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We evaluated the need for transurethral biopsy at first follow-up after intravesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder cancer. The records of 84 patients with superficial bladder cancer who received a 6- or 8-week course of BCG were reviewed. Pathological results before BCG, cystoscopic findings, urinary cytology, and biopsy results for evaluation of BCG therapy were reviewed. All 19 patients with positive urinary cytology had evidence of positive bladder biopsy results. Fifty-three of 54 patients (98.1%) with no visible recurrent tumor and negative urinary cytology demonstrated negative pathological results on bladder biopsy. When not found in conjunction with positive urinary cytology, erythematous mucosa on cystoscopy was not an indicator of tumor recurrence or residual cancer. In conclusion, routine transurethral biopsy of the bladder for evaluating the response to BCG intravesical therapy is not necessary in patients who have no visible tumor on cystoscopy and negative urinary cytology./

We investigated changes in drug disposition and toxicities with CPT-11 in 15 dialysis patients with gastrointestinal cancers to clarify whether CPT-11 could be administered safely in such patients. For comparison, the same parameters were also investigated in 10 cancer patients not undergoing dialysis. Items investigated included (1) plasma concentrations of SN-38, SN-38G and CPT-11 at 0, 1, 12, 24, 36, 48 and 72h after administration, together with a comparison of mean AUC values for 3 dose levels of CPT-11 (50, 60 and 70mg/m2) in dialysis patients and controls;and (2) occurrence of adverse events. Several findings emerged from this study:(1) No significant difference was observed in the AUC for SN-38 or CPT-11 between the dialysis and control groups;(2) The AUC for SN-38G at each dose was significantly higher in dialysis patients;and (3) Grade 1-4 leucopenia was observed in 11 of the dialysis patients. One patient developed grade 4 leucopenia and died due to sepsis. Anorexia, diarrhea, nausea, alopecia and interstitial pneumonia occurred in 6 dialysis patients. We found changes in drug dispositions of CPT-11, SN-38 and SN-38G in dialysis patients, suggesting that hepatic excretion, especially that of SN-38G, was increased. No significant difference in occurrence of adverse events was observed between the 2 groups. This indicates that CPT-11 can be administered safely in patients on dialysis.

Increased activation of alveolar macrophage, neutrophil and mast cell has been proven in cigarette smoking (CS)-related lung disorders (CSLD). An increased production of cysteinyl-leukotrienes (LTs), which are mediators secreted from the mentioned cells, in response to CS has been shown in humans. The protective effect of LT1 receptor-1 antagonist (LTR-1AT) on CSLD is, however, not known. In this study we aimed to determine whether there is any protective effect of a LTR-1AT, montelukast (MK), on CSLD in Wistar rats. Nine controls and twenty-three smoke-exposed rats were enrolled into this study. Controls were exposed to non-filtered air, and the smoke-exposed rats were exposed to CS for 6 h/day, 6 days/week for three weeks. The CS-exposed rats were also treated with 0.1 mg/kg/day of MK or saline. Morphometric criteria for lung injury were determined as the mean linear intercept of alveolar septa (Lm), the volume density of alveolar septa (Vvspt) and the density of the alveolar surface area per unit volume of lung parenchyma (Sva.pa). Lung mast cells (LMC), which are a major source of LTs, were also counted. Results showed that Lm of the control group was significantly lower and Vvspt, Sva.pa of the controls were significantly higher compared to those of the CS-exposed groups. Animals treated with MK had significant protection against CSLD. Lm was significantly higher and Vvspt, Sva.pa were lower in the saline group than in the MK-treated group. The number of LMC in the CS-exposed groups was also significantly higher than that in the control group. Based on these results, one can suggest that some part of the pathogenesis of CSLD may be related to an enhanced LTs synthesis and LTR-1AT. Therefore, montelukast may protect against active or passive smoking-induced lung injury and related disorders.

