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Biomedical subjects

K Fukiyama

Publications and source records attributed to K Fukiyama.

At least 19 recordsLinked to original sources

Sudden death in the general population in Okinawa: incidence and causes of death.

Sudden unexpected death is generally considered to be caused by acute myocardial infarction and/or arrhythmia. To document the incidence and causes of sudden death in Japan, where the incidence of myocardial infarction is low, the present study examined death certificates, hospital records, the forensic medical records, and the police records of residents of the southern part of Okinawa island who died at the age of 20-74 years during a 3-year period from January 1, 1992 to December 31, 1994. Sudden death was defined as death within 24 h from the onset of unexpected symptoms. The study documented 126 (87 men and 39 women) sudden deaths. The crude incidence rate was 0.37/1,000 person per year (0.51 in men and 0.23 in women). According to the death certificates, 78 cases died of heart diseases. However, the cause of death could be determined by examination of all available records in only 64 cases: myocardial infarction in 10, non-ischemic heart diseases in 13, and stroke in 23 cases. Even when the analysis was limited to the cases who died within 1 h from the onset of symptoms, heart disease was the cause of death in only 22% of the cases while the cause of death could not be determined in 53% of the cases. Only 13% of those diagnosed as heart diseases on the death certificate were verified. The agreement rate between the diagnosis reached by the re-evaluation of the records and that on the death certificate was 82% for stroke and 33% for other diseases. In Okinawa, Japan, the frequencies of heart disease and stroke as the cause of sudden death may be similar. Except for stroke, the diagnosis appearing on the death certificate has substantial inaccuracy.

Adult

Low serum cholesterol as a risk factor for hemorrhagic stroke in men: a community-based mass screening in Okinawa, Japan.

The relation between the level of total serum cholesterol and stroke is controversial. The relation between serum total cholesterol and subtypes of stroke was examined in the participants of a community-based mass screening program in Okinawa, Japan. A total of 38,053 subjects, whose serum level of cholesterol had been determined during a mass screening carried out in 1983, were examined to see whether they had experienced stroke during a 3-year period from 1988 to 1991. Of them, 315 subjects aged 33-93 years (174 men, 141 women) had had a stroke during that period. The types of stroke were cerebral infarction in 164, cerebral hemorrhage in 111, subarachnoid hemorrhage in 19, and others in 21. In men, the odds ratio of cerebral hemorrhage was 0.71 (95% confidence interval, 0.55-0.95), and the odds ratio of cerebral hemorrhage associated with serum level of cholesterol < or =167 mg/dl, 168-191 mg/dl, 192-217mg/dl, and > or =218mg/dl were 1.00 (reference), 0.70 (0.38-1.30), 0.77 (0.55-1.08), 0.73 (0.56-0.96), respectively. Lower serum cholesterol was an independent predictor of cerebral hemorrhage in men.

Adult

[Apical hypertrophic cardiomyopathy followed by midventricular obstruction and apical aneurysm: a case report].

A 72-year-old man presented with apical hypertrophic cardiomyopathy followed by midventricular obstruction and apical aneurysm. Doppler echocardiography revealed an abnormal blood flow from the apical aneurysm to the left ventricular outflow through the obstructive lesion during diastole. Myocardial perfusion scintigraphy showed no ischemic change in the apex. This case suggests that apical aneurysm may not be caused by ischemia, although previous reports showed ischemic degeneration or fibrosis may be a cause of an apical aneurysm.

Aged

Effects of meal ingestion and active standing on blood pressure in patients > or = 60 years of age.

