (RTX), a substance isolated from some species of Euphobia, is a specific C-fiber neurotoxin which produces desensitization rather than excitation. At first, we performed intravesical RTX therapy on eight patients with neurogenic detrusor overactivity. After we confirmed the safety and efficacy, a Japanese RTX study group was organized and a new protocol made. The multicenter trial was performed in Japan. However, the efficacy of the treatments was different among the institutions. Therefore, we have compared the results between the first protocol and the new one at our hospital. METHODS: The first and second protocol involved the RTX solution (30 mL of 500 nM, and 100 mL of 1 micro M, respectively) being instillated in the bladder for 30 min by almost the same procedures. Effects on bladder function were evaluated during treatment and at follow up. RESULTS: For the first and second protocols, six out of eight patients noted symptomatic improvement while two patients did not notice any change in the degree of incontinence for one month. The mean urodynamic bladder capacity had significantly increased from 138.0 +/- 64.4 mL to 227.3 +/- 112.4 mL and 133.1 +/- 43.3 mL to 247.0 +/- 102.3 mL 1 month after RTX treatment for the first and second protocols, respectively (P < 0.05). No severe side-effects were seen in either group. CONCLUSION: Intravesical RTX improved bladder capacity in patients with neurogenic detrusor overactivity in both protocols. The concentration of RTX did not exhibit any change in the effect and safety in our hospital. Intravesical RTX is a promising treatment for neurogenic detrusor overactivity.     

INGUINAL CYSTOCELES: A PREVIOUSLY OVERLOOKED ETIOLOGY OF PROSTATISM IN MEN WITHOUT BLADDER OUTLET OBSTRUCTION

Purpose

We determine whether inguinal cystoceles, a type of extraperitoneal herniation of the bladder, are responsible for symptoms consistent with prostatism in men without bladder outlet obstruction.

Materials and Methods

From January 1996 to February 1997 inguinal cystoceles were treated with surgical repair of the floor of the inguinal canal in 8 men with a relatively long history of symptoms consistent with prostatism. The diagnosis of inguinal cystoceles was based on the filling phase of video urodynamic studies done with the patient standing. The clinical outcome of surgery was assessed using the International Prostate Symptom Score and urodynamic findings.

Results

All inguinal cystoceles studied were physically occult but clearly detected as wide-mouthed, mild protrusions of the bladder wall in the inguinal region on cystograms obtained with the patient standing. Although clear cystoceles were present on radiography on the right side in 1 case, the left side in 2 and bilaterally in 5, apparent bilateral weakness in Hesselbach's triangle was noted in all at surgery. High detrusor opening pressure and a relatively long opening time were regarded as urodynamic parameters characteristics of this condition. These parameters and subjective symptoms dramatically improved after bilateral surgical repair of the floor of the inguinal canal.

Conclusions

Inguinal cystoceles negatively affect voiding dynamics by increasing opening pressure and opening time, indicating that they should be considered in the differential diagnosis of men with symptoms consistent with prostatism. Video urodynamics is mandatory to detect this condition, which to our knowledge has been previously overlooked on radiography and urodynamics.     

Isolation and characterization of growth hormone from a marine fish,bonito (Katsuwonus pelamis)

Growth hormone (GH) was extracted under alkaline conditions (pH 10) from pituitary glands (6.3 g) of bonito (Katsuwonus pelamis), and subsequently purified by gel filtration, ion exchange chromatography, and reversed-phase HPLC. The GH was monitored by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and by immunoblotting with yellowtail GH antiserum at each step of purification. GH activity was determined by an in vivo bioassay. The yield of this hormone was 4.8mg/g wet tissue. Intraperitoneal injection of bonito GH at doses of 0.1 and 1 μg/g body wt at 7-day intervals resulted in a significant increase in body weight and length of juvenile rainbow trout. Bonito GH antiserum exhibited both species and hormone specificity in radioimmunoassay. However, the bonito GH antiserum as well as yellowtail GH antiserum exhibited hormone specificity but not species specificity in immunoblotting. A molecular weight of 21 000 and an isoelectric point of 7.0 for bonito GH were estimated by SDS-PAGE and gel electrofocusing, respectively. The complete amino acid sequence of 185 residues was determined by sequencing fragment peptides prepared by chemical and enzymatic cleavages. Sequence comparison of bonito GH with other GHs revealed that there is a significant deletion in the middle of the molecule.     

A COMPARATIVE STUDY OF ETHANOL ABSORPTION IN THE CANINE JEJUNUM AFTER PRETREATMENT WITH CYANAMIDE OR PYRAZOLE

This report describes the retardation of ethanol absorptionfrom the intestinal tract and reduction of portal blood flowby high acetaldehyde concentrations in dogs using a jejunalsegment with the vascular supply intact. The cyanamide-pretreatmentgroup (CY), in which an extremely high acetaldehyde concentrationdeveloped, in comparison with the control and pyrazole-pretreated(PY) groups, showed a gradual increase of portal blood ethanol,a 25% reduction in the amount of absorbed ethanol, and an 85%smaller absorption rate constant value (K_a). These facts indicatethat the presence of a high acetaldehyde concentration in theblood results in a reduction of ethanol absorption and retardationof ethanol reaching the systemic circulation. The rapid reductionof portal blood flow and the lower ethanol level in the portalvein observed in the CY group, in comparison with the othertwo groups, also indicate that the reduction of ethanol permeabilitythrough the absorption site to the blood is an important retardingfactor induced by acetaldehyde.     

