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Biomedical subjects

Anna Lee

Publications and source records attributed to Anna Lee.

35 records · Page 2Linked to original sources

SHP-1 negatively regulates neuronal survival by functioning as a TrkA phosphatase.

Nerve growth factor (NGF) mediates the survival and differentiation of neurons by stimulating the tyrosine kinase activity of the TrkA/NGF receptor. Here, we identify SHP-1 as a phosphotyrosine phosphatase that negatively regulates TrkA. SHP-1 formed complexes with TrkA at Y490, and dephosphorylated it at Y674/675. Expression of SHP-1 in sympathetic neurons induced apoptosis and TrkA dephosphorylation. Conversely, inhibition of endogenous SHP-1 with a dominant-inhibitory mutant stimulated basal tyrosine phosphorylation of TrkA, thereby promoting NGF-independent survival and causing sustained and elevated TrkA activation in the presence of NGF. Mice lacking SHP-1 had increased numbers of sympathetic neurons during the period of naturally occurring neuronal cell death, and when cultured, these neurons survived better than wild-type neurons in the absence of NGF. These data indicate that SHP-1 can function as a TrkA phosphatase, controlling both the basal and NGF-regulated level of TrkA activity in neurons, and suggest that SHP-1 regulates neuron number during the developmental cell death period by directly regulating TrkA activity.

Animals↗

Level of prehospital care and risk of mortality in patients with and without severe blunt head injury.

OBJECTIVES: To determine the association between mortality and the level of prehospital care in severely injured blunt trauma patients with or without severe head injury. METHOD: Retrospective review of 2010 severe blunt trauma patients (injury severity score (ISS) >15) with or without severe head injury in a tiered trauma system involving ambulance officers (basic life support (BLS) and advanced life support (ALS)) and physicians, and a Level 1 trauma centre. RESULTS: After adjusting for age, type of head injury, glasgow coma scale score (GCS), systolic blood pressure, ISS and prehospital time, intensive care unit (ICU) admission modified the association between level of prehospital care and mortality. In those patients without ICU admission, patients in the paramedic and physician-staffed emergency services group were more likely to die than patients in the BLS ambulance group (odds ratio (OR) 2.18, 95% confidence intervals (CI): 1.05-4.55; 4.27, 95% CI: 1.46-12.45, respectively). Among patients who survived to ICU treatment, however, there was no association between level of prehospital care and risk of mortality. Presence or absence of a head injury did not modify the risk of mortality. CONCLUSIONS: The level of prehospital care was associated with the risk of mortality. This was modified by whether the patient survived long enough to be admitted to the ICU.

Adult↗

In utero herpes simplex encephalitis.

BACKGROUND: Transplacental intrauterine infection with herpes simplex virus is an extremely rare complication of primary herpes simplex in pregnancy. Overwhelming fetal sepsis might result in multiorgan failure, including fetal brain death. CASE: A 34-year-old multigravida presented with a healing ulcerative genital rash at 16 weeks' gestation. She subsequently reported at 28 weeks' gestation that there had been no fetal movements for 2 weeks. A cardiotocograph showed absent short- and long-term variability. At delivery, an infant was born with disseminated herpes simplex infection in poor condition. Active treatment was subsequently withdrawn, and postmortem examination confirmed disseminated herpes simplex type 2 infection. CONCLUSION: Transplacental herpes simplex is a rare and potentially lethal form of congenital herpes. Overwhelming in utero sepsis should be considered in the differential diagnosis of fetal brain death.

Adult↗

Agreements between the prothrombin times of blood treated In Vitro with heparinase during cardiopulmonary bypass (CPB) and blood sampled after CPB and systemic protamine.

