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Biomedical subjects

K Kario

Publications and source records attributed to K Kario.

At least 109 records · Page 6Linked to original sources
PubMed1997

Application of argatroban, direct thrombin inhibitor, in heparin-intolerant patients requiring extracorporeal circulation.

This study describes the present knowledge regarding the clinical application of argatroban, a direct competitive thrombin inhibitor for heparin-intolerant patients, including those with congenital and acquired antithrombin III deficiencies, those with heparin-induced thrombocytopenia, and those with high levels of polymorphonuclear granulocyte elastase. These patients are often associated with intracircuit clot formation with heparin anticoagulation during extracorporeal circulation. Therefore, argatroban may be chosen as one of the alternate anticoagulants. Because the anticoagulant effect of argatroban is reflected in the prolongation of activated thromboplastin time, monitoring is easy, similar to that for heparin. Because argatroban has a fast acting anticoagulant effect without any cofactors such as antithrombin III, this drug is a favorable anticoagulant for heparin-intolerant patients with antithrombin III deficiencies requiring extracorporeal circulation. In adverse reactions to heparin, heparin acts as an antigen after complexing with platelet factor 4, which leads to life-threatening heparin-induced thrombocytopenia. As argatroban prevents heparin-induced platelet aggregation, it is effective for use as a therapeutic anticoagulant. In other clinical applications, heparin decreases antithrombin activity and causes intracircuit clot formation during extracorporeal circulation when the polymorphonuclear granulocyte elastase level is very high. The antithrombin activity shows less decrease when argatroban is substituted for heparin. These findings indicate that argatroban is a useful alternative anticoagulant in these heparin-intolerant patients.

Anticoagulants↗
PubMed1997

Increased coronary heart disease mortality after the Hanshin-Awaji earthquake among the older community on Awaji Island. Tsuna Medical Association.

OBJECTIVES: To investigate the characteristics of earthquake (EQ)-induced coronary heart disease (CHD) deaths. SETTING AND PARTICIPANTS: On January 17, 1995, the south part of Hyogo Prefecture in Japan was struck by a major EQ (Hanshin-Awaji EQ) measuring 7.2 on the Richter scale. We investigated the characteristics of EQ-induced CHD deaths (myocardial infarction and sudden death) in the Tsuna region, which is a community with a large older population (31% of the total of 64,000 residents are 60 years of age or older) and includes the epicenter and one of the most heavily damaged areas. MEASUREMENTS: EQ-related CHD mortality on the basis of direct access to records of physicians who were able to continue services for the EQ victims without interruption by this disaster situation. RESULTS: Coronary heart disease deaths increased for a few months after the EQ, and the total number from January 17 to April 30, 1995, was 45, which was significantly (1.5 times) higher than the 31 deaths during the same period of the previous year (1994). The CHD deaths after the EQ all occurred in individuals more than 60 years of age and had a positive correlation with EQ-induced damages. Concerning the onset time, CHD deaths occurred 1.8 times more often (P < .05) in the nighttime (11 PM to 5 AM) and 1.4 times as often during the morning (5 AM to 11 AM), whereas their occurrence did not vary during a 12-hour period from 11 AM to 11 PM. CONCLUSION: Deaths of older individuals from CHD persisted for a few months after the EQ and were especially prominent during the nighttime and morning. Reduction of stress and related coronary risk factors in this period may suppress CHD deaths after a major EQ.

Aged↗
PubMed1997

Hypertensive nephropathy and the gene for angiotensin-converting enzyme.

To investigate the genetic determinants for microalbuminuria, we studied an insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene, which influences the plasma ACE level, in 333 consecutive hypertensive patients and 113 normotensive control subjects. The urinary albumin excretion rate was calculated by using a 12-hour urine collection (mean for two consecutive nights from 7 PM to 7 AM) in all 333 hypertensive patients. The ACE D allele frequency did not differ significantly between the hypertensive patients and the normotensive control subjects (0.37 and 0.33, respectively). Among the hypertensive patients, nephropathy (microalbuminuria and albuminuria) was more common (P < .001) in those with the ACE DD genotype than in those with other genotypes. The D allele frequency in the nephropathy group was significantly higher than that in the normoalbuminuric group (0.45 versus 0.32, chi 2 = 10.8, P < .001). These results indicate that ACE I/D polymorphism is a genetic determinant for hypertensive renal disease in hypertensive patients. This polymorphism might be a confounding factor involved in the association between hypertensive nephropathy and cardiovascular events.

