CSF glutamate/GABA concentrations in pyridoxine-dependent seizures: etiology of pyridoxine-dependent seizures and the mechanisms of pyridoxine action in seizure control.

Several lines of evidence suggest that the binding affinity of glutamate decarboxylase (GAD) to the active form of pyridoxine is low in cases of pyridoxine-dependent seizures (PDS) and that a quantitative imbalance between excitatory (i.e. glutamate) and inhibitory (i.e. gamma-aminobutyric acid, GABA) neurotransmitters could cause refractory seizures. However, inconsistent findings with GAD insufficiency have been reported in PDS. We report a case of PDS that is not accompanied by an elevated cerebrospinal fluid (CSF) glutamate concentration. Intravenous pyridoxine phosphate terminated generalized seizures which were otherwise refractory to conventional anti-epileptic medicines. No seizure occurred once oral pyridoxine (13.5 mg/kg per day) was started in combination with phenobarbital sodium (PB, 3.7 mg/kg per day). The electroencephalogram (EEG) normalized approximately 8 months after pyridoxine was started. The patient is gradually acquiring developmental milestones during the 15 months follow-up period. The CSF glutamate and GABA concentrations were determined on three separate occasions: (1) during status epilepticus; (2) during a seizure-free period with administration of pyridoxine and PB; and (3) 6 days after suspension of pyridoxine and PB and immediately before a convulsion. The CSF glutamate level was below the sensitivity of detection (<1.0 microM) on each of the three occasions; the CSF GABA level was within the normal range or moderately elevated. The CSF and serum concentrations of vitamin B6-related substances, before pyridoxine supplementation, were within the normal range. We suggest that (1) PDS is not a discrete disease of single etiology in that insufficient activation of GAD may not account for seizure susceptibility in all cases and (2) mechanism(s) of anti-convulsive effect of pyridoxine, at least in some cases, may be independent of GAD activation.

Comparison of CT findings with resected specimens after chemoembolization with iodized oil for hepatocellular carcinoma.

OBJECTIVE: We assessed the role of dynamic CT in the evaluation of the efficacy of transarterial chemoembolization with iodized oil for hepatocellular carcinoma. MATERIALS AND METHODS: We examined 41 hepatocellular carcinoma lesions (mean diameter, 5.0 cm) in 40 patients (mean age, 60.6 years) who underwent transarterial injection of iodized oil alone (n = 3) or emulsion of iodized oil and doxorubicin hydrochloride (n = 10) followed by gelatin sponge particles (n = 27) and subsequent hepatectomy. On dynamic CT performed within 3 weeks before oily transarterial chemoembolization and within 4 weeks before surgery, we calculated the rate of necrosis on the basis of the assumption that the portion that retained iodized oil represented necrosis. We also calculated the reduction rate of the tumor. CT findings were compared with pathologic findings of resected specimens. RESULTS: Pathologic specimens and the necrosis rate measured on CT showed a good correlation (r = 0.83) when the portion of tumor that retained iodized oil was considered necrosis. No correlation existed if the portion that retained iodized oil was considered viable. We noted no significant correlation (r = 0.38) between the reduction rate of the tumor and necrosis rate. Also, we noted no correlation (r = 0.52) between the interval between transarterial oily chemoembolization and surgery and the reduction rate of the tumor. CONCLUSION: CT is suitable for the evaluation of the efficacy of oily chemoembolization for hepatocellular carcinoma on the basis of the assumption that the portion of tumor that retains iodized oil is necrotic. The rate of tumor size reduction measured on CT did not correlate with the therapeutic effect of chemoembolization.

Antitumor effects of soybean hypocotyls and soybeans on the mammary tumor induction by N-methyl-n-nitrosourea in F344 rats.

