Effects of retrograde perfusion of the brain with combined drug therapy after focal ischemia in rat brain.

BACKGROUND AND PURPOSE: The ischemic edema associated with blood-brain barrier permeability changes and the excess production of free radicals are serious complications in prolonged cerebral ischemia. We examined the efficacy of transvenous perfusion of the brain, starting treatment 5 hours after occlusion of the middle cerebral artery for a period of 2 hours in rats with the combined agents mannitol (10 ml/2 hr) and dexamethasone (1 mg/2 hr) to counter edema and verapamil (0.05 mg/kg/2 hr) for vasodilation. METHODS: In experiment 1, blood-brain barrier permeability changes were examined in five groups with six rats each: group C rats underwent 7 hours of middle cerebral artery occlusion with no treatment; group V, treatment with verapamil alone; group VD, treatment with verapamil and dexamethasone; group VM, treatment with verapamil and mannitol; and group VDM, treatment with verapamil, dexamethasone, and mannitol. In experiment 2, we examined local cerebral blood flow, ischemic tissue damage volume, and water content of cerebral hemispheres in two groups of 16 rats each subjected to the same treatment as groups C and VDM rats in experiment 1. RESULTS: There was a significant reduction of blood-brain barrier permeability changes in the ischemic cortex of rats in group VDM compared with rats in the other groups. In the group undergoing transvenous perfusion of the brain with the three combined agents, there was a significant improvement of cerebral blood flow (39-58%, p < 0.05) in the ischemic cortex and reduction of ischemic cerebral damage volume (22%, p < 0.01) and water content of the ischemic hemisphere (p < 0.05) compared with the control group. CONCLUSIONS: The therapeutic approach using combined agents is effective treatment when initiated within 5 hours of focal cerebral ischemia in rats.

Efficacy of bypass between extracerebral artery and cerebral vein with retrograde verapamil infusion into focal cerebral ischemic tissue in rats.

We examined the efficacy of a bypass from an extracerebral artery to a cerebral vein (EA-CV) with retrograde verapamil infusion on acute focal cerebral ischemia in 35 rats. In 12 rats, within 1 hour after occlusion of the middle cerebral artery (MCAO), changes in blood-brain barrier permeability were examined by [14C]alpha-aminoisobutyric acid autoradiography after EA-CV bypass surgery; there were no significant changes during a period of 2 hours after EA-CV bypass. The other 18 rats having MCAO were divided into three groups of six each. Group A rats (control) underwent only cannulation of the cerebral vein. Group B rats had an EA-CV bypass. Group C rats received verapamil (0.1 mg/kg every 2 h) by transvenous perfusion of the brain (TVPOB) through the EA-CV bypass. In all rats in Groups A and C, local cerebral blood flow (LCBF) and quantitative measurement of early cerebral infarct volume were performed by autoradiography using [14C]iodoantipyrine and histochemical staining methods. Group B rats were examined only with the LCBF measurement. Group B (EA-CV bypass only) showed a nonsignificant improvement (18-40%) of LCBF in the ischemic cerebral cortical areas as compared with control Group A. Group C (EA-CV bypass with TVPOB with verapamil) showed an extensive and significant improvement in LCBF in the ischemic cortical areas (115-140%; P less than 0.05) and a slight increase in LCBF in the subcortical areas (17-29%), with a significant reduction (greater than 35%; P less than 0.05) in a total cerebral infarct volume in the ischemic cerebral hemisphere as compared with the control Group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute phenytoin intoxication associated with the antineoplastic agent UFT.

Antineoplastic drugs are known to affect the intestinal wall and suppress the absorption of phenytoin (PHT), resulting in a decrease in the serum PHT level. UFT (not an abbreviation) is a mixture of uracil, which enhances the activity of 5-fluorouracil (5-FU), and tegafur, a masked compound of 5-FU. The authors report three cases in which treatment of malignant brain tumors with UFT caused acute PHT intoxication. Two patients received PHT preoperatively at 150-200 and 270 mg/day, and showed serum PHT levels of less than 5 micrograms/ml. The third patient was started on 150 mg/day of PHT after surgery. Postoperatively, in addition to radiation therapy, each patient received 4 capsules of UFT (each containing 100 mg of tegafur) per day. Their serum PHT levels peaked at 48.2, 30.9, and 24.2 micrograms/ml, and all three exhibited clinical symptoms of acute PHT intoxication. The mechanism of interaction of these two drugs is obscure. Tegafur may compete with PHT in binding to metabolic enzymes in the liver and/or directly suppress PHT metabolism, leading to an increase in the serum PHT concentration. Therefore, when PHT is given in combination with a masked compound of 5-FU, the serum PHT level should be closely monitored.

[Brain metastases from carcinomas of the digestive organs--a comparative study with those from pulmonary carcinomas].

