Diagnostic accuracy and clinical usefulness of erythrocyte creatine content to predict the improvement of anaemia in patients receiving maintenance haemodialysis.

BACKGROUND: The improvement of anaemia over time by erythropoiesis stimulating agent (ESA) is associated with better survival in haemodialysis patients. We previously reported that erythrocyte creatine content, a marker of erythropoietic capacity, was a reliable marker to estimate the effectiveness of ESA. The aim of this study was to examine the accuracy and clinical usefulness of erythrocyte creatine content to predict the improvement of anaemia in haemodialysis patients. METHODS: ESA dose was fixed 3 months prior to the enrollment and was maintained throughout the study period. Erythrocyte creatine content and haematologic indices were measured at baseline in 92 patients receiving maintenance haemodialysis. Haemoglobin was also measured 3 months after. Improvement of anaemia was defined as ≥ 0.8 g/dL change in haemoglobin from baseline to 3 months. RESULTS: Erythrocyte creatine content was significantly higher in 32 patients with improvement of anaemia compared to 60 patients with no improvement of anaemia (2.47 ± 0.74 vs. 1.57 ± 0.49 µmol/gHb, P = 0.0001). When 9 variables (erythrocyte creatine content, ESA dose, reticulocyte, haptoglobin, haemoglobin at baseline, serum calcium, intact parathyroid hormone, transferrin saturation and serum ferritin) were used in the multivariate logistic regression analysis, erythrocyte creatine emerged as the most important variable associated with the improvement of anaemia (P = 0.0001). The optimal cut-off point of erythrocyte creatine content to detect the improvement of anaemia was 1.78 µmol/gHb (Area under the curve: 0.86). Sensitivity and specificity of erythrocyte creatine content to detect the improvement of anaemia were 90.6% and 83.3%. CONCLUSION: Erythrocyte creatine content is a reliable marker to predict the improvement of anaemia 3 months ahead in patients receiving maintenance haemodialysis.

Evaluation of recombinant human erythropoietin responsiveness by measuring erythrocyte creatine content in haemodialysis patients.

BACKGROUND: One of the main causes of anaemia in patients with end-stage renal disease is relative deficiency in erythropoietin production. Eythropoiesis stimulating agent (ESA), a potent haematopoietic growth factor, is used to treat anaemia in haemodialysis patients. The effect of ESA is usually assessed by haematological indices such as red blood cell count, haemoglobin concentration and haematocrit, but erythrocyte indices do not provide information of the rapid change in erythropoietic activity. As erythrocyte creatine directly assess erythropoiesis, the aim of this study was to evaluate the effect of ESA in haemodialysis patients by measuring the erythrocyte creatine content. METHODS: ESA dose was fixed 3 months prior to the enrollment and was maintained throughout the entire study period. Erythrocyte creatine was measured with haematologic indices in 83 haemodialysis patients. Haemoglobin was also measured 3 months after. RESULTS: ESA dose (152.4 ± 62.9 vs. 82.2 ± 45.5 units/kg/week, P = 0.0001) and erythrocyte creatine (2.07 ± 0.73 vs. 1.60 ± 0.41 µmol/gHb, p = 0.0003) were significantly higher in 27 patients with haemoglobin <10 g/dL compared to 56 patients with haemoglobin ≥10 g/dL. There was a fair correlation between ESA dose and the concentration of creatine in the erythrocytes (r = 0.55, P < 0.0001). Increase in haemoglobin (>0.1 g/dL) was observed in 37 patients, whereas haemoglobin did not increase in 46 patients. Erythrocyte creatine levels were significantly higher in those patients with an increase in haemoglobin compared to those without (2.04 ± 0.64 vs. 1.52 ± 0.39 µmol/gHb, p < 0.0001). When 8 variables (ESA dose, erythropoietin resistance index, C-reactive protein, intact parathyroid hormone, iron supplementation, presence of anaemia, erythrocyte creatine and reticulocyte) were used in the multivariate logistic analysis, erythrocyte creatine levels emerged as the most important variable associated with increase in haemoglobin (Chi-square = 6.19, P = 0.01). CONCLUSION: Erythrocyte creatine, a useful marker of erythropoietic capacity, is a reliable marker to estimate ameliorative effectiveness of ESA in haemodialysis patients.

