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1.  Pre-resuscitation Lactate and Hospital Mortality in Prehospital Patients 
Serum lactate elevations are associated with morbidity and mortality in trauma patients, but their value in prehospital medical patients prior to resuscitation is unknown. We sought to assess the distribution of blood lactate concentrations prior to intravenous (IV) resuscitation and examine the association of elevation on in-hospital death.
A convenience sample of adult patients over 14 months who received an IV line by eight EMS agencies in Western Pennsylvania had lactate measurement prior to any IV treatment. We assessed the lactate values and any relationship between these and hospital mortality (our primary outcome) and admission to the intensive care unit (ICU). We also compared the ability of lactate to discriminate outcomes with a prehospital critical illness score using age, Glasgow Coma Score, and initial vital signs.
We included 673 patients, among whom 71 (11%) were admitted to the ICU and 21 (3.1%) died in-hospital. Elevated lactate (≥2 mmol/L) occurred in 307 (46%) patients and was strongly associated with hospital death after adjustment for known covariates (odds ratio = 3.57, 95% confidence interval [CI]: 1.10, 11.6). Lactate ≥2 mmol/L had a modest sensitivity (76%) and specificity (55%), and discrimination for hospital death (area under the curve [AUC] = 0.66, 95%CI: 0.56, 0.75). Compared to the prehospital critical illness score alone (AUC = 0.69, 95% CI: 0.59, 0.80), adding lactate to the score offered modest improvement (net reclassification improvement = 0.63, 95%CI: 0.23, 1.01, p < 0.05).
Initial lactate concentration in our prehospital medical patient population was associated with hospital mortality. However, it is a modest predictor of outcome, offering similar discrimination to a prehospital critical illness score.
PMCID: PMC4240252  PMID: 24548128
emergency medical services; critical illness; lactic acid; prehospital; pre-resuscitation
2.  Extending our Reach: Use of mHealth to Support Patients after Emergency Care 
Annals of emergency medicine  2014;63(6):755-756.
PMCID: PMC4120244  PMID: 24486096
3.  Using online crowdsourcing to understand young adult attitudes toward expert-authored messages aimed at reducing hazardous alcohol consumption and to collect peer-authored messages 
Text message delivered prevention interventions have the potential to improve health behaviors on a large scale, including reducing hazardous alcohol consumption in young adults. Online crowdsourcing can be used to efficiently develop relevant messages, but remains largely understudied. This study aims to use online crowdsourcing to evaluate young adult attitudes toward expert-authored messages and to collect peer-authored messages. We designed an online survey with four drinking scenarios and a demographic questionnaire. We made it available to people who reported age 18–25 years, residence in the US, and any lifetime alcohol consumption via the Amazon Mechanical Turk crowdsourcing platform. Participants rated 71 sample text messages on instrumental (helpful) and affective (interesting) attitude scales and generated their own messages. All messages were coded as informational, motivational, or strategy facilitating. We examined differences in attitudes by message type and by drinking status and sex. We surveyed 272 participants in 48 h, and 222 were included in analysis for a total participant payment cost of $178. Sample mean age was 23 years old, with 50 % being female, 65 % being of white race, and 78 % scored as hazardous drinkers. Informational messages were rated the most helpful, whereas motivational messages were rated the most interesting. Hazardous drinkers rated informational messages less helpful than non-hazardous drinkers. Men reported messages less helpful and interesting than women for most categories. Young adults authored 161 messages, with the highest proportion being motivational. Young adults had variable instrumental and affective attitudes toward expert-authored messages. They generated a substantial number of peer-authored messages that could enhance relevance of future alcohol prevention interventions.
PMCID: PMC4332899  PMID: 25729452
Crowdsourcing; Young adult; Intervention
4.  Potential Utility of Near Infrared Spectroscopy in out-of-hospital cardiac arrest: An Illustrative Case Series 
We evaluated the measurement of tissue oxygen content (StO2) by continuous Near Infrared Spectroscopy (NIRS) during and following CPR, and compared the changes in StO2 and end-tidal CO2 (ETCO2) as a measure of return of spontaneous circulation (ROSC) or re-arrest.