Aged↗
PubMed1997

Autonomic nervous system dysfunction in elderly hypertensive patients with abnormal diurnal blood pressure variation: relation to silent cerebrovascular disease.

To investigate the relationships among diurnal blood pressure (BP) variations and autonomic nervous system dysfunction, we assessed heart rate variability (HRV) using power spectral analysis of the 24-hour RR interval in 51 asymptomatic elderly hypertensive patients with various patterns of nocturnal BP fall. The extreme-dippers with marked nocturnal BP fall (n=16) had lower asleep low-frequency power (LF)/high-frequency power (HF) ratios (a relative index of sympathetic nervous system activity), while the nondippers without nocturnal BP fall (n=18) had lower awake LF/HF ratios and asleep/awake ratio for HF (an index of parasympathetic nervous activity), when compared with dippers with appropriate nocturnal BP fall (n=17). The incidence of multiple lacunar infarction detected by brain magnetic resonance imaging was 56% in the extreme-dippers and 38% in the nondippers, and both were markedly higher than that (6.3%) in the dippers (both P<.01). There was no significant relationship between the BP level and any HRV parameter for either the daytime or nighttime period. The asleep/awake ratio for systolic BP was significantly correlated with the asleep/awake ratio for HF (r= -.363, P<.01) and with the asleep/awake ratio for the LF/HF ratio (r=.540, P<.001), regardless of whether multiple lacunar infarction was present. In conclusion, the autonomic nervous system activity is not related to high BP level per se, rather its diurnal variation is more important as a determinant of the diurnal BP patterns, regardless of the presence or absence of cerebrovascular disease.

Aged↗
PubMed1997

Serum insulin and lipoprotein(a) concentrations. The Jichi Medical School Cohort Study.

OBJECTIVE: To examine the relationship between serum insulin and lipoprotein (a) [Lp(a)] concentrations in both sexes in a large population. RESEARCH DESIGN AND METHODS: The authors conducted a cross-sectional investigation of fasting serum concentrations of insulin and Lp(a), other blood tests, blood pressures, anthropological measurements, physical activity index, smoking habit, alcohol consumption, and menopause. The subjects were 1,121 men and 1,480 women, ranging between 30 and 90 years of age, who were voluntary participants in the Jichi Medical Cohort Study and who resided in one of five rural communities in Japan. RESULTS: In men, insulin, age, BMI, LDL cholesterol, triglycerides, glucose, and fibrinogen were significantly correlated with Lp(a). In women, insulin, age, LDL cholesterol, fibrinogen, and activated coagulation factor VII were significantly correlated with Lp(a). However, all correlations were weak in either sex. Insulin was inversely correlated with Lp(a) in both sexes. However, the coefficients were weak (r = -0.16 in mean and r = -0.06 in women). In the partial correlation analyses, Lp(a) was not significantly associated with insulin in either sex. The result was not influenced by selecting the subjects on the basis of detectable values of insulin and Lp(a) and stratifying them by serum glucose level. CONCLUSIONS: There was no significant relationship found between serum insulin and Lp(a) concentrations in either sex of the cohort, which indicates that Lp(a) does not play a role in the increased risk of cardiovascular disease in hyperinsulinemic subjects.

Adult↗
PubMed1997

Altered circadian rhythm of blood pressure and cerebrovascular damage.

An abnormal circadian rhythm of blood pressure [i.e. a lesser or 'reverse' nocturnal fall of blood pressure (nondippers)] is associated with cerebrovascular damage including intracranial hemorrhaging, thrombosis, and vascular dementia. Silent cerebrovascular damage such as lacunae and periventricular hyperintensity lesions is not infrequently detected in apparently healthy hypertensive elderly subjects by brain magnetic resonance imaging and also is more common among nondippers than it is among dippers. Although no exact cause-effect relationship is known, a decrease in nocturnal fall of blood pressure might be secondary to a site-specific injury to the brain resulting in an impairment of central autonomic nervous system functioning. Besides nondipping, evidence suggests that the extreme dipping (a marked nocturnal fall of blood pressure) should be considered a type of abnormal diurnal blood pressure variation in elderly patients with hypertension who are likely to have advanced silent cerebrovascular damage. The pathogenic significance of 'extreme dipping' might be an 'artificial' excess reduction in blood pressure at night beyond the lower limit of blood pressure in the autoregulation of cerebral blood flow that is probably induced by antihypertensive agents. It is also possible that a greater blood pressure variability in extreme dippers itself accelerates the hypertensive target-organ damage. Prospective follow-up of subjects with these distinct subtypes of abnormal circadian blood pressure variation as well as trials comparing a group of treated patients with various degrees of dipping with a group of untreated counterparts may establish the validity of assessing these distinct circadian rhythms of blood pressure as a useful clinical parameter in the management of hypertension.

