Adiponectin prevents inflammation and atherosclerosis, but it is unclear whether overexpression of adiponectin protects the vasculature. The aim of the present study was to determine whether adiponectin overexpression promotes vascular repair after mechanical injury using adiponectin transgenic (Tg) mice. Studies were performed in 7–8-week-old C57/BL6 (wild-type; WT; n=50) and adiponectin Tg (n=46) mice. A damaged endothelium model was created by inserting a large wire into the femoral artery. Von Willebrand factor-positive cells were observed on the surface of the damaged area from 1 week after wire injury in Tg mice, and from 2 weeks in WT mice. At 1 week, both α-smooth muscle embryonic myosin heavy chain-positive cells and intercellular adhesion molecule-positive cells were observed in the neointima in WT but not Tg mice. The intima/media ratio was significantly smaller in Tg than WT mice. Adiponectin and tumor necrosis factor (TNF)-α mRNA expression was observed in non-injured Tg and WT mice, but serum and mesenteric adipose tissue adiponectin concentrations were significantly higher in Tg than WT mice. Higher adiponectin and lower TNF-α levels, brought about by adiponectin transgene expression, suppressed neointimal hyperplasia by attenuating the inflammatory response following the acceleration of endothelialization in damaged areas in adiponectin Tg mice.

View full abstract

In patients with implantable cardioverter defibrillators(ICD)or cardiac resynchronization therapy defibrillators(CRT-D), appropriate and inappropriate shocks lead to a higher risk of mortality. Cardiac rehabilitation(CR)is an established therapy for patients with ischemic heart disease and/or congestive heart failure. However, it is unclear whether CR could reduce the need for device therapies. The purpose of the present study was to investigate whether CR reduces device therapies and mortality in patients with severe cardiac dysfunction and ICD or CRT-D. Of the 390 patients who were implanted with an ICD or CRT-D between 1998 and 2015, 222(178 men, 44 women)with a low ejection fraction(EF; <45%)were investigated in this present study. The study cohort was divided into two groups, the CR group(n=70)and the non-CR group (n=152), and baseline clinical characteristics of the two groups were compared. Furthermore, the number of all device therapies, appropriate therapies, inappropriate therapies, and mortality for 1 year after ICD or CRT-D implantation were compared. There were no significant differences in baseline characteristics between the CR and non-CR groups(e.g. age 68.5 vs 66.2 years[P=0.16]; EF 27.9% vs 29.7%[P=0.14]). Kaplan-Meier analysis revealed that all device therapy events and inappropriate therapy events were lower in the CR than non-CR group(P=0.01 and P=0.03, respectively). Appropriate therapy events and mortality did not differ significantly between the two groups(5.7% vs 13.1%[P=0.09]and 11.4% vs 17.0%[P=0.28], respectively). CR may have beneficial effects in preventing therapy events, especially inappropriate therapy, in patients with an ICD or CRT-D.

View full abstract

Cardiac resynchronization therapy (CRT) is a well-established, efficient strategy for medically-refractory congestive heart failure (HF) with ventricular conduction disturbances. However, about 30% of patients who undergo CRT do not receive any benefit. Therefore, we investigated the usefulness of the QRS-left ventricle (LV) interval for predicting responders during CRT implantation. This study included 66 patients who underwent CRT implantation. The definition of responder was a ≥15% reduction in LV end-systolic volume or ≥20% increase in LV ejection fraction. The QRS-LV interval was measured from the beginning of the body surface electrocardiogram QRS complex to the LV potential recorded by LV leads. We analyzed the correlations between the QRS-LV intervals and CRT responders, admission for HF and mortality. The patients were 67±12 years old, and their mean LV ejection fraction was 26.3%±8.3%. During follow-up (27.2±19.9 months), 27 patients were admitted for HF (40.1%), and 17 died (25.7%); the median QRS-LV interval was 103±33 msec. Patients were divided into 2 groups: wide QRS-LV (>103 msec), and narrow QRS-LV (<103 msec). The wide QRS-LV group had a lower mortality rate than the narrow QRS-LV group (77% vs. 53%, P<0.05). In patients with dilated cardiomyopathy, the QRS-LV interval was significantly wider in responders, compared to non-responders (112±9.2 vs. 80.0±10 msec, P<0.05). The QRS-LV interval did not correlate with CRT responders or admission for HF. The mortality rate was lower in patients with wide QRS-LV intervals, compared to narrow QRS-LV intervals. Furthermore, a wide QRS-LV interval might be a predictor for CRT responders in patients with dilated cardiomyopathy.

