Expression of a single dopamine transporter cDNA can confer two cocaine binding sites.

Radiolabeled cocaine analogs can bind to low and high affinity sites on striatal dopamine transporters (DAT). Recently, a cDNA encoding a rat brain dopamine transporter pDAT1 has been cloned. COS cells transfected with the pDAT1 in a eukaryotic expression vector express both a high (KD = 3.4 nM) and low affinity (KD = 163.6 nM) cocaine binding sites, suggesting that both sites are provided by a single gene product.     

A classification for dry eyes following comparison of tear thinning time with Schirmer tear test.

In a double-blind study a non-invasive method of examining the stability of the precorneal tear film was used to record tear thinning time on a population of 34 independently diagnosed dry eye patients. The results were compared with those for tear output, as inferred from the standard Schirmer tear test, and a correlation coefficient of 0.20 determined. The mean tear thinning time and Schirmer results for the population sample were 6.87 +/- 2.97 sec, and 5.62 +/- 5.69 mm wetting in 5 min, respectively. From a plot of tear thinning time against Schirmer a simple classification for dry eyes can be made. A Type A with normal tear stability and low output accounting for 14.70% of the dry eyes. A Type B with low tear stability and normal output, also accounting for 14.70% of the dry eyes. A Type C with low stability (less than 9.84 sec), and low output (less than 11.31 mm wetting in 5 min) accounting for 70.60% of the dry eyes.     

A novel series of non-quaternary oxadiazoles acting as full agonists at muscarinic receptors

1 A novel series of non-quaternary oxadiazole-based muscarinic agonists demonstrated high affinity for muscarinic receptors. 2. These agonists possessed high efficacy in the nanomolar range at muscarinic receptors in the superior cervical ganglion, atrium and ileum but did not show selectivity across the tissue preparations. 3. Two amino oxadiazoles, one from a quinuclidine series (L-660,863) and one from a 1-azanorbornane series (L-670,207) possessed a high ratio of potency for displacing the binding of [3H]-N-methyl-scopolamine ([3H]-NMS) to potency for displacing the agonist [3H]-oxotremorine-M cortex. 4. The two azanorbornane derivatives L-670,548 and L-670,207 stimulated the turnover of phosphatidylinositol in the cortex with a potency higher than that obtained with any other known muscarinic agonist (ED50 0.26 and 0.18 microM respectively). 5. The maximum response obtained with L-670,207 was greater than that observed for carbachol but was comparable to that of the natural ligand acetylcholine. 6. These oxadiazole muscarinic agonists are among the most potent and efficacious non-quaternary muscarinic agonists ever described.     

Dose duration of nebulized nedocromil sodium in exercise-induced asthma.

The dose-duration effect of nebulized nedocromil sodium was studied in ten patients with exercise-induced asthma (7 males mean (SEM) age 30.1 (3.5) yrs and predicted forced expiratory volume in one second (FEV1) 102%). All of these patients showed > 40% protection of their exercise asthma with 4 mg of nedocromil sodium delivered via metered dose inhaler. Three concentrations of nedocromil sodium (0.5, 2.5 and 10 mg.ml-1) and placebo were administered in double-blind, randomized manner. One ml of each solution was nebulized via a Wright nebulizer. Effects were assessed from the mean maximal percentage fall in FEV1 after 6-8 min treadmill exercise at 15, 135 and 255 min following each treatment and expressed as percentage protection. The mean baseline FEV1 values before and after treatments were comparable on four days of testing. Nedocromil sodium inhibited exercise-induced fall in FEV1 at all concentrations (p < 0.001) and the inhibitory effect was still present at 255 min. No differences were observed between active treatments.     

Perioperative Complications of the Agility Total Ankle Replacement in 50 Initial, Consecutive Cases

Although functional and clinical outcomes after total ankle arthroplasty have been promising, a steep learning curve has been recognized. In addition, the performance of concomitant hindfoot realignment procedures is controversial. The purpose of this study was to report on a single surgeon's experience with the first 50 total ankle arthroplasty procedures. We wanted to define the characteristics of the learning curve and whether the rate of complications was increased in patients who required complex reconstruction for preexistent foot and ankle deformities. This was a retrospective study of 50 cases with an average follow-up of 24.2 months. The patient population consisted of 18 men and 30 women with an average age of 57.6 years. Twenty-six percent of the cases had concomitant bony realignment procedures, while 20% had prior history of major hindfoot corrective procedures. There were 19 cases with intraoperative malleolar fractures, 12 cases that exhibited some degree of malalignment, and 6 cases of syndesmotic nonunion, and 8 ankles required early component revision. Minor wound complications that resolved with local wound care occurred in 9 cases, while 1 patient had a major wound complication requiring flap coverage. Each of these complications, other than wound complications, decreased with the surgeon's experience. Our results also indicate that the performance of major realignment procedures at the same time of implant arthroplasty is not associated with an increased incidence of complications. The results of this study suggest that total ankle arthroplasty is associated with a learning curve. Perioperative complications may potentially decrease with surgeon experience.