Chemopreventive effects of nimesulide, a selective cyclooxygenase-2 inhibitor, on the development of rat urinary bladder carcinomas initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine.

The chemopreventive potential of a selective cyclooxygenase-2 inhibitor, nimesulide (NIM), against the development of rat superficial urinary bladder carcinomas after initiation with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. Six-week-old Fischer 344 male rats were given 0.05% BBN in their drinking water for 8 weeks, followed by diets supplemented with 0, 100, 200, or 400 ppm NIM for 12 weeks, and they were then sacrificed. NIM decreased, in a dose-dependent manner, the incidence of transitional cell carcinoma (TCC) to 12 of 20 (60.0%), 8 of 16 (50.0%), and 5 of 19 (26.3%) and the multiplicity of TCCs to 0.75 +/- 0.79, 0.56 +/- 0.63, and 0.37 +/- 0.78 per rat at 100, 200, and 400 ppm, respectively, as compared with the BBN alone group values of 18 of 20 (90.0%) and 2.35 +/- 1.23. NIM did not significantly affect the cell differentiation or invasiveness of TCCs. These results indicate clear chemopreventive potential of a selective cyclooxygenase-2 inhibitor against postinitiation development of superficial rat urinary bladder carcinomas.

[Electroejaculation and assisted reproductive techniques in the patients with spinal cord injury].

BACKGROUND: Most of the patients with spinal cord injury (SCI) have fertility problems by an ejaculation and a poor fertility of the ejaculate. The objective of this paper is to evaluate the clinical effectiveness of electroejaculation (EE) and combined use of EE and assisted reproductive techniques for the patients with SCI. PATIENTS AND METHODS: Using a Seager Model, EE was attempted on 69 patients with SCI. Of the 69 patients 14 (20%) had cervical, 49 (71%) thoracic and 6 (9%) lumbar paraplegia. Mean patient age was 30 years (range 19 to 47 years) and the mean interval from spinal injury to the first EE was 9 years (range 1 to 38 years). Artificial insemination of husband (AIH), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) were used to achieve a pregnancy. RESULTS: Antegrade ejaculation was obtained in 60 patients (86.9%). Patients with under-active bladder showed low induction rate (58.3%). Volume of ejaculate was ranged from 0.05 to 5.2 ml (average 1.0 ml) and sperm concentration was ranged from 0 to 546 x 10(6)/ml (average 40.3 x 10(6)/ml), but sperm motility was poor (range 0 to 70%, average 9.4%). Assisted reproductive techniques was attempted on 87 occasions (AIH 80, IVF 2, ICSI 5) on 15 couples. To date, there have been 4 pregnancies (AIH 2, ICSI 2) resulting in 3 healthy live births. CONCLUSION: Combined use of EE and assisted reproductive techniques is excellent management for the patients with SCI who wish to father children.

Infrequent Ki-ras and an absence of p53 mutations in hepatocellular carcinomas induced by a choline deficient L-amino acid defined diet in rats.

Mutations of Ki-ras and p53 genes in hepatocellular carcinomas (HCCs) induced by the choline deficient L-amino acid defined (CDAA) diet in rats were investigated by polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) analysis followed by direct sequencing. Male Fischer 344 rats, 6 weeks old, were continuously given a CDAA diet for 70 weeks and then sacrificed. Macroscopically detectable nodules which were histologically confirmed to be well-differentiated HCCs were dissected free from the surrounding tissue and subjected to gene mutation analysis along with samples of non-tumor areas. Conformational change in the Ki-ras gene was detected in 1 out of 7 HCCs, involving a GGC to GTC transversion at codon 13. No p53 mutations were detected in 7 HCCs and also neither Ki-ras nor p53 mutations were found in non-tumor areas. The results suggest that neither Ki-ras nor p53 genes play an important role in hepatocarcinogenesis caused by long term expose to a CDAA diet in rats.

Electroejaculation in patients with spinal cord injury: first report of a large-scale experience from Japan.

BACKGROUND: Ejaculatory dysfunction is a substantial obstacle for spinal cord-injured men who have a desire to father their own children. Electroejaculation can potentially solve this problem. Recently, Halsted et al. reported outstanding results of the rectal probe electrostimulation (RPE) using newly developed equipment (Seager Model). In this paper, we report the first large-scale clinical trial in Japan of RPE for spinal cord-injured men. METHODS: RPE using the Seager Model was attempted on 328 occasions in 53 patients with an age range of 19-47 years; 1-38 years had elapsed since injury. RESULTS: Antegrade ejaculation was obtained in 46 patients (86.8%). Ninety-three percent of patients with upper motor neuron lesion-type neurogenic bladder produced antegrade ejaculation by RPE, whereas the rate in patients with lower motor neuron lesion type one was 63.6% (P < 0.05). Semen analyses revealed affected sperm motility rate as low as 17.2%. Artificial insemination from these husbands (AIH) was attempted on 54 occasions in 11 wives of the patients. On April 2, 1992, we had the first recorded birth in Japan with the assistance of RPE and AIH. On July 21, 1993, we had another successful birth. CONCLUSIONS: These promising results will encourage Japanese researchers to use electro-ejaculation, although the low success rate in patients with lower motor neuron lesion-type neurogenic bladder and the low motility of the sperm are obstacles to be overcome.

