Search

An overview of treatment of brain metastasis from lung cancer in National Cancer Center is presented with respect to T and N categories in TNM classification. To know the rate of brain metastasis, CT scan on brain was performed for all the patients with lung cancer hospitalized for surgical treatment and revealed that 3 of 87 patients had brain metastasis without any neurological signs and symptoms. On the other hand, 105 out of 320 (32.8%) lung cancer patients who had taken CT scan for some reason from 1975-1983 in this hospital had shown the brain metastasis. Therefore, it should be memorized that only 3.4% was detected to have brain metastasis from the patients without any neurological signs and symptoms. Two hundred sixty-one patients with metastatic brain tumor from lung cancer were treated in 1963-1983 at National Cancer Center in Japan. Of these, 205 patients were evaluated for the median survival and the average survival according to various therapeutic modalities. Of this 205 patients, 123 had no operation with or without other treatment--chemotherapy or radiotherapy showed median survival of 3-5 months (range 2-25 months). Eighty-two had operation on brain metastasis with or without chemotherapy showed median survival of 6-11 months (range 2-112 months). Correlation between survival time and T and N categories in TNM classification at the diagnosis of lung cancer was studied and no remarkable difference was noted either in T or N categories in the average survival time and percent number of cases survived equal or more than 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

In the prepared brain microvessel (MV), it has been shown that the endothelial cells of the brain capillary play a vital role in the transport function of the blood-brain barrier (BBB) [3, 6, 20, 22]. It was also shown that there is a unipolar transport mechanism of sodium across the BBB, which is due to the anteluminal localization of the Na, K-ATPase in the endothelium [2, 3]. This mechanism may be important in the regulation of ion homeostasis as well as the volume control of the extracellular fluid (ECF) in the physiological state [2, 4] it may also be relevant to the mechanism of ischemic brain edema, since the sodium influx across the BBB was shown to correlate closely with the edema formation [2, 11]. In this regard, we have shown that production of hydroxy acids in the MVis enhanced following regional ischemia in rats [1], and that some radical scavengers, such as AVS, suppress both the lipoxygenase activity of the MVand edema formation [10, 15]. These results suggest that the production of hydroperoxides by the MV lipoxygenase is related to edema formation following ischemia. In this respect, lipid peroxides are known to reduce the activity of the Na, K-ATPase activity of the synaptosomes [17, 23]. However, since their effects on the Na, K-ATPase of the MV are unknown, the present study was carried out to study the effect of AA and its hydroperoxide, 15-HPAA, on the activity of the Na, K-ATPase of the MV.

Auditory evoked brain-stem responses (ABRs) were recorded in 19 out of 52 brain dead cases in Department of Emergency Medicine, University of Tokyo Hospital from May, 1981 to January, 1984. The causes of brain death were severe head injury (9 cases), cerebro-vascular disease (7 cases), anoxia (2 cases), hydrocephalus (1 case). Eleven cases of them fulfilled the clinical criteria which included absence of cortical and brain-stem functions excluding severe hypothermia and depressant drug intoxication. The remainders who were subjected to barbiturate therapy were diagnosed as brain death for non-filling phenomenon in cerebral angiography. Results were as follows; Fourteen cases (74%) had no identifiable ABR waves. One case (5%) had only 1st wave. Three cases (16%) had 1st and 2nd waves. One case (5%) had 1st, 2nd, and 3rd waves. In spite of definition of clinical brain death, 5 cases had at least 1st wave, and therefore these datum suggested that ABR might have less clinical utility in diagnosis of brain death. Each case did not necessarily demonstrate the total extinction of ABRs, as was shown in (2) to (4) mentioned above. The clinical status which met the criteria of brain death might therefore possibly imply any conditions in which brain death was impending gradually to result in the total brain death of cerebrum through medulla oblongata. Under these circumstances, how barbiturate might produce ABRs abnormality remained unsolved, though it has been said not to produce ABRs abnormality. Among 8 cases under barbiturate therapy, there were 5 cases with no identifiable waves and 3 cases with 1st and 2 nd waves.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors report a case in which left deep temporal fibrosarcoma with calcified area developed about 6 months after radiation therapy for left temporal astrocytoma. A 37 year-old woman was admitted to our clinic because of headache and visual deterioration. CT scan and angiography suggested left deep temporal glioma and on August 5, 1980, partial resection was performed. Histological sections showed astrocytoma G 2. Postoperative course was uneventful and she left the hospital after radiation therapy of 50 Gy. On March, 1981, right hemiparesis was noticed and progressed rapidly. CT scan suggested left temporal tumor recurred. On March 30, 1981, second operation was performed and this time, histological sections showed glioblastoma. After operation, beta-Interferon (IFN) was given intratumorally via Ommaya's reservoir (3 X 10(6) IU, daily). But in spite of IFN therapy, tumor became larger and she died on June 30, 1981. Autopsy revealed coexistence of glioblastoma and fibrosarcoma with metaplastic bone formation. A brief discussion concerning the problem of cerebral mixed tumors follows the description of the case.

This study reports the effect of intracisternal administration of papaverine in 15 patients with vasospasm due to rupture of aneurysm. All patients had undergone clipping of aneurysm and had neurological deterioration and decreasing level of consciousness. Bolus injection of 40 mg of 1% papaverine hydrochloride was started on day 6.3 +/- 1.7 and continued for 4.4 +/- 1.6 days. In seven cases serial angiogram after initial dose revealed dilatation of IC and/or anterior, middle cerebral arteries at 30 min and further dilatation up to 85% increase in diameter at 60 min, which continued at least 90 min. Arteries with marked vasospasm responded more to papaverine than those with less vasospasm. There was a close correlation between degree of vasospasm and vasodilatation effect (r = 0.88, p less than 0.01). In all but two cases vasodilatation tended to become prominent by repeat doses, twice a day, for two to seven days (r = 0.87, p less than 0.01). Vasodilatation was observed only in IC and proximal trunks of ACA and MCA where papaverine could make direct contact, but not in the distal branches beyond A3 or M3. Neurological examination showed improvement of paresis or level of consciousness in 7 cases but no effect in 6 cases. Intracerebral hematoma occurred in two cases (one by high concentration 4% papaverine) during the treatment. Therefore intracisternal papaverine is the treatment of choice in cases with symptomatic vasospasm with some cautions on concentration to be administered.