Isolation of thymidine-dependent and extended-spectrum-ß-lactamase-producing Escherichia coli small-colony variant from urine of a septuagenarian female patient with recurrent cystitis: A case report with genetic investigation.

Thymidine-dependent small-colony variant (TD-SCV) of Escherichia coli was isolated from urine of a septuagenarian female patient on hemodialysis suffering from recurrent cystitis. The patient had been treated with frequent administrations of trimethoprim sulfamethoxazole (SXT), every time her cystitis symptoms developed. In the TD-SCV isolate, the deletion was detected in the thyA gene associated with thymidylate synthase. Interestingly, the isolate was found to produce extended-spectrum ß-lactamase (ESBL), and the experiment on conjugational transfer of the resistance trait was successful. By means of genetic analysis, the isolate was found to carry blaCTX-M-1 group. To the best of our knowledge, this is the first report of urinary tract infection caused by the transmissible ESBL-producing TD-SCV of E. coli. MICs of the TD-SCV were obtained only on the Mueller Hinton agar media supplemented with appropriate concentrations of thymidine, which might lead to the difficulty for proper chemotherapy in daily medicine. Furthermore, transmission of the ESBL gene via plasmid should be of concern.

Shortened red blood cell age in patients with end-stage renal disease who were receiving haemodialysis: a cross-sectional study.

BACKGROUND: The causes of anaemia in patients with end-stage renal disease include a relative deficiency in erythropoietin production and complex clinical conditions. We aimed to investigate the underlying mechanisms of anaemia in patients with end-stage renal disease who were undergoing maintenance dialysis by measuring erythrocyte creatine levels. METHODS: In a cross-sectional study, we evaluated 69 patients with end-stage renal disease who were receiving haemodialysis (n = 55) or peritoneal dialysis (n = 14). Erythrocyte creatine level, a quantitative marker of mean red blood cell (RBC) age, was measured. RESULTS: The mean RBC age was significantly shorter in the haemodialysis group than in the peritoneal dialysis group (47.7 days vs. 59.8 days, p < 0.0001), although the haemoglobin levels were comparable between the groups. A Spearman correlation coefficient analysis revealed that shortened RBC age positively correlated with transferrin saturation (r = 0.54), ferritin level (r = 0.47), and haptoglobin level (r = 0.39) but inversely related with reticulocyte (r = - 0.36), weekly doses of erythropoiesis-stimulating agents (ESAs; r = - 0.62), erythropoietin resistance index (r = - 0.64), and intradialytic ultrafiltration rate (r = - 0.32). CONCLUSIONS: Shortened RBC age was observed in patients who were receiving maintenance haemodialysis and was associated with iron deficiency, greater haptoglobin consumption, higher ESA requirements, and poor erythropoietin responsiveness, as well as with greater intradialytic fluid extraction.

Effect of Tofogliflozin on Systolic and Diastolic Cardiac Function in Type 2 Diabetic Patients.

PURPOSE: Recent studies have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors have a favorable effect on cardiovascular events in diabetic patients. However, the underlying mechanism associated with a favorable outcome has not been clearly identified. The purpose of this study was to investigate the effect of tofogliflozin, SGLT2 inhibitor, on systolic and diastolic cardiac function in patients with type 2 diabetes mellitus (T2DM). METHODS: We enrolled 26 consecutive T2DM out-patients on glucose-lowering drugs who initiated tofogliflozin and underwent echocardiography before and ≥ 6 months after tofogliflozin administration. During this period, we also enrolled 162 T2DM out-patients taking other glucose-lowering drugs as a control group. Propensity score analysis was performed to match the patient characteristics. As a result, 42 patients (tofogliflozin group 21 patients and control group 21 patients) were finally used for analysis. Left ventricular systolic function was assessed by measuring 2D-echocardiographic left ventricular ejection fraction (LVEF) and diastolic cardiac function by pulsed wave Doppler-derived early diastolic velocity (E/e'). RESULTS: There were no significant differences in patient characteristics and echocardiographic parameters at baseline. The change in LVEF from baseline to follow-up was 5.0 ± 6.9% in the tofogliflozin group and - 0.6 ± 5.5% in the control group; difference significant, p = 0.006. The change in E/e' was - 1.7 ± 3.4 in the tofogliflozin group and 0.7 ± 4.1 in the control group; difference significant, p = 0.024. CONCLUSIONS: In addition to conventional oral glucose-lowering drugs, additional tofogliflozin administration had a favorable effect on left ventricular systolic and diastolic function in patients with T2DM.

