A case of severe progressive early-onset epileptic encephalopathy: unique GABAergic interneuron distribution and imaging.

Early-onset epileptic encephalopathies include various diseases such as early-infantile epileptic encephalopathy with suppression burst. We experimentally investigated the unique clinicopathological features of a 28-month-old girl with early-onset epileptic encephalopathy. Her initial symptom was intractable epilepsy with a suppression-burst pattern of electroencephalography (EEG) from 7 days of age. The suppression-burst pattern was novel, appearing during sleep, but disappearing upon waking and after becoming 2 months old. The EEG showed multifocal spikes and altered with age. Her seizures demonstrated various clinical features and continued until death. She did not show any developmental features, including no social smiling or head control. Head MRI revealed progressive atrophy of the cerebral cortex and white matter after 1 month of age. (123)IMZ-SPECT demonstrated hypo-perfusion of the cerebral cortex, but normo-perfusion of the diencephalon and cerebellum. Such imaging information indicated GABA-A receptor dysfunction of the cerebral cortex. The genetic analyses of major neonatal epilepsies showed no mutation. The neuropathology revealed atrophy and severe edema of the cerebral cortex and white matter. GAD-immunohistochemistry exhibited imbalanced distribution of GABAergic interneurons between the striatum and cerebral cortex. The results were similar to those of focal cortical dysplasia with transmantle sign and X-linked lissencephaly with ARX mutation. We performed various metabolic examinations, detailed pathological investigations and genetic analyses, but could not identify the cause. To our knowledge, her clinical and pathological courses have never been described in the literature.

Glomerulus proteome analysis with two-dimensional gel electrophoresis and mass spectrometry.

A proteome analysis of mammalian glomeruli was performed in mouse using two-dimensional-gel electrophoresis with separate Coomassie and silver staining and subsequent mass spectrometric identifications. Altogether, 414 protein spots were identified, revealing 232 different proteins representing a wide spectrum of activities, including enzymes (27%), cell-signalling proteins (22%), structural proteins (12%), protein folding and metabolism (13%), cell-growth-related proteins (6%), and replication, transcription and translation (4%). Only 53 of the proteins were detected in another proteome study, showing the value of analyses with different methodologies. However, 50 of the proteins were also identified in a proteome analysis of endothelial cells and 42 in one of glomerular mesangial cells, revealing distinct similarities between these tissues, but also unique differences. Finally, 80 of the proteins were not identified in a separate transcriptome analysis, while 10 of the present proteins were then indentifiable with genes implicated in glomerulus development and function, allowing direct correlation with expression data.

[A case of dopamine-secreting pheochromocytoma].

We report a case of a pheochromocytoma that exclusively secretes dopamine among a blend of catecholamines. A 66-year-old female was referred to our hospital for further examination of right adrenal tumor. She had no symptoms and no episodes of hypertension. Abdominal CT scan showed a large mass, 9 x 8 x 6 cm, in the right adrenal region. Plasma and urinary catecholamine measurements were repeatedly performed and showed normal adrenaline and noradrenaline but elevated dopamine levels. We performed right adrenalectomy. The tumor was completely removed surgically and histological examinations revealed it to be a pheochromocytoma.

[Vesical malacoplakia accompanied with bilateral hydronephrosis: a case report].

A 63-year-old female with a complaint of pollakisuria was referred to our clinic for the treatment of bilateral hydronephrosis. Ultrasonography, computerized tomography (CT) scan and magnetic resonance imaging (MRI) revealed bilateral hydronephrosis due to stenosis of the vesicoureteral junction, which was caused by a nodular mass on the posterior wall of the bladder. Cystoscopy revealed a yellowish-white mass on the trigone. Bilateral percutaneous nephrostomy for the treatment of chronic renal failure due to bilateral hydronephrosis and transurethral resection of bladder tumor were performed. Histological findings indicated a chronic granuloma with Michaelis-Gutmann body and the tumor was diagnosed as vesical malacoplakia. Oral administration of trimethoprim sulfamethoxazole, bethanecol chloride and vitamin C was done for the conservative therapy of malacoplakia. However, stenosis of the vesicoureteral junction remained. Then, bilateral vesicoureteroneostomy was performed and there was no obvious recurrence of malacoplakia 20 months postoperatively.

[Epidemiological study on diet, smoking and alcohol drinking in the relationship to prostatic weight].

