Endothelium-Independent Vasodilatory Effect of Sailuotong (SLT) on Rat Isolated Tail Artery.

BACKGROUND: Sailuotong (SLT) is a standardized three-herb formulation consisting of extracts of Panax ginseng, Ginkgo biloba, and Crocus sativus for the treatment of vascular dementia (VaD). Although SLT has been shown to increase cerebral blood flow, the direct effects of SLT on vascular reactivity have not been explored. This study aims to examine the vasodilatory effects of SLT and the underlying mechanisms in rat isolated tail artery. METHODS: Male (250-300 g) Wistar Kyoto (WKY) rat tail artery was isolated for isometric tension measurement. The effects of SLT on the influx of calcium through the cell membrane calcium channels were determined in Ca2+-free solution experiments. RESULTS: SLT (0.1-5,000 µg/ml) caused a concentration-dependent relaxation in rat isolated tail artery precontracted by phenylephrine. In the contraction experiments, SLT (500, 1,000, and 5,000 µg/mL) significantly inhibited phenylephrine (0.001 to 10 µM)- and KCl (10-80 mM)-induced contraction, in a concentration-dependent manner. In Ca2+-free solution, SLT (500, 1,000, and 5,000 µg/mL) markedly suppressed Ca2+-induced (0.001-3 mM) vasoconstriction in a concentration-dependent manner in both phenylephrine (10 µM) or KCl (80 mM) stimulated tail arteries. L-type calcium channel blocker nifedipine (10 µM) inhibited PE-induced contraction. Furthermore, SLT significantly reduced phenylephrine-induced transient vasoconstriction in the rat isolated tail artery. CONCLUSION: SLT induces relaxation of rat isolated tail artery through endothelium-independent mechanisms. The SLT-induced vasodilatation appeared to be jointly meditated by blockages of extracellular Ca2+ influx via receptor-gated and voltage-gated Ca2+ channels and inhibition of the release of Ca2+ from the sarcoplasmic reticulum.

Using 3D-UPLC-DAD and a new method-verification by adding mixture standard compounds to determine the fingerprint and eight active components of Naoluoxintong decoction.

Naoluoxintong decoction (NLXTD) is a traditional Chinese formula which has been used for the management of ischemic stroke in China for two hundred years. In this study, we developed a comprehensive and reliable analytical method to qualitatively analyze the components in NLXTD. This novel method was based on three-dimensional ultra-fast high performance liquid chromatography coupled with diode array detector (3D-UPLC-DAD) with an additional component validation method via incorporation of the mixture standard compounds during the verification step. In addition, the relationship between active components and "Monarch drug, Minster drug, Assistant drug, Guide drug" were determined. Our results showed that gradient elution with the mobile phase of 0.02% formic acid and methanol was the optimum condition to separate peaks. A total of 35 common peaks were established by comparing ten batches of NLXTD, and eight components were identified, including Calycosin, Calycosin-7-O-ß-d-glucoside and Ononin in Astragali radix (Monarch drug); Ligustrazine in Chuanxiong Rhizoma (Minster drug); 4-Hydroxbenzyl alcohol and Parishin A in Gastrodiae rhizome (Assistant drug); Ferulic acid in Angelicae sinensis radix (Guide drug). The validation method of verification by adding mixture standard compounds combined with 3D-UPLC-DAD method, with the merits of greater resolution, higher speed of analysis and higher sensitivity, provided a semi-quantitative and qualitative analysis method to assess traditional Chinese medicinal prescription consisting of many bio-active components. Finally, our study has provided systemic and scientific evidence to explain the relationship between the bio-active components in the NLXTD and traditional Chinese medicine theory.

An algorithm for the management of coagulopathy from postpartum hemorrhage, using fibrinogen concentrate as first-line therapy.