This is a case series of five patients who experienced out-of hospital cardiac arrest. Patients included those who had already experienced ROSC, were being transported to the hospital, or who were likely to have a reasonable amount of time remaining in the resuscitation efforts. Patients were continuously monitored from the scene using continuous ETCO2 monitoring, and a NIRS StO2 monitor until patients reached the hospital. ETCO2 and StO2 values were continuously recorded and analyzed for comparison of when patients were clinically identified to have ROSC or re-arrest.
Four of five patients had StO2 and EtCO2 recorded during an episode of CPR and all were monitored during the post-arrest period. Three patients experienced re-arrest en route to the hospital. Downward trends were noted in StO2 prior to each re-arrest, and rapid increases were noted after ROSC. StO2 data showed less variance than ETCO2 in the peri-arrest period.
This preliminary study in humans demonstrates that StO2 dynamically changes during periods of hemodynamic instability in post-arrest patients. These data suggest that a decline in StO2 level may correlate with re-arrest and may be useful as a tool to predict re-arrest in post cardiac arrest patients. A rapid increase in StO2 was also seen upon ROSC and may be a better method of identifying ROSC during CPR than pauses for pulse checks or ETCO2 monitoring.
PMCID: PMC4263912  PMID: 22823984
Resuscitation; Hemodynamics
5.  A Text Message Alcohol Intervention for Young Adult Emergency Department Patients: A Randomized Clinical Trial 
Annals of emergency medicine  2014;64(6):664-672.e4.
Opportunistic brief in-person Emergency Department (ED) interventions can be effective at reducing hazardous alcohol use in young adult drinkers, but require resources frequently unavailable. Mobile phone text messaging (SMS) could sustainably deliver behavioral support to young adult patients, but efficacy remains unknown. We report 3-month outcome data of a randomized controlled trial testing a novel SMS-delivered intervention in hazardous drinking young adults.
We randomized 765 young adult ED patients who screened positive for past hazardous alcohol use to one of three groups: SMS Assessments + Feedback (SA+F) intervention who were asked to respond to drinking-related queries and received realtime feedback through SMS each Thursday and Sunday for 12 weeks (n=384); SMS Assessments (SA) who were asked to respond to alcohol consumption queries each Sunday but did not receive any feedback (N=196); and a control group who did not participate in any SMS (n=185). Primary outcomes were number of binge drinking days and number of drinks per drinking day in the past 30 days collected by web-based Timeline Follow-Back method and analyzed with regression models. Secondary outcomes were the proportion of participants with weekend binge episodes and most drinks consumed per drinking occasion over 12 weekends collected by SMS.
Using web-based data, there were decreases in the number of binge drinking days from baseline to 3 months in the SA+F group (-.51 [95% confidence interval {CI} -.10 to -.95]), whereas there were increases in the SA group (.90 [95% CI .23 to 1.6]) and the control group (.41 [95% CI -.20 to 1.0]). There were also decreases in the number of drinks per drinking day from baseline to 3 months in the SA+F group (-.31 [95% CI -.07 to -.55]), whereas there were increases in the SA group (.10 [95% CI -.27 to .47]) and the control group (.39 [95% CI .06 to .72]). Using SMS data, there was a lower mean proportion of SA+F participants reporting a weekend binge over 12 weeks (30.5% [95% CI 25% to 36%) compared to the SA participants (47.7% [95% CI 40% to 56%]). There was also a lower mean drinks consumed per weekend over 12 weeks in the SA+F group (3.2 [95%CI 2.6 to 3.7]) compared to the SA group (4.8 [95% CI 4.0 to 5.6]).
A text message intervention can produce small reductions in binge drinking and the number of drinks consumed per drinking day in hazardous drinking young adults after ED discharge.
