Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists

The resolution of three 2-substituted derivatives of idazoxan is described. The enantiomers show large separations in activity in a variety of in vitro and in vivo tests, and the active isomers are all potent and selective antagonists at the alpha 2-adrenoreceptor. The significance of these results in relation to those published on the enantiomers of idazoxan and to those on optically active alpha 2-adrenoreceptor agonists is discussed.     

Synthesis of estradiol haptens

Synthesis of Estradiol Haptens Two estradiol haptens, 4-(3β,17β-dihydroxyestran-7α-yl)butanoic acid ( 9 ) and 7α-(4-aminobutyl)-3β,17β-estradiols ( 13 ), were prepared from 19-nortestosterone by partial synthesis. The binding activity for the cytosol estrogen receptor was determined by competition against [³H]-estradiol; at a concentration of 2×10^?7mol/l, compound 9 displaces 50% of [³H]-estradiol. Attached to AH-Sepharose 4B compound 9 allows the cytosol estrogen receptor from calf uterus to be concentrated 1800-fold by affinity chromatography.     

Telephone dissatisfaction in pediatric practice: Denver and Baltimore

A survey of pediatricians in private practice in the Denver and Baltimore metropolitan areas was conducted to assess pediatricians' satisfaction with the telephone in their practices. The response rates were 84% (89/106) in Denver and 72% (90/125) in Baltimore. In both cities, 42% of the physicians were dissatisfied with their telephone systems. Dissatisfied physicians were less likely to provide a morning telephone hour (P less than .02), less likely to delegate calls to office staff (P less than .01), more likely to believe that they lacked sufficient time to handle daytime calls (P less than .0001), and more likely to be in group rather than solo practice (P less than .05). Younger age of the respondent approached, but did not reach, statistical significance in its association with dissatisfaction.     

Practical value of a new serum digitoxin assay

The purpose of this study was to evaluate a new fluorescence polarization immunoassay, TDx, for digitoxin by comparing the results of this assay with those of a radioimmunoassay (RIA). Thirty-three serum samples were obtained from 15 patients during, and for 4 weeks after, a 4-week course of digitoxin therapy. Each sample was separated by centrifugation, coded, and frozen until analysis. At the time of analysis, each sample was divided and analyzed simultaneously by TDx and RIA. Nine samples yielded results less than 2 ng/ml (limit of assay sensitivity) by one or both methods and were excluded from further data analysis. Linear regression analysis of the results of the remaining 24 paired samples (x = TDx, y = RIA) revealed a strong correlation coefficient of r2 = 0.95, slope = 0.95, and a y intercept of -0.99 (y = -0.99 + 0.95x). Additionally, the TDx results were lower than the RIA values in only five of 33 paired samples; and these occurred in four patients who had a significantly lower mean estimated creatinine clearance than that of the other 11 patients (39.0 +/- 9.1 ml/min/1.73 m2 vs. 63.3 +/- 11.8 ml/min/1.73 m2, p less than 0.01). The TDx system is a comparable alternative to the RIA method, but differences in specificity and sensitivity may exist and should be evaluated more thoroughly.     

Ultrastructural observations of organelle accumulation in the equine recurrent laryngeal nerve

Summary The left recurrent laryngeal nerves from five horses with sub-clinical neuropathy were examined by light and electron microscopy in a study designed to examine accumulation of axonal organelles at paranodal and internodal locations. Transverse sections of the nerve showed scattered fibres with split myelin sheaths and axonal accumulation of organelles. On longitudinal sections these collections were seen to result from an axonal outpouching in which dense lamellar bodies and mitochondria had accumulated. These paranodal collections, which could be found on both sides of the node, were often associated with infoldings of the terminal loops of myelin and with occasional paranodal demyelination. The fact that many of the organelles in the outpouches were lysosomal in nature was confirmed by their positive staining for cathepsin D activity. Longitudinal sections demonstrated a number of axons which were swollen over a long distance and which contained focal accumulations of similar organelles. In places, however, there was a clear separation between these organelles and the cytoskeletal proteins. In each case these swollen axons were surrounded by Schwann cell nuclei and their processes, forming well-ordered onion bulbs. The possibility that these two types of changes, i.e. the paranodal accumulations and the axonal swellings could result from a disturbance in axonal transport in this distal axonopathy is discussed.