[Stereotaxic biopsy for deep-seated brain tumors using "BioTac biopsy cannula"].
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Biomedical subjects
Publications and source records attributed to H Handa.
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In an attempt to facilitate the long-term proliferative growth and subsequent cloning of cytotoxic T lymphocytes (CTL's) against syngeneic murine 203-glioma (20-methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin), sensitized T lymphocytes from tumor-bearing mice were cultured in the presence of T cell growth factor (TCGF). Of five clones established by a limiting dilution technique, two clones (G-CTLL 1 and 2) exhibited tumor-specific cytotoxicity. G-CTLL 1 cells, which possessed much higher cytotoxic activity than G-CTLL 2 cells, were further analyzed. G-CTLL 1 cells were maintained in a TCGF-dependent exponential proliferative culture for over 18 months and continued to mediate an extremely high cytotoxic activity with the target specificity (50- to 100-fold increases over the peak cytotoxic activity of sensitized T lymphocytes in tumor-bearing mice). Their phenotypes of surface antigens were Thy-1+ (weak positive), Lyt-1.-2.+3+, and asialo-GM1-, and their cytotoxicity was blocked by adding only anti-Lyt-2 monoclonal antibodies. These results indicated that the cloned cells originated from CTL's. The cloned cells were characterized by the production of immune interferon with the glioma antigen-stimulation, suggesting that the immune interferon could enhance the cytotoxic activity of the CTL clone at the site of a clone-target cell recognition event.
In a patient with glioblastoma treated with interferon (IFN-alpha) for a long period of time, a high titer of IFN-neutralizing antibody was detected in the serum during and after IFN therapy. Computerized tomography findings and neurological symptoms in this patient were unchanged during IFN therapy. General malaise, fever, anorexia, nausea, and decrease of leukocytes, platelets, erythrocytes, hemoglobin, and hematocrit were recognized transiently as side effects of IFN administration. These side effects were not serious and resolved spontaneously without discontinuation of therapy. The appearance of IFN-neutralizing antibody is clinically important because the antibody probably neutralizes the effect of systemically administered IFN before it reaches the site of action.
The effects of prostaglandin D2 (PGD2) on the growth of mouse malignant glioma cells were studied in vitro and in vivo. The in vitro studies consisted of various concentrations of prostaglandins (PG's) being added to cultures of mouse glioma cells. At concentrations above 2.5 micrograms/ml, PGD2 strongly inhibited the proliferation of glioma cells, whereas PGE2 had no effect at the same value. Exposure to 5.0 micrograms/ml PGD2 for more than 2 hours resulted in inhibition of glioma cell proliferation. This growth-inhibitory effect of PGD2 was related to the inhibition of DNA synthesis of the cells. The in vivo studies were performed with a subcutaneously transplanted mouse glioma model. Injection of 0.5 mg/kg PGD2 into the tumor was more effective than the same concentration given by intraperitoneal injection. In mice with intracranially transplanted glioma, daily intraperitoneal injection of 0.5 mg/kg PGD2 had no significant effect on survival time.
Four patients with glioblastoma and one patient with astrocytoma (grade III) were treated with recombinant IFN ( rIFN -alpha A, Ro 22-8181) and the effect of IFN on clinical symptoms, CT findings and side effects of IFN were studied. Neurological symptoms were improved in one patient, stable in one patient and worsened in three patients. In all cases, there was no remarkable change of CT findings but in one case a slight decrease in tumor size was recognized. With regards to IFN side effects general malaise, anorexia, fever, nausea and vomiting were observed clinically, decrease of leukocytes, platelets, erythrocytes, hematocrit, hemoglobin and increase of GOT, GPT, LDH, AL-P were noted in the laboratory findings. These symptoms and change in laboratory findings were not serious, and they recovered spontaneously during or after IFN therapy. In one patient, an increase in IFN neutralizing antibody titer was detected. Since the biological activity of IFN may be diminished and anti-tumor effect cannot be expected in such a patient, the appearance of IFN neutralizing antibody may indicate an important problem in IFN therapy.
