Mitochondrial toxins potentiate hydroxyl radical production in rat striatum during carbon monoxide poisoning.

Hydroxyl radical (•OH) production in the rat striatum during carbon monoxide (CO) poisoning, which inhibits complex IV, was enhanced synergistically by malonate, a mitochondrial complex II inhibitor, but not N-methyl-4-phenylpyridinium or NaCN, complex I and IV inhibitors, respectively. No such enhancement appeared in the case of NaCN combined with malonate. Intrastriatal dopamine, which is involved in •OH production by malonate, did not synergistically enhance CO-induced •OH production. Diphenyleneiodonium, a nonselective NADPH oxidase inhibitor, partly suppressed the potentiation of CO-induced •OH production by malonate. Impairment of mitochondrial functions might potentiate oxidative stress and intensify CO toxicity in the brain.

[Relationship between the nutritional status and the oral function among community-dwelling dependent elderly persons].

AIM: We herein examined the relationship between the nutritional status and the oral function among community-dwelling dependent elderly persons. METHODS: The subjects included 218 community-dwelling dependent elderly persons. The data were collected via questionnaires, including information regarding age, sex, the level of care required, nutritional status and swallowing function. We used the Mini Nutritional Assessment-Short Form (MNA-SF) to measure the nutritional status and the Dysphagia Risk Assessment for the Community-dwelling Elderly (DRACE) to evaluate the swallowing function. The tongue pressure and the labial closure force were measured using a tongue pressure measurement system (JMS Co. Ltd., Hiroshima, Japan) and the Lip de Cum (Cosmo-Instruments Co, Ltd, Tokyo, Japan). RESULTS: The mean MNA-SF score was 10.07±2.58. The mean DRACE score was 4.39±3.80. The mean tongue pressure was 23.89±10.61 kPa. The mean labial closure force was 10.17±6.04 N. The results of bivariate regression analyses showed that there was a poor correlation between the MNA-SF and the DRACE, tongue pressure and labial closure force. Furthermore, the multiple regression analysis with the MNA-SF as the dependent variable revealed a correlation between the DRACE and labial closure force (p<0.01, R(2)=0.02). CONCLUSIONS: Our results suggest that the nutritional status is significantly related to the swallowing function and labial closure force among community-dwelling dependent elderly persons.

[The association between health-related quality of life and voice as evaluated by an acoustic analysis in elderly Japanese nursing home residents].

PURPOSE: We carried out a cross-sectional study investigating the association between health-related quality of life (HRQOL) and voice, as evaluated by an acoustic analysis, in elderly residents of a nursing home. METHODS: The HRQOL of 61 elderly nursing home residents (mean age: 82.1±8.3 years) was assessed via the SF-8 Health Survey questionnaire, Japanese version (SF-8). The subjects' voices were recorded and analyzed by a voice assessment software program, which calculated the pitch period perturbation quotient (PPQ), amplitude perturbation quotient (APQ), and noise-to-harmonic ratio (NHR). RESULTS: Subjects who scored under the 25th percentile on general health (GH), vitality (VT), or physical summary (PCS) in the SF-8 showed significantly higher PPQ, APQ, and NHR scores in comparison to their counterparts (p<0.05). After adjustment for age, lower GH scores were found to be associated with higher PPQ, APQ, and NHR scores; lower VT scores were associated with higher APQ and NHR scores; and lower PCS scores were associated with higher APQ and NHR scores (p<0.05). CONCLUSION: The results of the acoustic analysis indicated that voice was associated with HRQOL in the elderly nursing home residents of the present study. Among the acoustic parameters that were analyzed, PPQ, APQ, and NHR may be an influential factor that can be used to assess HRQOL, independently of the effects of age, in elderly individuals.

[Relationship between the swallowing function and the health-related QOL among community-dwelling dependent elderly persons].

AIM: We examined the relationship between the swallowing function and the health-related QOL (quality of life) among community-dwelling dependent elderly persons. METHODS: The subjects included 191 community-dwelling dependent elderly persons. Data were collected via questionnaires, including information regarding age, gender, the level of care required, post-cerebrovascular disease, the health-related QOL and the swallowing function. We used the SF-8 to measure the health-related QOL and the DRACE (Dysphagia Risk Assessment for the Community-dwelling Elderly) to evaluate the swallowing function. RESULTS: The average DRACE score was 4.29±3.81. In addition, the swallowing risk was found to be related to the SF (social functioning) and MH (mental health) subscales of the SF-8. CONCLUSIONS: Our results suggest that the swallowing function is significantly related to the health-related QOL among community-dwelling dependent elderly persons.

