Experiments on the nature of the signal that induces spinal neuroplastic changes following a peripheral lesion.

This study aimed at identifying the signal(s) that elicit myositis-induced neuroplastic changes in background activity and responsiveness of spinal neurones. It is based on previous data suggesting that in dorsal horn neurones, responsiveness to peripheral input on one hand and background activity on the other are probably controlled by different mechanisms. In anaesthetized rats, myositis was induced in the gastrocnemius-soleus muscle and the activity of single dorsal horn neurones was recorded in segment L3. Impulse traffic and axoplasmatic transport in dorsal roots L4 and L5 were selectively blocked by lignocaine or vinblastine for various time periods relative to the induction of the myositis. The results show that the main triggering signal for the myositis-induced changes in both responsiveness and background activity is the altered impulse activity in primary afferent fibres. In contrast, 'no axonally transported chemical signal controlling the discharge behaviour of dorsal horn neurones was found. However, the time course of the electrical signals that cause the myositis-induced changes in background activity and responsiveness is different. For changes in responsiveness, a rather narrow time window of 2 h directly after induction of the myositis existed, during which the impulses from the inflamed muscle must reach the spinal cord. Accordingly, to prevent the increase in responsiveness, the electrical input had to be blocked during the first 2 h; a block of the same duration at another time had no effect. The change in background activity seems to be due to a continuous input from the inflamed muscle which adds up over the hours. Therefore, with regard to background activity, blocking the electrical signals is effective at any time, but only a block of long duration has a significant effect.     

The human major histocompatibility complex class Ib molecule HLA-E binds signal sequence-derived peptides with primary anchor residues at positions 2 and 9

Human histocompatibility leukocyte antigen E (HLA-E) and mouse major histocompatibility complex (MHC) class Ib antigen, Qa-1, share the same substitutions at two normally conserved positions 143 and 147, which are likely to affect binding of the C terminus of peptides. Qa-1 is able to bind a peptide derived from the leader sequence of H-2 D and H-2 L molecules. We developed a peptide binding assay in vitro to compare the binding specificity of HLA-E with the mouse MHC class Ib molecule Qa-1. We demonstrate that HLA-E binds, although poorly, the peptide which binds to Qa-1 and that it also binds nonamer signal sequence-derived peptides from human MHC class I molecules. Using alanine and glycine substitutions, we could define primary anchor residues at positions 2 and 9 and secondary anchor residues at position 7 and possibly 3.     

On the Limitations of Therapy Manuals

While the benefits of training manuals can hardly be questioned, they are exceedingly limited in reducing variability attributed to the "therapist factor." We propose that manuals provide a useful outline of the general principles of a therapeutic approach, but can only reduce therapist variability at the expense of other essential therapeutic phenomena. Manuals cannot adequately convey, for example, how the effective therapist functions as a model of adult living and as a person who provides guidance. We suggest that such an experience cannot readily be packaged in manualized form, though manuals may serve as a useful beginning. Recommendations for therapist manualized training include greater attention to the subtleties of human relationships and adequately conveying that any technique is effective only when catalysed by a living, relational process.     

Early and Late Results of the Self-Expanding Nitinol Stents: Interim Report from a Multicenter European Study

The experimental and clinical results of the self-expanding nitinol coil stent have been reviewed. Animal data have shown that the stent is safe and provokes a mild proliferative response, similar to previously studied balloon-expandable stents. Data from femoral and popliteal arteries are supportive of long-term patency in these arteries, which are typically associated with unfavorable results from other stents. Data from coronary implantations in patients show that the stent can be safely used to treat coronary lesions of both simple and complex natures. Long-term results of these patients compare favorably with existing data in similar lesions using other stents. A larger clinical trial using the new flat wire design stent is required to test whether further stent expansion may contribute to low restenosis rates.     

Measurement properties of quantitative urine benzoylecgonine in clinical trials research

Psychometric data are presented which examine the validity of using the concentration of benzoylecgonine in urine, a major metabolite of cocaine, as a measure of drug use, in studies of drug abuse treatments. In such research the standard biological indicator of drug use is usually a qualitative urine drug test, which merely indicates the presence or absence of a drug or its metabolite. A quantitative (i.e. continuous) outcome measure, such as the concentration of a drug or its metabolite in a biological fluid, has substantially more statistical power than a dichotomous measure and should, therefore, prove a more sensitive measure of drug use when viewed from a measurement perspective. Data from two placebo-controlled clinical trials of fluoxetine as an adjunct to treatment for cocaine abuse are analyzed to address this issue. Results indicate that urine benzoylecgonine level is closely related to self-reports of drug use and is independent of levels of anxiety, depression and hopelessness.