In this study the clinical and laboratory findings of 48 children with purulent meningitis were examined, prospectively, to determine the prognostic factors in childhood meningitis in a developing country. Patients were examined for the following variables: history of antibiotic use; period between onset of symptoms and hospital admission; age at presentation; sex; fever; convulsion; level of consciousness; malnutrition; anemia; leukocyte and thrombocyte counts; erythrocyte sedimentation rate; serum C-reactive protein (CRP) level; and cerebrospinal fluid (CSF) including white blood cell count; glucose, protein, and CRP concentrations; antibiotic treatment; neurological sequelae; and fatality rate during the hospital stay. Most of these parameters were re-evaluated in all patients 36-48 h after admission. Patients were divided into 3 groups: surviving without sequelae, surviving with sequelae, and not surviving (deceased). A total of 48 children, 19 girls (39.5%) and 29 boys (60.5%), aged 2 months to 13 years, were included in the study. Of the 48 patients, 29 (60.5 %) survived without sequelae, 13 (27%) survived with sequelae and 6 (12.5%) died. In a comparison among groups, we found that absence of anemia, low (< 1,000) CSF white blood cell (WBC) count, and high CRP level at admission were the indicative of poor prognosis. Thirty-six to 48 h after admission, the presence of fever, depressed level of consciousness, high (> 1,000) CSF WBC count, and low CRP level were also poor prognostic factors. In addition, we observed that mortality rate was lower in the penicillin G + chloramphenicol group than in the ampicillin-sulbactam + cefotaxime group (P < 0.05). The mean period between onset of symptoms and hospital admission was longer in the surviving with sequelae and in the not surviving groups than in the surviving without sequelae group (P < 0.05).

To improve the efficacy of interferon (IFN) treatment for chronic hepatitis C, we have proposed the twice-daily administration of IFN-beta as a promising induction therapy. In this study, we demonstrated differences between the clearance of circulating HCV-RNA and the induction of anti-viral actions during the first 2 weeks of treatment. Nine patients with a high viral load and genotype 1b were randomly assigned to 3 groups: group A received 3MU of IFN-beta twice a day at intervals of 5 and 19 h; group B received 3MU of IFN-beta twice a day at intervals of 10 and 14 h; group C received 6MU of IFN-alpha once a day with ribavirin. The expression of OAS2, PKR, and MxA in peripheral blood mononuclear cells (PBMCs) were quantified by real-time polymerase chain reaction method. The viral clearance showed a bi-phasic pattern, and those in the second phase of groups A and B were significantly steeper than that of group C. The peak level of OAS2 during the first phase was correlated with the first phase decay. The MxA expression tended to be higher in group A and B than in group C. The expression of these 3 proteins tended to decrease at day 6 in group C, but increase in groups A and B. These might make differences in the viral decay during the second phase

Chemical shift MRI is widely used for identifying adenomas, but it is not a perfect method. We determined whether combined dynamic MRI methods can lead to improved diagnostic accuracy. Fifty-seven adrenal masses were examined by chemical shift and dynamic MR imaging using 2 MR systems. The masses included 38 adenomas and 19 non-adenomas. In chemical shift MRI studies, the signal intensity index (SI) was calculated, and the lesions classified into 5 types in the dynamic MRI studies. Of the 38 adenomas studied, 37 had an SI greater than 0. In the dynamic MRI, 34 of 38 adenomas showed a benign pattern (type 1). If the SI for the adenomas in the chemical shift MRI was considered to be greater than 0, the positive predictive value was 0.9, and the negative predictive value was 0.94 and kappa = 0.79. If type 1 was considered to indicate adenomas in the dynamic MRI, the corresponding values were 0.94, 0.81 and kappa = 0.77 respectively. The results obtained when the 2 methods were combined were 1, 0.95 and kappa = 0.96 respectively. The chemical shift MRI was found to be useful for identifying adenomas in most cases. If the adrenal mass had a low SI (0 < SI < 5), dynamic MRI was also found to be helpful for making a differential diagnosis.