BACKGROUND: There have been no epidemiological studies on the relationship between the prostatic weight and blood examination data. This study was carried out to evaluate this relationship. SUBJECTS AND METHODS: Blood examination (beta-carotene, GOT, GPT, total cholesterol, etc.) and measurement of the prostatic weight were performed in 432 subjects aged 50 years or more of a town in Japan, and the possible relationship between blood analysis data and the prostatic weight was evaluated. The prostates were examined by transrectal ultrasonography (TRUS) and classified into the normal prostate and benign prostatic hypertrophy (BPH). The prostatic weight was measured by Watanabe's method based on TRUS images. In addition, the possible association between the prostatic weight and smoking, drinking, height, body weight, or age was evaluated. RESULTS: Analysis by the logistic procedure and the general linear models procedure showed a significant positive correlation between the normal prostatic weight and beta-carotene, height, as well as body weight and a significant negative correlation between the normal prostatic weight and smoking. Comparison between subjects with the normal prostate and those with BPH suggested that serum beta-carotene is a significant positive risk for BPH, and HDL-cholesterol, drinking, and smoking are negative risks by logistic procedure analysis. CONCLUSION: It was thought that serum beta-carotene and smoking are associated with the development of BPH.

[Clinical evaluation of nonseminomatous testicular germ cell tumors].

We treated 26 patients with nonseminomatous germ cell tumors (NSGCT) between January 1976 and March 1989. Histologically, 7 were embryonal carcinoma (27%), 4 were teratoma (15%), 2 were yolk sac tumor (8%), 10 were teratocarcinoma (38%) and 3 were other mixed tumors. As regards staging, 18 belonged to stage I (69%), 1 to stage II A (4%), 1 to stage IIB (4%), 1 to stage IIIA, 2 to stage III B1 (8%) and 3 to stage III B2 (12%). Patients in stage I were treated by orchidectomy with lymphadenectomy and occasionally chemotherapy before 1984, resulting in a 100% 5-year survival. However, after 1985, 5 cases in stage I were treated by orchidectomy alone according to a watch-and-see policy. Two cases among them relapsed within two years and both of them contained immature teratoma elements. Six patients with metastatic tumor were treated with PVB therapy of which response rate was 66.7%. The total 5-year survival rate of patients in stage I, II and III was 100%, 50%, 50%, respectively and that in overall cases was 84.6%.

[PVB therapy for advanced testicular cancer].

Twelve cases of advanced testicular cancer, including 5 cases of seminoma, 3 cases of teratocarcinoma, 1 case of yolk sac tumor, 1 case of embryonal carcinoma and 2 cases of mixed cell type, were treated with cisplatin-vinblastine-bleomycin (PVB) therapy. Among them, 10 cases had measurable metastatic lesions and the objective response rate was 80%. Three cases showed complete response. Ten cases showed nonexistent disease after PVB therapy and salvage operation. Though PVB therapy was useful for the treatment of advanced testicular cancer, a few cases having poor prognostic factors showed no response to the therapy.

[Prognosis of bladder tumor patients treated by TUR].

One hundred and eleven cases of bladder tumors were treated with transurethral resection (TUR) and transurethral electrocoagulation as the initial treatment from 1974 and 1983. Eighty nine cases were male and 22 cases were female. The average age was 60.1 years old. Of the 111 patients, 57, 33, 2, 1 and 15 patients had a tumor of Ta, T1, T2, T3a and Tx respectively. The number of grades G0, G1, G2, G3, GX cases was 1, 38, 40, 17, 12, respectively. Other than these, 2 cases of squamous cell carcinoma and 1 of adenocarcinoma were included. The actual survival rates for 5 years in Ta and T1 were 84.4 and 88.9% respectively, and the relative survival rates were 99.5 and 109.1%. TUR was recommended for superficial bladder tumor because of good prognosis. The 5-year recurrence rates for single tumors with and without prophylactic bladder instillation were 21.4 and 27.5% respectively, and those for multiple bladder tumors were 58.6 and 51.8%. There was no significant difference between the group with and without bladder instillation.

[Clinico-statistical study on bladder tumor].

A survey was performed on 277 cases of bladder tumor including 221 males and 56 females (3.9:1), treated in the Department of Urology, Kyoto Prefectural University of Medicine. The result was as follows. The age distribution was from 24 to 86 years old with the average of 65.7. Histologically, 2 cases were diagnosed as transitional cell papilloma, 53 cases as transitional cell carcinoma G1, 111 cases as G2, 88 cases as G3, 16 cases as GX, 5 cases as squamous cell carcinoma and 2 cases as adenocarcinoma. As to the relationship between the grade and the stage, all cases of papilloma or G1 were superficial, while 7.2% of G2 and 45.5% of G3 were invasive, showing a close correlation. As to the relationship of cystoscopic findings and the stage, invasive tumors occupied 1.7% of tumors less than 1 cm in diameter, 16.7% of those 1 to 3 cm, 48.0% of 3 to 5 cm and 41.7% of more than 5 cm in diameter. Also 7.1% of papillary pedunculated tumors, 57.1% of non-papillary pedunculated, 21.7% of papillary sessile and 53.5% of non-papillary sessile were invasive. Thus cystoscopic findings of tumors correlated with the stage. The 5 year survival rates were 61.7% in all cases, 81.4% in pTa, 70.5% in pT1, 58.7% in pT2, 50.0% in pT3a, 32.6% in pT3b and 25.0% in pT4. The stage of tumors reflected the prognosis well. Careful cystoscopy and accurate grading were thought to be helpful for correct staging and for choosing a suitable treatment.

