Selectivity of LG50643 for postjunctional muscarinic-receptor subtype in the guinea-pig trachea

The effects of (+/-)-LG50643, a new N-quaternary tropinic ester of phenylcyclohexene carboxylic acid, endowed with a potent antimuscarinic activity, have been investigated on muscarinic receptor-mediated responses of the guinea-pig trachea to electrical field stimulation. An isolated preparation which allows the simultaneous measurement of tritiated acetylcholine release (prejunctional effect) and smooth muscle contraction (postjunctional effect) was used. The guinea-pig epithelium-deprived trachea was stimulated with 500 pulses (20 Hz, 1 ms, 9 V for 5 s, 30 s apart) in the presence of indomethacin (1 microM). Three successive pre- and postjunctional responses were observed. The potencies (-logEC50) of (+/-)-LG50643 for pre- and postjunctional muscarinic receptors were determined and compared with those of selective muscarinic antagonists. In addition, the affinity values of (+/-)-LG50643 for muscarinic-receptor subtypes were determined in radioligand binding experiments in cerebral cortex, heart and salivary glands of rat as target tissues for M1, M2 and M3 receptors, respectively. The results obtained in both functional and binding assays indicate (+/-)-LG50643 is a potent and selective antagonist for the M3-receptor subtype.     

Analytic physics-based expressions for the empirical parameters ofthe Statz-Pucel MESFET model

The authors present a novel approach to the evaluation of the DC parameters of a semiempirical MESFET model: starting from the analytical expression of the drain current derived from a previously proposed physics-based model, they provide a method to calculate the empirical DC parameters of the so-called Raytheon model. The comparison between computed and measured DC characteristics is quite satisfactory on GaAs microwave FETs of 1 μm or more gate length. By adding to the results obtained in this work an adequate model of the stray capacitances, the circuit performance can be optimized using the technological characteristics of active devices     

Comparative review of the adverse effects of sedatives used in children undergoing outpatient procedures

Children often fear medical procedures and interventions. Sedative agents enhance the care of these children who undergo outpatient procedures by decreasing anxiety, increasing cooperativity, and providing amnesia. Although higher dosages and intravenous administration of sedatives often produce improved sedation, adverse effects and complications are more frequent. The goals of therapeutic efficacy and safety must be balanced in all patients. The presence or anticipation of anxiety and pain helps in deciding whether to use a sedative alone, or a regimen also providing analgesia. The patient's clinical cardiorespiratory or neurological status, other relative contraindications, the duration of the intended procedure, and the presence or absence of an intravenous line will help in choosing specific drugs. Drug complications are a common cause of adverse events in patients. The combination of a sedative and analgesic, especially a benzodiazepine and an opioid given intravenously, is associated with a higher risk of serious complications. The practitioner responsible for the administration of a sedative to a child must be competent in its use and have the ability to detect and manage complications. Patients who are deeply sedated should be continuously monitored and observed by an individual dedicated to this task. Vital signs and oxygen saturation should be documented at frequent intervals and the patient should be appropriately monitored until discharge criteria have been met. The risk of serious complications with these agents may be reduced with vigorous monitoring and a judicious choice of dosage.     

Percutaneous radiologic drainage of pancreatic abscesses

OBJECTIVE: The purpose of our study was to review and report the patient selection, techniques, and results of percutaneous drainage of pancreatic abscesses by retrospective review. MATERIALS AND METHODS: Fifty-nine patients (46 men and 13 women) with a mean age of 44 years old had 80 pancreatic abscesses that were drained percutaneously under radiologic guidance (CT, n = 77; sonography, n = 2; and fluoroscopy, n = 1). Abscesses had a wide spectrum of causes, with alcoholic pancreatitis being most common, trauma second most common, and gallstones third. Ten patients had undergone surgery for pancreatic necrosis or abscess. Patients with pancreatic pseudocysts, necrosis, or acute fluid collections were excluded from this study. RESULTS: Of the 59 patients, 51 (86%) were cured with percutaneous drainage and antibiotic therapy. Of the patients who were not cured with percutaneous drainage, seven required surgery and one underwent repeat percutaneous drainage. In the 59 patients, complications included non-life-threatening bleeding in three patients. Ten of 59 patients (17%) had fistulas that spontaneously formed into the gastrointestinal tract. The duration of catheterization ranged from 4 to 119 days, with a mean duration of 33 days. The rate of mortality at 30 days after completion of percutaneous drainage was 8% (5 of 59). CONCLUSION: Percutaneous drainage was an effective therapy for this defined group of patients with pancreatic abscesses. Factors leading to the relatively high success rate described in this study likely included selection of patients; catheters of adequate size, number, and location; careful follow-up with appropriate catheter manipulations; and an integrated, cooperative approach whereby surgeons were willing to permit drainage to effect its benefits, rather than operating prematurely.     