Postprandial hypotension and orthostatic hypotension occur often in elderly patients. In the present study, we examined hemodynamic and humoral responses to meal ingestion and active standing in 20 patients > or = 60 years of age who were free of apparent autonomic and cardiac dysfunction. For a time-control study, water was given instead of a meal to 19 of the 20 patients. After the meal ingestion, there was a fall in systolic blood pressure (BP) in 6 patients of > 20 mm Hg, whereas the fall in systolic BP during the control study was not > 20 mm Hg in any patient. The low-frequency power of the systolic BP wave, an index of peripheral sympathetic activity, was significantly increased only in the patients without postprandial hypotension. The postprandial changes in systolic BP were correlated with the changes in the low-frequency power of the systolic BP wave (r = 0.61; p < 0.01), but they were not correlated with the changes in plasma norepinephrine, insulin, cardiac output, or parameters obtained by the spectral analysis of the RR interval. The systolic BPs in the upright position were comparable after the meal and the water ingestion. Thus, the effects of meal ingestion and upright position on BP are not additive. Dysfunction of peripheral sympathetic control of vascular tone may contribute to the postprandial hypotension in elderly patients.

Aged

Contribution of alpha 2-adrenoceptors in caudal ventrolateral medulla to cardiovascular regulation in rat.

The inhibitory action of alpha 2-agonists on the cardiovascular neurons has been elucidated in the rostral ventrolateral medulla (RVLM) but not in the caudal ventrolateral medulla (CVLM). Our study aimed to clarify whether microinjection of clonidine into the CVLM elicits any cardiovascular effect and whether endogenous alpha 2-adrenoceptor-mediated mechanisms contribute to the tonic activity of the CVLM neurons. In male Sprague-Dawley rats (7-9 wk old, 270-320 g) anesthetized with urethan, unilateral microinjection of 8 nmol of clonidine into the CVLM (n = 10) increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) by 12.1 +/- 1.8 mmHg (mean +/- SE, P < 0.01) and 25.8 +/- 4.8% (P < 0.01), while heart rate (HR) remained unaltered. Unilateral microinjection of 2 nmol of SKF-86466, a selective blocker of the alpha 2-adrenoceptors, into the CVLM (n = 10) decreased MAP, HR, and RSNA (-11.6 +/- 2.6 mmHg, -26 +/- 7 beats/min, and -15.3 +/- 1.7%, respectively, P < 0.01 for each). Artificial cerebrospinal fluid caused neither a cardiovascular effect nor a sympathetic response. Prior injection of SKF-86466 into the ipsilateral CVLM attenuated the effects of clonidine. Bilateral microinjection of muscimol into the RVLM abolished the effects of both clonidine and SKF-86466 injected into the CVLM. The pressor and sympathoexcitatory effects of clonidine injected into the CVLM suggest a neuroinhibitory action of the drug on the CVLM neurons. In addition, the depressor and sympathoinhibitory effects of SKF-86466 injected into the CVLM indicated that activation of alpha 2-adrenoceptors by endogenous ligand inhibits CVLM neurons. The effects of clonidine and the alpha 2-adrenoceptor antagonist in the CVLM require the integrity of the RVLM.

Adrenergic alpha-Agonists

Prolonged NOS inhibition in the brain elevates blood pressure in normotensive rats.

Systemic inhibition of nitric oxide synthase (NOS) evokes hypertension, which is enhanced by salt loading, partly via augmented sympathetic activity. We investigated whether inhibition of brain NOS elevates blood pressure (BP) in normotensive rats and, if so, whether the BP elevation is enhanced by salt loading. After a 2-wk low-salt (0.3%) diet, male Sprague-Dawley (SD) rats were divided into four groups. Groups 1 and 2 received a chronic intracerebroventricular infusion of 0.5 mg . kg-1 . day-1 of NG-monomethyl-L-arginine (L-NMMA), and groups 3 and 4 were given artificial cerebrospinal fluid (aCSF). Groups 1 and 3 were placed on a high-salt (8%) diet, whereas groups 2 and 4 were on a low-salt diet. On day 9 or 10, group 1 showed significantly higher mean arterial pressure (MAP) in a conscious unrestrained state (129 +/- 3 mmHg vs. 114 +/- 3, 113 +/- 1, and 108 +/- 3 mmHg in groups 2, 3, and 4, respectively, P < 0.05). On a high-salt diet, response of renal sympathetic nerve activity but not of BP to air-jet stress was significantly larger in rats given L-NMMA than in rats given aCSF (29 +/- 4% vs. 19 +/- 3%, P < 0.05). When the intracerebroventricular infusions were continued for 3 wk, MAP was significantly higher in rats given L-NMMA than in rats given aCSF irrespective of salt intake, although the difference was approximately 7 mmHg. Thus chronic inhibition of NOS in the brain only slightly elevates BP in SD rats. Salt loading causes a more rapid rise in BP. The mechanisms of the BP elevation and its acceleration by salt loading remain to be elucidated.

