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.     

Robot-assisted thoracoscopic brachytherapy for lung cancer: comparison of the ZEUS robot, VATS, and manual seed implantation.

OBJECTIVE: Interstitial brachytherapy is becoming an accepted treatment option for lung cancer patients for whom surgery poses a high risk. Robotic surgery has the potential to deliver brachytherapy seeds into tumors while keeping surgeons at a safe distance from the radioactive source. Our aim was to compare the accuracy, number of attempts, and time needed to place seeds next to a target when using a manual technique, video-assisted thoracoscopic surgery (VATS), and the ZEUS robot for minimally invasive surgery (MIS). METHODS: A brachytherapy seed injector was developed and attached to one of the ZEUS robotic arms. Four subjects each inserted inactive dummy brachytherapy seeds into clear agar-gelatin cubes containing a 1.6-mm stainless steel ball target. Two orthogonal radiographs were taken of each agar cube, and the corresponding distances were measured in triplicate using ImageJ processing software. The mean distance between the center of each seed and the corresponding target was calculated using the Pythagorean theorem. Comparisons were made using analysis of variance, t-tests, and Kruskal-Wallis tests, as appropriate. RESULTS: A total of 384 tests (128 for each technique) were performed. The median accuracies for the manual technique, VATS, and ZEUS were 1.8 mm (range: 0.9-6.7 mm), 2.4 mm (range: 1.0-11.3 mm), and 3.6 mm (range: 1.3-16.7 mm), respectively (p < 0.01). The median numbers of attempts for the manual technique, VATS, and ZEUS were 1 (range: 1-5), 4 (range: 1-14), and 3 (range: 1-20), respectively (p < 0.01). The median times for the manual technique, VATS, and ZEUS were 3.0 s (range: 1-43 s), 86.5 s (range: 6-372 s), and 64.5 s (range: 5-356 s), respectively (p < 0.01). CONCLUSIONS: The manual technique is the most accurate, least traumatic, and fastest method of inserting seeds into tumors. The ZEUS robotic platform was able to place seeds beside a target within a clinically acceptable distance, with an acceptable amount of trauma and time required. It achieved results equal to or better than those obtained with VATS.     

A midface swelling in a child – A possible diagnostic dilemma

A lump on the midface of a child can pose as a diagnostic dilemma. There is a wide variety of possible differential diagnoses, ranging from simple benign conditions such as a sebaceous cyst, dermoid cyst, lipoma, neuroma and neurofibroma, to potentially devastating conditions such as odontogenic myxoma.A case of a child in which the formulation of a definite diagnosis was clinically and histologically challenging is presented.     

Noninvasive measurement of systemic vascular resistance using Doppler echocardiography.

BACKGROUND: Systemic vascular resistance (SVR) is an integral therapeutic component of patients with heart failure and shock. We hypothesized that the ratio of the peak mitral regurgitant velocity (MRV) (m/s) to left ventricular outflow time-velocity integral (TVI(LVOT)) (cm) by Doppler would provide a noninvasive correlate of SVR. METHODS: SVR was correlated to MRV/TVI(LVOT) in 33 patients undergoing right heart catheterization. Receiver operating characteristic curves were generated to determine the best-balanced sensitivity and specificity to identify SVR > 14 Wood units (WU) and <10 WU. RESULTS: MRV/TVI(LVOT) correlated well with SVR (r = 0.842, 95% confidence interval 0.7-0.92, P <.001, Y = 0.459 + 49.397*X). By receiver operating characteristics, MRV/TVI(LVOT) > 0.27 had a 70% sensitivity and a 77% specificity to identify SVR > 14 WU. MRV/TVI(LVOT) < 0.2 had a 92% sensitivity and a 88% specificity to identify SVR < 10 WU. CONCLUSION: Doppler echocardiography provides a reliable noninvasive assessment of SVR.     

A clinical procedure to predict the value of temporary occlusion therapy in keratoconjunctivitis sicca

PURPOSE: To evaluate the effects of dissolvable collagen punctal plugs on the symptoms, tear stability and volume in aqueous deficient dry eyes. METHODS: Sixty-two aqueous deficient dry eye patients of mixed aetiology underwent lacrimal punctal occlusion with dissolvable collagen plugs. The subjects were randomly allocated to one of two treatment groups: group I (n = 36) had their lower puncta occluded and group II (n = 26) had both their upper and lower puncta occluded. The effectiveness of this treatment was clinically assessed by (1). scoring subject symptoms and (2). measuring the tear parameters of tear thinning time (TTT) and tear meniscus height (TMH) as indicators of tear stability and volume, respectively. Following baseline measurements, patients were reviewed at time intervals of 5 and 12 days post-occlusion. A group of age- and gender-matched normals (n = 45) was recruited for comparison (group III). RESULTS: Tear volume and stability were significantly higher in group III compared with I and II at baseline. In the treated groups on both days 5 and 12: (1). symptom score reduced significantly from a median value of 7 to 3 (p = <0.001); (2). tear stability increased significantly from a median value of 3 to 5 s by day 5 (p 相似文献