View full abstract

Noninvasive methods for predicting the recurrence of atrial fibrillation (AF) after initial pulmonary vein isolation (PVI) have not been well described. The aim of the present study was to evaluate the usefulness of the P-wave signal-averaged electrocardiogram (P-SAECG) in predicting the recurrence of AF after initial PVI. The P-SAECG was recorded before and after (within 1 week) the initial PVI session. The filtered P-wave duration (FPD) and root mean square voltage of the last 20ms of the filtered P-wave (LP20) were measured in 87 consecutive idiopathic AF patients (ejection fraction ≥50%, B-type natriuretic peptide ≤200pg/ml). During the follow-up period (12±7 months), 22 of 87 (25%) patients had recurrence of AF (11 with paroxysmal AF and 11 with persistent AF). In the group with recurrence of paroxysmal AF, the post-PVI FPD was significantly shorter and the post-PVI LP20 was significantly larger than in the non-recurrence group. Furthermore, the post-PVI LP20/FPD ratio was significantly higher in the group with paroxysmal AF recurrence than in the non-recurrence group (0.024±0.009 vs 0.015±0.007µV/ms, respectively; P<0.05). Recurrence of paroxysmal AF was more frequently observed in patients with a post-PVI LP20/FPD >0.015µV/ms than in those with a post-PVI LP20/FPD ≤0.015µV/ms. The optimal post-PVI LP20/FPD cut-off value of 0.015µV/ms had a sensitivity of 90% and a specificity of 60%. The data also suggest that the post-PVI LP20/FPD may be a new parameter for predicting successful PVI in patients with idiopathic paroxysmal AF after PVI.

View full abstract

The risk of cardiogenic cerebral infarction is quantified by the CHA2DS2-VASc score in patients with atrial fibrillation, with female gender shown to be one of the risk factors. However, the relationships between gender and blood coagulation markers have not been investigated. Thus, the aim of the present study was to investigate relationships between gender and the coagulation and fibrinolysis systems. In the present study, 1025 patients(517 females[F group], 508 males[M group])who visited the outpatient clinic and had markers of the fibrinolytic and coagulation systems measured at the Division of Cardiology of Showa University Hospital from June 2011 to June 2014 were evaluated retrospectively. Thrombomodulin(TM), prothrombin fragment 1+2(PTF 1+2), thrombin-antithrombin complex(TAT), plasmin-α₂-plasmin inhibitor complex(PIC), and D-dimer levels were analyzed. Furthermore, patients without diabetes mellitus and vascular disease were divided into two groups according to age: a younger(Y)group(<75 years)and an elderly(E)group(≥75 years). In the Y group, TM levels were significantly lower in the F than M group(P<0.0001), but in the E group there was no significant difference in TM levels between these two groups. PTF 1+2 levels were significantly higher in the F group for each age group(Y group, P=0.0426; E group, P=0.0214). In the Y group, PIC levels were significantly higher in the F than M group(P=0.0015), but there was no difference in PIC levels between the F and M groups in the E group. Thus, in the F group, vascular endothelial dysfunction progressed in the E group. These observations suggest that the coagulation system is relatively accelerated, without any acceleration in the fibrinolytic system, in the F group with aging. The present study has shown that, in outpatients of a cardiovascular department, gender is a significant factor affecting blood coagulation systems.

View full abstract

Carbapenemase-producing Enterobacteriaceae (CPE) have been reported worldwide, but the types of carbapenemase vary between countries. Metallo-beta-lactamase (MBL) IMP (bla_IMP) is the most common type of carbapenemase in Japan. CPE outbreaks occurred in our hospital's neonatal intensive care unit (NICU) between October 2014 and October 2015. The aim of this study was to evaluate the results of active surveillance and to establish more effective CPE detection methods. We also investigated the molecular epidemiological characteristics of CPE in Japan. During the outbreak period, active surveillance was performed on a weekly basis by analyzing fecal cultures from all patients admitted to the NICU. Between January 2014 and December 2015, which included the outbreak period described above, Enterobacteriaceae strains isolated by fecal culture or from clinical specimens were analyzed by antimicrobial susceptibility testing and double-disc synergy testing (DDST) using ceftazidime or imipenem with sodium mercaptoacetic acid, polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE), and conjugal transfer experiments. During the outbreak period we analyzed 1073 isolates detected by fecal culture from 285 patients. Of these, we detected 64 bla_IMP-producing Enterobacteriaceae from 52 patients, all of whom were asymptomatic carriers (52/285, 18.2%). Klebsiella pneumoniae (33/64 strains, 51.6%) and Enterobacter cloacae (20/64 strains, 31.3%) were the predominant species. Of the 64 bla_IMP-producing Enterobacteriaceae, 7 strains were susceptible to imipenem and meropenem. Active surveillance by fecal culturing and DDST of carbapenem-resistant and third-generation cephalosporin-resistant pathogens may be an effective strategy for identifying CPE carriers. Therefore, this strategy may contribute to infection control and prevent further spread of disease in healthcare settings.

