Left Ventricular Longitudinal Myocardial Function of Heart Failure Patients With Transition From Reduced to Preserved Ejection Fraction and of Those With Preserved Ejection Fraction.

Background: Left ventricular (LV) longitudinal myocardial function is associated with the outcomes of heart failure (HF) patients. HF with improved ejection fraction (EF), known as HFimpEF, which is defined as current LVEF >40% but any previously documented LVEF ≤40%, has favorable outcomes compared with HF with preserved EF (HFpEF). However, LV longitudinal myocardial function in patients with previously reduced LVEF (<50%) but improved LVEF to within the normal range (≥50%) (HFnorEF) and its association with cardiovascular events remain unclear. Methods and Results: We studied 70 patients with HFpEF and 65 with HFnorEF. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS). The primary endpoint was defined as cardiovascular death or HF hospitalization during follow-up of 5.6±3.1 years. The GLS of HFpEF patients was significantly lower than that of HFnorEF patients (13.6±3.5% vs. 14.8±2.2%, P=0.02) even when the LVEF was similar. Multivariate Cox proportional hazards analysis showed that GLS was independently associated with cardiovascular events. Furthermore, of the entire study population, patients with GLS >15.0% had fewer cardiovascular events than those without (log-rank P=0.014) among all the patients. Conclusions: LV longitudinal myocardial dysfunction was more frequently observed in patients with HFpEF than in those with HFnorEF, even when LVEF was similar, and was independently associated with cardiovascular events for HF patients with current LVEF ≥50%.

Effect of increase in heart rate after anthracycline chemotherapy on subsequent left ventricular dysfunction.

BACKGROUND: Anthracycline chemotherapy-related cardiac dysfunction is believed to be refractory to conventional pharmacological therapy and is associated with a poor prognosis. Increased heart rate (HR) is a known marker of cardiovascular outcomes for various categories of heart failure (HF). However, little interest has been expressed regarding increased HR after anthracycline chemotherapy. Aim of this study was to investigate the effect of increased HR soon after completion of anthracycline chemotherapy on subsequent left ventricular (LV) ejection fraction (LVEF) in cancer patients. METHODS: We studied 172 patients with breast cancer and malignant lymphoma with preserved LVEF (≥ 50 %) and sinus rhythm treated with anthracyclines. Electrocardiography was performed before and soon after completion of anthracycline chemotherapy (2.3 months), and echocardiography before and late after completion of anthracycline chemotherapy (10.5 months). RESULTS: HR significantly increased from 74.2 ±â€¯14.2 bpm to 75.9 ±â€¯13.2 bpm (P = 0.05) soon after completion of anthracycline chemotherapy, while LVEF subsequently significantly decreased from 65.3 ±â€¯5.5 % to 62.4 ±â€¯6.1 % (P < 0.01) late after completion of anthracycline chemotherapy. Patients whose HR increased ≥10 bpm subsequently showed a significantly greater decrease in LVEF than those whose HR increased <10 bpm [-4.9 % (-32.7 % - 10.8 %) vs. -2.2 % (-21.2 % - 12.9 %), p = 0.04]. Multivariable logistic regression analysis showed that an increase in HR soon after completion of anthracycline chemotherapy was independently associated with a subsequent decrease in LVEF (odds ratio: 1.022, 95 % confidential interval; 1.008-1.037, P = 0.002). CONCLUSIONS: Our findings may have a novel effect on the management of cancer patients scheduled for anthracycline chemotherapy.

Longitudinal evaluation of apparent diffusion coefficient values as a predictor of Prostate Cancer Research International Active Surveillance reclassification.

PURPOSE: This study aimed to evaluate the effectiveness of apparent diffusion coefficient (ADC) parameters in distinguishing between Prostate Cancer Research International Active Surveillance (PRIAS) non-reclassification and reclassification groups during active surveillance (AS) of prostate cancer. METHODS: We included 55 patients who fulfilled the PRIAS criteria and underwent ≥ 2 magnetic resonance imaging (MRI) including diffusion-weighted imaging with an interval of ≤ 3 years between baseline and second MRI. A mono-exponential fitting model was used to automatically create ADC maps with minimum b-values of 0 and maximum of 2000 s/mm2. For detectable lesions on ADC maps, the lesions were manually segmented on each slice of the ADC maps. For undetectable lesions, the corresponding normal-appearing zone of the lobe on each slice of ADC maps was segmented. The ADC data for each slice were summed to obtain the 25th, 50th, and 75th percentile ADC values of the histogram at baseline and second MRI. These ADC parameters at baseline and second MRI, and the changes of ADC parameters from baseline to second MRI were compared between PRIAS non-reclassification and reclassification groups. RESULTS: The PRIAS reclassification group had significantly lower 25th, 50th, and 75th percentile ADC values at second MRI compared to the non-reclassification group. The non-reclassification group had significantly lower changes in ADC values in these percentiles compared to the reclassification group. CONCLUSION: The ADC parameters at second MRI and the changes from baseline to second MRI may be effective distinguishing factors between PRIAS non-reclassification and reclassification groups.

