Prevalence and correlates of carotid atherosclerosis among elderly Japanese men

We determined intima-media thickness (IMT) and diameter of carotid artery and estimated their correlations with cardiovascular risk factors in 1129 men aged 60-74 years, who participated in a cardiovascular risk survey in three Japanese communities. The multivariate odds ratios (95% confidence interval) for the maximum IMT > or = 1.1 mm in the common carotid artery (CCA) were 1.3 (1.1-1.5) per 4 years of age, 1.8 (1.4-2.5) for hypertension, 1.4 (1.2-1.7) for a 34.4 mg/dl increase in serum total cholesterol, 0.7 (0.6-0.8) for a 14.7 mg/dl increase in serum HDL-cholesterol, and 2.4 (1.1-5.0) for history of stroke, while the maximum IMT > or = 1.5mm in the internal carotid artery (ICA) were 1.6 (1.4-1.8) per 4 years of age, 1.9 (1.5-2.4) for hypertension, 1.6 (1.2-2.1) for current smoking, and 3.5 (1.6-7.6) for history of stroke. Age, height, hypertension, current smoking, ethanol intake and history of coronary heart disease were independent determinants of both the outer and inner CCA diameter. Maximum IMT correlated positively with the outer diameter and inversely with the inner diameter in the CCA. Carotid atherosclerosis suggests to be a risk factor for stroke among Japanese elderly men, although future prospective studies are required to confirm this finding.     

Detailed glomerular ultrastructure in Japanese type 2 diabetic patients by the quick-freezing and deep-etching method

Mesangial expansion and glomerular basement membrane (GBM) thickening did not correlate with urinary albumin excretion (UAE) in type 2 diabetic patients in our previous studies; therefore, it was necessary to elucidate more detailed ultrastructural changes in the early stages of diabetic nephropathy (DN) in type 2 diabetic patients. The quick-freezing and deep-etching (QF–DE) method allows us to examine three-dimensional ultrastructures of human renal glomeruli in vivo at high resolution. The QF–DE method was applied to six type 2 diabetic patients without definable renal diseases other than DN. Four patients were normoalbuminuric (NA) and the other two were microalbuminuria (MA). Three control specimens were the normal parts from nephrectomies due to renal cell carcinomas. Electron microscopic morphometric analyses provided quantitative glomerular structural changes. Replica membranes were prepared by the QF–DE method, and diameters of mesh structures at the GBM and mesangial matrix (MM) were measured on electron micrographs as previously described. By the QF–DE method, both the GBM middle layer and MM were composed of polygonal meshwork structures. The mesh pores of the GBM and MM were more enlarged and irregular in shape in NA diabetic patients than those of the controls, and these ultrastructural changes became more obvious in MA patients. The mesh diameters of the GBM and MM in the diabetic patients were also larger than those of the controls. Such a mesh diameter of the GBM was well correlated with the amount of UAE, while the mesh diameter of MM showed a slight correlation with UAE. Although there were small number of subjects in the present study, the detailed ultrastructural changes in NA and MA type 2 diabetic patients, which had not been disclosed by conventional electron microscopy, were revealed by the QF–DE method. Increased mesh diameters of GBM might be related with the increase of UAE.     

Fos plays no role in apoptosis of epithelia in the mouse male accessory sex organs and uterus

Roles of Fos in apoptosis of epithelia in the mouse male accessory sex organs and uterus were investigated using Fos-deficient mice. Normal 30- and 50-day-old and Fos-deficient 50-day-old male and female mice were castrated, and testosterone propionate and estradiol-17 beta were daily injected into male and female mice, respectively, for 5 days. An apoptotic index (a percentage of apoptotic cells) in the epithelium was examined from the day following the last injection (day 1) to day 8. The body weights and the weights of the ventral prostate (VP), coagulating gland (C), seminal vesicle (SV) and epididymis (Ep) and uterus of 50-day-castrated Fos-deficient mice on day 1 suggested that the development of these mice corresponded to that of 30-day-castrated normal mice at the most. The extents of apoptosis estimated by an apoptotic index in the VP, C, SV, Ep and uterus in 50-day-castrated Fos-deficient mice were comparable to those in 30-day-castrated normal mice. The extents of apoptosis in the SV, Ep and uterus in 30-day-castrated normal and 50-day-castrated Fos-deficient mice were similar to those in 50-day-castrated normal mice, while the extents of apoptosis in the VP and C in the former two groups of mice were less than those in the latter mice. The present results show that Fos-deficiency does not affect apoptosis in the SV, EP and uterus. However, the extents of apoptosis in the VP and C were less in 50-day-castrated Fos-deficient mice than in 50-day-castrated normal mice. This seems to be due to the retarded development of 50-day-castrated Fos-deficient mice, but not to a role of Fos in apoptosis.     

