The Effect of Convergence Gamification Training in Community-Dwelling Older People: A Multicenter, Randomized Controlled Trial.

OBJECTIVES: It is necessary to improve the health of older adults through exercise, but there is no concrete way to implement it or an environment in which they can exercise continuously. Our objective was to confirm the safety and efficacy of information technology (IT) convergence gamification exercise equipment for older adults. We tried to demonstrate equivalence to conventional exercise by comparing the functional improvement. DESIGN: Randomized controlled trial, with 8-week-long IT convergence exercises 3 times a week vs conventional exercise. SETTING AND PARTICIPANTS: 40 community-dwelling participants aged 60-85 years. METHOD: Participants were randomly divided into a conventional exercise group (group 1) and an IT convergence exercise group (group 2). Both groups were trained for 8 weeks, and functional assessment was performed before training (pre-evaluation), after training, and after 4 weeks of rest. RESULTS: There were functional improvements in both groups. A comparison of the differences in the functional assessment between pre-evaluation and after 8 weeks of training yielded the following results. In group 1, the mean Five Times Sit to Stand Test-30 seconds was scored as 3.60 ± 2.56 (P < .015); Five Times Sit to Stand Test-5 times, -1.75 ± 2.04 s (P < .015); Berg Balance Scale, 1.05 ± 1.39 (P < .015); Timed Up-and-Go test, -0.64 ± 0.64 s (P < .015); and 10-m Walking Test, -0.35 ± 0.47 s (P < .015). And in group 2, the mean Five Times Sit to Stand Test-30 seconds (s) was scored as 3.70 ± 2.62 (P < .015), Five Times Sit to Stand Test-5 times, -1.65 ± 1.59 s (P < .015); Berg Balance Scale, 1.05 ± 1.00 (P < .015); Timed Up-and-Go test, -0.93 ± 0.68 s (P < .015); 10-m Walking Test, -0.41 ± 0.489 s (P < .015); Chair Sit and Reach test, 2.23 ± 3.19 cm (P < .015); and Korean version of the Falls Efficacy Scale-International, -1.05 ± 1.43 (P < .015). CONCLUSION AND IMPLICATIONS: The results of this study suggest that the IT convergence gamification exercise equipment such as balpro110 has exercise effects similar to conventional exercise and also has advantages as an alternative to exercise for older adults in the next generation.

Effect of Phoxilium on prognostic predictors in patients undergoing continuous venovenous hemodiafiltration.

BACKGROUND: Phosphorus-containing dialysis solution is used to prevent hypophosphatemia in patients undergoing continuous venovenous hemodiafiltration (CVVHDF). This study evaluated the effect of phosphorus-containing dialysis solution on mortality in patients undergoing CVVHDF based on changes in phosphorus and red cell distribution width-coefficient of variation (RDW-CV) levels. METHODS: We included 272 patients with acute kidney injury (AKI) who underwent CVVHDF at the medical intensive care unit from 2017 to 2019 and classified them according to Phoxilium (Baxter Healthcare Ltd.), as a phosphorus-containing dialysis solution, use within 48 hours after CVVHDF initiation. Clinical data were collected at baseline and 48 hours after CVVHDF initiation. The primary outcome was all-cause mortality during the follow-up period. RESULTS: The non-Phoxilium (NP) group had higher phosphorus and lower RDW-CV levels than the Phoxilium (P) group (phosphorus, 7.3 ± 4.3 vs. 5.0 ± 2.8 mg/dL; RDW-CV, 14.6 ± 1.9 vs. 15.7 ± 2.6%; all p < 0.001). In the multivariable Cox proportional hazard regression of the NP group, an increase in phosphorus and RDW-CV at 48 hours of CVVHDF was associated with mortality (delta phosphorus: median, >0 mg/dL vs. <-2.0 mg/dL; hazard ratio [HR], 8.62; 95% confidence interval [CI], 2.10-35.32; p = 0.003/delta RDW-CV: median, >0% vs. <-0.2%; HR, 4.34; 95% CI, 1.49-13.18; p = 0.008). Meanwhile, in the P group, an increase in delta RDW-CV was associated with mortality (delta RDW-CV: >0% vs. >-0.2% and <0%; HR, 2.65; 95% CI, 1.12-6.24; p = 0.03), while an increase in delta phosphorus was not. CONCLUSION: In patients with AKI undergoing CVVHDF, the risk factors for all-cause mortality differed according to the initial phosphorus levels and use of Phoxilium.