Association between diabetic nephropathy and left ventricular longitudinal myocardial function in type 1 diabetes mellitus patients with preserved ejection fraction.

Left ventricular (LV) longitudinal myocardial dysfunction can be observed even in type 2 diabetes mellitus (DM) (T2DM) patients with preserved LV ejection fraction (LVEF), and is considered the earliest marker of DM-related cardiac dysfunction. Furthermore, diabetic nephropathy (DN), a common complication in DM, is strongly associated with LV longitudinal myocardial function in T2DM patients, but its association with type 1 DM (T1DM) has not been fully investigated. We studied 125 asymptomatic T1DM patients with preserved LVEF, and 75 age-, gender-, LVEF-matched non-diabetic healthy controls. Two-dimensional speckle-tracking strain LV was used to assess longitudinal myocardial function as global longitudinal strain (GLS). GLS of T1DM patients was significantly lower than that of normal controls (19.7 ± 3.6% vs. 20.6 ± 1.8%, P = 0.049). GLS of T1DM patients with DN was significantly lower that of T1DM patients without DN (17.3 ± 3.7% vs. 20.2 ± 3.5%, P < 0.001), but that of T1DM patients without DN was similar compared to normal controls (20.6 ± 1.8% vs. 20.2 ± 3.5%, P = 0.37). Moreover, multiple regression analysis identified DN the independent determinant parameters for GLS of T1DM patients also correlated significantly with duration of T1DM. Impaired LV longitudinal myocardial function was observed in asymptomatic T1DM patients with preserved LVEF, and DN was associated with LV longitudinal myocardial dysfunction. These findings are clinically useful for better management of T1DM patients to prevent impending development of cardiovascular disease.

Development of a protein assay with copper chelator chromeazurol B, based on the biuret reaction.

This study aimed to provide a novel and highly sensitive protein assay based on the biuret reaction and using chromeazurol B, a metal chelate compound. The method consists of two reagents and an automated analyzer. First, a complex of copper and protein (biuret reaction) is formed. Second, a chelating reagent containing chromeazurol B forms a three-dimensional complex of protein, copper, and chromeazurol B at neutral pH, resulting in highly sensitive coloration. The intra-assay (n = 20) variation for the three levels was 3.54 % or lower at each concentration. Each response with α, ß-, and γ-globulin was 103.8 % and 104.3 %, respectively, against albumin. The molar absorption coefficient (ε) of the present method was 2.5 × 105 m2/mol against human albumin, higher than that of the commercially available Lowry method (ε = 8.7 × 104 m2/mol), which is based on the same principle. The correlation test for the pyrogallol method with 30 urine samples showed good performance (r = 0.961). The method described here (the Biuret-based CAB method) is a more sensitive and rapid assay than the Lowry method, and it may also be applied to biological samples because of its similar reactivity towards various proteins.

Ruptured mediastinal mature teratoma causing severe mediastinitis: report of a surgically resected case and a literature review.

BACKGROUND: Mediastinal teratomas occasionally rupture into the thoracic cavity, which induces mediastinitis or various other severe complications. Surgical treatment is crucial for ruptured teratomas; however, few literature reviews to date have addressed the characteristics of ruptured mediastinal teratomas. CASE PRESENTATION: We report a 29-year-old woman with severe mediastinitis owing to a mediastinal mature teratoma that ruptured into the mediastinum and right pleural cavity. Surgical resection by median sternotomy was performed within 24 hours after emergency admission. Intraoperative findings demonstrated the ruptured wall of the tumor with exposure of its white contents, which appeared similar to skin and fat, and necrotic tissue in the anterior mediastinum. The tumor was adhered to the right upper lobe, the ascending aorta, and pericardium. Owing to the severe adhesion of the tumor caused by inflammation in the surrounding tissues, a small portion of the tumor could not be removed, and hence complete resection with a sufficient surgical margin was not achieved. Pathologically, the tumor consisted of a solid mass and a cystic mass with severe adhesion to the resected portion of the lung, which included skin and lipid tissue. The tumor was concluded to be a mature teratoma as neither an immature component nor malignant transformation was observed. The patient had an uneventful postoperative course. CONCLUSIONS: To our knowledge, this is the report of successful surgical resection of a ruptured mediastinal teratoma causing severe mediastinitis, with the first literature review of ruptured mediastinal teratomas. We also discuss relevant findings from reports in the literature.

