Concentration-response relationships for adenosine agonists during preconditioning of rabbit cardiomyocytes

Although adenosine receptors have been implicated in the induction of preconditioning in a variety of experimental models, there is controversy concerning the specific adenosine receptor subtypes mediating this effect. Concentration-protection relationships for adenosine and adenosine agonists in rabbit cardiomyocytes were used to characterize the role of adenosine receptor subtypes in preconditioning. Isolated cells were ischemically preconditioned or pre-incubated for 10 min with increasing concentrations of adenosine, CCPA (2-chloro-N6-cyclopentyladenosine), APNEA (N6-2-(4-aminophenyl)ethyladenosine), or BNECA (N6-benzyl-5'-N-ethyl-carboxamidoadenosine) in the presence or absence of 1 or 10 microM of the selective A1-adenosine antagonist DPCPX (8-Cyclopentyl-1,3-dipropylxanthine). Following a 30-min post-incubation period, cells were pelleted, layered with oil and ischemically incubated for 180 min. Injury was assessed by osmotic swelling and trypan blue exclusion of sequential samples, and determination of the areas beneath the mortality curves. Adenosine produced a broad concentration-protection curve which was displaced to the right by DPCPX. The curve for A1-selective agonist CCPA was biphasic, with an initial response below 1 nM and a second above 1 microM. DPCPX abolished the early response leaving a steep monophasic curve between 0.1 and 10 microM CCPA. The APNEA curve appeared moriophasic, the major slope occurring between 1-100 nM; DPCPX (1 microM) shifted the concentration-response curve approximately 30-fold and decreased the slope. Adenosine receptor agonist BNECA produced preconditioning characterized by a shallow monophasic concentration-protection curve with a maximal effect of 49% and an EC50 of approximately 5 nM; DPCPX shifted the BNECA concentration-protection relationship approximately 40-fold with only a modest increase in slope. Analysis of the data suggests that induction of preconditioning results from interaction of agonists with the A1 receptor and a second adenosine receptor having properties consistent with the A3 receptor. Adenosine, CCPA, APNEA, BNECA and DPCPX each appear to be selective for the A1 adenosine receptor subtype in isolated rabbit cardiomyocytes.     

Priapism: etiology and management

Priapism is a urologic emergency. All patients should receive prompt urologic consultation. Management is based on prompt recognition, differentiation between low- and high-flow priapism, reversal of any potential precipitating factors, and the use of corporal aspiration/irrigation combined with intracavernosal alpha-agonist injection therapy. It cannot be over-emphasized that severely prolonged erections are associated with the development of irreversible problems with erectile function and, therefore, immediate and aggressive management is mandatory.     

Image compression in digital mammography: effects on computerized detection of subtle microcalcifications

Our previous receiver operating characteristic (ROC) study indicated that the detection accuracy of microcalcifications by radiologists is significantly reduced if mammograms are digitized at 0.1 mm x 0.1 mm. Our recent study also showed that detection accuracy by computer decreases as the pixel size increases from 0.035 mm x 0.035 mm. It is evident that very large matrix sizes have to be used for digitizing mammograms in order to preserve the information in the image. Efficient compression techniques will be needed to facilitate communication and archiving of digital mammograms. In this study, we evaluated two compression techniques: full frame discrete cosine transform (DCT) with entropy coding and Laplacian pyramid hierarchical coding (LPHC). The dependence of their efficiency on the compression parameters was investigated. The techniques were compared in terms of the trade-off between the bit rate and the detection accuracy of subtle microcalcifications by an automated detection algorithm. The mean-square errors in the reconstructed images were determined and the visual quality of the error images was examined. It was found that with the LPHC method, the highest compression ratio achieved without a significant degradation in the detectability was 3.6:1. The full frame DCT method with entropy coding provided a higher compression efficiency of 9.6:1 at comparable detection accuracy. The mean-square errors did not correlate with the detection accuracy of the microcalcifications. This study demonstrated the importance of determining the quality of the decompressed images by the specific requirements of the task for which the decompressed images are to be used. Further investigation is needed for selection of optimal compression technique for digital mammograms.     

Resurgence of derived stimulus relations

Resurgence has been shown in human and nonhuman operant behavior, but not in derived relational responses. The present study examined this issue. Twenty-three undergraduates were trained to make conditional discriminations in a three-choice matching-to-sample paradigm. The training resulted in three equivalence classes, each consisting of four arbitrarily configured visual stimuli. The same 12 stimuli were then reorganized, and the conditional discrimination training was repeated such that three new classes were possible. In a subsequent test of derived relations, most subjects showed response patterns that were consistent with the altered conditional discriminations. Subjects were then exposed to conditional discrimination trials under extinction. Most subjects continued to respond consistently with the most recently reinforced conditional discrimination trials. During the next phase, subjects were exposed to symmetry and equivalence trials. Responses consistent with the most recent training produced feedback saying that the responses were incorrect, whereas other responses produced no feedback. Most subjects showed a resurgence of responding that was consistent with their earlier training. Finally, subjects were exposed to conditional discrimination trials carried out in extinction. Most subjects continued to show a resurgence of responding that was consistent with their early training.     