Effect of sodium glucose cotransporter 2 inhibitors on cardiac function and cardiovascular outcome: a systematic review.

A high incidence of left ventricular diastolic dysfunction and increased risk of cardiovascular events have been reported in patients with diabetes mellitus. Sodium glucose cotransporter 2 (SGLT2) inhibitors selectively inhibit kidney glucose and sodium reabsorption, and cardiovascular benefits of SGLT2 inhibitors beyond other antidiabetic drugs have been reported in type 2 diabetes mellitus (T2DM) clinical trials. However, underlying mechanisms contributing to the improvement of cardiovascular outcomes have not been clearly identified. In this review, likely mechanisms of SGLT2 inhibitors contributing to a favorable cardiovascular outcomes are discussed based on experimental and clinical studies on cardiac function.

Cardiac Rupture Due to Reinfarction in the Early Phase of Apical Myocardial Infarction.

A 72-year-old woman with hypertension, dyslipidemia, and diabetes mellitus presented to our hospital because of the sudden onset of chest pain. Emergency coronary angiography showed acute occlusion of the distal left anterior descending artery and coronary intervention with a drug-eluting stent was performed. Sudden cardiopulmonary arrest occurred on the sixth day of hospitalization, but coronary angiography showed no remarkable progression of the coronary artery diseases, including the site of stent implantation. An autopsy revealed that the cause of the sudden death was apical free wall rupture. In addition, the different timing of acute and sub-acute infarct findings were observed in the apical wall by histology, which indicated cardiac rupture was due to reinfarction at early phase of apical acute myocardial infarction. Although the rate of mechanical complications, including cardiac rupture, is decreasing in the era of primary coronary intervention, in addition to the well-known risk factors of cardiac rupture, the reinfarction of the culprit myocardial site in the early phase of acute myocardial infarction was considered as a possible risk factor of cardiac rupture.

Relationship between matrix metalloproteinase-3 serum level and pulmonary artery systolic pressure in patients with rheumatoid arthritis.

Activity of rheumatoid arthritis (RA) has been evaluated by various biomarkers including matrix metalloproteinase (MMP)-3, but the relationship between the levels of biomarkers and elevation of pulmonary artery systolic pressure (PAs) has not been evaluated in detail. We sought to determine the utility of MMP-3 with other biomarkers for the prediction of PAs in patients with RA. Blood samples for biomarkers and echocardiography were obtained in 100 consecutive patients with RA. PAs was measured by continuous-wave Doppler echocardiography and was correlated with laboratory findings. PAs had a fair correlation with MMP-3 (r = 0.53, p < 0.001) and a weak correlation with KL (Krebs von den Lungen)-6 (r = 0.36, p < 0.001) and rheumatoid factor (r = 0.25, p = 0.011). MMP-3 had a fair correlation with pulmonary vascular resistance (r = 0.42, p < 0.001), but MMP-3 was not related to cardiac output (r = 0.09, p = 0.352). Thirty-nine patients had impaired left ventricular diastolic function. There was no significant differences in PAs and pulmonary vascular resistance (PVR) between the patients with and without impaired left ventricular diastolic function. When 5 variables (age, MMP-3, C-reactive protein, KL-6, and rheumatoid factor) were used in the multivariate analysis, MMP-3 (partial regression coefficient = 0.553, p < 0.001) emerged as the most important variable related to the elevation of PAs. Nine patients (9%) were diagnosed to have pulmonary hypertension by echocardiography. MMP-3 value of 245 ng/ml was the optimal cut-off value for the prediction of pulmonary hypertension (sensitivity: 100%, specificity: 67%, area under the curve 0.89). Thus, a close relation of MMP-3 with PAs and PVR indicate that rise in PAs in patients with RA was ascribed to increase in PVR due to underlying systemic inflammation-mediated pulmonary vascular remodeling.

