Recent Publications by CFE Educators

Learning an innovative teaching method such as a problem-based learning is difficult for most faculty members because the method is based upon assumptions about learning that are often at variance with their beliefs. Faculty development can challenge assumptions about learning, provide experience with a new technique, and offer specific pedagogical skills that are needed to succeed as a tutor. A comprehensive approach to faculty development, derived from the literature in higher education, would include: instructional development, professional development, leadership development, and organizational development. Research on faculty development indicates positive results of such efforts. Faculty members who choose to learn about problem-based learning appear to progress through predictable stages of development that include: understanding and valuing the rationale for problem-based learning, acquiring general and content-specific tutor knowledge and skills, developing advanced skills in problem-based learning, and developing leadership and scholarship skills. Each of these steps, plus organizational vitality, are described along with recommendations for implementing such programs. Finally, five models of faculty development derived from medical schools with problem-based learning curricula are examined.

PURPOSE

To assess quantitative high-resolution CT (quantitative CT) as a diagnostic and prognostic tool in pulmonary lymphangioleiomyomatosis.

METHODS

Spirometry, lung volumes, diffusing capacity, exercise physiology, and expiratory high-resolution CT (HRCT) examinations were performed on a cohort of ten patients with the diagnosis of lymphangioleiomyomatosis (LAM) referred to a tertiary care center. HRCT examinations were also done on ten normal control subjects. A thresholding technique was used to quantitatively assess the amount of abnormal cystic parenchyma present on each of the two images obtained for each subject with LAM and for each normal control subject. This numeric index of cystic parenchyma, the quantitative CT index, was then examined (1) as a diagnostic measure to distinguish the subjects with LAM from the normal control subjects and (2) as a prognostic measure to assess disease severity in the subjects with LAM. Linear regression of the quantitative CT index against physiologic indexes of pulmonary function and exercise performance was analyzed to determine the relationship between this radiologic assessment of disease severity and functional impairment.

RESULTS

The quantitative CT index was significantly greater for the LAM patients, 37.2 +/- 6.9 (SEM), compared with the control group, 0.8 +/- 0.2 (p = 0.0001). Linear regression analysis demonstrated significant linear correlation between the quantitative CT index and measures of airflow (FEV1, r = -0.90, p = 0.0005), air trapping (residual volume, r = 0.70, p = 0.02), diffusing capacity (diffusing capacity for carbon monoxide, r = -0.76, p = 0.01), gas exchange (alveolar to arterial oxygen gradient) at rest, r = 0.69, p = 0.007, and at maximum exercise, r = 0.79, p = 0.007) and exercise performance (maximum workload, r = -0.84, p = 0.002), and oxygen utilization (oxygen utilization at maximum exercise, r = -0.76, p = 0.01).

CONCLUSION

Quantitative CT techniques can distinguish subjects with LAM from normal controls. Further, the quantitative CT index correlates well with physiologic measurements of airflow, lung volumes, diffusing capacity, and exercise performance and, thus, may provide a useful measure of disease severity.

Pulmonary histiocytosis X (PHX) is a diffuse, smoking-related lung disease characterized pathologically by bronchocentric inflammation, cyst formation, and widespread vascular abnormalities and physiologically by exercise limitation. The major mechanism underlying exercise impairment in this disease has not been previously defined. Spirometry, lung volumes, lung mechanics, and exercise physiology were performed on 23 patients with PHX. Two subgroups were identified on the basis of elastic recoil: 12 subjects had an elevated coefficient of elastic recoil with 11 demonstrating a predominant pattern of restriction, and 10 subjects had normal elastic recoil and relatively normal lung function. Exercise performance was severely limited in both subgroups (workload 53 +/- 3%). Abnormalities of ventilatory function and gas exchange were present but did not appear to be exercise-limiting in the majority of subjects. Indices reflecting pulmonary vascular function (DLCO, baseline VD/VT, exercise VD/VT) were abnormal. Strong correlations between overall exercise performance (% predicted VO2max) and indices of vascular involvement were present: DLCO (r = 0.68, p = 0.0004), baseline VD/VT (-0.65, 0.001), exercise VD/VT (-0.67, 0.0004). Similar correlations were found when exercise performance was measured by maximal workload achieved. We conclude that (1) subjects with PHX present with either normal or predominantly restrictive pulmonary physiology and that (2) exercise impairment is common and appears to reflect pulmonary vascular dysfunction.

Spontaneously hypertensive rats (SHRs) are typically less responsive to phasic noxious stimuli than are their normotensive controls. Here, we used the formalin test to compare behavioral and cardiovascular responses to persistent noxious stimuli. Hindpaw formalin injection produced exaggerated flinching, arterial pressure and heart rate responses in SHRs, suggesting that abnormalities in blood pressure control systems increase nociceptive responses to persistent noxious stimuli.

