Measurement of thickness of film deposited on the plasma-facing wall in the QUEST tokamak by colorimetry.

After several experimental campaigns in the Kyushu University Experiment with Steady-state Spherical Tokamak (QUEST), the originally stainless steel plasma-facing wall (PFW) becomes completely covered with a deposited film composed of mixture materials, such as iron, chromium, carbon, and tungsten. In this work, an innovative colorimetry-based method was developed to measure the thickness of the deposited film on the actual QUEST wall. Because the optical constants of the deposited film on the PFW were position-dependent and the extinction coefficient k1 was about 1.0-2.0, which made the probing light not penetrate through some thick deposited films, the colorimetry method developed can only provide a rough value range of thickness of the metal-containing film deposited on the actual PFW in QUEST. However, the use of colorimetry is of great benefit to large-area inspections and to radioactive materials in future fusion devices that will be strictly prohibited from being taken out of the limited area.

[Cranioplasty for isolated trigonocephaly with developmental disorder].

We reported 50 cases of mild to moderate trigonocephaly (most isolated type) treated by cranioplasty. All of them had clinical symptoms such as severe hyperactivity, speech delay, inability to communicate with others, self-mutilation (head banging), irritability, temper tantrum and mental retardation. Pre-operative CT scan and MRI showed no abnormal findings in the brain except for constricted frontal lobes. The 3 D-CT scan showed the most important diagnostic findings: a ridge of the metopic suture and narrow anterior fossa. TcECD SPECT was performed on 43 patients, and demonstrated in 31 cases some degree of decreased cerebral blood flow (CBF), mainly in the bilateral frontal lobes. Post-operatively, most patients improved to some degrees. The results were compared to those of trigonocephaly patients without cranioplasty. The operated group showed better improvement in the above clinical symptoms, especially, hyperactivity, indifference to others, understanding of verbal communication, self-mutilation, irritability and temper tantrum. The post-operative SPECT represented the increased CBF in 30 out of the 31 cases. MRI and CT scan revealed expanded frontal lobes. Thus, cranioplasty may alleviate the symptoms of patients with mild to moderate trigonocephaly and developmental disorders.

Four alkaloids, lucidine B, oxolucidine A, lucidine A, and lucidulinone from Lycopodium lucidulum.

The structures of four alkaloids extracted from Lycopodium lucidulum (Lycopodiaceae) were established by X-ray and 2D NMR spectroscopic analyses. The dihydro-derivative of oxolucidine A, which was obtained by NaBH4 reduction of oxolucidine A, was treated with p-bromobenzoyl chloride to afford crystals, whose X-ray crystallographic analysis established the stereostructure, including the absolute configuration. The 2D NMR spectra of tetrahydrodeoxylucidine B were fully analyzed to establish the full structure of lucidine B, and the hitherto unknown stereochemistry at the C-14 position was established as beta-H. The structure of a new alkaloid, lucidulinone, was determined by spectroscopic analysis to be luciduline lactam.

[Vertigo and dizziness related to platelet aggregability].

Platelet aggregates were measured in 82 cases with vertigo and dizziness and 60 cases with additional symptom of headache (so-called cervical vertigo). Results showed that patients with vertigo and dizziness had increased aggregability and patients with cervical vertigo were within normal range (p < 0.0001). 53 cases of these with vertigo and dizziness were administrated platelet aggregation inhibitors (mainly ticlopidine). After 1 approximately 2 weeks, most of patients became symptom free, and at this time platelet aggregates of these patients were suppressed to within normal range. Then patients were followed with chronological measurements of platelet aggregates. During this time, aggregabilities were attempted to be kept within the normal range, thus dose of platelet aggregation inhibitor was controlled depending on the result of aggregability. Also patients were encouraged to show good drug compliance by being informed of sudden increasing aggregability. One patient experienced recurrence of vertigo after ceasing the medicine. This study demonstrates that platelet aggregation may increase in most of patients with not only vertigo but also dizziness in whom administration of a platelet aggregation inhibitor is effective. It also stresses that chronological measurements of platelet aggregations are important to control the dose of medication.

[Clinical study on poor-risk patients with non-seminomatous germ cell tumor].