BACKGROUND: Soybeans are reported to have cancer inhibitory effects, probably due to their isoflavones. Soybean hypocotyls are embryo buds of soybeans and contain a higher amount of isoflavones and other factors than soybeans themselves. MATERIALS AND METHODS: The effects of soybean protein and soybean hypocotyls as diets on the development of N-methyl-n-nitrosourea (MNU) induced tumors were examined in female F344 rats. For this trial, 120 animals were used and at 6 weeks of age, groups of 30 animals were fed diets containing casein, soy protein isolate (SPI), 1.5% soybean hypocotyls and 5% soybean hypocotyls. Three weeks later all the animals except the control animals received a first dose (37.5 mg/kg body weight) of MNU by tail vein injection. At 29 weeks of age the animals received a second MNU dose (50 mg/kg body weight). Testing was performed 42 weeks after the first MNU dose. RESULTS: Analysis of cumulative palpable tumor incidence indicated that final tumor development of the SPI diet group and the hypocotyl diet groups was less than that of the casein diet group. Tumors were detected in one or more sites from 9 out of 24 rats in the casein diet group, 5 of 20 rats in SPI diet group, 6 out of 24 rats in the 1.5% hypocotyl diet group and 6 out of 23 rats in the 5% hypocotyl diet group. Pairwise comparisons indicated that the formation of tumors during the experiment was significantly less rapid in the SPI diet group and the hypocotyl diet groups than the casein group. No difference in tumor promotion was observed between the SPI diet group and the soybean hypocotyl diet groups. CONCLUSION: Our results suggest that dietary soybeans and soybean hypocotyls are capable of suppressing tumor promotion.

Inhibition by dietary tea polyphenols of chemical mediator release from rat peritoneal exudate cells.

Male Wistar rats were given purified diets containing safflower (SAF), perilla (PER), or palm (PAL) oils with or without 1% tea polyphenols (TP) for 3 weeks, and chemical mediator releasing activity from rat peritoneal exudate cells (PEC) was measured. Histamine releasing activity was not influenced by TP, while histamine release and intracellular histamine content were significantly increased in the PAL-fed group. On the contrary, leukotriene B4 (LTB4) release was significantly lower in rats fed PER than in those fed SAF and PAL, and TP significantly decreased the release in all fat groups. TP also significantly inhibited the release of LTB5, which was generated only in rats fed PER. TP significantly decreased the proportion of arachidonic acid (AA) in PEC in the SAF-fed group and that of eicosapentaenoic acid (EPA), the precursor of LTB5 in the PER-fed group, but did not influence that of AA in the PAL- and PER-fed group. These results suggest that ingestion of TP improves type I allergic symptom through the inhibition of LT release though the inhibition by TP could not be totally explained by the reduction of substrate fatty acid.

Sensitivity to the house dust mite and airway hyperresponsiveness in a young adult population.

BACKGROUND: The pathogenic mechanisms of airway hyperresponsiveness (AHR) in asthma are unknown and only a few studies have examined the importance of sensitivity to antigens in AHR in young adults. OBJECTIVE: We investigated the correlation between AHR and sensitivity to specific antigens, atopy, history of childhood asthma and spirometry in a young adult population. METHODS: Based on the results of interviews with 447 students at our university, 308 non-smoker students were classified into six groups. Group 1 comprised subjects with intermittent mild bronchial asthma; group 2, subjects with history of childhood asthma; group 3, subjects with atopic disease, and a RAST score for Dermatophagoides farinae (Def) of > or = 2; group 4, normal subjects with a RAST score for Def of > or = 2; group 5, subjects with cedar pollinosis; and group 6, normal subjects. We measured AHR to methacholine (MCh), spirometry, immunoglobulin E-radioimmunosorbent test (IgE-RIST), IgE-radioallergosorbent test to six common antigens, eosinophil cationic protein (ECP), and eosinophil count in peripheral blood in each subject. RESULTS: Airway hyperresponsiveness to MCh did not correlate with IgE-RIST, eosinophil count, or ECP. The highest AHR to MCh was present in groups 1 and 2 and lowest in groups 5 and 6. Multiple regression analysis showed that sensitivity to Def was the only factor that significantly influenced AHR to MCh. Airway hyperresponsiveness to MCh of groups with a RAST score for Def of 0/1 was lower than groups with a RAST score of 2 to 6. Airway hyperresponsiveness to MCh did not correlate with the degree of positivity to Def antigen among positive sensitized groups (RAST score 2 to 6). CONCLUSIONS: Sensitivity to mite antigen may be important in the pathogenesis of AHR and Def is a major contributing antigen in young adults in Japan. Once asthma occurs, AHR remains positive for a long time even after the disappearance of asthma-related symptoms.

A novel SCG10-related gene uniquely expressed in the nervous system.

We have isolated a novel cDNA (HiAT3: hippocampus abundant transcript 3) in the course of screening for genes that are preferentially expressed in neonatal mouse hippocampus using random 3'-directed cDNA sequencing approach. It encodes a 180-aa protein that has high similarity to SCG10, a neuron-specific negative regulator of microtubule dynamics during neurite outgrowth. The expression of HiAT3 is limited to neurons and peaks about 1 week after birth. The identification of HiAT3 suggests that there may be an elaborate destabilizing regulation for microtubule dynamics in neurons in addition to the stabilizing effect of multiple microtubule-associated proteins (MAPs).

