Proliferation signal inhibitor-induced decrease of vascular endothelial cadherin expression and increase of endothelial permeability in vitro are prevented by an anti-oxidant

BACKGROUND: Rapamycines, sirolimus (SRL) and everolimus (ERL), are proliferation signal inhibitors (PSIs). PSI therapy often leads to edema. We hypothesized that increased oxidative stress in response to PSIs may modulate the expression of vascular endothelial (VE)-cadherin on endothelial cells (ECs) and, subsequently, vascular permeability, which in turn may be involved in the development of edema. METHODS: Experiments were performed on human umbilical vein ECs (HUVECs). Oxidative stress was measured by dichlorofluorescein-diacetate. Expression of VE-cadherin was evaluated by immunofluorescent staining and western blot analysis. Endothelial "permeability" was assessed using a transwell model. RESULTS: SRL and ERL, at concentrations of 1, 10 and 100 nmol/liter, enhanced oxidative stress (SRL: 24 +/- 12%, 29 +/- 9%, 41 +/- 13% [p < 0.05, in all three cases]; ERL: 13 +/- 10%, 27 +/- 2%, 40 +/- 12% [p < 0.05, in the latter two cases], respectively) on HUVECs, which was inhibited by the anti-oxidant, N-acetyl-cysteine (NAC) and, to a lesser extent, by the specific inhibitor of nitric oxide synthase, N-Omega-nitro-L-arginine methylester. By the use of NAC, VE-cadherin expression remained comparable with control, according to both immunocytochemistry and western blot analysis. Permeability was significantly increased by SRL and ERL at 100 nmol/liter (29.5 +/- 6.4% and 33.8 +/- 4.2%, respectively); however, co-treatment with NAC abrogated the increased permeability. CONCLUSIONS: EC homeostasis, as indicated by VE-cadherin expression, may be damaged by SRL and ERL, but resolved by the anti-oxidant NAC.

Ultrasound-guided paravertebral puncture and placement of catheters in human cadavers: an imaging study

BACKGROUND: During paravertebral block, the anterolateral limit of the paravertebral space, which consists of the pleura, should preferably not be perforated. Also it is possible that, during the block, the constant superior costotransverse ligament can be missed in the loss-of-resistance technique. We therefore aimed to develop a new technique for an ultrasound-guided puncture of the paravertebral space. METHODS: We performed 20 punctures and catheter placements in 10 human cadavers. A sonographic view showing the pleura and the superior costotransverse ligament was obtained with a slightly oblique scan using a curved array transducer. After inline approach, injection of 10 ml normal saline confirmed the correct position of the needle tip, distended the space, and enabled catheter insertion. The spread of contrast dye injected through the catheters was assessed by CT scans. RESULTS: The superior costotransverse ligament and the paravertebral space were easy to identify. The needle tip reached the paravertebral space without problems under visualization. In contrast, the introduction of the catheter was difficult. The CT scan revealed a correct paravertebral spread of contrast in 11 cases. Out of the remaining, one catheter was found in the pleural space, in six cases there was an epidural, and in two cases there was a prevertebral spread of contrast dye. CONCLUSIONS: We successfully developed a technique for an accurate ultrasound-guided puncture of the paravertebral space. We also showed that when a catheter is introduced through the needle with the tip lying in the paravertebral space, there is a high probability of catheter misplacement into the epidural, mediastinal, or pleural spaces.

Patient exposure and image quality of low-dose pulmonary computed tomography angiography: comparison of 100- and 80-kVp protocols

