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Introduction Volar locking plate (VLP) fixation has become the gold-standard treatment for distal radius fractures (DRFs). Especially, internal fixation of the volar lunate facet fragment is essential for the treatment of AO C3-type DRFs. On the other hand, the necessity of the fixation of the dorsal lunate facet fragment (dorsoulnar fragment) remains unclear. The purpose of the present study was to measure three-dimensionally the size of the dorsoulnar fragments in AO C3-type DRFs using computed tomography (CT) images in detail, and to reveal relationships of the size and stabilization of the dorsoulnar fragment with postoperative fracture displacement after VLP fixation. Materials and methods We retrospectively reviewed the 101 consecutive Japanese patients who underwent surgical treatment for AO C3-type distal radius fractures. If patient had dorsoulnar fragment, the three-dimensional size of this fragment and the occupying ratio to the radiocarpal joint (RCJ) and the distal radioulnar joint (DRUJ) were anatomically evaluated using the preoperative CT images. In addition, we investigated the relationship of the size and stabilization of the dorsoulnar fragment with fracture displacement after VLP fixation. We statistically compared the size parameters and occupying ratio of the dorsoulnar fragment between the displaced group and the stable groups using a two-tailed t-test. We also statistically compared the numbers of screws inserted into the dorsoulnar fragments between the displaced and stable groups using a chi-square test. Results The mean dorsoulnar fragment size was 9.4 mm × 7.9 mm × 11.0 mm and the occupying ratio to the DRUJ and RCJ was 50% and 10%, respectively. The number of patients treated with volar locking plate fixation was 77, of which 12 patients had postoperative displacements. Although the size of the dorsoulnar fragment was not associated with postoperative displacement, stabilization following screw insertion into the dorsoulnar fragment was significantly associated with displacement. Conclusion Stabilization of the dorsoulnar fragment with at least one screw of the volar locking plate was necessary to prevent postoperative fracture displacement regardless of dorsoulnar fragment size in AO C3-type distal radius fractures.

To evaluate the incidence, risk factors and prognosis for solid tumors after hematopoietic stem cell transplantation (HSCT) in Japan, 809 patients who had received HSCT between 1981 and 2000 were retrospectively analyzed. In all, 19 newly diagnosed secondary cancers were observed. The risk for cancer development was 2.8 times as high as that for expected cases. The cumulative incidence ratios at 5 and 10 years were 1.9 and 4.2%, respectively. The risk was significantly elevated for buccal cavity cancer (standard incidental ratio (SIR), 44.42: 95% confidence interval (CI) 17.86-91.51), esophageal cancer (SIR, 22.36: 95% CI 6.09-57.25), and cervical cancer (SIR, 8.58: 95% CI 1.04-31.01). Of 15 patients who developed solid cancers following allografting, 12 had chronic graft-versus-host disease (GVHD), and all 10 patients with squamous cell carcinoma of the buccal cavity or esophagus had chronic GVHD. On multivariate analysis, extensive chronic GVHD and age over 45 years at the time of transplantation were associated with a higher risk for solid cancers. In all, 17 patients received therapy for secondary cancers, nine of whom are still alive and the 5-year probability of survival from the diagnosis is 42.8%. Our data suggest that early detection of secondary cancers is very important in prolonging overall survival.

Mycobacterium intracellulare causes infection in humans. Involvement of joint and bone, however, is extremely rare. We present the case of an immunocompetent 67-year-old female with chronic swelling of the wrist joint diagnosed as rheumatoid arthritis by her previous physician. Examination revealed an unclosed fistula associated with a puncture, and bone and joint destruction on radiographs. She was diagnosed with osteomyelitis and arthritis due to M. intracellulare on histological and microbiological examinations. She was successfully treated with radical surgical debridement and anti-tuberculous drugs for 1 year and there was no recurrence at 3 years postoperatively.

Background —Effects of walking on the risk of coronary heart disease morbidity and mortality have not been identified in the elderly. The purpose of this study was to determine whether walking is associated with a reduced risk of coronary heart disease in a sample of elderly men. Methods and Results —For this study, distance walked (mile/d) was examined at a baseline examination that occurred from 1991 to 1993 in the Honolulu Heart Program. Incident coronary heart disease from all causes was observed over a 2- to 4-year follow-up period. Subjects followed up were 2678 physically capable elderly men aged 71 to 93 years. During the course of follow-up, 109 men developed coronary heart disease. Men who walked 1.5 mile/d (5.1% versus 2.5%; P P Conclusions —Findings from the Honolulu Heart Program, which targeted physically capable elderly men, suggest that the risk of coronary heart disease is reduced with increases in distance walked. Combined with evidence that suggests that an active lifestyle reduces the risk of cardiovascular disease in younger and more diverse groups, this suggests that important health benefits could be derived by encouraging the elderly to walk.

OBJECTIVES: To assess the relationship of body weight and anthropometry to all-cause mortality in older men. DESIGN: A prospective cohort study of 3741 elderly Japanese-American men, enrolled in the Honolulu Heart Program. For this report, the follow-up began at baseline examinations (1991–1993), when the men were aged 71–93 y. MEASUREMENTS: Variables of interest were body mass index (BMI), waist-to-hip ratio (WHR), and the sum of the subscapular and triceps skinfold thickness. Possible confounders included age, education, physical activity index, smoking, alcohol consumption, systolic and diastolic blood pressure, cholesterol, glucose and insulin concentrations. RESULTS: After an average of 4.5 y of follow-up, 766 men (21%) had died. Higher BMI was associated with lower adjusted mortality risks (relative risk (RR)) highest vs lowest quintile-based category=0.5, 95% confidence interval (CI): 0.4–0.6, P-trend

Low-density lipoprotein (LDL) adsorption using a dextran sulfate cellulose column is brought about by electrostatic binding between the positive charges of apolipoprotein B in LDL and the negative charges of dextran sulfate cellulose. There is general agreement that the initial contact phase in the coagulation pathway may be activated by a negatively charged surface such as dextran sulfate cellulose, resulting in the generation of bradykinin. We investigated whether the increase in the generation of bradykinin during LDL adsorption is accompanied by the activation of endogenous production of nitric oxide (NO) in patients with peripheral atherosclerosis. LDL adsorption therapy was repeated ten times over a period of 3 months in ten peripheral atherosclerosis patients. Treatment significantly reduced serum total cholesterol and LDL cholesterol levels. This was associated with a significant improvement in Fontaine's classification and ankle pressure index. We also measured the kinin-kallikrein system and plasma levels of NO in the same patients. The results showed that coagulation factors of the intrinsic pathway including high-molecular-weight kininogen and prekallikrein decreased markedly after initial adsorption compared with the levels before treatment. There was a marked increase in bradykinin and NO concentrations after the initial adsorption, compared with their levels before adsorption. Our results suggest that the generation of bradykinin and increased plasma levels of NO may contribute to the improvement in peripheral circulation after LDL adsorption in peripheral atherosclerosis patients.

