The use of controlled-release oxycodone for the treatment of chronic cancer pain: a randomized, double-blind study

1. We have studied the effects of muscarinic cholinoceptor agonists and subtype-preferring antagonists on the isometric contraction of smooth muscle strips from dog prostate. 2. Acetylcholine and carbachol induced contraction of prostate strips from the peripheral zone, ('the capsule'). Bethanechol contracted the tissue but not at lower doses. McN-A-343 and oxotremorine-M showed the same effects. 3. Blocking alpha- and beta-adrenoceptors with phentolamine and propranolol, respectively, did not modify carbachol-induced contractions. 4. The nicotinic receptor blocker, hexamethonium (10(-6)-10(-4) M) did not affect the contractile response evoked by a single dose of carbachol (10(-5) M), whilst the muscarinic receptor antagonist, atropine (10(-11)-10(-9) M), inhibited it in a competitive manner. 5. The muscarinic M1 (pirenzepine), M2 [AF-DX 116, himbacine (M2/M4) and methoctramine], M3 (HHSID and f-F-HHSID), and putative M4 (tropicamide) antagonists reduced significantly the carbachol-induced contractions. The pIC50 values were: atropine (10.01) > himbacine (8.3) > methoctramine (7.85) > AF-DX 116 (7.60) > HHSID (7.21) > p-F-HHSID (7.10) > pirenzepine (7.30) > tropicamide (7.00). 6. The antagonist profile indicates that an predominant M2 receptor subtype could mediate the muscarinic contraction in the canine prostate.     

Activation of extracellular matrix metalloproteinases in equine laminitis

Samples of connective tissue obtained from the hoof of six laminitic and eight non-laminitic adult horses were analysed zymographically to investigate whether connective tissue matrix metalloproteinases are activated or induced during laminitis. The activity or matrix metalloproteinases was substantially greater in the tissues from the laminitic horses than in the tissues from the non-laminitic horses. A comparison of the collagenolytic activity in the laminitic and control tissues showed that collagenolytic activities corresponding to the 92 kDa (P < 0.001), 72 kDa (P < 0.01) and 66 kDa (P < 0.01) bands were induced in the laminitic tissues.     

Attenuated hematopoietic response to granulocyte-macrophage colony-stimulating factor in patients with acquired pulmonary alveolar proteinosis

The pathogenesis of acquired pulmonary alveolar proteinosis (PAP), a rare lung disease characterized by excessive surfactant accumulation within the alveolar space, remains obscure. Gene-targeted mice lacking the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) or the signal-transducing beta-common chain of the GM-CSF receptor have impaired surfactant clearance and pulmonary pathology resembling human PAP. We therefore investigated the hematopoietic effects of GM-CSF in patients with PAP. The hematologic response of 5 infants with congenital PAP to 5 microgram/kg/d was of normal magnitude. By contrast, despite normal expression of GM-CSF receptor alpha- and beta-common chains on peripheral blood myelomonocytic cells (n = 6) and normal binding affinity of bone marrow mononuclear cells for GM-CSF (n = 3), each of the 12 patients with acquired PAP treated displayed impaired responses to GM-CSF; 5 microgram/kg/d produced only minor eosinophilia, and doses of 7.5 to 20 microgram/kg were required to induce >/=1.5-fold neutrophil increments in the 3 patients who underwent dose-escalation. However, neutrophilic responses to 5 microgram/kg granulocyte colony-stimulating factor (G-CSF) were normal (n = 4). In vitro, the proportion of hematopoietic progenitors responsive to GM-CSF (16.1% +/- 8.9%; P = .042) or interleukin-3 (IL-3; 19.3% +/- 7.7%; P = .063), both of which utilize the beta-common chain of the GM-CSF receptor complex, were reduced among patients with acquired PAP (n = 4) compared with normal bone marrow donor controls (47.2% +/- 25.9% and 40.9% +/- 18.6%, respectively). In the one individual who had complete resolution of lung disease during the period of study, this was temporally associated with correction of this defective in vitro response to GM-CSF and IL-3 on serial assessment. These data establish that patients with acquired PAP have an associated impaired responsiveness to GM-CSF that is potentially pathogenic in the development of their lung disease. Based on these observations, we propose a model of the pathogenesis of acquired PAP that suggests the disease arises as a consequence of an acquired clonal disorder within the hematopoietic progenitor cell compartment.     