OBJECTIVE: Measures to reduce radiation exposure and injected iodine mass are becoming more important with the widespread and often repetitive use of pulmonary CT angiography (CTA) in patients with suspected pulmonary embolism. In this retrospective study, we analyzed the capability of 2 low-kilovoltage CTA-protocols to achieve these goals. MATERIALS AND METHODS: Ninety patients weighing less than 100 kg were examined by a pulmonary CTA protocol using either 100 kVp (group A) or 80 kVp (group B). Volume and flow rate of contrast medium were reduced in group B (75 mL at 3 mL/s) compared with group A (100 mL at 4 mL/s). Attenuation was measured in the central and peripheral pulmonary arteries, and the contrast-to-noise ratios (CNR) were calculated. Entrance skin dose was estimated by measuring the surface dose in an ovoid-cylindrical polymethyl methacrylate chest phantom with 2 various dimensions corresponding to the range of chest diameters in our patients. Quantitative image parameters, estimated effective dose, and skin dose in both groups were compared by the t test. Arterial enhancement, noise, and overall quality were independently assessed by 3 radiologists, and results were compared between the groups using nonparametric tests. RESULTS: Mean attenuation in the pulmonary arteries in group B (427.6 +/- 116 HU) was significantly higher than in group A (342.1 +/- 87.7 HU; P < 0.001), whereas CNR showed no difference (group A, 20.6 +/- 7.3 and group B, 22.2 +/- 7.1; P = 0.302). Effective dose was lower by more than 40% with 80 kVp (1.68 +/- 0.23 mSv) compared with 100 kVp (2.87 +/- 0.88 mSv) (P < 0.001). Surface dose was significantly lower at 80 kVp compared with 100 kVp at both phantom dimensions (2.75 vs. 3.22 mGy; P = 0.027 and 2.22 vs. 2.73 mGy; P = 0.005, respectively). Image quality did not differ significantly between the groups (P = 0.151). CONCLUSIONS: Using 80 kVp in pulmonary CTA permits reduced patient exposure by 40% and CM volume by 25% compared with 100 kVp without deterioration of image quality in patients weighing less than 100 kg.

Anti-HLA I antibodies induce VEGF production by endothelial cells, which increases proliferation and paracellular permeability

Anti-human leukocyte antigen class I (HLA I) antibodies were shown to activate several protein kinases in endothelial cells (ECs), which induces proliferation and cell survival. An important phenomenon in antibody-mediated rejection is the occurrence of interstitial edema. We investigated the effect of anti-HLA I antibodies on endothelial proliferation and permeability, as one possible underlying mechanism of edema formation. HLA I antibodies increased the permeability of cultured ECs isolated from umbilical veins. Anti-HLA I antibodies induced the production of vascular endothelial growth factor (VEGF) by ECs, which activated VEGF receptor 2 (VEGFR2) in an autocrine manner. Activated VEGFR2 led to a c-Src-dependent phosphorylation of vascular endothelial (VE)-cadherin and its degradation. Aberrant VE-cadherin expression resulted in impaired adherens junctions, which might lead to increased endothelial permeability. This effect was only observed after cross-linking of HLA I molecules by intact antibodies. Furthermore, our results suggest that increased endothelial proliferation following anti-HLA I treatment occurs via autocrine VEGFR2 activation. Our data indicate the ability of anti-HLA I to induce VEGF production in ECs. Transactivation of VEGFR2 leads to increased EC proliferation and paracellular permeability. The autocrine effect of VEGF on endothelial permeability might be an explanation for the formation of interstitial edema after transplantation.

Detection of pulmonary emboli with CT angiography at reduced radiation exposure and contrast material volume: comparison of 80 kVp and 120 kVp protocols in a matched cohort

The detection rate of pulmonary emboli (PE) with computed tomography angiography (CTA) using either a standard or a low-dose protocol, combining reduced radiation exposure and iodine delivery rate, was retrospectively analyzed in a matched cohort of 120 patients.

Detection of urinary stones at reduced radiation exposure: a phantom study comparing computed radiography and a low-dose digital radiography linear slit scanning system

OBJECTIVE: In this experimental study we assessed the diagnostic performance of digital linear slit scanning radiography compared with computed radiography (CR) for the detection of urinary calculi in an anthropomorphic phantom imitating patients weighing approximately 58-88 kg. CONCLUSION: Compared with CR, linear slit scanning radiography is superior for the detection of urinary stones and may be used for pretreatment localization and follow-up at a lower patient exposure.

