Quantification of prism induced metamorphopsia as a model for clinical retinal (and other) distortions

Metamorphopsia (all causes) results in perceived distortions in the visual field. A simple technique utilizing hyperacuity judgments was developed in this laboratory some years ago to allow quantification of such distortions. We ask here, how good is this assessment method at detecting a distortion? To control better investigations of metamorphopsia, a model providing constant optical distortions and resultant perceptual metamorphopsia was devised using plane prisms of 8Δ and 15Δ. The instrument includes a beam splitter and a CRT display controlled by an IBM PC computer and a‘mouse’. In this study, three short vertical lines (perpendicular to the prism base-apex line) were used to assess image distortion in the central retinal area. Positions of individual lines of this pattern were varied in order to determine perceived distortions induced by a prism. Normal observers were tested on multiple occasions. It is possible to measure accurately prism-induced directional biases (mean locations) using this method. We separated personal setting biases from the prism-related distortions. The test method devised mimics modest clinical metamorphopsia. Prism magnitude affected settings. We were able to make judgements to less than ±2% error.     

Identification of quaternary ammonium compounds as potent inhibitors of hERG potassium channels

The human ether-a-go-go-related gene (hERG) channel, a member of a family of voltage-gated potassium (K⁺) channels, plays a critical role in the repolarization of the cardiac action potential. The reduction of hERG channel activity as a result of adverse drug effects or genetic mutations may cause QT interval prolongation and potentially leads to acquired long QT syndrome. Thus, screening for hERG channel activity is important in drug development. Cardiotoxicity associated with the inhibition of hERG channels by environmental chemicals is also a public health concern. To assess the inhibitory effects of environmental chemicals on hERG channel function, we screened the National Toxicology Program (NTP) collection of 1408 compounds by measuring thallium influx into cells through hERG channels. Seventeen compounds with hERG channel inhibition were identified with IC₅₀ potencies ranging from 0.26 to 22 μM. Twelve of these compounds were confirmed as hERG channel blockers in an automated whole cell patch clamp experiment. In addition, we investigated the structure-activity relationship of seven compounds belonging to the quaternary ammonium compound (QAC) series on hERG channel inhibition. Among four active QAC compounds, tetra-n-octylammonium bromide was the most potent with an IC₅₀ value of 260 nM in the thallium influx assay and 80 nM in the patch clamp assay. The potency of this class of hERG channel inhibitors appears to depend on the number and length of their aliphatic side-chains surrounding the charged nitrogen. Profiling environmental compound libraries for hERG channel inhibition provides information useful in prioritizing these compounds for cardiotoxicity assessment in vivo.     

Scapular dyskinesis in trapezius myalgia and intraexaminer reproducibility of clinical tests

The aims were to test the intraexaminer reproducibility and report the presence of specific clinical variables of scapular dyskinesis in cases with trapezius myalgia and healthy controls, along with general health and work ability. A total of 38 cases and 23 controls were tested for scapular dyskinesis, general health, and work ability, and 19 cases and 14 controls participated in the reproducibility study. Intraexaminer reproducibility was good to excellent for 6 of 10 clinical variables (Intraclass Correlation Coefficient [ICC] 0.76-0.91; kappa 0.84-1.00), and fair to good for four variables (ICC 0.42-0.74), test for muscular weakness having the lowest ICC (0.42). Cases showed significantly larger medial border misalignment, larger lower horizontal distance of the inferior scapular angle and larger passive shoulder internal rotation, by 110% (1.02?cm), 15% (1.38?cm), and 8% (5.5°), respectively. Cases with the highest degree of scapular dyskinesis showed reduced work ability and general health. The present specific clinical variables on scapular dyskinesis showed satisfactory intraexaminer reproducibility. An increased standardization must be implemented to increase reproducibility of tests for muscular weakness, and the interexaminer reproducibility must be tested for all variables. Finally, scapular dyskinesis in cases with trapezius myalgia must be followed longitudinally for clinical importance.     

