Research ethics

This article explores the tenets of the responsible conduct of research. The proper treatment of human and animal subjects, recognition and avoidance of conflicts of interest, management of data to ensure privacy and confidentiality, authorship, academic freedom, and scientific misconduct are discussed. Historically significant events that have influenced the ethical climate, along with a review of guiding principles and regulations that define the conduct of ethical research are presented. Circumstances more specific to emergency medicine are examined in detail to provide meaningful guidance to practicing emergency medicine researchers.     

Prediction of soft-tissue injuries in Schatzker II tibial plateau fractures based on measurements of plain radiographs

BACKGROUND: Split-depression fractures of the lateral tibial plateau (Schatzker II) are associated with a significant risk of capsuloligamentous and meniscal injury. We hypothesized that the amount of fracture depression and widening on anteroposterior (AP) plain radiographs would correlate with the incidence of injury to these structures on magnetic resonance imaging (MRI). METHODS: Sixty-two consecutive patients with Schatzker II tibial plateau fractures had a knee x-ray series and MRI preoperatively. AP plain radiographs were measured for lateral joint line depression and condylar widening, and MRIs were evaluated for injury to soft-tissue structures around the knee. For each structure, the threshold of depression and widening that led to the greatest disparity in soft-tissue injury was determined. Multiple logistic regressions were applied to calculate whether depression and/or widening above the thresholds were predictive for injury to individual soft-tissue structures. RESULTS: When depression was greater than 6 mm and widening was greater than 5 mm, lateral meniscal injury occurred in 83% of fractures, compared with 50% of fractures with less displacement (p < 0.05). When either depression or widening was at least 8 mm, medial meniscal injury occurred more frequently (depression 53%, p < 0.05; widening 78%, p < 0.05; versus neither 15%). Lateral collateral ligament and posterior cruciate ligament tears were not seen with minimally displaced fractures (< 4 mm), but the incidence of injury approached 30% with increasing displacement. CONCLUSIONS: Due to the limited availability of MRI in some centers, correlation of lateral condylar depression and widening, as measured on plain radiographs, to injury of various soft-tissue structures may be extremely helpful in planning open or arthroscopic treatment methods. Using these guidelines, Schatzker II fractures with depression or widening approaching 5 mm deserve heightened vigilance in diagnosing and treating these concomitant soft-tissue injuries.     

Effects of self-administered alcohol concentration on the frequency and persistence of rats' attending to alcohol cues

Observing responses produce contact with stimuli that are to be discriminated and have been considered an animal model of attending. In the observing-response procedure, alternating periods of drug availability versus extinction for one response are not signaled, but a second response (i.e. the observing response) produces stimuli signaling whether drug is available or not. This experiment examined the effects of the concentration of self-administered alcohol and increases in observing-response requirement on rats' observing alcohol stimuli. In addition, the effects of alcohol concentration on the persistence of observing were examined when alcohol was no longer available. Results showed that observing tracked bitonic changes in the number of alcohol deliveries rather than monotonic increases in total alcohol consumption resulting from increases in alcohol concentration. Increasing the observing-response requirement decreased the number of stimulus presentations earned. The resultant decreases in time spent in the presence of the alcohol stimulus were associated with decreases in alcohol consumption. During extinction of alcohol responding, observing was more persistent when it produced a stimulus previously associated with a higher alcohol concentration. Finally, responding for alcohol was more resistant to extinction in the presence of an observing-response-produced alcohol stimulus than in its absence, but did not depend on alcohol concentration. These results suggest that increases in the difficulty of obtaining access to alcohol cues can decrease alcohol consumption by reducing contact with those cues. In addition, if observing behavior in the present procedure is analogous to attending to alcohol cues, the results suggest that attending to alcohol cues is more persistent with cues previously associated with higher doses, and that the persistence of attending to alcohol cues and their impact on drinking may be dissociable.     

Intramedullary fixation of tibial shaft fractures using an expandable nail: early results of 54 acute tibial shaft fractures

OBJECTIVE: To evaluate and present our experience using the expandable nail system for the treatment of acute tibial shaft fractures. DESIGN: Retrospective study. SETTING: Two level-1 trauma centers-University teaching hospitals. METHODS: Fifty-four consecutive patients were treated by this nail system for acute tibial shaft fracture. Two nail diameters were used, 8.5 mm and 10 mm. Operation, hospitalization and healing times, reaming versus nonreaming, isolated versus multiple injuries, and reoperations were recorded and analyzed statistically. RESULTS: Follow-up was obtained either until fracture healing or for a minimum of 1 year with an average of 14 months (12 to 24). All fractures healed in an average time of 72 days (21 to 204). The average healing times for patients treated with 8.5-mm and 10-mm nails were 77.2 days (27 to 204) and 63.4 days (21 to 121), respectively. Average operative time was 103 minutes (40 to 185) if reamed and 56 minutes (30 to 80) if unreamed. Average healing times were 65.4 days (21 to 190) if reamed and 79.5 days (42 to 204) if unreamed. There were 11 complications (20.4%) related to the nailing: 3 deep infections, 2 superficial infections, 2 bone shortenings of 1 cm secondary to nail protrusion in the knee, 1 compartment syndrome, 1 fracture propagation, 1 distal malalignment, and 1 delayed union. Hardware was removed in 6 patients (3 infections, 2 patients' request and 1 protrusion into the knee), and 1 additional patient underwent exchange nailing due to a delayed union. CONCLUSIONS: The expandable nail offers the theoretical advantages of improved load sharing and rotational control without the need for interlocking screws. This study demonstrates satisfactory healing and alignment for the treatment of tibial shaft fractures using this device. However, caution must be exercised when using this nail in cases of significant comminution and in cases where the fracture pattern involves the more proximal or distal aspect of the tibial shaft.     