Experimental fusion of different versions of the total laboratory automation system and improvement of laboratory turnaround time.

BACKGROUND: Use of total laboratory automation (TLA) system has expanded to microbiology and hemostasis and upgraded to second and third generations. We herein report the first successful upgrades and fusion of different versions of the TLA system, thus improving laboratory turnaround time (TAT). METHODS: A 21-day schedule was planned from the time of pre-meeting to installation and clinical sample application. We analyzed the monthly TAT in each menu, distribution of the "out of range for acceptable TAT" samples, and "prolonged time out of acceptable TAT," before and after the upgrade and fusion. RESULTS: We installed and customized hardware, middleware, and software. The one-way CliniLog 2.0 version track, 50.0-m long, was changed to a 23.2-m long one-way 2.0 version and an 18.7-m long two-way 4.0 version. The monthly TAT in the outpatient samples, before and after upgrading the TLA system, were uniformly satisfactory in the chemistry and viral marker menus. However, in the tumor marker menu, the target TAT (98.0% of samples ≤60 minutes) was not satisfied during the familiarization period. There was no significant difference in the proportion of "out of acceptable TAT" samples, before and after the TLA system upgrades (7.4‰ and 8.5‰). However, the mean "prolonged time out of acceptable TAT" in the chemistry samples was significantly shortened to 17.4 (±24.0) minutes after the fusion, from 34.5 (±43.4) minutes. CONCLUSIONS: Despite experimental challenges, a fusion of the TLA system shortened the "prolonged time out of acceptable TAT," indicating a distribution change in overall TAT.

Clinical utility of transthoracic echocardiography for screening abdominal aortic aneurysm: a prospective study in a Japanese population.

BACKGROUND: The aim of the present study was to evaluate the clinical utility of transthoracic echocardiography (TTE) for screening abdominal aortic aneurysm (AAA) and to identify important TTE indices associated with AAA in a Japanese population. METHODS: We prospectively studied 1912 patients who were referred for TTE. AAA was defined as ≥ 30 mm in size. RESULTS: The abdominal aorta was visualized in 95.1% (1818/1912) by TTE. AAA was identified in 2.6% (47/1818). The aortic root size was significantly larger in patients with AAA than those without (36.0 ± 4.1 vs. 31.7 ± 4.2 mm, p < 0.001). The aortic root size had a fair correlation with abdominal aortic size (r = 0.31, p < 0.001). The aortic root size of ≥ 34 mm was predictive of AAA by receiver operating characteristic curve analysis (area under the curve = 0.78, p < 0.001). Multiple logistic regression analysis revealed that aortic root size (Hazard ratio 1.23, p < 0.001) and age (Hazard ratio 1.05, p = 0.013) were the independent predictors of AAA. CONCLUSIONS: The feasibility of the abdominal aortic visualization during TTE was excellent. The aortic root size measured by TTE was the independent predictor of AAA. Screening for AAA during TTE appeared to be useful especially in the older patients with a large (≥34 mm) aortic root.

Evaluation of Intravascular Hemolysis With Erythrocyte Creatine in Patients With Aortic Stenosis.