It is important to evaluate the therapeutic and side effects of new therapy for malignant brain tumors in an adequate animal model prior to its initial clinical investigation. For decades, neurooncologists have argued for the use of primary, autochthonous tumors rather than transplanted tumors such as C 6 glioma cells and 9 L gliosarcoma cells. But unfortunately, no spontaneous animal astrocytomas are currently available as usable models. So we tried to establish the model of primary, autochthonous avian sarcoma virus-induced rat gliomas for experimental chemotherapy and immunotherapy. The present study was undertaken to determine the incidence and histologic pattern of tumors and the mean survival time of the animal model used. It was found that the intracerebral inoculation of 2 X 10(6) FFU/5 microliter of infectious cell free homogeneous subgroup D Schmidt-Ruppin avian sarcoma virus (SR-D-ASV) into 3-day-old inbred Fischer 344 rats induced small sized tumors in all rats 20 days later. The mean survival time of inoculated rats were 58.7 +/- 12 days. As to the classification of SR-D-ASV induced brain tumors in Fischer rats, astrocytoma was 70.6% (protoplasmic astrocytoma 23.5%, fibrillary astrocytoma 47.1%), sarcoma 17.6%, and mixed astrocytoma and sarcoma 11.8%. In conclusion, this SR-D-ASV induced tumor in the rat fulfilled the following criteria for the desirable animal model: (1) Spontaneously arising. (2) Glial origin. (3) Intraparenchymal growth. (4) Uniformly fatal within reasonable time period. Statistic evaluation of the effects of chemotherapy and immunotherapy was considered to be possible.

The histological classification, pathophysiology, and treatment modalities of malignant gliomas (glioblastoma, malignant astrocytoma) were reviewed with reference to the WHO classification of primary brain tumors and the recent progress made in glioma biology. Patients with glioblastoma and malignant astrocytoma showed, respectively, 10.6% and 22.2 of the five-year survival rate according to the All Japan Brain Tumor Registry. In order to improve the prognosis of malignant glioma patients, many clinical trials have been conducted throughout the world. Malignant gliomas that grow in and invade the brain parenchyma cannot be cured by surgical resection. One should treat the residual tumor with irradiation, chemotherapy and immunotherapy. Radiation therapy alone and radiation therapy plus chemotherapy using nitrosoureas or procarbazine have been proved statistically to be more effective for malignant gliomas than supportive care and radiation therapy alone, respectively. Prospective clinical trials support the view that malignant gliomas should be treated vigorously using a multimodal approach that includes surgical resection, high-dose radiation therapy, and prolonged maintenance chemotherapy.

We have compared the anti-tumor effects of beta- and gamma-interferons (IFN) against human glioma cells using in vitro model, flow cytometry and xenograft in nude mouse. Contrary to gamma-IFN which had a negligible effect on the growth of glioma cells, beta-IFN showed a dose dependent growth-inhibitory effect on glioma cells in vitro. Our flow cytometry studies revealed that proportion of DNA contents which represent the S and/or G2M phase of cell cycle was markedly increased in cells treated with beta-IFN. However, in cells treated with gamma-IFN, no perturbations in cell cycle distribution were observed. Regarding the anti-tumor effect examined using xenograft of human glioma cells in nude mouse, the tumor reduction rate which was calculated from the ratio of tumor volume between treated (T) and control (C) groups and expressed as T/C value, was 0.44 in animals treated with beta-IFN. However, T/C value in animals treated with gamma-IFN was 0.80 which was derived from the weaker anti-tumor effect of gamma-IFN as compared with that of beta-IFN. Beta-IFN was found to cause a partial suppression of the growth of glioma strain used in this study which confirms our previous report that beta-IFN is effective in reducing tumor size in 2 of 6 glioma strains tested. On the other hand the anti-tumor effect of gamma-IFN, at least in terms of direct effect, against glioma cells used in this study was minimum. However, the mechanism of gamma-IFN's anti-tumor effect may exert mainly through the potentiation of immuno-defence mechanism and the further studies on its pharmacodynamics will be necessary to evaluate the anti-tumor effect of gamma-IFN.

It is generally accepted that one effect of ouabain in the brain is the induction of swelling of brain cells through inhibition of Na, K-ATPase located at neuronal membranes. In the situation where ATP is depleted, as in cerebral ischemia, the swelling of brain cells is an early event, representing a cytotoxic aspect of ischemic edema formation. In this context, previous workers have already seen reduced neuronal Na,K-ATPase activity in experimental cerebral ischemia. Recently, however, another site of Na, K-ATPase activity has been found in the brain, viz. the capillaries. Goldstein and Betz [2] suggested that capillary Na, K-ATPase is present only on the abluminal side, pumping out Na+ from blood into the brain as a unidirectional active transport mechanism. Furthermore, evidence has arisen that the capillary Na, K-ATPase activity may be increased at certain stages of cerebral ischemia [1,5]. Should this be the case, it might be postulated that capillary Na, K-ATPase enhances pumping out of Na+ and the associated H2O shift in the presence of ion-pump failure in the neuronal membranes so that the total net result is an increase in brain Na+ and H2O in both intracellular and extracellular environments. Therefore, ischemic brain edema involves both cytotoxic and vasogenic factors in nature.

