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Hydrothermally stable silica-alumina composite membranes were synthesized through chemical vapor deposition (CVD) of tetraethylorthosilicate (TEOS) and aluminium tri-sec-butoxide precursor at 923 K on porous alumina supports. The membranes showed high hydrogen permselectivity (order of 10−7 mol m−2 s−1 Pa−1) comparable to that of pure silica membranes but with superior hydrothermal stability, and were used in a membrane reactor. The permeation of small gas species (H2, He, Ne) was well explained by a solid-state diffusion mechanism, involving jumps of the permeating species between solubility sites. The permeation mechanism of large gas molecules (CH4, CO2, N2) was explained by the gas translation mechanism involving large pore defects. Steam methane reforming (SMR) on a Ni/MgO-SiO2 catalyst was carried out at 923 K in the membrane reactor and in a conventional packed-bed reactor. The membrane contributed to an increase in the hydrogen production rate by the selective extraction of hydrogen from the reaction zone.

Supardi N, Sumarpo A, Sutejo R, Putra ABN, Kageyama N, Kawano M, Sugahara T. 2018. Short Communication: IgE production-suppressing effect of asam kandis (dried Garcinia xantochymus) extracts by mouse hybridoma aDNP-Hy Cells. Biodiversitas 19: 330-335. Asam kandis (dried Garcinia xanthocymus Hook.f.ex.T.Anderson) is popularly used as a spice in many Indonesian cuisines. Although Garcinia xanthocymus has been reported to possess various pharmacological properties, its immunologic functions have been poorly studied. Therefore, in this study, we aimed to determine immunoglobulin E (IgE) production-suppressing effect of Asam Kandis extract (AKE) using mouse hybridoma aDNP-Hy cells. AKE was prepared through 24 hours maceration in distilled water. IgE production-suppressing activity of AKE by aDNP-Hy cells was examined in time-wise manner. Cell viability and IgE mRNA expression were assessed using trypan blue assay and qRT-PCR, respectively. IgE production-suppressing activity of heat-treated (100°C) AKE was also examined. As a result, AKE significantly reduced IgE production by aDNP-Hy cells in a concentration-dependent manner both in 24 and 36 h incubation periods. Furthermore, AKE exhibited its IgE production-suppressing activity without any cytotoxicity and also significantly decreased IgE mRNA expression. Heat-treated AKE showed no IgE production-suppressing activity, indicating that the bioactive substances are heat labile. More interestingly, heat-treated AKE showed cytotoxic effect by aDNP-Hy cells. We showed that AKE exhibits IgE production-suppressing effect by aDNP-Hy cells. Further studies are necessary to discover underlying bioactive compounds of asam kandis and substance that responsible for the cytotoxic effect of heat-treated AKE.

The feasibility of harnessing the increase in moles in certain equilibrium-limited reactions to alleviate the pressure driving force requirement for permeation through membranes is demonstrated. The studies are conducted in a packed-bed membrane reactor operated as a semi-batch membrane reactor (SBMR) to capture the pressure generating potential of the reaction. The actual system investigated is the steam methane reforming, a reaction in which the number of moles doubles, carried out at various temperatures (873 K and 923 K) and pressures (0.5–1.5 MPa) with a Ni/MgAl2O4 catalyst. A silica-alumina membrane with a hydrogen permeance of 2.2 × 10−7 mol m−2 s−1 Pa−1 at 923 K prepared by chemical vapor deposition was used in the membrane reactor. The hydrogen productivities obtained in the SBMR were compared with the productivities obtained in a membrane reactor operated at the same conditions. At low pressures (0.5, 1.0 MPa) the hydrogen productivities of the SBMR were comparable to those obtained with the continuous membrane reactor, but at high pressure (1.5 MPa) the SBMR showed superior performance. One-dimensional modeling studies gave good agreement between simulated and experimental results obtained from both reactor types. Based on these calculations, further estimations on hydrogen productivities were made at high pressures. These results indicated that the SBMR improved the hydrogen production when the steam methane reforming was conducted above 1.5 MPa. The SBMR described here could be utilized in a system where multiple units would be arranged to undertake parallel filling and discharge operations, much akin to the arrangement used in a pressure swing adsorption system.

The steam methane reforming (SMR) reaction was studied on a Ni/MgO-SiO2 catalyst at 923 K (650 °C) and 0.40 MPa in a tubular packed-bed reactor. The partial pressures of CH4 and H2O were varied between 20 and 140 kPa and 80 and 320 kPa, respectively. Measurements were carried out without mass and heat transport limitations, as verified by the Weisz–Prater and Mears criteria. Experimentally, the CH4 conversion increased with the inlet partial pressure of H2O and decreased with the inlet partial pressure of CH4. However, at low CH4 inlet partial pressures, i.e., at 40 and 60 kPa, the conversion passed through a maximum. Rate expressions were derived based on a simple two-step sequence. A statistical analysis led to a globally significant, weighted regression and resulted in a good agreement between the model and the experimental data, as indicated by a low F value of model adequacy of 2.84. The rate and equilibrium coefficient parameters were statistically significant as indicated by narrow confidence inter...

