Electron microscopic cytochemistry was performed on the rat choroid plexus epithelium to reveal the enzymatic sites of the activities of glucose-6-phosphatase and thiamine pyrophosphatase. Glucose-6-phosphatase was mainly situated in the endoplasmic reticulum and nuclear envelope, and thiamine pyrophosphatase in the Golgi complex. The ultrastructure of these two enzyme localizations in these tissues, has not been described. These enzymes can thus be considered as marker enzymes for their respective organelles in the choroid plexus epithelial cells, as well as in other tissues. The function of these enzymes in the choroid plexus epithelial cells might be related to carbohydrate metabolism.

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To determine the ultracytochemical localization of Na⁺, K⁺-ATPase and Mg²⁺-ATPase activities on normal rat choroidal epithelium, the Mayahara et al.'s one-step lead citrate method and Wachstein and Meisel's technique were employed.
The electron dense reaction products which are sensitive to ouabain (10^-3-10^-4M) were observed to be abundant inside the microvilli and to be positively present along the outside of the basal plasmalemmas of the choroidal epithelium. The Mg²⁺-ATPase activity was seen as electron dense reaction along the outside of the choroidal basal plasmalemmas.
Na⁺, K⁺-ATPase activity is thought to be involved in cerebrospinal fluid secretion through the active movement of Na⁺ in the choroidal epithelial cell. The Na⁺-K⁺ exchange pumps are thought to localize both in the plasmalemma of the microvilli and in the basal plasmalemmas of the choroid plexus epithelial cell.

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The radiosensitizing effect of misonidazole was studied in an experimental system of intracranially transplanted 203-glioma in C57BL mice. When 5 × 10⁵ tumor cells were transplanted into the right frontal area of 4-week-old male mice, all the control mice died within 3 weeks after transplantation. The experimental mice were treated with 1, 000 rads of irradiation using ⁶⁰Co, with or without misonidazole administration, given after various lengths of time after transplantation. When used, misonidazole was given intraperitoneally in a dose of 20 mg, 30 to 60 minutes prior to irradiation. Misonidazole had no remarkable effect when the mice were treated 6 days after transplantation. However, when they were treated with misonidazole 10 days after transplantation and irradiated, the mean survival time of the mice was longer (about 6.5 weeks) than that of the mice treated by irradiation alone (about 4.5 weeks). In order to evaluate the radiosensitizing effect of misonidazole in the terminal stage to contain a large number of hypoxic tumor cells, the following in vivo assay was designed. Intracranial tumors, with or without misonidazole treatment, were removed immediately after irradiation. Then, 5×10⁵ viable tumor cells were retransplanted into other groups of mice, and their survival rates were observed. While all the mice retransplanted with tumor cells treated by irradiation alone died of tumor growth within 5 weeks, those retransplanted with tumor cells treated by irradiation and misonidazole became free of tumor and survived for the observation period of 8 weeks. These results suggest the radiosensitizing effect of misonidazole. As regards the side effects, there was no notable decrease in body weight after the administration of misonidazole. On histological examination there was no specific change ascribable to misonidazole, while there were many necrotic regions after irradiation with or without misonidazole.
As a clinical trial, misonidazole was given to 21 patients with brain tumors in an oral dose of 1.0 g/m², 4 to 6 hours prior to irradiation twice weekly. The total dose was limited to 10 g/m². Because the series of patients was not large enough and because most of them were also given chemotherapy, it was difficult to distinguish the effect of misonidazole from that of conventional radiotherapy and chemotherapy. There was no remarkable side effects due to misonidazole except for nausea and vomiting in some patients. It is clear, however, that the limiting factor in the clinical dose of misonidazole is its various toxicities, such as peripheral neuropathy and gastrointestinal symptoms, which have occasionally been reported, and so the local application of misonidazole may be the next step.

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The antifungal drug, 5-Fluorocytosine (5-FC) which is a derivative of 5-Fluorouracil (5-FU), lacks antineoplastic activity in human subjects because of the absence of cytosine deaminase (CDase) in mammalian cells. Therefore, intratumoral conversion of 5-FC to 5-FU by extrinsic CDase could be expected to induce antineoplastic effects at a local site with minimal systemic toxicity. The effects of combined administration of 5-FC and CDase in in vitro and in vivo were investigated. CDase was extracted from the E-Coli K-12 strain and purified.
In vitro studies resulted in a significant inhibition of cell proliferation on cultured glioma cells (EA-285 cells) with 5-FC concentration over 10 μg/ml. Fluorocytographic studies of the tumor cell cycle progression showed synchronization in the early S phase at lower concentrations and complete blocking at the G1 and the early S phase with over 25 μg/ml. In in vivo studies, tissue concentrations of 5-FC and converted 5-FU were serially measured by a bioassay method after simultaneous intratumoral injection of CDase and systemic administration of 150 mg/kg of 5-FC to brain tumor bearing rats. The maximum concentrations of the drugs in the tumor tissue were 85 μg/g 5-FC at 1 hour and 9.6 μg/g 5-FU at 2 hours, which were sufficient to kill tumor cells. They were kept at higher levels in the tumor tissue than in the normal brain. In comparison, the maximum 5-FU concentration in the serum was only 0.4 μg/ml. The survival times and histological examinations of the experimental brain tumor models by this combined therapy were evaluated. The median survival time of the treated group was significantly prolonged (38.3 days) when compared with that of the control group (28.2 days). No side effects were recognized. Histological studies of the animal brains 2 weeks after the therapy revealed necrosis in the treated tumor. This combined treatment of 5-FC and CDase could be an ideal therapy for brain tumor in the future.