In case of chemotherapy against brain tumors, it is most important to choose suitable drugs for brain tumors, since human tumors have different drug sensitivity and growth. Heretofore, human tumor clonogenic assays or human glioma-bearing nude mice models were usually used for predicting the drug sensitivity of brain tumor. Human tumor clonogenic assays are one of the best in vitro tests for anticancer drug activity. However, plating efficiency is low, sometimes preventing evaluation of drug sensitivity, and the slow growth of colonies means that culture time is long. Assays using immunodeficient mice are used for predicting the drug sensitivity of human tumors; usually results reflect the sensitivity of the parent tumor. However, procedure using athymic nude mice are slow and expensive. We took notice of Murphy's system for the chemosensitivity test, in which a human tumor is transplanted into the chorioallantoic membrane (CAM) of a chick embryo, because in this system, various kinds of human tumors could be grafted in high rate. By modifying the conventional Murphy's system, we studied the efficiency of this system in predicting the drug sensitivity of brain tumors. We compared the result of a drug sensitivity test using CAM of a chick embryo with that using nude mice. First, we studied the effect of chemotherapeutic agents such as ACNU, bleomycin. Next, we studied the effect of combination treatment of CAP or CAPF. The tumor reduction rate of the sensitivity test using a chick embryo tended to agree with that using nude mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Eicosanoids are thought to be important in the pathogenetic mechanism of ischemic brain damage. But little is known about lipoxygenase products and their roles in brain. In the present study, lipoxygenase metabolism in the brain and its relevancy to ischemic brain edema were studied using high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). The rat middle cerebral artery (MCA) occlusion model was used because the time course of ischemic edema formation has been well known. The rat brain was fixed by in situ freezing 24 and 72 hours after MCA occlusion, and removed. Identification and quantitative analysis of hydroxyeicosatetraenoic acids (HETEs) in normal and ischemic brain homogenates was performed by HPLC and GC-MS. The rat brain was divided into the microvessel (MV) fraction and the rest. Then the same analysis was carried out in the both fractions obtained from the normal rat brain. Only 11-HETE was detected in the normal and ischemic brain. Quantitatively, normal brains contained 1288 +/- 66 (mean +/- SE) of 11-HETE ng/g wet weight, while the hemispheres rendered ischemic for 24 and 72 hours after MCA occlusion contained 1101 +/- 48, and 1663 +/- 147, respectively. The 11-HETE content was significantly increased 72 hours after MCA occlusion (p less than 0.05). The MV fraction of rat brain contained 11-HETE (653 ng/mg protein) ten times as much as the other fraction. The identification of 11-HETE in the rat brain is a new finding.(ABSTRACT TRUNCATED AT 250 WORDS)

Since 1980, phase 1 and 2 clinical trials of Hu-IFN-beta have been done in the field of neurosurgery. In the present study, (1) the results of in vivo experiments of Hu-IFN-beta are reported and (2) the effectiveness of Hu-IFN-beta in patients with malignant brain tumors is also evaluated. (1) The antitumor activities of beta-IFN and poly ICLC in nude mice receiving subcutaneous transplants of human brain tumors (2 strains) were compared with those of conventional anticancer drugs. After 3 weeks of treatment with ACNU, vincristine, bleomycin, mitomycin C, beta-IFN and poly ICLC, tumor reduction rates were evaluated by the method of Battelle. The effectiveness of beta-IFN and poly ICLC was slightly inferior to that of ACNU and vincristine, although tumor reduction rates (treated/control values) of 43% and 39% were respectively obtained with beta-IFN and poly ICLC against one strain of glioblastoma. (2) Clinically, 7 patients with malignant brain tumors were given beta-IFN (4 by intratumor administration and 3 by intravenous injection) in a dose of 3 X 10(6) to 9 X 10(6) IU/day for 2 to 6 months to study the efficiency and side effects of IFN treatment. One of four patients given IFN intratumorally showed a reduction in tumor size (partial response) by CT scan; the three patients injected IFN intravenously were unchanged. There were no noteworthy side effects in the cases treated intratumorally except for fever occurring in one patient. In the patients treated intravenously, however, fever, general malaise, leukopenia and thrombocytopenia were noted.

The content of norepinephrine (NE) in the ventricular, basal cisternal and lumbar cerebrospinal fluid (CSF) was determined in 19 patients with ruptured cerebral aneurysms. The cisternal CSF in patients with vasospasm contained a significantly higher level of NE (0.246 +/- 0.0490 ng/ml) compared with those without vasospasm (0.075 +/- 0.001 ng/ml) (p less than 0.001). However, this increase is not considered to be high enough to constrict cerebral arteries, unless there is an increased NE-sensitivity in subarachnoid haemorrhage. Vascular responses to NE in vivo were then studied after reversing blood-induced prolonged vasospasm of the rabbit's basilar artery through a transclival approach as well as a newly developed basal cisternal irrigation model. However, NE in molar concentrations between 1 x 10(-10) and 10(-2) failed to produce further contraction of the artery. In conclusion, the increase in NE with vasospasm might be only a secondary phenomenon, and not a causative factor of vasospasm. Early removal of subarachnoid blood clots seemed to prevent the development of vasospasm.

The influence of breech and vertex delivery on intrapartum fetal and neonatal mortality was studied in 8,863 infants delivered at Kurashiki Central Hospital Perinatal Center. The rate of mortality was studied in cases without fatal congenital anomalies. The frequency of congenital anomaly was also studied in 8,863 infants delivered by breech and vertex presentation. Infants were divided into five groups according to their birth weight: 99g or less, 1,000-1,499g, 1,500-1,999g, 2,000-2,499g and 2,500g or more. Infants were also grouped into four by gestational age: 24-27 weeks, 28-31 weeks, 32-36 weeks and 37 weeks or more. The total infant mortality rate was 4.9% in breech delivery, and 0.5% in vertex delivery, respectively. This difference was statistically significant. The rate of major congenital anomaly in breech delivery was significantly higher than in vertex delivery. The rate of premature deliveries in breech presentation was also significantly higher than in vertex delivery. The rate of mortality in the group weighing 1,000-1,499g was 50.0% in breech delivery, and 17.6% in vertex delivery, respectively. This difference was statistically significant. The rate of mortality in the group delivered at 28-31 weeks gestational age was 62.5% in breech delivery, and 15.4% in vertex delivery, respectively (statistically significant). The rate of severe neonatal asphyxia in infants delivered at 28-31 weeks of gestational age was significantly higher in breech delivery than in vertex delivery.