Before the application of CT scan, the exact identification of extracranial extension of brain tumors was difficult. In the present paper, neuroradiological findings of eight brain tumors with extracranial extension were reviewed. These eight cases were composed of two sphenoidal meningiomas, one CP angle meningioma, one CP angle neurofibroma, two pituitary adenomas, and two jugular foramen chemodectomas. After the first application of CT scan on May, 1976, 841 cases of primary intracranial tumors have been experienced in our clinic. So the incidence of brain tumors with extracranial extension was about 1%. The mean age of the patients was 51 years and all of the patients were females. In the neuroradiological examinations, plain skull films, tomograms, angiograms and CT scans were reviewed. Plain skull films and tomograms showed indirect signs of extracranial extension, such as destruction or hyperostosis of the skull and enlargement of the foramina. Direct signs of extracranial extension in the plain films were not obtained except in the pituitary adenomas, which extended into the paranasal sinuses and pharynx. Angiograms showed direct signs of extracranial extension, when remarkable tumor stain existed. Occlusion of the internal jugular vein suggested the extension of the tumor through the jugular foramen. In the cases without tumor stains, angiograms were useless to identify the extracranial portion of the tumor. CT scans were useful in all cases to detect extracranial extension. From the findings of CT scan, extracranial extensions of brain tumors were classified into four types. Extracranial extension with destruction of the skull. Extracranial extension with hyperostosis of the skull. Extracranial extension with both hyperostosis and destruction of the skull. Extracranial extension with enlargement of the skull foramina. To detect extracranial extension of brain tumors, enhanced coronal CT scan seemed most useful.
High dose ACNU and radiation therapy with autologous bone marrow rescue was performed in a 3-year-old boy suffering from cerebellar medulloblastoma, whose main mass had been removed at operation when widespread subarachnoid tumor dissemination was already present. The myelosuppression, which is a major side effect of high dose chemotherapy, was successfully prevented by the autologous bone marrow grafting and the serial CT scans showed complete disappearance of the tumor. However, the patient died on the 53rd day after the administration of ACNU of respiratory complication which was most likely due to pulmonary fibrosis. Although the autologous bone marrow rescue therapy is a technical advance to cope with myelosuppression secondary to chemotherapy, side effects of the other organs, particularly of the respiratory system, remain to be solved. The optimal treatment schedule should be established as soon as possible.
The effect of intracranial use of an ultrasonic surgical aspirator on major cerebral vessels and nervous tissue was studied in anesthetised adult cats. Experiments were performed without suction in order to investigate only the effect of ultrasonic emulsification. The flow rate of irrigation saline over the tip of the ultrasonic aspirator was set at either slow (4 ml/min) or fast (24 ml/min). Flow in the common carotid artery and superior sagittal sinus was studied by ultrasonic Doppler flowmetry during direct or indirect (intermediated by muscle fragment) application to the vessels of ultrasonic vibration for periods of 5 min. each in increments of 20% from 20% of maximal intensity. Flow in both the carotid artery and the superior sagittal sinus changed only with direct application on vascular surface of ultrasonic vibration of at least 80% of maximal intensity; otherwise flow in these vessels was not changed. The temperature rise caused by ultrasonic vibration was studied by use of a thermister buried in the brain parenchyma of animals 2 mm from the ultrasonic vibratory probe tip. A rise above the physiological range could be prevented by sufficient irrigation. The effect of ultrasonic vibration on the brainstem was studied by using auditory brainstem evoked response (ABR) to monitor brainstem function. An ultrasonic vibratory probe was applied to the ventral surface of the brainstem exposed by transclival approach. ABR changed noticeably only when ultrasonic vibration of 60% or more of maximal intensity was applied directly; otherwise ABR was not changed. The effect of ultrasonic vibration on the intracranial acoustic nerve was also studied by ABR.(ABSTRACT TRUNCATED AT 250 WORDS)
The clinical courses and CT scan findings of 12 cases of supratentorial ependymoma and ependymoblastoma were reviewed. The age of the patient of ependymoma ranged from 3 years to 34 years, with an average age of 16 years. The follow-up time ranged from 2 months to 9 years and 10 months. All of the six patients are still alive. The age of the patients of ependymoblastoma ranged from 7 months to 34 years, with an average age of 17 years. During the follow-up period from 2 weeks to 6 years and 4 months, four patients died. Supratentorial ependymomas and ependymoblastomas show the following characteristic features of CT scans: Calcification: The incidence of calcification was 50% in ependymoma-group, and 100% in ependymoblastoma-group. Cyst formation, ring-enhancement: The cyst formation was noticed in both groups. In ependymoma-group a smooth ring-enhancement pattern and the strongly enhanced mural nodule-like contour were found, but in ependymoblastoma-group, the cyst wall was enhanced in irregular shape. Perifocal edema and mass effect: Considerable mass effect was noticed in both groups. Perifocal edema was slight in many cases of ependymoma-group, but mostly prominent in ependymoblastoma-group. CT scan findings of recurrent tumor: In ependymoma-group, recurrent tumor showed the same characteristics of CT scan as the initial ones. In ependymoblastoma-group, cystic portion decreased in size and irregular shaped solid portion increased in recurrence.
