Sustained release of locally delivered celecoxib provides pain relief for osteoarthritis: a proof of concept in dog patients.

OBJECTIVE: Drug delivery platforms that allow for gradual drug release after intra-articular administration have become of much interest as a treatment strategy for osteoarthritis (OA). The aim of this study was to investigate the safety and efficacy of an intra-articular sustained release formulation containing celecoxib (CXB), a cyclooxygenase-2 (COX-2) selective inhibitor. METHODS: Amino acid-based polyesteramide microspheres (PEAMs), a biodegradable and non-toxic platform, were loaded with CXB and employed in two in vivo models of arthritis: an acute inflammatory arthritis model in rats (n = 12), and a randomized controlled study in chronic OA dog patients (n = 30). In parallel, the bioactivity of sustained release of CXB was evaluated in monolayer cultures of primary dog chondrocytes under inflammatory conditions. RESULTS: Sustained release of CXB did not alleviate acute arthritis signs in the rat arthritis model, based on pain measurements and synovitis severity. However, in OA dog patients, sustained release of CXB improved limb function as objective parameter of pain and quality of life based on gait analysis and owner questionnaires. It also decreased pain medication dependency over a 2-month period and caused no adverse effects. Prostaglandin E2 levels, a marker for inflammation, were lower in the synovial fluid of CXB-treated dog OA patients and in CXB-treated cultured dog chondrocytes. CONCLUSION: These results show that local sustained release of CXB is less suitable to treat acute inflammation in arthritic joints, while safe and effective in treating pain in chronic OA in dogs.

Sensor Noise in LISA Pathfinder: In-Flight Performance of the Optical Test Mass Readout.

We report on the first subpicometer interferometer flown in space. It was part of ESA's Laser Interferometer Space Antenna (LISA) Pathfinder mission and performed the fundamental measurement of the positional and angular motion of two free-falling test masses. The interferometer worked immediately, stably, and reliably from switch on until the end of the mission with exceptionally low residual noise of 32.0_{-1.7}^{+2.4} fm/sqrt[Hz], significantly better than required. We present an upper limit for the sensor performance at millihertz frequencies and a model for the measured sensitivity above 200 mHz.

Analysis of the accuracy of actuation electronics in the laser interferometer space antenna pathfinder.

The Laser Interferometer Space Antenna Pathfinder (LPF) main observable, labeled Δg, is the differential force per unit mass acting on the two test masses under free fall conditions after the contribution of all non-gravitational forces has been compensated. At low frequencies, the differential force is compensated by an applied electrostatic actuation force, which then must be subtracted from the measured acceleration to obtain Δg. Any inaccuracy in the actuation force contaminates the residual acceleration. This study investigates the accuracy of the electrostatic actuation system and its impact on the LPF main observable. It is shown that the inaccuracy is mainly caused by the rounding errors in the waveform processing and also by the random error caused by the analog to digital converter random noise in the control loop. Both errors are one order of magnitude smaller than the resolution of the commanded voltages. We developed a simulator based on the LPF design to compute the close-to-reality actuation voltages and, consequently, the resulting actuation forces. The simulator is applied during post-processing the LPF data.

LISA Pathfinder Performance Confirmed in an Open-Loop Configuration: Results from the Free-Fall Actuation Mode.

We report on the results of the LISA Pathfinder (LPF) free-fall mode experiment, in which the control force needed to compensate the quasistatic differential force acting on two test masses is applied intermittently as a series of "impulse" forces lasting a few seconds and separated by roughly 350 s periods of true free fall. This represents an alternative to the normal LPF mode of operation in which this balancing force is applied continuously, with the advantage that the acceleration noise during free fall is measured in the absence of the actuation force, thus eliminating associated noise and force calibration errors. The differential acceleration noise measurement presented here with the free-fall mode agrees with noise measured with the continuous actuation scheme, representing an important and independent confirmation of the LPF result. An additional measurement with larger actuation forces also shows that the technique can be used to eliminate actuation noise when this is a dominant factor.

Beyond the Required LISA Free-Fall Performance: New LISA Pathfinder Results down to 20 µHz.

In the months since the publication of the first results, the noise performance of LISA Pathfinder has improved because of reduced Brownian noise due to the continued decrease in pressure around the test masses, from a better correction of noninertial effects, and from a better calibration of the electrostatic force actuation. In addition, the availability of numerous long noise measurement runs, during which no perturbation is purposely applied to the test masses, has allowed the measurement of noise with good statistics down to 20 µHz. The Letter presents the measured differential acceleration noise figure, which is at (1.74±0.05) fm s^{-2}/sqrt[Hz] above 2 mHz and (6±1)×10 fm s^{-2}/sqrt[Hz] at 20 µHz, and discusses the physical sources for the measured noise. This performance provides an experimental benchmark demonstrating the ability to realize the low-frequency science potential of the LISA mission, recently selected by the European Space Agency.

Charge-Induced Force Noise on Free-Falling Test Masses: Results from LISA Pathfinder.

