Recent Publications by CFE Educators

Idiopathic pulmonary fibrosis (IPF) and bronchiolitis obliterans with organizing pneumonia (BOOP) are interstitial lung diseases of unknown pathogenesis. Alveolar macrophages play a major role in the regulation of the inflammatory response in these diseases through their ability to produce cytokines that modify the inflammatory response. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) exhibit proinflammatory and anti-inflammatory actions, respectively, and thus an imbalance in the expression of these cytokines may contribute to the pathogenesis of IPF and BOOP. Therefore, we quantified IL-10 and TNF-alpha mRNA levels in alveolar macrophages obtained by bronchoalveolar lavage (BAL) from patients with IPF and BOOP and in normal healthy volunteers. The level of TNF-alpha mRNA in macrophages obtained from IPF and BOOP patients was not significantly different from normal healthy subjects. However, macrophages from patients with IPF and BOOP expressed increased levels of IL-10 mRNA compared with healthy controls. In addition, stimulation of alveolar macrophages with lipopolysaccharide in the presence of a neutralizing anti-IL-10 antibody augmented the production of TNF-alpha over that seen in the absence of anti-IL-10 antibody, suggesting that the increased expression of IL-10 by alveolar macrophages may act to control the expression of TNF-alpha. Paradoxically, measurement of IL-10 protein in cell-free BAL fluid revealed lower amounts of the protein in patients with IPF and BOOP compared with healthy controls.

It has been hypothesized that tolerance to the analgesic effects of morphine results from the development of a compensatory response in neurons that express the opioid receptor or in neural circuits in which those neurons participate. The compensatory response establishes a sensitized state in these neurons. To determine if administration of a noxious stimulus can unmask a sensitization of dorsal horn neurons in morphine-pelleted rats, we injected morphine-tolerant and control rats with formalin into the plantar surface of the hindpaw, counted the number of flinches for 2 h and then processed the lumbar cord for Fos immunocytochemistry. Although there was no significant difference in flinching behavior between the morphine-tolerant and control groups, we recorded significantly increased total Fos-like immunoreactivity at the L4/5 and L2 segments both ipsilateral and contralateral to the site of formalin injection in the morphine-tolerant rats compared to the control rats. These results suggest that lumbar spinal cord neurons are sensitized during the development of tolerance, that the sensitization can be unmasked by the administration of a noxious stimulus and that it is manifested as increased expression of the Fos protein in the lumbar cord.

Dorsal root ganglia (DRG) neurons synthesize and transport substance P (SP) to the spinal cord where it is released in response to intense noxious somatosensory stimuli. We have shown previously that SP release in vivo causes a rapid and reversible internalization of SP receptors (SPRs) in dorsal horn neurons, which may provide a pharmacologically specific image of neurons activated by SP. Here, we report that noxious heat (43 degrees, 48 degrees, and 55 degrees C) and cold (10 degrees, 0 degrees, -10 degrees, and -20 degrees C) stimuli, but not innocuous warm (38 degrees C) and cold (20 degrees C) stimuli, applied to the hindpaw of anesthetized rats induce SPR internalization in spinal cord neurons that is graded with respect to the intensity of the thermal stimulus. Thus, with increasing stimulus intensities, both the total number of SPR+ lamina I neurons showing SPR internalization and the number of internalized SPR+ endosomes within each SPR immunoreactive neuron showed a significant increase. These data suggest that thermal stimuli induce a graded release of SP from primary afferent terminals and that agonist dependent receptor endocytosis provides evidence of a spatially and pharmacologically unique "neurochemical signature" after specific somatosensory stimuli.

The current drive for efficient clinical teaching threatens the educational mission of academic medical centers. With pressures to increase clinical productivity, protected time and compensation for teaching have become scarce resources for clinical teachers in all settings. Although it may yield new approaches to education, the push for efficiency may ultimately result in insufficient time for teaching and may cause some clinical preceptors to stop teaching completely. Further, it may lead to the illusion that comprehensive teaching truly requires little time. Since the future of American health care depends upon the provision of high-quality clinical education to young physicians, this situation presents a potential national crisis. In this article, the authors discuss the complex nature of teaching, its time requirements, and the special challenges of teaching in outpatient settings. To avoid overemphasizing efficiency to the detriment of education they recommend adhering to two principles: (1) academic medical centers are educational as well as training institutions, and therefore should provide a broad-based education as well as training in clinical skills; and (2) the clinical teaching process is complex and adequate time must be provided for its many phases, including planning, instructing, and reflecting. Finally, the authors make recommendations for ensuring the delivery of high-quality education in ambulatory care settings.

BACKGROUND

Oral immunotherapy, if proven safe and effective, could be an alternative to subcutaneous immunotherapy.

OBJECTIVE

This pilot study investigated the clinic and immunologic effects of ragweed immunotherapy using a new microencapsulated, pH-sensitive, oral delivery system.