PMCID: PMC4254153  PMID: 25017822
6.  Lipid Emulsion Combined with Epinephrine and Vasopressin Does Not Improve Survival in a Swine Model of Bupivacaine-induced Cardiac Arrest 
Anesthesiology  2009;111(1):138-146.
We sought to evaluate the efficacy of lipid emulsion in reversing bupivacaine-induced cardiovascular collapse when added to a resuscitation protocol that included the use of epinephrine and vasopressin.
Following induction of general anesthesia and instrumentation, 19 mixed-breed domestic swine had cardiovascular collapse induced by an intravenous bolus of 10 mg/kg bupivacaine. After 5 minutes of resuscitation including chest compressions, epinephrine (100 μg/kg) and vasopressin (1.5 u/kg), animals were randomized to receive either a bolus of 20% lipid emulsion (4 mL/kg) followed by a continuous infusion (0.5 mL· kg−1 ·min−1) or an equal volume of saline. Investigators were blinded to the treatment assignment. The primary end-point was return of spontaneous circulation (mean arterial pressure of ≥ 60 mmHg for ≥ 1 minute).
Treatment groups were similar with respect to baseline measurements of weight, sex, hemodynamic and metabolic variables. The rates of return of spontaneous circulation were similar between groups, 3 of 10, in the lipid group, and 4 of 9, in the saline group (P = 0.65). Total serum bupivacaine concentrations were higher in the lipid group at the 10-minute time point, (mean ± SEM: 23.13 ± 5.37 ng/mL versus 15.33 ± 4.04 ng/mL, P = 0.004). More norepinephrine was required in the lipid group compared to the saline group to maintain a mean arterial pressure > 60 mmHg during the 60 minute survival period (mean ± SEM: 738.6 ± 94.4 vs. 487.3 ± 171.0 μg).
In this swine model, lipid emulsion did not improve rates of return of spontaneous circulation after bupivacaine-induced cardiovascular collapse.
PMCID: PMC4174466  PMID: 19512878
7.  Mobile phone text messaging intervention to improve alertness and reduce sleepiness and fatigue during shiftwork among emergency medicine clinicians: study protocol for the SleepTrackTXT pilot randomized controlled trial 
Trials  2014;15:244.
Mental and physical fatigue while at work is common among emergency medical services (EMS) shift workers. Extended shifts (for example 24 hours) and excessive amounts of overtime work increase the likelihood of negative safety outcomes and pose a challenge for EMS fatigue-risk management. Text message-based interventions are a potentially high-impact, low-cost platform for sleep and fatigue assessment and distributing information to workers at risk of negative safety outcomes related to sleep behaviors and fatigue.
We will conduct a pilot randomized trial with a convenience sample of adult EMS workers recruited from across the United States using a single study website. Participants will be allocated to one of two possible arms for a 90-day study period. The intervention arm will involve text message assessments of sleepiness, fatigue, and difficulty with concentration at the beginning, during, and end of scheduled shifts. Intervention subjects reporting high levels of sleepiness or fatigue will receive one of four randomly selected intervention messages promoting behavior change during shiftwork. Control subjects will receive assessment only text messages. We aim to determine the performance characteristics of a text messaging tool for the delivery of a sleep and fatigue intervention. We seek to determine if a text messaging program with tailored intervention messages is effective at reducing perceived sleepiness and/or fatigue among emergency medicine clinician shift workers. Additional aims include testing whether a theory-based behavioral intervention, delivered by text message, changes ‘alertness behaviors’.
The SleepTrackTXT pilot trial could provide evidence of compliance and effectiveness that would support rapid widespread expansion in one of two forms: 1) a stand-alone program in the form of a tailored/individualized sleep monitoring and fatigue reduction support service for EMS workers; or 2) an add-on to a multi-component fatigue risk management program led and maintained by employers or by safety and risk management services.