Adverse lipid and lipoprotein levels are clearly linked with increased risk of cardiovascular disease in middle age, but evidence in elderly and minority populations is less certain. In this study the distribution and correlates of lipids and lipoproteins were evaluated cross-sectionally in 3044 elderly (71 to 93 years) Japanese-American men from the Honolulu Heart Program who were recently reexamined (1991 to 1993). Mean±SD lipid concentrations were 189±33 mg/dL for total cholesterol, 51±13 mg/dL for HDL cholesterol, 109±31 mg/dL for LDL cholesterol, and 147±89 mg/dL for triglycerides. Prevalence of dyslipidemic patterns was relatively infrequent (total cholesterol ≥240 mg/dL: 6.7%; HDL cholesterol P P

Background Clinical studies suggest that hypertensives have lower mean corpuscular volume (MCVs) than do normotensives. Epidemiological studies show no relation or higher MCVs. In the present study of elderly men (71 to 93 years of age) of the Honolulu Heart Program, elements of both findings are confirmed. Methods and Results Three groups are identified: (1) those receiving no hypertension treatment, (2) those receiving treatment with any diuretic, and (3) those receiving treatment with nondiuretics only. MCV is lower in group 3 than in group 1 (−0.85 fL, P P r =−.45). In group 2, adjustment for RBC unmasks a direct relation between MCV and SBP (0.5 mm Hg/fL, P =.02) and DBP (0.3 mm Hg/fL, P =.02). In groups 1 and 3, relations between SBP and MCV are lost after adjustment for RBC (0.005 mm Hg/fL). For DBP, adding RBC plus an MCV×RBC interaction is significant ( P Conclusions The relation between blood pressure and red cell measures is probably mediated by whole blood viscosity. Hematocrit is a determinant of whole blood viscosity. Viscosity affects peripheral resistance to blood flow, and peripheral resistance affects DBP. At high RBC levels, MCV may be “downregulated.” This may lower whole blood viscosity and partially reduce DBP without compromising flow.

Abstract The role of insulin in cardiovascular disease is uncertain, and studies in elderly or minority populations are infrequent. Fasting and 2-hour insulin concentrations and their cross-sectional associations with cardiovascular risk factors were examined in 3562 elderly (aged 71 to 93 years) Japanese American men from the Honolulu Heart Program who were reexamined between 1991 and 1993. Insulin distributions were skewed (mean and median: 16.8 and 12 μU/mL for fasting; 117.2 and 93 μU/mL for 2-hour); fasting but not 2-hour insulin levels declined significantly with age ( P P =.54, respectively). Factors most strongly correlated with insulin included measures of obesity, fat distribution, and levels of triglyceride, glucose ( r =.38 to r =.50 fasting, r =.21 to r= .27 2-hour), and HDL cholesterol ( r =−.41 and r =−.22, respectively). Other correlates included fibrinogen, hematocrit, heart rate, blood pressure, cigarettes per day (all positive), alcohol, physical activity, and forced vital capacity (negative). Associations were also evident across risk factor quintiles. Insulin levels were significantly elevated in men with hypertension and diabetes. In multiple linear regression analyses, log 10 fasting insulin was positively and independently associated with body mass index, triglycerides, glucose, fibrinogen, hematocrit, heart rate, diabetes, and hypertension and negatively associated with HDL cholesterol, physical activity, and forced vital capacity. In general, results were similar for log 10 2-hour insulin and when subjects who fasted

While evidence suggests that obesity has an independent relation to coronary artery disease, similar findings for stroke have not been established. The purpose of this study was to examine the relation between body mass index and the risk of thromboembolic stroke independently of other risk factors. Since 1965, the Honolulu Heart Program has followed a cohort of men in a prospective study of cardiovascular disease. This article examines the relationship between the baseline measurement of body mass index and the risk of thromboembolic stroke in 1163 nonsmoking men in older middle age (55 to 68 years). Men who had an elevated risk of stroke due to hypertension, diabetes, and other risk factors were excluded from the analysis. After 22 years of follow-up, the rate of stroke increased significantly with increasing levels of body mass (P < .01). In the bottom tertile of the body mass index, the rate of thromboembolic stroke was 28.7 per 1000 (11/383). In the middle tertile, the rate was increased by 40% to 40.7 per 1000 (16/393), and in the top tertile, the rate of thromboembolic stroke was 55.4 per 1000 (21/387), a twofold excess compared with the bottom tertile. After adjustment for age and the residual effects of confounding risk factors, including systolic blood pressure and serum glucose, the estimated relative risk of stroke for the average body mass index in the top tertile (26.6 kg/m2) compared with that in the bottom tertile (20.3 kg/m2) was 2.1 (95% confidence interval, 1.1 to 4.1). These findings were not affected by coronary events that occurred in the course of follow-up, nor did they appear to be influenced by deaths from other causes. We conclude that elevated body mass is associated with an increased risk of thromboembolic stroke in nonsmoking men in older middle age who are free of commonly observed conditions related to cardiovascular disease.

The extent and number of metastatic lymph nodes in 52 patients with oesophageal carcinoma involving more than one lymph node were analysed to determine the efficacy of lymphadenectomy. The patients were divided into two groups according to the number of metastatic lymph nodes, group A: 1–4 nodes (34 cases) and group B: 5 or more nodes (18 cases). The survival of all patients in group A was statistically better than that of the patients in group B ( P = 0.02). In cases where metastatic nodes were restricted to one region, the survival of patients in group A was significantly better than that of patients in group B ( P = 0.006). By contrast, in cases where metastatic nodes extended to two or more regions, there was no difference between the groups. The present study suggests that lymphadenectomy is effective only for patients with 1–4 metastatic nodes that are restricted to a single region. Lymphadenectomy is less efficacious in cases with five or more metastatic nodes, even when the nodes are restricted to one region, and is similarly ineffective in cases with metastatic nodes extending to two or more regions, regardless of the number of positive nodes.

The number of nucleolar organizer region proteins identified by silver staining (AgNORs) and alterations in cell surface glycoproteins identified by Helix pomatia agglutinin (HPA) immunostaining were studied in 96 primary esophageal carcinomas. The number of AgNORs increased with increasing depth of cancer invasion, venous involvement, lymphatic invasion, and tumor stage. Positivity of HPA staining correlated significantly with increasing depth of cancer invasion, venous invasion, and tumor stage. Forty of 42 HPA negative cases had low AgNORs numbers (

To determine if levels of serum estradiol and testosterone can predict stroke in a population-based sample of elderly men.Serum 17beta estradiol and testosterone were measured in 2,197 men aged 71 to 93 years who participated in the Honolulu-Asia Aging Study from 1991 to 1993. All were free of prevalent stroke, coronary heart disease, and cancer. Participants were followed to the end of 1998 for thromboembolic and hemorrhagic events.During the course of follow-up, 124 men developed a stroke (9.1/1,000 person-years). After age adjustment, men in the top quintile of serum estradiol (or =125 pmol/L [34.1 pg/mL]) experienced a twofold excess risk of stroke vs men whose estradiol levels were lower (14.8 vs 7.3/1,000 person-years, p0.001). Among the lower quintiles, there were little differences in the risk of stroke. Findings were also significant and comparable for bioavailable estradiol and for thromboembolic and hemorrhagic events. After additional adjustment for hypertension, diabetes, adiposity, cholesterol concentrations, atrial fibrillation, and other characteristics, men in the top quintile of serum estradiol continued to have a higher risk of stroke vs those whose estradiol levels were lower (relative hazards = 2.2; 95% CI = 1.5 to 3.4, p0.001). Testosterone was not related to the risk of stroke.High levels of serum estradiol may be associated with an elevated risk of stroke in elderly men.

