Expression of transcription factor in Barrett's esophagus

Barrett's esophagus is the result of chronic injury which is usually caused by gastroesophageal reflux. NF-kappaB is expressed in the reflux esophagitis. Specialized columnar epithelium (SCE) is characteristic of Barrett's esophagus and has a malignant predisposition. SCE expresses Cdx1 and Cdx2. Adenocarcinoma in Barrett's esophagus is believed to develop through the metaplasia-dysplasia-carcinoma sequence. P53, beta-catenin, PPARgamma, and estrogen receptor beta are closely related to the development of esophageal carcinogenesis.     

Non‐invasive three‐dimensional power Doppler imaging for the assessment of acute cerebral blood flow alteration in a mouse model of subarachnoid haemorrhage

We aimed to evaluate the feasibility of a non‐invasive method of cerebral blood flow (CBF) measurement using high‐frequency power Doppler ultrasound imaging in a mouse model of subarachnoid haemorrhage (SAH). The 3‐dimensionally (3D) reconstructed blood flow signals (%vascularity) within the brain volume of the middle cerebral artery territory correlated well with reference parameters, baseline carotid artery blood flow (r² = 0.52, P < 0.0001) and normalized CBF changes (r² = 0.74 P < 0.0001). These data suggest that the 3D power Doppler analysis may have the potential for reflecting real‐time CBF changes during the acute phase of experimental SAH, which may be applicable to preclinical studies on early brain injury.     

Endoscopic ultrasound with double-balloon endoscopy in the evaluation of small-bowel disease

Background

Double-balloon endoscopy (DBE) has become a new standard in enteroscopy. However, it may be difficult to make a diagnosis or plan treatment strategy with endoscopic visualization alone. The addition of endoscopic ultrasonography (EUS) has the potential to improve the ability to establish the diagnosis and develop a treatment strategy. The present study was conducted to assess the feasibility and usefulness of EUS with DBE.

Methods

EUS with DBE was performed in 31 of 891 patients who underwent DBE from July 2004 to March 2011 at Jichi Medical University Hospital. We analyzed the EUS findings for lesions and evaluated the usefulness of EUS considering the following three factors: qualitative diagnostic value for lesions, depth grading of lesions, and evaluation of the structure of severe strictures prior to endoscopic balloon dilation.

Results

EUS was performed for 31/32 lesions (97 %) in 31 patients. EUS findings were informative for 29/32 lesions (91 %). EUS findings were useful for establishing a qualitative diagnosis in 15/25 lesions (60 %). EUS findings for depth grading provided useful information for determining the therapeutic strategy in 11/13 lesions (85 %). EUS with DBE was useful in the evaluation of strictures for all six lesions (100 %). The overall usefulness of EUS with DBE on decision making was 72 % (23/32) in this study.

Conclusions

EUS with DBE is feasible and useful. It provides additional information on small-bowel disease and contributes to establishing a precise diagnosis and selection of an appropriate therapeutic strategy.     

Ameliorating effect of FK614, a novel nonthiazolidinedione peroxisome proliferator-activated receptor gamma agonist, on insulin resistance in Zucker fatty rat

