Feasibility of Epicardial Adipose Tissue Quantification Using Non-electrocardiogram-Gated Chest Computed Tomography Images.

OBJECTIVE: Epicardial adipose tissue (EAT) is an important imaging indicator of cardiovascular risk. EAT volume is usually measured using electrocardiogram (ECG) gating. However, there are concerns regarding the influence of motion artifacts when measuring EAT volume on non-ECG-gated plain chest computed tomography (CT) images. Few studies have evaluated the EAT volume using non-ECG gating. This study aimed to validate the accuracy of EAT quantification using non-ECG-gated chest CT imaging. METHODS: We included 100 patients (64 males, 36 females) who underwent simultaneous coronary artery calcification score imaging (ECG gated) and plain chest CT imaging (non-ECG gated). Images taken using non-ECG gating were reconstructed using the same field of view and slice thickness as those obtained with ECG gating. The EAT capacity of each image was measured and compared. An AZE Virtual Place (Canon) was used for the measurements. The Mann-Whitney U test and intraclass correlation coefficient were used for statistical analyses. P values <0.05 were considered statistically significant. Concordance was evaluated using Bland-Altman analysis. RESULTS: The mean EAT volume measured by ECG-gated imaging was 156.5 ± 66.9 mL and 155.4 ± 67.9 mL by non-ECG-gated imaging, with no significant difference between the two groups ( P = 0.86). Furthermore, the EAT volumes measured using ECG-gated and non-ECG-gated imaging showed a strong correlation ( r = 0.95, P < 0.05). Bland-Altman analysis revealed that the mean error of the EAT volume (non-ECG-gated imaging - ECG-gated imaging) was -1.02 ± 2.95 mL (95% confidence interval, -6.49 to 4.76). CONCLUSIONS: The EAT volume obtained using non-ECG-gated imaging was equivalent to that obtained using ECG-gated imaging.

Coronary artery calcification score and common iliac artery calcification score in non-dialysis CKD patients.

AIM: Many studies have validated Agatston's coronary artery calcification score (CACS) for assessing vascular calcification (VC) in chronic kidney disease (CKD) patients. This study aimed to evaluate the CACS and common iliac artery calcification score (IACS) and to examine the variables related to each score. METHODS: The subjects were 145 non-dialysis CKD patients. The CACS and IACS were determined using the same thoracicoabdominal multi-detector computed tomography. Multiple regression analyses were performed to assess the factors associated with the CACS or IACS. The associations between progression to renal replacement therapy (RRT) and the CACS or IACS were studied using Cox hazards models. RESULTS: The subjects' median age, estimated glomerular filtration rate (eGFR), and follow-up period were 72 (62-78) years, 32 (18-50) mL/min/1.73m2 , and 864 (550-1425) days, respectively. Age, diabetes, the serum phosphate level, and the eGFR were found to be significant factors of the CACS [ß (95% CI): 0.38 (0.02-0.04), P < 0.0001, 0.28 (0.19-0.50), P < 0.0001, 0.16 (0.03-0.45), P < 0.05 and -0.15 (-0.02-0.00), P < 0.05, respectively]. Age and diabetes were shown to be significant factors of the IACS [ß (95% CI): 0.53 (0.04-0.06), P < 0.0001, and 0.18 (0.07-0.40), P < 0.01, respectively]. Progression to RRT occurred in 31 patients and was significantly associated with the CACS (hazard ratio: 1.01, P < 0.01), urinary protein level and eGFR, but not the IACS. CONCLUSION: Chronic kidney disease related risk factors for VC, such as the eGFR and hyperphosphataemia, are significantly associated with a high CACS, but not a high IACS, and the CACS is a significant predictor of progression to RRT.

Disseminated Nontuberculous Mycobacterial Infection in a Patient with Anti-IFN-γ Autoantibodies.

