Relationship between erythropoietin administration and the endothelial nitric oxide synthase gene polymorphism in patients with hemodialysis.
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Biomedical subjects
Publications and source records attributed to M Yokota.
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The aim of the present study was to evaluate endosseous implants in conjunction with the sinus lift procedure using periodontal parameters and computed tomography (CT) scanning. In 6 patients, 8 sinus lift procedures were performed to the atrophic posterior maxilla. Fourteen endosseous implants were placed. The condition of the peri-implant mucosa was assessed postoperatively at an average of 31 months using periodontal parameters such as plaque index, probing depth, clinical attachment level, and bleeding on probing. All the implants were maintained in a clinically healthy condition throughout the observation period. CT images revealed the difference in the morphology of the sinus floor between the locations of the block-shaped bone and the small pieces of bone which were both grafted. The results indicated that endosseous implants in conjunction with the sinus lift procedure could be maintained by monitoring the periodontal parameters.
OBJECT: Surgical or endovascular occlusion of the parent artery proximal to an aneurysm has been recommended for treatment of dissecting aneurysms of the intracranial posterior circulation. However, dissecting aneurysms may rupture even after proximal occlusion because distal progression of thrombus is necessary to occlude the dissecting aneurysm completely, and this may be delayed by the presence of retrograde flow. In this article the authors present their experience in treating six patients with ruptured dissecting aneurysms. METHODS: The authors report on six patients with a ruptured dissecting aneurysm in the posterior fossa who were successfully treated by endovascular occlusion of the aneurysm by using Guglielmi detachable coils. The procedure was particularly aimed at occluding the dissected site. CONCLUSIONS: At the present time, endovascular occlusion of the dissected site is a safe, minimally invasive, and reliable treatment for dissecting aneurysms when a test occlusion is tolerated and adequate collateral circulation is present.
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We identified 12 new cases of hypertrophic cardiomyopathy (HCM) and 3 new cases of dilated cardiomyopathy (DCM with echocardiography) in 72980 (aged 18-85 years, 43.1 +/- 14.1) industrial workers during an annual health check from April to October in 1996. Two of 3 patients with DCM were males, 21 and 25 years of age. No patients had symptoms. ST-T abnormalities by electrocardiography were found in 87% (13/15) of patients with cardiomyopathy and left ventricular hypertrophy (LVH) in 53% (8/15). Our findings suggest that echocardiography is important in mass screening for early detection of asymptomatic cardiomyopathy in middle-aged as well as young patients with ST-T abnormalities.
The role of cysteinyl leukotrienes (cys-LTs) and thromboxane A(2) (TXA(2)) in guinea pig models of aspects of bronchial asthma was investigated. In a novel antigen (BSA)-induced asthmatic model using passively sensitized guinea pigs, pretreatment with varying doses of indomethacin controlled the ratio of followed lipid mediators, LTC(4)/D(4)/E(4) and TXB(2), in lungs of challenged guinea pigs. The predominant mediator in indomethacin-untreated asthma was TXA(2), and complete inhibition of cyclooxygenase by i.v. injection of 5-mg/kg indomethacin-induced cys-LTs mainly mediated asthmatic response. Furthermore, a 1-mg/kg indomethacin dose induced an asthmatic state where both cys-LTs and TXA(2) equally participated. Either LTD(4) or TXA(2) receptor antagonists given alone inhibited the asthmatic response in conditions where the corresponding mediator plays a predominant role. The combination of LTD(4) and TXA(2) receptor antagonists exhibited significant effects irrespective of the condition used. Under conditions where both mediators equally participate, a combination of both receptor antagonists showed additive inhibition. YM158, a newly synthesized and orally active dual antagonist for LTD(4) and TXA(2) receptors, showed the same antiasthmatic effect as a combinated LTD(4) receptor antagonist and a TXA(2) receptor antagonist mixture. Therefore, broad-acting compounds such as YM158 are expected to have antiasthmatic efficacies in a broader class of asthmatic patients than single-acting drugs.
We operated on 10 cases diagnosed as congenital coronary artery fistula, including 2 critical neonates. Such neonates needed special care for perfusion pressure drop at the beginning of cardiopulmonary bypass and imperfect delivery of cardioplegia. This phenomenon is likely to depend on the shunt size of a fistula, that is much larger in such neonates than in older patients who could be operated on electively. It was helpful in the situation to crossclamp the main PA, compress the fistula and crossclamp the aorta quickly for a standstill. We prefer the closure of a fistula in the recipient chamber especially when an important area is supplied distally to the origin of the fistula. However, if a ventricle is a recipient chamber, the closure through coronary incision should be done as the neonates in our series. There were two hospital deaths due to vascular leakage syndrome and hypoxia, respectively. Aortic regurgitation (AR) got worse in two after the operation. They were found to have more dilatation and distortion in the Valsalva's sinus which appeared to affect the aortic annulus to some extent. It is likely due to long-standing larger shunt. Contrary to them, the patient operated on during neonatal period was followed by no increase of AR, though she had the largest shunt of our series. We have an impression it could be prevented by earlier operation.
