Search

In recent years, it has been reported that the acute-phase proteins C-reactive protein(CRP) and serum amyloid A(SAA), the sera levels of which are elevated in inflammation, are also elevated in coronary artery disease such as acute myocardial infarction. Also, high-sensitivity CRP assay is thought to be useful in predicting the prognosis of coronary heart disease. While investigating complexes of acute-phase proteins and low-density lipoprotein(LDL), we found a complex of LDL and SAA(SAA/LDL complex). The SAA/LDL complex in blood are formed from LDL and HDL by an oxidation reaction. Therefore, we developed an ELISA using anti-human SAA antibody and anti-human apoB, and determined a new method for measuring SAA/LDL complex in sera. We evaluated SAA/LDL complex as a new marker for prediction of prognosis in addition to the ordinary markers in consecutive 140 patients with stable coronary heart disease who had at least 1 coronary artery stenosis more than 50% in diameter at the diagnostic coronary angiography. Of these 140 patients, 2 developed fatal myocardial infarction, 2 cerebral infarction, and 17 angina pectoris requiring coronary revascularization therapy during 1 year and 6 months after blood examinations. The SAA/LDL complex value in this EVENT group of 21 patients was significantly higher than that in the control group of 119 individuals. High-sensitivity CRP (hs-CRP) assay and SAA measurement showed no significant difference between the 2 groups. The SAA/LDL complex reflects intravascular inflammation directly and can be a new marker more sensitive than hs-CRP or SAA for prediction of prognosis in patients with stable coronary artery disease.

Traumatic neuroma of the bile duct is not a true neoplasm, but a reactive proliferation of pericholangial nerve tissue induced by injury. A 60-year-old Japanese man was admitted to investigate obstructive jaundice. He had undergone cholecystectomy and common bile duct exploration 17 years previously. Ultrasonography and computed tomography showed a pneumobilia with dilatation of the intrahepatic biliary ducts. Endoscopic retrograde cholangiography and spiral-computed tomography cholangiography revealed biliary stenosis in the hepatic hilus with dilatation of the intrahepatic biliary ducts. Celiac angiography and arterial portography showed neither tumor stains nor signs of vessel invasion. At surgery, the confluent portion of the intrahepatic biliary ducts in the hepatic hilus was hardly palpable and deformed, but frozen-section microscopic examination confirmed that no malignant cells were present. Anastomosis of the right and left extrahepatic bile duct to the jejunum, reconstructed by Roux-en-Y hepaticojejunostomy, was performed. Histological examination revealed a nodule composed of a haphazard proliferation of nerve fascicles in the fibromuscular layer of the bile duct which were positively stained for S-100 protein. The pathological diagnosis was traumatic neuroma of the bile duct. Thus, the possibility of traumatic neuroma should be considered in the differential diagnosis of patients with late-onset jaundice after biliary tract surgery.

Objectives: The aim of this retrospective study was to determine the predictors of diffuse in-stent restenosis (ISR) among the lesions causing the first ISR by intravascular ultrasound (IVUS) studies., Background: Although some predictors of diffuse ISR have been reported, parameters on IVUS relating to diffuse ISR are not well characterized., Methods: We classified 52 ISR lesions that had undergone successful stent implantation and led to restenosis into two types--focal and diffuse ISR--using quantitative coronary angiography. Restenosis was defined as > or =50% diameter stenosis, and diffuse ISR as lesion length > or =10 mm at follow-up. The remodeling index (RI) was defined as the vessel area at the target lesion divided by that of averaged reference segments., Results: There were no significant differences in patient, angiographic, and procedural characteristics between the focal (n = 25) and diffuse (n = 27) ISR groups. Baseline RI was significantly greater in the diffuse ISR group (1.03 +/- 0.18 vs. 0.88 +/- 0.24, p = 0.0159). Negative remodeling, defined as RI <0.9, was detected in 60% of the focal ISR group and in only 26% of the diffuse ISR group. By logistic regression analysis, baseline RI was the only independent predictor of diffuse ISR (p = 0.0341). Moreover, volumetric analyses revealed that lesions developing into diffuse ISR had less capacity to compensate for further plaque growth., Conclusions: Among the first ISR lesions, baseline positive remodeling was the most powerful predictor of diffuse ISR. Measuring pre-interventional arterial remodeling patterns by IVUS may be helpful to stratify lesions at higher risk.