Journal Article↗
PubMed1997

Factor VII and fibrinogen levels examined by age, sex, and other atherosclerotic risk factors in a Japanese population. The Jichi Medical School Cohort Study.

Factor VII coagulant activity (FVIIc) and fibrinogen (Fbg) levels have been investigated as cardiovascular risk factors. We studied these two factors with stratification for age, sex and blood pressure, and the relation with other atherosclerotic risk factors in a Japanese general population. The subjects were 3,139 Japanese (1,315 males and 1,824 females) aged 30 to 89 in 1992 and 1993. A linear increase with age was observed in the levels of Fbg in both men and women, but no differences were observed between men and women in each age group. A linear increase with age was also seen in the levels of FVIIc in women, but the levels of FVIIc in men were significantly higher for the age group 40-49 years than for any other age group. The levels of FVIIc in women were significantly higher than in men at age > or = 60 years. As concerning the effect of alcohol intake status, Fbg had a tendency to decrease with alcohol intake. Fbg and FVIIc levels were associated with an increase in smoking status in men, but no association was seen in women in either Fbg or FVIIc. FVIIc was positively correlated with age, body mass index, total cholesterol, triglycerides and fasting insulin level. Fbg was positively correlated with age, systolic blood pressure, diastolic blood pressure, total cholesterol, LDL-cholesterol and triglycerides in women, but Fbg had few positive correlations with risk factors in men. A comparison with previous Western studies showed that the Fbg levels of our Japanese population were lower than those of the Caucasians studied, but the present FVIIc levels were nearly the same level or slightly higher than theirs. The association of Fbg and FVIIc and with other cardiovascular risk factors in Japanese was similar to those observed in Caucasians.

Adult↗
PubMed1996

Clinical significance of activated protein C resistance as a potential marker for hypercoagulable state.

The activated protein C (APC)-resistance test is a simple and reliable method for detecting reduced sensitivity to the anticoagulant action of this protein. We investigated the sensitivity to APC in 180 Japanese controls and in 96 Japanese patients with venous and arterial thrombosis (28 with deep vein thrombosis; 13 with pulmonary thromboembolism; 41 with cerebral infarction; and 14 with coronary artery disease). All of the patient groups showed significantly reduced sensitivity to APC, reflected by the lower normalized APC-sensitivity ratio (n-APC-SR), as compared with healthy control. The APC-sensitivity ratio was negatively correlated with plasma activated factor VII levels. These results suggest that the low n-APC-SR is related to venous or arterial thrombotic disease. The APC resistance may serve as a potential marker for assessing the hypercoagulable state.

Adult↗
PubMed1996

Ischemic stroke and the gene for angiotensin-converting enzyme in Japanese hypertensives.

BACKGROUND: The ACE insertion/deletion (I/D) polymorphism is reported to be associated with myocardial infarction in both whites and Japanese. However, there have been no reports on the association of this polymorphism with stroke in each race. Furthermore, there are some racial differences in the demographics of cardiovascular disease. In Japanese, stroke (especially that which occurs in preexisting hypertension) is more common and coronary artery disease much less common than in whites. We propose that the ACE I/D polymorphism might be associated with hypertensive cerebrovascular disease in Japanese. METHODS AND RESULTS: To study the association between the ACE I/D polymorphism and hypertensive cerebrovascular disease, we identified the ACE I/D genotype in 228 hypertensive and 104 normotensive Japanese subjects. Compared with its frequency (0.31) in the 90 hypertensives without lacunae detected by magnetic resonance imaging, the ACE*D allele frequency was significantly higher (0.47; P<.001) in the 138 hypertensives with silent or clinically overt ischemic stroke, whereas there was no significant difference between its frequency in hypertensives without lacunae and in 104 normotensive control subjects (0.34). The positive association between the ACE I/D genotype and ischemic stroke in hypertensive patients was independent of other risk factors. CONCLUSIONS: We found a positive association between the ACE*D allele and ischemic stroke in Japanese hypertensives in our study. The ACE*D allele may be an independent risk factor for the development of cerebrovascular disease in hypertensive patients.

Adult↗
PubMed1996

Molecular and cellular basis for type I heparin cofactor II deficiency (heparin cofactor II Awaji).