The authors experienced thirty brain deaths including eighteen head injuries and seven cerebrovascular accidents during the period from Nov. 1980 to Dec. 1982 and encountered with some practical problems on clinical diagnosis of brain death. In sixteen patients subjected to barbiturate (pentobarbital) therapy, the attempt to meet the criteria of brain death made it necessary to confirm the total cerebrocirculatory arrest as well as to measure the serum concentration of pentobarbital and assure its level low enough. But as a result of the angiograms performed in twenty-four cases the cerebral angiography sometimes failed to give sufficient evidence to confirm it not merely because of the angiographical intracranial delayed opacification but also because of the dissociation of filling between supra- and infratentorial spaces or between right and left hemispheres. And besides the contrast enhancement of cerebral vessels was verified in computed tomograms of two cases among ten cases who had already met the criteria and demonstrated angiographical nonfilling phenomenon. The angiographical narrowing of C 1-2, A 1, M 1 portions or basilar artery observed on serial angiograms preceding the angiographical nonfilling phenomenon was regarded as direct vascular compression by cerebral swelling or vasospasm and considered to suggest that brain death might be impending. At present the continuous monitoring of intracranial pressure performed in twenty-six cases proved to be a convincing guide to suspicion of brain death or impending brain death according to decrease in cerebral perfusion pressure and appearance of so-called plateau waves recorded in four cases.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors examined the preoperative factors affecting the reduction of chronic subdural hematoma (CSDH). A new method was developed to calculate the reduction rate of CSDH using CT volumetry technique. Postoperative serial CT films were examined and each hematoma volume was calculated by microcomputer. A postoperative exponential decrease of hematoma volume was observed, and the log-transformation of the hematoma volume turned the curve to a linear decrease. The least square method was used to fit an exponential curve, and the half reduction date (HRD) was calculated from the fitting curve. This HRD represents a mathematical indicator of the reduction rate of CSDH. Using this technique, the relationships between this HRD and the following parameters were examined in 61 patients. The preoperative factors examined are as follows; 1) patient's age, 2) preoperative hematoma volume, 3) CT number of the hematoma, 4) time interval between the head injury and the onset of symptom, and 5) the degree of cerebral atrophy. The degree of cerebral atrophy was calculated by means of a simple approximate formula as described by one of the authors (K.N.). Patient's age and the hematoma volume were correlated with HRD, and the correlation coefficients were 0.346 (p less than 0.01) and 0.298 (p less than 0.05) respectively. On the other hand, preoperative CT findings and the duration from the trauma had no correlation with HRD. Cerebral atrophy has hitherto been thought to affect the reduction of hematoma. However, our quantitative study revealed no correlation between cerebral atrophy and the reduction of hematoma rate. This unexpected result may be attributed to the difference between cerebral atrophy and cerebral elasticity.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled, prospective, randomized studies were performed to evaluate the effects of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3- (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and ACNU plus tegafur as additions to radiotherapy for the treatment of malignant gliomas. In the first trial, 105 patients with glioblastoma or anaplastic astrocytoma were randomly divided into two groups after surgery and received radiotherapy (RT, 40 to 60 Gy to the whole brain), or radiotherapy plus concomitant chemotherapy with ACNU (100 mg/m2 on day 1 and 42). Effects of the treatment were compared in 82 evaluable patients from results of CT scans taken before and one month after the completion of radiotherapy. The regression rates more than 50% of the tumor size were observed in 15.0% of patients treated with RT alone and in 47.6% of patients treated with RT plus ACNU. The difference was statistically significant (p less than 0.005). In the second trial, 87 patients were randomly divided into two groups and received RT plus ACNU, or RT plus combined chemotherapy with ACNU and tegafur (400 mg/m2, daily for 8 weeks). Sixty-nine patients were within the valid study group. The regression rates more than 50% of the tumor size were observed in 34.2% of patients treated with RT plus ACNU: and in 41.2% treated with RT, ACNU plus tegafur. No statistical difference was noted in the response rate between the groups. These results indicate that ACNU is an effective agent in conjunction with radiotherapy for patients with malignant gliomas, and that tegafur does not enhance the effectiveness of ACNU.

The present study was conducted to overcome some of disadvantages of cerebral blood flow study by radionuclide, such as poor regionality of flow values and errors involved in pathological brains. Serial CT scanning was carried out during and after inhalation of 50 to 70% non-radioactive xenon in humans. Diffusible gas with high atomic number enhanced gray matter first 19 +/- 4 HU (mean +/- SD) on an average in Hounsfield unit (HU) and later white matter 24 +/- 4 HU. In seven normal subjects, blood flow in gray matter was 82 +/- 11 and that in white matter 24 +/- 5 ml/100 gm/min. Partition coefficient which is not readily obtainable by radionuclide study was 0.9 +/- 0.1 in normal gray matter and 1.4 +/- 0.2 in normal white matter. Two cases were presented to show k-map (clearance rate), lambda-map (partition coefficient) and CBF map, which displayed images of values calculated automatically, in black and white or color on CRT. The first case was a patient with metastatic brain tumor from lung in the left parietal region. The blood flow of the tumor was close to that of gray matter, whereas blood flow of edematous white matter surrounding the tumor was decreased to below 10 ml/100 g/min with partition coefficient ranged from 0 to 0.9. The second case was presented to demonstrate the resolution of the blood flow map obtained by this method. Multiple lacunar infarcts of the basal ganglia and white matter in the size of 1 to 3 mm, which were hardly identified on regular CT picture, were well visualized on CBF map. This method appeared to have several advantages over conventional isotope method and to provide useful clinical and research informations.