BACKGROUND: We constructed an algorithm for the management of coagulopathy from massive postpartum hemorrhage. Fibrinogen concentrate was administered preferentially, and the dose of both fibrinogen concentrate and fresh frozen plasma given was determined by the plasma fibrinogen concentration and prothrombin time. The efficacy of the algorithm and the amount of fibrinogen concentrate and fresh frozen plasma transfused were determined. METHODS: The study was conducted in a single teaching perinatal center. Nineteen patients were included between April 2011 and March 2014 (patient group). For a historical comparison group, we retrospectively analyzed the records of 19 patients who had been treated for coagulopathy from massive postpartum hemorrhage between April 2006 and March 2011 (control group). RESULTS: Blood loss was significantly lower in the patient group. No adverse events were associated with this management in either group. The dose of fibrinogen concentrate administered was significantly higher and that of fresh frozen plasma administered was significantly lower in the patient group. CONCLUSION: This algorithm appeared to help reduce blood loss and the total amount of fresh frozen plasma transfused when treating coagulopathy from postpartum hemorrhage, and may represent another strategy for achieving hemostasis in this setting.

A randomized, placebo-controlled trial of the benzoquinone idebenone in a mouse model of OPA1-related dominant optic atrophy reveals a limited therapeutic effect on retinal ganglion cell dendropathy and visual function.

Dominant optic atrophy (DOA) arises from mutations in the OPA1 gene that promotes fusion of the inner mitochondrial membrane and plays a role in maintaining ATP levels. Patients display optic disc pallor, retinal ganglion cell (RGC) loss and bilaterally reduced vision. We report a randomized, placebo-controlled trial of idebenone at 2000 mg/kg/day in 56 Opa1 mutant mice (B6;C3-Opa1(Q285STOP)), with RGC dendropathy and visual loss, and 63 wildtype mice. We assessed cellular responses in the retina, brain and liver and RGC morphology, by diolistic labeling, Sholl analysis and quantification of dendritic morphometric features. Vision was assessed by optokinetic responses. ATP levels were raised by 0.57 nmol/mg (97.73%, p=0.035) in brain from idebenone-treated Opa1 mutant mice, but in the liver there was an 80.35% (p=0.011) increase in oxidative damage. NQO1 expression in Opa1 mutant mice was reduced in the brain (to 30.5%, p=0.002) but not in retina, and neither expression level was induced by idebenone. ON-center RGCs failed to show major recovery, other than improvements in secondary dendritic length (by 53.89%, p=0.052) and dendritic territory (by 2.22 × 10(4) µm(2) or 90.24%, p=0.074). An improvement in optokinetic response was observed (by 12.2 ± 3.2s, p=0.003), but this effect was not sustained over time. OFF-center RGCs from idebenone-treated wildtype mice showed shrinkage in total dendritic length by 2.40 mm (48.05%, p=0.025) and a 47.37% diminished Sholl profile (p=0.029). Visual function in wildtype idebenone-treated mice was impaired (2.9 fewer head turns than placebo, p=0.007). Idebenone appears largely ineffective in protecting Opa1 heterozygous RGCs from dendropathy. The detrimental effect of idebenone in wildtype mice has not been previously observed and raises some concerns.

Plasma Low-density Lipoprotein Receptor-related Protein 1 Concentration is not Associated with Human Abdominal Aortic Aneurysm Presence.