Trial Registration NCT02063737, Registered on 10 January 2014
PMCID: PMC4080698  PMID: 24952387
Shiftwork; Sleepiness; Fatigue; Alertness; Emergency medicine; Randomized controlled trial
8.  Prehospital dynamic tissue oxygen saturation response predicts in-hospital lifesaving interventions in trauma patients 
Tissue oximetry (StO2) plus a vascular occlusion test is a noninvasive technology that targets indices of oxygen uptake and delivery. We hypothesize that prehospital tissue oximetric values and vascular occlusion test response can predict the need for in-hospital lifesaving interventions (LSI).
We conducted a prospective, blinded observational study to evaluate StO2 slopes to predict the need for LSI. We calculated the DeO2 slope using Pearson’s coefficients of regression (r2) for the first 25% of descent and the ReO2 slope using the entire recovery interval. The primary outcome was LSI defined as the need for emergent operation or transfusion in the first 24 hours of hospitalization. We created multivariable logistic regression models using covariates of age, sex, vital signs, lactate, and mental status.
We assessed StO2 in a convenience sample of 150 trauma patients from April to November of 2009. In-hospital mortality was 3% (95% confidence interval [CI], 1.1–7.6); 31% (95% CI, 24–39) were admitted to the intensive care unit, 6% (95% CI, 2.8–11.1) had an emergent operation, and 10% (95% CI, 5.7–15.9) required transfusion. Decreasing DeO2 was associated with a higher proportion of patients requiring LSI. In the multivariate model, the association between the need for LSI and DeO2, Glasgow Coma Scale, and age persists.
Prehospital DeO2 is associated with need for LSI in our trauma population. Further study of DeO2 is warranted to determine whether it can be used as an adjunct triage criterion or an endpoint for resuscitation.
III, observational study.
PMCID: PMC3770128  PMID: 22491607
Prehospital; near-infrared spectroscopy; trauma
9.  Mobile phone text message intervention to reduce binge drinking among young adults: study protocol for a randomized controlled trial 
Trials  2013;14:93.
Heavy episodic (binge) drinking is common among young adults and can lead to injury and illness. Young adults who seek care in the Emergency Department (ED) may be disproportionately affected with binge drinking behavior, therefore provide an opportunity to reduce future risk through screening, brief intervention and referral to treatment (SBIRT). Mobile phone text messaging (SMS) is a common form of communication among young adults and has been shown to be effective at providing behavioral support to young adult drinkers after ED discharge. Efficacy of SMS programs to reduce binge drinking remains unknown.
We will conduct a three parallel arm, randomized trial. A convenience sample of adults aged 18 to 25 years attending three EDs in Pittsburgh, PA and willing to participate in the study will be screened for hazardous alcohol consumption. Participants identified as hazardous drinkers will then be allocated to either 12 weeks of weekly SMS drinking assessments with feedback (SA+F), SMS drinking assessments without feedback (SA), or a control group. Randomization will be via an independent and remote computerized randomization and will be stratified by study site. The SA+F group will be asked to provide pre-weekend drinking intention as well as post-weekend consumption via SMS and will receive feedback messages focused on health consequences of alcohol consumption, personalized normative feedback, protective drinking strategies and goal setting. Follow-up data on alcohol use and injury related to alcohol will be collected through a password-protected website three, six and nine months later. The primary outcome for the study is binge drinking days (≥4 drinks for women; ≥5 drinks for men) during the previous month, and the main secondary outcome is the proportion of participants who report any injury related to alcohol in the prior three months.
This study will test the hypothesis that a mobile phone text-messaging program will result in immediate and durable reductions in binge drinking among at-risk young adults. By testing an intervention group to an assessment-only and control group, we will be able to separate the effect of assessment reactivity. By collecting pre-weekend drinking intentions and post-weekend consumption data in the SA+F group, we will be able to better understand mechanism of change.
