Recent Publications by CFE Educators

BACKGROUND

We employed DNA microarray technology to investigate the host response to Streptococcus pneumoniae in a mouse model of asymptomatic carriage. Over a period of six weeks, we profiled transcript abundance and complexity in the Nasal Associated Lymphoid Tissue (NALT) to identify genes whose expression differed between pneumococcal-colonized and uncolonized states.

RESULTS

Colonization with S. pneumoniae altered the expression of hundreds of genes over the course of the study, demonstrating that carriage is a dynamic process characterized by increased expression of a set of early inflammatory responses, including induction of a Type I Interferon response, and the production of several antimicrobial factors. Subsequent to this initial inflammatory response, we observed increases in transcripts associated with T cell development and activation, as well as wounding, basement membrane remodeling, and cell proliferation. Our analysis suggests that microbial colonization induced expression of genes encoding components critical for controlling JAK/STAT signaling, including stat1, stat2, socs3, and mapk1, as well as induction of several Type I Interferon-inducible genes and other antimicrobial factors at the earliest stages of colonization.

CONCLUSION

Examining multiple time points over six weeks of colonization demonstrated that asymptomatic carriage stimulates a dynamic host response characterized by temporal waves with distinct biological programs. Our data suggest that the usual response to the presence of the pneumocccus is an initial controlled inflammatory response followed by activation of host physiological processes such as response to wounding, basement membrane remodeling, and increasing cellular numbers that ultimately allow the host to maintain an intact epithelium and eventually mount a preventive adaptive immune response.

Ionizing radiation (IR) is a physiologically important stress to which cells respond by the activation of multiple signaling pathways. Using a panel of immortalized and transformed breast epithelial cell lines, we demonstrate that IR regulation of protein synthesis occurs in nontransformed cells and is lost with transformation. In nontransformed cells, IR rapidly activates the MAP kinases ERK1/2, resulting in an early transient increase in cap-dependent mRNA translation that involves mTOR and is radioprotective, enhancing the translation of a subset of mRNAs encoding proteins involved in DNA repair and cell survival. Following a transient increase in translation, IR-sensitive (nontransformed) cells inhibit cap-dependent protein synthesis through a mechanism that involves activation of p53, induction of Sestrin 1 and 2 genes, and stimulation of AMP kinase, inhibiting mTOR and hypophosphorylating 4E-BP1. IR is shown to block proteasome-mediated decay of 4E-BP1, increasing its abundance and the sequestration of eIF4E. The IR signal that impairs mTOR-dependent protein synthesis at late times is assembly of the DNA damage response machinery, consisting of Mre11, Rad50, and NBS1 (MRN); activation of the MRN complex kinase ATM; and p53. These results link genotoxic signaling from the DNA damage response complex to the control of protein synthesis.

OBJECTIVES

Many patients present with bilateral stones. There is a unique group of patients, however, that presents with stones exclusively on one side. We hypothesize that in such situations, 24-hour urine collections may not reveal specific defects on the affected stone-bearing kidney. We therefore evaluated selective 12-hour urine collections after percutaneous nephrolithotomy (PNL) to help determine if there is differential renal excretion.

METHODS

We collected urine specimens from patients with nephrolithiasis who underwent unilateral PNL. Urine samples were collected and analyzed from nephrostomy tubes, representing the affected kidneys, and from Foley bladder catheters, representing the contralateral mate kidney.

RESULTS

Thirty-one patients were studied (14 with unilateral nephrolithiasis and 17 with bilateral). Treated kidneys from patients with unilateral nephrolithiasis displayed lowered urine excretion of uric acid, sodium, chloride, calcium, and total osmoles when compared to patients with bilateral nephrolithiasis. Stone size and length of procedure were not predictive of urine composition after PNL.

CONCLUSIONS

Treated kidneys from patients with a history of unilateral stone disease revealed marked differences in urine excretion compared to those with bilateral nephrolithiasis after unilateral PNL. These findings could be secondary to the surgical insult, urinary stone disease, or could be a responsible factor for stone pathogenesis.

Postmortem studies show reductions in brain serotonin 2A (5-HT(2A)) receptors in Alzheimer's disease (AD). Converging evidence also suggests that serotonergic dysregulation may contribute to behavioral symptoms that frequently occur in AD. This study aimed to define regional reductions in 5-HT(2A) binding in AD patients and to examine their behavioral correlates. Nine patients with probable AD and eight elderly controls were studied using a constant infusion paradigm for equilibrium modeling of [(18)F]deuteroaltanserin with positron emission tomography (PET). Region of interest analyses were performed on PET images coregistered to MRI scans. The outcome measures BP(P) (ratio of specific brain uptake to total plasma parent concentration) and BP(ND) (ratio of specific to nondisplaceable uptake) were obtained for pertinent cortical and subcortical regions. AD patients showed a statistically significant decrease in the anterior cingulate in both BP(P) and BP(ND), but in no other region. Within the AD patient sample, no significant correlations were observed between regional 5-HT(2A) binding and behavioral measures, including depressive and psychotic symptoms. These results confirm a reduction in cortical 5-HT(2A) receptors in AD, specifically in the anterior cingulate. However, in a limited AD patient sample, they fail to demonstrate a relationship between regional 5-HT(2A) binding and major behavioral symptoms.