[Oral diadochokinesis among Japanese aged over 55 years: analysis of standard values].

AIM: We investigated oral diadochokinesis (OD) among 212 Japanese aged over 55 years to assess the standard values of articulation ability. METHODS: Each subject repeatedly produced the OD syllables /pa/, /ta/, and /ka/. Subjects were divided into three age-groups (55-64 years, 65-74 years, and over 75 years) and by gender to compare the number of OD syllables per second. We also calculated the lower limit of values that determined the standard range for OD syllables. RESULTS: The number of all OD syllables in the over-75 age-group was significantly lower than in the 55-64 group. The number of OD /pa/ syllables in the over-75 group was significantly lower than in the 65-74 group. The number of OD /ta/ syllables in the 65-74 group was significantly lower than in the 55-64 group. The lower limit of the standard values for OD /pa/, /ta/, and /ka/ was, respectively, as follows: 4.9, 4.7, and 4.5 times in the 55-64 group; 3.8, 4.1, and 3.7 times in the 65-74 group; and 3.8, 3.3, and 2.6 times in the over-75 group. Among women, the number of OD /pa /, /ta/, and /ka/ syllables was significantly lower in the over-75 group than in other age-groups. CONCLUSIONS: We demonstrated that the lower limit of standard OD values is a means of assessing articulation in elderly subjects. We found that OD /ta/ tends to decrease from age 65 years. The decline in articulation ability clearly begins earlier in women than in men.

[Relationship between comprehensive quality of life and factors related to chewing and swallowing function among community-dwelling elderly individuals].

AIM: The purpose of the present study was to examine the relationship between comprehensive quality of life (QOL) and some factors regarding chewing and swallowing function among community-dwelling elderly individuals. METHODS: The subjects were 675 independent elderly persons residing in the northern area of Miyazaki Prefecture, and we obtained the self-administered questionnaires from 545 elderly people. We used "active scale for the elderly (ASE)" and "dysphagia risk assessment for the community-dwelling elderly (DRACE)" to evaluate their comprehensive QOL and function of chewing and swallowing, respectively. Furthermore, we examined some factors such as age, gender, subjective satisfaction with diet and verbal communication. RESULTS: The score of ASE showed a significant decline with age (p<0.01) while the DRACE score increased significantly with age (p<0.01). Pearson's correlation coefficients revealed that the ASE score was significantly related to all of the factors regarding regulation of food intake. Partial correlation coefficients adjusted for age also revealed the same tendency. From the multiple regression analysis, subjective satisfaction with verbal communication, DRACE score, age and appetite were extracted as factors influencing ASE score (adjusted R(2)=0.43, p<0.01). CONCLUSION: Among independent elderly persons residing in the community, the comprehensive QOL was significantly related to factors such as subjective satisfaction with verbal communication, dysphagia risk, age, and appetite.

[Association between activities of daily living and oral diadochokinesis among Japanese elderly individuals in a nursing home].

AIM: We studied the association between the activities of daily living (ADL) and oral diadochokinesis (OD) among 84 Japanese elderly individuals residing in a nursing home. METHODS: We assessed OD in terms of speech and articulation. Each subject repetitively produced the syllables /pa/, /ta/, /ka/ and the sequence /pataka/. We also evaluated comprehensive ADL (basic, BADL; instrumental, IADL; and communicative, CADL) based on the criteria of the ADL-20 and intellectual ability using the revised Hasegawa Dementia Scale (HDS-R). We classified types of OD into a hypokinesia group (less than 3 times per second for OD /pa//ta//ka/ or less than once per second for OD /pataka/) and a repetition exercise maintenance group (more than 3 times per second for OD /pa//ta/ /ka/ or more than once per second for OD /pataka/). RESULTS: After adjusting for age, sex, and HDS-R score, the ADL-20 total score of the hypokinesia group was significantly lower than that of the maintenance group for OD (/pa/ and /pataka/) (p<0.01). The BADL for mobility (BADLm) score in the hypokinesia group for all OD sections was significantly lower than that in the maintenance group (p<0.05). The BADL for self-care score (BADLs) in the hypokinesia group for OD (/pataka/) was lower than that in the maintenance group (p<0.01). The CADL score in the hypokinesia group for OD (/pa/) was lower than that in the maintenance group (p<0.05). CONCLUSION: A decline in OD may have been associated with a decline in ADL in our subjects, suggesting that the rate of decline in OD may affect overall ADL in elderly individuals.

