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

Bone turnover markers are correlated with total skeletal uptake of 99mTc-methylene diphosphonate (99mTc-MDP)

ABSTRACT: BACKGROUND: Skeletal uptake of 99mTc labelled methylene diphosphonate (99mTc-MDP) is used for producing images of pathological bone uptake due to its incorporation to the sites of active bone turnover. This study was done to validate bone turnover markers using total skeletal uptake (TSU) of 99mTc-MDP. METHODS: 22 postmenopausal women (52-80 years) volunteered to participate. Scintigraphy was performed by injecting 520 MBq of 99mTc-MDP and taking whole body images after 3 minutes, and 5 hours. TSU was calculated from these two images by taking into account the urinary loss and soft tissue uptake. Bone turnover markers used were bone specific alkaline phosphatase (S-Bone ALP), three different assays for serum osteocalcin (OC), tartrate resistant acid phosphatase 5b (S-TRACP5b), serum C-terminal cross-linked telopeptides of type I collagen (S-CTX-I) and three assays for urinary osteocalcin (U-OC). RESULTS: The median TSU of 99mTc-MDP was 23% of the administered activity. All bone turnover markers were significantly correlated with TSU with r-values from 0.52 (p = 0.013) to 0.90 (p < 0.001). The two resorption markers had numerically higher correlations (S-TRACP5b r = 0.90, S-CTX-I r = 0.80) than the formation markers (S-Total OC r = 0.72, S-Bone ALP r = 0.66), but the difference was not statistically significant. TSU did not correlate with age, weight, body mass index or bone mineral density. CONCLUSION: In conclusion, bone turnover markers are strongly correlated with total skeletal uptake of 99mTc-MDP. There were no significant differences in correlations for bone formation and resorption markers. This should be due to the coupling between formation and resorption

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

Accuracy of the quantification of organ activity from planar gamma camera images

The accuracy in determination of organ activity of Tc-99m was investigated, with activity estimated from gamma camera images of phantoms, using the, conjugate view method. The accuracy depends on several parameters such as the choice of background correction method, the accuracy in determination of the effective attenuation coefficient and the thickness of the body and organs and on the determination of the gamma camera sensitivity. The background correction method has a major influence on the quantification of the activity. Methods which take the volume of the source organ into consideration are recommended The discrepancy in the determined organ activity varied between an underestimation of 26% and an overestimation of 16% in the MIRD phantom, depending on which organ was studied and on the correction method used To correct for absorption and scattering, an effective attenuation coefficient was used. A theoretical analysis showed that a change in the effective attenuation coefficient of 0.01 cm(-1) resulted in a 15% change in the calculated activity. Also the thickness of the body and the organ of interest influences the calculated activity. A 2 cm deviation in the body thickness causes a deviation of approximately 10% in the calculated activity. The quantification is improved if the attenuation coefficient is determined by transmission measurements