A model to assess the effectiveness of topical antipruritics

A model has been developed to determine the effectiveness of topical antipruritics. It utilizes controlled, experimentally induced itch and has demonstrated the effectiveness of the direct action on cutaneous receptor sites of a topical anesthetic, benzocaine, in a topical antipruritic formulation, and has been used to differentiate between two effective topical antipruritics. Three studies are presented: The first study examined the reliability of the experimentally induced itch. Several indices of reliability were computed from the data of this first study. Cronbach's alpha was 0.92. Winer's theta also was 0.92. Simple test-retest reliability, computed at intervals of 29 min, 1 day, and 6-7 days, resulted in Pearson correlations of 0.84, 0.73, and 0.60, respectively. In the second study, the model differentiated statistically between the itch relief resulting from the topical application of a formulation with 6% benzocaine and the same formulation without benzocaine. The third study examined 2 known topical antipruritics: one containing 6% benzocaine and the other 1% hydrocortisone. Both topical antipruritics were found to relieve itch; however, the benzocaine antipruritic produced statistically significantly greater itch relief in more subjects than the hydrocortisone antipruritic at both 1 and 30 min after application. These results demonstrate that OTC antipruritics can be differentiated for effectiveness.     

Confirmatory factor analysis of the Wechsler Memory Scale-Revised in a sample of clients with alcohol dependency

Previous analyses of the Wechsler Memory Scale-Revised (WMS-R; Wechsler, 1987) have reported one-, two-, and three-factor solutions and raised questions about the validity of the visual memory subtests. These various findings may stem in part from different methods of analysis, and from the study of different participant samples. To address these issues, we analysed data from the WMS-R and a spatial maze test administered to 154 participants with a history of alcohol dependence. Results from confirmatory factor analysis supported the interpretation of three factors underlying the WMS-R subtests and the spatial maze score in this sample, namely, attention-concentration, immediate memory, and delayed recall. This result held despite the inclusion of the maze score which is a well-validated measure of visuo-spatial memory.     

p53 expression in neurofibroma and malignant peripheral nerve sheath tumor. An immunohistochemical study of sporadic and NF1-associated tumors

OBJECTIVES--(1) to evaluate regional cerebral blood flow (rCBF) with single photon emission computed tomography and 99mTc-hexamethylpropyleneamine oxime in patients with the idiopathic adult hydrocephalus syndrome (IAHS); (2) to examine regional cerebral blood flow (rCBF), gait, and psychometric functions before and after CSF removal (CSF tap test); (3) to assess abnormalities in subcortical white matter by MRI. METHODS--Thirty one patients fulfilling the criteria for IAHS (according to history and clinical and neuroradiological examination) were studied. Quantified gait measurements, psychometric testing, and rCBF before and after removal of CSF were obtained. Pressure of CSF and CSF outflow conductance were investigated with a constant pressure infusion method. Brain MRI was used to quantify the severity of white matter lesions and periventricular hyperintensities. In IAHS a widespread rCBF hypoperfusion pattern was depicted, with a caudal frontal and temporal grey matter and subcortical white matter reduction of rCBF as the dominant feature. Removal of CSF was not accompanied by a concomitant increase in rCBF. Significant white matter lesions were detected only in a minority of patients by MRI. An altered CSF hydrodynamic state with a higher CSF pressure and lower conductance was confirmed. IAHS is characterised by an abnormal CSF hydrodynamic state, associated with a widespread rCBF reduction with preference for subcortical white matter and frontal-temporal cortical regions. Furthermore in most patients MRI did not show white matter changes suggestive of a coexistent subcortical arteriosclerotic encephalopathy. At least in the idiopathic group of patients with AHS, measurements of rCBF before and after temporary relief of the CSF hydrodynamic disturbance will not provide additional information that would be helpful in the preoperative evaluation but is suggestive of a preserved autoregulation of rCBF.     

Estimating confidence intervals for cost-effectiveness ratios: an example from a randomized trial

Cost-effectiveness ratios usually appear as point estimates without confidence intervals, since the numerator and denominator are both stochastic and one cannot estimate the variance of the estimator exactly. The recent literature, however, stresses the importance of presenting confidence intervals for cost-effectiveness ratios in the analysis of health care programmes. This paper compares the use of several methods to obtain confidence intervals for the cost-effectiveness of a randomized intervention to increase the use of Medicaid's Early and Periodic Screening, Diagnosis and Treatment (EPSDT) programme. Comparisons of the intervals show that methods that account for skewness in the distribution of the ratio estimator may be substantially preferable in practice to methods that assume the cost-effectiveness ratio estimator is normally distributed. We show that non-parametric bootstrap methods that are mathematically less complex but computationally more rigorous result in confidence intervals that are similar to the intervals from a parametric method that adjusts for skewness in the distribution of the ratio. The analyses also show that the modest sample sizes needed to detect statistically significant effects in a randomized trial may result in confidence intervals for estimates of cost-effectiveness that are much wider than the boundaries obtained from deterministic sensitivity analyses.