Radiological, histological and molecular findings in an uncommon adult case of cerebellar medulloblastoma suggested an external granular cell precursor origin. This 19-year-old woman had a 1-month history of progressively worsening headache. Neuroimaging studies demonstrated a homogeneously enhanced well-circumscribed mass lesion in the right cerebellar hemisphere and she underwent surgery. Postoperative neuronal imaging studies showed that the tumor located in the cerebellar folia had been removed totally. Pathological examination identified it as a desmoplastic medulloblastoma with subpial and subarachnoid infiltration and some infiltration into the molecular and granular layer via the perivascular space. Polymerase chain reaction and immunohistochemical findings revealed the presence of MATH-1, expressed in cerebellar external granule cell precursors during fetal development, in the tumor cells. These findings suggest that the tumor arose from external granule cell precursors of the cerebellum and that it was therefore of neuronal lineage.

Characteristic findings of the pituitary stalk on magnetic resonance (MR) imaging, which suggest a damming-up phenomenon of neurosecretory granules, were reported. Neurosecretory granules containing vasopressin influence the signal intensity on MR T1-weighted image (T1WI). The normal posterior lobe of the pituitary gland appears as a bright signal on T1WI. The bright signal of the posterior lobe represents the normal content of neurosecretory granules and disappears in patients with central diabetes insipidus. The normal pituitary stalk appears as a low-intermediate intensity signal on sagittal and coronal T1WIs with 3 mm-slice thickness. The pituitary stalk appeared as a bright signal in 20 patients; 13 with pituitary adenoma, 4 with an intrasellar cystic lesion, one with cavernous sinus mass, and 2 with no abnormal MR findings. The pituitary stalk was not severed in any of the cases. The normal bright signal of the posterior lobe disappeared in 17 patients. No patients suffered from symptoms of central diabetes insipidus when the bright pituitary stalk appeared. It is suggested that the origin of the bright signal in the pituitary stalk is the damming up and accumulation of neurosecretory granules in the nerve fibers of the hypothalamohypophyseal tract obstructed by adenoma, postoperative scarring, cystic mass and so on. Probably, the damming-up phenomenon on MR imaging represents the functional integrity of the hypothalamo-neurohypophyseal system, and should be distinguished from an ectopic posterior lobe formation which is caused by stalk transection.

There has been accumulating evidence that pituitary adenomas which cause Cushing's disease are located not only in sella turcica but also in various extrasellar and intracranial regions. We describe a case of Cushing's disease caused by a supra- and extrasellar ACTH-producing microadenoma, which originated in the anterior pituitary and extended upward without connecting to the stalk. The pituitary microadenoma was identified and removed by transsphenoidal microsurgery. After the surgery the patient experienced complete remission. This type of pituitary microadenoma is considered to be rare, but in order to accomplish successful surgical treatment, it is necessary to consider that pituitary adenomas which cause Cushing's disease may be located in such an unusual position.

The regional distribution of dopamine (DA) and norepinephrine (NE) was investigated in dog cerebral arteries using high performance liquid chromatography with electrochemical detection. The distribution patterns of these two amines differed and there was a wide fluctuation in the ratio between the amounts of DA and NE. The ratios of DA to NE in the anterior cerebral artery and the anterior inferior cerebellar artery were 2-4 times higher than in the basilar or middle cerebral arteries, thereby suggesting that DA plays a role other than that of precursor of NE. The concentrations of both amines following pre- or postganglionic sympathetic denervation (superior cervical ganglion) were investigated. After preganglionic denervation (decentralization), neither amine showed significant changes in concentration. Postganglionic denervation one week prior to sacrifice resulted in a reduction in the concentrations of both amines; however, decrease in the former was less. These results suggest that the origin of dopamine in the cerebral arteries differs from that of the sympathetic nerves, via the superior cervical ganglion.

Quantitative evaluation of radioisotope (RI) cisternography was performed by single photon emission computed tomography (SPECT) in eight patients suspected of chronic hydrocephalus or malfunction of a shunt system, showing symptoms for 2 to 24 months and one control patient with cerebrospinal fluid (CSF) leakage ten years after head trauma. Regular evaluations were scheduled after the injection of 1 ml of 1 mCi Indium-111 diethylene triamine pentaacetic acid. The region of interest, about 1.3 cm in radius and 0.8 cm in height, was placed in the cisterna magna (CM), lateral cistern Sylvii (LCS), basal cistern (BC), interhemispheric cistern (IHC), and in the lateral ventricle (LV) using a reconstructed image of a horizontal section by SPECT. Decay curves were calculated with estimating decreasing count of RI each time by the least square method.

It is well known that dementia is one of the major symptoms of the patients with “normal pressure hydrocephalus (NPH).” However, the pathogenesis of the symptom has not fully been understood. Many scientific contributions have appeared on the recently proposed “cholinergic hypothesis of geriatric memory dysfunction.”