Association between Irritable Bowel Syndrome and Risk of Osteoporosis in Korean Premenopausal Women.

OBJECTIVE: The objective of this study is to evaluate irritable bowel syndrome (IBS) as a risk factor for osteoporosis and osteoporotic fracture in Korean women after controlling for basic confounding factors and considering detailed demographic and clinical information. SUBJECTS AND METHODS: We performed a nationwide population-based retrospective cohort analysis and matched every IBS case with a non-IBS case at a 1:4 frequency ratio based on age. The population consisted of female patients with data in the Health Insurance Review and Assessment (HIRA) database from 2002 to 2010. To determine the risk of osteoporosis and osteoporotic fracture in IBS and non-IBS patients, hazard ratios (HRs) with 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models, adjusting for confounding variables, such as the area of residence, health insurance type, and economic status. RESULTS: We identified 1,017,468 patients in the HIRA database with data from 2002 to 2010 who could potentially be included in the cohort. Among these, we identified 1,545 (11.4%) women (age >19 years) with newly diagnosed IBS (IBS group). Additionally, 6,180 patients without IBS and age-matched to the IBS group were selected. Cox modeling revealed that the crude HRs for osteoporosis and osteoporotic fractures in patients with IBS were 1.476 (95% CI, 1.241-1.754) and 1.427 (95% CI, 1.086-1.876), respectively. CONCLUSION: Our data showed an increased incidence of osteoporosis and osteoporotic fractures in women with IBS compared with age-matched controls.

The Analysis of Electroencephalography Changes Before and After a Single Neurofeedback Alpha/Theta Training Session in University Students.

The underlying mechanisms of alpha/theta neurofeedback training have not been fully determined. Therefore, this study aimed to test the changes in the brain state feedback during the alpha/theta training. Twenty-seven healthy participants were trained during a single session of the alpha/theta protocol, and the resting quantitative electroencephalography (QEEG) was assessed before and after training. QEEG was recorded at eight scalp locations (F3, F4, C3, C4, T3, T4, O1, and O2), and the absolute power, relative power, ratio of sensory-motor rhythm beta (SMR) to theta (RST), ratio of SMR-mid beta to theta (RSMT), ratio of mid beta to theta (RMT), ratio of alpha to high beta (RAHB), and scaling exponent of detrended fluctuation analysis by each band were measured. The results indicated a significant increase of absolute alpha power, especially the slow alpha band, at all electrodes except T3 and T4. Moreover, the relative alpha power, especially the slow alpha band, showed a significant increase at all electrodes. The relative theta power showed a significant decrease at all electrodes, except T3. A significant decrease in relative beta power, relative lower beta power and relative mid beta power was observed at O1. RST (at C4, O1, and O2), RSMT and RMT (at F4, C4, O1 and O2), and RAHB (at all electrodes) showed significant increase. Scaling exponents at all electrodes except T3 showed a significant decrease. These findings indicate that a one-time session of alpha/theta training might have the possibility to enhance both vigilance and concentration, thus stabilizing the overall brain function.

Alterations in transcranial Doppler indices of pregnant women with complicated preeclampsia.