Respiratory insufficiency following acutely elevated intracranial pressure (ICP) may occur as a result of pulmonary edema which is supposed to be caused by increased sympathetic discharge from the central nervous system. Supporting experimental studies have been reported concerning this immediate respiratory consequence, while delayed respiratory consequences with an elevated ICP remain poorly characterized clinically. We studied delayed effects of an increased ICP on respiratory functions (pulmonary shunt ratio (Qs/Qt), respiratory index (A-aDO2/PaO2), oxygenation index (PaO2/FIO2) ), extravascular lung water (EVLW), and hemodynamics [cardiac index (CI), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR)] in 15 cases with head injury, 4 with cerebrovascular diseases, and one with hypoxic brain damage. Ten cases had either aspiration, long bone fractures (the syndrome of fat embolism), or pneumonia, and the 10 cases without these pulmonary insults were defined as the cases without pulmonary complications and studied further. Pulmonary functions deteriorated as the ICP rose in the total cases, but in the cases without pulmonary complications, the correlations between the pulmonary functions and the ICP were not significant. None of the hemodynamic parameters correlated with the ICP in both the total cases and the cases without pulmonary complications.(ABSTRACT TRUNCATED AT 250 WORDS)

In 1982, Hassoun et al. reported two cases of differentiated neuroblastoma with the clinical and light microscopic appearance of intraventricular oligodendroglioma and gave a name of "central neurocytoma" to this tumor. Jerdan et al. (1983) called the similar tumor as "differentiated cerebral neuroblastoma in adults". As the tumor can be diagnosed only by ultrastructural study, the established cases so far reported are very rare. In this paper we present five cases identical to those presented by Hassoun et al. and clarify the essential nature of this new category of brain tumors. All of our cases of central neurocytoma occurred in the lateral ventricles of young adults. Clinically there was no evidence of leptomeningeal or ventricular dissemination of tumor cells. After subtotal resection of the tumor and 6000 rads of whole brain irradiation, the tumor mass disappeared and no evidence for recurrence of the tumor was noted on CT scan. All cases showed almost the same histology. The tumor cells contained a small round and/or oval nucleus, and had eosinophilic thin delicate cytoplasmic processes. There were no Homer Wright rosette, but were anuclear spaces consisting of fine fibrillar structures, like so called "broad rosettes" or "large rosettes". Capillary mesh was found among the tumor cells, but there was no endothelial proliferation. The tumor cells were monotonous, lacking pleomorphism, mitotic figures, and necrotic foci. Calcifications were observed in two cases. In the areas where the tumor cells arranged loosely, cytoplasms became clear, showing perinuclear halo, like those of oligodendrogliomas. Immunohistochemical examination showed GFAP and vimentin positive cells were all reactive astrocytes around capillaries and near calcifications. No tumor cells contained GFAP and vimentin. The tumor cells were also negative for neurofilament both of 70 KD and 200 KD. NSE was more or less positive for tumor cell cytoplasm as well as fine fibrils. Anti-Leu7 antibodies stained only fine cytoplasmic processes, but not cytoplasm. Some reactive astrocytes were stained with anti-Leu7 antibodies. Electron microscopic examination showed nuclei of the tumor cells were roughly round or oval without nuclear indentations and contained finely dispersed nuclear chromatin. In the cytoplasm, there were numerous free ribosomes, mitochondria, Golgi apparatus and electron dense various-shaped granules. Microtubules were found in the periphery of the cells, but filamentous structures were not identified.(ABSTRACT TRUNCATED AT 400 WORDS)

During the 1985 annual meeting of the Congress of Neurological Surgeons in Honolulu, neurosurgical training and practice in India, Korea, Japan, and Australasia were discussed at the International Committee symposium. This article summarizes the information presented. India has about 300 neurosurgeons for a population of 650 million, while Japan has about 4,000 neurosurgeons and trainees for a population of 120 million. Korea has 424 neurosurgeons for a population of 41.5 million, and Australasia has 92 neurosurgeons and 19 trainees for 17.5 million people. Various other demographic, institutional, organizational, and economic aspects of neurological health care and delivery, education, and quality control are described. While financing and availability of adequate neurosurgical care remains a major problem in India, it appears that reducing the number of neurosurgical trainees remains, as it is in North America, a major issue in Japan and, to a lesser extent, in Korea. This problem, as well as certification of the quality of training, is being managed effectively in Australasia.

In the present study, the authors analysed the serial angiographical findings progressing to brain death and their relation to the intracranial pressure (ICP) and the cerebral perfusion pressure (CPP). Seventy two patients, from four to eighty four years old (fourty six males and twenty six females) admitted in the Department of Emergency Medicine, University of Tokyo Hospital during the period from January, 1981 to April, 1986, were studied. Their underlying diseases were supratentorial primary brain lesions except two cases with asphyxias which progressed to brain death. ICP was continuously measured and CPP was calculated as the pressure gradient between the mean arterial blood pressure (MAP) and ICP. The direct carotid angiography was performed to follow the cerebral circulation. Fourty five patients were subjected to barbiturate (pentobarbital sodium) therapy. The degree of the intracranial filling staged as "Non-filling", "Siphon-filling", "Partial-filling", "Delayed-filling", "All-filling" correlated significantly with ICP and CPP. These relationships, however, disappeared once ICP exceeded MAP. When "Non-filling" angiogram was obtained, clinical signs had already showed brain death. On the other hand, minimal flow ("Siphon-filling", "Partial-filling", "Delayed-filling") were still demonstrated in six brain death cases while ICP was approaching its "peak" value. This study showed that clinical diagnosis of brain death preceded the Non-filling phenomenon, suggesting that, for the demonstration of the cerebral circulatory arrest, the angiograms should be performed after the clinical diagnosis of brain death was established and CPP became zero. The evaluation of the extremely slow and minimal filling is still a matter of discussion.(ABSTRACT TRUNCATED AT 250 WORDS)

The Invar characteristics has been examined for Co‐Fe alloys. The measurements of the magnetization and the thermal expansion over the temperature 20°C∠1050°C carried out for the alloys containing 59 to 100 at.%Co. The concentration dependence of the saturation magnetization around 850°C shows a sharp minimum at about 68 at.%Co. The thermal expansion coefficient of 77 at.%Co alloy is invariant over a temperature range from about 900°C to 750°C and the value of the coefficient decreases and the temperature range becomes narrower with decreasing Co concentration. The small thermal expansion coefficient and the extremely large volume magnetostriction estimated from the expansion curves are found around 74 at.% Co alloy at about 820°C. These characteristics are quite similar to that of Fe‐Ni Invar alloys at room temperature, and may be explained by the local fluctuation model in martensitic phase transition.