✓ The levels of two calcium-binding proteins, S-100 protein and calmodulin, were measured serially in the cerebrospinal fluid (CSF) of patients after subarachnoid hemorrhage (SAH) and aneurysm surgery. These two proteins have a similar molecular structure and are highly concentrated in the central nervous system (CNS). The levels of S-100 protein found in the earliest postoperative CSF samples correlated with the preoperative SAH grades. High S-100 protein levels in the CSF were found in patients with poor SAH grades. Moreover, the prognosis of the patients correlated with the S-100 protein levels in the CSF samples taken during the immediate postoperative period and with the daily changes of the S-100 protein levels. Severe diffuse cerebral vasospasm was followed by a sharp S-100 protein increase. These results suggest that S-100 protein levels in the CSF provide a useful index of organic damage in the CNS, and furthermore that S-100 protein levels and their changes may have prognostic value for patients after SAH. On the other hand, there was a lack of correlation between the calmodulin levels and the preoperative grade or outcome. It would be inappropriate, however, to speculate from the results of this study that these calcium-binding proteins in the CSF play any causative role in pathological processes such as cerebral vasospasm or brain ischemia after SAH, since changes in the levels of these proteins followed the onset of clinical signs of deterioration.

✓ The authors report the results of internal irradiation with labeled chromic phosphate (32P) and gold-198 (198Au) colloid in eight cases of cystic craniopharyngiomas. They used a newly developed dosimetric formula, by which the radiation dose at the cyst wall and at any point far from the radioactive source can be calculated. Ten courses of irradiation in eight patients were carried out by injection of either 32P or 198Au colloid into the cyst through an Ommaya drainage system that had been placed at craniotomy. Follow-up studies ranging from 13 to 156 months revealed that all cysts were effectively treated, with elimination of fluid or collapse of the cyst. This was confirmed by Conray cystography and/or computerized tomography. Not only the dose delivered to the wall but also the thickness of the cyst wall and the location of the cyst are important factors in planning internal irradiation. A safe and adequate dose to the cyst wall could range between 9000 to 30,000 rads for craniopharyngioma. This treatment is suitable for large cysts that are thought to be difficult to remove radically, recurrent cysts resistant to previous treatment, or multiple cysts. Internal irradiation may also be applicable in other cystic intracranial tumors if dosimetry is calculated accurately.

Since Vale et al isolated and sequenced a 41 amino acid peptide with corticotropin-releasing factor (CRF) activity from ovine hypothalami, intensive works have been done about its physiological activity and intracerebral distribution. However, little has been done yet about CRF metabolism in human cerebrospinal fluid (CSF). Using a specific ovine CRF radioimmunoassay (RIA), we measured the levels of CRF in CSF from 16 patients with Cushing's disease (group I), 8 patients with Acromegaly (group II), 5 patients with Prolactinoma (group III) and 10 patients without endocrine abnormalities (group IV). Moreover diurnal changes of CRF in CSF from 2 patients with Acromegaly and 2 patients with Cushing's disease were examined. Dilution curves of CRF in CSF were parallel to that of synthetic ovine CRF standard. The intraassay coefficient of variation was 9.2% and the interassay coefficient of variation 12.6%. The concentrations of CRF in CSF of groups I, II, III and IV were 38.83 +/- 9.02 pg/ml (mean +/- SD), 44.24 +/- 4.71, 47.62 +/- 8.05 and 49.45 +/- 12.86, respectively. Group I was significantly lower than group IV (p less than 0.05). On the other hand, group II or III was not significantly different from group IV. A diurnal rhythm of CRF in CSF was observed in 2 patients with Acromegaly. However, there was almost no change in the 2 patients with Cushing's disease. In considering rich amount of CRF in hypothalamus and CRF-positive fibers surrounding the third ventricle, CRF content in CSF seems to reflect mainly its metabolic activity in hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical presentations, findings of neuroradiological examinations, laboratory findings, pathological diagnoses, methods of treatment, and results of follow-up of 43 cases of pineal tumor collected at the Nagoya University Hospital from 1958 to 1979 are reviewed. The definitions of calcification of the pineal body and of pineal tumor are given. There is a significant difference in the incidence of calcification of the pineal body between pineal teratomas and pineal germinomas. Although there is a 100% rate of calcification of the pineal body in cases of pineal germinoma, the rate is very low in cases of pineal teratoma; calcification appears in only a small percentage of the cases of teratoma mixed with germinoma or embryonal carcinoma, or both. In male patients with susprasellar germinoma, there is a high frequency of an associated pineal calcification. No pineal calcification is seen in cases of basal ganglia germinoma. The computed tomographic (CT) findings of pineal teratoma and germinoma are characteristic. CT scanning is superior for early diagnosis of suprasellar and basal ganglia germinomas.