Comparison of the antidiabetic effects of linagliptin among groups with a normal renal function and a mild or severe renal impairment – retrospective observation study of Japanese patients with type 2 diabetes mellitus

Objective: The clinical course > 6 months after the initiation of linagliptin in patients with type 2 diabetes was compared among the groups divided by their renal function.

Methods: Two hundred and sixteen Japanese patients with type 2 diabetes treated with 5 mg once daily linagliptin were studied as the treated set. One hundred and forty-five subjects whose medications were not changed during the observation period were investigated as the full analysis set to assess the effectiveness. The subjects were divided into three groups based on an eGFR: eGFR ≥ 60, 59 – 45 and < 45 ml/min/1.73 m². The parameters were analyzed separately in the patients receiving monotherapy and additional therapy of linagliptin.

Results: The HbA1c (NGSP) levels significantly improved in both the patients receiving monotherapy and additional therapy. The changes in the HbA1c levels at 6 months were not significantly different between the groups with an eGFR ≥ 60, 59 – 45 and < 45 ml/min/1.73 m² receiving monotherapy (?1.0, ?0.8 and ?0.8%, respectively). Similarly, those were not significantly different between the different groups receiving additional therapy (?0.6, ?0.5 and ?0.7%, respectively).

Conclusions: Linagliptin is considered to be effective for patients with type 2 diabetes and renal impairment in the present analysis performed at our institution.     

Clinicopathologic features and prognostic factors of resected solitary small-sized hepatocellular carcinoma

BACKGROUND/AIMS: Solitary small-sized HCCs tend to be considered as less aggressive cancer, and non-surgical treatments have recently been preferred. The aim of this study was to clarify the clinicopathological features and the prognostic factors of small-sized HCCs and to evaluate the significance of hepatic resection for them. METHODOLOGY: Eighty patients with HCC up to 2cm in diameter who had undergone hepatic resection were enrolled in this study. We investigated the clinicopathological features and evaluated the prognostic factors by univariate and multivariate analyses. RESULTS: The overall survival rates at 3, 5 and 10 years were 83%, 69% and 36%, respectively, and the corresponding disease-free survival rates were 63%, 41% and 10%. Well-differentiated, moderately differentiated and poorly differentiated HCC were detected in 29%, 65% and 6% of the patients, respectively. Furthermore, microscopic portal vein invasion (vp), hepatic vein invasion (vv) and intrahepatic metastasis (im) were positive in 15%, 4% and 10% of the patients, respectively. Multivariate analysis revealed that Child-Pugh classification (p=0.005) and vp (p=0.0008) were independent prognostic factors for survival rate and that platelet count (p=0.002) and tumor differentiation (p=0.0016) were independent prognostic factors for disease-free survival rate. CONCLUSIONS: Even solitary small-sized (up to 2cm in diameter) HCC already have the characteristics of advanced HCC. When hepatic function is well preserved, hepatic resection should be the first choice for local control, especially in cases of moderately to poorly differentiated HCC, because the frequency of microscopic vascular invasion is high.     