View full abstract

A significant genetic component is involved in the development of the craniofacial form. Recently, the growth hormone receptor gene (GHR) variants rs6180 and rs6184 were associated with variations in mandibular form. To confirm these findings we evaluated the relationship between these GHR variants and mandibular form in a cohort of Egyptian individuals with a normal skull form. The patients consisted of 191 unrelated Egyptian adults (92 males, 99 females; 18-55 years). Allele frequencies of the rs6180 and rs6184 variants were determined from genomic DNA extracted from saliva using the Taqman genotyping assay. Lateral and posteroanterior cephalometric tracings were used to obtain 19 mandibular measurements. The association between the GHR variants and the mandibular measurements was examined using regression analysis. The frequency of the minor rs6184 variant was very low at 1.5%: therefore, association studies were not performed for this variant. The rs6180 variant was not associated with any of the measurements representing mandibular form in our study cohort. The frequency of the rs6184 variant was very low in our cohort of Egyptian subjects. We also found no association between the rs6180 variant and the measurements representing the mandibular form. By excluding the involvement of these GHR variants in influencing mandibular form, our results may help to identify the actual variant(s) affecting the mandibular form in the Egyptian population.

View full abstract

The therapeutic effect found histologically after surgery following neoadjuvant chemotherapy (NAC) correlates with patient prognosis. Such correlations must consider the remaining invasive lesions as well as intra-ductal components and lymph node metastasis. To this end, we compared the residual cancer burden (RCB) index with the conventional method of judging the histopathological therapeutic effect. We also took into account the clinicopathological features of patients related to recurrence and prognosis by the RCB index. We studied 244 cases of primary breast cancer in 238 patients who had undergone surgery after NAC in Showa University Hospital from 2005 to 2014. We classified the cases into groups based on the Japanese Breast Cancer Society's criteria for evaluating the histological therapeutic effect and the RCB index. The cases were also analyzed in regard to various clinicopathological factors. The prognosis was evaluated by drawing recurrence-free survival curves using the Kaplan-Meier method, and the log rank test was used to test statistical significance. The RCB index was evaluated for cases of Grade 0–1b that had a certain degree of residual tumor tissue. Comparison of the recurrence-free survival rates in each of the RCB index groups indicated a significant correlation, although only for patients with some degree of residual malignancy even after chemotherapy. We conclude that the RCB index can be used for providing a more precise prediction of recurrence.

View full abstract

The effectiveness of botulinum toxin type A(BoNT-A)therapy for reducing muscle spasticity has been reported. We examined changes in the plantar contact area and plantar pressure after BoNT-A injection therapy in stroke patients with spastic hemiparesis. The study participants were 12 male hemiparetic stroke patients treated in our outpatient clinic(right hemiparesis, 7; left, 5), who were able to walk without orthoses. They were requested to walk barefoot at their normal walking speed on a sheet with pressure measurement sensors, before, and at one and three months after BoNT-A therapy. Simultaneously the maximum plantar pressures and maximum plantar contact areas of both feet during the standing phase of walking were analyzed using a pressure distribution measuring system. The ratios of the measured values for the affected side to that of the unaffected side were calculated. The mean ratio of the maximum plantar pressure of the affected/unaffected limb on standing changed from 61.5%±12.4% to 75.0%±9.5% at one month, and 61.2%±7.3% at three months after BoNT-A therapy. The mean maximum plantar contact area ratios also changed from 75.3%±11.7% to 87.9%±8.7% at one month and 77.8%±8.8% at three months. For both parameters, the ratios were significantly increased at one month after BoNT-A, compared to the other time points(P<0.01). These results suggest that BoNT-A therapy reduces muscle spasticity of the lower limbs, which improves the range of motion of the ankle joints, leading to improved plantar contact during the standing phase of walking. This pressure measurement system may be useful for assessing the effectiveness of BoNT-A therapy.

View full abstract