Chronic cadmium treatment induces tubular nephropathy and osteomalacic osteopenia in ovariectomized cynomolgus monkeys.

In an attempt to establish a primate model of chronic cadmium toxicosis, we ovariectomized cynomolgus monkeys and treated them with CdCl2 by repeated intravenous injections for 13 to 15 months. The animals showed normocytic-normochromic anemia. The cadmium treatment resulted in increases of urinary enzyme activity indicative of renal tubular degeneration. Histopathology of the kidney revealed renal proximal tubular atrophy accompanied by interstitial fibrosis. Decreased bone mineral density was evident in the trabecular and cortical zones of the lumbar vertebra and femur, with osteoid accumulation around the trabeculae and Haversian canals. Iron deposition at the mineralization front and osteoclasts hyperplasia were indicative of impairment of bone mineralization and an increase of resorption. Blood inorganic phosphorus and 1α,25(OH)2 vitamin D3 levels decreased and urinary deoxypyridinoline level increased in cadmium-treated animals. The renal and bone lesions closely resemble those of itai-itai disease patients, the most severe case of cadmium toxicosis in terms of clinical chemistry and histopathology. Thus, ovariectomized monkeys chronically exposed to cadmium can serve as a primate itai-itai disease model, which is beneficial for developing novel therapeutic methods, investigating the mechanisms of the renal and bone lesions, and establishing more clearly defined criteria for diagnosing the disease.

Gene transfer of CD40-ligand to dendritic cells stimulates interferon-gamma production to induce growth arrest and apoptosis of tumor cells.

In this study, we present evidence that gene transfer of the CD40-ligand (CD154) into human immature dendritic cells (DC) imparts direct antitumor effects on tumor cells. DC infected with adenovirus directed to express human CD154 on the cell surface (CD154-DC) elicited significantly higher levels of immune accessory molecules commonly found on mature DC. We found that co-cultivation with a human squamous cell carcinoma cell line (OSC-70) with CD154-DC significantly inhibited cell growth. We further demonstrate that OSC-70 cells stimulated with CD154-DC were more susceptible to apoptosis via TNF-related apoptosis inducing ligand (TRAIL). Importantly, tumor cells co-cultured with CD154-DC in transwell plates expressed upregulated cell surface TRAIL-R2. CD154-DC produced higher levels of interferon (IFN)-gamma, IL-12p70 and soluble CD154, but the ability of CD154-DC to inhibit tumor cell growth was significantly abrogated by a neutralizing antibody to IFN-gamma, indicating that this was mainly mediated by IFN-gamma. Furthermore, intratumoral injection of CD154-DC significantly suppressed OSC-70 tumor growth in a xenograft model. Overall, these results reveal that CD154-DC have potential as an anti-cancer therapy by producing IFN-gamma to arrest adjacent tumor cell growth and increase the susceptibility of apoptosis via TRAIL.

Predictive assay of neoadjuvant chemotherapy in management of oral cancer.

Neoadjuvant chemotherapy (NAC) for oral squamous cell carcinoma has a positive impact on organ preservation and/or survival only in patients who achieve an excellent anti-tumour effect with this therapy. Predictive assay for NAC can play an important role in establishing tailor-made treatments for oral squamous cell carcinoma. In this retrospective study, the anti-tumour effects of cisplatin-based NAC in 70 patients with oral squamous cell carcinoma were reviewed in relation to biological markers of tumour cell proliferation activity: tumour grade, cellular DNA content, mitotic index, apoptotic index, ki-67 positive rate, and p53 and Bax expression. Tumour grade, Bax expression, apoptotic index and cellular DNA content were significantly correlated with the anti-tumour effects of NAC in univariate analysis. Tumour grade, Bax expression and apoptotic index were selected as independent predictive factors by means of multiple logistic analysis. Using the regression equation from these results, the prediction rate for anti-tumour effects was 70%. For patients in whom NAC is predicted to be ineffective, it may be necessary to choose another treatment option in order to improve their survival and quality of life.

Aberrant expression of beta- and gamma-catenin is an independent prognostic marker in oral squamous cell carcinoma.