OBJECTIVES

The first-attempt success rate of intubation was compared using GlideScope video laryngoscopy and direct laryngoscopy in an emergency department (ED).

METHODS

A prospective observational study was conducted of adult patients undergoing intubation in the ED of a Level 1 trauma center with an emergency medicine residency program. Patients were consecutively enrolled between August 2006 and February 2008. Data collected included indication for intubation, patient characteristics, device used, initial oxygen saturation, and resident postgraduate year. The primary outcome measure was success with first attempt. Secondary outcome measures included time to successful intubation, intubation failure, and lowest oxygen saturation levels. An attempt was defined as the introduction of the laryngoscope into the mouth. Failure was defined as an esophageal intubation, changing to a different device or physician, or inability to place the endotracheal tube after three attempts.

RESULTS

A total of 280 patients were enrolled, of whom video laryngoscopy was used for the initial intubation attempt in 63 (22%) and direct laryngoscopy was used in 217 (78%). Reasons for intubation included altered mental status (64%), respiratory distress (47%), facial trauma (9%), and immobilization for imaging (9%). Overall, 233 (83%) intubations were successful on the first attempt, 26 (9%) failures occurred, and one patient received a cricothyrotomy. The first-attempt success rate was 51 of 63 (81%, 95% confidence interval [CI] = 70% to 89%) for video laryngoscopy versus 182 of 217 (84%, 95% CI = 79% to 88%) for direct laryngoscopy (p = 0.59). Median time to successful intubation was 42 seconds (range, 13 to 350 seconds) for video laryngoscopy versus 30 seconds (range, 11 to 600 seconds) for direct laryngoscopy (p 0.01).

CONCLUSIONS

Rates of successful intubation on first attempt were not significantly different between video and direct laryngoscopy. However, intubation using video laryngoscopy required significantly more time to complete.

CONTEXT

Concerns about the quality of medical student learning experiences during traditional clerkships have prompted calls to restructure clinical education around continuity. Many US medical schools have added longitudinal out-patient attachments to enhance student continuity with patients and supervising doctors. However, continuity with patients can be difficult to achieve and little is known about the independent effect of continuity with a supervising doctor and setting. This study describes students' perceptions of the types of continuity experienced in longitudinal attachments and the learning associated with continuity.

METHODS

This is a qualitative study using a grounded theory approach. Interviews were conducted with 12 Year 3 medical students about their continuity experiences with patients, supervisors and settings during their attachment. The resulting data were subjected to thematic analysis.

RESULTS

Continuity with supervising doctors provided students with career mentorship and personal support. Student autonomy varied and was most dependent on the supervisor and setting. Students with patient continuity were more likely to report learning about chronic illness and communication skills. Students described the longitudinal attachment as helping them to develop their clinical skills and gain self-confidence within their role as future doctors, and as influencing their career choice.

CONCLUSIONS

There is much variation in student experiences of patient continuity during a longitudinal attachment. Continuity with patients, supervisors and settings affects student learning in different ways. Additional dimensions of the experience, such as the nature of the patient-doctor relationship, the pace of work and the patient population, impact learning outcomes and should be considered when continuity experiences are being designed.

The spectrum of benign thoracic disease in the elderly includes structural abnormalities, infectious disease and their complications, benign neoplastic growths, and autoimmune disease. Differences in physiologic reserve in this population make diagnosis difficult, as elderly patients may not present in the classic fashion, as well as complicate treatment. Benign thoracic disease in the elderly can pose a challenging clinical problem. Older patients with comorbid diseases may have poor tolerance of unnecessary surgical interventions. However, benign disorders of the chest associated with symptoms attributable to effusion or obstruction of airways can limit quality of life. Minimally invasive techniques (eg, video-assisted thoracoscopic surgery) can limit the morbidity associated with intervention. Additionally, prompt intervention may spare the patient more invasive treatments. For example, early effusions can be managed with simple drainage rather than thoracotomy and decortication. With respect to suspected benign thoracic lesions in the elderly, guiding principles for management include avoiding unnecessary interventions while not overlooking potential malignancies. Close surveillance of progressive symptoms, ensuring no radiographic change in the size of the lesion over 2 years, and use of positron-emission tomography remain the diagnostic keys to accurate management.