OBJECTIVES: We aimed to investigate alterations in transcranial Doppler indices (TCD) of the cerebral arteries between normotensive and preeclampsia (PE) pregnancies according to the presence of cerebral symptoms. STUDY DESIGN: This cross-sectional study included 48 PE and 20 normotensive pregnancies, respectively. Doppler indices of the anterior, middle, and posterior cerebral arteries (ACA, MCA, and PCA, respectively) were compared between the PE and normotensive group. MAIN OUTCOME MEASURES: Mean cerebral velocity (MCV), pulsatility index (PI), and resistance index (RI) were calculated using cerebral velocities. The cerebral perfusion pressure (CPP), resistance area product (RAP), and cerebral flow index (CFI) were computed using velocity and blood pressure. The PE group was subdivided according to the presence of cerebral symptoms and the TCD indices were compared between these groups. RESULTS: MCV and CFI of the PCA as well as CPP and RAP of all arteries were significantly higher, while PI and RI were significantly lower in PE group (P < 0.05). PI of the MCA had the highest sensitivity (91.7%), while PI of the PCA and RAP of the MCA had the highest specificity (95.0% each) for predicting PE-related cerebral complications. The positive likelihood ratio was highest in PI of the PCA (14.58). Among these parameters, CPP and RAP of the PCA were higher in PE patients showing cerebral symptoms than in those without symptoms. CONCLUSIONS: These results suggest that pregnant women with PE had altered TCD indices and that prominent changes, thereof, especially in the PCA, contribute to the development of cerebral symptoms.

Bruch's membrane opening-minimum rim width and visual field loss in glaucoma: a broken stick analysis.

AIM: To determine the Bruch's membrane opening-minimum rim width (BMO-MRW) tipping point where corresponding visual field (VF) damages become detectable. METHODS: A total of 85 normal subjects and 83 glaucoma patients (one eye per participant) were recruited for the study. All of the patients had VF examinations and spectral-domain optical coherence tomography to measure the BMO-MRW. Total deviation values for 52 VF points were allocated to the corresponding sector according to the Garway-Heath distribution map. To evaluate the relationship between VF loss and BMO-MRW measurements, a "broken-stick" statistical model was used. The tipping point where the VF values started to sharply decrease as a function of BMO-MRW measurements was estimated and the slopes above and below this tipping point were compared. RESULTS: A 25.9% global BMO-MRW loss from normative value was required for the VF loss to be detectable. Sectorally, substantial BMO-MRW thinning in inferotemporal sector (33.1%) and relatively less BMO-MRW thinning in the superotemporal sector (8.9%) were necessary for the detection of the VF loss. Beyond the tipping point, the slopes were close to zero throughout all of the sectors and the VF loss was unrelated to the BMO-MRW loss. The VF loss was related to the BMO-MRW loss below the tipping point. The difference between the two slopes was statistically significant (P≤0.002). CONCLUSION: Substantial BMO-MRW loss appears to be necessary for VF loss to be detectable in patients with open angle glaucoma with standard achromatic perimetry.

Addition of nonalbumin proteinuria to albuminuria improves prediction of type 2 diabetic nephropathy progression.

BACKGROUND: Albuminuria is generally accepted as a sensitive marker of diabetic nephropathy but has limitations in predicting its progression. The aim of this study was to evaluate the use of nonalbumin proteinuria in addition to albuminuria for predicting the progression of type 2 diabetic nephropathy. METHODS: In this retrospective observational study, the urine albumin-to-creatinine ratio (ACR) and the nonalbumin protein-to-creatinine ratio (NAPCR) were measured in 325 patients with type 2 diabetes and estimated glomerular filtration rates (eGFR) ≥30 mL/min/1.73 m2. The patients were divided into four groups based on the cutoff points for the urinary ACR (30 mg/g) and NAPCR (120 mg/g). The renal outcomes were chronic kidney disease (CKD) progression and accelerated eGFR decline. RESULTS: During the 4.3-year follow-up period, 25 (7.7%) patients showed CKD progression and 69 (21.2%) patients showed accelerated eGFR decline. After adjusting for nine clinical parameters, the group with a NAPCR greater than 120 mg/g exhibited higher cumulative incidences of CKD progression (hazard ratio 6.84; P = 0.001) and accelerated eGFR decline (hazard ratio 1.95; P = 0.011) than the group with a NAPCR < 120 mg/g. In patients with normoalbuminuria, the group with NAPCR levels greater than 120 mg/g also exhibited a higher cumulative incidence than that with NAPCR levels <120 mg/g of CKD progression (hazard ratio 21.82; P = 0.005). The addition of NAPCR to ACR improved the model fit for CKD progression and accelerated eGFR decline. CONCLUSION: Nonalbumin proteinuria showed additional value over and above that of albuminuria for predicting the progression of CKD in patients with type 2 diabetes.