Effect of 3-(2,4-dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3H-benzimidazole-5-carboxamide (FK614), a novel nonthiazolidinedione peroxisome proliferator-activated receptor (PPAR) gamma agonist, on glucose tolerance and insulin resistance in peripheral tissues and in liver using Zucker fatty rats (genetically obese and insulin-resistant) was evaluated and compared to other insulin sensitizers. FK614 (0.32, 1 and 3.2 mg/kg), two thiazolidinedione PPAR gamma agonists, rosiglitazone (0.1, 0.32, 1 and 3.2 mg/kg) and pioglitazone (1, 3.2 and 10 mg/kg), and a biguanide, metformin (320 and 1000 mg/kg), were orally administered to Zucker fatty rats once a day for 14 days. Zucker fatty rats treated with FK614 and rosiglitazone were subjected to evaluation by oral glucose tolerance test. Ameliorating effect of each compound on peripheral and hepatic insulin resistance was evaluated using a euglycemic-hyperinsulineamic clamp procedure. FK614 and rosiglitazone dose-dependently improved impaired glucose tolerance in Zucker fatty rats. In addition, FK614 dose-dependently ameliorated peripheral and hepatic insulin resistance in Zucker fatty rats, with the degree of its effect in peripheral tissues almost equivalent to that in liver when compared at each dose tested. Similar data indicating ameliorating effects on insulin resistance was obtained for rosiglitazone and pioglitazone. Metformin showed less potent effects than other insulin sensitizers and its effect in liver tended to be greater than that in peripheral tissues. These findings suggest clinical potential for FK614 as a treatment of type 2 diabetes, acting by ameliorating insulin resistance both in peripheral tissues and liver.     

Noninvasive flow evaluations of coronary artery bypass grafting using dynamic cardiac CT

We aimed to investigate the correlation of graft flow measurements between transit-time flow measurement (TTFM) during coronary artery bypass grafting (CABG) surgery and dynamic cardiac CT after the surgery.Fourteen patients underwent CABG with TTFM and postoperative dynamic cardiac CT; 11 internal thoracic artery (ITA) grafts and 15 saphenous venous grafts (SVGs) were included for analysis. Pearsons correlation analysis was performed for the comparisons of the TTFM and cardiac dynamic CT flow parameters.TTFM was not significantly correlated with the CT flow of the ITA grafts (r = −0.23, P = .49), but it had a very strong correlation with the CT flow of the SVGs (r = 0.83, P < .01).In patients who underwent CABG surgery, dynamic cardiac CT enabled quantitative evaluation of SVG flow, with good correlation with TTFM.     

The impact of body temperature abnormalities on the disease severity and outcome in patients with severe sepsis: an analysis from a multicenter,prospective survey of severe sepsis

Introduction

Abnormal body temperatures (T_b) are frequently seen in patients with severe sepsis. However, the relationship between T_b abnormalities and the severity of disease is not clear. This study investigated the impact of T_b on disease severity and outcomes in patients with severe sepsis.

Methods

We enrolled 624 patients with severe sepsis and grouped them into 6 categories according to their T_b at the time of enrollment. The temperature categories (≤35.5°C, 35.6–36.5°C, 36.6–37.5°C, 37.6–38.5°C, 38.6–39.5°C, ≥39.6°C) were based on the temperature data of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring. We compared patient characteristics, physiological data, and mortality between groups.

Results

Patients with T_b of ≤36.5°C had significantly worse sequential organ failure assessment (SOFA) scores when compared with patients with T_b >37.5°C on the day of enrollment. Scores for APACHE II were also higher in patients with T_b ≤35.5°C when compared with patients with T_b >36.5°C. The 28-day and hospital mortality was significantly higher in patients with T_b ≤36.5°C. The difference in mortality rate was especially noticeable when patients with T_b ≤35.5°C were compared with patients who had T_b of >36.5°C. Although mortality did not relate to T_b ranges of ≥37.6°C as compared to reference range of 36.6–37.5°C, relative risk for 28-day mortality was significantly greater in patients with 35.6–36.5°C and ≤35.5°C (odds ratio; 2.032, 3.096, respectively). When patients were divided into groups based on the presence (≤36.5°C, n = 160) or absence (>36.5°C, n = 464) of hypothermia, disseminated intravascular coagulation (DIC) as well as SOFA and APACHE II scores were significantly higher in patients with hypothermia. Patients with hypothermia had significantly higher 28-day and hospital mortality rates than those without hypothermia (38.1% vs. 17.9% and 49.4% vs. 22.6%, respectively). The presence of hypothermia was an independent predictor of 28-day mortality, and the differences between patients with and without hypothermia were observed irrespective of the presence of septic shock.

