Protective effect of phenytoin and its enhanced action by combined administration of mannitol and vitamin E in cerebral ischemia

Phenytoin is well known as the anticonvulsant agent and also said to protect the brain against ischemic damage. The purpose of the present experiment is to study the therapeutic effect of phenytoin on cerebral ischemia and confirm whether the effectiveness of phenytoin could be enhanced by combination of free radical scavengers such as mannitol and vitamin E. In this experiment, twenty-five dogs were subjected to ischemia, using the "canine model of complete ischemic brain regulated with a perfusion method" in which it is possible to control the degree of blood flow to a cerebral hemisphere via a perfusion pump at will. Five animals served as untreated control, fifteen received treatment with phenytoin (7 mg/kg in five dogs, 10 mg/kg in five dogs and 30 mg/kg in five dogs) and five treated with 10 mg/kg phenytoin, 2 g/kg of mannitol and 30 mg/kg of vitamin E. These drugs were administered intravenously 20 minutes prior to the production of ischemia, when cerebral blood flow was reduced to one-tenth its normal volume. After one hour, cerebral blood flow was restored and the recovery of electrical activity of the brain and the degree of brain swelling were observed for three hours. With regard to the recovery of EEG, no recovery of EEG was seen subsequent to recirculation except one dog in the control group. Whereas in the group treated with phenytoin, gradual emergence of slow wave ws observed soon after recirculation. The higher the administered dosage is, the better the degree of recovery of EEG was seen. Thus, the dose-related recovery of EEG was observed within the dose ranges tested.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravesical chemotherapy with 4′-epi-Adriamycin in patients with superficial bladder tumors

Summary We evaluated the effects of 4-epi-Adriamycin (EPI), a derivative of Adriamycin (ADR), in intravesical instillation chemotherapy. The patients received two courses of three daily instillations of 50–80 mg EPI dissolved in 30 ml physiological saline on 3 consecutive days, with an interval of 4 days between courses. Full evaluation was possible in 33 of 35 patients with superficial bladder tumors treated with EPI. Complete response was observed in 4 cases and partial response in 14 cases, giving a response rate of 55%. Side effects such as pollakiuria and pain on micturition occurred in 9 cases. EPI appears to be an effective agent for intravesical instillation chemotherapy in patients with superficial bladder tumors.     

Phase I clinical and pharmacokinetic study ofN 4-behenoyl-1-β-d-arabinofuranosylcytosine

A phase I study ofN ⁴-behenoyl-1-β-d-arabinofuranosylcytosine (BHAC) was conducted in 66 patients, 41 with solid tumors and 25 with hematological malignancies. The patients received either a 2-h single intravenous (i.v.) drip infusion (Schedule 1) or consecutive daily 2-h i.v. infusions (Schedule 2). In Schedule 1 the daily dose was initiated with 1.5 mg kg^?1 which was escalated up to 7 mg kg^?1. Side-effects were mild, and included nausea, vomiting, epilation, and hot flushes. Because of the presence of the solvent vehicle, HCO-60 and in consideration of the mechanism of action of BHAC, the dose escalation was stopped at 7 mg kg^?1. In Schedule 2, the daily dose was started with 1.5 mg kg^?1 which was escalated up to 8 mg kg^?1 and given for 2–16 days. Myelosuppression was found to be dose-limiting toxicity. The maximum tolerated dose (MTD) in patients with non-hematological solid tumors was assumed to be 5 mg kg^?1 daily × 5 days. The plasma disappearance curve of BHAC looked biphasic, and when 4 mg kg^?1 of BHAC were administered the half-lives of the initial phase (t _1/2α) and the second phase (t _1/2β) were calculated as 0.798 and 5.76 h respectively. In Schedule 2 complete remission was observed in 5 out of 21 patients with acute leukemia, one partial remission in Hodgkin’s disease, and one 1-B response (Karnofsky) in thyroid papillary adenocarcinoma.     

Surgical treatment of AVMs occluding these feeders during removal--utilizing the intraoperative balloon catheter and brain protective substances ("Sendai cocktail"

The ideal treatment of cerebral arteriovenous malformations (AVMs) is thought to be the total resection of nidus. We have been reporting the importance of temporary occlusion of the feeding arteries with the aid of the brain protective substances to prolong the permissible time of occluding these arteries. Because of the difficulty of access to the feeding arteries, some cases are difficult or even impossible to operate. In this communication, four cases of AVM which were successfully resected utilizing intraoperative balloon occlusion of feeders under the administration of the brain protective substances are reported. Case 1. A 14-year-old female was admitted to our clinic because of subarachnoid hemorrhage with ventricular rupture and left cerebellar hemorrhage. Angiography disclosed a large left cerebellopontine angle AVM fed by left anterior inferior cerebellar artery (AICA) and left superior cerebellar arteries (SCAs). Prior to the operation, two balloon catheters were introduced via transfemoral approach; one into the AICA and the other into the basilar artery where left SCAs originated. To prolong the permissible time of occluding these arteries, "Sendai cocktail" (20% mannitol, vitamin E and dexamethazone) and perfluorochemicals were administered. Auditory brain stem response (ABR) was monitored continuously during the operation. The nidus was resected totally with safe using temporary inflation of these balloon catheters. The patient returned to normal life. Case 2. A 35-year-old male was admitted to our clinic complaining of the attack of generalized convulsive seizure.(ABSTRACT TRUNCATED AT 250 WORDS)     