Between 1988 and 1996, we treated 11 poor-risk patients with non-seminomatous germ cell tumors (NSGCT) at Nagoya University Hospital. "Poor-risk" was defined as i) advanced disease equal to or greater than class 7 of the Indiana University Classification (7 patients), ii) primary mediastinal extragonadal NSGCT (2), iii) tumor markers not normalized by the induction chemotherapy (1) or iv) primary retroperitoneal NSGCT with multiple lung metastases (1). Two patients with mediastinal tumors died during the chemotherapy. The minimal volume of fluid must be administered to patients with giant mediastinal tumors. The tumor marker normalized during the induction chemotherapy in only three patients. Three patients, whose tumor markers elevated during or one month after the induction chemotherapy, eventually died of cancer. The tumor markers in five of the seven patients which had not normalized during the induction chemotherapy, had decreased to the normal range during the salvage chemotherapy and two of the five subsequently achieved the status of "no evidence of disease" (NED). Six patients with and two without normalized tumor markers underwent retroperitoneal lymph nodes dissection and/or resection of residual tumors. Pathological examination of the resected tumors showed necrosis/fibrosis in five patients and two had elevated tumor markers immediately after the surgery and eventually died of the disease. Overall, eight (73%) of 11 poor-risk patients achieved a complete response but only five (45%) eventually achieved a NED status that was maintained (6.6 +/- 3.0 years). Our results were not satisfactory, and we believe that new strategies, such as early high-dose chemotherapy, are required for poor-risk patients, who are not likely to respond well to the induction chemotherapy.

Quantitative evaluation of the IL-1 beta and IL-1 receptor antagonist obtained from BALF macrophages in patients with interstitial lung diseases.

Our previous reports demonstrated the concomitant release of IL-1 beta and IL-1 inhibitory activity in the culture supernatants of BALF macrophages in both healthy subjects and patients with interstitial lung diseases. IL-1 inhibitory activities decreased in healthy smokers (HS), and patients with sarcoidosis (Sar), or idiopathic pulmonary fibrosis (IPF), compared with those in healthy nonsmokers (HNS), though an increase in IL-1 beta release was not detected. IL-1 inhibitory activity was mainly characterized as IL-1 receptor antagonist (IL-1ra). In this study, we confirmed a decrease in IL-1ra in terms of the amounts of protein (enzyme-linked immunoassay) and gene transcripts (reverse transcriptase polymerase chain reaction followed by high performance liquid chromatography). Imbalance between IL-1ra and IL-1 beta was expressed as a molar ratio of IL-1ra/IL-1 beta protein: (Sar; 4.20 +/- 2.06, IPF; 4.26 +/- 3.41, HS; 3.44 +/- 3.09 versus NS 8.33 +/- 2.77: P < 0.001). These results were similar in terms of the amounts of gene transcripts. In conclusion, the imbalance of IL-1 beta and IL-1ra production was confirmed at three levels: biological activity, amounts of protein, and gene transcript obtained from BALF macrophages in chronic inflammatory processes in the lungs.

M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for poor prognosis patients with urothelial tumors and effect of dose intensity.

The effects of the M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) regimen, which has been reported to improve the outcome of patients with urothelial cancers, were studied on 41 patients treated at our hospital. The patients were divided into adjuvant (24 patients), neoadjuvant (5 patients), and salvage (12 patients) groups. We investigated the dose intensity, the cause-specific survival, response rate and toxicities in the three groups. Although 36 patients received > or = 95% of the initial doses projected, the mean dose intensity (+/-standard deviation) in the adjuvant, neoadjuvant, and the salvage groups was 77 (+/-11), 73 (+/-4), and 74 (+/-12)%, respectively. The five-year cause-specific survival in the adjuvant group was 69% (95% confidence limit: 50-88%). Only 2 of the 5 patients (40%) in the neoadjuvant group survived 23 months after the initiation of the treatment, and all patients in the salvage group died of cancer or treatment-related toxicity within 33 months. The median survival was 38 months in the adjuvant group, 21 months in the neoadjuvant group, and 7 months in the salvage group. A dose intensity > or = 75% did not improve survival in any group. The overall response rate was 33% in 15 patients with evaluable lesions. A complete response was noted in 1 patient and a partial response was noted in 1 patients. Two patients died of treatment-related complications. Nausea and vomiting were observed in all patients. Leukopenia, thrombocytopenia and anemia > or = WHO grade 3 were observed in 25 (61%), 4 (10%), and 7 (17%) patients, respectively. Thrombocytopenia, anemia, and pyrexia > or = grade 3 were seen relatively more often in the patients receiving a dose intensity < 75%. Stomatitis > or = grade 3 appeared to be more frequent in the patients receiving a dose intensity > or = 75%. Adjuvant M-VAC might be beneficial, while its efficacy was limited in the neoadjuvant and salvage settings. Although dose intensity is considered to be important, it did not appear to be related to survival, the response rate, or the toxicity of M-VAC.