Existence of a threshold for hydroxyl radical generation independent of hypoxia in rat striatum during carbon monoxide poisoning.

We examined the role of hypoxia in the carbon monoxide (CO)-induced generation of the hydroxyl radical (•OH) in the striatum, which could contribute to brain damage due to CO poisoning. Exposure of free-moving rats to 1,000 and 3,000 ppm CO or 8 and 5% O2 for 40 min caused concentration-dependent hypoxic conditions in terms of carboxyhemoglobin (COHb), deoxyhemoglobin, oxyhemoglobin, and O2 contents in arterial blood. The hypoxic conditions seemed comparable between 3,000 ppm CO and 5% O2, although alterations of pH and partial O2 pressure (PO2) were complex and concentration independent. In the striatum, CO and low O2 decreased tissue PO2 levels in a concentration-dependent and concentration-independent manner, respectively, but levels at the end of exposure were comparable among all groups. This was also the case for the increase in striatal blood flow. Although the increases in extracellular glutamate (excitatory), taurine (inhibitory), and alanine (non-neurotransmitter), in the striatum in response to CO and low O2 were complex, 3,000 ppm CO and 5% O2 had comparable effects. Thus, 3,000 ppm CO and 5% O2 seemed to induce comparable hypoxic conditions. Nevertheless, the former more strongly stimulated (•OH generation in the striatum than the latter. In addition, in contrast to low O2 which caused a concentration-dependent increase in (•OH, 1,000 ppm CO had no effect. The findings suggest that striatal •OH generation due to CO poisoning may be independent of hypoxia per se and that a threshold might exist.

Relationship between Psychological Status and Health Behaviors during the Coronavirus Disease Pandemic in Japanese Community-Dwelling Older Adults.

The coronavirus disease (COVID-19) continues to be a widespread pandemic. We investigated the relationship between anxiety/stress and health behaviors during the COVID-19 pandemic in homebound Japanese older adults during January and February 2021. We surveyed 1507 community-dwelling, older Japanese adults using a self-administered questionnaire on primary attributes, including family structure, evaluation of psychological anxiety/stress, and health behaviors. Participants were divided into four anxiety/stress groups based on the frequency of experiencing anxiety/stress, and their association with health behaviors was analyzed using bivariate and multivariate analyses. Responses were received from 469 (31.1%) respondents. In the bivariate analysis, age and family structure were significantly associated with anxiety/stress (p < 0.01). The health behaviors significantly associated with anxiety/stress were walking, balanced eating habits, limited snacking, regular lifestyle, and dental visits. Logistic regression analysis was performed using the variables in the bivariate analysis that showed a significant association with anxiety/stress status as independent variables. Finally, age and dietary habits were significantly associated with anxiety/stress status. No significant associations were found between any other variables. Among older adults living in the rural areas of Japan during the COVID-19 pandemic, anxiety/stress status was significantly associated with age and dietary habits but not with other health behaviors.

Blockade of the renin-angiotensin system suppresses hydroxyl radical production in the rat striatum during carbon monoxide poisoning.

Oxidative stress has been suggested to play a role in brain damage during carbon monoxide (CO) poisoning. Severe poisoning induced by CO at 3000 ppm, but not 1000 ppm, enhances hydroxyl radical (˙OH) production in the rat striatum, which might be mediated by NADPH oxidase (NOX) activation associated with Ras-related C3 botulinum toxin substrate (Rac) via cAMP signaling pathway activation. CO-induced ˙OH production was suppressed by antagonists of angiotensin II (AngII) type 1 receptor (AT1R) and type 2 receptor (AT2R) but not an antagonist of the Mas receptor. Suppression by an AT1R antagonist was unrelated to peroxisome proliferator-activated receptor γ. Angiotensin-converting enzyme inhibitors also suppressed CO-induced ˙OH production. Intrastriatal AngII at high concentrations enhanced ˙OH production. However, the enhancement of ˙OH production was resistant to inhibitors selective for NOX and Rac and to AT1R and AT2R antagonists. This indicates a different mechanism for ˙OH production induced by AngII than for that induced by CO poisoning. AT1R and AT2R antagonists had no significant effects on CO-induced cAMP production or ˙OH production induced by forskolin, which stimulates cAMP production. These findings suggest that the renin-angiotensin system might be involved in CO-induced ˙OH production in a manner independent of cAMP signaling pathways.

