Recent Publications by CFE Educators

Patients with idiopathic pulmonary fibrosis (IPF) are often cigarette smokers and are often being treated with corticosteroids at the time of bronchoalveolar lavage. We addressed the question of whether or not the bronchoalveolar lavage fluid (BALF) neutrophil content of patients with IPF undergoes changes in smokers different from those in nonsmokers after institution of corticosteroids. Eighteen patients were studied (10 smokers and 8 nonsmokers). Fourteen patients (6 smokers and 8 nonsmokers) were treated orally with prednisone. The histologic assessment of alveolar inflammation and inflammatory small airways disease was no different in smokers than in nonsmokers. None of the smokers treated with prednisone had pathologic evidence of emphysema in addition to IPF. Five of 6 smokers showed an increase in BALF neutrophils after 3 months of prednisone (p less than 0.05), whereas the nonsmokers' BALF neutrophils decreased or remained unchanged. This increase in BALF neutrophils in smokers was not associated with concomitant or subsequent clinical deterioration but, in fact, with clinical improvement after 3 months of therapy. These data indicate that the combination of cigarette smoking and corticosteroid therapy influences the BALF neutrophil content in patients with IPF and suggest that interval changes in BALF neutrophil content may not reflect the status of the inflammatory process or structural derangements in the lungs of some patients with IPF.

In order to develop a reproducible, quantifiable means of assessment of the clinical status of patients with idiopathic pulmonary fibrosis (IPF), a composite clinical-radiographic-physiologic (CRP) scoring system was devised, using 7 variables: dyspnea, chest radiograph, spirometry, lung volume, diffusion capacity, resting alveolar-arterial PO2, and exercise O2 saturation. To assess this scoring system, we examined the relationships between CRP scores and histopathologic findings, including a cellular pathology score composed of abnormalities deemed to be potentially reversible, a fibrotic pathology score based on abnormalities felt to be essentially irreversible, and an index of overall pathologic derangement (total pathology score), derived from the sum of the cellular and fibrotic scores. The initial CRP determination at the time of open lung biopsy correlated significantly with the total pathology score (r = 0.61, p less than 0.001). The CRP score determined after 6 months of corticosteroid therapy showed a significant correlation with the fibrotic pathology score present on open lung biopsy (r = 0.76, p less than 0.001). The change in CRP after 6 months of corticosteroid therapy tended to reflect the cellular histopathologic component of the open lung biopsy (r = -0.43, p less than 0.10). Moreover, in none of these relationships did any individual component of the CRP score correlate better with the respective histopathologic index than did the CRP score itself. These data suggest that this CRP score is useful for the estimation of the severity of underlying pathologic derangement and for the longitudinal quantitative assessment of clinical impairment in patients with IPF.

Electrophysiological and immunocytochemical techniques were used in the abdominal ganglion of Aplysia to identify neurons containing immunoreactive FMRFamide. Large numbers of neurons were immunoreactive for FMRFamide, including R2, L2, L3, L4, L5, L6, 2 cells tentatively identified as L12 and L13, and a previously unidentified cluster on the ventral surface of the right lower quadrant. There was also heavy labelling of fibers, often with beaded varicosities, throughout the neuropil, the cell layers, and the sheath overlying the ganglion. This data provides further evidence that FMRFamide is an important neurotransmitter in Aplysia. The demonstration of immunoreactive FMRFamide in the giant cholinergic neurons R2 and LP1(1) suggests that these well-studied and experimentally convenient cells use acetylcholine and an FMRFamide-like peptide as cotransmitters.

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.