Chronic intravascular hemolysis has been identified in patients with cardiac valve prostheses, but only a few case reports have evaluated intravascular hemolysis in patients with native valvular heart disease. To detect intravascular hemolysis in patients with aortic stenosis, erythrocyte creatine was evaluated with hemodynamic indices obtained by echocardiography.Erythrocyte creatine, a marker of erythrocyte age, was assayed in 30 patients with aortic stenosis and 10 aged matched healthy volunteers. Peak flow velocity of the aortic valve was determined by continuous-wave Doppler echocardiography. Twenty of 30 patients with aortic stenosis had high erythrocyte creatine levels (> 1.8 µmol/g Hb) and erythrocyte creatine was significantly higher as compared with control subjects (1.98 ± 0.49 versus 1.52 ± 0.19 µmol/g Hb, P = 0.007). Peak transvalvular pressure gradient ranged from 46 to 142 mmHg and peak flow velocity ranged from 3.40 to 5.95 m/second. Patients with aortic stenosis had a significantly lower erythrocyte count (387 ± 40 versus 436 ± 42 × 10(4) µL, P = 0.002) and hemoglobin (119 ± 11 versus 135 ± 11 g/L, P < 0.001) as compared with control subjects. Erythrocyte creatine had a fair correlation with peak flow velocity (r = 0.55, P = 0.002).In conclusion, intravascular hemolysis due to destruction of erythrocytes was detected in patients with moderate to severe aortic stenosis and the severity of intravascular hemolysis was related to valvular flow velocity of the aortic valve.

Differentiation of infiltrative cardiomyopathy from hypertrophic cardiomyopathy using high-sensitivity cardiac troponin T: a case-control study.

BACKGROUND: Because infiltrative cardiomyopathy and hypertrophic cardiomyopathy (HCM) share clinical and hemodynamic features of left ventricular (LV) hypertrophy and abnormal diastolic function, it is often difficult to distinguish these entities. METHODS: We investigated the potential role of high-sensitivity cardiac troponin T (hs-cTnT) for differentiation of infiltrative cardiomyopathy from HCM. RESULTS: The study group consisted of 46 consecutive patients with infiltrative cardiomyopathies or HCM in whom sarcomere protein gene mutations were identified at Kochi Medical School Hospital; of these, there were 11 patients with infiltrative cardiomyopathy (cardiac amyloidosis in 8 patients and Fabry disease in 3 patients) and 35 HCM patients. Serum hs-cTnT level was significantly higher in patients who had infiltrative cardiomyopathy than in those who had HCM (0.083 ± 0.057 ng/ml versus 0.027 ± 0.034 ng/ml, p < 0.001), whereas brain natriuretic peptide levels did not differ between the two groups. In two age-matched the 2 cohorts (patients evaluated at > 40 years at age), hs-cTnT level, maximum LV wall thickness, posterior wall thickness, peak early (E) transmitral filling velocity, peak early diastolic (Ea) velocity of tissue Doppler imaging at the lateral corner and E/Ea ratios at both the septal and lateral corners were significantly different between the two groups. As for diagnostic accuracy to differentiate the two groups by using receiver operating characteristic analysis, hs-cTnT was the highest value of area under the curve (0.939) and E/Ea (lateral) was second highest value (0.914). CONCLUSIONS: Serum hs-cTnT is a helpful diagnostic indicator for accurate differentiation between infiltrative cardiomyopathy and HCM.

Autoimmunity and pulmonary hypertension in patients with Graves' disease.

A link between hyperthyroidism and pulmonary hypertension has been reported, but the underlying mechanisms of these two conditions have not been clearly identified. The aim of this study was to determine the clinical correlates of pulmonary hypertension in patients with Graves' disease. Among 50 consecutive patients with Graves' disease referred for echocardiography, 18 patients (36 %) had pulmonary hypertension measured by continuous-wave Doppler echocardiography (pulmonary artery systolic pressure >35 mmHg). The patients with pulmonary hypertension had significantly higher pulmonary vascular resistance (PVR), cardiac output and thyroid-stimulating hormone receptor antibody (TRAb) compared to those without (p < 0.001, p = 0.028 and p < 0.001, respectively). Pulmonary artery systolic pressure had a good correlation with TRAb (r = 0.74, p < 0.001), but was not related to free T4 (r = 0.12, p = 0.419) and free T3 (r = 0.22, p = 0.126). To determine the important variables present in patients with Graves' disease that may be related to pulmonary artery systolic pressure, 4 variables (PVR, cardiac output, TRAb and free T3) were used in the multivariate analysis. In addition to PVR (standard regression coefficient = 0.831, p < 0.001) and cardiac output (standard regression coefficient = 0.592, p < 0.001), TRAb (standard regression coefficient = 0.178, p < 0.001) emerged as a significant variable related to pulmonary artery systolic pressure. Thus, in addition to the effect of thyroid hormone on the cardiovascular system, autoimmune-mediated pulmonary vascular remodeling may play a role in Graves' disease-linked elevated pulmonary artery systolic pressure.