The effect of estrogen on prolactin (PRL) synthesis at a single-cell level was studied by in situ hybridization and immunohistochemistry. Long-term estrogen treatment increased PRL-containing cells fr

There have been many references to the complications that result from the surgical treatment for hydrocephalic children, but only a few papers about radiological changes of skull following the procedure have been reported. During the last 6 years 120 cases of pediatric hydrocephalic patients were treated with ventriculo-atrial (V-A) or ventriculo-peritoneal (V-P) shunts. Significant skull changes were observed radiologically in those patients who showed increased head circumference at the time of initial surgical procedure performed after the age of one year. Selection of cases for this study was made upon the following criteria. 1. The diagnosis of hydrocephalus with enlarged skull and dilated ventricles was confirmed on the basis of cerebral pneumoencephalography and other diagnostic studies. 2. The shunting procedure was performed after one year of age. 3. The head circumference at the initial operation was over 50 cm. 4. The patients had been followed for at least 2 years after the initial operation. 5. Adequate pre and postoperative skull films were available. 20 cases were selected using the above criteria, and 15 cases among these cases showed significant radiological skull changes. The radiological abnormalities of the skull are as follows: 1) Thicking of the vault, 12 cases. 2) Premature fusion of sutures, 12 cases. 3) Marked reduction in size of the sella turcica, 9 cases. 4) Lamination of the diploe, 6 cases. 5) Others: thickening of the cribriform plate, thickening of the planum sphenoidale and calcification of subdural hematoma etc. These alterations of the skull are due to inward growth of the inner table of the skull in response to the prolonged cerebrospinal fluid shunting precedure and probably due to reduction of cerebrospinal fluid pressure and pulsation. Marked skull changes were observed in cases of marked hydrocephalus with brain atrophy or hypoplasia, but no difference were observed between the patients with V-A and V-P shunting procedures. These skull changes, especially premature fusion of sutures, may affect prognosis of children. But adequate treatment of these patients with the apparatus available at present seems to be difficult. We feel that it is important to make diagnosis in early stage and that the surgical treatment for infantile hydrocephalus should be performed before the size of the skull and ventricles are makedly increased. The appropriate shunting apparatus to prevent excessive low intracranial pressure should be selected for the operative procedure for these patients.

Previously the authors have studied local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) in rats 1 hour after the occlusion of the left middle cerebral artery. It was found that LCGU was decreased in the ipsilateral cerebral cortex and the lateral striatum, where LCBF was also reduced. On the other hand, LCGU was increased in the ipsilateral medial striatum, olfactory tubercle, globus pallidus, subthalamic nucleus, and lateral habenula. They have also investigated changes in catecholamine metabolism in these regions and found very close relationship between LCGU, LCBF, and dopamine metabolism. In the present work, changes in serotonin metabolism were investigated measuring tryptophan (TRP), serotonin (5-hydroxytryptamine, 5-HT), and its metabolite, 5-hydroxy-indoleacetic acid (5-HIAA) in certain regions of the cerebral cortex, basal ganglia, and brain stem using the same ischemic model rats. The results were compared with the changes in LCGU and LCBF. The concentration of TRP was significantly increased in the “ischemic” regions, such as the ipsilateral cerebral cortex and lateral striatum. On the other hand, 5-HT was significantly decreased not only in the “ischemic” regions but also in the “nonischemic” regions such as the globus pallidus. There was a tendency for 5-HT to decrease in the ipsilateral substantia nigra and raphe nuclei. 5-HIAA showed no significant change in the “ischemic” regions but was significantly increased in the globus pallidus and raphe nuclei and had a tendency to increase in the substantia nigra. There was no significant change in any of these parameters in the regions of the contralateral side. The changes in 5-HT metabolism in the “ischemic” regions, such as the ipsilateral cortex and lateral striatum indicate that the synthesis of 5-HT was reduced, but its release was unchanged. Increase in 5-HT metabolism in the “nonischemic” regions, such as the globus pallidus, substantia nigra, and raphe nuclei indicates a presence of neuronally-mediated biochemical diaschisis.

Patients with optic glioma were classified into two types: infant type and childhood. The infant type was usually immature astrocytomas that had an aggressive course and had a poor prognosis. On the other hand, the childhood type was usually mature astrocytomas with a rather benign, self-limiting course, even when the tumor had been left untreated. To make a long-term assessment, 11 patients with optic glioma were studied and 6 long-term survivors with chiasmal tumor invasion, in whom total removal of the tumor had not been feasible, were followed up for 8–12 years. Most of them had a stable course both clinically and radiologically.

Two cases of sellar-parasellar chordomas were experienced, the main symptoms of which were slowly progressive cranial nerve palsies. Localized destruction of the sella turcica and a soft tissue mass protruding into the sphenoid sinus detected by CT and hypocycloid tomography were suggestive of sellar-parasellar chordomas. Endocrinological findings, size of the sella turcica and findings on contrast enhanced CT were helpful in differentiating them from pituitary adenomas. Cerebral angiography, metrizamide CT and hypocycloid tomography of the sella turcica suggested that the main mass was restricted to the epidural spaces, infiltrating into the sphenoid bone. The authors adopted transsphenoidal microsurgery, rather than craniotomy, to avoid injury to the dura mater and dissemination of the tumor cells in the cerebrospinal fluid pathway. The tumors were soft with few vessels and they were easily removed by suction and curettage, preserving the dura mater intact.