[Detection of precancerous lesions of the bladder by contact-micro-cystoscopy].

Contact-micro-cystoscopy is a new method to examine the bladder epithelium by micro-endoscope after staining. According to this method, normal epithelium was stained slightly and showed smooth surface and small, sparse nuclei. Neoplastic lesions were stained deeply and showed irregular surface and large, dense nuclei. One hundred and sixty nine biopsy specimens of cystoscopically normal bladder mucosa were analyzed. The diagnostic accuracy of neoplastic lesions by this method was 75.9%. In vivo mapping of the bladder epithelium was also possible using this method in association with random biopsy. Contact-micro-cystoscopy was thought to be useful to detect precancerous lesions or flat carcinoma of the bladder which was difficult to be detected by conventional cystoscopy.

[Treatment of hormonal refractory adenocarcinoma of the prostate with ifosfamide (IFM) and the combination of vincristine ifosfamide and peplomycin (VIP)].

Nineteen patients with hormonal refractory adenocarcinoma of the prostate were treated with ifosfamide (IFM) and the combination of vincristine, ifosfamide and peplomycin (VIP). Nine of them were treated with IFM, and nine with VIP, and one with IFM and also VIP. In the case of the IFM therapy, the over-all response rate was 0% by the Karnofsky's category of response, 20% by the response criteria of Shida et al., 50% by the National Prostatic Cancer Project (NPCP) criteria, and 0% by the response criteria of Koyama and Saito. In the case of the VIP therapy, the over-all response rate was 30% by the Karnofsky's category, 30% by the response criteria of Shida et al., 70% by the NPCP criteria and 20% by the response criteria of Koyama and Saitoh. The one-year survival rates of these patients treated with IFM and VIP were both about 20%. Only one patient treated with VIP therapy showed a partial response. Therefore, a more effective regimen for hormonal refractory adenocarcinoma of the prostate must be developed.

[Complete remission of brain metastasis of bladder cancer treated by M-VAC therapy].

A case of brain metastasis from transitional cell carcinoma of the bladder that attained complete remission by methotrexate-vinblastine-adriamycin-cisplatin (M-VAC) therapy was reported. The patient was a 53-year-old male, already treated with total cystectomy and CAP therapy against pulmonary metastasis, which disappeared completely. At 8 months after complete remission of pulmonary metastasis, brain metastasis was found. One course of M-VAC therapy brought a complete remission persisting for 7 months. He is alive with no relapse.

[The primary mucinous adenocarcinoma of renal pelvis: a case report].

A case of primary mucinous adenocarcinoma of the renal pelvis is reported. A 55-year-old man visited our clinic with lumbar pain. He had a history of left renal stone and had left partial nephrectomy four years previously. Physical examination revealed a hard, child-head-sized, unmovable and uneven tumor in the left side of the abdomen. Intravenous pyelography revealed the non-functioning left kidney with calcification, in which hydronephrosis was detected by computed tomography. In transabdominal sonography a huge mass with mixed echo pattern was observed. Aspiration biopsy under interventional ultrasound was performed, aspirating yellow-white semi-transparent mucinous substance, which was highly suspicious of malignancy by cytology. He died 74 days after the first admission. Autopsy revealed primary mucinous adenocarcinoma of the renal pelvis. This was thought to be the 14th case of primary mucinous adenocarcinoma of the renal pelvis reported in the Japanese literature.

[Combination chemotherapy of cyclophosphamide, adriamycin and cisplatin in advanced urothelial cancer].

Sixteen patients with advanced evaluable urothelial cancer were treated with a chemotherapy regimen of cyclophosphamide, adriamycin and cisplatin (CAP). Cisplatin 50 mg/m2 and adriamycin 30 mg/m2 were given on the first day and cyclophosphamide 200 mg/m2 was given from the second to the fifth day. This course was repeated every 3 weeks. The objective response rate was 25% (4 of 16 patients), with 1 patient achieving complete remission. The survival time of responders was longer than that of nonresponders, although the difference was not significant (generalized Wilcoxon method). As side effects, nausea with vomiting (43.8%), renal dysfunction (6.3%), anemia (12.5%), leucopenia (12.5%), thrombocytopenia (25.0%), alopecia (68.8%), heart failure (6.3%) and peripheral neuropathy (6.3%) were noticed. One patient died of sepsis due to agranulocytosis and another died suddenly of heart failure.