Prediction of left ventricular reverse remodeling after therapy with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and ß blockers in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Predictors of left ventricular reverse remodeling (LVRR) after therapy with angiotensin converting enzyme inhibitors or angiotensin-receptor blockers and ß blockers in patients with idiopathic dilated cardiomyopathy (IDC) remains unclear. METHODS: We studied 44 patients with IDC who had been treated with the therapy. LVRR was defined as LV end-diastolic dimension ≤ 55 mm and fractional shortening ≥ 25% at the last echocardiogram. RESULTS: During a mean follow-up period of 4.7 ± 3.3 years, LVRR occurred in 34% (15/44) of the patients. We divided the patients into 2 groups: (1) patients with LVRR (n = 15); (2) patients without LVRR (n = 29). The presence of atrial fibrillation was 40% in patients with LVRR and 14% in those without (p = 0.067). Initial LV end-diastolic dimension was significantly smaller (62 ± 6 vs. 67 ± 6 mm, p = 0.033) in patients with LVRR than in those without. Initial LV end-diastolic dimension of 63.5 mm was an optimal cutoff value for predicting LVRR (sensitivity: 67%, specificity: 59%, area under the curve: 0.70, p = 0.030). When patients were further allocated according to initial LV end-diastolic dimension ≤ 63.5 mm with atrial fibrillation, the combined parameter was a significant predictor of LVRR by univariate logistic regression analysis (odds ratio, 5.78, p = 0.030) (sensitivity: 33%, specificity: 97%, p = 0.013). CONCLUSIONS: Combined information on LV end-diastolic dimension and heart rhythm at diagnosis is useful in predicting future LVRR in patients with IDC.

Clinical Application of the DiversiLab Microbial Typing System Using Repetitive Sequence-Based PCR for Characterization of Helicobacter pylori in Japan.

We evaluated the DiversiLab (DL) system with universal primers, a semiautomated repetitive extragenic palindromic sequence-based polymerase chain reaction (PCR) (rep-PCR) system, for the characterization of Helicobacter pylori in Japan. All 135 isolates from Japanese patients with gastric cancer (GC, n = 55) or non-GC (n = 80) were used and subjected to the drug susceptibility examinations (amoxicillin, AMPC; metronidazole, MNZ; and clarithromycin, CAM) by E-test. There were 28 MNZ-resistant (20.7%), 35 CAM-resistant (25.9%), and 16 MNZ/CAM-resistant (11.9%) isolates. DL rep-PCR fingerprinting analysis at the level of 95% similarity revealed five major groups (A-E) and the other including 45 isolates. The occupation rates of GC-derived isolates in groups B (54.2%) and E (58.8%) were higher than in the other groups: A (26.7%), C (28.6%), D (30.0%), and the other (40.0%). Relative higher occupation rates of drug resistants, such as MNZ-, CAM- and double MNZ/CAM-resistant isolates, were observed in groups B (45.8%), C (42.6%), and D (40%). Five of eight GC-derived isolates with MNZ/CAM resistance were significantly assigned to group B (P = 0.0312, χ(2) -test). These results suggest that the isolates classified in group B have a potential to contribute to the development of severe gastric disorders. The DL system, rapid and high sensitive technology, would be widely available in clinical laboratory for pathological and epidemiological analyses even in H. pylori.

Less deep vein thrombosis due to transcutaneous fibular nerve stimulation in total knee arthroplasty: a randomized controlled trial.