Trial registration NCT01688245
PMCID: PMC3652768  PMID: 23552023
Alcohol misuse; Intervention; Randomized controlled trial; Effectiveness
11.  Knowledge translation in emergency medical services: A qualitative survey of barriers to guideline implementation 
Resuscitation  2010;81(7):836-840.
The American Heart Association (AHA) released guidelines to improve survival rates from out-of-hospital cardiac arrest in 2005. We sought to identify what barriers delayed the implementation of these guidelines in EMS agencies.
We surveyed 178 EMS agencies as part of a larger quantitative survey regarding guideline implementation and conducted a single-question semi-structured interview using the Grounded Theory method. We asked “What barriersm if any, delayed implementation of the (2005 AHA) guidelines in your EMS agency?” Data were coded and member validation was employed to verify our findings.
176/178 agencies completed the quantitative survey. Qualitative data collection ceased after reaching theoretical saturation with 34 interviews. Ten unique barriers were identified. We categorized these ten barriers into three themes. The theme Instruction Delays (reported by 41% of respondents) included three barriers: booking/training instructors (9%), receiving training materials (15%), and scheduling staff for training (18%). The second theme, Defibrillator Delays (38%), included two barriers; reprogramming defibrillators (24%) and receiving new defibrillators to replace non-upgradeable units (15%). The third theme was Decision-Making (38%) and included five barriers; coordinating with allied agencies (9%), government regulators such as state and provincial health authorities (9%), medical direction and base hospitals (9%), ROC participation (9%), and internal crises (3%).
Many barriers contributed to delays in the implementation of the 2005 AHA guidelines in EMS agencies. These identified barriers should be proactively addressed prior to the 2010 Guidelines to facilitate rapid translation of science into clinical practice.
PMCID: PMC3209799  PMID: 20398994
heart arrest; emergency medical services
12.  Delayed Prehospital Implementation of the 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care 
In 2005, the American Heart Association (AHA) released guidelines to improve survival rates from out-of-hospital cardiac arrest (OHCA).
To determine if, and when, emergency medical services (EMS) agencies participating in the Resuscitation Outcomes Consortium (ROC) implemented these guidelines.
We contacted 178 EMS agencies and completed structured telephone interviews with 176 agencies. The survey collected data on specific treatment protocols before and after implementation of the 2005 guidelines as well as the date of implementation crossover (the “crossover date”). The crossover date was then linked to a database describing the size, type, and structure of each agency. Descriptive statistics and regression were used to examine patterns in time to crossover.
The 2005 guidelines were implemented by 174 agencies (99%). The number of days from guideline release to implementation was as follows: mean 416 (standard deviation 172), median 415 (range 49–750). There was no difference in time to implementation in fire-based agencies (mean 432), nonfire municipal agencies (mean 365), and private agencies (mean 389, p = 0.31). Agencies not providing transport took longer to implement than agencies that transported patients (463 vs. 384 days, p = 0.004). Agencies providing only basic life support (BLS) care took longer to implement than agencies who provided advanced life support (ALS) care (mean 462 vs. 397 days, p = 0.03). Larger agencies (>10 vehicles) were able to implement the guidelines more quickly than smaller agencies (mean 386 vs. 442 days, p = 0.03). On average, it took 8.9 fewer days to implement the guidelines for every 50% increase in EMS-treated runs/year to which an agency responded.
ROC EMS agencies required an average of 416 days to implement the 2005 AHA guidelines for OHCA. Small EMS agencies, BLS-only agencies, and nontransport agencies took longer than large agencies, agencies providing ALS care, and transport agencies, respectively, to implement the guidelines. Causes of delays to guideline implementation and effective methods for rapid EMS knowledge translation deserve investigation.
PMCID: PMC3209500  PMID: 20388032
heart arrest; emergency medical services; knowledge translation; prehospital care; guidelines; implementation
13.  Sleep Quality and Fatigue Among Prehospital Providers 
Fatigue is common among medical professionals and has been linked to poor performance and medical error.