METHODS

A double-blind, placebo-controlled trial was conducted in 23 patients with allergic rhinitis to short ragweed. Following a baseline nasal challenge with ragweed allergen, oral immunotherapy with encapsulated short ragweed extract or placebo was administered once daily, 6 days/week. Dosed began at 3 micrograms Amb a 1 per day and were increased by 3 micrograms every three days as tolerated, to a maximum daily maintenance dose of 24 micrograms. A nasal challenge was repeated 6 weeks, later, followed by the continuation of maintenance therapy through the natural ragweed season. Daily allergy symptoms and relief medication usage was recorded. A final nasal challenge was performed at the end of the natural season. Short ragweed-specific serum IgE, IgG, and IgG4 antibody levels were measured every 2 weeks during the study.

RESULTS

Maximum tolerated doses ranged from 6 to 24 micrograms Amb a 1 per day (74% reached 24 micrograms). Adverse events were not serious or different between the active and placebo groups. The active group showed increased in short ragweed-specific serum IgG and IgG4 antibody levels. Symptom scores during the natural season were numerically but not statistically lower in the active treatment group. This group also experienced a greater reduction from baseline in nasal reactivity as assessed by nasal challenge.

CONCLUSIONS

These pilot data suggest that the encapsulated, pH-sensitive oral immunotherapy delivery system was safe, induced a brisk serologic response, and attenuated the symptomatic response to both experimental and environmental ragweed exposure.

PURPOSE

To describe the decision-making processes reported by graduating medical students in choosing primary care (PC) or non-primary-care (NPC) specialties.

METHOD

Members of the University of Washington School of Medicine's graduating class of 1995 were invited to participate in focus groups. Six specialty-choice pathways were defined based on a previously administered survey of recalled preferences at matriculation and stated choice at the time of the National Resident Matching Program. Students were assigned to focus groups based on specialty-choice pathway. Transcribed discussions and summaries were thematically coded and analyzed using grounded theory and quantitative comparisons.

RESULTS

Of 157 students, 140 (89%) completed the initial survey, and 133 (85%) provided enough information to be classified by pathway. In all, 47 students participated in the focus group discussions. The PC students cited PC orientation, diversity of patients and activities, role models and mentors, interaction with patients, and overall medical school culture as having influenced their choice. The NPC students cited lifestyle, controllable hours, opportunities to do procedures, therapeutic urgency and effect, active tempo, exciting settings, and intellectual challenge. Role models influenced PC career choice much more than NPC career choice, and often served to refute negative stereotypes. The sense of personal fit between themselves and specialties was important to the students in all groups, but differed in emphasis according to career-choice pathways. Those whose preferences did not change experienced a confirmation of pre-existing beliefs, while those who switched specialty areas developed a sense of fit through the inclusion or elimination of different practice aspects. Those who switched specialty areas reported more negative influences and misunderstanding of their initially preferred specialties.

CONCLUSION

The process of specialty choice can be described usefully as a socially constructed process of "trying on possible selves" (i.e., projecting oneself into hypothetical career and personal roles). This may explain role models' exceptional influence in disproving negative stereotypes. Medical students' choices can best be facilitated by recognizing their needs to gain knowledge not only about specialty content, but also about practitioners' lives and the students' own present and possible selves.

Transneuronal tracing of a nociceptive pathway, the spino-(trigemino)-parabrachio-amygdaloid pathway, was performed using an alpha-herpes virus, the Bartha strain of pseudorabies virus (PRV). Microinjection of PRV into the central nucleus of the amygdala (Ce) resulted in progressive retrograde and transneuronal infection of a multisynaptic circuit involving neurons in the brainstem and spinal cord as detected immunocytochemically. At short survival (26 hr), retrogradely labeled neurons were concentrated in the external lateral nucleus of the parabrachial complex (elPB) but were absent from both the trigeminal nucleus caudalis (TNC) and the spinal cord. At longer survivals (52 hr), labeled cells were present in lamina I of both the TNC and spinal dorsal horn. Retrograde labeling from the Ce with Fluoro-gold demonstrated that elPB neurons have long dendrites extending laterally into the terminal field of spinal and trigeminal afferents, where transneuronal passage of PRV to these afferents could occur. Even longer survivals (76 hr) resulted in a columnar pattern of cell labeling in the TNC and spinal dorsal horn that extended from lamina I into lamina II. At this longest survival, primary sensory neurons became infected. Bilateral excitotoxic lesions of the elPB blocked almost all viral passage from the Ce to superficial laminae of the TNC and spinal dorsal horn. These results demonstrate that nociceptive input to the amygdala is relayed from neurons in lamina I through the elPB. We propose that this modular arrangement of lamina I and II neurons may provide the basis for spinal processing of peripheral input to the amygdala.