Microvascular response in guinea pig skin to histamine challenge with and without application of skin window.

We measured the microvascular response to histamine in guinea pig skin. Histamine (40 mg ml-1) was given either as a skin prick test or applied topically onto a skin window. The skin window was prepared by applying suction and gentle warming to the skin so that a blister was formed, and by removing the top of the blister. The microvascular response was measured as the accumulation of radiolabelled transferrin in the skin in vivo, reflecting a combination plasma exudation and vasodilatation. In the control (saline) challenge, the response was slightly greater in the skin window than after skin prick challenge and the scatter was larger. Histamine challenge resulted in a significant microvascular response with respect to the control situation when measured immediately after provocation for both challenge techniques. Ten minutes after challenge, a smaller response was measured, which was still significantly greater than control for the skin prick challenge, but not for topical provocation using the skin window technique. We conclude that the microvascular response to histamine after provocation with the skin prick technique is similar to that after topical provocation using the skin window technique. The skin window technique may have a lower sensitivity than the skin prick technique owing to a higher scatter in the control situation. This difference should be considered when performing and interpreting studies of the microvascular reaction in the skin

A 14-year prospective study of autonomic nerve function in Type 1 diabetic patients: association with nephropathy.

Aims Prospective studies of autonomic nerve function are rare. We have followed the progression of autonomic dysfunction in relation to nephropathy over 14 years in Type 1 diabetic patients. Methods Autonomic nerve function was assessed by heart-rate responses to deep breathing (E/I ratio) and tilting (acceleration and brake indices) and by the postural blood pressure reaction in 58 patients, 43 of whom were reassessed after 14 years. Nephropathy was evaluated by the degree of albuminuria (albuminuria > 20 µg/min or > 0.03 g/24 h) and glomerular filtration rate (51Cr-EDTA plasma clearance). The acceleration index had deteriorated after 7 years (P = 0.0155), whereas the E/I ratio (P = 0.0070) and the diastolic postural blood pressure reaction (P = 0.0054) had deteriorated 14 years after the baseline examination (age-corrected values). All those with albuminuria at the third examination showed signs of autonomic neuropathy at baseline (10 of 10) compared with only nine of 22 without (P = 0.0016). Multiple regression analysis showed that the association between autonomic dysfunction and future albuminuria was due to the E/I ratio. In addition, individuals with an abnormal postural diastolic blood pressure fall (n = 7) at baseline showed a greater fall in glomerular filtration rate more than others 7-14 years later [29 (16.5) ml/min/1.72 m2 vs. 11 (9) ml/min/1.72 m2; P = 0.0074]. Conclusion Autonomic nerve function had deteriorated after 14 years. Autonomic neuropathy and abnormal postural diastolic blood pressure falls at baseline were associated with future renal complications

Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection

In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naive patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-alpha (pegIFN-alpha), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-alpha, or (iii) standard-of-care (SOC) ribavirin dosing concurrent with pegIFN-alpha. Four weeks of ribavirin mono-therapy resulted in a mean 0.46 log(10) IU/mL HCV RNA reduction differentially regulated across IL28B genotypes (0.89 vs. 0.21 log(10) IU/mL for CC and CT/TT respectively; P = 0.006), increased likelihood of undetectable HCV RNA week 4 after initiating pegIFN-alpha and thus shortened treatment duration (P <0.05), and decreased median IP-10 concentration from 550 to 345 pg/mL (P <0.001). Both experimental strategies impacted on ribavirin concentrations, and high levels were achieved after one week of double dosing. However, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an antiviral effect differently regulated across IL28B genotypes.Peer reviewe

An investigation of the iterative reconstruction method iDose(4) on a Philips CT Brilliance 64 using a Catphan 600 phantom

The number of CT examinations giving a relatively high patient exposure is increasing. It is therefore important to optimize the imaging conditions at these investigations. Many steps have been taken to reduce the radiation doses in CT examinations. Currently much work is related to iterative image reconstruction methods as alternative to the filtered back projection method. The aim of this work was to evaluate quality parameters in images from a CT (Philips Brilliance 64) equipped with the iterative reconstruction method iDose(4) using a Catphan 600 phantom with and without body simulating ring. CT scans using abdomen protocol were taken with various tube currents and tube voltage and keeping collimation and pitch unchanged for all scans. All collected data were reconstructed with different levels of iDose(4) (Level 2, 4, 6) and traditional filtered back projection. Image quality parameters were evaluated using AutoQA Lite (TM) (Version 2.3 2007 Iris QA, LLC). Results from the study shows that the iterative reconstruction method decreases the noise with 15-45% compared with filtered back projection depending on which level of iDose(4) is used. The percentage reduction in noise level is the same with and without body simulating ring. Low contrast was improved with iDose(4) and spatial resolution is only marginally affected by the method of reconstruction. However by reducing the image noise, the detectability can be improved. Our conclusion is that there is great potential to reduce the noise and thereby improve the image quality by using iterative reconstruction methods. This can also be used to lower radiation dose and maintain image quality or improve image quality

MODEL BASED ITERATIVE RECONSTRUCTION IMR GIVES POSSIBILITY TO EVALUATE THINNER SLICE THICKNESSES THAN CONVENTIONAL ITERATIVE RECONSTRUCTION iDOSE4 – A PHANTOM STUDY

Computed tomography (CT) is one of the most important modalities in a radiological department, which produces images with high diagnostic confidence, but in some cases contributes to a high radiation dose to the patient. The radiation dose can be reduced by the use of advanced image reconstruction algorithms. This study was done on a Philips Brilliance iCT with iterative reconstruction iDose(4) and model-based iterative reconstruction IMR. The purpose was to investigate the effect on the image quality with thin slice images reconstructed with IMR, compared to standard slice thickness reconstructed with iDose(4). Objective measurements of noise and contrast-to-noise ratio were performed using an image quality phantom, an anthropomorphic phantom and clinical cases. Subjective evaluations of low-contrast resolution were performed by observers using an image quality phantom. IMR gives strong noise reduction and enhanced low-contrast and thereby enable selection of thinner slice thickness. Objective evaluation of image noise shows that thin slices reconstructed with IMR provides lower noise than thicker slice images reconstructed with iDose(4). With IMR the slice thickness is of less importance for the noise. With thinner slices the partial volume artefacts becomes less pronounced. In conclusion, we have shown that IMR enables reduction of the slice thickness and at the same time maintain or even reduce the noise level compared to iDose(4) reconstruction with standard slice thickness. This will subsequently result in an improvement of image quality for images reconstructed with IMR