Background/aims: In spite of many technical advances in liver surgery, optimal nutritional support after hepatectomy has not been established., Methodology: We clarified the actual nutritional state in 16 patients with total parenteral nutrition (TPN group), and 16 patients without total parenteral nutrition (PPN group), after hepatectomy for hepatocellular carcinoma without biliary tract reconstruction, in terms of preoperative clinical data, intraoperative indexes, postoperative management and complications, liver function data, nutritional state, and changes in metabolic parameters., Results: There were no significant differences in any occurrences of postoperative complications, liver function data, or nutritional parameters between the two groups. On the other hand, the TPN group needed more doses of insulin than the PPN group. The beginning of each water and food intake was earlier in the PPN group than in the TPN group. The blood glucose level was higher in the TPN group than in the PPN group. The serum sodium and chloride levels were lower, but the serum potassium level was higher, in the TPN group compared to the PPN group. Thus, problems such as hyperglycemia and serum electrolyte abnormalities were more conspicuous in the TPN group than in the PPN group., Conclusions: In the actual clinical care after hepatectomy for hepatocellular carcinoma without biliary tract reconstruction, in which oral feeding is started early, total parenteral nutrition is considered unnecessary.

A patient with 3-vessel coronary artery disease and left ventricular aneurysm underwent coronary artery bypass grafting combined with the Dor approach. Five days later, ventricular tachycardia following short-coupled ventricular premature contractions suddenly occurred and was not responsive to class IB drugs (lidocaine and mexiletine), requiring frequent electrical cardioversion. After the administration of a novel class III drug, nifekalant hydrochloride, this electrical storm of ventricular tachycardia was completely suppressed together with the disappearance of ventricular premature contractions. Nifekalant hydrochloride (MS-551), a pure K(+) channel blocker, might be effective for postoperative recurrent ventricular tachyarrhythmias that are refractory to other antiarrhythmic agents.

Oral administration and nasal instillation of glucocorticoids are currently being conducted and are producing satisfactory results for the treatment of olfactory dysfunctions. However, there are still many unanswered questions about the actions of glucocorticoids on the olfactory cells. In the present study, the effects of glucocorticoids on the olfactory response in mouse olfactory cells were examined by measuring changes in the intracellular Ca2+ concentration. The olfactory cells isolated from the BALB/c female mouse mucosa were stained with a Fura-2/AM and the changes in the intracellular Ca2+ concentration were observed by using a fluorescent microscopic image processing device, ARGUS50. The cells were exposed to the following olfactory stimuli, 3-ethoxy-4-hydroxy-benzaldehyde, caprylic acid, nonanoic acid, phenethyl alcohol and n-amyl acetate. When 0.1 and 0.01% betamethasone was applied to the olfactory cells for short periods(1 or 3 minutes), no changes were observed. However, long-term(7 minutes) application of 0.1 and 0.01% (but not 0.001 and 0.0001%) betametathone significantly decreased intracellular Ca2+ concentration, which was increased by olfactory stimulation. The inhibitory effect of betamethasone on Ca2+ influx into olfactory cells was attenuated by pre-treatment olfactory cells with RU486, a glucocorticoid receptor antagonist.

Background/aims: Postoperative hyperamylasemia after hepatectomy occurs frequently, but the mechanism is not clear., Methodology: We studied the postoperative evaluation of 11 patients with hyperamylasemia after hepatectomy (Hyper-Amy group), compared with 35 patients without hyperamylasemia (Norm-Amy group), in terms of preoperative features, intraoperative findings or procedures, postoperative management and complications, parameters for pancreatitis, and comparisons in serum amylase and lipase levels between patients with chronic liver disease and those with normal livers., Results: In preoperative features, viral infection and chronic liver disease presented much more in the Hyper-Amy group than in the Norm-Amy group, and indocyanine green 15-minute retention rate was higher in the Hyper-Amy group than in the Norm-Amy group. There were no significant differences in the intraoperative findings or procedures, or postoperative management and complications between the two groups. In parameters for pancreatitis, the serum amylase and lipase levels were higher in the Hyper-Amy group than in the Norm-Amy group on days 3, 7 and 14. In comparison, between patients with chronic liver disease and normal livers, the serum amylase levels were higher in patients with chronic liver disease than in patients with normal livers on days 7 and 14., Conclusions: We should pay attention to the incidence of hyperamylasemia after hepatectomy in patients with chronic liver disease, so we can give rapid treatment for pancreatitis.