For the purpose of forecasting the prevalence ofJapanese encephalitis in Japan, we tried to find out the correlation of factors between median and mode dates of epidemic time curve of prevalence on one hand, and average atmospheric temperatures of prefectures in June and July (T6,7 in short) (X¹), the time when HI reaction of swine became positive to the degree of 50 per cent (D. pos. swine in short) (X²), the latitude (x³) and longitude (x4) in respective prefectures (in 1965 and 1967). On the other we also estimated the median and mode dates of this epidemic curve of the prevalence in 1968 and 1969, from the regression equation of one variable and multiple regression equation from the above factors using an electronic computer. The usefulness of adding factors concerned with mosquitoes to the above four factors is proven by the accuracy of estimation. And the following results were obtained. 1) Phenomenally speaking, the prevalence of Japanese encephalitis follows the principle of "advancing of prevalence towards the north and east" and essentially speaking, it depends upon high atmospheric temperature and the outbreak of many hazardous mosquitoes by the high atmospheric temperature. 2) To estimate median date (y) and mode rate (z) of the epidemic time curve of the prevalence, we can use the next equations; The regression equations to estimate y and z from T 6,7(X) are as follows. y = - 3. 75X¹ + 144.47 σ = 12.4.·. [1] z = - 3. 80X¹ + 157 .26 σ = 14.9.. · [1]' The regression equation from D. pos. swine (X²) are as follows. y = 0. 68X² + 31. 82 σ = 9.2· .. [2] z=0. 76X² +40. 71 σ= 12.0 .. · [2]' The multiple regression equation from T6 ,7 and D. pos. swme are as follows. y = -1. 07X¹ +0 .62x² +59. 37 σ= 9.7 ... [3] z= -0. 79x¹ +0. 71x² +61.02 σ= 12.0· .. [3]' The multiple regression equations from T 6•7, D. pos. swine, latitude and longitude are as follows Y= -1.01x¹ +0.58x² -0.26x³+0 .37x4 + 18.50 σ= 9.8･･･ [4] z = -0. 32x¹ +0. 52x² +2 .05x³ +0 .54x4 -87. 81 σ= 11.8 [4]' 3) We Obtained the estimated value of median date in 17 prefectures in Kyushu, Chugoku, Shikoku, Kinki and Kanto provinces in 1968 and in 13 prefectures in 1969 from [l] or [2] or [3] or [4] equation. Nine prefectures out of 17 by [l], 12 prefectures by [2], 13 by [3J and [4] in 1968. [4] could be estimated with about 10 days error or less. And in 1969, 9 out of 13 by [3] and 7 out of 13 by [4] could be accurately esti· mated. The estimation by the multiple regression equation using many factors is most useful for the calculation. 4) The time when the number of patients increases at maximum can be pointed out by the lower limit of prediction region obtained from data in each prefecture. And the lower limit was the estimated median value minus about 20 days by [1] and about 16 days by [2] or [3] or [4] under the next condition; α = 0. 1, N= 75. 5) The mode dates in 17 prefectures out of 19 were estimated by [1]', [2]', [3]' and [4]'. 12 prefectures out of 17 by [1]', 7 by [2]', 10 by [3]' and 13 by [4]' could be estimated with about 12 days error or less in 1968 and 9 out of 13 was correctly estimated by [3]' and [4]' in 1969. The estimation by the regression line of one factor was s~mewhat different from each other, but when multiple regression line of four factors was used the estimation became more correct. Judging from these results, it is adequate to use the multiple regression equation of [4] and [4]' when we want to forecast the median date or mode date ofJapanese encephalitis time cure. 6) In the case of adding two factors concerned with mosquitoes to T6,7 (X¹), D. pos. swine (x²), latitude (x³), longitude (x4), multiple regression equations become as follows. y= -1.46x¹+0.14X²+0.068x5+89.03 σ= 6.9.. ·[5] z= -3. 29x¹+0 .13x²-0. 010x5+ 143.63 σ= 18.6··· [5]' y=-4.20x¹+0.35x²+0.29x6 + 53.70 σ= 4.2 .. ·[6] z=-2.56x¹-0.0lx²-0.02x6 +128.96 σ=11.4 [6]' y= 4.76x¹+0.41x²+0.13x5+0.22x6-72.78 σ= 4.5 [7] z = - 2. l0x¹ + 0. 05x²+ 0. 11 x5 - 0. 08x6+ 113.4 σ= 10. 7.. · [7]' where x5 is the time when the number of mosquitoes (C. T. collected by light trap reached the maximum and X6 is the time when hazardous mosq uitoes were dected. In the case of median date, 5 prefectures out of 6 prefectures by [5], 2 out of 6 by [6] and 2 out of 5 by [7], and in the case of mode date, 5 out of 6 by [5]', 4 out of 5 by [6]' and 4 out of 5 by [7]' could be accurately estimated in 1969.

