Recent Publications by CFE Educators

Behavioral responses to painful stimuli require peripheral sensory neurons called nociceptors. Electrophysiological studies show that most C-fiber nociceptors are polymodal (i.e., respond to multiple noxious stimulus modalities, such as mechanical and thermal); nevertheless, these stimuli are perceived as distinct. Therefore, it is believed that discrimination among these modalities only occurs at spinal or supraspinal levels of processing. Here, we provide evidence to the contrary. Genetic ablation in adulthood of unmyelinated sensory neurons expressing the G protein-coupled receptor Mrgprd reduces behavioral sensitivity to noxious mechanical stimuli but not to heat or cold stimuli. Conversely, pharmacological ablation of the central branches of TRPV1(+) nociceptors, which constitute a nonoverlapping population, selectively abolishes noxious heat pain sensitivity. Combined elimination of both populations yielded an additive phenotype with no additional behavioral deficits, ruling out a redundant contribution of these populations to heat and mechanical pain sensitivity. This double-dissociation suggests that the brain can distinguish different noxious stimulus modalities from the earliest stages of sensory processing.

Descending projections arising from brainstem serotonergic (5HT) neurons contribute to both facilitatory and inhibitory controls of spinal cord "pain" transmission neurons. Unclear, however, are the brainstem networks that influence the output of these 5HT neurons. To address this question, here we used a novel neuroanatomical tracing method in a transgenic line of mice in which Cre recombinase is selectively expressed in 5HT neurons (ePet-Cre mice). Specifically, we injected the conditional pseudorabies virus recombinant (BA2001) that can replicate only in Cre-expressing neurons. Because BA2001 transports exclusively in a retrograde manner, we were able to reveal a subset of the neurons and circuits that are located upstream of the Cre-expressing 5HT neurons. We show that diverse brainstem regions differentially target the 5HT neurons of the dorsal raphe (DR) and the nucleus raphe magnus of the rostroventral medulla (RVM). Among these are several catecholaminergic and cholinergic cell groups, the periaqueductal gray, several brainstem reticular nuclei, and the nucleus of the solitary tract. We conclude that a brainstem 5HT network integrates somatic and visceral inputs arising from various areas of the body. We also identified a circuit that arises from projection neurons of deep spinal cord laminae V-VIII and targets the 5HT neurons of the NRM, but not of the DR. This spinoreticular pathway constitutes an anatomical substrate through which a noxious stimulus can activate 5HT neurons of the NRM and in turn could trigger descending serotonergic antinociceptive controls.

OBJECTIVE

The purpose of this study was 2-fold: (1) to analyze the degree and the location of lumbar multifidus asymmetry among patients scheduled for L4-L5 microdiscectomy, and (2) to determine the amount of asymmetry recognizable by a radiologist on magnetic resonance imaging.

DESIGN

Bilateral multifidi cross-sectional areas were measured on magnetic resonance axial images of 20 patients scheduled to undergo L4-L5 microdiscectomy. The sides were compared and the location and amount of asymmetry (%)determined. The axial slices were assigned to two different categories based on their anatomical proximity to the L4-L5 disc (Disc(Ref)) and to the fascicles of the lumbar multifidus attaching to the spinous process of L5 (Muscle(Ref)). The maximal percent difference in cross-sectional area was compared between these categories. A radiologist rated the degree of asymmetry visually. These ratings were compared slice by slice to the computed percent difference in the cross-sectional area.

RESULTS

Mean differences in multifidus cross-sectional area were 11.5 +/- 5.6% in the Disc(Ref) and 15.8 +/- 9.5% in the Muscle(Ref) categories and were statistically significant (P = 0.03). The radiologist recognized asymmetry when the quantitative difference was at least 12.6%. This level of asymmetry was identified in the Muscle(Ref) category in 45% of cases and in Disc(Ref) in 30% of cases.

CONCLUSIONS

Nearly half of the cases scheduled for lumbar microdiscetomy exhibited asymmetry of at least 12.6% in the lumbar multifidus innervated by the L5 nerve root, which is located below the level of the injured disc. A trained radiologist can readily identify this multifidus asymmetry.

Priapism is defined as a persistent penile erection (typically 4 h or longer) that is unrelated to sexual stimulation. Priapism can be classified as either ischemic or nonischemic. Ischemic priapism, the most common subtype, is typically accompanied by pain and is associated with a substantial risk of subsequent erectile dysfunction. Prompt medical attention is indicated in cases of ischemic priapism. The initial management of choice is corporal aspiration with injection of sympathomimetic agents. If medical management fails, a cavernosal shunt procedure is indicated. Stuttering (recurrent) ischemic priapism is a challenging and poorly understood condition; new management strategies currently under investigation may improve our ability to care for men with this condition. Nonischemic priapism occurs more rarely than ischemic priapism, and is most often the result of trauma. This subtype of priapism, which is generally not painful, is usually initially managed with conservative treatment.

OBJECTIVES

To perform the first population-based measurement of clinical and economic outcomes after thyroid and parathyroid surgery in pregnant women and identify the characteristics of this population and the predictors of outcome.

DESIGN

Retrospective cross-sectional study.

SETTING

Health Care Utilization Project Nationwide Inpatient Sample (HCUP-NIS), a 20% sample of nonfederal US hospitals.

PATIENTS

All pregnant women, compared with age-matched nonpregnant women, who underwent thyroid and parathyroid procedures from 1999 to 2005.

MAIN OUTCOME MEASURES

Fetal, maternal, and surgical complications, in-hospital mortality, median length of stay, and hospital costs.