Background/aims: In spite of recent advances in liver surgery, biliary complications remain a common cause of major morbidity after hepatectomy., Methodology: We studied the postoperative evaluation of 28 hepatectomied patients with transcystic duct tube (C-tube) drainage (C-group), compared with 38 hepatectomied patients without C-tubes (NC-group), in terms of preoperative clinical profiles of patients, intraoperative findings and procedures, postoperative management and bile leakage, daily output of bile, liver function and postoperative infections., Results: There were no significant differences in the preoperative clinical profiles of patients and postoperative management between the two groups. In intraoperative findings and procedures, the tumor size, weight of the resected liver, operation time and operative blood loss were higher in the C-group than those in the NC-group. Therefore, the operative procedure was more serious in the C-group than that in the NC-group. However, bile leakage was observed in only one of 28 patients (3.6%) in the C-group and 10 of 38 patients (26.3%) in the NC-group, that is, bile leakage occurred less frequently in the C-group than in the NC-group. The daily output of bile in the C-group was thought to be enough to decompress the biliary tree. In liver function, aspartate aminotransferase and alanine aminotransferase had lower levels in the C-group than those in the NC-group with bile leakage. White blood cell count, C-reactive protein and body temperature were closer to the normal range in the C-group than those in the NC-group with bile leakage., Conclusions: C-tube drainage after hepatectomy is thought to be useful for decreasing postoperative complications, especially bile leakage.

Background/aims: We studied the postoperative evaluation of transcystic duct tube drainage (C-tube), T-tube drainage (T-tube), and retrograde transhepatic biliary drainage after common bile duct exploration for patients with choledocholithiasis., Methodology: We analyzed the preoperative clinical features of patients, intraoperative findings, postoperative status and management, daily output of bile, liver function, postoperative infections, and postoperative complications for patients who underwent common bile duct exploration including 16 C-tube, 17 T-tube, and 8 retrograde transhepatic biliary drainage cases., Results: There were no significant differences in the preoperative clinical features, intraoperative findings, or the daily output of bile from the tube. The removal day of the biliary drainage tube and postoperative hospital stay were shorter in the C-tube group than in the T-tube and retrograde transhepatic biliary drainage groups. Aspartate amino-transferase level and body temperature in the C-tube group on day 7 were lower than those in the T-tube group, and the total bilirubin level in the C-tube group on day 14 was lower than in the T-tube and retrograde transhepatic biliary drainage groups. Moreover, postoperative complications occurred significantly less frequently in the C-tube group (25.0%) than in the T-tube group (76.5%)., Conclusions: C-tube drainage is thought to be most useful after common bile duct exploration for patients with choledocholithiasis.

Cefcapene pivoxil hydrochloride (CFPN-PI), an ester cephem antibiotic, was orally given at a dose of 100 mg three times daily in patients with infection and soft stool or diarrhea, and its absorption was determined using the recovery ratio of 12-h urine pooled after the initial administration as an index. The primary endpoint, the recovery ratio of 12-h urine pooled after oral administration, could be evaluated in six of the eight patients finally gathered, and the mean value was 30.1 +/- 5.8%, which was not considered to differ from the mean value of 34.4 +/- 5.5% obtained in six healthy adult volunteers in the previous phase I study. Clinical efficacy in the eight patients was rated as very effective, effective, and ineffective in two, five, and one patients, respectively, with an effective ratio of 87.5% (7/8). Neither adverse drug reactions nor abnormal laboratory data were observed in any patient. These results indicate that CFPN-PI, at the routine oral dose, does not cause any problems in terms of absorption, efficacy, and safety when it is used in patients with infection and soft stool or diarrhea.

