Gender difference in the impact of coexisting diabetes mellitus on long-term clinical outcome in people with heart failure: a report from the Korean Heart Failure Registry.

AIM: Few data are available on the gender-related differences in the prognostic impact of diabetes in people with heart failure. This study was performed to investigate whether there is a gender difference in the association between diabetes and long-term clinical outcomes in people hospitalized for heart failure. METHODS: A total of 3162 people hospitalized with heart failure (aged 67.4 ± 14.1 years, 50.4% females) from the data set of the nationwide registry were analysed. The primary endpoint was a composite of all-cause mortality and heart failure readmission. RESULTS: People with diabetes (30.5% for males vs. 31.1% for females, P = 0.740) were older and had more unfavourable risk factors and laboratory findings than those without diabetes in both genders. During a median follow-up period of 549 days, there were 1418 cases of composite events (44.8%). In univariable analysis, the coexistence of diabetes was significantly associated with a higher incidence of composite events in both genders (P < 0.05 each for males and females). In multivariable analysis, the prognostic impact of diabetes on the development of composite events remained significant in females even after controlling for potential confounders (hazard ratio 1.43, 95% confidence intervals 1.12-1.84; P = 0.004). However, an independent association between diabetes and composite events was not seen in males in the same multivariable analysis (P > 0.05). CONCLUSIONS: In people with heart failure, the impact of diabetes on long-term mortality and heart failure readmission seems to be stronger in females than in males. More careful and intensive management is needed especially in females with heart failure and diabetes.

Predictive value of a fragmented QRS complex in diagnosing patients with myocardial ischemia.

BACKGROUND: A fragmented QRS complex (fQRS) is caused by conduction abnormalities of the ventricle secondary to myocardial ischemia and/or scar in patients with myocardial infarction. However, the implications of the fQRS in the development of coronary artery disease with myocardial ischemia in those without a scar remain unknown. METHODS: We studied electrocardiograms (ECGs) obtained from 150 patients (60.5 ± 8.5 years, 102 men) with myocardial ischemia, which was confirmed by performing both, a nuclear exercise stress test and coronary angiography. We also studied ECGs obtained from 601 patients (58.5 ± 10.0 years, 315 men) who showed a negative nuclear exercise stress test (control group). Patients in whom the nuclear exercise stress test showed a myocardial scar were excluded. RESULTS: An fQRS was more commonly observed in patients with myocardial ischemia (n = 48, 32.0%) than in the control group (n = 133, 22.1%) (P = 0.011). The sensitivity, specificity, positive, and negative predictive values of fQRS in diagnosing myocardial ischemia were 32.0, 77.9, 26.5, and 82.1%, respectively. The fQRS (odds ratio 1.580, 95% confidence interval 1.020-2.446, P = 0.040) was an independent predictor of myocardial ischemia after adjusting for age, sex, current smoking habits, ST-T changes on ECG, as well as histories of hypertension, diabetes, and dyslipidemia. Moreover, the fQRS showed an incremental prognostic value over conventional risk factors (χ2 = 5, P = 0.032) and over a combination of conventional factors and ST-T changes (χ2 = 9, P = 0.014). CONCLUSIONS: The fQRS is a moderately sensitive and independent predictor of myocardial ischemia.

Phylogenetic relationships of chrysanthemums in Korea based on novel SSR markers.

Chrysanthemums are well known for their esthetic and medicinal values. Characterization of chrysanthemums is vital for their conservation and management as well as for understanding their genetic relationships. We found 12 simple sequence repeat markers (SSRs) of 100 designed primers to be polymorphic. These novel SSR markers were used to evaluate 95 accessions of chrysanthemums (3 indigenous and 92 cultivated accessions). Two hundred alleles were identified, with an average of 16.7 alleles per locus. KNUCRY-77 gave the highest polymorphic information content value (0.879), while KNUCRY-10 gave the lowest (0.218). Similar patterns of grouping were observed with a distance-based dendrogram developed using PowerMarker and model-based clustering with Structure. Three clusters with some admixtures were identified by model-based clustering. These newly developed SSR markers will be useful for further studies of chrysanthemums, such as taxonomy and marker-assisted selection breeding.