Bacteroides forsythus is an important pathogen in periodontal diseases and has been associated with advanced and refractory periodontitis. The difficulties associated with culturing this species have meant that the distribution and pathogenic mechanisms of B. forsythus remain unclear. In this study, the arbitrarily primed polymerase chain reaction (AP-PCR) method was used to investigate the genotype distribution of B. forsythus in a Japanese periodontitis population, as well as the relationship between AP-PCR genotypes and periodontal status. B. forsythus reference strain, ATCC 43037T and 137 clinical bacterial isolates from 64 subjects were separated into 11 distinct AP-PCR genotypes using a single randomly-sequenced primer, 5'-CCGGCGGCG-3' (A-05). The majority (80.9%) of B. forsythus strains examined belonged to AP-PCR genotypes I, II, III and IV (accounting for 39.7%, 20.6%, 10.3% and 10.3%, respectively). Types I and III primarily consisted of isolates from chronic periodontitis subjects (80.8% and 85.7%, respectively), while Types II and IV consisted mainly of isolates from aggressive periodontitis subjects (85.7% and 100%, respectively). Except for three subjects who harbored two different B. forsythus genotypes in the oral cavity, all subjects only infected with one genotype intraindividually. These results demonstrate that the AP-PCR method is useful for genotypic analysis of B. forsythus. This species showed a genetic diversity among the investigated population. A clonal nature of B. forsythus infection is suggested. Furthermore, different AP-PCR genotypes of B. forsythus appear to be associated with different types of periodontitis.

Although low ankle/brachial blood pressure index (ABI) is a marker of generalized atherosclerosis in the elderly, it has not been identified as a risk factor for stroke. The purpose of this report is to examine the relation between ABI and stroke in elderly men. ABI was measured from 1991 to 1993 in 2767 men aged 71 to 93 years in the Honolulu Heart Program without a history of stroke and coronary heart disease. Subjects were followed for 3 to 6 years for fatal and nonfatal thromboembolic and hemorrhagic stroke. During follow-up, there were 91 strokes. There was an age-adjusted 2-fold excess in men with an ABI0.9 (6.0%) versus men with an ABIor = 0.9 (2.9%, P0.01). Thromboembolic events occurred in 4.6% of men with an ABI0.9 and in 2.0% in those with an ABIor = 0.9 (P0.01). Hemorrhagic stroke was also more frequent in men with a low ABI (0.9) versus a higher ABI (1.9 vs. 0.8%, respectively). After adjusting for other factors, the risk of total and thromboembolic strokes increased with declining ABI (P = 0.019 and P = 0.004, respectively). The relation between ABI and stroke was similar and statistically significant in the presence and absence of diabetes and hypertension (P0.05). Findings suggest that ABI is inversely related to the incidence of stroke. Simple measurement of ABI in an outpatient setting could be an important tool for assessing the risk of stroke in the elderly.

We sought to demonstrate the prevalence, incidence and prognostic value of the Brugada-type electrocardiogram (ECG) in a general population.The Brugada syndrome is characterized by evidence of right bundle branch block and ST segment elevation in the right precordial leads, as well as sudden death caused by ventricular fibrillation. However, the natural history of the Brugada-type ECG remains unclear.We investigated 4,788 subjects (1,956 men and 2,832 women) who were50 years old in 1958 and had undergone biennial health examinations, including electrocardiography, through 1999. The Brugada-type ECG was defined as a terminal r' wave in lead V(1) and ST segment elevationor =0.1 mV in leads V(1) and V(2). Unexpected death was defined as sudden death or unexplained accidental death.There were a total of 32 Brugada-type ECG cases; the prevalence and incidence were 146.2 in 100,000 persons and 14.2 persons per 100,000 person-years, respectively. The incidence was nine times higher among men than women, and the average age at presentation was 45 +/- 10.5 years. The Brugada-type ECG appeared intermittently in most cases and was found in 26% of subjects who died unexpectedly. Cox survival analysis revealed that mortality from unexpected death was significantly higher in subjects with a Brugada-type ECG than in control subjects (p0.01). Unexpected deaths were more frequent among subjects with the Brugada-type ECG who had a history of syncope (p0.05).The Brugada-type ECG is not a very rare condition in the adult Japanese population. Subjects with a Brugada-type ECG have an increased risk of unexpected death.

To determine diagnostic accuracy for AD in a population-based study of Japanese-American men. AD is neuropathologically confirmed for more than 80% of cases at major referral centers (primarily Caucasians); however, information on diagnostic accuracy in population-based studies and studies of different ethnic groups is limited.There were 3,734 men who participated in the Honolulu-Asia Aging Study 1991 through 1993 dementia examination and 2,603 in the 1994 through 1996 examination. Diagnoses were based on published criteria. Neuropathologists blinded to clinical data quantified neurofibrillary tangles (NFT) and neuritic plaques (NP).Of 220 autopsied subjects, clinical evaluation revealed 68 with normal cognition, 73 intermediate, and 79 with dementia: 20 AD, 27 vascular dementia, 19 AD + other, and 13 other dementia. Among 20 cases with pure AD, the median value for maximum neocortical NFT density was 6.9/mm(2) and for neocortical NP density was 8.0/mm2. Corresponding densities for other groups were3.0/mm2. Using established neuropathologic criteria, 25% (5/20) of clinical AD cases had enough NP to meet definite AD criteria, whereas 65% (13/20) had sufficient NP to meet neuropathologic definite or probable AD criteria. Among nine AD cases with moderately severe dementia, only two (22%) had NP densities great enough to meet definite neuropathologic criteria, whereas seven (78%) met neuropathologic criteria for probable AD.Neuropathologic confirmation and NP density among decedents with clinical AD in this population-based study were lower than reported by referral centers and similar to reports from two other community studies. Ethnic differences in propensity for amyloid deposition as well as differences in clinical severity and representativeness of cases might contribute to these findings.

Many articles pertaining to quality of life (QOL) following stem cell transplantation have been published in the US and western Europe. However, since the actions of health insurance systems and overall cultural aspects are strongly associated with QOL, investigations into QOL should be carried out within all countries. Therefore, we have investigated the QOL of adult patients following stem cell transplantation at 31 hospitals in Japan. The survivors, who were surveyed by mail questionnaire, were 20 years or older at the time of this study. The underlying diseases were acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, myelodysplastic syndrome, and multiple myeloma. Median age at the time of the study was 36 years, and median interval after transplantation was 35.3 months. Of 383 patients surveyed, 282 (73.6%) responded to the questionnaire. One hundred and ninety-two patients were treated with an allogeneic-related transplantation, 52 with allogeneic-unrelated, and 38 with an autologous transplantation. Our data revealed that the length of time since transplantation and the diagnosis of chronic GVHD were associated with QOL. When unrelated and related transplantation recipients were compared, ratings on relief from pain, stability in weight, and confidence in dealing with daily life were lower among unrelated transplantation patients.

