Neurologia medico-chirurgica

Effect of Perfluorochemicals on BCNU Chemotherapy in a 9L Rat Brain Tumor Model

Takashi KOKUNAI, Keiichi KUWAMURA

1982 Volume 22 Issue 10 Pages 777-783
Published: 1982
Released on J-STAGE: November 10, 2006

DOIhttps://doi.org/10.2176/nmc.22.777

JOURNAL FREE ACCESS

Show abstractHide abstract

Perfluorochemicals are characterized by their small size and high propensity for carrying oxygen and carbon dioxide. This study was undertaken to identify the combined effect of a perfluorochemical (Fluosol-43, 20 ml/kg) and a chemotherapeutic agent (BCNU, LD₁₀ dose: 13.3 mg/kg) in a 9L rat brain tumor model. Brain tumor was induced by intracerebral implantation of 9L rat glioma cells (7×10⁵ cells) into male CD Fisher 344 rats weighing about 100 g. The tumor growth curve of this model was exponential, and at 7 days after implantation, the control animals had a macrotumor weighing about 51 mg. The tumor-bearing rats on day 7 after implantation were randomly divided into 5 groups: control; BCNU alone; Fluosol-43 with oxygen; Fluosol-43 plus BCNU; and Fluosol-43 plus BCNU with oxygen. High oxygen was produced in an oxygen chamber with 95% oxygen and 5% carbon dioxide, and the PaO₂ was maintained between 300 and 400 mmHg. Control animals had a mean survival time of 15.23 ± 2.84 (S.D.) days, and the Fluosol-43 with oxygen group showed no prolongation of the mean survival time (p>0.2). BCNU treatment alone prolonged the mean survival time to 20.90 ± 3.80 days (p<0.05), whereas the Fluosol-43 plus BCNU group had no further prolongation of the mean survival time: The Fluosol-43 plus BCNU with oxygen showed a mean survival time of 32.27 ± 4.80 days, which was significantly longer than that of the BCNU treatment alone (p < 0.005).
Perfluorochemicals (Fluosol-43) with oxygen may have a synergistic effect on BCNU chemotherapy for malignant brain tumor. Fluosol-43 with oxygen might have oxygenated the hypoxic cells so that they became sensitized to BCNU. Also, the transport of BCNU into hypoxic and hypovascular areas might have been enhanced by Fluosol-43 and oxygen.

View full abstract

Download PDF (560K)
Anti-neoplastic Effect of Human Fibroblast Interferon on Human Malignant Gliomas Transplanted into Nude Mice and Its Clinical Application

Yoshimasa MIKI

1982 Volume 22 Issue 10 Pages 785-796
Published: 1982
Released on J-STAGE: November 10, 2006

DOIhttps://doi.org/10.2176/nmc.22.785

JOURNAL FREE ACCESS

Show abstractHide abstract

Transplantability of three different tumor cell lines derived from human malignant astrocytoma (Gl-MK) and glioblastomas (Gl-AK and Gl-WI) in nude mice was established. All these tumors histologically resembled the original ones, and immunoperoxidase preparations demonstrated the presence of S-100 protein and glial fibrillary acidic protein (GFAP).
Using two of these tumors (Gl-MK and Gl-AK), experimental studies were carried out to determine the antitumor effect of the human fibroblast interferon (IFN-β). 6×10² to 6×10⁴ IU/ml IFN-β supressed the growth of cultured Gl-MK cells. In a flow-cytometric study, tumor cell growth in the S phase 48 hours after administration of IFN-β and after 72 hours, inhibition of tumor cell growth in the early S phase were observed. When administerd repeatedly, 100 IU/ml of IFN-β showed an adequate anti-tumor effect.
Intraperitoneal administration of IFN-β 50×10⁴IU every other day for four weeks resulted in transient regression of Gl-MK tumor transplanted into nude mice. Intra-tumoral injection of IFN-β 60×10⁴ IU every day for six or ten weeks produced a significant inhibitory effect on tumor growth of both tumor cell lines transplanted into nude mice, and significant degenerative changes in the tumor tissue were revealed by histological and electron microscopical examinations.
Eight clinical cases consisting of four glioblastomas, three malignant astrocytomas, and one medulloblastoma—seven of which were recurrent—were treated intrathecally and/or intravenously with IFN-β in doses of 30×10⁴ to 600×10⁴IU every day. The results were evaluated according to Karnofsky's scale, and the tumor size on CT scans were as follows: one showed partial remission (glioblastoma), four were stable, and three showed progression. High fever, leukocytopenia, and thrombocytopenia occurred in one case and were considered to be side effects of the medication.