Hydroxyl radical generation dependent on extracellular ascorbate in rat striatum, as determined by microdialysis.

Ascorbate (AA), an antioxidant substance known as vitamin C, exists in the brain at a high concentration, although transfer into the brain after systemic administration of AA itself is limited. Intraperitoneal administration of dehydroascorbate (DHA) resulted in a rapid and progressive increase in extracellular AA in rat striatum in a dose-dependent manner. DHA administration increased 2,3- and 2,5-dihydroxybenzoate (2,3- and 2,5-DHBA) formation from salicylate in parallel with the increase in extracellular AA. Intrastriatal administration of active AA oxidase (AAO), but not the inactivated enzyme, completely suppressed the increase in 2,3- and 2,5-DHBA formation after the DHA administration. These findings suggest that extracellular AA might stimulate hydroxyl radical (OH) generation in the striatum. This is supported by the observation of dose-dependent OH generation upon intrastriatal administration of AA itself. In addition, deferoxamine, an iron chelator, decreased basal 2,3- and 2,5-DHBA formation and strongly, though not completely, suppressed the DHA-induced increase of 2,3- and 2,5-DHBA formation. Therefore, increased extracellular AA might function as a prooxidant and stimulate OH generation in cooperation with iron in rat striatum.

Hydroxyl radical production via NADPH oxidase in rat striatum due to carbon monoxide poisoning.

Severe poisoning induced by carbon monoxide (CO) at 3000 ppm, but not 1000 ppm, enhances hydroxyl radical (OH) production in rat striatum, which is greatly susceptible to inhibitors of NADPH oxidase (NOX), including diphenyleneiodonium (DPI), but not xanthine oxidase. The quantitative real-time PCR confirmed the previous microarray finding that CO at 3000 ppm, but not 1000 ppm, enhanced mRNA expression of dual oxidase 2 (DUOX2), but not DUOX1, in rat striatum, both of which are NOX family members producing reactive oxygen species. However, the protein levels of DUOX2 and DUOX1 were decreased by 3000 ppm CO. The CO-induced OH production was resistant to chelerythrine and SB230580, inhibitors of protein kinase C and p38MAPK, respectively, which are reported to mediate activation of DUOX1 and DUOX2, respectively. Deprivation of Ca2+, which is required for activation of both DUOXs, failed to suppress the CO-induced OH production. The CO-induced OH production was strongly suppressed by EHT1864, an inhibitor of Rac (Ras-related C3 botulinum toxin substrate), which is a factor for activation of NOX1, NOX2 and NOX3 (the role of Rac on Nox3 activation is controversial) as much as that was suppressed by DPI. In addition, EHT1864 in combination with DPI further suppressed the CO-induced OH production. There were no significant changes in the protein levels of NOX1 through NOX4 and Rac1. It is likely that the CO-induced OH production is mediated through the activation of Rac-dependent NOX enzymes, such as Nox1, Nox2, and Nox3.

Role of nitric oxide system in hydroxyl radical generation in rat striatum due to carbon monoxide poisoning, as determined by microdialysis.

We explored the possible role of the nitric oxide (NO) system in hydroxyl radical (*OH) generation induced by carbon monoxide (CO) poisoning in rat striatum by means of microdialysis with the use of NO synthase (NOS) inhibitors, N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-monomethyl-L-arginine (L-NMMA), as well as L-arginine (L-Arg; the NOS substrate) and D-arginine (D-Arg). The CO-induced *OH generation was suppressed by both L-Arg and D-Arg. It was also suppressed by L-NAME, which inhibits generation of reactive oxygen species (ROS) via neuronal NOS (nNOS) and inducible NOS, but not via endothelial NOS. In contrast, L-NMMA, which inhibits only ROS generation via inducible NOS, potentiated the *OH generation. L-Arg completely reversed the L-NAME effect and partly reversed the L-NMMA effect. D-Arg reversed the L-NAME effect more potently than did L-Arg, resulting in much more *OH generation than was observed with CO alone, and also potentiated the L-NMMA effect. On the other hand, W-7, an antagonist of calmodulin, which is critical for nNOS activity, had no effect on the CO-induced *OH generation. These findings suggest that complex mechanisms operate in *OH generation in rat striatum upon CO poisoning and that the NO system might not be included among those mechanisms.

Gene expression in rat striatum following carbon monoxide poisoning.