We examined p53 protein expression, proliferating cell nuclear antigen (PCNA), and argyrophilic nuclear organizer regions (AgNOR), in 102 patients with surgically-treated non-small cell lung cancer (NSCLC). p53 positive cases with DO-1 were defined when more than 10% of the tumor cell nuclei were stained. Mean AgNOR count and PCNA LI were 2.80 and 40.7 and there were no significant differences of AgNOR count and PCNA LI between p53 positive and negative cases. We assessed the relationship between the p53 immunoreactivity and various clinical or pathological parameters. p53 positive rate of stage III disease (46.3%) was significantly higher than that of stage II disease (28.6%). The p53 positive rate of squamous cell carcinoma (42.1%) tended to be higher than that of adenocarcinoma (33.9%). In the survival curves of patients with NSCLC according to the p53 immunoreactivity, there was no significant difference between p53 positive and negative cases. Eight potential prognostic parameters (p53 immunoreactivity, AgNOR count, PCNA LI, sex, age, year of operation, histology, and stage) were also estimated, using univariate and multivariate analysis. In univariate analysis, PCNA LI and AgNOR count, and stage were significantly related to shortened survival. In multivariate analysis, PCNA LI, Age, and stage were independently associated with shortened survival of NSCLC patients. PCNA staining may be more useful than p53 and AgNOR staining in assessing the aggressiveness of surgically-treated NSCLC, although the most useful clinical prognostic parameter should be achieved by the combined analysis of several prognostic indicators.

Plasma fibrinogen levels were determined using comparable methods for 329 Japanese men in Hiroshima Japan, and 3571 Japanese-American men in Honolulu Hawaii, aged 71-93 years. The age-adjusted mean fibrinogen level in Japanese-American men (307 mg/dl) was significantly higher (p0.0001) than in native Japanese men (270 mg/dl). In multiple linear regression models, the fibrinogen level was associated significantly and positively with white blood cell count (WBC) and total cholesterol, and inversely with HDL cholesterol and hematocrit in both study samples. The strongest association with fibrinogen was shown for WBC, and this association was not mediated through cigarette smoking. The observed difference in fibrinogen levels could not be fully explained by WBC, total and HDL cholesterol, triglyceride, hematocrit, body mass index, and diabetes. Some unmeasured environmental or lifestyle variables such as diet and physical activity may be partly responsible for the observed difference in fibrinogen levels between native Japanese men and Japanese-American men in Hawaii.

Some patients with variant angina show both ST segment elevation at rest and exercise-induced ST segment elevation. Magnesium deficiency has also been observed in patients with variant angina. This study investigated the correlation between the degree of magnesium deficiency and the efficacy of intravenous administration of magnesium in patients with variant angina. Fifteen patients with angiographically confirmed variant angina were assessed for magnesium deficiency and whether intravenous administration of magnesium (19.2 mEq/l) suppressed exercise-induced ST segment elevation. All 15 patients were studied with a magnesium retention test (0.2 mEq/kg over 4 hr) to analyze magnesium deficiency. In our study, magnesium retention rate in patients with variant angina was not higher than that of controls (57 +/- 24% vs 45 +/- 10%, NS). All 15 patients had anginal attacks during accelerated exercise combined with hyperventilation after placebo infusion, whereas only 8 patients had anginal attacks after magnesium administration. ST segment elevation occurred in 14 patients after placebo infusion, but in only 4 patients after magnesium administration. There were no correlations between disease activity, degree of magnesium deficiency or failure of suppression of ST elevation by the intravenous administration of magnesium. Intravenous administration of magnesium can suppress exercise-induced coronary spasms in some patients with variant angina, but the degree of magnesium deficiency did not correlate with the suppressions of exercise-induced ST elevation after magnesium administration. Intravenous administration of magnesium had limited efficacy in patients with variant angina and exercise-induced ST segment elevation.

Low-density lipoprotein (LDL) adsorption using a dextran sulfate cellulose (DSC) column is commonly performed for extracorporeal removal of LDL in hypercholesterolemic patients with peripheral arterial obstructive disease. We investigated whether the use of heparin or nafamostat mesilate as anticoagulants in a single LDL apheresis produced different clinical effects, or brought about the production of bradykinin and endogenous nitric oxide (NO) in these patients. LDL apheresis was performed in ten patients with peripheral arterial obstructive disease. We measured plasma levels of bradykinin, NO and nitrosylhemoglobin as well as skin temperature. Plasma levels of bradykinin increased 12-fold during LDL apheresis with heparin, but did not increase during LDL apheresis with nafamostat mesilate. LDL adsorption resulted in an immediate rise in skin temperatures (1-2 degrees C) of the lower ischemic legs irrespective of the type of anticoagulant used, and this persisted after the end of LDL apheresis for up to 60 min. There was a progressive and significant increase in plasma NO after the commencement of single LDL apheresis in both groups (heparin group: 64.0 +/- 17.3 micromol/l at baseline, 73.3 +/- 15.2 micromol/l 60 min after apheresis, P

The effect of metabolic abnormalities of myocardial fatty acids on ventricular arrhythmias was evaluated by myocardial imaging with iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) in 27 patients with coronary heart disease. The disturbance of myocardial blood flow was also evaluated using thallium-201 (Tl). The patients were divided into 2 groups based on the character of the premature ventricular contractions: Group A: number of contractionsor = 120 per day and/or consecutive contractions (n = 9, mean age 63.7 yr), and Group B, number of contractions120 per day and no consecutive contractions (n = 18, mean age 64.2 yr). Left ventricular ejection fraction was measured by left ventriculography, and significant coronary artery stenosis was defined as stenosis of 75% or greater. Cardiac scintigraphy was performed using single photon emission computed tomography with BMIPP at rest in 27 patients and in the early phase (early Tl) and delayed phase of Tl (delayed Tl) in 20 patients. BMIPP and Tl uptakes were scored as 0: absent, 1: moderately reduced, 2: mildly reduced and 3: normal in 7 segments of the left ventricular wall and then the total scores were calculated in each patient. Ejection fraction significantly correlated with the scores of BMIPP, and early and delayed Tl(p0.001, respectively), although the ejection fraction in Group A was significantly less than in Group B (51.2 +/- 16.7% vs 68.2 +/- 14.4%, p0.02). The BMIPP scores in Group A were significantly less than those in Group B (14.2 +/- 4.3 vs 17.2 +/- 3.1, p0.05), but the early and delayed Tl scores in Group A were not significantly different compared with those in Group B. The BMIPP scores showed no significant differences between the patients with and without significant coronary artery stenosis, but the early and delayed Tl scores in the patients with stenosis were significantly less than those in patients without stenosis (early Tl: 19.8 +/- 2.6 vs 16.8 +/- 2.8, p0.01; delayed Tl: 19.6 +/- 2.5 vs 16.8 +/- 3.1, p0.05). More patients had values of Tl minus BMIPP scores of at least 3 in Group A than in Group B (early Tl-BMIPPor = 3: 66.7% vs 7.7%, p0.01; delayed Tl-BMIPPor = 3: 50.0% vs 7.7%, p0.05). In patients with coronary heart disease, decreased ejection fraction is thought to be a major cause of ventricular arrhythmias, and also associated with abnormal myocardial metabolism and abnormal myocardial blood flow. Furthermore, ventricular arrhythmias were more closely correlated with abnormal metabolism of fatty acids than with disturbance of blood flow in the myocardium, and large mismatching between the 2 images may be related to risky ventricular arrhythmias in coronary heart disease.