Intravesical bacillus Calmette-Guérin (Tokyo 172 strain) therapy for carcinoma in situ of the bladder.

To evaluate the clinical response to intravesical instillation therapy with bacillus Calmette-Guérin (BCG) Tokyo 172 strain for carcinoma in situ (CIS) of the bladder and subsequent patient prognosis, we reviewed data for 30 patients treated between 1985 and 1994. Median follow-up was 56 months. The CIS cases comprised two groups: primary (19 patients) and subsequent to development of a gross neoplasm (11 patients). Either 40 mg (n = 20) or 80 mg (n = 10) doses of BCG were instilled weekly for 8 weeks. This intravesical therapy resulted in apparent eradication of tumour cells in 25 of the 30 patients for a complete response (CR) rate of 83%, with no difference found between primary and secondary groups. Tumours later recurred in 6 of the 25 patients (24%) and disease progression was found in only 3 (12%). In contrast, progression occurred in 3 of 5 patients (60%) for which a complete response was not achieved with intravesical BCG therapy. The difference between these two groups was significant (p = 0.04). Total cystectomy was performed in 2 of 25 CR patients (8%) first and in 4 of the 5 unresponsive (80%), the statistical difference being highly significant (p = 0.003). The 5-year survival rate was 96% for the study subjects as a whole. In conclusion, CIS unresponsive to BCG therapy should be treated with immediate total cystectomy while cases demonstrating a complete response should be followed up for a long period.

A case of intraperitoneal testicular cancer with ascites.

We report an initial case of intraperitoneal testicular cancer with ascites. Although the cytology of aspirated ascites revealed no tumor cells, the beta-HCG and AFP values were high. Preoperative cisplatin-based combination chemotherapy was used without any pathological diagnosis. Following 2 cycles of chemotherapy, the beta-HCG and AFP values normalized. Furthermore, no ascites was observed on CT scan. Although an accurate histological diagnosis was not established before treatment, it was thought that the ascites originated from the disseminated testicular cancer cells in the peritoneum.

Angiomyolipoma of the kidney with extension into the inferior vena cava.

Renal angiomyolipoma is a benign, nonaggressive hamartoma which rarely invades the vascular system. A case of angiomyolipoma of the right kidney with extension into the inferior vena cava, detected by ultrasonography, computed tomography (CT scanning), and magnetic resonance imaging (MRI) is presented. This tumor was found incidentally in a 31-year-old female who underwent CT scanning for unrelated abdominal problems. To our knowledge, only eight cases of angiomyolipoma with caval involvement have been reported in the world medical literature.

Growth of human tumor xenografts on chorioallantoic membrane of chick embryo.

We evaluated the success rates of transplantation and growth conditions of 33 human tumor xenografts transplanted on the chorioallantoic membrane of chick embryos. Eleven out of 14 renal cell carcinomas (78.6%), 7 out of 9 urothelial carcinomas (77.8%), 2 out of 3 testicular tumors (66.7%), an adenocarcinoma of the colon and an adenocarcinoma of the ovary but none of the 5 prostatic carcinomas were transplanted successfully. Histologically, carcinoma cells survived on the chorioallantoic membrane forming organoids the structure of which was well preserved. Several regions of the grafts frequently became necrotized. However, the viability of carcinoma nests was not influenced by the inflammatory changes surrounding necrotic tissues. Renal cell carcinomas survived diffusely with prominent angiogenesis. Immunostaining with anti-bromodeoxyuridine (BrdU) and Ki-67 monoclonal antibodies demonstrated a strong correlation between the %BrdU labeling index of the cancer cells on the chorioallantoic membrane and %Ki-67 index of the original tumors. No difference in %BrdU indexes was found between small and large cancer nests. Growth conditions remained constant for 8 days after inoculation. The growth potential of cancer nests surviving on the chorioallantoic membrane, which was identical to that of the original carcinomas, appeared to be unchanged during incubation. However, it might be difficult to exploit the chorioallantoic membrane for anticancer chemosensitivity tests except for renal cell carcinoma since few cancer cell nests were produced in spite of the high transplantation success rates.

Surgical treatment of renal cell carcinoma metastases: prognostic significance.