Arachidonic acid metabolites mediate inflammatory responses at a cellular level. The affinity of the newly synthesized compound YM158, 3-[(4-tert-butylthiazol-2-yl)methoxy]-5'-[3-(4-chlorobenzenesuf onyl)propyl-2'-(1H-tetrazol-5-ylmethoxy)benzanilide monosodium salt monohydrate, for leukotriene D4 and thromboxane A2 receptors was examined in radioligand binding assays. YM158 inhibited [3H]leukotriene D4 and [3H]U46619 (9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F2alpha) binding to guinea pig lung membrane preparations, with Ki values of 0.64+/-0.06 nM for leukotriene D4 and 5.0+/-0.88 nM for thromboxane A2 receptors. The Hill coefficients (nH) did not significantly differ from unity, indicating that this antagonism is competitive. In contrast, YM158 showed no affinity for several other receptors, including neurotransmitter-related (alpha1-, alpha2-, beta-adrenoceptors, histamine, 5-HT, muscarinic, sigma), C5a, opioid, Ca2+ channel, K+ channel, protein kinase C, bradykinin, endothelin, neurokinin and platelet activating factor receptors. These studies indicate that YM158 is a highly selective dual antagonist for leukotriene D4 and thromboxane A2 receptors, and this has potential clinical and research applications.
BACKGROUND: Although several genes or genetic loci that are responsible for or confer susceptibility to familial dilated cardiomyopathy (DCM) have been identified, genetic defects that underlie nonfamilial DCM remain to be characterized. Mice lacking manganese superoxide dismutase exhibit DCM, suggesting that impairment of the defense mechanisms against oxidative stress is an important susceptibility factor for DCM. Plasma platelet-activating factor (PAF) acetylhydrolase also acts as a key defense against oxidative stress by hydrolyzing PAF and oxidized phospholipids. Thus, abnormalities in the activity of this enzyme may result in predisposition to myocardial damage. METHODS AND RESULTS: The possible association of a G994 (M allele)-->T (m allele) missense mutation in the plasma PAF acetylhydrolase gene with genetic susceptibility to nonfamilial DCM has now been investigated in 122 Japanese individuals with this condition and 226 healthy control subjects. PAF acetylhydrolase activity in plasma was significantly associated with plasma PAF acetylhydrolase genotype in both DCM patients and healthy control subjects. The frequency of the mutant m allele was significantly higher in DCM patients than in control subjects. Left ventricular mass (LVM) and the LVM index in DCM patients with Mm or mm genotypes were significantly greater than those in patients with the MM genotype. CONCLUSIONS: The G994-->T mutation in the plasma PAF acetylhydrolase gene is associated with nonfamilial DCM in Japanese subjects. Although the mutation is unlikely to be a causative factor, it may contribute to genetic susceptibility to or progression of nonfamilial DCM.
We investigated the association between variations in the endothelial constitutive nitric oxide synthase (ecNOS) gene and the presence of myocardial infarction. The results indicate that the mutant allele (ecNOS'4a) is an independent risk factor for myocardial infarction in the Japanese population, especially in those lacking other conventional risk factors.
An accelerated weight gain is noted in the heart of Ca-deficient, hypertensive chick embryos maintained in a shell-less culture in vitro. We previously observed that the Ca handling property of cardiomyocytes isolated from the shell-less embryo is altered, i.e., faster Ca uptake, suggesting a requirement for adequate Ca supply and/or proper Ca handling in embryonic cardiac development. In this study, we have examined the function of Ca on cardiomyocytes by analyzing the effects of 1) various Ca concentration in the culture medium (NCa, 1.8 mmol/ L; HCa, 2.8 mmol/L; LCa, 0.9 mmol/L), and 2) various modulators of Ca handling on cell proliferation and phenotype regulation in chick embryonic cardiomyocytes. The analytical parameters included cell number, DNA content, expression of cell cycle-specific and cardiomyocyte-specific proteins, and creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) enzyme activities. Cell number and total DNA were significantly larger (P < 0.01) in LCa cultures compared with those in NCa. The level of LDH was elevated (P < 0.01), but that of CPK was lowered in LCa. Expression of the G1-S-specific protein PCNA was raised, but that of the contractile proteins myosin and tropomyosin was substantially suppressed in LCa; in HCa, the cells did not proliferate as well, whereas the level of contractile proteins was higher. Thapsigargin, a sarcoplasmic reticulum (SR)-specific, Ca-ATPase inhibitor, simulated the effects of LCa by enhancing cell proliferation and lowering the expression of tropomyosin. These results suggest that culturing in low Ca concentration and inhibition of SR Ca pumping enhance myocardial cell proliferation and suppress sarcomeric protein expression, perhaps by inducing cellular de-differentiation. The in vitro effects of medium Ca concentration and Ca handling modulators on cardiomyocytes also suggest that the in vivo cardiomegaly of the SL embryos is a direct result of Ca-deficiency, and that Ca is important in the phenotype regulation of cardiomyocytes.