Alteration in expression of E-cadherin and catenins is associated with loss of differentiation, acquisition of an invasive phenotype and poor clinical outcome in many types of cancer. To identify molecular prognostic markers, membrane expression levels of E-cadherin, and alpha-, beta- and gamma-catenin in biopsy samples (n=135) of oral squamous cell carcinoma (OSCC) were evaluated immunohistochemically in relation to preoperative tumour-related features, clinical course and prognostic value, and were found to be significantly correlated with an endophytic growth pattern and pathologically proved lymph-node metastasis. Alteration of expression of E-cadherin, and alpha-, beta- and gamma-catenin was also significantly correlated with poor disease-specific 5-year survival (P=0.0096, 0.0434, 0.0005 and 0.0005, respectively). Multivariate Cox proportional hazard regression analysis showed that alteration of beta- and gamma-catenin expression was a significantly independent prognostic parameter for survival (P=0.0112 and 0.0088, respectively), as was the case with endophytic growth pattern and advanced N-category. These results indicate that patients with OSCC and absent or reduced membrane expression of beta- and gamma-catenin should be considered a high-risk group for regional lymph-node metastasis and poor prognosis.

Lymphocyte subpopulations and T-cell subsets in human oral cancer tissues: immunohistologic analysis by monoclonal antibodies.

A series of T-cell-specific monoclonal antibodies (Leu-1, Leu-2a, and Leu-3a) and B-cell-specific monoclonal antibody (HLB-1) were used to detect the localization and intensity of infiltration of lymphocyte subpopulations and T-cell subsets in frozen sections of 17 patients with the oral cancer. The vast majority of the lymphocyte infiltrates in the oral cancer tissues were reactive with Leu-1. In contrast, B cells were detectable with HLB-1 in only 2 of 17 cases. Leu-2a-positive cells were dominant in four cases, whereas Leu-3a positive cells were dominant in only three cases. In seven cases, both cells infiltrated to the same degree. Leu-2a positive cells tended to be dominant in the cases with earlier clinical stages.

Transapical aortic perfusion with a double-barreled cannula.

The transapical aortic perfusion method is a new approach to cardipulmonary bypass and is performed with an infusion cannula placed in the ascending aorta through the left ventricular apex. The technique is applicable to almost all varieties of open-heart surgery, and is the most efficient method in infants and small children. A double-barreled forked cannula performs the two functions of aortic infusion and left ventricular decompression. With a Bakelite obturator, its cannulation to the aorta is very quick and easy. The transapical aortic perfusion method with a double-barreled cannula has been utilized in 156 open-heart operations with 17 perioperative fatalities and 1 late death. The 138 surviving patients have done well for periods up to four years. The perfusion method was developed from the left heart bypass and assisted circulation technique independently invented by Chardack's group and by us in 1966 and 1969, respectively.

Discrepancies among CT, histological, and blood-brain barrier findings in early cerebral ischemia.

The development of ischemic edema and blood-brain barrier (BBB) disruption during the 1st day of experimental cerebral infarction induced by transorbital occlusion of the middle cerebral artery (MCA) in cats was evaluated by computerized tomography (CT) scanning and compared to gravimetric and pathological studies. Regional cerebral blood flow was measured using the hydrogen clearance technique or stable xenon-enhanced CT scanning. Edema was observed gravimetrically and microscopically as early as 1 hour after the onset of ischemia in the cortex and at 3 hours or later in both the cortex and white matter. However, a significant decrease of Hounsfield numbers on the CT scans was not detectable at 1 or 3 hours and was scarcely visible at 9 hours after occlusion. Disruption of the BBB was detected by leakage of Evans blue dye at 3 hours after the occlusion in two of six animals and at 9 hours in five of five animals. However, CT scanning after infusion of contrast material showed no significant increase in Hounsfield number even 24 hours after MCA occlusion. These discrepancies should be emphasized when the dynamics of ischemic edema and BBB disruption are evaluated for clinical therapy by CT scanning.

Evaluation of periventricular hypodensity in experimental hydrocephalus by metrizamide CT ventriculography.