Pulmonary lymphangiomyomatosis has been associated with renal angiomyolipoma in case reports, but the prevalence of this association has not been well documented. The objective of this study was to determine the frequency of renal angiomyolipoma in a series of subjects with pulmonary lymphangiomyomatosis. Eighteen consecutive patients with pulmonary lymphangiomyomatosis were seen at a single institution between 1989 and 1994. Of these, one patient was excluded because she did not have an abdominal computed tomographic (CT) scan. We found eight out of 17 (47%) patients with pulmonary lymphangiomyomatosis to have renal angiomyolipomas. These were found either at surgery or on abdominal CT scanning. Thus, renal angiomyolipomas occur commonly in association with pulmonary lymphangiomyomatosis. Consequently, the early detection of renal angiomyolipoma by abdominal CT may be important, because lesions with dimensions larger than 4 cm may present an increased risk for complications related to tumor growth or hemorrhage. Serial follow-up by ultrasonography or CT scanning is important in identifying and monitoring high-risk patients. Prophylactic treatment (partial or total nephrectomy) may be considered for patients with tumors that show significant growth or other complications, such as hemorrhage.

The formalin test produces persistent pain in animals and is believed to provide a better model of the pain experienced by humans than do tests that measure reflex nociceptive thresholds. The present study evaluated whether tolerance to morphine develops in the formalin test in the rat. Morphine (75 mg) or vehicle pellets were implanted subcutaneously for 5 consecutive days. On the 6th day, a subcutaneous (s.c.) dose of either morphine (10 mg/kg) or saline was given 30 min prior to the injection of 50 microliters of 5% formalin into the left hindpaw of the rats. In vehicle-pelleted rats administered saline, formalin evoked characteristic pain behavior consisting of licking, biting and flinching of the affected hindpaw. The pain behavior in morphine-tolerant rats given morphine did not differ significantly from the saline control; i.e., tolerance to the analgesic effect of morphine was demonstrable in the formalin test. These results do not agree with previous published reports. Rather, these results suggest that the mechanisms involved in morphine analgesia in the formalin test and in reflex nociceptive tests are similar and subject to the same problem of tolerance with chronic opioid administration.

Hindpaw injection of formalin produces acute (Phase 1) and persistent (Phase 2) nociceptive behaviors. This model has provided critical evidence supporting a contribution of central sensitization (hyperexcitability of spinal neurons) to the expression of persistent pain. Here, we evaluated the contribution of ongoing peripheral nerve inputs to Phase 2 pain responses. In addition to pain behavior (flinching), we measured formalin-evoked increases in arterial pressure and heart rate; these cardiovascular responses were also biphasic in nature. The arterial pressure response correlated highly with behavior, and was dependent on formalin concentration (0.625-5.0%), indicating that it was largely driven by noxious input. Lightly anesthetized (0.7% halothane) rats exhibited robust increases in blood pressure in the absence of pain behavior, indicating cardiovascular responses did not reflect somatomotor-cardiovascular coupling. Animals obtained from Charles River exhibited slightly larger Phase 2 flinching and heart rate responses compared to those obtained from Bantin and Kingman, suggesting cardiovascular-related pain responses can vary with the source of animal. We next evaluated the contribution of ongoing peripheral nerve activity to the expression of the Phase 2 pressor, tachycardia, and flinch responses. After Phase 1 subsided, but before Phase 2 began, we locally anesthetized the ipsilateral or contralateral (control) hindpaw with a hydrophilic lidocaine derivative, QX-314 (2%). Intraplantar QX-314 blocked Phase 2 pressor, tachycardia and behavioral responses only when injected into the paw that received formalin (2.5% or 10.0%). We conclude that persistent ongoing activity in peripheral afferent fibers during Phase 2 is required for the persistent pain evoked by formalin.

The interstitium of the fibrotic lung possesses a contractile capability that is unusual for nonmuscle tissue. An abundance of actin filament-laden cells have been demonstrated in animal and human studies of fibrotic lung tissue and have frequently been termed myofibroblasts. The origin and significance of these cells remain unclear. Proliferation of cells with the capability to contract and thereby generate force within the parenchyma is potentially a significant contribution to the increased lung elastic recoil of advanced pulmonary fibrosis. In the present study, we immunohistochemically examined these intermediate phenotypes of filament-laden cells with a focus on those expressing smooth muscle-associated isoforms of actin. The monoclonal antibody HHF35 was used to study the presence and distribution of cells expressing alpha and gamma smooth muscle actin in idiopathic pulmonary fibrosis (IPF). Adjacent sections of tissue from open lung biopsies of eight patients with IPF were stained with a pentachrome stain and with multiple antibodies (HHF35, polyclonal anti-actin, anti-vimentin, anti-keratin, anti-procollagen I, and anti-von Willebrand Factor VIII) to identify specific cell types. In addition, anti-laminin antibody was used to stain basement membrane. Many tightly packed, HHF35-reactive cells were found to be architecturally dissociated from airways and blood vessels in all eight patients with IPF. Some HHF35-reactive bundles were composed of loosely associated cells, and single smooth muscle cell types (SMC) were distributed in the fibrotic interstitium. Interestingly, some of the SMC were distinctly negative for anti-laminin and stained atypically with pentachrome. Moreover, some single SMC were found to be anti-procollagen type I reactive with double staining technique.(ABSTRACT TRUNCATED AT 250 WORDS)