Automated zebrafish chorion removal and single embryo placement: optimizing throughput of zebrafish developmental toxicity screens

The potential of the developing zebrafish model for toxicology and drug discovery is limited by inefficient approaches to manipulating and chemically exposing zebrafish embryos-namely, manual placement of embryos into 96- or 384-well plates and exposure of embryos while still in the chorion, a barrier of poorly characterized permeability enclosing the developing embryo. We report the automated dechorionation of 1600 embryos at once at 4 h postfertilization (hpf) and placement of the dechorionated embryos into 96-well plates for exposure by 6 hpf. The process removed ≥95% of the embryos from their chorions with 2% embryo mortality by 24 hpf, and 2% of the embryos malformed at 120 hpf. The robotic embryo placement allocated 6-hpf embryos to 94.7% ± 4.2% of the wells in multiple 96-well trials. The rate of embryo mortality was 2.8% (43 of 1536) from robotic handling, the rate of missed wells was 1.2% (18 of 1536), and the frequency of multipicks was <0.1%. Embryo malformations observed at 24 hpf occurred nearly twice as frequently from robotic handling (16 of 864; 1.9%) as from manual pipetting (9 of 864; 1%). There was no statistical difference between the success of performing the embryo placement robotically or manually.     

Thawing of lamb loin chops in air and CO(2). Effect on colour and drip

Colour retention and drip loss was assessed during retail display for chilled lamb chops displayed fresh or stored in CO(2) for 7 weeks before display, and for chops frozen for various times and thawed in air or CO(2). A sensory panel found fresh lamb chops to have an acceptable display life of 1 day, while chops which had been frozen for 1 day and then thawed lasted 2 days. Holding chops for 7 weeks in a CO(2) atmosphere at - 1·5°C improved display life to 3 days, but frozen chops held for 7 weeks before thawing had deteriorated in colour, and only one group was acceptable on the initial day of display. Initially there were no differences in Hunter L values (brightness) due to treatment, but chilled chops or those frozen for 1 day showed a greater increase in L values by the second day than those frozen for 7 weeks, after which there was no change in brightness. Hunter a values (redness) were higher in chilled chops and those thawed after 1 day's frozen storage than those frozen for 7 weeks before thawing. Hunter b values (yellowness) were greater at all times in chilled chops held for 7 weeks and varied amongst the other treatments. The measured per cent drip from chops frozen for only 1 day was greater on thawing than drip from chops frozen for 7 weeks before thawing. Drip during display, assessed by a sensory panel, increased more in those chops stored either chilled or frozen for 7 weeks before display.     

Effect of tray liners on the drip loss of lamb chops during retail display

The amount of drip lost by lamb chops during display was affected by the type of tray liner used. In one study involving chilled and frozen/thawed meat, the use of an absorbent paper liner increased the drip loss and influenced whether or not the quantity of drip was affected by freezing/thawing. In another study, thawed chops held for 24 h on plastic coated trays without liner or on a plastic coated liner had less than 2% drip loss, whereas adjacent chops from the same loin processed and held in the same way but displayed on liners of absorbent paper or paper pouches of diatomaceous earth lost 4·3% and 5·6% drip, respectively. This effect of the material in contact with the meat should be considered when reporting drip loss data and when comparing results with those of other researchers.     

Development and validation of a Monte Carlo simulation of photon transport in an Anger camera

The geometric component of the point spread function (PSF) of a gamma camera collimator can be determined analytically, and the penetration component can be calculated readily by numerical ray-tracing. A Monte Carlo simulation of photon transport which includes collimator scatter is developed. The simulation was implemented with an array processor which propagates up to 1024 photons in parallel, allowing accurate estimates of the total radial PSF in less than a day. The simulation was tested by imaging monoenergetic point sources of Tc-99m, Cr-51, and Sr-85 (140, 320, and 514 keV, respectively) on a General Electric Star Cam with low-energy, general-purpose, and medium-energy collimators. Comparisons of measured and simulated PSFs demonstrate the validity of the model and the significance of collimator scatter in the degradation of image quality.     

Combining teacher-Led and technology-assisted instruction to improve phoneme blending to read words for elementary students with disabilities

Technology-assisted instruction has potential for helping students improve their reading skills. In the current studies, PowerPoint software was used to supplement teacher-led reading instruction for elementary-aged students with disabilities who struggled with phoneme blending to read words. The effectiveness of the intervention was assessed using two multiple probe design studies across sets of words based on an onset-rime (word family) strategy. In Study 1, teacher-led instruction was paired with technology-assisted instruction for all intervention sessions for three students in first and second grade. In Study 2, teacher-led instruction occurred between baseline and technology-assisted intervention sessions for three students in third and fourth grade. During the initial instruction sessions, participants recorded their own voices onto PowerPoint slides so that their technology-assisted instruction included self-modelling. Results of both studies indicated that technology-assisted instruction can be effective for helping students learn how to blend phonemes to read words; however, performance varied and there were limitations in each study that should be addressed in future research. Relevant implications for classroom instruction are emphasized.     

VPR-Bench: An Open-Source Visual Place Recognition Evaluation Framework with Quantifiable Viewpoint and Appearance Change

International Journal of Computer Vision - Visual place recognition (VPR) is the process of recognising a previously visited place using visual information, often under varying appearance...