Sensitivity analysis of TWT's small signal gain based on the effectof rod shape and dimensions

An extensive study aiming at analyzing the effect of rod shapes and dimensions on the gain of helix traveling wave tubes (TWTs) is performed. The evaluation of tube small-signal gain is obtained by making use of a rigorous field analysis which takes into account the helix tape model and the dielectric inhomogeneous loading conditions. Computing time to perform the analysis is extremely low compared with the time required in the case of a full wave, three-dimensional (3-D) electromagnetic simulator. The accuracy of the simulation approach has been extensively verified in a previous paper. A novel expression for the attenuation constant has been introduced in the model to improve the quality of results. The proposed study allows a better understanding of tube behavior before fabrication highlighting the contribution of the shape, the mechanical tolerances and the ϵ_r variation of the rods to the small-signal gain     

Tracing enteric viruses in the European berry fruit supply chain

In recent years, numerous foodborne outbreaks due to consumption of berry fruit contaminated by human enteric viruses have been reported. This European multinational study investigated possible contamination routes by monitoring the entire food chain for a panel of human and animal enteric viruses.     

The effects of reverse micelles on the reaction mechanism of alpha-chymotrypsin

Reverse micelles were employed to test the accuracy of the widely accepted mechanism for alpha-chymotrypsin in a highly structured aqueous system similar to intracellular conditions. Results yielded from spectrophotometrical assays of the alpha-chymotrypsin catalyzed hydrolysis of both p-nitrophenyl acetate (p-NPA) and p-nitrophenyl trimethylacetate (p-NPTA) were kinetically analyzed to determine constants typical of the proposed mechanistic model. This was accomplished through the establishment of a control, i.e. the well studied buffer system, for comparison between the reverse micellular environment and a bulk aqueous solution. Control group results yielded kinetic constants in favor of the proposed mechanism (Km = 1.55 x 10(-5) +/- 1.40 x 10(-6) M for p-NPA and a Km = 4.97 x 10(-6) +/- 2.29 x 10(-7) M, Km(app) = 4.92 x 10(-6) +/- 2.33 x 10(-8) M, k2 = 4.34 x 10(-3) +/- 1.31 x 10(-3), k(cat) = 1.96 x 10(-3) +/- 2.47 x 10(-4), and Ks = 1.60 x 10(-5) +/- 4.61 x 10(-6) M for p-NPTA). In contrast, similar reactions of the enzyme in a reverse micellular system produced kinetic constants atypical to that representative of the textbook mechanism. (Km = 1.59 x 10(-4) +/- 2.70 x 10(-5) M, Ks = -8.67 x 10(-5) +/- 4.46 x 10(-5) M and Km(app) = -4.80 x 10(-5) +/- 7.05 x 10(-5) M for p-NPA and Km = 1.95 x 10(-4) +/- 9.28 x 10(-5) M, Km(app) = -1.79 x 10(-4) +/- 2.36 x 10(-5) M, and Ks = -3.95 x 10(-4) +/- 1.18 x 10(-4) M for p-NPTA). In addition to negative kinetic constants, alpha-chymotrypsin seemed to display characteristics indicative of super-activity and a hysteretic response. Overall, the widely accepted mechanism for alpha-chymotrypsin appeared to fail within the confines of reverse micelles, due to the direct influence of the system's highly structured form.