To estimate pulmonary hypertension, we measured postural differences in pulmonary blood flow for the lateral decubitus positions on perfusion lung scintigrams with Tc-99 m macro-aggregated albumin, applying the method devised by Tanaka et al (Eur J Nucl Med 17: 320-326, 1990). Utilizing a scintillation camera coupled to a minicomputer system, changes in the distribution of pulmonary blood flow caused by gravitational effects, namely, changes in the total count ratios for the right lung versus the left lung in the right and left lateral decubitus positions (R/L), were obtained for 44 patients with lung disease, 95 patients with valvular heart disease, and 23 normal subjects. Mean standard deviation in the R/L ratios was 3.09 +/- 1.28 for the normal subjects, 1.97 +/- 0.89 for the patients with lung disease, and 1.59 +/- 0.59 for the patients with valvular heart disease. The R/L ratios correlated with mean pulmonary arterial pressure and cardio-thoracic ratios in the lung disease and valvular heart disease groups, with pulmonary arteriolar resistance in the former, and with pulmonary capillary wedge pressure in the latter. Defining pulmonary hypertension (20 mmHg) as an R/L ratio of less than 1.81, which is the mean-1 standard deviation for normal subjects, the sensitivity and the specificity of the R/L ratio for the diagnosis of pulmonary hypertension were 62.9% and 76.2%, respectively, for the lung disease patients, and 80.3% and 61.8%, respectively, for the valvular heart disease patients. This method seems to be useful for the pathophysiologic evaluation of pulmonary perfusion in cases of lung disease and valvular heart disease.

The endoscopic diagnosis of early esophageal and gastric cancers located within 2 cm above and below the esophagogastric junction (EGJ) is discussed. We reviewed 25 cases (10 mucosal cancers and 15 submucosal cancers). Histologically, early cancers frequently appeared as type IIc lesions (16/25: 64%). There was no relationship between tumor size and the depth of invasion of cancer lesions, and most of the lesions were well or moderately differentiated carcinomas. Endoscopically, homogenous redness with a thin white coating, some granular appearance, and easy bleeding were very important factors for the diagnosis of early gastric cancer. For superficial esophageal cancer, differential diagnosis from reflux esophagitis is correctly performed with the endoscopic dye (lugol)-staining method and biopsy. In order not to overlook early cancer at the EGJ, this area should be observed with sufficient air inflation by the U-turn or J-turn method using a frontal-view panendoscope.

This study investigated whether the maximal dose of 50 micrograms acetylcholine for the induction of coronary spasm in the right coronary artery is adequate. The acetylcholine test was performed in 388 consecutive patients to evaluate spasm from January 1994 to December 1997. Coronary spasm in the right coronary artery was induced in 43 patients, 37 men and 6 women with a mean age of 63 +/- 8 years by intracoronary injection of 80 micrograms of acetylcholine rather than 50 micrograms. These included 15 patients (35%) with rest angina, 23 patients with ischemic heart disease other than rest angina and 5 patients (12%) with non-ischemic heart disease. Acetylcholine was injected in incremental doses of 20, 50 and 80 micrograms into the right coronary artery. Positive spasm was defined as induction of more than 90% reversible narrowing associated with either usual chest pain or ischemic electrocardiographic changes. Clinical and angiographical characteristics was studied in these patients. Fifteen (35%) patients had rest angina and 4 patients had variant angina with ST elevation in the inferior leads. Two thirds of the patients had coronary spasm in the distal portion of the right coronary artery and one third of those disclosed spasm focally. Coronary spasm was induced in 38 (15%) of 246 patients with ischemic heart disease and in 5 (4%) of 142 patients with non-ischemic heart disease. The prevalence of positive spasm in patients with ischemic heart disease was significantly higher (p0.01) than in patients with non-ischemic heart disease. A dose of 80 micrograms of acetylcholine, more than the maximal standard dose, might be clinically useful for the induction of spasm in the right coronary artery if coronary spasm of this artery is strongly suspected.

In 39 patients with idiopathic paroxysmal atrial fibrillation (PAF group), the incidence of the abnormal P wave morphology (prolonged P wave and mitral P in lead II and increased P terminal force in lead V1: PTF V1) was examined, and the relationships to the electrophysiologic findings of the atrial muscle were investigated. The control group consisted of 42 patients with various cardiac arrhythmias other than sick sinus syndrome. P wave duration was significantly longer in the PAF group than in the control group (112 +/- 12 vs 98 +/- 10 msec, p0.0001). PTF V1 was greater in the PAF group than in the control group (0.051 +/- 0.018 vs 0.028 +/- 0.010 msec, p0.0001). P mitrale occurred in only 5 patients (12%) in the control group as compared to 25 patients in the PAF group (64%, p0.0001). The longest duration of the right atrial electrograms was longer in the PAF group than in the control group (101 +/- 17 vs 85 +/- 10 msec, p0.0001), as was the maximal number of the fragmented deflections (8.0 +/- 2.5 vs 5.8 +/- 1.4, p0.0001). Repetitive atrial firing zone and also fragmented atrial activity zone were longer in the PAF group than in the control group (34 +/- 24 vs 12 +/- 19 msec, p0.02 and 47 +/- 27 vs 24 +/- 19 msec, p0.001, respectively). Interatrial conduction delay zone was longer in the PAF group than in the control group (55 +/- 25 vs 38 +/- 18 msec, p0.001). P wave duration and PTF V1 had significant and/or borderline correlations with the longest duration of the right atrial electrocardiograms (r = 0.75, p0.0001 and r = 0.68, p0.0001, respectively), and the maximal number of its fragmented defections (r = 0.50, p0.002 and r = 0.40, p0.05, respectively). Furthermore, P wave duration had a correlation with the repetitive atrial firing zone (r = 0.55, p0.01). Prolonged P wave duration and increased PTF V1 are electrocardiographic indicators for the coexistence of electrophysiologic abnormalities in patients with idiopathic paroxysmal atrial fibrillation.

Although oral clonidine premedication is known to reduce the hemodynamic response under general anesthesia, effects of the hemodynamic response during sedated fiberoptic nasal intubation have not yet been examined. Our aim was to compare the effects of clonidine premedication on hemodynamic responses with those of atropine and hydroxyzine premedication during sedated fiberoptic nasal intubation. Thirty adult patients were randomly assigned to one of two groups: Group 1 patients (n = 15) were premedicated with atropine sulfate (0.01 mg/kg) and hydroxyzine hydrochloride (1mg/kg) intramuscularly, and group 2 patients (n = 15) were premedicated with clonidine (5 micrograms/kg) orally. We compared the hemodynamic response and sedation level in fiberoptic nasal intubation between the two groups. there were no significant differences in sedation levels and postoperative complaints between the two groups. But the oral clonidine premedication (Group 2) blunted hemodynamic changes during the fiberoptic intubation. No profound hypotension or marked bradycardia was noted in group 2. We concluded that the oral clonidine premedication might contribute to hemodynamic stability during sedated fiberoptic nasal intubation.