PURPOSE: It has been known for years that deep vein thrombi (DVT) start to develop during total joint arthroplasty. Previously, we reported effective prevention of venous stasis by transcutaneous electrical nerve stimulation (TENS). It is hypothesized that TENS might be a thromboprophylactic tool for the limb undergoing surgery. The purpose of this study is to clarify the clinical efficacy and safety of TENS in patients during total knee arthroplasty (TKA). METHODS: Ninety patients undergoing primary TKA were involved and randomly allocated to the TENS or control group. In the TENS group, electrical stimulation of the common fibular nerve, which produced a brisk dorsiflexion of the ankle, was performed for the operated leg during surgery. In the control group, no electrical stimulation was applied. Serum D-dimer and soluble fibrin monomer complex (SFMC) levels were measured before surgery, immediately after surgery, and post-operative day (POD) 1. Ultrasonography was performed on POD 1. RESULTS: Immediately after surgery, D-dimer and SFMC levels of each group were significantly lower in the TENS group compared with control (p < 0.05). The incidence of DVT was 11 % (five cases) in the TENS group while 31 % (14 cases) in control (p = 0.02). There were no adverse effects related to TENS. CONCLUSIONS: TENS during TKA showed significant effects on preventing DVT. Sustaining muscle pump activation during surgery prevented not only venous stasis, but also hypercoagulability of blood. Intraoperative TENS is a safe and novel strategy against early post-operative thromboembolism, which is difficult to be completed through existing prophylaxis after total joint arthroplasty. LEVEL OF EVIDENCE: Randomized controlled trial, Level I.

Clinical significance of high-sensitivity cardiac troponin T in patients with dilated cardiomyopathy.

Although conventional cardiac troponin T (cTnT) and I (cTnI) markers have been reported to predict adverse outcome in dilated cardiomyopathy (DCM), the usefulness of a new-generation high-sensitivity assay of cardiac troponin T (hs-cTnT) compared with these conventional biomarkers is unclear.We performed clinical evaluation including measurements of troponin markers in 54 patients with DCM under a clinically stable condition. At baseline, the serum concentration of hs-cTnT was 0.014 ± 0.016 ng/mL and 17 (31%) of the patients showed abnormal hs-cTnT values (> 0.014 ng/mL). During a mean follow-up period of 5.1 ± 1.6 years, there were 16 cardiac events: heart failure death in 6 patients, sudden cardiac death in 2 patients, and hospitalization for heart failure in 8 patients. Patients with abnormal hs-cTnT or abnormal cTnT (> 0.01 ng/mL) values had significantly more frequent cardiac events than did those with normal hs-cTnT or cTnT values. On the other hand, abnormal cTnI (> 0.03 ng/mL) value did not reach statistical significance for these adverse events. Multivariate analysis showed that only an abnormal hs-cTnT value was an independent predictor of all cardiac events (HR: 5.68, P = 0.003). When the patients were divided into 4 groups according to the degree of hs-cTnT levels, the clinical course was significantly worse in patients with higher hs-cTnT values.These results suggest that the serum concentration of hs-cTnT provides better risk stratification in DCM patients.

[Molecular-pathological analysis of Helicobacter pylori-associated disorders and clinical laboratory testing].

Helicobacter pylori (H. pylori) infection causes gastro-duodenal diseases and a wide variety of non gastrointestinal tract conditions, such as idiopathic thrombocytopenic purpura (ITP). Many reports have provided robust evidence for understanding the pathogenesis of H. pylori. However, its cell division process is little known. H. pylori exhibits marked genetic diversity to survive under various stress conditions, leading to the emergence of a variety of clones with novel characteristics. In this report, we briefly summarize our results. H. pylori urease is essential to live in a low-pH environment. Bacterial motility and urea taxisis are also important features for persistent infection. The urease is controlled in response to the pH via post translational regulation. Genetic rearrangement occurs during persistent infection of an individual's stomach, which results in the appearance of a variety of new strains with novel characteristics. The cdrA (cell division-related gene A)--dysfunctional strain had acquired such novel characteristics: increased viability, long-term survival, and tolerance to antibiotics. Furthermore, colonization by a cdrA-dysfunctional strain results in decreased IL-8 production and, hence, attenuates the host's immunity to cause persistent infection. Among the factors involved in the bacterium-host interaction and pathogenesis, we describe the H. pylori CagA, BabA, SabA, and SOD. We discovered two H. pylori phages, including a new type of spherical phage, which cannot be classified into any existing virus category. The phages probably contribute to the evolution and pathogenesis of H. pylori. Eradication therapy covered by health insurance was approved for H. pylori-associated ITP. We reported an extra mechanism, the immunocomplex model (platelets, bacterial molecules, and anti H. pylori antibodies), in the development of H. pylori associated ITP. On the other hand, increased cases of unsuccessful eradication therapy are due to the increased occurrence of drug-resistant H. pylori. Non-antibiotic substances with anti-H. pylori activity are attracting much attention.