In the present study, we examined the effect of two salts of aluminum (Al), aluminum maltolate (Almal) and aluminum chloride (AlCl(3)), on the cell viability of PC12 cells in the absence and presence of nerve growth factor (NGF). A 72-h exposure of PC12 cells to Almal (300 microM) resulted in a marked increase of lactic dehydrogenase (LDH) release from the cells and a decrease of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) activity. These results indicate that Almal induces a decrease in the cell viability. Under the same conditions, Almal also caused DNA ladder formation and chromatin condensation. In contrast, AlCl(3) did not showed an increased LDH release and a decreased MTT activity in the concentration range of the salt tested (0.1-1 mM). The extent of LDH release and MTT activity decrease induced by Almal treatment closely depended on the amount of Almal incorporated into the cells. An increase in the fluorescence intensity of 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate, di(acetoxymethyl ester) (C-DCDHF-DA) which was loaded into the cell by Almal treatment and its prevention by pyrrolodine dithiocarbamate, a potent antioxidant, suggested that Almal-induced cell death partly proceeds via reactive oxygen species (ROS) production. NGF effectively inhibited the increase of LDH release and the decrease of MTT activity, as well as DNA fragmentation and chromatin condensation. However, NGF did not inhibit the increase of C-DCDHF-DA fluorescence in the cells induced by Almal treatment. From these results, it is suggested that ROS production associated with accumulation of Al is one possible important factor in the onset of Al neurotoxicity via apoptotic cell death and that NGF protects against cell degeneration associated with Al accumulation, but independently of ROS production.

Purpose: We investigated the vasodilatory action of FK 409 on bovine retinal arteries using a microvessel perfusion system in vitro., Materials and Methods: Bovine retinal arteries were obtained from bovine eyes. The arteries, 3 mm long and 110 microns in diameter, were attached to the microvessel perfusion system. The arteries were perfused with Tyrode solution containing 10(-6) M U46619, followed by 10(-6) M U46619 and FK 409 (10(-3) M or 10(-4) M). We also perfused the arteries with carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide. The inner diameter of the arteries was measured under a microscope and analyzed by computer., Results: FK 409 prevented contraction of bovine retinal arteries induced by perfusion of 10(-6) M U46619 when the arteries were perfused with 10(-3) to 10(-4) M FK 409. Addition of 100 microM PTIO, an nitric oxide (NO)-specific extinction agent, into the mixture of U46619 and FK 409 hadan antagonistic effect on the contractive action of FK 409., Conclusion: These results suggest that FK 409 has a dilatational effect on bovine retinal arteries and that the dilatational action of FK 409 is possibly produced by NO.

The main mechanism of restenosis after directional coronary atherectomy (DCA) remains obscure. We investigated mechanisms of restenosis after DCA in different coronary artery remodeling patterns. DCA was performed in 51 de novo lesions. The lesions were evaluated by intravascular ultrasound (IVUS) before, immediately after, and 6 months after the procedure. According to the IVUS findings before DCA, we classified the lesions into the following 3 groups: (1) positive (n = 10), (2) intermediate (n = 25), and (3) negative (n = 16) remodeling. We measured lumen area, vessel area, and plaque area using IVUS before DCA, immediately after DCA, and at follow-up. Lumen area increase after DCA was mainly due to plaque area reduction in the positive and intermediate remodeling groups (90 plus minus 15% and 80 plus minus 25% increase in lumen area, respectively), whereas that in the negative remodeling group was due to both plaque area reduction (57 plus minus 22% increase in lumen area) and vessel area enlargement (43 plus minus 33% increase in lumen area). The plaque area increase correlated strongly with late lumen area loss in the positive and intermediate remodeling groups (r = 0.884, p <0.001; r = 0.626, p <0.001, respectively), but the decrease in vessel area was not correlated with lumen area loss. In contrast, both an increase in plaque area and a decrease in vessel area were correlated with late lumen area loss (r = 0.632, p = 0.009; r = 0.515, p = 0.041) in the negative remodeling group. Coronary artery restenosis after atherectomy was primarily due to an increase in plaque in the positive and/or intermediate remodeling groups. However, in the negative remodeling group, late lumen loss might have been caused by both an increase in plaque and vessel shrinkage.

In a patient referred for the evaluation of non-sustained monomorphic ventricular tachycardia on Holter recordings, ventricular fibrillation was electrically induced during electrophysiologic study. Despite the absence of structural heart diseases, his ECG revealed J wave and ST segment elevation in the inferior leads, which showed circadian variation and were augmented by the sodium channel blocker, pilsicainide. This case might lead us to notice a new concept, a 'latent' type of variant Brugada syndrome, and these ECG findings and changes might serve as its diagnostic sign.