To examine the association between coffee consumption and the development of stroke in men at high risk for cardiovascular disease.Coffee intake was observed from 1965 to 1968 in a cohort of men enrolled in the Honolulu Heart Program with follow-up for incident stroke over a 25-year period. Subjects were 499 hypertensive men (having systolic or diastolic blood pressures at or above 140 and 90 mm Hg, respectively) in older middle-age (55 to 68 years) when follow-up began. Past and current cigarette smokers were excluded from follow-up.In the course of follow-up, 76 men developed a stroke. After age-adjustment, risk of thromboembolic stroke increased significantly with increases in coffee consumption (P = 0.002). No relationships were observed with hemorrhagic stroke. When adjusted for other factors, the risk of thromboembolic stroke was more than doubled for men who consumed three cups of coffee per day as compared to nondrinkers of coffee (RR = 2.1; 95% CI = 1.2-3.7).Although in need of further confirmation, consumption of coffee appears to be positively associated with an increased risk of thromboembolic stroke in hypertensive men in older middle-age. Findings suggest that it may be prudent to advise older middle-aged men with hypertension who consume large amounts of coffee to consider reducing their coffee intake.

The usefulness of thallium-201 (201Tl) myocardial scintigraphy was studied in 109 patients with vasospastic angina who had nearly normal coronary arteries (degree of stenosis50%). Coronary spasm was confirmed by pharmacologic agents in all 109 patients from January 1991 to June 1996. The appearance rate of visual redistribution on 201Tl myocardial scintigraphy was compared between four groups, 34 patients performing graded bicycle ergometer exercise starting at a work load of 50 W with increments of 25 W every 3 min [Ergo (3) group], 14 patients performing hyperventilation for 5 min [HV (5) group], 31 patients performing bicycle ergometer exercise with increments of 25 W every 1 min after 5 min hyperventilation [HV (5) + Ergo (1) group], and 30 patients at rest (Rest group). The value of the visual redistribution rate on 201Tl myocardial scintigrams in the HV(5) + Ergo (1) group (65%) was higher than that in the patients of other groups [Ergo (3) 41%, HV (5) 43%, Rest 33%]. However, there were no significant differences between the four groups. Stress 201Tl imaging after hyperventilation and accelerated exercise is useful to disclose ischemic evidence in about two thirds of patients with vasospastic angina and nearly normal coronary arteries, whereas about 40% of patients had visual redistribution on 201Tl myocardial scintigrams by performing standard procedures.

Abstract —Hyperinsulinemia has been associated with cardiovascular disease (CVD), but whether this relation is independent of other CVD risk factors is uncertain. Most studies have focused on coronary heart disease (CHD), but few have included peripheral vascular disease (PVD) and stroke. Moreover, evidence in elderly and minority populations is limited. Between 1991 and 1993, 3562 elderly (71 to 93 years) Japanese-American men from the Honolulu Heart Program were examined and had fasting insulin levels measured. Hyperinsulinemia, defined as a fasting insulin ≥95th percentile among nonobese men with normal glucose tolerance and no diabetic history or medication use, was observed in 22% of the population. Subjects with hyperinsulinemia had a more adverse CVD risk factor profile and had higher age-adjusted prevalences of CHD, angina, PVD, thromboembolic stroke, and hemorrhagic stroke compared with those without hyperinsulinemia. Age-adjusted fasting insulin levels but not 2-hour levels were also significantly elevated ( P P =.069). In subjects with elevated total cholesterol levels, somewhat stronger associations were observed for PVD and stroke but not for CHD. Although further prospective studies are indicated, particularly for PVD and stroke, these cross-sectional results are consistent with an indirect role for insulin in CVD, wherein hyperinsulinemia or an underlying insulin-resistant state may adversely affect other CVD risk factors or serve as a marker for an atherogenic or thrombogenic state.

Two-dimensional echocardiographic (2-D) planimetry and the Doppler pressure half-time (PHT) method have been used to estimate mitral valve area (MVA) in patients with mitral stenosis (MS). Recently, the proximal isovelocity surface area (PISA) method has been shown to be accurate for calculating MVA. The purpose of this study was to compare the PISA method with previous methods. Thirty patients with MS were studied; 17 had pure MS, 4 combined mild MR, 6 combined mild AR, and 3 combined MR and AR. Color Doppler flow mapping was performed at an aliasing (blue-red interface) velocity of 14 cm/sec using the zero-baseline shift. MVA was calculated as 2 x 3.14 x R2 x 14 x (theta/180) / PFV, where R is the distance from aliasing to orifice, 14 is the aliasing velocity, theta is the internal angle of the mitral valve, and PFV is the peak flow velocity at the mitral orifice. MVA was also calculated using the 2-D and PHT methods, and compared with the PISA method. MVA calculated using the PISA method correlated well with the 2-D (r=0.90, p0.01, SEE = 0.18 cm2) and PHT methods (r=0.82, p0.01, SEE = 0.24 cm2). Compared with the 2-D method, the standard error of the estimate of the PISA method was - 0.14+/-0.18 cm2 and the percent error was -10.4+/-18.9%. Compared with the PHT method, the standard error of the estimate of the PISA method was + 0.01+/-0.24 cm2 and the percent error was +3.4+/-34.6%. MVA calculated using the PISA method correlated well with the 2-D and PHT methods in patients with pure MS or with MS combined mild regurgitation. The PISA method may be useful for calculating MVA as an alternative method.

The potential benefit of low-intensity activity in terms of longevity among older men has not been clearly documented. We examined the association between walking and mortality in a cohort of retired men who were nonsmokers and physically capable of participating in low-intensity activities on a daily basis.We studied 707 nonsmoking retired men, 61 to 81 years of age, who were enrolled in the Honolulu Heart Program. The distance walked (miles per day) was recorded at a base-line examination, which took place between 1980 and 1982. Data on overall mortality (from any cause) were collected over a 12-year period of follow-up.During the follow-up period, there were 208 deaths. After adjustment for age, the mortality rate among the men who walked less than 1 mile (1.6 km) per day was nearly twice that among those who walked more than 2 miles (3.2 km) per day (40.5 percent vs. 23.8 percent, P=0.001). The cumulative incidence of death after 12 years for the most active walkers was reached in less than 7 years among the men who were least active. The distance walked remained inversely related to mortality after adjustment for overall measures of activity and other risk factors (P=0.01).Our findings in older physically capable men indicate that regular walking is associated with a lower overall mortality rate. Encouraging elderly people to walk may benefit their health.