To characterize sleep quality and its association with severe fatigue in emergency medical services (EMS) providers.
We studied a convenience sample of EMS providers who completed three surveys: the Pittsburgh Sleep Quality Index (PSQI), the Chalder Fatigue Questionnaire (CFQ), and a demographic survey. We used established measures to examine survey psychometrics and performed t-tests, analysis of variance (ANOVA), and chi- square tests to identify differences in PSQI and CFQ scores.
One hundred nineteen surveys were completed. The eight-hour shift was most commonly reported (35.4%). A majority of subjects were overweight (41.9%) or obese (42.7%), and 59.6% had been diagnosed with one or more health conditions (e.g., diabetes). Results from psychometric tests were positive. The mean (± standard deviation) PSQI score was 9.2 (± 3.7). A CFQ score >4, indicating severe mental and physical fatigue, was present in 44.5% of the subjects. The mean PSQI score was higher among those reporting severe fatigue (11.3 ± 3.2) than among those not reporting fatigue (7.5 ± 3.0, p < 0.0001).
The results from this study suggest that the sleep quality and fatigue status of EMS workers are at unhealthy levels. The health and safety of the EMS worker and patient population should be considered in light of these results.
PMCID: PMC2895322  PMID: 20199233
emergency medical services; sleep; fatigue
14.  Effects of pre-arrest and intra-arrest hypothermia on ventricular fibrillation and resuscitation 
Resuscitation  2008;80(1):126-132.
Hypothermia has been shown to improve survival and neurological outcomes for ventricular fibrillation (VF) cardiac arrest. The electrophysiological mechanisms of hypothermia are not well-understood, nor are the effects of beginning cooling during the resuscitation.
Methods and Results
We hypothesized that inducing hypothermia prior to the onset of VF would slow the deleterious changes seen in the ECG during VF and that inducing hypothermia at the start of resuscitation would increase the rates of ROSC and short-term survival in a porcine model of prolonged VF. We randomly assigned 42 domestic swine (27.2 ±2.3 kgs) to either pretreatment with hypothermia before induction of VF (PRE), normothermic resuscitation (NORM) or intra-resuscitation hypothermia (IRH). During anesthesia, animals were instrumented via femoral cutdown. Lead II ECG was recorded continuously. PRE animals were cooled before the induction of VF, with a rapid infusion of 4° normal saline (30 mL/kg). VF was induced electrically, left untreated for 8 minutes, then mechanical CPR began. During CPR the NORM animals got 30 mL/kg body-temperature saline and the IRH animals got 30 mL/kg 4° saline. In all groups first rescue shocks were delivered after 13 minutes of VF. We calculated the VF scaling exponent (ScE) for the entire 8 minute period (compared using GEE). ROSC and survival were compared with Fisher's exact test. Mean temperature in °C at the onset of VF was PRE=34.7° (±0.8), NORM=37.8 (±0.9), and IRH=37.9 (±0.9). The ScE values over time were significantly lower after 8 minutes in the PRE group (p=0.02). ROSC: PRE=10/14 (71%), NORM=6/14 (43%) and IRH=12/14 (86%); p for IRH vs. NORM=0.02. Survival: PRE=9/14 (64%), NORM=5/14 (36%), IRH 8/14 (57%).
Hypothermia slowed the decay of the ECG waveform during prolonged VF. IRH improved ROSC but not short-term survival compared to NORM. It is possible to rapidly induce mild hypothermia during CPR using an IV infusion of ice-cold saline.
PMCID: PMC2720166  PMID: 18952346
heart arrest; cardiopulmonary resuscitation; ventricular fibrillation; hypothermia
15.  Increasing CPR duration prior to first defibrillation does not improve return of spontaneous circulation or survival in a swine model of prolonged ventricular fibrillation 
Resuscitation  2008;79(1):155-160.