We evaluated postoperative function in 98 patients who underwent surgery for early gastric cancer between 1995 and 1998 to compare the results of pylorus-preserving procedures to those of conventional distal gastrectomy with Billroth I (B-I). The pylorus-preserving procedures included endoscopic mucosal resection (EMR), performed in 12 patients; local resection (Local), performed in 14 patients; segmental resection (Seg), performed in 8 patients; and pylorus-preserving gastrectomy (PPG), performed in 19 patients. B-I was performed in 45 patients. The nutritional status and serum albumin (Alb) levels after PPG, the hemoglobin (Hb) levels after EMR, Local, and PPG, and the present/preoperative body weight ratios after EMR, Local, Seg, and PPG were superior to those after B-I. The time before oral intake was recommenced after EMR and Local, the volume of oral intake tolerated after EMR, Local, Seg, and PPG, and the postoperative hospital stay after EMR were all superior to those after B-I. Moreover, significantly fewer patients suffered reflux symptoms after EMR, Local, and PPG, abdominal fullness after EMR, and early dumping syndrome after EMR, Local, and PPG than after B-I. There was also less evidence of gastritis after EMR, Local, and PPG, and of bile reflux after EMR, Local, and PPG, than after B-I. These findings indicate that pylorus-preserving procedures may result in a better postoperative quality of life for selected patients with early gastric cancer.

cAMP and IP3 act as secondary messengers in olfactory signal transduction and when activated, stimulate calcium levels in olfactory receptor cells. Little is known however, about the causal mechanism. We studied calcium kinetics in mouse olfactory receptor cells after odorant stimuli. Olfactory receptor cells were isolated from female BALB/c mice, treted with trypsin, and stained with Fura-2/AM. Changes in intracellular Ca2+ concentrations in stained cells were measured with a fluorescent microscopic image-processing device (ARGUS-50; Hamamatsu Photonix, Japan). We found that intracellular Ca2+ concentrations rose after exposure to a set of odorants, including 3-ethoxy-4-hydroxy-benzaldehyde, caprylic acid, heptanoic acid, nonanoic acid, eugenol, phenethyl alcohol, and n-amyl acetate. Adding 2', 5'-dideoxyadenosine, a cAMP inhibitor, beforehand suppressed olfactory receptor cell response to odorants. Intracellular Ca2+ concentrations increased substantially in response to stimulation by odorants in calcium-free Ringer's solution, but only a slight increase was seen in intracellular calcium concentration in response stimulation by a high concentration of K+ (145.6 mM) in calcium-free Ringer's solution. The increase in intracellular Ca2+ concentration after odorant stimuli was suppressed when olfactory receptor cells were pretreated with ryanodine, which releases Ca2+ from intracellular stores. These findings suggest that elevated Ca2+ concentrations may be involved in releasing Ca2+ from intracellular calcium stores in mouse olfactory receptor cells, in which cAMP functions as a secondary messenger in olfactory signal transduction.

We assessed the difference between transcortical sensory aphasia (TCSA) following the left frontal lesions (F-TCSA) and TCSA following the left posterior lesions (P-TCSA). All the patients were right-handed and the 7 patients had the lesions in the only frontal lobe and the 10 patients had the lesions only in the left temporo-parieto-occipital regions. We administered pointing tasks, using 90 line drawings representing single nouns. We presented 6 line drawings a pointing board, and we used two kinds of pointing boards: one showed the line drawings each belonging to different categories (random categorized pointing task), the other showed the line drawings each belonging to only either two different categories (two categorized pointing task) and we presented 15 pointing boards each alternatively. The result was that regarding the patients of P-TCSA showed different number of correct answers between the random categorized pointing task and the two categorized pointing task with statistical significance. Regarding the patients of F-TCSA showed no difference between them. The results indicated that disturbance of P-TCSA on the pointing task was the disturbance of semantic process per se. And the disturbance of F-TCSA on the pointing task was that of not only semantic process but also the whole process including comprehending the presented words, searching the line drawings, comparing the line drawings with the presented word and final selection, which demanded persistent multiple memory process consistent with working memory.

Successive electro-acupuncture (EA) stimulation applied to bilateral anterior tibial muscles, where Zusanli (ST36) acupoints are located, once a day (30 min) for 3 successive days significantly enhanced splenic natural killer (NK) cell activity in BALB/c mice. The percentage of splenic NK cells, as measured by flow cytometry, was not affected in these mice. Interferon (IFN)-gamma level in splenic aqueous extract, prepared from the ST36 acupoint-stimulated mice, was significantly higher than that of the controls. In vivo treatment with neutralizing monoclonal antibody against mouse IFN-gamma completely abrogated the increase in splenic NK cell activity induced by ST36 acupoint stimulation. The same stimulation also significantly increased the concentration of splenic beta-endorphin, which coincided with the significant increase in splenic IFN-gamma production. Pre-administration of 10 mg/kg naloxone before initiation of EA stimulation every day reduced the enhancements of NK cell activity and IFN-gamma level. These observations strongly suggest that endogenous IFN-gamma mediates the up-regulation of NK cell activity by EA stimulation at the ST36 acupoints. Furthermore, endogenous beta-endorphin secreted by EA stimulation also plays an important role in the up-regulation of NK cell function, which may be realized through regulating IFN-gamma production.