We treated a 72-year-old Japanese female with sustained high fever and overall body exhaustion. An infectious liver cyst and right lung pneumonia were suspected causes. Hepatic cystectomy and various antibiotics did not resolve symptoms. Pneumonia exacerbation and ascitic fluid retention, left lumbar spinal osteomyelitis, and peri-gastric lymph node abscess penetrating the stomach were observed. Mycobacterium avium was identified in sputum, ascites, vertebral body abscess puncture specimen, and pus mucus secretion in the stomach. We diagnosed a disseminated nontuberculous mycobacterial infection. She seemed immunocompetent, without signs of AIDS or hematological malignancy. Serum anti-IFN-γ autoantibodies tested positive and were suspected to be involved in the illness onset.

[A case in which dihydropyrimidine dehydrogenase deficiency was strongly suspected during adjuvant chemotherapy with capecitabine for colon cancer].

Severe toxicity in patients with a deficiency of dihydropyrimidine dehydrogenase(DPD), an enzyme that reduces fluoropyrimidine, is very rare, and reports on this condition are few. Accordingly, diagnosis is very difficult. The patient was 70-year-old man who was admitted for adjuvant chemotherapy with capecitabine(3,600mg/day)for rectal cancer. He was admitted to our hospital because of severe oral mucositis(grade 3)and hand-foot syndrome(grade 3). After hospitalization, he experienced complications with neutropenia(grade 4)and thrombocytopenia(grade 4). The patient died 25 days after the onset of chemotherapy. Despite the measurement of the DPD value in mononuclear cells of peripheral blood and urophanic uracil and dihydrouracil, we were unable to diagnose DPD deficiency. However, we suspected a partial deficiency of DPD on the basis of the clinical course.

[A case of primary adenocarcinoma of small intestine responding to XELOX chemotherapy and leading to a partial metabolic response].

We report a case of adenocarcinoma of the small intestine responding to XELOX chemotherapy, leading to a partial metabolic response(PMR). The patient was a 58-year-old male with multiple peritoneal dissemination of adenocarcinoma of the small intestine. Chemotherapy with XELOX(L-OHP 130 mg/m² on day 1 , and capecitabine 1,000 mg/m2 on days 1-14)was performed. After 4 courses, a significant tumor reduction was obtained. This case suggests that chemotherapy with XELOX is a potential regimen for small intestinal adenocarcinoma.

The impact of donor age on the outcome of adult living donor liver transplantation.

BACKGROUND: The negative effects of increased donor age on liver transplantation became evident in deceased donor liver transplantation. In living donor liver transplantation (LDLT), the details remain unclear. METHODS: Initially, 137 adult LDLT recipients from August 1996 to May 2005 were divided into two groups (donors <50 years of age: n=99, donors >or= 50 years of age: n=38) for the retrospective study. Then, 24 recipients who received LDLT from June 2005 to July 2006 were divided into two groups: group 1 (donors <50 years of age, n=14) and group 2 (donors >or= 50 years of age, n=10) and enrolled in the prospective study to analyze their clinical course and prognostic factors in the aged graft. RESULTS: In the retrospective study, the younger donor group had significantly better survival than that of the aged donor group (P=0.015, Log rank test). In the prospective study, the postoperative graft functions showed that the serum total bilirubin levels were significantly lower in group 1 (P<0.02, by ANOVA analysis). The phosphorylated-Signal Transducer and Activator of Transcription3 expression at 4 hr after reperfusion (RT2) in group 2 was significantly lower than that in group 1. At RT2, the expressions were up-regulated in group 1, but were down-regulated in group 2. The serum 8-hydroxydeoxyguanosine value became significantly higher in group 1 two weeks after LDLT. CONCLUSIONS: In the near term, Signal Transducer and Activator of Transcription3 gene induction during cold preservation may be of great use in improving the outcome of aged grafts in LDLT.

Beta2-adrenergic receptor stimulation inhibits LPS-induced IL-18 and IL-12 production in monocytes.