In the present communication the recent works done by the Rheumatism Research Group of Department of Orthopedic Surgery, Okayama University, are described. The principal findings may briefly be summarized as follows. 1. Pathohistological pictures of the synovial membrane are classified into six types. Among them, Fibrinoid type and Follicular-Fibrosis type are the representative ones of chronic rheumatoid arthritis. 2. For the evaluation of the systemic as well as the local activities in rheumatoid arthritis and for judging the therapeutic effect, some indices have been established. 3. Injection of steroid hormones into the local joints fails to give satisfactory results in advanced, chronic rheumatoid arthritis. In such instances the flushing of the joint with physiological saline solution is effective. 4. In the case of chronic rheumatoid arthritis where the inflammation of hand and phalangeal joints is marked, RA-test gives rapid and more intense reaction, and most of such cases are of Follicular-Fibrosis type. 5. When lymph follicles appearing in the synovial membrane are stained when methyl green pyronine, the arrangement of lymphoid cells and plasma cells becomes distinctly clear. By micro-autoradiographic observations it can be seen that ³H-thymindine injected into the joint cavity is mostly ingested by the lymphoid cells in lymph follicles. 6. In the observation by the fluorescent antibody method multinuclear leucocytes found in the joint fluid and in the peripheral blood react with 19S and 7S-gamma-globulins. 7. When the serum and the joint fluid of the patient with rheumatoid arthritis are fractionated, they separate into three peaks at 19S, 7S, and 4S. Both S. S. C. A.-test and L. F. T. tests reveal the peak at 19S. The serum of chronic hepatitis positive to RA-test and the serum of rheumatoid arthritis are found to react immunologically the same to anti-β2 M globulin sheep serum. 8. When the reticulo-endothelial system of rat is blocked by 900,000 molecules of poly-vinyl-pyrroridon, the ability of antibody production is diminished. 9. Chemical synovectomy of injecting osmic acid is effective to FibrinoidCoating type. Its action mechanism lies in the complete cleaning of the surface of synovial membrane. 10. By radiating synovectomy with 193Au a fairly good result can be expected. 198Au is ingested by those cells in the surface layer of the synovial membrane and also by histiocytes in the synovial membrane. When 5 mc of 198Au are injected into the knee joint, a marked necrosis of the synovial membrane occurs. When 198Au is added to the ascites cells of rabbit during the tissue culture, in the concentration of over 14 μC degeneration of these cells can be recognized. 11. From the examination results of prognosis on those 25 cases with 41 rheumatoid knee joints after surgical synovectomy, it is considered that this method is indicated for Follicular-Fibrosis type. Ones with rheumatoid knee joint of Fibrinoid-Coating type gold sol treatment should be resorted to. In the cases of hand joints, surgical synovectemy is to be recommended at a relatively early stage.