Tumour specific and various tumour-associated antigens expressed on human glioma cells were reported from many laboratories. These have been identified by xeno-, allo-, or auto-sera and more recently by utilizing monoclonal antibodies produced by hybridoma technique. In this article, the results of reports are summarized comparing the studies with conventional antisera and monoclonal antibodies. The present and future clinical applications of these monoclonal antibodies are described.

Though radiographically-proven calcifications in pituitary adenomas are rare, a higher incidence of microscopically-proven calcified adenomas has been recently reported. Therefore, the incidence of radiological and microscopical calcifications in various types of pituitary adenomas in a consecutive series of 169 cases (71 acromegalies, 54 prolactinomas, 24 Cushing's diseases, 2 FSH-producing adenomas, 1 TSH-producing adenoma and 17 non-functioning adenomas) were reviewed. Intra or supra-sellar calcifications visible on plain skull films or sellar tomograms were counted only in 4 cases (3 prolactinomas and 1 acromegaly). Including these 4, 22 of the 169 cases had microscopicallyproven calcifications, the majority (20 cases) were prolactinomas and only 2 acromegalies. Histologically, these calcifications in pituitary adenomas were divided into 3 types; that is, 1) calcifications in the intratumoral hematoma, 2) calcifications in the degenerative adenoma tissue, and 3) scattered psammoma bodies between the adenoma cells. The last type of calcification seemed to be characteristic of almost all of the calcified prolactinomas. The first and second types of calcification were seen in 2 cases of acromegaly, and were thought to be the result of degenerative or hemorrhagic change of the adenoma. No significant differences between calcified and non-calcified prolactinomas were detected as regards serum PRL levels, the length of hyperprolactinemic state, patient's age and sex, or operative findings.

Experimental study was made on magnetic induction hyperthermia for brain tumor using ferromagnetic implant with low Curie temperature. Thermoseed (implant) was made of nickel-palladium alloy, which was confirmed to produce enough heat by eddy current and also to have low Curie point between 43 °C–58 °C. Using this implant heating system, the effect of hyperthermia on normal rat brain and intracutaneously innoculated rat gliosarcoma (T9) were studied. Heat conduction from seed was twice as much in tumor tissue as in normal brain. It was also found that the intradermal brain tumors were completely diminished within 4 weeks by single local hyperthermia at 45 °C for 60 min.

Twenty-four patients with histologically verified brain metastasis of choriocarcinoma were analyzed regarding autopsy and operative findings, signs and symptoms, diagnosis, method of treatment, and prognosis. The autopsy incidence of brain metastasis was 66.7% in patients with choriocarcinoma, and the predominance of single brain lesions was confirmed. Most of the metastatic lesions were hemorrhagic. The hemorrhages were intratumoral, peritumoral, and/or subarachnoid. These findings were well correlated with the findings on computed tomographic (CT) scans and the acute onset with rapid progression of symptoms. The history of molar pregnancy, measurements of urinary chorionic gonadotropin, and findings on CT scans were diagnostic. Surgical removal of the lesion followed by chemotherapy combined with irradiation is the treatment of choice in patients with progressive neurological deterioration in whom chemotherapy alone is ineffective.

Responses of plasma ACTH and cortisol to corticotropin-releasing factor (CRF) were evaluated in 31 normal human males. 1.0μg/kg of sterilized synthetic ovine CRF was administered to the subjects, aged 19 to 53 yr and weighing 50 to 78 kg, at between 9: 30 a.m. and 10: 30 a.m. as an intravenous bolus injection after an overnight fast. Blood specimens were drawn before and 15, 30, 60, 90 and 120 min after injection for later determination of plasma ACTH and cortisol concentrations by radioimmunoassays. Plasma ACTH and cortisol levels for all subjects rose significantly (p

The humoral and cellular immunity of fifty-two patients with malignant brain tumor was analysed by measurement of various immunological parameters with regard to their clinical condition, which was divided into three stages; initial, recurrent and terminal. Immunological parameters analysed in this study were the level of immunoglobulin, number of lymphocytes, percentage of IgG Fc receptor positive T cells, blastogenesis with PHA, PPD skin test and T cell subsets. T cell subsets were studied by flow cytometry using OKT monoclonal antibodies. The immunity of the patients with malignant brain tumor was almost normal in the initial stage and decreased in the recurrent and terminal stages. Especially, the percentage of OKT 4 positive cells in lymphocytes decreased and the percentage of OKT 8 positive cells in T cells increased with deterioration of the clinical stages. Consequently the ratio of OKT 4 to OKT 8 positive cells decreased markedly. The effect interferon (IFN) as a biological response modifier was also analysed by T cell subsets in nine patients with recurrent malignant brain tumor. After administration of IFN, the percentage of OKT 4 positive cells in T cells increased and consequently the ratio of OKT 4 to OKT 8 positive cells increased.

✓ Intracranial anastomosis between the distal anterior cerebral arteries (ACA's) was performed on two patients. One patient had isolated occlusion of the proximal ACA on one side causing monoparesis in the leg, and the other patient suffered from occlusion of the internal carotid artery and a small anterior communicating artery. The weakness of the legs improved immediately after surgery and cerebral angiography revealed a good filling of the bilateral ACA's. Technical aspects and indications for the procedure are discussed.