Benzimidazolone as potent chymase inhibitor: modulation of reactive metabolite formation in the hydrophobic (P1) region.

A new class of chymase inhibitor featuring a benzimidazolone core with an acid side chain and a P(1) hydrophobic moiety is described. Incubation of the lead compound with GSH resulted in the formation of a GSH conjugate on the benzothiophene P(1) moiety. Replacement of the benzothiophene with different heterocyclic systems such as indoles and benzoisothiazole is feasible. Among the P(1) replacements, benzoisothiazole prevents the formation of GSH conjugate and an in silico analysis of oxidative potentials agreed with the experimental outcome.

Clinical outcomes of exercise-induced pulmonary hypertension in subjects with preserved left ventricular ejection fraction: implication of an increase in left ventricular filling pressure during exercise.

OBJECTIVE: To investigate clinical outcomes of exercise-induced pulmonary hypertension (PH) and implications of an increase in left ventricular (LV) filling pressure during exercise in subjects with preserved LV ejection fraction. DESIGN: Longitudinal follow-up study. SETTING: Subjects who were referred for diastolic stress echocardiography. PATIENTS AND METHODS: The ratio of transmitral and annular velocities (E/Ea) and pulmonary artery systolic pressure (PASP) at rest and during exercise were measured in 498 subjects (57±11 years; 201 male). Exercise-induced PH was defined as present if PASP ≥50 mm Hg at 50 W of exercise, and an increase in LV filling pressure during exercise was present if E/Ea ≥15 at 50 W. MAIN OUTCOME MEASURES: A combination of major cardiovascular events and any cause of death. RESULTS: During a median follow-up of 41 months, there were 14 hospitalisations and four deaths. Subjects with exercise-induced PH had significantly worse clinical outcomes than those without (p=0.014). Subjects with exercise-induced PH associated with an increase in E/Ea during exercise had significantly worse outcomes than other groups (p<0.001). However, prognosis was similar between subjects with exercise-induced PH without an increase in E/Ea and those without exercise-induced PH. In subjects with exercise-induced PH, E/Ea at 50 W was an independent predictor of adverse outcomes (HR 1.37; 95% CI 1.02 to 1.83; p=0.036). CONCLUSIONS: Exercise-induced PH provides prognostic information in subjects with preserved LV ejection fraction. The excess risk of exercise-induced PH is restricted to subjects with an increase in estimated LV filling pressure during exercise.

Impact of left ventricular longitudinal diastolic functional reserve on clinical outcome in patients with type 2 diabetes mellitus.

BACKGROUND: Left ventricular longitudinal diastolic functional reserve (DFR), as assessed by the change in early diastolic mitral annular velocity (E') during exercise, is abnormal in patients with type 2 diabetes mellitus (DM). However, the impact of left ventricular longitudinal DFR on clinical outcome has not been explored. This study evaluated the incremental prognostic value of left ventricular DFR in patients with type 2 DM without overt heart disease. METHODS: Of 1485 patients who were referred for exercise stress echocardiography, 197 consecutive patients (mean age, 58 years; 84 men) with type 2 DM without overt heart disease were identified. Left ventricular longitudinal DFR was defined as the change in E' from resting to exercise (ΔE'). The endpoint was a composite of death and hospitalisation for heart failure (HF). RESULTS: During a median follow-up of 57 months (range 6-90), 18 of 197 patients (9.1%) had adverse events (12 deaths, six hospitalisations for HF). Independent predictors of adverse events in a Cox regression analysis were estimated glomerular filtration rate (HR 0.97; 95% CI 0.95 to 0.98; p<0.001), DM duration (HR 1.07; 95% CI 1.01 to 1.14; p=0.018) and ΔE' (HR 0.58; 95% CI 0.40 to 0.85; p=0.005). In an incremental model, the addition of stress echo data significantly increased the χ² of the clinical and resting left ventricular function model, from 40.5 to 46.6 (p=0.005). CONCLUSION: Assessment of left ventricular longitudinal DFR during exercise provided incremental prognostic information in patients with type 2 DM without overt heart disease.