The clinical appearance of foramen magnum tumor is protean and, even at the stage when serious neurological deficits are present, the lesions are often misdiagnosed as another disease, especially cervical spondylosis and multiple sclerosis, and patients may undergo improper concervative or even surgical treatments. The best guarantee against misdiagnosis, we believed, was to establish a definition of "Foramen Magnum Syndrome" to facilitate the recollection of its peculiar clinical findings. "Foramen Magnum Syndrome" is composed of: 1. Cape distribution of sensory loss; 2. Atrophy of the intrinsic muscles of the hands; 3. Neck or suboccipital pain; 4. Dysesthesia of the hands (numbness, tingling, and cold sensation); 5. Eleventh cranial nerve palsy; 6. Stereoanesthesia. (Remember the mnemonic CANDES or DESCAN) Among these, cape distribution of sensory loss, eleventh cranial nerve palsy and cold dysesthesia (not numbness or tingling sensation) are of great importance for topological diagnosis. We also pointed out the similarities between the clinical picture of syringomyelia and that of the advanced stage of foramen magnum tumor. The syringomyelic syndrome, often seen in Arnold-Chiari malformation and basilar impression, has been attributed to the concurrent syrinx of cervical cord. But the clinical analysis of foramen magnum tumors showed that this is not always true and that compressive lesions at the foramen magnum alone can cause syringomyelic syndrome.

A clinical and pathologic analysis was made of 101 patients with surgically treated metastatic brain tumors. The most common primary site was the lung (58.4%), followed by th breast (11.9%), gastrointestinal tract (6.9%), and uterus (5.)%). In 14 patients, the disease began with cerebral symptoms. The overall average survival after craniotomy was 8.0 months, the longest survival being 8l/2 years; patients with one-year survivals composed 18.8% of the cases. The histologic features were almost the same in primary and metastatic tumors. The undifferentiated tumor metastasized most frequently to the brain, and adenocarcinoma of the papillary type also seemed to find the brain fertile ground for metastatic growth.

The effect of high frequency jet ventilation (HFJV) on intracranial pressure (ICP) in the series of seven patients with severe head injury was studied. These patients received mechanical ventilation for respiratory failure accompanied with neural damage or circulatory shock and for ICP control by decreasing PaCO2. ICP was measured continuously by subarachnoid catheter method connected to Gould P-50 strain-gage transducer and controlled by hyperventilation and/or osmotic diuretics during acute phase. Arterial pressure, central venous pressure and intratracheal pressure were measured continuously in the same way. Arterial blood gases were analysed by BG-I of Technicon Co. Ltd. At the weaning from respirator, two methods were applied. One was conventional IMV (with PEEP) and/or CPAP by using IMV mode of Servo 900 respirator or T-piece together with PEEP valve and another was new-fashioned HFJV. Mean intratracheal pressure (mPit) was fixed at 0 mmHg (control value), 5, 10 and 15mmHg in both methods by adjusting PEEP valve or driving pressure of HFJV. The result is that in the same patients ICP was significantly lower during HFJV than IMV/CPAP when mPit was 5 and 10mmHg. Only three cases having been studied at 15mmHg of mPit because circulatory condition would not permit it, significant difference of ICP between HFJV and IMV/CPAP was not detected. PaCO2, being suspected to be the cause of lower ICP of HFJV group, was studied too. But blood gas analysis showed no significant difference neither PaCO2 nor PaO2. The fluctuation of CVP reflecting the change of intrathracic pressure was smaller in HFJV group than in IMV/CPAP group.(ABSTRACT TRUNCATED AT 250 WORDS)

The preliminary results from the clinical use a prototype whole body nuclear magnetic resonance (NMR) machine constructed by Toshiba Inc. are presented. Cranial NMR scans were performed on more than 30 cases with broad spectrum of neurologic diseases using saturation-recovery and inversion-recovery sequences with a field strength of 1500 Gauss. Selective excitation sequence was used for the slice selection and filtered backprojection was used to reconstruct the images. They were displayed on a 256 X 256 matrix as 12 mm thick sections. Data acquisition time varied between 3 and 12 minutes. Our initial experiences with six cases harboring cerebellopontine angle lesions disclosed advantages and disadvantages of NMR imaging in comparison with X-ray CT. The advantages were the absence of linear artifacts from the surrounding bone, the marked gray-white matter differentiation, and the variety of tomographic planes available. The disadvantages included the lack of bone detail, the lack of visualization of the major intracranial vessels, and the long time required for scanning (several minutes per slice). Although much continued evaluation is necessary, NMR seems to have vast potential as a diagnostic tool.

The existence of insulin receptors and biological responses to insulin on macromolecular synthesis have been studied in C6 glioma cells. Binding of 125I-insulin to C6 glioma cells was specific, time- and PH-dependent. Porcine insulin competed for 125I-insulin binding in a dose-dependent manner. Unlabeled polypeptides, including glucagon, bovine growth hormone, bovine prolactin did not compete for 125I-insulin binding. Scatchard analysis of the binding data gave a curvilinear plot which may indicate negative co-operativity or the existence of both high and low affinity (Ka = 7.55 x 10(10) - 4.25 x 10(9] sites. Incubation of cultures with insulin caused a time and dose-dependent stimulation of DNA, RNA and protein synthesis in C6 glioma cells (measured by 3H-thymidine, 3H-uridine or 3H-leucine incorporation into DNA, RNA, or protein respectively). The increase of macromolecular synthesis was admitted at more than 2 nM concentration of insulin. Maximal stimulation of DNA synthesis (142% of control) occurred 6 hours after incubation with 167 nM insulin. The same concentration of insulin caused a 45% increase in 1 hour on RNA synthesis, a 37% increase in 2 hour on protein synthesis. These results indicate that C6 glioma cells have specific insulin receptors capable of mediating effects of insulin on macromolecular synthesis. Insulin in the brain and even blood may be an important growth factor in the glioma cells of the patients with disrupted blood-brain-barrier.