Carbon monoxide (CO) poisoning causes brain damage, which is attenuated by treatment with hydrogen [1], [2], a scavenger selective to hydroxyl radical (•OH) [3]. This suggests a role of •OH in brain damage due to CO poisoning. Studies have shown strong enhancement of •OH production in rat striatum by severe CO poisoning with a blood carboxyhemoglobin (COHb) level > 70% due to 3000 ppm CO, but not less severe CO poisoning with a blood COHb level at approximately 50% due to 1000 ppm CO [4]. Interestingly, 5% O2 causes hypoxia comparable with that by 3000 ppm CO and produces much less •OH than 3000 ppm CO does [4]. In addition, cAMP production in parallel with •OH production [5] might contribute to •OH production [6]. It is likely that mechanisms other than hypoxia contribute to brain damage due to CO poisoning [7]. To search for the mechanisms, we examined the effects of 1000 ppm CO, 3000 ppm CO and 5% O2 on gene expression in rat striatum. All array data have been deposited in the Gene Expression Omnibus (GEO) database under accession number GSE94780.

[Possible influence of psychotropic drugs detected in blood when determining the cause of death in medicolegal autopsy cases in the Tokyo Medical Examiner's Office].

We reviewed the records of 118 medicolegal autopsy cases, in which psychotropic drugs were detected in blood, in the Tokyo Medical Examiner's Office in 1997, to explore how the drug levels were considered in determining the cause of death. Names and doses of the drugs were clear in 70 of 118 cases, and in most cases of the 70 cases, multiple drugs (up to 13 drugs) were prescribed to a person. It was also evident that 75 of the 118 cases had demonstrated psychosis for several months to 38 years prior to death. No information concerning prescriptions or history of psychosis could be obtained in the other cases. The causes of death in these 118 cases were as follows: deaths from specific diseases, 30 cases (25.4%); deaths from extrinsic factors excluding drug intoxication, 22 cases (18.6%); suicide related to drug intoxication, 31 cases (26.3%); deaths from extrinsic factors related to drug intoxication suggestive of suicide, but not confirmed, 19 cases (16.1%); non-suicide, including probable drug intoxication, 13 cases (11.0%); and deaths from malignant syndrome, 3 cases (2.5%). There were cases diagnosed as death from specific diseases based on morphological findings, though drug concentrations in blood were at a toxic or even lethal level. In some cases, drug intoxication was suspected, but drug levels in their blood were at a therapeutic level and there were no identifiable morphological changes directly associated with deaths, resulting in a cause of death other than drug intoxication being indicated. Thus, drug levels detected in the cadaver's blood are not always useful for determining the cause of death. This might be due to poor information on interactions between drugs (including alcohol), pathological changes or genetic variability of drug metabolism and excretion, and so on. Thus, further studies of these aspects are needed in order to make information on drugs detected in the cadaver more useful for determination of cause of death.

Characterization of hydroxyl radical generation in the striatum of free-moving rats due to carbon monoxide poisoning, as determined by in vivo microdialysis.

Carbon monoxide (CO) poisoning caused by CO exposure at 3000 ppm for 40 min resulted in stimulation of hydroxyl radical (*OH) generation (estimated by measuring 2,3-dihydroxybenzoic acid (2,3-DHBA) production from salicylic acid) in the striatum of free-moving rats, as determined by means of brain microdialysis. Pretreatment with a voltage-dependent Na+ channel blocker, tetrodotoxin (TTX), lowered the basal level of 2,3-DHBA and strongly suppressed the increase in 2,3-DHBA induced by CO poisoning. CO poisoning significantly, though only slightly, increased extracellular glutamate in the striatum, and glutamate (Glu) receptor antagonists, such as MK-801 (dizocilpine) and NBQX, failed to suppress the CO-induced increase in 2,3-DHBA. These findings suggest that CO poisoning may induce Na+ influx via the voltage-dependent Na+ channels, resulting in stimulation of *OH generation in rat striatum. This effect may be independent of Glu receptor activation by increased extracellular Glu.

Characterization of suppression of nitric oxide production by carbon monoxide poisoning in the striatum of free-moving rats, as determined by in vivo brain microdialysis.