Relationship between serum biochemical markers of myocardial fibrosis and diastolic function at rest and with exercise in hypertrophic cardiomyopathy.

BACKGROUND AND OBJECTIVES: Recent studies have demonstrated the usefulness of biochemical markers of collagen turnover as markers of myocardial fibrosis in various diseases. In this study, we hypothesized that increased collagen markers in patients with hypertrophic cardiomyopathy (HCM) were correlated with diastolic function at rest and diastolic functional reserve during exercise. SUBJECTS AND METHODS: Thirty-six patients with HCM and 21 controls with normal left ventricular thickness were studied. Mitral septal annular velocities and mitral inflow velocities were measured at rest and during graded supine bicycle exercise (25 W, 3-minute increments) for the assessment of diastolic function at rest and during exercise. By radioimmunoassay, a byproduct of collagen III synthesis (PIIINP) and peptides resulting from collagen I synthesis (PINP) and degradation (ICTP) were measured. The patients with HCM were divided into two groups according to the median value of the PINP/ICTP ratio in the group. RESULTS: At rest, the mitral annular early diastolic velocity (E') was lower and the E/E' was higher in the patients with HCM with high a PINP/ICTP ratio compared with patients with HCM with a low PINP/ICTP ratio and controls (p<0.001, p=0.012). With exercise, the Doppler parameters were increased in all groups, but there was no significant difference in the change in E' and E/E' during exercise according to collagen turnover markers. CONCLUSION: A higher PINP/ICTP ratio was associated with resting diastolic dysfunction in patients with HCM; however, there was no relationship with augmented diastolic dysfunction during exercise. We suggest that the type I collagen synthesis-to-degradation ratio is a useful marker of resting diastolic function in patients with HCM.

Effects of pericardiectomy on early diastolic mitral annular velocity in patients with constrictive pericarditis.

BACKGROUND: In patients with constrictive pericarditis (CP), early diastolic mitral annular velocity (E') is usually normal or exaggerated due to limitation of lateral expansion by the constricting pericardium. Although pericardiectomy is the treatment of choice for CP, it is difficult to evaluate its effectiveness. Theoretically, E' may decrease after successful pericardiectomy. However, little data are available regarding the effect of pericardiectomy on E'. The purpose of this study was to assess the change in E' after pericardiectomy in patients with CP. METHODS: We studied 16 patients (12 males, mean age 62.3+/-7.0 years) with surgically confirmed CP for changes in pre-discharge Doppler parameters following pericardiectomy. CP was secondary to previous cardiac surgery in 4 patients, tuberculosis in 4 patients, radiation-induced in 1 patient, and idiopathic in 7 patients. Ten patients underwent complete pericardiectomy (62.5%). E' was measured at the septal annulus before pericardiectomy and a mean duration of 10 (+/-6) days after. RESULTS: E' significantly decreased from 9.2+/-2.7 cm/s to 7.4+/-2.6 after pericardiectomy (p=0.013). The mean percent change of E' after pericardiectomy was 17.9+/-25.9%. The decrement of E' was significantly higher in patients with complete pericardiectomy than in patients who underwent a partial pericardiectomy (2.7+/-2.3 vs. 0.4+/-2.1, p=0.042). Also, more than 15% decrease of E' was significantly higher in patients with improvement of symptom after pericardiectomy (9 (100.0%) vs. 3 (42.9%), p=0.019). CONCLUSION: E' decreased following pericardiectomy in most of the patients with CP. The change of E' after pericardiectomy may be useful in evaluating the effectiveness of pericardiectomy.

Gender-related difference in left ventricular diastolic elastance during exercise in patients with diabetes mellitus.