BACKGROUND AND HYPOTHESIS: Although the immediate effects of sleep apnea on hemodynamics and the neurological system have been studied, little is known about the circadian rhythm of heart rate variability in patients with obstructive sleep apnea syndrome (OSAS). The purpose of the present study was to investigate the effects of sleep apnea on the autonomic activity during daytime, which may play some role in the pathogenesis of cardiovascular complications in OSAS. METHODS: We studied 18 middle-aged male patients with OSAS and 10 age-matched control subjects. Patients with OSAS were classified according to the severity of OSAS: patients with an apnea index (AI) < 20 were considered to have mild OSAS (Group 1, n = 8) and patients with an AI > or = 20 were considered to have severe OSAS (Group 2, n = 10). Heart rate variability was calculated from the 24-h ambulatory electrocardiograms by the Fourier transformation. Power spectra were quantified at 0.04-0.15 Hz [low frequency power (LF)ln(ms2)] and 0.15-0.40 Hz [high frequency power (HF)ln(ms2)]. The HF component and the ratio of LF to HF were used as indices of the parasympathetic and sympathetic activity, respectively. RESULTS: The circadian rhythms of the LF, HF, and LF/HF ratio differed significantly in Group 2 compared with Group 1 and control subjects (p < 0.05). Hypertension (> 160/95 mm Hg) was found in 7 (70.0%) of 10 patients in Group 2, and in 1 (12.5%) of 8 patients in Group 1. Echocardiographic evidence of left ventricular hypertrophy (LVH) (an interventricular septal thickness or a left ventricular posterior wall thickness > or = 12 mm) was found in 3 (30.0%) of 10 patients in Group 2, and in 1 (12.5%) of 8 patients in Group 1. The mean HF from 4 A.M. to 12 noon was significantly lower in Group 2 than in Group 1 and the control group, and it correlated significantly with the lowest nocturnal SaO2 (r = 0.58, p < 0.05). The mean LF/HF ratio during the same period was significantly higher in Group 2 than in Group 1 and the control group, and it correlated significantly with total time of the nocturnal oxygen saturation < 90% (r = 0.64, p < 0.005) and the lowest nocturnal SaO2 (r = 0.56, p < 0.05). Ventricular tachycardia was found in the early morning in one patient, ST-T depression in two patients, and sinus arrest in two patients in Group 2. CONCLUSION: These findings suggest that sleep-disordered breathing associated with severe oxygen desaturation might influence heart rate variability not only during sleep but also during daytime. OSAS per se might contribute to altered circadian rhythm in autonomic activity leading to the development of cardiovascular diseases.
BACKGROUND: Although nocturnal pulseoximetry is routinely performed in obstructive sleep apnea syndrome (OSAS), pulseoximetry over a 24-h period has not been studied. HYPOTHESIS: The purpose of the study was to determine whether simultaneous 24-h oxygen desaturation and electrocardiographic (ECG) recording might be used to screen for daytime sleep sequelae in patients with OSAS. METHODS: Simultaneous recording of arterial oxygen saturation (SpO2) and ECG was conducted over a 24-h period in 18 male patients with OSAS (mean age 51.3 years) who were diagnosed by standard polysomnography (PSG), and in 15 age-matched healthy subjects (mean age 52.7 years) as controls to evaluate circadian variation of these parameters. The measures of heart rate variability (HRV) were calculated from 24-h ambulatory ECGs. Seventeen patients with OSAS showed excessive daytime sleepiness (EDS). We calculated the duration in which SpO2 decreased to < 90% (duration of SpO2 < 90%). The number of apnea/hypopneas per hour (AHI) during sleep was investigated with Apnomonitors (Chest MI, Co., Tokyo) on the same day as the SpO2 recordings. RESULTS: Controls showed no episodes of oxygen desaturation. In patients with OSAS, driving (33.3% of patients with OSAS) was the most common activity in which SpO2 decreased to < 90%, followed by daytime napping (27.8%) and resting after meals (22.2%). The duration of SpO2 < 90% over a 24-h period correlated significantly with the duration levels recorded during sleep (r = 0.99, p < 0.05) and in the afternoon (r = 0.62, p < 0.05), and with the AHI (r = 0.55, p < 0.05), but not with the duration of SpO2 < 90% in the morning. The number of ventricular premature beats correlated significantly with the duration of SpO2 < 90% for a 24-h period, but not with measures of HRV. Ventricular tachycardia was found in two (11.1%) and ST-T depression in three patients (16.6%) with underlying cardiac diseases. CONCLUSION: Our results suggest that daytime sleep attacks accompanied by oxygen desaturation in patients with moderate to severe OSAS may contribute to the occurrence of traffic or cardiovascular accidents. We conclude that 24-h ambulatory recordings of SpO2 and ECG are useful for screening for daytime sleep sequelae associated with the potential risk of this pathology in OSAS during social activities.