UNLABELLED: The prothrombin time (PT) is useful for identifying coagulation factor deficits after cardiopulmonary bypass (CPB). However, long processing times and the need for fresh frozen plasma (FFP) to be thawed cause delays in factor replacement. We hypothesized that, by treating with heparinase, blood sampled toward the end of CPB can provide PT results that help to determine the requirement for FFP after CPB. Laboratory delays can be eliminated with point-of-care monitors. We studied 158 adults undergoing nonemergent cardiac surgery. Blood taken before separation from CPB was mixed with heparinase, and PT was measured in the laboratory with a HemoTec timer. Agreements between these results and laboratory measurements of blood taken after systemic protamine were compared by using Bland and Altman plots with the threshold of +/-1.0 s. We found that the laboratory PT measurements during CPB versus after CPB were compara-ble, but the limits of agreement exceeded these thresholds. Similarly, there was unsatisfactory agreement between the HemoTec and laboratory PT results measured before, during, and after CPB. For each PT measured during CPB, the corresponding confidence interval for the postprotamine PT was calculated. During CPB, a laboratory PT of < or =16 s or > or =18 s suggests a > or =83% or > or =93% probability of not requiring or potentially requiring, respectively, FFP after CPB. We conclude that the majority of PT measurements obtained from blood taken before weaning from CPB and treated in vitro with heparinase was associated with a high probability of whether or not FFP would be needed after CPB. IMPLICATIONS: Coagulation dysfunction after cardiopulmonary bypass may contribute to bleeding. Obtaining coagulation tests and fresh frozen plasma requires time and delays treatment in patients who need fresh frozen plasma. We have devised a technique to provide early estimation of postbypass coagulation status.

Aged↗

Survey of current status of intensive care teaching in English-speaking medical schools.

OBJECTIVE: To identify a consensus of opinion regarding the content of an intensive care core syllabus for undergraduate medical students and factors that may limit its teaching. DESIGN: Cross-sectional postal survey containing 35 items ranging from department structure to curriculum content and factors that limit the teaching of intensive care. SETTING: English-speaking medical schools (n = 210) listed in the 1986 World Health Organization Directory. MEASUREMENTS AND MAIN RESULTS: Of 122 (58%) returned questionnaires, a 45% return was achieved from the United States and 86% from non-U.S. countries. Most respondents (84%) considered teaching undergraduate intensive care to be essential; however, teaching intensive care was compulsory in only 31% of schools. Many schools (43%) reported recent changes to their intensive care curriculum. Most respondents (60%) thought that intensive care specialists should teach and that each student required a median (interquartile range) of 20 (10-80) hrs of teacher contact time. Resuscitation skills were taught in 98% of schools. In comparison, 63% of schools had no intensive care syllabus. More than 90% of respondents thought that the intensive care syllabus should include the following: cardiopulmonary resuscitation, assessment and management of the acutely ill patient; management of respiratory, circulatory, and multiple organ system failure (including systemic inflammatory response syndrome and sepsis); management of the unconscious patient; early postoperative care; and communication skills and ethics as they relate to end-of-life issues. Factors that limited intensive care teaching were lack of staff, funding, and time dedicated to teaching and excessive clinical workload. Student performance in intensive care was assessed by 66% of schools, but only 28% used a written or oral examination. CONCLUSIONS: By surveying a wide range of medical schools internationally, we have been able to define an undergraduate intensive care syllabus that could be delivered in 20 hrs or 1 wk of dedicated teaching time. Factors that impede the provision of undergraduate intensive care teaching are a lack of staff, funding, and dedicated teaching time.

Critical Care↗

Educating patients about anesthesia: a systematic review of randomized controlled trials of media-based interventions.

UNLABELLED: In this systematic review, we compared the effectiveness of media-based patient education about anesthesia. Fifteen randomized controlled trials (n = 1506) were identified after a systematic search of electronic databases (MEDLINE, EMBASE, CINAHL, PSYCINFO, The Cochrane Controlled Trials Registry), published articles, and contact with authors. Outcomes assessed were anxiety, knowledge, and patient satisfaction. Anxiety levels before anesthesia were less intense in subjects receiving the video and printed information compared with those receiving no intervention (weighted mean difference of 3; 95% confidence interval [95%CI], 1-5 Spielberger's State and Trait Anxiety Inventory). Patients in the video group were more likely to answer all knowledge questions correctly compared with patients with no intervention (relative risk of 6.64; 95%CI, 2.05-21.52). The level of knowledge about pain management was higher in the video group compared with patients with no intervention (weighted mean difference of 17%; 95%CI, 9-25). However, the level of patient satisfaction with the intervention (expectation versus actual anesthetic experience) was similar between the groups (relative risk of 1.06; 95%CI, 0.93-1.22). This systematic review supports the use of video and printed information about general process and risks of anesthesia for patient education before surgery. IMPLICATIONS: The effectiveness of media-based interventions for educating patients about general process and risks of anesthesia were compared in this systematic review. The use of video and/or printed information can decrease patient anxiety and increase patient knowledge. However, patient satisfaction was similar between media-based intervention and nonintervention groups.