Animals

Relationship between serum cholesterol and the risk of acute myocardial infarction in a screened cohort in Okinawa, Japan.

Coronary heart disease (CHD) is rare in Japanese subjects and serum cholesterol levels are low. However, no data have been published relating the effect of serum cholesterol levels to the incidence of acute myocardial infarction (AMI) in Japan. Data from a large community-based mass screening registry are available for the geographically isolated island of Okinawa, Japan (1980 census, 1.11 million). A total of 38,053 participants (17,859 men and 20,194 women) whose serum cholesterol levels were determined in the 1983 mass screening were examined to determine whether they had experienced AMI. Every case of AMI that occurred during a 3-year period (1 April 1988 to March 1991) throughout Okinawa was recorded in a separate registry. The total number of cases of AMI was 1,021 (674 men and 347 women). Of these, 65 patients (41 men and 24 women) were identified by name, sex, birth date, and zip code in the mass screening registry. The cumulative incidence of AMI increased with the serum level of cholesterol: 42.1 (serum cholesterol < or = 167 mg/dl), 133.5 (serum cholesterol 168-191 mg/dl), 188.9 (serum cholesterol 192-217 mg/dl), and 323.0 (serum cholesterol > or = 218 mg/dl) per 100,000 screened subjects. Multiple logistic analysis was conducted to examine the effect of serum cholesterol on the risk of AMI with adjustment for other variables such as sex, age, systolic and diastolic blood pressure, and proteinuria. The adjusted odds ratio (95% confidence interval) of the observed serum levels of cholesterol was 1.66 (1.29-2.15) with a reference serum cholesterol level of < or = 167 mg/dl. The risk of AMI increased in proportion to the serum level of cholesterol. Serum cholesterol is an independent predictor of AMI in Okinawa, Japan.

Adolescent

Ouabain-like immunoreactivity in the medulla oblongata of rats.

An isomer of ouabain, the ouabain-like compound (OI,C), may participate in the regulation of body fluid volume and vascular tone. Forebrain regions, especially the hypothalamus, are reported to be sites of OLC action in the central nervous system. The medulla oblongata is another critical area involved in central cardiovascular regulation. We reported that the microinjection of either monoclonal antibody to ouabain T8B11 or Fab fragment of digoxin-specific antibody into the rostral ventrolateral medulla significantly decreased mean arterial pressure and renal sympathetic nerve activity in anesthetized normotensive rats (TERUYA et al.: J. Clin. Invest. 99: 2791-2798, 1997). Using T8B11, we examined the ouabain-like immunoreactivity in the medulla oblongata of normotensive rats. In periodate-lysine-paraformaldehyde fixed tissues, ouabain-like immunoreactive neurons were detected in the nuclei and regions in the medulla oblongata including the ventrolateral medulla, ventromedial medulla, nucleus ambiguus, caudal raphe nuclei, nucleus of solitary tract, and dorsal motor nucleus of the vagus. When an Fab fragment of digoxin-specific antibody was used as a first antibody, the digoxin-like immunoreactive neurons were distributed in almost the same pattern as those observed with the use of T8B11. In the brain fixed with the "three-step" procedure developed by YAMADA et al. (1987), which was used in a previous ouabain immunohistochemical study of the hypothalamus, ouabain-like immunoreactivity in the medulla oblongata was much weaker in intensity and less restricted in distribution than that in the hypothalamus. These findings suggest that ouabain-like immunoreactivities are present in the medulla oblongata with a manner of distribution different from that seen in the hypothalamus. Some ouabain-immunopositive nuclei and regions in the medulla oblongata, especially the rostral ventrolateral medulla, may be other OLC action sites.

Animals

Demographic study of first-ever stroke and acute myocardial infarction in Okinawa, Japan.