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High-dose BCNU therapy (supralethal chemotherapy) with autologous bone marrow rescue after Hochberg was performed on a 7-year-old boy suffering from a recurrent brain stem glioblastoma multiforme. CT scan in December 1979 showed a pontine glioma (low density area at the upper half of the pons). X-ray therapy and chemotherapy were done twice with remissions (5, 000 rads + 4, 500 rads). At the time of the third neurological exacerbation in March 1981, CT scan disclosed the tumor extending up to the left basal ganglia. Therefore, 500 mg of BCNU (600 mg/sq. m) was given in preparation for autologous bone marrow grafting. Eight weeks after this procedure, CT scan showed the complete disappearance of the tumor shadow and good neurological recovery was obtained. However, the patient expired on the 61st day due to pulmonary fibrosis. The technical simplicity of this method of bone marrow grafting (preservation of aspirated bone marrow at 4°C) was compared with cryopreservation methods. However, many side effects of high-dose. chemotherapeutic drugs, other than myelosupression, remained to be solved.

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Clinical symptoms, endocrinological findings, neuroradiological findings, and the results of treatments were studied in 24 patients with pituitary adenoma with hyperprolactinemia (over 30 ng/ml). The excised tumor tissues were examined light-microscopically and electron-microscopically, and hormones in the tumor culture medium were measured. The subjects in this study were 19 female and 5 male patients. All of the female patients had had amenorrhea and 14 of them had shown galactorrhea. Nine of the 24 patients had had visual disturbance and 2 had had diplopia or blephaloptosis. These 24 patients were classified into 3 groups according to the prolactin (PRL) values and the neuroradiological findings. The first group consisted of 4 patients who were rather aged (mean age, 44.5 years) and had low PRL values ranging from 30 to 112 ng/ml. The tumor showed suprasellar extension, and all the 4 patients had had visual disturbance. Electron microscopy and immunological staining did not yield confirmation of PRL-productive pituitary adenoma. The second group consisted of 12 patients who had high PRL values ranging from 116 to 1, 040 ng/ml. The tumor was intrasellarly localized. PRL value returned to normal after surgery in 18% of the patients. Menstruation started again in 27% of them. After administration of CB154 the PRL value was restored to normal in 75% of them, and menstruation started again in all of the 12 patients. The third group consisted of the remaining 8 patients where the tumor showed parasellar extension. Sufficient effects could not be obtained by surgery alone. Even after administration of CB154, the PRL value was restored to normal in only 2 of the 8 patients, and menstruation and pregnancy were observed in only 1 of the 4 female patients. Thus, patients who belong to the second and third groups with PRL-productive pituitary adenoma should be treated as follows: In patients with PRL-productive intrasellarly localized pituitary adenoma, the tumor should be totally excised. In patients with PRL-productive pituitary adenoma which invades the cavernous sinus and so cannot be totally excised, CB154 should be administered after surgery.

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Seven male cases with prolactin-secreting pituitary adenomas were studied. The mean age was 29.4 years (range: 19 to 34 years). All had visual impairment, decreased libido/impotence, and lessened general body hair. Plain X-ray films of the skull and sellar tomograms revealed destruction of the sella turcica and upper clivus in all cases. Marked suprasellar extension of the tumor was noted in 5 of 6 patients who underwent pneumoencephalography. Endocrinological evaluation disclosed hyperprolactinemia (≥ 2, 000 ng/ml) in all cases. Other pituitary hormones were measured in 6 cases. Subnormal or absent GH reserves were evidenced by the lack of response to insulin induced hypoglycemia in 6. FSH and LH were measured before and after stimulation by 100 μg of LH-RH iv.. Three of 6 patients had normal responses in each, one for FSH/LH, a second for FSH, and the rest for LH. On the other hand, normal or above normal responses of TSH to 500 μg of TRH iv. were noted in all cases. Urinary 17-OHCS were of subnormal levels in 3 of the 7. Plasma testosterone, measured in 3, were all of low values. In two who had small testicles it was impossible to induce erection and ejaculation, and one of the two showed delayed puberty. The third patient, who was able to ejaculate, had azoospermia.
Six of 7 patients undertook transsphenoidal surgery, and the subfrontal approach was performed in one. None of them became normoprolactinemic postoperatively. Therefore, all patients needed bromocriptine administration (10 to 15 mg/day) to decrease serum prolactin levels. Remarkable reduction of pituitary tumor size after treatment with bromocriptine was observed in one patient. Bromocriptine was withdrawn because of side effects in one patient who complained of visual disturbance 2 months later. Reoperation was performed and pituitary carcinoma was found. Cerebrospinal fluid rhinorrhea associated with symptoms of pituitary apoplexy was observed in one patient before surgery, who was treated with bromocriptine. It was probably due to regression of the tumor. Loss of libido/impotence after surgery were successfully managed with additional treatment of human chorionic gonadotropin (HCG) injections.