View full abstract

Download PDF (1375K)
High-dose, Few Fractions Radiotherapy for Brain Metastases

Yoshihiko YOSHII, Yutaka MAKI, Tadao NOSE, Taihei EGASHIRA, Kiyoshi OH ...

1982 Volume 22 Issue 10 Pages 797-804
Published: 1982
Released on J-STAGE: November 10, 2006

DOIhttps://doi.org/10.2176/nmc.22.797

JOURNAL FREE ACCESS

Show abstractHide abstract

From November 1976 through September 1981, 28 patients with brain metastases received the conventional therapy and 9 patients received a high-dose, few fractions radiotherapy. There were two types of deaths—neurological and systemic death. In the conventional therapy group, neurological death occurred in 61% of all cases, but no neurological death was observed in the high dose radiotherapy group. Sequential computerized tomography (CT) scans were performed to estimate the therapeutic effect in 6 patients who received the conventional therapy and in 6 patients who received the high dose radiotherapy. Therapeutic effect was estimated by palliative indices which rated changes in the volume of the contrastenhanced area and of the perifocal low density area, and changes in the degree of contrast-enhancement of the tumor on CT scan. Many patients who received the high dose rediotherapy showed a reduction in tumor size and in the degree of contrast-enhancement, necrotic tumor tissue surrounded by lipid-laden macrophages on pathology, and a few months of neurological improvement.
Preliminary results of this study suggest that high-dose, few fractions radiotherapy is effective for brain metastasis treatment.

View full abstract

Download PDF (617K)
Change in the Ionic Environment of Cerebral Arteries after Subarachnoid Hemorrhage

Especially of Potassium Ion Concentration in Subarachnoid Hematoma

Michio SHIGUMA

1982 Volume 22 Issue 10 Pages 805-812
Published: 1982
Released on J-STAGE: November 10, 2006

DOIhttps://doi.org/10.2176/nmc.22.805

JOURNAL FREE ACCESS

Show abstractHide abstract

The possible role of electrolytes in the induction of vasospasm has not been well evaluated. These electrolytes are known to have vasomotor effects, and this study especially investigated potasium ion, which is liberated in the process of blood clot hemolysis. Under pentobarbital anesthesia, the basilar arteries of adult rats were exposed by the transclival approach under the operating microscope. Subarachnoid hemorrhage was induced by puncture on a small branch artery. At 10 minutes, two hours, and 24 hours after subarachnoid bleeding, fresh arterial strips were removed and immediately frozen in liquid nitrogen, cryosectioned, and freeze-dried. Electron probe X-ray microanalysis of the dry cryosections was performed to determine the elemental compositions of the vascular smooth muscle, extravasated erythrocyte, and periarterial space. Cytoplasmic concentrations in normal vascular smooth muscle were-K: 133±5; Cl: 12±3; Na: 22±4 (mmol/kg wet weight±SEM). The potassium concentration increased in the extracellular space to up to 8 times above the baseline 24 hours after subarachnoid bleeding, and the cytoplasmic concentrations of Ca, Na, and Cl also increased. The potassium concentration of the extravasated erythrocyte decreased over 24 hours. The time course of potassium ion liberation from extravasated erythrocytes was also studied. Fresh rat and human arterial bloods were withdrawn in sterile test-tubes and stored at 37°C. Hypertensive intracerebral hematomas were also collected during surgery. With a flamephotometer, the potassium concentrations of the stored blood serum and of the hematoma supernatants were measured chronologically. The potassium ion level almost reached its peak valve within two days, although a gradual increase persisted in rat and human incubated blood. On the other hand, the potassium ion level peak of the intracerebral hematoma was reached around day 3 or 4 post hemorrhage, and the level gradually decreased back to normal in approximately three weeks. Potassium has been known to have potent vasomotor effects.
This study shows that the potassium environment is of critical importance in cerebral vasospasm caused by subarachnoid hemorrhage.

