Recent Publications by CFE Educators

A previously healthy young man presented with acute respiratory distress and diffuse bilateral infiltrates on chest radiograph. Eosinophilic pneumonia was diagnosed by bronchoalveolar lavage and confirmed by transbronchial lung biopsy. There was no evidence of an infectious etiology, and the patient rapidly improved with corticosteroid therapy. Most cases of eosinophilic pneumonia reported previously have followed a chronic course. The case presented here was acute in onset, suggesting a hypersensitivity reaction. High levels of bronchoalveolar lavage eosinophils indicate the diagnosis but not the etiology of eosinophilic pneumonia.

In this study we characterized the distribution of glycine receptor immunoreactivity in the spinal cord of the rat by using monoclonal antisera directed against the purified glycine receptor. There was dense, punctate glycine receptor immunoreactive staining in all regions of the gray matter ventral to the substantia gelatinosa. The densest staining was found in laminae III and IV of the dorsal horn. There were also distinct, tributarylike bands of punctate staining that extended well into the white matter of the lateral and ventral funiculi. The only consistent cell body staining was found in small neurons of the ventral horn. The labelled neurons were distributed among larger, unlabelled motoneurons. In general, the pattern of glycine receptor immunoreactivity was similar at all levels of the spinal cord and was comparable to that seen with binding of a tritiated glycine receptor antagonist, strychnine, to sections of rat spinal cord (Zarbin et al.: J. Neurosci. 1:532-547, '81). Two important exceptions, however, were observed. In contrast to the high levels of strychnine binding reported in the substantia gelatinosa, we found almost no glycine receptor immunoreactivity in laminae I and II of the superficial dorsal horn of the spinal cord or of the trigeminal nucleus caudalis. There was also a notable absence of antibody staining in the intermediolateral cell column of the thoracic cord. The presence of dense glycine receptor immunoreactivity in the region of lamina V and its absence in the superficial dorsal horn are discussed in terms of a possible differential glycinergic control of nociceptive neurons of laminae I and V.

Cigarette smoking alters the presence and function of alveolar macrophages. It has been speculated that these cigarette smoke-induced alterations contribute to the depressed pulmonary defense mechanisms commonly demonstrated in smokers. Studies of the phagocytic and bactericidal activities of alveolar macrophages from smokers and nonsmokers have yielded conflicting results. We tested whether alveolar macrophages from normal nonsmokers versus normal smokers differed in their ability to phagocytose and to kill the facultative intracellular bacterium Listeria monocytogenes. No significant differences in phagocytosis between nonsmokers and smokers were found. The alveolar macrophages from nonsmokers, however, killed Listeria, whereas those from smokers had no bactericidal or bacteriostatic activity. Thus, these data demonstrate that alveolar macrophages from normal smokers are able to phagocytose Listeria but express a selective functional deficiency in their ability to kill this facultative intracellular bacteria and, therefore, imply a defect in the immunoregulation of alveolar macrophages in smokers.

1. We have recently shown that leukotriene B4 (LTB4), a product of the 5-lipoxygenase pathway of arachidonic acid metabolism, sensitizes nociceptors to mechanical stimuli. The present study examined whether LTB4 also induces a heat sensitization of cutaneous C-fiber nociceptors. The C-fiber nociceptors studied had von Frey hair thresholds greater than 5 g and were characterized according to their responses to noxious heat and chemical stimuli, including glacial acetic acid, bradykinin, and capsaicin. Thirty-four of the C-fibers that were activated by intense thermal stimulation were also activated by topical application of glacial acetic acid. They were classified as C-polymodal nociceptors (2, 28). Those that were activated by intense mechanical and thermal stimulation, but were unresponsive to acid, were classified as C-mechanoheat nociceptors (27). 2. Ninety-four percent of C-polymodal nociceptors and 60% of C-mechanoheat nociceptors were sensitized by LTB4. All C-fiber nociceptors that showed a decrease of their heat threshold also had a decrease of their mechanical threshold. LTB4 (75 ng) lowered the average heat threshold from 45 degrees C to 35 degrees C and produced an average decrease in the mechanical threshold of 86%. 3. The magnitude of the LTB4-evoked decrease in thermal threshold was similar to that produced by 75 ng of prostaglandin E2 (PGE2). These data demonstrate that LTB4 sensitizes C-mechanoheat nociceptors to both mechanical and thermal stimuli. 4. We conclude that LTB4 may contribute to the component of hyperalgesia that is resistant to nonsteroidal anti-inflammatory agents.

PURPOSE

It is likely that the relationship between lung volume changes and gas exchange in patients with idiopathic pulmonary fibrosis (IPF) and patients with sarcoidosis is different since the two conditions vary widely in histopathology and prognosis. Few studies, however, have examined this relationship. The goal of this investigation was to measure diffusing capacity and gas exchange in patients with IPF and sarcoidosis in whom the reduction of lung volume was equivalent.

PATIENTS AND METHODS

In 21 patients with IPF and 20 patients with pulmonary sarcoidosis with comparable reductions in lung volume, the single breath diffusing capacity for carbon monoxide and gas exchange at rest and during exercise were compared.