[Urinary managements of 332 stroke patients in the chronic phase].

Urinary managements of 332 stroke patients in the chronic phase were performed at Bobath hospital. Cerebrovascular accidents (CVA) were caused by cerebral infarction in 178 (53.6%), intracerebral hemorrhage in 123 (37.1%) and subarachnoid hemorrhage in 31 (9.3%). Voluntary urination appeared in 124 patients before treatment, however in 29 of them occasional incontinence were observed. One hundred forty-three patients used diapers and 64 were controlled by indwelling catheters. The remaining one patient was treated by intermittent catheterization. Sixty-two patients who seemed to have communicative abilities in daily living were assessed with regard to their cerebrovascular dementia by Hasegawa's Dementia Rating Scale. After treatment 235 patients (70.8%) were able to urinate voluntarily, and only 15 of them remained incontinent and could use small pads successfully. TURP was effective for the stroke patients with benign prostatic hypertrophy (BPH) or bladder neck sclerosis (BNS). Fifty-three patients (16.0%) with persistent urinary incontinence were managed by diapers or a system of condom drainage. Thirty-nine patients (11.7%) were kept dry with intermittent catheterization at home, and long-standing use of indwelling catheters were required in the remaining 5 patients (1.5%). These results indicate that the lower level of activity, mobility and mental state tended to prevent the stroke patients from improvement of urinary disorders.

[Clinical evaluation of Cernilton on benign prostatic hypertrophy--a multiple center double-blind study with Paraprost].

A multiple center double blind study was performed to study the effectiveness of Cernilton (CN) on benign prostatic hypertrophy in comparison to Paraprost (PP). Among a total of 192 patients, overall effect was studied on 159 patients, overall safety rate on 178 patients and rate of effectiveness on 159 patients. There were no differences between the two groups in the selected patients, criteria for exclusion and drop out cases or background data of the patients. Impression of patients and overall effect by committee and physician judgment were slightly higher in the CN group compared to the PP group, but there was no significant difference between the two groups. For the improvement in subjective symptoms, the rate of moderate improvement or more after 4 weeks by committee judgement was higher in the CN group compared to the PP group. The rate of improvement in protracted miction, which is an effective marker of urinary disturbance, was also higher in the CN group compared to the PP group. An analysis of objective symptoms showed a significant improvement in residual urinary volume, average flow rate, maximum flow rate and prostatic weight in the CN group. A significant improvement in the phased change of residual urinary volume was also seen in the CN group. No side effects or abnormalities in clinical test levels were noted in the CN group. By committee judgement, the rate of more than moderate effectiveness was 49.1% in the CN group compared to 41.2% in the PP group, but there was no significant difference between the two groups. By physician's judgment, the rate of more than moderate effectiveness was 49.4% in the CN group compared to 46.3% in the PP group, but there was also no significant difference between the two groups. These results suggested that Cernilton was an effective drug for benign prostatic hypertrophy.

Transcatheter arterial embolization of vesical artery in the treatment of invasive bladder cancer.

Transcatheter arterial embolization was performed in a total of 70 patients with invasive bladder cancer from October 1980 to December 1987. It was performed as a part of multidisciplinary treatment in patients with invasive bladder cancer. Microencapsulated mitomycin C, gelatin sponge and lipiodol (iodized oil) were used as the embolic material. As a result, reduction of tumor size was noted in 56.7%, but there was no embolic materials-related significant difference. Stage reduction was noted in 72.7% of patients where pathological stages were confirmed by operation. Hemostatic effects were noted in 76.5%. The symptoms of side effects included fever, leukocytosis, urinary frequency and pain, but none of them was severe. The results of the present study indicate that embolization of the vesical artery is useful in the treatment of bladder cancer.

[The clinical evaluation of hochuekkito for symptoms of malignant neoplasm patients].

Hochuekkito was administered in 2.5 g doses three times a day to 162 patients who complained of anorexia or lassitude because of genitourinary cancer. The efficacy rate was 63.0%. The rate of effectiveness on anorexia was 48.4% and that on lassitude was 36.6%. Side effects were observed in 12 patients (7.4%), but most of them were mild gastrointestinal disorders. No severe adverse effects were noted.