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Metabolic changes in the ischemic brains of cats were investigated in vivo with high energy phosphate compounds as parameters by using a topical magnetic resonance (TMR) spectrometer. The experimental focal cerebral ischemia was made in four cats by modifying the method of O'Brien and Waltz. The stem of left middle cerebral artery was exposed and set the occlusive device 5-7 days before the in vivo measurement. 31P-NMR spectrum was taken under general anesthesia with Ketamine HCI and with decreased blood flow. The following points must be considered in obtaining 31P-TMR spectrum in a cat brain: Firstly, as much muscle as possible must be removed from the detective area because it contains phosphate compounds. Our experiment showed that bone and blood had little or no effect on the 31P-TMR spectrum. Secondly, although same procedure was repeated, it was difficult to obtain constant ischemic lesion; in site and size. The detective area in setting was not changed in the particular area. However there was a possibility of the detective area also including various non-ischemic regions. Thirdly, 31P-TMR spectrum had several peaks in a cat brain; which were sugar phosphate, inorganic phosphate, phosphodiesters, phosphocreatine, gamma-, alpha-, beta-ATP in the pre-occlusive conditions. These peaks did not appear in clear volume separation with one another. We drew the perpendicular line from through between two neighbour peaks to the horizontal base line and artificially divided two peaks. The area of each peak did not represent correctly the density of each component. Fourthly, unnecessary components were rationalistically excluded from the 'raw' spectrum.(ABSTRACT TRUNCATED AT 250 WORDS)
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Twenty-two patients with posterior inferior cerebellar artery (PICA) aneurysms were treated in our department from 1965 to 1982. Except for six cases with peripheral PICA aneurysms, all aneurysm were located on the vertebral artery at the origin of PICA (VA-PICA aneurysm). Direct approach to the aneurysm was carried out in 11 cases out of 16 with VA-PICA aneurysm. We encountered difficulties in access to the aneurysm in 5 cases (case 2,4,6,13,15) and in clipping procedures in 4 cases (cases 6, 7, 10, 15). Surgical procedures through either bilateral (case 2,4) or unilateral suboccipital craniotomy included exploration in 1 case; wrapping in 1, proximal vertebral artery clipping in 3 and neck clipping in 6. These difficulties encountered during operation were evaluated in relation to angiographical findings. The aneurysms located between 0 to 5 mm from the midline or more than 21 mm from the lateral point of the foramen magnum could be reached with difficulty through unilateral suboccipital craniotomy (Figure 3,4). The aneurysms with the dome directed posteriorly had to be treated carefully because of their possible adhesion to or invagination into the medullar oblongata. The aneurysms with the dome directed medially were difficult to be clipped because they existed on the opposite side of the vertebral artery. Although all aneurysms overlying the lower third of the clivus, even on the midline, can be exposed through unilateral suboccipital craniotomy, great care should be taken especially to the aneurysms located in high position, with the dome directed medially or posteriorly, and with the distal vertebral artery running medially.(ABSTRACT TRUNCATED AT 250 WORDS)
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The efficacy of glioma-specific cytotoxic T-lymphocyte for a syngeneic murine malignant glioma (a 20-methylcholanthrene-induced ependymoblastoma, 203-glioma) was investigated. The cytotoxic clone (G-CTLL 1), established and expanded exponentially by T-cell growth factor, has retained target specificity for more than 6 months. In adoptive therapy and Winn assay, the in vivo antitumor activity of G-CTLL 1 was demonstrated against mice inoculated intracranially with 203-glioma cells. The therapeutic effects in adoptive immunotherapy were largely dependent on dose and time of i.v. administration, although the therapy was rather ineffective in condition of increased intracranial pressure due to the tumor growth. The mechanisms responsible for the in vivo protection were probably related to the killing activity of G-CTLL 1 or the tumor-specific production of immune interferon by G-CTLL 1.