Platelet-activating factor (PAF) acetylhydrolase may play important roles in the pathophysiology of thrombosis and atherosclerosis related to its catalytic action in the degradation of PAF and oxidized phospholipids. A missense mutation (G--> T transversion at nucleotide 994) in the plasma PAF acetylhydrolase gene results in a Val--> Phe substitution at amino acid 279 of the mature protein and a consequent loss of catalytic activity. However, the role of a deficiency or low activity of this enzyme caused by the missense mutation in the etiology of coronary artery disease (CAD) has not been determined. The relation between this mutation and the incidence of CAD in the Japanese population is investigated herein. The genotype of plasma PAF acetylhydrolase (MM, normal; Mm, heterozygote; and mm, deficient homozygote) was determined with a polymerase chain reaction (PCR) assay for 454 patients with myocardial infarction (MI) and 602 control subjects. The frequency of the m allele was significantly higher in male patients with MI (odds ratio, 1.8) than in controls, an association that was more marked in a low-risk subgroup (odds ratio, 2.3). In contrast, the m allele was not associated with MI in women. These results indicate that the G994--> T missense mutation in exon 9 of the plasma PAF acetylhydrolase gene is an independent risk factor for CAD in Japanese men, especially low-risk individuals, but not in women.
Surplus blood often remains after routine clinical tests using EDTA-anticoagulated samples. To use this blood for DNA analysis, we isolated white cells by adherence to polyethylene terephthalate fibers, which could be stored for several weeks transported by mail after methanol fixation. DNA yield was sufficient and correlated with white cell count. Extracted DNA was free of hemoglobin contamination and durable to polymerase chain reaction and enzyme digestion, which yielded products visualized as well-separated bands on electrophoresis. We found our method to be practical for the routine clinical laboratory.
The long-term natural course of obstructive sleep apnea syndrome (OSAS) is studied in order to determine whether severity of nocturnal oxygen desaturation associated with apnea/hypopnea, body mass index (BMI), and hypertension influence survival in young (<40 years), middle-aged (40-64 years), and aged (> or = 65 years) using a questionnaire survey. One hundred and forty-eight patients with OSAS aged 17-78 years (136 men, 12 women, mean 52.0+/-12.3 years), who were diagnosed by standard polysomnography (PSG) between 1983 and 1993, participated in the study. The survey revealed 15 deaths and 101 survivors; 32 subjects could not be located. The survival rate was 71.4% (95% confidence interval: 55.6-87.2%). The survival rate in patients with OSAS was significantly lower than that in the age and sex-adjusted control Japanese population (87.6%). In the young group, only one death (a 19-year-old woman) occurred unexpectedly during sleep. The patient showed an apnea/hypopnea index (AHI) of 33 per h and the length of time that the nocturnal oxygen saturation (SaO2) fell below 90% (time of SaO2 <90%) of 205 min. The survival rate in middle-aged patients with OSAS was significantly lower than that in the age and sex-adjusted control Japanese population (79.2 vs 91.0%), but this pattern was not seen among the aged. Time of SaO2 <90% was significantly longer in the middle-aged patients than in the aged patients, but AHI did not differ between the two groups. Moreover, it was significantly correlated with AHI in middle-aged patients, but not in the aged patients. The survival rate was significantly lower in patients with hypertension than in the patients without such complications in the middle-aged group (57.9 vs 90.4%). Cox proportional-hazard regression model including age, hypertension, BMI, AHI, lowest SaO2, and time of SaO2 <90% showed that hypertension was only significantly associated with lower survival rate in total group and middle-aged patients, but not in the young or aged patients. The prognosis in patients with OSAS may differ among the generations. The prognosis in the middle-aged population may depend on the role of OSAS on the complications of hypertension or severity of oxygen desaturation, but not on AHI only.
We evaluated the rate of automobile accidents and daytime sleepiness using the Epworth sleepiness scale (ESS) in 44 patients with obstructive sleep apnea syndrome (OSAS). We defined the automobile accident score as a sum of two points for every one automobile accident and one point for every near-miss accident. Automobile accidents and near-misses were found in 54.5% and 50.0% in patients with OSAS. Automobile accident score was significantly correlated with the ESS score (r=0.56, P < 0.01). Our findings suggest that ESS score may be useful in detecting patients with the potential risk of automobile accidents associated with daytime sleepiness.