View full abstract

Download PDF (755K)
Cerebral Blood Flow in Patients with Putaminal Hemorrhage

Using ¹³³Xe Inhalation Method

Ryoji ISHII, Shigekazu TAKEUCHI, Shigeaki OHSUGI, Ryuichi TANAKA, Hiro ...

1982 Volume 22 Issue 10 Pages 813-821
Published: 1982
Released on J-STAGE: November 10, 2006

DOIhttps://doi.org/10.2176/nmc.22.813

JOURNAL FREE ACCESS

Show abstractHide abstract

A total of 116 measurements of regional cerebral blood flow (rCBF) were performed on 44 patients with putaminal hemorrhage using the ¹³³Xe inhalation method. An initial slope index (ISI), which has advantages in many clinical applications due to its greater stability, particularly in various abnormal cases, was calculated from an early part of the recirculation-corrected ¹³³Xe clearance curves. Recently, serial ¹³³Xe studies have been possible without exposing patients to risk, and we hoped to use this method to determine those patho-physiological conditions indicative of the prognosis of cerebral functions. The results were as follows: (1) A marked decrease of the flow in both hemispheres was found and the degree of flow decrease was well correlated with the volume of hematoma which was estimated using preoperative CT scan. (2) The generalized decrease of flow found in both hemispheres was more marked in the ipsilateral hemisphere without exception. (3) A continuing decrease in the flow in both hemispheres was found in patients with ventricular dilatations or prominent mass effects. A similar tendency was observed even in patients with concave deformity of the skin flap following decompressive craniectomy. (4) In patients who had good activity or volition for rehabilitation, the values of the flow were less depressed or showed a tendency to increase.

View full abstract

Download PDF (578K)
Clinical Aspects and Prognosis of Intraventricular Hemorrhage with Cerebrovascular Disease

CT Findings and Etiological Analysis

Yukio IKEDA, Shozo NAKAZAWA, Hiroshi HIGUCHI, Kenji UEDA, Kouzo YAJIMA

1982 Volume 22 Issue 10 Pages 822-828
Published: 1982
Released on J-STAGE: November 10, 2006

DOIhttps://doi.org/10.2176/nmc.22.822

JOURNAL FREE ACCESS

Show abstractHide abstract

This paper discusses the clinical aspects and prognosis of intraventricular hemorrhages with cerebrovascular diseases diagnosed by CT scan.
Intraventricular hemorrhage with cerebrovascular disease was identified in 81 cases and death occurred within seven days in 34 cases. Hypertension was the most common etiological factor, accounting for 40 of the 81 cases. Cerebral aneurysm was the second most common cause accounting for 27 cases, arteriovenous malformation accounted for 9 of the cases, and 5 were of other causes. The clinical signs analyzed on admission were the vital signs, consciousness level, ocular signs, motor function, and pathological reflexes. Signs of primary or secondary brain stem dysfunction were mainly seen in cases with hypertension and aneurysm, while cases with arteriovenous malformation had benign courses. The mortality depended on the severity of intraventricular hemorrhage; i.e., the distribution, site, and the number of cast formation. The presence of intraventricular clot in the third and/or fourth ventricles was correlated with a high mortality rate, especially in cases accompanied by cast formation and third and fourth ventricular dilatation, which affects hypothalamus and brain stem function. Analysis of CT findings for the mechanism of intraventricular hemorrhage revealed three types: extension type; in which massive intracerebral hematomas extended and ruptured into ventricles; the direct type, which bled directly into ventricles without forming definite intracerebral hematomas; and the reflux type, which was characterized by reflux of the subarachnoid blood.
Pathophysiology in the acute stage of intraventricular hemorrhage was closely related to increased intracranial pressure or intraventricular fluid pressure. Though ventricular drainage seemed to be of limited value, it would be the first therapeutic step to be performed for reducing intracranial pressure or intraventricular fluid pressure.

View full abstract

Download PDF (540K)
Dynamic CT in the Acute Stage of Head Injury

Eiji YOSHINO, Tarumi YAMAKI, Toshihiro HIGUCHI, Kimiyoshi HIRAKAWA, Yo ...