Adult↗

Heliox vs air-oxygen mixtures for the treatment of patients with acute asthma: a systematic overview.

OBJECTIVE: To evaluate, by systematic review, the efficacy of heliox on respiratory mechanics and outcomes in patients with acute asthma. METHODS: The search strategy included searching electronic databases (MEDLINE, EMBASE, and The Cochrane Library) and the references of relevant articles. Study quality was assessed based on allocation concealment. Randomized controlled trials (RCTs) comparing heliox to an air-oxygen mixture (airO(2)) as an adjunct treatment in patients with acute asthmatic attacks were analyzed. For the qualitative portion of the analysis, all reports of the use of heliox in patients with acute asthma were included. RESULTS: Four RCTs (n = 278) were found to have a common respiratory parameter (peak expiratory flow rate as a percentage of predicted) suitable for meta-analysis. Within the 92% confidence interval (CI), there was a small benefit with the use of heliox compared to airO(2) (weighted mean difference, + 3%; 95% CI, - 2 to + 8%). There was also a slight improvement in the dyspnea index (weighted mean difference, 0.60; 95% CI, 0.04 to 1.16) with the use of heliox over airO(2). Overall, five RCTs, one nonrandomized unblinded parallel trial, one retrospective case-matched control trial, three case series, and one case report had results in favor of heliox; one RCT and one case series showed no improvement with heliox; one RCT showed a possible detrimental effect with heliox; and 1 small RCT was inconclusive. Most investigators did not prevent entrainment of room air during heliox use or compensate for the lower nebulizing efficiency of heliox. CONCLUSION: Based on surrogate markers, heliox may offer mild-to-moderate benefits in patients with acute asthma within the first hour of use, but its advantages become less apparent beyond 1 h, as most conventionally treated patients improve to similar levels, with or without it. The effect of heliox may be more pronounced in more severe cases. There are insufficient data on whether heliox can avert tracheal intubation, or change intensive care and hospital admission rates and duration, or mortality.

Acute Disease↗

Efficiency of Iε promoter-directed switch recombination in GFP expression-based switch constructs works synergistically with other promoter and/or enhancer elements but is not tightly linked to the strength of transcription.

One key unresolved issue in immunoglobulin class switch recombination (CSR) is how the accessibility of the switch region for CSR is controlled. To better understand the nature of accessibility control for human Ig CSR, we developed a novel inducible switch recombination assay based on expression of green fluorescence protein (GFP) from switch constructs undergoing substrate switch recombination (SSR). Efficient SSR depends on the cytokine-inducible Iepsilon promoter and co-stimulation with IL-4+anti-CD40. Characterization of SSR reveals that both S-S deletional recombination and S-S inversion occur. We show that the IL-4-inducible Iepsilon promoter (pIepsilon) selectively determines the efficiency of the accessibility for SSR. However, the pIepsilon-induced transcription, by itself,is not sufficient to direct efficient SSR. For efficient SSR, both pIepsilon-driven transcriptional activity and an additional promoter/enhancer-derived activity are required. The efficiency of SSR is not tightly correlated with the strength of the combined transcriptional activity. Our results suggest that the mechanism(s) underlying the transcriptional activity, e.g. DNA modification is important for controlling the accessibility for efficient switch recombination.

Animals↗

Spinal ropivacaine for cesarean delivery: a comparison of hyperbaric and plain solutions.