Hydrocephalus was induced in 13 dogs by injecting kaolin into the cisterna magna and was evaluated by computerized tomography (CT) scans. Modification of periventricular hypodensity was observed by metrizamide-enhanced CT ventriculography. Periventricular hypodensity was seen as early as 12 hours after kaolin injection. On CT ventriculography, metrizamide stayed longer in the ventricles of hydrocephalic dogs than in those of normal dogs, and migrated into the areas of periventricular hypodensity; the changes became significant within 12 to 24 hours. Four of the dogs were killed immediately after CT ventriculography, and the iodine concentration was measured. Iodine concentration was highest in the periventricular white matter, followed by the basal ganglia, and it was low in the cerebral and cerebellar cortex. When the change in Hounsfield units found by CT ventriculography at the regions of interest was compared to the actual iodine concentrations, the figures were quite compatible. Similarly, the specific gravity was measured in tissue from various parts of the brain of two hydrocephalic dogs, and compared against the value of that from five normal dogs. The specific gravity values were particularly low in the periventricular white matter of the hydrocephalic brains, suggesting a higher water content in that region. Since the increased migration of metrizamide occurred at the same region, it is suggested that development of periventricular hypodensity is due to increased transit of cerebrospinal fluid from the ventricles to the white matter.

Oral malignant melanoma: long-term follow up in three patients.

Three patients with oral malignant melanoma, who survived for at least ten years after initial examination, are presented. The depth of tumor invasion was 5 mm or less in all patients. The first patient received surgery and postoperative immunotherapy and she had no recurrence more than 18 years after treatment. The second patient underwent surgery but had local recurrence after 11 years. He underwent resection and postoperative chemotherapy and was still alive more than 14 years after initial examination. The third patient received radiotherapy and had metastasis nine months after treatment. Resection and radiotherapy were performed and the patient was alive more than 14 years after first presentation.

Acute toxicity of cadmium in rats with or without cadmium pretreatment.

The acute toxicity of cadmium (Cd) in male rats was examined with or without Cd pretreatment. Firstly, the metallothionein (MT) contents in the liver and kidney after Cd exposure (2.0 mg/kg, i.v.) were determined. The MT contents in the liver increased immediately to a peak (36.0 +/- 5.5 n mol/g wet tissue) 2 days after Cd exposure and were 55-fold higher than that at 0 day (0.64 +/- 0.25 n mol/g wet tissue). On the other hand, the MT contents in the kidney increased slightly but steadily for 14 days after Cd exposure. In the study for comparison of Cd-induced toxicity, the LD50 value of the Cd-pretreatment group (Group II) was approximately 2-fold higher than that of the non-pretreatment group (Group I). In microscopic findings, differences between rats in Group I and Group II were recognized in the kidney. Cytoplasmic vacuolation of the proximal tubular epithelium in the kidney was observed in Group I, while degeneration or coagulative necrosis in the proximal tubular epithelium was observed in some rats in Group II in addition to the cytoplasmic vacuolation. Because the toxic changes other than in the kidney in Group II were almost equal to or less than that in Group I, in spite of the doubled dosage of Cd, the toxic effects of Cd, except on the kidneys, were considered to be reduced by the pretreatment with Cd.

Cadmium accumulation in rats treated orally with cadmium chloride for 8 months.

To investigate the accumulation pattern of cadmium (Cd) in the liver and kidney following Cd intake from diet, female SD rats were fed cadmium chloride (CdCl2)- contained diets (1.24 and 4.96 ppm Cd) for 2 or 4 months. The other rats were fed CdCl2-contained diets (8, 40, 200, and 600 ppm Cd) for 2, 4 or 8 months. The control rats were given diet without Cd addition (lower than 0.01 ppm Cd). The concentrations of Cd in the liver and kidney derived from all rats were determined. The concentrations of Cd in the liver and kidney increased depending on the dosage of Cd. The concentrations of Cd in the liver did not reach plateau level even in the 200 and 600 ppm groups. On the other hand, the concentrations of Cd in the kidney in the 200 and 600 ppm groups reached a plateau level, which was approximately 250 micrograms/g. In the 600 ppm group, the concentrations of Cd in the kidney reached 250 micrograms/g at 2 months, but did not exceed that level at 4 months. In the 200 ppm group, the concentrations of Cd in the kidney increased to nearly the level of 250 micrograms/g at 8 months. The ratio of the concentrations of Cd in the kidney versus liver decreased as the dosage of Cd increased, suggesting that a low dosage of Cd was distributed preferentially to the kidney, but a high dosage of Cd was distributed to the liver. The relation curves between total amounts of Cd intake and Cd levels in the kidney in the 2-, 4-, and 8-month groups showed a parabola. The curves were shifted in parallel in the direction of higher levels of ingested Cd in order of length of Cd exposure period. These results suggested that when Cd is ingested over a long time at low concentrations, the amount of Cd accumulation in the kidney is small even for equal amounts of total ingested Cd.