OBJECTIVE/BACKGROUND: Recent genetic data suggest that a polymorphism of LRP1 is an independent risk factor for abdominal aortic aneurysm (AAA). The aims of this study were to assess whether plasma and aortic concentrations of low-density lipoprotein receptor-related protein 1 (LRP1) are associated with AAA, and to investigate the possible relevance of LRP1 to AAA pathophysiology. METHODS: Three analyses were conducted. First, plasma LRP1 concentrations were measured in community-dwelling men with and without AAA (n = 189 and n = 309, respectively) using enzyme-linked immunosorbent assay. Second, Western blotting analyses were employed to compare the expression of LRP1 protein in aortic biopsies collected from patients with AAA and nonaneurysmal postmortem donors (n = 6/group). Finally, the effect of in vitro LRP1 blockade on matrix metalloprotease 9 (MMP9) clearance by vascular smooth muscle cells was assessed by zymography. RESULTS: Plasma LRP1 concentrations did not differ between groups of men with and without AAA (median concentration 4.56 µg/mL [interquartile range {IQR} (3.39-5.96)] and 4.43 µg/mL [IQR 3.44-5.84], respectively; p = .48), and were not associated with AAA after adjusting for other risk factors (odds ratio 1.10 [95% confidence interval: 0.91-1.32]; p = 0.35). In contrast, LRP1 expression was approximately 3.4-fold lower in aortic biopsies recovered from patients with AAA compared with controls (median [IQR] expression 1.72 [0.94-3.14] and 5.91 [4.63-6.94] relative density units, respectively; p < .01). In vitro LRP1 blockade significantly reduced the ability of vascular smooth muscle cells to internalize extracellular MMP9. CONCLUSIONS: These data suggest that aortic but not circulating LRP1 is downregulated in patients with AAA and indicates a possible role for this protein in clearing an aneurysm-relevant ligand.

Diabetes Mellitus, Cognitive Impairment, and Traditional Chinese Medicine.

Diabetes mellitus (DM) is a metabolic disorder affecting a large number of people worldwide. Numerous studies have demonstrated that DM can cause damage to multiple systems, leading to complications such as heart disease, cancer, and cerebrovascular disorders. Numerous epidemiological studies have shown that DM is closely associated with dementia and cognition dysfunction, with recent research focusing on the role of DM-mediated cerebrovascular damage in dementia. Despite the therapeutic benefits of antidiabetic agents for the treatment of DM-mediated cognitive dysfunction, most of these pharmaceutical agents are associated with various undesirable side-effects and their long-term benefits are therefore in doubt. Early evidence exists to support the use of traditional Chinese medicine (TCM) interventions, which tend to have minimal toxicity and side-effects. More importantly, these TCM interventions appear to offer significant effects in reducing DM-related complications beyond blood glucose control. However, more research is needed to further validate these claims and to explore their relevant mechanisms of action. The aims of this paper are (1) to provide an updated overview on the association between DM and cognitive dysfunction and (2) to review the scientific evidence underpinning the use of TCM interventions for the treatment and prevention of DM-induced cognitive dysfunction and dementia.

Immunogenicity of dormancy-related antigens in individuals infected with Mycobacterium tuberculosis in Japan.

SETTING: DosR regulon genes are considered essential for Mycobacterium tuberculosis dormancy, and their products are demonstrated to have immunogenicity in M. tuberculosis-infected individuals, suggesting that DosR regulon-encoded proteins are suitable targets for vaccines to control the reactivation of dormant M. tuberculosis. OBJECTIVE: Prospective analysis of T-cell and antibody responses against DosR regulon-encoded antigens in M. tuberculosis-infected individuals in Japan to identify effective vaccine targets. DESIGN: T-cell responses against 33 DosR regulon-encoded antigens were investigated in 26 consecutive M. tuberculosis-infected individuals--14 with latent tuberculosis infection (LTBI) and 12 with active pulmonary tuberculosis (PTB)--using enzyme-linked immunosorbent spot assay, and antibody responses in 42 consecutive individuals, 14 with LTBI and 28 with PTB. RESULT: Six antigens (Rv0570, Rv1996, Rv2004c, Rv2028c, Rv2029c and Rv3133c) induced stronger T-cell responses in LTBI than in PTB, In contrast, antigen-specific antibody responses to five antigens (Rv0080, Rv1738, Rv2007c, Rv2031c and Rv2032) were found to be stronger in PTB than in LTBI cases. CONCLUSION: T-cell responses to six antigens might contribute to natural protection against dormant M. tuberculosis. These antigens are therefore considered to be potential targets of novel vaccines to control M. tuberculosis reactivation in the Japanese population.