MR angiography of infrapopliteal arteries in patients with peripheral arterial occlusive disease by using Gadofosveset at 3.0 T: diagnostic accuracy compared with selective DSA

To prospectively compare the diagnostic accuracy of steady-state, high-spatial-resolution magnetic resonance (MR) angiography of the lower leg, performed with a blood pool contrast agent, with selective digital subtraction angiography (DSA) as the reference standard in patients with symptomatic peripheral arterial disease.

Thoracoabdominal-aortoiliac multidetector-row CT angiography at 80 and 100 kVp: assessment of image quality and radiation dose

OBJECTIVE: To compare image quality and radiation dose of thoracoabdominal computed tomography (CT) angiography at 80 and 100 kVp and to assess the feasibility of reducing contrast medium volume from 60 to 45 mL at 80 kVp. MATERIALS AND METHODS: This retrospective study had institutional review board approval; informed consent was waived. Seventy-five patients who had undergone thoracoabdominal 64-section multidetector-row CT angiography were divided into 3 groups of 25 patients each. Patients of groups A (tube voltage, 100 kVp) and B (tube voltage, 80 kVp) received 60 mL of contrast medium at 4 mL/s. Patients of group C (tube voltage, 80 kVp) received 45 mL of contrast medium at 3 mL/s. Mean aortoiliac attenuation, image noise, and contrast-to-noise ratio were assessed. The measurement of radiation dose was based on the volume CT dose index. Three independent readers assessed the diagnostic image quality. RESULTS: Mean aortoiliac attenuation for group B (621.1 +/- 90.5 HU) was significantly greater than for groups A and C (485.2 +/- 110.5 HU and 483.1 +/- 119.8 HU; respectively) (P < 0.001). Mean image noise was significantly higher for groups B and C than for group A (P < 0.05). The contrast-to-noise ratio did not significantly differ between the groups (group A, 35.0 +/- 13.8; group B, 31.7 +/- 10.1; group C, 27.3 +/- 11.5; P = 0.08). Mean volume CT dose index in groups B and C (5.2 +/- 0.4 mGy and 4.9 +/- 0.3 mGy, respectively) were reduced by 23.5% and 27.9%, respectively, compared with group A (6.8 +/- 0.8 mGy) (P < 0.001). The average overall diagnostic image quality for the 3 groups was graded as good or better. The score for group A was significantly higher than that for group C (P < 0.01), no difference was seen between group A and B (P = 0.92). CONCLUSIONS: Reduction of tube voltage from 100 to 80 kVp for thoracoabdominal CT angiography significantly reduces radiation dose without compromising image quality. Reduction of contrast medium volume to 45 mL at 80 kVp resulted in lower but still diagnostically acceptable image quality.

Is body weight the most appropriate criterion to select patients eligible for low-dose pulmonary CT angiography? Analysis of objective and subjective image quality at 80 kVp in 100 patients

The objective of this retrospective study was to assess image quality with pulmonary CT angiography (CTA) using 80 kVp and to find anthropomorphic parameters other than body weight (BW) to serve as selection criteria for low-dose CTA. Attenuation in the pulmonary arteries, anteroposterior and lateral diameters, cross-sectional area and soft-tissue thickness of the chest were measured in 100 consecutive patients weighing less than 100 kg with 80 kVp pulmonary CTA. Body surface area (BSA) and contrast-to-noise ratios (CNR) were calculated. Three radiologists analyzed arterial enhancement, noise, and image quality. Image parameters between patients grouped by BW (group 1: 0-50 kg; groups 2-6: 51-100 kg, decadally increasing) were compared. CNR was higher in patients weighing less than 60 kg than in the BW groups 71-99 kg (P between 0.025 and <0.001). Subjective ranking of enhancement (P = 0.165-0.605), noise (P = 0.063), and image quality (P = 0.079) did not differ significantly across all patient groups. CNR correlated moderately strongly with weight (R = -0.585), BSA (R = -0.582), cross-sectional area (R = -0.544), and anteroposterior diameter of the chest (R = -0.457; P < 0.001 all parameters). We conclude that 80 kVp pulmonary CTA permits diagnostic image quality in patients weighing up to 100 kg. Body weight is a suitable criterion to select patients for low-dose pulmonary CTA.

