Recent Publications by CFE Educators

In previous studies we reported that although morphine dose dependently inhibits noxious stimulus-evoked expression of the c-fos proto-oncogene in the rat spinal cord, morphine was without effect in certain populations of presumed nociresponsive neurons, even under conditions of complete behavioral analgesia. To determine whether the neurons that continue to express the c-fos gene include projection neurons, we evaluated the effect of morphine on noxious stimulus-evoked c-fos expression in spinoparabrachial neurons retrogradely labeled with Fluoro-gold. In the formalin test, we found that morphine analgesia was associated with a significant reduction in the number of Fos-like-immunoreactive spinoparabrachial projection neurons in the lateral reticulated area of the neck of the dorsal horn. Morphine, however, did not reduce the number of Fos-like-immunoreactive spinoparabrachial projection neurons either in the superficial dorsal horn or in the area around the central canal. These results indicate that under conditions of morphine analgesia two distinct populations of spinoparabrachial neurons can be recognized on the basis of their expression of the c-fos gene in response to noxious stimulation. Since the expression of the c-fos gene has been correlated with neuronal activity, these data suggest that activity, and central transmission of nociceptive information, persists in certain nociresponsive projection neurons during morphine analgesia. Alternatively, if activity has, in fact, been blocked in these neurons, our results indicate that injury can produce significant molecular changes in neurons even though the neuronal activity and pain associated with the injury is blocked by morphine.

Teaching in response to case presentations is an essential feature of clinical teaching in medicine. Yet, this form of case-based teaching is often done poorly. Using qualitative methods of interviews, observations, and recordings of teaching rounds, the author describes three different yet exemplary pedagogical strategies for organizing teaching rounds in general internal medicine. These include: (1) case-bedside teaching that involves case discussion in a conference room followed by demonstrations at the bedside, (2) case-lecture teaching that blends quick reviews of cases with more formal presentations on relevant topics, and (3) case-iterative teaching that involves discovery-learning using complex cases. From these three case studies, five general principles of experiential learning in clinical settings are derived: anchoring instruction in cases, actively involving learners, modeling professional thinking and action, providing direction and feedback, and creating a collaborative learning environment. These three approaches to teaching rounds overcome common problems associated with learning in clinical settings.

Sarcoidosis is a systemic granulomatous disease of unknown etiology in which CD4+ T cells seem to be critically involved. In the lungs of patients with pulmonary disease, CD4+ T cells accumulate in large numbers, and a subset of these cells is activated. By using both quantitative PCR and anti-V beta mAbs, we analyzed the TCR repertoire of total and activated bronchoalveolar lavage T cells, the latter subset being defined by the ability to proliferate in short-term culture supplemented with IL-2. Overall, there was little difference when TCR V beta expression of freshly isolated lung and peripheral blood cells was compared in individual patients. Some individuals did demonstrate a modest increase in a few V beta-expressing subsets. However, after 1 to 2 wk of in vitro growth in IL-2-supplemented media, bronchoalveolar lavage cells from most patients, but not from any healthy individuals, demonstrated a selective expansion of particular V beta-expressing subsets. Interestingly, different V beta-bearing subsets were expanded in different patients. Junctional region sequencing indicated that the proliferating T cells in culture were strikingly oligoclonal and were derived from T cell clones already selectively expanded in vivo. These results provide evidence for a disease process that involves recognition of local Ag(s) by specific subsets of CD4+ T cells. Analysis of the Ag specificity of these IL-2-expanded populations is likely to provide insight into the pathogenesis of this disease.

PURPOSE

To review the historical evolution and rationale for the development of new techniques of cardiopulmonary resuscitation (CPR).

DATA SOURCES

English-language studies published after 1960 were identified by computer and manual search using MEDLINE and Index Medicus. Historical references were obtained through a HISTLINE search. Additional information was acquired from personal files and bibliographies of existing literature.

STUDY SELECTION

Critical review with emphasis on study size, methods, and reproducibility of results.

RESULTS

Survival after in-hospital cardiac arrest and institution of CPR is approximately 10% to 15%. Investigation of the physiology of blood flow during CPR has led to the conclusion that flow may occur because of direct cardiac compression or thoracic pump forces. Based on these observations, several new techniques of CPR have been introduced. Interposed abdominal compression, pneumatic vest, and active compression-decompression resuscitation have been shown to improve cardiopulmonary hemodynamics in animal models and humans after cardiac arrest. Only interposed abdominal compression CPR has been shown to improve long-term survival in human subjects after in-hospital cardiac arrest. Although these techniques have shown promising results in animal studies and a limited number of clinical trials, none has gained widespread use.

CONCLUSIONS

Improved methods of CPR are now available. Selective use of CPR in the hospital and community training in the use of these new adjunctive techniques should have the greatest impact on improved survival after sudden cardiac arrest.

1. Nicotine, a major active component of tobacco smoke, has been shown to modulate the inflammatory response via both peripheral and central nervous system pathways. Recently we found that spinal intrathecal administration of nicotine dose-dependently inhibits bradykinin-induced plasma extravasation (BK-induced PE) in the knee joint of the rat and that the dose-response curve for the inhibition of BK-induced PE by intrathecal nicotine is shifted to the left, by six orders of magnitude, after surgical interventions in the abdominal cavity, which might have interrupted visceral afferents to the neuraxis. Therefore we focused, in this study, on the contribution of the vagal afferents to depression of BK-induced PE by intrathecal nicotine. Furthermore, the effect of acute spinalization at the level C6-C8 was investigated. The hypothesis was that impulse activity in vagal afferents has a pronounced inhibitory effect on the modulation of BK-induced PE by intrathecal nicotine and that spinal pathways are important in mediating this effect. 2. Chronic subdiaphragmatic vagotomy and elimination of vagal afferents, by neonatal capsaicin treatment or by application of kainic acid to the nodose ganglia, enhanced the potency of intrathecal nicotine depression of BK-induced PE, by six to seven orders of magnitude when compared with the control. 3. Acute subdiaphragmatic vagotomy enhanced the potency of intrathecal nicotine-induced depression of BK-induced PE (without changing its maximum effect), by about three to four orders of magnitude when compared with the sham-operated (control) animals (with intact vagus nerves).(ABSTRACT TRUNCATED AT 250 WORDS)

The N-methyl-D-aspartate (NMDA) receptor has been implicated in a variety of systems that undergo plastic changes in the central nervous system. We used electron microscopic immunocytochemistry with an antibody directed against an alternatively spliced exon near the C terminus of NMDAR1, the essential functional subunit of the NMDA receptor, to study the distribution of the NMDA receptor in the spinal cord and CA1 region of the hippocampus, two regions where NMDA-mediated long-term plasticity has been demonstrated. In CA1, we found that the NMDA receptor is exclusively expressed on postsynaptic structures. By contrast, in the spinal cord we found that in about one-third of labeled synapses, the receptor is located in the presynaptic terminal, immediately adjacent to the vesicle release site at the active zone. Using combined postembedding immunocytochemistry, we also showed that > 70% of the NMDA receptor immunoreactive terminals are glutamate positive, which suggests that the presynaptic NMDA receptor is an autoreceptor. Nerve ligation studies demonstrated that the receptor is transported in dorsal roots and sciatic nerve to the spinal cord and periphery, respectively. These data indicate that an NMDA autoreceptor is located in terminals of primary afferent fibers, where it could facilitate the transmission of inputs to the spinal cord by increasing the release of neurotransmitter from the primary afferent terminal.