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Three cases of a rare complication of the shunt operation in hydrocephalus with high intracranial pressure were experienced, in which the extension of the cerebrospinal fluid (CSF) into the cerebral parenchyma along the ventricular catheter and the gradual disappearance of the fluid following shunt revision were clearly demonstrated on computed tomography (CT).
In one of the cases, a brain biopsy was carried out which revealed no definite ultrastructural change in the cortex, but did show definite changes in the subcortical white matter, such as a spongy appearance with vacuoles of various sizes, the absence of active destruction of the myelin sheath, and the absence of fat granule cells.
These complications were considered similar to CSF edema or infusion edema in animal experiments reported by Marmarou et al.. The phenomenon has not yet been reported in clinical cases.

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A case of a cerebral aneurysm coexisting with an arteriovenous malformation in addition to multiple vascular malformations was reported. A 47-year-old female suddenly developed severe headache and vomiting. Neurological examination revealed slight disorientation, memory disturbance, and positive Kernig's sign. CT scan demonstrated a right temporo-parietal intracerebral hematoma with ventricular rupture in addition to small calcifications at the site of hemorrhage. Right retrograde brachial angiography demonstrated an arteriovenous malformation at the right posterior temporal lobe, a basilar top aneurysm, and a parietal small vascular malformation. Marked dilatation of the right posterior communicating artery and posterior cerebral artery were also demonstrated. Left carotid angiography showed a small vascular malformation at the parietal lobe, symmetrical to the right side. A right frontotemporo-parietal craniotomy bone-flap was raised. With a subtemporal approach, neck clipping of the basilar aneurysm was done and then the nidus of the temporal malformation and liquefied hematoma were totally excised. The two small vascular malformations on both parietal lobes were left. The postoperative course was uneventful and the patient was discharged with mild homonymous hemianopsia on the left side.
In the present case, it is possible to suppose that not only the increased blood flow due to the arteriovenous malformation, but also other congenital factors might have played an important role in the production or development of the saccular aneurysm situated at the artery proximal to the arteriovenous malformation.

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A case of epidermoid cyst in the posterior fossa showing a characteristic finding upon metrizamide CT cisternography is reported.
A 42-year-old man was admitted with gait disturbance. The abnormal signs were trunucal ataxia, gait ataxia, left cerebellar sign and nystagmus. A CT scan revealed a large, low-density area and the fourth ventricle could not be seen clearly. Absorption values were in the range of 5-18 Hounsfield units. There was no change in the absorption values of the lesion following intravenous injection of contrast medium. Metrizamide CT cisternography was performed. No remarkable change was seen 1 hour after intrathecal injection of metrizamide. However, metrizamide irregularly surrounded the left margin of the low-density area 3 hours after intrathecal injection. Moreover, metrizamide stained the area heterogeneously like a honeycomb or sponge at 6 hours. Finally, only a small amount of metrizamide remained in this area after 24 hours. Suboccipital craniectomy revealed a pearly tumor in the cisterna magna, wrapped in a thin white capsule and partially adherent to the cerebellomedullary junction. The tumor was totally removed. Histopathological investigation showed stratified squamous epithelium with keratinous material.
A honeycomb- or sponge-like image seems to be a characteristic finding in metrizamide CT cisternography of the epidermoid cyst. This finding has not been previously reported. However, pneumoencephalographical findings in some cases of epidermoid were reported as crumb or sponge-like images. These images were thought to be caused by air covering the surface of the pearly tumor. These images should be similar to the one found in the present study using CT cisternography.

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Twenty-three cases of chronic subdural hematoma were observed soon after head injury for the relationship between its CT findings and clinical symptoms. It has been found that the chronic subdural hematoma is a slowly growing and expanding intracranial disease that starts in an early period of head injury. Chronic subdural hematoma did not present any signs or symptoms initially, except for the gradual occurrence of headache, but finally it presented signs of intracranial hypertension and focal signs. Chronic subdural hematoma in the hygroma-like period did not show any signs and symptoms. In the capsulated period, when changes in CT density suggested intracapsular hemorrhage, a heavy sensation of the head was noted. It was recognized as an abnormal feeling or a full sensation of the head. When the bleeding continued in the cavity, headache became continuous and focal signs gradually appeared.

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