We assessed the faculty of confrontation naming and word fluency of the 11 patients afflicted with frontal lobe infarction or hemorrhage. All the patients were right-handed and manifested transcortical motor aphasia due to cerebrovascular diseases. We carried out the Western Aphasia Battery, and we adopted V-A; the naming task involved confrontation naming of 20 objects, and V-B; the word fluency task involved the naming as many animals as possible in a one minute period. Six patients who have lesions in the left medial frontal lobe performed excellency in the confrontation naming task but exhibited poor word fluency, and 5 patients who have lesions in the left dorso-lateral frontal lobe performed poorly in both tasks. This results suggests that the left dorso-lateral frontal lobe is important in confrontation naming, while the left medial frontal lobe is important in word fluency. Mushiake et al. (1991) showed that the premotor area was involved in visually guided sequential movements, and the supplementary motor area was involved internally determined sequential movements in primates. Regarding language function as analogous to movement, confrontation naming is analogous to visually guided movements and word fluency is analogous to internally determined movements. Thus, our results suggest that the functional difference between the left medial frontal lobe, which includes the supplementary motor area, and the left dorso-lateral frontal lobe, which includes the premotor area, which was demonstrated in primates for movement is also true of language function in humans.

Mitochondrial DNA (mtDNA) control regions from 40 Japanese wild boars were examined by direct sequencing after amplification by PCR. From the DNA sequences obtained, we found eight haplotypes, whose differences arose via transitions. The geographical distribution of these different haplotypes indicated that wild boar populations inhabited limited areas and that there was some restricted gene flow between local populations. Eight mtDNA haplotypes from Eastern and Western domestic pigs and the Ryukyu wild boar were also analyzed as references to those from Japanese wild boars. The cluster analyses of the control-region sequences showed that those from Japanese wild boars belong to the Asian type as do those from Eastern domestic pigs and the Ryukyu wild boar, which differed from the European type (Western domestic pigs).

An autopsy case of meningeal spreading of glioblastoma multiforme (GBM) probably originating in the cervical cord was reported. In contrast to autopsy findings, main symptoms were similar to subacute meningitis, and any signs of myelopathy could not be detected during the clinical course. The patient was a 22-year-old man who was hospitalized because of a 2-week history of progressive headache following cough and slight fever. Vomiting and somnolence, developing 5 days before admission, were improved the day after a lumbar puncture performed at another hospital. On admission, meningeal signs, mild right abducens palsy, and depressed deep tendon reflexes were detected. There was no muscle weakness, sensory loss, or Babinski sign. Lumbar puncture yielded CSF with an opening pressure of 280 mmH2O, 21 mononuclear cells/mm3, a protein level of 645 mg/dl, and a glucose level of 7 mg/dl. Cytology for malignancy and multiple cultures were negative. Brain CT scan showed mild hydrocephalus and swelling of the brainstem and cerebellum. Intravenous administration of antimicrobial drugs was started and ventriculoperitoneal shunt surgery was performed. During the third hospital week, however, meningeal signs progressed and somnolence reappeared, followed by progressive multiple cranial neuropathy and polyradiculopathy characterized by flaccid tetraparesis, muscle atrophy, and sensory impairment without a level. Babinski sign could not be detected. MRI revealed an intramedullary lesion in the lower cervical cord, swelling of the brainstem, cerebellum, spinal cord and nerve roots, and a diffuse or nodular thickning of leptomeninges. Repeated CSF cytology disclosed atypical cells. Examinations for extraneural malignancies were negative. During the 9th hospital week, flaccid tetraplegia progressed and stupor developed, and the patient died 2 weeks later. The pathological study was limited to the brain. The brain showed a diffuse opalescent thickening of the leptomeninges, especially over the ventral aspect of the brainstem and cerebellum, where the blood vesseles and cranial nerves were obscured. Histological examination revealed the appearance of GBM. The malignant cells filled the subarachnoid space, and to a variable extent penetrated the brainstem and cerebellum along perivascular spaces. Hypertrophied optic tracts and trigeminal nerves were also infiltrated by the cells. However, there were no mass lesions assumed to be primary ones anywhere in the cerebral parenchyma. Therefore, it was thought that GBM primarily growing in cervical cord metastasized to intracranial subarachnoid space by way of the cerebrospinal fluid pathway. Spinal cord GBM usually presents signs of myelopathy from the early stage. The present case was characterized by no signs of myelopathy during the clinical course. It is speculated that the intramedullary GBM, originating near the surface of cervical cord, had been rapidly disseminated into the subarachnoid space up to the intracranial cavity before myelopathy appeared, and caused cranial and spinal nerve roots dysfunction, which covered signs of myelopathy. Cord GBM should be always considered as a differential diagnesis in a case of subacute meningitis.

