Recent Publications by CFE Educators

Monitoring the quality of well-established multisite clerkships can be aided by the use of trend analysis and graphic-oriented presentations. Five years of data on student performance, experience, and perceptions are reported for an obstetrics and gynecology clerkship offered at eight geographically dispersed sites. Of the five measures of student performance, two (final written and oral examinations) showed major changes. Trends also appeared in student participation in deliveries and student ratings of teaching over time. The results of these analyses were communicated to faculty at each site and used to make improvements in the clerkship. The implications and use of these longitudinal evaluation procedures are discussed.

Using immunocytochemistry, we have identified important differences in the distribution of immunoreactive dynorphin and enkephalin cells and terminals in the trigeminal nucleus caudalis and in the spinal dorsal horn of the cat. Dynorphin immunoreactive processes are more closely associated with those regions of cord that process nociceptive information, specifically laminae I and V. Enkephalin neurons and terminals are more widespread. Based on the staining pattern with an antiserum to the octapeptide-metenkephalin-arg-gly-leu, we suggest that the dense enkephalin terminal immunoreactivity in the inner part of the substantia gelatinosa derives from cells in lamina III. There are also significant differences in the anatomical relationship of the two opioid peptides with the organization of parasympathetic autonomic preganglionic neurons. The functional significance of these observations must await physiological analysis; nevertheless, it is almost certain that differences will be found and that these will be important in understanding the mechanisms through which exogenous opiates and a variety of descending control systems exert their effects on spinal cord neurons.

Cavitation following bland pulmonary infarction is not commonly considered in the differential diagnosis of cavitary lung disease. In a 4-year period we have found 10 cases of cavitating pulmonary infarction (CPI) by reviewing serial chest radiographs from autopsies with pulmonary infarction and in all cases with positive ventilation-perfusion lung scans. We have compared these cases to 31 previously reported cases in the English literature that met our criteria for CPI. In our 10 patients, there were 12 radiographic cavities; 5 in the upper lobes, 5 in the lower lobes and 2 in the middle lobe. This distribution was consistent with a relative upper-lobe predominance in the literature review. In nine patients the cavitation appeared rapidly (mean, 5 days) and was associated with fever, purulent sputum, and leukocytosis. Sputum cultures were obtained in eight patients, revealing Pseudomonas aeruginosa and Escherichia coli in three each and Proteus species in two. In four patients, pulmonary infarction was not considered and the diagnosis was made at autopsy, a situation also common in previously reported cases. We have seen a high incidence of CPI in a retrospective review of patients with pulmonary infarction, and we believe that it is important to consider this diagnosis when evaluating cavitary lesions.

The release of the peptide neurotransmitter substance P from the peripheral terminals of nociceptive afferent neurons and the release of catecholamines from postganglionic sympathetic efferent neurons produce physiologic changes associated with acute inflammation. The contribution of these neurogenic mechanisms to inflammatory diseases has not been determined. Activation of central neural circuits elicits similar physiologic changes, and lesions of the peripheral and central nervous system are associated with alteration in activity of inflammatory diseases. We have evaluated the contribution of neurogenic inflammation to the severity of joint injury in experimentally induced arthritis in the rat. The finding of a greater density of substance P-containing nociceptive afferents in a joint that develops more severe arthritis (ankle) suggests a role of substance P in joint injury. Direct evidence that the proinflammatory factor released from these nociceptors is substance P is provided by the finding that the injection of substance P into a joint which normally develops less severe arthritis (knee) increases the severity of arthritis in that joint. A contribution of catecholamines to the severity of joint injury was suggested by the finding that both guanethidine-induced sympathectomy and reserpine-induced depletion of catecholamines attenuated the severity of joint injury. Finally, a contribution of central neural circuits to inflammatory processes was studied in a model in which activation of nociceptive afferents elicited swelling and tenderness at a remote site. This reflex neurogenic inflammation was inhibited by intracerebroventricular injections of morphine, which also attenuated the severity of arthritis. These studies provide evidence that elements of the peripheral afferent and sympathetic efferent neurons and of descending supraspinal, opioid-mediated, circuits in the central nervous system modulate the severity of joint injury in experimental arthritis in the rat.