Cellular synchronization chemoradiotherapy was performed in 122 patients with glioblastoma and malignant astrocytoma (GrIII) registered between April 1977 and August 1982. The study was a non-randomized clinical phase II trial. The chemotherapeutic agents employed as synchronizers during the irradiation were VM26 (epipodophyllotoxin) and vincristine (VCR) as plant alkaloids and ACNU as a nitrosourea. Either VM26 or VCR was administered on D1, D2 and D3 at the dosage of 1 mg/kg (0.025 mg/kg-VCR) body weight. ACNU was administered on D2 and D3 at the dosage of 1 mg/kg body weight. The duration of the chemotherapy was eight to fourteen days at the initial induction stage and almost eight weeks at the maintenance stage. Thus, two synchronization arms of VM26 + ACNU and VCR + ACNU were employed. The regimen-VM 26 + ACNU + Radiation (Rad) could yield the initial induction of CR + PR-30%, NC-50%, and PG-15% in 58 cases. Long-term survival, calculated by the cumulative survival rate, was as follows: one year, 58%; two years, 42%; three years, 32%; four years, 30%, and five years, 25%. The regimen VCR + ACNU + Rad could yield the initial induction of CR + PR-28%, NC-49%, and PG-23% in 64 cases. The cumulative survival rate was calculated as follows: one year, 55%; two years, 42%; three years, 27%; four years, 22%, and five years, 22%. As a control, particularly for the survival rate, the data of the All-Japan Registry were revised to correspond to our study population. The survival rate of simple radiation cases thus revised was as follows: one year, 43%; two years, 23%; three years, 11%; four years, 7%, and five years, 5%. The comparison between VM 26 plus ACNU and VCR plus ACNU yielded a higher initial induction response of 35% for the former (vs. 28% for the latter), although it is difficult to make a judgement on the excellence of the regimen involving VM 26 plus ACNU, because this trial was clinical phase II. On the other hand, compared with the data from the All-Japan Registry, each regimen of cellular synchronization radiation therapy could achieve statistically more excellent responses both in the initial induction and the long-term survival (p less than 0.01). Thus, cellular synchronization radiation therapy is a hopeful therapeutic method for malignant glioma, with less side effects and statistically confirmed higher responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Cisplatin, vinblastine and bleomycin (PVB) combination chemotherapy was undertaken in 30 patients with primary intracranial malignant germ cell tumors in 11 neurosurgical clinics. The response rate of 17 evaluable patients with nonrecurrent tumors was 64.7% (eight CR and three PR), and that in eight patients with recurrent tumors was 50% (two CR and two PR). The one-year and two-year survival rates were 76.2% and 67.7%, respectively, which are better than the treatment results by radiation therapy alone, i.e., 69.8% and 46.5%. These findings suggest that PVB therapy is effective for intracranial malignant germ cell tumors.

The role of Interferon-beta (IFN-beta) as maintenance therapy for malignant gliomas and medulloblastomas was described. The low dose but continuous long-term administration of IFN-beta as a maintenance treatment for malignant gliomas after the induction therapy with surgery and chemoradiotherapy demonstrated the complete remission of the tumor in six cases of malignant gliomas. Such method of IFN-beta administration did not induce any serious side effects and might be useful for treatment of malignant gliomas. In addition, recent advance of adoptive immunotherapy using lymphokine activated killer cells (LAK) was briefly reviewed.

Despite the widespread use of glucocorticoids in patients with severe head injury, the usefulness is still controversial. In the past, the effect was investigated only in terms of dose-response relationship. We have, however, studied the time factor for the administration of dexamethasone to obtain maximal beneficial effect together with investigating the influence of actinomycin-D, an inhibitor of messenger RNA synthesis, before dexamethasone treatment. Awake male mice of dd-strain were restrained and subjected to head injury using a bakelite weight of 30 g dropped from a height of 17.8 cm above the skull. This injury resulted in immediate loss of consciousness in 100%, convulsive seizure in about 70% and death in about 30% of animals. The severity of consciousness disturbance was evaluated by a pair of indices in time interval: time required for the recovery of righting reflex (RR) and for the recovery of spontaneous movement (SM). 4 mg/kg of dexamethasone phosphate was given intraperitoneally 0.5, 4, 6, 12, 18 or 24 hours before injury. Actinomycin-D of 0.5 mg/kg was injected intravenously 1 h before each dexamethasone treatment in separate animals. In the other group of animals, dose was changed with varying time course of dexamethasone pretreatment, e.g., 2, 4, 6 or 8 mg/kg given 0.5, 2 or 4 h before injury. It was found that dexamethasone of 4 mg/kg pretreatment 4-12 hours significantly improved the recovery from consciousness disturbance and death rate. Actinomycin-D given before dexamethasone treatment completely abolished the protective effect of dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)

In the present paper we discussed whether a new method of chemosensitivity test could be developed using FCM (flow cytometry) and applied to malignant brain tumor cells labelled with BrdU monoclonal antibody. For this purpose, a basic study was performed with an ACNU-resistant C6 cell line and a sensitive one to see if this method was able to detect the difference of sensitivity between these cell lines. After 8 hours treatment with ACNU (concentration: 10 micrograms/ml), ACNU-sensitive cells revealed on LI (labeling index) of 46%, which was very high in comparison with controls, whereas the figure for ACNU-resistant cells was 34%, which was almost the same LI value as non-treated control cells. This means that change in the BrdU labeling index after chemotherapy in vitro can be used to determine the chemosensitivity of malignant brain tumors when FCM is employed. Furthermore, this method can detect the chemosensitivity of each clone in polyclonal human tumors which is impossible for the HCSA method, since the latter can reveal only the chemosensitivity as a whole in such tumors.