The immunoregulatory effects of TCGF (T-cell growth factor) on the generation and growth of syngeneic murine malignant glioma (20-methylcholanthrene-induced 203-glioma)-specific killer T-cell were investigated in C57BL/6 adult mice in order to clarify the immunopotential usefulness for anti-tumor local adoptive immunotherapy against malignant brain tumor. TCGF was prepared and assayed. Briefly, 5 x 10(6) ml mouse spleen cells were cultured with 2 microgram/ml concanavalin A in RPMI-1640 medium supplemented with 2% fetal calf serum for 24 hours. Culture supernatants were concentrated by ammonium sulphate precipitation (55 to 80% saturation) and purified by gel filtration (Sephadex G-100, a molecular weight from 30 to 36,000 daltons) and ion exchange chromatography (DEAE-cellulose, elution with 0.15 M in NaCl at ph 7.4). The purified TCGF had no IFN activity. Assays for TCGF was performed for quantitative analysis using 203-glioma-specific killer T cell clone (G-CTLL), which was obtained by limiting dilution method (0.3 cells/well in 96 well microtiter plate) and maintained for over 6 months in the presence of TCGF. Titer (U/ml) of TCGF was defined as the quantity of TCGF required to obtain one-half of the maximal stimulation of G-CTLL proliferation assay. It was confirmed that the specific killer T-cell against 203-glioma was generated in mice after intracranial as well as subcutaneous inoculation of the tumor cells. The killer T-cell activity of spleen cells, however, began to be severely impaired 2 weeks after intracranial inoculation concurrently with the increased intracranial pressure due to developing the tumor growth. Sensitized lymphocytes obtained from intracranial and subcutaneous tumor-bearing mice were assessed for CTL (cytotoxic T-lymphocyte) activity in MLTC (mixed lymphocyte-tumor cell culture) for 18 hours by microcytotoxicity assay. The specific cytotoxicity against 203-glioma cells was enhanced when sensitized lymphocytes from intracranial and subcutaneous tumor-bearing mice were pre-cultured with optimal TCGF (20 U/ml) for over 5 days. After the treatment of sensitized lymphocytes with anti-Thy-1 monoclonal antibody and complement, however, the specific cytotoxicity of sensitized lymphocytes was eliminated almost completely. Therefore, it was thought that TCGF possesses immunoregulatory effects of enhancement of killer T-cell activity. On the contrary, TCGF had no influence on normal T lymphocytes and the growth of 203-glioma cells in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)
With an increase in intracranial pressure during epidural balloon inflation, epidural pulse waveform, which is polyphasic under normal conditions, becomes monotonous at about 30 mmHg. This change in waveform is considered closely related to the apparent increase in arterial driving pressure to the brain and to a disturbance of venous outflow. When cerebral vasodilatation is prominent, the waveform becomes monotonous at a significantly lower intracranial pressure. These findings correlate well with the results of spectral analysis of the pulse wave. The usefulness of change in epidural pulse waveform, which can indicate an alteration of intracranial pressure dynamics in a relatively low pressure range, is discussed with comparison to other techniques used to determine intracranial pressure dynamics.
The surgical approach to the jugular foramen has been considered to be very difficult and troublesome, because of the location in which important structures, such as the internal jugular vein, internal carotid artery and lower cranial nerves, converge in the narrow deep space. A case of huge neurofibroma, which extended from the tentorium cerebelli through the dilated jugular foramen to the level of the vertebral body of C3 was presented. A 12-year-old girl was admitted with complaints of visual disturbance and palsy of the V-XII cranial nerves of the left side. Plain skull film showed prominent widening of the cranial sutures and enlargement of the sella turcica. Horizontal CT scan with contrast showed symmetrical ventricular dilatation and a heterogeneously enhanced mass, which was situated mainly in the left CP angle. Coronal CT scan with contrast revealed a huge mass and enlarged jugular foramen, through which the tumor extended to the level of the vertebral body of C3. Occlusion of the sigmoid sinus and the internal jugular vein of the left side was noticed in the vertebral angiography. Two-stage approach, the first one for removal of the intracranial tumor and the second one for extracranial tumor, was performed for its huge tumor. Several authors have reported excellent surgical approaches for the tumors situated in the jugular foramen. By our approach, modifying Gardner's original one, a wide operative field was obtained to remove the tumor around the jugular foramen with success. Our approach for the jugular foramen was described with illustrations.