Between January 1980 and March 1993, 166 patients with renal cell carcinoma were treated at Nagoya University Hospital. Among them 16 (9.6%) underwent surgical removal of 21 metastatic lesions: 12 patients had distant metastases at diagnosis and the other 4 demonstrated new distant metastases during their clinical course after nephrectomy. The metastatic lesions involved the brain in 6 patients, bone in 4, lung in 2, contralateral adrenal glands in 2, soft tissues in 2, lymph nodes in 2, pleura in 1, pancreas in 1, and contralateral renal pelvis in 1. All of the 16 patients underwent nephrectomy and 15 of them (93%) received interferon-alpha therapy. Patients with lesions which were completely resected had significantly longer survival than those with lesions which were palliatively treated and those with metastatic lesions at other sites (p = 0.02). Improvement of performance status was observed in 5 of 6 (83%) patients undergoing palliative surgical treatment. The present study suggests that surgical removal of metastatic lesions prolongs survival in a limited number of renal cell carcinoma patients and that it improves performance status in those symptoms related to metastasis.

TNF alpha mRNA, but not IL-1 beta, is differentially expressed in lung macrophages of patients with active pulmonary sarcoidosis.

In pulmonary sarcoidosis or experimental granuloma formation, interleukin-1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF alpha) seem to play important roles during the inflammatory process. In order to examine whether IL-1 beta or TNF alpha mRNA expression in lung macrophages relates to disease activity or clinical course, ten cases with pulmonary sarcoidosis were divided into two groups: five cases with disease duration of more than 10 years (14.6 +/- 4.4 yrs; group A), and 5 cases with a duration of less than 3 years (1.7 +/- 1.1 yrs; group B). All cases showed both abnormal chest X-rays and elevated serum angiotensin converting enzyme activities. We compared these ten cases with 12 healthy subjects (6 nonsmokers: NS and 6 current smokers: S), and 5 cases with idiopathic pulmonary fibrosis (IPF) as disease control. Lavage macrophages were purified using the rosette forming method followed by plastic adhesion for one hour. Thereafter, RNA was extracted according to the AGPC method and amplified by the reverse transcription-polymerase chain reaction (RT-PCR). The results showed that IL-1 beta mRNA was detected in all samples studied, but TNF alpha mRNA expression was different among the groups: 5/5 (100%) in group A, 1/5 (20%) in group B, 5/5 (100%) in IPF, and 12/12 (100%) in healthy subjects. A constitutive expression was seen in healthy controls. On the other hand, no detection of TNF alpha mRNA was shown in pulmonary sarcoidosis. This fact may relate to a spontaneous regression of inflammation in sarcoidosis, as a substantial number of cases in group B may in time regress spontaneously.

[Results of treatment for advanced non-seminomatous germ cell tumors of the testis based on Indiana University classification].

From 1980 to 1990, we treated 45 patients with non-seminomatous germ cell tumors of greater than or equal to stage II according to the Japanese general rule for clinical and pathological studies on testicular tumors. The patients were divided into 2 groups based on the Indiana University Classification: 26 good risk patients (score < or = 6) and 19 poor risk patients (score > or = 7). The clinical results, the % dose intensity of Cisplatin and half-lives of tumor makers were analyzed in the two groups. The per cent dose intensity of Cisplatin of the induction chemotherapy was 61 +/- 24% in 1980-1985 and 87 +/- 18% in 1986-1990. The NED rate improved from 66.7% (10/15) to 81.8% (9/11) in the good risk patients and from 33.3% (3/9) to 50.0% (5/10) in the poor risk patients between the above two periods. When the % dose intensity of Cisplatin exceeded 80%, the NED rate increased from 66.7% (10/15) to 90.0% (9/10) in good risk patients and from 33.3% (2/6) to 45.5% (5/11) in poor risk patients. The NED rate was only 25.0% (4/16) in the poor risk patients whose residual tumors were not resected. The half-lives of AFP and beta-HCG from the latter part of the first course to the second course were 6.8 +/- 1.9 days and 4.4 +/- 1.4 days, respectively, in the patients with a good prognosis, while they were 6.5 +/- 1.5 days and 4.4 +/- 2.9 days, respectively, in with a poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized trial of early intravesical instillation of epirubicin in superficial bladder cancer. The Nagoya University Urological Oncology Group.