Evolution of the domain topology in a ferroelectric.

Topological materials, including topological insulators, magnets with Skyrmions and ferroelectrics with topological vortices, have recently attracted phenomenal attention in the materials science community. Complex patterns of ferroelectric domains in hexagonal REMnO(3) (RE: rare earths) turn out to be associated with the macroscopic emergence of Z(2)×Z(3) symmetry. The results of our depth profiling of crystals with a self-poling tendency near surfaces reveal that the partial dislocation (i.e., wall-wall) interaction, not the interaction between vortices and antivortices, is primarily responsible for topological condensation through the macroscopic breaking of the Z(2) symmetry.

Direct observation of the proliferation of ferroelectric loop domains and vortex-antivortex pairs.

We discovered stripe patterns of trimerization-ferroelectric domains in hexagonal REMnO(3) (RE=Ho,···,Lu) crystals (grown below ferroelectric transition temperatures (T(c)), reaching up to 1435 °C), in contrast with the vortex patterns in YMnO(3). These stripe patterns roughen with the appearance of numerous loop domains through thermal annealing just below T(c), but the stripe domain patterns turn to vortex-antivortex domain patterns through a freezing process when crystals cross T(c) even though the phase transition appears to not be Kosterlitz-Thouless-type. The experimental systematics are compared with the results of our six-state clock model simulation and also the Kibble-Zurek mechanism for trapped topological defects.

Self-organization, condensation, and annihilation of topological vortices and antivortices in a multiferroic.

The interaction among topological defects can induce novel phenomena such as disclination pairs in liquid crystals and superconducting vortex lattices. Nanoscale topological vortices with swirling ferroelectric, magnetic, and structural antiphase relationships were found in multiferroic h-YMnO(3). Herein, we report the discovery of intriguing, but seemingly irregular configurations of a zoo of topological vortices and antivortices. These configurations can be neatly analyzed in terms of graph theory and reflect the nature of self-organized criticality in complexity phenomena. External stimuli such as chemistry-driven or electric poling can induce the condensation and eventual annihilation of topological vortex-antivortex pairs.

IAN5 polymorphisms are associated with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a representative autoimmune disease, which is frequently associated with lymphopenia. Biobreeding (BB) rat is a typical animal model which develops autoimmune diseases with lymphopenia which results from a frame-shift mutation in the immune-associated nucleotide (IAN) 5 gene. IAN5 is involved in the regulation of T-cell activation and survival. To examine the association of IAN5 gene with SLE, we scrutinised the single nucleotide polymorphisms (SNPs) in the IAN5 gene. We conducted a case-control study where 132 SLE patients, 505 rheumatoid arthritis (RA) patients, and 546 controls were genotyped for four SNPs in the IAN5 gene. Two SNPs (+2071C > T and +2677G > A) were associated with susceptibility to SLE (P = 0.040 and 0.045, respectively), and -4432G > A SNP was associated with the development of leukopenia (P = 0.028) and the requirement of steroid pulse therapy (P = 0.040) in SLE patients. Haplotype analyses showed that Ht1(CTCG) was associated with susceptibility to SLE (P = 0.036), and Ht4(ACCG), Ht5(ACTA) and Ht6(GCCG) were associated with the development of nephritis (P = 0.017, 0.019, 0.022, respectively). In conclusion, the IAN5 polymorphisms were associated with susceptibility to SLE and the development of clinical disease manifestations in a strictly Korean population.

Occurrence of both unipolar memory and threshold resistance switching in a NiO film.

We observed two types of reversible resistance switching (RS) effects in a NiO film: memory RS at low temperature and threshold RS at high temperature. We were able to control the type of RS effects by thermal cycling. These phenomena were explained using a new dynamic percolation model that can describe the rupture and formation of conducting filaments. We showed that the RS effects are governed by the thermal stability of the filaments, which arise from competition between Joule heating and thermal dissipation. This work provides us understandings on basic mechanism of the RS effects and their interrelation.