1982 Volume 22 Issue 10 Pages 829-837
Published: 1982
Released on J-STAGE: November 10, 2006

DOIhttps://doi.org/10.2176/nmc.22.829

JOURNAL FREE ACCESS

Show abstractHide abstract

Dynamic computed tomography (CT) was performed on 14 patients with acute head injury. Patients were classified into three groups according to the Glasgow Coma Scale (GCS). Four patients with severe head injury (GCS 3-6) had acute subdural hematoma with diffuse cerebral swelling on the initial CT scan. Seven patients with moderate head injury (GCS 8-13) had massive acute epidural hematoma or acute subdural hematoma without diffuse cerebral swelling. Three patients with slight head injury (GCS 15) had thin acute epidural hematoma, cerebral contusion, or normal scan. Dynamic CT of the brain consisted of performing eight rapid serial scans after a bolus intravenous injection of 50 ml of contrast material. Data from these scans were analized utilizing the time-density curves of four brain regions—the arteries, gray and white matters, and the cerebral hemispheres.
In patients with slight head injury, the time-density curves of these four regions on the lesional side were nearly similar to those of the opposite side. An obvious peak was observed in the artery, gray matter, and cerebral hemisphere and the peak time of these regions nearly accorded. In patients with moderate head injury, the peak time of the gray matter was slightly retarded, especially in the side ipsilateral to the acute subdural hematoma. In two cases of four head injured patients who had acute subdural hematoma with marked diffuse cerebral swelling, the time-density curves of the artery, gray matter, and cerebral hemispheres of the bilateral or lesional side were flat. In the remaining two patients, an obvious peak was observed in the artery and gray matter, but the peak time of the gray matter was greatly retarded from that of the artery.
It is possible that the diffuse cerebral swelling seen on CT scans during the acute stage of head injury is due either to hyperemia or to acute cerebral edema. In the presence of diffuse cerebral swelling, the cerebral circulation of the arterioles or capillary bed may be greatly disturbed, even if the cerebral circulation of the arteries, which can be demonstrated on the dynamic CT images, is maintained.

View full abstract

Download PDF (679K)
Classification of Computerized Tomography and Prognosis of Traumatic Primary Brain Stem Injury

Shiro KOBAYASHI

1982 Volume 22 Issue 10 Pages 838-848
Published: 1982
Released on J-STAGE: November 10, 2006

DOIhttps://doi.org/10.2176/nmc.22.838

JOURNAL FREE ACCESS

Show abstractHide abstract

Clinical signs, computerized tomography (CT), continuous monitoring of intracranial pressure (ICP), serial recording of auditory brain stem response (ABR), and autopsy were examined in 40 cases of primary brain stem injury (PBSI) which showed clinical symptoms of prolonged coma, abnormal motor responses (decorticate, decerebrate or flaccid), impaired oculocephalic and/or pupillary responses, and no evidence of focal mass lesions on initial CT scanned within 2 hours after the injury. The consciousness levels of the 40 cases of PBSI on admission were 5 or less by the Glasgow Coma Scale; 5 in 12 cases; 4 in 15 cases; 3 in 13 cases. CT findings of the brain stem region (mesencephalon, pons, and medulla oblongata) of PBSI were classified into 7 types: brain stem hemorrhage (Type I); IVth ventricle hemorrhage (Type II); subarachnoid hemorrhage in the basal cisterns (Type III); compressed basal cisterns (Type IV); pneumocephalus in the basal cisterns (Type V); combined abnormal findings in the brain stem regions (Type VI); no abnormal findings in the brain stem regions (Type VII). Those cases of PBSI with initial CT findings of Type I, Type II, Type III, Type V, and Type VI all died. On the other hand, 7 cases of PBSI (17.5%) demonstrating good recovery or moderate disability by the Glasgow Outcome Scale (6 months after injury) were of Type IV (mortality 66.7%) and Type VII (mortality 50%); 5 of these cases (71.5%) were children.
It has become obvious that there are many types of CT findings in PBSI besides brain stem hemorrhage that continuous ICP monitoring is very important to protect against secondary brain damage caused by increased ICP and that serial ABR recording predicts the outcome of PBSI very well as it provides reliable information about the function of the brain stem.