BACKGROUND: Because the ratio of mitral inflow and annular velocity to stroke volume has been reported as an index of diastolic elastance (Ed), the hypothesis tested in the present study was that Ed during exercise would be more abnormal in female than in male patients with type 2 diabetes. METHODS AND RESULTS: Ed was measured at rest and during graded supine bicycle exercise (25W, 3-min increments) in 53 patients (27 males, mean age 53+/-14 years) with type 2 diabetes and 53 age- and gender-matched controls. The patients with diabetes were divided into 2 groups by gender. Ed was not significantly different at rest between men and women, but was significantly higher during exercise in women than in men (25 W, 0.15+/-0.04 vs 0.20+/-0.07, p=0.009; 50 W, 0.16+/-0.05 vs 0.21+/-0.08, p=0.0175). CONCLUSION: Left ventricular (LV) diastolic elastance is abnormal during exercise, but not at rest, in patients with diabetes without overt heart disease. Female gender was associated with increased LV stiffness during exercise among patients with type 2 diabetes.

Baicalein stimulates osteoblast differentiation via coordinating activation of MAP kinases and transcription factors.

The identification of anabolic agents that directly stimulate bone formation has recently attracted greater interest. Here, baicalein was identified as a natural compound that stimulates the differentiation of mouse osteoblastic MC3T3-E1 subclone 4 cells. Baicalein induced the activation of NF-kappaB in the initiation stage of osteoblast differentiation, and it activated the MAP kinase/NF-kappaB signaling pathway and induced the expression of osteoblast differentiation markers in the early stage. In the late stage, baicalein stimulated the calcium deposition with the activation of MAP kinases and AP-1 family members such as Fra-1 and Fra-2. Another transcription factor, NFATc1, was slightly induced by baicalein in the late stage. Thus, baicalein could stimulate the osteoblast differentiation via the activation of complexly coordinated signaling pathways that include MAP kinases and transcription factors such as NF-kappaB, AP-1, and NFATc1.

Gender-related difference in arterial elastance during exercise in patients with hypertension.

Exercise intolerance and heart failure with preserved ejection fraction are common in females. Recently, arterial stiffness has been suggested to be a significant contributor in the development of heart failure. How gender difference affects arterial stiffening and its response to exercise is not well known. We hypothesized that arterial elastance index during exercise would be more abnormal in females with hypertension than males. Arterial elastance index was estimated as arterial end systolic pressure/stroke volume controlled for body surface area and was measured at rest and during graded supine bicycle exercise (25 watts, 3-minute increments) in 298 patients with hypertension (149 males; 149 females; mean age, 59). The subjects were divided into 2 groups by gender. Exercise duration was significantly shorter in females compared to males (692+/-222 versus 483+/-128 seconds, P<0.001). Although arterial elastance index at baseline was significantly higher in males, the magnitude of increase was steeper in females with the magnitude of change at 75 W of exercise being significantly higher in females compared to males (0.69+/-0.83 versus 0.43+/-0.69, P=0.018). Arterial elastance index at each stage of exercise up to 75 W was independently associated with decreased exercise duration. In conclusion, despite lower arterial elastance index at rest, the increase during exercise was steeper in women with hypertension, suggesting a gender-related difference in dynamic arterial stiffness. The arterial elastance index during exercise was significantly associated with exercise duration in patients with hypertension.

Time course of recovery of left ventricular filling pressure after exercise in healthy subjects.