We examined the effects of beta2-adrenergic receptor (beta2-AR) agonists on monocyte-derived cytokines, interleukin (IL)-18 and IL-12 production in lipopolysaccharide (LPS)-stimulated monocytes derived from human peripheral blood mononuclear cells (PBMCs), as in vitro model of sepsis. The study found that beta2-AR agonists inhibited IL-18 and IL-12 production in monocytes, and that AR agonist activity was antagonized by the selective beta2-AR antagonist, butoxamine. The selective beta2-AR agonists salbutamol and terbutaline induced a similar inhibitory pattern of IL-18 and IL-12 production. IL-12 production induced by LPS was inhibited by anti-IL-18 Ab, but IL-18 production by LPS was not inhibited by anti-IL-12 Ab, showing that LPS induced IL-18 production without IL-12 production. Therefore, the stimulation of beta2-AR might be beneficial in the treatment of sepsis through inhibiting LPS-elicited IL-18.

High blood pressure, bone-mineral loss and insulin resistance in women.

Increasing evidence indicates that high blood pressure is associated with abnormalities in calcium metabolism. Sustained calcium loss may lead to increased bone-mineral loss in subjects with elevated blood pressure. Furthermore, recent findings indicate a possible linkage between abnormal calcium metabolism and insulin resistance. In the present study, we investigated the relationship(s) among bone-mineral density (BMD), blood pressure, calcium-related and bone metabolic parameters (plasma intact parathyroid hormone (I-PTH), 1,25-dihydroxyvitamin D [1,25(OH)2D], osteocalcin, and urinary deoxypyridinoline), and insulin resistance, as assessed by a conventional homeostasis model (HOMA-R). We compared non-diabetic women with essential hypertension (WHT, n=34) with age-, body mass index- and menopause (yes or no)-matched normotensive, non-diabetic women (WNT, n=34). The BMD for WHT was significantly lower than that for WNT (0.596+/-0.019 vs. 0.666+/-0.024 g/cm2, p<0.05). The BMD was correlated inversely with systolic blood pressure in all subjects examined (r=-0.385, p<0.05). The 24-h urinary calcium/sodium excretion ratio (Ux-Ca/Na) was significantly greater in WHT compared with WNT (p<0.01). In addition, a negative relationship was apparent between Ux-Ca/Na and BMD (r=-0.58, p<0.05). The plasma levels of PTH and 1,25(OH)2D, and HOMA-R were significantly higher in WHT compared with WNT (p<0.01, p<0.05, and p<0.05, respectively), whereas the serum ionized calcium was lower in WHT compared with WNT (p<0.05). There were no significant differences in serum total calcium, inorganic phosphorus, osteocalcin, or urinary deoxypyridinoline between the two groups. These results indicate that high blood pressure is associated with abnormalities in calcium metabolism and insulin resistance in WHT.

Preservation of arterial arcades during duodenum-preserving total pancreatic head resection for intraductal papillary tumor.

Duodenum-preserving pancreatic head resection with preservation of the bile duct or without, has been performed in cases of benign or low-grade malignancies, such as intraductal papillary tumors, of the head of the pancreas. However, the selection of the patients, the area of resection in the head of the pancreas, and the operative procedures for the preservation of the pancreaticoduodenal vessels has not been realized among surgeons to apply duodenum-preserving pancreatic head resection as a radical treatment of intraductal papillary tumors. In our experience, duodenum-preserving pancreatic head resection can be applied in the majority of the patients with the branch type of intraductal papillary tumors, and it is necessary to resect completely the head of the pancreas to avoid tumor remnant and pancreatic fistula from the remaining pancreatic rim. Therefore, we modified it to include a total resection of the pancreatic head and the preservation of both anterior and posterior arterial arcades, due to the multiformity of the location of the tumor, the variation of the branch duct in the head of the pancreas, the closure of the minor papilla in some patients, and the unbalanced development of the arterial arcades of the pancreaticoduodenal region. We performed a duodenum-preserving total pancreatic head resection with preservation of the bile duct and the both anterior- and posterior-arterial arcades for 6 patients with the normal gland involving intraductal papillary tumors. The blood flow in this organ was based on the blood supply from both preserved arterial arcades, and the duodenum had retained good color, and the postoperative results were satisfactory.