Combinational therapy using hypothermia and the immunophilin ligand FK506 to target altered pial arteriolar reactivity,axonal damage,and blood–brain barrier dysfunction after traumatic brain injury in rat

This study evaluated the utility of combinational therapy, coupling delayed posttraumatic hypothermia with delayed FK506 administration, on altered cerebral vascular reactivity, axonal injury, and blood–brain barrier (BBB) disruption seen following traumatic brain injury (TBI). Animals were injured, subjected to various combinations of hypothermic/FK506 intervention, and equipped with cranial windows to assess pial vascular reactivity to acetylcholine. Animals were then processed with antibodies to the amyloid precursor protein and immunoglobulin G to assess axonal injury and BBB disruption, respectively. Animals were assigned to five groups: (1) sham injury plus delayed FK506, (2) TBI, (3) TBI plus delayed hypothermia, (4) TBI plus delayed FK506, and (5) TBI plus delayed hypothermia with FK506. Sham injury plus FK506 had no impact on vascular reactivity, axonal injury, or BBB disruption. Traumatic brain injury induced dramatic axonal injury and altered pial vascular reactivity, while triggering local BBB disruption. Delayed hypothermia or FK506 after TBI provided limited protection. However, TBI with combinational therapy achieved significantly enhanced vascular and axonal protection, with no BBB protection. This study shows the benefits of combinational therapy, using posttraumatic hypothermia with FK506 to attenuate important features of TBI. This suggests that hypothermia not only protects but also extends the therapeutic window for improved FK506 efficacy.     

Staged carotid endarterectomy under local anaesthetic in patients requiring cardiac surgery

INTRODUCTION

There is no clear guidance as to the management of carotid stenotic disease prior to cardiac surgery. We aimed to review the results of a single centre performing carotid endarterectomy (CEA) under local anaesthesia prior to cardiac surgery.

PATIENTS AND METHODS

All patients referred for cardiac surgery in our tertiary referral unit between January 1998 and August 2008 were identified and data relating to those 100 undergoing CEA prior to cardiac surgery were reviewed. Eighty had coronary artery bypass grafting (CABG) alone, 15 combined valve surgery and CABG and three underwent isolated valve surgery. Two patients died prior to cardiac surgery.

RESULTS

One hundred patients were prospectively identified after screening by clinical features and carotid duplex scanning to require CEA from a total of 11,394. The stroke rate was 1% between CEA and cardiac surgery, 2% following cardiac surgery and 3% in total. Ninety-eight patients proceeded to cardiac surgery (two deaths post-CEA). The cumulative event rate (stroke, myocardial infarct [included in view of the nature of the patients in our cohort] and/or death) was 10.2% following all cardiac surgery (CABG and valve). In 80 patients undergoing CABG only, the cumulative event rate was 7.5% after CABG. Including the two deaths pre-cardiac surgery, the rates were 12% and 8%. The risk of peri-operative stroke and 30-day mortality were reduced to that of patients undergoing cardiac surgery without significant carotid arterial disease, 3% versus 3.3% and 5.1% versus 6.5%, respectively.

CONCLUSIONS

This study demonstrates that a policy of selective screening for significant carotid artery disease in cardiac surgical patients combined with a strategy of CEA under local anaesthesia prior to unselected cardiac surgery (CABG with or without valve surgery) leads to rates of peri-operative CVA, myocardial infarction and death comparable to rates published for CEA prior to isolated CABG surgery. Furthermore, it reduces the risk of peri-operative stroke and 30-day mortality to that observed in patients undergoing cardiac surgery without significant carotid arterial disease.     

Marinobufagenin levels in preeclamptic patients: a preliminary report

Preeclampsia is a disorder resulting in significant fetomaternal complications with no definitive pharmacological intervention. A bufadienolide, marinobufagenin, has been implicated in the etiology of preeclampsia. We investigated both the blood and urine levels of marinobufagenin in preeclamptic and control subjects. Preeclamptic and normotensive pregnant women were recruited at various gestational age periods. Blood and urine specimens were obtained and analyzed for marinobufagenin levels and creatinine. The former determination was performed utilizing a new, novel chemifluorescent enzyme-linked immunosorbent assay. The marinobufagenin levels were higher in preeclamptics than in the controls in both serum and urine at various gestational age periods. Additionally, the mean level of marinobufagenin in the preeclamptic group was significantly greater than in controls in both blood and urine specimens ( P?相似文献   

protection by vitamin E against endothelial cell injury by linoleic acid hydroperoxides

Exposure to 90 μM albumin-bound linoleic acid (18:2) for 24 hours significantly increased the rate of albumin transfer across cultured endothelial monolayers. Linoleic acid hydroperoxides (18:2-OOH) further accelerated the rate of albumin transfer over that of 18:2. Cells exposed to 18:2-OOH but not 18:2 caused a marked release of lactate dehydrogenase (LDH) into the media. Prior cellular incubation with media containing 25 μM vitamin E for 24 hours protected endothelial cells from injury by 18:2 and 18:2-OOH, as evidenced by a decreased rate of albumin transfer across the endothelium as well as reduced release of LDH into the media. These results suggest that vitamin E may provide protection against endothelial cell injury resulting from expusure to fatty acid hydroperoxides