Novel hypoglycemic effects of Ganoderma lucidum water-extract in obese/diabetic (+db/+db) mice.

In this study, we evaluated the pharmacological effects of Ganoderma lucidum (G. lucidum) (water-extract) (0.003, 0.03 and 0.3g/kg, 4-week oral gavage) consumption using the lean (+db/+m) and the obese/diabetic (+db/+db) mice. Different physiological parameters (plasma glucose and insulin levels, lipoproteins-cholesterol levels, phosphoenolpyruvate carboxykinase (PEPCK), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) and isolated aorta relaxation of both species were measured and compared. G. lucidum (0.03 and 0.3g/kg) lowered the serum glucose level in +db/+db mice after the first week of treatment whereas a reduction was observed in +db/+m mice only fed with 0.3g/kg of G. lucidum at the fourth week. A higher hepatic PEPCK gene expression was found in +db/+db mice. G. lucidum (0.03 and 0.3g/kg) markedly reduced the PEPCK expression in +db/+db mice whereas the expression of PEPCK was attenuated in +db/+m mice (0.3g/kg G. lucidum). HMG CoA reductase protein expression (in both hepatic and extra-hepatic organs) and the serum insulin level were not altered by G. lucidum. These data demonstrate that G. lucidum consumption can provide beneficial effects in treating type 2 diabetes mellitus (T2DM) by lowering the serum glucose levels through the suppression of the hepatic PEPCK gene expression.

Inhibitory effects of epoxyeicosatrienoic acids on volume-activated chloride channels in rat mesenteric arterial smooth muscle.

Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by cytochrome P450 epoxygenases in endothelial cells. It has previously been shown that EETs activate K(+) channels, which are important for the hyperpolarization and dilation of blood vessels. However, the effects of EETs on other ion channels have been less well studied. We investigated the effects of EETs on volume-activated Cl(-) channels (VACCs) in rat mesenteric arterial smooth muscle cells. Whole-cell patch clamp recording demonstrated that hypotonic solution and guanosine 5'-[gamma-thio]triphosphate (GTPgammaS) induced a 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB)- and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)-sensitive VACC current in the primary cultured rat mesenteric arterial smooth muscle cells. The VACC current was inhibited by EETs and the order of potency was 8,9-EET>5,6-EET>11,12-EET>14,15-EET. The inhibitory effects of EETs could be reversed by 14,15 epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, an EET analog), Rp-cGMP and KT-5823 (protein kinase G inhibitors). Interestingly, the inhibitory effects of EETs on VACCs were not influenced by Rp-cAMP (a protein kinase A antagonist) but it could be abolished by NF-449 (a Gs protein inhibitor), indicating the involvement of cAMP but not protein kinase A. In conclusion, our results demonstrate that EETs inhibit VACCs in rat mesenteric arterial smooth muscle cells through a cGMP-dependent pathway, which is probably due to the cross-activation by cAMP. This mechanism may be involved in the regulation of cell volume and membrane potential.

Butyric acid induces apoptosis in inflamed fibroblasts.

Butyric acid, an extracellular metabolite from periodontopathic bacteria, induces apoptosis in murine and human T- and B-cells, whereas intact gingival fibroblasts isolated from healthy humans are resistant to butyric-acid-induced apoptosis. We examined the susceptibility of inflamed gingival fibroblasts isolated from adult persons with periodontitis to butyric-acid-induced apoptosis. Butyric acid significantly suppressed the viability of inflamed gingival fibroblasts and induced apoptosis in a dose-dependent manner. The incubation of inflamed gingival fibroblasts with butyric acid induced DNA fragmentation and apoptotic changes such as chromatin condensation, hypodiploid nuclei, and mitochondrial injury. Furthermore, butyric-acid-induced apoptosis in inflamed gingival fibroblasts was reduced by caspase-3/7, -6, -8, and -9 inhibitors. Thus, inflamed gingival fibroblasts from adult persons with periodontitis appear to be highly susceptible to mitochondria- and caspase-dependent apoptosis induced by butyric acid, compared with healthy gingival fibroblasts.