BACKGROUND: It has been recently demonstrated that the hemodynamic consequences of exercise-induced increase in left ventricular (LV) filling pressure can be demonstrated noninvasively with supine bicycle exercise Doppler echocardiography. One of the practical drawbacks of Doppler echocardiography for assessing LV filling during exercise is the technical difficulty obtaining adequate signals for meaningful analysis during the rapid heart rates achieved during exercise. The purpose of this study was to assess LV filling pressures during the recovery period, as well as at rest, in healthy subjects to establish reference values of Doppler LV filling indices during recovery after exercise. METHODS AND RESULTS: Seventy-three healthy subjects (age 38+/-14 years, 62 males) underwent supine bicycle exercise. Mitral inflow and annular velocities were recorded at baseline and during recovery at 2, 5, and 10 min after cessation of exercise. The ratio of the mitral inflow early diastolic filling velocity (E) to the mitral annular early diastolic velocity (E') was used as an estimation of mean left atrial pressure (E/E'). The mean E/E' ratio at rest was 7.6+/-1.8 and it was <15 in all patients. Mean exercise duration was 837+/-184 s (range, 390-1,260). The E/E' ratio during recovery 2, 5, and 10 min after cessation of exercise was 8.8+/-1.9, 8.2+/-2.0 and 7.8+/-1.8, respectively, and none of the patients had an E/E' >15 during the recovery phase. CONCLUSION: In healthy subjects, the E/E' is less than 15 at rest, as well as during the recovery period up to 10 min after cessation of exercise. Because the E/E' is not elevated in healthy subjects, an elevated E/E' during the recovery period may be helpful for detecting exercise-induced diastolic dysfunction in subjects with tachycardia, even with low levels of exercise.

Incremental value of left ventricular diastolic function reserve index for predicting exercise capacity in patients with hypertrophic cardiomyopathy.

The changes of left ventricular diastolic function during exercise are heterogeneous in patients with hypertrophic cardiomyopathy (HCM). We sought to investigate whether exertional changes of mitral annular velocities and plasma N-terminal-pro-B-type natriuretic peptide (BNP) concentration are associated with exercise capacity in patients with HCM. After a comprehensive echocardiographic study, 32 patients with HCM performed symptom-limited graded supine bicycle exercise. Echocardiographic Doppler parameters were measured at each stage of exercise. Blood samples were collected at rest and immediately after exercise to determine the concentration of pro-BNP. Resting pro-BNP (r = -0.620, P < .001), E'(base) (r = 0.414, P = .018), and DeltaE'(50W) (change of E' from base to 50 W of exercise) (r = 0.367, P = .039) were significantly correlated with exercise duration. Left ventricular longitudinal diastolic function reserve index, defined as DeltaE' x E'(base), significantly correlated with exercise duration (at 50 W, r = 0.540, P = .001) independent of age, sex, body mass index, and resting pro-BNP level. When combining DeltaE' x E'(50W) (<5.85 cm(2)/s(2)) and resting pro-BNP (>740 mg/dL), the predictive accuracy for exercise capacity could be improved (for <500 seconds, global chi(2) = 5.84 in pro-BNP vs 8.10 in pro-BNP + DeltaE' x E'(50W), P = .023). The assessment of left ventricular longitudinal diastolic function reserve can provide incremental information to pro-BNP for the prediction of exercise capacity in patients with HCM.

Anti-tumor activity of ex vivo expanded cytokine-induced killer cells against human hepatocellular carcinoma.

Cytokine-induced killer (CIK) cells are ex vivo expanded T cells with natural killer cell phenotypes and functions. In this study, the anti-tumor activity of CIK cells against hepatocellular carcinoma was evaluated in vitro and in vivo. In the presence of anti-CD3 antibody and IL-2 for 14 days, human peripheral blood mononuclear cell population changed to heterogeneous CIK cell population, which comprised 96% CD3(+), 3% CD3( inverted exclamation mark(c))CD56(+), 32% CD3(+)CD56(+), 11% CD4(+), 75% CD8(+), and 30% CD8(+)CD56(+). CIK cells produced significant amounts of IFN-gamma and TNF-alpha; however, produced only slight amounts of IL-2, IL-4, and IL-5. At an effector-target cell ratio of 30:1, CIK cells destroyed 33% of SNU-354 human hepatocellular carcinoma cells, which was determined by the (51)Cr-release assay. In addition, a dose of 1x10(6) CIK cells per mouse inhibited 60% of SNU-354 tumor growth in irradiated nude mice. This study suggests that CIK cells may be used as an adoptive immunotherapy for patients with hepatocellular carcinoma.

Incremental value of combining systolic mitral annular velocity and time difference between mitral inflow and diastolic mitral annular velocity to early diastolic annular velocity for differentiating constrictive pericarditis from restrictive cardiomyopathy.