We report a 48-year-old woman with dentatorubral-pallidoluysian atrophy (DRPLA). She is the only patient in her 15 family members in two generations. She developed cerebellar ataxia and epilepsy at age 43. On admission at 48, she showed mild dementia and choreic movement in her face and extremities as well as truncal and limb ataxia. Routine laboratory examinations were normal. The point mutations in the tRNALys gene of mitochondrial DNA specific for MERRF were not found. A cranial CT scan and MRI showed mild atrophy of the cerebellum and prominent atrophy in the pons, especially in the tegmentum. Although she was thought to have DRPLA from the clinical point of view, absence of family history made the diagnosis difficult. Her parents were healthy until their 80's and died of cerebrovascular diseases and her 5 siblings had no symptoms. Hereditary DRPLA is known as an autosomal dominant disorder, with a high rate of penetrance and low rate of new mutation. According to our recent findings of a CAG repeat expansion in the DRPLA gene, this patient was diagnosed as a sporadic DRPLA. Considering the wide varieties of clinical manifestations, it is essential to examine this gene abnormality for diagnosing sporadic DRPLA.

We report here 3 patients who showed marked improvement of clonic and intentional perseverations following the administration of amantadine. Patient 1 had a subacute encephalitis of unknown etiology. Magnetic resonance imaging documented lesions predominantly in the bilateral putaminal and frontal subcortical areas, and positron emission tomography revealed frontal glucose hypometabolism. Daily amantadine hydrochloride of 200 mg with or without 10 mg of trihexyphenidyl, reduced his clonic and intentional perseverations. The diagnosis of patients 2 and 3 was vascular dementia with multiple subcortical ischemic lesions, and single photon emission CTs showed reduced cerebral blood flow in the frontal lobes. Their clonic perseveration subsided and intentional perseveration disappeared after the administration of 150 mg of daily amantadine hydrochloride. Associated Parkinsonism and confusional state also improved in patient 1, but not in patients 2 or 3. Amantadine increases the pre-synaptic synthesis and release of dopamine, and works as a dopamine system activator. Our findings suggest that the disturbance of dopamine system, especially meso-limbofrontal projection, has some contributions to the perseveration of these patients.