We performed a cross-sectional survey of stroke and acute myocardial infarction (AMI) in Okinawa, Japan with a census population of about 1.2 million. A total of 3,644 cases of first-ever stroke and 898 cases of initial acute myocardial infarction (AMI) were detected. The age-adjusted annual incidence rate for stroke was 105 per 100,000 standard population of Japan, and that of AMI was 26. The case-fatality rate of stroke within 28 days of onset was 12.8%, and that of AMI was 22.2%. Of the stroke cases, 51.4% were diagnosed as brain infarction, 38.7% as brain hemorrhage, and 9.3% as subarachnoid hemorrhage. The diagnosis of stroke subtypes were confirmed by computed tomography or magnetic resonance imaging in 98.4% of all stroke cases. In Okinawa, the incidence rate of AMI was still considerably lower than that in the Western population, and the rate of stroke was similar to that in the Western population.

Adult

[A female case of Fournier's gangrene in a patient with lupus nephritis].

Infection is one of the common causes of death in patients with systemic lupus erythematosus (SLE). It is associated with the use of immunosuppressive agents, renal failure, and increased disease activity. Fournier's gangrene is a necrotizing fasciitis occurring in the genital region. It is rare, but can be crucial if surgical drainage is delayed. We report a female case of Fournier's gangrene occurring in a patient with lupus nephritis and chronic renal failure. The patient was a 21-year-old female with chronic renal failure due to lupus nephritis. She had suffered from watery diarrhea one month before admission. It improved after increasing the dose of prednisolone, but, she was complicated with Bartholin abscess. The vaginal pain rapidly spread to the left lower quadrant abdomen despite treatment with oral cephalosporin. Focal incision was performed and black fluid emerged with a foul smell. Pelvic computed tomography (CT) revealed many bubbles in that region. She was found to have septic shock on transfer to our hospital. Thereafter, emergency debridement was performed, followed by antibiotic therapy and hyperbaric oxygen therapy. Organisms were found to be 5 anerobes, such as Bacteroides species, and 3 aerobics, such as Morganella morganii. Fournier's gangrene was improved via these treatments, but she needed maintenance hemodialysis. Fournier's gangrene complication should be considered in SLE with urogenital infection.

Adult

Role of ouabain-like compound in the rostral ventrolateral medulla in rats.

To determine whether ouabain-like compound (OLC) exerts modulatory influences on the activity of vasomotor neurons in the rostral ventrolateral medulla (RVLM), we examined the effects of microinjecting ouabain, digoxin-specific antibody Fab fragments, and mAb against ouabain on the rat RVLM. Microinjection of ouabain into the unilateral RVLM of anesthetized normotensive rats elicited dose-dependent increases in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). The pressor and sympathoexcitatory effects of ouabain in the RVLM were reversed by microinjections of an M2 muscarinic antagonist, gallamine, or digoxin-specific antibody Fab fragments. Furthermore, a prior microinjection in the RVLM of gallamine, digoxinspecific antibody Fab fragments, or kainic acid or intravenous injection of hexamethonium all prevented the pressor and sympathoexcitatory effects induced by a subsequent microinjection of ouabain. Microinjections of either digoxinspecific antibody Fab fragments or gallamine per se significantly decreased baseline MAP and RSNA. Injection of digoxin-specific antibody Fab fragments attenuated the effects of a subsequent injection of gallamine. Microinjection of mAb against ouabain, but not nonspecific IgG, also significantly decreased baseline MAP and RSNA. These results suggest that OLC in the RVLM contributes to the tonic activity of vasomotor neurons in anesthetized normotensive rats, and the action of OLC in the RVLM is at least partly mediated by M2 muscarinic mechanisms.

Animals

Sympathetic skin responses of the hand in normal subjects: shorter latency at distal phalanx.