UNLABELLED: We compared, in this prospective, randomized, double-blinded study, the characteristics of spinal anesthesia with plain and hyperbaric ropivacaine for elective cesarean delivery. We hypothesized that the addition of glucose would change the onset, offset, and extent of motor and sensory block from intrathecal ropivacaine. Forty ASA physical status I--II women were given 25 mg of either ropivacaine (n = 20) or ropivacaine in 8.3% glucose (n = 20) intrathecally, via a combined spinal/epidural technique in the right lateral position. Sensory changes to ice and pinprick and motor block (Bromage score) were recorded at 2.5-min intervals. Adequate anesthesia for surgery was achieved in all patients in the Hyperbaric group, whereas in the Plain group, five (25%) patients required epidural top-up because of insufficient rostral spread (P < 0.05). With hyperbaric ropivacaine, we found the following: higher cephalic spread (median [range] maximum block height to pinprick, T1 [T4 to C2] versus T3 [T11 to C3], P < 0.001); lower coefficient of variation of maximum block height (17.7% vs 21.9%); faster onset to T4 dermatome (mean [SD] 7.7 [4.9] vs 16.4 [14.1] min, P = 0.015); and faster recovery to L1 (189.0 [29.6] vs 215.5 [27.0] min, P = 0.01). The onset of complete motor block (9.9 [5.3] vs 13.8 [5.4] min, P = 0.027) and complete recovery (144.8 [28.4] vs 218.5 [56.8] min, P < 0.001) was also faster. No neurologic symptoms were found at 24 h. IMPLICATIONS: We compared hyperbaric and plain ropivacaine for combined spinal/epidural analgesia in the lateral position in patients undergoing elective cesarean delivery. Hyperbaric ropivacaine produced more rapid block with faster recovery and less requirement for epidural supplementation compared with plain ropivacaine.

Amides↗

A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery.

UNLABELLED: This quantitative systematic review compared the efficacy and safety of ephedrine with phenylephrine for the prevention and treatment of hypotension during spinal anesthesia for cesarean delivery. Seven randomized controlled trials (n = 292) were identified after a systematic search of electronic databases (MEDLINE, EMBASE, The Cochrane Controlled Trials Registry), published articles, and contact with authors. Outcomes assessed were maternal hypotension, hypertension and bradycardia, and neonatal umbilical cord blood pH values and Apgar scores. For the management (prevention and treatment) of maternal hypotension, there was no difference between phenylephrine and ephedrine (relative risk [RR] of 1.00; 95% confidence interval [CI], 0.96-1.06). Maternal bradycardia was more likely to occur with phenylephrine than with ephedrine (RR of 4.79; 95% CI, 1.47-15.60). Women given phenylephrine had neonates with higher umbilical arterial pH values than those given ephedrine (weighted mean difference of 0.03; 95% CI, 0.02-0.04). There was no difference between the two vasopressors in the incidence of true fetal acidosis (umbilical arterial pH value of <7.2; RR of 0.78; 95% CI, 0.16-3.92) or Apgar score of <7 at 1 and 5 min. This systematic review does not support the traditional idea that ephedrine is the preferred choice for the management of maternal hypotension during spinal anesthesia for elective cesarean delivery in healthy, nonlaboring women. IMPLICATIONS: Phenylephrine and ephedrine to manage hypotension during spinal anesthesia for elective cesarean delivery were compared in this systematic review. Women given ephedrine had neonates with lower umbilical cord blood pH values compared with those given phenylephrine. However, no differences in the incidence of fetal acidosis (pH value of <7.2) or neonatal Apgar scores were found.

Anesthesia, Obstetrical↗

Safety of air travel following acute myocardial infarction.

BACKGROUND: A randomized, single-blind, controlled trial was carried out to: 1) examine the safety of patients flying on commercial airlines 2 wk after a myocardial infarction; 2) determine whether or not the use of supplemental oxygen was associated with a reduced risk of in-flight adverse events; and 3) determine the need for a medical escort. METHODS: There were 38 patients who were prospectively and randomly assigned supplemental continuous oxygen therapy (2 L x min(-1) via nasal prongs; n = 19) or no oxygen (n = 19) during the flight. Prior to flying, an escorting doctor completed a medical questionnaire for each patient. Both groups underwent Holter monitoring throughout the flight. The major end-point was the development of inflight myocardial ischemia, as detected by Holter monitoring. Minor end-points included patients complaining of chest pain or dyspnea; the detection of bigeminy or trigeminy by Holter monitoring; or oxygen desaturation to less than 90%, as measured by pulse oximetry. RESULTS: Of the 38 patients enrolled, there was only 1 major end-point. This patient had a brief, self-limiting, asymptomatic episode of myocardial ischemia diagnosed by Holter monitoring. Minor end-points occurred in 13 (34%) patients. One patient had asymptomatic evidence of S-T depression on a transport monitor, but not on the Holter. Five patients had transient low (<90%) oxygen saturations, two complained of chest pain, and five had complex ventricular ectopic beats or periods of transient ventricular tachycardia. None of the minor end-points were associated with Holter evidence of myocardial ischemia. Of the 30 patients with completed questionnaires and Holter results, there was no difference in the incidence of minor end-points between the oxygen (5/13) and no oxygen groups (6/15) (p = 0.93). Intervention by the medical escort consisted of commencing oxygen therapy on those patients with low oxygen saturations and those with chest pain. Use of an already dispensed glyceryl trinitrate spray was initiated in one patient with chest pain that turned out to be non-ischemic when the Holter traces were later analyzed. CONCLUSIONS: This study suggests that, provided that care is taken during the immediate preflight and postflight phases not to overexert the patients, neither supplemental oxygen nor medical escorts are needed in the transportation of patients who fly 2 wk after acute myocardial infarction.