Association study of hypoxia inducible factor 1alpha (HIF1alpha) with osteonecrosis of femoral head in a Korean population.

OBJECTIVE: Disruption of the vascular supply to the bone and subsequent hypoxia has been implicated in the pathogenesis of osteonecrosis (ON) of the femoral head (ONFH). To evaluate the genetic effect of HIF1alpha, a key transcription factor in controlling hypoxia condition, on ONFH, we analyzed HIF1alpha polymorphism and its genetic association with ONFH. METHODS: We directly sequenced the HIF1alpha gene in 24 Korean individuals and identified four sequence variants. Four polymorphisms (-2755C>A, +41224T>C, +45319C>T, +51610C>T) were genotyped in ONFH (n=384). ONFH patients were divided into three subgroups based on etiological factors: idiopathic (129 cases), steroid (59 cases) and alcohol (196 cases) ON groups. RESULTS: We found that the allele frequency of -2755C>A and the genotype frequencies of +41224T>C and +51610C>T were significantly associated with idiopathic ONFH in men (P=0.0409, 0.0113, 0.0269, respectively). In addition, haplotype (CTCC) of HIF1alpha was also significantly associated with idiopathic ONFH in men (P=0.017). CONCLUSIONS: We found that HIF1alpha polymorphisms are associated with idiopathic ONFH in men. These results suggest that variations in HIF1alpha may play an important role in the pathogenesis and risk factor for ONFH.

Transient expression of a mitochondrial gene cluster including rps4 is essential for the phase-shift of Dictyostelium cells from growth to differentiation.

Using synchronized Dictyostelium discoideum Ax-2 cells and the differential display method, a mitochondrial gene cluster (referred to as differentiation-associated gene 3; dia3) was isolated as one of the genes expressed specifically during the transition of Ax-2 cells from growth to differentiation. The dia3 gene encodes for a mitochondrial protein cluster (NADH dehydrogenase (NAD) subunit 11, 5, ribosomal protein S4 (RPS4), RPS2, and NAD4L). Northern blot analysis using nonsynchronized Ax-2 cells has shown that the dia3 RNA of about 8 kb is scarcely expressed during the vegetative growth phase, and the maximal expression was attained at 2 h after starvation. To analyze the gene function of dia3, we tried inactivation of rps4 by means of homologous recombination and obtained several transformed clones showing mitochondrial DNA heteroplasmy. The transformed cells grew normally in nutrient medium, but their development after starvation was greatly impaired, thus resulting in the failure of many cells to differentiate. In this connection, the cAMP receptor 1 (car1) expression, which is one of the earliest markers of differentiation, was found to be markedly reduced in the rps4-inactivated cells.

Underexpression of a novel gene, dia2, impairs the transition of Dictyostelium cells from growth to differentiation.

In Dictyostelium discoideum Ax-2 cells, a specific point (PS-point) in the cell cycle from which they initiate differentiation in response to starvation has been specified. Using synchronized Ax-2 cells and the differential display method, a novel gene (differentiation-associated gene 2; dia2) was isolated as one of the genes expressed specifically during the shift of Ax-2 cells from growth to differentiation. The dia2 gene codes a lysine- and leucine-rich protein with a predicted molecular mass of 16.9 kDa. Northern blot analysis has shown that the dia2 mRNA, of 0.7 kb, accumulates in differentiating cells starved just before the PS-point, while there is no detectable expression in vegetatively growing cells. Antisense-mediated gene inactivation of dia2 greatly inhibited the progress of differentiation, presumably through the reduced expression of cAMP receptor 1 (car1). Thus, the DIA2 expression was suggested to have an essential role in the initiation of differentiation, closely relating to the cAMP signaling system.

Preferential expression of the cDNA encoding the proteasome subunit during the growth/differentiation transition of Dictyostelium cells.

