Receptor affinity and pharmacological potency of a series of narcotic analgesic, anti-diarrheal and neuroleptic drugs.

A series of 26 drugs was tested for in vitro binding to opiate receptors in the presence and absence of 0.1 M NaCl. The results were correlated with assays for in vivo pharmacological potency. Highly significant correlation was found between binding in the presence and absence of sodium ions and analgesic potency. For 10 drugs tested for anti-diarrheal potency significant correlation was observed with binding to brain opiate receptors when binding was carried out in sodium-containing medium. These data add support to the hypothesis that stereospecific opiate binding sites are pharmacological receptors which mediate analgesia and anti-diarrheal action. We found that neuroleptics can bind to opiate receptors with affinities in the micromolar range, in agreement with reports by others. The anti-diarrheal compound loperamide exhibits no significant central opiate effects but binds to opiate receptors from brain in vitro with high affinity. Evidency is presented suggesting that the lack of specific analgesic effect is the result of poor penetration through the blood--brain barrier. Our results lend further support to the similarity of opiate receptors in the brain and in the intestinal tract.     

Proteinases in inflammatory demyelinating disease

Conclusion Proteinases are likely to be involved in the generation of the immune response and the tissue injury found in inflammatory demyelination of the CNS and PNS. The mechanisms whereby proteinases effect changes in these disorders are imprecisely understood but may be important in terms of understanding susceptibility, the extent of tissue damage, and possibly as an avenue for therapeutically controlling the disease by inhibition of proteinases. Several recent observations on the role of proteinases in the immune response for antigen processing, B cell activation, production of selected peptides which may have autosensitization potential and in the cytotoxic damage of tissue indicate the importance which proteinases, acting alone, in sequence, or in combination, may have in inflammatory demyelination.     

Gender differences in respiratory, nasal and skin symptoms: 6-7 versus 13-14-year-old children

ISAAC questionnaires were completed by the parents of 6432 children, aged 6-7 y and by themselves by 2864 children 13-14-y-old. Prevalence rates of respiratory and nasal symptoms and a diagnosis of asthma and hay fever were higher in 6-7-y-old boys than in girls, while girls aged 13-14 y had higher rates for most symptoms, except asthma. Underdiagnosis of asthma in 13-14-y-old girls cannot be excluded as an explanation, but our data suggest under-reporting of respiratory and nasal symptoms in 13-14-y-old boys.     

Marden-Walker-like syndrome without psychomotor retardation: Report of a Brazilian girl born to consanguineous parents

We report on a Brazilian girl, born to consanguineous parents and presenting a multiple congenital anomaly (MCA) syndrome, mainly characterized by blepharophimosis, cleft palate, and arachnodactyly. The clinical aspects involving this patient suggest an apparently undescribed “new” autosomal recessive syndrome.     

Performance of the dynamic single photon emission computed tomography (dSPECT) method for decreasing or increasing activity changes

Radionuclide imaging is now widely used whenever functional information is required. We present a new approach to dynamic SPECT imaging (dSPECT method) that uses a single slow rotation of a conventional camera and allows us to reconstruct a series of 3D images corresponding to the radiotracer distribution in the body at various times. Using simulations of various camera configurations and acquisition protocols, we have shown that this method is able to reconstruct washout half-lives with an accuracy greater than 90% when used with triple-head SPECT cameras. Accuracy decreases when using fewer camera heads, but dual-head geometries still give an accuracy greater than 80% for short and 90% for long half-lives and about 50-75% for single-head systems. Dynamic phantom experiments have yielded similar results. Presence of attenuation and background activity does not affect the accuracy of the dSPECT reconstructions. In all situations investigated satisfactory dynamic images were produced. A preliminary normal volunteer study measuring renal function was performed. The reconstructed dynamic images may be presented as a three-dimensional movie showing movement of the tracer through the kidneys and the measurement of the regional renal function can be performed. The time-activity curves determined from this dSPECT data are very similar to those obtained from dynamic planar scans.     

Measurement of passive ankle stiffness in subjects with chronic hemiparesis using a novel ankle robot

Our objective in this study was to assess passive mechanical stiffness in the ankle of chronic hemiparetic stroke survivors and to compare it with those of healthy young and older (age-matched) individuals. Given the importance of the ankle during locomotion, an accurate estimate of passive ankle stiffness would be valuable for locomotor rehabilitation, potentially providing a measure of recovery and a quantitative basis to design treatment protocols. Using a novel ankle robot, we characterized passive ankle stiffness both in sagittal and in frontal planes by applying perturbations to the ankle joint over the entire range of motion with subjects in a relaxed state. We found that passive stiffness of the affected ankle joint was significantly higher in chronic stroke survivors than in healthy adults of a similar cohort, both in the sagittal as well as frontal plane of movement, in three out of four directions tested with indistinguishable stiffness values in plantarflexion direction. Our findings are comparable to the literature, thus indicating its plausibility, and, to our knowledge, report for the first time passive stiffness in the frontal plane for persons with chronic stroke and older healthy adults.     

Effect of gravity on robot-assisted motor training after chronic stroke: a randomized trial

Conroy SS, Whitall J, Dipietro L, Jones-Lush LM, Zhan M, Finley MA, Wittenberg GF, Krebs HI, Bever CT. Effect of gravity on robot-assisted motor training after chronic stroke: a randomized trial.ObjectivesTo determine the efficacy of 2 distinct 6-week robot-assisted reaching programs compared with an intensive conventional arm exercise program (ICAE) for chronic, stroke-related upper-extremity (UE) impairment. To examine whether the addition of robot-assisted training out of the horizontal plane leads to improved outcomes.DesignRandomized controlled trial, single-blinded, with 12-week follow-up.SettingResearch setting in a large medical center.ParticipantsAdults (N=62) with chronic, stroke-related arm weakness stratified by impairment severity using baseline UE motor assessments.InterventionsSixty minutes, 3 times a week for 6 weeks of robot-assisted planar reaching (gravity compensated), combined planar with vertical robot-assisted reaching, or intensive conventional arm exercise program.Main Outcome MeasureUE Fugl-Meyer Assessment (FMA) mean change from baseline to final training.ResultsAll groups showed modest gains in the FMA from baseline to final with no significant between group differences. Most change occurred in the planar robot group (mean change ± SD, 2.94±0.77; 95% confidence interval [CI], 1.40–4.47). Participants with greater motor impairment (n=41) demonstrated a larger difference in response (mean change ± SD, 2.29±0.72; 95% CI, 0.85–3.72) for planar robot-assisted exercise compared with the intensive conventional arm exercise program (mean change ± SD, 0.43±0.72; 95% CI, –1.00 to 1.86).ConclusionsChronic UE deficits because of stroke are responsive to intensive motor task training. However, training outside the horizontal plane in a gravity present environment using a combination of vertical with planar robots was not superior to training with the planar robot alone.