A total of 135 patients with superficial bladder cancer diagnosed as totally resectable were entered into a randomized multicenter trial to investigate the efficacy of early intravesical epirubicin instillation after resection in comparison with transurethral resection (TUR) alone. Epirubicin (40 mg/40 ml saline) was given within 24 h of TUR and once during the 1st week, weekly for 4 weeks and then monthly for 11 months. In all, 122 patients (90.4%) were eligible and 119 (88.1%) were evaluable. The interval to initial recurrence was significantly longer (P = 0.02) in the epirubicin group (36 months; 95% confidence interval, 32-40 months) than in the group receiving TUR alone (28 months; 95% confidence interval, 24-32 months). The recurrence rate per year in the epirubicin group was less than that in the TUR-alone group (0.13 versus 0.29 annual recurrences). Disease progression was observed in only one patient in the epirubicin-instillation group. The main toxicity encountered was bladder irritation (13.8%). These results demonstrate that early intravesical epirubicin instillation is efficacious in preventing local recurrence.

Evaluation of testicular germ cell tumor proliferation using DNA flow cytometry and nucleolar organizer silver staining.

We studied 41 testicular germ cell tumors (TGCT) using DNA flow cytometry and argyrophilic (silver staining) nucleolar organizer region (Ag-NOR) quantitation to evaluate the proliferative characteristics of TGCT and the significance of those analytical techniques. In nonseminomatous germ cell tumor (NSGCT), the percentage of S + G2M phase cells (%S + G2M) in DNA aneuploid tumor was higher than in DNA of diploid tumors. Likewise, in NSGCT the aneuploid Ag-NOR sites per nucleus (Ag-NOR count) were significantly higher in DNA aneuploid than in DNA diploid tumors. There was also a significant linear correlation between % S + G2M phase cells and the Ag-NOR count in TGCT. However, the DNA ploidy pattern and the % S + G2M phase cells, and Ag-NOR counts, did not correlate significantly with the patient survival rate or clinical stage. In conclusion, our study suggests that Ag-NOR enumeration is an effective technique for assessing cellular proliferative activity that is somewhat less expensive than DNA flow cytometry.

Clinicopathological characteristics of small renal cell carcinomas.

To clarify the clinicopathological characteristics of small renal cell carcinomas (RCCs) the authors reviewed data for 154 RCC patients treated between January 1980 and September 1992. Of 20 patients with tumours of 3 cm or less in diameter, 12 (60%) had no related symptoms: 6 (30%) were found during routine physical check-ups and 6 (30%) were incidentally detected during examinations for diseases other than RCC. The remaining 8 (40%) patients demonstrated indicative symptoms. Most small tumours showed expansive growth and nuclear atypia was minimal or moderate. In all 20 cases, the lesions of 3 cm or less were confined to the kidney (pT1 to pT2b) and no lymph node metastasis was found. Only one (5%) had a distant metastasis, and venous involvement was also microscopically observed in only one patient (5%). The 5-year survival rates were 95% for patients with tumours of 3 cm or smaller, 74% for those of 3.1 to 5 cm, and 68% for those of greater than 5 cm. These findings revealed small RCC to demonstrate biologically less malignant behaviour. Early detection of such small lesions by ultrasonography should therefore improve the overall survival of patients with RCC.

[Quantitative evaluation of gene expression of IL-1 beta and IL-1 receptor antagonist (IL-1ra) from alveolar macrophages in idiopathic pulmonary fibrosis (IPF) and sarcoidosis].

Our previous studies demonstrated the concomitant release of IL-1 and IL-1ra in the culture supernatants of alveolar macrophages in both healthy subjects and patients with interstitial lung diseases. IL-1ra was decreased in healthy smokers (HS), IPF, and sarcoidosis, compared to healthy nonsmokers (HNS), although an increase in IL-1 release could not be detected. In this study, we examined whether such findings could be found at the gene level, or reflect posttranscriptional regulation in patients with IPF (n = 8), sarcoidosis (n = 7), healthy smokers (n = 6) and healthy nonsmokers (n = 5). The expression of IL-1 beta, IL-1ra and a house keeping gene (glucose 6 phosphate dehydrogenase: G6PD) was investigated using reverse transcription polymerase chain reaction (RT-PCR). After RT-PCR, analysis and quantification of PCR products were performed by high-performance liquid chromatography. We used 26 cycle for IL-1 beta and IL-ra mRNA and 29 for G6PD, because amplification of mRNA was in the exponential phase on that cycles, respectively. The results were expressed as the ratio of each mRNA to G6PD mRNA. IL-1ra/G6PD ratio in patients with IPF and sarcoidosis, was lower than that in HNS. On the other hand, IL-1 beta/G6PD ratio was similar in all groups. IL-1ra/IL-1 beta ratio was decreased in patients with IPF and sarcoidosis, compared to HNS. These results suggest that decreased expression of IL-1ra gene may contribute to the development of chronic low grade inflammation of the lung.