A proteasome subunit-1 gene (DAPS-1) was isolated as one preferentially expressed during the transition from growth to differentiation in Dictyostelium discoideum cells, using the differential display method. The DAPS-1 cDNA sequence with a length of 882 bp encodes a protein (Mr. 23.4 kDa) consisting of 213 amino acids. The deduced amino acid sequence of DAPS-1 showed 61% and 58% identity to the proteasome subunit Y of Xenopus laevis and Homo sapiens, respectively and 48% and 47% identity to the proteasome subunit LMP2 of Homo sapiens and Orizas latipes, respectively. Northern analysis revealed that a 1.0 kb of DAPS-1 mRNA is predominantly expressed during the early stage of differentiation induced by starvation. This seems to indicate that the DAPS-1 protein may be involved in proteolysis coupled with active exchange of the cellular protein composition during the phase-shift of Dictyostelium cells from the proliferative to differentiated state.

Metastatic pleural cancer in radionuclide angiocardiography. A pulmonary time-activity curve mimicking left-to-right cardiac shunt.

A 55-year-old man, with a history of nephrectomy for renal cell carcinoma, was evaluated using radionuclide angiocardiography to exclude cardiac shunts as the cause of vascular bruits heard at auscultation. A pulmonary time-activity curve derived from the right lung showed a pattern typical of a large left-to-right shunt, whereas that from the left lung was normal. Increased systemic arterial flow to the lateral right chest was noted in early dynamic images. Subsequent studies revealed that this flow and the abnormal time-activity curve of the right lung were due to systemic arterial supply to metastatic pleural cancer, originating from the kidney. The authors conclude that special caution should be undertaken in the interpretation of the radionuclide angiocardiography for determining left-to-right cardiac shunts, especially in those showing a asymmetric pulmonary time-activity curve.

Thallium-201 uptake in keloid tissue masquerading as a pulmonary neoplasm.

Tl-201 imaging is useful in the diagnostic work-up of tumors. However, Tl-201 uptake is not specific for tumor and is also noted in other conditions. A case is described in which Tl-201 was taken up by a keloid.

Biokinetics of thallium-201 in normal subjects: comparison between adenosine, dipyridamole, dobutamine and exercise.

UNLABELLED: There are currently four common types of stress used with thallium-201 imaging in the diagnosis of coronary artery disease and risk assessment. The objective of this study was to examine the thallium biokinetics during exercise, adenosine, dipyridamole and dobutamine stress testing in 15 healthy volunteers. METHODS: Each subject underwent planar 201Tl imaging during maximal treadmill exercise testing, adenosine infusion (140 micrograms/kg/min for 6 min), dipyridamole infusion (142 micrograms/kg/min for 4 min) and dobutamine infusion (40 micrograms/kg/min). RESULTS: Absolute myocardial thallium activity was greater after pharmacologic testing than exercise, (p < 0.001 each). Thus, the activity was 505 counts/pixel with adenosine, 491 counts/pixel with dipyridamole, 517 counts/pixel with dobutamine and 409 counts/pixel with exercise. The myocardial thallium clearance was lower with pharmacologic testing than exercise; 9.7%/hr with adenosine, 9.9%/hr with dipyridamole, 11.3%/hr with dobutamine and 13%/hr with exercise (p < 0.01 each). The thallium uptake and clearance in the lung and liver were also greater with pharmacologic stress testing than exercise (p < 0.05). CONCLUSIONS: Thus, thallium biokinetics are different during pharmacologic stress testing with adenosine, dipyridamole and dobutamine than during exercise. Diagnostic criteria for quantitative analysis of myocardial perfusion imaging must therefore be specific for the type of stress used.

Independent and incremental prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging in coronary artery disease.

