Critical appraisal of neuroprotection trials in head injury: What have we learned?

To date, despite very encouraging preclinical results, almost all phase II/III clinical neuroprotection trials in traumatic brain injury (TBI) have failed to show any consistent improvement in outcome for TBI patients. To understand the reasons behind such developments we need to review and evaluate the evolution of trial design as a result of our changing understanding of the pathophysiology of brain cell death and progress of translational research from the laboratory bench to the bedside. This paper attempts to critically appraise these neuroprotection trials, rationalize the paucity of effectiveness, review any recent developments in the field, and try to draw some conclusions on how to move forward.     

User interface paradigms for patient-specific surgical planning: lessons learned over a decade of research.

This paper covers work in virtual reality-based, patient-specific surgical planning over the past decade. It aims to comprehensively examine the user interface paradigms and system designs during that period of time and to objectively analyze their effectiveness for the task. The goal is to provide useful feedback on these interface and implementation paradigms to aid other researchers in this field. First, specialized systems for specific clinical use were produced with a limited set of visualization tools. Later, through collaboration with NASA, an immersive virtual environment was created to produce high-fidelity images for surgical simulation, but it underestimated the importance of collaboration. The next system, a networked, distributed virtual environment, provided immersion and collaboration, but the immersive paradigm was found to be of a disadvantage and the uniqueness of the framework unwieldy. A virtual model, workbench-style display was then created using a commercial package, but limitations of each were soon apparent. Finally, a specialized display, with an integrated visualization and simulation system is described and evaluated. Lessons learned include: surgical planning is an abstract process unlike surgical simulation; collaboration is important, as is stereo visualization; and that high-resolution preoperative images from standard viewpoints are desirable, but interaction is truly the key to planning.     

Endorectal surface coil MR imaging of prostatic carcinoma with the inversion-recovery sequence

The value of inversion-recovery (IR) sequences in the diagnosis and staging of prostatic carcinoma with magnetic resonance (MR) imaging was studied. Twenty-six patients with carcinoma of the prostate were imaged at 1.5 T with an endorectal surface coil and with a variety of IR sequences and a set of spin-echo (SE) sequences for comparison. Ex vivo prostate specimens were imaged again at the same field strength. The two images were correlated with histologic sections. Cancer was identified with MR imaging in 96% of patients. Of the tumors more than 4 mm in diameter, 87% were identified on T2-weighted SE images, whereas only 26% were identified on IR images. However, IR images may be more useful in local staging of carcinoma. Gross capsular infiltration was present in only two patients; however, it was detectable (and excluded in five other patients) by means of IR images. It was not detectable on SE images. The high quality of images obtained with the endorectal coil was confirmed. The authors conclude that addition of the IR sequence to MR imaging with the endorectal coil may improve the usefulness of this examination.     

Regulation of adrenal chromaffin cell development by the central monoaminergic system: differential control of norepinephrine and epinephrine levels and secretory responses

In the mature rat, reflex sympathetic stimulation by insulin-induced hypoglycemia resulted in profound depletion of adrenal epinephrine, and to a lesser extent, norepinephrine. In the developing rat, insulin evoked little or no secretory response from the adrenals prior to 1 week of age. By 7 days, a moderate depletion of epinephrine was seen and the magnitude of the response increased with age. In contrast, during the first 3 weeks of postnatal life, insulin failed to deplete norepinephrine from the adrenal medulla and in fact, produced an increase. This chiefly resulted from de novo biosynthesis of the amine, as the rise was blocked by alpha-methyl-p-tyrosine. These results suggest that the ontogeny of the two chromaffin cell types (norepinephrine and epinephrine-containing) in the adrenals and the maturation of their secretory responses are under differential regulation. Because descending supraspinal catecholaminergic and serotonergic systems have been implicated to play key roles in regulating adrenomedullary function, the ontogeny of the sympatho-adrenomedullary axis was evaluated after neonatal central lesioning with 6-hydroxydopamine or 5,7-dihydroxytryptamine. 6-Hydroxydopamine resulted in a preferential elevation of epinephrine in the developing adrenals as well as an increase in the responsiveness of the adrenals to reflex stimulation by insulin; the mature secretory pattern was obtained as early as at 4 days postnatally for epinephrine and 9 days for norepinephrine. In contrast, 5,7-dihydroxytryptamine led to a preferential reduction of basal adrenal norepinephrine content.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of antidepressant medication on sexual function: a controlled study

There has been little systematic study of the types of sexual dysfunction produced by antidepressant medication or of the frequency with which this type of adverse effect occurs. The authors report results of a double-blind study in which the effects of imipramine, phenelzine, and placebo on specific aspects of sexual function were assessed in depressed outpatients before and after 6 weeks of treatment. Both active treatments were associated with a high incidence of adverse changes in sexual function and produced significantly more adverse effects on sexual function than placebo. Orgasm and ejaculation were impaired to a greater extent than erection. Adverse sexual function changes secondary to antidepressant medication occurred frequently in both men and women, although men reported a higher incidence. Antidepressant-related sexual dysfunction may be of clinical importance for medication compliance in view of current recommendations that antidepressants be administered for longer periods as maintenance therapy or for prophylaxis.