We are reporting the results of internal irradiation using P-32 chromic phosphate and Au-198 colloid for cystic craniopharyngiomas. The irradiation schedules were made by a newly developed dosimetric formula, by which the radiation dose can be calculated at the cyst wall and at the point far from the radioactive source as well as simultaneously. Using this formula, untoward effects of irradiation on surrounding brain tissues can be eliminated, especially in cases in which the cyst wall is thin and can be penetrated by beta emission. Eight cysts out of 6 cases with craniopharyngioma were treated in this series by injection of radioactive phosphate or gold into the cyst through Ommaya reservoir and tube which had been placed beforehand at the time of craniotomy. All cysts were effectively treated to eliminate fluid retention or the collapse of the cyst for 3 to 33 months, which had been confirmed by follow-up conray cystography and computerized tomography. The effectiveness of irradiation was also shown histologically with a collapsed cyst removed at the second craniotomy. The side effect of irradiation, oculomotor palsy, was found only in a case with small cyst (5.0 ml of volume) at supra and intrasellar region 10 days after the injection of 5 me of P-32 chromic phosphate. The thickness of the cyst wall was less than 0.5 mm and the oculomotor nerves were thought to be adherent to the cyst wall by retrospective analysis. From these experiences, it was concluded that not only the amount of wall dose but also the thickness of cyst wall and the localization of the cyst were important factors for planning internal irradiation. Sufficient and safer doses to the cyst wall, which kills the tumor cells in the wall without side effects, would be between 9, 000 to 30, 000 rad for cystic craniopharyngiomas. Regarding the indications of internal irradiation, we are setting up some criteria to choose this method of treatment for cystic craniopharyngiomas. Large cysts of more than 10 ml and which are thought to be difficult to remove radically, would be the first choice of this treatment. Another indication will be cases with recurrent cyst resisting to the previous treatments or cases with multiple cysts. In conclusion, internal irradiation is effective not only for cystic craniopharyngiomas but also is applicable to cystic intracranial tumors other than craniopharyngioma if the dosimetry is done accurately.

The effect of a novel intracellular calcium antagonist, HA1004, on local cerebral blood flow (LCBF) was examined in rats. LCBF was measured in the striatum by the hydrogen clearance method. In the control rats, HA1004 (10 mg/kg, intravenously: IV) increased striatal LCBF by a maximum of 26% despite a transient drop in mean arterial blood pressure (MABP). The LCBF increased for a period of over 100 minutes after the infusion of HA1004. Nicardipine, a calcium entry blocker (0.1 mg/kg, IV), caused a decrease in MABP similar to that induced by HA1004 and increased LCBF by a maximum of 13% for up to 90 minutes after injection. In a second group of rats, the middle cerebral artery (MCA) was occluded by direct ligature of its proximal portion. After MCA occlusion, the LCBF rapidly dropped to 30% of the control value and gradually recovered to the control level during the next 60 minutes. However, in rats prophylactically treated with a small dose of HA1004 (1 mg/kg, IV), LCBF recovered more quickly than in untreated rats. The results of this study suggest that HA1004 increases LCBF by enhancing collateral blood flow to ischemic regions and may be useful for the treatment of ischemia.

Four cases of growing skull fracture are presented. Pneumoencephalography done on these cases showed a moderate to extensive degree of focal ventricular dilatation beneath the skull defect. An important factor, heretofore overlooked in explaining this focal ventricular enlargement, is our hypothesis that the force exerted on the particular area of the ventricular wall represents a pulsatile CSF movement damped in the region which is liable to yield to this compression wave in the absence of covering resistant dura mater. Because of the importance of early diagnosis in order to avoid possible delayed neurologic complications such as convulsive disorders, it is advisable to carry on repeated radiological examinations of the skull following fracture in this particular age group until the fracture heals by the progressive apposition of the bone on either side of the fractured line.

A sensitive and simple radioreceptor assay system for measuring methionine(met)-enkephalin-like substance in human cerebrospinal fluid (CSF) was developed using a particulate fraction of rat brain as a receptor preparation and [3H]dihydromorphine as a radiolabeled ligand in the presence of 1 mM ethylenediamine tetraacetate (EDTA) and 2 mM magnesium acetate. Metenkephalin-like substance was purified from CSF by the combination of Sephadex G-10 and SP-Sephadex (H+) column chromatographies to be free of sodium and large molecular weight substance such as β-endorphin. The assays were carried out on samples obtained from normal subjects and patients with the disease of the brain or pituitary by lumbar or ventricular puncture. Mean level in samples obtained from normal subjects by lumbar puncture was 2.6 ± 1.0 pmoles/ml.