OBJECTIVES: The objective of this study was to examine the independent and incremental prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging in patients with angiographically defined coronary artery disease. BACKGROUND: Previous studies showed the importance of exercise thallium-201 in risk stratification. However, most of these studies used planar imaging techniques. METHODS: Follow-up data were obtained in 316 medically treated patients with coronary artery disease. Cox proportional hazards regression models were used to examine the independent and incremental prognostic values of clinical, exercise, thallium and cardiac catheterization data. RESULTS: There were 35 events (cardiac death or nonfatal myocardial infarction) at a mean follow-up time of 28 months. Univariate analysis showed that gender (chi-square = 5.1), exercise work load (chi-square = 3.1), extent of coronary artery disease and left ventricular ejection fraction (chi-square = 14.8) and thallium variables (chi-square = 22.7) were prognostically important. The thallium data provided incremental prognostic value to catheterization data (chi-square = 33.7, p < 0.01). The extent of the perfusion abnormality was the single best predictor of prognosis (chi-square = 14). Patients with a large perfusion abnormality had a worse prognosis than that of patients with a mild or no abnormality (Mantel-Cox statistics = 10.6, p < 0.001). CONCLUSIONS: In medically treated patients with coronary artery disease, exercise SPECT thallium imaging provides independent and incremental prognostic information even when catheterization data are available. The extent of the perfusion abnormality is the single most important prognostic predictor.

Changes in spectral indices of heart rate variability during exercise in acute myocardial infarction.

Physical exertions are related to sudden cardiac death following acute myocardial infarction (AMI). Abnormalities in the autonomic modulation during exercise were noted in animals with AMI that were susceptible to potentially lethal arrhythmias. This study was done to evaluate the changes in the autonomic activity during exercise and recovery in AMI patients with good exercise capacity, using spectral analysis of R-R intervals of electrocardiogram (ECG). Symptom-limited treadmill exercise test was done on 17 patients of AMI with mild heart failure (in 7-10 days after the attack) and 21 healthy controls. The exercise was divided into 7 stages; rest, early exercise, mid-exercise, peak exercise, early recovery, mid-recovery, and late recovery. Power spectral analysis of R-R intervals of ECG was performed for each stage. Low frequency (0.04-0.15 Hz) and high frequency (0.15-0.40 Hz) powers, and their ratio were obtained. These parameters were observed throughout the stages in both groups. The trend of their changes during exercise and recovery was essentially the same for both groups; high and low frequency powers progressively decreased during exercise and abruptly increased during early recovery, but did not return to the values at those of rest until 9 minutes into the recovery. When the parameters were compared between the groups, there was a significantly greater decrease of high frequency power during the early exercise (p < 0.05), and a higher ratio of low to high frequency power during the early recovery (p < 0.05) in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of extensive coronary artery disease in women by exercise single-photon emission computed tomographic (SPECT) thallium imaging.

OBJECTIVES: The aim of this study was to examine the ability of exercise single-photon emission computed tomographic (SPECT) thallium imaging to identify high risk women with left main or three-vessel coronary artery disease using a stepwise discriminant analysis. BACKGROUND: Previous studies have used statistical methods to identify high risk men with coronary artery disease. Only limited data are available in women. METHODS: Exercise SPECT thallium imaging and coronary arteriography were performed for evaluation of chest pain in 243 women. Group 1 comprised 58 women with left main or three-vessel coronary disease and group 2 comprised 185 women with no or one- or two-vessel disease. Stepwise discriminant analysis was used to determine predictors of left main or three-vessel disease. RESULTS: On univariate analysis, women in group 1 were older (p < 0.03) and had a lower exercise work load (p < 0.02), lower exercise heart rate (p < 0.004), higher prevalence rate of diabetes mellitus (p < 0.0003) and more multivessel thallium abnormality (p < 0.0001) compared with women in group 2. On multivariate analysis, only multivessel thallium abnormality (F = 43) and exercise heart rate (F = 6) were independent predictors of left main or three-vessel coronary disease. A model based on these two variables separated the women into three risk groups: 99 patients with 9%, 70 patients with 23% and 74 patients with 45% prevalence of left main or three-vessel disease (p < 0.0001). CONCLUSIONS: High risk women with left main or three-vessel coronary disease can be identified by exercise SPECT thallium imaging.