The RNA extracted from Rous sarcoma virus (RSY)induced mouse ascites sarooma cells (SR·C3H, N. P.) by means of the cold SDS-phenol was examined by the electron microscopy on the specimens spread wi th or wi thout urea according to the protein mono· layer technique. The majority of RNA molecules was found in a collapsed agglomerated form, derived from matured ribosomal RNA. Using sucrose gradient, linear molecules of RNA were observed in the interspace of the agglomerated form of RNA at the region of high molecular weight of the band sedimentation. The histogram of the distribution in length of the linear molecules involved up to 6 /1 in length wi th a modal length of 2. 28 f1 and 2.0 to 2. 2 f1 in a pro. minent peak; longer molecules up to 18 f1 in length were scarcely observed. Species of the linear RNA molecules is not exactly known, although this is not mature ribosomal RNA and likely to be messenger RNA or nascent RNA molecules, some of which might associate with RSY·RNA.

We detected an antibody to HCV envelope protein (E1) in sera of patients with HCV-related chronic liver diseases (20 patients with chronic hepatitis and 5 patients with liver cirrhosis) by Western blotting using the fusion protein of E1 envelope protein and beta-galactosidase as an antigen. The antibody to HCV E1 (anti-HCV E1) was detected in 8 (42%) of 19 patients positive for HCV-RNA (16 were positive and 3 were negative for antibody to C100-3) and in 1 (17%) of 6 patients negative for HCV-RNA but positive for antibody to C100-3. HCV-RNA was detected in 8 (89%) of 9 anti-HCV E1 positive sera. The value of alanine aminotransferase was significantly higher in patients positive for anti-HCV E1 than in patients negative for the antibody. Although an antibody to the envelope protein of HCV is suspected to be one of the candidates of virus-neutralizing antibodies, our results suggest this hypothesis appears to be unlikely.

We performed pulmonary artery angioplasty in 19 patients with lung cancer. The procedure consists of segmental or wedge resrection of the infiltrated pulmonary artery stem followed by reconstruction to avoid pneumonectomy and preserve pulmonary function. Among these cases "double sleeve resection" was performed in 10 cases. The 5-year survival of the angioplasty patients was poor at a rate of 11％, but not significantly different from the survival rates for those patients who underwent bronchoplasy alone or pneumonectomy. A promising prognosis may be expected in cases with N0 and N1 lymph node metastasis. However, this procedure may not replace pneumonectmy in patients with intact pulmonary function.

1. When chicken sarcoma virus is serially inoculated on the mouse brain, it loses its carcinogenecity, but when it is inoculated on young chicken, granuloma develops in the liver and lung. When this granuloma is transplanted on adult chicken, a transplantable fibrosarcoma is obtained. 2. According to literature, the originaltumor of the Brown-Pearce cancer is a basal cell cancer, but that imported to Japan in 1953 presented a histological picture of carcinosarcoma. The metastasized tumor of the eye presents a purely cancer tissue, but when this is inoculated on the testis, carcinosarcoma is reproduced. It is therefore considered that the mother cell of the sarcoma is of host origin. 3. MY sarcoma is not a sarcoma, but is a spindle cell cancer. It might be a sarcoma which transformed into a cancer during serial transplantation, but perhaps it was originally a cancer but had been erroneously diagnosed as sarcoma. 4. The tumors we obtained by means of the feeding tests of Yoshida tumor all developed at organs other than those of the digestive tract. They are chiefly reticulo-sarcoma, but others which develop are malignant granuloma in the liver and lung, malignant adenoma in the kidney, papilloma of pelvis, and ependymoma in the cerebral ventricle. Since the discovery of the Yoshida tumor in 1943, serial transplantation has been conducted for 19 years with this tumor not only in Japan but also in foreign countries, but there has been no report to this date that a transformed strain has developed by cell transplantation. It therefore must be considered that the carcinogenesis observed in our feeding tests is a carcinogenesis due to a mechanism completely unlike that of cell transplantation. It has been confirmed by electron microscopy that in the early stage of transplantation of this tumor into the abdominal cavity there was an additional tumor growth due to the anaplastic proliferation of serous cells. 5. During the serial transplantation of viral tumors and/or virus dependent tumors, the tumor sometimes undergoes a morphological change. Though the cause of this is not yet sufficiently elucidated, it is suspected that there is some relationship with virus in the wide sense.