Comparison of 25 and 75 mg/day naftopidil for lower urinary tract symptoms associated with benign prostatic hyperplasia: A prospective, randomized controlled study

BACKGROUND: The present study investigated the efficacy, safety, and utility of starting an alpha(1d)-selective antagonist, naftopidil, at 75 or 25 mg/day in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). METHODS: In this prospective comparative study, the subjects comprised 153 patients with LUTS associated with BPH. Patients were randomized to receive either 25 mg/day (Group LD) or 75 mg/day (Group HD) of naftopidil for 4 weeks. The lower urinary tract disease symptom score (LUTDSS), the International Prostate Symptom Score (IPSS), the Quality of life assessment index, the maximum flow rate (Q(max)), and the residual urine volume were compared between the groups. RESULTS: In both groups, the LUTDSS and the IPSS were significantly improved at the endpoint and no significant intergroup differences were identified. However, the improvement in the Q(max) was significantly better for Group HD than for Group LD. The overall efficacy did not differ significantly between the groups. The degree of improvement in voiding symptoms and LUTDSS among patients with moderate symptoms was significantly greater for Group HD than for Group LD. The frequency of adverse reactions did not differ significantly between the groups. CONCLUSIONS: Starting administration at 75 mg/day rather than 25mg/day is helpful for LUTS associated with BPH for patients with moderate symptoms, particularly in improving voiding symptoms. The 75 mg/day administration was considered to be a recommendable therapeutic dose in some patients.     

Isolation and characterization of glycosylated and non-glycosylated prolactins from alligator and crocodile

Two molecular forms of prolactin (PRL). glycosylated and non-glycosylated, were isolated from pituitary glands of two reptiles, alligator and crocodile. The reptilian PRLs were extracted under alkaline conditions from the precipitate obtained after pituitaries were first extracted with 0.25 m sucrose, 1 mM NH₄HCO₃, pH 6.3. Purification was performed by ion exchange chromatography on DE-52, gel filtration on Sephadex G-75 superfine, and reversed phase high performance liquid chromatography. Two forms of both alligator and crocodile PRL, designated PRLI and PRLII, with molecular weights of 26000 and 24000 were isolated. Alligator and crocodile PRLI and PRLII were stained specifically in immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis revealed that both forms of alligator and crocodile PRLs consisted of 199 amino acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position 60 in alligator and crocodile PRLs with a molecular weight of 26000 (PRLI). In contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular weight of 24000 (PRLII). The sequences of alligator PRLs differed from crocodile PRLs only in position 134: Val for alligator PRLs and He for crocodile PRLs. There is a high degree of structural conservation between the reptilian PRLs isolated in this study and avian PRL; each showed 92% sequence identity with chicken PRL and 89% with turkey PRL.     

HIGH INCIDENCE OF OCCULT NEUROGENIC BLADDER DYSFUNCTION IN NEUROLOGICALLY INTACT PATIENTS WITH THORACOLUMBAR SPINAL INJURIES

Purpose

We determine the relationship between lower urinary function and somatic neurological status after thoracolumbar fracture.

Materials and Methods

Within 72 hours of thoracolumbar vertebral fracture we evaluated 44 consecutive patients, including 30 men and 14 women 17 to 84 years old (mean age 38.7), with occult neurogenic bladder dysfunction following incomplete thoracolumbar spinal injuries (American Spinal Injury Association impairment classifications C to E). The neurological level and degree of injury were established, and testing for perianal pinprick sensation and bulbocavernosus reflex was done. Video urodynamic evaluation was then performed between 3 and 14 days after injury but before spinal surgery.

Results

Urodynamics revealed neurogenic lower urinary tract dysfunction in all 10 patients with classification C, 82% with D and 41% with E (otherwise completely intact neurologically) impairment. Although pinprick sensation deficiency and decreased bulbocavernous reflex correlated with injury classification, lower urinary tract dysfunction was present in 62% of the patients with intact pinprick sensation and in 59% with intact bulbocavernous reflex.

Conclusions

Neurologically intact patients with thoracolumbar spinal injuries may have neurogenic lower urinary tract dysfunction on urodynamics. Pinprick sensation and bulbocavernosus reflex are specific but not sensitive indicators of lower urinary tract dysfunction after spinal cord injury. Although these indicators, which demonstrate somatic nerve function, were absent in all patients with detrusor areflexia, intact pinprick sensation and bulbocavernosus reflex are not sensitive for predicting lower urinary tract function, which depends on autonomic nerve function. Urodynamic evaluation is mandatory for the complete evaluation of patients with incomplete lumbosacral spinal injuries.