We report on electrostatic measurements made on board the European Space Agency mission LISA Pathfinder. Detailed measurements of the charge-induced electrostatic forces exerted on free-falling test masses (TMs) inside the capacitive gravitational reference sensor are the first made in a relevant environment for a space-based gravitational wave detector. Employing a combination of charge control and electric-field compensation, we show that the level of charge-induced acceleration noise on a single TM can be maintained at a level close to 1.0 fm s^{-2} Hz^{-1/2} across the 0.1-100 mHz frequency band that is crucial to an observatory such as the Laser Interferometer Space Antenna (LISA). Using dedicated measurements that detect these effects in the differential acceleration between the two test masses, we resolve the stochastic nature of the TM charge buildup due to interplanetary cosmic rays and the TM charge-to-force coupling through stray electric fields in the sensor. All our measurements are in good agreement with predictions based on a relatively simple electrostatic model of the LISA Pathfinder instrument.

A comparison between fixation methods of femoral diaphyseal fractures in cats - a retrospective study.

OBJECTIVES: To compare the outcome of three different fixation methods and to determine prognostic factors in cats with diaphyseal femoral fractures. METHODS: Retrospective analysis of case records of cats with diaphyseal femoral fractures surgically corrected using external fixators, bone plate or plate-rod construct. Outcome was evaluated by estimating the time to bone healing and by calculating the complication rate. RESULTS: In total, an external fixator was used in 30 cases, a bone plate in 20 cases and a plate-rod construct in 56 cases. All methods were successful in achieving bone healing without significant differences. There was a significant difference between the categorized complication rates between the treatment groups. The external fixation group had the most complications overall. When only the major and catastrophic complications were taken into account, it had the fewest complications. The plate-rod construct had the fewest complications overall, with most being major complications. The bone plate group had a complication rate between that of the external fixation and plate-rod construct groups. It had the most catastrophic complications in relative terms. CLINICAL SIGNIFICANCE: There was no statistically significant difference in the time to achieve bone healing but there was a significant difference in categorized complication rates between the groups.

Comparison of three closure methods and two absorbable suture materials for closure of jejunal enterotomy incisions in healthy dogs.

The macroscopic and histological appearance of jejunal antimesenteric incisions approximated with two different absorbable suture materials (monofilament versus multifilament) and three closure techniques (appositional single layer, crushing single layer, and double layer) were compared in healthy dogs at 14 or 28 days, postoperatively. No significant differences between the two suture materials were observed for most of the macroscopic or histological variables. However, the monofilament suture material caused significantly more fibrous tissue reaction in the muscular layer of the jejunum than did the multifilament suture material. Of the three enterotomy closure techniques used in this study, the appositional single-layer method proved to be the best. The double-layer closure method caused a significant decrease in the incisional circumference, the relative circumference, and volume of the jejunum, and a significant increase in jejunal wall thickness. Our findings suggest that canine jejunal enterotomy incisions can be closed using an appositional suture pattern with relatively rapidly absorbable monofilament suture material. The use of double-layer suture patterns for closure of jejunal enterotomy incisions should be avoided because the size of the intestinal lumen may be reduced.

Influence of orchiectomy on canine behaviour.

One hundred and twenty-two dog owners were interviewed to obtain information about the effects of orchiectomy on the behaviour, unwanted side effects, and testosterone-dependent disease processes in their dogs. Behavioural problems were the main reason for orchiectomy, unwanted sexual behaviour being the most common, together with roaming, aggression, and abnormal urination behaviour. Objectionable sexual behaviour, inter-male aggression, roaming, and abnormalurination were reduced after orchiectomy in approximately 60 per cent of the dogs. The side effects of orchiectomy included increased bodyweight, increased appetite and decreased activity in less than 50 per cent of the dogs, and there was a significant relationship between increased appetite and bodyweight. The clinical signs of testosterone-dependent disease in most of the dogs either decreased or disappeared after orchiectomy.

Comparison of two suture materials for intradermal skin closure in dogs.

The macroscopic and histological appearance of cutaneous incisions closed with polyglecaprone 25 (Monocryl) and polyglactin 910 (Vicryl) suture materials were compared in four dogs. Polyglecaprone 25 compared favourably to polyglactin 910 suture material for closure of canine skin incisions, and was associated with significantly less tissue reaction in the early phases of the healing process than was polyglactin 910 suture material. This difference was not present at later evaluation times.

[Lameness in a dog following gunshot wound; case report and management protocol]. / Kreupelheid van een hond na schotverwonding; casuïstiek en een plan van aanpak.

The clinical signs and surgical treatment of a 3-year old German wirehair Pointer with chronic intermittent lameness due to a gunshot injury are presented. In addition to routine radiography, ultrasound investigation and positive contrast arthrography of the radiocarpal joint showed that a bullet was located in the lateropalmar part of the radiocarpal joint cavity. Surgical removal of the bullet led to complete clinical recovery. A diagnostic and therapeutic protocol is presented for dogs and cats with gunshot injuries.