A palpable mass was unexpectedly found in the upper abdomen of a 67-year-old woman. Computed tomography (CT) and abdominal angiography both indicated an aneurysm of the right gastroepiploic artery. An aneurysmectomy was performed, and the aneurysm was found to be spherical with a diameter of 7.5 x 7.7 cm. The patient was eventually discharged in good condition. The histological findings of the aneurysmal wall revealed medial fibrosis and atherosclerosis. Gastroepiploic artery aneurysms are rare among splanchnic artery aneurysms and most such aneurysms are found to be ruptured. The present report described a quite rare case of an asymptomatic giant gastroepiploic artery aneurysm and also includes a review of the 10 reported cases of gastroepiploic artery aneurysms in the English literature to date. Since gastroepiploic artery aneurysms have a high risk of rupture it is essential that appropriate surgical measures be taken immediately.

Coronary flow reserve is used as an indicator to assess coronary microvascular function in the absence of obstructive coronary atherosclerosis. Diabetic patients, even with angiographically normal coronary arteries, show significantly reduced coronary flow reserve. This study evaluated coronary microcirculation in coronary artery disease complicated by glucose intolerance. Thirty-three patients with coronary artery disease were divided into three groups: Fourteen patients without glucose intolerance (control group), 8 with impaired glucose tolerance (IGT group), and 11 with noninsulin dependent diabetes mellitus (DM group). A Doppler guide wire was used to measure phasic coronary blood flow velocity in the left anterior descending artery without significant stenosis (or = 40% diameter narrowing). Coronary flow reserve was determined by intracoronary 10 mg papaverine hydrochloride administration which induced maximal hyperemia. Coronary flow reserve was decreased in the DM group compared with the control group (2.1 +/- 0.6 vs. 3.1 +/- 0.9, p = 0.004), and that in the IGT group (2.5 +/- 0.9) did not show a significant difference compared with the other two groups. Vessel characteristics, such as infarct- or noninfarct-related artery and previous coronary angioplasty, did not have an influence on the results. Other coronary risk factors, left ventricular function, and hemodynamic findings were comparable in the three groups. This study demonstrates that diabetes mellitus may cause functional microvascular abnormalities in coronary artery disease.

Plasma high density lipoprotein (HDL) levels are strongly genetically determined and show a general inverse relationship with coronary heart disease (CHD). The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to other lipoproteins and is a key participant in the reverse transport of cholesterol from the periphery to the liver. A high prevalence of two different CETP gene mutations (D442G, 5.1%; intron 14G:A, 0.5%), was found in 3,469 men of Japanese ancestry in the Honolulu Heart Program and mutations were associated with decreased CETP (-35%) and increased HDL chol levels (+10% for D442G). However, the overall prevalence of definite CHD was 21% in men with mutations and 16% in men without mutations. The relative risk (RR) of CHD was 1.43 in men with mutations (P < .05); after adjustment for CHD risk factors, the RR was 1.55 (P = .02); after additional adjustment for HDL levels, the RR was 1.68 (P = .008). Similar RR values were obtained for the D442G mutation alone. Increased CHD in men with mutations was primarily observed for HDL chol 41-60 mg/dl; for HDL chol > 60 mg/dl men with and without mutations had low CHD prevalence. Thus, genetic CETP deficiency appears to be an independent risk factor for CHD, primarily due to increased CHD prevalence in men with the D442G mutation and HDL cholesterol between 41 and 60 mg/dl. The findings suggest that both HDL concentration and the dynamics of cholesterol transport through HDL (i.e., reverse cholesterol transport) determine the anti-atherogenicity of the HDL fraction.

A number of studies have shown that regular chelation therapy with deferoxamine is effective in patients with secondary hemochromatosis. However, compliance with these regimen is difficult to obtain in most cases because long-term administration is burdensome. In 3 patients, one each with myelodysplastic syndrome, aplastic anemia and thalassemia intermedia, self-administered subcutaneous one-shot administration of deferoxamine at a dose of 500 mg once or twice daily was carried out over a long period. In all three patients serum ferritin level decreased significantly and the progression of hemochromatosis was prevented. Liver density on computed tomography scan also decreased in one patient. This regimen, in which the patient self-administered deferoxamine subcutaneously one or twice a day is seems to be the most practical method to protect against the progression of hemochromatosis.

Adrenergic stimulation induces contraction of hypertrophied prostatic tissue via the alpha 1 adrenoceptor, and the results of pharmacological studies suggested the existence of adrenoceptor subtypes. Recently three subtypes (alpha 1a, alpha 1b, and alpha 1d) were cloned. Using probes for these subtypes, we demonstrated their expression in the tissues of ten cases of benign prostatic hypertrophy, using in situ hybridization. To determine the ratio between these subtypes, an RNase protection assay was also performed in three cases. Expression of the alpha 1a and alpha 1d adrenoceptors was diffuse in the smooth muscles of the interstitium, but was absent in glandular epithelial cells. On the contrary, the alpha 1b adrenoceptor was hardly detectable. The RNase protection assay confirmed the absence of the alpha 1b adrenoceptor, the ratio of alpha 1a and alpha 1d being 4:1. These results supported the idea that the differences in prostatic contractile response to several adrenergic drugs are based on the affinities of these drugs for the different subtypes.

In 55 gastrointestinal cancer patients the mean change ratios for platelets were, respectively, 1.22 +/- 0.75 and 0.67 +/- 0.45, in the romurtide administration (30 cases) and non-administration (25 cases) groups, [statistically significant difference (p0.005)]. The number of cases in each group with a decrease in platelet count was 13 (43%) and 20 (80%) with and without romurtide, respectively. The difference was statistically significant, (p0.01). In addition, the number of cases with a marked decrease (6 x 10(4)/mm3) in platelet count was 2 (7%) and 7 (28%) with and without romurtide, respectively, reaching statistical significance (p0.05). For patients treated with a bolus administration of 450 mg/m2 carboplatin (27 cases), the mean change ratios for leukocytes and platelets in the romurtide administration group (13 cases) were 1.10 +/- 0.52 and 1.23 +/- 0.59, respectively. Meanwhile, in the romurtide non-administration group the mean change ratios for leukocytes and platelets were, respectively, 0.74 +/- 0.27 and 0.74 +/- 0.42, a statistically significant reduction (p0.05) compared with the romurtide administration group. The number of cases with an increase in the number of lymphocytes after i.v. administration was significantly more than that observed after s.c. administration (p0.01). These results indicate that romurtide has a restorative effect on thrombocytopenia similar to that displayed for leukocytopenia when given as concomitant therapy with anticancer drugs and/or irradiation in patients undergoing intensive treatment for gastrointestinal cancer.

Levcromakalim (BRL 38227, CAS 94535-50-9) is a new antihypertensive drug with vasodilator activity due to activation of potassium channels in vascular smooth muscle. In this study, we treated 14 patients with essential hypertension on an out-patient basis to investigate the antihypertensive effect of levcromakalim by 24-h blood pressure monitoring for a 12-weeks treatment period. Levcromakalim significantly lowered blood pressure for 24 h without affecting standard deviation, range of variation and pulse rate. When 24-h monitoring period was divided into daytime (6:00-22:00) and nighttime (22:30-5:30), there were no statistically significant differences in magnitude of fall in blood pressure at night between baseline and end of treatment values. Four patients (28.5%) reported 6 adverse events, including headache, facial hot flushes, oedema and floating feeling. All symptoms were mild or moderate. These data show that levcromakalim controls ambulatory blood pressure both in the daytime and nighttime without changing the circadian rhythm of blood pressure, and suggest that levcromakalim will be an efficacious and safe antihypertensive drug.