[Treatment of hepatocellular carcinoma by segmental SMANCS Lipiodol-TAE].

Segmental SMANCS Lipiodol TAE (Seg. SMANCS Lp-TAE) using SMANCS was used to treat HCC in 58 patients and was evaluated in comparison with Seg. Lp-TAE using Epirubicin performed in 50 patients with respect to the course of atrophy of the embolized area, recurrence rate and side effects. On serial CT (Lp-CT) performed after TAE, in cases with P type in which the tumor is present in the periphery of the embolized area and showing Type I homogeneous accumulation of Lp within the tumor, the incidence of atrophy in the embolized area including the tumor was high and the recurrence rate was low. Although no significant difference in the recurrence rate was noted between the groups in which SMANCS and EPI were used, there were more cases with marked atrophy and a lower recurrence rate in the former. No difference was found in post-procedural side effects such as fever between the two groups, while hypotension was rarely observed during the procedure in the group in which SMANCS was used and was easily managed with intravenous steroids. The present results suggest that Seg. SMANCS Lp-TAE is an effective local treatment for HCC limited to a subsegment or segment.

Optimal lipiodol volume in transcatheter arterial chemoembolotherapy for hepatocellular carcinoma: study based on lipiodol accumulation patterns and histopathologic findings.

To clarify the optimal dose of Lipiodol (Andre Guerbet, Aulnay-sous-Bois, France) during Lipiodol-transcatheter arterial embolization (L-TAE) and segmental L-TAE used to treat hepatocellular carcinoma, we studied the relationship between the volume of Lipiodol used during these procedures and the necrosis rates in resected specimens, as well as the correlation with the Lipiodol accumulation pattern based on the computed tomography findings (L-CT) and the volume of Lipiodol in resected and nonresected cases after L-TAE or segmental L-TAE. The L-CT and the dose of Lipiodol injected (mL) were studied correlatively in 198 cases (28 resected cases and 170 nonresected cases; tumor size < or = 5 cm in 52 cases and > 5 cm in 118 cases) that underwent L-TAE and in 80 cases (14 resected cases and 66 nonresected cases, tumor size < or = 5 cm in 52 cases and > 5 cm in 14 cases) that underwent segmental L-TAE. The L-CT was classified into four types: type I, homogeneous accumulation (type Ia, accumulation around the tumor; type Ib, no accumulation around the tumor); type II, partial defect; type III, sporadic accumulation; and type IV, punctate or no accumulation. In the 42 resected cases (L-TAE, 28 cases; segmental L-TAE, 14 cases), type I was seen in 68% (Ib, 100%) of the L-TAE cases and 93% (Ia, 79%; Ib, 14%) of the segmental L-TAE cases. The necrosis rate of the cases with type Ib L-CT was 90% to 100%, and all type Ia cases showed complete necrosis. In the 236 nonresected cases (L-TAE, 170 cases; segmental L-TAE, 66 cases), the volume of Lipiodol injected correlated with the L-CT type. In the L-TAE cases with a tumor size < or =5 cm, the frequency of the injected Lipiodol volume (D) being greater than the tumor diameter (d) (D > or = d) was 90%, and 87% of the cases with D > or = d showed type Ib L-CT. In the group whose tumor diameter (d) was more than 5 cm, the frequency of D > or = d was 25%, and 70% of the cases of D > or = d were type Ib. The frequency of D < d was 75%, and in 13% of these cases the L-CT was type Ib and the maximum dose was approximately 10 mL. In segmental L-TAE using the same dose of Lipiodol as in L-TAE, the frequency of D > or = d was 83%, and 93% of those cases showed type I, including 85% of type Ia. There was a correlation between the L-CT type and the necrosis rate, and type I, especially Ia in segmental L-TAE, showed complete necrosis in almost all cases. In L-TAE, standards for the optimal dose of Lipiodol are thought to be as follows: D > or = d in cases with d < or = 5, and slightly D < d and 10 mL maximally in cases with d > 5. In segmental L-TAE using the same dose of Lipiodol as in L-TAE, enhancement of the therapeutic effect was seen compared with L-TAE. This is surmised to have been because of the higher Lipiodol volume with anticancer agents per unit volume of the tumor in segmental L-TAE.