View full abstract

Download PDF (1133K)
Relationship between Ventricular Configuration and Intelligence after Surgery in Infantile Hydrocephalus

Makoto KATO

1982 Volume 22 Issue 10 Pages 849-854
Published: 1982
Released on J-STAGE: November 10, 2006

DOIhttps://doi.org/10.2176/nmc.22.849

JOURNAL FREE ACCESS

Show abstractHide abstract

The author studied the ventricular configurations after shunt operation on 60 cases of infantile hydrocephalus followed for more than two years using computed tomography (CT). Follow-up periods ranged from two years to 14 years and six months. The cases consisted of 24 cases of congenital hydrocephalus (19 of which were followed up for more than five years), 10 cases associated with meningocele (7 cases followed more than five years), 4 with malformation (3 cases), 9 cases after bleeding (3 cases), and 13 cases after meningitis (7 cases). Excluding those cases accompanying apparent encephalodysplasia, 39 cases were followed for more than 5 years and the relationship between their intelligence and ventricular configuration on CT was investigated. They were classified into four categories of intelligence based on school performance and conditions of daily life, and into six types of ventricular configulations on CT: I) slit like ventricle; II) normal; III) slightly dilated; IV) extremely dilated; V) irregular shape; and VI) accompanying cerebral atrophy. The ventricular configulation after operation correlated with the intelligence. Cases with excellent or good intelligence were found in CT Types I, II, and III. Cases of congenital hydrocephalus operated in infancy often showed slit-like ventricle and excellent or good intelligence. There was no discrepancy between verbal IQ and performance IQ of WISC in the excellent intelligence group. Ventricular configurations became stable almost within one year after operation.

View full abstract

Download PDF (452K)
Total Removal of Glioma at the Base of the Fourth Ventricle

Case Report

Shoji MASHIYAMA, Teruaki MORI, Kazuyo KAMIYAMA, Hitoshi OKADA, Jiro SU ...

1982 Volume 22 Issue 10 Pages 855-858
Published: 1982
Released on J-STAGE: November 10, 2006

DOIhttps://doi.org/10.2176/nmc.22.855

JOURNAL FREE ACCESS

Show abstractHide abstract

A case of a successfully removed glioma at the base of the IVth ventricle was reported. The patient was a 43-year-old woman who had complained of gait and visual disturbances four years before admission. Plain and enhanced CT showed remarkable hydrocephalus, dilatation of Sylvian aqueduct, and deformity of the IVth ventricle. An exploratory craniotomy was performed and the tumor, 25×15×7 mm in size, was found at the base of the IVth ventricle and was macroscopically totally removed. Histological diagnosis was fibrillary astrocytoma. Post-operative course was favorable. Symptoms, diagnosis, and operation of the tumor were discussed.

View full abstract

Download PDF (461K)
Leptomeningeal Angiomatosis of the Left Occipital Surface Detected by CT Scan

With Special Reference to Sturge-Weber Disease

Masaki NIIRO, Tadahiro MIHARA, Yoshiki MAEDA, Hiroshi AWA, Koki KADOTA ...

1982 Volume 22 Issue 10 Pages 859-865
Published: 1982
Released on J-STAGE: November 10, 2006

DOIhttps://doi.org/10.2176/nmc.22.859

JOURNAL FREE ACCESS

Show abstractHide abstract

A case of left occipital leptomeningeal angiomatosis was reported.
The patient was a 12-year-old boy who had episodes of severe vascular type headache accompanied by transient right homonymous hemianopsia. CT scan showed localized superficial high density area in the left occipital pole. Remarkable enhancement of the lower and inner surface of the left occipital lobe was demonstrated. Angiography showed poor filling of the distal portion of the left posterior cerebral artery. Skull tomograms showed linear calcifications in the left occipital region. Brain scan showed increased RI uptake in the left occipital region. During operation, the surface of the left occipital lobe was covered by excesive, fine, vascular networks which extended over the arachnoid membrane. The abnormal vessels were cauterized by a CO₂ laser as throughly as possible. The occipital pole, felt gritty. Histologically, the abnormal vessels had spread into the subarachnoid space and were predominantly veins with thin and enlarged walls. The abnormal vessels followed the leptomeninges in the sulci of the cerebral cortex. Underneath the abnormal vessels, in the external layers of the cerebral cortex, calcium deposits were scattered and gliosis and degeneration of the ganglion cells were observed. The lesion was comparable with leptomeningeal angiomatosis. Though the pathological findings of the specimen, CT findings, and brain scan findings were extremely similar to those of Sturge-Weber disease, in this case, the typical clinical and roentgenographic findings of Sturge-Weber disease were all absent.

View full abstract

Download PDF (767K)

Register with J-STAGE for free!