The optimum duration of cardiopulmonary resuscitation (CPR) prior to first rescue shock is unknown. Clinical trials have used 90s and 180s. Neither of these durations may be optimal. We sought to determine the optimum duration of CPR prior to first defibrillation attempt and whether this varied depending on the duration of ventricular fibrillation (VF). In this porcine model of basic life support, our outcomes were rates of return of spontaneous circulation (ROSC), survival, and coronary perfusion pressure (CPP).
We anesthetized and instrumented 45 swine and then induced VF. After 5 or 8 minutes of untreated VF, we randomized the swine to mechanical CPR for 90, 180, or 300s. A single rescue shock (150J biphasic) was then administered. If this shock failed, 2 minutes of mechanical CPR were completed prior to the next rescue shock. CPP was calculated for each 30 second epoch. ROSC was defined as a blood pressure >80mmHg sustained for 60s. Survival was defined as sustained ROSC for 20 minutes. Data were analyzed with descriptive statistics, Fisher’s exact test, and ANOVA.
In the 5 minute VF cohort, the rate of ROSC did not differ between the three groups (90s: 25%; 180s: 38%; 300s: 38%, p>.05). Survival rates did not differ (90s: 25%; 180s: 25%; 300s: 25%, p>0.05). In the 8 minute VF cohort, no animals experienced ROSC or survival. CPP were calculated by 30 second epoch and did not differ between the three groups (p>0.05). CPPs decline after 180s of CPR.
ROSC and survival were equivalent regardless of VF duration and CPR duration. When CPR begins late, CPPs are low, stressing the importance of early CPR. We do not recommend 300s of CPR unless a defibrillator is unavailable.
PMCID: PMC2582345  PMID: 18620793
Cardiopulmonary resuscitation (CPR); Resuscitation; Heart Arrest; Drugs
17.  Peripheral myelin of Xenopus laevis: Role of electrostatic and hydrophobic interactions in membrane compaction 
Journal of structural biology  2007;162(1):170-183.
P0 glycoprotein is the major structural protein of peripheral nerve myelin where it is thought to modulate inter-membrane adhesion at both the extracellular apposition, which is labile upon changes in pH and ionic strength, and the cytoplasmic apposition, which is resistant to such changes. Most studies on P0 have focused on structure-function correlates in higher vertebrates. Here, we focused on its role in the structure and interactions of frog (Xenopus laevis) myelin, where it exists primarily in a dimeric form. As part of our study, we deduced the full sequence of Xenopus laevis P0 (xP0) from its cDNA. The xP0 sequence was found to be similar to P0 sequences of higher vertebrates, suggesting that a common mechanism of PNS myelin compaction via P0 interaction might have emerged through evolution. As previously reported for mouse PNS myelin, a similar change of extracellular apposition in frog PNS myelin as a function of pH and ionic strength was observed, which can be explained by a conformational change of P0 due to protonation-deprotonation of His52 at P0’s putative adhesive interface. On the other hand, the cytoplasmic apposition in frog PNS myelin, like that in the mouse, remained unchanged at different pH and ionic strength. The contribution of hydrophobic interactions to stabilizing the cytoplasmic apposition was tested by incubating sciatic nerves with detergents. Dramatic expansion at the cytoplasmic apposition was observed for both frog and mouse, indicating a common hydrophobic nature at this apposition. Urea also expanded the cytoplasmic apposition of frog myelin likely owing to denaturation of P0. Removal of the fatty acids that attached to the single Cys residue in the cytoplasmic domain of P0 did not change PNS myelin structure of either frog or mouse, suggesting that the P0-attached fatty acyl chain does not play a significant role in PNS myelin compaction and stability. These results help clarify the present understanding of P0’s adhesion role and the role of its acylation in compact PNS myelin.
PMCID: PMC2435285  PMID: 18065238
x-ray diffraction; membrane-membrane interactions; protein zero cDNA; PNS; detergents; hydroxylamine; adhesion protein; frog; mass spectrometry

Results 1-17 (17)