Relationship between toxicity and cadmium accumulation in rats given low amounts of cadmium chloride or cadmium-polluted rice for 22 months.

To clarify toxic effects of long-term oral administration of low dose cadmium (Cd) on the liver and kidney, six groups of female Sprague-Dawley rats were fed a diet containing Cd-polluted rice or CdCl2 at concentrations up to 40 ppm, and killed after 12, 18, and 22 months. With toxicological parameters, including histopathology, there was no evidence of Cd-related hepato-renal toxicity, despite a slight decrease of mean corpuscular volume and mean corpuscular hemoglobin of red blood cells with 40 ppm CdCl2. Dose-dependent accumulation of Cd was observed in the liver and kidneys with peak levels of 130 +/- 42 micrograms/g and 120 +/- 20 micrograms/g, respectively, at 18 months in animals treated with 40 ppm CdCl2. A dose-dependent increase in urinary Cd levels became evident with time. Induction of metallothionein (MT) was also observed in the liver and kidney with a high correlation to the corresponding Cd levels. In the proximal renal tubular epithelia of 40 ppm CdCl2-treated rats at 22 months, prominent accumulation of Cd was observed in secondary lysosomes associated with MT deposits in their exocytotic residual bodies. The results demonstrated that, in contrast to the case with high-dose Cd-administration, renal toxicity is not induced by long-term oral administration of low amounts of Cd, although tissue accumulation does occur. Possible protective mechanisms may be operating.

Anatomical structure and surface epithelial distribution in the nasal cavity of the common cotton-eared marmoset (Callithrix jacchus).

To validate use of the common cotton-eared marmoset (Callithrix jacchus) in inhalation toxicity studies, its nasal morphology was examined. The nasal turbinates each consisted of one maxilloturbinate and one ethmoturbinate: these were more planar in structure than the comparable structures of rodents or dogs. The nasal cavity epithelia comprised squamous epithelium (SE), nasal transitional epithelium (NTE), respiratory epithelium (RE) and olfactory epithelium (OE), listed in order of occurrence from anterior to posterior positions. NTE was distributed as a narrow band lying between SE and RE. OE was limited to the dorsal part of the cavity, which was structurally similar to that of the macaque or man. Overall, this study revealed structural the similarity of the whole nasal cavity in the marmoset to that of macaques or humans. Prediction of nasal cavity changes in man based on extrapolation from experimentally induced changes in the common marmoset therefore seems likely to be feasible, making it a useful animal model for inhalation studies.

Polyvinyl alcohol as a useful indicator on iodometry: volumetric and spectrophotometric studies on iodine-PVA and iodine-starch complexes.

Iodometry is one of the easiest, most rapid and accurate methods for the determination of a relatively small amount of oxidizing agent, such as residual chlorine. Starch has long been used as a useful color indicator in iodometry. However, we found that PVA (polyvinyl alcohol with partially saponificated; e.g., saponification degree of 88%) is a more useful color indicator than starch. For example, at 20 degrees C, the PVA indicator gave similar profiles of iodine concentration vs. titration efficiencies (percent recoveries) to those of starch at 0 degrees C. At 0 degrees C, the PVA indicator detected 1.1 mg I2/L (11 microg I2: with 10 mL sample volume) with a high percentage of recovery (=95%). Furthermore, at 20 degrees C an iodine concentration of 0.36 mg/L (which corresponds to a residual chlorine concentration of 0.1 mg Cl2/L) could be detected using PVA color indicator assuming an appropriate correction.

Transfer of radioisotope from CSF to nasal secretion.

The physiological range of radioisotope (RI) transferred from the CSF to the nasal secretions was observed in 17 subjects without CSF rhinorrhea. A combination of RI cisternography and insertion of cotton pledgets in the nose was used in order to detect the RI transfer in the nasal secretion. The RI ratio was calculated, and those of the 17 subjects were less than 0.3. This is likely to be the normal physiological range of RI transfer.

[Radioisotope cisternographic study on cerebrospinal fluid circulation after subarachnoid hemorrhage].