Effect of pioglitazone on arterial baroreflex sensitivity and sympathetic nerve activity in patients with acute myocardial infarction and type 2 diabetes mellitus.

Pioglitazone has been shown to reduce the occurrence of fatal and nonfatal myocardial infarction (MI) in type 2 diabetes mellitus (DM). However, the mechanisms of such favorable effects remain speculative. The aim of this study was to investigate the effect of pioglitazone on arterial baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA) in 30 DM patients with recent MI. Patients were randomly assigned to those taking pioglitazone (n = 15) and those not taking pioglitazone (n = 15) at 4 weeks after the onset of MI. BRS, MSNA, calculated homeostasis model assessment of insulin resistance index (HOMA-IR), and plasma adiponectin were measured at baseline and after 12 weeks. Pioglitazone increased plasma adiponectin (from 6.9 ± 3.3 µg/dL to 12.2 ± 7.1 µg/dL) and reduced HOMA-IR (from 4.0 ± 2.2 to 2.1 ± 0.9). In the pioglitazone group, MSNA decreased significantly (from 37 ± 7 bursts/min to 25 ± 8 bursts/min) and BRS increased significantly (from 6.7 ± 3.0 to 9.9 ± 3.2 ms/mm Hg) after 12 weeks. Furthermore, a significant relationship was found between the change in MSNA and HOMA-IR (r = 0.6, P = 0.042). Thus, pioglitazone decreased the sympathetic nerve traffic through the improvement of insulin resistance in DM patients with recent MI, which indicate that the sympathoinhibitory effects of pioglitazone may, at least in part, have contributed to the beneficial effects of pioglitazone.

Superoxide dismutase activity of Helicobacter pylori per se from 158 clinical isolates and the characteristics.

We investigated the correlation between the SOD activity of Helicobacter pylori (H. pylori) and gastroduodenal diseases and the characteristics of strains exposed to oxidative stress. Two sequenced strains, 26695 and J99, and clinical isolates from 156 Japanese patients with gastroduodenal diseases such as gastric cancer (n= 59) and non-cancer (n= 97) were used. SOD activities of all 158 isolates were measured and were divided into three groups: high-SOD activity (>0.22, n= 2), moderate-SOD activity (0.15≦≦0.22, n= 16) and low-SOD activity (<0.15, n= 140). Expressions of H. pylori Fe-SOD were examined by western blotting with anti-H. pylori Fe-SOD antibody prepared inhouse, and the profiles of Fe-SOD activity were investigated by zymogram with activity staining in native-PAGE. The characteristics of strains from high-SOD and low-SOD groups were examined under oxidative stress by paraquat. The average of H. pylori SOD activity was significantly higher in the cancer group than in the non-cancer group (P < 0.05). However, irrespective of SOD activity level, the amount of Fe-SOD expressed was variable among individual strains. Zymogram revealed a single band in moderate-SOD and low-SOD strains, but multiple bands in high-SOD strains were observed. These bands were confirmed as H. pylori Fe-SOD. Under oxidative stress with paraquat, low-SOD strains were drastically eliminated without inducible SOD activity; however, high-SOD strains were still viable with increased SOD activity. This study is the first to exhibit the characteristics of high-SOD activity strains representing multiple bands in zymograms and the correlation between H. pylori SOD activity and gastric cancer.