Monitoring hepatic venous hemoglobin oxygen saturation during Appleby operation for pancreatic cancer.

BACKGROUND/AIMS: When an Appleby operation is performed for pancreatic body and tail carcinoma, it is necessary for prevention of hepatic ischemia to estimate accurately the hepatic circulation after resection of the celiac artery, the common hepatic artery and the portal vein. We studied the hepatic circulation by monitoring the ShvO2 (hepatic venous hemoglobin oxygen saturation) during an Appleby operation. METHODOLOGY: We performed an Appleby operation on 8 patients with pancreatic cancer. In 6 of 8 patients, a 7-Fr fiberoptic flow direct catheter was inserted in the right hepatic vein. The ShvO2 values were monitored continuously during surgery. RESULTS: The ShvO2 value was 76 +/- 3.5% just after laparotomy, and reduced to 61 +/- 13.2% after clamping the common hepatic artery. The values of the ShvO2 returned to 70.8 +/- 10.9% one hour after clamping. But, one patient underwent reconstruction of the common hepatic artery, because the ShvO2 value still stood at 50%. Combined resection of the portal vein was performed in 5 out of 8 patients. Two patients underwent resection of the portal vein without reconstruction due to the development of the collateral vein, one patients; resection of the portal vein with reconstruction, and two patients; wedge resection. In all 5 patients, the ShvO2 was stable during resection of the portal vein. CONCLUSIONS: Monitoring the ShvO2 is a useful method to evaluate at real time the hepatic circulation during the Appleby operation, and to decide if reconstruction of the common hepatic artery or the portal vein is needed or not.

Suppression of advanced glycation and lipoxidation end products by angiotensin II type-1 receptor blocker candesartan in type 2 diabetic patients with essential hypertension.

OBJECTIVE: This study investigated whether the angiotensin II type-1 receptor blocker (ARB) candesartan affects markers of oxidative stress in type 2 diabetes mellitus (DM) patients with essential hypertension (EH). METHODS: Urinary excretion of pyrraline (PR), pentosidine (PT), acrolein (AC), and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and microalbuminuria were assessed in patients with DM complicated by EH who were treated with candesartan 4 mg/day for 3 months. RESULTS: In a total of 25 patients urinary excretion of PR (nmol/g · cr), PT (pmol/g · cr), and 8-OH-dG (ng/mg · cr) was significantly (all P < 0.05) decreased from (mean ± SEM) 11.9 ± 1.9, 30.6 ± 2.4, and 7.9 ± 0.6, respectively, at baseline to 8.4 ± 1.4, 27.1 ± 2.0, and 6.9 ± 0.6, respectively, at 3 months. Meanwhile, excretion of AC was unaltered from 209.6 ± 40.0 to 189 ± 24.8 nmol/mgcr (P = NS). Urinary albumin excretion was significantly (P < 0.05) reduced from 27.7 ± 4.6 to 14.1 ± 1.1 mg/g · cr. There were weak but statistically significant positive correlations between the change of urinary 8-OH-dG excretion and that of albumin (r = 0.414; P < 0.05) and change of hemoglobin (Hb) A1c (r = 0.45; P < 0.05). CONCLUSION: Candesartan exerts protective effect(s) on the cardiovascular system by suppression of oxidative stress--mainly through inhibiting production of advanced glycation end products (AGEs) rather than of advanced lipoxidation end products (ALEs)--in type 2 DM patients with EH.

Fluvastatin increases bone mineral density in postmenopausal women.