Although recent advance in neurological surgery has diminished mortality rate of aneurysmal surgery, there still exist several complex problems for the management of aneurysms. Persistent neurological deficits or clinical deterioration after subarachnoid hemorrhage can result from subsequent communicating hydrocephalus which can be treated by shunting operation. We have studied alterations in the cerebrospinal fluid (CSF) circulation after SAH in 43 patients. Sources of hemorrhages were aneurysm in 30 cases, arteriovenous malformation in 6 and unknown in 7. Radioisotope cisternography was performed using 0.5 to 1.0 mCi of 169Yb-DTPA which was given intrathecally by lumbar injection. Results of cisternogram were classified into 4 groups and 7 subgroups; group 0: non filling (4%), group I: persistent ventricular filling (45%), A) absence of convexity flow (11%), B) partial convexity flow (34%), group II: transient ventricular filling (23%), A) delayed convexity flow (11%), B) normal convexity flow (12%), group III: no ventricular filling (28%), A) delayed convexity flow (17%), B) normal convexity flow (11%). The radioactivity in serial blood samples was measured by a well-type scintillation counter. Three types of curves for transfer of 169Yb-DTPA from CSF to blood were classified; delayed type, medium type, and normal type. In delayed type, the count ratio of blood activity at 24 hr to that at 3 hr is over 30%. In normal type, it is below 10%. There was a close correlation between cisternogram and transfer curve. In most cases with persistent ventricular filing, the transfer curve showed a delayed type. The relationship of cisternogram to classification of patient's condition by Hunt was studied. The grade of patient's condition was found to be closely related to the degree of abnormality in CSF circulation. The existence of rebleeding in the patients history was also found to influence the degree of abnormality in CSF circulation. However, single bleeding may also cause abnormality, such as persistent ventricular filling on cisternogram. In regard to the site of aneurysms, those of anterior communicating artery appeared to cause communicating hydrocephalus more frequently. Laterality of convexity flow was analyzed in 17 cases. All cases with internal carotid aneurysms showed decreased activity on the side of bleeding. Shunt operation was performed on 10 cases according to the results of cisternography, transfer curve, pneumoencephalography, and angiography. Seven cases showed improvement and 2 died of other complications soon after the shunt, and the effect of the procedure cannot be evaluated. Patients with clinical signs of NPH and abnormal cisternogram (group I) with evidence of ventricular dilatation are indicated for shunting operation.

[A mechanism of development and resolution of vasogenic brain edema].

To investigate the mechanism of development and resolution of vasogenic brain edema, authors have infused the mock CSF containing 35S-sodium thio-sulfate via a thin needle into the white matter of either normal cat's brain or into the edematous brain. The animals which were used in these experiments were divided into four groups (L20, L45, C20, C45). In the groups of animals subjected to a cold lesion (L20, L45), a small craniotomy was performed over the right frontal pole. A cold injury edema was produced 24 hours prior to the experiment. Na-Fluorescein (2 ml/kg) was given intravenously just prior to the cold lesion to later visualize the extent of the edema. For the positioning of the four needles in the brain, the coordinates were used according to the Horsley-Clark method and the atlas of Reinoso-Suarez. The location of tissue infusion (TIP) corresponds to a point approximately 3.0 mm before the frontal apex of the right lateral ventricle. The infused artificial CSF was mixed with 35S sodium-thiosulfate and stained with Evans Blue to check the extent of propagation of the infused solution. This solution was infused into the tissue at the point TIP with a rate of 0.20 ml/hr in groups C20 and L20 and 0.45 ml/hr in groups C45 and L45. Both lateral ventricles and cisterna magna were cannulated, and a ventriculo-cisternal perfusion with an artificial CSF was established through the right lateral ventricle with a perfusor. The perfusion rate was 2.25 ml/hr. The cisternal outflow was collected during every 15 min. for the activity and volume measurement. Tissue water content was determined by the drying method.(ABSTRACT TRUNCATED AT 250 WORDS)

[Brain scanning of the posterior fossa tumors (author's transl)].

It has been generally accepted that the scanning of the posterior fossa yield less accuracy in comparison with that of the supratentorial region. It seems that the difficulties are primarily attributable to the parotid gland, the overlying venous sinuses, and the heavy investment of the muscles with their rich vascular supply at the posterior fossa. These problems are compounded by poor patient positioning in the posterior view. We believe that the brain scanning of the posterior fossa is, however, nearly as successful as that of the supratentorial region, when the following procedures are carried out. We performed 99mTc-pertechnetate brain scanning 41 times and 169 Yb-DTPA cisternography 7 times on 25 posterior fossa tumors, from August 1970 to September, 1974. The diagnosis of these cases were confirmed by operation or autopsy. These include six neurinomas, six astrocytomas, three medulloblastomas, three hemangioblastomas, three metastatic tumors, one meningioma, one arteriovenous malformation, one osteochondroma and one microglioma.