Blood biochemical and nutritional metabolism indices were examined in eight patients who received infusion containing glucose, fructose, and xylitol in a 4:2:1 ratio (group GFX) after liver resection compared with those in six patients who received only glucose (group G). Preoperative patient-selection criteria consisted of a parabolic oral glucose tolerance test level over time, a total activity of coagulation factors II, VII, and X of > or = 60%, and an indocyanine green disappearance rate (ICG K) of > or = 0.13. Total parenteral nutrition (TPN) was started on the 3rd postoperative day. Levels of blood biochemical indices, rapid-turnover proteins, and urinary 3-methylhistidine were measured, and amino acids and nitrogen balance were analyzed preoperatively and on the 2nd, 5th, and 7th postoperative days. In group GFX, serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase levels decreased soon after TPN was begun, being 47 +/- 8 and 84 +/- 14 U/L, respectively, on the 7th postoperative day. This level was significantly lower (p < 0.05) than that in group G on the same day (94 +/- 18 and 141 +/- 22 U/L, respectively). There was no difference between the two groups in levels of rapid-turnover proteins or in Fischer ratio of amino acids. Urinary 3-methylhistidine level decreased soon after TPN in group GFX. Nitrogen balance became positive on the 7th postoperative day in group GFX, whereas it remained negative until the 7th postoperative day in group G.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic intoxication of phenytoin (PHT) is a well known cause of cerebellar atrophy or irreversible cerebellar ataxia. Little attention, on the other hand, is paid for acute PHT intoxication because its clinical signs are believed to be reversible. We here report a patient with acute PHT intoxication, which resulted in irreversible cerebellar ataxia with radiologically definite cerebellar atrophy. A 39-year-old man admitted to our hospital because of cerebellar ataxia and confusional state. He had been treated with PHT for convulsive seizures after receiving craniotomy for left parietal brain abscess 9 years before. The concentration of his serum PHT had been 4 to 7 micrograms/ml because he had frequently omitted taking drug, and the dose of PHT had been increased to 600 mg/day one year before. He had admitted to another hospital 2 months before for left Bell's palsy and had been obliged to take drug regularly. Cerebellar signs and confusion had gradually developed for 7 weeks. On admission to our hospital, he was awake but in severe confusional state with slurred speech and nystagmus. His serum PHT was 86 micrograms/ml, which returned to therapeutic range 2 weeks after the discontinuation of PHT. His consciousness normalized and nystagmus disappeared. However, slurred speech continued and neurological examination revealed postural tremor and severe limb ataxia. During the subsequent 10 months, his cerebellar signs showed minimal improvement. Computed tomographies of his brain on 3rd and 5th month after the onset of his cerebellar dysfunction showed the definite cerebellar atrophy which had not been noted on the CTs 7 months before and 7 weeks after the onset.(ABSTRACT TRUNCATED AT 250 WORDS)

Triethylene tetramine (trien), in increasing dose from 1.0-2.0 g/day to 2.5-3.0 g/day, was used for 4 Japanese patients with Wilson's disease who were intolerant of D-penicillamine (D-PC). Before the treatment, urinary copper excretion (UCE) was 70-96 micrograms/day. UCE increased to 1,512-2,352 micrograms/day on the day of initial administration, and remained at levels between 350-1,100 micrograms/day, thereafter. During 2 months of trien therapy, neurological deficits regressed in three patients, and only slightly in one patient. No adverse effects were observed. These results and the retrospective survey on 17 patients treated with D-PC confirmed that trien is less potent but a safer copper chelating agent than D-PC. The transient aggravation of neurological deficits seen in two patients during the early stage of the treatment suggested that trien, as D-PC, should be started in small doses and gradually increased.

An essential part of gene expression and regulation is the binding of a regulatory protein (transcription factor) to the recognition sequence of the appropriate gene. A novel protein motif for nucleic acid recognition (called 'zinc finger') is one of such transcription factors. A relationship between gene expressions of a transcription factor and heat shock protein (HSP) 70 has been suggested. Possible inductions of mRNA for 'zinc finger' and HSP70 were examined after transient focal ischemia in rat cerebral cortex by Northern blot analysis using a synthetic oligonucleotide probe for 'zinc finger' gene expression, and a human genomic DNA probe for HSP70 gene expression. After 30 min of middle cerebral artery (MCA) occlusion, the rats recovered for 1, 3, 8h, 1, 2, and 7 days (n = 5). Zinc finger gene is normally expressed in rat cerebral cortex, and is induced by transient ischemia with a maximum at 1 h after the reperfusion. In contrast, HSP70 mRNA is not expressed in normal condition, but is greatly induced by transient ischemia with a maximum at 8 h of reperfusion. These results indicate that the gene expression for a transcription factor changes in the early stage of reperfusion after cerebral ischemia before HSP70 induction begins.

Japanese encephalitis viruses (JEV) were well propagated in human glioma cells, 118MGC until the first 24 hrs after virus infection. However, after 24 hrs, virus growth rate was quickly reduced. This unusual pattern of virus growth was different from the cases in others cells, e.g. IMR-32, Vero and C6/36 cells. The fact that actinomycin-D retained the high yields of JEV in 118MGC cells suggests that some suppressing factors against JEV replication are produced in MGC cells. Interestingly, culture fluids of 118MGC cells indicated inhibitory effect to JEV reproduction, but other culture fluids from several cell lines had no effect. This inhibitory effect of the MGC-culture fluids was lost by heat-treatment at 60 C. In addition, the infectivity of JEV was rapidly decreased by the incubation with MGC-culture fluids. These findings suggest that 118MGC cells produce and secret some inhibitory factors against JEV replication.