During the past 11 years, we have experienced 7 cases of a metastatic brain tumor with the primary lesion in the digestive organs. Their clinical courses were retrospectively compared with those of 19 cases with a brain metastases from pulmonary carcinomas. Leptomeningeal carcinomatosis was found in 2 patients of the former group but none in the latter. Six out of 7 brain metastases in the former group were found to have averaged 13 months before their appearance after the diagnosis of the primary lesion. In contrast, 14 out of 19 patients in the latter group had an onset with symptoms of a brain metastasis. The average survival after intracranial surgery on the metastatic tumor was 174 days for the former group and 268 days for the latter. The prognosis of a brain metastasis from a carcinoma of the digestive organ appears to be extremely probable.

Ruptured intracranial aneurysm in a 19-day-old infant--case report.

The authors describe the case of a 19-day-old infant with a ruptured intracranial aneurysm. She had suddenly become lethargic after drinking milk. Cerebral angiography demonstrated a large aneurysm arising from the right middle cerebral artery. Because the aneurysm was fusiform, the parent artery was clipped. Histological examination of a specimen taken from the aneurysmal dome showed an organized thrombus with deposition of a calcium-like substance in the wall, which appeared on histochemical examination to be pseudolime. The postoperative course was uneventful and she was discharged without neurological deficits.

[A case report of fibromuscular dysplasia presenting symptoms like moyamoya disease: "string of beads" appearance of the pericallosal artery].

We report a case of fibromuscular dysplasia (FMD) presenting a transient ischemic attack (TIA) like Moyamoya disease. The patient, a 16-year-old woman, had recurrent attacks of right hemiparesis induced by hyperventilation. Neurological examinations revealed no abnormality. Angiography showed severe stenosis of both anterior cerebral arteries at the proximal portion with "string of beads" appearance in the left pericallosal artery, and tubular stenosis of the left internal carotid artery at the level of the second cervical vertebra. Renal artery stenosis was not seen. A cerebral-blood-flow (CBF) study with 133Xe SPECT showed marked reduction of CBF in the left cerebral hemisphere at times of hyperventilation. Extracranial-intracranial bypass surgery was performed and histological examination of the superficial temporal artery (STA) revealed intimal fibroplasia which was compatible with FMD. Postoperative angiography showed good filling of the middle cerebral arteries from the STA. The patient has had no recurrence of TIA for a year since the operation. CBF study showed mild low CBF in the region of the left anterior cerebral arterial circulation at hyperventilation. There is no report of intracranial FMD presenting an ischemic symptom induced by hyperventilation. Clinical diagnosis of Moyamoya disease should be made carefully when extracranial vascular lesion accompanies it.

Amnesia due to bilateral hippocampal glioblastoma. MRI finding.

The authors report a unique case of glioblastoma which caused permanent amnesia. Magnetic resonance imaging showed the lesion to be limited to the hippocampal formation bilaterally. Although glioblastoma extends frequently into fiber pathways and expands into the opposite cerebral hemisphere, making a "butterfly" lesion, it is unusual for it to invade the limbic system selectively to this extent.

Cavernous hemangioma of the optic nerve. Case report.

A case of cavernous hemangioma of the optic nerve of a 24-year-old pregnant woman is reported. The visual disturbance with subacute onset was thought to be related to the delivery of a child. The lesion was totally removed through the subfrontal approach, resulting in satisfactory recovery of visual symptoms. Cavernous hemangioma involving the optic nerve and chiasm is extremely rare. Only two similar cases have been reported previously.

[AUFRAP therapy: combined modality treatment of malignant gliomas with intraarterial infusion of ACNU].

A method of combination therapy was proposed for the treatment of malignant gliomas, and the clinical results were reported. This combination consisted of ACNU (nimustine), UFT (tegafur + uracil), Radiation, vitamin A and PSK (krestin), and was named AUFRAP therapy. Intracarotid infusion of ACNU (100 or 150 mg/body) was done after the administration of vitamin A (100,000 units), in the first and last week of radiation therapy with a total dose of 60-70 Gy. UFT (400-600 mg/day) and PSK (3g/day) were also given orally. After the induction of remission, patients were treated in the outpatient clinic under a similar maintaining protocol. Two patients who received 150 mg of ACNU and daily 600 mg of UFT in combination with radiation therapy showed severe myelosuppression in the early stage of treatment, and the combination therapy was aborted. Two of four patients who received 100mg of ACNU and daily 400mg of UFT did not show such severe side effects and two showed transient, moderate myelosuppression and vomiting. The serum phenitoin concentration doubled and was thought to be a side effect of tegafur. All four patients completed the induction protocol and follow-up CT scans disclosed shrinkage of the remained tumors, decreased contrast enhancement or no evidence of recurrence. Interactions of these drugs and radiation were discussed and the literature was reviewed.