In the present study, the anti-edema effect of AVS [1,2-bis (nicotineamide)-propane] was evaluated using the cat MCA occlusion model with or without recirculation. In the prolonged ischemia (PI) group, cortical edema as assessed by the changes in specific gravity, developed in those cortical areas where the mean 1-CBF was less than 25-30 ml/100 g/min during MCA occlusion (4 hours). In the recirculation group (2 hours' ischemia followed by 2 hours' recirculation: RC group), the ischemic threshold for edema development was almost the same as in the PI group. In both groups, the drop in cortical specific gravity was significantly suppressed by AVS. Regarding the time-course of 1-CBF, there was no difference between the PI-AVS-treated and PI-saline-treated groups. In the RC group, however, the postischemic hypoperfusion was significantly ameliorated by AVS. Based on the present and previous data showing the antiedema effect of AVS, the mechanism of action of AVS was discussed in relation to the pathomechanism underlying ischemic brain edema. Our new concept of ischemic brain edema is briefly stated below. Related in vitro studies have shown the followings: (i) the influx of sodium not of proteins is the principal cause of ischemic brain edema: (ii) the eicosanoid synthetic capacity of the brain microvessel (MV) is increased simultaneous to edema development (iii) an elevation in the level of hydroperoxides enhances the activities of Na+, K+-ATPase as well as the arachidonate cascade of MV. These data suggest that free fatty acids and free radicals liberated following cerebral ischemia stimulate the activity of the MV-Na+, K+-ATPase, which results in increased sodium influx across the BBB. AVS was shown to scavenge hydroxyl radicals and to inhibit the stimulatory effects of a lipid hydroperoxide (15-HPAA) on the activities of Na+, K+-ATPase and the arachidonate cascade of the MV. These actions of AVS may be linked to its antiedema effect.

The effects of chronic-hypoxic hypoxia on cerebral blood flow and its regulating mechanisms were investigated by means of intracardiac injection of radioactively labelled microspheres. In a gas chamber designed and constructed for the purpose, adult cats were exposed to stepwise decreasing inspiratory oxygen concentrations (for 4.5 months with a final O2 concentration of 8 vol%). Using animals adapted to hypoxic hypoxia, responsiveness of cerebral blood flow either to alterations in systemic arterial pressure (SAP) or to alterations in arterial blood oxygen tension (PaO2) were assessed. Flow measurement was done under three different conditions: normoxic normotension (PaO2 greater than 100 mmHg; SAP greater than 100 mmHg), hypoxic normotension (PaO2 = 30 mmHg; SAP greater than 100 mmHg), or normoxic hypotension (PaO2 greater than 100 mmHg; SAP = 60 mmHg). Hematocrit values continuously increased to 56% during the process of adaptation to hypoxia. There was also a remarkable increase in cardiac output of hypoxia-adapted animals subjected to hypoxia and to normoxia. Chronic-hypoxic hypoxia led to increased cerebral blood flow, which persisted even when animals were returned to normoxia. Under hemorrhagic hypotension, cerebral blood flow fell significantly in animals adapted to chronic-hypoxic hypoxia but did not fall short of the absolute values in controls. The relative reduction in cerebral blood flow might be attributable to the decrease in cardiac output and to altered blood viscosity. This implied that, even in animals subjected to long-standing graded hypoxic hypoxia, autoregulatory capacity might be partly preserved.

Following permanent occlusion of the middle cerebral artery (MCA) in cats, the effect of delayed administration of pentobarbital (PBT) and a novel imidazole derivative (Nizofenone or Y-9179) on the regional cerebral blood flow (rCBF) was studied. The rCBF was measured for one week by the hydrogen clearance technique without anesthesia. The overall effects of these drugs on histological changes were also assessed. Twenty-four animals, in which platinum electrodes were chronically implanted in the ten predetermined positions, were divided into following three groups. The control, PBT and Y-9179 groups received the vehicle, PBT (25 mg/kg/day) and Y-9179 (6.25 mg/kg/day), respectively. Drug administration was started 30 min after MCA occlusion and continued for three days. In the affected hemisphere of the animals which survived for one week, histological examination revealed ischemic lesions composed of the marginal, reactive and central zones. The infarction ratio calculated as the ratio of the damaged area to the whole hemispheric area was significantly smaller in the drug treated groups than in the control. In the Y-9179 group, the reduction of the area comprizing the central and reactive zones was particularly prominent. There were no apparent differences in the time-course of the rCBFs between the control and Y-9179 groups. Each channel showed reduction of the rCBF following MCA occlusion. Although slight fluctuations of the rCBF were seen during the first three to four hours, the initially dropped rCBF remained stable in both groups. In the PBT group, on the other hand, an increase of the rCBF took place following the administration of the drug in the area where the rCBF was initially reduced less than about 40 ml/100g/min after MCA occlusion. Most of the electrodes showing such an increase in the rCBF topographically corresponded to the reactive or boundary zone. In the control group, vasogenic edema characterized by the perivascular exudation of plasma fluid was prominent in the periphery of the central zone as well as in the inner layer of the reactive zone. Such changes were almost absent in the Y-9179 group, whereas it was more evident and close to the control in the PBT group. So far as the correlation between the course of the rCBF and the final histological outcome was examined, there was no evidence indicating the beneficial effect of the redistribution of the rCBF by PBT. Y-9179 had no significant action on the course of the rCBF but its anti-edema effect might be related to its cerebral protective action. The mechanism of cerebral protection by PBT or Y-9179 needs further clarification.