Low-grade central osteosarcoma mimicking fibrous dysplasia: a report of two cases.

Low-grade central osteosarcoma is an unusual variant of conventional osteosarcoma. We present here two rare cases of low-grade central osteosarcoma resembling fibrous dysplasia. A 24-year-old woman diagnosed as fibrous dysplasia was treated with intra-lesional excision and curettage of the tumor but tumor recurred at 4 months after surgery. Distal femoral en-bloc resection was performed followed by arthroplasty with mega-prosthesis of the knee. A 57-year-old man diagnosed as central osteosarcoma was treated with wide excision of the tumor, followed by reconstruction with the vascularized fibula graft combined with an autogenous irradiated bone graft. Because of the difficulty in distinguishing low-grade central osteosarcoma from a benign lesion, open biopsy is needed to obtain a large tumor sample. Careful clinical and pathological evaluation is required to obtain a definite diagnosis. The treatment of low-grade central osteosarcoma is en-block resection with wide surgical margins.

Long-term follow-up of 5 patients with intracranial germinoma initially treated by chemotherapy alone.

BACKGROUND: High rates of overall- and event-free survival have been reported in patients with intracranial germinoma treated by radiotherapy. We report the long-term results after treatment initially with chemotherapy, but without radiation. PATIENTS AND METHOD: Five patients with an intracranial germinoma were treated with 2 cycles of etoposide and cisplatin, without radiotherapy. All achieved complete remission; 3 suffered recurrence within 2 years and were again treated with 2 cycles of etoposide and cisplatin followed by radiotherapy. RESULTS: At long-term follow-up, each of the 5 patients was in complete remission without further recurrence. Each patient with a neurohypophyseal germinoma who presented with endocrinopathy had initially recovered endocrinological function. CONCLUSION: In a patient with a germinoma chemotherapy, and restriction of radiation to those with recurrence may allow restoration of hypophyseal function damaged by the intracranial germinoma without compromising long term survivial.

Modulation by simvastatin of iberiotoxin-sensitive, Ca2+-activated K+ channels of porcine coronary artery smooth muscle cells.

BACKGROUND AND PURPOSE: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors) have been demonstrated to reduce cardiovascular mortality. It is unclear how the expression level of HMG CoA reductase in cardiovascular tissues compares with that in cells derived from the liver. We hypothesized that this enzyme exists in different cardiovascular tissues, and simvastatin modulates the vascular iberiotoxin-sensitive Ca2+-activated K(+) (BK(Ca)) channels. EXPERIMENTAL APPROACHES: Expression of HMG CoA reductase in different cardiovascular preparations was measured. Effects of simvastatin on BK(Ca) channel gatings of porcine coronary artery smooth muscle cells were evaluated. KEY RESULTS: Western immunoblots revealed the biochemical existence of HMG CoA reductase in human cardiovascular tissues and porcine coronary artery. In porcine coronary artery smooth muscle cells, extracellular simvastatin (1, 3 and 10 microM) (hydrophobic), but not simvastatin Na+ (hydrophilic), inhibited the BK(Ca) channels with a minimal recovery upon washout. Isopimaric acid (10 microM)-mediated enhancement of the BK(Ca) amplitude was reversed by external simvastatin. Simvastatin Na+ (10 microM, applied internally), markedly attenuated isopimaric acid (10 microM)-induced enhancement of the BK(Ca) amplitude. Reduced glutathione (5 mM; in the pipette solution) abolished simvastatin -elicited inhibition. Mevalonolactone (500 microM) and geranylgeranyl pyrophosphate (20 microM) only prevented simvastatin (1 and 3 microM)-induced responses. simvastatin (10 microM ) caused a rottlerin (1 microM)-sensitive (cycloheximide (10 microM)-insensitive) increase of PKC-delta protein expression. CONCLUSIONS AND IMPLICATIONS: Our results demonstrated the biochemical presence of HMG CoA reductase in different cardiovascular tissues, and that simvastatin inhibited the BK(Ca) channels of the arterial smooth muscle cells through multiple intracellular pathways.