A new superselective balloon catheter--all-silicone catheter with a floppy tip

We have introduced concept of "chemical" embolization and have tried to develop a new agent which would enable us to embolize the lesion with one-shot injection. Such an agent must be able to occlude diffusely the lesion distal to the catheter. This has made it mandatory to develop a new catheter which can be introduced into the vessel as close to the lesion as possible with fewer risks of clot formation and/or vessel damage. A new superselective balloon catheter for angiography and infusion of liquid embolizing materials has been developed. This catheter consists of a proximal relatively stiff silicone catheter, a short distal thin-walled flexible silicone catheter and silicone balloon. These three silicone components are connected by silicone adhesives. The distal catheter allows us to catheterize fine arteries such as lenticulostriates, while the proximal catheter assures easy manipulation. This balloon catheter can be used for superselective angiography and infusion of liquid embolizing materials. It has been used on nine patients; one with a dural arterio-venous malformation (AVM), four with meningiomas, and four with brain and spinal cord AVMs. In the case of dural AVM and meningiomas, it was possible to easily introduce into the middle meningeal artery distal to the foramen spinosum. In addition, in one of the cases of meningioma, we were able to catheterize one of the main feeding pedicles beyond the pterion. Chemical embolization was carried out in 5 cases with good results. In the case of brain and spinal cord AVM, useful information was obtained from the superselective angiography.(ABSTRACT TRUNCATED AT 250 WORDS)     

The protective effect of vitamin E on cerebral ischemia

Using the "canine model of the completely ischemic brain regulated with a perfusion method," the effects on cerebral ischemia of vitamin E, which is known to act as an antioxidant, were investigated. After pretreatment with vitamin E by oral or intravenous administration, cerebral blood flow was reduced to 1/10th the normal state and, 1 hour later, allowed to return to normal. Subsequent changes in electrical activity were observed, and the effects of vitamin E were evaluated. In the control group, no recovery of electrical activity was seen. In the groups given vitamin E, the recovery time was significantly shortened in the dogs given 30 mg/kg of vitamin E intravenously. Furthermore, in the groups treated with vitamin E, distinct recovery of electroencephalographic potentials at 3 hours after recirculation was apparent. These effects were more favorable in the case of intravenous administration than in the case of oral administration. These experimental results indicate that the administration of vitamin E is effective in protecting the brain from cerebral ischemia.     

Carpal Tunnel Syndrome Due to Iatrogenic Amyloidosis After Domino Liver Transplantation From Hereditary Transthyretin Amyloidosis: A Case Report

BackgroundCarpal tunnel syndrome is the most common compression syndrome of the peripheral nerve. Transthyretin amyloidosis and dialysis-related β2-microglobulin amyloidosis are known causes of carpal tunnel syndrome.Case ReportA Japanese woman showed carpal tunnel syndrome 16 years after a domino liver transplantation (DLT) from the donor with hereditary transthyretin amyloidosis. DLT indication was congenital extrahepatic portosystemic shunt, and the patient had been put on maintenance hemodialysis because of chronic kidney disease 6 years before DLT. Moreover, the amyloid precursor protein of the patient was histologically confirmed not to be β2-microglobulin, but transthyretin.ConclusionsThe existence of amyloid was speculated when the patient who underwent DLT from hereditary transthyretin amyloidosis showed carpal tunnel syndrome. Additionally, elucidating the amyloid precursor protein when the patient has another cause of amyloidosis is necessary.     

ASO Author Reflections: Perspectives of Laparoscopic Hepatectomy with Venous Tumor Thrombectomy for Hepatocellular Carcinoma

Annals of Surgical Oncology -     

ASO Author Reflections: Laparoscopic Arantius’ Approach as Shortcut Access for Major Hepatic Veins

Annals of Surgical Oncology -     

Investigation of the renal injury caused by liver ischemia-reperfusion in rats

To explain the mechanism of renal injury caused by liver ischemia-reperfusion, we investigated biochemical and morphological changes in the liver and kidney in rats. After reperfusion following 60 min of liver ischemia, numerous changes were found. The level of serum transaminases and lipid peroxide formation in the liver tissue increased significantly. Electron microscopic studies revealed that most of the hepatocytes had swollen mitochondria and clumping of the nuclear chromatin. The sinusoidal endothelium was disrupted and the sinusoidal lumen was filled with numerous erythrocytes. Blood endotoxin concentration, plasma lipid peroxide levels, and serum -glucuronidase activities were significantly higher than in the control group. Biochemical and morphological renal injury was also observed. Tissue lipid peroxide levels increased in both the kidney and the liver. Microscopic examination revealed damage to the renal tubules, including interstitial edema, dilatation of the lumen, and granular casts derived from necrotic cells in the proximal convoluted tubule. The levels of urinary N-acetyl--d-glucosaminidase (NAG) in the liver ischemia-reperfusion group were also higher than in the control group. These results suggest that the renal injury was caused by an increase in endotoxin, lipid peroxide, and lysosomal enzymes in the blood following the liver injury induced by the ischemia-reperfusion.