RESULTS

A total of 201 pregnant women underwent thyroid (n = 165) and parathyroid (n = 36) procedures and were examined together. The mean age was 29 years, 60% were white, 25% were emergent or urgent admissions, and 46% had thyroid cancer. Compared with nonpregnant women (n = 31 155), pregnant patients had a higher rate of endocrine (15.9 vs 8.1%; P .001) and general complications (11.4 vs 3.6%; P .001), longer unadjusted lengths of stay (2 days vs 1 day; P .001), and higher unadjusted hospital costs ($6873 vs $5963; P = .007). The fetal and maternal complication rates were 5.5% and 4.5%, respectively. On multivariate regression analysis, pregnancy was an independent predictor of higher combined surgical complications (odds ratio, 2; P .001), longer adjusted length of stay (0.3 days longer; P .001), and higher adjusted hospital costs ($300; P .001). Other independent predictors of outcome were surgeon volume, patient race or ethnicity, and insurance status.

CONCLUSIONS

Pregnant women have worse clinical and economic outcomes following thyroid and parathyroid surgery than nonpregnant women, with disparities in outcomes based on race, insurance, and access to high-volume surgeons.

PURPOSE

Poor performance on a medical school comprehensive clinical skills assessment after core clerkships requires remediation. Little is known about techniques used to remedy students' skills deficits and their effectiveness. The authors identified remediation strategies used at U.S. medical schools and determined instructors' confidence in remediation.

METHOD

In the fall of 2007, the authors surveyed persons responsible for remediation at U.S. medical schools that conduct comprehensive clinical assessments and remediation. Respondents reported their use of four types of remediation strategies: (1) clinical activities, (2) independent study, (3) precepted video review of exam recording, and (4) organized group activities for deficits in history-taking, physical examination, knowledge, clinical reasoning, professionalism, and communication. The authors assessed confidence in remediation for the six skill areas and analyzed these measures using repeated-measures analysis of variance.

RESULTS

Fifty-three of 71 (74.6%) participants responded. Educators most commonly employ the precepted video review remediation activity across the six skill areas, and they use the clinical activities least commonly. Confidence in remediating the six skill areas was below the "agree" level. Confidence was highest for remediating history-taking and physical examination problems and lowest for professionalism.

CONCLUSION

Educators express modest confidence in remediating fourth-year students' clinical skills deficiencies. The finding that schools employ primarily video review for remediation suggests a potential need to augment opportunities for mentored skills practice to address deficits more effectively. The remediation literature similarly stresses the importance of multiple approaches tailored to particular deficits.

PURPOSE

Medical schools increasingly employ comprehensive standardized patient assessments to ensure medical students' clinical competence. The consequences of poor performance on the assessment and the institutional factors associated with imposing consequences are unknown.

METHOD

In 2006, the investigators surveyed 122 U.S. medical school curriculum deans about comprehensive assessments using standardized patients after core clerkships, with questions about exam characteristics, institutional commitment to the examination (years of experience, exam infrastructure, clerkship director involvement), academic consequences of failing the assessment, and satisfaction with remediation.

RESULTS

Ninety-three of 122 (76%) deans responded. Eighty-two (88%) conducted a comprehensive assessment in years three or four of medical school. Of those, required remediation was the only consequence of failing employed by 61 schools (74%), and only 39 (47%) required retesting for graduation. Participants were somewhat satisfied with (mean 3.45 out of maximum 5, SD 1.08) and confident in (3.37, SD 1.17) their remediation process. Satisfaction and confidence were associated with requiring remediation (P = .003) and retesting (P .001), but experience with the exam, exam infrastructure, and clerkship director involvement were not. No school demographic characteristics or measures of institutional commitment were related to external reporting of students' comprehensive assessment scores.

CONCLUSIONS

Despite the prevalence of comprehensive assessments, schools attach few academic consequences to poor performance. Educators are only moderately satisfied with their efforts to remediate poor performers. However, schools with greater trust in their remediation process than other schools are more likely to enforce consequences of poor performance.

Activation of primary afferent nociceptors produces acute, short-lived pain, and tissue or nerve injury induces long-term enhancement of nociceptive processing, manifested as hypersensitivity to thermal and mechanical stimulation. Here we used a chemical-genetic and pharmacological approach to study the contribution of the receptor tyrosine kinase, type 2 (TrkB) to the generation and maintenance of injury-induced persistent pain. We performed the studies in wild-type mice and transgenic (TrkB(F616A)) mice that express mutant but fully functional TrkB receptors. By injecting a small molecule derivative of the protein kinase inhibitor protein phosphatase 1 (1NM-PP1), it is possible to produce highly selective inhibition of TrkB autophosphorylation in adult mice, without interfering with the activity of other protein kinases. We report that oral administration of 1NM-PP1, at doses that blocked phosphorylation of TrkB in the spinal cord, had no effect in behavioral tests of acute heat, mechanical, or chemical pain sensitivity. However, the same pretreatment with 1NM-PP1 prevented the development of tissue- or nerve injury-induced heat and mechanical hypersensitivity. Established hypersensitivity was transiently reversed by intraperitoneal injection of 1NM-PP1. Although interfering with TrkB signaling altered neither acute capsaicin nor formalin-induced pain behavior, the prolonged mechanical hypersensitivity produced by these chemical injuries was prevented by 1NM-PP1 inhibition of TrkB signaling. We conclude that TrkB signaling is not only an important contributor to the induction of heat and mechanical hypersensitivity produced by tissue or nerve injury but also to the persistence of the pain.