Although normal or exaggerated early diastolic mitral annular velocity (E') provides an excellent specificity for differentiating constrictive pericarditis (CP) from restrictive cardiomyopathy (RCM), its sensitivity has been shown to be lower, especially in patients with CP who had underlying myocardial abnormality. This study sought to evaluate the incremental value of systolic mitral annular velocity (S') and time difference between onset of mitral inflow and onset of E' (T(E'-E)) for differentiation between CP and RCM. This study included 44 participants (28 male, 16 female; mean age 47 years, range 10-76): 17 patients with CP, 12 with RCM, and 15 control subjects. Standard mitral inflow Doppler and tissue Doppler echocardiography were performed. E' (9.5 +/- 1.7 vs 4.7 +/- 1.6 cm/s, P < .001) and S' (7.7 +/- 1.3 vs 4.6 +/- 1.9 cm/s, P < .001) were significantly higher, whereas T(E'-E) (21.0 +/- 32.0 vs 53.1 +/- 30.4 milliseconds, P = .02) was significantly shorter in patients with CP than with RCM. Diagnostic accuracy of E' for differentiation of CP from RCM was higher than S' or T(E'-E) (area under curve 0.99 vs 0.87 vs 0.74, respectively). E' of 8 cm/s had excellent specificity (100%) for differentiation of CP from RCM but sensitivity (70%) was relatively low. However, when combining E' with S' and T(E'-E), the sensitivity could be increased when compared with E' alone (70% with E', 88% with E' + S', and 94% with E' + S' + T(E'-E)), P = .001). In conclusion, the measurement of S' and T(E'-E) can be helpful for differentiating between CP and RCM by providing incremental diagnostic information to E'.

Abnormal left ventricular longitudinal functional reserve in patients with diabetes mellitus: implication for detecting subclinical myocardial dysfunction using exercise tissue Doppler echocardiography.

BACKGROUND: Subclinical myocardial dysfunction occurs in a significant number of patients with type 2 diabetes. Assessment of ventricular long-axis function by measuring mitral annular velocities using tissue Doppler echocardiography (TDE) is thought to provide a more sensitive index of systolic and diastolic function. We hypothesised that augmentation of left ventricular (LV) longitudinal contraction and relaxation during exercise would be blunted in patients with type 2 diabetes. METHODS: Mitral annular systolic (S') and early diastolic (E') velocities were measured at rest and during supine bicycle exercise (25 W, 3 min increments) in 53 patients (27 male, mean age 53+/-14 years) with type 2 diabetes and 53 subjects with age and gender-matched control. None had echocardiographic evidence of resting or inducible myocardial ischaemia. RESULTS: There were no significant differences in mitral inflow velocities at rest between the two groups. E' and S' at rest were also similar between the groups. However, S' (7.1+/-1.3 vs 8.3+/-1.8 cm/s at 25 W, p = 0.0021; 8.1+/-1.5 vs 9.1+/-2.0 cm/s at 50 W, p = 0.026) and E' (8.5+/-2.3 vs 9.9+/-3.1 cm/s at 25 W, p = 0.054; 9.1+/-2.1 vs 10.9+/-2.5 cm/s at 50 W, p = 0.0093) during exercise were significantly lower in patients with diabetes compared with controls. Longitudinal systolic and diastolic function reserve indices were significantly lower in patients with diabetes compared with that of controls (systolic index, 0.6+/-0.70 vs 1.2+/-1.5 cm/s at 25 W, p = 0.029; 1.2+/-1.2 vs 2.1+/-1.6 cm/s at 50 W, p = 0.009; diastolic index, 1.9+/-1.2 vs 2.5+/-2.2 cm/s at 25 W, p = 0.07; 2.3+/-1.3 vs 3.2+/-2.2 cm/s at 50 W, p = 0.031). CONCLUSION: In conclusion, unlike resting mitral inflow and annular velocities, changes of systolic and diastolic velocities of the mitral annulus during exercise were significantly reduced in patients with type 2 diabetes compared with the control group. The assessment of LV longitudinal functional reserve with exercise using TDE appears to be helpful in identifying early myocardial dysfunction in patients with type 2 diabetes.