Immobilization of proteins onto microbeads using a DNA binding tag for enzymatic assays.

A novel DNA-binding protein tag, scCro-tag, which is a single-chain derivative of the bacteriophage lambda Cro repressor, has been developed to immobilize proteins of interest (POI) on a solid support through binding OR consensus DNA (ORC) that is tightly bound by the scCro protein. The scCro-tag successfully bound a transglutaminase 2 (TGase 2) substrate and manganese peroxidase (MnP) to microbeads via scaffolding DNA. The resulting protein-coated microbeads can be utilized for functional analysis of the enzymatic activity using flow cytometry. The quantity of bead-bound proteins can be enhanced by increasing the number of ORCs. In addition, proteins with the scCro-tag that were synthesized using a cell-free protein synthesis system were also immobilized onto the beads, thus indicating that this bead-based system would be applicable to high-throughput analysis of various enzymatic activities.

Highly sensitive reversed-phase high-performance liquid chromatography assay for the detection of Tamm-Horsfall protein in human urine.

BACKGROUND: Tamm-Horsfall protein (also known as uromodulin) is the most abundant urinary protein in healthy individuals. Since initially characterized by Tamm and Horsfall, the amount of urinary excretion and structural mutations of Tamm-Horsfall protein is associated with kidney diseases. However, currently available assays for Tamm-Horsfall protein, which are mainly enzyme-linked immunosorbent assay-based, suffer from poor reproducibility and might give false negative results. METHODS: We developed a novel, quantitative assay for Tamm-Horsfall protein using reversed-phase high-performance liquid chromatography. A precipitation pretreatment avoided urine matrix interference and excessive sample dilution. High-performance liquid chromatography optimization based on polarity allowed excellent separation of Tamm-Horsfall protein from other major urine components. RESULTS: Our method exhibited high precision (based on the relative standard deviations of intraday [≤2.77%] and interday [≤5.35%] repetitions). The Tamm-Horsfall protein recovery rate was 100.0-104.2%. The mean Tamm-Horsfall protein concentration in 25 healthy individuals was 31.6 ± 18.8 mg/g creatinine. There was a strong correlation between data obtained by high-performance liquid chromatography and enzyme-linked immunosorbent assay (r = 0.906), but enzyme-linked immunosorbent assay values tended to be lower than high-performance liquid chromatography values at low Tamm-Horsfall protein concentrations. CONCLUSIONS: The high sensitivity and reproducibility of our Tamm-Horsfall protein assay will reduce the number of false negative results of the sample compared with enzyme-linked immunosorbent assay. Moreover, our method is superior to other high-performance liquid chromatography methods, and a simple protocol will facilitate further research on the physiological role of Tamm-Horsfall protein.

Preliminary evaluation of an improved enzymatic assay method for measuring potassium concentrations in serum.

BACKGROUND: K(+) has important physiological functions. K(+) concentrations in serum are generally determined using ion-selective electrodes (ISEs), though measurement using reagents in aqueous medium is also useful. METHODS: K(+) concentrations were measured using recombinant inosine 5'-monophosphate dehydrogenase (IMPDH), which was activated only by K(+) and NH4(+). Exogenous NH4(+) and endogenous NH4(+) were eliminated using glutamine synthase. RESULTS: Regression analysis of the enzymatic assay (y) vs. the ISE method (x) gave the following relation: y=1.03x+0.09 (n=54, Sy,x=0.06 mmol/l). The linear range was up to 12 mmol/l when 1 U/ml IMPDH was used. CONCLUSION: Advantages of the proposed assay method are: (i) the measured range is wider than that of existing enzymatic methods; (ii) the conditions for K(+) determination can be maintained constant, regardless of the amount of NH4(+) in the analyte and reagents; and (iii) the elimination system is simpler because the recombinant IMPDH is stimulated by only K(+) and NH4(+) and is unaffected by biological materials.