Although several studies have reported a lower risk of osteoporotic fracture in hypercholesterolemic patients (WHO IIa) treated with statin, longitudinal studies on the effects of statins on bone are lacking. The aim of the present study was to evaluate bone mineral density (BMD) and bone turnover changes induced by 3-year fluvastatin treatment in postmenopausal women. Twenty-eight consecutive postmenopausal non-diabetic, normotensive hypercholesterolemic women (64.0±3.6 years) were treated for 36 months with 30 mg/day fluvastatin and 28 non-diabetic, normotensive normocholesterolemic age- and body mass index-matched postmenopausal women served as the control subjects. The result revealed a significant increase of the BMD as compared with the level at the base line (p< 0.001) in the fluvastairn-treated group, from 6 months on ward after the start treatment. Significant differences of the BMD were found between the controls and fluvastatin-treated group (p< 0.001) were at 6, 12, 24 and 36 months after the start of the study. In conclusion our results, although obtained small sample of postmenopausal hypercholesterolemic women, suggest a probable favorable effect of fluvastatin on bone formation and BMD.

Preoperative assessment of the risk factors that help to predict the prognosis after living donor liver transplantation.

BACKGROUND: The purpose of this study was to analyze various risk factors and to assess the preoperative risk score, which can predict the prognosis after living donor liver transplantation (LDLT). METHODS: From February 2002 to August 2007, 84 adult to adult living donor liver transplantation donors and recipients were analyzed. First, the donor, recipient, and intraoperative factors were examined by univariate and multivariate analyses. We then gave a score of one point for each significant marginal factor (total point scores were called "risk score") and each risk score was examined by univariate analyses. RESULTS: Recipients with the donor age 50 years or older, Model for End-Stage Liver Disease (MELD) score (> or =21), and hepatitis C virus-positive status had a significantly poor survival. Recipients between the risk score of 0 vs. scores of 2 + 3 (p < 0.001, log-rank) and risk score of 1 vs. scores of 2 + 3 (p = 0.003, log-rank) had significantly different survival. CONCLUSIONS: Preoperative assessment of the risk score might help to predict recipient outcomes after living donor liver transplantation.

Effects of prophylactic splenic artery modulation on portal overperfusion and liver regeneration in small-for-size graft.

BACKGROUND: The small-for-size (SFS) syndrome is caused by excessive portal inflow into a small-sized liver graft. Various approaches for portal decompression have been used, but details of their impact on liver regeneration in SFS graft remain unclear. We examined the effect of prophylactic splenic artery modulation (SAM). METHODS: We conducted a retrospective cohort study. The study group was 39 consecutive adult-to-adult living liver transplantation recipients, with a graft-to-recipient body weight ratio of less than 0.8. Patients were assigned into the non-SAM group (n=18, without any portal inflow attenuation) or SAM group (n=21, preoperative embolization in 15 patients and intraoperative ligation in 6 patients). Hepatic hemodynamics, graft function, liver regeneration, and outcome were evaluated. RESULTS: In the SAM group, the excessive portal flow was significantly reduced (P<0.01) and the effect of embolization on portal decompression was equivalent to that of ligation. In the acute postoperative phase, serum transaminases, interleukin-6, and tumor necrosis factor-alpha, were lower in the SAM group than in non-SAM group. In both groups, a negative correlation was observed between graft-to-recipient body weight ratio and liver regeneration rate at 2 weeks after living donor liver transplantation. Splenic artery modulation was advantageous for liver regeneration, and significantly improved clinical features, hyperbilirubinemia, and prolonged ascites. Small-for-size syndrome occurred in five patients of the non-SAM group, and only one of SAM group (P=0.038). CONCLUSION: In SFS graft with severe portal hypertension, prophylactic splenic embolization/ligation seems to relieve portal overperfusion injury and contributes in improvement of posttransplantation prognosis through liver regeneration.

The immunosuppressive effects of ciprofloxacin during human mixed lymphocyte reaction.