Modulation by homocysteine of the iberiotoxin-sensitive, Ca2+ -activated K+ channels of porcine coronary artery smooth muscle cells.

We evaluated the acute effect of homocysteine on the iberiotoxin-sensitive, Ca(2+)-activated K(+) (BK(Ca)) channels of the porcine coronary artery smooth muscle cells. NS 1619 (1 to 30 microM) caused a concentration-dependent enhancement of the BK(Ca) amplitude (recorded using the whole-cell, membrane-rupture configuration) only with an elevated [Ca(2+)](i) of approximately 444 nM, but not with [Ca(2+)](i) of approximately 100 nM. Homocysteine (30 microM) caused a small inhibition ( approximately 16%) of the BK(Ca) amplitude ([Ca(2+)](i)= approximately 444 nM), and a greater inhibition ( approximately 77%) was observed with 100 microM NADH present in the pipette solution. The inhibition persisted after washing. With NADPH (100 microM), a smaller magnitude of inhibition ( approximately 34%) of the BK(Ca) amplitude was recorded. The NS 1619-mediated enhancement of the BK(Ca) amplitude (with elevated [Ca(2+)](i) plus NADH in the pipette) was attenuated by homocysteine. The homocysteine-mediated inhibition of the BK(Ca) amplitude was suppressed by Tiron (10 mM) or diphenylene iodonium (30 nM), applied alone, but not by superoxide dismutase (500 U/ml) and catalase (500 U/ml). Generation of superoxide (O(2)(-)) of the smooth muscle cells (with NADH presence), measured using the lucigenin-enhanced chemiluminescence, was markedly increased by angiotensin II (100 nM) and homocysteine (30 microM). The chemiluminescence signal was sensitive to apocynin (300 microM) or Tiron, applied alone, but not to superoxide dismutase and catalase. In conclusion, our results demonstrate that acute homocysteine application inhibits the iberiotoxin-sensitive BK(Ca) channels (with elevated [Ca(2+)](i) and NADH present) which is probably caused by the NADH oxidase activation and the concomitant generation of intracellular superoxide.

Transient antiphospholipid antibodies associated with acute infections in children: a report of three cases and a review of the literature.

We describe two previously healthy children who had multiple ecchymoses several days after acute infection. In both cases, the prothrombin time (PT) and the activated partial thromboplastin time (APTT) were prolonged. Further examinations revealed the presence of lupus anticoagulant (LA), phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT), and low serum complement. In both cases, we confirmed the presence of a serum immune complex. The patients' symptoms improved spontaneously within 1 week, and all laboratory data normalized within several months. We also describe another asymptomatic case positive for LA and aPS/PT presumably associated with cytomegalovirus infection. The prevalence of transient antiphospholipid antibodies associated with viral infections in children must be much higher than we expected. We have to take it into consideration when we see abnormal coagulation results, but the occurrence of significant bleeding symptoms is rare.

How HIV infected haemophiliacs in Japan were informed of their HIV-positive status.

The purpose of this study is to find out how HIV-infected haemophiliacs were informed and notified of their HIV infection. Self-reporting questionnaires were mailed to approximately 500 patients, about one half of the haemophiliac patients with HIV in Japan. The response rate was about 57% (n=283); and 270 (male=269) patients, apart from secondary and tertiary infected patients, were eligible as subjects for the study. The mean age was 31.2 +/- 9.9 years. Of these subjects, approximately 60% did not receive explanation regarding the risk of HIV infection via unheated blood products. More than 60% did not receive notification until 1990, or five years after the test became available in Japan. Contents of the explanations being given at the time of notifications were poor. In this paper, some problems of notifications of medically induced HIV are discussed, and the lack or delay of explanation/notification is concluded to be a consequence of the paternalistic attitudes of Japanese physicians and the iatrogenic nature of HIV infection.