[Metrizamide CT cisternography in skull base tumors (author's transl)].

Twenty-three cases suspected of skull base tumors were examined by CT cisternography (CTC) with CT scanner (EMI 1010) from April, 1977 to March, 1978. The lesions in 20 cases were diagnosed as positive and confirmed by operation and/or autopsies. These include five acoustic neurinomas, six pituitary adenomas, two craniopharyngiomas, two skull base meningiomas, one arachnoid cyst and miscellaneous tumors. Isotonic Metrizamide solution four of 2-10 ml was injected via lumbar route. Patients were kept in 30 degrees Trendelenburg position for 60 minutes until the first scanning. Scannings were obtained 1, 3, 6, 24 and in some cases 48 hours after lumbar injection. No side effects except for headache, nausea, vomiting occurred. There were no convulsions. In diagnosing cerebellopontine angle tumors, the indirect signs such as asymmetrical ambient cisterns are of importance, when combined with direct signs, i.e. a shadow defect. Parasellar tumors are usually difficult to diagnose with conventional CT due to streak artifact caused by adjacent bony structure. In CTC the extrasellar extension of pituitary tumors were clearly visible. The size, shape, dimensions and the relationship to the adjacent structures of the craniopharyngiomas were easily demonstrated with CTC especially when a coronal view was added. In arachnoid cyst, CTC demonstrated the delayed turnover of Metrizamide between the cyst cavity and the adjacent subarachnoid space. In conclusion, CTC is an useful neuroradiological diagnostic adjunct because of minimal bony streak artifact and high spatial resolution. It would be expected that small tumors of even 2-3 mm in diameter might be diagnosed, from the fact that the middle cerebral artery in the suprasellar cistern is clearly visible as a shadow defect.

[Meningioma in the aged--on its differential diagnosis (author's transl)].

Despite vast improvement in diagnostic techniques in neurosurgery during the past few decades, there still remain a significant number of intracranial tumors in geriatric age group, which are not recognized in the early course of the disease or during life. We are now focusing on the diagnostic problems of meningiomas in the geriatric age group and stressing the significant value of brain scanning in the differential diagnosis of brain tumors from cerebral vascular disease or other conditions. During about 10-year period, a total of 36 intracranial tumours in cases over 60 year old have been studied. Sixteen of these tumors are meningiomas and form the basis of this report. The age of these cases was between 60 and 83 years with average of 70.5. There were two males and 14 females. As to the location, four were parsagittal and falx meningiomas, three were at tuberculum sellae, two were at sphenoidal ridge, one was at tentorium in location. Twelve cases were erroniously diagnosed and confusion with cerebrovascular disease was most common. We analysed the onset and the progression of symptoms of our 16 cases, and picked up and stressed the four peculiarities of geriatric meningiomas. The first one is that the onset of symptoms is very sudden, almost precipitate, and the subsequent clinical course may be so rapidly progressive. The six patients in our cases were included in this group. A case among those was verified to be complicated with intratumoral hemorrhage, and another one with a subdural hematoma. The vast contrast to the first group is the second peculiarity. The meningioma especially in the geriatric age group may frequently unfold a clinical picture, which by its very insidious onset and slow development may be even unrecognized during life. The third is that patients developed dementia, at the onset in two cases and in any course of this disease in six. All too frequently in these instances the tumor has been overlooked and wrongly diagnosed as a senile dementia or psychosis. The fourth is that the meningioma developed with intermittent, recurrent and streotyped cerebral symptoms including epilepsy. We presented a case with intermittent aphasia due to a convexity meningioma on the dominant side. In almost all cases, manifestation of increased intracranial pressure was absent or not significant. There was found a papilledema in only one case, and cerebrospinal fluid revealed a normal pressure in six out of eight cases in which lumbar puncture was performed. It was proved that brain scanning was one of the most useful adjuncts in the diagnosis of brain tumor in the aged even in serious conditions. Changing brain scan patterns in association with clinical course is a useful diagnostic guide in differentiating tumors from cerebrovascular accidents. The serial scan density change is more meaningful if the clinical course is considered. Scanning should be done as soon as possible when the brain tumor is suspected and should be rescanned if necessary.