Aerospace Medicine↗

Prophylactic ephedrine prevents hypotension during spinal anesthesia for Cesarean delivery but does not improve neonatal outcome: a quantitative systematic review.

PURPOSE: The objective of this systematic review was to assess the effectiveness and safety of ephedrine compared with control when given prophylactically to prevent hypotension during spinal anesthesia for Cesarean delivery. SOURCE: Randomized, controlled trials obtained through MEDLINE, EMBASE, the Cochrane Controlled Trials Registry, contact with leading experts, and a reference list of published articles were analyzed. The following keywords were utilized: spinal anesthesia, hypotension, Cesarean section, pregnancy complications, pregnancy outcome, fetal outcome, neonatal outcome, umbilical blood cord gases, vasopressor and ephedrine. Clinical trials were considered if they compared prophylactic ephedrine, given by any dose or route, vs control. PRINCIPAL FINDINGS: The 14 clinical trials identified included data from a total of 641 patients. Ephedrine was more effective than control for preventing hypotension (relative risk [RR], 0.73; 95% confidence interval [CI], 0.63 to 0.86). Most importantly, there was no difference in the risk of fetal acidosis, defined as umbilical arterial pH < 7.2 (RR, 1.36; 95% CI, 0.55 to 3.35) or the incidence of low Apgar scores (< 7 or < 8) at one minute (RR, 0.77; 95% CI, 0.29 to 2.06) and five minutes (RR, 0.72; 95% CI, 0.24 to 2.19). CONCLUSIONS: Prophylactic ephedrine is more effective than control for preventing hypotension during spinal anesthesia for elective Cesarean delivery but a clinically relevant positive effect on neonatal outcome was not observed. Therefore, the routine use of prophylactic ephedrine to prevent any adverse effects of maternal hypotension following spinal anesthesia for Cesarean delivery is not supported by the current systematic review.

Acidosis↗

Ocular tracking as a measure of auditory motion perception.

Motion is a potent sub-modality of vision. Motion cues alone can be used to segment images into figure and ground and break camouflage. Specific patterns of motion support vivid percepts of form, guide locomotion by specifying directional heading and the passage of objects, and in case of an impending collision, the time to impact. Visual motion also drives smooth pursuit eye movements (SPEMs) that serve to stabilize the retinal image of objects in motion. In contrast, the auditory system does not appear to be particularly sensitive to motion. We review the ambiguous status of auditory motion processing from the psychophysical and electrophysiological perspectives. We then report the results of two experiments that use ocular tracking performance as an objective measure of the perception of auditory motion in humans. We examine ocular tracking of auditory motion, visual motion, combined auditory + visual motion and imagined motion in both the frontal plane and in depth. The results demonstrate that ocular tracking of auditory motion is no better than ocular tracking of imagined motion. These results are consistent with the suggestion that, unlike the visual system, the human auditory system is not endowed with low-level motion sensitive elements. We hypothesize however, that auditory information may gain access to a recently described high-level motion processing system that is heavily dependent on 'top-down' influences, including attention.

Acoustic Stimulation↗

Estimating with confidence the risk of rare adverse events, including those with observed rates of zero.

Omission of a confidence interval (CI) associated with the risk of a serious complication can lead to inaccurate interpretation of risk data. The calculation of a CI for a risk or a single proportion typically uses the familiar Gaussian (normal) approximation. However, when the risk is small, "exact" methods or other special techniques should be used to avoid overshooting (risks that include values outside of [0,1]) and zero width interval degeneration. Computer programs and simple equations are available to construct CIs reasonably accurately. In the special case in which the complication has not occurred, the risk estimated with 95% confidence is no worse than 3/n, where n is the number of trials.

Anesthesia↗