We studied the conduction of the sympathetic skin response (SSR) in the hands of 35 normal subjects by simultaneous recording at five sites. The mean latency of the SSR in all subjects increased from the wrist (W) to the middle phalanx (M), but the SSR latency at the distal phalanx (D) was shorter than that at the middle phalanx. The mean conduction time and conduction velocity from W to M was 197.5 ms and 0.87 m/s, respectively, and that from W to D was 48.8 ms and 2.34 m/s, respectively. For evaluation of the cause of the shorter latency at D, digital nerve blocking was performed in two subjects. The blocking of the volar digital nerves at the proximal phalanx abolished SSR at M and D. It was postulated that the initiation or conduction of sudomotor nerve impulse to the distal phalanx would be facilitated compared with those to the other proximal sites in the hand. The SSR conduction time between W and M may be a means of detecting alteration of sympathetic sudomotor nerve activity.

Adult

Risk factors of end-stage renal disease and serum creatinine in a community-based mass screening.

This study evaluated risk factors for end-stage renal disease (ESRD) and the prognostic significance of serum creatinine levels in a community-based mass screening. We used the registries of both community-based mass screening and chronic dialysis programs. In 1983, a total of 107,192 subjects over 18 years of age (51,122 men and 56,070 women) participated in a mass-screening program in Okinawa, Japan. Among them, serum creatinine data were available for 14,609 participants (5,613 men and 8,996 women). During 10 years of follow-up, we identified 60 dialysis patients (29 men and 31 women) among this group. Logistic regression analysis on the risk of ESRD was performed to determine the significance of serum creatinine levels in comparison with other clinical variables. The adjusted odds ratio (95% confidence interval) was 5.31 (3.39 to 8.32) in men and 3.92 (2.88 to 5.34) in women when compared to baseline serum creatinine levels of less than 1.0 mg/dl in women and 1.2 mg/dl in men. Diastolic blood pressure was not a significant predictor of ESRD. Results demonstrated the prognostic significance of serum creatinine in a community-based mass screening. Gender difference in the incidence of ESRD was explained, at least partly, by differences between clinical predictors and baseline serum creatinine levels.

Adolescent

Low diastolic blood pressure, hypoalbuminemia, and risk of death in a cohort of chronic hemodialysis patients.

In a previous report, we showed that nutritional status and especially serum albumin had great predictive value for death in chronic hemodialysis patients, whereas blood pressure did not. In the present study, we analyzed the causes of death in consideration of the relationship between serum albumin and blood pressure. A total of 1,243 Okinawan patients (719 males, 524 females) undergoing hemodialysis in January 1991 were followed up through the end of 1995. Three hundred forty-two of the patients died, 45 received transplants, and 12 were transferred by the end of the follow-up period. The total duration of observation was 5,110.3 patient-years. Blood pressure as well as clinical and laboratory variables were determined immediately prior to the first dialysis session in January 1991. The crude death rate was 40.0% when the diastolic blood pressure (DBP) <70 mm Hg, 35.0% at 70 to 79 mm Hg, 25.0% at 80 to 89 mm Hg, 25.0% at 90 to 99 mm Hg, and 13.0% at >100 mm Hg. The death rate showed an inverse correlation with DBP. DBP showed a significant positive correlation with serum albumin (r = 0.137, P < 0.001) and age (r = -0.325, P < 0.0001). The adjusted odds ratio (95% confidence interval) of death was 0.84 (0.71 to 0.99) with 10 mm Hg increments in DBP when the reference DBP was less than 69 mm Hg. Low DBP may be a manifestation of malnutrition and/or cardiovascular disease in chronic hemodialysis patients. Target DBP levels may be higher levels in chronic hemodialysis patients than the general population.

Blood Pressure

[Endogenous digitalis-like factor].

Evidence suggests the existence of a Na,K-ATPase inhibitor, so called endogenous digitalis-like factor (EDLF), in plasma. This substance has been postulated to enhance renal tubular sodium excretion and to increase peripheral vascular resistance. Recently, plant ouabain or its isomer (ouabain-like compound, OLC) was purified from human plasma and bovine hypothalamic extract. The OLC is considered to be a candidate for the EDLF. The OLC has been implicated in the pathogenesis of sodium-dependent hypertension. Furthermore, accumulating evidence suggests central nervous system as a site of hypertensinogenic action of OLC.

Animals

Predictors of end-stage renal disease and body mass index in a screened cohort.