Conclusions

In patients with severe sepsis, hypothermia (T_b ≤36.5°C) was associated with increased mortality and organ failure, irrespective of the presence of septic shock.

Trial registration

UMIN-CTR ID UMIN000008195     

Multiple modes of action of tacrolimus (FK506) for neuroprotective action on ischemic damage after transient focal cerebral ischemia in rats

While the immunosuppressant tacrolimus (FK506) is known to be neuroprotective following cerebral ischemia, the mechanisms underlying its neuroprotective properties are not fully understood. To determine the mode of action by which tacrolimus ameliorates neurodegeneration after transient focal ischemia, we therefore evaluated the effect of tacrolimus on DNA damage, release of cytochrome c, activation of microglia and infiltration of neutrophils following a 60-min occlusion of the middle cerebral artery (MCA) in rats. In this model, cortical brain damage gradually expanded until 24 h after reperfusion, whereas brain damage in the caudate putamen was fully developed within 5 h. Tacrolimus (1 mg/kg) administered immediately after MCA occlusion significantly reduced ischemic damage in the cerebral cortex, but not in the caudate putamen. Tacrolimus decreased both apoptotic and necrotic cell death at 24 h and reduced the number of cytochrome c immunoreactive cells at 8 h after reperfusion in the ischemic penumbra in the cerebral cortex. In contrast, tacrolimus did not show significant neuroprotection for necrotic cell death and reduction of cytochrome c immunoreactive cells in the caudate putamen. Tacrolimus also significantly decreased microglial activation at 8 h and inflammatory markers (cytokine-induced neutrophil chemoattractant and myeloperoxidase [MPO] activity) at 24 h after reperfusion in the ischemic cortex but not in the caudate putamen. These results collectively suggest that tacrolimus ameliorates the gradually expanded brain damage by inhibiting both apoptotic and necrotic cell death, as well as suppressing inflammatory reactions.     

Cerebral bone subtraction CT angiography using 80 kVp and sinogram-affirmed iterative reconstruction: contrast medium and radiation dose reduction with improvement of image quality

Introduction

The purpose of this study was to evaluate the feasibility of a contrast medium (CM), radiation dose reduction protocol for cerebral bone-subtraction CT angiography (BSCTA) using 80-kVp and sinogram-affirmed iterative reconstruction (SAFIRE).

Methods

Seventy-five patients who had undergone BSCTA under the 120- (n = 37) or the 80-kVp protocol (n = 38) were included. CM was 370 mgI/kg for the 120-kVp and 296 mgI/kg for the 80-kVp protocol; the 120- and the 80-kVp images were reconstructed with filtered back-projection (FBP) and SAFIRE, respectively. We compared effective dose (ED), CT attenuation, image noise, and contrast-to-noise ratio (CNR) of two protocols. We also scored arterial contrast, sharpness, depiction of small arteries, visibility near skull base/clip, and overall image quality on a four-point scale.

Results

ED was 62% lower at 80- than 120-kVp (0.59 ± 0.06 vs 1.56 ± 0.13 mSv, p < 0.01). CT attenuation of the internal carotid artery (ICA) and middle cerebral artery (MCA) was significantly higher on 80- than 120-kVp (ICA: 557.4 ± 105.7 vs 370.0 ± 59.3 Hounsfield units (HU), p < 0.01; MCA: 551.9 ± 107.9 vs 364.6 ± 62.2 HU, p < 0.01). The CNR was also significantly higher on 80- than 120-kVp (ICA: 46.2 ± 10.2 vs 36.9 ± 7.6, p < 0.01; MCA: 45.7 ± 10.0 vs 35.7 ± 9.0, p < 0.01). Visibility near skull base and clip was not significantly different (p = 0.45). The other subjective scores were higher with the 80- than the 120-kVp protocol (p < 0.05).

Conclusion

The 80-kVp acquisition with SAFIRE yields better image quality for BSCTA and substantial reduction in the radiation and CM dose compared to the 120-kVp with FBP protocol.