A case of pulmonary hypertrophic osteoarthropathy associated with primary lung cancer in a young adult successfully treated with gefitinib]

The patient was a 39-year-old woman admitted with complaints of fever, clubbed fingers and arthralgia. A chest roentgenogram and chest computed tomographic scan revealed a mass in the left lower lobe. Transbronchial lung biopsy was performed, and a diagnosis of moderately differentiated adenocarcinoma was made. Physical examination confirmed finger clubbing in both hands. Bone scintigram showed marked accumulation of 99mTc-MDP in the long bones, bones of the elbows, and patellae. These findings yielded a diagnosis of pulmonary hypertrophic osteoarthropathy associated with primary lung cancer in young adult. The patient had fever and disturbance of gait of arthralgia on admission, and was treated with an oral non-steroidal anti-inflammation drug (NSAID). Advanced non small cell lung cancer (clinical stage T2 N3 M1, Stage IV) was then diagnosed. Gefitinib was administered after EGFR mutation was found in the tumor specimen. NSAID therapy alleviated the fever and arthralgia. After starting gefitinib and discontinuing the NSAID, She had kept a remission of rational symptom with cytoreductive effect. The abnormal findings of bone scintigrams subsequently disappeared and the patient's serum ICTP dropped.     

Successful catheter ablation of left ventricular epicardial tachycardia originating from the great cardiac vein: a case report and review of the literature.

A patient underwent radiofrequency (RF) catheter ablation for a drug-refractory ventricular tachycardia, but RF energy application at an endocardial site of the left ventricular outflow tract and at the left sinus of Valsalva could not eliminate the tachycardia. The earliest ventricular activation during the arrhythmia, which preceded the onset of the QRS complex by 32 ms, was found within the great cardiac vein and complete elimination of the tachycardia was finally achieved with RF application at that site.     

Role of electrophysiologic study (EPS)-guided preventive therapy for the management of ventricular tachyarrhythmias in patients with heart failure.

BACKGROUND: Ventricular tachyarrhythmias (VT/VF) are 1 of the most important factors determining the prognosis of patients with heart failure (HF). Although priority is given to implantable cardioverter defibrillator (ICD) therapy for the prevention of sudden cardiac death, electrophysiologic-study (EPS)-guided preventive therapy could be important for reducing the number of cardiac events. METHODS AND RESULTS: Of 864 patients with a history of HF, an EPS was performed in 168 and 121 had inducible VT/VF. Under the basic therapy of an ICD, additional catheter ablation was attempted for 95 of 124 monomorphic VT foci in 74 patients, and 78 of the VT were successfully ablated. The prognoses were compared among 5 patient groups with different results for the EPS and catheter ablation: (1) success group (n=43), (2) failure group (n=15), (3) not attempted group (n=16), (4) VF group (n=47), and (5) no inducible VT/VF group. During a follow-up period of 31+/-22 months, the incidence of VT/VF was lower in the success and no inducible VT/VF groups than in the other groups (p=0.0018), although a significant difference was not observed for the total deaths. CONCLUSION: EPS-guided preventive therapy using an ICD and catheter ablation can be useful, at least for the reduction of arrhythmic events in patients with HF.     

Splenectomy-reduced hepatic injury induced by ischemia/reperfusion in the rat

Abstract: In the present study, we investigated the role of the spleen in experimental hepatic ischemia/reperfusion in the rat. After a 90-min period of ischemia in the left and middle hepatic lobes, the ischemia was released and the liver was reperfused for up to 24 h. Plasma alanine aminotransferase reached a peak 3 h after the onset of reperfusion, and gradually decreased thereafter. A histological examination revealed evidence of hepatocellular necrosis and degeneration, especially 24 h after the onset of reperfusion. In addition, there was a noticeable accumulation of polymorphonuclear cells in the liver following ischemia/reperfusion. A splenectomy performed just prior to ischemia/reperfusion reduced both biochemical and histological hepatocellular injury. The number of polymorphonuclear cells in the liver following ischemia/reperfusion was significantly reduced in rats subjected to splenectomy, suggesting that the increase in polymorphonuclear cells may contribute to liver injury. The number of mononuclear cells also increased in the marginal zones of the spleen following ischemia/reperfusion, and appeared to be derived from the splenic monocyte/macrophage population, based on immunohistochemical studies. The spleen plays an important role in the pathogenesis of hepatic ischemia/reperfusion injury and the splenic monocyte/macrophage population contributes to liver damage.