The effect of body mass index (BMI) on the risk of developing end-stage renal disease (ESRD) has not been critically evaluated. To investigate this issue we used the registries of community-based mass screening and chronic dialysis programs. In 1983, a total of 101,516 subjects (47,901 men and 53,615 women) participated in a mass screening program in Okinawa, Japan. A total of 187 (101 men and 86 women) entered an ESRD program by March 31, 1994. Body mass index was calculated as weight in kilograms divided by the square of the height in meters. Subjects were categorized into six groups based on BMI: < 20.0, 20.0-21.9, 22.0-23.9, 24.0-25.9, 26.0-27.9, and > or = 28.0 kg/m2. The cumulative incidence of ESRD, per 100,000 subjects was calculated in each BMI subgroup for men and women. In men, the cumulative incidence of ESRD increased with BMI, except in the range of 24.0 to 25.9 kg/m2. In women, the association between the cumulative incidence of ESRD and BMI was not clear, but was lowest in the range of 24.0 to 25.9 kg/m2. The adjusted odds ratio (95% confidence interval) was 0.99 (0.92 to 1.13) in men and 0.83 (0.72 to 0.96) in women.

Adult

Impact of the initial levels of laboratory variables on survival in chronic dialysis patients.

Besides the age at start of dialysis and the presence of diabetes mellitus, serum albumin has been shown to be a significant predictor of survival in prevalent dialysis patients. However, this was not evaluated in incipient dialysis patients. The initial biochemical variables were retrieved for a large dialysis population (N = 1,982) who were started on chronic dialysis in Okinawa, Japan from 1971 to 1990. Biochemical data that included blood urea nitrogen, serum creatinine, serum electrolytes (sodium, potassium, calcium, and phosphate), total cholesterol, triglyceride, total protein, serum albumin, and hematocrit obtained just before the first dialysis session were available for 1,491 (75.2%) patients. Six hundred sixty-four (43.2%) patients died by the end of 1993. Cox proportional analysis adjusted for sex, age, year of start of dialysis, presence of diabetes mellitus, and the laboratory variables was performed to examine the significance of the initial biochemical data on survival. The risk ratio was 0.577 (P = 0.0025) in serum albumin, 1.291 (P = 0.0138) in serum potassium, and 0.966 (P = 0.0202) in serum sodium. The study results support the notion that nutritional status is important for survival in chronic dialysis patients. Causes of hypoalbuminemia, hyperkalemia, and hyponatremia should be evaluated carefully at initiation of dialysis.

Adolescent

Risk of developing end-stage renal disease in a cohort of mass screening.

The prognostic significance of abnormal findings has not been demonstrated in a setting of mass screening. To evaluate the relative risk of end-stage renal disease (ESRD) indicated by various results of community-based mass screening, we utilized the registries of both community mass screening and chronic dialysis programs. In 1983, a total of 107,192 subjects over 18 years of age (51,122 men and 56,070 women) participated in dipstick urinalysis and blood pressure measurement in Okinawa, Japan. During ten years of follow-up, we identified 193 dialysis patients (105 men and 88 women) among them. Logistic regression analysis of clinical predictors of ESRD over 10 years was done and the adjusted odds ratio and 95% confidence interval were calculated in each of the predictors with adjustment to others. In the clinical predictors such as sex, age at screening, proteinuria, hematuria, systolic and diastolic blood pressure, proteinuria was the most potent predictor of ESRD (adjusted odds ratio 14.9, 95% confidence interval 10.9 to 20.2), and the next most potent predictor was hematuria (adjusted odds ratio 2.30, 95% confidence interval 1.62 to 3.28). Being of male gender was a significant risk factor for ESRD (adjusted odds ratio 1.41, 95% confidence interval 1.04 to 1.92). Diastolic blood pressure was also a significant predictor of ESRD (adjusted odds ratio 1.39, 95% confidence interval 1.17 to 1.64), but systolic blood pressure was not. In a mass screening setting, positive urine test, high diastolic blood pressure, and male sex were identified as the significant predictors of ESRD. Effect of glycosuria and other possible predictors of ESRD remained to be determined.

Adolescent