Heparin cofactor II (HCII) is a serine proteinase inhibitor in human plasma that rapidly inhibits thrombin in the presence of dermatan sulfate or heparin. To understand the molecular mechanism for HCII deficiency in a patient with reduced circulating HCII antigen, we studied a Japanese patient with type I HCII deficiency who suffered from angina pectoris and coronary artery disease. Polymerase chain reaction (PCR)-based sequence analysis showed that the propositus' gene for HCII (HCII Awaji gene) had a thymine insertion after codon (GAT) for Asp88 in exon II, resulting in a frameshift mutation. Consequently, the abnormal HCII Awaji protein was suggested to have an altered amino acid sequence from position 89 and terminate at 107, thus being composed of the NH2-terminal one fifth of normal HCII and dysfunctional for thrombin inhibition. The molecular weight and pI value of HCII Awaji were calculated to be 12,040 and 3.6, respectively, without posttranslational modification. Mutagenic PCR followed by the Tsp509I digestion showed that a half of the PCR products derived from the propositus and his sister was cleaved, suggesting that his sister also has the same mutant allele. Crossed-immunoelectrophoresis and Western blot analyses of plasma and urine from the the propositus and of plasma from his sister did not provide evidence for the existence of the abnormal HCII, suggesting that little truncated HCII was circulating in the patient's blood. However, stable expression assay using human kidney 293 cells transfected with the expression vector containing cDNA encoding wild-type or Awaji-type HCII showed that mutant as well as wild-type HCII was secreted into culture medium normally. These results suggest that the abnormal HCII Awaji protein is secreted normally, but rapidly degraded in the circulating blood.

Amino Acid Sequence↗
PubMed1996

A common mutation in methylenetetrahydrofolate reductase gene among the Japanese population.

Hyperhomocysteinemia has been reported as an independent risk factor for atherosclerotic cerebrovascular and coronary heart diseases. 5, 10-Methylenetetrahydrofolate reductase (MTHFR) is one of the enzymes responsible for hyperhomocysteinemia. The C to T transition of the MTHFR gene at nucleotide position 677 results in decreasing the enzymatic activity and increasing the plasma homocysteine level. We studied the distribution of the MTHFR gene mutation among the Japanese population. The subjects were 129 Japanese males (aged 40-59 years). The allele frequency of the mutation was 0.38. The frequencies of the three genotypes were as follows: +/+, 11%; +/-, 54%; -/-, 35% (+ and-indicate the presence and absence of the mutation, respectively). We also studied the frequency of the MTHFR gene mutation in the middle-aged Japanese males with hypertension to investigate the possibility that this mutation is related to essential hypertension. The normotensive and hypertensive subjects were identical in the distribution of the mutated allele and the frequencies of the three genotypes. Furthermore, the prevalence of hypertension in each genotype group was same, although the mean diastolic pressure of the group with homozygous mutation was significantly higher than that of other groups (p < 0.05). Therefore, we concluded that there was no significant relationship between the MTHFR gene mutation and hypertensive subjects studied in this study.

Adult↗
PubMed1996

Characteristics of the insulin resistance syndrome in a Japanese population. The Jichi Medical School Cohort Study.

We investigated the relationships between hyperinsulinemia (a major indicator of the insulin resistance syndrome), blood pressure, dyslipidemia, and coagulation factors in 2606 community-dwelling Japanese individuals as part of the Jichi Medical School Cohort Study. An age-related decrease of the fasting insulin level was found in men but not in women. Body mass index, systolic and diastolic blood pressure, triglyceride and fasting glucose levels, and factor VII activity all increased in both sexes as the insulin level became higher, while the HDL cholesterol level decreased. In addition, total cholesterol and LDL cholesterol levels increased as the insulin level became higher and lipoprotein(a) levels decreased in the men. Fibrinogen levels were not related to the insulin level in either sex. Multiple logistic regression analysis revealed that fasting insulin levels were positively correlated with body mass index and fasting glucose and factor VII activity levels, whereas they were negatively correlated with HDL cholesterol in both sexes. In addition, fasting insulin levels were positively correlated with LDL cholesterol levels in men and with triglyceride levels in women. Our results indicate that hyperinsulinemia is associated with high factor VII activity in a general Japanese population as well as with high blood pressure and dyslipidemia. The accumulation of these cardiovascular risk factors in hyperinsulinemic subjects appears to contribute to cardiovascular events in the Japanese as well as in westerners.

Adult↗