In order to investigate the relationship between cerebral vasospasm and microvasculature in the hypothalamus and brain stem, colloidal carbon was infused into the vertebral artery at various time intervals after experimental subarachnoid haemorrhage in dogs. Experiments which demonstrated vasospasm on angiogram were always accompanied by ischaemic changes in serial sections taken from the anterior hypothalamus to the brain stem. However, when it was demonstrated by angiography that the vasospasm had disappeared, the micro-circulation was restored to normal. Electron microscopy of the hypothalamus 48 hours and one week after subarachnoid haemorrhage, demonstrated swelling of the endothelial cells, enlargement of the perivascular glia and increase in number of the pinocytic vesicles in the cytoplasm, thus showing vasogenic oedema in this area. It is assumed that in addition to the vasogenic substance in extravasated blood, changes in irritability of cerebral vessels through the vasomotor pathways in the hypothalamus and brain stem might play an important role in the production of cerebral vasospasm.

Human interferon-β (HuIFN-β) entrapped in liposomes composed of egg phosphatidylcholine, cholesterol, and sulfatide was examined for its antitumor activity against brain tumor cells in vitro and its pharmacokinetics in vivo. HuIFN-β did not lose its biological activity during the preparation of the liposomes. The liposomes entrapped 7-14% of the HuIFN-β used, suggesting that the majority of HuIFN-β was embedded in the liposomal membranes. Cytotoxicity of the liposome-entrapped HuIFN-β against human tumor cells was comparable with that of free HuIFN-β. Intravenous injection of the liposome-entrapped HuIFN-β resulted in higher interferon levels in the blood, liver, spleen, brain, and transplant of human brain tumor, compared with free HuIFN-β. These data show that the liposome-entrapped HuIFN-β should be useful in the treatment of human brain tumors.

1. We studied serum PRL abnormalities inpatients with various disorders of hypothalamo-hypophyseal system. When the basal serum PRL level was above 300 ng/ml, the presence of pituitary adenoma was strongly suggested. 2. Of 16 pituitary adenomas with hyperprolactinemia, 9 were associated with acromegaly (6 males, 3 females) and 7 with Forbes-Albright syndrome (amenorrhea-galactorrhea syndrome). Galactorrhea was also found in 6 of these 9 acromegalic patients, interestingly 3 of them were male cases. Amenorrhea was seen in all female cases with hyperprolactinemia except for one acromegalic case. 3. Serum PRL levels ranged from 46.2 to 508.2 ng/ml (mean: 203.2 ng/ml) in acromegalic patients and from 222.0 to 2100.0 ng/ml (mean: 1289.9 ng/ml) in patients with Forbes-Albright syndrome. Thus, the latter showed significantly higher levels of serum PRL. 4. Acromegalic patients showed more than 50% increment of serum PRL to TRH infusion, whereas, almost all patients with Forbes-Albright syndrome did less than 50%. 5. Intratumoral hemorrhage was found in 4 patients with Forbes-Albright syndrome by surgery. Two of them had episodes of pituitary apoplexy preoperatively. 6. It should be emphasized that early diagnosis and treatment is essential to normalize the dysfunction of hypothalamo-hypophyseo-gonadal axis. We consider that in patients with Forbes-Albright syndrome, visual disturbances and galactorrhea could be cured in almost all patients and ovarian dysfunction could also be normalized about more than half by transsphenoidal surgery combined with CB-154 and/or irradiation.

✓ The authors have examined the effects of the HA compounds HA1004(N-(2-guanidinoethyl)-5-isoquino-linesulfonamide) and HA1077(l-(5-isoquinolinesulfonyl)homopiperazine), which are intracellular calcium antagonists, on delayed cerebral vasospasm from subarachnoid hemorrhage (SAH). The modes of action of these compounds were compared with those of the more commonly used calcium entry blockers. Calcium ionophore A23187 (4.8 × 10−6 M)-induced contraction of a canine basilar artery strip was completely antagonized by the HA compounds (10−5 M) but not by the entry-blocking calcium antagonists nicardipine, diltiazem, and verapamil (10−5 M), suggesting that the HA compounds act differently. Delayed cerebral vasospasm was induced by a “two-hemorrhage” canine model. The magnitude of the vasospasm and the effects of the HA compounds were determined angiographically. On SAH Day 7, a significant vasospasm was observed in every dog. The diameter of the basilar artery had diminished to 59% ± 2% (mean ± standard error) of the control value obtained before SAH (on Day 1). The intravenous administration of HA1004 caused a mild dilation of the basilar artery of 10% and 11% at doses of 3 and 10 mg/kg, respectively; however, HA1077 produced a more marked dilation of 19% and 27%, respectively, at the same doses. Both of these drugs lowered mean arterial blood pressure to about 80% and 50% at doses of 3 and 10 mg/kg, respectively. Intracisternal administration of the HA compounds (6 mg) completely reversed cerebral vasospasm without much effect on the blood pressure. The intracellular calcium antagonists of the HA compound group appear to be promising agents for the treatment of intractable cerebral vasospasm.