The combined chemotherapy of SN-38, active metabolite of CPT-11, and 5-FU in vitro was examined using human cell lines and primarily cultured cells obtained at surgery. The percent survival of the Suit-2 cell line treated with a single modality of SN-38 at the concentration of 0.95-61 nM was 70% to 86%, while, when treated with SN-38 and 5-FU, the percent survival of these cells decreased at even 1 microM of 5-FU. The enhanced ratios (percent survival at 0 nM SN-38/percent survival at 61 nM SN-38) at 1 microM and 4 microM of 5-FU were 1.56 and 1.33, respectively. The enhanced ratio became lower when the concentration of 5-FU was increased. When topoisomerase I activity in Suit-2 cells incubated with 5-FU was examined, 5-FU at a high dose (or = 4 microM) in the medium caused a strong inhibition of the relaxation of Suit-2 DNA by topoisomerase I, but 5-FU at low dose (or = 2 microM) barely inhibited topoisomerase I activity. These results indicated that topoisomerase I synthesis in the Suit-2 cell line might be suppressed by a high dose of 5-FU in the medium but not by a clinically achievable level of 5-FU. The cancer cells obtained from clinical cancer tissues were treated with these drugs at a clinically achievable dose in the medium. Judging from the results of a sensitivity test, in 7 out of 10 cases, the percent survivals under the combined treatment were lower than those estimated under the single modality treatment. Therefore, by the addition of 5-FU, the antitumor effect of CPT-11 would seem to be further enhanced.

MPC-1304 ((+-)-methyl 2-oxopropyl 1,4-dihydro 2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate, CAS 86780-90-7), a new calcium antagonist, was orally administered to 10 outpatients with mild essential hypertension. It was observed that MPC-1304 inhibited elevations of blood pressure both at rest and under exercise loading without any adverse hemodynamic effects. The findings obtained indicated that MPC-1304 would be clinically useful in the treatment of hypertensive patients undergoing therapy while continuing normal everyday activities including physical exertion.

The effects of thromboxane A2 synthetase inhibitor and hyperdynamic therapy on delayed cerebral ischaemia following aneurysmal subarachnoid haemorrhage were evaluated in a series of twenty eight patients, who underwent aneurysmal clipping with 72 hours after subarachnoid haemorrhage. Postoperatively, 13 patients were treated with thromboxane A2 synthetase inhibitor, Xanbon [sodium (E)-3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoate]. Hyperdynamic therapy with dobutamine was given to the remaining 15 patients. Of the 13 patients treated with Xanbon, nine patients (69%) developed delayed cerebral ischaemia and cerebral infarcts occurred in eight patients (62%). On the other hand, of the 15 patients treated with hyperdynamic therapy, only three patients (20%) manifested delayed cerebral ischaemia and two patients (13%) developed cerebral infarcts. In the present study, the patients treated with hyperdynamic therapy met an expected incidence of ischaemic events after subarachnoid haemorrhage by today's standards, while those treated with thromboxane A2 synthetase inhibitor did not.

BACKGROUND Antiatherogenic effects of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) have been suspected for more than 30 years, yet the available evidence to support or refute such effects in humans is inconclusive. The hypothesis has not been adequately tested in large-scale epidemiological studies. METHODS AND RESULTS The present study used a cohort of men initially free of clinically detectable coronary heart disease, stroke, and cancer to compare DHEAS levels measured in sera obtained in 1968-1971 between 238 cases who had definite coronary heart disease during the subsequent 18 years and 476 age-matched controls who survived the follow-up period and remained free of clinically detectable coronary heart disease. In a separate study, the relation of DHEAS levels to extent of atherosclerosis was examined among 82 cohort men who died during the follow-up period and had protocol autopsies. Age-adjusted DHEAS levels were lower among fatal cases of coronary heart disease than among controls (94.7 versus 106.9 micrograms/dl, respectively; p < 0.05). After adjustment for eight coronary risk factors, the odds ratio for fatal coronary heart disease comparing a 100-micrograms/dl difference in DHEAS level was 0.46 (95% confidence intervals, 0.19-1.07). In contrast, age-adjusted DHEAS levels did not significantly differ between nonfatal cases of myocardial infarction and controls (107.2 versus 106.9 micrograms/dl, respectively). Furthermore, DHEAS levels were not related to extent of atherosclerosis at autopsy. CONCLUSIONS These findings do not support a role of DHEAS in the development of nonfatal myocardial infarction or the progression of atherosclerosis. The association of DHEAS with fatal coronary heart disease and possibly with death from all causes merits further investigation. These findings suggest continued skepticism that DHEAS has an important role in coronary disease etiology or prevention.

In the studies of stress 201Tl single photon emission computed tomography, we have developed a computer method to discriminate reversible from irreversible defect, then quantify each area and display the area on the polar map. Initial percent uptake (%Ui) and delayed percent uptake (%Ud) were expressed as percent of the maximum uptake area and were defined as regional myocardial 201Tl uptake in initial and delayed image, respectively. The %Ud/%Ui ratio was defined as redistribution ratio (RD-ratio). The values of %Ui obtained from each pixel of short axis slices were plotted against the values of RD-ratio on XY co-ordinates. In this graphic display, normal area, ischemic viable area and non viable area were separated by the following four lines. A; The straight line (Y = 2.0-0.012X) indicating the relationship between %Ui and RD-ratio for the group with ischemic viable myocardium. B; The parallel line to A and shifted to -1.5 SD from A. C; The vertical line at 67.0% level (ischemic upper level). D; The vertical line at 27.6% level (viable lower level). Each area was discriminated by color display and calculated relative area values were displayed on the polar map. Criteria for discriminating each area were derived from the results of ischemic pre-transluminal coronary angioplasty (PTCA) lesions (n = 21) in which viability was confirmed by successful PTCA and previous results of 66 cases with single vessel disease and 16 cases of control group. This new computerized technique was applied for evaluation of another group with successful PTCA (n = 15).(ABSTRACT TRUNCATED AT 250 WORDS)

In the past 4 years, 11 patients with cardial varix bleeding were experienced. The cardial varices were of 2 types, nodular and serpentine. The nodular varices were caused by gastro-renal shunt and the site of bleeding often existed on the posterior wall. The serpentine cardial varices were an extension of esophageal varices, and the site of bleeding was often on the lesser curvature. The nodular varices had an abundant blood flow. When EIS was performed to these varices independently, the time of contact with the sclerosing agent was so short that no therapeutic effect was obtained. For the purpose of decreasing the blood flow in these varices, TIO was performed first and then EIS was used in the treatment of four cases of nodular varix bleeding. Hemostasis was obtained in two of the four cases with TIO alone, and after the addition of EIS a good hemostatic and varix-reducing effect was noted in all four cases.