Effect of tea polyphenols on histamine release from rat basophilic leukemia (RBL-2H3) cells: the structure-inhibitory activity relationship.

We studied the effect of tea polyphenols on histamine release from rat basophilic leukemia (RBL-2H3) cells. Among tea polyphenols, (-)- epigallocatechin gallate (EGCG) most strongly and dose-dependently inhibited histamine release from cells stimulated with a calcium ionophore, A23187. (-)-Epigallocatechin (EGC) and (-)-epicatechin gallate (ECG) with a triphenol residue moderately inhibited histamine release, whereas diphenolic (+)-catechin (C) and (-)-epicatechin (EC) did not. The magnitude of the inhibitory effect was in the order EGCG > ECG > EGC. Among simple polyphenols, the triphenol compounds, pyrogallol (PG) and gallic acid (GA) exerted inhibitory activity, but the diphenols, pyrocatechol, hydroquinone, and resorcinol did not. In addition, the mixture of PG and GA inhibited histamine release as strongly as EGCG with two triphenol residues. Similarly, they inhibited histamine release induced by IgE-antigen complex stimulation more efficiently than that induced by A23187 stimulation. EGCG did not inhibit the increase of intracellular Ca2+ in RBL-2H3 cells stimulated with A23187 or IgE antigen. These results indicate that the triphenol structure plays an important role in the inhibitory activity of tea polyphenols. Their activity seemed to be exerted through the metabolic events occurring after the elevation of intracellular Ca2+ concentration.

Effects of gamma-linolenic acid and its positional isomer pinolenic acid on immune parameters of brown-Norway rats.

Male Brown-Norway rats given purified diets containing safflower oil (SFO, linoleic acid, 18:2 n-6), evening primrose oil (EPO, gamma-linolenic acid, 6,9,12- 18:3 n-6) or Korean pine seed oil (PSO, 5,9,12- 18:3) at the 10% level were immunized twice with intraperitoneal ovalbumin, on days 14 and 35 of the feeding diets, and killed one day after the second booster. The relative population of CD4+ T-lymphocytes in the spleen was significantly lower in rats fed SFO than in those fed EPO or PSO, while that of CD8+ subsets remained unchanged. There was a significant increase in the splenic production of IgG and IgE in the PSO group compared to the SFO group, while EPO significantly increased IgE. The periodical response patterns of the serum levels of IgG and IgE varied depending on the source of dietary fats, and the initial rise of total immunoglobulins tended to be higher in the EPO group. The release by peritoneal exudate cells of histamine was comparable among three groups irrespective of saturation by calcium ionophore A23187, while PSO significantly increased leukotriene B4 production. These observations not only indicate specific roles of gamma-linolenic acid but also diverse influences of different octadecatrienoic acids in various immune measurements.

Inhibitory effect of tea polyphenols on histamine and leukotriene B4 release from rat peritoneal exudate cells.

The effect of tea polyphenols on the release of chemical mediators, histamine and leukotriene B4 (LTB4), from rat peritoneal exudate cells (PEC) was studied. Among polyphenols, (-)-epigallocatechin gallate (EGCG) most strongly inhibited the histamine release from the cells stimulated with a calcium ionophore, A23187 or compound 48/80. Though (+)-catechin (C) and (-)-epicatechin (EC) had no effect, (-)-epigallocatechin (EGC) and (-)-epicatechin gallate (ECG) moderately inhibited the histamine release. Similarly, EGCG, ECG, and EGC inhibited LTB4 release from PEC, whereas C and EC were not effective. The magnitude of the inhibitory effect on the release of these mediators of tea polyphenols was in the order of EGCG > ECG > EGC. These results indicated an important role of the triphenol structure in the inhibitory activity. Therefore, the possible antiallergic effect of tea polyphenols can be expected.

[Chemoembolization therapy in small hepatocellular carcinoma].

As chemoembolotherapy (TAE) for relatively small hepatocellular carcinoma (HCC) including small HCC of less than 2 cm in diameter, which is restricted to a sub-subsegment, subsegment or segment of the liver, segmental Lp-TAE using Lipiodol (Lp) mixed with an anticancer agent, which includes subsegmental and sub-sub-segmental therapy, not restricted to the tumor-bearing segment, is expected to move to the forefront of HCC treatments and also causes fewer complications and less strain to the patient. Of the 15 cases that underwent surgery following segmental Lp-TAE, complete necrosis was found histopathologically in more than 80% of the main tumor, satellite nodules in the embolized region and areas of capsular invasion. Its therapeutic efficacy for 51 cases with tumors smaller than 3 cm was comparable to that of surgery.