Dependence on initial conditions of an adsorption-desorption process.

A one-dimensional irreversible adsorption-desorption process is simulated. The critical parameters as well as the critical exponents are measured. At the critical point, the crossover between the accumulative state and the depleted state is described by a universal characteristic function.

The effects of body mass index on age at menopause.

OBJECTIVE: We examined which of body mass index (BMI, kg/m(2)), serum cholesterol (mg/dl), or systolic blood pressure (SBP, mm Hg) affected age at natural menopause. DESIGN: A population-based follow-up program. METHODS: We determined the age at natural menopause in 1136 women followed biennially since their first examination in 1958-1959 through the 16th examination in 1988-1989. Four-hundred and ninety-three naturally menopausal women were classified into three groups by BMI, serum cholesterol and SBP measurement levels at age 40 or 41 y: the upper 25%, middle 50%, and lower 25%. We then studied whether there was a difference in age at menopause among the three groups thus classified. The 1136 natural menopausal women were also classified as early (n=454; 45-49 y at menopause (48.3+/-1.2 y)) or late (n=682; >or=50 y at menopause (52.3+/-1.6 y)) menopausal and compared for premenopausal trends in BMI, serum cholesterol and SBP in the early and late menopausal women by means of a longitudinal data analysis model. RESULTS: When women were classified into the three groups based on a BMI that was measured at 40 or 41 y, age at menopause in the upper 25% (50.4+/-2.8 y) was significantly higher (P<0.05) than that in the lower 25% (49.7+/-2.8 y). The entire premenopausal trend in BMI in late menopausal women shifted upward compared to that in early menopausal women. On the other hand, the premenopausal trend more than 4 y before menopause in serum cholesterol and the entire premenopausal trend in SBP in late menopausal women were identical to those in early menopausal women. CONCLUSION: Among the variables studied, only BMI is related to age at menopause, and the greater the BMI, the later the age at menopause.

Correlation between fatty liver and coronary risk factors: a population study of elderly men and women in Nagasaki, Japan.

The relation between fatty liver, detected by ultrasonography as a marker of visceral fat accumulation, and coronary risk factors was studied in 810 elderly men and 1,273 elderly women in Nagasaki, Japan from 1990 to 1992. The prevalence of fatty liver was 3.3% in the male and 3.8% in the female non-obese participants (BMI, body mass index < 26.0 kg/m2) and 21.6% in the male and 18.8% in the female obese participants (26.0 kg/m2 < or = BMI). Fatty liver was significantly (p < 0.01) related to hypercholesterolemia and hypertriglyceridemia in the men and to hypertension, hypercholesterolemia, low-HDL cholesterol, hypertriglyceridemia and diabetes mellitus or impaired glucose tolerance (DM+IGT) in the women independent of age, obesity, smoking and drinking. Non-obesity with fatty liver, rather than obesity with or without fatty liver, had the highest odds ratio for hypertension and low-HDL cholesterol in the men and for hypercholesterolemia, low-HDL cholesterol, hypertriglyceridemia and DM+IGT in the women. The prevalence of fatty liver is the same in elderly men and women, and fatty liver is an independent correlate of coronary risk factors in the elderly.

The prevalence, incidence and prognostic value of the Brugada-type electrocardiogram: a population-based study of four decades.

OBJECTIVES: We sought to demonstrate the prevalence, incidence and prognostic value of the Brugada-type electrocardiogram (ECG) in a general population. BACKGROUND: 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. METHODS: We investigated 4,788 subjects (1,956 men and 2,832 women) who were <50 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 elevation > or =0.1 mV in leads V(1) and V(2). Unexpected death was defined as sudden death or unexplained accidental death. RESULTS: 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 (p < 0.01). Unexpected deaths were more frequent among subjects with the Brugada-type ECG who had a history of syncope (p < 0.05). CONCLUSIONS: 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.