RESULTS

The relationship between lung volume and gas transfer differed in the two groups of patients. Resting and exercise gas exchange tended to be relatively normal and the diffusing capacity was higher in patients with sarcoidosis than in those with IPF. These differences could not be attributed to disparities in race, age, smoking habits, or the radiographic stage of sarcoidosis.

CONCLUSION

The preservation of gas exchange in sarcoidosis as opposed to IPF, despite equivalent degrees of volume restriction, suggests that different pathophysiologic mechanism underlie the volume loss and gas exchange defects seen in these disorders. Furthermore, these findings suggest that diffusing capacity may not be a sensitive indicator of pulmonary pathology in sarcoidosis since lung volume can be altered independently of abnormalities in the diffusing capacity.

A clinical teaching assessment form was used to evaluate the teaching by faculty and residents in the required third-year medicine clerkship over a two-year period. Data from 1,627 forms were analyzed for differences between groups of teachers at different experience levels and for comparison of teaching programs at different training sites. The level of involvement of instructor with student correlated with ratings by the students. Among groups of instructors, chief medical residents received the highest overall ratings. Faculty were rated higher than first-, second-, and third-year residents when degree of involvement of instructor with student was high. Ratings among faculty of different academic ranks were not significantly different. Analysis of data from different clinical settings showed that the teaching efforts by clinical faculty members in the ambulatory setting received the highest ratings from students. Although increased involvement of instructors with students or other factors may have led to the higher ratings in the ambulatory setting, the results are encouraging for the use of ambulatory teaching sites for the basic medicine clerkship.

Controversy exists as to the appropriate methods to use in the processing of bronchoalveolar lavage (BAL) fluid for total cell numbers and cellular differential analysis. It has been shown that cell losses (primarily lymphocytes) occur by the most commonly employed methods. Therefore, we examined the total cell and differential counts obtained by several methods of cytocentrifuge preparation and by the filter preparation in 46 consecutive patients with interstitial lung disease and 29 healthy volunteers undergoing bronchoalveolar lavage. The retrieved lavage fluid was pooled, and an aliquot was used to determine the total cell count, cell viability, and the differential cell count by the filter and cytocentrifuge techniques. The remaining fluid was centrifuged (800 g for 10 min), and the cell pellet was resuspended in Hank's balanced salt solution without Ca2+ and Mg2+. An aliquot of these centrifuged and resuspended cells was used for repeat determination of the cell viability, total cell count, and cellular differential by cytocentrifuge technique. Autologous serum was added to another aliquot of these centrifuged and resuspended cells to arrive at a 10% protein solution, and the cellular differential obtained by cytocentrifuged preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

We have studied (i) the contribution of specific adrenergic receptors to the proinflammatory effects of the sympathetic nervous system in experimental arthritis and (ii) the phases of the disease during which the sympathetic nervous system influences joint injury. Severity of joint injury was measured radiographically 28 days after induction of adjuvant arthritis in control rats and in rats treated with a variety of sympatholytic agents at various times during the course of the disease. Rats treated with a nonspecific catecholamine depletor (reserpine) or a beta-adrenergic receptor antagonist (propranolol) had a delayed onset and significantly less severe joint injury than saline-treated controls when treatment began prior to injection of the adjuvant and continued to day 28 after the injection. When administered over the same treatment period, neither nonselective (phenoxybenzamine) nor selective [prazosin (alpha 1) and yohimbine (alpha 2)] alpha-adrenergic receptor antagonists affected the onset or severity of joint injury. Metoprolol, a beta 1 antagonist, was also without effect. In contrast, two beta 2 antagonists (butoxamine and ICI 118,551) significantly retarded disease onset and reduced the severity of joint injury. When reserpine or butoxamine treatment was initiated after the onset of clinically apparent arthritis, it was still possible to favorably influence the course of the disease. These data indicate an important contribution of the beta 2-adrenergic receptor to joint injury in experimental arthritis.

A 40 year old woman at 30 weeks of her eighth pregnancy presented with acute onset of dyspnoea and a large left pleural effusion after the onset of premature labour. A barium enema showed diaphragmatic rupture with intestinal contents in the thorax. Repair was accomplished through simultaneous left subcostal and thoracic incisions.

In experimental models of spinal cord trauma there is often a relatively poor correlation between light microscopic histological changes and motor recovery. Previously it was shown that spinal cord levels of immunoreactive TRH and substance P, by radioimmunoassay, are significantly reduced caudal to the injury site. Since much of the substance P and TRH in the spinal cord derives from cells within the ventral medulla, many of which also contain serotonin, we examined changes in serotonin immunoreactivity within the spinal cord caudal to the injury site in rats subjected to varying degrees of impact trauma to the thoracic cord. Reductions in immunocytochemical staining of serotonin in ventral gray matter of the lumbar region at two weeks after trauma were significantly correlated with the degree of injury severity as reflected by motor impairment. Changes in the region of the central canal, but not dorsal horn, were also correlated with injury severity. These findings indicate that serotonin immunocytochemical analysis may permit better correlation between anatomical and functional outcome after spinal cord injury than generally utilized light microscopic methods.