Valproic acid overdose and L-carnitine therapy.

A healthy, nonepileptic 16-month-old child ingested a massive overdose (approximately 4000 mg) of valproic acid (VPA). Upon admission to the hospital, he was in a deep coma and had generalized hypotonicity and no response to pain. His serum and urinary concentrations of VPA were 1316.2 and 3289.5 micrograms/mL, respectively. Urinary concentrations of the beta-oxidation metabolites of VPA were low, whereas concentrations of omega- and omega 1-oxidation metabolites were high. Moreover, 4-en-valproate (a potential hepatotoxin) was detected in the urine. Gastric lavage and general supportive measures were undertaken, including intravenous infusion to increase urine output and oral L-carnitine to correct hypocarnitinemia. Subsequently, the beta-oxidation metabolites increased, the omega- and omega 1-oxidation metabolites decreased, and 4-en-valproate was no longer detected. The patient recovered completely and was discharged on the eighth hospital day without any sequelae. This case suggests that enhanced drug excretion and L-carnitine supplementation may prevent potentially fatal hepatic dysfunction after VPA overdose.

Rotundial, a new natural mosquito repellent from the leaves of Vitex rotundifolia.

A new natural mosquito repellent was isolated from fresh leaves of Vitex rotundifolia. Its structure was elucidated by an extensive NMR spectral analysis to be a cyclopentene dialdehyde named rotundial. This compound possessed potent repelling activity against Aedes aegypti.

Combined transjugular intrahepatic portosystemic shunt and segmental Lipiodol hepatic artery embolization for the treatment of esophagogastric varices and hepatocellular carcinoma in patients with cirrhosis: preliminary report.

PURPOSE: To evaluate the feasibility of combining placement of a transjugular intrahepatic portosystemic shunt (TIPS) and transcatheter hepatic segmental artery chemoembolization with Lipiodol (Seg-Lp-TAE) in patients with cirrhosis, esophagogastric varices, and hepatocellular carcinoma (HCC). METHODS: Five patients with bleeding or large, high-flow esophagogastric varices and HCC were treated by TIPS and Seg-Lp-TAE. RESULTS: The mean portosystemic pressure gradient decreased from 20.8 cm H2O to 7.8 cm H2O after TIPS. The direct portogram and endoscopic examination revealed reduction of varices. At 6 months, one shunt had functionally occluded and could not be reopened; the other TIPS remained functional. Follow-up CT and the changes of alpha fetoprotein indicated effective therapy of Seg-Lp-TAE for HCC. Four patients are in stabile clinical condition at 9, 6, 1, and 1 months after the combined therapy; one died after 14 months due to decompensated liver cirrhosis. CONCLUSION: The combined therapy of TIPS and Seg-Lp-TAE will become a new interventional approach for patients with HCC and esophagogastric varices.

Segmental transarterial chemoembolization with Lipiodol mixed with anticancer drugs for nonresectable hepatocellular carcinoma: follow-up CT and therapeutic results.

We developed segmental Lp-TAE, which is transcatheter hepatic sub-subsegmental, subsegmental, or segmental chemoembolization using Lipiodol introduced into the tumor-bearing hepatic sub-subsegment, subsegment, or segment as the target area. A total of 98 patients with nonresectable hepatocellular carcinoma (HCC) undergoing segmental Lp-TAE (Seg-Lp-TAE) were studied, and the relationship between the CT pattern observed after Seg-Lp-TAE (Seg-Lp-CT) and the therapeutic results obtained in those patients was evaluated. Seg-Lp-CT was classified into four types (type I, homogeneous; type II, defective; type III, inhomogeneous; and type IV, only slight accumulation, if any) according to the Lipiodol accumulation pattern observed after Seg-Lp-TAE. The cumulative nonrecurrence rates of type I were higher than those of types II-IV. The cumulative survival rates of type Ia, in which Lp accumulation is also seen around the main tumor, were the highest (93.8% at 1 year, 85.9% at 2 years, 85.9% at 3 years, and 57.3% at 4 years). The cumulative survival rates achieved with Seg-Lp-TAE were 89.2% at 1 year, 69.4% at 2 years, 58.9% at 3 years, 44.0% at 4 years, and 30.2% at 5 years, which were higher than those achieved with conventional Lp-TAE. Seg-Lp-TAE is very useful in the treatment of HCC limited to one sub-subsegment, subsegment, or segment, and it is important to choose sub-subsegmental, subsegmental, or segmental Lp-TAE on the basis of the size and site of the tumor as well as the type and the number of feeding arteries.