Interleukin (IL)-18, which is elevated in the plasma during acute rejection after organ transplantation, is known to induce the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40 and CD40 ligand (CD40L) on monocytes, the production of interferon (IFN)-gamma and IL-12 and the proliferation of lymphocytes during the human mixed lymphocyte reaction (MLR). Ciprofloxacin (CIP), which is useful for the clinical treatment of infections due to its antibacterial properties after transplantation, was shown to suppress the IFN-gamma and IL-12 production, the lymphocyte proliferation and the ICAM-1, B7.1, B7.2 and CD40 expression on monocytes during MLR in the presence of IL-18. CIP also induced the production of prostaglandin (PG) E2. In order to determine whether the effects of CIP on the expression of the activation markers were due to CIP-dependent production of PGE2, we examined the effect of cyclooxygenase (COX)-2 and protein kinase A (PKA) inhibitors on the actions of CIP. Thereby, the inhibitors were found to abolish the actions of CIP. These results therefore suggest that CIP might exert its immune modulatory effects via the production of PGE2.

Nafamostat mesilate induces production of interleukin-12 and -18 in human peripheral blood mononuclear cells.

Little has been reported on the drugs inducing production of monocyte-derived cytokines like interleukin (IL)-18 and IL-12. We found that nafamostat mesilate elicits IL-12, IL-18, tumor necrosis factor-alpha and interferon-gamma production, and the expression of intercellular adhesion molecules-1, B7.1, B7.2, CD40, and CD40 ligand in human peripheral blood mononuclear cells. The cytokine production and adhesion molecule expression were abolished by anti-IL-12 and IL-18 antibodies. Therefore, IL-18 and IL-12 may play roles in the significant and immediate effects of nafamostat mesilate.

Effect of ciprofloxacin-induced prostaglandin E2 on interleukin-18-treated monocytes.

Ciprofloxacin, a fluorinated 4-quinolone, is useful for the clinical treatment of infections due to its antibacterial properties and also modulates the immune response of monocytes isolated from human peripheral blood mononuclear cells. In the present study, we found that ciprofloxacin induced the production of prostaglandin E(2) in monocytes in a concentration-dependent manner regardless of the presence of interleukin-18 by enhancing the expression of cyclooxygenase-2 protein and that this in turn led to the elevation of intercellular cyclic AMP in monocytes via the stimulation of prostaglandin receptors. The prostaglandin E(2) and cyclic AMP production increased by ciprofloxacin was inhibited by indomethacin, a nonselective cyclooxygenase-2 inhibitor, and NS398, a selective cyclooxygenase-2 inhibitor. In addition, ciprofloxacin suppressed the interleukin-18-induced production of tumor necrosis factor alpha, gamma interferon, and interleukin-12 in peripheral blood mononuclear cells by inhibiting the expression of intercellular adhesion molecule 1, B7.1, B7.2, and CD40 on monocytes, and this effect could be reversed by the addition of indomethacin or NS398. These results indicate that ciprofloxacin exerts immunomodulatory activity via the production of prostaglandin E(2) and imply therapeutic potential of ciprofloxacin for the treatment of systemic inflammatory responses initiated by interleukin-18.

Multiple endocrine disorders and Rathke's cleft cyst with Klinefelter's syndrome: a case report.

A 46-year-old Japanese male was admitted for the evaluation of severe hypertension. He was obese and had a eunuchoidal body habitus. Chromosomal analysis revealed a 46, XY/47, XXY karyotype. Serum LH, FSH and testosterone levels were low, indicating hypogonadotropic hypogonadism. Endocrinological dynamic tests disclosed presence of hypothalamic panhypopituitarism, partial diabetes insipidus, type 2 diabetes mellitus and low renin essential hypertension. Brain computed tomography and magnetic resonance imaging revealed intra- and extrasellar masses. Histological examination of the tissue obtained at transsphenoidal surgery showed a Rathke's cleft cyst (RCC). To the best of our knowledge, this is the first case report of mosaic Klinefelter's syndrome accompanied by symptomatic RCC, type 2 diabetes mellitus and low renin essential hypertension.