Endoleak detection with CT angiography in an abdominal aortic aneurysm phantom: effect of tube energy, simulated patient size, and physical properties of endoleaks

To analyze the detection of endoleaks with low-tube-voltage computed tomographic (CT) angiography.

Effect of automatic tube current modulation on radiation dose and image quality for low tube voltage multidetector row CT angiography: phantom study

RATIONALE AND OBJECTIVES: To evaluate the effect of automatic tube current modulation on radiation dose and image quality for low tube voltage computed tomography (CT) angiography. MATERIALS AND METHODS: An anthropomorphic phantom was scanned with a 64-section CT scanner using following tube voltages: 140 kVp (Protocol A), 120 kVp (Protocol B), 100 kVp (Protocol C), and 80 kVp (Protocol D). To achieve similar noise, combined z-axis and xy-axes automatic tube current modulation was applied. Effective dose (ED) for the four tube voltages was assessed. Three plastic vials filled with different concentrations of iodinated solution were placed on the phantom's abdomen to obtain attenuation measurements. The signal-to-noise ratio (SNR) was calculated and a figure of merit (FOM) for each iodinated solution was computed as SNR(2)/ED. RESULTS: The ED was kept similar for the four different tube voltages: (A) 5.4 mSv +/- 0.3, (B) 4.1 mSv +/- 0.6, (C) 3.9 mSv +/- 0.5, and (D) 4.2 mSv +/- 0.3 (P > .05). As the tube voltage decreased from 140 to 80 kVp, image noise was maintained (range, 13.8-14.9 HU) (P > .05). SNR increased as the tube voltage decreased, with an overall gain of 119% for the 80-kVp compared to the 140-kVp protocol (P < .05). The FOM results indicated that with a reduction of the tube voltage from 140 to 120, 100, and 80 kVp, at constant SNR, ED was reduced by a factor of 2.1, 3.3, and 5.1, respectively, (P < .001). CONCLUSIONS: As tube voltage decreases, automatic tube current modulation for CT angiography yields either a significant increase in image quality at constant radiation dose or a significant decrease in radiation dose at a constant image quality.

Dual energy subtraction: principles and clinical applications

Two technical solutions using single or dual shot offer different advantages and disadvantages for dual energy subtraction. The principles of these are explained and the main clinical applications with results are demonstrated. Elimination of overlaying bone and proof or exclusion of calcification are the primary aims of energy subtraction chest radiography, offering unique information in different clinical situations.

Image quality of supine chest radiographs: intra-individual comparison of computed radiography and low-dose linear-slit digital radiography

The purpose of this retrospective study was to intra-individually compare the image quality of computed radiography (CR) and low-dose linear-slit digital radiography (LSDR) for supine chest radiographs. A total of 90 patients (28 female, 62 male; mean age, 55.1 years) imaged with CR and LSDR within a mean time interval of 2.8 days +/- 3.0 were included in this study. Two independent readers evaluated the image quality of CR and LSDR based on modified European Guidelines for Quality Criteria for chest X-ray. The Wilcoxon test was used to analyse differences between the techniques. The overall image quality of LSDR was significantly better than the quality of CR (9.75 vs 8.16 of a maximum score of 10; p < 0.001). LSDR performed significantly better than CR for delineation of anatomical structures in the mediastinum and the retrocardiac lung (p < 0.001). CR was superior to LSDR for visually sharp delineation of the lung vessels and the thin linear structures in the lungs. We conclude that LSDR yields better image quality and may be more suitable for excluding significant pathological features of the chest in areas with high attenuation compared with CR.

Learning for sustainability - LforS: Simulation games - a creative tool for interactive learning

Description of simulation and training games as tool for awareness and capacity development in multi steakeholder processes

Self-help extension: Farmer-to-farmer extension

As staff and mobility cost have the lion share of the costs of extension work, there have been many alternatives to assign farmers the job of facilitators, trainers and advisors. The arguments behind are that they are geopraphically closer to the clients, but also mentally and culturally, because they are members of the client group themselves, speak their language and share their experience and daily life. The article starts with the origins of the larger movement in Latin-America, and then discusses potentials and limitations, and finally experience from elsewhere.