Segmental transcatheter hepatic artery chemoembolization with iodized oil for hepatocellular carcinoma: antitumor effect and influence on normal tissue.

PURPOSE: Segmental transcatheter arterial embolization (TAE) with use of iodized oil mixed with an anticancer drug, followed by injection of gelatin sponge particles, was undertaken to evaluate its antitumor effect and its influence on normal tissue in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Histologic findings in 12 patients who underwent hepatectomy after segmental TAE were compared with findings on plain radiographs and computed tomographic (CT) scans. Visualization of the portal veins contiguous to the tumor on radiographs and the pattern of iodized oil accumulation in the tumor and vicinity on CT scans after TAE were assessed. RESULTS: Complete necrosis of the tumor was achieved in 10 cases (83%), while complete necrosis of daughter nodules and capsular invasion was observed histologically in eight of these 10 patients (80%). The degree of tumor necrosis correlated with the pattern of iodized oil accumulation in and near the tumor. Partial necrosis of normal tissue near the tumor correlated with accumulation of iodized oil. CONCLUSION: Segmental TAE may be an excellent therapeutic method for treatment of HCC that is localized in one or a few segmental or subsegmental regions.

The hair-organ relationship in mercury concentration in contemporary Japanese.

The hair-organ relationship of mercury concentration was investigated in 46 autopsy samples in Tokyo, Japan. Hair mercury levels were highly significantly correlated with organ Hg levels in the cerebrum, cerebellum, heart, spleen, liver, kidney cortex, and kidney medulla, when the total mercury or methyl mercury value in the organ was compared with the hair total mercury or organic mercury, respectively. When the inorganic mercury value was tested, significant correlations remained, with weaker coefficients in all the organs but the spleen. Stepwise multiple regression analysis evidenced that the hair organic mercury value was the major explanatory variable for the organ total mercury or organ methyl mercury value in all the organs. To explain the organ inorganic mercury value, the hair organic mercury value was the major variable for the cerebrum and kidney (both cortex and medulla), the hair inorganic mercury value was the major variable for the cerebellum and heart, and the hair phosphorous and hair organic mercury were the major variables for the liver; no explanatory variable existed for the spleen. Auxiliary explanatory variables accounted for the organ total mercury and inorganic mercury levels, among which the hair selenium value was conspicuous with negative regression coefficients.

Segmental embolotherapy for hepatic cancer: keys to success.

Transcatheter chemoembolization using Lipiodol (Lp) mixed with chemotherapeutic agents followed by Gelfoam particle injection only to the tumor-bearing hepatic segment (segmental Lp transcatheter hepatic artery embolization) (TAE) was applied to more than 100 patients with hepatocellular carcinoma and metastatic liver cancer. For segmental Lp-TAE, knowledge of the variations of intrahepatic arterial anatomy is important. Furthermore, the catheters and guidewires, volume of Lp, kinds and dose of chemotherapy, preparation of the mixture of Lp and chemotherapy (Lp-emulsion), method of injection of Lp-emulsion and Gelfoam particles, as well as the follow-up computed tomography examination are key items to the success of the procedure and are reviewed.

Symmetrical thalamic lesions on CT in influenza A virus infection presenting with or without Reye syndrome.

In Reye encephalopathy, diffuse brain swelling is a well known CT finding, but focal CT lesions have not been documented. We report 2 children with Reye encephalopathy and 2 children with non-Reye encephalopathy both associated with influenza A virus infection in whom symmetrical low density lesions of the thalamus and brainstem were detected on CT. These symmetrical low density lesions were present in the acute phase and decreased in size within a few weeks in all, and are still seen 2 years later as clearly defined small round areas in 3 surviving patients. Paired influenza A virus titers in blood showed 4-fold or more increase in all. Myelin basic protein (MBP) in CSF was increased in 2 of the 3 subjects studied. Liver biopsy showed diffuse lipid droplet infiltration in 2, focal infiltration in 1, and normal morphology in 1. The above data suggest that the symmetrical low density lesions were associated with influenza A virus infection, most likely consisting of edema, demyelination, and necrosis. We suspect that there is a continuum of Reye syndrome and virus-associated encephalopathy with significant overlap.