Effect of ergot alkaloids on (3H)-nucleosides uptake by dispersed cells from fresh female bovine anterior pituitary glands was examined, because we had interested in the mechanism of pituitary tumor regression following bromocriptine treatment and considered nucleic acid synthesis as an important process in the metabolism of these cells. The anterior pituitary cells were implanted on culture tubes using D-valine minimal essential medium with serum to suppress the overgrowth of fibroblasts and then maintained in L-valine Dulbecco's modified Eagle medium. (3H)-Uridine uptake by these cells was suppressed by bromocriptine, at-ergocriptine or ergotamine at a concentration varing from 10(-6) M to 10(-5) M, but not 10(-5) M of lergotrile. Among these alkaloids, bromocriptine had most strong inhibitory effect and suppressed the uptake to below 25% of control value at the concentration of 10(-5) M. Bromocriptine also inhibited the uptake of (3H)-thymidine, (3H)-cytidine, (3H)-adenosine or (3H)-guanosine in the same manner as (3H)-uridine. But neither (3H)-uracil, the base of uridine, nor (3H)-galactose uptake by cells was affected by bromocriptine. The incorporation of (3H)-uridine or (3H)-thymidine into TCA-insoluble fraction of the cells was also inhibited by bromocriptine as that in the total cells. It was suspected that bromocriptine acted on distinct transport site of both ribonucleoside and deoxyribonucleoside, because a high concentration (3.3 X 10(-5) M) of radio-inactive thymidine did not modify (3H)-uridine uptake by these cells as well as inhibitory effect of bromocriptine on it. These effect of bromocriptine were not blocked by haloperidol, known as dopamine antagonist, at the same concentration as bromocriptine, and dopamine had no effect on (3H)-uridine uptake by the cells. In addition, by adding 5 X 10(-4) M of dibutyryl cyclic AMP into the medium, the effect of bromocriptine was also not affected. These data suggest that the effect of bromocriptine on nucleoside transport in anterior pituitary cells may be dependent on the other binding site than D-2 dopamine receptor in the anterior pituitary cell membrane.

Recently ventriculo-peritoneal shunt (V-P shunt) operations are being performed widely in pediatric patients with hydrocephalus. One of the problems in the management of shunt dependent hydrocephalic infants is the evaluation of the patency of the shunt system. This is a report of shuntgraphy and flushing device manometric test to determine the function of the V-P shunts utilizing the Pudenz valve. A 23 gauge needle is inserted into the Pudenz flushing device. The needle is connected with vinyl tube of 50 cm in length. The ventricular pressure can be measured by this technique when the proximal tube is patent. The vinyl tube is filled with normal saline or cerebrospinal fluid. The fluid slowly moves down to the level of 50-150 mmH2O in cases of normal function of the shunt, but if the distal catheter is obstructed the fluid will not descend and stay in the vinyl tube. Then Conray 60%, or Dimer X 1.0 ml is injected with pressure into the flushing device under fluoroscopic control. In most of the cases the dye flows to distal tube even though the distal shunt system is not well functioning, then 1-4 ml of Conray 60% is added for better visualization and spot films are taken. If reflux of the dye into the lateral ventricle occurs, further injection of contrast material is abandoned. We have performed this test for 50 V-P shunt implanted hydrocephalic children aged between 3 months and 8 years, who have had 54 shuntgrams in all. The locations and causes of the distal catheter blockage were determined in 34 patients. Several kinds of malfunction of V-P shunt distal catheter were demonstrated. The findings of shuntgrams are as follows: 1). Capsule formation of the whole distal catheter. 7 cases 2). Blockage of the lower end of the catheter. 6 3). High ventricular pressure without blockage of the shunt system. 4 4). Cyst formation at the lower end of distal catheter. 4 5). Kinking of the distal catheter at the cervical region. 3 6). Disconnection of the distal catheter. 3 7). Localized perfusion of the contrast material in the peritoneal cavity. 3 8). Others. 4 This test has been proved to be simple, safe and reliable in the evaluation of the eventriculo-peritoneal shunt evaluation.

✓ A randomized clinical study of irradiation and irradiation combined with ACNU in the treatment of malignant gliomas was performed in order to determine if there was an enhancing therapeutic effect of ACNU given in addition to radiotherapy. An effect was defined as a reduction in tumor size, changes in neurological signs and performance status within 1 month after the completion of radiotherapy, or statistically improved survival times. Seventy-seven patients from 14 neurosurgical clinics were included in this validated study group. Radiotherapy with a total dose of 5000 to 6000 rads, given in 25 to 30 subdoses, was applied to the whole brain and to a generous field surrounding the tumor. Patients who were assigned to receive chemotherapy were given ACNU intravenously once or twice during radiotherapy at a dose of 100 mg/sq m of body surface area. The response rate (more than 50% reduction of the tumor size) was 13.5% in the group treated by radiotherapy alone and 47.5% in the group with radiotherapy and ACNU. The hematological toxicity was more severe in the group treated with radiotherapy and ACNU. Other toxicity was mild and acceptable. The survival rates of patients with astrocytoma grade III and glioblastoma multiforme at 36 months after the surgery were 48.9% and 0% for radiotherapy alone and 59.0% and 16.3% for radiotherapy plus ACNU, respectively. The differences between the survival curves were not significant at the p = 0.05 level. This study has demonstrated that, although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone, the survival time was not extended significantly. It is necessary to continue to search for an effective chemotherapeutic regimen to prolong survival of patients with malignant gliomas.