We examined the effect of carbon monoxide (CO) poisoning on the nitric oxide (NO) system in the striatum of free-moving rats by means of in vivo brain microdialysis. The extracellular levels of the oxidative NO products, nitrite (NO(2)(-)) and nitrate (NO(3)(-)), decreased during exposure to CO at 3000 ppm for 40 min, a condition which causes CO poisoning. The extracellular levels of citrulline (Cit; a by-product of NO production) and arginine (Arg; an NO precursor) also decreased during CO exposure. Following reoxygenation by withdrawal of CO, the NO(2)(-) and NO(3)(-) levels gradually recovered to the control values, though Arg and Cit remained at lower levels, except for a rapid, but transient, recovery shortly before and after reoxygenation, respectively. Simultaneous application of exogenous L-Arg (50 and 100 mM) with CO exposure attenuated the decreases in NO(2)(-) and NO(3)(-) during the CO exposure and accelerated their recovery following reoxygenation. However, D-Arg (100 mM) had no effect on the decrease in NO(2)(-) and NO(3)(-), except for slight and transient attenuation shortly after reoxygenation. Exogenous L-Cit (10 and 100 mM) failed to attenuate the CO-induced decrease in NO(2)(-) and NO(3)(-) levels. The decrease in the NO(2)(-) and NO(3)(-) levels during 8% O(2) exposure for 40 min, which was comparable with that in response to 3000 ppm CO, was resistant to exogenous 100 mM L-Arg, but the recovery of the NO(2)(-) and NO(3)(-) levels following reoxygenation was strongly accelerated. These findings suggest that CO poisoning suppresses NO production in rat striatum in vivo though a mechanism which may not be common with that in hypoxic hypoxia.

Different response to exogenous L-arginine in nitric oxide production between hippocampus and striatum of conscious rats: a microdialysis study.

We previously showed that systemic administration of a nitric oxide (NO) precursor, L-arginine (L-Arg), failed to reverse suppression by NO synthase (NOS) inhibitors of chemically induced shaking behavior in rats, leading to the hypothesis that exogenous L-Arg might be non-uniformly supplied to brain regions susceptible to NOS inhibitors. In the present study, therefore, we examined the effect of exogenous L-Arg on the extracellular levels of the oxidative nitric oxide (NO) products, nitrite (NO2-) and nitrate (NO3-), in two different brain regions, the hippocampus and the striatum, of conscious rats by means of in vivo brain microdialysis. The basal NO2- levels in the two brain regions were comparable, while the NO3- level was significantly lower in the hippocampus than the striatum. The addition of 10 mM L-Arg, but not D-Arg, to the perfusing solution significantly increased NO2- and NO3- in the hippocampus and NO2- alone in the striatum. These increases were abolished by 1 mM N(omega)-nitro-L-arginine, an NOS inhibitor. L-Arg at 1mM was able to significantly increase NO2-, but not NO3-, in the hippocampus to a level comparable with that at 10 mM L-Arg, while it had no effect in the striatum. L-Arg (500 mg/kg, i.p.) induced a significant increase in NO2- and NO3- in the hippocampus, but not in the striatum. These results suggest that the striatum may have a lower ability to enhance NO production by utilising exogenous L-Arg than the hippocampus, despite higher basal NO production.

Rupture of abdominal aortic aneurysm associated with long-term steroid therapy--a case report.

We report an autopsy case of bronchial asthma patient with a specific abdominal aortic aneurysm. The aneurysm did not show arteriosclerosis, and a specific saccular morphology was noted above the bifurcation. Histologically, necrosis of the media resembling acute aortic dissociation was observed. However, angiitis was ruled out. In addition, the aneurysm showed a cicatrized, old intimal crack in addition to the rupture site, suggesting repeated failures. The long-term steroid therapy-related fragility of the arterial wall may have been involved in the etiology of the aneurysm.

An autopsy case of bilateral adrenal pheochromocytoma-associated cerebral hemorrhage.

The autopsy findings of a 30-year-old woman who died of cerebral hemorrhage induced by bilateral adrenal pheochromocytoma are presented. The cerebral hemorrhage was shown on the left cerebral hemisphere widely. Her both adrenal glands were severe swelling, and their parenchyma was occupied by a dark red-brown tumorous positive for chromogranin A. The serum catecholamine and their metabolite, vanillylmandelic acid (VMA) levels were markedly high. Furthermore, cardiac hypertrophy and sclerosis of the arteries of various organs had progressed, suggesting an influence of persistent endocrinal hypertension. The measurement of serum VMA level was thought to be valuable for a postmortem diagnosis of pheochromocytoma. Bilateral adrenal pheochromocytoma may have excessively secreted catecholamine and subsequently caused secondary hypertension, leading to cerebral hemorrhage.