Undersökning av retrobulbärområdet på hund med hjälp av ultraljud

This study was performed in order to investigate the difficulty in diagnosing retrobulbar disease with ultrasound. A retrospective study was accomplished to investigate the use of ultrasound in patients with suspected retrobulbar problems, and how often the examination is diagnostic. The computer based patient files, at the University of Agricultural Science in Uppsala, were searched for dogs with suspected retrobulbar disease. During 1999-01-01-2004-04-14, 14 patients fulfilling the search criteria were found. The patient records were studied, and the written reports from the ultrasound examinations were compared with the printed pictures from the examinations. This study indicated that the most common ultrasound diagnoses were abscess and foreign body. Ultrasound was diagnostic regarding prominent abscesses. When the changes were more subtle, diagnoses such as cellulitis, neoplasia and abscess were considered. Foreign bodies were often on the list of differential diagnoses, but seldom verified. The conclusion is that it is difficult to confidently diagnose pathological changes in the retrobulbar area using ultrasound. Another aim was to increase the knowledge of the normal variation of the appearance of the retrobulbar area, examined with ultrasound. Ultrasound examinations of the retrobulbar area was done on four clinically healthy beagles. The examinations showed a very similar retrobulbar appearance, with the characteristic retrobulbar cone, containing nervus opticus, optic disc, fat and muscles. The skeleton was seen medially, and the zygomatic salivary gland laterally. Finally we wanted to investigate if it can be diagnostically valuable to measure resistive index (RI) of the ciliary arteries in dogs whith retrobulbar disease. We measured RI on retrobulbar arteries on four clinically healthy beagles. Two different types of sedation were used, Domitor vet. together with Torbugesic®, and Plegicil® vet.. The RI differed between types and degree of sedation, with a mean RI for Domitor vet. and Torbugesic® of 0,28, and a mean RI of 0,40 for Plegicil. The conclusion is that RI varies with sedation and is time consuming and thus difficult to use in a clinical situation unless the examiner is specially trained in ocular ultrasoud

Liability of a Surgeon for the Extension of an Authorized Operation

Polyunsaturated fatty acids modulate the voltage dependence of several voltage-gated ion channels, thereby being potent modifiers of cellular excitability. Detailed knowledge of this molecular mechanism can be used in designing a new class of small-molecule compounds against hyperexcitability diseases. Here, we show that arginines on one side of the helical K-channel voltage sensor S4 increased the sensitivity to docosahexaenoic acid (DHA), whereas arginines on the opposing side decreased this sensitivity. Glutamates had opposite effects. In addition, a positively charged DHA-like molecule, arachidonyl amine, had opposite effects to the negatively charged DHA. This suggests that S4 rotates to open the channel and that DHA electrostatically affects this rotation. A channel with arginines in positions 356, 359, and 362 was extremely sensitive to DHA: 70 mu M DHA at pH 9.0 increased the current greater than500 times at negative voltages compared with wild type (WT). The small-molecule compound pimaric acid, a novel Shaker channel opener, opened the WT channel. The 356R/359R/362R channel drastically increased this effect, suggesting it to be instrumental in future drug screening

Nodule detection in digital chest radiography: part of image background acting as pure noise

There are several factors that influence the radiologist's ability to detect a specific structure/lesion in a radiograph. Three factors that are commonly known to be of major importance are the signal itself, the system noise and the projected anatomy. The aim of this study was to determine to what extent the image background acts as pure noise for the detection of subtle lung nodules in five different regions of the chest. A receiver operating characteristic (ROC) study with five observers was conducted on two different sets of images, clinical chest X-ray images and images with a similar power spectrum as the clinical images but with a random phase spectrum, resulting in an image background containing pure noise. Simulated designer nodules with a full-width-at-fifth-maximum of 10 mm but with varying contrasts were added to the images. As a measure of the part of the image background that acts as pure noise, the ratio between the contrast needed to obtain an area under the ROC curve of 0.80 in the clinical images to that in the random-phase images was used. The ratio ranged from 0.40 (in the lateral pulmonary regions) to 0.83 (in the hilar regions) indicating that there was a large difference between different regions regarding to what extent the image background acted as pure noise; and that in the hilar regions the image background almost completely acted as pure noise for the detection of 10 mm nodule

An electrostatic potassium channel opener targeting the final voltage sensor transition