No current theory of the mechanisms involved in the pathophysiology of rheumatoid arthritis (RA) explains its important clinical features. We hypothesize that neural mechanisms are involved in this pathophysiology and they explain at least 3 clinical features: specific high risk joints are more likely to develop arthritis; specific high risk joints have more severe arthritis; and RA is bilaterally symmetric. If our hypothesis is correct, it will provide a rationale for the development of new therapies for what is now an inadequately treated disease.

Recent studies of the mechanism of neurogenic inflammation have focused on the contribution of neuropeptides released from peripheral terminals of primary afferent sensory neurons. In this study we addressed the contribution of humoral and neural factors to the hyperalgesia and swelling that are produced contralateral to an injured hindpaw, a phenomenon which we refer to as reflex neurogenic inflammation. The contralateral inflammatory response develops gradually, over a period of hours, and shows no tachyphylaxis with repeated application of the same stimulus. Denervation of either limb significantly attenuated the contralateral responses. Selective lesions of small-diameter, presumed nociceptive afferent fibers with capsaicin, or of sympathetic postganglionic efferents by immunosympathectomy, also reduced swelling and hyperalgesia of the uninjured paw. Interruption of venous circulation to the injured limb by vein ligation did not alter the response in the contralateral paw. Taken together, these data suggest that reflex neurogenic inflammation is neurally mediated, via connections across the spinal cord.

In this study we examined the distribution of two different endogenous opioid peptides in the nucleus of the solitary tract of the rat medulla. As a marker for immunoreactive enkephalin, we used an antiserum directed against one of the proenkephalin products, methionine enkephalin-arg-gly-leu (m-Enk). To identify immunoreactive dynorphin we used an antiserum directed against the prodynorphin product, dynorphin B (Dyn B). The PAP method was used on both colchicine and normal animals. Caudal to the obex, within the commissural nucleus, there is extensive overlap of both immunoreactive m-Enk and Dyn B terminals and cells. While the cells are morphologically similar, the immunoreactive dynorphin cells are somewhat larger. Rostral to the obex, there is a marked difference in the distribution of the two compounds. Immunoreactive m-Enk terminals are concentrated medial to the solitary tract; there is minimal staining laterally. In contrast, immunoreactive Dyn B terminals are concentrated lateral to the solitary tract. The rostral cellular distribution of the two opioid peptides follows a similar pattern. The morphology of the medially located m-Enk and laterally located Dyn B cells is also readily distinguished. The former are small, round cells with minimal dendritic labelling; the latter are larger, pyramidal neurons with prominent apical and basal dendrites. Since the medial and lateral nuclei of the solitary tract have been associated with cardiovascular and respiratory control, respectively, these data suggest that different endorphin families have different functional actions within the nucleus of the solitary tract.

Influenza A virus has been demonstrated to enhance superoxide generation and chemoluminescence (CL) in human polymorphonuclear leucoytes (PMNs) under in vitro conditions. Although the mechanisms of virus-enhanced neutrophil activity is not established, calmodulin concentrations are known to increase in some virus-transformed cells. In the following experiments, we evaluated the PMN response to the calmodulin-inhibitor trifluoperazine (TFP) after an incubation with influenza A virus. Human PMNs were isolated from whole blood and were incubated with either influenza A virus (at 50% egg-infective dose per 1 leukocyte) or noninfected allantoic fluid. After incubation with influenza virus, the CL response of isolated PMNs to opsonized zymosan particles was measured. The influenza virus-treated PMNs had a mean (+/- SEM, n = 16) increase in light emission of 59.5 +/- 7.7%. TFP, in concentrations of 6 micron, 8 micron, and 10 microM, inhibition of CL was similar in influenza virus and allantoic fluid-treated neutrophils. These data suggest that, although the influenza A virus enhanced the PMN "respiratory burst" to opsonized zymosan particles, it did not alter the cell response to one calmodulin inhibitor, TFP.