Ethanol-maintained responding of rats is more resistant to change in a context with added non-drug reinforcement

Alternative non-drug reinforcers reliably decrease drug-maintained responding in self-administration procedures. Studies of the resistance to change of food-maintained behavior, however, have found that responding in the presence of a stimulus associated with an alternative reinforcer is more resistant to disruption. This increase in persistence occurs despite lower response rates when the alternative reinforcer is present. The present experiment examined if, in addition to decreasing response rates, an alternative non-drug reinforcer also increases the persistence of drug-maintained responding. Rats self-administered oral ethanol in a multiple schedule of reinforcement in which responding was reinforced in two components signaled by different stimuli. In one component, response-independent food was delivered in addition to the earned ethanol. The effects of the alternative food reinforcer on response rates and resistance to extinction in the two components were examined. As in previous experiments on the resistance to change of food-maintained operant behavior, response rates were lower, but more resistant to extinction in the presence of the stimulus associated with the alternative reinforcer. These findings suggest that all the reinforcers obtained in a context in which drugs are consumed may contribute to the persistence of drug seeking in that context. This increase in persistence may occur even if the alternative reinforcers interfere with drug seeking.     

D-Amphetamine reinstates behavior previously maintained by food: importance of context

The drug self-administration reinstatement procedure provides an important animal model of relapse. While the procedure is widely used, there has been little investigation of the basic processes involved. This experiment determined the specificity of reinstatement by examining reinstatement of food seeking by D-amphetamine. During training, 24 rats pressed levers for food. Eight rats received 3.0 mg/kg D-amphetamine before and saline after sessions. Eight rats received saline before and after sessions. The final eight rats received saline before and 3.0 mg/kg D-amphetamine after sessions. All rats then experienced saline injections and extinction. During a reinstatement test, all rats received 3.0 mg/kg D-amphetamine. D-Amphetamine significantly increased lever pressing for rats with prior exposure to amphetamine as a predictive cue for food (pre-session) and for rats with no prior exposure to amphetamine. The effect was larger for rats with pre-session exposure to amphetamine than for rats with no previous exposure. Rats with exposure to amphetamine but not as a predictive cue for food (after sessions) did not show significant reinstatement of lever pressing. Therefore, the reinstating effects of amphetamine are not restricted to behavior previously maintained by amphetamine self-administration. In animal models of relapse, reinstatement of drug seeking could be due, in part, to discriminative and direct effects of self-administered drug.     

Virion-associated cholesterol is critical for the maintenance of HIV-1 structure and infectivity

OBJECTIVE: HIV-1 particles are enriched with cholesterol; however, the significance of this cholesterol enrichment is unknown. This study examines the structural and functional roles of cholesterol in HIV-1 replication. METHODS: Using methyl-beta-cyclodextrin (CD) to remove cholesterol from the HIV-1 envelope, buoyant density and infectivity of the cholesterol-deficient HIV-1 particles were compared with the untreated control. The specificity and requirement of cholesterol as an HIV-1-associated lipid were investigated by replenishing cholesterol-deficient HIV-1 with cholesterol, cholestenone (a cholesterol structural analogue) or sphingomyelin (a structurally unrelated yet virion-associated lipid). RESULTS: CD-mediated removal of virion cholesterol increased the buoyant density of virion particles and reduced HIV-1 infectivity. Trans-supplementation of exogenous cholesterol rescued the defects associated with CD-induced cholesterol depletion in HIV-1. However, the restoration of viral infectivity could not be achieved by trans-supplementation of either cholestenone or sphingomyelin. CONCLUSION: This study provides the first direct evidence that HIV-1-associated cholesterol is important for the maintenance of virion structure and infectivity. While the buoyant density of cholesterol-defective HIV-1 can be restored by a cholesterol structural analogue, cholestenone, the requirement for cholesterol is essential for HIV-1 infectivity.     

Occipital extra- and intracranial lipoencephalocele associated with tectocerebellar dysraphia

Objects Tectocerebellar dysraphism was first described by Padget and Lindenberg, together with occipital encephaloceles, cerebellar midline defects, tectal beaking, posterior kinked and displaced brainstem, and inverted cerebellum. We present a unique case of lipoencephalocele associated with tectocerebellar dysraphia and discuss the etiologies of both pathologies. The importance of the developmental comprehension of posterior fossa malformations is stressed.Case report A 9-month-old girl in good health was referred for a huge occipital mass. On local examination, the patient had a rounded mass about 10×12 cm in size, covered by alopecic skin, with a small eccentric dimple without any discharge. Magnetic resonance imaging revealed a lipoencephalocele with an intra- and an extracranial part, associated with tectocerebellar dysraphia with no aspect of inverted cerebellum as originally described in the tectocerebellar dysraphia. Resection of the extracranial part of the lipoma was performed for esthetic reasons. The intracranial part remained in situ.Conclusion The association of lipoencephalocele and tectocerebellar dysraphia is extremely rare. The functional prognosis seems to be less severe for this combination than for the isolated tectocerebellar dysraphia. This association favors the dysraphic theory for the embryogenesis of the lipoma. It seems safe to restrict the surgery of this bizarre malformation to its external part.Commentaries on this paper are available at , , , , and