Free polyunsaturated fatty acids (PUFAs) modulate the voltage dependence of voltage-gated ion channels. As an important consequence thereof, PUFAs can suppress epileptic seizures and cardiac arrhythmia. However, molecular details for the interaction between PUFA and ion channels are not well understood. In this study, we have localized the site of action for PUFAs on the voltage-gated Shaker K channel by introducing positive charges on the channel surface, which potentiated the PUFA effect. Furthermore, we found that PUFA mainly affects the final voltage sensor movement, which is closely linked to channel opening, and that specific charges at the extracellular end of the voltage sensor are critical for the PUFA effect. Because different voltage-gated K channels have different charge profiles, this implies channel-specific PUFA effects. The identified site and the pharmacological mechanism will potentially be very useful in future drug design of small-molecule compounds specifically targeting neuronal and cardiac excitability

The role of activation functions 1 and 2 of estrogen receptor-α for the effects of estradiol and selective estrogen receptor modulators in male mice

Estradiol (E2) is important for male skeletal health and the effect of E2 is mediated via estrogen receptor (ER)-α. This was demonstrated by the findings that men with an inactivating mutation in aromatase or a non-functional ERα had osteopenia and continued longitudinal growth after sexual maturation. The aim of the present study was to evaluate the role of different domains of ERα for the effects of E2 and SERMs on bone mass in males. Three mouse models lacking either ERαAF-1 (ERαAF-1(0)), ERαAF-2 (ERαAF-2(0)) or the total ERα (ERα(−/−)) were orchidectomized (orx) and treated with E2 or placebo. E2 treatment increased the trabecular and cortical bone mass and bone strength, while it reduced the thymus weight and bone marrow cellularity in orx wild type (WT) mice. These parameters did not respond to E2 treatment in orx ERα(−/−) or ERαAF-2(0) mice. However, the effects of E2 in orx ERαAF-1(0) mice were tissue-dependent, with a clear response in cortical bone parameters and bone marrow cellularity, but no response in trabecular bone. To determine the role of ERαAF-1 for the effects of SERMs, we treated orx WT and ERαAF-1(0) mice with Raloxifene (Ral), Lasofoxifene (Las), Bazedoxifene (Bza) or vehicle. These SERMs increased total body areal bone mineral density (BMD) and trabecular volumetric BMD to a similar extent in orx WT mice. Furthermore, only Las increased cortical thickness significantly and only Bza increased bone strength significantly. However, all SERMs showed a tendency towards increased cortical bone parameters. Importantly, all SERM-effects were absent in the orx ERαAF-1(0) mice. In conclusion, ERαAF-2 is required for the estrogenic effects on all evaluated parameters, while the role of ERαAF-1 is tissue specific. All evaluated effects of Ral, Las and Bza are dependent on a functional ERαAF-1. Our findings might contribute to the development of bone specific SERMs in males

Testing Cost Containment of Future Healthcare with Maintained or Improved Quality—The COSTCARES Project

Increasing healthcare costs need to be contained in order to maintain equality of access to care for all EU citizens. A cross-disciplinary consortium of experts was supported by the EU FP7 research programme, to produce a roadmap on cost containment, while maintaining or improving the quality of healthcare. The roadmap comprises two drivers: person-centred care and health promotion; five critical enablers also need to be addressed: information technology, quality measures, infrastructure, incentive systems, and contracting strategies

Reduced Bone Mass and Muscle Strength in Male 5α-Reductase Type 1 Inactivated Mice

Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1−/− mice. Four-month-old male Srd5a1−/− mice had reduced trabecular bone mineral density (−36%, p<0.05) and cortical bone mineral content (−15%, p<0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male Srd5a1−/− mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized Srd5a1−/− mice. Male Srd5a1−/− mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05). Female Srd5a1−/− mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1−/− mice, is an indirect effect mediated by elevated circulating androgen levels

Testing Cost Containment of Future Health Care with Maintained or Improved Quality – The COST CARES project Running title: Cost Containment of Future Health Care

Abstract Background Increasing healthcare costs need to be contained in order to maintain equality of access to care for all EU citizens. A cross‐disciplinary consortium of experts was supported by the EU FP7 research programme, to produce a roadmap on cost containment, while maintaining or improving the quality of healthcare. The roadmap comprises two drivers: person‐centred care and health promotion; five critical enablers also need to be addressed: information technology, quality measures, infrastructure, incentive systems, and contracting strategies. Method In order to develop and test the roadmap, a COST Action project was initiated: COST−CARES, with 28 participating countries. This paper provides an overview of evidence about the effects of each of the identified enablers. Intersections between the drivers and the enablers are identified as critical for the success of future cost containment, in tandem with maintained or improved quality in healthcare. This will require further exploration through testing. Conclusion Cost containment of future healthcare, with maintained or improved quality, needs to be addressed through a concerted approach of testing key factors. We propose a framework for test lab design based on these drivers and enablers in different European countries